Inhibition of glycine transporter-1 in the dorsal vagal complex improves metabolic homeostasis in diabetes and obesity

Impaired glucose homeostasis and energy balance are integral to the pathophysiology of diabetes and obesity. Here we show that administration of a glycine transporter 1 (GlyT1) inhibitor, or molecular GlyT1 knockdown, in the dorsal vagal complex (DVC) suppresses glucose production, increases glucose tolerance and reduces food intake and body weight gain in healthy, obese and diabetic rats. These findings provide proof of concept that GlyT1 inhibition in the brain improves glucose and energy homeostasis. Considering the clinical safety and efficacy of GlyT1 inhibitors in raising glycine levels in clinical trials for schizophrenia, we propose that GlyT1 inhibitors have the potential to be repurposed as a treatment of both obesity and diabetes

Multidirectional Time-Dependent Effect of Sinigrin and Allyl Isothiocyanate on Metabolic Parameters in Rats

Sinigrin (SIN) and allyl isothiocyanate (AITC) are compounds found in high concentrations in Brassica family vegetables, especially in Brussels sprouts. Recently, they have been used as a nutrition supplement for their preventive and medicinal effect on some types of cancer and other diseases. In this research, nutritional significance of parent glucosinolate sinigrin 50 μmol/kg b. w./day and its degradation product allyl isothiocyanate 25 μmol/kg b. w./day and 50 μmol/kg b. w./day was studied by the evaluation of their influence on some parameters of carbohydrate and lipid metabolism in an animal rat model in vivo after their single (4 h) and 2 weeks oral administration. Additionally, the aim of this trial was to evaluate the direct action of AITC on basal and epinephrine-induced lipolysis in isolated rat adipocytes at concentration 1 μM, 10 μM and 100 μM in vitro. Sole AITC after 4 h of its ingestion caused liver triacylglycerols increment at both doses and glycaemia only at the higher dose. Multiple SIN treatment showed its putative bioconversion into AITC. It was found that SIN and AITC multiple administration in the same way strongly disturbed lipid and carbohydrate homeostasis, increasing esterified and total cholesterol, free fatty acids and lowering tracylglycerols in the blood serum. Additionally, AITC at both doses elevated insulinaemia and liver glycogen enhancement. The in vitro experiment revealed that AITC potentiated basal lipolysis process at 10 μM, and had stimulatory effect on epinephrine action at 1 μM and 10 μM. The results of this study demonstrated that the effect of SIN and AITC is multidirectional, indicating its impact on many organs like liver as well as pancreas, intestine in vivo action and rat adipocytes in vitro. Whilst consumption of cruciferous vegetables at levels currently considered “normal” seems to be beneficial to human health, this data suggest that any large increase in intake could conceivably lead to undesirable effect. This effect is potentiated with time of action of the examined compounds, whose influence is rather adverse for the majority of metabolic pathways (liver steatosis at short duration and insulinaemia, cholesterolaemia at long time treatment). Beneficial action of AITC concerned intensified hydrolysis of TG in the blood serum with a simultaneous lipolysis in adipocytes

Complete genome characterization of two wild-type measles viruses from Vietnamese infants during the 2014 outbreak

A large measles virus outbreak occurred across Vietnam in 2014. We identified and obtained complete measles virus genomes in stool samples collected from two diarrheal pediatric patients in Dong Thap Province. These are the first complete genome sequences of circulating measles viruses in Vietnam during the 2014 measles outbreak

Genome sequences of a novel Vietnamese bat bunyavirus

To document the viral zoonotic risks in Vietnam, fecal samples were systematically collected from a number of mammals in southern Vietnam and subjected to agnostic deep sequencing. We describe here novel Vietnamese bunyavirus sequences detected in bat feces. The complete L and S segments from 14 viruses were determined

Does in-utero transfusion for homozygous α0-thalassemia depend on hemoglobin level alone?

Objectives: To determine hematological parameters in fetusesaffected by α0-thalassemiaMethods: This was a retrospective cross-sectional study of 546 fetalor cord blood collected at 12–40 weeks’ gestation for the prenataldiagnosis of α0-thalassemia or other indications from 1993 to 2006.The proportion of hemoglobin (Hb) fractions was determined byelectrophoresis of hemolysate on cellulose acetate.Results: In homozygous α0-thalassemia (n = 183), the median Hblevel, proportion of Hb Bart’s(γ4) and Hb Portland 1(ξ2γ2)were6.4 g/dl, 77.5% and 22.5% respectively. While the Hb level andthe proportion of Hb Bart’s increased significantly with gestation,the proportion of Hb Portland 1 (ξ2γ2) decreased. Although mildanemia (with reference to the gestation) was present in 27.5% of the affected fetuses, the mean Hb level contributed by HbPortland 1(ξ2γ2), with normal ability to release oxygen, was only1.4 g/dl from 12 to 40 weeks’ gestation. There were no differences inthe hematological parameters between hydropic and non-hydropicfetuses. In one affected case, the middle cerebral artery peaksystolic velocity (MCAPSV) was 49cm/s (> 1.5MoM) at gestation of21 weeks. Cordocentesis showed Hb level of 6.5 g/dl, hematocrit of0.266, pO2 of 6.2 kPa, and pH of 7.42. First in-utero transfusion(IUT) was given. At 29 weeks’ gestation, MCAPSV was increasedagain to 56 cm/s (> 1.5MoM). Cordocentesis showed mild anemia(Hb of 9.1g/dl), but acidosis (pH of 7.35) and hypoxia (pO2 of3.4kPa). After correction of fetal anemia by the second IUT, boththe fetal pH (7.43) and pO2 (6.9 kPa) returned to normal. Theaffected baby was subsequently delivered at term, and survived.Conclusion: Although the degree of anemia is mild in around one-quarter of the affected fetuses, the Hb level contributed by HbPortland 1(ξ2γ2) is very low in all affected fetuses from 12 weeks’gestation. Whether to give IUT to an affected fetus depends not juston fetal Hb level, but also on ultrasound signs of severe anemia,oxygen and pH status