Drug-induced haemolysis in glucose-6-phosphate dehydrogenase deficiency

People with the variants of glucose-6-phosphate dehydrogenase (GPD) deficiency common in the southern Chinese (Canton, B(-)Chinese, and Hong Kong-Pokfulam) have a moderate shortening of red-cell survival but no anaemia when they are in the steady state. With a cross-transfusion technique, primaquine, nitrofurantoin, and large doses of aspirin were found to aggravate the haemolysis while sulphamethoxazole did so only in some people. Individual differences in drug metabolism may be the reason for this. Many commonly used drugs reported to accentuate haemolysis in GPD deficiency did not shorten red-cell survival.     

An autosomal glucose-6-phosphate dehydrogenase (hexose-6-phosphate dehydrogenase) polymorphism in human saliva

Glucose-6-phosphate dehydrogenase (hexose-6-phosphate dehydrogenase) from human saliva has been demonstrated by the zymogram technique. Three phenotypes were found. Family and population studies suggested that these phenotypes are the products of an autosomal locus with two alleles Sgd-1 and Sgd-2.     

Molecular genetics of glucose-6-phosphate dehydrogenase deficiency in Mexico

PURPOSE: To report the results of a prospective study of the incidence of peripheral visual field loss after macular hole surgery. METHODS: Prospectively, 30 eyes of 30 consecutive patients with full-thickness macular holes operated on between December 1995 and April 1996 had preoperative and postoperative Goldmann visual field tests. The surgical procedure consisted of three-port pars plana vitrectomy, posterior hyaloid removal, nonexpansile fluid-hexafluoroethane (C2F6) exchange, and, in 19 of 30 patients, autologous platelet injection, followed by face-down positioning. RESULTS: Twenty-nine of these 30 cases were considered to be anatomic successes. Comparison of preoperative and postoperative visual fields disclosed that four patients (13%) had a peripheral scotoma, including one patient with stage 4 macular hole. Three other patients (10%) had a postoperative relative arcuate defect. Mean postoperative intraocular pressure was higher in the latter group. None of the patients complained of peripheral scotoma. CONCLUSIONS: Overall, seven of 30 patients (23%) had a postoperative visual field defect. Two categories of scotomas were observed: peripheral and relative arcuate. The cause of peripheral visual field loss is unclear. Increased intraocular pressure may be the cause of relative arcuate scotomas.     

Synthesis and loss of activity of glucose-6-phosphate dehydrogenase in dividing plant cells

1. Using the technique of density-labelling with deuterium oxide, evidence has been obtained for the de novo synthesis of glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate:NADPH+ 1-oxidoreductase, EC 1.1.1.49), during the culture of synchronously growing plant cells. 2. The entire increase in enzyme activity during the early cell cycles in this material can be accounted for by the appearance of an enzyme species with increased buoyand density. 3. A method is described for resolving overlapping distribution profiles after density centrifugation, which allows estimation of the amount of each species present at different times, and calculation of the loss of activity of the light species present from the start of culture. 4. Loss of activity of glucose-6-phosphate dehydrogenase in normal growing conditions in the presence of 2,4-dichlorophenoxyacetic acid is very much faster than in conditions which do not lead to cell division: in the absence of 2,4-dichlorophenoxyacetic acid, or in the presence of the inhibitor of RNA synthesis, 6-methylpurine.     

Importance of glucose-6-phosphate dehydrogenase activity for cell growth

The intracellular redox potential, which is determined by the level of oxidants and reductants, has been shown to play an important role in the regulation of cell growth. The principal intracellular reductant is NADPH, which is mainly produced by the pentose phosphate pathway through the actions of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the pentose phosphate pathway, and by 6-phosphogluconate dehydrogenase. Previous research has suggested that an increase in G6PD activity is important for cell growth. In this article, we suggest that G6PD activity plays a critical role in cell growth by providing NADPH for redox regulation. The results show the following: 1) inhibition of G6PD activity abrogated growth factor stimulation of [3H]thymidine incorporation in all cell lines tested; 2) overexpression of G6PD stimulated cell growth, as measured by an increase in [3H]thymidine incorporations as compared with cells transfected with vector alone; 3) inhibition of G6PD caused cells to be more susceptible to the growth inhibitory effects of H2O2; 4) inhibition of G6PD led to a 30-40% decrease in the NADPH/NADP ratio; and 5) inhibition of G6PD inhibited cell anchorage and significantly decreased the growth-related stimulation of tyrosine phosphorylation.     

