dietary supplements

35
Dietary Dietary Supplements Supplements Juanita Escamilla, MS Juanita Escamilla, MS Sodexo Distance Education Dietetic Sodexo Distance Education Dietetic Intern Intern Professional Research Presentation Professional Research Presentation December 11, 2012 December 11, 2012

Upload: tamarr

Post on 15-Jan-2016

60 views

Category:

Documents


2 download

DESCRIPTION

Dietary Supplements. Juanita Escamilla, MS Sodexo Distance Education Dietetic Intern Professional Research Presentation December 11, 2012. Background and Research. BS, Food and Nutrition and MS Human Nutrition (Food Biotechnology and Molecular Nutrition) - PowerPoint PPT Presentation

TRANSCRIPT

Page 1: Dietary Supplements

Dietary Dietary SupplementsSupplements

Juanita Escamilla, MSJuanita Escamilla, MSSodexo Distance Education Dietetic Sodexo Distance Education Dietetic

InternInternProfessional Research Presentation Professional Research Presentation

December 11, 2012December 11, 2012

Page 2: Dietary Supplements

Background and Background and ResearchResearch

BS, Food and Nutrition and MS Human Nutrition BS, Food and Nutrition and MS Human Nutrition (Food Biotechnology and Molecular Nutrition)(Food Biotechnology and Molecular Nutrition)

Thesis: Role of Gut Microflora in Colon Cancer Thesis: Role of Gut Microflora in Colon Cancer MetastasisMetastasis

Studied various strains of probiotic bacteria (Studied various strains of probiotic bacteria (L. casei, L. casei, L. rhamnosus GG, B. longum)L. rhamnosus GG, B. longum)Looked at metastasis Looked at metastasis in vitro, in vitro, usingusing various assays various assays such as the Boyden Chamber, Western Blot, and such as the Boyden Chamber, Western Blot, and ZymographyZymography

Community and Clinical Nutrition ExperienceCommunity and Clinical Nutrition ExperienceSan Marcos, A Tu Salud (low-income Spanish San Marcos, A Tu Salud (low-income Spanish speaking women)speaking women)San Marcos, Nutrition 101, Hernandez Intermediate San Marcos, Nutrition 101, Hernandez Intermediate SchoolSchoolMEND (Mind, Exercise, Nutrition, Do It)MEND (Mind, Exercise, Nutrition, Do It)El Hospital Para el Niño PoblanoEl Hospital Para el Niño Poblano

Page 3: Dietary Supplements

Gap in KnowledgeGap in KnowledgeWhat is the Mechanism of Action of What is the Mechanism of Action of Probiotics, D-Mannose, and Cranberry? We Probiotics, D-Mannose, and Cranberry? We know they work, but how do they work?know they work, but how do they work?

Page 4: Dietary Supplements

ObjectivesObjectivesAudience will be able to:Audience will be able to:

State the definition of a Dietary State the definition of a Dietary supplement, Nutraceutical, and a supplement, Nutraceutical, and a Functional FoodFunctional Food

State the regulation of Dietary State the regulation of Dietary supplements in the marketsupplements in the market

State the Mechanism of Action of State the Mechanism of Action of Probiotics, D-mannose and CranberryProbiotics, D-mannose and Cranberry

State the recommended uses for State the recommended uses for Probiotics, D-mannose and CranberryProbiotics, D-mannose and Cranberry

Page 5: Dietary Supplements

Raise your hand if Raise your hand if you’ve taken a you’ve taken a

Dietary Dietary Supplement?Supplement?

Page 6: Dietary Supplements

Quick FactsQuick FactsU.S. adult population. Over 40% used U.S. adult population. Over 40% used supplements in 1988–1994, and over 50% in supplements in 1988–1994, and over 50% in 2003–20062003–2006

Multivitamins/multiminerals are the most Multivitamins/multiminerals are the most commonly used dietary supplements, with commonly used dietary supplements, with approximately 40% of men and women approximately 40% of men and women reporting use during 2003–2006reporting use during 2003–2006

Dietary supplements have been taken by Dietary supplements have been taken by more than half of American adults; more than half of American adults; consumers spent $26.7 billion on consumers spent $26.7 billion on supplements in 2009supplements in 2009

2011 Survey found that 1 in 4 people take a 2011 Survey found that 1 in 4 people take a fish oil supplementfish oil supplement

