Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 55-year-old woman was referred to our ward for further evaluation of marked hyperuricaemia and suspected tophi. On physical examination, huge subcutaneous nodules were observed on the knee joints as well as a small nodule on the lateral side of the left sole. Blood chemistry showed marked hyperuricaemia (0.85 mmol/l), hypokalaemia (2.7 mmol/l) and a mild degree of renal insufficiency. Arterial blood gas analysis showed signs of metabolic alkalosis. Daily urinary uric acid excretion on a purine non-restricted diet was 8.9 mmol/day. Uric acid clearance and fractional uric acid clearance were 0.8 ml/min and 2.6%, respectively. Plasma renin activity was 21.8 ng/ml/h, and plasma angiotensin II and aldosterone concentrations were 61 and 121 pg/ml, respectively. However, pressor response to an intravenous administration of angiotensin II was normal. The urinary calcium to creatinine molar ratio was 0.069, and serum magnesium concentration was normal to supranormal. A biopsy of the subcutaneous nodule showed a typical appearance of tophus. Based on these findings, the patient was diagnosed with an atypical case of renal tubular hypokalaemic metabolic alkalosis, with marked hyperuricaemia and tophi as the initial manifestations. So far, only four cases of Bartter's syndrome with gout and/or hyperuricaemia have been described in Japan. This rare case is presented and its mechanism of hyperuricaemia discussed.
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PMID:An atypical case of primary renal tubular hypokalaemic metabolic alkalosis with chronic tophaceous gout. 1164 22

Chronic exposure to high altitude is associated with the development of erythrocytosis, proteinuria, and, in some cases, hyperuricemia. We examined the relationship between high-altitude polycythemia and proteinuria and hyperuricemia in Cerro de Pasco, Peru (altitude, 4,300 m). We studied 25 adult men with hematocrits less than 65% and 27 subjects with excessive erythrocytosis (EE; hematocrit > 65%) living in Cerro de Pasco, Peru and compared them with 28 control subjects living in Lima, Peru (at sea level) and after 48 hours of exposure to high altitude. Serum urate levels were significantly elevated in patients with EE at altitude, and gout occurred in 4 of 27 of these subjects. Urate level strongly correlated with hematocrit (r = 0.71; P < 0.0001). Urate production (24-hour urine urate excretion and urine urate-creatinine ratio) was increased in this group compared with those at sea level. Fractional urate excretion was not increased, and fractional lithium excretion was reduced, in keeping with increased proximal reabsorption of filtrate. Significantly higher blood pressures and decreased renin levels in the EE group were in keeping with increased proximal sodium reabsorption. Serum urate levels correlated with mean blood pressure (r = 0.50; P < 0.0001). Significant proteinuria was more prevalent in the EE group despite normal renal function. Hyperuricemia is common in subjects living at high altitude and associated with EE, hypertension, and proteinuria. The increase in uric acid levels appears to be caused by increased urate generation secondary to systemic hypoxia, although a relative impairment in renal excretion also may contribute.
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PMID:Hyperuricemia, hypertension, and proteinuria associated with high-altitude polycythemia. 1204 23

Uric acid (UA) is a purine metabolite that selectively inhibits peroxynitrite-mediated reactions implicated in the pathogenesis of multiple sclerosis (MS) and other neurodegenerative diseases. Serum UA levels are inversely associated with the incidence of MS in humans because MS patients have low serum UA levels and individuals with hyperuricemia (gout) rarely develop the disease. Moreover, the administration of UA is therapeutic in experimental allergic encephalomyelitis (EAE), an animal model of MS. Thus, raising serum UA levels in MS patients, by oral administration of a UA precursor such as inosine, may have therapeutic value. We have assessed the effects of inosine, as well as inosinic acid, on parameters relevant to the chemical reactivity of peroxynitrite and the pathogenesis of EAE. Both had no effect on chemical reactions associated with peroxynitrite, such as tyrosine nitration, or on the activation of inflammatory cells in vitro. Moreover, when mice treated with the urate oxidase inhibitor potassium oxonate were fed inosine or inosinic acid, serum UA levels were elevated markedly for a period of hours, whereas only a minor, transient increase in serum inosine was detected. Administration of inosinic acid suppressed the appearance of clinical signs of EAE and promoted recovery from ongoing disease. The therapeutic effect on animals with active EAE was associated with increased UA, but not inosine, levels in CNS tissue. We, therefore, conclude that the mode of action of inosine and inosinic acid in EAE is via their metabolism to UA.
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PMID:Therapeutic intervention in experimental allergic encephalomyelitis by administration of uric acid precursors. 1245 Nov 83

