vol 2, issue 1

i

Aims and Scope

El Mednifico Journal is an open access, quarterly, peer-reviewed journal from Pakistan that aims to

publish scientifically sound research across all fields of medicine. It is the first journal from Pakistan that

publishes researches as soon as they are ready, without waiting to be assigned to an issue. The journal

has certain unique characteristics:

EMJ is one of the first journals from Pakistan that publishes articles in provisional versions as

soon as they are ready, without waiting for an issue to come out. These articles are then

proofread, copyedited and arranged into four issues per volume and one volume per year

EMJ is one of the few journals where students and undergraduates form an integral part of the

editorial team

EMJ is one of the few journals that provides incentives to students and undergraduates

EMJ is published once every 3 months by Mednifico Publishers.

Editorial correspondence should be addressed to:

The Editor-in-Chief, El Mednifico Journal,

C2 Block R, North Nazimabad, Karachi, Sindh - 74700 - Pakistan.

Tel: (92-334-2090696); Email: [email protected]; Website: http://mednifico.com

Articles should be sent to:

Submissions EMJ, C2 Block R, North Nazimabad, Karachi, Sindh - 74700 - Pakistan.

Email: [email protected]

Want to partner with EMJ? Send your proposal to: [email protected]

We’re hiring! Send your CVs to: [email protected]

Volume 2, Issue 1 January - March, 2014

ii

Editorial Board

Senior Editor-in-Chief

Prof. Nazeer Khan

Executive Editors

Syed Salman Ahmed,

Sajid Ali

Editor-in-Chief

Asfandyar Sheikh

Managing Editor

Syed Arsalan Ali

Assistant Editor-in-Chief

Haris Sheikh

Assistant Managing Editor

Shanawer Khan

Dr. Mansoor Husain,

Dr. Muzaffar H Qazilbash,

Dr. Tasneem Z Naqvi,

Prof. Haruhiro Inoue,

Dr. Athanassios Kyrgidis,

Dr. Asim A Shah,

Dr. Kothandam Sivakumar,

Dr. Samina Abidi,

Dr. Rashid Mazhar,

Senior Editors

Dr. Gautam Sikka,

Dr. Mosaddiq Iqbal,

Prof. Javed Akram,

Prof. Abdul Bari Khan,

Prof. Ashraf Ganatra,

Dr. Raza Ur Rehman,

Dr. Waris Qidwai,

Dr. Muhammad Ishaq Ghori,

Dr. Akber Agha,

Dr. Adnan Mustafa Zubairi,

Dr. Saqib Ansari,

Dr. Mohsina Ibrahim,

Dr. Qamaruddin Nizami,

Dr. Samra Bashir,

Dr. Nabeel Manzar,

Muhammad Ashar Malik

Section Editors

Ali Sajjad,

Hafiz Muhammad Aslam,

Syed Askari Hasan,

Muhammad Uzair Rauf,

Syed Mumtaz Ali Naqvi,

Manish Khazane,

Smitha N Gowda,

Supriya Kumar,

Zeba Unnisa,

Suhasis Mondal

Statistics Editors

Mehwish Hussain,

Syed Ali Adnan

Editors

Dr. Hussain Muhammad

Abdullah,

Asfandyar Khan Niazi,

Muhammad Danish Saleem,

Smith Giri,

Iqra Ansari

Production Editors

Muhammad Hamid

Chaudhary,

Bushra Mufti,

Parisa Aijaz,

Adnan Salim

Assistant Editors

Gulrayz Ahmed,

Raza Mahmood Hussain,

Uzair Ahmed Siddiqui,

Maheen Anwer,

Anum Saleem,

Hira Hussain Khan,

Imran Jawaid,

Hina Azhar Usmani,

Shayan Ali,

Shoaib Bhatti,

Hira Burhan,

Quratulain Ghori,

Bushra Iqbal,

Maria Rahim

Layout Editor

Shahzad Anwar

v

Table of Contents

FrontPage i Editorial Board ii Call for Papers iii Health Poster iv Table of Contents v

Editorial

From freshman to sophomore Syed Salman Ahmed

1

Original Articles

Framingham Risk Score for the prediction of cardiovascular risk in Saudi population Yasmeen Hetari, Archana Iyer, Said S M Eldesouky, Nabil Alama, Saleh M Aldaqal, Taha Kumosani

2

Audit of prescribing patterns of doctors for the management of acute respiratory infections in children Muhammad Irfanullah Siddiqui, Akhtar Ali Baloch, Syed Ishtiaq Ahmed, Syed Imtiaz Ahmed Jafri

6

Comparison of oral health knowledge, attitudes, practices and oral hygiene status of Central Reserve Police Force officials in Srinagar, Kashmir Swapnil S Bumb, D J Bhasker, Chandan R Agali, Himanshu Punia, Vikas Singh, Safalya Kadtane

10

Review

Pharmacology, neurobiology and neurotoxicity of methamphetamine Zia Choudhry, Azadeh A Rikani, Adnan Maqsood Choudhry, Sadaf Tariq, Fozia Zakaria, Saifal Anwar, Muhammad Harris Laghari, Kamran Haider, Afia Ansar Shafiq, Nusrat Jahan Mobassarah

15

Opinions and Debates

Health issues: The leading cause of deaths worldwide Aqsa Sajjad

23

Essays

SNARE proteins and membrane fusion Zia Choudhry, Azadeh A Rikani, Adnan Maqsood Choudhry, Sadaf Tariq, Fozia Zakaria, Muhammad Waheed Asghar, Muhammad Khan Sarfraz, Numan Majeed, Huma Ikram, Nusrat Jahan Mobassarah

25

vi

Icosapent ethyl: A novel drug for hypertriglyceridemia Atta Abbas, Farrukh R Ahmed

28

Letters to Editor

Extensive endomyocardial calcification of unknown cause: a rare manifestation of left ventricular non-compaction? Ahmed Bashir, Richard Paul Steeds

30

Detection of multiple pseudoaneurysms of mitral-aortic intervalvular fibrosa by multislice computed tomography in a patient with aortic valve replacement Melike Rusen Metin, Hasan Aydın, Evrim Özmen, Ömer Faruk Ateş

32

Cerebroprotein hydrolysate in traumatic brain injury Sagar Karia, Priyanka Thukral Mahajan, Nilesh Shah, Sushma Sonavane, Avinash De Sousa

34

The association between type II diabetes mellitus and Parkinson’s disease: A case report Atta Abbas

36

Appendices

Instructions to Authors vii Sponsorship Information xi Best of Blogemia xiv

Ahmed SS 1

http://www.mednifico.com/index.php/elmedj/article/view/56

Open Access Editorial

From freshman to sophomore Syed Salman Ahmed1

Editorial December 17th, 2012 marks the day when a casual conversation with my associates about the persistent lack of biomedical research cul-ture and the disinterest shown by the civil authorities throughout South Asia encouraged us to lay the foundation of El Mednifico Jour-nal (EMJ) [1]. From the very beginning, EMJ was founded as a journal that would eventually provide biomedical and allied professionals and undergraduates from different institutes a healthy platform to utilize their potentials for research conduction and presentation, with special emphasis on recent advancements and discoveries made throughout the field of medicine. An attached blogging plat-form named Blogemia was also launched in order to inculcate a sense of research in biomedical students by promoting healthy writ-ing practices that would eventually benefit them in their professional life.

Throughout its first year, EMJ has emerged as a trendsetter. It has the honor of being one of the first Open Journal Systems (OJS) based medical journals from Pakistan that publishes articles in provisional ahead-of-print versions as soon as they are ready. These articles are then proofread, copyedited and arranged into four issues per vol-ume and one volume per year. OJS is a dedicated journal system that streamlines the editorial process, and provides tools for indexation and archiving. It is also continuously being developed, which made it a perfect candidate for EMJ to be based on.

The first call for papers was sent out in mid-December and the re-sponse that we received was overwhelming. We received as many as 12 submissions within the first month. The submissions were mostly from Pakistan and India, the latter being due to our partnership with The Medical Students Association of India. In the months thereafter, the breadth of the submissions in terms of countries of origin ex-panded. We now have submissions from more than 10 countries that include Pakistan, India, United Kingdom, Turkey, Saudi Arabia, United States, Iran, Nigeria, Nepal and Germany. All articles continue to be free and open access. No charges are requested for article submis-sion, processing or publishing and no fees are charged for readers to access full text content.

Right from the very beginning, emphasis has been laid on online submission and guidelines and instructions have been uploaded on the website. Although EMJ’s institutional manifesto does not limit the scope of submissions which traverses all fields and specialties in

1Dow University of Health Sciences, Pakistan Correspondence: Syed Salman Ahmed Email: [email protected]

medicine, no compromise is made on the quality of the content re-ceived. Hence, many articles are rejected either upon receipt, or after undergoing peer-review. Annual statistical reports from our submis-sions department show that out of the 47 submissions that were re-ceived during the year 2013, only 27 were accepted giving an ac-ceptance rate of 57%.

Our team believes in a fast and accurate editorial process. Hence, we have maintained high processing speeds for the year 2013 in order to ensure that scientifically sound work is presented to the audience as soon as it is ready, and to ensure that authors do not have to face undue delays in case their submission is rejected. Acknowledgement emails were sent to the respected author, on average, within 18 ± 2 hours. The average time taken for editorial screening was 4 ± 1 days, for in-house review 6 ± 1 days and for sending out for external peer review 2 ± 1 days. The average time taken for peer reviewers to send in reports was 34 ± 4 days. The average time taken for the first edi-torial decision was 3 ± 1 days. The authors took, on average, 16 ± 5 days for returning a revised version. The second editorial decision was made within 2 ± 1 days after receipt. Hence, the whole process from submission to acceptance takes 2 months on average.

In just 12 months, EMJ has had the privilege of getting indexed at DOAJ, Index Copernicus, Ulrichs Web, Open-J-gate, Genamics and Google Scholar. Further efforts are underway to get the journal in-dexed in other indexes such as Scopus and Medline. The annual print version is also under production. All of this has been made possible by the combined efforts of the editorial team that we have at EMJ. I would like to congratulate the Editors-in-Chief, Executive Editors, Ed-itors and Reviewers for their contribution to the cause. A special to-ken of appreciation goes to our partners (S.O.C.H, Justuju and MSA-India) whose support had a crucial role in the debutant year for EMJ. Lastly, I would like to thank the readers for appreciating and citing our content in their research works.

Competing interests: The author is an Executive Editor at El Mednifico Journal Received: 5 December 2013 Accepted: 7 December 2013 Published Online: 7 December 2013

References 1. Sheikh A, Ahmed SS, Ali S: El Mednifico Journal: Objectively galvanizing

research culture in students. El Mednifico Journal 2012, 1(1):1.

2 Framingham Risk Score for the prediction of cardiovascular risk…

Vol 2, No 1

Open Access Original Article

Framingham Risk Score for the prediction of cardiovascular risk in Saudi population Yasmeen Hetari1, Archana Iyer1, Said S M Eldesouky1, Nabil Alama1, Saleh M Aldaqal1, Taha Kumosani1

Introduction Over the past 150 years, there have been numerous efforts to explain the complex events associated with the development of atheroscle-rosis. Many previous studies confirmed that the cardiovascular dis-ease (CVD) development has a strong relationship with many risk factors; therefore the risk factors are important to prognosis and pre-diction of CVD development.

The Framingham Risk Score (FRS) is one of the most widely used risk assessment methods for prediction of coronary artery disease (CAD) risk [1]. FRS was derived from the Framingham Heart Study (FHS) cohort and was designed to predict 10-year risk of hard coronary events, including mortality due to coronary heart disease and non-fatal myocardial infarction (MI) by considering the presence or ab-sence of important risk factors [2].

Risk factors of CVD have been categorized in two major groups: modifiable and non-modifiable. Age, genetic family history, race, and gender for CVD have been indicated as non-modifiable risk factors of CVD among men and women. Major modifiable risk factors of CVD include high blood pressure, abnormal blood lipids (high total cho-lesterol, LDL-C and triglyceride levels, and low levels of HDL-C), to-bacco use, physical inactivity, obesity, unhealthy diets, and diabetes mellitus [3, 4].

Several studies have documented the association between obesity and cardiovascular disease. On the basis of the FRS, the risk of CHD is categorized as high (˃20%), intermediate (10%–20%), and low risk (˂10%) [5]. American Heart Association (AHA) guidelines (2002) for primary prevention of cardiovascular disease and stroke recommend that risk factor screening in adults should begin at age 20 and should be repeated at least every 5 years in the absence of risk factors and

1King Abdul Aziz University, Kingdom of Saudi Arabia. Correspondence: Archana Iyer Email: [email protected]

every 2 years if risk factors are present [6]. The score sheets (or points systems) that enable clinicians to determine the 10-year risk of CAD are separate for men and women. To use the score sheets, a clinician simply totals the points associated with the patient’s age, their cho-lesterol and smoking status, which in turn depend on age, high den-sity lipoprotein (HDL) and systolic blood pressure, either treated or untreated. A point total is computed by summing all the points for the risk factor profile. The 10-year coronary risk is then determined based on the point total as indicated in the table at the bottom of the score sheet (NCEP 2002) [7].

The present study has been conducted on two hundred and twelve volunteers, all of whom were Saudi nationals. The required parame-ters for the FHS were included and the correlation of risk of develop-ing cardiovascular heart disease and obesity has been analyzed.

Materials and Methods

Study Population This study was approved by the ethics committee of the King Abdul Aziz University Hospital, Jeddah, Saudi Arabia for sample collection. Written informed consent was obtained from all participants prior to the study. The participants completed an investigator-developed questionnaire on health history. Various demographic variables were assessed, including age in years, marital status, education level, med-ication, tobacco use, physical activity and history of gastric bypass. All were classified by yes/no based self-report.

Study Population The following inclusion and exclusion criteria were established to identify subjects for this investigation.

Abstract Background: Many previous studies confirm that cardiovascular disease (CVD) development has a strong relationship with many risk factors. The Framingham Risk Score (FRS) is one of the most widely used risk assessment methods for prediction of coronary artery disease risk (CAD). The objective of this study was to study the FRS with relation to obesity in a Saudi population and associate it with risk of cardiovascular diseases. In the present study, we compare Framingham risk factors among normal weight and obese for both genders. Methods: This study was conducted on 212 unrelated individuals. 106 were non-obese (BMI = 18.5-24.9 kg/m2) while 106 were obese (BMI ≥ 30 kg/m2). Major risk factors identified by the Framingham Heart Study, including sex, age, smoking, systolic blood pressure, total cholesterol and high-density lipoprotein (HDL) were incorporated into a scoring system that identifies subjects at high (˃20%), intermediate (10%–20%), and low (˂10%) risk for developing CAD over the next 10 years. Results: The results show that CVD risk factors were more prevalent among obese than normal weight subjects. In male subjects, the difference was statistically significant with regards to hypertension (p=0.000), triglycerides (p=0.033), HDL (p=0.048), fasting blood glucose (p=0.038). In female subjects, the difference was statistically significant for age (p=0.008), cholesterol (p=0.015), triglycerides (p=0.011), low density lipoprotein (p=0.017) and fasting blood glucose (p=0.000). Conclusion: These findings carry implications for clinical practice: Obese adults without clinical cardiovascular disease may already have a clustering of traditional cardiovascular risk factors. Institution of early and aggressive preventive measures in this population could delay or arrest progression to clinical cardiovascular disease. (El Med J 2:1; 2014) Keywords: Obesity, Framingham Heart Study, Cardiovascular disease

Hetari Y, Iyer A, Eldesouky SSM et al 3


Inclusion Criteria Self-identity as Saudis. 20-70 years of age. Body mass index (BMI) of 18.5 to 24.9 kg/m2 for the normal weight

category or a BMI ≥ 30 kg/m2 for the obese category.

Exclusion Criteria Pregnancy and/or currently breastfeeding. Chronic diseases (cancer, chronic renal disease, heart disease

and stroke). Use of hormone replacement therapy, steroids, and/or cholesterol

lowering medications such as statins.

Study Design This study was conducted on two hundred and twelve unrelated in-dividuals. One hundred and six were non obese (BMI = 18.5 to 24.9 kg/m2) while one hundred and six were obese (BMI ≥ 30 kg/m2). The subjects were recruited to the study from November, 2011 to June, 2012 at King Fahd Medical Research Center (KFMRC), Mada’en Al-Fahad Medical Center and medical administration for males at King Abdulaziz University. Morbidly obese individuals were recruited from the obesity clinic at the Department of General Surgery, King Abdul Aziz University Hospital. Figure 1 gives the study population chart.

Figure 1: Study Population

Anthropometric Assessment Height and weight measurements were obtained from each partici-pant by the same investigator. Subjects were required to remove shoes and heavy outer garments before the measurements of height and weight.

Body Mass Index (BMI) Body Mass Index (BMI) was calculated by the equation:

BMI = Weight in kg/(height in m)2 Using BMI the subjects were graded for obesity using Quetelet's in-dex (Garrow and Webster, 1985) and nomogram of WHO (1995).

Table 1: BMI Classification Subjects BMI

Normal 18.5-24.9

Obesity Grade I 30.0-34.9

Obesity Grade II 35.0-39.9

Obesity Grade III ≥ 40

Biochemical Analysis After 10-12 hours overnight fasting, five millilitres of blood was drawn from each participant by using standard venipuncture tech-nique in plain vacutainer tubes for serum separation. The serum was separated by centrifugation at 2000 rpm for 10 minutes in a Hettich centrifuge, USA. The serum was separated into eppendorf tubes and stored at -80°C for further analysis. Quantitative determination of to-tal cholesterol, HDL and LDL concentration in human serum was measured spectrophotometrically by a time-endpoint method [8].

Results The FRS was calculated from the National Cholesterol Education Pro-gram (NCEP) Adult Treatment Panel III (ATP III) algorithm, based on six coronary risk factors: gender, age, total cholesterol, HDL-choles-terol (HDL-c), systolic blood pressure (BP) and smoking habit. Blood pressure was categorized according to Joint National Committee (JNC VII) criteria. Cholesterol, triglycerides, HDL-c and LDL-c levels were categorized according to ATP III guidelines. Participants were classified in two groups: non-smokers (never smoked or ex-smokers) and smokers (current smokers). Finally, the corresponding point was assigned to each individual and the total score was used as the indi-vidual’s CHD risk level.

On the basis of the FRS, the risk of CHD is categorized as high (˃20%), intermediate (10%–20%), and low (˂10%) risk. Results of Framingham CVD risk scores are shown in table 2. Analysis of these scores revealed that about 96.4% of non-obese males had low risk while 1.8% had intermediate risk and 1.8% had high risk score. In obese males, 84.3% had low risk, 5.9% were categorized as interme-diate risk and 9.8% as high risk. In non-obese female subjects, 98.0% were scored as high risk, while 2.0% had intermediate risk and none had >20% risk. In obese female subjects, 90.9% were in the low risk category and 9.1% were categorized as high risk.

Table 2: Cardiovascular risk for all subjects based on Framingham risk score

Gender Framingham 10 year risk* Obese

Non-obese P-value

Males

LR (<10%) 54 (96.4%) 43 (84.3%)

0.121 IR (10%-20%) 1 (1.8%) 3 (5.9%)

HR (>20%) 1 (1.8%) 5 (9.8%)

Females

LR (<10%) 49 (98.0%) 50 (90.9%)

0.039 IR (10%-20%) 1 (2.0%) 0 (0.0%)

HR (>20%) 0 (0.0%) 5 (9.1%) *LR = Low Risk; IR = Intermediate Risk; HR = High Risk

In males subjects, the difference was statistically significant with re-gards to blood hypertension (P=0.000), triglycerides (P=0.033), HDL (P=0.048). In females subjects, the difference was statistically signif-icant with regards to age (P=0.008), cholesterol (P=0.015), triglycer-ides (P=0.011) and LDL (P=0.017). The distribution of cigarettes smoking as risk factor was 36.4% for males and 18.1% for females. 33.9% of non-obese males were smokers, while 39.2% of obese males were smokers. 14.0% of non-obese females were smokers and 21.8% of obese females were smokers.

Study Population (N=212)

Non-obese (N=106)

Male

(N=56)

Female

(N=50)

Obese (N=106)

Male

(N=51)

Female

(N=55)

4 Framingham Risk Score for the prediction of cardiovascular risk…

Vol 2, No 1

Discussion The Framingham Heart Study introduced the concept of risk factors for coronary heart disease (CHD) and has served as the standard for risk assessment over the years [6, 9]. Our results show that cardio-vascular disease risk factors were more prevalent among obese than normal weight subjects. These findings are similar to the results of the Multi-Ethnic Study of Atherosclerosis, which examined the rela-tion of obesity in older individuals 45 to 84 years old [10].

In our study, Saudi women had a high prevalence of cardiovascular disease risk factors. Our result is coincident with several studies [11, 12]. These studies have further reported that African Americans who are obese have a greater chance of having high blood pressure, dia-betes, and high blood levels of triglycerides and cholesterol than those who are not obese, and these conditions increase the risk of developing cardiovascular disease. The distribution of males and fe-males in our study was (50.5% and 49.5%). Similar results were ob-served in Qazvin population (50.2% and 49.8%), but not in a Jorda-nian study (78.3% and 21.7%) [13, 14].

Our results showed the prevalence of smoking among obese people is more than reported in US. The proportion of adults who smoke and are obese in the US is relatively low: the total number being 9 million (4.7%). Overall, 5.3% of men and 4.2% of women who smoke are obese [15]. Previous studies of Saudi smoking behavior have in-vestigated the prevalence of smoking among adults in Saudi Arabia. The prevalence of current smoking among adults in Saudi Arabia range from 11.6-52.3%. Only one study investigated the prevalence of current smoking among elderly people (50-89 years) and found that 25% of them were current smoker. The prevalence of current smoking in males ranges from 13-38%, while in females it ranges from 1-16% [16-18]. Other studies in the Kingdom and in other Arab countries have reported similar findings [19, 20]. This differs from Western societies, where female smoking is more common [21, 22]. Our result agreed with the result of another study, in which the au-thors reported that Arab women were less involved in active smok-ing, but suffered more from passive smoking [23].