Page 7: Dietary Supplements

Reasons for Taking Reasons for Taking Dietary SupplementsDietary Supplements

Page 8: Dietary Supplements

Definition of a Definition of a Dietary Dietary

SupplementSupplementAs defined by Congress in the: As defined by Congress in the: Dietary Supplement Health and Education Act (DSHEA), which became law in 1994, a dietary supplement is a product (other than tobacco) that

is intended to supplement the diet;is intended to supplement the diet;

contains one or more dietary ingredients (including contains one or more dietary ingredients (including vitamins; minerals; herbs or other botanicals; amino acids; and other substances) or their constituents;

is intended to be taken by mouth as a pill, capsule, is intended to be taken by mouth as a pill, capsule, tablet, or liquid; andtablet, or liquid; and

is is labeled on the front panel as being a dietary supplement.

Page 9: Dietary Supplements

Regulation of Regulation of Dietary Dietary

SupplementsSupplementsThe Federal Government regulates The Federal Government regulates dietary supplements through the U.S. dietary supplements through the U.S. Food and Drug Administration (FDA). Food and Drug Administration (FDA). The The regulations for dietary supplements are regulations for dietary supplements are not the same as those for prescription or not the same as those for prescription or over-the-counter drugsover-the-counter drugs. In general, the . In general, the regulations for dietary supplements are regulations for dietary supplements are less strictless strict. .

Dietary supplements are not required by Dietary supplements are not required by federal law to be tested for safety and federal law to be tested for safety and effectiveness before they are marketedeffectiveness before they are marketed, , so the amount of scientific evidence so the amount of scientific evidence available for various supplement available for various supplement ingredients varies widely. ingredients varies widely.

Page 10: Dietary Supplements

My Dietary My Dietary Supplements Mobile Supplements Mobile

AppApphttps://myds.nih.gov.

Page 11: Dietary Supplements

Modern TermsModern TermsNutraceutical: Nutraceutical:

Coined from “nutrition” and “pharmaceutical”Coined from “nutrition” and “pharmaceutical”, , 1989 by Stephen DeFeleice, MD, founder and 1989 by Stephen DeFeleice, MD, founder and chairman of the Foundation for Innovation in chairman of the Foundation for Innovation in Medicine (FIM)Medicine (FIM)

““a food (or part of a food) that provides medical or a food (or part of a food) that provides medical or health benefits, including the prevention and/or health benefits, including the prevention and/or treatment of a disease”treatment of a disease”, go beyond , go beyond supplementation, more therapeutic.supplementation, more therapeutic.

Differ from dietary supplements by the following Differ from dietary supplements by the following aspects:aspects:

Nutraceuticals must not only supplement the diet but Nutraceuticals must not only supplement the diet but should also aid in the prevention and/or treatment of should also aid in the prevention and/or treatment of disease and/or disorderdisease and/or disorder

Nutraceuticals are used as conventional foods or as Nutraceuticals are used as conventional foods or as sole items of a meal or dietsole items of a meal or diet

Examples: Green Tea, Vitamin D, Lycopene, Examples: Green Tea, Vitamin D, Lycopene, Phytochemicals, Probiotics, etcPhytochemicals, Probiotics, etc

Page 12: Dietary Supplements

Nutraceutical

Nutraceutical

Pharmaceutical

Pharmaceutical NutritionNutrition

Scientific EvidenceScientific Evidence

Page 13: Dietary Supplements

Functional Foods: Functional Foods: Are similar in appearance to conventional Are similar in appearance to conventional foods and consumed as part of a normal foods and consumed as part of a normal dietdietDemonstrated physiological benefits and Demonstrated physiological benefits and can reduce the risk of chronic disease can reduce the risk of chronic disease beyond basic nutritional functionsbeyond basic nutritional functions, , including maintenance of gut healthincluding maintenance of gut health

Academy of Nutrition and Dietetics Academy of Nutrition and Dietetics Definition:Definition:

All foods as functional at some All foods as functional at some physiological level because they provide physiological level because they provide nutrients or other substances that furnish nutrients or other substances that furnish energy, sustain growth, or maintain/repair energy, sustain growth, or maintain/repair vital processes.vital processes. However, functional foods However, functional foods move beyond necessity to provide move beyond necessity to provide additional health benefits that may reduce additional health benefits that may reduce disease risk and/or promote optimal disease risk and/or promote optimal health. Functional foods include health. Functional foods include conventional foods, modified foods (ie, conventional foods, modified foods (ie, fortified, enriched, or enhanced), medical fortified, enriched, or enhanced), medical foods, and foods for special dietary usefoods, and foods for special dietary use

