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Gout

Gout. Elevation of serum uric acid level: hyperuricemia primary risk factor ,predisposes to gout > 6.8mg/dl Deposition of uric acid crystals (monosodium urate) in the joint Acute inflammatory arthritis Management of the disease Between flares Normalize urate level: goal below 6 mg/dl

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Gout

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  1. Gout • Elevation of serum uric acid level: hyperuricemia primary risk factor ,predisposes to gout > 6.8mg/dl • Deposition of uric acid crystals (monosodium urate) in the joint • Acute inflammatory arthritis • Management of the disease • Between flares • Normalize urate level: goal below 6 mg/dl • Maintain health joint • During flares: control and resolution of inflammation

  2. Pathogenesis • 2 major pharmaceutical targets: • Inhibition of xanthine oxidase: e.g. allopurinol, febuxostat • Increase renal uric acid excretion: e.g. probenecid Endogenous source: cellular break down nucleic acids Purines: Hypoxanthine Guanine Xanthine oxidase Guanine deaminase Xanthine Xanthine oxidase Food rich in purine Uric acid Uricase: Non primates Allantoin Joint: Monosodium urate crystals Inflammation Gout Gastro-intestinal elimination 33% Renal elimination 66%

  3. Normalize urate level • Gastro-intestinal tract: probiotics • Inhibition of xanthine oxidase • Methanol extract of Chrysanthemum sinense (china) • Methanol extract of Larix laricinia ( North America) • Methanol extract of Coccinia grandis (India) • Methanol extract of Vitex negundo (India) • Chloroform extract of Erythrina stricta (India, China, Vietnam, Thailand) • Various plant extracts containing rutin and quercetin (Biota orientalis and others) • Cassia oil from Cinnamomum cassia • Increase renal uric acid excretion: • Methanol extract of Orthosiphon stamineus • Lignans from Phyllanthus niruri ( Southeast Asia and Latin America) • Mixed: (XOI and renal): Paedaria scandens ( China)

  4. Maintain joint health • DMOADs: glucosamine, chondroitin, insaponifiable fraction of soja and avocado • Promotion of resolution of inflammation: DHA and EPA • Plant derived anti-inflammatory agents • Curcuma • Meadowsweet • Black current

  5. Natural gout prevention program

  6. Inflammation targets during gout flare Blood vessel Neutrophil migration Monocytes Endothelium Synovium O2- Enzymes Cytokines Complement DHA + EPA Resolvins Protectins Maresins Inflammatory monosodium urate crystals Resident macrophages Dendritic cells . . . . Apoptosis . Apolipoproteins . . . . . . . . Resident macrophages TGFβ Clean up by macrophages Noninflammatory monosodium urate crystals Resolution of inflammation

  7. Goals during flares for natural anti-inflammatory • Inhibition of cytokine production: IL-1β , IL -6, IL-8 and TNF-α • Neutralize oxygen radicals and enzymes produced by activated macrophages • Promotes TGF β production • Promote resolution of inflammation

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