Hypertension has been identified as the most common risk factor for coronary heart disease events [24]. Obesity and weight gain have been identified as the most important determinants of hypertension [25, 26]. The association between obesity and hypertension forms part of a broader relationship between body weight and blood pres-sure (BP). Our results in general revealed that most of Saudi popula-tion was classified as pre-hypertensive. A higher percentage of the obese male group compared with non-obese group was found to exhibit stage 1 hypertension. In female population, a higher percent-age of obese groups compared with non-obese group was found to exhibit pre-hypertension and stage 1 hypertension. Furthermore, it was found that obesity had the strongest association with pre-hy-pertension and hypertension. This finding is in line with the pub-lished data from Iran [27].

However, social and cultural differences, the subject’s characteristics, the age span as well as the methodology used, may account for the observed discrepancies among the previous studies. Nonetheless, although direct comparisons with other studies are not possible, it is rather self-evident that the prevalence of pre-hypertension is high in

both developed and developing countries, and in eastern and west-ern populations. It, therefore, needs further in-depth clarification.

Previous studies on the prevalence of hypertension in KSA have demonstrated persistently increasing figures [28]. Several reasons such as lifestyle change in KSA towards urbanization and adopting new dietary habits, are likely to result in hypertension and increasing prevalence of obesity.

Conclusion These findings carry implications for clinical practice: Obese adults without clinical cardiovascular disease may already have a clustering of traditional cardiovascular risk factors. Institution of early and ag-gressive preventive measures in this population could delay or arrest progression to clinical cardiovascular disease.

Competing interests: The authors declare that no competing interests exist. This study is a part of a doctoral thesis and the experiments were performed at the King Fahd Medical Research Centre, Jeddah, Kingdom of Saudi Arabia. Received: 25 November 2013 Accepted: 2 January 2014 Published Online: 2 January 2014

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Physiological reviews 2004, 84(4):1381-1478. 2. Lee GK, Lee LC, Liu CW, Lim SL, Shi LM, Ong HY, Lim YT, Yeo TC: Framingham

risk score inadequately predicts cardiac risk in young patients presenting with a first myocardial infarction. Annals of the Academy of Medicine, Singapore 2010, 39(3):163-167.

3. Appel SJ, Harrell JS, Deng S: Racial and socioeconomic differences in risk factors for cardiovascular disease among Southern rural women. Nursing research 2002, 51(3):140-147.

4. Grundy SM, Pasternak R, Greenland P, Smith S, Jr., Fuster V: Assessment of cardiovascular risk by use of multiple-risk-factor assessment equations: a statement for healthcare professionals from the American Heart Association and the American College of Cardiology. Circulation 1999, 100(13):1481-1492.

5. Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB: Prediction of coronary heart disease using risk factor categories. Circulation 1998, 97(18):1837-1847.

6. Pearson TA, Blair SN, Daniels SR, Eckel RH, Fair JM, Fortmann SP, Franklin BA, Goldstein LB, Greenland P, Grundy SM et al: AHA Guidelines for Primary Prevention of Cardiovascular Disease and Stroke: 2002 Update: Consensus Panel Guide to Comprehensive Risk Reduction for Adult Patients Without Coronary or Other Atherosclerotic Vascular Diseases. American Heart Association Science Advisory and Coordinating Committee. Circulation 2002, 106(3):388-391.

7. Sullivan LM, Massaro JM, D'Agostino RB, Sr.: Presentation of multivariate data for clinical use: The Framingham Study risk score functions. Statistics in medicine 2004, 23(10):1631-1660.

8. Roeschlau P, Bernt E, Gruber W: Enzymatic determination of total cholesterol in serum. Zeitschrift fur klinische Chemie und klinische Biochemie 1974, 12(5):226.

9. Anderson KM, Wilson PW, Odell PM, Kannel WB: An updated coronary risk profile. A statement for health professionals. Circulation 1991, 83(1):356-362.

10. Bild DE, Detrano R, Peterson D, Guerci A, Liu K, Shahar E, Ouyang P, Jackson S, Saad MF: Ethnic differences in coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation 2005, 111(10):1313-1320.

11. Diez-Roux AV, Northridge ME, Morabia A, Bassett MT, Shea S: Prevalence and social correlates of cardiovascular disease risk factors in Harlem. American journal of public health 1999, 89(3):302-307.

12. Flegal KM, Carroll MD, Ogden CL, Johnson CL: Prevalence and trends in obesity among US adults, 1999-2000. JAMA : the journal of the American Medical Association 2002, 288(14):1723-1727.

13. Fakhrzadeh H, Bandarian F, Adibi H, Samavat T, Malekafzali H, Hodjatzadeh E, Larijani B: Coronary heart disease and associated risk factors in Qazvin: a population-based study. Eastern Mediterranean health journal = La revue de

Hetari Y, Iyer A, Eldesouky SSM et al 5


sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit 2008, 14(1):33-41.

14. Hammoudeh AJ, Izraiq M, Al-Mousa E, Al-Tarawneh H, Elharassis A, Mahadeen Z, Badran N, Haddad J: Serum lipid profiles with and without CAD: Jordan Hyperlipidaemia and Related Targets Study (JoHARTS-1). Eastern Mediterranean health journal = La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit 2008, 14(1):24-32.

15. Healton CG, Vallone D, McCausland KL, Xiao H, Green MP: Smoking, obesity, and their co-occurrence in the United States: cross sectional analysis. BMJ (Clinical research ed) 2006, 333(7557):25-26.

16. Abdalla AM, Al-Kaabba AF, Saeed AA, Abdulrahman BM, Raat H: Gender differences in smoking behavior among adolescents in Saudi Arabia. Saudi medical journal 2007, 28(7):1102-1108.

17. Almas K, Al-Hawish A, Al-Khamis W: Oral hygiene practices, smoking habit, and self-perceived oral malodor among dental students. The journal of contemporary dental practice 2003, 4(4):77-90.

18. Hasim TJ: Smoking habits of students in College of Applied Medical Science, Saudi Arabia. Saudi medical journal 2000, 21(1):76-80.

19. Hamadeh RR: Smoking habits of medical students in Bahrain. J Smoking Related Dis 1994, 5:189-195.

20. Awidi AS: Patterns of cigarette smoking in Jordan: A study of greater Amman area. Annals of Saudi medicine 1991, 11(2):144-147.

21. Felimban F: The smoking practices and attitudes towards smoking of female university students in Riyadh. Saudi medical journal 1993, 14(3):220-224.

22. WHO: Guidelines for controlling and monitoring the tobacco epidemic,. Geneva; 1996.

23. Jabara R, Namouz S, Kark JD, Lotan C: Risk characteristics of Arab and Jewish women with coronary heart disease in Jerusalem. The Israel Medical Association journal : IMAJ 2007, 9(4):316-320.

24. Greenland P, Knoll MD, Stamler J, Neaton JD, Dyer AR, Garside DB, Wilson PW: Major risk factors as antecedents of fatal and nonfatal coronary heart disease events. JAMA : the journal of the American Medical Association 2003, 290(7):891-897.

25. Oliveria SA, Lapuerta P, McCarthy BD, L'Italien GJ, Berlowitz DR, Asch SM: Physician-related barriers to the effective management of uncontrolled hypertension. Archives of internal medicine 2002, 162(4):413-420.

26. Ahmed A, Mahmoud M: The prevalence of hypertension in Saudi Arabia. Saudi medical journal 1992, 13(6):548-551.

27. Rahmanian K, Shojaie M: The prevalence of pre-hypertension and its association to established cardiovascular risk factors in south of Iran. BMC research notes 2012, 5:386.

28. Al-Nozha MM, Ali MS, Osman AK: Arterial hypertension in Saudi Arabia. Annals of Saudi medicine 1997, 17(2):170-174.

6 Management of acute respiratory infections in children…

Vol 2, No 1


Audit of prescribing patterns of doctors for the management of acute respiratory infections in children Muhammad Irfanullah Siddiqui1, Akhtar Ali Baloch2, Syed Ishtiaq Ahmed3, Syed Imtiaz Ahmed Jafri4

Introduction Acute respiratory infections (ARI) are considered as one of the major public health problems and are the leading cause of morbidity and mortality in many developing countries. They have been estimated to cause 18% to 33% of all deaths of children under five years. Pneu-monia kills more children than any other illness, more than HIV, ma-laria and measles combined. Effective interventions to reduce pneu-monia deaths are available but reach too few children. More than a million lives could be saved if prevention and treatment interven-tions were implemented universally. Preventing children under five from developing pneumonia in the first place is key [1-4].

In Pakistan, 80% of morbidity and mortality is due to lower respira-tory infection [5, 6]. ARI are responsible for 33% of death among chil-dren and most of the cases are treated by general practitioners (GPs) [7, 8]. This large number of deaths is due to the reason that manage-ment of ARI is not appropriate and many deaths can be prevented by appropriate intervention [9]. World Health Organization (WHO) has developed a protocol for the management of ARI especially for developing countries like Pakistan [10]. However, it is rarely followed by GPs, resulting in large number of deaths among children [11]. This study was conducted to audit the prescriptions of GPs, to determine their practices regarding ARI management and compliance to WHO protocols, and to provide recommendations to improve their prac-tices in the area of identified needs [12].

Methods Study Setting Bulleda, situated in District Turbat (Balochistan), is small village cum town surrounded by date trees. It is about 75 km towards the north

1Umm Al-Qura University, Saudi Arabia 2Medical Officer, Turbat, Pakistan 3Hamdard University, Pakistan

of the city of Turbat. Turbat is the second largest city of Balochistan province. It is a subdivision and has a population of 45,000 with very few basic facilities. Most of the people are illiterate and have very little information regarding health issues.

Study Design This was a cross-sectional study conducted from October, 1 to Octo-ber, 31 for a period of one month.

Sampling Procedure The sampling technique used was two-stage random sampling, to select registered general practitioner during first phase and later, to select their prescriptions. Randomly selected general practitioners, practicing in Bulleda were visited and their prescriptions for the month were randomly selected (thereby forming the sample size) after obtaining consent. A total of five such practitioners were se-lected.

The sample size was estimated using 95% confidence interval and keeping 5% level of significance [13]. A total of 202 prescriptions were obtained and then compared with WHO protocol to observe whether they were consistent with the recommendations. Collected prescriptions were analyzed using the standard ARI case manage-ment guidelines of WHO [10]. All the GPs were assured of confiden-tiality and the data collected was kept confidential and entered into the computer to be analyzed in EPI Info software version 6, devel-oped by Center for Disease Control Atlanta, USA. The variables in-cluded were gender, weight, chief complaints, temperature, pulse rate, respiratory rate, provisional diagnosis and the type of antibiotic prescribed.

4Baqai University, Pakistan Correspondence: Muhammad Irfanullah Siddiqui Email: [email protected]

Abstract Background: Acute respiratory infections (ARI) account for 80% of all children reporting to outpatient departments (OPD). In most of the cases the cause of morbidity is a viral infection that does not require antibiotic treatment, but in spite of this, antibiotics are used much too frequently. The guidelines for the management of ARI have been developed by World Health Organization (WHO), but generally, the physicians do not follow the recommended guidelines. This study was conducted to audit the prescriptions of general practitioners, to determine their practices regarding ARI management and to provide recommendations to improve their practices in the area of identified needs. Methods: Practitioners working in District Bulleda (Turbat), Balochistan were surveyed and five of them were selected randomly using simple random sampling technique for this cross sectional study. They were informed about the objectives of the study and consent was obtained. Their prescriptions of cases of ARI management for one month were obtained. Results: The results of the study show that a total of 202 patients of ARI were seen by the 5 selected physicians of the district. It was seen that in 60% cases the chief complaints were recorded. Temperature was recorded in 48% case. Respiratory rate was recorded in 33% cases. The diagnosis was noted down in 44% cases. In 97% cases, antibiotics were prescribed and in 37.5% cases the dose was not according to recommendation. Conclusion: It is concluded that most physicians in Bulleda are not following the WHO recommended protocol of ARI management. Refresher courses and training programs for physicians are recommended. Use of electronic media may be helpful in increasing awareness both in the health care provider and health care recipient. (El Med J 2:1; 2014) Keywords: Acute respiratory infections, WHO Guidelines, Audit

Siddiqui MI, Baloch AA, Ahmed SI et al 7


Results A total of 202 prescriptions were collected from the 5 GPs during one month of the survey. The number of ARI prescriptions ranged from 24 to 56 with a mean of 40.4 per physician (Table 1). A total of 57 (28.2%) children were under 1 year and 168 (83.2%) were less than 5 years of age. Only 8 children were over 10 years of age. 112 (55.4%) patients were males.

Table 1: Distribution of the number of ARI cases seen by each physician Physician Number Frequency Percentage

D1 56 27.7 D2 49 24.2 D3 24 11.9 D4 48 23.8 D5 25 12.4

Total 202 100.0

Seventy (34.7%) patients were weighed during their visit. Only 121 (59.9%) prescriptions had an entry of the chief complaints. 84 (69.4%) of the complaints were of fever and cough combined, fol-lowed by 21 (17.4%) of only fever (Figure 1). Temperature was rec-orded for only 96 (47.5%) children and 10 (10.4%) of them were afe-brile. The pulse was recorded only in 25 (12.4%) cases and ranged from 78 to 120. The respiratory rate was recorded only for 67 (33.2%) patients and in 43 (64.2%) cases it was above 40 per minute.

Figure 1: Distribution of the chief complaints of the children coming to OPD

The diagnosis was noted down in 90 (44.6%) patients (Table 2). In 5 (5.6%) cases the diagnosis was severe pneumonia (Figure 2). 196 (97.0%) patients were prescribed antibiotics. In 177 (90.3%) cases, only one antibiotic was prescribed and in 18 (9.2%) cases, 2 antibi-otics were prescribed. It was seen that different brands of amoxicillin were prescribed most frequently (21.4%), followed by first genera-tion cephalosporins (19.9%). Co-trimaxazole (14.3%) was the third most prescribed drug. Ceftriaxone was prescribed in 12 (6.1%) cases (Figure 3). Combination of antibiotics were used in 19 (9.7%) cases.

Among the combination drugs, Gentamicin was the first choice of the physicians in 7 (36.8%) cases.

Table 2: Distribution of the recording of various variables required to help diagnosis Features Recorded Yes No Weight 70 132 Chief Complaints 121 81 Temperature 96 106 Pulse 25 177 Respiratory Rate 67 135 Provisional Diagnosis 90 112

Figure 2: Distribution of the diagnosis of the children coming to OPD

Antipyretic drugs were used in 163 (80.7%) cases and in 154 (94.5%) cases, only one antipyretic was prescribed. In 86 (52.8%) cases, the drugs of choice were different brands of Paracetamol. Combination of antipyretics was used in 9 (5.5%) cases. 58 (28.7%) cases were pre-scribed cough syrup and among the prescriptions, Sancos (36.2%) and Benatus (32.8%) were the most prescribed cough syrups.

It was observed that in 74 (37.8%) cases, the dose of antibiotic pre-scribed was not according to the recommendation. It was observed that only 3 out of the 5 doctors recorded weights of the children at least once during the month. One physician did not record chief complaints at all, whereas another one recorded chief complaints of only three patients. Only 3 physicians recorded respiratory rate. Each doctor on the average prescribed correct dosage according to the recommendation of WHO in 63% of cases (p=0.2934).

Discussion The present study was conducted to audit the prescribing practices of GPs regarding management of ARI, and then to make recommen-dations to improve the practices so that unnecessary deaths among the children, which are as high as 80,000 deaths annually, can be avoided [14]. Previously, a number of studies have been conducted with the aim of determining the knowledge, attitude and practices of mothers regarding management of ARI in children [15-18]. How-ever, data regarding the practices of healthcare providers via pre-scription auditing is scarce [19].

0

20

40

60

80

100

Fre

qu

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Chief Complaints

Distribution of the chief complaints of the children

6%

21%

73%

Distribution of the diagnosis of the children

Severe Pneumonia

Pneumonia

Common Cold /

Cough

8 Management of acute respiratory infections in children…

Vol 2, No 1

Figure 1: Distribution of the chief complaints of the children coming to OPD

Our results show that 28.5% children were under one year and 83% were under five years. A study conducted by Sarfaraz observed the occurrence of ARI as 91% among under-five children [20]. The pre-senting complaint was fever and cough in 69.4% of the prescriptions and fever alone in 17.4%. A study conducted at Multan found the chief complaints of cough and fever in 95% and 83% respectively [21]. Diagnosis was noted down in only 44.6% of cases and in 94% cases it was lower respiratory tract infection (LRTI). In the study con-ducted by Sarfaraz, LRTI constituted 28% of the total cases [20].

In our study 97% of the patients were prescribed at least one antibi-otic while the study conducted by Imran found antibiotic prescrip-tion rate as 83%. The study conducted by Tambe et al found that a substantial number of episodes (27.3%) did not receive any treat-ment [16]. The drug of choice was amoxicillin in 21% of the cases, followed by first generation cephalosporins (20%). Cotrimoxizole was the third most prescribed drug. According to WHO recommen-dations co-trimaxazole and ampicillin should be given as the first choice drugs [10]. The study conducted by Tanveer found prescrip-tion rate of antibiotics as high as 73%. None of the physician in our study prescribed doses according to recommendations.

Conclusion The results of the study indicate that the practices of physicians working in Bulleda show great deviation from the WHO recom-mended protocol for ARI management. This is resulting in increased morbidity and mortality among the children of this underdeveloped area of Pakistan. Comparative results show that antibiotic prescrip-tions are more frequent among GPs of Bulleda, compared to other parts of Pakistan. The diagnosis is not made in most of the cases, and if made, is not on justified grounds.

Recommendations It is recommended that this study should be taken as pilot study and a multicenter study should be conducted in other parts of Pakistan. If the results are similar, a team of trainers should be prepared who

should visit different geographical areas and conduct training pro-grams in collaboration with local authorities and NGOs. Rational use of antibiotics should be emphasized in the training programs. Re-fresher courses should be conducted by the district health officer for already trained health care providers. Media should be involved ef-fectively and management programs of ARI should be broadcasted on TV and radio to increase awareness, not only in the community, but also among health care providers.

Competing interests: The authors declare that no competing interests exist. Received: 29 November 2013 Accepted: 4 January 2014 Published Online: 4 January 2014

References 1. UNICEF | The State of World Children 2013

[http://www.unicef.org/sowc2013/] 2. Yousuf TK, Khaliq BA: Epidemiology of acute respiratory infections among

children under 5 years old attending Tikrit General Teaching Hospital. 2006;14(3). Middle East Journal of Family Medicine 2006, 4(3):4-23.

3. Pneumonia: the forgotten killer of children [http://www.unicef.org/sowc08/docs/sowc08_panel_1_5.pdf]

4. Bryce J, Boschi-Pinto C, Shibuya K, Black RE: WHO estimates of the causes of death in children. Lancet 2005, 365(9465):1147-1152.

5. Pio A, Leowski J, ten Dam HG: The magnitude of the problems of acute respiratory infection in ARI in childhood. Proceeding of an international workshop, Sydney, 1984.

6. Mughal MJ: Health seeking behavior of mother belonging to different Ethic groups regarding home management / Remedies of acute respiratory infections. Dissertation submitted for MPH requirement. Baqai Medical University Karachi (1996).

7. Grant JP: The state of world’s children. New York, Oxford University Press, 1993. 8. Ilyas M: Community Medicine. 7th ed., Karachi, Time Publishers, 2008:553. 9. Myat KKS, Kyi S, Lwin TT: Indoor Air Pollution: Impact of Intervention on Acute

Respiratory Infection (ARI) in Under-five Children. Regional Health Forum 2005, 9(1):30.

10. WHO. Acute Respiratory infection in children, case management in small hospital in developing countries. Federal ARI cell 1993.

11. Lawn JE, Wilczynska-Ketende K, Cousens SN: Estimating the causes of 4 million neonatal deaths in the year 2000. International journal of epidemiology 2006, 35(3):706-718.

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25

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Antibiotics

Distribution of the chief complaints of the children

Siddiqui MI, Baloch AA, Ahmed SI et al 9


12. Schuetz P, Muller B, Christ-Crain M, Stolz D, Tamm M, Bouadma L, Luyt CE, Wolff M, Chastre J, Tubach F et al: Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections. Evidence-based child health : a Cochrane review journal 2013, 8(4):1297-1371.

13. Huley SB: Designing clinical research. William and Wilkins, Baltimore; 1998:220. 14. David RM, Haq IU, Qureshi AF: Childhood ARI in Pakistan. J Pak Med Assoc

1993, 43:14-20 15. Tambe MP, Shivaram C, Chandrashekhar Y: Acute respiratory infection in

children: a survey in the rural community. Indian journal of medical sciences 1999, 53(6):249-253.

16. Khan AJ, Khan JA, Akbar M, Addiss DG: Acute respiratory infections in children: a case management intervention in Abbottabad District, Pakistan. Bull World Health Organ 1990, 68(5):577-585.

17. Oyejide CO, Oke EA: An ethnographic study of acute respiratory infections in four local government areas of Nigeria. African journal of medicine and medical sciences 1995, 24(1):85-91.

18. Formento Tirado JA, Prieto Esteban I, Celemin Colomina I, Alvarez Rodriguez F, Crespo Llorden A, Arenas Abad A: [Analysis of prescriptions of antibiotics for acute respiratory infections at a health center]. Atencion primaria / Sociedad Espanola de Medicina de Familia y Comunitaria 1995, 16(5):281-284.

19. Sarfaraz T: Acute respiratory infection in children. Pak Armed Forces Med J 1996, 46(2):28-32.

20. Iqbal I, Pervaiz S, Baig S: Management of the children with Acute Respiratory Infection (ARI) by General Practitioners in Multan. An Observational study. JPMA The Journal of the Pakistan Medical Association 1997, 47(1):24-28.

