To elucidate the pathogenesis of hyperuricemia in type VII glycogenosis (muscle and erythrocyte phosphofructokinase deficiency), we studied the effect of exercise on purine catabolism in the muscle in two unrelated patients with this disorder. The patients performed semi-ischemic forearm exercise tests and metabolites appearing in cubital venous blood were measured. In contrast to the lack of increase in lactate, marked increases in ammonia, inosine and hypoxanthine were observed in both patients. These findings demonstrated there is an accelerated purine degradation in exercising muscle of type VII glycogenosis. Inosine and hypoxanthine are precursors for uric acid synthesis. We propose that the enhanced production of mosine and hypoxanthine in muscle and their subsequent release from muscle are responsible for the development of hyperuricemia in type VII glycogenosis.
This paper described a familial aggregation of subjects with xanthinuria, in which 3 of 4 siblings were affected. The propositus was a 31- year old female in whom hypouricemia was discoverd incidentally during an investigation of her major medical problem , diabetes mellitus. Her serum urate was 0.9 mg/dl and 24-hour urinary excretion of uric acid was 17 mg. Her plasma oxypurine concentration was 0.62 mg/dl and 24-hour urinary oxypurine excretion was 292.7 mg , 70 percent of the latter was xanthine. Her older brother and younger sister, who were entirely asymptomatic, were found to have xanthinuria during investigation of the family. Her father exhibited a slightly elevated excretion of oxypurines in his 24-hour urine and plasma xanthine of her mother was slightly increased. These findings suggest that they are heterozygotes. Xanthine oxidase activity in their tissues will be determined in the near future.
The purpose of this study was to investigate the effects of high purine intake on serum uric acid level. College students ingested a high purine diet containing 107 mg/day of purine nitrogen for twenty-eight days (N= 8), 174mg/day for seven days (N= 2), and 189mg /day for twenty-eight days (N= 7). In addition, we investigated the effects of high fat intake on serum uric acid level. Subjects ingested a high fat diet containing 50g/day of butter and 72 mg/day of purine nitrogen for thirty days (N= 14). During high purine intake, serum uric acid level increased after the 4th day, reaching a peak on Day 7 , and remained at this level. However after the intake period, serum uric acid level decreased and returned to pre - intake level on Day 7. Serum uric acid level during and after high fat intake showed a similar tendency. The increase ratio in serum uric acid level was 8.0-15.5% during high purine intake, but was 20% during high fat intake. During high purine intake, serum uric acid level reached a peak on Day 7, and remained at the level because uric acid clearance increased in parallel with serum uric acid level (+0.50∼+4.25 ml/min) , and therefore the balance between production and excretion of uric acid was maintained.
The purpose of this study was to examine the effects of weight training on uric acid metabolism. The subjects were eight male students training regularly. The weight training program consisted of dead- lift, bench- press and half - squat. The load weight used in the experiments was 30%,60% and 80% load weight of the maximum muscle strength of each subjects. The subjects exercised with each to ad until exhaution. One subject continued weight training with 30% or 80% load for a weak, respectively. Increases in ser um uric acid and blood lactate were significantly higher with 30% and 60% loads than with 80% load, but that of urinary excretion of uric acid was not. In contrast, serum creatine phosphokinase was significantly higher with 80% load than with 30% and 60% loads. There were no significant differences in uric acid clearance among the three experiments. Serum uric acid with 30% load continued to incre ase for a week with 30% load, but not with 80% load. The mean urinary excretion of uric acid for a week was 963±122 mg/day with 30% load and 559±90 mg/day with 80% load. These results suggest that the main cause of increased serum uric acid with 80% load is injury of muscle tissue and the main cause with 30% and 60% loads is increased degradation of skeletal muscle ATP.
We investigated serum lipoprotein levels and hyperlipoproteinemic phenotypes in 195 patients with primary gout, in order to clarify the frequency and magnitude of hyperlipoproteinemia. The patients were divided into two groups, one that had not received treatment prior to the first visit to our gout clinic, and the other that had compared with health control subject without hyperuricemia. The serum levels of cholesterol (CH) and triglyceride (TG) were increased, and high density lipoprotein cholesterol (HDL-C) levels were decreased in both groups, The frequency of hyperlipoproteinemia was 50% in the gouty group, and 56% untreated group. Phenotypes of hyperlipoproteinemia was determined by using with poJyacrylamide gel disc electrophoresis. The frequency of type IV was higher. in the gouty group than that in 877 primary hyperlipoproteinemic patients, that of type II a was, however lower. We compared the changes of serum lipid levels and phenotypes between before and after treatment by anti - hyperuricemic agents. The phenotypes of 21 cases (15%) changed from hyperlipidemia to normolipidemia, that of 13 ca. ses (14%), from normolipidemia to hyperlipidemia. The phenotypes of 10 cases (12%)varied between type II and IV, suggesting a possible linkage of combined hyperlipidemia with gout. Furtheremore, we assessed the influence of alcohol intake and obesity on occurrence of hyperlipoproteinemia in gout. In order to neglect the effect of two factors, we investigated the levels serum lipids and hyperlipoproteinemic phenotypes of ten non-drinkers who had body weight within 80-120% of the ideal body weight. Those of CH and TG were still higher in them than in controls, and those of HDL-C were lower. In conclusion, alcohol intake and obesity might be promoting factors of hyperlipoproteinemia in gout, but not initiating factors.
