Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Urate production (miscible urate pool and turnover, daily production, glycine incorporation into urate) and urate excretion (24 hour urinary urate excretion on a purine free diet, renal clearances of urate and creatinine, per cent renal excretion of labelled urate, extra-renal elimination of urate) were measured in members of five families who demonstrated varying degrees of deficiency of the X-linked condition hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency. The hemizygous males, all of whom eventually developed symptoms, showed consistent overproduction of urate with a renal excretion of urate that varied from moderately to considerably increased. The nine heterozygotes, of whom seven were asymptomatic, also showed abnormalities of urate production, although all but two had normal serum urate concentrations. The one heterozygote who had developed gouty arthritis had the lowest renal excretory capacity for urate, whereas the one heterozygote who had developed an episode of renal colic had the highest urate clearance. In the heterozygotes with normal serum urate concentrations, the increase urate production was balanced by the renal excretion of urate. This demonstrates the importance of the relation between urate. This demonstrates the importance of the relation-between urate production and urate excretion in determining the clinical expression of abnormal urate metabolism.
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PMID:Urate kinetics in hypoxanthine-guanine phosphoribosyltransferase deficiency: their significance for the understanding of gout. 76 40

Benzbromarone, a potent uricosuric agent, is a benzofuran derivative with a bromine on the 3rd and 5th positions of the benzene ring. Readily absorbed after oral administration, it is promptly dehalogenated in the liver and excreted via the biliary system. Peak drug concentration usually precedes maximal uricosuria following a single dose of 40 mg of benzbromarone, since benzarone, one of the two metabolites, likewise has a uricosuric action. Longterm studies in 24 gouty patients indicate that the drug is well tolerated. It has not produced any skin rash or renal colic. Renal hemodynamics, blood picture, and liver enzymes were unchanged. Since it is eliminated by the biliary tract, it may cause diarrhoea in some patients. Being a very potent uricosuric agent, it is not advocated in patients with a history of uric acid lithiasis. The uricosuric effect is not liable to be counteracted when used in conjunction with hyperuricemic diuretics. The drug is particularly useful in patients with chronic gouty arthritis and tophi, either refractory or allergic to probenecid, sulfinpyrazone, or allopurinol.
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PMID:Pharmacokinetic and clinical studies of a new uricosuric agent - benzbromarone. 97 66

Thirty patients with gouty arthritis were studied over 3 years. The diagnosis was established with the help of polarised light microscopy. All the patients were males, with a median age of 45 years. They belonged to the middle or upper socio-economic class and were obese (mean body mass index 29.7). Chronic alcoholism, diabetes mellitus and hypertension were present in one patient each. No patient had symptomatic coronary artery disease. Although 6 patients had a history of renal colic, only one had gouty nephropathy with chronic renal failure. Six patients had a positive family history of gout. The disease involved mostly the joints of the lower extremity and podagra was observed in 70% of patients. Eight patients had tophi at various sites. There were 17 'over producers' and 13 'under excretors' of uric acid. The treatment consisted of patient education, symptomatic control with non steroidal anti-inflammatory drugs and/or colchicine and antihyperuricaemic therapy. The overproducers were treated with allopurinol while the under excretors were treated with [corrected] sulfinpyrazone. In general, there was a good response to therapy as indicated by lowering of serum uric acid and the number of painful episodes per year. The overall profile of the disease appears similar to that seen in the West.
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PMID:Clinical profile, therapeutic approach and outcome of gouty arthritis in northern India. 238 54

Overactivity of phosphoribosylpyrophosphate synthetase (PRS) is an X chromosome-linked disorder of purine metabolism that is characterized by gout with uric acid overproduction and, in some families, neurodevelopmental impairment. We present the case of a 24-year-old Spanish woman with renal colic and hyperuricemia, which first manifested at age 11 years. Results of enzymatic and genetic studies supported the view that accelerated purine nucleotide and uric acid production in this woman resulted from defective allosteric regulation of PRS activity, which is, in turn, a consequence of a mutation in one of the patient's PRPS1 genes: an A-to-T substitution at nucleotide 578, encoding leucine for histidine at amino acid residue 192 of the mature PRS1 isoform. A previous example of disordered regulation of PRS1 activity in a family with a different substitution at the same amino acid residue strengthens this proposed mechanism. This is the first reported instance of PRS overactivity in which the propositus and sole affected family member is a woman.
Arthritis Rheum 2003 Jul
PMID:Phosphoribosylpyrophosphate synthetase overactivity as a cause of uric acid overproduction in a young woman. 1284 98