10 Oral health of Central Reserve Police Force officials…

Vol 2, No 1


Comparison of oral health knowledge, attitudes, practices and oral hygiene status of Central Reserve Police Force officials in Srinagar, Kashmir Swapnil S Bumb1, D J Bhaskar1, Chandan R Agali1, Himashu Punia1, Vikas Singh1, Safalya Kadtane1

Introduction Health is a theme in most cultures and is fundamental human right without distinction of race, religion and political belief, economic and social condition [1]. The work environment constitutes an im-portant part of man’s total environment, so health to a large extent is affected by working conditions. Although several types of environ-ments exist, it is the physical environment that renders an important effect on health [2]. Oral health is an integral part of general health and is one of the determinants of quality of life. Oral health and gen-eral health are determined by various factors such as lifestyle, dietary habits, socioeconomic conditions, occupational environment etc [3]. Oral health is the standard of health of oral and related tissues that enables an individual to eat, speak and socialize without active dis-ease, discomfort or embarrassment and contributes to general well-being. It is concerned with maintaining the health of the craniofacial complex, the teeth and gums as well as the tissue of face and head that surrounds the mouth. Loss of teeth and deterioration of oral tissue substantially reduces the quality of life [1].

As military defends the country from external threats, the role of po-lice is for the maintenance of internal law and order [4]. Police per-sonnel are law enforces with busy work schedule. The nature of the job is such that they are subjected to physical, mental and emotional stress. The irregular shifts in their work schedule leads to neglecting of their regular diet and indulging in regular, often detrimental hab-its. The work shifts also deprive them of their routine sleeping pat-tern and social activities [5].

The target population on which we conducted this study were police of Central Reserve Police Force (CRPF), Srinagar, Kashmir. CRPF is the largest of India's central armed police forces. It functions under the

1Teerthanker Mahaveer Dental College and Research Centre, India Correspondence: Swapnil S Bumb Email: [email protected]

aegis of Ministry of Home Affairs of the Government of India. The CRPF's primary role lies in assisting the State/Union territories in po-lice operations to maintain law and order and contain insurgency. It came into existence as the Crown Representative's Police on 27 July 1939. After Indian Independence, it became the CRPF on enactment of the CRPF Act on 28 December 1949 [6].

The rigors of physical, mental and social discipline insisted upon the military personnel is also applicable on the police. One of the aims of the military training given to soldiers is to achieve the required physical and mental fitness for the mission to be carried out. This requires sufficient general and oral health for training and taking part in exercises, maneuvers and deployments [7]. For years, the police profession has been ranked among the top five of most stressful oc-cupations. The constant risk of uncertainty and tension which are inherent in law enforcement and the vast amounts of human suffer-ing and violence can lead susceptible individuals to stress, anxiety, depression and alcoholism. Many studies have shown relationship of stress factors to periodontal diseases [8]. All the above factors might have an effect on general as well as oral health. It is, therefore, the responsibility of society to safeguard the health of their defenders.

Literature regarding oral health status of these officials is not availa-ble. A clear picture of oral diseases will help us in organizing preven-tive and curative programs for containment of oral disease [9]. This information is very important for establishing priority and determin-ing the type and quantity of prevention and treatment services re-quired, as well as the type of personnel needed to provide the same. This study was, therefore, conducted to determine the oral health knowledge, attitudes, practices and oral hygiene status of CRPF offi-cials in Srinagar, Kashmir.

Abstract Background: Central Reserve Police Force (CRPF) police officials are at constant risk of uncertainty and tension, leading to stress, anxiety, depression and alcoholism. All the above factors may have an effect on oral health. Literature regarding the oral health situation of CRPF officials is scarce. This study was, therefore, conducted to determine the oral health knowledge, attitudes, practices and oral hygiene status of CRPF officials. Methods: A cross sectional questionnaire survey was conducted among 321 CRPF officials who voluntarily participated. A questionnaire consisting of 21 questions was used to determine the knowledge, attitudes and practices. Clinical examination was done to assess oral hygiene status. Results: Out of 321 officials, only 57.6% were aware of the fact that tooth brushing helps in preventing caries and gum diseases. Only 26.5% were aware of the role of fluoridated toothpaste in the prevention of caries. 80.4% were of the view that regular visit to a dentist is necessary. 84.4% used toothpaste with toothbrush for cleaning of teeth, 5.0% used toothpowder with fingers and 10.6% used toothpowder with brush. 27.7% had never visited a dentist in their lives. Conclusion: Deficiencies were found in the CRPF officials’ knowledge about gum diseases, use of fluoridated toothpaste and oral hygiene aids. Among the officials interviewed, 82% had poor and 18% had fair oral hygiene status. None of them had good oral hygiene status. Most of CRPF officials did not have knowledge about the causes and prevention of dental diseases. (El Med J 2:1; 2014) Keywords: Central Reserve Police Force, Oral Hygiene, Caries, Oral Health, India

Bumb SS, Bhaskar DJ, Agali CR et al 11


Materials and Methods The present study was conducted on 321 CRPF officials who volun-tarily participated. The subjects were in the age group of 20-60 years. Ethical clearance was obtained from Institutional Review Board of Teerthanker Mahaveer University. Permission to conduct the study was obtained from commanding officer as well as medical officer of CRPF Srinagar unit. Convenience sampling was used to collect the sample based on subjects present during the conduction of study. A cross-sectional questionnaire-based survey was conducted. The questionnaire consisted of 21 questions. Clinical examination was done to assess the oral hygiene status (via Simplified Oral Hygiene Index).

Sufficient number of instruments were taken to avoid any interrup-tion during examinations. Following instruments were used to con-duct clinical examination: plane mouth mirror, explorer, tweezers, kidney trays, chip blowers, cotton holders, disposable mouth masks, disposable gloves, sterilized cotton and gauze pieces, towels and soaps. A single trained examiner who was expert in the department conducted all the examinations. A well-trained assistant was taken for recording the data. A schedule was prepared for data collection. The questionnaires were distributed and were required to be com-pleted within half an hour.

Knowledge, attitude and practice scores were calculated separately. The significance value was set at p<0.05. Statistical analysis was per-formed using the Statistical Package for Social Sciences software ver-sion 18 and MS Excel. Mean, Frequency and percentage were calcu-lated.

Inclusion Criteria Subjects who were present on the day of examination and were willing to give Informed consent.

Exclusion Criteria Subjects who did not give informed consent.

Results Oral health knowledge and opinions (Table 1) Majority of the officials (57.6%) were aware of the fact that tooth brushing helps in preventing caries and gum diseases. Only 26.5% were aware about the role of fluorides and fluoridated tooth paste in prevention of dental caries. 54.8% were aware that tobacco con-sumption leads to oral cancer.

Table 1: Oral health knowledge and opinions* Questions Options N (%)

Sets of dentitions One 80 (24.9%) Two 210 (65.4%) Three 12 (3.7%) Four 10 (3.1%) Don’t Know 9 (2.8%)

No of milk teeth 10 7 (2.2%) 16 49 (15.3%) 20 161 (50.2%) 32 60 (18.7%) Don’t Know 44 (13.7%)

No of permanent teeth

16 9 (2.8%) 20 3 (0.9%) 24 34 (10.6%) 32 240 (74.8%) Don’t Know 35 (10.9%)

Purpose of tooth brushing

Clean bright teeth 88 (27.4%) Reducing the cost of dental care

30 (9.4%)

Prevention of tooth decay and gum dis-ease

185 (57.6%)

Prevention of oral can-cers

10 (3.1%)

Don’t know 8 (2.5%) Interval for change of tooth brush

1-3 months 199 (62.0%) 4-6 months 83 (25.9%) 7-12 months 29 (9.0%) More than 1 year 3 (0.9%) Don’t know 7 (2.2%)

Plaque means Soft deposit teeth 106 (33.0%) Hard deposit on teeth 10 (3.1%) Discoloration of teeth 69 (21.5%) White patches on teeth

26 (8.1%)

Don’t know 110 (34.3%) Dental plaque leads to

Staining of teeth Oral ulcers

72 (22.4%)

Oral ulcers 34 (10.6%) Tooth decay and gum disease

78 (24.3%)

White patches on teeth

31 (9.7%)

Don’t know 106 (33.0%) Gum bleeding means

Healthy gum 69 (21.5%) Tooth infection 44 (13.7%) Calcium deficiency in body

59 (18.4%)

Gum disease (inflammation)

136 (42.4%)

Don’t know 13 (4.1%) Reasons for gum bleeding

Calcium deficiency 53 (16.5%) Excess sweet Eating

33 (10.3%)

Gum disease due to improper brushing

195 (60.8%)

Tooth infection 31 (9.7%) Don’t know 9 (2.8%)

Reason of tooth decay

Tobacco chewing 122 (38.0%) Worms 28 (8.7%) Improper brushing 125 (38.9%)

Vit C deficiency 28 (8.7%) Don’t know 18 (5.6%)

Fizzy soft drinks affect the teeth adversely

Yes 186 (57.9%) No 65 (20.2%) Don’t know 70 (20.9%)


Vol 2, No 1

Table 1 (Continued) Questions Options N (%)

Methods to prevent bleeding from gums

Regular tooth brushing and flossing

188 (58.6%)

Calcium supplements 41 (12.8%) Reduction in sweet consumption

62 (19.3%)

Eat soft food 23 (7.2%) Don’t know 7 (2.2%)

Effect of sweet retention on dentition

Mobility of teeth 75 (23.4%) Yellowish staining of teeth

45 (13.0%)

Leads to tooth decay 153 (47.7%) Leads to bleeding of gums

30 (9.4%)

Don’t know 18 (5.6%) Methods to prevent tooth decay

Avoid tobacco chewing

107 (33.3%)

Vit C supplements 18 (5.6%) Regular brushing with fluoridated toothpaste

166 (51.7%)

Calcium supplements 19 (5.9%) Don’t know 11 (3.4%)

Effect of fluorides on dentition

Gives clean bright teeth

59 (18.4%)

Prevents tooth decay 73 (22.7%) Prevents mobility of teeth

85 (26.5%)

Prevents gum disease 57 (17.8%) Don’t know 47 (14.6%)

Reason for development of oral cancer

Improper brushing 96 (29.9%) Tobacco chewing or smoking

176 (54.8%)

Vit C deficiency 36 (11.2%) Excess sweet eating 7 (2.2%) Don’t know 6 (1.9%)

Reasons of tooth loss in old age

Gums disease 197 (61.4%) Tooth decay 42 (13.1%) Old age 71 (22.1%) Reduced dietary intake 8 (2.5%) Don’t know 3 (0.9%)

Decayed teeth can affect the appearance of the person

Yes 226 (70.4%) No 50 (15.6%) Don’t know 45 (14.0%)

Health of mouth and dentition impact the health of body

Yes 300 (93.5%) No 10 (3.1%) Don’t know 11 (3.4%)

Is it possible to move irregularly placed teeth in correct position?

Yes 274 (85.4%) No 13 (4.1%) Don’t know 34 (10.6%)

Loss of teeth can interfere with speech

Yes 272 (84.7%) No 14 (4.4%) Don’t know 35 (10.9%)

*Options marked in bold are correct answers

Oral health attitudes (Table 2) 80.4% of officials were of the view that regular visits to the dentist are necessary. 54.8% opined that immediate replacement of missing natural teeth is necessary. 90.3% agreed that gutkha chewing and smoking is a bad habit.

Table 2: Oral health attitudes Questions Options N (%)

Regular visit to dentist is necessary

Yes 258 (80.4%) No 30 (9.3%) Don’t know 33 (10.3%)

Immediate replacement of missing natural teeth by artificial teeth is necessary

Yes 176 (54.8%) No 21 (6.5%) Don’t know 124 (38.6%)

Guthka chewing / smoking is a bad habit

Yes 290 (90.3%) No 26 (8.1%) Don’t know 5 (1.6%)

Dentists care only about treatment & not prevention

Yes 251 (78.2%) No 43 (13.4%) Don’t know 27 (8.4%)

Treatment of toothache is as important as any other organ in body

Yes 227 (70.7%) No 28 (8.7%) Don’t know 66 (20.6%)

Oral health behavior (Table 3) 52.3% of the officials reported brushing once a day, whereas 44.9% brushed twice a day. 84.4% used toothpaste with toothbrush for cleaning of teeth, 5.0% used toothpowder with fingers and 10.6% used toothpowder with brush. 62.6% reported changing their brush due to fraying of bristles.

Table 3: Oral health behavior Questions Options N (%)

How many times in day do you brush your teeth?

Once 168 (52.3%) Twice 144 (44.9%) Thrice or more 9 (2.8%)

When do you brush your teeth?

In morning 167 (52.0%) In morning & before going to bed

135 (42.1%)

In morning, before going to bed & after sweet eating/meals

19 (5.9%)

Use fluoridated toothpaste

Yes 125 (38.9%) No 38 (11.8%) Don’t know 158 (49.2%)

Bumb SS, Bhaskar DJ, Agali CR et al 13


Table 3 (Continued) Questions Options N (%)

Material you use for brushing your teeth

Toothpaste with brush 271 (84.4%) Toothpowder or others with finger

16 (5.0%)

Toothpowder with brush

34 (10.6%)

Reason to change the toothbrush

Fraying of bristles 201 (62.6%) New toothbrush de-sign in market

61 (19.0%)

After breakage 59 (18.4%) Do you clean your tongue?

Yes 164 (51.1%) No 157 (48.9%)

Do you use any oral hygiene aid?

Dental floss 62 (19.3%) Mouthwash 77 (24.0%) No 182 (56.7%)

Have you ever visited a dentist, what was the driving factor?

Routine checkup 76 (23.7%) Severe dental pain 62 (19.3%) Treatment of common dental diseases

94 (29.3%)

Never visited dentist 89 (27.7%) How many times in a day you eat sweets?

1-3 times 244 (76.0%) 4-6 times 36 (11.2%) Not at all 41 (12.8%)

Do you take care of your teeth as much as other part of body?

Yes 229 (71.3%) No 92 (28.7%)

Any habits like pan chewing, guthka chewing, cigarette smoking

Yes 222 (69.2%) No 99 (30.1%)

Descriptive statistics Table 4 provides an overview of the descriptive statistics for the offi-cials examined.

Table 4: Descriptive Statistics Age Debris

Index Calculus

Index OHI-S

Minimum 20 0.83 0.66 1.49 Maximum 59 3.00 3.00 5.83 Mean 36.2741 1.9910 1.8388 3.8298 Standard Deviation

9.3307 0.4734 0.5122 0.8943

Standard Error of Mean

0.5208 0.0264 0.0286 0.0499

Clinical examination Table 5 provides an overview of the clinical examination based on the Simplified Oral Hygiene Index.

Discussion The present study was aimed in gathering epidemiology data re-garding oral health knowledge, attitude and behavior among CRPF

Table 5: Oral hygiene index - Simplified group Frequency Percentage

Poor 264 82.2% Fair 57 17.8% Total 321 100%

officials of Srinagar, Kashmir and to measure oral hygiene status. CRPF official’s knowledge about gum diseases and use of fluoridated dentifrices was found to be low, dental visits were frequent and con-sumption of sweets was found to be very high. Officials must be pro-vided with oral health education at such settings along with physical and general health education.

In the present study, majority of officials were not aware of whether they used fluoride containing dentrifices, similar to findings of Ab-hinav Singh who conducted a study to assess the oral health knowledge, attitude & practice among NCC cadets in South India [10]. Majority of officials did not know that dental floss helps in pre-venting dental caries and gum disease. But most of the officials were aware of the fact that tooth brushing prevents caries. Lack of knowledge regarding dental floss and gum diseases can be at-tributed to low level of dental education of CRPF officials. About 58% of the officials considered soft drinks to be harmful to teeth.

Peterson et al, in study conducted among 12 year old urban and rural school children in southern Thailand, reported that consumption of sweets is an important predicator of high caries experience [11]. In the present study, 76% of officials reported consumption of sweets 1-3 times a day, 12% consumed 4-6 times a day and only 13% did not consume sweets at all. Similar findings were reported in Singh among NCC cadets in South India in which 49% of cadets reported consumption of sweets very often and 14.4% reported its consump-tion all the time [10].

Our findings indicate that most of the officials lacked knowledge about the causes and prevention of dental disease. Findings similar to the present study regarding oral health knowledge and attitudes were reported by Al-Hussaini et al, Christensen et al and El-Qaderi and Taani [12-14]. The results of the present study showed that offi-cials appeared to be interested in receiving more information on a substantial number of different dental issues. A significant number of officials wanted further information, so it can be safely concluded that officials had a positive attitude towards oral health.

Conclusion Therefore, the study suggests and recommends that proper oral health education is required to improve attitude and behaviors of CRPF officials. Health authorities should implement oral disease pre-vention and health programs for CRPF officials. Prevention of oral disease is considered to be the most effective, acceptable and effi-cient method implicated to pave the way to oral health. Ideally, adults should be educated to prevent the initiation and progression of the spectrum of dental disease they are likely to encounter throughout life.



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References 1. Bhardwaj V, Sharma K, Jhingta P, Luthra R, Sharma D: Assessment of oral health

status and treatment needs of police personnel in Shimla city, Himachal Pradesh: A cross-sectional study. International Journal of Health & Allied Sciences 2012, 1(1):20.

2. Satapathy D, Behera T, Tripathy R: Health status of traffic police personnel in Brahmapur city. Indian journal of community medicine: official publication of Indian Association of Preventive & Social Medicine 2009, 34(1):71.

3. Sohi R, Bansal V, Veeresha K, Gambhir R: Assessment Of Oral Health Status And Treatment Needs Of Police Personnel Of Haryana, India. The Internet Journal of Epidemiology 2010, 9(1).

4. Badraiah V: Karnataka Police Manual. Bangalore: Lions Law Book. 5. Silbert MH: Job stress and burnout of new police officers. Police Chief 1982,

49(6):46-106. 6. Central Reserve Police Force

[http://en.wikipedia.org/wiki/Central_Reserve_Police_Force]{First Reference} 7. Bhardwaj V, Sharma K, Jhingta P, Luthra R, Sharma D: Assessment of oral health

status and treatment needs of police personnel in Shimla city, Himachal Pradesh: A cross-sectional study. International Journal of Health & Allied Sciences 2012, 1(1):20.

8. Okamoto A, Ohnishi T, Bandow K, Kakimoto K, Chiba N, Maeda A, Fukunaga T, Miyawaki S, Matsuguchi T: Reduction of orthodontic tooth movement by

experimentally induced periodontal inflammation in mice. European journal of oral sciences 2009, 117(3):238-247.

9. Naveen N, Reddy C: Oral health status and treatment needs of police personnel in Mysore city, Karnataka. SRM University Journal of Dental Sciences 2010, 1(2):156-160.

10. Singh A: Oral health knowledge, attitude and practice among NCC Navy Cadets and their correlation with oral hygiene in south India. Oral health & preventive dentistry 2009, 7(4):363.

11. Petersen PE, Hoerup N, Poomviset N, Prommajan J, Watanapa A: Oral health status and oral health behaviour of urban and rural schoolchildren in Southern Thailand. International Dental Journal 2001, 51(2):95-102.

12. Al-Hussaini R, Al-Kandari M, Hamadi T, Al-Mutawa A, Honkala S, Memon A: Dental health knowledge, attitudes and behaviour among students at the Kuwait University Health Sciences Centre. Medical Principles and Practice 2003, 12(4):260-265.

13. Christensen LB, Petersen PE, Bhambal A: Oral health and oral health behaviour among 11-13-year-olds in Bhopal, India. Community dental health 2003, 20(3):153-158.

14. El-Qaderi SS, Taani DQ: Oral health knowledge and dental health practices among schoolchildren in Jerash district/Jordan. International journal of dental hygiene 2004, 2(2):78-85.

Choudhry Z, Rikani AA, Choudhry AM et al 15


Open Access Review

Pharmacology, neurobiology and neurotoxicity of methamphetamine Zia Choudhry1,2,3*, Azadeh A Rikani1,2*, Adnan Maqsood Choudhry3, Sadaf Tariq4, Fozia Zakaria5,6, Saifal Anwar7, Muhammad Harris Laghari7, Kamran Haider8, Afia Ansar Shafiq9, Nusrat Jahan Mobassarah10

Introduction Methamphetamine (MA) is a synthetic, powerfully addictive central nervous system (CNS) stimulant drug, derived from amphetamine (AMP) having a similar chemical structure [1]. It is used for both me-dicinal and illegal recreational proposes. MA causes an increase in activity, decrease in appetite, and a strong feeling of euphoria, also referred to as “high” or “rush” [1-3].

MA is a schedule II stimulant, i.e. a drug with high potential of abuse available only through a prescription that cannot be refilled. It has been used, for the treatment of: (1) narcolepsy, (2) attention deficit disorder and (3) obesity (short-term use), but this use is limited [3]. Medicinal MA or “Desoxyn” is available in pure 5-10mg tablet form. Illegal MA or “speed” is available on the street and is normally pre-sented as a white, odorless, bitter-tasting crystalline powder that eas-ily dissolves in water or alcohol. It can be in pure or adulterated form, which may be diluted with non-psychoactive /psychoactive drugs. In 1995 the DEA reported street MA to be 54% pure at gram/and ounce level [2-5].

Epidemiological studies reports 34 million global MA users [6]. The US 2000 Substance Abuse and Mental Health Services Administration (SAMSHA) National Household Survey on Drug Abuse showed: (i) 4% of people had some lifetime MA use, (ii) 1.1% had used it in the past year and (iii) 0.5% had used in the past month [7]. In 2002, 5.3% had used MA in their lifetime, 0.7% in the last year [8]. The frequency of emergency room visits due to acute MA intoxication data has shown a dramatic increase in the past few years [7]. MA is highly abused by different age groups [5]. Greatest use is among men be-tween the ages of 19 and 40 years, especially college students and young professionals involved in the club scene or attending rave par-ties [3-5, 8-11]. Use of MA by gay and bisexual males is very high

1Douglas Hospital Research Centre, Canada 2McGill University, Montreal, Canada 3International Maternal and Child Health Foundation, Canada 4Clifton Hospital, Pakistan 5Millbourne Mall Medical Centre, Primary Care Network, Canada 6Meadowbrook Medical Clinic, Primary Care Network, Canada 7University of Alberta, Canada

[12]. MA dependence studies have shown that in certain popula-tions, 50% to 75% of individuals with multiple AMP exposure de-velop dependence [13]. MA holds allure because it is cheap, easy to use and easily accessible. It has the potential to induce an abuse ep-idemic and become the most abused drug.

