G6PD Deficiency in an HIV Clinic Setting in the Dominican Republic.

Because human immunodeficiency virus (HIV)-infected patients receive prophylaxis with oxidative drugs, those with glucose-6-phosphate dehydrogenase (G6PD) deficiency may experience hemolysis. However, G6PD deficiency has not been studied in the Dominican Republic, where many individuals have African ancestry. Our objective was to determine the prevalence of G6PD deficiency in Dominican HIV-infected patients and to attempt to develop a cost-effective algorithm for identifying such individuals. To this end, histories, chart reviews, and G6PD testing were performed for 238 consecutive HIV-infected adult clinic patients. The overall prevalence of G6PD deficiency (8.8%) was similar in males (9.3%) and females (8.5%), and higher in Haitians (18%) than Dominicans (6.4%; P = 0.01). By logistic regression, three clinical variables predicted G6PD status: maternal country of birth (P = 0.01) and a history of hemolysis (P = 0.01) or severe anemia (P = 0.03). Using these criteria, an algorithm was developed, in which a patient subset was identified that would benefit most from G6PD screening, yielding a sensitivity of 94.7% and a specificity of 97.2%, increasing the pretest probability (8.8-15.1%), and halving the number of patients needing testing. This algorithm may provide a cost-effective strategy for improving care in resource-limited settings.

Anti-Diabetic Effect of Aster sphathulifolius in C57BL/KsJ-db/db Mice.

In this study, we investigated the anti-diabetic effect of Aster sphathulifolius (AS) extract in C57BL/KsJ-db/db mice. The db/db mice were orally administered with AS 50% ethanol extract at concentrations of 50, 100, and 200 mg/kg/day (db/db-AS50, db/db-AS100, and db/db-AS200, respectively) for 10 weeks. Food and water intake, fasting blood glucose concentrations, blood glycosylated hemoglobin levels, and plasma insulin levels were significantly lower in the db/db-AS200 group than in the vehicle-treated db/db group; whereas glucose tolerance was significantly improved in the db/db-AS200 group. Moreover, AS dose dependently increased both insulin receptor substrate 1 and glucose transporter type 4 expression in skeletal muscle, significantly increased glucokinase expression, and decreased glucose 6-phosphatase and phosphoenolpyruvate carboxykinase expressions in the liver. The expressions of transcription factors, such as sterol-regulatory element-binding protein, peroxisome proliferator-activated receptor γ, and adipocyte protein 2, were upregulated in adipose tissue. Furthermore, immunohistochemical analysis showed that AS upregulated insulin production by increasing pancreatic ß-cell mass. In summary, AS extract normalized hyperglycemia by multiple mechanisms: inhibition of glyconeogenesis, acceleration of glucose metabolism and lipid metabolism, and increase of glucose uptake. Using in vivo assays, this study has shown the potential of AS as a medicinal food and suggests the efficacy of AS for the use of prevention of diabetes.

Isothiocyanate-rich Moringa oleifera extract reduces weight gain, insulin resistance, and hepatic gluconeogenesis in mice.

SCOPE: Moringa oleifera (moringa) is tropical plant traditionally used as an antidiabetic food. It produces structurally unique and chemically stable moringa isothiocyanates (MICs) that were evaluated for their therapeutic use in vivo. METHODS AND RESULTS: C57BL/6L mice fed very high fat diet (VHFD) supplemented with 5% moringa concentrate (MC, delivering 66 mg/kg/d of MICs) accumulated fat mass, had improved glucose tolerance and insulin signaling, and did not develop fatty liver disease compared to VHFD-fed mice. MC-fed group also had reduced plasma insulin, leptin, resistin, cholesterol, IL-1ß, TNFα, and lower hepatic glucose-6-phosphatase (G6P) expression. In hepatoma cells, MC and MICs at low micromolar concentrations inhibited gluconeogenesis and G6P expression. MICs and MC effects on lipolysis in vitro and on thermogenic and lipolytic genes in adipose tissue in vivo argued these are not likely primary targets for the anti-obesity and anti-diabetic effects observed. CONCLUSION: Data suggest that MICs are the main anti-obesity and anti-diabetic bioactives of MC, and that they exert their effects by inhibiting rate-limiting steps in liver gluconeogenesis resulting in direct or indirect increase in insulin signaling and sensitivity. These conclusions suggest that MC may be an effective dietary food for the prevention and treatment of obesity and type 2 diabetes.

