Preventive Urology
Transcript of Preventive Urology
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Preventive UrologyPreventive Urology
Why talk about it?
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Preventive UrologyPreventive UrologyWhy talk about it?
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Preventive UrologyPreventive Urology Do we have substantial areas?
Stone disease
UTI Cancer Prostate
Prostatitis
Erectile dysfunction
Analyze role of Pharmaco-manipulationONLY. The Chemoprevention
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Stone Prevention StrategiesStone Prevention Strategies
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Preventing StonesPreventing Stones
Stone
Obesity
Diabetes
Diet
Fluids
K
Citrate
Juices
Drinks
Thiazides
Allopurinol
Na Bicarb
Drugs
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Stone Preventing PillsStone Preventing Pills K Citrate
Thiazides
Magnesium
Pyridoxine
K Citrate Thiazides
Magnesium
Pyridoxine
Obesity Gouty DiathesisDiabetes
AllopurinolNa Bicarb
STONA 1
STONA 2
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Oxalobacter FormigenesOxalobacter Formigenes
First strain isolatedfrom sheep rumen
Beneficial intestinalbacteria present in allvertebratesEnzymatically breaksdown oxalate to getenergy for its survival
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IxOC-4 TherapeuticIxOC-4 Therapeutic
Purified recombinant oxalatedegrading enzyme (OxalateDecarboxylase)
Formulated to degrade oxalate in thestomach
Indication: prevention ofenteric/absorptive hyperoxaluria andrecurrin calcium oxalate kidne stones
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Cancer Prostate PreventionStrategiesCancer Prostate PreventionStrategies
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Will controlling prostatic inflammationbe helpful in cancer prostate?Will controlling prostatic inflammationbe helpful in cancer prostate?
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COX-2COX-2 COX-2 enzyme over expression has been
reported in human prostate cancer
Cohen, et al 2007: COX-2 expression anindependent predictor of disease progressionin multivariate analysis in a sample of 60patients
COX-2 has role in proliferation, angiogenesisand also resistance to apoptosis
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COX-2COX-2 expression of the enzyme is correlated with
tumor progression
Liu et al, 2000: mice inoculated with humanprostate cancer cells produced tumors ofreduced size when treated with NSAID
Liu et al, 2002: PG E2 production(upregulation of COX-2) was found to inducePIN; could also stimulate this behavior usingIL-6
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NSAID & risk of prostate cancerNSAID & risk of prostate cancer Harris et al, 2005: reviewed 91 epidemiologic
studies & found a significant exponentialdecrease in cancer risk with heavier NSAIDregimens for7 out of10 cancer type
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NSAID and risk of prostate cancerNSAID and risk of prostate cancer Mahmud et al, meta-analysis of studies
published before 2003: use of aspirin reducedthe odds of prostate cancer
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NSAID & prostate cancer outcomesNSAID & prostate cancer outcomes There is reduced likelihood of highly
aggressive disease (Gleason score 8)forNSAID users
Selective COX-2 inhibition was able tosuppress the rate of PSA after curativetreatment
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Prostatitis Prevention strategiesProstatitis Prevention strategies
AllopurinolAlpha
BlockersFinasteride
Dutasteride
1980 2010
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UTI Prevention strategies in femalesUTI Prevention strategies in females
Antibioticprophylaxis
VaginalProbiotic
gels
CranberryJuice
B-Mannose ?
1980 2010
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The Need in the era of potent antibioticsThe Need in the era of potent antibiotics
The Extent:
Lifetime incidence of UTI : in every 5 women
Of these women, 3% experience recurrent disease
11 million women receive medication for UTI annually
Significant health problem worldwide
Why antibiotics alone may not be enough
Antibiotic resistance Side effects
Economic aspects
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Alternative, preventive and economic options to antibioticsare urgently needed
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Bacterial Adherence: essential step in theinitiation of UTI.
E-coli expresses 100-400 fimbria(pili) on itssurface by which it attaches itself to epithelialsurface of urinary tract and vagina.
Types: 1( Mannose sensitive, Most common)
P ( Mannose Resistant, Pyelonephritic)
S ( Sialic acid)
Others
Role of E-coli in UTIRole of E-coli in UTI
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BACTERIAL ADHERENCEBACTERIAL ADHERENCE
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Electron Microscopy view of E coliElectron Microscopy view of E coli
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Decrease bacterial adherence/wash them off
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CranberryCranberry
Cranberry (Vacciniummacrocarpon) is a fruit native toNorth America.
Massachusetts and Wisconsin:
main areas of present-daycommercial production ofcranberry.Major constituents of cranberry juice
glucose (3.1%),fructose (1%),citric acid (1.1%),quinic acid (1.1%),malic acid (0.8%).Cranberry juice cocktail is a 25% dilution of the native juice
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Clinical Evidence supporting cranberry use
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BMJ. 2001 Jun 30;322(7302):1571.
