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)

The enzyme guanine aminohydrolase (guanase) is inhibited by low levels of Pb2+. The inhibition is noncompetitive and the Ki is 3.0 X 10(-6) M. The only other heavy metals that are inhibitory at low concentrations are Ag+, which is 36% more, and Hg2+, which is about 50% less inhibitory than Pb2+. The inhibition of guanase by Pb2+ and Hg2+ is synergistic and the inhibition of the enzyme was readily reversed by EDTA. The relationship of these studies with guanase and to the etiology and treatment of saturnine gout, which appears in humans suffering from lead poisoning, is discussed.
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PMID:Effects of plumbous ion on guanine metabolism. 11 6

Intravenous injection of a sublethal dose of lead acetate into a domestic pig resulted in a 4.5-fold increase of guanine in the urine, indicating an impairment in the conversion of guanine to xanthine. This impairment is probably due to the inhibition of guanine aminohydrolase (guanase), since the activity of this enzyme is inhibited by Pb2+ (the inhibition constant being 3.0 X 10(-6)M). Postmortem histological examination revealed concretions of crystalline material in the epiphyseal plate of the femoral head. Extraction of the section containing the concretions showed that they were guanine. The relation of these findings to saturnine gout is discussed.
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PMID:Saturnine gout: lead-induced formation of guanine crystals. 62 68

Lead may exert toxic effects on several organ systems, but those in the kidney are the most insidious. Acute lead nephropathy is characterized by proximal tubular dysfunction with the development of a Fanconi-type syndrome, alterations in mitochondrial structure and the development of cytosolic and nuclear inclusion bodies. Intracellular lead is associated with specific high affinity proteins and can also bind to metallothionein. Chronic lead nephropathy is irreversible and is typically accompanied by interstitial fibrosis, both hyperplasia and atrophy of the tubules, glomerulonephritis and, ultimately, renal failure. In addition, lead produces renal neoplasms in experimental animals. Chronic lead exposure is also implicated in the development of saturnine gout and hypertension. The metal interacts with renal membranes and enzymes and disrupts energy production, calcium metabolism, glucose homeostasis, ion transport processes and the renin-angiotensin system. This review summarizes the biochemical effects of lead on the kidney to understand the mechanisms of lead-induced nephropathy and other associated disorders.
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PMID:Lead nephrotoxicity and associated disorders: biochemical mechanisms. 131 92

Lead intoxication was recognised as early as 2000 BC and the widespread use of lead has been a cause of endemic chronic plumbism in several societies throughout history. In the twentieth century, lead intoxication is still a common problem. In children it is largely due to ingestion of pica and environmental exposure, whereas adult groups at greatest risk are the industrially exposed: thus, screening of these workers should be undertaken at regular intervals. The clinical features of lead intoxication are nonspecific and often go unrecognised. The early manifestations are largely neuropsychiatric, followed by more significant disturbances of the central and peripheral nervous systems, symptomatic gastrointestinal, musculoskeletal, haematological and endocrine abnormalities. The association of lead poisoning with renal disease is well documented and must be considered, particularly if there is associated hypertension and/or gout. Blood lead concentrations are an unreliable predictor of body lead stores as they are indicative only of recent exposure. Haematological parameters have been used to assess those at risk of toxicity, but although more reliable than blood concentrations, they also fail to predict those patients at risk of toxicity. The recommended assessment for patients with suspected lead intoxication is a calcium disodium edetate chelation test, which is a sensitive marker for assessing body stores and subsequent intoxication. In children the dosage should be 50 mg/kg up to 1000 mg, and in adults 1000 mg administered intravenously or 2000 mg intramuscularly in divided doses 12 hours apart with subsequent 72 hour urinary lead estimations. Lead excretion levels greater than 350 micrograms/72 hours should be considered as suggestive of intoxication, particularly if supported by historical, clinical or biochemical evidence of lead exposure. Treatment of patients with positive chelation tests involves symptomatic treatment and a course of chelation therapy utilising calcium disodium edetate in doses similar to those used for testing, and in the more severely intoxicated patient, the addition of dimercaprol in doses of 75 mg/m2 every 4 hours to a total of 300 mg/m2/day. The safety of these treatment regimens is well documented.
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PMID:Lead intoxication. 354 May 17

Lead intoxication in human beings has been documented since the second century B.C. Renal disease, hypertension, and gout have all been linked to lead by strong circumstantial evidence. Both acute and chronic nephropathy can occur as a result of lead poisoning. Acute renal failure develops following acute lead intoxication and is often associated with gastrointestinal, neurologic, and hematologic disorders. Both blood and urinary laboratory abnormalities are associated with acute intoxication and are often diagnostic. Chronic lead nephropathy, a chronic tubulointerstitial nephritis on biopsy, occurs in the setting of long-term lead exposure and is often associated with hypertension and gout. Diagnosis of chronic lead nephropathy is more difficult since the laboratory abnormalities seen with acute lead intoxication are not present with chronic lead exposure. The typical clinical picture and the exclusion of other causes of renal disease allow the diagnosis of chronic lead nephropathy to be made. Evaluation of lead stores by either the calcium disodium edetate (EDTA) mobilization test or K-x-ray fluorescence are helpful in clinching the diagnosis. Treatment with EDTA lead mobilization is effective for acute lead poisoning while avoidance of further lead exposure prevents recurrence of lead intoxication. Treatment of chronic lead nephropathy with EDTA lead mobilization is useful if renal failure is modest; however, EDTA mobilization is of no benefit in patients with more severe renal insufficiency.
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PMID:Lead and the kidney: nephropathy, hypertension, and gout. 890 77