Hormonal imbalance and disturbances in carbohydrate metabolism associated with chronic feeding of high sucrose low magnesium diet in weanling male wistar rats.

This study was designed to determine chronic effect of high sucrose low magnesium (HSLM) diet in weanling rats on plasma thyroid profile, catecholamines and activities of key hepatic glycolytic, and gluconeogenic enzymes. Compared to control diet fed group, significantly elevated levels of plasma triiodothyronine, tetraiodothyronine, catecholamines (epinephrine, norepinephrine, and dopamine) and activity of hepatic glycolytic (hexokinase and glucokinase), and gluconeogenic (glucose-6-phosphatase) enzymes were observed in high sucrose and low magnesium fed groups. However, HSLM diet had an additive effect on all these three parameters. The study thus, assumes significance as it shows that hormonal imbalance and disorders in carbohydrate metabolism at an early stage of development can be due to dietary modification or due to deficiency of key element magnesium.

Umbelliferone ß-D-galactopyranoside from Aegle marmelos (L.) corr. an ethnomedicinal plant with antidiabetic, antihyperlipidemic and antioxidative activity.

BACKGROUND: Aegle marmelos (L.) Corr. (Rutaceae), commonly known as bael, is used to treat fevers, abdomen pain, palpitation of the heart, urinary troubles, melancholia, anorexia, dyspepsia, diabetes and diarrhea in Indian traditional systems of medicine. The object of the present study was to evaluate the antidiabetic, antihyperlipidemic and antioxidant oxidative stress of umbelliferone ß-D-galactopyranoside (UFG) from stem bark of Aegle marmelos Correa. in STZ (streptozotocin) induced diabetic rat. METHODS: Diabetes was induced in rat by single intraperitoneal injection of STZ (60 mg/kg). The rat was divided into the following groups; I - normal control, II - diabetic control, III - UFG (10 mg/kg), IV - UFG (20 mg/kg), V - UFG (40 mg/kg), VI - Glibenclamide (10 mg/kg, p.o., once a daily dose). Diabetes was measured by change the level blood glucose, plasma insulin and the oxidative stress were assessed in the liver by estimation of the level of antioxidant markers i.e. superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and Malondialdehyde (MDA) and antihyperlipidemic effect was measured by estimation of total cholesterol, triglycerides, LDL (low density lipoprotein) cholesterol, HDL (high density lipoprotein) cholesterol, VLDL (very low density lipoprotein) cholesterol. However in a study, the increased body weight was observed and utilization of glucose was in the oral glucose tolerance test. RESULT: Daily oral administration of different dose of UFG for 28 days showed significantly (P < 0.001) decreased in fasting blood glucose level and improve plasma insulin level as compared to the diabetic control group. Also it significantly (P < 0.001) decreased the level of glycated hemoglobin, glucose-6-phosphatase, fructose-1-6-biphosphate and increased the level of hexokinase. UFG treatment decreased liver MDA and increased the level of SOD, GPx and CAT. UFG treatment of lipids it's increased the level of cholesterol, triglycerides, VLDL, LDL cholesterol and decreased the level of HDL cholesterol. Histologically, inflammatory cell in blood vessels, intercalated disc, fat degeneration and focal necrosis observed in diabetic rat organ but was less obvious in UFG treated groups. The mechanism of action of UFG may be due to the increased level of pancreatic insulin secretion and effect on the antioxidant marker. CONCLUSION: UFG posses an antidiabetic, antioxidant and antihyperlipidemic effect on the STZ induced diabetic rat. Hence it could be the better choice to cure the diabetes.

Survival with 98% methemoglobin levels in a school-aged child during the "festival of colors".

