brains vol 1

BRAINs| Vol. I November 2013 | I/XI/2013/EAMSC 2014 1


Bundle Regular of AMSA-Indonesia National Competitions (BRAINs) is a full compilation of all works submitted in every national competitions held by Asian Medical Students’ Association (AMSA) Indonesia. The previous bundle is named AMSA Indonesia National Competition Bundle (AINCB). Each year, AMSA Indonesia held three national competition events entitled Pre-conference competition for East Asian Medical Students’ Conference (PCC for EAMSC), National Paper Poster Training, and also Pre-conference competition for Asian Medical Students’ Conference (PCC for AMSC). This third bundle, compile all works participated in PCC for EAMSC 2014, which aimed to choose Indonesia representative in EAMSC 2014 in Seoul — South Korea, on January 12-16th. The theme for this competition is “Walking side by side: acompanying the patientson their lifelong strugle with chronic disease” In this competition, Indonesia will send 1 Scientific Paper, 1 Scientific Poster, and Health Campaign consist of 1 Film and1 Public Poster. Once compiled, Bundle of AMSA will be both distributed to all local AMSA and published via the AMSA-Indonesia web so that all members could easily access and obtain useful information gather in this bundle. Enjoy and keep involved in academics!

Judges • dr. Dimas Bayu, SpPD • dr. Forman Erwin Siagian, MBiomed • dr. Dhanasari Vidiawati, MSc, CM-FM

Total Team of PCC for EAMSC

2014 Scientific Paper 23

Scientific Poster 12

Health Campaign 19

EAMSC 2014 will be held in Seoul – South Korea, on January 12-16th

Contributors Regional Chairperson Garda Widhi Nurraga Universitas Diponegoro

Secretary of Academics Fabianto Santoso Universitas Indonesia

A-Team Creative Project Ayudhea Tannika Universitas Kristen Krida Wacana

Introduction


PLACE PHOTO HERE, OTHERWISE DELETE BOX

Table of Content

Introduction .………………………...……………………………………………..................................…….2 Table of Content …………………………………………...………………………..............…………………..3 Scientific Paper 1st winner: A Prototype of the Ideal Restaurant to Shift Consumers from Junkfood to Healthy Eating Habit in order to Prevent Obesity as a Predisposing Factor of Type 2 Diabetes Mellitus - Denisa Valianty, Raissa Alfaathir, Jean Vibertyn................................……………………............………………………….....5 2nd winner: Influence of Education Level in Breast Cancer Patienton Short-term Survival - Amadisto Gerwindrawan, Ariadne Aulia, Anditta Syifarahmah, Susanna Hilda Hutajulu, Femiko Mora Sitohang, Kartika Widayati Taroeno-Hariadi, Ibnu Purwanto, Johan Kurnianda……….................................................……..14 3rd winner: Direct Cost on Diabetes Type 2 In-patient Care in Jakarta, Indonesia - Fitriana Nur Rahmawati, Fabianto Santoso, Alviani Gloria Sisti, Shafiq Advani……….....................................................................20 Burden And Quality Of Life In Caregiver Of Cancer Patient In Cancer Community Jakarta – Afria Beny Safitri, Rifa Roazah, Ridho Ahmad Jabbar..............................................................................................................26 Breaking The Vicious Cycle of Malnutrition: The Role of Lentinula edodes (Shiitake mushroom) as Nutrition Intervention in Lung Cancer - Agnes Tamrin, Ingrid Melisa Makahinda...........................................32 Da-moms (diabetes-mellitus type 2 aware moms): a modified lifestyle intervention program for patients with type 2 diabetes mellitus in Indonesia - Athaya Febriantyo Ppurnomo, Isma Dewi Masithah, Nayla Rahmadiani…………………………...........................................................................................................41 Proliver (protection for liver) -Revolutionary Inventiontherapy For Liver Fibrosis Based On Regenerative Medicine Empowering Extracted Mint Leaf (mentha spicata l.) : experimental study - Ayu Pramitha Wulandari, Khrisna Rangga Permana, Shanti Andri Sakarisa, Depy Irmayanti………………….................49 The Effect Of Turmeric (Curcuma Domestica) Extract And Exercise To Myocardial Fibrosis In Streptozotocin-Induced Diabetic Mice - Edward Sutanto, Agatha Novell H, Andyta Nalaresi, Lathifa Putry Fauzia, Sarah Dyaanggari Akip , M. Ali Sobirin ....................................................................…………….57 Scientific Poster 1st Winner: Influence Of Education Level In Breast Cancer Patient On Short-Term Survival - Amadisto Gerwindrawan, Ariadne Aulia, Anditta Syifarahmah, Susanna Hilda Hutajulu, Femiko Mora Sitohang, Kartika Widayati Taroeno-Hariadi, Ibnupurwanto, Johan Kurnianda..………………………………………………....64 2nd winner: Direct Cost on Diabetes Type 2 In-patient Care in Jakarta, Indonesia - Fitriana Nur Rahmawati, Fabianto Santoso, Alviani Gloria Sisti, Shafiq Advani..................................................................………...65 3rd winner : Proliver (Protection For Liver) -Revolutionary Invention Therapy For Liver Fibrosis Based On Regenerative Medicine Empowering Extracted Mint Leaf (Menthaspicata L.) :Experimental Study - Ayu Pramitha Wulandari, Khrisna Rangga Permana, Shanti Andri Sakarisa, Made Pradnyawati Chania……………………………………………………………………………………….............................................66 REGENTS: Renal Regeneration through Hematopoietic Stem Cells Induced by Saccharomyces cerevisiae – Ayu Pramitha Wulandari, Putu Nina Belinda Saka, Made Pradnyawati Chania…….........…...67


Table of Content

Health Campaign 1st Winner: Care For Cancer – Felicia, Hoshea Jefferson, Jonathan Kevin, Shelly, Thong Felicia.............................................................................................………………………………………………....68 2nd winner: With Love and Faith Could Grows Hope - Astriani A, Kurniawan ND.................................. 69 3rd winner: Be Aware By Prepare - Annisa Ayu Asmiragani………..........................................................70 Fight Together Against Diabetes - Gweta Saldana Henry............................................................................71 Go Rushed: Hypertension Treatments - Dea Nathania..........................................................................................72 Cancer Caregiver : Unsung Hero - Kartika Rizky L., Afria B. Safitri, Geulissa Addini Abidin .............73 From the Young to the Elders, Embrace Alzheimer’s Patients - Devina Wangsa, Hadi Tjong, Harry Leksono Adiputro, Yita Gayatri Willyani ...................................................................................................................74


A Prototype of the Ideal Restaurant to Shift Consumers from Junkfood to Healthy Eating Habit in order to Prevent Obesity as a Predisposing Factor of Type 2

Diabetes Mellitus Denisa Valianty, Raissa Alfaathir, Jean Vibertyn

Faculty of Medicine, Universitas Hasanuddin, Indonesia

ABSTRACT Background: Type 2 diabetes mellitus is increasingly observed among children, adolescents and younger adults.The International Diabetes Foundation (IDF) says, “Diabetes and obesity are the biggest public health challenge of the 21st century”. Of the people diagnosed with type II diabetes, about 80 to 90 percent are also diagnosed as obese. This fact provides an interesting clue to the link between diabetes and obesity, and surprisingly eating fastfood is one of most popular way to get obese Material and Methods: In this study, we combine survey and literature review. We did two sections of random sampling survey to 100 junk food consumers directly on junk food restaurants in Makassar, South Celebes, Indonesia to get some data to support this study. This survey aims to prove consumers choosing fastfood restaurants either because of the taste or facilities and services, and consumers’ reasons on why they choose fastfood restaurants rather than healthier one based on price, servingtime, place, availability, and facilities. In the end, we try to analyze and combine between what consumers want and what consumers need to get the prototype ofideal restaurant to shift consumers from junk food to healthy eating habit. Results: 53,8%of our respondents believe the price of fast food is affordable enough which is around Rp20.000,00 to Rp40.000,00. About 50% respondents stated they could spend only 5-15 minutes in average to get their food served. 83,3% respondents love fast food restaurants in public places. 89,7% respondents stated that they choose fast food restaurant due to the convenience.All of our respondents agreed that every fast food restaurant facilitated by free Wi-Fi service, other thing is because they also can get extra souvenirs from the food they buy. But more respondents (64,1%) stated souvenir is not something they can get based on the food they choose in the restaurant. 94,9% respondents stated they are satisfied with the parking lot of fast food.In the poin of availability, respondents agreed that an ideal restaurant should be 24 hours available. Conclusion:Consumers choose fastfood restaurant rather than healthier one more because of proper facilities and good services provided rather than the taste. What they love from facilities, which also becoming the prototype of ideal restaurant to change their habit are TEFA which stands for Tolerable prices, Easily reached location, Fast serving time and Additional services (wifi, toys, parking lot and 24 hours availability).

Introduction Type 2 diabetes mellitus is a metabolic

disease that is diagnosed on the basis of sustained hyperglycemia. People with type 2 diabetes are at elevated risk for a number of serious health problems, including cardiovascular disease, premature death, blindness, kidney failure, amputations, fractures, frailty, depression, and cognitive decline (Goff, D.C.Jr., et al., 2007). The cause of Diabetes Mellitus is poorly

understood. Changes in diet and life style due to rapid economic development are fore most among the principle drives of diabetes in developing and developed country (Mohan, V., 2004; 468-474).

Over the past three decades, the number of people with diabetes mellitus has more than doubled globally, making it one of the most important public health challenges to all nations (Chen, L., et al., 2012).The International Diabetes Federation predicts

Scientific Paper – 1st Winner


that the number of people living with diabetes will to rise from 366 million in 2011 to 552 million by 2030 (IDF, 2011).Type 2 diabetes mellitus and prediabetes are increasingly observed among children, adolescents and younger adults (Chen, L., et al., 2012).According to the Center for Disease Control, we are eating ourselves into a diabetes epidemic. The International Diabetes Foundation (IDF) says that, “Diabetes and obesity are the biggest public health challenge of the 21st century.”

The Asia-Pacific region is at the forefront of the current epidemic of diabetes. There are currently more than 30 million people with diabetes in the Western Pacific region alone. The World Health Organization predicts that this number will rise dramatically by the year 2025, by which time India and China may each face the problem of dealing with 50 million affected individuals. The most important lifestyle changes relate to changes in dietary habits and physical activity and diabetes risk, particularly in younger individuals, is associated with the development of obesity and particularly central obesity (Cockram, C.S., 2000).The predisposing factors of type 2 Diabetes Mellitus consists of non modifiable and modifiable type. The non modifiable predisposing factor can not be modified, therefore there is no such way to prevent or reduce it. Genetic factor is a non modifiable factor. The modifiable predisposing factors is every factors which can be modified. For example, a number of lifestyle factors, including obesity, lack of physical activity, poor diet, stress, and others are known to be important to the development of type 2 Diabetes Mellitus (Williams textbook of Endocrinology. 12th edition. 1371-1435).Although both diabetes and obesity risk factors are often associated with race, age, and family history, it’s becoming more and more clear that the conveniences of modern life also contribute to the development of both diseases. For example, sedentary lifestyles (reduced physical activity) and the popularity of high fat, high energy diets (think “Super Size

Me”) and convenient foods are known to lead to obesity.

Obesity can lead the type 2 Diabetes Mellitus, Of the people diagnosed with type II diabetes, about 80 to 90 percent are also diagnosed as obese. This fact provides an interesting clue to the link between diabetes and obesity. Understanding what causes the disease will hopefully allow us to preventdiabetes in thefuture.

Being overweight places extra stress on your body in a variety of ways, including your body’s ability to maintain proper blood glucose levels. In fact, being overweight can cause your body to become resistant to insulin. If you already have diabetes, this means you will need to take even more insulin to get sugar into your cells. And if you don’t have diabetes, the prolonged effects of the insulin resistance can eventually cause you to develop the Type 2 Diabetes Mellitus. (Hussain, A,. et al.,2010)

Type 2 Diabetes Mellitus develops through abnormal insulin action and insulin secretion. Diabetes is diagnosed with blood glucose levels over 126mg/dL with a fasting blood glucose test and with levels over 200 mg/dL with an oral glucose tolerance test . Many patients may not realize that they have diabetes; some may have no signs or may have only mild, seemingly common symptoms that do not appear to directly implicate diabetes. The burdens of the disease with its dangerous complications include a seriously increased need for amputations and a higher risk for heart attack, stroke, retinopathy, and nephropathy.

Cortisol Regulation and Dysregulation: A Potentially Influential Contribution to Obesity & Diabetes

A direct relationship between diabetes and cortisol concentration has not been fully established, and many studies show a range of results. Circulating levels of cortisol are determined by the metabolism of cortisol, by the rate of its secretion from the adrenal cortex, and by the receptor sensitivity to cortisol. Therefore, cortisol may be increased by various mechanisms, which include impaired metabolism, stress, and


conversion of cortisone to cortisol. Although some studies have illustrated that type 2 diabetics do not have higher levels of ACTH or hypothalamic-pituitary-adrenal (HPA) axis activity than normal individuals, other studies have alternatively illustrated that cortisol levels are increased in diabetics by the risk factors : such as emotional or physical chronic stressors, advanced age, and adverse childhood stressors. These stressors, or others such as smoking, alcohol, depression, or dysphoria, may contribute to abnormal HPA axis activity. If the HPA axis activity is increased, excess cortisol may be secreted and correlated with insulin resistance, visceral obesity, and dyslipidemia.

The particular techniques used, however, greatly affect the interpretation of the cortisol measurements. Active glucocorticoids impair the activity of growth hormone, pituitary gonadotropin, and thyroid stimulating hormone. Cortisol is also involved in increasing target tissue resistance to these hormones. Because glucocorticoids are antagonists of insulin, they increase lipolysis and promote hepatic gluconeogenesis. Cortisol can stimulate caloric intake; this may contribute to obesity. Researchers have proposed a variety of pathways that may be involved in developing excess adiposity and diabetes, and cortisol appears to be particularly essential. The most important effects of cortisol on diabetes appears to be mechanisms that involve the overall HPA axis and also complex mechanisms that implicate 11 beta-hydroxysteroid dehydrogenase type 1, adipokines, and free fatty acids with effects in adipose tissue, liver, muscle, and pancreas.

So, how did the cortisol (has been explaned before), and lifestyle factors lead the Type 2 Diabetes Meliitus? Thats occur when the Lifestyle Factors (Stress, Excess caloric intake, Low physical activity) affect HPA activity and increases cortisol in the body, after that, the higher cortisol in adipose tissue (visceral fat) have been correlated with excess hepatic glucose production and lower levels of glucose

removal, (Abdominal adiposity is a strong predictor of type 2 diabetes, may be an indication of dysfunctional adipose tissue. Abdominal adiposity is often accompanied by metabolic disturbances, including insulin resistance, hypertriglyceridemia, hyperinsulinemia, glucose intolerance, hypertension, reduced levels of HDL, increased small and dense LDL, glucose intolerance, and hypertension). After that, Adipose tissue is exposed to an increased cortisol concentration when there is a rise in 11β-HSD1 action. There are more glucocorticoid receptors in visceral adipocytes compared to subcutaneous adipocytes, so 11β-HSD1 locally converts more cortisone to cortisol in visceral adipocytes. Because there is a constant supply of cortisone in the plasma, well-regulated target tissues may adjust cortisol concentrations through this conversion mechanism. Under some conditions in vitro, 11β-HSD1 may increases the convert of cortisol to cortisone, but the extent of this dehydrogenase activity in the body is unknown.After that, increased cortisol to liver through portal vein was occured. Because the liver is a major target for glucocorticoids, the effects on the liver leading to insulin resistance likely affect the entire body. This is likely because the liver is responsible for most of the glucose overproduction involved in type 2 diabetes. The measurements of glucocorticoid metabolism for the body as a whole usually reflect the activity in the liver. The high levels of glucocorticoids in visceral obesity increase the activity of lipoprotein lipase (LPL), so lipoprotein triglycerides are converted to free fatty acids (FFA). Visceral adipocytes are more sensitive to glucocorticoid stimulation. Therefore, lipolysis of fat, inhibited by insulin, is more pronounced in visceral fat than in subcutaneous fat; This increases the release of free fatty acids (FFA) in visceral adipose tissue (VAT); because VAT drains into the portal vein, this may increase the free fatty acids, glucocorticoids, and adipokines that reach the liver through the blood and contribute to hepatic insulin resistance. In


contrast, subcutaneous adipose tissue (SAT) drains free fatty acids into systemic circulation so the liver would not be directly affected. In the liver, the free fatty acids promote gluconeogenesis and inhibit the suppression of glycogenolysis. Specifically, the increased glucocorticoids promote expression of phosphoenolpyruvate carboxykinase (PEPCK) and upregulate the glucose-6-phosphatase system (G-6-Pase), which increases the production of glucose. The glucose overproduction contributes to hepatic insulin resistance and eventually insulin resistance throughout the body and Type 2 Diabetes Mellitus succesfully occured. In obese individuals, though 11β-HSD1 expression is typically increased in adipose tissue, many studies show that its expression is usually decreased in the liver. (Liebman, Tracey., 2001)

In this modern era, people tend to be more selective in choosing something, include foods. we assume that taste is not becoming the only priority in choosing foods, but facilities also play a big role. Therefore we think it is really important to make a research about whether facility really play a big role, and what are factors that involved, so in the end we can create an ideal restaurant to shift consumers’ mindset from junk food restaurant to healthy eating habits in order to prevent obesity as a predisposing factor of type 2 diabetes mellitus. This study also aims to give wider perspective for government and any stakeholders that willing to create a health restaurant for society and more information to restaurants’ owner regarding what their consumers really want.

Material and Methods

Fast food has becoming a very popular food worldwide. There are actually some definitions about fast food, but we make it more specific in this study. What we mean by fast food is a typical of fast food chains which has so many counters in public places although standing for one brand.

In this study, we combine survey and literature review. After doing the introduction which includes background and

several theories regarding type 2 diabetes mellitus, then we do two sections of random sampling survey to 100 junk food consumers directly on junk food restaurants in Makassar, South Celebes, Indonesia to get some data to support this study.

At the first section, we gave several basic questions (frequency of consuming and basic knowledge regarding what they consume). This section aims to know how far the consumers know about junk food. In this section, we also has one question as our exclusion criteria. So, we are going to exclude the consumers for the next section if they choose junk food because of the taste, because we are going to only focus on facility for the next section.

The second section is the focus of our study. This section aims to know consumers’ reasons on why they choose junk food restaurants rather than healthier one based on certain aspects, which are price, serving time, place, availability, and facilities. Those data then converted to certain charts and accompanied by several explanations. After finishing all survey results, then we try to search for several theories and previous researches about what goods about ideal restaurant based on aspects that we put on our survey. At the end of this research, we try to analyze and combine between what consumers want (based on our survey) and what theories stated (based on our literature review) to get the prototype of ideal restaurant to shift consumers from junk food to healthy eating habit in order to prevent obesity as a predisposing factor of type 2 diabetes mellitus. Results

Based on survey that we have done on September 7th 2013 at several fast food chain restaurants in Makassar, South Celebes, Indonesia with 100 respondens whom later been restricted into 78 samples after exclusion criteria, then here we got several results of first section of our survey regarding general information about consumers’ habit in the form of charts as shown below:


Chart 3.1 Frequency of fast food

consuming per month

Chart 3.1 above shows us that most of our respondents, as many as 47 persons (47%), consume fast food approximately 5-8 times in a month; 28 persons (28%) consume even more than 8 times a month; and only 25 persons (25%) consume 4 times a month or more rarely.

Chart 3.2 Reasons to choose fast food

rather than the halthier one

Chart 3.2 above shows us that the main reason consumers choose fast food rather than the healthier food is better facilities and services (78%). The rest of them are about taste (10%). Due to the highly subjectivity of taste in individual, taste, as one of the reason consumers choose fast food, becomes our criteria of exclusion. So, our next questions and study will not including the consumers who choose fast food because of the taste.

After the first section, then we exclude 22 of our respondens for the next section, because they does not fullfil our criteria of inclusion. Then we come with 78 consumers that chose junk food because of facilities and services provided. This section will focus on respondens’ opinion about junk food restaurant facilities and services that make them choose junk food restaurants rather than the healthier one. Here are the result:

Chart 3.3 Price

Chart 3.3 above shows as that, most

of our respondens (53,8%) think, the price of fast food is affordable enough. The rest of them stated that the price of fast food is very affordable (25,6%) and for less respondents (20,5%) the price is barely affordable.

Chart 3.4 Serving time

Chart 3.4 above is about serving

time, one of the reason people choose fast food, because they could spend less time to get the food. As much as 50% stated that they could spend only 5-15 minutes in average, much lesser than time they need to spend to get their other food served. As

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Services

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much as 28,2% stated that the serving time is more than 15 minutes. And even 21,7% stated that they could spend less than 5 minutes to get their food served.

Chart 3.5 Location

Chart 3.5 above shows us the comparison between consumers who choose fast food restaurants placed in public places and independent restaurants placed outside public places. Most of the respondents (83,3%) go to the fast food restaurants in public places, such as malls, airport, schools, hospitals, and others. The rest of them (16,7%) choose the fast food restaurant outside the public places.

Chart 3.6 Money spent

Chart 3.6 above shows us that most of our respondents (74,4%) spent approximately Rp20.000,00 to Rp40.000,00 for fast food, which they considered it as affordable enough. The rest of the respondents spent less than Rp20.000,00

(10,3%) and a little bit more spent more than Rp40.000,00 (15,4%).

Chart 3.7 Facilities Chart 3.7 above explains the

consumers’ opinions regarding poin of facilities of fast food restaurant.

Most of our respondents (89,7%) stated that they choose fast food restaurant due to the convenience, and only the rest of them (10,2%) stated conversely.All of our respondents agreed that every fast food restaurant facilitated by free Wi-Fi service, which makes them choose to go to fast food restaurant, to get food and free Wi-Fi.As much as 39,9% of our respondents stated that one of the reason they choose fast food restaurant to get food is because they also can get extra souvenirs from the food they buy. But more respondents (64,1%) stated that souvenir is not something they can get based on the food they choose in the restaurant. Most of our respondents (94,9%) stated that they are satisfied with the parking lot of fast food restaurant, as one of the facilities the restaurants serve. And only a very few of the rest of our respondents (5,1%) stated conversely.In the poin of restaurant availability, all of our respondents are satisfied by fast food restaurant, because those restaurants are available in most time. There are even many restaurants which are available for 24 hours a day. Discussion

0 10 20 30 40 50 60 70

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Independent

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Rp20.000,00 -‐

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posi*ve

nega*ve


In this study, we have five focus of criterias, which are price, serving time, location, money spent, and facilities. Our explanation below will be regarding those criterias and our final goal is to propose a better concept of an ideal health restaurant.

First is about the price of fast food. Our survey shows that most fast food consumers believe that the average price of fast food is affordable enough. It explains us enough why many people have no problem in spending their money for fast food. Most consumers, represented by our respondents, spend approximately Rp20.000,00 to Rp40.000,00 to get their fast food. With that amount of money, regardless their knowledge about the danger of consuming fast food in a long time, the consumers can enjoy a bunch of food they love. The declining real price of food and the relative low cost and convenience of energy dense food, in particular, are hypothesized as key contributors to overweight (Lakdawalla and Philipson, 2002; Cutler et al., 2003; Drewnowski and Darmon, 2005).

On the poin of serving time, fast food spend time approximately 5 to 15 minutes to serve their food. Here, we can conclude that 5-15 minutes to serve food is the tolerable time for the consumer to get their food served. This is the thing that we want to propose to the healthier restaurant with longer time of serving.

Location is also the reason people choose fast food restaurant. Most of fast food restaurants in town, especially in Makassaar, South Celebes, Indonesia, are located in public places and only a very few of them located as an independent building. This is related to the fact that people choose fast food because they can also get those food while they do their other activities in those public places, such as at school, the airport, malls, and others.

Our last criteria of inclusion consist of

five subpoins, which are convenience, free Wi-Fi service, souvenirs, parking lot, and availability of the fast food restaurant. In most of those poins, except souvenirs, most consumers are satisfied by the facilities

provided by the restaurant. They feel comfortable with the standard design of the restaurants to spend their time with their friends or family to eat delicious those energy dense food. They also choose fast food restaurant because they surely can get free Wi-Fi service, to do their assignment for example, or simply to do online surfing to spend their time. Souvenirs did not significantly impact the high rate consumption of fast food. Most of fast food restaurants only provide souvenirs for kids, and adult consumers do not see that as a weak poin of fast food restaurant, so they do not see any reason to stop getting fast food. A proper parking lot is also a determine factor of a success restaurant, including fast food restaurant. Most of the consumers feel satisfied by the proper parking lot the fast food restaurants provide. A proper parking lot here is a good parking lot, in size and security. People tend to choose restaurants or any other public places with good security for their vehicle. Last subpoin is about the availability of the restaurant. Fast food restaurant are chosen more than any other restaurant because they serve consumers more often than other restaurants do. Some of them even available for 24 hours a day. So when people starve for food in the middle of the night, the restaurant that can serve them food is much more likely to be fast food restaurant. According to the research, there are greater numbers of available total restaurant, including fast food, to be significantly associated with higher adult obesity (Chou et al., 2004).