This review will present: (i) an overview of the neurochemical and pharmacological effects of MA administration, (ii) a summary of the clinical effects of MA administration and (iii) evidence of MA’s neu-rotoxic effects.

Neurochemical and Pharmacological effects MA exerts powerful effects on several neurochemical systems throughout the brain. These include dopamine, GABA and GLU [14]. MA is highly lipophilic. This allows rapid and efficient transport across the blood-brain barrier and results in increased CNS penetra-tion [1, 2, 15-18]. MA causes massive release of newly synthesized catecholamines (dopamine (DA), norepinephrine (NE) and serotonin (5HT)) and blocks their reuptake from the synapse in several areas of the brain, including the nucleus accumbens (NAc.), the prefrontal cortex (PFC) and the striatum [1, 9, 10, 19-24]. Studies with trans-genic knockout mice have shown that AMP targets the dopamine transporter (DAT) which is critical for the reuptake of dopamine at the synapse and regulation of dopaminergic transmission [1, 2, 20, 21]. MA/ AMP: (i) act on DAT and block DA reuptake, (ii) reverse the direction of DA transport through the channel, (iii) displace DA from vesicular stores by occupying vesicular monoamine transporter (VMAT2), leading to increased DA release (iv) and also potently in-hibit monoamine oxidase (MAO) [1, 2, 20, 25-27]. Collectively these effects increase the catecholamine concentration in the synapse and the brain. Studies have shown that alpha-methyl-tyrosine (AMT) at-tenuates, whereas reserpine potentiates the releasing action of AMP [27, 28]. Acute and prolonged MA exposure can elevate postsynaptic

8Medicentres, Canada 9Jinnah Post Graduate Medical Centre, Pakistan 10Institute of Integrated Cell-Material Science, Japan *Equal Contributors Correspondence: Adnan Maqsood Choudhry Email: [email protected]

Abstract Methamphetamine (MA) is a synthetic, powerfully addictive central nervous system stimulant drug, derived from amphetamine. It is used for both medicinal and illegal recreational proposes. MA causes an increase in activity, decrease in appetite, and a strong feeling of euphoria. MA exerts powerful effects on several neurochemical systems throughout the brainincluding dopamine, GABA and GLU. MA is highly lipophilic, which allows rapid and efficient transport across the blood-brain barrier and results in increased CNS penetration. It causes massive release of newly synthesized catecholamines, and blocks their reuptake from the synapse in several areas of the brain, including the nucleus accumbens, the prefrontal cortex and the striatum. This review presents: (i) an overview of the neurochemical and pharmacological effects of MA administration, (ii) a summary of the clinical effects of MA administration and (iii) evidence of MA’s neurotoxic effects. Due to its toxic potential, It is very important to develop research strategies towards prospective designs looking at large cohorts of young people belonging to a risk group for recreational drug use. (El Med J 2:1; 2014) Keywords: Methamphetamine, Crystal Meth, Pharmacology, Neurobiology, Neurotoxicity

16 Pharmacology of methamphetamine…

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nigrostriatal DA [14, 22]. Acute MA administration can result in in-creased dopamine turnover in the caudate nucleus, and changes in monoamines and peptides in the basal ganglia [14, 29, 30]. Acute administration of high and repeated doses of MA/AMP in monkeys, results in a transitory decline in DA in various brain regions. This might be due to temporary inhibition of tyrosine hydroxylase activity [28, 31-33] In rats, repeated administration of low dose AMP results in a reduction in the number of DA receptors, but chronic admin-istration of AMP in young guinea pigs results in behavioral supersen-sitivity [34, 35]. Inconsistencies in rodent data can be explained by the observation that chronic AMP treatment induces persistent changes in dopamine receptor sensitivity. This yields increased stria-tal DA receptor sensitivity and decreased response of dopamine re-ceptors in the NAc [36].

Pharmacological effects of MA depend on the dose and pattern of administration. In animal studies, different effects are observed in rodents with (i) administration of a single dose, (ii) repeated admin-istration of low doses at long intervals, (iii) repeated administration of high doses at short intervals and (iv) high-dose runs superim-posed on chronic low-dose administration [37]. In humans, MA is usually ingested, smoked, snorted, or injected intravenously. The amount administered at every dose varies depending on factors such as; (i) route of administration, (ii) individual tolerance and (iii) purity. However, smoked or injected MA results in immediate and intense euphoria which lasts for several minutes and Ingested or snorted MA results in a less immediate, less intense, but longer lasting “high”. Intranasal and oral users experience euphoria after 3-5 minutes and 15-20 min of administration, respectively. This “high” may last 8–12 hours. AMP has a longer duration of action than cocaine (8–13 hours versus 1–3 hours) and thus has higher addiction potential [1-3]. Nearly 45% of MA is metabolized to amphetamine, and both are ex-creted by the kidneys [1].

Clinical Effects In human clinical studies, MA naïve users show heightened alertness, attentiveness, and energy at low doses due to excessive stimulation of the sympathetic nervous system. Higher dose intoxication results in a sense of well-being, euphoria, and enhanced self-esteem that can approach hypomania and grandiosity [1]. Sexual activity and pleasure is increased with initial use, this decreases with time and use. Longer use is associated with impaired sexual functioning in males, a phenomenon known as "crystal dick" [12]. Adverse effects include restlessness, insomnia, bruxism and excessive weight loss due to appetite suppression [11, 38]. Fetal studies show that MA crosses the placenta and concentrates in fetal tissue. Further studies have shown decreases in: (i) visual recognition memory, (ii) IQ, (iii) mathematical and language skills, (iv) poor social adjustment, and (v) aggressive behavior in children with prenatal stimulant exposure [2].

Chronic use of MA results in catecholamine depletion, and leads to “crash” (almost lifeless state lasting 1-3 days). Marked psychiatric complaints such as psychotic and anxiety disorder-like states are as-sociated with chronic MA abuse [39-42]. Obsession with minute de-tails progressing to compulsive repetitious behaviors is also ob-served. Skin picking is very common and is accompanied by “delu-

sional parasitosis”. Psychiatric complaints are usually observed dur-ing (i) intoxication, (ii) withdrawal and (iii) long-term abstinence as residual symptoms. These can be exacerbated by reuse or by psy-chological stress in chronic users [39-42]. Abrupt cessation in chronic MA users results in withdrawal symptoms: (i) depression, (ii) dyspho-ria leading to lethal suicidal ideation, (iii) irritability and (iv) agitation [1, 43]. These last for days. Their increased severity and duration is believed to be the clinical manifestations of residual neurotoxicity from chronic MA abuse [44]. Most studies of neurotoxicity, however, have been performed in animal models [2].

Neurotoxicity of Methamphetamine “Neurotoxicity” is commonly recognized as: (i) cell death, (ii) loss of presynaptic nerve terminals, and (iii) an increase in the expression of glial fibrillary acidic protein (GFAP), a marker of gliosis. MA neurotox-icity, as defined in this paper does not require (i) permanency of le-sion, (ii) permanent loss of cell bodies and/or (iii) functional conse-quences. It refers to the potential of MA/AMP to produce long lasting reductions in the brain markers of DA and/or 5-HT axon terminals (i.e. a distal axotomy) which cannot be explained by MA’s acute phar-macological effects or the neuroadaptive response to these pharma-cological effects.

The neurotoxic potential of MA towards brain DA was first reported in monkeys and rats. Repeated administration of high systemic doses of MA produced persistent reductions in brain markers of DA axons and axon terminals [45, 46]. Further studies research showed that: (i) MA damages brain 5-HT axons and axon terminals and (ii) MA and its analogs have the potential to damage DA and/or 5-HT axon ter-minals [44, 47, 48]. Miller et al showed that toxic doses of MA in-crease the expression of GFAP in the striatum of the C57BL/6J mice [49]. Similar effects were seen in other brain regions including cere-bellum and hippocampus [14, 50]. Prolonged MA exposure causes neurotoxicity by apoptotic and neurotoxic mechanisms in striatal cells [10, 51]. This neurotoxicity is associated with a marked decrease in tyrosine hydroxylase (TH) activity, DA, and DAT binding sites in the striatum [45, 52]. MA use leads to neurotoxicity to both the DAT and SERT systems across a wide variety of mammalian species [2]. Studies have also shown that repeated doses of MA for several weeks show losses of the 5HT transporter (SERT), 5HT depletion, depletion of the major 5HT metabolite, 5-hydoxyindole acetic acid, and reduc-tions in tryptophan hydroxylase (TPH) [47, 53]. Animal studies show that, MA treated animals develop long-lasting reductions in vesicular monoamine (VMAT) transporters [54-56]. Silver staining studies have shown that MA treatment results in axon terminal degeneration in the striatum [49]. Seen collectively, all the data mentioned above strongly suggest that MA produces a distal chemical axotomy of brain DA and 5-HT neurons.

Evidence for Neurotoxicity

Animal studies Since the 1970s, it has been observed that repeated administration of high doses of AMP/MA in animals leads to long-lasting depletions of central monoamine levels. These depletions are accompanied by changes in other neurochemical markers suggesting permanent neuron damage induced by AMP. Initially researchers investigated effects of MA administration in rhesus monkeys. The monkeys were



given low dose MA eight times per day. This dose was increased as they became tolerant to the debilitating effects of the drug. They were receiving a total dose of 52 mg/kg per day for a period of four to six months. They were sacrificed after six months and regional brain assay of transmitter levels was conducted. It was observed that MA treated monkeys had significantly reduced regional DA and NE levels with respect to control monkeys. This experiment clearly showed that the repeated administration of MA caused permanent neuron changes [22, 46, 57]. Further studies exploring species differ-ences to MA administration showed, a marked decrease in nigral and striatal TH activity of rats following repeated doses of methamphet-amine [45]. MA metabolism studies showed that rhesus monkeys, guinea pigs and humans metabolize MA through oxidative deami-nation, while rats metabolize the compound primarily through para-hydroxylation [58]. In another study, Wagner et al administered high doses of MA to groups of rats and guinea pigs for a period of 30 days. The total daily dose of 50 mg/kg was divided into two subcu-taneous injections spaced twelve hours apart. The animals were sac-rificed two weeks following the last injection and regional brain as-says were performed. Results showed that: (i) striatal DA levels of drug-treated subjects were depleted to about 50% of control values and (ii) these depletions appeared to be dose dependent [59]. These findings collectively showed that repeated administration of MA caused long-lasting depletions of central DA lasting six months in rhesus monkeys and two weeks in rodents. Wagner et al in the same experiment administered high doses of MA to another sub group of rats for 30 days. The rats were sacrificed 2, 4, or 8 weeks after the last injection and regional brain assay was done. Results showed signifi-cant depletion of striatal DA after all three waiting periods. No recov-ery was observed over the 8-week waiting period, and depletion was the same even after 6 months of the last injection [60, 61].

In another study, groups of rats received different daily doses of MA (12.5, 25, or 50 mg/kg per day) for 40, 20, or 10 days, respectively, such that each rat received the same total dose of MA. After 2 weeks from the last injection they were sacrificed. The results showed sig-nificant striatal DA depletions in rats receiving two higher doses of MA. In a counterpart to this study, groups of rats received 12.5, 25, 50, or 100 mg/kg per day for four days; all other parameters were the same. Similarly, rats receiving two larger daily doses of MA showed DA depletions [60]. These findings suggest that low clinical dose of MA even for prolonged periods resulted in minimal brain dysfunction and might not be associated with neuronal damage in humans. Further exploration in primates showed higher sensitivity to AMP compared to rodents. In recent studies researchers adminis-tered 2.0 mg/kg of AMP or MA to vervet monkeys in two IM injec-tions, 4-hours apart. They observed substantial and long-lasting de-pletion of striatal DA after one month, but reported a partial recovery by three months [31, 62]. The 2.0 mg/kg dose used in these studies was considerably lower than those used in earlier rodent studies, but the magnitude of the DA depletion was quite comparable. This find-ing indicates that primates have higher AMP neurotoxicity sensitivity than rats. DA recovery was observed in monkeys, but not in the ro-dents, nor in the monkeys treated with the higher doses of MA. This might be because the MA doses administered to the vervet monkeys were comparatively low doses administered in just a few injections via a different route as compared to earlier rhesus monkey and ro-dent studies.

More recent rat studies have shown degeneration of DA nerve fibers, loss of tyrosine hydroxylase, DA transporter, tryptophan hydroxylase, and loss of 5-HT-immunoreactive axons and axon terminals follow-ing a high dose of MA [10, 63, 64] Many studies have shown that MA use results in damaged striatal DA nerve terminals and DA cell bod-ies in substantia nigra (SN), pars compacta, and ventral tegmental area (VTA) [64]. These finding provided neuroanatomical evidence of neurotoxic effects of MA. Studies profiling duration of neurotoxi-city in animals have shown long term neurotoxicity following admin-istration of high doses MA, which spans from months in rats to years in monkeys [32]. The extent of dopaminergic and serotonergic neu-rotoxicity caused by AMP analogs depends on several factors includ-ing: (a) specific amphetamine analogs, (b) animal species, (c) mouse strain, (d) dosage and frequency of drug administration and (e) the ambient temperature of drug administration and the thermoregula-tory effect of the drug [22, 49, 65]. Rats administered with 10 to 15 mg/kg MA every 6 hours for 5 doses, showed decreased TH activity and DA content in the neostriatum within 18 hours after the first dose [66, 67]. Administration of 5 mg/kg of MA, every 3 hours to Swiss Webster mice caused selective depletion of striatal DA, DA me-tabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and DAT binding sites, with no evidence of 5-HT depletion [23]. MA induced neurochemical deficits persist for extended periods of time even after the drug is discontinued in rats and monkeys (4 years) [68, 69]. Thus, from the above mentioned data we can con-clude that MA/AMP exert toxic effects in a variety of animal species and the MA-induced changes appear to be long-lasting and in some cases, may be permanent. Further experiments across species are necessary to elucidate the functional consequences of MA induced neurotoxicity.

Human studies In 1990s researchers started looking at the effects of AMP/MA in hu-mans. Wilson et al in 1996 conducted post-mortem analyses of brain tissue from humans who had abused AMP long before they had died and controls. They reported that, AMP abusers had deficits in DA, TH activity, and the DAT in the NAc, caudate, and putamen indicating that AMP abuse damaged the striatal DA system [70]. These findings might explain the rationale for the dose escalation and dysphoria that are frequently found in MA abusers, and also help us better un-derstand persistent psychosis and paranoia reported by MA abusers [41, 70]. Neuropsychological studies in MA abusers have shown an association between severity of AMP dependence and poorer per-formance on measures of memory, attention and concentration [71, 72].

Preliminary neuroimaging studies in MA abusers suggest that MA may be neurotoxic. Magnetic resonance imaging (MRI) has showed cerebral infarcts and hemorrhage in some individuals who develop neurological complications after MA use [73, 74]. Two qualitative SPECT ([99mTc]-HMPAO) studies demonstrated ‘multiple perfusion defects’ in both active users and in abstinent METH users [75, 76]. Recent PET studies have shown that there are long-lasting reduc-tions in striatal DAT in previous MA or methcathinone abusers [48]. Lower DAT density in NAc, PFC, and the caudate/putamen of MA users is seen compared to controls. MA users also exhibited psychi-atric symptoms, the severity of which was significantly correlated with the duration of MA use [77]. Volkow et al, showed significant


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reduction in the DAT density of MA abusers in the caudate (28%) and putamen (21%), which was associated with motor slowing and memory impairment [78]. Chang et al, in 20 abstinent MA abusers, found deficits in working memory tasks compared to matched con-trols Perfusion magnetic resonance imaging (pMRI) studies of these subjects showed an increase in regional cerebral blood flow (rCBF) in several parietal regions and a decrease in rCBF in putamen re-gions. These changes indicate possible neuronal damage [79]. Using FDG-PET, Volkow et al showed decreased glucose metabolism in the thalamus and striatum, but increased metabolism in the parietal cor-tex of abstinent MA users [80]. Ernst et al, using Proton MR spectros-copy (1H MRS), reported decreased concentrations of N-acetyl (NAA) compounds in the frontal white matter and the basal ganglia, and increased choline (Cho) and myoinositol in the frontal cortex of ab-stinent MA abusers. These results suggest neuronal damage of frontal white matter and the basal ganglia; and gliosis of frontal cor-tex [19]. Other MRS studies have found: (i) evidence of abnormally low normalized NAA (i.e., NAA/Cr) levels and higher normalized Cho (i.e., Cho/Cr) levels in the anterior cingulum (ACC), with no evidence of such findings in the primary visual cortex in recently abstinent MA subjects, and (ii) evidence of low NAA in the anterior cingulum and a trend toward a low NAA value for the basal ganglia [1, 81]. These MRS findings are interpreted as consistent with neural damage to the frontostriatal regions. A functional MRI study of 10 METH users reported decreased prefrontal activation and elevated parietal acti-vation during tasks that involved decision-making [82]. The imaging findings show that chronic MA abuse causes alterations in brain structure and function.

Moszczynska et al, in a recent post mortem study compared dopa-mine levels in autopsied brain tissue of chronic MA users with those in patients with Parkinson’s disease and in a control group. They re-ported reductions in mean dopamine levels in the MA users more in the caudate (–61%) than in the putamen (–50%) [83]. This finding of reduction in the caudate explains cognitive disturbances in chronic MA users. Chang et al, in a structural MRI study, recently reported both striatal and pallidal enlargement in abstinent MA abusers. MA abusers showed larger globus pallidus (9.6%) and putamen (9.9%) volumes compared to age and gender comparable controls. Chang has suggested structural enlargement might be due to inflammation and reactive gliosis induced by striatal injury caused by long term MA abuse [84].

Studies profiling duration of MA neurotoxicity in humans have been mixed, with conflicting findings. McCann et al in a PET study showed reduced striatal DAT density in chronic MA abusers after three years of abstinence. This suggests that chronic MA abuse leads to destruc-tion of DA nerve terminals or cell bodies [48]. In a recent PET study, Volkow et al reported DAT normalization, but no change in cognitive deficits following DAT normalization in a paired study of five subjects that were initially examined in early abstinence and then in late ab-stinence (1.5 to 2 years). Volkow et al have suggested that DAT re-covery might be due to increased arborisation or transporter protein up regulation on surviving DA terminals. This could lead to normal-ized ligand binding in imaging studies, but it may not be sufficient to fully restore the dopaminergic neurotransmission that subjects need in order to resume baseline neuropsychological functioning

[85]. This finding suggests that chronic exposure to methampheta-mine does not necessarily cause permanent deficits or damage to the DA system in human users. Autopsy studies in MA abusers have shown marked decreases in striatal TH, DAT, and DA, but preserva-tion of the presynaptic DA markers VMAT and DOPA decarboxylase without any signs of pigmented cell loss in the substantia nigra [70, 83]. Collectively, these findings suggest that MA-induced neurotoxi-city leads to selective destruction/down-regulation of particular DA synthetic and functional proteins rather than to general destruction of DA terminals or cell bodies [70]. Thus, findings from neuroana-tomical, neurochemical, neuropsychological, imaging and postmor-tem data support the conclusion that methamphetamine abuse causes damage to multiple transmitter systems that are distributed throughout the brain. Whether the ensuing damage is permanent or reversible over time has not yet been determined, but additional studies are needed to address this important issue.

Mechanisms of Neurotoxicity The mechanisms involved in MA induced neurotoxicity are still un-clear. Studies have implicated reactive oxygen species and the re-sultant oxidative stress. Studies investing the role of DA in inducing MA neurotoxic response, showed that pre-treatment with DA syn-thesis inhibitors, such as alpha-methyl-p-tyrosine (AMT) provide pro-tection against MA induced neurotoxicity to both DA and 5HT sys-tems. Similarly, treatment with L-DOPA restored the capability of MA to induce neurotoxicity. These findings provide evidence indicating that endogenous DA is required for MA induced neurotoxicity [44, 53, 86]. In addition, Seiden et al in a rat study showed that following a single injection of MA (100 mg/kg), 6-hydroxydopamine (0.39 +/- 0.31 nanograms/mg of tissue at 2 hr) was formed in the caudate nu-cleus. They also showed a 50% depletion of caudate dopamine at 2 weeks post MA administration. This suggest that MA treatment leads to the formation of 6-hydroxydopamine from endogenous dopa-mine which is responsible for the MA induced neurotoxicity to do-pamine terminals [87]. Severity of MA-induced neurotoxicity studies showed that MA induced neurotoxic insult is influenced by the levels of: (i) reducing enzyme super-oxide dismutase (SOD), (ii) ROS-pro-ducing enzyme neuronal nitrous oxide synthase (nNOS), and (iii) an-tioxidant ascorbic acid [23, 65, 88]. Studies of VMAT-2 knockout mice showed, increased damage to DA system after MA treatment. This finding suggests that MA might redistribute DA from the synaptic vesicle (reducing environment) into the neuron’s cytoplasm (oxidiz-ing environment). This redistribution would result is the generation of free radicals and reactive metabolites that likely lead to protein and cell membrane destruction [21].