Randomised trial of cranberry-lingonberry juice and Lactobacillus GG drink for the prevention
of urinary tract infections in women.
A 20% reduction in absolute risk in the cranberry group compared with the control group (95%confidence interval 3% to 36%, P=0.023, number needed to treat=5, 95% confidence interval 3 to 34).
CONCLUSION: Regular drinking of cranberry juice but not lactobacillus seems to reduce therecurrence of urinary tract infection.
Can J Urol. 2002 Jun;9(3):1558-62.A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry
products as prophylaxis against urinary tract infection in women.
RESULTS: Both cranberry juice and cranberry tablets statistically significantly decreased the numberof patients experiencing at least 1 symptomatic UTI/year (to 20% and 18% respectively) comparedwith placebo (to 32%) (p2symptomatic UTI's per year (assuming 3 days antibiotic coverage) and had >2 days of missed workor required protective undergarments for urgency incontinence. Total antibiotic consumption wasless annually in both treatment groups compared with placebo. Cost effectiveness ratiosdemonstrated cranberry tablets were twice as cost effective as organic juice for prevention.CONCLUSIONS: Cranberry tablets provided the most cost-effective prevention for UTI.
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DosageDosage
Recommended dosing for UTIprophylaxis
300-400mg BD (tablet of
concentrated cranberry extract)
8 oz of pure unsweetened
cranberryjuice TDS.
[About 700ml daily]
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Adverse effectsAdverse effects
No significant herb-drug reactions have been reported.
It may increase urinary oxalate levels.
Caution:Regular use of cranberry may increase the risk ofkidney stone formation in patients with a history ofoxalate calculi.
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D-MANNOSE is a sterioisomer of Glucose andnaturally present in fruits like pineapple andcranberry & also in plants and fungi.
Mannose binds to lectins ( glycoprotein onfimbriae of E-coli. ), preventing them fromcolonization .
D- MANNOSE IN UTID- MANNOSE IN UTI
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Absorbed from the upper GIT at a slower ratebut not stored as glycogen.
Most of it in blood stream is excreted in theurine unchanged.
Quality: possibility of dilution with other sugars.So analyzed by HPLC assay- ensure thatmannose content is > 99%.
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Available as capsules and in powder form.
Suggested Use: Three (3) capsules, two tothree times (2-3x) daily.
Powder: one spoon (3) times daily, mixed with
water, with or between meals.
Precaution: Diabetic (regular monitoring ofsugar levels is recommended).
FormulationsFormulations
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Probiotics
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Probiotics:Probiotics are defined as LIVE microorganisms which when
administered in adequate amounts confer a health benefit to the
host
Rationale:
The bacterial flora of the skin and mucosal surfaces is an
important barrier to infection and disruption of this natural flora
renders patients prone to infections which may be severe/
involving multiple organisms
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Mechanism of ActionMechanism of Action
Competitive Theory:
Probiotics administered orally/ applied togenital area overgrow pathogenic flora andrestore an environment resistant to infections
Compete for space/nutrition.
Produce metabolites which are bactericidal/bacteriostatic to pathogenic flora.
Non competitive Theory:
Immunomodulation
May influence the production of immunoglobulins thus altering the bodysimmune defense.
May contribute to a specific immune response against pathogenicbacteria
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Clinical Evidence supporting Probiotic use
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Can J Microbiol. 1988 Mar;34(3):339-43. Links
Intravaginal instillation of lactobacilli for prevention of recurrent urinary tract
infections.
Bruce AW, Reid G.
Department of Surgery, Toronto General Hospital, Ont., Canada.
Urinary tract infections remain a common problem, particularly in the femalepopulation. New methods are required to manage recurrent cystitis, and extensiveresearch to date has suggested that restoration of the lactobacilli flora of theurogenital tract may prevent these infections. In this study, five females sufferingfrom recurrent urinary tract infections were treated twice weekly with intravaginaland perineal implantation of Lactobacillus casei GR-1. These organisms colonizedthe epithelium and prevented the emergence of coliform bacteria in most instances,
but did not appear to affect enterococcal colonization. In vitro studies showed that L.casei GR-1 inhibited the growth of the coliforms but did not inhibit enterococci. Eachof the five patients had infection-free periods ranging from 4 weeks to 6months. The treatment was well tolerated, had no side effects, led to an improvedwell-being, and was preferred to antibiotic treatment by all of the patients. Thesehuman studies, albeit of a limited nature, are the first to examine the potential forlactobacillus therapy in the prevention of urinary tract infections. The results showthat lactobacilli therapy, using carefully selected organisms to treat patients who areclosely followed, may be effective in the prevention of recurrent urinary tractinfections.
Probiotic released from vaginal pessary
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Though there is insufficient data to
support routine use of probiotic in UTI, itmay be regarded as the single mostpowerful alternative option under
clinical development for the preventionand treatment of chronic infection
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Thank youThank you