Methemoglobin levels more than 70% have almost always been reported to have been fatal. The case of a 4-year-old boy who survived with methemoglobin levels of 98% is presented here. He was brought to the emergency department with complaints of vomiting, pain abdomen, and altered sensorium following accidental ingestion of paint thinner mixed with "Holi" colors. On examination, the child was in altered sensorium, cyanosed with saturations of 55%, who did not respond despite positive pressure ventilation with 100% oxygen. A possibility of toxic methemoglobinemia was considered and confirmed by finding of elevated methemoglobin levels of 98%. The child survived with definitive therapy with methylene blue and aggressive goal-directed approach.

Improved glycemic control, pancreas protective and hepatoprotective effect by traditional poly-herbal formulation "Qurs Tabasheer" in streptozotocin induced diabetic rats.

BACKGROUND: The present study was undertaken to evaluate the antihyperglycemic, antihyperlipidemic and hepatoprotective effect of a traditional unani formulation "Qurs Tabasheer" in streptozotocin (STZ) induced diabetic wistar rats. Up till now no study was undertaken to appraise the efficacy of "Qurs Tabasheer" in the diabetic rats. Qurs Tabasheer is a unani formulation restraining preparations from five various herbs namely Tukhme Khurfa (Portulaca oleracea seed), Gule Surkh (Rosa damascena flower), Gulnar (Punica granatum flower), Tabasheer (Bambusa arundinasia dried exudate on node), Tukhme Kahu (Lactuca sativa Linn seed). METHODS: Effect of Qurs Tabasheer was assessed in STZ (60 mg/kg, i.p single shot) induced diabetic wistar rats. STZ produced a marked increase in the serum glucose, Total Cholesterol, LDL cholesterol, VLDL Cholesterol, Triglycerides and trim down the HDL level. We have weighed up the effect of Qurs Tabasheer on hepatic activity through estimating levels of various liver enzymes viz. Hexokinase, Glucose-6-Phosphatase and Fructose-1-6-biphosphatase in STZ diabetic wistar rats. RESULTS: In STZ-induced diabetic wistar rats level of Hexokinase, and Glucose-6-Phosphatase was decreased to a significant level while the level of fructose-1-6-biphophatase was augmented. Therapy with Qurs Tabasheer for 28 days to STZ-induced diabetic rats significantly reduces the level of serum glucose, total cholesterol, triglycerides, glucose-6-phosphatase and fructose-1-6-biphosphatase, while magnitude of HDL cholesterol and hexokinase was amplified. CONCLUSION: Antihyperglycemic, antihyperlipidemic activity of Qurs Tabasheer extract in STZ- induced wistar rats was found to be more effective than standard oral hypoglycemic drug Glimepiride.

[Carbohydrates metabolism disturbances when simulating prenatal alcohol intoxication].

The influence of prenatal alcohol intoxication on carbohydrate metabolism markers has been investigated at different terms of postnatal offspring development (15, 30 and 60 days). Plasma glucose decreased as compared with the same in control group was detected. In the liver homogenates an increase of phosphorylase activity and a decrease of glucose-6-phosphatase, aldolase and glucose-6-phosphate dehydrogenase activities were found. These changes were accompanied by the incease in the lactate/pyruvate index attributed to increased lactate content in the liver tissue. The obtained data indicate essential disturbances of carbohydrate metabolism markers in prenatal alcoholized offspring, which include stable hypoglycemia, suppression of glycolytic and pentosephosphate pathways of glucose metabolism and lactate accumulation in the liver.

Mercury chloride increases hepatic alanine aminotransferase and glucose 6-phosphatase activities in newborn rats in vivo.