The characteristic phenomena of acute gouty arthritis are acute arthritis in a middle-aged male, associated with serum uric acid above 6 mg. per 100 cc. and a satisfactory response to colchicine. Roentgenographically observable changes do not occur early. In recent years uric acid metabolism has been studied by means of isotope techniques utilizing labeled substances. Uric acid is excreted in relatively constant amounts by humans and is little affected by variations in dietary intake, except for purine or nucleic acid substances. Persons with gout have a greater total amount of uric acid and a lower turnover than normal persons. In the treatment of acute attacks of gout colchicine is still the most practical single drug, even though its pharmacologic action remains unknown. Benemid (probenecid) is a powerful uricosuric agent of low toxicity which has been subjected to extensive clinical trial for three years. It causes inhibition of the resorption of urate from the glomerular filtrate; the site of action is believed to be the tubular cells. The author's usual dose is 2 gm. a day. This has caused a lowering of the uric acid in the serum and an increase in the urinary output.
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PMID:Diagnosis and treatment of gouty arthritis. 1308 23

Urate, a purine metabolite, is a cause of gout(hyperuricemia), which is an independent risk factor for cardiovascular disease. Urate is a scavenger of reactive oxygen radicals that are involved in numerous diseases. Because humans have a renal urate reabsorption system and have lost hepatic uricase by mutational silencing in evolution, urate is present in human blood at high levels. We identified the long-hypothesized urate transporter in the human kidney (URAT1, encoded by SLC22A12), a urate anion exchanger regulating blood urate levels and targeted it with uricosuric and antiuricosuric agents. Moreover, we demonstrated that patients with renal hypouricemia have mutational defects in SLC22A12.
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PMID:[Urate transporter and renal hypouricemia]. 1456 Jun 59

Uric acid, an antioxidant, is reduced in multiple sclerosis (MS). Patients with gout have a reduced incidence of MS. Optic neuritis (ON), often the first manifestation of MS, is not known to be associated with reduced uric acid. Patients with recent onset of ON were investigated to determine whether uric acid levels were reduced at presentation. Twenty-one patients with ON were included, 17 females and 4 males. The mean (SD) serum uric acid in the ON female group was 184.4 ( +/-55.1) micromol/L (range, 116-309 micromol/L), whilst in the control group it was 235.2 (+/- 50.2) micromol/L (range, 172-381 micromol/L). The difference was statistically significant (chi2 = 8.93, P = 0.003). In the small male cohort, mean (SD) serum uric acid was 305 (+/- 52.1) micromol/L, whilst in the control group it was 328 (+/- 80.4) micromol/L. These differences were not statistically significant. Reduced antioxidant reserve is possibly an early pathogenic mechanism in inflammatory demyelination, and raises the possibility that low uric acid levels could be an indicator of disease activity. Since optic neuropathies of other causes were not investigated, future research needs to determine whether low uric acid represents a unique feature of optic neuritis or is seen in other optic neuropathies.
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PMID:Serum uric acid levels in optic neuritis. 1522 91

