Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0451641 (urolithiasis)
 3,973 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Because of the discovery of uric acid urolithiasis in rats after end-to-side portacaval anastomosis (PCA), uric acid metabolism was studied in these animals and in appropriate controls. Hyperuricemia and hyperuricosuria were observed in all experimental rats. The fraction of purine catabolites excreted in the urine as uric acid increased from an average of 4.8% to 15.3%. If 14C-uric specifically labeled at position 6 (6-14C-ua) was infused intravenously and the exhalation of 14CO2 was used to calculate a hepatic uric acid clearance, it decreased from 2.14 to 0.97 ml/min/100 gm despite a normal content of hepatic uricase activity as measured in liver homogenates. The fraction of the filtered amount of uric acid excreted in the urine increased from an average of 11% to 30%. Increased supersaturation of the urine with uric acid after PCA may be expected to contribute to the formation of uric acid urolithiasis. This investigation defines a hepatic and renal functional defect in uric acid metabolism which occurs as a result of the PCA.
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PMID:The defect of uric acid metabolism in Eck-fistula rats. 1 44

After introducing into developmental aspects of "Dalmatian dog research" uric acid excretion is explained on the basis of new results by the loss of a specific transport system in liver cell membranes. Therefore, uricase which is present in normal activities is supplied only to a limited extent with uric acid for the transformation into the easily soluble allantoin. As indicated by feeding experiments, the plasma urate level is increased from about 32 mumol/l (no purine intake) up to 150-200 mumol/l at very high levels of purine intake. Thus, the influence of nutrition on plasma urate level is extraordinary. The diseases urate-urolithiasis and "bronze syndrome" associated with dalmatian urate metabolism are characterized in view of the typical pattern of the diseases and of the therapeutical and prophylactical measures to be taken.
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PMID:[Why Dalmatians excrete uric acid. Causes and consequences of a classical metabolic disorder]. 407 31

There are three stages in the management of gout: (i) treating the acute attack; (ii) lowering excess stores of uric acid to prevent flares of gouty arthritis and to prevent tissue deposition of urate; and (iii) providing prophylaxis to prevent acute flares. It is important to distinguish between therapy to reduce acute inflammation in acute gout and therapy to manage hyperuricaemia in patients with chronic gouty arthritis. During the acute gouty attack nonpharmacological treatments such as topical ice and rest of the inflamed joint are useful. NSAIDs are the preferred treatment in acute gout. The most important determinant of therapeutic success is not which NSAID is chosen, but rather how soon NSAID therapy is initiated. Other treatments include oral and intravenous colchicine, intra-articular and systemic corticosteroids, and intramuscular corticotropin. Optimal treatment of chronic gout requires long-standing reduction in serum uric acid. The urate-lowering drugs used to treat chronic gout are the uricosuric drugs, the uricostatic drugs, which are xanthine oxidase inhibitors, and the uricolytic drugs. Xanthine oxidase inhibitors such as allopurinol, oxipurinol and febuxastat should be used as first-line treatment in patients with renal calculi, renal insufficiency, concomitant diuretic therapy and ciclosporin (cyclosporine) therapy, and urate overproduction. Uricosuric drugs include probenecid, benzbromarone, micronised fenofibrate and losartan. They are the urate-lowering drugs of choice in allopurinol-allergic patients and underexcretors with normal renal function and no history of urolithiasis. The use of recombinant urate oxidase in patients with chronic gout is limited by the need for parenteral administration, the potential antigenicity and production of anti-urate oxidase antibodies, and declining efficacy. The effectiveness of colchicine prophylaxis as an isolated therapy is still to be confirmed by placebo-controlled trials. Another issue is prophylaxis with NSAIDs. There are no comparative studies with colchicine.
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PMID:Management of acute and chronic gouty arthritis: present state-of-the-art. 1548 99

Uricase (EC 1.7.3.3, UC) catalyzes the oxidation of uric acid (UA) to more soluble allantoin thereby lowering plasma UA levels. In humans, when concentration of UA exceeds >7mg/dl, it leads to hyperuricemia, gout, nephrolithiasis and urolithiasis. A new remedy to cure such metabolic diseases is the enzyme supplementation therapy by UC but with high degree of antigenic independence. Therefore screening of new uricase sources to expand its usefulness and reduced antigenecity is needed. Present study employed cheminformatics approach to construct models of reported UC from different sources viz. Bacillus megaterium, Streptomyces bingchenggensis BCW-1, Paenibacillus sp, Solibacter usitatus Ellin6076, Truepera radiovictrix DSM 17093 and Ktedonobacter racemifer DSM 4496 in order to study their structure-function relationship for enzyme mass production and modification for improved characteristics. BioMed CAChe version 6.1 was further used to study enzyme-substrate interactions of models with uric acid using docking approach. Results indicated that models for UC of Streptomyces bingchenggensis BCW-1 accounted for better regio-specificity towards UA, supporting the interested metabolism and thus may further be implicated in enzyme supplementation therapy for hyperuricemic associated disorders.
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PMID:Comparative structural modeling and docking studies of uricase: possible implication in enzyme supplementation therapy for hyperuricemic disorders. 2253 75

Urate is the end product of purine metabolism in humans, owing to the evolutionary disruption of the gene encoding urate oxidase (UOx). Elevated urate can cause gout and urolithiasis and is associated with cardiovascular and other diseases. However, urate also possesses antioxidant and neuroprotective properties. Recent convergence of epidemiological and clinical data has identified urate as a predictor of both reduced risk and favorable progression of Parkinson's disease (PD). In rodents, functional UOx catalyzes urate oxidation to allantoin. We found that UOx KO mice with a constitutive mutation of the gene have increased concentrations of brain urate. By contrast, UOx transgenic (Tg) mice overexpressing the enzyme have reduced brain urate concentrations. Effects of the complementary UOx manipulations were assessed in a mouse intrastriatal 6-hydroxydopamine (6-OHDA) model of hemiparkinsonism. UOx KO mice exhibit attenuated toxic effects of 6-OHDA on nigral dopaminergic cell counts, striatal dopamine content, and rotational behavior. Conversely, Tg overexpression of UOx exacerbates these morphological, neurochemical, and functional lesions of the dopaminergic nigrostriatal pathway. Together our data support a neuroprotective role of endogenous urate in dopaminergic neurons and strengthen the rationale for developing urate-elevating strategies as potential disease-modifying therapy for PD.
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PMID:Disrupted and transgenic urate oxidase alter urate and dopaminergic neurodegeneration. 2324 82