Limitations of Methamphetamine Neurotoxicity Research

Animal studies Animal research advocates have claimed “animal models” to be reli-able models of human conditions as they are conducted in “con-trolled” laboratory environments. Considerable work has been done with regards to MA neurotoxicity in animals. These studies have re-ported consistent positive findings, showing that MA administration results in neurotoxicity. However, there are concerns with regards to the clinical relevance of these studies. These are: (i) interspecies dif-ferences in anatomy and physiology, (ii) differences in cause and course of MA neurotoxicity between human and animal, and (ii)



stress (due to caging, social disruption, restraint, transport, and re-peated handling) experienced by animals in laboratories. These fac-tors can invariably alter research results. Many MA neurotoxicity studies have shown disparity across different species with regards to (i) MA exposure, (ii) severity of MA induced insult, (iii) duration to which toxic effects are observed, and (iv) pattern of recovery from MA induced neurotoxic insult. Most rodent studies have used an acute regimen of a high dose of MA/AMP given within 8-72 hours. This is in complete contrast to the human pattern of MA abuse which extends over a period of weeks, months and years. Scientist involved in rodent studies have advocated the use of “acute model” claiming its relevance to the final outcome i.e. MA induced neurotoxicity. Skeptics of this model are of the opinion that patterns of abuse in-fluence the degree of neurotoxic damage. Explanation given by ani-mal researchers to this concern is that “acute dosing model” in ro-dents may resemble the “binge pattern” of drug abuse in humans. The issue of “sensitivity” differences to psychoactive drugs is another important concern in MA animal model research. It has been ob-served that “sensitivity” differences do exist in rodents and humans: the dosage of AMPs given to rodents exceeds the dosage abused by humans. These dose differences are explained by difference in di-verse pharmacokinetics and pharmacodynamics of the drug in ro-dents and humans. Animal model studies are not good predictors of clinical symptoms/behavioral effects due to AMP/MA neurotoxicity, as animals cannot reveal subjective effects (headache or psycholog-ical effects) post MA administration. Thus, animal studies have lim-ited functional significance in their ability to predict MA neurotoxi-city in humans.

Human studies Since the 1990s researchers have been looking at the effects of AMP/MA in humans. Many studies have been conducted looking at the neuroanatomical, neurochemical, neuropsychological, imaging and postmortem changes associated with MA abuse. They have shown that MA abuse causes damage to multiple transmitter sys-tems, distributed throughout the brain. Although these studies showed positive findings, they have significant methodological limi-tations. Earlier studies have failed to capture vital data on: (i) the parallel use of other drugs, (ii) length of abstinence periods. Drug specificity is an important parameter in assessing neurotoxicity. Poly-drug abuse (alcohol, cannabis, cocaine) in human MA abusers makes it difficult to delineate the specific neurotoxic effects of MA. Thus data from studies, utilizing poly-drug abusers and reporting neuro-toxic effects of AMP/MA is not very credible, as it does not show the specific effects of MA on human subjects. Data from studies examin-ing the effects of low prescribed MA doses (for minimal brain dys-function or reduction in food intake) can help in understanding spe-cific deleterious effects on the dopaminergic system caused by MA. Length of abstinence periods is important in assessing duration of MA induced neurotoxicity and recovery. Failure to capture this data impairs our ability to interpret the long-term effects of MA. Recent studies also exhibit methodological weaknesses without an obvious solution to date, i.e. (i) inadequate MA dependent group, (ii) ques-tionable reliability of statements/histories by the subjects them-selves on their current and earlier drug abuse habits, (iii) difficulties recruiting adequate control groups, (iv) uncertainties related to the precise chemical composition of “cut” MA. Robust sample size is im-portant in elucidating clinical neurotoxic effects of MA. Many studies

reporting MA induced deficits lack sample size and/or both genders. These factors decrease the significance of their results and its appli-cation to the general MA user population. Inaccuracy in clinical his-tory and history of drug use by the subjects is a serious limitation in interpreting human MA neurotoxicity results. Most of the studies are retrospective, relying on participants’ self-report. This makes it diffi-cult to ascertain the amount and type of drug used by the partici-pants, thus reducing the reliability of the findings. Retrospective studies also lack in their ability to determine differences between control and user groups prior to MA use. Control groups are im-portant in assessing the extent of neurotoxicity caused by MA. Many studies have used poorly matched control groups that include non-users, and poly-drug users with overall moderate use patterns than the poly-drug MA users. Studies have shown illegal/street MA to be impure as it is diluted /cut with other psychoactive active substances (ketamine, dextromethorphan, AMP, MDMA, ephedrine and salicy-lates), which makes it very difficult to confirm whether the neuro-toxic effects exhibited by MA abuser are MA specific or are the cu-mulative effects of other psychoactive substances. Recently, brain imaging studies have provided much needed insight in the structural and functional aspects of the brains of living MA abusers. These stud-ies provide important information on how MA changes the structure and functioning of specific brain regions. However, limitations of this technique in humans make it difficult to determine conclusively that brain cells are damaged or destroyed as result of MA abuse. Another important limitation observed in some brain imaging studies was that neuropsychological and cognitive testing was performed in MA abusers and not in controls. Thus, it is not possible to determine the extent to which MA abusers differed from controls. Thus, human MA neurotoxicity research has a number of significant limitations which impair our understanding of the extent of MA induced neurotoxicity. At present, we are unable to completely rule out the influence of comorbid factors. More methodologically sound research is required to fully understand the extent and duration of neurotoxicity induced by MA.

Remaining challenges Since 1976, significant progress has been made in elucidating the neurobiology of MA/AMP, but still a number of challenges are re-maining. The exact mechanism of MA induced neurotoxicity is very elusive. Studies have shown the possible involvement of transporter and temperature in the expression of MA induced toxicity of the DA and 5HT neurons [49]. However, studies in this area haven’t explored the resistance of NE neurons to this toxic effect. NE neurons exhibit similar properties as DA and 5HT neurons, with the exception of re-sisting MA/AMP induced neurotoxicity. Studies exploring differences between DA and NE neurons may help in identifying features of DA neurons that predispose them to MA/AMP neurotoxicity. Studies have shown that DA and 5HT cell bodies are spared from MA /AMP neurotoxicity, even in the worst case of MA administration. Research in the area of neuron vitality should explore factors vital to the health of the axons and axon terminals. This would help in identifying can-didate processes involved in AMP-induced injury. If candidate genes important to axonal integrity are identified, focused and testable hy-potheses regarding mechanisms underlying neurotoxicity could be generated using present advances in genomics and proteomics.


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Different species respond differently to MA insults. Murine research has shown increased DA toxicity (possible vulnerability) and no or little 5-HT toxicity (possible resistance) following MA/AMP admin-istration. Further analysis of a possible selective response mechanism could help in: (i) predicting the effects of AMP in other animal spe-cies, and (ii) may also help in understanding the mechanisms of AMP toxicity. Primates exhibit long-lasting toxicity, whereas rodents tend to recover from AMP analogue neurotoxicity over time. Similarly, Volkow et al (2001) have shown DAT recovery in human MA abusers with protracted abstinence [85]. Exploration of factors involved in the duration of toxic injury across different species, could help in de-vising methods for reversing injury. Studies exploring possible neu-ronal recovery factors would have great implications for a variety of neurodegenerative conditions. These studies should also define pos-sible recovery characteristics if it occurs (reinstatement of original, normal neuronal pathways/aberrant re-innervation) and its conse-quences.

Functional consequences are integral to MA neurotoxicity research. Animal studies have discussed abnormal dopamine-mediated be-haviors following MA/AMP -induced DA and 5-HT neurotoxicity [89]. Functional research in this area could provide potential clues to: (i) similar damage in humans, and (ii) further findings in the role of DA and 5-HT in normal behaviors.

Many researchers have shown evidence of MA-induced DA neuro-toxicity in humans [48, 77, 85]. There are still grey areas in this field with regards to the (i) doses and drug regimens needed to produce neurotoxicity in humans, (ii) the functional consequences of neuro-toxicity, and (iii) potential long-term clinical implications of MA tox-icity (vulnerable to Parkinson’s disease with advanced age). Further-more, epidemiological studies focusing on the prevalence of a vari-ety of neurologic and psychiatric conditions (e.g. movement disor-ders, depression, anxiety disorders, sleep disorders) in individuals ex-posed to these drugs relative to the general population are in order.

Conclusions & Future directions MA exerts powerful effects on several neurochemical systems throughout the brain including dopamine, GABA and GLU. It causes a strong feeling of euphoria, which creates a potential for addiction and abuse. Epidemiological data suggests a progressive increase in the MA epidemic all over the world, with its use highest in younger male cohorts. MA has a longer half-life: this may produce exception-ally long-lasting toxic effects. Abrupt cessation results in depression, dysphoria, suicidal ideation, irritability, and agitation. Neuro-cogni-tive impairments that affect information processing, verbal memory and other domains of cognition are commonly seen in MA abusers.

MA neurotoxicity research has shown a number of factors influenc-ing the nature and degree of toxicity. These include (i) dose, (ii) dos-ing interval, (iii) route of administration, and (iv) temperature. Up-to-date neurotoxicity research shows that MA abuse causes: (i) serious cognitive impairments in humans, and (ii) DA and 5HT neurons dam-age in rodents. Focused research elucidating functional conse-quences of MA induced toxicity in animals and humans is needed. Concentrated efforts should focus on (i) mechanisms by which MA leads to selective DA and/or 5-HT damage, (ii) mechanisms, time

course and features of recovery and (iii) MA’s involvement in neuro-degenerative diseases (Parkinson’s disease).

It is very important to develop research strategies towards prospec-tive designs, looking at large cohorts of young people (not MA users) belonging to a risk group for recreational drug use (attendants of rave parties/ bisexual and gays). Following-up on them over years and re-examining them, recording drug histories using psychometric instruments and carrying out neuropsychological tests. These efforts, could help in better understanding of (i) relation between drug use and “sub-clinical” psychological symptoms or “neuro-cognitive” fail-ures and, (ii) questions regarding progression, persistency and re-versibility (if any) of the MA induced alterations. There will always be debate about ethical aspects of such studies, but they are definitely needed to determine the answers to the important questions around possible long-lasting adverse effects of MA on the human brain.

Competing interests: The authors declare that no competing interests exist. Received: 8 October 2013 Accepted: 12 January 2014 Published Online: 12 January 2014

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Sajjad A 23


Open Access Opinion and Debate

Health issues: The leading cause of deaths worldwide Aqsa Sajjad1

Introduction Health is a state of being free from physical and psychological dis-ease, illness or malfunction. The World Health Organization (WHO) defines health as “a state of complete physical, mental and social wellbeing and not merely the absence of disease and infirmity’’. Gen-erally, it is increasingly observed that health is maintained and im-proved not only through the application and advancement of health sciences, but also through the struggle and the lifestyle of the indi-viduals and society. The main elements of health, such as the social, economic and physical environment, and the person’s individual characteristics and behavior help to build up and promote the qual-ity of life and health status [1].

Health issues are higher on the international work list and getting better health of people is a central issue in development. They are especially relevant for the developing world, where they have a higher mortality rate due to limited access to healthcare and social protection. The importance of these basic causes of health must, therefore, be composed into development policies.

Global Health Issues Although there have been improvements in health since 1950, many challenges still remain that require urgent attention:

1 billion people lack access to health care systems [2]. 36 million deaths each year are caused by non-communicable

diseases (NCDs) such as cancer, diabetes, cardiovascular diseases and chronic heart diseases. Over 56 million deaths occur each year worldwide [2].

Cardiovascular diseases (CVDs) are the most common condition causing death globally. An estimated 17.5 million people died from CVDs in 2005, representing 30% of all global deaths. Over 80% of CVDs deaths occur in low and middle income countries [2].

Over 7.5 million children under the age of 5 die from malnutri-tion and mostly preventable disease each year [2].

6.7 million people died as a result of infectious diseases in 2008 [2].

AIDS/HIV has spread rapidly, UNAIDS estimates 33.4 million liv-ing with HIV, 2.7 million new infections of HIV and 2 million deaths from AIDS [2].

1Ziauddin Medical University, Pakistan Correspondence: Aqsa Sajjad Email: [email protected]

With 9.4 million new cases, tuberculosis kills 1.7 million people each year [2].

225 million acute illnesses are caused by malaria and over 780,000 deaths annually are attributed to the disease [2].

In 2008, 164,000 people, mostly children under the age of 5, died from measles even though effective immunization costs less than 1 US dollar and has been available for more than 40 years [2].

Every year, 1.6 million people still die from pneumococcal dis-eases, making it the number one vaccine preventable cause of deaths worldwide. Most of the victims are children [2]

Factors Poverty is a major problem. Although health facilities have improved in developing countries, this has created a health divide between those who can afford them and those who cannot. In addition, a huge number of people does not have access to these facilities. This leads to a vicious cycle: poverty aggravates poor health which in turn makes it difficult to overcome of poverty. Most of the world’s health care systems depend on the most inequitable methods for financing health care services. Over 100 million people around the world are pushed into poverty each year due to catastrophic health care ex-penditure [3].

Food and nutrition are also fastidious factors that influence the health of poor people. Almost 800 million people in developing countries are chronically undernourished. This in turn affects the im-mune system, increase the severity of diseases and thereby leading to child mortality [4]. Lifestyle changes such as tobacco and alcohol use along with injuries now contribute an increasing share of deaths. NCDs, such as cancer, circulatory systems aliments, psychiatric disor-ders, infectious disease and child malnutrition are major contributors to the global disease burden. Other risk factors such as tobacco, in-sufficient physical activity, unhealthy diet, raised blood pressure, obesity, raised cholesterol, cancer-associated infections also contrib-ute significantly.

An analysis of existing data on mental illness reveals that depression, epilepsy, schizophrenia and substance abuse are responsible for ris-

Abstract The World Health Organization (WHO) defines health as “a state of complete physical, mental and social wellbeing and not merely the absence of disease and infirmity’’. Health issues are higher on the international work list and getting better health of people is a central issue in development. They are especially relevant for the developing world, where they have a higher mortality rate due to limited access to healthcare and social protection. The importance of these basic causes of health must, therefore, be composed into development policies. (El Med J 2:1; 2014) Keywords: Health Issues

24 Health issues: The leading cause of deaths worldwide

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ing suicide rates in many parts of the world. Due to this, mental ill-ness has been frequently attributed to the upsurge of poverty, polit-ical instability, violence, unemployment and other social evils.

Approaches To promote growth, budget should be governed by social poli-

cies in areas such as education, labor, and primary health care. Investing in education (universal primary education) helps to di-

minish health inequalities and furnishes people to obtain health literacy, better jobs, preventive health care measures and avoid risky health behavior.

To promote primary and essential health care, the slogan of “health for all” should be strictly followed.

Non-governmental organization should work in conjunction with the government to deliver health services through different segments of society.

Mobilizing community resources is the modern way to upgrade the health of people. Approaches include comprehensive train-ing of community-based health workers, involvement of tradi-tional leaders and local development of health services [3].

Establishing health financing approaches through appropriate taxation or insurance helps in promoting roper utilization of health care services.

Conclusion To conclude, we need to focus on overcoming structural barriers of health. Inadequate medical diagnosis and inept treatment squander many resources that lead to additional suffering and mortality. Pre-ventive intervention that achieves health equity for all people world-wide is needed. Although there is a decrease in mortality and a con-sequent increase in life expectancy, strong plans need to be made to overcome current and future challenges.

Competing interests: The authors declare that no competing interests exist. Received: 2 December 2013 Accepted: 5 December 2013 Published Online: 9 December 2013

References 1. Report of the Consultative Forum Subgroup on Population Health/Health

Promotion [http://www.dohc.ie/issues/health_strategy/reppop.pdf?direct=1] 2. Global Health Issues [http://www.globalissues.org/issue/587/health-issues] 3. Primary Health Care, Now More Than Ever | WHO World Report 2008

[http://www.who.int/whr/2008/whr08_en.pdf] 4. Poverty and Health in Developing Countries: key actions

[http://www.oecd.org/development/povertyreduction/33965811.pdf]



Open Access Essay

SNARE proteins and membrane fusion Zia Choudhry1,2,3*, Azadeh A. Rikani1,2*, Adnan Maqsood Choudhry3, Sadaf Tariq4, Fozia Zakaria5,6, Muhammad Waheed Asghar7, Muhammad Khan Sarfraz8, Numan Majeed8, Huma Ikram9, Nusrat Jahan Mobassarah10

Introduction Diverse proteins catalyze membrane fusion reactions. These mediate recognition of the membranes for fusion and pull the membranes close together to destabilize the lipid/water interface and to initiate mixing of the lipids [1]. In the nervous system, membrane fusion is vital for neuro-exocytosis, neurotransmitter release and chemical synaptic transmission [2, 3]. Three neuronal soluble NSF (N-ethyl-ma-leimide-sensitive fusion protein) attachment receptor (SNARE) pro-teins exist, namely: (i) vesicle associated membrane protein (VAMP-2), also called synaptobrevin; (ii) 25 kDa synaptosome-associated protein (SNAP-25); (iii) and syntaxin 1A (STX1). The SNAREs are in-volved in the neuronal membrane fusion process [4, 5]. VAMP-2 is a v-SNARE (‘v’ stands for vesicle) and STX1 is a t-SNARE (‘t’ stands for target). Both of these are single-pass transmembrane proteins in the vesicular and plasma membrane. SNAP-25 is a t-SNARE and contains two SNARE domains flanking a region of palmitolyated cysteines which associates it with the plasma membrane [4, 5].

SNAREs contain conserved heptad repeat sequences that form coiled-coil structure and are thought to promote synaptic vesicle ex-ocytosis via SNARE complex formation [6, 7]. In this brief review the literature supporting the following hypotheses will be presented:

(i) SNARE proteins are necessary for membrane fusion; (ii) SNARE pairing is sufficient for in vitro membrane fusion.

Furthermore, the application of the SNARE mediated membrane fu-sion model to membrane fusion in vivo will also be discussed.

Are SNARE proteins necessary for membrane fusion? Sollner et al. developed a cell free assay system for Golgi membrane fusion. They used an affinity purification procedure utilizing NSF and SNAP proteins to isolate SNAREs from bovine brain. Four principal proteins were isolated, one in the vesicle and another in the plasma membrane. This finding suggests:

1Douglas Hospital Research Centre, Canada 2McGill University, Canada 3International Maternal and Child Health Foundation, Canada 4Clifton Hospital, Pakistan 5Millbourne Mall Medical Centre, Primary Care Network, Canada 6Meadowbrook Medical Clinic, Primary Care Network, Canada 7University of Alberta, Canada

(i) a simple vesicle docking mechanism between vesicle and tar-get exists;

(ii) NSF and SNAPs are components of a vesicle fusion apparatus; (iii) SNARE proteins provide vesicle-to-target specificity thus help

in membrane fusion [8].

Experimental data form numerous in vitro neurotoxin studies con-ducted to assess neuro-exocytosis clearly provides evidence support-ing a direct correlation between SNARE protein proteolysis and inhi-bition of neurotransmitter release. Clostridium neurotoxins (CNT) se-lectively cleave SNARE proteins and abolish synaptic transmission. Tetanus neurotoxin (TeNT) and botulinum neurotoxin (BoNT)-A, B, C are zinc endoproteases which cleave VAMP, syntaxin and SNAP-25 respectively [9-11]. Many researchers observed cells intoxicated with TeNT or BoNT in which SNARE proteins were cleaved in synapto-somes. This resulted in a corresponding inhibition in neuro-exocyto-sis [12, 13]. This finding supports the notion that SNARE proteins are necessary in the membrane fusion process. This suggests that SNARE proteins inhibited by CNTs results in the negative regulation of neu-rotransmitter release. In accordance with this study, peptides present at the cleavage site of VAMP inhibited TeNT and BoNT/B in Aplysia and squid neurons [14, 15]. Furthermore, VAMP-specific antibody in-hibits TeNT and BoNT/B, thereby preventing cleavage of SNAREs and inhibition of neurotransmitter release in Aplysia neurons [16]. All these experimental findings suggest that SNAREs are responsible for membrane fusion and neurotransmitter release.

Drosophila lacking VAMP or syntaxin showed normal docking of ves-icles at active zones and a complete block of synaptic transmission. Broadie et al investigated the level of this blockade. Ultra-structural analyses revealed that docked vesicles were mature and functional without VAMP; this may be due to spontaneous vesicle fusion. Vesi-cle fusion triggered in the absence of syntaxin may be due to hyper-osmotic saline. Schulze et al demonstrated that drosophila mutants of syntaxin-1A gene had an alteration in morphology and secretion.

8Services for Public Health and Research, Pakistan 9Jinnah Postgraduate Medical Centre, Pakistan 10Kyoto University, Japan *Contributed equally to this work Correspondence: Adnan Maqsood Choudhry Email: [email protected]

Abstract Diverse proteins catalyze membrane fusion reactions. These mediate recognition of the membranes for fusion and pull the membranes close together to destabilize the lipid/water interface and to initiate mixing of the lipids. In the nervous system, membrane fusion is vital for neuro-exocytosis, neuro transmitter release and chemical synaptic transmission. Three neuronal soluble NSF (N-ethyl-maleimide-sensitive fusion protein) attachment receptor (SNARE) proteins exist, namely: (i) vesicle associated membrane protein (VAMP-2), also called synaptobrevin; (ii) 25 kDa synaptosome-associated protein (SNAP-25); and (iii) syntaxin 1A (STX1). The SNAREs are involved in the neuronal membrane fusion process. (El Med J 2:1; 2014) Keywords: SNARE Proteins, Membrane fusion, Nervous system

26 SNARE proteins and membrane fusion

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Electrophysiological recordings in partial loss-of-function mutants in-dicated lack of endogenous synaptic transmission at the neuromus-cular junction and an 80% reduction of evoked transmission. In com-plete absence of syntaxin-1A gene, subtle morphological defects in the nervous system were observed and this affected secretory events, resulting in complete inhibition of neurotransmitter release. These combined results provide evidence that syntaxin and VAMP play key roles in non-neuronal secretion, membrane fusion and neu-rotransmitter release, and that syntaxin is absolutely required for evoked neurotransmission [17, 18].

Nickel et al used a novel complementary oligonucleotide assay sys-tem to demonstrate membrane bilayer fusion, mediated by v-SNAREs and t-SNAREs. These were initially present in separate pop-ulations of liposomes but when mixed, they fused with high effi-ciency at a physiologically meaningful rate. This showed that SNARE proteins are sufficient to mediate complete membrane fusion ac-companied by mixing of luminal content. The experiment also re-vealed that SNARE-mediated membrane fusion did not compromise the integrity of liposomes [19]. Thus SNAREs in an isolated system can fuse membranes.