Based on our study, fast food chains actually serve people everything good, except the fundamental one, which is the nutrition value of the food. Several studies have examined associations between fast food consumption and energy and nutrient intake and weight outcomes. Fast food consumption has ben associated with higher total energy intake and higher intake of fat, saturated fat, carbohydrates, sugar, and carbonated soft drinks and lower intake of micronutrients and fruit and vegetables (Lin et al., 1999; Binkley et al., 2000; French et al., 2000, 2001; Paeratakul et al., 2003;


Bowman et al., 2004; Bowman and Vinyard, 2004; Befort et al., 2006). To solve this kind of problem in order to create an ideal restaurant, we have two choices of actions; either solve the nutritional problem in fast food chains or create a healthier restaurant with fast food chains facilities. We clearly can not apply the first choice, because all those fast food chains are private business, not the part of governmental entity. Those kinds of energy dense food are their signature product which defines them. So, the other way we can propose is a healthier restaurant with at least exactly same facilities as fast food chains provide (relatively low cost, tolerable serving time, good location, convenience, free Wi-Fi service, proper parking lot, and great availability).

This prototype of restaurant will involve some specific job diciplines in running it. First, to maintain the nutritional value and balance of the food, the restaurant needs a nutritionist or clinical nutrition doctor. Second, the restaurant certainly needs great chefs to serve (relatively) delicious food for everybody in an efficient time of serving. And the last but surely not the least, the restaurant needs professional waiters/waitresses, great cleaning service and security in order to support the convenience and security of the restaurant. Restaurant with healthier food and good facilities actually grows more nowadays. The problem is those restaurant have a barely affordable cost for their food. That is why this is also the problem that the nutritionist and the chefs should solve. They should provide healthier food which cost relatively low. This will be a new concept of a multidisciplinary job which final goal is to shift consumers from fast food to healthy eating habit in order to prevent obesity as a predisposing factor of many kind of diseases, especially type 2 Diabetes Mellitus. Conclusion

After doing survey and literature review, here we conclude several things,

1. Most of our respondents choosing junk food not because of the taste, but more because of facilities and services provided. So basically, health restaurants that already exist are competitive enough on taste, they only need to repair themselves more on facilities and services.

2. In order to create an ideal restaurant to shift consumers from junk food to healthy eating habit, we need to consider several things as the prototype, a. The price of junk food restaurants are

mostly considered as moderate, therefore the range of this price could become a consideration in making an ideal restaurant for healthier food.

b. Serving time that is considered as tolerable for most consumers is approximately 5 to 15 minutes.

c. Any healthier ideal restaurant should be placed on public places in order to be easily reached, because that is what consumers love the most.

d. Most consumers spending 20.000 to 40.000 in one visit, therefore it could become considerations for healthier ideal restaurant in putting prices.

e. There are several facilities that should be considered most to be put whenever healthier ideal restaurant created, which are free Wi-Fi service, good restaurant design, proper parking lot, and available for 24 hours. If it is possible, interesting souvenirs should be provided.

This study has several limitations during the process, therefore we have several suggestions for the next researcher, 1. This study is only ended up with

prototypes, so we need the next research project to test the prototype to make sure this prototype is really work to shift consumers from junk food to healt eating habits.

2. The characteristic of consumers is different in any countries, so this study should be conducted in any other area that has different characteristic of consumers before being implemented


REFERENCES Befort, C., Kaur, H., Nollen, N., Sullivan, D.K.,

Nazir, N., Choi, W.S., et al., 2006. Fruit, vegetable, and fat intake among non-Hispanic black and non-Hispanic white adolescents: associations with home availability and food consumption setting. Journal of the American Dietetic Association 106 (3), 367-373

Bowman, S.A., Gortmaker, S.L., Ebbeling, C.B., Pereira, M.A., Ludwig, D.S., 2004. Effects of fast food consumption on energy intake and diet quality among Children in a national household survey. Pediatrics 113 (1 Pt 1), 112-118

Bowman, S.A., Vinyard, B.T., 2004. Fast food consumption of US adults: impact on energy and nutrient intakes and overweight status. Journal of the American College of Nutrition 23 (2), 163-168

Binkley, J.K., Eales, J., Jekanowski, M., 2000. The relation between dietary change and rising US obesity. International Journal of Obesity 24 (8), 1032-1039

Chen, L., Magliano, D.J., Zimmet, P.Z., 2012. The worldwide epidemiology of type 2 diabetes mellitus-present and future perspective

Chou, S.Y., Grossman, M., Saffer, H., 2004. An Economic Analysis of Adult Obesity: results from the Behavioral Risk Factor Surveillance System. Journal of Health Economics 23 (3), 565-587

Cockram, C.S., 2000.The epidemiology of diabetes mellitus in the Asia-Pacific region.Hongkong: Hongkong Med J

Cutler, D.M., Glaeser, E.L., Shapiro, J.M., 2003. Why have Americans become more obese? Journal of Economic Perspective 17, 93-118

Drewnowski, A., Darmon, N., 2005. Food choices and diet costs: an economic analysis. Journal of Nutrition 135 (4), 900-904

French, S.A., Harnack, L., Jeffery R.W., 2000. Fast food restaurant use among women in the Pound of Prevention study: dietary, behavioral, and demopraphic correlates. International Journal of Obesity 24 (10), 1353-1359

Goff, D.C. Jr., Gerstein, H.C., Ginsberg, H.N., et al., Prevention of cardiovascular disease in persons with type 2 diabetes mellitus: current knowledge and rationale for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Am J Cardiol 2007;99:4i-20i

Hussain, A; Hydrie, M.Z.I; Clausen, B; Asghar, S. (2010). Type 2 Diabetes and Obesity : A Review. Journal of Diabetology. 1-3

Lakdawalla, D., Philipson, T., 2002. The Growth of Obesity and Technological Change: A Theoretical and Empirical Examination. NBER Working Paper #8946

Liebman, Tracey. 2001. The Role of Cortisol and Abdominal Obesity in the Epidemic of Type 2 Diabetes Mellitus. Undergraduate Research Journal for the Human Sciences. 1-end.

Lin, B.H., Guthrie, J., Frazao, E., 1999. Quality of Children’s diets at and away from home: 1994-96. Food Review 22 (1), 2-10

Mohan, V., 2004.Why are Indians more prone to Diabetes?, in J.Assoc Physicians India 52: 468-474

One adult in ten will have diabetes by 2030. International Diabetes Federation. November 14, 2011

Paeratakul, S., Ferdinand, D.P., Champagne, C.M., Ryan, D.H., Bray, G.A., 2003. Fast Food Consumption among US Adults and Children: dietary and nutrient intake profile. Journal of the American Dietetic Association 103 (10), 1332-1338

Williams textbook of endocrinology.12th edition. Philadelphia: Elsevier/Saunders. Pp: 1371-1435


Influence of Education Level in Breast Cancer Patienton Short-term Survival Amadisto Gerwindrawan,1 Ariadne Aulia,1 Anditta Syifarahmah,1

Susanna Hilda Hutajulu,2Femiko Mora Sitohang,3 Kartika Widayati Taroeno-Hariadi,2 Ibnu Purwanto,2 Johan Kurnianda2

1Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia 2Division of Hematology and Medical Oncology, Department of Internal Medicine, University of

Gadjah Mada/Dr Sardjito General Hospital, Yogyakarta, Indonesia

3Department of Internal Medicine, Bekasi General Hospital

ABSTRACT Introduction:Cancer is a major public health problem in Indonesia and many parts of the world. Breast cancer has the highest prevalence and incidence ratio among the most cancers in Indonesian women. One of the most influenced factor of cancer overall survival are patient’s compliance, which depends on the educational and economical background level. Educational status has been observed as having impact in determining overall survival rate. Studies in some developed countries have shown that survival rate among cancer patients increased along with patient’s educational background level. This study aimed to analyse distribution of educational level in cases with breast cancer patient and determine short term survival rate across the groups with different educational status. Material and methods: An observational cross-sectional study was done on data of breast cancer patients diagnosed in January 2007 to December2008 in Tulip Integrated Cancer Clinic Dr Sardjito General Hospital Yogyakarta Indonesia. One hundred and forty-six data were eligible for their completeness and grouped to five different educational level (illiterate, primary school, secondary school, high school and university degree). Short term survival rate, defined as one year survival, was analysed among those groups. Results:From 146 cases of breast cancer, only one was male patient. Most breast cancer patients were 41-50 years old (40.4%). It was more common in patients who were married (89.0%). Patients mostly use insurance to pay the medical expenses (73.3%). The majority of the patients were diagnosed with breast cancer at advanced stage (42.5%), followed by early, locally advanced breast cancer (LABC), and unknown (30.1%; 22.6%; 4.8%, respectively). Significant results were found on short-term survival comparison between primary school versus secondary school, primary school versus high school, and primary school versus higher education (p=.009, p=.004, and p=.001, respectively). Conclusion: Higher education level was associated with higher short-term survival in breast cancer. Health promotion and education should be concerned in order to increase short-term survival of breast cancer patients. Keywords : Breast Cancer, Short-term Survival, Education Level Introduction

Cancer is a major public health problem in many parts of the world. Among women, breast cancer is the most common cancer, with more than 1.1 million women newly diagnosed globally every year. Annual mortality rate of breast cancer is 1,6% of

total female deaths worldwide. The rates vary among different communities and countries. Recent publication showed that the overall survival rate tends to be lower in developing countries (Lan, Laohasiriwong, & Stewart, 2013).

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In Indonesia, breast cancer is also the most prevalent malignancy in women, occupying 40.58% from all cancer cases found in Jakarta, Indonesia in 2003-2007. Furthermore, this malignancy is the first cause of cancer death. However, this data were only derived from Jakarta cancer registry since in Indonesia there is no comprehensive cancer registration (National Cancer Center, 2007).

The prognostic factors of cancer have been observed by multiple studies. These include demography, socioeconomics, hormone receptor and psychology. (Lan et al., 2013). Socioeconomic factors such as poverty, inadequate education, and lack of health insurance appeared to be far more important than biological differences (Ward et al., 2010).

In term of socioeconomic, some publications emphasized the role of educational level in predicting overall survival. Recently, Kim et al. demonstrated that mortality among cervical cancer was highest among cases with lowest educational level and highest among cases with highest educational level (Kim, Song, Kim, Park, & Ko, 2013). This indicates that educational status has impact in determining overall survival rate.

In Indonesia there is no comprehensive data of survival rate that is associated to educational status for all types of cancer. Thus, knowledge of educational status in cancer patients is highly important in health promotion program. Considering that breast cancer is the most frequent cancer in women, this present study aimed to determine the distribution of educational level in cases with breast cancer patient. Furthermore, distribution of short term survival rate across the groups with different educational status was determined.

Material and methods Study Subject

This study was conducted in a retrospective descriptive design.Observational cross-sectional analysis was done on 269 casesof breast cancer diagnosed in January 2007 to

December 2008 in Tulip Integrated Cancer Clinic Dr Sardjito General Hospital Yogyakarta Indonesia. However, only 146 data were eligible for their completeness. Data without patient’s educational background status, date of diagnosis, and date of last visit were excluded. Assessment of Education Level and Short-term Survival

Education levels were categorized into 5 groups, illiterate (never graduated from primary school), primary school (6 years of study), secondary school (9 years of study), high school (12 years of study), and higher education (more than 12 years of study), based on government regulation in Indonesia.Short-term survival was defined as one-year survival or less of breast cancer patients calculated from date of diagnosis to date of last visit or last follow up. Data Collection

The one year or less survivors were compared to the more than one year survivors in term of their education level. Data from the recently developed organ-specific cancer registry was used. Case report form was designed to accomodate all data including demography, diagnosis, treatment, monitoring, and follow-up. Only data on demography (age, marital status, educational level, form of payment), date of diagnosis, date of first visit, date of last visit, follow-up, and staging at the diagnosis were obtained. Statistical Analysis

All demographic data and stages were described by table and figure. Analyses of the educational levels and short term survival was done by Mann-Whitney test.Each group of educational level was compared to another group, one by one. p<0.05 reflected the significance of the analysis. In addition, Kruskal-Wallis test was used to analyze correlation between all categories.

Results

One hundred and forty-six cases were included in the study. The age variables were stratified into seven groups: unknown, aged 20 or less, 21-30, 31-40, 41-50, 51-60,


60 or more. Marital status was recorded as married or unmarried, based on the date of diagnosis. Form of payment in the cases was classified as insurance or no insurance. Stage at diagnosis was analyzed as unknown, early, locally advanced breast cancer (LABC), and advanced. Several unknown data were found in the secondary data from Tulip Integrated Cancer Clinic Dr Sardjito General Hospital Yogyakarta Indonesia, but were not affecting the study.

Demographic data of study subject showed that the most frequent age group was 41-50 years (40.4%). The mean age of patients at the time of diagnosis was 46.5 years old. From 146 patients only 1 patient was male. Most of the patients were married (89.0%), 13 were unmarried, and 3 were unclear. One hundred and seven patients were covered by insurance (73.3%), others had no insurance (25.3%), and the rest (1.4%) was unclear. The majority of the patients had been diagnosed with breast cancer at advanced stage (42.5%). The rest were diagnosed at early, LABC, and unknown, making up 30.1%, 22.6%, and 4.8% of the patient, respectively. Data showed that most of the patients had primary school (38.4%) as their education level, followed by high school, higher, secondary school, and illiterate (29.5%; 19.9%; 10.3%; 2.1%), respectively (see Table 1 for demographic data of the patients).

When analyzed for survival rate, groups were divided into two, one with one year or less survival and the other with more than one year survival. There are 90 cases that were included in the first group. In this group, the most frequent education level was primary school (45 cases). All patients that are illiterate were in the one year or less group. The patients with secondary school, high school, and higher education as their educational level had almost the same frequency of cases between one year or less and more than one year group (7 and 8; 23 and 20; 12 and 17, respectively) (see Figure 2).

We found significant results, using Mann-Whitney Test, on short-term survival

comparison between primary school versus secondary school, primary school versus high school, and primary school versus higher education (p=.009, p=.004, and p=.001, respectively). Other short-term comparison between education levels, such as illiterate versus all other education level, showed no significant result (p>0.05). Significant result was also shown from Kruskal-Wallis test (p=.001).

Discussions

The study showed that breast cancer was more common in women aged between 41-50. This is consistent with study conducted in another South-East Asian country, Vietnam. The incidence of breast cancer in that study was peak among women aged between 40 and 49 (Lan et al., 2013). There was a significance comparison of education level in short-term survival. Those were happened in short-term survival comparison between primary school and all other educational level higher than that. Patients with education level higher than primary school was shown to have better short-term survival compared to those who only graduated from primary school. Comparison between illiterate and all others educational level were insignificant, caused by the number of cases on that group was inadequate, only 3 cases.

Patients with primary school as their education level came when the disease were not in early stage, this will contribute to their survival rate. Those patients had inadequate knowledge about breast cancer and its screening test, as they only had 6 years of study.

This is consistent with another study that showed the ratio of death rates between breast cancer patients with lower education level and those with higher education level is 1.16 (Oemiati, Rahajeng, & Kristanto, 2011). Women with breast cancers and higher education level had 10% risk reduction of death compared to those with lower education level(Siegel, Ward, Brawaley, & Jemal, 2011).

Some studies showed that education level influences mortality rate in every type


of cancer; men with lower education level had more than 50% of mortality incidences compare to those with higher education level, meanwhile in women, 40% mortality incidences happened to those with lower education level (Oemiati et al., 2011). Mortality rates could be decreased if every breast cancer patients had the same higher education level. This statement supported by findings in American Cancer Society in United States(Siegel et al., 2011).

Education also influence the increasing or decreasing overall survival in some factors, such as environmental and lifestyle, hormonal factors, early detection, participation and awareness and alternate therapy. Environmental and lifestyle factors that influence cancer occurrence are associated with socioeconomic status such as alcohol consumption, dietary habits, or physical activity. Hormonal factors that influence the occurrence of cancer such as child bearing, age of menarche, age of menopause, and breastfeeding. More educated women or those in higher socioeconomic groups are more likely to undergo screening like mammography and then increase their survival. Lower socioeconomic groups have lower participation in screening and treatment compliance. Most of lower socioeconomic groups came to alternate therapy at the time they had already diagnosed with cancer by the doctor.

Financial problem is also one of the obstacles faced by breast cancer patients in Indonesia. Therapy for breast cancer is very expensive and unaffordable for most of the patients, because they have low financial background. Those people with low financial background also had to quit school so they had lower education level and weren’t aware of their health problem.

Stage at diagnosis strongly influences breast cancer survival and in the few studies investigating socioeconomic status and stages of diagnosis, women of lower socioeconomic status with breast cancer were more likely to be diagnosed at a later stage, because they denied the abnormalities they have found in their breast, try a variety

of alternative treatment. The stage of breast cancer was increasing further.

For the society, cancer is still considered as a huge problem. People think that once they diagnosed with cancer, they will have short survival time. This kind of problem can be overcome if they do routine screening so the cancer can be detected as soon as possible.

A number of limitations should be considered when interpreting the findings of this study. The study population were quite small as almost half (45.7%) of breast cancer patients were excluded caused by its record incompleteness on patient’s education level, date of diagnosis, and date of last visit. Survival rate was counted based on the date of last visit, not the date of death. This may lead into time bias. Lack of information in the cancer registry file was the problem. Patients also could not be contacted as there were no recorded contact number. This study used data that were passively collected from patients in Tulip Integrated Clinic dr Sardjito General Hospital Yogyakarta Indonesia. As dr Sardjito general Hospital Yogyakarta Indonesia is one of the biggest hospital in Indonesia, the generalizability of the study findings should be considered.

Despite the limitations, this is the first study in Indonesia that compared short-term survival in term of education level on breast cancer patients. Future similar studies with bigger subjects and better data collection can be conducted with this study as its base.

According to Lan et al., detection at an earlier stage of the disease and better access to effective treatment have been recommended as solutions to improve the life expectancy of breast cancer patients. Government should improve the educational level in Indonesia by giving the free tuition until high school (12 years of study), so the society had an equal level of education and higher awareness of their health. Expected an increase on short-term survival can be reached by promoting health and giving more information to the society about breast cancer and its screening. Primary health care is the most accessible place for those with


lower education level to find information about health. Government should supported and be more concern to those primary health care, especially in health promotion, such as promoting breast-self examination. Another desirable plan is a cancer control program aimed to improve cure rates to reduce the death rates and improve quality of life of breast cancer patients.

There is a lack of control to alternative treatment that had not yet approved by the health department caused society to choose those alternative treatment other than approved treatment, as the alternative are much cheaper. Government should be aware of this situation. Another group of society that can contribute to rise the awareness of health are medical students. They have higher education level, can contribute to give information and promote health by coming to community, as they have the capability to do so. Conclusion

The most frequent education level from breast cancer patients in Tulip Integrated Clinic Dr Sardjito General Hospital Yogyakarta, Indonesia was primary school. Higher education level was associated with higher short-term survival in breast cancer, especially comparison between patients with primary school as its education level and those with above primary school education level. Health promotion and education should be concerned in order to increase short-term survival of breast cancer patients. Acknowledgement

We would like to thank the Division of Hematology and Medical Oncology, Department of Internal Medicine, Universitas Gadjah Mada/Dr Sardjito General Hospital Yogyakarta Indonesia for financial support and Sindhu Wisesa, MD and Via Wahyu Ferianti,MD for technical assistance. References Kim, M., Song, Y., Kim, B., Park, S., & Ko,

G. P. (2013). Trends in Cervical Cancer Mortality by Socioeconomic

Status in Korean Women between 1998 and 2009, 34(4), 258–264.

Lan, N. H., Laohasiriwong, W., & Stewart, J. F. (2013). Survival probability and prognostic factors for breast cancer patients in Vietnam, 1, 1–9.

National Cancer Center (2007). Registrasi Kanker Berbasis Rumah Sakit di Rumah Sakit Kanker “Dharmais“. Indonesian Journal of Cancer, 1993–2007.

Oemiati, R., Rahajeng, E., & Kristanto, A. Y. (2011). Prevalensi Tumor dan Beberapa Faktor yang Mempengaruhinya di Indonesia. Badan Penelitian dan Pengembangan Kesehatan.

Schmeisser, N., Conway, D. I., Stang, A., Schmeisser, N., Conway, D. I., Stang, A., … Ahrens, W. (2013). A population-based case – control study on social factors and risk of testicular germ cell tumours. British Medical Journal Open, 3. doi:10.1136/bmjopen-2013-003833

Siegel, R., Ward, E., Brawaley, O., & Jemal, A. (2011). The Impact of Eliminating Socioeconomic and Racial Disparities on Premature Cancer Deaths. Cancer Statistics, 2011. doi:10.3322/caac.20121.Available

Ward, E., Jemal, A., Cokkinides, V., Singh, G. K., Cardinez, C., Ghafoor, A., & Thun, M. (2010). Cancer Disparities by Race / Ethnicity and Socioeconomic Status. Cancer Disparities.


Table 1:

Characteristic of Breast Cance

r Patien

ts

Figure 1. Education Level of Breast Cancer Patients. Patients of breast cancer are mostly having primary school as education level.

Figure 2. Education Level Frequencies based on Short-term Survival. Shown that most of cases that in one-year or less group are primary school and the most of cases that in more than one-year group are high school.

2.10% 38.40%

10.30% 29.50%

19.90% Illiterate

Primary School

Secondary School High School

Higher

Characteristic Number of Patients

Percent

Educational Level

Illiterate 3 2.1% Primary School 56 38.4% Secondary School

15 10.3%

High School 43 29.5% Higher Education

29 19.9%

Age n/a 2 1.4% <21 years 0 0.0% 21-30 years 5 3.4% 31-40 years 29 19.9% 41-50 years 59 40.4% 51-60 years 39 26.7% >60 years 12 8.2% Gender Male 1 0.7% Female 146 99.3% Marital Status n/a 3 2.1% Unmarried 13 8.9% Married 130 89.0% Payment n/a 2 1.4% Insurance 107 73.3% No insurance 37 25.3% Stadium n/a 7 4.8% Early 44 30.1% LABC 33 22.6% Advanced 62 42.5%


Direct Cost on Diabetes Type 2 In-patient CareinJakarta, Indonesia

Fitriana Nur Rahmawati, Fabianto Santoso, Alviani Gloria Sisti, Shafiq Advani Asian Medical Student Association-AMSA-Universitas Indonesia

Faculty of Medicine Universitas Indonesia, Indonesia

ABSTRACT

Background:Diabetes Mellitus Type 2 (DM) is still the most concerning disease worldwide due to its increasing prevalence rate annually, particularly in developing country, such as in Indonesia. The impacts of DM which are our concern now are disability and high economic cost. There is no study that evaluates the direct cost on in-patient DM before in Indonesia (even limited in Asia). This direct cost data is important for health professionals and patient with DM to be aware of the current and future economic impact of this disease.This study is aimed to evaluate the cost of DM in Indonesia in order to develop and implement public health and prevention policies. Material and methods:Cross-sectional descriptive study was used to estimate the health care cost of Indonesian in-patients with DM. 184 subjects were taken with total random sampling technique (fulfilled inclusion criterion and exclusion criterion). The information on socio-demographic and clinical characteristic was collected from the medical record of patients. Component of health care cost assessed in this study only consists of direct cost which is calculated from patient’s billing and hospital data. We also analyze demographic data statistically to know their correlation with direct cost. Result:For social demographic, age (p=0.347), sex (p=0.723), and origin of province (p=0.207) were not correlated significantly with direct cost. The type of payment that patients use is difference statistically with direct cost (p=0.002). The same result went with complication and length of stay which were correlated significantly with direct cost (both of them, p<0.001). The correlation between number of complication and length of stay itself was also significant (p<0.001). Conclusion:This study evaluated the direct cost on diabetic type 2 in-patient care which helps to describe the impact that society faces from that disease. INTRODUCTION

Diabetes Mellitus Type 2 (DM) is still the most concerning disease worldwide due to its increasing prevalence rate annually, particularly in developing country. In 2012, according to WHO, there are 347 million people suffering from DM worldwide (WHO, 2012). In Indonesia, the prevalence of DM – based on the latest research conducted in 2007 - is approximately 5.7% and only 1.5% of them aware they have diabetes (Kesehatan, 2007). In National Hospital of Indonesia, Cipto Mangunkusumo Hospital, there are 13.707 patients diagnosed with DM who came to metabolic endocrine polyclinic and 1.590

patients had received treatment in 2012 (Darmowidjojo, et al., 2012).