Severe neonatal hyperbilirubinemia. A potential complication of glucose-6-phosphate dehydrogenase deficiency

G-6-PD deficiency is frequently associated with neonatal hyperbilirubinemia, which may be severe enough to cause kernicterus and death. Because of its association with acute trigger-induced hemolytic crises, G-6-PD deficiency-associated neonatal hyperbilirubinemia has been labelled as hemolytic in origin. In this article, the authors summarize recent evidence demonstrating that hemolysis cannot in and of itself be responsible for jaundice and that decreased bilirubin elimination plays a major role in its pathogenesis.     

Mortality in a cohort of men expressing the glucose-6-phosphate dehydrogenase deficiency

The objective of this study was to test the hypothesis of a lower mortality from cancer and cardiovascular diseases among men expressing glucose-6-phosphate dehydrogenase (G6PD) deficiency. We designed a mortality study based on death certificates from January 1, 1982 through December 31, 1992 in a cohort of G6PD-deficient men. Cohort members were 1,756 men, identified as expressing the G6PD-deficient phenotype during a 1981 population screening of the G6PD polymorphism. The setting was the island of Sardinia, Italy. Outcome measures were cause-specific standardized mortality ratios (SMRs), which were computed as 100 times the observed/expected ratio, with the general Sardinian male population as the reference. Deaths from all causes were significantly less than expected due to decreased SMRs for ischemic heart disease (SMR, 28; 95% confidence interval [CI], 10 to 62), cerebrovascular disease (SMR, 22; 95% CI, 6 to 55), and liver cirrhosis (SMR, 12; 95% CI, 0 to 66), which explained 95.6% of the deficit in total mortality. All cancer mortality was close to the expectation, with a significant increase in the SMR for non-Hodgkin's lymphoma (SMR, 545; 95% CI, 147 to 1,395). A decrease in mortality from cardiovascular diseases was one of the study hypotheses, based on an earlier human report and experimental evidence. However, selection bias is also a likely explanation. Further analytic studies are warranted to confirm whether subjects expressing the G6PD-deficient phenotype are protected against ischemic heart disease and cerebrovascular disease. This cohort study is consistent with more recent case-control studies in rejecting the hypothesis of a decreased cancer risk among G6PD-deficient subjects. The observed increase in mortality from non-Hodgkin's lymphoma and decrease in mortality from liver cirrhosis were not previously reported.     

Genetic analysis of the glucose-6-phosphate dehydrogenase deficiency in a southern Croatia

PURPOSE: To evaluate objectively the effects of a microbubble contrast agent on the color Doppler ultrasound (US) examination of breast lesions. MATERIALS AND METHODS: Forty-seven patients aged 23-71 years underwent color Doppler US before and after intravenous injection of a microbubble contrast agent. A 3-minute computer-assisted assessment of the color pixel density (CPD) was used to evaluate objectively the increase in the number of color Doppler US signals, the transit time of the microbubble bolus, and the potential additional differential diagnostic information. RESULTS: Peak CPD at contrast agent-enhanced color Doppler US was 14.3% +/- 8.1 (mean +/- 1 standard deviation) for carcinomas and 9.3% +/- 4.9 for benign lesions (P = .04). The time to peak enhancement was shorter in carcinomas (38 seconds +/- 20) than in benign tumors (71 seconds +/- 48, P = .02). Final CPD was close or equal to baseline values. With the median of 13% for peak CPD as a threshold, the sensitivity for this parameter was 55%, the specificity was 79%, and the accuracy was 62% (P = .04). For a median time to peak of 50 seconds, the sensitivity was 84%, the specificity was 57%, and the accuracy was 76%. CONCLUSION: After microbubble contrast agent injection, carcinomas and benign lesions behave differently in degree, onset, and duration of Doppler US enhancement. High interindividual variability and temporal variations in the Doppler US signal still limit the value of these criteria for prospective diagnosis.     