Page 14: Dietary Supplements

ProbioticsProbiotics

Page 15: Dietary Supplements

Human Gut Human Gut MicrofloraMicrofloraHuman GI tract is Human GI tract is

sterile at birth, sterile at birth, microflora develops microflora develops after birthafter birth

Colonization rate Colonization rate varies according to varies according to factors:factors:

Mode of BirthMode of Birth

Infant NutritionInfant Nutrition

Antibiotic UseAntibiotic Use

DietDiet

AgeAge

Page 16: Dietary Supplements

Microorganisms that Microorganisms that reside on and inside reside on and inside humans outnumber humans outnumber somatic cells somatic cells

Influence host Influence host metabolism, metabolism, physiology, gene physiology, gene expressionexpression

GI contains ~100 GI contains ~100 trillion microorganisms trillion microorganisms that represent 1000 that represent 1000 separate bacteria, separate bacteria, yeasts, parasitesyeasts, parasites

Increase in numbers Increase in numbers from the mouth to the from the mouth to the anusanus

Page 17: Dietary Supplements

Probiotics and Probiotics and Gastrointestinal HealthGastrointestinal Health

Probiotic bacteria are defined as : Probiotic bacteria are defined as : ““live microorganisms which when live microorganisms which when administered in adequate amounts administered in adequate amounts confer a health benefit on the hostconfer a health benefit on the host””

Ingestion of probioticsIngestion of probiotics has been has been shown to aid in overall shown to aid in overall gastrointestinal health:gastrointestinal health:

Modulating the intestinal flora Modulating the intestinal flora

Decreasing the number of toxin Decreasing the number of toxin (carinogenic) producing bacteria in the (carinogenic) producing bacteria in the large intestine.large intestine.

Reduce the risk of colorectal cancerReduce the risk of colorectal cancer

Decrease intestinal permeabiltyDecrease intestinal permeabilty

Stimulation of immune functionsStimulation of immune functions

Improved digestion and absorption of Improved digestion and absorption of nutrientsnutrients

Synthesis of vitaminsSynthesis of vitamins

Page 18: Dietary Supplements

Enterococci

Bifidobacteria

Bacteroides

Streptococci

LactobacilliE. coli

Veillonellae

Clostridia

Staphylococci

Proteus sp.

Ps. aeruginosa 2

11 No./g faeces (log scale)

Inhibition of growthof exogenous and harmful bacteria(diarrhoea, IBD, UC, Crohn’s disease, colon cancer)

Stimulate immune function

Digestion/ absorption of undigested foods and minerals

Lipid lowering

Diarrhea, constipation,infections, liver damage, cancer, toxigenesis.

Production ofcarcinogens

Intestinalputrefaction

Large Intestine Microflora

Page 19: Dietary Supplements

1. Disruption of TJ proteins

2. Invasion through the ECM (increase MMP-9 activity)

3. Entrance into circulation

4. Metastasis into liver and lungs

Primary Tumor

Mechanism of Mechanism of Action in the Action in the

Context of CancerContext of Cancer

Extracellular Membrane

Page 20: Dietary Supplements

• Separation of single tumor cells from primary Separation of single tumor cells from primary tumortumor• Tight junctions regulate the epithelial barrier Tight junctions regulate the epithelial barrier

function by the apical intercellular junctions function by the apical intercellular junctions formed in normal epithelial cells and tumor cells. formed in normal epithelial cells and tumor cells.

• Decreased expression of ZO-1 been implicated in Decreased expression of ZO-1 been implicated in cancer metastasiscancer metastasis

ZO-1

ZO-2

ZO-3

JAM

Occludin

Actin

Paracellular Space

ClaudinClaudin

Page 21: Dietary Supplements

Lactobacillus sp. Lactobacillus sp. Decrease MMP-9 Decrease MMP-9 Protein LevelsProtein Levels

*Indicates (P = < 0.05)

MMP-9

Ponceau S

Control L. casei L. rhamnosus

* *

74.22% 61.38%

Control L. casei L. rhamnosus

Page 22: Dietary Supplements

β-actin

ZO-1

Control L. casei L. rhamnosus

P = 0.060

*

Lactobacillus sp. Lactobacillus sp. Increase ZO-1 Protein Increase ZO-1 Protein LevelsLevels

*Indicates (P = < 0.05)

170.15%

134.06%

Control L. casei L. rhamnosus

Page 23: Dietary Supplements

What does the Data What does the Data mean?mean?