Another concern about DM is it may lead

to disability and high economic cost. This becomes another great concern that DM is not merely a health care problem but also a burden for both government and patients. In United States, the total economic costs of diabetes in 2012 is $245 billion, and estimated each patient spend $13,700 in a year (American Diabetes Association, 2013). In addition, the health care expenditures for patients with diabetes is 5 times higher than patients without diabetes. Subsequently, the risk of being hospitalized among diabetic patients is 3 times higher

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than in non-diabetic patients (Bjork, 2001).The cost is estimated to increase 130% in patients with chronic complications (Soewondo, Ferrario, & Tahapary, 2013). Overall, diabetes and its complication is ranked 17th as one of the most 20 expensive diseases in US (Russo & Andrews, 2006). Nevertheless, chronic complication declines the patients’ productivity that worsens the economic burden. The best way to solve this problem is to initiate and augment prevention programs against this disease.

Studies about the cost of DM in Indonesia are limited (even In Asia) and there is no study that evaluates the direct cost on in-patient before. In this era of changing economic trends it is important for health professionals and patient with DM to be aware of the current and future economic impact of this disease. Therefore, the cost-of-illness is urgently needed as an approach to assess the diabetes and its complication in degrading the quality of life of DM patients seen from its economic cost.This study aimed to evaluate the cost of DM in Indonesia in order to develop and implement public health and prevention policies.

MATERIAL AND METHODS

Cross-sectional descriptive study was used to estimate the health care cost of Indonesian in-patients with DM. This study was conducted in Cipto Mangunkusumo Hospital, Jakarta as a tertiary care multispecialty hospital and center of referral in Indonesia. Jakarta as the capital city of Indonesia is a city with a populationmore than 10 million and Indonesia’s economic, cultural, and political center.

This study was carried out in in-patient setting from 1st January 2013 until 27th September 2013. To be included in this study, patients must have diabetes mellitus type 2 or its complication as a primary diagnosis. Diabetes mellitus was diagnosed according to WHO criteria. The complication defined as health problems that can occur as a result of consistently high blood glucose levels in diabetes including acute complications such as diabetic ketoacidosis, hyperglycemia hyperosmolar

state, hypoglycemia, diabetic coma and chronic complication grouped under microvascular and macrovascular disease (Fauci, et al., 2012).

Diabetic subjects who fulfilled that inclusion criterion were selected using total random sampling technique and a total of 184 eligible subjects were found. The subjects excluded from the study were patients whose medical record is not complete and people less than 20 yearsand more than 79 yearsof age.

The information on socio-demographic and clinical characteristic was collected from the medical record of patients. Socio-demographic data consists of age, sex, origin provinces of patients, and type of payment. Meanwhile the clinical characteristics consist of the occurrence of complication and length of stay. Component of cost of care assessed in this study only consist of direct cost. Direct cost was defined as the actual monetary expenditure related to treatment of an illness. It included hospitalization cost, drug cost, laboratory cost, radiology cost, supportive examination cost, medical procedures cost, doctor cost, and consultation cost. Information required to calculate costs was obtained from patient’s billing and hospital data. Costs were measured in Indonesian Rupiah (IDR) or equal to 11.486 IDR per US$. Ethical approved was taken from ethical committee of Cipto Mangunkusumo Hospital and written permission was given to get all of the information needed.

Statistical analyses of the data were done using SPSS-16. Descriptive statistics in terms of frequency counts and percentages were used for categorical variables such as sex, origin provinces of patients, type of payment, and complication. For the numerical variables that is age and length of stay, mean and standard deviations were calculated if the data distribution is normal or median and minimum maximum if data distribution not normal. The statistical analysis performed by using Pearson correlation coefficients tests to determine the association of direct cost with age and length of stay. For association of direct cost


with sex, origin provinces of patients, type of payment, and complication, bivariate analysis was carried out by Kruskal Wallis and Mann Whitney U test. Results are displayed in a tabular manner in the result section below.

RESULTS

A total of 184 DM patients were included in this study with mean (SD) age 56.28 years old (range 20-79 years) with majority (56.5%) were female patients. Most patients came from Jakarta (66,67%) and another were from some provinces in Indonesia. By type of payment, the majority (86.4%) had health insurance and most of them came from Jakarta (69.8%). About 96.7% of patient already had complication. We also found that on average each patient stayed around 14 days during the hospitalization (Table 1). Table 1: Distributions of socio-demographic and clinical characteristics among diabetic patients in Cipto Mangunkusumo Hospital (n=184)

Characteristics N (%) Age (in years), Mean (SD)

56.28 (11.05)

Sex Male 80 43.5 Female 104 56.5

Origin Provinces Jakarta 122 66.3 Other provinces 62 33.7

Payment Out of pocket 25 13.6 Health Insurance 159 86.4

Complication No Complication 6 3.3 1 Complication 57 31 Multiple Complications

121 65.8

Length of Stay (in days), Median (Min-Max)

14,16 (1-83)

Total direct cost of DM over this period

amounted to IDR 28.787.444. The mean cost for medical procedures compromised a

large proportion of direct cost (IDR 10.506.723) followed by drug cost (IDR 9.622.597). Money spent on hospitalization and laboratory was almost similar. The mean cost for doctor, supportive examination, and radiology were much less. The consultation cost was minimal (Table 2). Table 2: Direct cost in Indonesia Rupiah of studied patient during hospitalization*

Variables Mean (SD)

Hospitalization cost 5.362 (6.600) Drug cost 9.622 (16.765) Laboratory cost 5.103 (6.814) Radiology cost 875 (1.498) Supportive examination cost

1.051 (4.160)

Medical procedures cost

10.506 (17.789)

Doctor cost 2.582 (3.252) Consultation cost 496 (1.443)

Total cost 28.787 (40.290) * Measured in thousands IDR, we

considered 11.486 IDR per US$. For social demographic, age was not

correlate significantly with direct cost (p=0.347). The same result went with sex in which direct cost was higher for male. By origin provinces the direct cost was higher in patients who came from Jakarta although the difference was not significant (p=0.743). Patients who paid their medical bills using health insurance expended more on diabetic care and this difference was significant (p=0.002). As expected, the number of complications and length of stay were found to be significant (p<0.001 for both). The correlation between number of complication and length of stay itself was also significant (p<0.001) (Table 3).


Table 3: Socio-demographic andclinical characteristics correlated with diabetic direct cost*

Characteristics Direct Cost

Mean (SD) p value Age 28.787 (40.290) 0.347 Sex

Male 31.044 (49.592) 0.723 Female 27.051 (31.476)

Origin of Province Jakarta 31.566 (43.916) 0.207 Other provinces 23.318 (31.597)

Payment Out of Pocket 9.561 (2.137) 0.002 Health Insurance

31.810 (3.360)

Complication No Complication

21.446 (64.041) <0.001

1 Complication 42.923 (38.151) Multiple Complications

42.541 (64.041)

Length of Stay (in days), Median (Min-Max)

28.787 (40.290) <0.001

* Measured in thousands IDR, we considered 11.486 IDR per US$.

DISCUSSION

Diabetes mellitus is an expensive disease to treat and it affects both of the patient and government. Determining the cost of disease is claimed to provide information for health policy making and help nation to determine funding priorities and cut down where inefficiencies may exist and saving could be make. Several studies that analyze the diabetic cost of care have already done before in Indonesia but this is the first study that evaluates the cost of care on hospitalized patients and correlate it to the social demographic and clinical characteristics of the patient. Through this study we produced some important information that may contribute to better diabetic healthcare planning.

The total direct cost during 14 days length of stay was estimated around IDR

28.787.444 per patient in this study. There is no other study that reported direct cost on in-patient study; therefore it cannot be compared to other study. The total cost in this study also cannot be compared with studies done in other developed country since the methodological and vast difference in economic set ups between each country.

From another study that reported direct cost of treatment on out-patient in Yogyakarta, Indonesia, it is estimated that each patient spend IDR 208.500-745.500/month (Andayani, 2006). Unfortunately this study did not include patient’s income as one of socio-demographic parameter but we still can see that both cost of care (in-patient and out-patient clinic) is way bigger than regional minimum income in Jakarta (IDR 2.200.000). Although 86.4% of patients already had health insurance to cover their medical bills, the health care budget would not meet the need of diabetes cost of care since diabetic patients have more frequent and intensive encounter with health care system. Moreover we also found that patients with health insurance expended more on diabetic care since they did not need to pay the bills by themselves and the same mind set also applied on the health professionals. It already seen in 2012 that health care budget of Jakarta (around IDR 800.000.000.000) is still lack to cover up all of the health care expenses (Berita Satu, 2012). If this problem happens repeatedly every year it will stunt economic growth. These expenses can be suppressed by increasing the awareness of health professionals about the diabetic cost thus they can be wiser on treating the diabetic patients with minimal budget but maximal outcome.

In the other hand 13.6% of patients still paid their medical bills by out-of-pocket. The choice between healthcare expenses and food or education can decrease the family’s standard of living and trap them in poverty. Indonesia have not implemented universal health coverage yet and patients can get health insurance if they work as civil servant, military, police, work in company


which ensures the health insurance, buy commercial insurance, or get health insurance from local government for poor population. This kind of system is not ensuring that every citizen has access to health care especially for people who live right above the poverty line but cannot afford the healthcare expenses by their income and did not get insurance from local government. By looking at the origin province of the patients we found that 30.2% of patients who paid out-of-pocket came from other provinces than Jakarta. They are having lack of access to health care insurance since they need Jakarta identity cards to get health insurance from Jakarta’s government and it is difficult thing to make (Indonesia have not implemented single identity card and still based on living region). There is a strong need to develop universal health coverage to protect their household budget and increase treatment compliance. Fortunately in 2014 Indonesia will implement the universal health coverage and it may help to decrease economic burden for both of patients and government.

The greatest bulk of the costs were made up of money spent on medical procedures and buying drugs. It is similar with other studies in different countries (Grover, Avasthi, Bhansali, Chakrabakti, & Kulhara, 2005). Most of these expenses attributed to the complication such as debridement for gangrene or hemodialysis for chronic kidney disease. In this study we also found that number of complications is the most important determinant of direct cost and hospitalization cost and it significantly correlate with the longer length of stay.

Majority of patient in this study already developed complication especially multiple complications (65.8%) such as diabetic ketoacidosis, hypoglycemic, renal, ophthalmic, and peripheral circulatory complications, which indicate that glycemic control had not been adequately over the years or due to the late of diagnosis thus resulting in acute and chronic complications. Implementing prevention program is the ultimate way to solve this problem and this

can be done by strengthening primary care. Early diagnosis of DM and prompt treatment should also be made by doing routine wide scale screening program.

CONCLUSSION

This study evaluated the direct cost on diabetic type 2 in-patient care which helps to describe the impact that society faces from that disease. The principal findings of this initial study can lead to further research in which cost-effective intervention could be evaluated leading to a potential reduction in the economic burden of diabetes in Indonesia.

There are some limitations in this study which should be considered in making further research. Firstthe costs do not include patient out-of-pocket costs, direct nonmedical costs, and indirect costs. Second, another social demographic variable such as education background and patient’s income was not included. Another research to evaluate not only direct but also indirect cost should be made since indirect cost can reflect patient’s loss of productivity due to the disease.

Any efforts at economic burden reduction should be done together by policy maker, health professional, NGO, and patients themself. Policy makers need to augment and strengthen the prevention programs at primary health care and provide cheaper drug to reduce medication cost. In addition the implementation of universal health coverage must be succeeded to decrease the brunt of economic burden that patient have to bear. Increase awareness of these facts among health professionals and encourage them to update on current management of the disease will facilitate prevention strategies and develop rational prescribing and investigations. As a medical student our role is not quite different with health professionals. We can help by doing prevention program such us hold screening program using blood glucose test, giving health education and promote awareness. Hopefully by doing all of those change together the cost-effective but high quality diabetes care can be achieved in Indonesia.


REFERENCES American Diabetes Association. (2013).

Economic Cost of Diabetes in the US in 2012. Diabetes Care(36), 1033-1046.

Andayani, T. (2006). Analisis Biaya Terapi Diabetes Mellitus di Rumah Sakit dr. Sardjito Yogyakarta. Majalah Farmasi Indonesia, 17(3), 130-135.

Badan Penelitian dan Pengembangan Kesehatan. (2007). Laporan Riskesdas. Jakarta: Batlitbangkes.

Berita Satu. (2012, November 12). Tutupi Utang, Anggaran Kartu Jakarta Sehat Capai Rp 800M. Retrieved from Berita Satu.com: http://www.beritasatu.com/peristiwa-megapolitan/82631-tutupi-utang-anggaran-kartu-jakarta-sehat-capai-rp800-m.html

Bjork, S. (2001). The Cost of Diabetes and Diabetes Cure. Diabetes Research and Clinical Practice(54), 13-18.

Darmowidjojo, B., Tahapary, D. L., Wisnu, W., Tarigan, T. J., Purnamasari, D., & Harbuwono, D. S. (2012). Diabetes Mortality Rate and Pattern in Indonesia: Data from a Tertiary Teaching Hospital. 17th AFES Congress.

Fauci, A. S., Braunwald, E., Kasper, D. L., Hauser, S. L., Longo, D. L., Jameson , J., & Loscalzo, J. (2012). Harrison's Principles of Internal Medicine (Vol. 18th). New York: McGrawHill Companies.

Grover, S., Avasthi, A., Bhansali, A., Chakrabakti, S., & Kulhara, P. (2005). Cost of Ambulatory Care of Diabetes Mellitus: A Study from North India. Postgrad Med J(81), 391-295.

Russo, C. A., & Andrews, R. M. (2006). The National Hospital Bill : The Most Expensive Conditions. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK63505/

Soewondo, P., Ferrario, A., & Tahapary, D. L. (2013). Challenges in Diabetes Management in Indonesia: A Literature Review. Globalization and Health.

WHO. (2012, September). Diabetes. Retrieved from WHO: http://www.who.int/mediacentre/factsheets/fs312/en/index.html


Burden And Quality Of Life In Caregiver Of Cancer Patient In Cancer Community

Jakarta

Afria Beny Safitri, Rifa Roazah, Ridho Ahmad Jabbar Medical Faculty of Pembangunan Nasional “Veteran” Jakarta University, Indonesia

ABSTRACT

Background: Cancer is one of the deadliest diseases in the world. Prevalence ofcancerinIndonesia4.3% per1000 population. Familymembers are considered toplay an important roleas thefirstinformalcaregiversto cancer patients. Cancer can causes patients and caregivers losing control over their lives, has an adverse effect on their social life, work, family/marital life, and causes their health and quality of life to deteriorate. Material and Methods: The data collected by using three kind of questionnaires : demographic data form, The Zarit Burden Interview, and WHOQOL-BREF Questionnaires. The demographic data form include name, age, gender, education, occupation, income, health finance, and relationship to patient. 8 participants were selected by cross sectional in Cancer Club Jakarta. Results: Zarit Burden Score is 36.88 ± 9.643 (mild to moderate burden). The three domains of caregiver’s quality of life (psychological health, social relationships, and environment) are good enough (WHOQOL-BREF Score more than 50.00) but physical health domain score is 45.63 ± 3.443 (under 50.00). The result of Pearson and Spearman correlation test shows that caregiver burden and quality of life have negative correlation. Conclusions: The result of this study demonstrate that caregiver burden and quality of life have weak correlation. It is found that burden caregiver has small impact to their quality of life. The positive aspects of caregiving can be strengthened by psychological and social support. Keywords: Burden, Caregiver, Quality of Life INTRODUCTION

Cancer is one of non-communicable disease that considered to be the most deadly and has been a health problem in the world. According to World Health Organization (WHO), cancer is one of the deadliest diseases in the world, counted for 7,6 million deaths (around 13% of all deaths) in 2008. WHO estimated that in 2040, 11,4 million people will die because of cancer (WHOa, 2013).

3.6millionmenand4millionwomen in Asian countries arelivingwithcanceranddiagnosedwithinthe last 5 years. (McDonald, Hertz, Susan, Pitman, 2008). There are 15 countries with high incidence of cancer in Asia, including Indonesia, by comparison 48% of the total cancer population in the world. Health ResearchDatain 2007showedthe prevalence ofcancerin

Indonesia4.3% per1000 population(Indonesian Cancer Foundation, 2012).

Familymembers are considered toplay an important roleas thefirstinformalcaregiversto cancer patients(Sonet al, 2012). LaurelL.Northousesaidthat thepatientandfamilycaregiverhas areciprocal relationshiptocancer (Northouse et al, 2010). Family caregiver has responsibility for the patient’s physical and emotional care, activities of daily living, medication management, transportation, and household tasks, as well as communicating with healthcare providers and insurance companies. (Williams, Bakitas, 2012). In one study, more than 50% of caregivers spend about 8 hours a day in the care of cancer patients receiving chemotherapy (American Cancer Society, 2012). With all of these responsibility, caring for cancer patient can be a burden to the family caregiver in various aspects such as psychological, physical, spiritual, social, financial, work, and family/marital life (National Cancer Institute, 2013). Familycaregiverwas oftenreported


haveemotional stress, anxietyordepressionthat same as thepatient.

Cancer can cause patients and caregivers losing control over their lives and quality of life to deteriorate (Turkoglu, 2012). Based on this problem, the researchers want to know how strong correlation between caregiver burden and caregiver’s quality of life. MATERIAL AND METHODS

The aim of this study was to find out is there correlation between the caregiver burden and family caregiver of cancer patient’s quality of life in a cancer club in Jakarta. This study utilized an analitic design. Participants

The participants were family caregivers of cancer patients in a cancer club in Jakarta. The cancer patients along with their family caregivers stay in a house that specially rented for cancer patients and their family caregivers. To be included, caregiver had to be : able to read and understand Indonesian Language, giving care to patient at least for four weeks, living with the patients during caregiving, and willing to participate in this study. The family caregivers were informed about the purpose of this study and the researchers explained them that they have right to refuse participation. The total cancer patients in this cancer club are 13 patients but there are only eight patients who accompanied by caregivers. It means that the total population are eight caregivers. All of them fulfill the criteria above, so the researchers got eight samples (saturated sample) for this study. Instruments

The data collected by using three kind of questionnaires : demographic data form, The Zarit Burden Interview, and WHOQOL-BREF Questionnaires. The demographic data form include name, age, gender, education, occupation, income, health finance, and relationship to patient.

The Zarit Burden Interview is a questionnaire consist of 22 questions (items) that used to assess caregiver burden. For each items, caregivers are to indicate how

often they felt that way (never, rarely, sometimes, quite frequently, or nearly always. (Zarit, Reever, & Bach-Peterson, 1980)

The WHOQOL-BREF was developed by World Health Organization (WHO). It assesses the individual's perceptions in the context of their culture and value systems, and their personal goals, standards and concerns. The WHOQOL-BREF instrument comprises 26 items, which measure four broad domains: physical health, psychological health, social relationships, and environment. (WHOb, 1993) Design

This study is a cross-sectional study. The researchers explain about the study first to the manager of the house where the cancer patients and their family caregivers stay to ask for permission and ask the amount of caregivers there to know the total population. After knowing the amount of caregivers there, the data then collected by using questionnaires. The questionnaires took approximately 15 minute to complete and could be understood by the family caregivers there.

SPSS was used to analyze the data. Descriptive statistic were computed for demographic variables of family caregivers. The correlation between caregiver burden and quality of life (psychological health and environment domain) was analyzed with Pearson correlation test. Correlation between caregiver burden and quality of life (physical health and social relationships domain) analyzed with Spearman correlation test for the two domains do not have normal data distribution.

RESULT

A total of eight caregivers were recruited and interviewed. The demographic characteristics of the sample are listed in Table 1. The sample of family caregivers comprised of four male and four female with prodominantly at range >40 years old (50%). All participant was literate, 37.5% had elementary education level and rest higher. 37,5% was working and rest of caregivers unemployeed. Participants who


have income below one million rupiahs per month are seven people (87,5%) and one person between 1 – 5 million rupiahs (12,5%). Participants cared for patients mostly with breast cancer and nasofaring cancer (not shown). They related to the patients as spouses and adult children and lived with the patient. Most of participants’ health finance supported by health insurance (75%).

Table 2 shows that mean score of Zarit Burden Score is 36.88 ± 9.643 (mild to moderate burden). The three domains of caregiver’s quality of life (psychological health, social relationships, and environment) are good enough (WHOQOL-BREF Score more than 50.00) but physical health domain score is 45.63 ±3.443 (under 50.00). The result of Pearson and Spearman correlation test shows that caregiver burden and quality of life have negative correlation, it means that the more burden felt by caregiver, the less caregiver quality of life. The result shows that there’s weak correlation between caregiver burden and three domains of quality of life (physical health, psychological health, and social relationships) and very weak correlation between caregiver burden and environment domain of quality of life.

DISCUSSION

Cancer is a broad group of disease involving unregulated cell growth. This terms correlate to the course of malignant neoplasm. Malignant neoplasms invade surrounding tissue and, in most cases, can metastasize to distant organs. To become neoplastic, a normal cell must develop mutations that allow it to no longer obey boundaries of adjacent cells, thus allowing for uncontrolled growth, and the neoplasm must be able to produce its own blood supply. Malignant neoplasm also gain the ability to invade the basement membrane and surrounding tissue, enter the blood stream, and spread to and grow within distant organs.

Although the development of many neoplasms is a sporadic event, certain heritable conditions predispose to the

development of malignancy. These hereditary causes of neoplasms may be grouped into autosomal dominant neoplasia syndromes and defective DNA repair syndromes, most of which are autosomal recessive. Importantly, although certain mutations are associated with the development of certain malignancies, one mutation alone is not enough to result in the development of a neoplasm. Although there are familial neoplasms associated with specificinherited mutations, most familial neoplasms have noidentifiable inherited mutation. A familial neoplasm is definedas a neoplasm seen in many generations in the same family.

Thefeatures of familial neoplasms include early onset, tumors intwo or more close relatives, and multiple or bilateral tumors.Examples include breast, ovarian, and colon cancers. The riskfor these neoplasms can be increased in families, most times with no well-defined hereditary condition. For example, themutations of the BRCA-1 and BRCA-2 genes are associatedwith breast carcinoma; however, only 2–4% of families withfamilial breast cancer have an identified mutation in either ofthese two genes.In addition to familial neoplasms, both with and withoutan identifiable inheritable mutation, certain preneoplasticconditions, exogenous toxins (i.e., carcinogens), and viral infections also predispose to the developmentof neoplasms (Kemp, Burns, & Brown, 2008).

