Serum uric acid concentration, uric acid and creatinine clearance (CUA and CCr), and daily amount of purine-N ingestion were determined in 37 patients with type II diabetes mellitus. Nine patients showed hypouricemia of 2 mg/dl or less. A negative correlation was noted between the serum uric acid concentration and the CUA /CCr ratio. Seven of 9 patients with hypouricemia showed increased CUA and 7 of 8 patients with CUA over 12.8 ml/min had hypouricemia. In addition, the serum uric acid concentration was associated with the daily amount of purine - N ingestion. Hypouricemia observed in the patients with diabetes was suggested to result mainly from the excessive renal clearance and partly from the decreased amount of purine-N ingestion.
We investigated interleukin 1 (IL-1) production from various cells stimulated with monosodium urate (MSU) to clarify the pathogenesis of gouty arthritis. Potent IL-1 activity was detected in culture supernatants from peripheral blood monocyte stimulated with MSU crystals but not those treated with hydroxyapatite or calcium pyrophosphate dihydrate. MSU crystals (over 4μg/ml)strongly induced IL-1production from synovial cells of a gouty patient. Cloned synovial cells (fibroblast-like cells and macrophage-like cells) produced a significant amount of IL-1 in response to MSU. In contrast, dendritic cells responded only to hydroxyapatite.
We report a patient with xanthinuria who showed hypouricemia during management of diabetes mellitus and hypertension. The patient was an 81 - years - old female. Serum and urinary uric acid were not detectable. Xanthinuria was suspected, and oxypurine level in serum and urine was measured at several laboratories. Serum xanthine level was 2.05,3.85 and 2.83 μg/ml, serum hypoxanthine level was 1.73,2.09 and 2.27 μg/ml, urinary xanthine level was 23.3 and 12.64 mg/dl, urinary hypoxanthine level was 3.81 and 1.86 mg/dl, which indicate a significant increase in urinary excretion of oxypurine. Xanthine oxidase activity in duodenal mucosa was not detectable at one laboratory, it was found to be extremely low compared with control at another laboratory. Thus, a diagnosis of xanthinuria of the patient was established. Although uric acid and oxypurine levels of serum and urine were measured in 28 relatives, neither xanthinuria nor its heterozygote was found.
We established a method for measuring uric acid in serum by reversed-phase liquid chromatography with ultraviolet detection. Serum (0.1ml) was mixed with 1.0 ml of 0.3 mol/l perchloric acid. After vortexmixing for 10 sec, the samples were centrifuged at 3,000 × rpm for 10 min. The supernatant diluted two-fold with 0.2 mol/l disodium hydrogen phosphate was injected onto a reversed-phase ODS column. The mobile phase was a 75 m mol/l pH 2.2sodium phosphate buffer, containing 2 % methanol. The eluent was monitored at 284nm. Analytic recovery of added uric acid was 100.6%±0.4% (× ±S. D. ) and the C. V. was 0.7∼0.9 %. The values obtained by this method correlated with those obtained by the uricase-catalase method of Kageyama (r=0.996).
Preliminary treatment of a few patients with allopurinol for 6 months resulted in a decrease in fractional uric acid clearance, which was already observed even after 3months of treatment. Therefore, we evaluated its effect on forty - one patients who were considered to have primary gout. The gouty patients were given allopurinol orally 100 mg twice a day for 6 months, and creatinine clearance (Ccr) and uric acid clearance (CUA), urine N-acetyl-β-Dglucosaminidase (NAG) and urine specific gravity based on Fishberg concentration test were measured before and 6 months after the beginning of the treatment. As the degree of deterioration on renal function may be associated with the alteration of the fractional uric acid clearance, the changes of Ccr and. CUA were compared with the value of renal function - related parameters before the treatment. In all groups, Ccr tended to elevate and CUA tended to fall after the treatment. However, the fall of fractional uric acid clearance was more attributed to the elevation of Ccr (p<0.001 )than the decrease of CUA, especially in the groups whose pretreatment Ccr was less than 60 ml/min. Therefore, we concluded that allopurinol may have a beneficial effect in preserving renal function.
Semiischemic forearm exercise tests were carried out in 14 patients with hypocalcemia (hypoparathyroidism) (n = 6), hypercalcemia (hyperparathyroidism) (n = 3), hypopotassemia (n = 3), hypothyroidism (n = 1), and drug - induced myopathy (n = 1) to investigate purine degradation in skeletal muscles. In control subjects, an increase in cubital venous ammonia was correlated with that in lactate (p<0.001). Two patients with hypoparathyroidism with elevated serum creatine kinase levels showed exaggerated ammonia and hypoxanthine responses although lactate responses were normal. The abnormal responses of ammonia and hypoxanthine were normalized 3 months after treatment with 1α-hydroxyvitamin D3. Ammonia and lactate responses in 12 other patients showed a similar correlation with that of controls. These findings suggest that excess purine degradation occurred in exercising muscles of patients with hypoparathyroidism (hypocalcemia) with elevated creatine kinase levels.