Probiotics play a role in gene Probiotics play a role in gene expression!!!!!expression!!!!!

Page 24: Dietary Supplements

Probiotics can decrease intestinal permeability which Probiotics can decrease intestinal permeability which has been implicated in autoimmune disorders such ashas been implicated in autoimmune disorders such as

Thyroid disorder, Celiac Disease, Parkinson’s, Type 1 Thyroid disorder, Celiac Disease, Parkinson’s, Type 1 DiabetesDiabetes

Page 25: Dietary Supplements

D-Mannose and D-Mannose and CranberryCranberry

Page 26: Dietary Supplements

Urinary Urinary TractTractWorks with the lungs, skin, Works with the lungs, skin,

and intestines to excrete and intestines to excrete wastes to maintain wastes to maintain homeostasis in the body.homeostasis in the body.

Urinary tract infections can Urinary tract infections can occur and are caused by occur and are caused by bacteria in the urinary tract.bacteria in the urinary tract.

CAUTI, Cystitis (bladder), CAUTI, Cystitis (bladder), pyelonephritis (kidney)pyelonephritis (kidney)

In the United States, 1 in 5 In the United States, 1 in 5 women report reoccurring women report reoccurring UTI, eleven million women UTI, eleven million women receive medication for UTIs receive medication for UTIs annuallyannually

Treatments include: Treatments include: antibiotics, increasing fluid antibiotics, increasing fluid intake to flush out bacteriaintake to flush out bacteria

Page 27: Dietary Supplements

Urinary Tract and Urinary Tract and InfectionInfection““Bacterial adherence to the uroepithelium is Bacterial adherence to the uroepithelium is

recognized as an important mechanism in the initiation recognized as an important mechanism in the initiation and pathogenesis of urinary tract infections (UTI). The and pathogenesis of urinary tract infections (UTI). The uropathogens originate predominantly in the intestinal uropathogens originate predominantly in the intestinal tract and initially colonize the periurethral region and tract and initially colonize the periurethral region and ascend into the bladder, resulting in symptomatic or ascend into the bladder, resulting in symptomatic or asymptomatic bacteriuria.”asymptomatic bacteriuria.”

Page 28: Dietary Supplements

D-mannose and D-mannose and CranberryCranberry

d-Mannose is the end product of d-Mannose is the end product of the digestion of various the digestion of various polysaccharides and polysaccharides and glycoproteins found in the diet. glycoproteins found in the diet.

d-Mannose is a monosaccharide d-Mannose is a monosaccharide found in fruits such as apples, found in fruits such as apples, blueberries, and cranberries.blueberries, and cranberries.

Cranberries (Cranberries (Vaccinium Vaccinium macrocarpon)macrocarpon) contain high levels contain high levels of d-Mannose as well as of d-Mannose as well as proanthocyanins (PACs). proanthocyanins (PACs).

Both d-Mannose and PACs have Both d-Mannose and PACs have been shown to prevent and treat been shown to prevent and treat UTI infections in both men and UTI infections in both men and womenwomen

Page 29: Dietary Supplements

Mechanism of Mechanism of ActionAction

Eroepithelial Cells

E. coli

d-Mannose

Cranberry

d-Mannose Receptor

Page 30: Dietary Supplements

SummarySummaryDietary Supplements, nutraceuticals, and Dietary Supplements, nutraceuticals, and functional foods fall under DSHEA and are functional foods fall under DSHEA and are regulated by the federal government with regulated by the federal government with more lenient standards. more lenient standards.

Probiotics aid in overall GI Health by Probiotics aid in overall GI Health by mechanisms that affect gene expression, mechanisms that affect gene expression, specifically through Tight Junction specifically through Tight Junction Proteins and MMP-9 in the context of Proteins and MMP-9 in the context of cancer.cancer.

D-mannose and Cranberry have been D-mannose and Cranberry have been shown to prevent and treat urinary tract shown to prevent and treat urinary tract infections by preventing pathogenic infections by preventing pathogenic bacteria from binding to uroepithelium.bacteria from binding to uroepithelium.