Cancer survivors generally have higher rates of functional limitations. The most frequently cited type of limitation pertains to the ability to work. Thirty-one percent of middle-aged men and 30% of middle-aged women are limited in the amount or kind of work they can do, or are unable to work at all (Pharmaceutical, 2003). We can conclude that suffering cancer really influence cancer patient’s life. Cancer Caregiver Burden

Caregiverburden is commonly used to describe multiple dimensions of distress that result from an imbalance between care demands and the availability of resources to meet those demands. Many cancer patients


today receive part of their care at home. There are now treatments that don't need an overnight hospital stay or can be given outside of the hospital. Many patients want to be cared at their home soon. This care is often given by family caregivers. These caregivers may be spouses, partners, children, relatives, or friends. Caregiving includes everyday tasks such as helping the patient with medicines, doctor visits, meals, schedules, and health insurance matters. It also includes giving emotional and spiritual support, such as helping the patient deal with feelings and making decisions. (Institute, 2013). All of those tasks can be burden to the caregivers and influence their own quality of life. The caregiver may feel emotions that are as strong as or stronger than those felt by the patient too. Impacts of Caregiving on the Caregiver’s Quality of Life

Family caregivers usually begin caregiving without training and are expected to meet many demands without much help. A caregiver often neglects his or her own quality of life by putting the patient's needs first. When caregiver strain affects the quality of caregiving, the patient's well-being is also affected. Helping the caregiver also helps the patient. Physical Impact

Caregiving may be solely limited to physical care such as helping with toileting or eating but can also include lifting, positioning, transferring, massaging, and operating medical equipment. Cumulative sleep disruption and fatigue are common among caregivers who are on duty 24 hours a day or only during nighttime hours. Behaviors such as not getting enough rest or exercise and neglecting their own health can mimic depression in caregivers but can also contribute to the impairment of their health and quality of life (Carter, 2002). Psychological Impact

Family members confronting serious illness have been found to experience as much distress as, if not more distress than, the patient with cancer. This distress arises from the caregiver role itself as well as

witnessing the patient’s suffering (Weitzner, McMillan, & Jacobsen, 1999). Psychological distress is the most common effect of caregiving on the caregiver's quality of life. Caring for a cancer patient is a difficult and stressful job. Caregiver distress comes from the practical demands of the caregiver role as well the emotional ones, such as seeing the patient suffer. Social Impact

Social roles and relationships are profoundly affected by cancer. The nature and quality of the preexisting patient-caregiver relationship are important considerations in the assessment and treatment of caregiverburden. If marital or relationship strain predates the onset of cancer or pain, the caregiver may approach caregiving grudgingly. In addition, caregiving is time consuming and can lead to feelings of social isolation (Carter, 2002). Financial Impact

The financial impact and hidden costs of cancer may affect caregiver burden. Families can incur financial burden from insurance deductibles, copayments, uncovered services such as transportation and home care, and lost salaries. Additional costs to caregivers, in terms of time associated with caring for a patient with cancer, include the following: traveling to and from medical appointments, waiting with patients for appointments, missing work, preparing for surgery and medical procedures, neglecting their usual activities and relationships, and attending to patients who are hospitalized (Kim, Duberstein & Soronsen, 2008). Quality of Life and Burden Caregiver among Participants

Based in result in our study, we explored the correlates quality of life and burden in caregivers . The correlation test shows negative correlation that means the higher caregiver burden the poorer quality of life of cancer caregivers. There are weak correlation between caregiver burden and four domains of WHO quality of life. That result can happen because all of the patients and caregivers in our study were receiving support from each other. In that club, they


were sharing about their burden and feel like they’re not alone suffering from cancer. Patients and caregivers also have parallel spiritual tasks when dealing with cancer, such as finding meaning and hope in the disease process. In addition, maintaining faith and finding meaning have been shown to mitigate the adverse effects of caregiving stress on mental health, based on the participants explanation. This findings has the same result with Kim et al. that higher levels of spirituality are associated with lower psychological distress and improved well-being for caregiver (Kim, Wellisch, & Spillers, 2007). In that club, there are psychological support and practical assistance with problem solving from their manager and health care professionals. This also give positive impacts and strengthened them to have better quality of life.

Our study has limitation, we were limited here by the sample amount. Next research should include more sample in future studies. However, we have used an internationally validated questionnaire that was found to have adequate reliability and validity indices in our setting.

Government and society along with medical students can play role to help the caregivers of cancer patients. We can visit caregivers directly and regularly in cancer club house or in hospital to give them health information and support to reduce their burden, so their quality of life will increase. With improving caregiver’s quality of life, we can help the cancer patient. Conclusion

The result of this study demonstrate that caregiver burden and quality of life have weak correlation. This study found that caregiver burden has small impact to the quality of life of cancer caregiver. It can happen because the caregiver receive support from the othar caregivers, having strong spiritual faith, getting psychological support and practical assistance with problem solving from their manager and health care professionals. All of them can be improve caregiver’s quality of life.

REFERENCE

American Cancer Society (2012). What about my needs and feelings? Accessed from http://www.cancer.org/acs/groups/cid/documents/webcontent/003199-pdf.pdf, 19 September 2013.

Anna-leila Williams, Ph.D., M.P.H.I and Marie Bakitas, D.N.Sc.2. Cancer Family Caregivers: A New Direction for Interventions. Journal of Palliative Medicine. Volume 15, Number 7, 2012

Arsuma, Galuh Nindya. 2010. Caregiver Burden dan Strategi Coping pada Family Caregiver Penderita HIV/AIDS. Surabaya

Carter, P. (2002). Caregivers' descriptions of sleep changes and depressive symptoms. Oncol Nurs Forum 29 (9), 1277-1283.

Dahlan, Sopiyudin. 2012. Langkah – langkah Membuat Proposal Penenelitian Bidang Kedokteran dan Kesehatan. Sagung Seto : Jakarta

Dewi, Ikhsani Utami. 2010. Hubungan Karakteristik Caregiver Skizofrenia dengan Beban Caregiver Skizofrenia di Rumah Sakit Pusat Angkatan Darat Gatot Soebroto. Jakarta

Sekarwiri, Edesia. 2008. Hubungan Antara Kualitas Hidup dan Sense dari Community pada Warga DKI Jakarta yang Tinggal di Daerah Rawan Banjir. Jakarta

Institute, N. C. (2013). Family Caregivers in Cancer. Retrieved from National Cancer Institute at the National Institute of Health: http://www.cancer.gov/cancertopics/pdq/supportivecare/caregivers/patient/page1

Kemp, W. L., Burns, D. K., & Brown, T. G. (2008). The Big Picture Pathology. New York: The McGraw-Hill Companies, Inc.

Ki Young Son., et all . The Factors Associated with the Quality of Life of the Spouse Caregivers of Patients with Cancer:A Cross-Sectional Study. Journal of palliative medicine 2012, volume 15, number 2 ; p 15 1-9


Kim, Y., Wellisch, D., & Spillers, R. (2007). Psychological distress of female cancer caregivers: effects of type of cancer and caregivers' spirituality. Support Care Cancer 15 (12), 1367-1374.

Kumar, V., Abbas, A. K., & Fausto, N. (2005). ROBBINS AND COTRAN PATHOLOGIC BASIS OF DISEASE 7 Edition. Philadelphia: Elsevier Inc.

Laurel L. Northouse, Maria C. Katapodi, Lixin Song, Lingling Zhang, Darlene W. Mood.(2010). Interventions With Family Caregivers of Cancer Patients, Meta-Analysis of Randomized Trials. CA CANCER J CLIN;60:317–339

Mohammad Ali Heidari Gorji1†, Zinnatossadat Bouzar2,3, Mohsen Haghshenas4†, Ali Akbar Kasaeeyan5†, Mohammad Reza Sadeghi6* and Maryam Didehdar Ardebil7†, Heidari Gorji et al.Quality of life and depression in caregivers of patients with breast cancer.BMC Research Notes 2012, 5:310h http://www.biomedcentral.com/1756-0500/5/310

McDonald Margaret PhD, Hertz Robin P. PhD, Lowenthal Susan W. Pitman MD MPH. (2008). The Burden Cancer in Asia. Accessed fromhttp://www.pfizer.com/files/products/cancer_in_asia.pdf, 19 september 2013

National Cancer Institute (2013). The Caregiver’s Quality of Life.Accessed fromhttp://www.cancer.gov/cancertopics/pdq/supportivecare/caregivers/patient/page4, 19 September 2013

Northouse L. (2005). Helping families of patients with cancer. Oncology Nursing Forum.32:743–750

Pharmaceutical, P. G. (2003). The Burden of Cancer in American Adults. Retrieved from Pfizer Facts: http://www.pfizer.com/files/products/The_Burden_of_Cancer_in_American_Adults.pdf

Rachela Pellegrino, Vincenzo Formica, Ilaria Portarena, Sabrina Mariotti,Italia Grenga, Girolamo Del Monte And Mario Roselli. (2010). Caregiver Distress In

The Early Phases Of Cancer.Anticancer Research 30: 4657-4664

Susan K. Lutgendorf , Mark L. Laudenslager (2009). Care of the Caregiver: Stress and Dysregulation of Inflammatory Control in Cancer Caregivers. Journal of Clinical Oncology, volume 27, number 18; p 1-2

Turkoglu, Nihan. Kilic, Dilek (2012). Effect of Care Burdens of Caregivers of Cancer Patients on Their Quality of Life. APJCP

Weitzner, M., McMillan, S., & Jacobsen, P. (1999). Family caregiver quality of life: differences between curative and palliative cancer treatment settings. J Pain Symptom Manage 17 (6), 418-428.

World Health Organization (2013). Fact sheet. Accessed from http://www.who.int/mediacentre/factsheets/fs297/en/, 19 September 2013

WHOb. (1993). WHO Quality of Life-BREF (WHOQOL-BREF). Retrieved from World Health Organization: http://www.who.int/substance_abuse/research_tools/whoqolbref/en/

Yayasan Kanker Indonesia (2011). Apakah kanker itu?Accessed fromhttp://yayasankankerindonesia.org, 25 September 2013

Zarit, S. H., Reever, K., & Bach-Peterson, J. (1980). Relatives of the impaired elderly: correlates of feelings of burden. Gerontologist, 649-655.


Breaking The Vicious Cycle of Malnutrition: The Role of Lentinula edodes (Shiitake

mushroom) as Nutrition Intervention in Lung Cancer Agnes Tamrin, Ingrid Melisa Makahinda

Faculty of MedicineUniversitas Katolik Atma Jaya

ABSTRACT Background: Lung cancer is the most common cancer found in men in Indonesia. The incidence of this chronic disease is increasing dramatically due to cancer-associated lifestyle choices, especially tobacco smoking. Lung cancer is highly associated with malnutrition, particularly cancer cachexia. The relationship between lung cancer and cachexia is best described as a vicious cycle. This would eventually lead to the deterioration of the course of disease, and worsen the condition of the patient. Attention should be shifted to nutrition in order to break this vicious cycle and increase the patients’ quality of life. In this review, we would like to evaluate the possible role of Lentinula edodes as nutrition intervention in lung cancer. Material and methods:We use systematic review method as our study design. We initially selected 97 articles published in the last 10 years. Other relevant references and texts are used. 28 articles and references are included in the review, including research journals, systematic review journals and textbooks. Results: L. edodes is proven to have a high nutritional content. Lentinan, a β-glucan found in the cell wall of this mushroom posseses an immunomodulation effect. This specific property of L. edodes enhances both innate and adaptive immune systems to fight cancer cells. Conclusion: L. edodes is a highly potential food to be given to lung cancer patients due to its high nutrition content and immunomodulation effect. The use of this mushroom as a nutrition intervention is highly beneficial, as a double sword towards facing lung cancer. This is one of the solutions to break the vicious cycle between lung cancer and cachexia in Indonesia, and furthermore to increase the patient’s quality of life. Keywords: chronic disease, cancer, lung cancer, cachexia, nutrition, immune system, immunomodulation, anticancer, mushroom, medicinal mushroom, Lentinula edodes, lentinan, β-glucan Introduction

Chronic diseases are diseases of long duration and generally slow progression. It is by far the leading cause of mortality all around the world, accounting for 63% of all deaths. This group of diseases include cancer, heart disease, diabetes, stroke, and chronic respiratory diseases. In 2008, cancer accounted for 13% of all deaths worldwide, which translates to 7.6 million deaths. Its impact is massive and it is projected to continue rising with an estimated 13.1 million deaths in 2030.(“WHO | Chronic diseases,” n.d.)

The burden of cancer is currently increasing in economically developing countries, including Indonesia. It is presumed to be the result of population aging, growth, and the adoption of cancer-

associated lifestyle choices, such as physical inactivity, smoking, and westernized diet. According to GLOBOCAN 2008, lung cancer is the most common cancer found in men in Indonesia. Lung cancer is a chronic, progressive disease which involves unregulated cell growth targeting the respiratory epithelium, such as bronchi, bronchiolus, and alveolus. The incidence and mortality rate of lung cancer in Indonesia is estimated to be 19.4% and 22.3% respectively.(International Agency for Research on Cancer, 2008) One of the highly associated risk factors is cigarrette smoking, which contributes to 80-90% of lung cancer incidence. According to the WHO Report on Global Tobacco Epidemic 2008, Indonesia ranks third among the proportions of world smokers.(World Health


Organization, 2008) This might be due to both the highly developing tobacco industry and the high consumption of tobacco in the community itself.

Malnutrition is highly associated with cancer. Most cancer patients will suffer from a progressive loss of body fat and lean body mass which is accompanied by profound weakness, anorexia, and anemia.(Kumar, Abbas, Fausto, & Aster, 2009) This condition is referred as cancer cachexia. It is most likely caused by the increased basal metabolic rate found in cancer patients, despite the reduced food intake. Cytokines produced by tumor cells act as an intermediate to the process. Cachexia itself causes an impairment in immune status and therefore reduces the body’s defense against the cancer. It is also correlated with reduced cancer treatment tolerance.(Fearon, Glass, & Guttridge, 2012) It worsens the condition of the patient, impeding the recovery process and decreasing the patient’s quality of life. Therefore, the relationship of cancer and malnutrition is best described as a vicious cycle.

Nutrition is frequently neglected in cancer treatment, drowned beneath the glimpse of pharmacologic therapy. Evenmore, some pharmacological therapies contribute plenty of side effects to the patient. Attention needs to be shifted to nutrition, because it plays a major role in the comprehensive care, support, and treatment of cancer. Good nutrition would also improve the quality of life of cancer patients, giving them a better chance of living as they struggle their way into the effort of convalescence.

Breaking the vicious cycle of cancer and malnutrition requires adequate nutritional support for cancer patients. Nutrition for cancer patients includes proteins, fats, carbohydrates, water, vitamins, minerals, antioxidants, phytonutrients, and herbs. High protein foods are especially important in the nutritional support, because metabolic processes in cancer gives rise to hypermetabolism. Hypermetabolism, in turn, affect the body’s use of proteins, fats, and

carbohydrates. This results in an increased demand for calorie and protein intake.

Lentinus edodes, or as it is more commonly known as shiitake mushroom, is a species of legume native to Asia. It is one of the world’s most cultivated medicinal and edible mushroom. Indonesia, a well-known world’s leading mushroom shed in the world, has been cultivating this mushroom since 1980 (Widyastuti, 2011). Nevertheless, this mushroom is not widely known and eaten among the society. However, it is considered as a functional food, which definition is foods that provide health benefits beyond basic nutrition. In addition to its nutritional content, a polysaccharide inside the L. edodes is strongly believed to have an immunomodulating effect. L. edodes has been reported to increase host defense mechanisms against murine and human tumors, which suggests its immuno adjuvent effects (Kyakulaga, Ogwang, Obua, Nakabonge, & Mwavu, 2013).

Based on all the facts proposed, L. edodes is a potential food to be given to cancer patients. It might be the newly proposed nutrition intervention to be prescribed in lung cancer patients in Indonesia. This study aims at exploring the nutritional benefit and anticancer mechanism of L. edodes and furthermore, its possible rolein the management of lung cancer.

Materials and Methods

This paper is developed using a systematic review method, which is a protocol driven comprehensive review of data focusing on a topic or on related key questions. We searched for articles through various search engines such as EBSCO HOST, Springerlink, and Clinical Key. The following keywords are used, including “lung cancer”, “malnutrition”, “cachexia”, “management of lung cancer”, “Lentinula edodes”, “immunomodulatory effect of L. edodes”. Other relevant references and texts are included in the study. The search was conducted on August to September 2013. We limited the search for articles published


within the last 10 years. Two authors are involved in the selection process as well as data extraction. Any disagreement is resolved by discussion.

Results

We evaluated 97 studies in the selection process. 65 studies are excluded due to its irrelevance. The remaining 32 studies and reference books are used in the systematic review. Pathologic Basis of Lung Cancer

Lung cancer is one of the most common cause of cancer deaths worldwide, including Indonesia. It is defined as tumors arising from the respiratory epithelium, which includes bronchi, bronchioles, and alveoli.(Longo et al., 2011) According to WHO classification, the histological classification of lung cancer is as follows: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) which consists of adenocarcinoma, squamous cell carcinoma and large cell carcinoma. Squamous cell carcinoma, SCLC, and adenocarcinoma are most associated with tobacco smoking.

The development of cancer is due to a series of steps which offers initiation, promotion, and progression. Cigarette smoking is the predominant cause of lung cancer. It is proposed that carcinogens found in cigarette induces genetic mutations. Accumulation of genetic mutations will eventually result in the formation of cancer cells. A wide range of mutations occur in lung cancer pathologies, but one of the most important class, known as “driver mutations” are responsible in driving initiation and maintenance of tumor cells (Longo et al., 2011).

Driver mutations target both oncogenes and tumor-suppresor genes (TSG) (Longo et al., 2011). Epidermal growth factor receptor (EGFR) mutations are one of the oncogene mutations commonly found in adenocarcinoma and squamous cell carcinoma. Moreoverly, TP53 and RB1 are a class of TSG that is found inactivated during the pathogenesis of lung cancer. Driver mutations are one of the key components

promoting lung cancer. It is very crucial, and on the other hand, it might as well be the hotspot target to prevent further progression and to aid in the recovery of lung cancer patients.

Patients with lung cancer display various clinical manifestations, depending on the stage and progression of the disease. Several signs and symptoms commonly presented by patients include cough, weight loss, dyspnea, chest pain, bone pain, and hemoptysis. Paraneoplastic syndromes are frequently encountered in lung cancer. This includes the presence of cachexia, anorexia, weight loss, fever, endocrine symptoms, and electrolyte disturbances. Immune Responses to Tumor

The effector mechanisms of both innate and adaptive immunity against tumor cells are described as follows. Innate Immune Response to Tumors 1. NK cells

NK cells destroy all viral-infected cells through its detection for class I MHC expression. Similar to the viral-infected cells, NK cells are detecting any tumor cells through its class I MHC expression. (Figure 1) A virally infected cell and tumor cell will be done away if there is a down-regulated expression of surface MHC class I molecule. In addition, NK cells can be targeted to IgG antibody-coated tumor cells by Fc receptors (FcγRIII or CD 16)(Abbas, Lichtman, & Pillai, 2011). The tumoricidal capacity of NK cells is increased by cytokines, including interferon γ , IL-15, and IL-12, and the anti-tumor effects of these cytokines are partly attributable to stimulation of NK cell activity. IL-2—activated NK cells, called lymphokine-activated killer (LAK) cells are derived by culture of peripheral blood cells or tumor infiltrating lymphocytes from tumor patients with high doses of IL-2.(Lindemann, Herrmann, Oster, & Mertelsmann, 1989)

2. Macrophage Macrophages are capable of both inhibiting and promoting the growth and spread of cancers. These cells can kill


many tumor cells more efficiently than they can kill normal cells. However, how the activation mechanism is still unknown. The likely mechanisms include direct recognition of some surface antigens of tumor cells and activation of macrophages by IFN-γ. (Figure 2) M1 macrophages can put to death tumor cells by several mechanisms, include the release of lysosomal enzyme, reactive oxygen species, nitric oxide and the cytokine tumor necrosis factor (TNF).(Abbas et al., 2011)

Adaptive Immune Responses to Tumor 1. T lymphocytes

The principal mechanism of adaptive tumor immunity is killing of tumor cells by T lymphocytes, especially CD8+ CTLs. CTLs perform a surveillance function by recognizing and killing potentially malignant cells that express peptides that are derived from tumor antigens and are presented that are derived from tumor antigens and are presented in association with class I MHC molecules.(Abbas et al., 2011) The CTLs mobilizes multiple killing mechanisms that induce apoptosis of the target cell, including the secretion of perforin that creates pores for the entrance of granzyme into the target cell and stimulation of Fas molecules on the target cell surface by Fas ligand (FasL) on the CTL.CTLs kill abnormal cells that continue to express MHC I. The great deal different is, NK cell kills cells without expression of MHC I molecule, but, the similarity falls on its killing mechanism (McCance & Huether, 2006).

2. Antibodies Antibodies may kill tumor cells by activating complement or by antibody-dependent cell mediated cytotoxicity, in which Fc receptor-bearing macrophages or NK cells mediate the killing (Abbas et al., 2011).

Cancer Cachexia

Cachexia is of great importance to the progression of lung cancer. It is defined as

the progressive loss of body fat and lean body mass accompanied by profound weakness, anorexia, and anemia (Kumar et al., 2009). Although cancer patients are often anorexic, cachexia probably results from the action of soluble factors, such as cytokines produced by the tumor and the host rather than reduced amount of food intake. Cytokines such as TNF, IL-1, interferon-γ, and leukemia inhibitory factors play a major role in the development of cachexia. High concentration of TNF mobilizes fats from tissue stores and suppress appetite. Aside from that, catabolism of muscle and adipose tissue are increasing in cancer patients due to proteolysis-inducing factor and lipid-mobilizing factor (Abbas et al., 2011).

Reduction in protein synthesis is also shown in cachexic cancer patients. This condition results in a decrease in mRNA translation and it will further stimulate protein catabolism through the activation of ATP-dependent ubiquitin-proteasome pathway (Abbas et al., 2011). However, it turns out that cachexia took on more than just the body’s flesh. It slows anticancer treatment by lowering the given chemotherapy drug doses. It is also correlated with an increased risk of severe hematological toxicity following anticancer chemotherapy (Santarpia, Contaldo, & Pasanisi, 2011).

The presence of cachexia worsens the condition of lung cancer patients. It causes an impairment in immune status and therefore reduces the body’s defense against the cancer (Santarpia, Contaldo, & Pasanisi, 2011). Cachexia is also well known for aggravating therapy responsiveness and survival in NSCLC. It also causes a decline in the patient’s quality of life and a progressive impairment of physical function. Therefore, cancer and malnutrition is very strongly related, in a vicious cycle relationship(Abbas et al., 2011).

Management of Lung Cancer

The management of lung cancer is strongly dependent on the staging of the disease. In both SCLC and NSCLC,


treatment for early stages of the disease remains to be surgical resection. Stage III NSCLC patients require a combination of radiation and chemotherapy delivered concurrently. In limited stage SCLC, treatment regimens are similar to NSCLC, that of which involves chemoradiotherapy. The presence of an extensive stage SCLC is treated with combination of platinum agent and topoisomerase inhibitor.(Detterbeck, Lewis, Diekemper, Addrizzo-Harris, & Alberts, 2013) Finally, management of patients of stage IV lung cancer is aimed at improving the quality of life through palliative care (Longo et al., 2011).

Complementary therapies and integrative medicine are also thought to play a role in lung cancer management. Complementary therapy focuses on alleviating physical and emotional symptoms, improving the patient’s quality of life, and improving adherence to cancer treatments.(Detterbeck et al., 2013) Integrative medicine describes the role of complementary therapy in the overall management of cancer. These therapies include nutrition, exercise, acupuncture, and massage therapy.

Many people were diagnosed with cancer at the late stage, where they may have already experienced weight loss and cachexia. Patients undergoing cancer treatments also firmly experience significant untreated nausea and vomiting, which will lead to further weight loss.(Kumar et al., 2009) While it is highly variable on the type of cancer and stage at diagnosis, cancer can cause profound metabolic and physiological alterations that can affect the nutrient requirements for both macro and micronutrients.Symptoms such as anorexia, early satiety, changes in taste and smell, and disturbances of the bowel are common side effects of both cancer and cancer treatments (Giannousi et al., 2012).It can lead to inadequate nutrient intake and subsequent malnutrition. Therefore, nutrition, in specific, plays a very large role in the management of lung cancer, and should not be taken for granted. Optimal nutrition improves therapeutic modalities and clinical

course and outcome in cancer patients (Rock et al., 2012).

Nutrition for lung cancer patients can be delivered through oral, enteral, or parenteral route. This is dependent on several factors such as the patient’s current condition, gastrointestinal tract function, and hemodynamic instability. Feeding formulas are variable, but they must contain complete nutrition. Carbohydrates represent the major source of calories. High calorie and protein supplements as nutritional adjunct are substantial in patients experiencing weight loss while undergoing treatment of lung cancer. Fats are also essential, and are supplied as triglycerides or vegetable oil (American Cancer Society, 2013). Functional foods affect one or more target functions in the body, beyond adequate nutritional effects (Lobo, Patil, Phatak, & Chandra, 2010). These foods may provide both immunologic and metabolic benefits for the patient. Lentinus edodes Habitat and Distribution

Lentinus edodes is a wood-decaying basidiomycetes. It belongs to the kingdom-Fungi, Phylum-Basidiomycota, Class-Basidiomycetes, order-Agaricales, family-Agaricaceae, genus-Lentinus and species-edodes(Hirasawa, Shouji, Neta, Fukushima, & Takada, 1999). (Table 1)(Wasser, 2005). It is mainly found living gregariously on fallen wood of a wide variety of deciduous trees, especially shii, oak, chestnut, beech, maple, sweet gum, poplar (aspen, cottonwood), alder, hornbeam, ironwood, chinquapin, mulberry in a warm, moist climate. L. edodes is more commonly known as shiitake mushroom. The word shii in Japan refers to the oak treeon which the mushroom grows, and take means mushroom.(P S Bisen, 2010) (Figure 3) (Wikipedia, n.d.). Chemical Constituents and Bioactive Components

Studies have shown significant results upon the health-promoting activity of L. edodes. Fruit bodies of L. edodes contains 88–92% water, protein, lipids, carbohydrates as well as vitamins and minerals (Table 2)


(Wasser, 2005)(P S Bisen, 2010). Shiitake mushroom holds within a wide range of vitamins (Table 3), especially provitamin D2 (ergosterol), which under ultraviolet (UV) light and heat yields calciferol (vitamin D2). It also contains B vitamins such as B1 (thiamine), B2 (riboflavin) and B12 (niacin). The fatty acids account for 3.38% (Table 4) of the total lipids with an appreciable amount of amino acids (Table 5)(P S Bisen, 2010). Anticarcinogenic and Antitumor Effect

The fruiting body of L. edodes contains lentinan, a cell wallβ-glucan having an effective antitumor and immunopotentiating activity.(Chan, Chan, & Sze, 2009) The structure of lentinan is a (13)-β-glucan which consists of five(13)-β-glucose residues in a linear linkage and two (16)-β-glucopyranoside branches in side chains which result in a right-handed triple helical structure (Figure 4) (Zhang, Li, Xu, & Zeng, 2005)

Lentinan has a molecular weight of about 400-800x103, and its molecular formula is (C6H10O5)n. It is water soluble, heat stable, and alkali labile. β glucan binds to lymphocyte surfaces or serum-specific proteins, which activate macrophage, T-helper cells, natural killer (NK) cells, and other effector cells.(Firenzuoli, Gori, & Lombardo, 2008). The water soluble property of lentinan is associated with an enhancement of both innate and adaptive immunity through the rapid hematogenous distribution. These processes subsequently increase the production of antibodies, interleukins (IL-1, IL-2) and interferon (IFN-γ) which are released upon activation of effector cells. Thus, the carcinostatic effect of lentinan results from the activation of the host’s immune system (TECK, 2004).

