Glucose-6-phospate Dehydrogenase Research Articles

Artemisinin-naphthoquine plus lower-dose primaquine to treat and prevent recurrence of Plasmodium vivax malaria: an open-label randomized and non-inferiority trial.

Plasmodium vivax malaria, with the widest geographic distribution, can cause severe disease and death. Primaquine is the main licensed antimalarial drug that can kill hypnozoites. The dose-dependent acute haemolysis in individuals with glucose-6-phospate dehydrogenase (G6PD) deficiency is the main safety concern when using primaquine. The recommended treatment regimen for P. vivax malaria is chloroquine plus primaquine for 14days (CQPQ14) in Myanmar. The study aimed to evaluate the therapeutic efficacy, safety and adherence for the regimen of artemisinin-naphthoquine plus primaquine for 3days (ANPQ3) in patients with P. vivax infections compared to those with CQPQ14. The patients in the ANPQ3 group were given fixed-dose artemisinin-naphthoquine (a total 24.5mg/kg bodyweight) plus a lower total primaquine dose (0.9mg/kg bodyweight) for 3days. The patients in the CQPQ14 group were given a total chloroquine dose of 30mg/kg body weight for 3days plus a total primaquine dose of 4.2mg/kg bodyweight for 14days. All patients were followed up for 365days. A total of 288 patients completed follow-up, 172 in the ANPQ3 group and 116 in the CQPQ14 group. The first recurrence patients were detected by day 58 in both groups. By day 182, 16 recurrences had been recorded: 12 (7.0%) patients in the ANPQ3 group and 4 (3.4%) in the CQPQ14 group. The difference in recurrence-free patients was 3.5 (-8.6 to 1.5) percentage points between ANPQ3 and CQPQ14 group (P = 0.2946). By day 365, the percentage of recurrence-free patients was not significant between the two groups (P = 0.2257). Mean fever and parasite clearance time of ANPQ3 group were shorter than those in CQPQ14 group (P ≤ 0.001). No severe adverse effect was observed in ANPQ3 group, but five (3.9%) patients had acute haemolysis in CQPQ14 group (P = 0.013). Medication percentage of ANPQ3 group was significantly higher than that of CQPQ14 group (P < 0.0001). Both ANPQ3 and CQPQ14 promised clinical cure efficacy, and the radical cure efficacy was similar between the ANPQ3 and CQPQ14 group. ANPQ3 clears fever and parasites faster than CQPQ14. ANPQ3 is safer and shows better patient adherence to the regimen for treatment of P. vivax malaria along the China-Myanmar border. ChiCTR-INR-17012523. Registered 31 August 2017, https://www.chictr.org.cn/showproj.html?proj=21352.

Acute Hemolytic Anemia Following Semaglutide Injection: A Case Report

Background: Drug-induced immune hemolytic anemia is a serious adverse reaction that may result from drug administration, especially in cases of glucose-6-phospate dehydrogenase (G6PD) deficiency. Objective: To report a case of acute hemolytic anemia in a 30-year-old Saudi male after receiving Semaglutide injection. Case Report: A 30-year-old Saudi male with G6PD deficiency presented to the Emergency Department of Aseer Central Hospital, Abha City, Saudi Arabia with acute onset of yellow discoloration of the eyes, palpitation, mild backache, fatigue, and dark urine. The symptoms started one day after receiving the second dose of Semaglutide injection. He looked pale and the sclera were slightly icteric. Laboratory investigations showed high serum levels of liver enzymes and the total bilirubin. The RBCs count as well as the hemoglobin and the hematocrit were low, while reticulocyte count was high. The diagnosis was acute hemolytic anemia, most probably triggered by a recent Semaglutide injection. Following the discontinuation of Semaglutide, his clinical condition improved. Conclusions: G6PD deficiency should be considered in all clinical settings, and the hemolytic conditions that can possibly be precipitated by drugs not well known to cause hemolysis. Screening of newborn infants to early detect G6PD deficiency early is highly recommended, especially in those with positive family history of G6PD. Key Words: Semaglutide, Hemolytic anemia, G6PD deficiency, Case report.