This work investigated the in vivo and in vitro effects of HgCl2 and ZnCl2 on metabolic enzymes from tissues of young rats to verify whether the physiological and biochemical alterations induced by mercury and prevented by zinc are related to hepatic and renal glucose metabolism. Wistar rats received (subcutaneous) saline or ZnCl2 (27 mg/kg/day) from 3 to 7 days old and saline or HgCl2 (5.0 mg/kg/day) from 8 to 12 days old. Mercury exposure increased the hepatic alanine aminotransferase (∼6-fold) and glucose 6-phosphatase (75%) activity; zinc pre-exposure prevented totally and partially these mercury alterations respectively. In vitro, HgCl2 inhibited the serum (22%, 10 µM) and liver (54%, 100 µM) alanine aminotransferase, serum (53%) and liver (64%) lactate dehydrogenase (10 µM), and liver (53%) and kidney (41%) glucose 6-phosphatase (100 µM) from 10- to 13-day-old rats. The results show that mercury induces distinct alterations in these enzymes when tested in vivo or in vitro as well as when different sources were used. The increase of both hepatic alanine aminotransferase and glucose 6-phosphatase activity suggests that the mercury-exposed rats have increased gluconeogenic activity in the liver. Zinc prevents the in vivo effects on metabolic changes induced by mercury.

Dapsone salvage therapy for adult patients with immune thrombocytopenia relapsed or refractory to steroid and rituximab.

Dapsone is an antibacterial sulfonamide with anti-inflammatory property, which showed therapeutic activity in patients with immune thrombocytopenia (ITP); the activity in patients who showed refractoriness to rituximab is unknown. We evaluated the effect of dapsone in 20 consecutive adult patients, median age 51 years, with primary ITP previously treated at least with steroids and rituximab. Median baseline platelet count was 19 × 109/L, and the median interval between diagnosis of ITP and dapsone therapy was 46 months. Response (platelet count ≥ 30 × 109/L) and complete response (CR; platelet count ≥ 100 × 109/L) were 55 and 20%, respectively; median time to response (TTR) was 1 month. All responders were able to interrupt any other specific anti-ITP treatment. The median duration of dapsone therapy in responders and the median response duration were 31 and 42 months, respectively. None of responders lost response during treatment. One patient in CR interrupted dapsone after 9 months and still maintained the response after 48 months. None of the patients interrupted the treatment for toxicity. All the patients were screened for normal glucose-6-phosphate-dehydrogenase (G6PD); two patients showed mild increase of methemoglobin (MHb). These results highlight the therapeutic activity and good safety profile of dapsone in patients with ITP who previously failed rituximab treatment.

Arginine rich coconut kernel protein modulates diabetes in alloxan treated rats.

Diabetes mellitus is a syndrome characterized by the loss of glucose homeostasis due to several reasons. In spite of the presence of known anti-diabetic medicines in the pharmaceutical market, remedies from natural resources are used with success to treat this disease. The present study was undertaken to investigate the effect of coconut kernel protein (CKP) on alloxan induced diabetes in Sprague-Dawley rats. Diabetes was induced by injecting a single dose of alloxan (150mg/kg body weight) intraperitoneally. After inducing diabetes, purified CKP isolated from dried coconut kernel was administered to rats along with a semi synthetic diet for 45 days. After the experimental period, serum glucose, insulin, activities of different key enzymes involved in glucose metabolism, liver glycogen levels and the histopathology of the pancreas were evaluated. The amount of individual amino acids of CKP was also determined using HPLC. Results showed that CKP has significant amount of arginine. CKP feeding attenuated the increase in the glucose and insulin levels in diabetic rats. Glycogen levels in the liver and the activities of carbohydrate metabolizing enzymes in the serum of treated diabetic rats were reverted back to the normal levels compared to that of control. Histopathology revealed that CKP feeding reduced the diabetes related pancreatic damage in treated rats compared to the control. These results clearly demonstrated the potent anti-diabetic activity of CKP which may be probably due to its effect on pancreatic ß cell regeneration through arginine.

Screening for glucose-6-phosphate dehydrogenase deficiency in blood donors.

AIM: Our purpose was to determine the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency in blood donors of Jahrom, Iran. METHODS: Blood samples were obtained from the 706 blood donors who referred to Jahrom Blood Transfusion Organization between June and September 2008. Enzyme assays were performed three times, on day 1 (day of blood sampling), 7 and 45 days after blood storage. G6PD activity was measured using a quantitative assay. RESULTS: A total of 706 samples were examined. 97.7% males and 2.3% females, mean age 32.6 years (18-64 years). Based on enzyme activity less than 1.62 IU/g hemoglobin (Hb), prevalence of G6PD deficiency in three separate measurements was 16.3, 19.1 and 33.3% respectively. Four percent of donor had an enzyme level of zero on day 1 which increased to 7.4 and 10.7% on the seventh and the forty-fifth days. CONCLUSION: The results of this study support the screening for G6PD as part of the routine workup of blood donors in areas with a high prevalence of G6PD deficiency.