Lentinan (β-glucan) has been shown to have effective antitumor action against a variety of transplantable experimental animal tumours, and have been successfully used in clinical treatments. The elimination of target tumor cells are achieved through cell-mediated immune response and cytotoxicity (Firenzuoli et al., 2008). Macrophage-lymphocyte interactions are

crucial in the part of cell-mediated immune response, and cytoxicity is induced by antibodies. (Figure 5) Immunomodulating Effect

The anticarcinogenic mechanism of lentinan and other polysaccharides from shiitake mushrooms is not obtained through direct attack on cancer cells. It is rather achieved through the activation different immune responses in the host (called as Host Defense Potentiators = HDP) (COoi & Liu, 2000). Lentinan appears to act as a HDP, which restores and augments the responsiveness of host cells to lymphocytokines, hormones, and other biologically active substances by stimulating maturation, differentiation, or proliferation of cells involved in host defense mechanisms. Lentinan is able to increase host resistance against various kinds of cancer and infectious diseases, including Acquired Immunodeficiency Syndrome (AIDS), Alzheimer’s disease (by activating glial cells in brain), and Leishmaniasis. There is also a transitory but notable increase in several serum protein components in the α- and β- globulin region, namely, complement C3, hemopexin, and ceruloplasmin (Wasser, 2005).

Lentinan stimulates various kinds of NK cell-, T cell-, B cell-, and macrophage-dependent immune reactions. Innate immune cells are capable of recognizing antigens through Pattern Recognition Receptors (PRRs) that recognize certain molecules on the surface of invading microorganism and are known as Pathogen-Associated Molecular Patterns (PAMPs). Macrophages detect PAMPs through a number of different receptors (Abbas et al., 2011). Macrophage receptors for β-glucan recognition include TLR-2 (Toll-like receptor 2), dectin-1, CR 3 (complement receptor 3), and lactosycleramide. The effect of lentinan was also inhibited by antimacrophage agents, e.g., carrageenan (Wu, Wu, & Ho, 2007).

Unlike other well-known immunostimulants, lentinan is in a unique class of distal tubular (DT)-cell-oriented assistant, in which macrophages play some


part. Thus, the various effects of lentinan are thought to be due to potentiation of the response of precursor T-cells and macrophages to cytokines produced by certain classes of lymphocytes after specific recognition of tumour cells. In addition, the induction of a marked increase in the amounts of CSF, IL-1 and IL-3 by lentinan results in maturation, differentiation and proliferation of the immunocompetent cells for host defense mechanism. Similarly, lentinan is able to restore the suppressed activity of helper T-cells in the tumour-bearing host to their normal state, leading to complete restoration of humoral immune responses. Moreoverly, it is reported that the delayed-type hypersensitivity response induced by lentinan are consistent with the antitumor activity of lentinan in the tumor-bearing mice. (Firenzuoli et al., 2008) Figure 6 (Wu et al., 2007).

Discussion

The management of lung cancer mainly focuses on the eradication of tumor, through surgical resection or chemoradiotherapy. In the present discussion, nutrition is brought up as a crucial part of the therapeutic modalities of lung cancer patients. It is important to further appreciate the significance of nutrition role in the clinical outcome and prognosis of lung cancer patients. Nutrition is not only beneficial to overcome cachexia and its subsequent complications to lung cancer pathogenesis, but it also plays an important role in increasing the patient’s quality of life (Lis, Gupta, Lammersfeld, Markman, & Vashi, 2012).

Lung cancer patients suffer from a decreased quality of life. This might be due to the malignant tumor growth itself, or therapeutic modalities such as chemotherapy. The chronic course of the disease is also one of the contributing factors. Patients will have the mindset that this burden will be on their shoulders for a timeframe they cannot determine. The mainstays of the therapy will always remain as it is, and accordingly to the staging and clinical findings. It is the center of lung

cancer management, but it is also important for health care professionals to consider the patient’s emotional being (Aubin et al., 2011).

Improved quality of life would lead to a better prognosis of disease. It will also certainly enlighten the path the patient must walk as we accompany patients in their struggle towards battling lung cancer. This is where nutrition plays its role. It is essential to the prevention and management of cachexia, which breaks the vicious cycle of malnutrition. Thereafter, it prevents subsequent complications possible in the course of the disease, and at the same time, improves the patient’s quality of life. Bringing forward nutrition as one of the interventions of lung cancer is indeed a judicious step of action.

L. edodes is a mushroom of high nutritional content. It is very rich in carbohydrates, proteins, lipids, vitamins and minerals. Its high protein content is especially beneficial to prevent and treat cachexia in lung cancer patients. Lentinan, a polysaccharide found in L. edodes cell walls is also shown to augment immune responses to tumor cells, which is advantageous in lung cancer treatments. Fungal β-glucans acts as PAMPs and are recognized by appropriate cell surface receptors, initiating immune responses. Among dectin-1, complement receptor 3 (CR3), scavenger receptors, lactosylceramide (LacCer), and the toll-like receptor (TLR) evidence suggests that dectin-1 is most important in the initiating innate immune responses in macrophages (Schorey & Lawrence, 2008). Blocking with an

anti-dectin-1 antibody and knockout of the dectin-1 gene resulted in the abolition of all macrophage-mediated responses (Steele C et al., 2003). A research study also discovers that lentinan is able to inhibit cell cycle by inducing the elevation of the p53. P53 is a central factor that plays major role in determining the fate of cancer cells, whether the cells will undergo senescence, quiescence, or apoptosis (Abbas et al., 2011)(Kumar et al., 2009).


To sum up, this systematic review finds that L.edodes is highly beneficial due to its nutritional benefits and immunomodulatory effects. Thus, it is possible for this mushroom to be included in part of the nutritional intervention of lung cancer patients. This study has several limitations. The literature studies were of limited amount of articles. Resources are abundant, but the short period of time limits us to conduct further exploration.

Conclusion

The presence of cachexia in lung cancer is an aggravating factor to the course of the disease. It results in a vicious cycle, which keeps the course of the disease running out of control. As we accompany these patients towards their struggle in the course of their disease, it is very important to consider these factors. We strongly suggest that attention be shifted to nutrition in order to break this vicious cycle and increase the patient’s quality of life. L. edodes is a highly potential food to be given to lung cancer patients due to its high nutritional content and immuno-boosting activity. It might be the new solution in overcoming the obstacles faced by lung cancer patients.

References Abbas, A. K., Lichtman, A. H. H., & Pillai,

S. (2011). Cellular and Molecular Immunology: with STUDENT CONSULT Online Access. Elsevier Health Sciences.

American Cancer Society. (2013, March 15). Nutrition for the Person With Cancer During Treatment: A Guide for Patients and Families. Retrieved from http://www.cancer.org/acs/groups/cid/documents/webcontent/002903-pdf.pdf

Aubin, M., Vézina, L., Verreault, R., Fillion, L., Hudon, É., Lehmann, F., … Morin, D. (2011). Family physician involvement in cancer care and lung cancer patient emotional distress and quality of life. Supportive Care in Cancer, 19(11), 1719–1727. doi:10.1007/s00520-010-1010-y

COoi, V. E., & Liu, F. (2000). Immunomodulation and anti-cancer

activity of polysaccharide-protein complexes. Current medicinal chemistry, 7(7), 715–729.

Detterbeck, F. C., Lewis, S. Z., Diekemper, R., Addrizzo-Harris, D., & Alberts, W. M. (2013). Executive SummaryExecutive SummaryDiagnosis and Management of Lung Cancer: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. CHEST Journal, 143(5_suppl), 7S–37S.

Fearon, K. C., Glass, D. J., & Guttridge, D. C. (2012). Cancer cachexia: mediators, signaling, and metabolic pathways. Cell metabolism. Retrieved from http://www.sciencedirect.com/science/article/pii/S1550413112002483

Firenzuoli, F., Gori, L., & Lombardo, G. (2008). The medicinal mushroom Agaricus blazei murrill: review of literature and pharmaco-toxicological problems. Evidence-Based Complementary and Alternative Medicine, 5(1), 3–15.

Giannousi, Z., Gioulbasanis, I., Pallis, A. G., Xyrafas, A., Dalliani, D., Kalbakis, K., … Papandreou, C. N. (2012). Nutritional status, acute phase response and depression in metastatic lung cancer patients: correlations and association prognosis. Supportive Care in Cancer, 20(8), 1823–1829. doi:10.1007/s00520-011-1282-x

Hirasawa, M., Shouji, N., Neta, T., Fukushima, K., & Takada, K. (1999). Three kinds of antibacterial substances from Lentinus edodes (Berk.) Sing. (Shiitake, an edible mushroom). International journal of antimicrobial agents, 11(2), 151–157.

International Agency for Research on Cancer. (2008). GLOBOCAN 2008 FAST STATS. International Agency for Research on Cancer. Retrieved from http://globocan.iarc.fr/factsheet.asp

Kumar, V., Abbas, A. K., Fausto, N., & Aster, J. C. (2009). Robbins and Cotran Pathologic Basis of Disease, Professional Edition: Expert Consult - Online. Elsevier Health Sciences.


Kyakulaga, A. H., Ogwang, P. E., Obua, C., Nakabonge, G., & Mwavu, E. N. (2013). Immunomodulatory Effects of Aqueous Extracts of Auricularia sp and Pleurotus sp Mushrooms in Cyclophosphamide-Immunosuppressed Wistar Rats. British Journal of Pharmaceutical Research, 3(4), 2011.

Lindemann, A., Herrmann, F., Oster, W., & Mertelsmann, R. (1989). Lymphokine activated killer cells. Blut, 59(4), 375–384. doi:10.1007/BF00321208

Lis, C. G., Gupta, D., Lammersfeld, C. A., Markman, M., & Vashi, P. G. (2012). Role of nutritional status in predicting quality of life outcomes in cancer – a systematic review of the epidemiological literature. Nutrition Journal, 11(1), 27. doi:10.1186/1475-2891-11-27

Longo, D., Fauci, A., Kasper, D., Hauser, S., Jameson, J., & Loscalzo, J. (2011). Harrison’s Principles of Internal Medicine, 18th Edition. McGraw Hill Professional.

McCance, K. L., & Huether, S. E. (2006). Pathophysiology: The Biologic Basis for Disease in Adults And Children. Elsevier Mosby.

P S Bisen, R. K. B. (2010). Lentinus edodes: a macrofungus with pharmacological activities. Current medicinal chemistry, 17(22), 2419–30. doi:10.2174/092986710791698495

Rock, C. L., Doyle, C., Demark-Wahnefried, W., Meyerhardt, J., Courneya, K. S., Schwartz, A. L., … Gansler, T. (2012). Nutrition and physical activity guidelines for cancer survivors. CA: A Cancer Journal for Clinicians, 62(4), 242–274. doi:10.3322/caac.21142

Santarpia, L., Contaldo, F., & Pasanisi, F. (2011). Nutritional screening and early treatment of malnutrition in cancer patients. Journal of Cachexia, Sarcopenia and Muscle, 2(1), 27–35. doi:10.1007/s13539-011-0022-x

Schorey, J. S., & Lawrence, C. (2008). The Pattern Recognition Receptor Dectin-1: From Fungi to Mycobacteria. Current drug targets, 9(2), 123–129.

Steele C, Marrero L, Swain S, Harmsen AG, Zheng M, Brown GD, … Kolls JK. (2003). Alveolar macrophagemediated killing of Pneumocystis carinii f. sp. muris involves molecular recognition by the dectin-1 b-glucan receptor. Journal of Experimental Medicine 198: 1677–1688.

TECK, Y. A. (2004). To determine the immunological responses stimulated by beta-D glucan, lentinan and their effects on cancer cells. Retrieved from https://scholarbank.nus.edu.sg/handle/10635/13779

Wasser, S. P. (2005). Shiitake (Lentinus edodes). Encyclopedia of Dietary supplements, 653–664.

WHO | Chronic diseases. (n.d.). WHO. Retrieved September 29, 2013, from http://www.who.int/topics/chronic_diseases/en/

Widyastuti, N. (2011). LIMBAH GERGAJI KAYU SEBAGAI BAHAN FORMULA MEDIA JAMUR SHIITAKE (LENTINULA EDODES). JURNAL TEKNOLOGI LINGKUNGAN, 9(2). Retrieved from http://ejurnal.bppt.go.id/index.php/JTL/article/view/544

Wikipedia. (n.d.). Shiitake mushroom. Retrieved from http://commons.wikimedia.org/wiki/File:Shiitake_mushroom.jpg

World Health Organization. (2008). WHO Report On The Global Tobacco Epidemic 2008. World Health Organization.

Wu, C.-H., Wu, C.-C., & Ho, Y.-S. (2007). Antitumor activity of combination treatment of Lentinus edodes mycelium extracts with 5-fluorouracil against human colon cancer cells xenografted in nude mice. J. Cancer Mol, 3, 15–22.

Zhang, L., Li, X., Xu, X., & Zeng, F. (2005). Correlation between antitumor activity, molecular weight, and conformation of lentinan. Carbohydrate research, 340(8), 1515–1521. doi:10.1016/j.carres.2005.02.032


DA-MOMS (DIABETES-MELLITUS TYPE 2 AWARE MOMS): A MODIFIED

LIFESTYLE INTERVENTION PROGRAM FOR PATIENTS WITH TYPE 2

DIABETES MELLITUS IN INDONESIA Athaya Febriantyo Purnomo1, Isma Dewi Masithah1, Nayla Rahmadiani1

1Brawijaya University, Malang, Indonesia ABSTRACT

Background:Type 2 Diabetes Mellitus (T2DM) is a major and serious health problem globally. Indonesia is in the top 10 countries with highest number of people with Diabetes Mellitus, with most of the cases are account to T2DM, which makes T2DM one of the most problematic non communicable disesase in Indonesia. Current management in Indonesia is still not adequate in dealing with patients who already had T2DM, mainly because there is lack of follow ups from medical professionals, no clear health policies for the management of T2DM from government, and poor knowledge and motivation of the patients regarding T2DM while many patients are self-treating themselves at home, making the control of the disease is also poor and a higher chance of the disease to develeop into a more severe complications. Lifestyle intervention is a method that is proven beneficial in the management of T2DM, thus, this method has the potential in becoming a part of management procedures of T2DM in Indonesia with some adjustments to Indonesian cultures, and DA-MOMS is the result of that thought with its involvement of mothers (wives) in its program. Methods:A systematic review study, using two approaches, namely expositional method and analytic method. Result:T2DM is the most common form of diabetes and is caused by mainly by lifestyle factor.It is found that lifestyle intervention and its constituent, namely exercise and education to the patients have a clear benefit for the patients, mainly by helping to control glycaemic level of the patients, thereby improving health status of the patients, while family members especially mothers hold a very important role in shaping and maintaining their family’s lifestyle. Conclusion:DA-MOMS is a program that will involve women (mothers, wives) in Family Welfare Education group (Pendidikan Kesejahteraan Keluarga or PKK), in activities such as self-control management by sharing session, diabetic exercise, routine check-up done by medical practitioner equipped with assessment form collection for daily activity of patients in their families or themselves to monitor and control the progression of the disease, and lastly cooking class and nutrition class for mothers in Family Welfare Education group meeting to get recipes for Diabetes Mellitus’s proper food. The basis of DA-MOMS program is lifestyle intervention which effectiveness has been proven, and with the support of all components in Indonesia, this program will become even more effective to be implemented in Indonesia. INTRODUCTION

Diabetes Mellitus’ global prevalence is rapidly increasing as a result of ageing, urbanization and, lifestyle changes.In 2010, approximately 285 million people worldwide had Diabetes Mellitus, and about 90% of them had Type 2 Diabetes mellitus (T2DM). The percentage of people with Diabetes Mellitus is now higher in developing country rather than developed country, with about 80% of the people with Diabetes Mellitus live in developing country.Asia has emerged as the ‘diabetes

epicenter’ in the world, as a result of rapid economic development, urbanization and nutrition transition over a relatively short period of time.(Chen, L. et al.2011).

Among the 10 countries with the largest numbers of people predicted to have diabetes mellitus in 2030, five are in Asia (China, India, Pakistan, Indonesia and Bangladesh).(Chen, L. et al.2011).While usually most of the cases of Diabetes Mellitus in Asian race are dominated by type 2 Diabetes Mellitus .(CDC. 2011). This shows that Diabetes Mellitus type 2 is


indeed one of the most problematic chronic diseases in Indonesia.

There are several problems with the status quo of T2DM in Indonesia. Firstly, In general, poor glycemic control is associated with worse patient outcomes. (Howard Wild, BS Pharm, RPh.2012). Complications which may occur may include heart and blood vessel disease, neuropathy, nephropathy, eye damage, foot damage, skin and mouth conditions, osteoporosis, and Alzheimer’s disease, and hearing disease. (Mayo clinic. 2013). Many patients in Indonesia still have poor education about Diabetes Mellitus in terms of general overview about the disease and its management. Many problems can arise from this condition, such as uncontrolled glycaemic level. While actually with adequate education, their attitude towards dealing with the disease will change, and can even improve their health conditions.(Abdo, et al,2010).

Secondly, medical professionals and the government still haven’t established any integrated program that will make it possible for medical professionals to monitor, control, and educate the society, especially patients with T2DM, about T2DM. The methods of management used by medical professionals in Indonesia are the use of medications (in hospital or out hospital), and also monitoring and controlling process for T2DM patients in hospital, (the ones who had developed serious complications), while many of the patients with T2DM are self-treated at home.

All of these problems and conditions indicate the need of a solution that will help the process of monitoring, controlling, and educating the patients with T2DM, improve patients’ health status, and also eventually will improve the quality of life of T2DM patients.

Lifestyle intervention is an essential component in the treatment of chronic disease that can be as effective as medication, but without the risks and unwanted side-effects. The aim of lifestyle intervention generally is to change the lifestyle of the patient.(American College of

Lifestyle Medicine. 2011). Lifestyle modification of the patients, which is the result of a lifestyle intervention effort, can result in the improvement of health status of the patients. (Klein, et al., 2004). Lifestyle intervention program, therefore, is proven to be effective in managing patients with T2DM because of its monitoring, controlling, and educating process of T2DM. Based on this program, we come up with a solution to all the above problems and conditions, a program called DA-MOMS (Diabetes-Mellitus Type 2 Aware Moms) designated for mothers or wives in Indonesia, making them a “Diabetes Mellitus Type 2 ambassador” who will be taking part in the monitoring, controlling, and educationg process of T2DM for their families. In this paper, we will discuss about the program itself, the effectiveness of the implementation of this program in Indonesia to improve patients’ health status regarding the current status quo. METHODS

Methods used in this paper is systematic review, and all the data collected are based on up to date informations, both through digital and non-digital information from up to date and relevant literatures such as journals and medical books. Two approaches of data analysis are used in this method, namely:

1. Exposition method : seeking the correlations between each data and informations presented in this paper

2. Analytic method : conclusion making is achieved through logical thinking process in analyzing data and informations

RESULTS Type 2 Diabetes Mellitus

Diabetes mellitus is a major emerging clinical and public health problem accounting currently for 5.2% of all deaths world-wide.According toWHO estimates (2007), 190 million people suffer fromdiabetes world-wide and about 330


million ones are expected to bediabetic by the year2025. (Lorenzo, Williams, Hunt, Haffner, 2007). Diabetes mellitus (or diabetes) is a chronic, lifelong condition that affects your body's ability to use the energy found in food. There are three major types of diabetes: type 1 diabetes, type 2 diabetes, and gestational diabetes. (WebMD, 2012).

Type 2 is the most common form of diabetes, accounting for about 85-90% of all cases of Diabetes Mellitus. (Diabetes Australia, 2008). Type 2 Diabetes Mellitus or T2DM consists of dysfunctions characterized by hyperglycemia and resulting from the combination of resistance to insulin action, inadequate insulin secretion, and excessive or inappropriate glucagon secretion. Poorly controlled type 2 diabetes is associated with an array of microvascular, macrovascular, and neuropathic complications. (Khardori,. 2013).

In T2DM, insulin resistance is compensated by increased insulin secretion (hyperinsulinemia), which allows glucose metabolism to remain normal. The beta cells in genetically susceptible individuals become impaired, leading to delayed and insufficient insulin secretion. Due to decreasing beta-cell function, the individual with insulin resistance first develops postprandial hyperglycemia and subsequently develops fasting hyperglycemia(Lebovitz, MD). Amongst other etiologic factors, lifestyle is the most common cause of development of T2DM in developing countries such as Indonesia (Nchanchou, 2008)

The pathogenesis of type 2 diabetes ordinarily involves the development of insulin resistance associated with compensatory hyperinsulinemia, followed by progressive beta-cell impairment that results in decreasing insulin secretion and hyperglycemia. Hyperglycemia itself causes additional inhibition of insulin secretion and more insulin resistance (glucose toxicity), which further accentuates the hyperglycemia. Thus, the development of type 2 diabetes is usually characterized by 2 abnormalities: impaired insulin action and

deficient insulin secretion. Both impairments are made worse by hyperglycemia. Normal beta cells can compensate for insulin resistance. Type 2 diabetes, therefore, cannot occur in the absence of beta-cell abnormalities. (Lebovitz, MD).

Currently, management of T2DM includes appropriate goal setting, dietary and exercise modifications, medications, appropriate self-monitoring of blood glucose, regular monitoring for complications, and laboratory assessment. The objectives of T2DM management are to eliminate symptoms and to prevent or at least slow the onset of complications occurence. If not treated well, various complications may occur (Khardori, 2013).

Medications for T2DM have several mechanisms of work, each one is different from the others. A drug for T2DM may work by stimulating pancreas to produce more insulin, inhibiting the breakdown of carbohydrate by stomach enzymes, inhibiting glucose release from the liver, or improving cell’s sensitivity to insulin. Classes of drugs commonly used to treat T2DM are meglitinides, sulfonylureas, dipeptidy peptidase – 4 inhibitors, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, amylin mimetics, an incretin mimetics. (Mayo clinic, 2013). Lifestyle Intervention in Patients with Type 2 Diabetes Mellitus

Many studies support the fact that lifestyle intervention plays an important role in the management of type 2 diabetes. Educational interventions with or without physical activity and dietary advice have resulted in beneficial effects on glycemic control, diabetes knowledge and quality of life (Vadstrup, Frølich, Perrild, Borg, Røder, 2012), and even the possibility of reversal of obesity-associated complications through healthy eating habits and increased duration and intensity of physical activity. (Wimalawansa, 2013).