Is SNARE pairing/complex sufficient for membrane fusion in vitro? The SNARE complex consists of four helices, in which one is from the v-SNARE, VAMP and three are from the t-SNAREs, SNAP-25 and syn-taxin [20, 21]. Rothman and coworkers used an in vitro method to study vesicle fusion by measuring lipid content mixing from two sep-arate liposomal vesicles, each one reconstituted with v-SNARE and t-SNAREs, respectively. They observed the v-SNARE and t-SNARE pro-teins reconstituted into separate lipid bilayer vesicles assembled into SNARE pins/SNARE complexes linking two membranes. This linkage led to spontaneous fusion of the docked membranes at physiologi-cal temperature. This data implied that SNARE pins/SNARE com-plexes are the most integral machinery for cellular membrane fusion and promotes fusion between lipid vesicles [22-24]. McNew et al used an in vitro method to test v-SNAREs encoded in the yeast ge-nome for their ability to trigger fusion by partnering with t-SNAREs that marked the Golgi, the vacuole and the plasma membrane. It was observed that the pattern of cellular membrane flow is encoded and recapitulated by its isolated SNARE proteins. This finding proposes that vesicles dock specifically to target membranes when cognate SNAREs link-up, and that the assembly of these SNARE complexes initiates the mechanism of bilayer fusion [24, 25].

In yeast there are 4 proteins orthologous to the SNARE proteins, namely: Sed5, Bos1, Sec22 and Bet1 [26]. Parlati F et al in an in vitro study explored the effects of anchoring arrangement of the four hel-ices of the yeast SNARE complex and their ability to mediate fusion. Two populations of phospholipid bilayer vesicles were reconstituted, with the individual SNARE proteins distributed in all possible combi-nations between them. Interestingly, one out of the eight non-re-dundant permutations of four subunits distributed over two vesicle populations, resulted in membrane fusion. Fusion only occurred when the v-SNARE Bet1 was on one membrane and the syntaxin heavy chain Sed5 and its two light chains, Bos1 and Sec22, were on the other where they constituted a functional t-SNARE. Thus, it was

concluded that SNARE proteins are topologically restricted by design to function either as a v-SNARE or as part of a t-SNARE complex [24, 27].

Is SNARE pairing/complex sufficient for membrane fusion in vivo? Washbourne et al generated a mouse model lacking the SNAP-25 gene. This resulted in embryonic lethality of the mutant mice (death at E17.5-18.5). SNAP-25 null embryos had abolished evoked synaptic exocytosis/transmission at neuromuscular junctions and central syn-apses. These results show that SNAP 25 is enough for Ca++ evoked synaptic transmission and neurotransmitter release [23]. Further-more, Schoch et al showed that VAMP2 homozygous knockout mice died immediately after birth, and spontaneous synaptic vesicle fu-sion was decreased by 10-fold, but fast Ca++ triggered fusion by 100-fold. Thus, VAMP2 is suggested to function in catalyzing fusion reac-tions and stabilizing fusion intermediates but is not absolutely re-quired for synaptic fusion [28]. In a recent study by Deak, et al it was suggested that VAMP2 is a crucial factor in fast recycling of synaptic vesicles. After depletion of the readily releasable vesicle pool, replen-ishment of the pool is delayed in VAMP2-null mice. This is because the shape and size of vesicles are altered in the absence of VAMP2. Finally, mouse gene Syn4 (syn1 in humans), which is a widely ex-pressed t-SNARE, is essential for early embryonic development since Syn4-null embryos die before E7.5.

As observed in the gene knockout studies in mice, SNARE proteins and SNARE complex play an integral role in membrane fusion, neu-rotransmitter release and consequently, synaptic activity. Absence of SNAREs results in embryonic lethality and the inability to exert indi-vidual or collective effects of SNARE proteins. These results are in accordance with the experimental outcomes of the aforementioned in vitro studies performed on SNARE proteins and the SNARE com-plex.

Conclusion Current research has provided a more progressive more logical mo-lecular model of SNARE-mediated membrane fusion. This recent out-burst of knowledge with regards to the SNAREs, the SNARE model and the SNARE mediated membrane fusion is due to new research both in vitro as well as in vivo. However, till now many things about this model remain mysterious. More research is required to ascertain the principle of membrane fusion utilized by the SNAREs. This new research would have far reaching effects as it can help us better un-derstand the phenomenon of membrane fusion. SNARE proteins can be used to develop artificial fusion systems which can be used for drug delivery in vivo. In addition to a greater understanding of the mechanistic of SNARE proteins and their effects lipid membranes, we need to explore the key regulatory mechanisms of in vitro membrane fusion, such as Ca++ and Rab-GTPase. More in vivo studies are re-quired in mammalian knockouts to better understand this mecha-nism in a living model.

Competing interests: The authors declare that no competing interests exist. Received: 1 November 2013 Accepted: 7 December 2013 Published Online: 7 December 2013



References 1. Jahn R, Lang T, Sudhof TC: Membrane fusion. Cell 2003, 112(4):519-533. 2. Lledo PM, Zhang X, Sudhof TC, Malenka RC, Nicoll RA: Postsynaptic membrane

fusion and long-term potentiation. Science (New York, NY) 1998, 279(5349):399-403.

3. Chen YA, Scheller RH: SNARE-mediated membrane fusion. Nature reviews Molecular cell biology 2001, 2(2):98-106.

4. Lin RC, Scheller RH: Mechanisms of synaptic vesicle exocytosis. Annual review of cell and developmental biology 2000, 16:19-49.

5. Duman JG, Forte JG: What is the role of SNARE proteins in membrane fusion? American journal of physiology Cell physiology 2003, 285(2):C237-249.

6. Rossi V, Banfield DK, Vacca M, Dietrich LE, Ungermann C, D'Esposito M, Galli T, Filippini F: Longins and their longin domains: regulated SNAREs and multifunctional SNARE regulators. Trends in biochemical sciences 2004, 29(12):682-688.

7. Weimbs T, Mostov K, Low SH, Hofmann K: A model for structural similarity between different SNARE complexes based on sequence relationships. Trends in cell biology 1998, 8(7):260-262.

8. Sollner T, Whiteheart SW, Brunner M, Erdjument-Bromage H, Geromanos S, Tempst P, Rothman JE: SNAP receptors implicated in vesicle targeting and fusion. Nature 1993, 362(6418):318-324.

9. Banerjee A, Kowalchyk JA, DasGupta BR, Martin TF: SNAP-25 is required for a late postdocking step in Ca2+-dependent exocytosis. The Journal of biological chemistry 1996, 271(34):20227-20230.

10. Lawrence GW, Foran P, Mohammed N, DasGupta BR, Dolly JO: Importance of two adjacent C-terminal sequences of SNAP-25 in exocytosis from intact and permeabilized chromaffin cells revealed by inhibition with botulinum neurotoxins A and E. Biochemistry 1997, 36(11):3061-3067.

11. Xu T, Binz T, Niemann H, Neher E: Multiple kinetic components of exocytosis distinguished by neurotoxin sensitivity. Nature neuroscience 1998, 1(3):192-200.

12. Blasi J, Chapman ER, Yamasaki S, Binz T, Niemann H, Jahn R: Botulinum neurotoxin C1 blocks neurotransmitter release by means of cleaving HPC-1/syntaxin. The EMBO journal 1993, 12(12):4821-4828.

13. Capogna M, McKinney RA, O'Connor V, Gahwiler BH, Thompson SM: Ca2+ or Sr2+ partially rescues synaptic transmission in hippocampal cultures treated with botulinum toxin A and C, but not tetanus toxin. The Journal of neuroscience : the official journal of the Society for Neuroscience 1997, 17(19):7190-7202.

14. Schiavo G, Poulain B, Rossetto O, Benfenati F, Tauc L, Montecucco C: Tetanus toxin is a zinc protein and its inhibition of neurotransmitter release and protease activity depend on zinc. The EMBO journal 1992, 11(10):3577-3583.

15. Hunt JM, Bommert K, Charlton MP, Kistner A, Habermann E, Augustine GJ, Betz H: A post-docking role for synaptobrevin in synaptic vesicle fusion. Neuron 1994, 12(6):1269-1279.

16. Poulain B, Rossetto O, Deloye F, Schiavo G, Tauc L, Montecucco C: Antibodies against rat brain vesicle-associated membrane protein (synaptobrevin) prevent inhibition of acetylcholine release by tetanus toxin or botulinum neurotoxin type B. Journal of neurochemistry 1993, 61(3):1175-1178.

17. Broadie K, Prokop A, Bellen HJ, O'Kane CJ, Schulze KL, Sweeney ST: Syntaxin and synaptobrevin function downstream of vesicle docking in Drosophila. Neuron 1995, 15(3):663-673.

18. Schulze KL, Broadie K, Perin MS, Bellen HJ: Genetic and electrophysiological studies of Drosophila syntaxin-1A demonstrate its role in nonneuronal secretion and neurotransmission. Cell 1995, 80(2):311-320.

19. Nickel W, Weber T, McNew JA, Parlati F, Sollner TH, Rothman JE: Content mixing and membrane integrity during membrane fusion driven by pairing of isolated v-SNAREs and t-SNAREs. Proceedings of the National Academy of Sciences of the United States of America 1999, 96(22):12571-12576.

20. Sutton RB, Fasshauer D, Jahn R, Brunger AT: Crystal structure of a SNARE complex involved in synaptic exocytosis at 2.4 A resolution. Nature 1998, 395(6700):347-353.

21. Lonart G, Sudhof TC: Assembly of SNARE core complexes prior to neurotransmitter release sets the readily releasable pool of synaptic vesicles. The Journal of biological chemistry 2000, 275(36):27703-27707.

22. Weber T, Zemelman BV, McNew JA, Westermann B, Gmachl M, Parlati F, Sollner TH, Rothman JE: SNAREpins: minimal machinery for membrane fusion. Cell 1998, 92(6):759-772.

23. Washbourne P, Thompson PM, Carta M, Costa ET, Mathews JR, Lopez-Bendito G, Molnar Z, Becher MW, Valenzuela CF, Partridge LD et al: Genetic ablation of the t-SNARE SNAP-25 distinguishes mechanisms of neuroexocytosis. Nature neuroscience 2002, 5(1):19-26.

24. Xue M, Zhang B: Do SNARE proteins confer specificity for vesicle fusion? Proceedings of the National Academy of Sciences of the United States of America 2002, 99(21):13359-13361.

25. McNew JA, Weber T, Parlati F, Johnston RJ, Melia TJ, Sollner TH, Rothman JE: Close is not enough: SNARE-dependent membrane fusion requires an active mechanism that transduces force to membrane anchors. The Journal of cell biology 2000, 150(1):105-117.

26. Novick P, Field C, Schekman R: Identification of 23 complementation groups required for post-translational events in the yeast secretory pathway. Cell 1980, 21(1):205-215.

27. Parlati F, McNew JA, Fukuda R, Miller R, Sollner TH, Rothman JE: Topological restriction of SNARE-dependent membrane fusion. Nature 2000, 407(6801):194-198.

28. Schoch S, Deak F, Konigstorfer A, Mozhayeva M, Sara Y, Sudhof TC, Kavalali ET: SNARE function analyzed in synaptobrevin/VAMP knockout mice. Science (New York, NY) 2001, 294(5544):1117-1122.

28 Icosapent ethyl: A novel drug for hypertriglyceridemia

Vol 2, No 1

Open Access Essay

Icosapent ethyl: A novel drug for hypertriglyceridemia Atta Abbas1, Farrukh R Ahmed2

Introduction Icosapent ethyl (IE) is a lipid regulating drug which was recently given a green signal from FDA. It is used as an adjunct drug along with diet control to decrease triglycerides (TG) in those patients who present with very high levels. It lowers the production and/or secre-tion of very low-density lipoprotein triglycerides (VLDL-TG) in liver and augments TG clearance from VLDL particles. The exact mecha-nism is still unknown. However, probable mechanisms consist of in-hibition of acyl-CoA and 1,2-diacylglycerol acyltransferase (DGAT); increased β-oxidation, decreased hepatic lipogenesis and increasing the activity of plasma lipoprotein lipase.

The drug is de-esterified throughout its journey after oral administra-tion and the active metabolite eicosapantaenoic acid (EPA) is ab-sorbed by means of the thoracic duct lymphatic system. It takes ap-proximately 5 hours for EPA to reach its peak plasma concentration following an oral dose. EPA has a mean volume of distribution of approximately 88 liters at steady-state and the bulk of EPA that cir-culates in plasma is normally integrated in triglycerides, cholesteryl esters, phospholipids and less than 1% is in the form of free un-es-terified fatty acid. Hence, more than 99% of EPA in un-esterified form is bound with plasma proteins.

Metabolism of EPA is carried out by the liver passing mainly through β-oxidation pathway analogous to dietary fatty acids. It splits the long carbon chain of EPA into acetyl coenzyme A, which is then used to release energy via Krebs cycle. However, EPA is also metabolized and eliminated through cytochrome P450-mediated pathway to a very little extent. The plasma elimination half-life (t1/2) of EPA at steady state is approximately 89 hours and it does not go through the renal pathway of excretion [1-4].

The drug has been studied at 4g/day dose in conjunction with omeprazole 40mg, rosiglitazone 4mg, atorvastatin 80mg/day and warfarin 25mg which are typical substrates of cytochrome P450 en-zymes, and no drug-drug interactions were observed. The drug, however, does interact with anti-coagulants. In addition, a study con-ducted on the efficacy and safety of IE on adults having very high levels of fasting triglycerides concluded that the drug had remarka-bly reduced lipoproteins and undesired lipids in the target popula-tion. IE has also been subjected to a 2-year rat carcinogenicity study and a 6-month transgenic mice carcinogenicity study and both have

1University of Sunderland, England, United Kingdom 2Ziauddin University, Pakistan Correspondence: Atta Abbas Email: [email protected]

reported no drug related neoplasm. It has also been subjected to in vivo mouse micronucleus assay and has not been found to be muta-genic. In lactating rats, the drug is excreted in the milk, reaching levels that are 6-14 times those in plasma. However, in rat fertility test, increased anogenital distance in female pups and increase cer-vical ribs in males have been observed by exposure to the highest strength of the dose which is seven times the human systemic expo-sure. The most common adverse effect of IE is arthralgia, which has an occurrence rate of greater than 2%. The drug may also prolong bleeding time. Periodic monitoring is required in patients receiving anti-platelet therapy as well as in patients having hepatic impair-ment. The drug is contraindicated in patients who have a history of hypersensitivity to fish and/or shellfish [5-8]. The daily dose of IE is 4g and can be in the form of two capsules twice daily along with food. The capsule should be swallowed, but not chewed, crushed or broken [9].

Discussion The safety and efficacy of IE is a case of ambiguity for nursing moth-ers, since the drug is excreted in breast milk and the effect of that is still undetermined; therefore, the patient should exercise caution es-pecially those having borderline high triglyceride levels. Additional studies of the drug are required to ascertain the risk of pancreatitis and to establish cardiovascular mortality and morbidity. The phar-macokinetics of the drug in patients with renal and hepatic impair-ment is not yet known. However, it is advised that the ALT and AST levels be monitored regularly during the therapy as the drug is elim-inated through hepatic route. Recently, an FDA approved study (RE-DUCE-IT) was initiated to evaluate the drug’s ability to reduce cardi-ovascular events in high-risk patients having elevated triglyceride levels and who were already on statins. The study will end in Novem-ber, 2016. As of September 2013 over 6000 patients have been en-rolled in the study at 400 trials sites/centers spanned in over 11 coun-tries.

Conclusion In short, although a host of studies have been carried out on IE which has given it an approved status for populations having high triglyc-eride levels, but it has yet to undergo major trials in order to ensure the safety of the drug in all segments of the patient population hav-ing various manifestations of dyslipidemia.

Abstract Icosapent ethyl is a lipid regulating drug which was recently given a green signal from FDA. It is used as an adjunct drug along with diet control to lower triglycerides in those patients who present with very high levels. It lowers the production and/or secretion of very low-density lipoprotein triglycerides (VLDL-TG) in liver and augments triglyceride clearance from VLDL particles. (El Med J 2:1; 2014) Keywords: Icosapent ethyl, Hypertriglyceridemia, Very low-density lipoproteins

Abbas A, Ahmed FR 29


Competing interests: The authors declare that no competing interests exist. Received: 29 October 2013 Accepted: 9 December 2013 Published Online: 9 December 2013

References 1. Amarin Announces FDA Approval of Vascepa(TM) (icosapent ethyl)

[http://files.shareholder.com/downloads/AMRN/0x0x586350/7f7dbe6f-10f4-477a-98a2-1439493b53b5/AMRN_News_2012_7_26_General_Releases.pdf]

2. Highlights of prescribing information: VASCEPA™ (icosapent ethyl) [http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/202057S000lbl.pdf]

3. Food and drug authority. FDA; 2012. Monthly Approvals [http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Reports.MonthlyApprovalsAll]

4. Icosapent ethyl capsules (Vascepa™) approved in US as adjunct to diet to reduce triglyceride levels in patients with severe hypertriglyceridaemia [http://www.nelm.nhs.uk/en/NeLM-Area/News/2012---July/30/Icosapent-ethyl-capsules-Icosapentethyl approved-in-US-as-adjunct-to-diet-to-reduce-triglyceride-levels-in-patients-with-severe hypertriglyceridaemia-/]

5. Bays HE, Braeckman RA, Ballantyne CM, Kastelein JJ, Otvos JD, Stirtan WG, Soni PN: Icosapent ethyl, a pure EPA omega-3 fatty acid: effects on lipoprotein particle concentration and size in patients with very high triglyceride levels (the MARINE study). Journal of clinical lipidology 2012, 6(6):565-572.

6. Wood SJ, Cocchi L, Proffitt TM, McConchie M, Jackson GD, Takahashi T, Pantelis C, McGorry PD, Berger GE: Neuroprotective effects of ethyl-eicosapentaenoic acid in first episode psychosis: a longitudinal T2 relaxometry pilot study. Psychiatry research 2010, 182(2):180-182.

7. Ballantyne CM, Bays HE, Kastelein JJ, Stein E, Isaacsohn JL, Braeckman RA, Soni PN: Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). The American journal of cardiology 2012, 110(7):984-992.

8. Bays HE, Ballantyne CM, Kastelein JJ, Isaacsohn JL, Braeckman RA, Soni PN: Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] trial). The American journal of cardiology 2011, 108(5):682-690.

9. Prescribing information for Vascepa TM. Amarin Pharma Inc; 2011. [http://cerealkiller.it/wp-content/uploads/ICOSAPENT ETHYL_label.pdf]

30 Extensive endomyocardial calcification of unknown cause

Vol 2, No 1

Open Access Letter to Editor

Extensive endomyocardial calcification of unknown cause: a rare manifestation of left ventricular non-compaction? Ahmed Bashir1, Richard Paul Steeds1

Case Description A 44 year old female complained of severe headache associated with sudden onset of a visual field defect, confirmed by ophthalmology to be due to an embolic infarct within the superotemporal circula-tion of the right eye. At the age of 18, the patient had suffered a non-disabling stroke soon after starting an oral contraceptive. She went on to have three children by normal vaginal delivery without com-plications, although all pregnancies were covered by subcutaneous heparin. Following her final pregnancy over 15 years ago, she was incidentally found to have extensive endomyocardial calcification on CT, which was performed to investigate single episode of hemopty-sis. She remained under follow-up on an annual basis without further clinical event until her current presentation when she was started on warfarin and lisinopril.

The patient reported taking citalopram, but has not received any other pharmacotherapy in the intervening years. She has no other past medical history of note, no history of major trauma and has no risk factors for coronary artery disease. There is no history of family illness or inherited disease. She has never used recreational drugs or been exposed to industrial dust or toxins. Her husband works in property management and the patient has been a housewife living in a rural environment all her adult life.

Clinical examination was unremarkable. Her resting 12-lead ECG showed sinus rhythm with left axis deviation and left bundle branch block. Investigations on this admission included normal full blood count, clotting (including pro-thrombotic screen), serum electro-lytes, liver function tests, serum calcium, magnesium and phosphate, serum immunoglobulins and protein electrophoresis, 25-hydroxy-vitamin D, 24-hour urine calcium excretion, ACE levels, thyroid func-tion tests, negative autoimmune profile (ANA, ENA, ANCA, comple-ment titers, RA latex and anticardiolipin antibodies for IgG and IgM), negative Bence Jones urinalysis and negative HIV test. Her total cho-lesterol was 5.9 mol/L and CRP was 42 mg/L. Coronary angiography was normal.

Transthoracic and transesophageal echocardiography confirmed a bicuspid aortic valve with fused left and right coronary cusps with

1Queen Elizabeth Hospital, Birmingham, United Kingdom Correspondence: Ahmed Bashir Email: [email protected]

no aortic stenosis and mild aortic regurgitation. The left ventricle was normal in size with gross calcification throughout the endocardium (Figure 1), combined with extensive mobile and sessile thrombus. The right heart was normal. Cardiac MRI (CMR) confirmed normal left ventricular size with mild reduction in systolic function and normal left ventricular mass. There was marked myocardial thinning with hy-pertrabeculation of the left ventricular apex and extensive signal voids due to calcification attached to the distal end of the trabecu-lation (Figure 2). There was no evidence of late enhancement on gadolinium imaging. A whole body CT confirmed multiple foci of calcification within the left ventricular endomyocardium (Figure 3) but there was no evidence of ectopic calcification anywhere else out-side the heart. This extensive endomyocardial calcification was also demonstrated on fluoroscopy (Figure 4). Her three children had nor-mal 12-lead ECGs and normal transthoracic echocardiography.