Peas, beans, and the Pythagorean theorem - the relevance of glucose-6-phosphate dehydrogenase deficiency in dermatology.

Glucose-6-phosphate (G6PD) deficiency is a common disease characterized by acute hemolysis induced by oxidative stress. More than 400 million subjects throughout the world carry the hereditary enzyme defect with the highest prevalences in Africa, Asia, and the Mediterranean region. In individuals affected by the erythrocytic enzymatic disorder, besides infectious diseases and diet, acute hemolytic crisis can be triggered by numerous drugs frequently used for the treatment of dermatoses. Taking into account the increasing number of immigrants from geographic regions with high prevalences of G6PD deficiency, dermatologists should be alert to the presence of disease.

Hypoglycemic and other related effects of Boswellia glabra in alloxan-induced diabetic rats.

The hypoglycemic effect of the aqueous extract of the leaves and roots of Boswellia glabra was examined using alloxan-induced diabetic rats. A single oral administration of Boswellia glabra leaf and root extract decreased the blood glucose level. The continued use of leaf and root extract for 28 days produced significant hypoglycemic effects; also there was a decrease in serum glucose, cholesterol, triglyceride, urea and creatinine levels and enzyme activities (alkaline phosphatase and glucose-6-phosphatase). Ultra structural studies of beta cell of alloxan-induced diabetic rats treated with root extract showed numerous granulated sacs in comparison to rats treated with leaf extract. Thus, rats treated with root extract showed less degranulated sacs and more number of filled secretory granules in comparison to diabetic rats. Thus the use of aqueous extract of Boswellia glabra increased the synthesis of secretory granules in the beta-cell.

Annona squamosa seed extract in the regulation of hyperthyroidism and lipid-peroxidation in mice: possible involvement of quercetin.

Annona squamosa (Custard apple) seeds are generally thrown away as waste materials. The extract of these seeds was evaluated for its possible ameliorative effect in the regulation of hyperthyroidism in mouse model. Serum triiodothyronine (T(3)), thyroxine (T(4)) concentrations, hepatic glucose-6-phospatase (G-6-Pase) and 5'-mono-deiodinase (5'DI) activity were considered as the end parameters of thyroid function. Simultaneously hepatic lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) activities were investigated to observe its hepatotoxic effect, if any. L-T(4) administration (0.5 mg/kg/d for 12 days, i.p.) increased the levels of serum T(3) and T(4), activity of hepatic G-6-Pase, 5'DI and LPO with a parallel decrease in SOD and CAT activities. However, simultaneous administration of the Annona seed extract (200 mg/kg) or quercetin (10 mg/kg) to T(4)-induced hyperthyroid animals for 10 days, reversed all these effects indicating their potential in the regulation of hyperthyroidism. Further, the seed extract did not increase, but decreased the hepatic LPO suggesting its safe and antiperoxidative nature. Quercetin also decreased hepatic LPO. When relative efficacy was compared with that of propyl thiouracil (PTU), a standard antithyroidic drug, experimental seed extract appeared to be more effective. Phytochemical analyses including HPLC revealed the presence of quercetin in the seed extract and the results on the effects of quercetin suggested the involvement of this phytochemical in the mediation of antithyroidal activity of Annona squamosa seed extract.

Effect of pterostilbene on hepatic key enzymes of glucose metabolism in streptozotocin- and nicotinamide-induced diabetic rats.