Page 31: Dietary Supplements

THANK THANK YOU!!!!YOU!!!!

Merci

Grazie

Gracias

Page 32: Dietary Supplements

ResourceResourcess

Dietary Supplement Health and Education Act of 1994. U.S. Food and Dietary Supplement Health and Education Act of 1994. U.S. Food and Drug Administration Web site. Accessed at Drug Administration Web site. Accessed at http://www.fda.gov/RegulatoryInformation/Legislation/ on November on November 24, 2012.24, 2012.

Dietary supplements: background information. Office of Dietary Dietary supplements: background information. Office of Dietary Supplements Web site. Accessed at Supplements Web site. Accessed at ods.od.nih.gov/factsheets/DietarySupplements_pf.asp on November on November 20, 2012.20, 2012.

Dietary supplements: overview. U.S. Food and Drug Administration, Dietary supplements: overview. U.S. Food and Drug Administration, Center for Food Safety and Applied Nutrition Web site. Accessed at Center for Food Safety and Applied Nutrition Web site. Accessed at www.fda.gov/Food/DietarySupplements/ on November 20, 2012. on November 20, 2012.

Natural Medicines Comprehensive Database. Product monographs. Natural Medicines Comprehensive Database. Product monographs. Accessed at www.naturaldatabase.com on November 20, 2012.Accessed at www.naturaldatabase.com on November 20, 2012.

Radimer K, Bindewald B, Hughes J, et alRadimer K, Bindewald B, Hughes J, et alDietary supplement use by US adults: data from the National Health and Nutrition Examination Survey, 1999–2000. . American Journal of Epidemiology.American Journal of Epidemiology. 2004;160(4):339–349. 2004;160(4):339–349.

What’s behind our dietary supplements coverage. Consumer Reports. What’s behind our dietary supplements coverage. Consumer Reports. Accessed http://www.consumerreports.org/cro/2012/04/what-s-behind-Accessed http://www.consumerreports.org/cro/2012/04/what-s-behind-our-dietary-supplements-coverage/index.htmour-dietary-supplements-coverage/index.htm

Page 33: Dietary Supplements

Radimer K, Bindewald B, Hughes J, Ervin B, Swanson C, Picciano MF. Radimer K, Bindewald B, Hughes J, Ervin B, Swanson C, Picciano MF. Dietary supplement use by US adults: data from the National Health and Dietary supplement use by US adults: data from the National Health and Nutrition Examination Survey, 1999-2000. Nutrition Examination Survey, 1999-2000. Am J Epidemiol.Am J Epidemiol. 2004;60(4):339-49. 2004;60(4):339-49.

FAO/WHO: Regulatory and clinical aspects of dairy probiotics. Food and FAO/WHO: Regulatory and clinical aspects of dairy probiotics. Food and Agriculture Organization of the United Nations and World Health Agriculture Organization of the United Nations and World Health Organization Expert Consultation Report. 2001.Organization Expert Consultation Report. 2001.

Supplement Use Widespread Among Americans. Medline Plus U.S Supplement Use Widespread Among Americans. Medline Plus U.S National Library of Medicine NIH website. Assessed at National Library of Medicine NIH website. Assessed at http://www.nlm.nih.gov/medlineplus/news/fullstory_131502.html on http://www.nlm.nih.gov/medlineplus/news/fullstory_131502.html on November 22, 2012.November 22, 2012.

Bajzer M, Seeley RJ. The intestinal bacteria in obese humans and mice Bajzer M, Seeley RJ. The intestinal bacteria in obese humans and mice differ from those lean individuals. Are these bacteria involved in how we differ from those lean individuals. Are these bacteria involved in how we regulate body weight, and are they a factor in the obesity epidemic? regulate body weight, and are they a factor in the obesity epidemic? NatureNature 2006; 444: 1009-1010. 2006; 444: 1009-1010.

Cencic A, Chingwaru W. The Role of Functional Foods, Nutraceuticals, and Cencic A, Chingwaru W. The Role of Functional Foods, Nutraceuticals, and Food Supplements in Intestinal Health. Food Supplements in Intestinal Health. NutrientsNutrients 2010; 2: 611-625. 2010; 2: 611-625.

Position of the American Dietetic Association: Functional Foods. Position of the American Dietetic Association: Functional Foods. J Am Diet J Am Diet Assoc.Assoc. 2009; 109(4): 735-746. 2009; 109(4): 735-746.