Abstract We present a case of a 44 year old female who presented with a second episode of embolic stroke. She was noted to have extensive endomyocardial calcification on computed tomography. Cardiac MRI (CMR) showed myocardial thinning with hypertrabeculation of the left ventricular apex and extensive signal voids due to calcification attached to the distal end of the trabeculation. She was extensively investigated to find out the etiology of endomyocardial calcification but no cause of either metastatic or dystrophic calcification was found. We believe this may reflect a variant of left ventricular non-compaction (LVNC) in view of the CMR findings. Association between extensive endomyocardial calcification and left ventricular non-compaction has not been reported in literature before. (El Med J 2:1; 2014) Keywords: Endomyocardial Calcification, Ventricular Non-compaction

Figure 1: Mid-esophageal 4 chamber view showing gross intracavity calcification and multiple mobile masses, consistent with partly calcified thrombus (arrow).

Figure 2: CT scan chest showing multiple foci of calcification related to the LV endo-myocardium extending into the left AV groove where some of this is also epicardial.

Figure 3: Cardiac MRI vertical long axis view showing marked myocardial thinning with hyper trabeculation of the left ventricle and extensive calcification attached to the distalends of the this trabeculation.

Figure 4: Fluoroscopy showing extensive endomyocardial calcification

Bashir A, Steeds R 31


Discussion and Conclusion Endomyocardial calcification may be either of metastatic or endo-crine origin, due to significant disturbances in calcium and phos-phate metabolism, or more commonly dystrophic, which is second-ary to direct myocardial damage [1]. Metastatic or endocrine calcifi-cation that involves the heart is characterized by deposits elsewhere. Dystrophic calcification is usually secondary to ischemic damage, alt-hough in this case, the patient had no relevant history, a normal cor-onary angiogram and no evidence of late enhancement on CMR [2]. Less common causes of dystrophic calcification include infection (usually tuberculosis), endomyocardial fibro-elastosis, or local tumor infiltration which are unlikely given the general well-being of the pa-tient and the longevity of the documented calcification. One hypoth-esis is that this may reflect a variant of left ventricular non-compac-

tion (LVNC) in view of the CMR findings, although an association with extensive endomyocardial calcification has not been reported in lit-erature before.


References 1. van Kruijsdijk RC, van der Heijden JJ, Uijlings R, Otterspoor LC: Sepsis-related

myocardial calcification. Circulation Heart failure 2011, 4(5):e16-18. 2. El-Bialy A, Shenoda M, Saleh J, Tilkian A: Myocardial calcification as a rare cause

of congestive heart failure: a case report. Journal of cardiovascular pharmacology and therapeutics 2005, 10(2):137-143.

32 Pseudoaneurysms of mitral-aortic intervalvular fibrosa…

Vol 2, No 1


Detection of multiple pseudoaneurysms of mitral-aortic intervalvular fibrosa by multislice computed tomography in a patient with aortic valve replacement Melike Rusen Metin1, Hasan Aydın2, Evrim Özmen1, Ömer Faruk Ateş1

Introduction Mitral-aortic intervalvular fibrosa (MAIF) pseudoaneurysms are a rare entity that may complicate mitral valve surgery and management of infective endocarditis and thorax trauma [1, 2]. Anginal symptoms caused by direct compression to left coronary artery may be the ini-tial manifestation in such patients. They may also be seen as a pul-satile cavity enlarging during systole in echocardiography or can be incidentally detected during cardiac computerized tomography (CT) angiography.

MAIF pseudoaneurysms may result in disastrous consequences in-cluding fistulisation, valve dysfunction, pericardial rupture and mass effect to the adjacent organs [3, 4]. To the best of our knowledge, detection of multiple pseudoaneurysms by using multislice CT (MSCT) has not yet been documented. Here we present the first re-ported case of multiple pseudoaneurysms detected by 64 slices CT.

Case Presentation and Technique Due to severe aortic insufficiency, a 40-year old male underwent aor-tic valve replacement therapy and postoperative follow-up was per-formed in our clinic. One year after the procedure, he complained of shortness of breath with increased exertion for two months when he visited our clinic for routine MSCT angiography. Total calcium score was 0, no coronary artery pathology was detected. Posterior de-scending artery and posterolateral artery originated from right coro-nary artery and normal interventricular septum thickness was ob-served during MSCT angiography. Metallic aortic valve implant was seen at aortic valve level. At this level as well as inferior and superior adjacent levels, numerous pseudodiverticuli were seen, with a maxi-mum diameter of 10 mm (figures). Multi-planar reconstruction (MPR) method was performed with MSCT to demonstrate pseudodiverticuli (figures) and they were evaluated dynamically. Dynamic evaluation failed to show significant change in size of those diverticuli, but this is thought to be caused by the milimetric dimensions

Discussion and Conclusion MAIF pseudoaneurysm is a rare but life threatening condition that is believed to be caused by secondary injury at the fibrous tissue ex-tending between mitral and aortic valves [5]. Therefore, although

1Ankara Ataturk Education and Research Hospital, Turkey 2Dışkapı Yıldırım Beyazıt Education and Research Hospital, Turkey Correspondence: Hasan Aydın Email: [email protected]

mostly solitary, multiple lesions may occur depending upon the site and severity of the injury.

These pseudoaneurysms are mostly detected as cavities having pseudolumens and expanding during systole often spotted during

Abstract Mitral-aortic intervalvular fibrosa pseudoaneurysms are a rare entity that may complicate mitral valve surgery and the management of infective endocarditis and thoracic trauma. They may result in fistulisation, valve dysfunction, pericardial rupture and mass effect to the adjacent organs. Here we present a patient of aortic insufficiency with aortic valve replacement and multiple pseudoaneurysms, detected by 64 slices CT. (El Med J 2:1; 2014) Keywords: Multislice Computerized Tomography, Pseudoaneurysm, Aortic Valve Replacement

Figure 1 (a) Figure 1 (b)


Figure 3


Metin MR, Aydın H, Özmen E et al 33


transesophageal and transthoracic echocardiography. Several au-thors have reported that echocardiography has 90% sensitivity in detecting these lesions, but localization, size and quantity is essen-tial in diagnosis and small pseudoaneurysms may be ignored when echocardiography is performed. MSCT with simultaneous electrocar-diography is a practical method in diagnosis and detection of site and size of the lesions. It has several advantages including high spa-tial resolution, ability to observe pulsatility with showing dynamic cardiac cycle and post-processing 3-D evaluation. It is also sug-gested that MCST may be helpful in follow-up of patient with valve replacement. Competing interests: The authors declare that no competing interests exist. Received: 17 November 2013 Accepted: 9 January 2014 Published Online: 9 January 2014

References 1. David TE, Kuo J, Armstrong S: Aortic and mitral valve replacement with

reconstruction of the intervalvular fibrous body. The Journal of thoracic and cardiovascular surgery 1997, 114(5):766-771; discussion 771-762.

2. Espinosa-Caliani JS, Montijano A, Melero JM, Montiel A: Pseudoaneurysm in the mitral-aortic intervalvular fibrosa. A cause of mitral regurgitation. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 2000, 17(6):757-759.

3. Sousa L, Branco L, Abreu J, Rasteiro R, Salomao S, Antunes AM: [A pseudoaneurysm of the mitral-aortic intervalvular fibrosis after aortic valve replacement]. Revista portuguesa de cardiologia : orgao oficial da Sociedade Portuguesa de Cardiologia = Portuguese journal of cardiology : an official journal of the Portuguese Society of Cardiology 1999, 18(2):177-178.

4. Delgado C, Barturen F: [Pseudoaneurysm of the mitral-aortic fibrosa secondary to the partial detachment of a mechanical aortic prosthesis]. Revista espanola de cardiologia 1999, 52(5):348-350.

5. Grimaldi A, Ho SY, Pozzoli A, Sora N, Taramasso M, Benussi S, La Canna G, Alfieri O: Pseudoaneurysm of mitral-aortic intervalvular fibrosa. Interactive cardiovascular and thoracic surgery 2011, 13(2):142-147.

34 Cerebroprotein hydrolysate in traumatic brain injury

Vol 2, No 1


Cerebroprotein hydrolysate in traumatic brain injury Sagar Karia1, Priyanka Thukral Mahajan1, Nilesh Shah1, Sushma Sonavane1, Avinash De Sousa1

Introduction Traumatic brain injuries (TBI) are a steadily increasing and major cause of morbidity, mortality, and loss of productivity in resource-limited settings, particularly among younger age groups [1]. CNS in-juries are divided into two main categories: primary, which occur (mainly) at the moment of a trauma, and secondary, that develop after the initial injury. The secondary injury process involves exces-sive synthesis of nitric oxide and oxidative stress, microglia activa-tion, local inflammation, disturbance of microcirculation, blood-brain barrier dysfunction and the most recently acknowledged “delayed mechanisms of cell death”. This leads to disastrous consequences of neuronal necrosis, neuronal apoptosis, scar and/or cyst hygroma for-mation, with further pathogenic effects on CNS tissue such as demy-elination and disruption of morpho-functional nerve pathways [2]. Secondary brain injury is the leading cause of hospital deaths after TBI [3]. Thus, minimizing the secondary damage cascade may result in maximizing post-injury favorable evolution/recovery, including more rapid and consistent neuro-rehabilitative outcomes [3].

Cerebroprotein hydrolysate (CH) is a unique neurotrophic peptider-gic mixture produced by standardized enzymatic breakdown of lipid-free porcine brain proteins [4]. It has unique neurotrophic activity that enhances neurogenesis, neuronal survival, provides neuromod-ulatory action, increases neuronal plasticity and neuronal repair and has neuro-immunotrophic actions [5]. It has been found in animal studies that early intervention with cerebrolysin reduces permeabil-ity changes in blood-brain and blood-cerebrospinal fluid barriers, at-tenuates brain pathology and brain edema, and mitigates functional deficits caused by TBI [6]. It has been found useful in improving out-comes in patients of moderate and severe head injury [7]. It im-proves brain bioelectrical activity i.e. reduced EEG ratio by increasing fast frequencies and reducing slow activities and also enhanced cog-

1Lokmanya Tilak Municipal Medical College, India Correspondence: Avinash De Sousa Email: [email protected]

nitive performance in tasks evaluating attention and memory func-tions in post-acute TBI patients [8]. Here we report a case of trau-matic brain injury where CH was found helpful in improvement of patient’s condition.

Case Presentation A 50 year old male had a road traffic accident and suffered from head injury. He did not have any other bone fractures or other serious in-juries. Computed tomography of the brain showed right temporal intraparenchymal hemorrhage, right frontal hemorrhagic contusion, subarachnoid hemorrhage in right temporo-parietal region and an undisplaced linear fracture of right squamous temporal bone. After gaining consciousness, the patient did not remember anything about the events that had transpired. He would complain of head-ache in frontal and right temporal regions. He started having diffi-culty in remembering names and would forget about recent events. He also had difficulty in walking and standing by himself and diffi-culty in maintaining balance. He started having difficulty in taking self-care as he had to be told to brush and bathe, and had to be taken to the bathroom. On mental status examination, the patient had impairments in immediate and recent memory but remote memory was intact. Confabulation was present as he would make up things to fill the gaps in memory and would tell wrongly what he had eaten previous night and who had come to meet him etc. Mini-Mental Status Examination (MMSE) score was 12/30. He was diag-nosed as having neurocognitive deficits post-head injury. All his rou-tine investigations were within normal limits.

A neuro-medicine opinion was sought and they gave a diagnosis of anterograde amnesia secondary to contusional injury, while recom-mending to observe the patient for recovery of memory spontane-ously. Neurosurgery opinion was also taken and they too advised to observe for further improvement or deterioration. He was receiving

Abstract Introduction: Traumatic brain injury (TBI) is the most common cause of death and disability worldwide, especially in young people. Cerebroprotein hydrolysate (CH) exhibits complex neuroprotective and neurotrophic actions and is thus useful in patients of TBI. Here we report a case of TBI, where CH was found helpful in improving the patient’s condition. Case Presentation: A 50 year old male had a road traffic accident and suffered from head injury. Computed tomography of the brain showed right temporal intra parenchymal hemorrhage, right frontal hemorrhagic contusion, subarachnoid hemorrhage in right temporo-parietal region and an undisplaced linear fracture of right squamous temporal bone. After gaining consciousness the patient did not remember anything, and suffered cognitive deficits. Anterograde amnesia secondary to contusional injury was diagnosed, and patient observation for spontaneous recovery of memory was recommended. Even after 20 days post-accident, there was not much improvement in the patient’s condition. Relatives were given an option of trying out injectable CH, which they agreed. CH was started and the patient started showing signs of improvement. On the night prior to the day of discharge, he suffered from right sided hemiplegia whose cause could not be ascertained. Conclusion: Cerebroprotein hydrolysate is a medication that acts at the brain level and provides us with an effective tool for improving levels of activities of daily living in patients of head injury, thereby decreasing their dependence on caregivers. However, further randomized, controlled trials involving large populations are required. (El Med J 2:1; 2014) Keywords: Cerebroprotein hydrolysate, Traumatic brain injury

Karia S, Mahajan PT, Shah N et al 35


Tab. Eptoin (100mg) thrice a day and Tab. Citicholine (500mg) + Tab. Piracetam (800mg) combination thrice a day in the ward.

Even after 20 days post-accident, there was not much improvement in the patient’s condition. Relatives were given an option of trying out injectable CH which they agreed to. CH was started at a dose of 60mg intravenous slowly over 1hr. After 11th consecutive injection he started receiving 30mg intramuscular of cerebroprotein as an in-tramuscular preparation which was available in the market.

His MMSE score improved to 21/30 after 7th injection and to 26/30 after 20th injection. He also started showing improvements clinically. He started feeding by himself, taking self-care, would be able to stand and walk on his own. He started conversing normally. On the night prior to the day of discharge, he suffered from right sided hem-iplegia and got transferred to medicine ward. Cause of the same could not be ascertained.

Discussion Traumatic brain injury causes functional disability in the patient and only a handful of medications are available for its management. As such, CH may prove to be beneficial in such patients. A complex study of cognitive and emotional status, levels of serum serotonin and brain-derived neurotrophic factor performed in 72 patients with acute TBI, with a special focus on middle brain injuries, treated with cerebrolysin found that it promotes activation of neurotrophic pro-cesses and improves outcomes of closed craniocerebral injury [9]. A double-blind, placebo-controlled, randomized study showed that cerebrolysin improves the cognitive function of patients with mild TBI at 3rd month after injury, especially for long-term memory and drawing function tested on MMSE and Cognitive Abilities Screening Instrument (CASI) scores [10].

Conclusion Cerebroprotein hydrolysate is a medication that acts at the brain

level and provides us with an effective tool for improving levels of activities of daily living in patients of head injury and decreasing their dependence on caregivers though further trials in large populations and clinical trials is warranted.

Competing interests: The authors declare that no competing interests exist. Received: 3 November 2013 Accepted: 7 December 2013 Published Online: 7 December 2013

References 1. Gururaj G: Epidemiology of traumatic brain injuries: Indian scenario. Neurol

Res 2002;24(1):24-8. 2. Onose G, Mureşanu DF, Ciurea AV, Daia Chendreanu C, Mihaescu AS, et al:

Neuroprotective and consequent neurorehabilitative clinical outcomes, in patients treated with the pleiotropic drug cerebrolysin. J Med Life 2009;2(4):350–60.

3. Marshall LF, Gautille T, Klauber MR, et al: The outcome of severe closed head injury. J Neurosurg 1991;75:S28–36.

4. Hartbauer M, Hutter-Paier B, Skofitsch G, Windisch M: Antiapoptotic effects of the peptidergic drug cerebrolysin on primary cultures of embryonic chick cortical neurons. J Neural Transm 2001;108(4):59-73.

5. Cerebrolysin - A Unique Treatment Option for Alzheimer’s Disease. [http://www.touchbriefings.com/pdf/28/gh031_t_Ebewe.pdf]

6. Sharma HS, Zimmermann-Meinzingen S, Johanson CE: Cerebrolysin reduces blood-cerebrospinal fluid barrier permeability change, brain pathology, and functional deficits following traumatic brain injury in the rat. Ann N Y Acad Sci 2010;1199:125-37.

7. Wong GK, Zhu XL, Poon WS: Beneficial effect of cerebrolysin on moderate and severe head injury patients: result of a cohort study. Acta Neurochir Suppl 2005;95:59-60.

8. Alvarez XA, Sampedro C, Pérez P, Laredo M, Couceiro V, Hernández A, et al: Positive effects of cerebrolysin on electroencephalogram slowing, cognition and clinical outcome in patients with postacute traumatic brain injury: an exploratory study. Int Clin Psychopharmacol 2003;18(5):271-8.

9. Selianina NV, Karakulova IV: [The effect of neurotrophic treatment on the activation of reparative processes in patients with acute traumatic brain injury.] Zh Nevrol Psikhiatr Im S S Korsakova. 2012;112(5):46-9.

10. Chen CC, Wei ST, Tsaia SC, Chen XX, Cho DY: Cerebrolysin enhances cognitive recovery of mild traumatic brain injury patients: double-blind, placebo-controlled, randomized study. Br J Neurosurg 2013 [Epub ahead of print].

36 Type II diabetes mellitus and Parkinson’s disease…

Vol 2, No 1


The association between type II diabetes mellitus and Parkinson’s disease: A case report Atta Abbas1

Introduction Diabetes mellitus (DM), if uncontrolled, can lead to deteriorating health consequences. One of the manifestations of DM is related to the brain: high blood sugar levels can damage the brain and lead to depression [1, 2]. Previous studies have pointed towards a link be-tween DM and Parkinson’s disease (PD). For example, a study re-ported that patients who suffered from DM were diagnosed with PD at a later stage in their life, with a rate of diagnosis of PD with DM being 3.6 as opposed to 2.1 without DM [3]. Other studies have fur-ther elaborated the link [4]. The present case study is based on a patient of type II DM who was diagnosed with PD recently.

Case Presentation This case report is based on a male patient of 65 years suffering from DM over the last 7 years. The patient was a smoker and also con-sumed alcohol. He had a positive family history of DM. In terms of medication adherence, it was observed that the patient did not com-ply with the medications and therefore had uncontrolled type II DM. Apart from DM, the patient did not have any major co-morbidity, but he did complained of depressed mood. The records revealed that the patient’s medication therapy was altered in the beginning and the dose of metformin was adjusted according to the blood glucose targets. Type II DM is a known risk factor for cerebrovascular and cardiovascular complications which warrants effective management from the physician and the patient.

Management The main goal of management was to lower the blood glucose and bring it in the recommended target range, or as close as possible. The NICE guidelines recommend a target blood glucose range of 90-130mg/dl or HBA1c<7% for patients with DM [5]. Secondly, focus is placed on the prevention of microvascular and macrovascular com-plications associated with the disease. Calculation of cardiovascular risk has also been recommended [5]. The medication regimen for our patient included a 2nd generation sulphonyl urea, Glicazide 80mg

1University of Sunderland, England, United Kingdom. Correspondence: Atta Abbas Email: [email protected]

tablet BD, initially. Later, after the diagnosis of PD, a biguanide Met-formin 1000mg OD modified release tablet was added to the therapy and the dose of Glicazide was reduced to 40mg BD. The EASD and NICE guidelines recommend the use of metformin as first-line treat-ment, or combination of metformin + 2nd generation sulphonyl urea for management of type II DM [5]. Metformin is also reported to re-duce the risk of PD in patients who are diagnosed with DM [6]. The goal of management of Parkinson’s disease was to control the motor and non-motor signs and symptoms of the disease for maximum time and to minimize the adverse events associated with drug ther-apy. Although the disease is lifelong and tends to worsen over time, pharmacological intervention can ameliorate the stiffness of the body and improve motor functions and mobility. Increasing disease acceptance by patient and treating associated illnesses such as de-pression may cause improvement in the overall quality of life [7].

Parkinson’s therapy consisting of Co-careldopa 62.5mg OD was initi-ated and continued without any alteration in therapy. This drug is a combination of Carbidopa and Levodopa and is a gold standard in treatment of Parkinsonism and has also been recommended by AAN guidelines for the treatment of non-motor symptoms of Parkinson-ism [7]. Co-careldopa is associated with many adverse effects such as depression, GI tract disturbances and, rarely, orthostatic hypoten-sion [7, 8]. Renal function was regularly checked for our patient, and symptoms of hypoglycemia such as lethargy and general body weak-ness were monitored.

Discussion The care plan for type II DM is prepared using an empirical approach to the disease. The NICE and EASD guidelines recommend a set of approaches in devising a care plan for the management of the dis-ease. By setting individualized targets and glucose lowering thera-pies, help can be provided in devising a treatment strategy which will be individualized and sensitive to that particular patient. Dietary modifications are must for patients with DM, such as reducing the

Abstract Introduction: Diabetes mellitus (DM), if uncontrolled, can lead to deteriorating health consequences. One of the manifestations of DM is related to the brain; high blood sugar levels can damage the brain and lead to depression. Recently, it was reported that it can also lead to Parkinson’s disease (PD). However, no study has reported the actual association during practice in a clinical setting. The present case study is based on a patient of type II DM who was diagnosed with PD in a hospital in England. Case Presentation: The case report is based on a male patient of 65 years suffering from DM for the last 7 years. The pharmaceutical care was focused on the management of DM. The main goal of management was to lower the blood glucose and bring it as close as possible to the recommended target range, and to prevent microvascular and macrovascular complications associated with the disease. Later, PD was diagnosed and the goal of management was to control motor and non-motor signs and symptoms of the disease and to minimize the adverse events associated with drug therapy. Conclusion: This report presents a case with an association between DM and PD. By following the guidelines, the risk of morbidity caused by PD can be lowered in patients who are diagnosed with DM. (El Med J 2:1; 2014) Keywords: Metabolic disorders, Diabetes mellitus, Parkinson’s disease

Atta Abbas 37


carbohydrates intake along with saturated fats. It is highly recom-mended to ensure incorporation of exercises such as jogging and walking in daily routine as these activities have been shown to effec-tively lower down cholesterol and blood glucose. Since this is a case of DM which has an established link with cardiovascular and meta-bolic complications, reduction in cardiovascular and thromboembo-lism risks are very important. Special emphasis should be placed on monitoring blood glucose and blood cholesterol regularly and rou-tine follow up with a GP must be ensured. Routine checkup of feet and eyes is also recommended. The counseling points for patient include education about the disease and its management and social aspects such as limiting alcohol consumption and smoking cessation [5, 6].