G6PD Polymorphisms and Hemolysis After Antimalarial Treatment With Low Single-Dose Primaquine: A Pooled Analysis of Six African Clinical Trials.

Primaquine (PQ) is an antimalarial drug with the potential to reduce malaria transmission due to its capacity to clear mature Plasmodium falciparum gametocytes in the human host. However, the large-scale roll-out of PQ has to be counterbalanced by the additional risk of drug-induced hemolysis in individuals suffering from Glucose-6-phospate dehydrogenase (G6PD) deficiency, a genetic condition determined by polymorphisms on the X-linked G6PD gene. Most studies on G6PD deficiency and PQ-associated hemolysis focused on the G6PD A- variant, a combination of the two single nucleotide changes G202A (rs1050828) and A376G (rs1050829), although other polymorphisms may play a role. In this study, we tested the association of 20 G6PD single nucleotide polymorphisms (SNPs) with hemolysis measured seven days after low single dose of PQ given at the dose of 0.1 mg/kg to 0.75 mg/kg in 957 individuals from 6 previously published clinical trials investigating the safety and efficacy of this drug spanning five African countries. After adjusting for inter-study effects, age, gender, baseline hemoglobin level, PQ dose, and parasitemia at screening, our analysis showed putative association signals from the common G6PD mutation, A376G [−log10(p-value) = 2.44] and two less-known SNPs, rs2230037 [−log10(p-value] = 2.60), and rs28470352 [−log10(p-value) = 2.15]; A376G and rs2230037 were in very strong linkage disequilibrium with each other (R2 = 0.978). However, when the effects of these SNPs were included in the same regression model, the subsequent associations were in the borderline of statistical significance. In conclusion, whilst a role for the A- variant is well established, we did not observe an important additional role for other G6PD polymorphisms in determining post-treatment hemolysis in individuals treated with low single-dose PQ.

Phospholipase C signal mediated the glucose-induced changes of glucose absorption and lipid accumulation in the intestinal epithelial cells of yellow catfish Pelteobagrus fulvidraco.

In present study, we explored the effects and the underlying mechanisms of phospholipase C (PLC) mediating glucose-induced changes in intestinal glucose transport and lipid metabolism by using U-73122 (a PLC inhibitor). We found that glucose incubation activated the PLC signal and U-73122 pre-incubation alleviated the glucose-induced increase in plcb2, plce1 and plcg1 mRNA expression. Meanwhile, U-73122 pre-treatment blunted the glucose-induced increase in sodium/glucose co-transporters 1/2 mRNA and protein expressions. U-73122 pre-treatment alleviated the glucose-induced increase in TAG content, BODIPY 493/503 fluorescence intensity, lipogenic enzymes (glucose 6-phospate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), malic enzyme and fatty acid synthase (FAS)) activity and the mRNA expressions of lipogenic genes and related transcription factors (6pgd, g6pd, fas, acca, srebp1 and carbohydrate response element-binding protein (chrebp)) in intestinal epithelial cells of yellow catfish. Further research found that U-73122 pre-incubation mitigated the glucose-induced increase in the ChREBP protein expression and the acetylation level of ChREBP in HEK293T cells. Taken together, these data demonstrated that the PLC played a major role in the glucose-induced changes of glucose transport and lipid metabolism and provide a new perspective for revealing the molecular mechanism of glucose-induced changes of intestinal glucose absorption, lipid deposition and metabolism.

The Role of Methemoglobin and Carboxyhemoglobin in COVID-19: A Review.