Lynch, DM. Cranberry for Prevention of Urinary Tract Infections. Lynch, DM. Cranberry for Prevention of Urinary Tract Infections. Am Fam Am Fam Physician. Physician. 2004; 70(11):2175-2177.2004; 70(11):2175-2177.

Page 34: Dietary Supplements

Millen AE, Dodd KW, Subar AF. Use of vitamin, mineral, nonvitamin, Millen AE, Dodd KW, Subar AF. Use of vitamin, mineral, nonvitamin, and nonmineral supplements in the United States: The 1987, 1992, and nonmineral supplements in the United States: The 1987, 1992, and 2000. National Health Interview Survey results. and 2000. National Health Interview Survey results. J Am Diet Assoc.J Am Diet Assoc. 2004;104(6):942-50. 2004;104(6):942-50.

Reid G, Sobel JD. Bacterial Adherence in the Pathogenesis of Urinary Reid G, Sobel JD. Bacterial Adherence in the Pathogenesis of Urinary Tract Infection: A Review. Tract Infection: A Review. Clin Infect Dis. Clin Infect Dis. 1987; 9(3):470-487.1987; 9(3):470-487.

Visser J, Rozing J, Sapone A, Lammers K, Fasano A. Tight junctions, Visser J, Rozing J, Sapone A, Lammers K, Fasano A. Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N Y Acad Sci. 2009; 1165: 195-205.diabetes paradigms. Ann N Y Acad Sci. 2009; 1165: 195-205.

Miele L, Valenza V, La Torre G, Montalto M, Cammarota G, Ricci R, Miele L, Valenza V, La Torre G, Montalto M, Cammarota G, Ricci R, Masciana R, Forgione A, Gabrieli ML, Perotti G, Vecchio FM, Rapaccini Masciana R, Forgione A, Gabrieli ML, Perotti G, Vecchio FM, Rapaccini G, Gasbarrini G, Day CP, Grieco A. Increased intestinal permeability G, Gasbarrini G, Day CP, Grieco A. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease. and tight junction alterations in nonalcoholic fatty liver disease. Hepatology. 2009; 49(6):1877-87.Hepatology. 2009; 49(6):1877-87.

Perez-Lopez FR, Haya J, Chedraui P. Vaccinium macrocarpon: an Perez-Lopez FR, Haya J, Chedraui P. Vaccinium macrocarpon: an interesting option for women with recurrent urinary tract infections interesting option for women with recurrent urinary tract infections and other health benefits. and other health benefits. J Obestet Gynaecol Res. J Obestet Gynaecol Res. 2009; 35(4):630-2009; 35(4):630-639.639.

Pappas E, Schaich KM. Phytochemicals of cranberries and cranberry Pappas E, Schaich KM. Phytochemicals of cranberries and cranberry products: characterization, potential health effects, and processing products: characterization, potential health effects, and processing stability. stability. Crit Rev Food Sci Nutr. Crit Rev Food Sci Nutr. 2009; 49(9):741-781.2009; 49(9):741-781.

Page 35: Dietary Supplements

D-Mannose for UTI Pain Relief, Treatment, and Prevention. Integrative D-Mannose for UTI Pain Relief, Treatment, and Prevention. Integrative Health Review A Resource from the National University System Center Health Review A Resource from the National University System Center for Integrative Health. Assessed at for Integrative Health. Assessed at http://www.integrativehealthreview.com/eating-nutrition/d-mannose-http://www.integrativehealthreview.com/eating-nutrition/d-mannose-the-simple-sugar-that-prevents-and-can-cure-urinary-tract-infections/. the-simple-sugar-that-prevents-and-can-cure-urinary-tract-infections/. December 01, 2012.December 01, 2012.

Reid G, Sobel J. Bacterial Adherence in the Pathogenesis of Urinary Reid G, Sobel J. Bacterial Adherence in the Pathogenesis of Urinary Tract Infection: A Review. Tract Infection: A Review. Clin Infect Dis. Clin Infect Dis. 1987; 9(3):470-487.1987; 9(3):470-487.

Kaper J, Nataro J, Mobley HLT. Pathogenesis of urinary tract infection Kaper J, Nataro J, Mobley HLT. Pathogenesis of urinary tract infection caused by uropathogenic caused by uropathogenic E. coli.E. coli. 2004; 2:123-140. 2004; 2:123-140.