Numerous success trial about lifestyle intervention in managing T2DM usually due to the fact that lifestyle intervention gave patients better knowledge about T2DM and


succeed in changing patients’ lifestyle, but the controversial problem is how to deliver lifestyle intervention. Recent research shows that group-based lifestyle intervention is more effective than individual lifestyle intervention in improving overall patients’ health status (Vadstrup, Frølich, Perrild, Borg, Røder, 2012). And according to most researches, most successful programs have involved combinations of diet, exercise, and behavior modification (Vadstrup, Frølich, Perrild, Borg, Røder, 2012) Effect of Exercise in Patients with Type 2 Diabetes Mellitus

The result of exercise in T2DM patients usually include weight loss and increasing physical activity, which will result in better patients’ health status viewed by several indicators such as glycaemic level, (Sigal, Kenny, Wasserman, Sceppa, and Russell, 2006). Short-term weight loss has been shown to have beneficial effects on diabetes and cardiovascular disease.(Medscape Medical News, 2002). Long term exercise has also shown beneficial effect on patients, with the reduction of high glycaemic level, reduction of LDL-cholesterol and total cholesterol and increase of HDL-cholesterol. (Wochenschrift, 2006.) Effect of Education in Patients with Type 2 Diabetes Mellitus

T2DM patients’ health status is determined by many factors, and one of them is glycaemic level. Glycaemic control can be achieved by improving patient’s knowledge,attitude, practice and self efficacy. There is increasing amount of evidence that patient education is the most effective way to improve those aspects on patients. (Goodarzi1,Ebrahimzadeh1,Rabi2,Saedipoor1 and Jafarabadi, 2012).

Educations for T2DM can include a brief overviewof T2DM (definitions, etiology, signs and symptoms, manifestations, complications, and treatment), exercise plans, and nutrition informations like calory intake, how to eat healthily, managing portions, etc (Johns Hopkins Medicine.). However, this is not the exact outline of all patients education for T2DM. Patient

education materials varies depending on the creator of the education material and the targets.

Educations for T2DM is essential especially for the self-management of the patients. Patients need to be aware of their conditions related to coping up with T2DM. Although education alone is not a cure, patients will not be able to control their conditions well, if they do not know about the basic principles of nutrition, physical activity, care of the lower extremities, and other necessary informations (Polikandrioti, 2010). Educations for T2DM patients have shown a positive result for patients’ health status. One of the study shows that education for the patients can successfully change patients’ lifestyle in a positive way (Ghazanfari, Ghofranipour,Tavafian, Ahmadi, Rajab , 2007).Other study shows that the change of knowledge and attitude of the patients toward T2DM as the result of patients education can even lower patients’ glycaemic level, therefore improving patients’ health status (Abdo, et al, 2010). Role of Mothers (Wives) in Family

Family support is an essential part of diabetic patients treatment. Family nutritional support is useful in improving metabolic outcome of diabetic patients. Self-treatment practice needs to be supported with good family support, especially in the elderly. (Watanabe K, Kurose T, Kitatani N, Yabe D, Hishizawa M, Hyo T, Seino Y, 2010). Mothers play an essential role in any family in determining and maintaining her family’s lifestyle, because mothers have traditional role as the nurturer of the family (Rintala, M., et al. 2013).

DISCUSSION

Considering the magnitude of this issue, it is important that all parties involved in healthcare play a role in the fight against this health problem. The thousands of medical students in 72 medical schools across the country is a force to be reckoned with in health promotion efforts, taking part of cases’ management, and perform researches through group-based lifestyle intervention.


Health Promotion

On the lifestyle disease like Diabetes Mellitus, lifestyle intervention is crucial to be modified in order to reduce the tendency complication happened in the future. One way to maximize the efforts of the government after conducting such health promotion, material provisions for primary health care, and do supervising function is creating society awareness by any mass education. DA-MOMS will be presented by the medical students and will include an overview on the clinical signs and symptoms of the disease, foot care and managing glycaemic level, treating and evaluating Diabetes Mellitus.

DA-MOMS is working together with government’s primary health care to conduct DA-MOMS. The targets will be the mothers who become member of Family Welfare Education group (bahasa: Pendidikan Kesejahteraan Keluarga or PKK). Family Welfare Education group is a group consisting of womens from each household in a region. Every region has its own Family Welfare Education group, DA-MOMS has several mechanism for the executions of the program: 1. Self-control management by sharing

session 2. Diabetic exercise with the family

members of women in Family Welfare Education group who are diabetics

3. Routine check-up done by medical practitioner equipped with assessment form collection for daily activity of patients to maintain the progress of the disease.

4. Cooking class and nutrition class for mothers in Family Welfare Education group meeting to get recipes for Diabetes Mellitus’s proper food

In DA-MOMS, mothers are expected to act as a controller for their family members who had T2DM or themselves if they had T2DM. In families, mothers naturally act as the controller of the nutrition intake of their families and their lifestyle, due to the traditional role of women. Through this program, we would like to direct the

function into helping to improve the conditions of patients with T2DM who happen to be family members of these women.

For women whose family members or herself did not have T2DM, they can still participate in this program in order to prevent T2DM.

The main purpose of the implementation of DA-MOMS is to sucessfully create mothers and wives who act as ambassador of T2DM for themselves and their families, that will eventually results in the improvement of the health status of T2DM patients. Effectiveness

Concerning the significance of group-based management, DA-MOMS is a match solutions for the problem presented by the status quo. Firstly, in term of creating effective way to control poor glycaemic level. Recent study shows that type 2 Diabetes Mellitus patients are not motivated when they should through their diabetes life alone. This study based on meta-analyses in favour of group-based diabetes education programmes were reduced glycated haemoglobin at four to six months (1.4%; 95% confidence interval (CI) 0.8 to 1.9; P < 0.00001), at 12-14 months (0.8%; 95% CI 0.7 to 1.0; P < 0.00001) and two years (1.0%; 95% CI 0.5 to 1.4; P < 0.00001); reduced fasting blood glucose levels at 12 months (1.2 mmol/L; 95% CI 0.7 to 1.6; P < 0.00001); reduced body weight at 12-14 months (1.6 Kg; 95% CI 0.3 to 3.0; P = 0.02); improved diabetes knowledge at 12-14 months (SMD 1.0; 95% CI 0.7 to 1.2; P < 0.00001) and reduced systolic blood pressure at four to six months (5 mmHg: 95% CI 1 to 10; P = 0.01). There was also a reduced need for diabetes medication (odds ratio 11.8, 95% CI 5.2 to 26.9; P < 0.00001; RD = 0.2; NNT = 5). Therefore, for every five patients attending a group-based education programme we could expect one patient to reduce diabetes medication. (Deakin T, McShane CE, Cade JE, Williams RD, 2005).

According to all of the data in the aforementioned results, lifestyle intervention


and the activities included in it such as education process and exercise has proven its benefits for T2DM patients. So, theoretically, this program is a suitable management procedure to be established. All that is left is the question about the establishment of the program in Indonesia regarding of the status quo. DA-MOMS is the way medical students in Indonesia could contribute in solving the problems of T2DM. So program’s aids come from the government and society also as the answer for second problem. Diabetes Mellitus become more complicated because there’s no any bureaucracy made by the government. Government’s roles should be the supervisor and funding source of DA-MOMS policy in Indonesia and then supervise the execution of DA-MOMS policy because this is the role of the government to fulfill society’s demand. It’s necessary to apply the policy for the betterment of country because it’s already been a duty of government to do so.

Society’s role is just following the program made by the government for their welfare as well. Not to mention, through this, the burden that T2DM patients suffered can be made light if the society support the program and the policy. Thus, DA-MOMS become a channel which could bring type 2 Diabetes Mellitus patients and society work to collect efforts for the cure of Diabetes Mellitus, with the empowerment of mothers and wives through the Family Welfare Education group. If all components work synergistically, then the implementation of this program in Indonesia will become even more effective.

CONCLUSION

DA-MOMS is a program that will involve women (mothers, wives) in Family Welfare Education group (Pendidikan Kesejahteraan Keluarga or PKK), in activities such as self-control management by sharing session, diabetic exercise, routine check-up done by medical practitioner equipped with assessment form collection for daily activity of patients in their families or themselves to monitor and control the

progression of the disease, and lastly cooking class and nutrition class for mothers in Family Welfare Education group meeting to get recipes for Diabetes Mellitus’s proper food. The basis of DA-MOMS program is lifestyle intervention which effectiveness has been proven, and with the support of all components in Indonesia, this program will become even more effective to be implemented in Indonesia.

REFERENCES American College of Lifestyle Medicine.

(2011). What is Lifestyle Medicine. Retrieved from http://www.lifestylemedicine.org/define.

Bigaard, J, Tjønneland, A, Thomsen, BL, Overvad, K, Heitmann, BL, Sørensen, TI. (2003). Waist circumference, BMI, smoking, and mortality in middle-aged men and women. Obes. Res. 11(7), 895–903.

Chen, L. et al.(2011).The worldwide epidemiology of type 2 diabetes mellitus—present and future perspectives. Nat. Rev. Endocrinol. 8, 228–236 (2012); published online 8 November 2011; doi:10.1038/nrendo.2011.183

CDC. (2011). Centers for Disease Control and Prevention . Retrieved from www. cdc.gov. chronicdisease/resources/publications/AAG/ddt.htm.

Diabetes Australia. (2008). Understanding-Diabetes. Retrieved fromhttp://www.diabetesaustralia.com.au/en/Understanding-Diabetes/What-is-Diabetes/Type-1-Diabetes/Type 2 Diabetes

Eisenmann JC, Katzmarzyk PT, Perusse L, Tremblay A, Després JP, Bouchard C. (2005). Aerobic fitness, body mass index, and CVD risk factors among adolescents: the Québec family study. Int. J. Obes. (Lond.) 29(9), 1077–1083.

Lebovitz, H. E., Pathogenesis of Type 2 Diabetes. Retrieved from http://www.medscape.com/viewarticle/412682_4


Howard Wild, BS Pharm, RPh. (2012). The

Economic Rationale for Adherence in theTreatment of Type 2 Diabetes Mellitus. Am J Manag Care 2012;18:S43-S48

Goodarzi1, Iran_Mandana., Ebrahimzadeh, Issa., Rabi, Alireza., Saedipoor, Bahman., and Jafarabadi, Mohammad Asghari. (2012). Impact of distance education via mobile phone text messaging on knowledge, attitude, practice and self efficacy of patients with type 2 diabetes mellitus. Journal of Diabetes & Metabolic Disorders, 11:10.

Janiszewski PM, Ross R. (2010). Effects of weightloss among metabolically healthy obese men and women. Diabetes Care 33(9), 1957–1959.

Johns Hopkins Medicine. Diabetes Self Management Patient Education Materials http://www.hopkinsmedicine.org/gim/core_resources/Patient%20Handouts.

Khardori, R. (2013). Retrieved from http://emedicine.medscape.com/article/117853-overview#aw2aab6b2b2 _ 2013 _ Type 2 DiabetesMellitus.

Khardori, R.(2013).Type 2 Diabetes Mellitus Treatment & Management. Retrieved from http://emedicine.medscape.com/article/117853-treatment.

Klein,S., Sheard, N. F., Pi-Sunyer, X., Daly, A., Wylie-Rosett, J., Kulkarni, K, and Clark, N., G. (2004). Weight Management Through Lifestyle Modification for the Prevention and Management of Type 2 Diabetes: Rationale and Strategies: A statement of the American Diabetes Association, the North American Association for the Study of Obesity, and the American Society for Clinical Nutrition_Diabetes Care August 2004 27:2067-2073.

Polikandroti, Maria. (Eds.). (2010).The role of education in diabetes mellitus type 2 management. health science journal_volume 4, issue 4.

Mayo clinic. (2013). Complication of type 2 diabetes. Retrieved from http://www.mayoclinic.com.

Medscape Medical News. ( 2002). Study to Examine Long-Term Effects of Weight Loss and Exercise in Type 2 Diabetes. Retrieved from http://www.medscape.com/viewarticle/428778

Naglaa M. Abdo, Mohamed E. Mohamed_J. (2010). Effectiveness Of Health Education Program For Type 2 Diabetes Mellitus Patients Attending Zagazig University Diabetes Clinic, Egypt. Public Health of Association Vol. 85 No. 3 & 4.

Nchanchou, M.A, 2008. Type 2 Diabetes and its association with lifestyle factors. Thesis of University Oslo.

Nicklas BJ, Ambrosius W, Messier SP et al. (2004). Diet-induced weightloss, exercise, and chronic inflammation in older, obese adults: a randomized controlled clinical trial. Am. J. Clin. Nutr. 79(4), 544–551.

Rintala, M., et al. 2013. Interrelation Between Adult Persons With Diabetes and Their Family: A Systematic Review of the Literature_Tuula. Journal of Family Nursing February 2013 vol. 19 no. 1 3-28

Ronald J. Sigal, Glen P. Kenny, David H. Wasserman, Carmen Castaneda-Sceppa, and Russell D. 2006. White_Physical Activity/Exercise and Type 2 Diabetes: A consensus statement from the American Diabetes Association_Diabetes Care June 2006 29:1433-1438

Watanabe K, Kurose T, Kitatani N, Yabe D, Hishizawa M, Hyo T, Seino Y. (2010). The role of family nutritional support in Japanese patients with type 2 diabetes mellituS. Intern Med. 2010;49(11):983-9. Epub 2010 Jun 1.

Wimalawansa, S. J. (2013).Thermogenesis-Based Interventions for Obesity and Type 2 Diabetes Mellitus. http://www.medscape.com/viewarticle/803917. Expert Rev Endocrinol Metab. 2013;8(3):275-288.

W Lorenzo C , Williams K, Hunt KJ, Haffner SM.(2007). The National Cholesterol Education Program-Adult Treatment Panel 111, International Diabetes Federation, and World Health


Organization Definitions of the Metabolic Syndrome as Predictors of Incident Cardiovascular Disease and Diabetes. International Diabetes Federation (IDF). [cited 2010 June 31 Available from: http:/ /care.diabetesiour~1als.or~/content/30/1/8.full)

WebMD. (2012). Types of Diabetes Mellitus . Retrieved from http://diabetes.webmd.com/types-of-diabetes-mellitus.

Wiener Medizinische Wochenschrift. 2006. The metabolic effects of long term exercise in Type 2 Diabetes patients_Edmund Cauza, Ursula Hanusch-Enserer, Barbara Strasser, Karam Kostner, Attila Dunky, Paul

Haber. Volume 156, Issue 17-18, pp 515-519.

Vadstrup, Eva Soelberg., Frølich, A., Perrild,

H., Borg, E., Røder, M.(2012).Lifestyle intervention by group-based rehabilitation versus individual counseling in type 2 diabetes: 1-year follow-up of the Copenhagen type 2 diabetes rehabilitation project . Journal of Diabetes Mellitus_Vol.2 No.3, Article ID:22187,8 pages

Z Ghazanfari, F Ghofranipour, SS Tavafian,

F Ahmadi, A Rajab. (2007). Lifestyle Education and Diabetes Mellitus Type 2: A Non-Randomized Control Trial. Iranian J Publ Health, Vol. 36, No.2, , pp.68-72.


PROLIVER (PROTECTION FOR LIVER) -REVOLUTIONARY

INVENTIONTHERAPY FOR LIVER FIBROSIS BASED ON REGENERATIVE

MEDICINE EMPOWERING EXTRACTED MINT LEAF (Mentha spicata L.)

:EXPERIMENTAL STUDY Ayu Pramitha Wulandari1, Khrisna Rangga Permana1, Shanti Andri Sakarisa1, Depy Irmayanti2

17th Semester Medical Student, Faculty of Medicine, University of Brawijaya, Indonesia 23rd Semester Medical Student, Faculty of Medicine, University of Brawijaya, Indonesia

ABSTRACT

Background: Liver fibrosis is the major chronic disease among communities worldwide in both incidence and mortality, accounting for nearly 1.5 billion cases worldwide and 90% of them leads to severe complications like liver cirrhosis, portal hypertension, liver cancer, even death. There was already 250,000 deaths in Indonesia in 2013 and approximately 200,000 new cases and 40,000 deaths every year are expected to occur in 2020. In fact, Indonesian people aren't really aware because it doesn't show symptom until reaching late stadium, so most of them often come with complications.There is no therapy that can be widely accepted in the world until now. Some drugs that often used actually make liver worse due to liver overload of their work. And when it reaches the stage of cirrhosis, liver transplantation is the most effective therapy. However, the complication is often to occur due to the use of immunosuppressants in a long time. Mint leaf (Mentha spicata L.) is the plant that mostly contains Luteolin in its leaf. Luteolin has critical roles as antiinflammation, antioxidant, and anticancer. Luteolin can be used as revolutionary therapy for liver fibrosis by suppressing its progession and by accelerating liver regeneration. Objective: To show how Luteolin as revolutionary therapy for liver fibrosis can suppress its progession and accelerate liver regeneration. Material and Methods: An experimental study using male mices which were divided into positive control, negative control, and treatment group. Thus, induced with CCl4 to injure the liver to make liver fibrosis. Then we took their blood to do serum blood analysis to count SGOT/SGPT rate and MMP-9 ELISA .We also took livers to measure mass,collagen deposition, histopatology-anatomy analysis by Mason Trichrome, TGF-beta1, and Hematoxylin Eosin staining. Next, we processed the data by using SPSS method. Results and Discussion: We got significant (p <0,5) data showing lower rate of liver mass, SGOT/SGPT and higher rate of MMP-9 after conducting SPSS analysis in treatment groupswere given Luteolin high dose.These were better than positive group that we took to see the speed of liver regeneration alone without Luteolin. We also found decrease of collagen deposition accumulation and others structural repairs. Conclusions: Luteolin has high potential as revolutionary therapy to develop because it can suppress liver fibrosis progession. Besides, it can also accelerate liver regeneration itself. Keywords: Liver Fibrosis, New Therapy, Luteolin, Progession, Acceleration

INTRODUCTION Liver fibrosis is the major chronic

disease among communities worldwide in both incidence and mortality, accounting for nearly 1.5 billion cases worldwide and 90% of them leads to severe complications even death (WHO,2002). There was already 250,000 deaths in Indonesia in 2013 and approximately 200,000 new cases and

40,000 deaths every year are expected to occur in 2020. Liver fibrosis might develop becoming liver cirrhosis (Rasyid, 2006). Once cirrhosis has developed, the serious complications of liver disease may occur, including portal hypertension, liver failure and liver cancer. The risk of liver cancer is greatly increased once cirrhosis develops, and cirrhosis should be considered to be a


pre-malignant condition. Cirrhosis and liver cancer are now among the top ten causes of death worldwide, and in many developed countries liver disease is now one of the top 5 causes of death in middle-age. It is essential to discover new therapeutic strategies to increase the survival rate and improve the clinical outcomes of liverfibrosispatients.In fact, Indonesian people aren't really aware because it doesn't show symptom until reaching late stadium, so most of them often come into hospital with severe complications (Kumar et al, 2007)

Liver fibrosis is the scarring process that represents the liver’s response to injury. In the same way as skin and other organs heal wounds through deposition of collagen and other matrix constituents so the liver repairs injury through the deposition of new collagen. Over time this process can result in cirrhosis of the liver, in which the architectural organization of the functional units of the liver becomes so disrupted (Zhang and Qingcai, 2005). Our knowledge of the cellular and molecular mechanisms of liver fibrosis has greatly advanced. Activated hepatic stellate cells (HSC), portal fibroblasts, and myofibroblasts of bone marrow origin have been identified as major collagen-producing cells in the injured liver. Yang et al. (2010).These cells are activated by fibrogenic cytokines such as TGF (Transforming Growth Factor) -beta1. Once liver gets injured, this phenomenon is also followed by increase of SGOT(Serum Glutamic Oxaloacetic Transaminase)/SGPT(Serum Glutamic Piruvic Transaminase) rate and liver mass and by decrease of MMP (Matrix Metaloproteinases) -9 and liver regeneration and we can use them as indicators for liver fibrosis and liver regeneration in this experimental study (Leasket al.,2004)

There is no therapy that can be widely accepted in the world until now. Some drugs that often used such as propranolol and lansoprazoleactually make liver worse due to liver overload of their work. And when it reaches the stage of cirrhosis, liver transplantation is the most effective therapy.

However, the complication is often to occur due to the use of immunosuppressants in a long time and the supply of organ donor is very rare (Chen Chiu-Yuan, Wen Peng, dan Shih-Lan Hsu, 2010).For these reasons the development of liver fibrosis therapy is very important in order to reduce morbidity, mortality, and the need for liver transplantation. Therefore, we need a new innovation for liver fibrosis therapy which is safer and more natural. Therapeutic use of natural materials in Indonesia gets a lot of attention. Besides, because the side effects are minimal, the price can be obtained by all people, especially those from the low-middle economy class (Rockey , 2006)

Mint (Menthaspicata L.) is the plant that contains many flavonoids. Luteolin, one of flavonoids, is mostly contain in Mint in its leaf. Luteolin(3′,4′,5,7-tetrahydroxyflavone) has critical roles as antiinflammation, antioxidant, and anticancer. Until now, there is no further experimental study for the use ofLuteolin for liver fibrosis therapy (Domitrovićet al., 2009).

Because of those facts, liver fibrosis absolutely has high influence as a chronic disease and major burden in health communities and it can be problematic in several ways such as it can decrease patient's quality of live, physically debilitate the patient, and lead to impairment in social capability (Yang Jong In, Jung-HwanYoon, and Yung-Jue Bang, 2010). As medical students, we can do active participation in research to explore the potential of Luteolinfor liver fibrosis therapy as a revolutionary novel inovation. We can also encourage the government and pharmacy industry to develop any protection for liver fibrosis from all fronts so that liver fibrosis won't be a great source of economic burden to not only the patient but also the society and it won't be a hindrance to proper medical care of chronic disease patients. OBJECTIVE OF THE STUDY

Hence, this research paper wants to show how Luteolin works to inhibit liver fibrosis progession and to accelerate liver regeneration, to explore the potential of Luteolin as a new therapy solution for liver


fibrosisin communities, and to draw attention to the need to raise people and government awareness' about silent chronic or degenerative disease and its deadly complication effect so that it won't be a great source of economic burden to not only the patient but also the society and it won't be a hindrance to proper medical care of chronic disease patients. MATERIALS AND METHODS

The design of this research study using True Experimental Design in the laboratory in vivo using draft Post Test Only Randomized Controlled Group Design. Induction of CCl4 dose refers Sahreen et al., (2011), of 0.5 ml / kg, twice a week for six weeks. Extract dose refers to research Domitrovic et al., (2009).Male mices 6-7weeks months were used and the usage of animal model had been sertified ethically. Research had been done from March-June 2013 in Pharmacology Laboratory, Biomedical Laboratory, Biochemical&Biomolecular Laboratory, Patology Anatomy Laboratory, and Physiology Laboratory of Medical Faculty, Brawijaya University. Research Procedure: A. Experimental Animals Preparation

MicesBalb/c age 6-7 weeks were adapted in Pharmacology Laboratory for 7 days and divided into 6 groups, negative control group (-), positive control group 1 (C+1) and positive control group 2 (C+2), and treatment group 1,2,3 (T1,T2,T3) (Domitrovicet al., 2009). B. Induction ofLiver Fibrosis Model Mice

CCl4 dissolved in corn oil before it was used. BALB/c mices were fasted overnight and then injected intraperitoneally with CCl4twice a week for six weeks (Yang, 2009). C. Mint Leaf Extract Production and Administration

Mint leaves were dried and cut into small pieces. Then 100 g of sample was mixed with methanol overnight, filtered, and evaporated. We used rotary evaporator and water bath heater. We got about half of the sample used. Extraction result was saved in

the sterile plastic bottle and stored in a freezer. The extract was administrated by using sonde orally. D. Mice Dissection to Get Blood and Liver Sample

Anesthesia using chloroform perinhalation. Taking blood from the heart with a 1ml syringe and livers were fixed in 10% formalin. E. Liver Histopatology Staining usingHematoxylin Eosin

Liver histology making preparations by using paraffin method and then see the progression of liver repair. Results were observed in the microscope to see liver regeneration (Ellis, 2010). F. Liver Collagen Stainingusing Masson’s Trichrome

Liver tissue was cut in the form of paraffin thickness of 5 µm, deparaffined, and rehydrated with alcohol 100%, 95%, and 70%. Rinse with aquades, proceed with Weigert's iron hematoxylin working solution for 10 minutes. Rinse with warm water for next 10 minutes. GaveBiebrich scarlet-acid fuchsin solution 10-15 minutes, rinse.Differentiated in phosphomolybdic-phosphotungstic acid solution for 10-15 minutes. Moved the pieces on aniline blue, colorized it for 5-10 minutes. Washed quickly, gived a solution of 1% acetic acid for 2-5 minutes, washed with aquades. Dehidrated with 95% ethyl alcohol, pure alcohol, wipe. Collagen deposition as a sign of fibrosis had blue color. G. MMP-9 and TGF-β1 Staining usingImmunostaning

Deparaffinizationto prepare heparslide,then incubated overnight at 4°C. Slides were incubated, drops of distilled water, allowed to stand on 10 minutes. Blocking incubation with hatching 100 mL / slide and allowed to stand on 60 minutes. Washing with PBS 3x5 minutes, blocking use H2O2 3% before the primary antibody, washed again with PBS 3x5 minutes. Primary antibody incubation MMP-9 and TGF-β1 1:50 in PBS-FBS 10%, 100 mL solution spilled to each slide, incubation at 4 ° C overnight. Incubation SAHRP 1:200 in PBSand let it stand in 40 minutes. Wash it


using PBS in 3x5 minutes. Wash with distilled water and DAB incubation, Wait 30 minutes until brown color appearon the network. Meyer dye incubation in tap water, wait 20 minutes until purple color appearon the network. Then wash with tap water until the remains Meyer lost (Ogawa K, Chen F, Kuang C, Chen Y, 2004). H. MMP-9 Measurement using ELISA

Samples stored at -800oC. Wash cassette with deionized water. Fill 10 mL protein molecular, placed on the mini-electrode cell and connect with 125V power supply for 90 minutes, monitor the bubbles circulation thatbecame an indicator gel. Monitor every 15 minutes and use bromophenol blue and buffer. Perform renaturing and developing gel, then perform data analysis. Scan the gel and save using TIFF format. I. SGPT andSGOT LevelsMeasurement

Preparing cuvette 5: GOT (2 cuvette), GPT (2 cuvette), and distilled water (1 cuvette), each cuvette added: solution serum / plasma GOT 50µL, 50µLGPT, and reagents (1) 500µL GOT, GPT500µL mixed and allowed to stand 1 minute, reagent (2)

GOT 125µL GPT125µL, make sure the solution was mixed well, it characterized by no sediment in the bottom of cuvette, silencing at room temperature (25o) for 5 minutes, read using spectrophotometer at 365 nm wavelength, use cuvette contained 1 mL of distilled water formakingthe instrument zero, everymeasurement must make zero use distilled water. The calculationwas the enzyme activity = Az x F where the As was the sample absorption and F = 39.71. J J.Tabulation and Data Analysis

MMP-9 expression measurement result, the level ofhepaticcollagendeposition, SGPTandSGOTin the controlandtreatmentwere statisticallyanalyzedusingSPSS17.0with significance level0.05(p =0.05) and95% confidentiallevel(α =0, 05). Steps to test hypothesiscomparativeandcorrelative are usingnormality data test, variance of homogeneitytest, one-way ANOVA test, post hoctest(Least Significant Difference test) andPearsoncorrelation test.