Following the outbreak of a novel coronavirus (SARS-CoV-2) associated with pneumonia in China (Corona Virus Disease 2019, COVID-19) at the end of 2019, the world is currently facing a global pandemic of infections with SARS-CoV-2 and cases of COVID-19. Since severely ill patients often show elevated methemoglobin (MetHb) and carboxyhemoglobin (COHb) concentrations in their blood as a marker of disease severity, we aimed to summarize the currently available published study results (case reports and cross-sectional studies) on MetHb and COHb concentrations in the blood of COVID-19 patients. To this end, a systematic literature research was performed. For the case of MetHb, seven publications were identified (five case reports and two cross-sectional studies), and for the case of COHb, three studies were found (two cross-sectional studies and one case report). The findings reported in the publications show that an increase in MetHb and COHb can happen in COVID-19 patients, especially in critically ill ones, and that MetHb and COHb can increase to dangerously high levels during the course of the disease in some patients. The medications given to the patient and the patient’s glucose-6-phospate dehydrogenase (G6PD) status seem to be important factors determining the severity of the methemoglobinemia and carboxyhemoglobinemia. Therefore, G6PD status should be determined before medications such as hydroxychloroquine are administered. In conclusion, MetHb and COHb can be elevated in COVID-19 patients and should be checked routinely in order to provide adequate medical treatment as well as to avoid misinterpretation of fingertip pulse oximetry readings, which can be inaccurate and unreliable in case of elevated MetHb and COHb levels in the blood.

Effects of dietary vegetable oils on growth, lipogenic enzyme activities and tissue fatty acid composition of Heterobranchus longifilis

Abstract Feasibility of total replacement of fish oil (FO) with vegetable oils (palm oil (PO) and soybean oil (SO)) in practical diet for Heterobranchus longifilis fingerlings was evaluated. Six iso-nitrogenous and iso-caloric diets were prepared. Control diet (A) used FO as the lipid source, diets B–F contained various blends of palm and soybean oils. Fish were fed to apparent satiation twice daily for twelve weeks. No significant (P &gt; 0.05) differences were observed for feed intake, weight gain, feed conversion ratio or specific growth rates among dietary treatments. Activities of glucose-6-phospate dehydrogenase (G6PDH) and malic enzyme (ME) were significantly (P &lt; 0.05) higher in fish fed diet C (1.5 % PO). Generally, hepatic G6PDH activity was about 3-4 times higher than ME activity in fish fed the experimental diets. The tissue fatty acid (FA) profiles in fillet and liver reflected the dietary FA compositions. However, the concentrations of eicosapentaenoic acid and docosahexaenoic acid were higher in fish tissue (fillet and liver) than in the diets. Results from the present study indicate that replacement of fish oil with vegetable oil resulted in satisfactory growth and body composition characteristics in Heterobranchus longifilis. Compared with soybean oil, palm oil is relatively cheap and readily available; therefore, diet F (6 % PO) is recommended for use in H. longifilis diet.

Cell-derived microparticles after exercise inindividuals with G6PD Viangchan.

Glucose-6-phospate dehydrogenase (G6PD) deficient cells are sensitive to oxidative damage leading to the formation of microparticles (MPs). Therefore, we examined the concentration of MPs and changes in the antioxidant balance after an acute strenuous exercise (SEx) and moderate-intensity exercise (MEx). Eighteen healthy females (18-24 years) with G6PD normal and eighteen age-matched females with G6PD Viangchan (871G>A) were tested by running on a treadmill at their maximal oxygen uptake for SEx and at 75% of their maximal heart rate for MEx. It was found that SEx triggered the release of total microparticles (TTMPs) above baseline levels and remained significantly higher 45 minutes after the exercise in G6PD normal individuals. However, SEx-induced increase in TTMPs was significantly higher in G6PD Viangchan as compared to G6PD normal. In contrast, MEx did not to alter the release of TTMPs in both G6PD normal and Viangchan. Moreover, TTMPs concentrations were inversely correlated with G6PD activity (r =-0.82, P < 0.05) but positively correlated with MDA concentrations (r = 0.74, P < 0.05). Using cell specific antibodies, we determined that MPs were mainly derived from platelets and erythrocytes. Altogether, the present study indicates that G6PD Viangchan may participate in MEx without higher MPs concentration and oxidative stress compared with G6PD normal.