Compatible organic osmolytes in rat liver sinusoidal endothelial cells

Vanadium has been found to be orally active in lowering plasma glucose levels; thus it provides a potential treatment for diabetes mellitus. Bis(maltolato)oxovanadium(IV) (BMOV) is a well-characterized organovanadium compound that has been shown in preliminary studies to have a potentially useful absorption profile. Tissue distributions of BMOV compared with those of vanadyl sulfate (VS) were studied in Wistar rats by using 48V as a tracer. In this study, the compounds were administered in carrier-added forms by either oral gavage or intraperitoneal injection. Data analyzed by a compartmental model, by using simulation, analysis, and modeling (i.e., SAAM II) software, showed a pattern of increased tissue uptake with use of 48V-BMOV compared with 48VS. The highest 48V concentrations at 24 h after gavage were in bone, followed by kidney and liver. Most ingested 48V was eliminated unabsorbed by fecal excretion. On average, 48V concentrations in bone, kidney, and liver 24 h after oral administration of 48V-BMOV were two to three times higher than those of 48VS, which is consistent with the increased glucose-lowering potency of BMOV in acute glucose lowering compared with VS.     

HLA antigens and erythrocyte glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in Sardinia

Wind enhances the carcinogenic effect of chronic Iltraviolet radiation (UVL). This was demonstrated in hairless mice that were irradiated for 42 weeks with mercury are lamps. One group of animals was exposed to continuous wind flow of 2.7 m/s except for the daily I-2 min time interval when they were removed from the wind tunnel and irradiated. Another group of animals received identical irradiation but were protected from wind. The first tumour appeared in the UVL and wind group after 105 days of irradiation, and at 164 days of irradiation all surviving mice in the group had developed tumours. The group of mice receiving identical irradiation but protected from wind had their first tumour appear at 154 days of irradiation, and by 164 days of irradiation only 40% of the mice had developed tumours.     

Crystallization and preliminary x-ray data for glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides

The enzyme glucose-6-phosphate dehydrogenase from Leuconostoc mesenteroides has been crystallized from phosphate buffer in a form suitable for x-ray crystallographic studies. The crystals diffract to better than 2.4 A. The spacegroup is P3121 (P3221) a = 105.8 A, c = 225.1 A, V = 2.18 X 10(6) A3. The asymmetric unit probably contains a single dimer.     

Enhanced expressions of glucose-6-phosphate dehydrogenase and cytosolic aldehyde dehydrogenase and elevation of reduced glutathione level in cyclophosphamide-resistant human leukemia cells

PURPOSE: To determine the involvement of p53 in ionizing radiation-induced excision and recombination repair. MATERIALS AND METHODS: Shuttle vector pZ189 containing radiation-induced single strand breaks plus base damage (ocDNA), ultraviolet-radiation damage (uvDNA), or a restriction enzyme-produced double strand break (linDNA) were processed in unirradiated or irradiated p53wt and p53mut lymphoblasts. Mutation frequencies in the supF-tRNA target gene and survival of plasmids processed in p53wt and p53mut hosts were compared. RESULTS: Mutation frequencies of oc-, uv- or linDNA were similar after processing in unirradiated p53wt and p53mut hosts. However, the mutation frequency of ocDNA and uvDNA decreased 50% when processed in irradiated p53wt hosts but was unaltered in irradiated p53mut hosts. In contrast, linDNA mutation frequencies varied similarly whether processed in irradiated p53wt or p53mut hosts: mutation frequency decreased twofold when linDNA was transfected immediately after host irradiation but increased twofold when transfection was delayed by 2h. Double strand break rejoining capacity, determined by the ratio of the number of progenies from linDNA to that from undamaged pZ189, differed both qualitatively and quantitatively in irradiated p53wt and p53mut hosts. CONCLUSIONS: These studies show induction of DNA repair in mammalian cells by ionizing radiation and indicate the involvement of p53 in the modulation of excision repair fidelity and double strand break rejoining capacity.