We measured the levels of serum uric acid and serum lipid peroxides generated by oxygen radicals in 19 healthy young males. There were no significant correlations between serum uric acid levels and body weights, nor between serum blood urea nitrogen levels and serum creatinine levels. However, there was a significant correlation between serum uric acid levels and serum lipid peroxides levels. As uric acid is thought to be an important scavenger of singlet oxygen and radicals, these results suggests that serum uric acid competes with the increase of serum lipid peroxides.
In order to elucidate the influence of parathyroid function on uric acid metabolism, a case of primary gout with parathyroid adenoma was studied before and after adenectomy. The serum calcium level was 5.13±0.15(mean±SE)rnEq/l and serurn 1,25(OH)2D was 71.5pg/ml(normal: 24.9-65.5) before adenectomy. After the operation the serum calcium and 1,25(OH)2D levels decreased significantly to 4.35±0.12mEq/l and 18.0 pg/ml, respectively. Although the serum urate remained almost unchanged before and after the operation, the ratio of urate to creatinine clearance increased considerably from 4.93±0.75% to 6.80±0.74%. These data suggest that parathyroid function such as regulation of serum calcium and 1,25 (OH)2D might influence uric acid metabolism.
Gout is usually seen in the middle aged male. Onset before the age of 30 raise the question of an unusual form of gout. We report a case of gout initially occurring in a 16-year-old male. He was transferred to us at the age of 23 when multiple tophi could be seen at the elbow, wrist, hand, knee and ankle joints. Laboratory findings showed hyperuricemia and renal insufficiency. The patient was treated successfully with urinom, an uricosuric agent. He was also treated surgically by removing several tophi at the elbows and knee joints. An enzymatic study revealed an enzymatic defect resulting in overproduction of purine.
Most neurosurgeons regard cerebral vasospasms as one of the most significant prognostic factors for patients with ruptured intracranial aneurysms. Its etiology and pathogeneis are still unknown, though there have been many clinical and experimental studies. In this report we assessed the clinical value of sequential measurement of CSF uric acid level in patients with ruptured aneurysm. CSF was investigated postoperatively in controls and 31 cases with ruptured aneurysm. The initial CSF uric acid level in patients with unruptured aneurysm was decreased but normalized within a few days after operation. In the patients with ruptured aneurysm associated with or without mild vasospasm, the CSF uric acid level was within normal or increased slightly and transiently. In the patients with ruptured aneurysm associated with severe vasospasm, the CSF uric acid level was increased markedly. The sequential measurement of uric acid in CSF in patients with ruptured aneurysm is important for evaluating intracranial tissue damage and for predicting their prognosis.
The serum uric acid ( SUA ) was measured in 21 malignant lymphoma (ML) patients and 11 multiple myeloma (MM) patients. Hyperuricemia, represented by a SUA level over 8.0 mg/dl, was found in 19.1% of the patients with ML and 9.1% of those with MM Hypouricemia (SUA below 2.5mg/dl) was noted in 4.9% and 9.1% of the patients with ML and MM, respectively. The mean SUA levels in ML were not significantly different in terms of sex, type of histology and stage of the disease. Moreover, no correlation was seen between the mean SUA levels and serum LDH activity in ML. After chemotherapy, nearly parallel decreases were observed in SUA and serum LDH in ML. The mean SUA levels were highest in Bence-Jones type among subtypes of immunogloblin in MM. The mean decrease in SUA concentration after chemotherapy without allopurinol was about 1.0 mg/dl in both MM and ML. There were no cases. There were no cases of acute hyperuricemic renal failure in either ML or MM.
We investigated luminol-dependent chemiluminescence (LDCL) of peripheral blood polymorphonuclear neutrophils (PMNs) from gouty patients. The reaction mixture consisted of peripheral PMN, luminol solution and opsonized Zymosan. In acute gouty arthritis, LDCL of PMNs was enhanced more prominently than that of asymptomatic patients and healthy volunteers. A serial measurement of LDCL revealed that enhancement of LDCL was only associated with episodes of acute gouty. When colchicine was administered during acute gouty attacks, enhancement of LDCL was suppressed. However, this suppression was more prominent in patients with Behcet's disease who were administered colchicine continuously. No significant correlation was found between serum uric acid levels and LDCL.
Hypouricemia in a 41-year-old male is reported. His serum urate was 0.4-0.8 mg/dl Through laboratory studies and roentgenology, known causes other than renal tubular dysfunction were ruled out as a mechanism of his hypouricemia. Detailed clearance study was performed to clarify his urate homeostasis. His fractional excretion of urate (ratio of urate to creatinine clearance), exceeding 100% in the basal state, slightly increased to 114% by benzbromarone and decreased to 99% by the serial administration of pyrazinamide. This finding demonstrates that his hypouricemia was due to a combined type of renal urate reabsorption defect. We also reviewed 69 reported cases of renal hypouricemia and discussed the relevance of serum urate levels and types of tubular defects.