Glucose‐6‐phosphate dehydrogenase deficiency in neonatal hyperbilirubinaemia: Hacettepe experıence

The aim of this study was to investigate the prevalence of glucose-6-phospate dehydrogenase (G6PD) deficiency in newborn infants with neonatal hyperbilirubinaemia and to compare the clinical features of G6PD-deficient and G6PD-normal newborn infants. A total of 4906 term and preterm neonates with indirect hyperbilirubinaemia were retrospectively evaluated according to demographic, neonatal features, bilirubin levels, erythrocyte G6PD levels, other risk factors and treatments. Among 4906 newborn infants with indirect hyperbilirubinaemia, 55 (1.12%) neonates were G6PD-deficient. In our study, no statistically significant difference was detected between G6PD-deficient and G6PD-normal infants in relation to the time of onset of jaundice, bilirubin levels and duration of phototherapy. However, the incidence of exchange transfusion in G6PD-deficient infants was 16.4% while it was only 3.3% in G6PD normal infants (P < 0.05). Testing for G6PD must be ordered to all newborns who are receiving phototherapy and especially to those who are coming from the high incident geographical regions and less responsive to phototherapy.

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Severe hemolysis and methemoglobinemia following fava beans ingestion in glucose-6-phosphatase dehydrogenase deficiency—case report and literature review

Reduced concentrations of glucose-6-phospate dehydrogenase (G6PD) render erythrocytes susceptible to hemolysis under conditions of oxidative stress. In favism, the ingestion of fava beans induces an oxidative stress to erythrocytes, leading to acute hemolysis. The simultaneous occurrence of methemoglobinemia has been reported only scarcely, despite the fact that both phenomena are the consequence of a common pathophysiologic mechanism. The presence of methemoglobinemia has important diagnostic and therapeutic consequences. We report a previously healthy boy who presented with combined severe hemolytic anemia and cyanosis due to methemoglobinemia, following the ingestion of fava beans. His condition was complicated by the development of transient acute renal failure. A G6PD-deficiency was diagnosed. We review the literature on the combination of acute hemolysis and methemoglobinemia in favism. Pathophysiologic, diagnostic, and therapeutic aspects of this disorder are discussed.

Protein partitioning in poly(ethylene glycol)/sodium polyacrylate aqueous two-phase systems

The partition of hemoglobin, lysozyme and glucose-6-phospate dehydrogenase (G6PDH) in a novel inexpensive aqueous two-phase system (ATPS) composed by poly(ethylene glycol) (PEG) and sodium polyacrylate (NaPA) has been studied. The effect of NaCl and Na 2SO 4, pH and PEG molecular size on the partitioning has been studied. At high pH (above 9), hemoglobin partitions strongly to the PEG-phase. Although some precipitation of hemoglobin occurs, high recovery values are obtained particularly for lysozyme and G6PDH. The partitioning forces are dominated by the hydrophobic and electrochemical (salt) effects, since the positively charged lysozyme and negatively charged G6PDH partitions to the non-charged PEG and the strongly negatively charged polyacrylate enriched phase, respectively.

Moderate G6PD deficiency increases mutation rates in the brain of mice

Mice that harbored the x-ray-induced low efficiency allele of the major X-linked isozyme of glucose-6-phospate dehydrogenase (G6PD), Gpdx a-m2Neu, and, in addition, harbored the transgenic shuttle vector for the determination of mutagenesis in vivo, pUR288, were employed to further our understanding of the interdependence of general metabolism, oxidative stress control, and somatic mutagenesis. The Gpdx a-m2Neu mutation conferred moderate G6PD deficiency in hemizygous males ( Gpdx a-m2Neu/y) displaying residual enzyme activities of 27% in red blood cells and 13% in brain (compared to wild-type controls, Gpdx a/y males). In spite of this mild phenotype, the brains of G6PD-deficient males exhibited a significant distortion of redox control (∼3-fold decrease in the ratio of reduced glutathione to oxidized glutathione), a considerable accumulation of promutagenic etheno DNA adducts (∼13-fold increase in ethenodeoxyadenosine and ∼5-fold increase in ethenodeoxycytidine), and a substantial elevation of somatic mutation rates (∼3-fold increase in mutant frequencies in lacZ, the target and reporter gene of mutagenesis in the shuttle vector, pUR288). The mutation pattern in the brain was dominated by illegitimate genetic recombinations, a presumed hallmark of oxidative mutagenesis. These findings suggested a critical function for G6PD in limiting oxidative mutagenesis in the mouse brain.