RESULTS SGOT Level

Table 1.SGOT 1 Level Table 2.SGOT 2 Level

No Group (n=5) SGOT level U/mL ( ±SD) No Group (n=5) SGOT Level U/mL(

±SD) 1 Negative control 0,21 ± 0,02a 1 Negative control 0,21 ± 0,03a 2 Positive control1 2,75 ± 0,44b 2 Positive control1 2,82 ± 0,43b 3 Positive control 2 2,88± 0,35 b 3 Positive control 2 2,87± 0,46 b 4 P1 (15 ml/KgBW) 1,16 ± 0,14ba 4 P1 (15 ml/KgBW) 1,08 ± 0,05ba 5 P2 (30 ml/KgBW) 0,79 ± 0,03 a 5 P2 (30 ml/KgBW) 0,78 ± 0,05 a 6 P3 (60 ml/KgBW) 0,49 ± 0,37a 6 P3 (60 ml/KgBW) 0,48 ± 0,37a

Different notation showedsignificantly different (p<0,05) SGPT Level

Table3.SGPT 1 Level Table 4.SGPT 2 Level

No Group (n=5) SGPT Level U/mL

( ±SD) No Group (n=5) SGPT Level U/mL

( ±SD) 1 Negatve control 0,20 ± 0,04a 1 Negatve control 0,20 ± 0,04a 2 Positive control 1 2,83 ± 0,53b 2 Positive control 1 2,84 ± 0,55b 3 Positive control 2 3,18± 0,39 b 3 Positive control 2 3,14± 0,38 b 4 P1 (15 ml/KgBW) 1,16 ± 0,41ba 4 P1 (15 ml/KgBW) 1,21 ± 0,41ba 5 P2 (30 ml/KgBW) 0,90 ± 0,04 a 5 P2 (30 ml/KgBW) 0,91 ± 0,07 a 6 P3 (60 ml/KgBW) 0,53 ± 0,16a 6 P3 (60 ml/KgBW) 0,56 ± 0,12a

Different notation showedsignificantly different (p<0,05)


Hepatic Relative Mass MMP 9 Level Table5.Hepatic Mass Table6.MMP9 Level

No Group (n=5) Hepatic Mass

( ±SD) No Group (n=5) MMP9 Level ( ±SD)

1 Negatve control 0,64 ± 0,14a 1 Negatve control 0,54 ± 0,12a 2 Positive control 1 2,96 ± 0,16b 2 Positive control 1 0,49 ± 0,17b 3 Positive control 2 2,83 ± 0,32 b 3 Positive control 2 0,77± 0,10 b 4 P1 (15 ml/KgBW) 2,09 ± 0,12b 4 P1 (15 ml/KgBW) 1,42 ± 0,51a 5 P2 (30 ml/KgBW) 2,05 ± 0,10ab 5 P2 (30 ml/KgBW) 2,40 ± 0,11c 6 P3 (60 ml/KgBW) 1,37 ± 0,27a 6 P3 (60 ml/KgBW) 3,21 ± 0,12c

Different notation showedsignificantly different (p<0,05) Histopathology Result usingHematoxylin Eosin

MMP 9

Masson’s Trichrome K- K+1 K+2 P1 P2 P3

TGF-β1 K- K+1 K+2 P1 P2 P3

DISCUSSION SGPT

In our study, on one way ANOVAtest resultsobtainedSGPTvalue levelof significance0.000(p <0.05), itmeansthere are

at leasttwogroupshavesignificant differences. Frompost hoc analysisfoundsignificant differencesbetweenK(-),K(+)1and K(+)2. Andalsofound significant differencebetween

P1

P2

P3

K-‐

K -

P2 P1 K+22+2

K+2

K+1 P1 K+2 P3

K- P1 P2 P3

K+1


thelast percentageof theK(-) inallgroups were givenmint leafextract. Thus, it can be concludedthatalldoseshadefficacyin decreasing SGPTlevel. SGOT

In our study, on one way ANOVAtest resultsobtainedSGOTvalue level of significance0.000(p <0.05), itmeansthere are at leasttwogroupshavesignificant differences. Frompost hoc analysisfoundsignificant differencesbetweenK(-),K(+)1, and K(+)2. Andalsofoundsignificant differencebetween thelast percentage of theK(-) inallgroups were given mint leafextract. Thus, it can be concludedthatalldoseshadefficacyin decreasing SGOT level.

Histopathology examination stained usingHematoxylin Eosin

In this study, negative controlgroup(KN) showednormalhepaticarchitectureinallareas. Inpositive controlgroup(K+1andK+2) which is givenCCl4, there arehepatocytesballooningdegeneration/necrosis, hyalineinclusionsandcongestionof bloodflow. In control grouptreatment with dose15ml/KgBW,itstillfoundhepatocyteswithballooningdegenerationwith hyaline andcongestioninclusionsof bloodflow. In control group treatment with dose30ml/KgBW, it hasreductionofhepatocytes lesion, but,lesionstillpresents insmaller amountsandnolongerfoundcongestionof bloodflow. In control grouptreatment withdose 60ml/KgBW, it seems in normal condition. It can be concluded that giving mint leafextract can changehepatic architectureclose to normalcondition. Hepatic Relative Mass to Mice Body Mass

Onhepatic fibrosis condition, the fibrous tissue mass increases hepaticrelative mass to all body mass (Yang, 2010). In this study, Kolmogorov-Smirnov normality test result showed thatliver relativemass data has normal distribution (p> 0,05). On the homogenity test, it obtained significant value 0.150. It means that data have homogeneous variance (p> 0:05). Afterboth

ofrequirements fulfilled, one way ANOVA test did and obtained significancevalue 0.000 which means there are two groupshave significant differences. From post hoc analysis, it found significant differences between K (-) and K (+) 1, k (+) 2, P1, P2 and P3 sequentially. It can be concluded that P3 dose was able to decrease hepatic relative mass significantly compared to K (+) 1 and k (+) 2. Thus, administration of mint leaf extract can reduce hepatic relative mass (Domitrovic, 2009).

Liver collagen deposition stained usingMasson’sTrichrome

On negative control group (KN) section showedfew collagen deposition (blue tissue). Onpositive control group (K +1 and K +2) which is given CCl4only, has a little more collagen deposition. On the treatment control group I with dose 15 ml / KgBW, it still found collagen deposition. On the treatment control group II with dose 30 ml / KgBWshowed significant decrease of collagen deposition. On the treatment control group III with dose 60 ml / KgBW, liver seems like normal condition.

MMP-9usingELISAandImmunostaining

In this study, One way ANOVAtest result ofMMP-9 immunopositive area, it obtainedsignificance value 0.000(p <0.05). Itmeans that there aretwogroups, havesignificant difference. Frompost hoc analysisis, it foundsignificant differencesbetweenKNandK(+), between P1,P2andP3. Thus, it can be concludedthat onP1-dose (15 ml/ kg), it could increaseMMP-9 expressionof liver inliverfibrosiscondition.It alsoobtainedsignificantimprovementthroughP3level with dose60ml/kgBW that higher thanpositive control.

From MMP-9 examinationused immune staining, it obtained that on negative control (KN) picture showed normal liver. On positive control (K +1 and K +2), there is decrementofMMP-9 expression that describesliver damage. Ontreatment group, P1showed that there is improvement characterized by increasedof MMP-9


expression,as showed both on P2 and P3doses. Thus, it can be concluded thatmint leaf extraction was able to increase MMP-9 expression. TGF-β1 with Immunostaining

TGF-β1 has major role in the formation of fibrous tissue. On hepaticfibrosis, there is increment level of TGF-β1. From this study, negative control group (KN) TGF-β1 showed normal level. In positive control group (K +1 and K +2) which is given CCl4only, it found an increase level of TGF-β1. In treatment group, with dose 15 ml / KgBW, there is decrement on TGF-β1 levels. In treatment group with dose of 30 ml / KgBWshowed decrement alsoon TGF-β1 level significantly. In treatment groupwith dose 60 ml / KgBW,TGF-β1 level appeared close to normal condition.

CONCLUSION 1. Mint leaf extract(Menthaspicata L.)can

repairhepatic structure histologicallyonhepatic fibrosis mice model.

2. Mint leaf extract(Menthaspicata L.)candecreasehepatic collagendepositiononhepatic fibrosis mice modelmacroscopicallyand microscopically.

3. Mint leaf extract(Menthaspicata L.)can increaseTGF-β1, MMP-9 expression onhepatic fibrosis mice model.

4. Mint leaf extract(Menthaspicata L.)canrepairhepatic damage and secretion functionofliver onhepatic fibrosis mice model.

SUGGESTION 1. It still needed further experimental

research to find optimum dose of Mint leaf extract(Menthaspicata L.)on human.

2. It needed further experimental research aboutMint leaf extract(Menthaspicata L.)to anotherhepatic fibrosis parameterto knowspecific effectwhich didn’t reveal yet in this research, like αSMA, PDGF, NFκBetc.

ACKNOWLEDGMENT

We thank to Prof. Dr. dr. M. RasjadIndra and MS and Mr.Wibi Riawan, S.si for his guidance to finish this paper into a great experimental research. Also Mr.Memed, miss Ami, laboratory analyse. We hope this scientific paper will becomethe basis for the future hepatic fibrosis therapy. REFERENCES Anom, T. I., and I. D. N. Wibawa. (2010).

Pendekatan Diagnosis dan Terapi Fibrosis Hati. J Peny Dalam. 11;57-67. Location: Publisher.

Anshory, M. (2008). Efek Pemberian Cornmeal dan Cornmeal-soy terhadap Ketebalan Aorta Tikus Rattus norvegicus yang Diberi Diet Aterogenik. (Thesis, Medical Faculty Brawijaya University).

Bataller R, Brenner DA. (2005) . Liver Fibrosis. Journal Clinical Investigation 115: 209–218.

Beeton, Hu X. (2010). Detection of Functional Matrix Metalloproteinases by Zymography. J. Vis. Exp. (45), e2245. DOI: 10.3791/2445

Bissell DM, Roulot D, George J. (2001). Transforming Growth Factor-B and The Liver. Hepatology 34: 859–67.Location: Publisher.

Chen Chiu-Yuan, Wen Peng, dan Shih-Lan Hsu. (2010). Luteolin Ameliorates Experimental Lung Fibrosis Both in Vivo and in Vitro: Implications for Therapy of Lung Fibrosis.J. Agric. Food Chem. 58 (22): 653– 661.

Consultative Group on International Agricultural Research. (2004). Groundnut (Arachis hypogaea Linnaeus). Retrieved From http://www.cgiar.org /impact/research/groundnut. html).

Domitrović Robert, Hrvoje Jakovac, JelenaTomac, Ivana Šain. (2009). Liver Fibrosis in Mice Induced by Carbontetrachloride and Its Reversion by Luteolin.Toxicology and Applied Pharmacology 241): 311–321.

Ellis, Roy. (2010). Hematoxylin and Eosin (H&E) Staining Protocol. Retrieved


Fromhttp://www.imvs.or.au/read.thp?id=36s6.

Friedman SL. (2003). Liver Fibrosis—From Bench to Bedside. J Hepatol 38, Suppl 1: S38–S53.

Gow-Chin, Yen dan Pin-Der Duh. (1995). Antioxidant Activity and the Variations of Components in Methanolic Extracts of Peanut Hulls.Retrieved from http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T6RYYT6FB-.htm.

Gow-Chin, Yen., Pin-Der, Duh., dan Cherng-Liang, Tsai. (1993). Relationship between Antioxidant Activity and Maturity of Peanut Hulls. Taiwan: Department of Food Science. 4:67-70.

Hu, X., Beeton, C. (2010). Detection of Functional Matrix Metalloproteinases by Zymography. J. Vis. Exp. (45), e2445, DOI: 10.3792/2445

Highleyman, Liz. (2011). Disease Progression What is Fibrosis. San Fransisco: Hepatitis C Support Project3:1-2.

Iredale JP. (2007). Models of Liver Fibrosis: Exploring The Dynamic Nature of Inflammation and Repair in A Solid Organ.J Clin Invest117: 539–548.

Kumar, Abbas, Mitchell, et al.(2007). Basic Pathology 8th.Elsevier. Location: Publisher.

Leask A, Abraham DJ. (2004). TGF-b Signaling and The Fibrotic Response.FASEB J 18:816–27.

Lopez-Lazaro, Miguel. (2009). Distribution and Biological Activities of The Flavonoid Luteolin. Retrieved From http://www.ingentaconnect.com/ ben /2009/ 0000009/00000001/art00004

M, Toth, A, Sohail, R, Fridman. (2012). Assesment of Gelatinases (MMP-9 and MMP-2) by Gelatin Zymography. Methods Mol Biol. 878: 121-35

Maestri, D.M., Nepote V., Lamarque, A.L., and Zygadlo J.A. (2006).Natural Products as Antioxidants. Phytochemistry: Advances in Research. 105-135.

Naveau S, Gaudé G, Asnacios A, Abella A, Barri-Ova N, Dauvois B, Prévot S. (2009). Diagnostic and Prognostic Values of Non-Invasive Biomarkers of Fibrosis in Patients with Alcoholic Liver Disease.Hepatology 49:97-105.

Ogawa K, Chen F, Kuang C, Chen Y. (2004) .Suppression Of Matrix Metalloproteinase-9 Transcription by Transforming Growth Factor-B Is Mediated By A Nuclear Factor-Kb Site. Biochem J 381: 413–22.

Pin-Der, Duh., Dong-Bor, Yeh., dan Gow-Chin, Yen. (1992). Extraction and Identification of an Antioxidative Component of Peanut Hulls. Taiwan: department of Food Science. 69: 8-11.

Rasyid, A. (2006). Temuan Ultrasonografi Kanker Hati Hepatoselular (Hepatoma). Majalah Kedokteran Nusantara 2;100-103

Rockey, Don C, Friedman, Scott L. (2006). Hepatic Fibrosis and Cirrhosis.Hepatology 87-110.

Seelinger Günter, Irmgard Merfort, dan Christoph M. Schempp. (2008). Anti-carcinogenic Effects of the Flavonoid Luteolin. Molecules 13: 2628-2651.

Tsigbey, F.K., R. L. Brandenburg , and V. A. Clottey.( 2003). Peanut Production Methods in Northern Ghana and Some Disease Perspectives. Retrieved from http://www.lanra. uga.edu/peanut/base/

WHO. (2002). Revised global burden of disease estimates.Retrieved From http://www.who.int/healthinfo/global_burden_disease/index.html

Yang Jong In, Jung-HwanYoon, dan Yung-Jue Bang. (2010). Synergistic Antifibrotic Efficacy of Statin and Proteinkinase C Inhibitor in Hepatic Fibrosis. J Physiol Gastrointest Liver Physiol 298:45-65.

Zhang, Qingcai. (2005). Classification of Liver Fibrosis. New York: Sinomed Research Institute.


THE EFFECT OF TURMERIC (Curcuma domestica) EXTRACT AND EXERCISE

TO MYOCARDIAL FIBROSIS IN STREPTOZOTOCIN-INDUCED DIABETIC

MICE

Edward Sutanto, Agatha Novell H, Andyta Nalaresi, Lathifa Putry Fauzia, Sarah Dyaanggari Akip* , M. Ali Sobirin **

*Medical Student of Diponegoro University, Semarang ** Lecturer staff of Pharmacology Departement of Medical Faculty, Diponegoro

University, Semarang

ABSTRACT Backgrounds:Diabetic cardiomyopathy is a complication of diabetes mellitus (DM) which is a myopathy condition characterized by myocardial fibrosis. Turmeric (Curcuma domestica) with curcumin as its active ingredients is one of traditional herbal medicine that has been used for DM treatment, and also exercise. It is not known the effect of turmeric extract and exercise combination on myocardial fibrosis in diabetic cardiomyopathy. Aims: To analyze the difference effect between turmeric extract, exercise, also combination of turmeric extract and exercise on myocardial fibrosis in streptozotocin-induced diabetic mice. Methods: This research was an experimental study with post-test only control group design using 3 months old male Swiss mice with weight 25–35 g. DM was induced by streptozotocin (STZ) injection. 35 samples were randomly divided into five groups which were healthy control (C), diabetic (D), diabetic treated turmeric extract (D + Tur), diabetic treated with exercise (D + Exe), and diabetic treated with turmeric extract and exercise combination (D + Com). Body weight and blood glucose were examined at the beginning and end of treatment while myocardial fibrosis was examined using Masson’s Trichrome staining at the end of treatment (21 days). Data was analyzed by using One Way ANOVA followed by LSD test for post-hoc analysis. Results: Body weight was decreased in D group, but was attenuated in D + Tur, D + Exe, and D + Com groups (p=0.034, p=0.046, p=0.044). Blood glucose was increased in D group, but was attenuated in D + Tur and D + Com groups (p=0.030, p=0.032). Myocardial fibrosis area was increased in D group, but was tend to decreased in in D + Tur, D + Exe, and D + Com groups (p=0.061, p=0.074, p=0.054). Conclusion: Combination of turmeric extract and exercise treatment tend to decrease myocardial fibrosis, however there is no difference with turmeric extract or exercise treatment. Keywords: Diabetes Mellitus, Diabetic Cardiomyopathy, Fibrosis, Streptozotocin, Turmeric (Curcuma domestica) extract, Exercise Training

INTRODUCTION Unhealthy lifestyle phenomenon in

Indonesia has been increasing so that there is a transition in epidemiological pattern of disease which is shifted from infectious diseases to chronic degenerative diseases, such as coronary heart disease, hypertension, hyperlipidemia, and diabetes.

With the aging of populations in developing countries there is both a demographic and an epidemiological transition which affects the impact of chronic degenerative diseases on the health

status of the populations. Demographic transition takes place in countries where there are effective programmes of disease control which allow for survival during the early years of childhood and adolescence. This results in an increase in life expectancy which places larger proportions of the population in the age range (60 years and older) in which chronic degenerative diseases become the major determinants of health status.1

Diabetes mellitus (DM) is a group of metabolic diseases characterized by


hyperglycemia caused by abnormal insulin secretion, insulin action, or both.2 Based on International Diabetic Federation, the number of people with diabetes in the world reached 171 million people in 2000 and is expected to reached 366 million in 2030.3

According to recent epidemiological study, the incidence of diabetes in Indonesia ranges between 1.4% - 1.6%.4 This incidence will continue to rise according to theestimation put forward by the World Health Organization (WHO),Indonesia will be rank five worldwide by the number of people with diabetes as much as 12.4 million people in 2025, up 2 rank than in 1995.5

According to the American Diabetes Association , there are four classifications of impaired glucose tolerance which are: Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, Gestational Diabetes Mellitus, and other specific types of diabetes.6

Implications arising from diabetes itself are plenty, starting from increased health care costs to decline in quality of life, with the main threat of the diabetes mellitus complication. Complications of diabetes can be divided into acute metabolic complications and chronic vascular complications.6

Acute metabolic complications may include hypoglycemia, diabetic keto-acidosis, lactic acidosis coma and hyperosmolar non-ketotic coma. Chronic vascular complications are divided into: diabetic microangiopathy if it is affecting the small blood vessels or capillaries including diabetic retinopathy and diabetic nephropathy, and diabetic macroangiopathy if it is affecting the large blood vessels including diabetic cardiomyopathy.7

Diabetic cardiomyopathy is a myopathic condition related to diabetes that occurs independently from atherosclerosis, coronary artery disease, and hypertension with the main characteristics is cardiac diastolic dysfunction.7 Framingham Heart Study suggests that heart failure is 2 times more common in men with diabetes and 5 times more in women with diabetes, compared with control subjects of the same age.9 Cardiovascular complications are a

major cause of morbidity and mortality in patients with DM.10

In Indonesia, traditional herbal medicines to treat diabetes are already familiar within the community. Turmeric (Curcuma domestica), which has an active substance known as curcumin, is one of commonly used medicinal plants. Curcumin has shown biological activity as an antidiabetic.11 Sports or exerciseis also an important interventionin dealing with chronic diseases such as diabetes, chronic renal failure, and heart failure.12

As a chronic disease, diabetes can not be cured. What can be done is preventing the complications of diabetes, diabetic cardiomyopathy in this case. As mentioned above, individually both turmeric extract and exercise are effective to interfere progression towards diabetic cardiomyopathy. However, to date, there has been no studies done on the effect of turmeric extract and exercise combination on the incidence of diabetic cardiomyopathy. Thus the aim of this study is to analyze the effect of turmeric extract and exercise combination on the myocardial fibrosis in streptozotocin-induced diabetic mice. MATERIALS AND METHOD Experimental Animals

This research was an experimental study using post-test only control group design.Thirty-five male Swiss mice (25–35 g) were purchased from Faculty of Biology, Semarang State University. Before experiments, all mice were fed with basal diet (BD) for one week. Animal protocols were carried out with approval from the Ethical Clearance Commission at Faculty of Medicine, Diponegoro University under permit number 137/EC/FK/RSDK/2013. All procedures were performed under minimize suffering. Induction of Experimental Diabetes on Rats

Diabetes was induced by a single intraperitoneal injection of streptozotocin (Tocris Bioscience, Bristol, UK) at the dose of 180 mg/kg dissolved in phosphate buffer saline pH 4.5.13 Control rats were


administered an equivalent volume of phosphate buffer saline. The rats were considered diabetic and used for the study only if they had hyperglycemia (fasting blood glucose ≥ 306 mg/dL) at 72 h after streptozotocin (STZ) injection.13 Blood glucose levels were measured on basal fasting state using hand-held glucometer by tail vein puncture blood sampling. Experimental Protocol

Three days after STZ injection, normal and diabetic rats were randomly selected and divided into five groups (n = 7 each), namely, healthy control (C), diabetic (D), diabetic treated with turmeric extract (D + Tur), diabetic treated with exercise (D + Exe) and diabetic treated with turmeric extract and exercise combination (D + Com). Curcumin was purchased from Integrated Research and Testing Laboratory (LPPT) of Gadjah Mada University. Treatment lasted for 21 days, the D + Tur and D + Com groups received a suspension of curcumin (3 mg/day, per oral).14While D + Exe and D + Com groups received swimming exercise 6 days per week, each days have 2 sessions with duration of swimming 15 minutes and increasing by 15 minutes per day until 60 minutes is achieved.15 Body weight and blood glucose was measured at the beginning and end of treatment. All the animals were provided with food and water ad libitum. Measurement of Myocardial Fibrosis

Mice were anesthetized with 2% halothane in O2 and subjected to surgical procedures for heart excision. The hearts were fixed with 4% paraformaldehyde, sectioned into 2 mm thick transverse slices and parallel to the atrioventricular ring, then embedded in paraffin, and cut into 4 mm slices.16 Paraffin-embedded tissue sections were stained with Masson’s Trichrome in laboratory of pathology anatomy in Dr.Kariadi Hospital, Semarang.