The purpose of this study was to investigate the effect of pterostilbene and its effect on key enzymes of glucose metabolism. Diabetic rats were orally administered with pterostilbene (10, 20, 40 mg/kg) for 2, 4 and 6 weeks on glucose was determined. Administration of pterostilbene at 40 mg/kg significantly decreases plasma glucose. Based on these data, the higher dose, 40 mg/kg pterostilbene, was selected for further evaluation. Oral administration of pterostilbene for 6 weeks on glucose, insulin levels and hepatic enzymes in normal and streptozotocin (STZ)-nicotinamide-induced diabetic rats. A significant decrease in glucose and significant increase in plasma insulin levels were observed in normal and diabetic rats treated with pterostilbene. Treatment with pterostilbene resulted in a significant reduction of glycosylated hemoglobin and an increase in total hemoglobin level. The activities of the hepatic enzymes such as hexokinase was significantly increased whereas glucose-6-phosphatase, fructose-1,6-bisphosphatase were significantly decreased by the administration of pterostilbene in diabetic rats. A comparison was made between the action of pterostilbene and the antidiabetic drug--metformin.

Longitudinal study of urban malaria in a cohort of Ugandan children: description of study site, census and recruitment.

BACKGROUND: Studies of malaria in well-defined cohorts offer important data about the epidemiology of this complex disease, but few have been done in urban African populations. To generate a sampling frame for a longitudinal study of malaria incidence and treatment in Kampala, Uganda, a census, mapping and survey project was conducted. METHODS: All households in a geographically defined area were enumerated and mapped. Probability sampling was used to recruit a representative sample of children and collect baseline descriptive data for future longitudinal studies. RESULTS: 16,172 residents living in 4931 households in a densely-populated community (18,824 persons/km2) were enumerated. A total of 582 households were approached with at least one child less than 10 years of age in order to recruit 601 children living in 322 households. At enrollment, 19% were parasitaemic, 24% were anaemic, 43% used bednets, and 6% used insecticide-treated nets. Low G6PD activity (OR = 0.33, P = 0.009) and bednet use (OR = 0.64, P = 0.045) were associated with a decreased risk of parasitaemia. Increasing age (OR = 0.62 for each year, P < 0.001) and bednet use (OR = 0.58, P = 0.02) were associated with a decreased risk of anaemia CONCLUSION: Detailed surveys of target populations in urban Africa can provide valuable descriptive data and provide a sampling frame for recruitment of representative cohorts for longitudinal studies. Plans to use a multi-disciplinary approach to improve the understanding of the distribution and determinants of malaria incidence and response to therapy in this population are discussed.

Effect of Hibiscus rosa sinensis Linn. ethanol flower extract on blood glucose and lipid profile in streptozotocin induced diabetes in rats.

Blood glucose and total lipid levels were determined in streptozotocin induced diabetic rats after oral administration of an ethanol flower extract of Hibiscus rosa sinensis. A comparable hypoglycemic effect was evidenced from the data obtained after 7 and 21 days of oral administration of the extract and glibenclamide. Maximal diminution in blood glucose (41-46%) and insulin level (14%) was noticed after 21 days. The extract lowered the total cholesterol and serum triglycerides by 22 and 30%, respectively. The increase in HDL-cholesterol was much higher (12%) under the influence of the extract as compared to that of glibenclamide (1%). The hypoglycemic activity of this extract is comparable to that of glibenclamide but is not mediated through insulin release. Other possible mechanisms are discussed.

Antihyperglycaemic effect of Casearia esculenta root extracts in streptozotocin-induced diabetic rats.

The present study was carried out to evaluate the antihyperglycaemic effect of Casearia esculenta root extract and to study the activities of liver hexokinase and gluconeogenic enzymes such as glucose-6-phosphatase and fructose-1,6-bisphosphatase in liver and kidney of normal and streptozotocin-induced diabetic rats. Oral administration of aqueous extract of root (300 mg/kg body weight) for 45 days resulted in a significant reduction in blood glucose from 250.79 +/- 12.65 to 135.70 +/- 8.90 and in a decrease in the activities of glucose-6-phosphatase and fructose-1,6-bishosphatase and an increase in the activity of liver hexokinase. However, in the case of 200 mg/kg body weight of extract, less activity was observed. The study clearly shows that the root extract of C. esculenta possesses potent antihyperglycaemic activity but weaker than that of glibenclamide.