Aldehyde dehydrogenase and glucose-6-phosphate dehydrogenase as markers for enzyme-altered foci in the liver of dab ( Limanda limanda L.)

The activities of the most important aldehyde oxidizing enzymes, the aldehyde dehydrogenases (ALDH), were detected histochemically in liver cryosections of dab ( Limanda limanda L.) caught at differently polluted stations along the North Sea coast. In parallel, glucose-6-phospate dehydrogenase (G6PDH) as an NADPH-generating enzyme was measured. Increased activities of both enzymes localized putatively preneoplastic hepatocytes (foci), but ALDH in combination with propionaldehyde and NAD marked 50% more foci than G6PDH alone. Nevertheless, at the more contaminated stations with highest prevalences of foci, ALDH activities showed a shift in substrate and coenzyme dependence from propionaldehyde and NAD to benzaldehyde and NADP in altered hepatocytes, a possible result of physiological adaption to the toxic environment. Increased G6PDH activities in focal hepatocytes indicated elevated NADPH production in contrast to the injured extrafocal liver parenchyma showing reduced G6PDH activities compared to normal livers. Using the ALDH inhibitor disulfiram, the existence of a specific tumor-associated isozyme previously found in rats could not be clearly demonstrated in early enzyme-altered hepatocellular foci of dab. However, based on the total inhibition of Bz-NADP-dependent ALDH, the presence of a xenobiotic-induced ALDH isozyme can be anticipated.

Long-term effect of a high-protein/non-carbohydrate diet on the primary liver and kidney metabolism in rainbow trout ( Salmo gairdneri)

Several aspects of the metabolic adaptation of trout liver and kidney to a high-protein diet were studied. Under this nutritional situation there were significant increases in the activities of the glycolytic enzymes phosphofructokinase (PFK) and pyruvate kinase (PK) from both tissues but with a different molecular basis. PFK activity was increased at subsaturating substrate concentrations, with a decrease in Michaelis constant ( K m) values of about 70% in both tissues and without changes in the maximum velocity ( V max). The activity of PK was increased all along the saturation curve, approximately 70% and 20% in liver and kidney respectively. However, no changes in the activities of glucose 6-phospate dehydrogenase (G6PDH) were detected. On the other hand, the activity of the gluconeogenic enzyme fructose 1,6-bisphosphatase (FBPase) from both tissues was increased only at cellular substrate concentrations. With respect to amino acid metabolism, liver alanine aminotransferase (AAT) was enhanced at all substrate concentrations, with a significant increase of almost 50% in the V max, without changes in the renal activity. Glutamate dehydrogenase (GDH) activity was almost 300% and 100% of control values, in liver and kidney respectively, observations which are in good agreement with the role of this enzyme in the two tissues.

Enzyme markers for Vibrio cholerae: identification of classical, El Tor and environmental strains

Enzyme electrophoretic variants were studied in 49 strains of Vibrio cholerae using zymovar analysis. The following seven enzymes were selected for use: alanine dehydrogenase (ADH), isocitrate dehydrogenase (IDH), malate dehydrogenase (MDH), phosphoglucomutase (PGM), glucosephosphate isomerase (GPI), 6-phosphogluconate dehydrogenase (6PGDH) and glucose-6-phospate dehydrogenase (G6PDH). The results indicated the presence of three main groups defined chiefly by their GPI and 6PGDH variants. The first group, defined by possessing the variants GPI-2 and 6PGDH-3, contained all the 01 serovar and ElTor biovar isolates from cholera cases. The second group, defined by possessing the variants GPI-3 and 6PGDH-2, contained all the 01 serovar and classical biovar isolates; the third group was heterogeneous and included the 01 serovar isolates from environmental sources as well as isolates of other serovars (the so called NAGs, non-agglutinable with 01 antisera or NCVs). It is thus now possible to separate the epidemic strains of 01 serovar from other members of this serovar isolated from the environment. Zymovar analysis deals with differences which are a direct expression of the genome and seems to be unaffected by gross phenotypic changes such as smooth-rough variation and phage resistance. It is a promising tool for investigating bacteriological and epidemiological questions, in particular the significance of an environmental reservoir of cholera.