The area of myocardial fibrosis was quantified by a color image analyzer (Image-J, National Institute of Health, USA), using the difference in color (blue fibrotic area as opposed to red myocardium). The extent of myocardial fibrosis was taken

as the ratio of the fibrosis area to the whole area of the myocardium.16 Statistical Analysis

Data are expressed as mean ± SEM while data normality were examined using Shapiro-Wilk test. One-way analysis of variance (ANOVA) was used to compare values between groups followed by LSD test for post hoc analysis. A value of p < 0.05 was considered statistically significant. RESULT Biochemical parameters before STZ injection

Differences in body weight before injection of STZ in each group are shown in Table 1. The distribution of body weight data was tested using the Shapiro-Wilk test and the result was distribution of data in each group (p> 0,05) is normal. Body weight data is then analyzed further by One-way ANOVA and no notable difference in blood glucose levels between the groups (p= 0.818) was found.

Differences in blood glucose before injection of STZ in each group are shown in Table 1. The distribution of blood glucose data was tested using the Shapiro-Wilk test and the result was distribution of data in each group (p> 0,05) is normal. Blood glucose data is then analyzed further by One-way ANOVA and no notable difference in blood glucose levels between the groups (p= 0.996) was found. Biochemical parameters after 21 days of treatment

Differences in body weight after 21 days of treatment in each group are shown in Table 2. The distribution of body weight data was tested using the Shapiro-Wilk test and the result was distribution of data in each group (p> 0,05) is normal. Body weight data is then analyzed further by One-way ANOVA followed by LSD test. In D group, there was a significant decrease in body weight compared to the N group (p< 0.05). Compared with the D group, there was a significant increase in body weight (p< 0.05) of the other three groups (D + Tur, D + Exe, and D + Com).

Differences in blood glucose after 21 days of treatment are shown in Table 2.


Blood glucose data distribution was tested using the Shapiro-Wilk test and the result was distribution of data in each group (p> 0,05) is normal. Blood glucose data is then analyzed further by One-way ANOVA followed by LSD test. In D group, there was a significant increase in blood glucose compared to N group (p< 0.05). In D + Tur and D + Com group, there was a significant decrease in blood glucose compared to D group (p> 0.05), while in D + Exe blood glucose tend to decrease (p= 0.051). Histopathological changes after 21 days of treatment

Histopathological changes of myocytes tissue in each group can be seen in Figure 1. With Masson's Trichrome staining, fibrosis will be stained blue (as shown in the direction of the arrow) compared to red stained myocytes.

Quantitative analysis of myocardial fibrosis area ratio compared to the total area done with Image J is shown in Figure 2. Fibrosis area data distribution was tested using the Shapiro-Wilk test and distribution data on each group is normal (p> 0,05).Fibrosis ratio of each group was then analyzed using One-way ANOVA followed by LSD test. On D group, there was a significant increase of myocardial fibrosis area than group N (p<0.05). Compared with the D group, myocardial fibrosis area in the other three groups (D + Tur, D + Exe, D + Com) was tend to decrease (p = 0.061, p = 0.074, p = 0.054). DISCUSSION

This study aims to analyze the effect of turmeric extract and exercise combination to myocardial fibrosis in streptozotocin-induced diabetic mice. This research was an experimental study with post-test only control group design which use animal as test subject, by comparing result that has been obsereved in control and treatment groups. Biochemical parameters before STZ injection

As shown in Table 1, there are differences in body weight and blood glucose between each groups before STZ injection. However, according to one-way

ANOVA, these differences are not statistically significant (p>0,05) thus overall it does not affect the result of the study.

In D group, there was a significant increase in body weight, blood glucose, and myocardial fibrosis area after STZ injection. This finding suggests diabetic cardiomyopathy condition which also occurred in group D + Tur, D + Exe, and D + Com. Biochemical parameters after 21 days of treatment

Based on Table 2, the mean blood glucose in the D + Tur group was 398.4 mg /dL. Turmeric extract can lower blood glucose significantly (p= 0.030) , although still within the category of hyperglycemia ≥ 306 mg / dL. These results are similar to studies conducted by Soetikno which there was a significant decrease in blood glucose to 597.1 mg / dl after curcumin treatment for 8 weeks in wistar rats.17 This study is also similar to the study conducted by Yu which found a significant decrease in blood glucose after curcumin treatment both at a dose of 100 mg/kg and 200 mg/kg to 235.8 mg/dL and 156.5 mg/dL.16

The mean blood glucose in the D + Exe group was 408 mg /dL. Provision of exercise tends to lower blood glucose (p = 0.051) although they remain in the category of hyperglycemia . This result is in contrast to research conducted by Silva which found a significant decrease in blood glucose to 379 mg /dL after the administration of exercise for 10 weeks.12

The mean blood glucose in the D + Com group was 399 mg / dL. Combination of turmeric extract and exercise can lower blood glucose significantly (p= 0.032), although still in the category of hyperglycemia.

Based on Table 2, the mean of body weight in group D + Tur is 37.9 g. By giving turmeric extract, body weight can increase significantly (p = 0.034). This result is similar to research study conducted by Yu which there was a significant increase of body weight to 332 g by giving curcumin 200 mg / kg.16This result is in contrast to research done by Soetikno, that stated


although wistar rats gains weight to 363 g after curcumin treatment, it was not statistically significant.17

The mean of body weight in group D + Exe is 37.6 g. Exercise training can increase body weight significantly (p = 0.046). These results are consistent with research conducted by Silva, that stated there was a significant increase of body weight to 282 g after administration of exercise training.12

The mean of body weight in group D + Com is 37.7 g. Giving a combination of curcumin and exercise training can increase body weight significantly (p = 0.044). Histopathological changes after 21 days of treatment

Myocardial fibrosis is signs of diabetic cardiomyopathy which exact pathogenesis mechanism has not been known. However, an important component of the pathological alterations observed in diabetic cardiomyopathy includes the accumulation of extracellular matrix proteins, in particular collagens.18

Based on Figure 3, the mean area of myocardial fibrosis in the group D + Tur is 8,033%. Turmeric extract tends to reduce myocardial fibrosis area (p= 0.061). This result is not consistent with research studies conducted by Soetikno and Yu, that stated there was a significant reduction in myocardial fibrosis area after curcumin treatment.16, 17 This difference perhaps can be explain that previous studies conducted curcumin treatment for over a period of 8 to 16 weeks, while this study was conducted for a period of 3 weeks using turmeric extract treatment thus the long term result of curcumin treatment has not been shown.

The mean area of myocardial fibrosis in group D + Com is 7.94%. The administration of turmeric extracts and exercise combination tends to reduce fibrosis area (p = 0.054).

This shows a synergistic effect between turmeric extract and exercise in alleviating diabetic cardiomyopathy. The occurrence of myocardial fibrosis in diabetic cardiomyopathy is inhibited by curcumin contained in turmeric extract. Curcumin has an activity to suppress advanced glycation

end products (AGE) accumulation that has role in the inflammation process.16Curcumin also has an activity to inhibit reactive oxygen species (ROS) through PKC-MAPK pathway inhibition and lowering blood glucose, thereby reducing oxidative stress.17This is achieved through its ability as antioxidant, as its antioxidant capacity is 100-fold stronger than that of vitamin E/C.16Inflammation and oxidative stress are two important processes in the pathogenesis of diabetic cardiomyopathy.19

A possible mechanism that partially explains the cardiac dysfunction observed in diabetic cardiomyopathy is the decrease in calcium-sensing receptors. Studies have shown that additional autonomic dysfunction can contribute to a reduction in sarcoplasmic reticulum Ca2+transport ATPase (SERCA-2) expression in myocardial infarction. Previous study shows with regard to the echocardiographic parameters is that previous exercise training had a preventative effect on cardiac structure and function, induced by diabetes, an import factor favoring preconditioned exercise. Thus exercise training intervention attenuates autonomic dysfunction, increases SERCA-2 expression and improves functional capacity.12Moreover, it also able to decrease O-GlcNAcylation protein that is involved in many pathological conditions in heart.20 These mechanism alleviate the calcium homeostasis disorder that has an important role in diabetic cardiomyopathy pathogenesis.19Therefore both mechanisms of curcumin and exercise training have synergistic effect to prevent myocardial fibrosis.

CONCLUSION AND SUGGESTION Based on the results, the study can be summarized as follows : 1. Streptozotocin injection can be used to

increase blood glucose , lose weight , and increase myocardial fibrosis area compared with healthy control group .

2. Turmeric extract intake for 21 days after streptozotocin injection can lower blood glucose and increase body weight, also myocardial fibrosis areatend to decrease.


3. Exercise training for 21 days after streptozotocin injection can increase body weight, both blood glucose and myocardial fibrosis area tend to decrease.

4. Combination of turmeric extract and exercise for 21 days after streptozotocin injection can lower blood glucose, increase body weight, andmyocardial fibrosis area tend to decrease.

5. There is no difference on decreasing myocardial fibrosis area between groups which got combination of turmeric extract & exercise treatment and single treatment of curcumin or exercise

Suggestions for further research are as follows: 1. Further research is necessary to analyze

long-term (more than 21 days) effects of turmeric extract and exercise combination on myocardial fibrosis

2. Further research is necessary to analyze to the effect of turmeric extract and exercise combination on other parameters of diabetic cardiomyopathy such as myocyte apoptosis, heart weight / body weight ratio, inflammatory cytokines, and accumulation of AGE.

REFERENCE Manton KG. The Global Impact of

Noncommunicable Diseases: Estimates and Projections. World Health Stat Q [Internet]. 1988 [cited 2013 October 2]; 41(3-4): 255-266.

Gustaviani, Diagnosis dan Klasifikasi Diabetes Melitus. In: Aru WS, Bambang S, Idrus A, Marcellus SK, Siti S, editors. Buku ajar ilmu penyakit dalam jilid III edisi IV. Jakarta: Pusat Penerbitan Departemen Ilmu Penyakit Dalam FKUI; 2006. p. 1857-1859.

Wild S, Roglic G, Green A, Sicree R, King H. Global Prevalence of Diabetes Estimates for the year 2000 and projections for 2030. Diabetes Care [Internet]. 2004[cited 2013 October 1]; 27: 1047-1053.

Suyono S. Diabetes Melitus di Indonesia. In: Sudoyo AW, Setiyohadi B, Alwi I, Simadibrata M, Setiadi S, editors. Buku ajar ilmu penyakit dalam jilid III edisi

IV. Jakarta: Pusat Penerbitan Departemen Ilmu Penyakit Dalam FKUI; 2006. p. 1852.

King H, Aubert RE, Herman WH. Global Burden of Diabetes, 1995 – 2025: Prevalence, numerical estimates, and projections. Diabetes Care [Internet]. 1998 [cited 2013 Sept 27]; 21: 1414-1431.

Schteingart DE, Pankreas : Metabolisme glukosa dan Diabetes Melitus. In: Price SA, Wilson LM. Patofisiologi “Konsep Klinis Proses –Proses Penyakit” edisi VI volume II. Jakarta : EGC, 2006; p. 1259-1275.

World Health Organization (WHO). Definition, Diagnosis and Classification of Diabetes Melitus and its Complications [Internet]. Geneva : World Health Organization Department of Non-Communicabe Disease Surveillance; 1999 [cited 2013 Sept 30].

Boudina S, Abel ED. Diabetic Cardiomyopathy Revisited. Circulation [Internet]. 2007 [cited 2013 Sept 29]; 115: 3213-3223.

Kannel WB, McGee DL. Diabetes and cardiovascular disease: the framingham study. JAMA [Internet]. 1979 [cited 2013 Sept 27]; 241: 2035-2038.

Garcia MJ, McNamara PM, Gordon T, Kannel WB. Morbidity dan mortality in diabetics in the Framingham population: sixteen year follow-up study. Diabetes [Internet]. 1974 [cited 2013 Sept 30]; 23:105-111.

Setiawan AS, Yulinah E, Adnyana IK, Permana H, SudSepta P. Efek Antidiabetes Kombinasi Ekstrak Bawang Putih (Allium sativum Linn.) dan Rimpang Kunyit (Curcumma domestica Val.) dengan Pembanding Glibenklamid pada Penderita Diabetes Melitus Tipe 2. MKB [Internet]. 2011 [cited 2013 Sept 27]; 43(1):26–34.

Silva KAdS, Luiz RdS, Rampaso RR, Abreu NP, Moreira ED, Mostarda CT, et al. Previous Exercise Training Has a Beneficial Effect on Renal and Cardiovascular Function in a Model of


Diabetes. PLoS ONE [Internet]. 2012 [cited 2013 Sept 1]; 7(11): e48826.

Arora S, Ojha SK, Vohora D. Characterisation of Streptozotocin Induced Diabetes Melitus in Swiss Albino Mice. Global Journal of Pharmacology [Internet]. 2009 [cited 2013 Sept 22]; 3(2): 81-84.

Somchit MN, Zuraini A, Bustaman AA, Somchit N, Sulaiman MR, Nurotunlina R. Protective Activity of Turmeric (Curcuma longa) in Paracetamol-induced Hepatotoxicity in Rats. International Journal of Pharmacology [Internet]. 2005 [cited 2013 Sept 26];1(3):255-256.

Bennett CE, Johnsen VL, Shearer J, Belke DD. Exercise training mitigates aberrant cardiac protein O-GlcNAcylation in streptozotocin-induced diabetic mice. Life Science [Internet]. 2012 [cited 2013 Oct 3].

Yu W, Wu J, Cai F, Xiang J, Zha W, et al. Curcumin Alleviates Diabetic Cardiomyopathy in Experimental Diabetic Rats. PLoS ONE [Internet]. 2012 [cited 2013 Sept 22]; 7(12):

e52013. Soetikno V, Sari FR, Sukumaran V,

Lakshmanan AP, Mito S, Harima M, et al. Curcumin prevents diabetic cardiomyopathy in streptozotocin-induced diabetic rats: Possible involvement of PKC–MAPK signaling pathway. European Journal of Pharmaceutical Sciences [Internet]. 2012 [cited 2013 Oct 3]; 47: 604–614.

Asbun J, Villareal FJ. The Pathogenesis of Myocardial Fibrosis in the Setting of Diabetic Cardiomyopathy. J Am Coll Cardiol [Internet]. 2006 [cited 2013 Oct 1]; 47:693–700.

An D, Rodrigues B. Role of changes in cardiac metabolism in development of diabetic cardiomyopathy. Am J Phsyiol Heart Circ Physiol [Internet].2006 [cited 2013 Sept 29]; 291: 1489-1506.

Bennett CE, Johnsen VL, Shearer J, Belke DD. Exercise training mitigates aberrant cardiac protein O-GlcNAcylation in streptozotocin-induced diabetic mice. Life Science [Internet]. 2012 [cited 2013 Oct 3].


Scientific Poster – 1st Winner


Scientific Poster – 2nd Winner


Scientific Poster – 3rd Winner


Cancer is one of the chronic diseases which becomes primary concern in Indonesia because of its high prevalence. There are many possible aspects that contribute to cancer, some of which are genetic factors, environmental exposures, and lifestyle factors. The impacts of cancer are not only limited to the patients, but also to the surrounding people. Cancer affects people physically – degradation of one’s quality life –, socially – social incapability –, and emotionally – sadness, fear –. Besides, the financial costs during the care of this long term disease affect both the patients and society. Those problems become the foundation of our public campaign, which show people the hardship which the patient is facing, the difficulties that can arise during the care, and how the surrounding people can take part in supporting the patients through their hardest time. That all finally leads to the main purpose of this public campaign, which enhances the understanding and empathy of the society toward the patient’s feeling and makes the society understand the importance of their role in improving the patient’s quality of life. As stated before, there are difficulties during the care of this long term disease, which are experienced by the patient, medical professionals, and society. Patients, as the subject of cancer, tend to get distressed by their physical condition and their social incapability. The difficulty that can be faced by the medical professionals is when there is an absence of trust, which hinders the progress of patient’s treatment. On the other hand, the economic burden that the society has to face is also one of those difficulties during the management of cancer. Therefore, patients need companions that can walk together and accompany them through all their hardship. The one that can understand, empathize, and encourage them.

Key words: cancer, care, chronic disease, support

Health Campaign – 1st Winner


With Love and Faith Could Grows Hope

Objective : To describe the content of HIV video and posterwhich have target the society who don’t know how being people with HIV (called ODHA).The development of numerous opportunistic infections in an AIDS patient can ultimately lead to death. There is no cure yet for HIV/AIDS. Treatments can make the disease’s development slower.- some infected people can live for a long time. By interviewing one of them, this public campaign assigned HIV positive individuals depending upon how their diagnose has affected their life.Being diagnosed HIV positive must be very distressing, and frightening.This health campaign describes some of their life, social, and psychological’s process through the disease, and the consequences for their life. The interviewed person in this video describes how his life is, what has influenced him, how his feeling is, how he has survived with his conditon and what he has done after got diagnosed. This could change the way people see the people with HIV. They shouldn’t be ignored. By supporting them, obviously will gain their passion to being an active people, productive, and ambitious about life.Conclusion : Most of the society don’t know how to be an infected people, this health campaign also raises the society, governments, and medical’s professional’s empathy. It has purpose to change their paradigma about people with HIV (ODHA) , because over time most of people think that people with HIV (ODHA) should be ignored. This is the salient variable in this proccess. It could influence people to support them.

Health Campaign – 2nd Winner


Diabetes mellitus represents a

group of chronic diseases characterized by high levels of glucose in the blood resulting from defects in insulin production, insulin action, or both. Worldwide, the number of cases of diabetes has been estimated to be 171 million, and by 2025, this number is projected to reach 366 million (Wild et al, 2004). Based on International Diabetes Federation (IDF) 2012, prevalence of diabetes in 20-79 yo in Indonesia was 7 million cases and its prior to 9th position among 10 country with the highest case of diabetes in the world in 2010, and it is estimated increased to 6th prior in 2030 with 12 million cases. Diabetic Foot ulcerations (DFUs) are one of the most common complications in patients with diabetes. Patients with diabetes are at risk for developing serious health problems that may affect the eyes, kidneys, feet, skin, and heart.

Approximately 15% of DFUs result in lower-extremity amputation (Ramsey, 1999; Sanders, 1994).

DFUs prevalence in Indonesia is about 15%, amputation rate 30%, mortality rates 32% and diabetes ulcer is the leading cause 80% to the hospital admission for diabetes mellitus. The cost for patients with diabetes ulceration in Indonesia was 1,3-1,6 million rupiah for a month, and 43,5 million rupiah a year (Rini, 2008). The mortality rates after lower-extremity amputation range from 50% to 76% (ADA, 2003). In Indonesia one of the key issue in diabetes care is “lack of awareness” (Oberman et al, 2012).

So this health campaign is aimed to diabetes patients to prevent them from DFUs by inreasing their awareness with those small things, such as ; 1) Choose a proper shoes, because a proper shoes could reduce the friction between the feet and shoes, so it couldn’t create a trauma. 2) Choose a proper foot care (Toenail cutting, keep the moisturized, and wash the feet regularly). 3) Avoiding sharp things. As u know once diabetic patient got wounded it could be really hard to be healed. With those small things could reduce the possibility that leads to Diabetic Foot Ulcerations (DFUs).

Health Campaign – 3rd Winner


Fight Together Against Diabetes Diabetes is one of the most common non-communicable diseases globally. Diabetes mellitus is a chronic syndrome of disordered metabolism characterized by hyperglycemia due either to an absolute deficiency of insulin secretion or a reduction in the biologic effectiveness of insulin (or both). Indonesia ranks 4th in terms of diabetes mellitus prevalence right after China, India and U.S. WHO predicts that number of diabetes mellitus case in Indonesia will increase from 8,4 million in 2000 to 21,3 million in 2030. Without comprehensive treatment, this syndrome can lead to several complications such as retinopathy, chronic heart disease, and gangrene. In order to improve their quality of life and prevent premature death, people with diabetes must be aware of their lifestyle. This includes monitoring blood glucose, maintaining physical activity, and compliance to medication. Our video wants to tell that to change their lifestyle, that have been established for years, are not easy. Education about management of the disease is important, not only for the patients but also for their closest ones and need to be continued for the rest of patient’s life. Health care professionals need to be sensitive in patient’s condition and their need concerning management of diabetes, and always be ready to counsel. Carer and peer encouragement helps these lifestyle changes and also community has to understand and help them control their condition. The idea of our poster is the same with our video. Three people who try to climb the sugar jar and try to help the people who drown inside the sugar tells that diabetes patient need support from others to get out from his unhealthy lifestyle.


Go Rushed: Hypertension Treatments Objective: Promoting treatments of hypertension

Hypertension is one of the most common worldwide disease affecting humans. It is associated with high morbidity and mortality. It is estimated to cause 4,5% of the global disease burden (Tee et al, 2010). In Indonesia, hypertension is also very common. From a recent study in a rural area in Indonesia, the rate of hypertension among 111 respondents is 17,1% (Widjaja et al, 2013). Hypertension is the leading cause of several more complex diseases. Hypertension can cause coronary heart disease (the leading cause of death in North America), stroke (the third leading cause), congestive heart failure, end-stage renal disease, and peripheral vascular disease.

As medical students, we shall not only learn how to cure patients but also how to prevent diseases and how to educate patients (as patients also need to know about their problems so that they will be able to manage their life themselves). Because hypertension is a controllable disease, we create a new abbreviation to make short the five most essentials treatments and managements of hypertension. We intend to promote these five hypertension treatments and managements in an easy way. Thus, we hope people with and without hypertension can easily remember our tagline. GO RUSHED, our tagline, means “we shall go for rushed”, it stands for:

1. RUn a little 2. Salt and Smoking are restricted 3. High vegetables diet 4. Ethanol moderation 5. Drugs are taken daily

We hope our new innovation, Go Rushed, can be popular in society, so that

hypertension treatments and managements will attach deeply in the people’s mind. Go Rushed is easy to be done. We intend to make people understand how to survive hypertension without having to endure the more advanced complications.


Cancer Caregiver : Unsung Hero

Cancer is a chronic disease which is found 4,3% from 1000 population in Indonesia. Cancer treatment center is not available in all region in Indonesia, it is only provided in some of big city, so cancer patient from remote area have to manage a referral letter from the doctor at their region, then take it to the one of the big city that provide cancer treatment facility. Regulation of new patient admission at the referral hospital here is still complicated, so the patients have to wait about 2 months until they get the cancer treatment. At this point, cancer caregivers plays an important role. Even though caregivers are important, not many of us gives them more appreciation. Our video raised about the struggle of a cancer caregiver during accompany a cancer patient, walk to the hospital almost everyday to manage documents of patient’s health insurance, and also describe a little bit about how is the life inside cancer guest house by some photos we inserted into it, as our participants in this video are live in there. Our public poster describes the psychological burden and conflicts felt by the caregivers. We drew two hands holding each other while they are sorrounded by words represent condition the caregivers have to through besides cancer patient itself. The background of our poster is a symbol of cancer, a lavender ribbon, which means support to cancer patients. We also wrote “CARE FOR CANCER CAREGIVERS”, a message to people to give the cancer caregivers more support and appreciation.


From the Young to the Elders, Embrace Alzheimer’s Patients

Alzheimer’s disease is the most common form of dementia among elderly. It begins slowly. First, it involves the parts of the brain that control thought, memory, and language. Symptoms can get worse. People who sufferAlzheimer’s disease may have trouble in speaking, reading,and writing or even may not recognize his own family members. In Indonesia, the prevalence of Alzheimer’s disease is increasing exponentially. Most Indonesian do not go to the doctor or medical practitionerswhen theysustain Alzheimer’s Disease. Usuallyfamily memberseither abandon or left them in nursing homes without visiting them. Care and attention from their family and close friends will delay the progressiveness of Alzheimer’s disease. The patient should be provided with predictable daily activities such aseating, excercising , dressing-up, and sleepingwith the usual routine.Allthe procedures and activitiesshould be explained to the patient in asimplified language and tasks.For orientation to time, use calendars, clocks, and newspapers.For orientation in the home environment, use color-coded or graphic labels as cues.Use lighting to reduce confusion and restlessness at night.Reduce excess stimulation and outings to crowded places (overexposure to environmental stimuli can lead to agitation and disorientation).Some games can slow the progress of Alzheimer’s Disease such as Sudoku, Chess, Bingo, and crosswords. Consider using a day care program for patients with Alzheimer's disease.

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