Uric acid, rise

Of the water-soluble vitamins, intakes of nicotinic acid [59-67-6] on the order of 10 to 30 times the recommended daily allowance (RE)A) have been shown to cause flushing, headache, nausea, and moderate lowering of semm cholesterol with concurrent increases in semm glucose. Toxic levels of foHc acid [59-30-3] are ca 20 mg/d in infants, and probably approach 400 mg/d in adults. The body seems able to tolerate very large intakes of ascorbic acid [50-81-7] (vitamin C) without iH effect, but levels in excess of 9 g/d have been reported to cause increases in urinary oxaHc acid excretion. Urinary and blood uric acid also rise as a result of high intakes of ascorbic acid, and these factors may increase the tendency for formation of kidney or bladder stones. AH other water-soluble vitamins possess an even wider margin of safety and present no practical problem (82). 

Lesch-Nyhan syndrome, an overproduction hyperuricemia characterized by frequent episodes of uric acid hthiasis and a bizarre syndrome of self-mutilation, reflects a defect in hypoxanthme-guanine phosphoribo-syl transferase, an enzyme of purine salvage (Figure 34—4). The accompanying rise in intracellular PRPP results in purine overproduction. Mutations that decrease or abohsh hypoxanthine-guanine phosphoribosyltrans-ferase activity include deletions, frameshift mutations, base substitutions, and aberrant mRNA splicing. 

All patients with major patterns are monitored for rhabdomyolysis and renal failure. An early sign of rhabdomyolysis is an elevated serum uric acid, associated with an increase in serum CK. Within 8 to 12 hours, the serum tests are repeated. If the uric acid falls and the CK rises, rhabdomyolysis is likely. Renal function tests may also be increased at this time. When the diagnosis of rhabdomyolysis is made, the patient is treated with 40 mg furose-mide IV once, and IV fluids. Urine myoglobin concentrations are obtained. If the patient develops renal failure, hemodialysis or peritoneal dialysis may be necessary. In all cases, multiple drug intoxication, trauma, and rhabdomyolysis are ruled out or treated. All patients are kept under observation until they are asymptomatic. 

The nature of the species that gives rise to the more negative cathodic peak observed on cyclic voltammetry of uric acid (Fig. 2) is not clear. It must be due to some relatively transient species since the peak is not pronounced at the com-pletation of the electrolysis nor is a large amount of parabanic acid formed,... 

Lesch-Nyhan syndrome A deficiency of hypoxanthine-guanine phosphoribosyltransferase results in accumulation of purine bases (Chapter 10). This causes a marked increase in the plasma level of uric acid, and hence can give rise to gout, but it also causes a severe neurological disorder, known as Lesch-Nyhan syndrome, the symptoms of which include... 

Side-effects of thiazide diuretics predominantly consist of metabolic changes, such as hypokalaemia and rise of plasma uric acid levels, glucose, and lipids (total cholesterol and triglycerides). These metabolic changes are clearly less pronounced when... 

During long-term treatment with nicotinic acid, uric acid concentrations tend to rise slightly, but the change is clinically insignificant (25). ... 

The issues of whether hyperuricemia is an independent risk factor for cardiovascular disease and the clinical relevance of the rise in serum uric acid caused by diuretic treatment are controversial (SED-14, 660 351). In the Systolic Hypertension in the Elderly Program (SHEP), diuretic-based treatment in 4327 men and women, aged 60 years or more, with isolated systolic hypertension was associated with significant reduction in cardiovascular events (SED-14, 657). Serum uric acid independently... 

Dietary purines are not an important source of uric acid. The quantitatively important amounts of purine are formed from amino acids, formate, and carbon dioxide in the body. Those purine ribonucleotides not incorporated into nucleic acids and those derived from the degradation of nucleic acids are converted to xanthine or hypoxanthine and oxidized to uric acid (Figure 36-7). When this last step is inhibited by allopurinol, there is a fall in the plasma urate level and a decrease in the size of the urate pool with a concurrent rise in the more soluble xanthine and hypoxanthine. 

In pre-eclampsia, a rise in uric acid correlates with poorer outcome for both mother and baby. If creatinine is found to be elevated early in the disease process, underlying renal disease should be suspected. Falling platelet count is associated with worsening disease and is itself a risk to the mother. If count is less than 100 x 106/L there may be associated coagulation abnormalities, and delivery should be considered. An AST level >75 IU/L is significant and >150 IU/L is associated with increased morbidity to the mother. 

The diuretic properties of indocrinone have been reported to improve by manipulation of the enantiomers rario (22) Although the diuretic property is predominantly ascribed to R(-)-indocrinone, both enantiomers possess urisocuric activity. The uricosuric effect is desirable as it counteracts the diuretic-induced rise in plasma uric acid concentration. However, this property of racemic indocrinone is transient. Examination of the overall pharmacodynamic profile of various formulations of indocrinone suggests that the patients remain isouricemic during a 7-day treatment period with an R S ratio of 10 40. 

In addition to a rise in serum potassium, timolol increases plasma uric acid concentrations (207). In the TOMHS study, acebutolol increased serum urate by 7 pmol/1 (196). 

In all clinical studies carried out to date, G-CSF has been well tolerated, whether given subcutaneously or intravenously. At the recommended doses (5-10 micrograms/ kg), generalized musculoskeletal and transient bone pains, headache, and mild rash are the commonest adverse effects (2). No additional adverse effects or delayed consequences have been so far reported in neonates treated at birth for presumed bacterial sepsis (SEDA-20, 337). An increase in the size of the spleen has been reported (3,4). Transient rises in alkaline phosphatase, lactate dehydrogenase, and uric acid are considered to be normal physiological consequences of the rise in the neutrophil count (5). Long-term G-CSF administration in patients with severe congenital neutropenia has also been considered to be relatively safe, with discontinuation or temporary withdrawal in only seven of 44 patients (6). 

The transient and moderate rises in leukocyte alkaline phosphatase and uric acid serum concentrations that are often observed after G-CSF treatment are considered to arise from an increased neutrophil count (SEDA-17, 396). Similarly, serum lactate dehydrogenase and alkaline phosphatase activities are often increased, and this should be interpreted as the consequence of enzyme release after growth factor-induced leukocyte recovery (SED-13, 1115). 

A transient, moderate, and reversible rise in leukocyte alkaline phosphatase, lactate dehydrogenase (LDH) and serum uric acid concentrations is usually observed in cancer patients receiving supportive treatment with GM-CSF or G-CSF. Serum LDH increased from 37 to 85% and there was a linear relation between increased leukocyte production and the rise in serum LDH (32). Increases in serum LDH activity should therefore not be interpreted as indicative of disease progression, unless LDH activity remains high after growth factor withdrawal. 

Nitrogenous excretory products are removed from the body mainly in the urine. In renal failure, these products will be retained. Blood urea nitrogen (BUN), creatinine, and uric acid levels will rise. 

Lesch-Nyhan syndrome is caused by a defective hypoxanthine-gua-nine phosphoribosyl transferase (HGPRT). Purine bases cannot be salvaged (i.e., reconverted to nucleotides). The purines are converted to uric acid, which rises in the blood. Mental retardation and self-mutilation are characteristics of the disease. 

Measurement of plasma uric acid is predominantly used in the investigation of gout, either as a result of a primary hyperuricemia or caused by other conditions or treatments that give rise to secondary hyperuricemias. It is also used in the diagnosis and monitoring of pregnancy-induced hypertension (preeclamptic toxemia). 

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