Objective: This prospective study examined purine metabolism in relation to free oxygen radical activity, as reflected by lipid peroxide levels in umbilical cord blood at birth. Setting: Departments of Obstetrics and Gynaecology and of Chemical Pathology, the Chinese University of Hong Kong, Hong Kong, and Purine Research Laboratory, UMDS of Guy’s and St. Thomas’ Hospitals, London, UK. Methods: Umbilical cord arterial and venous blood samples were collected from 132 singleton term deliveries for determination of hypo-xanthine, xanthine, inosine, uric acid, organic hydroperoxides (OHP) and malondialdehyde. Oxygen saturation, pO₂, PCO₂, pH, and base excess (BE) were also measured. Results: There was a significant correlation between umbilical arterial and venous levels of hypoxanthine, xanthine, inosine, uric acid and all acid-base parameters (p < 0.001). Significant arteriovenous differences were observed for all parameters with the exception of inosine, uric acid and OHP. Umbilical arterial xanthine and potassium correlated significantly with OHP, but hypoxanthine, inosine and uric acid did not. In 13 babies classified as severely asphyxiated at birth (umbilical arterial pH < 7.15, BE < -8), xanthine and OHP levels were significantly elevated when compared with non-asphyxiated babies. No significant differences were observed for hypoxanthine, inosine or uric acid. Conclusion: The findings indicate that OHP, either in cord arterial or venous blood, is the best marker of free oxygen radical activity in the fetus, and that this correlates with other evidence of cellular hypoxia-reperfusion injury. We propose OHP is a better measure of perinatal outcome than either acid-base balance or hypoxanthine.

The enzyme inosine triphosphate pyrophosphatase (ITPase) catalyses the pyrophosphohydrolysis of ITP to IMP. ITPase deficiency is a clinically benign autosomal recessive condition characterised by the abnormal accumulation of ITP in erythrocytes. A deficiency of ITPase may predict adverse reactions to therapy with the thiopurine drug 6-mercaptopurine and its prodrug azathioprine. In this study, we examine the frequencies of ITPA polymorphisms in 100 healthy Japanese individuals. The allele frequency of the 94C > A variant in the Japanese sample was 0.135 (Caucasian allele frequency 0.06). The IV2 + 21A > C polymorphism was not found in Japanese (Caucasian allele frequency 0.130). Allele frequencies of the 138G > A, 561G > A and 708G > A polymorphisms were 0.57, 0.18 and 0.06 respectively in the Japanese population, and with the exception of the 138G > A polymorphism, similar to allele frequencies in Caucasians.

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We have investigated an unusual nucleotide that accumulates, with precursors, in the erythrocytes of patients in uraemia. This nucleotide is related chemically to the NAD breakdown product, N1-methyl-2-pyridone-5-carboxamide (Me2Py), found in high concentrations in the plasma of uraemic patients. Both Me2Py and the nucleotide accumulate to high concentrations in the blood during uraemia: our investigations of samples from renal out-patients have provided information on a plausible link between the two compounds.

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