For PD, the care plan contains pharmacological and social approach to effectively managing the disease. The drug therapy should be continued with strict compliance and routine follow up to review the improvements in signs and symptoms, and the therapy should be modified accordingly. The patient should be encouraged to work with an occupational therapist to improve/manage any difficulty in movements. Over the course of the disease, it is very important to take the patient’s caregivers on board in order to educate and give the patient moral support and confidence and also to educate them on managing the patient at home.

The failure of prior assessment of Parkinson’s disease in this case has exposed a loop hole in the health care strategies and therefore needs revision. The inclusion of metformin in the therapy of the patient should have been done initially to get a double impact on managing DM and PD, but this again resulted from not following the guide-lines. In this case, patient education, medication and non-pharmaco-logical therapy and lifestyle modifications, coupled with regular as-sessment, can lead to better control of the medical condition as a whole and may improve the quality of life in the long run.

Conclusion This report presents a case with an association between DM and PD. By following the guidelines, the risk of morbidity caused by PD can be lowered in patients who are diagnosed with DM.

Consent: Prior to recording the information, an informed, written consent was obtained from the patient. Competing interests: The author declares that no competing interests exist. Received: 18 October 2013 Accepted: 30 November 2013 Published Online: 30 November 2013

References 1. Cereda E, Barichella M, Pedrolli C, Klersy C, Cassani E, Caccialanza R, Pezzoli G:

Diabetes and risk of Parkinson's disease: a systematic review and meta-analysis. Diabetes care 2011, 34(12):2614-2623.

2. Sandyk R: The relationship between diabetes mellitus and Parkinson's disease. The International journal of neuroscience 1993, 69(1-4):125-130.

3. Sun Y, Chang YH, Chen HF, Su YH, Su HF, Li CY: Risk of Parkinson disease onset in patients with diabetes: a 9-year population-based cohort study with age and sex stratifications. Diabetes care 2012, 35(5):1047-1049.

4. Hu G, Jousilahti P, Bidel S, Antikainen R, Tuomilehto J: Type 2 diabetes and the risk of Parkinson's disease. Diabetes care 2007, 30(4):842-847.

5. TYPE 2 DIABETES | National clinical guideline for management in primary and secondary care (update) [http://www.nice.org.uk/nicemedia/live/11983/40803/40803.pdf]

6. Wahlqvist ML, Lee MS, Hsu CC, Chuang SY, Lee JT, Tsai HN: Metformin-inclusive sulfonylurea therapy reduces the risk of Parkinson's disease occurring with Type 2 diabetes in a Taiwanese population cohort. Parkinsonism & related disorders 2012, 18(6):753-758.

7. Parkinson Disease [http://emedicine.medscape.com/article/1831191-overview]

8. Co-Careldopa | Side effects [http://www.nhs.uk/medicine-guides/pages/medicinesideeffects.aspx?condition=parkinson%60s+disease&medicine=co-careldopa&preparation=co-careldopa+50mg%2f200mg+modified-release+tablets]

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viii

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ix

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El Mednifico Journal

C2 Block R, North Nazimabad, Karachi 74700, Sindh, Pakistan

[email protected] [email protected] [email protected]

http://www.mednifico.com/index.php/elmedj http://www.linkedin.com/profile/view?id=222294632 https://www.facebook.com/elmednifico

Company Profile Mednifico Publishers, which started as an entity run by medical students, has now evolved into an organization that

has a target audience that traverses a wide range of health professionals. The organization is responsible for publishing

“El Mednifico Journal” (EMJ). It also has to its credit, “Blogemia” and “Pakistan Research Evolution Scientific Society”

(PRESS). The main target audience for these products, as previously mentioned, is students. The word "students"

encompasses medical, pharmaceutical, dental, nursing and allied students, residents, fellows, professors and beyond.

This notion is consistent with the fact that health professionals never leave the learning curve during their lifetime.

El Mednifico Journal http://www.mednifico.com/index.php/elmedj

El Mednifico Journal (ISSN: 2307-7301) is an open access, quarterly, peer-reviewed journal from Pakistan that aims to

publish scientifically sound research across all fields of medicine. It is the first journal from Pakistan that publishes

researches as soon as they are ready, without waiting to be assigned to an issue.

The journal has certain unique characteristics:

EMJ is one of the first journals from Pakistan that publishes articles in provisional versions as soon as they are

ready, without waiting for an issue to come out. These articles are then proofread, copyedited and arranged

into four issues per volume and one volume per year

EMJ is one of the very few OJS based journals from Pakistan

EMJ is one of the few journals that provides incentives to students and undergraduates

Blogemia http://blogemia.com/

Blogemia deals with providing proper exposure and spreading awareness among medical-related individuals, by

keeping them updated regarding the latest interventions and techniques being currently deployed in health related

activities around the world. Niches include, but are not limited to medical education, public health and technological

advancements.

Pakistan Research Evolution Scientific Society http://press.net.pk/

Pakistan Research Evolution Scientific Society (PRESS) is a venture undertaken to inculcate a sense of research in

Pakistani medical and allied students and professionals, by promoting active indulgement in healthy investigative

practices. We at PRESS firmly believe that a true research culture cannot be guaranteed in the absence of active

involvement. In Pakistan, research is more of an insignificant formality and is placed lower down in the list of priorities.

PRESS has, therefore, been established to shun this very mentality. PRESS has published a number of manuscripts

recently in peer-reviewed and Pubmed-indexed journals throughout the world.









Sponsorship Proposal We are currently looking for sponsors for El Mednifico Journal. Pharmaceutical companies, publishers, representatives

and retailers are welcome to apply. We also accept advertisements on both the website and the print version. Expected

print audience ~ 1000; Current online audience ~ 15,000/month from Pakistan, India, Saudi Arabia, Iran, Turkey,

Bangladesh, Nepal, Sri Lanka, UAE, Egypt, Germany, UK, USA, China and other countries.

We have flexible options for advertisement and sponsorship. Advertisements are placed on both the website and the

print version. Sponsorship results in the placement of the sponsor’s logo on both the website and the print version.

Sponsors automatically get free advertisement placements on the websites and print versions.

Send your proposals at [email protected].

Platinum Sponsor Platinum sponsorship is awarded to a single entity placing the highest bid

Results in a “Platinum Sponsor:” followed by the sponsor’s logo next to the journal’s logo on the website, and

on the front cover of print version

Choice of advertisement on the inside front cover, back cover or inside back cover

Header advertisement on website

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Results in a “Gold Sponsors:” followed by the sponsor’s logo on the homepage of the website, and on the

first page of print version

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first page of print version

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Sidebar advertisement on website

Donations Mention of the amount donated and company name/logo in the print version

Mention of the amount donated and company name/logo on the website





Ratesheet Advertisement

Website 728x90 Header 728x90 Footer 120x240 Left Sidebar 120x240 Left Sidebar

El Mednifico Journal US$75/month US$50/month US$50/month US$50/month

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Platinum US$3500/year US$3500/year

Gold US$2500/year US$2500/year

Silver US$1500/year US$1500/year

_________________________

Asfandyar Sheikh,

Editor-in-Chief


_________________________

Syed Arsalan Ali,

Managing Editor


xiv

Best of Blogemia

Clearing Misconceptions

About Psoriasis

Sobia Anees

http://blogemia.com/clearing-

misconceptions-about-psoriasis/

The term psoriasis is derived from Greek

language, Psora means itch and sis means

condition, making psoriasis literally mean

“itch condition.”It affects 10% of the total

world population.It is an autoimmune con-

dition with strong hereditary link. However,

some people believe that psoriasis is caused

by bacteria or virus but the fact is that it is a

skin condition in which body’s own T cells

see the skin cells as foreign bodies and

attack them. Another common misconcep-

tion is to think psoriasis as being a form of

cancer or leprosy. Because of rapid skin

turnover, it may appear similar in appear-

ance and give a false warning sign but in-

tact, it is neither malignant nor contagious

as leprosy. It was a common belief in olden

times that psoriasis spread via skin contact

and it affects people with poor standards of

hygiene because of which such patients

were victimized by the negative attitude of

the society,.But the truth is, being hygienic

has nothing to do with its cause which lies

in the body’s immune system. Jerry

Mathers was the spokesperson for the

National Psoriasis Foundation’s awareness

campaign entitled “Step into my skin”.

When asked about the effect the disease

had on his life Mathers stated, “Living with

psoriasis is no picnic. When you’re covered

with flaky, scaly, unsightly skin it’s difficult

to live comfortably. People think it is conta-

gious and they shun you, which can be

humiliating.”

Patients with psoriasis frequently under-

goes remissions. The disease pattern goes

through cycles, sometimes better and other

times worst, but it can never be fully eradi-

cated. There is no total cure for psoriasis

and it responds slowly to treatment. Not all

treatment methods have the same effects

on each patient, but its signs and symptoms

can be managed and treated to minimize

the severity of flare ups. Although there are

some well-recognized triggering factors that

bring in an increased severity of signs and

symptoms, but not every person with psori-

asis have same triggering factors making it

quite difficult to treat.

Psoriasis is a complex disease with variable

presentation and types. The first sign and

symptom usually appears between 10-35

years of age. The most common sites of

psoriasis are scalp, elbows and knees.

Symptoms include itchy dry flaky skin cov-

ered with white plaques, joint pain, genital

sores in males.

There are five forms of psoriasis:

Plaque psoriasis: The most common form,

characterized by inflamed skin lesions

topped with white scales

Guttate: Characterized by small dot-like

lesions

Pustular: Characterized by pus-filled, blister-

like lesions and intense scaling

Inverse: Characterized by intense inflamma-

tion in the folds of the skin

Erythrodermic: Characterized by intense

shedding and redness of the skin.

Psoriasis is not just a skin problem. It is a

chronic systemic disorder that can affect

other systems aside skin.

Approximately 10 percent to 30 percent of

people with psoriasis will develop psoriatic

arthritis. This form of arthritis is similar to

rheumatoid arthritis. It can develop at any

time, but for most people it appears be-

tween the ages of 30 and 50. In psoriatic

arthritis, the joints and the soft tissue

around them become inflamed and stiff.

Psoriatic arthritis can affect the fingers and

toes and may involve the neck, lower back,

knees and ankles. Having psoriasis does not

guarantee that all of the patients will even-

tually develop psoriatic arthritis. Psoriatic

patients may be at the risk of other chronic

conditions like depression, heart disease,

obesity, high blood pressure, diabetes,

cancer etc however the risk varies from one

individual to another depending on other

factors as well.

Treatment options for psoriasis can be

broadly divided into topical, systemic and

phototherapy. Topical medications include

topical corticosteroids, vitamin D analogue

creams like calcitriol, topical retinoids,

moisturizers, topical immunomodulators,

coal tar, anthralin, and others. The best

treatment is individually determined by the

treating physician and depends, in part, on

the type of disease, the severity, and the

total body area involved. Phototherapy in

the form of sunlight has long been used

effectively for treatment. Wavelengths of

311–313 nm are most effective and special

lamps have been developed for this applica-

tion. The three main traditional systemic

treatments are methotrexate, cyclosporine

and retinoids. Methotrexate and cyclospor-

ine are immuno-suppressant drugs; retin-

oids are synthetic forms of vitamin A.

Apart from the above mentioned treatment

options, home remedies can also be used to

control psoriasis.Following are some skin

care tips and home remedies for psoriasis:

Dietary supplements such as fish oil, milk,

evening primrose oil.

Creams or lotions, baths, or soaks to keep

skin moist.

Avoid soaps and perfumes as they can irri-

tate the skin.

Avoid red meat and fatty foods.

Apply olive or vegetable oil to troublesome

plaques as it helps loosen them.

Lukewarm bath with Epsom salt, mineral

oil, milk, or olive oil can soothe the itching

and infiltrate scales and plaques.

Try short exposure to sunlight or ultraviolet

(UV) light.

Gently soften and remove psoriasis crusts

by putting cream on the crusts and then

peeling the loose crusts off.

There is no known way to prevent psoria-

sis.Using some of the tips mentioned above,

as well as using other treatment options

one can custom-tailor their daily routine to

keep problem itching and flaking to a mini-

mum.

xv

Psychological Effects Of

Acne

Ambreen Fatima

http://blogemia.com/physiological-effects-

of-acne/

Acne can have profound social and psycho-

logical effects. These are not necessarily

related to its clinical severity. Even mild

acne can be significantly disabling. Acne can

affect people of all ages but it predominant-

ly occurs during the teenage years, approx-

imately 85% of people between the ages of

12 and 25 develop acne. What problems

does it cause?

The psychological and social impacts of

acne are a huge concern especially because

it affects adolescents at a time they are

developing their personalities. During this

time, peer acceptance is very important to

the teenager and unfortunately it has been

found that physical appearance and attrac-

tiveness is highly linked with peer status.

In recent years, open discussions between

patients and medical professionals have

revealed the impact acne has on one’s

psyche. The following are some of the prob-

lems that patients with acne may face.

• Self esteem and body image

o Some embarrassed acne patients avoid

eye contact.

o Some acne sufferers grow their hair long

to cover the face. Girls tend to wear heavy

make-up to disguise the pimples, even

though they know this sometimes aggra-

vates the condition. Boys often comment,

acne is not such a problem for girls because

they can wear make-up.

o Truncal acne can reduce participation in

sport such as swimming e.t.c

• Social withdrawal/relationship building

o Acne, especially when it affects the face,

provokes cruel taunts from other teenagers.

o At a time when teenagers are learning to

form relationships, those with acne may

lack the self-confidence to go out and make

these bonds. They become shy and even

reclusive. The main concern is a fear of

negative appraisal by others. in extreme

cases a ‘social phobia’ can develop.

• Education/work

o Some refuse to go school leading to poor

academic performance and possibly future

unemployment.

o Some take sick days from work, risking

their jobs or livelihood.

o Acne may reduce career choices, ruling

out occupations such as modelling that

depend upon personal appearance.

o Acne patients are less successful in job

applications; their lack of confidence being

as important as the potential employers’

reaction to their spotty skin.

o More people who have acne are unem-

ployed than people who do not have acne

are.

Does acne cause depression?

In some patients the distress of acne may

result in depression. This must be recog-

nised and managed. Signs of depression

include:

• loss of appetite

• lethargy

• mood disturbance

• behavioral problems

• wakefulness

• spontaneous crying

• feelings of unworthiness.

In teenagers depression may manifest as

social withdrawal (retreat to the bedroom

or avoidance of peers) or impaired school

performance (lower grades or missed as-

signments). Worse still, severe depression

from acne has resulted in attempted suicide

and, unfortunately, successful suicide. Wor-

rying statements include I don’t want to

wake up in the morning; I’d be better off

dead; I’m worthless; You’d be better off

without me. Parents, friends and school

counsellors need to take heed when they

start to hear these types of comments.

Rarely, depression can be associated with

acne treatment, particularly isotretinoin.

There is much controversy about whether

the drug causes depression. However, it is

clear that depression does result from the

acne and psychological disturbances de-

scribed above.

Regardless of the cause, depression must

be recognised and managed early. If you

think you may be depressed, contact your

dermatologist or family doctor urgently for

advice.

What is dysmorphophobic acne?

Some patients with only minor acne suffer

from disturbed body image. Even in the

absence of lesions, they consider they have

severe acne and may suffer many of the

psychological and social symptoms de-

scribed above. They are said to have “dys-

morphophobic acne”.

If this is their only abnormal behavioural

symptom, they respond well to oral isotret-

inoin therapy. A low dose of this may be

required long term as even slight recur-

rence of oily skin may unduly concern the

patient. Some severe cases of dysmorpho-

phobia have a more global mental disorder

similar to anorexia nervosa. They require

expert dermatological and psychiatric assis-

tance.

Where do I go for help?

If your acne is interfering significantly with

your life, particularly if it is resulting in any

of the problems described above, seek help

promptly from your family physician or

dermatologist.

Suitable treatments may include:

• Antidepressant medication.

• Psychological treatments to overcome the

negative thinking, anxiety and avoidance

that often accompany depression.

• Counselling to help build confidence and

rebuild self-esteem.

• Group therapy.

It is important that a teenager’s anxiety

over their acne is managed appropriately.

xvi

General principles of treatment

• Acne can be effectively treated, although

response may sometimes be slow.

• Where possible, avoid excessively humid

conditions such as a sauna, working in an

unventilated kitchen or tropical vacations.

• Follow a low-glycaemic (avoid sugars),

low-protein and low-dairy diet. Avoid pro-

tein or amino acid supplements, particularly

if they contain leucine. Eat plenty of fresh

fruit and vegetables.

• If you smoke, stop. Nicotine increases

sebum retention and increased scale within

the follicles, forming comedones (black-

heads and whiteheads).

• Minimise the application of oils and cos-

metics to the affected skin.

• Abrasive skin treatments can aggravate

both comedones and inflammatory lesions.

• Try not to scratch or pick the spots.

• Exposure to sunlight filtered through

window glass can help – To avoid sunburn,

protect your skin outdoors using a sun-

screen and protective clothing. Wash af-

fected areas twice daily with a mild cleanser

and water or an antiseptic wash.

Dengue Fever: A Growing

Problem

Saima Fahim http://blogemia.com/dengue-fever-a-

growing-problem/

Dengue has been a great problem for physi-

cians and patients worldwide. Throughout

the world it has been affecting great num-

ber of people. WHO currently estimates

there may be 50–100 million dengue infec-

tions worldwide every year. More than

10,000 cases of the fatal disease have been

reported in various parts of Pakistan in year

2013. However, the illness is more promi-

nent in Southeast Asia and the western

Pacific islands. The infection may be clinical-

ly asymptomatic or give rise to undifferenti-

ated fever, dengue fever, dengue hemor-

rhagic fever or dengue shock syn-

drome.Dengue is a mosquito borne viral

infection, belongs to the family of Flavivirus

and is transmitted to humans by the bite of

female Aedes mosquito. Its four serotypes

(DENV-1, DENV-2, DENV-3, and DENV-4) can

be distinguished.

Mosquitoes become infected while feeding

on the blood of an infected person, and

spread infection to other individuals they

bite. An infected mosquito transmits the

infection for rest of the life when it bites

another person. It multiplies inside the

blood of an infected person and an infected

person is a source of virus for uninfected

mosquitoes. Aedes is a day biting mosquito

with increased biting 2 hours after sunrise

and 2 hours before sunset.

Signs n symptoms start to appear 4 days

after the bite of an infected mosquito. The

typical symptoms include:

High grade, severe , step ladder pattern

fever up to 106 F

Frontal headache

Lumber (backache) ache

There may be pain in retro-orbital region

(eye pain)

Nausea and vomiting

Rashes may also occur throughout the body

Minor bleeding from nose and gums may be

noticed

The Common Laboratory investigations

show:

Drop in platelets count (thrombocytopenia)

Low level of white blood cells ( leucopenia

Decrease HB level

Elevated level of the enzyme serum ami-

notransferases.

Diagnosis of dengue fever is usually con-

firmed in laboratory by serologic tests on

blood samples from patients

This is done by:

Antigen-detection ELISA or PR-PCR during

acute phase of disease

IgM ELISA or paired serology during recov-

ery phase of dengue fever.

SOME OF THE REASONS OF LOW PLATELETS

COUNT IN DENGUE FEVER:

Dengue virus induces bone marrow sup-

pression. Bone marrow is a manufacturing

centre of blood cells and its suppression

cause deficiency of blood cells leading to

low platelet count

Dengue virus can even bind to platelets of

human blood in presence of virus-specific

antibody.

Even the antiplatelet antibodies that are

produced after the infection of dengue virus

can contribute to destruction of platelets.

When vascular endothelial cell that are

infected with dengue virus get combined

with platelets they tend to destroy plate-

lets, leading to low platelet count.

Low platelet count in dengue fever leads to

life threatening condition that is, hemor-

rhagic dengue fever that is categorized by

spontaneous bleeding tendency and shock.

Typical dengue usually does not result in

death. The acute phase of the illness with

fever, myalgias and the rest of the symp-

toms lasts for about one to two weeks.

Convalescence is accompanied by a feeling

of weakness. However, full recovery often

takes several weeks.

Treated DHF/DSS is associated with a 3%

mortality rate.

Untreated DHF/DSS is associated with a

50% mortality rate.

There is no specific treatment for dengue

fever, doctors may suggest intake of lots of

water to prevent dehydration due to high

fever and vomiting.

Pain and fever can be treated with aceta-

minophens.

Severe cases of dengue fever may require

hospitalization which include supportive

care, blood pressure monitoring , blood

transfusion and intravenous administration

of fluids and electrolyte.

xvii

The best way for prevention of dengue virus

is avoid contact from mosquitoes. The peak

biting time is early morning and evening so

avoid going out at this time. Use of mosqui-

tos’ repellants and sprays are also suggest-

ed.Vaccine against dengue virus is still cur-

rently on its developing stage. It is hoped

and expected that with all the researches

and vigorous efforts being made in this

regard, mankind will soon defeat this viral

infection and relieve the globe of this men-

ace.

We require avid bloggers and medical writers to lead our sister blog, Blogemia. We are looking for section heads, editors and contributors.

Those hired will be responsible for submitting at least five blogs (>500 words) per month. Individuals working in any of the aforementioned

capacities will receive a share of the advertisement revenue. To apply, send your CVs along with samples at: [email protected]

We accept Original Articles, Review Articles, Case Reports, Opinions and Debates, Essays, Letters to the Editor. There are no paper submission charges. Submit your articles via the online system or send as an email to: [email protected]

We require editors, programmers, layout designers and proofreaders for our editorial staff. We also require avid medical bloggers for our sister website, http://blogemia.com. We are also looking for journal representatives from different medical schools. To apply, send your CV to: [email protected]

El Mednifico Journal, Address: C2 Block R, North Nazimabad, Karachi – 74700 – Pakistan. Email: [email protected]. Phone: (92-334)2090696.

vol 2, issue 1

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