In humans, uric acid is the final breakdown product of unwanted purine nucleotides. Uric acid is the last stage in purine degradation, because humans lack the enzyme uricase which converts uric acid into allantoin. Uric acid has profound beneficial effects since it scavenges potential harmful radicals in our body. However, in conjunction with genetic or environmental factors, uric acid can cause significant health problems, leading to kidney stones when it builds up in the kidneys and to gout when crystals accumulate in the joints. The levels of uric acid in the blood must be tightly controlled to minimize these detrimental effects. Normally, the body eliminates enough uric acid in the kidney, and in part also through the intestines, to keep its concentration at a healthy level in the blood (approximately 300 microM). In patients with gout or kidney stone disease, however, the body either produces excessive amounts of uric acid or its ability to eliminate uric acid is disturbed in some way. In the kidney, uric acid is reabsorbed via the uric acid transporter URAT1. This transporter is the major mechanism for regulating blood uric acid levels and therefore may prove an interesting target for future drug development.
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PMID:[Physiology and biochemistry of uric acid]. 1549 12

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Its etiology is not known, but it is well established that auto-reactive T-cells and monocytes play an important pathogenetic role. Experimental allergic encephalomyelitis (EAE) of mice serves as disease model for MS. In both EAE and MS inflammatory cells produce nitric oxide and its oxidizing congeners such as peroxynitrite. Peroxynitrite and other reactive nitrogen oxide species exert a toxic effect on neurons, axons and glia cells and enhance apoptosis. In addition, they increase the blood-CNS-barrier permeability and can therefore promote invasion of inflammatory cells into the CNS. On the other hand, uric acid, a peroxynitrite scavenger inhibits blood-CNS-barrier permeability changes, CNS inflammation and tissue damage in EAE. Epidemiological studies have shown that MS and gout are almost mutually exclusive diseases. Uric acid levels in MS patients are lower than in controls and in patients with active disease lower than in MS patients in remission. Inosine, a uric acid precursor, can be used to raise uric acid levels in serum and may provide some benefit in MS patients. A small study of ten patients with progressive MS has demonstrated some improved function in three of them and no sign of progression or relapse in the other. However, this study does not justify a recommendation for use of inosine in MS patients yet. At present, uric acid can solely be regarded as a marker of disease activity in MS. In addition, the current knowledge of uric acid and MS supports hypotheses which predict a positive effect of radical scavengers in MS.
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PMID:[Uric acid and multiple sclerosis]. 1549 14

Uric acid stones occur in 10% of all kidney stones and are the second most-common cause of urinary stones after calcium oxalate and calcium phosphate calculi. The most important risk factor for uric acid crystallization and stone formation is a low urine pH (below 5.5) rather than an increased urinary uric acid excretion. Main causes of low urine pH are tubular disorders (including gout), chronic diarrhea or severe dehydration. Uric acid stone disease can be prevented and these are one of the few urinary tract stones that can be dissolved successfully. The treatment of uric acid stones consists not only of hydration (urine volume above 2000 ml daily), but mainly of urine alkalinization to pH values between 6.2 and 6.8. Urinary alkalization with potassium citrate or sodium bicarbonate is a highly effective treatment, resulting in dissolution of existing stones. Urinary uric acid excretion can be reduced by a low-purine diet. Potassium citrate is the treatment of choice for the prevention of recurrence of uric acid calculi. Allopurinol reduces the frequency of stone formation in hyperuricosuric patients with recurrent uric acid stones and/or gout.
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PMID:[Diagnosis and prevention of uric acid stones]. 1549 18

Humans excrete uric acid as the final breakdown product of unwanted purine nucleotides. Urate scavenges potential harmful radicals in our body. However, in conjunction with genetic or environmental (especially dietary) factors, urate may cause gout, nephrolitiasis, hypertension, and vascular disease. Blood levels of urate are maintained by the balance between generation and excretion. Excretion requires specialized transporters located in renal proximal tubule cells, intestinal epithelial cells, and vascular smooth muscle cells. The recently identified human urate transporters URAT1, MRP4, OAT1, and OAT3 are thought to play central roles in homeostasis and may prove interesting targets for future drug development.
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PMID:Molecular physiology of urate transport. 1577 1


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