Role of chromium supplementation in Indians with type 2 diabetes mellitus

Type 2 diabetes mellitus is a complex metabolic disorder with adverse cardiovascular risk. The role of micronutrients has not yet been well clarified in this condition, especially in India.THE OBJECTIVES OF THIS STUDY WERE TO: (1) evaluate chromium status in Indian subjects with type 2 diabetes mellitus, (2) assess the effect of chromium picolinate (200 &mgr;g trivalent chromium twice daily) administration on glycaemic control and lipid profile in these subjects and (3) comment on the possible mechanism of any beneficial effect noted above.Fifty subjects were studied in a double blind, placebo-controlled, crossover fashion, with each treatment arm (chromium/placebo) lasting 12 weeks and 4 weeks' wash-off period in between. 50 healthy age- and sex-matched volunteers served as controls. Serum chromium level appeared to be higher in the general population in our country compared to western countries (36.5-59.5 nmol/L as compared to 2.3-40.3 nmol/L) However, the local diabetics were found to have a lower serum chromium level than the healthy controls (32.3 nmol/L against 44.7 nmol/L; p < 0.0001) and a mean increase of 3.5 nmol/L was noted after 12 weeks of chromium supplementation that was, expectedly, not seen in the placebo phase (p < 0.0001).Significant improvement in glycaemic control was noted in the chromium-treated group (DeltaFasting serum glucose = 0.44 mmol/L, p < 0.001; DeltaPost-prandial serum glucose = 1.97 mmol/L, p < 0.001; Deltaglycated hemoglobin = 0.01; p = 0.04, in comparison to placebo) This was accompanied by a significant greater fall in fasting serum insulin in the chromium-treated group, p < 0.05.The change in lipid parameters (total serum cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and triglycerides) did not show significant difference between the chromium and placebo groups.Clinically significant hematological, renal or hepatic toxicity were excluded by routine hemogram, serum urea, creatinine, alanine amino transferase (ALT) and alkaline phosphatase estimations.In conclusion, chromium supplementation seems to improve glycaemic control in type 2 diabetic patients, which appears to be due to an increase in insulin action rather than stimulation of insulin secretion.     

Surface functionalization of inorganic nano-crystals with fibronectin and E-cadherin chimera synergistically accelerates trans-gene delivery into embryonic stem cells

Stem cells holding great promises in regenerative medicine have the potential to be differentiated to a specific cell type through genetic manipulation. However, conventional ways of gene transfer to such progenitor cells suffer from a number of disadvantages particularly involving safety and efficacy issues. Here, we report on the development of a bio-functionalized inorganic nano-carrier of DNA by embedding fibronectin and E-cadherin chimera on the carrier, leading to its high affinity interactions with embryonic stem cell surface and accelerated trans-gene delivery for subsequent expression. While only apatite nano-particles were very inefficient in transfecting embryonic stem cells, fibronectin-anchored particles and to a more significant extent, fibronectin and E-cadherin-Fc-associated particles dramatically enhanced trans-gene delivery with a value notably higher than that of commercially available lipofection system. The involvement of both cell surface integrin and E-cadherin in mediating intracellular localization of the hybrid carrier was verified by blocking integrin binding site with excess free fibronectin and up-regulating both integrin and E-cadherin through PKC activation. Thus, the new establishment of a bio-functional hybrid gene-carrier would promote and facilitate development of stem cell-based therapy in regenerative medicine.     

Safety and Immunogenicity of a Live Oral Recombinant Cholera Vaccine VA1.4: A Randomized,Placebo Controlled Trial in Healthy Adults in a Cholera Endemic Area in Kolkata,India

Background

A live oral cholera vaccine VA 1.4 developed from a non-toxigenic Vibrio cholerae O1 El Tor strain using ctxB gene insertion was further developed into a clinical product following cGMP and was evaluated in a double-blind randomized placebo controlled parallel group two arm trial with allocation ratio of 1∶1 for safety and immunogenicity in men and women aged 18–60 years from Kolkata, India.

Method

A lyophilized dose of 1.9×10⁹ CFU (n = 44) or a placebo (n = 43) reconstituted with a diluent was administered within 5 minutes of drinking 100 ml of a buffer solution made of sodium bicarbonate and ascorbic acid and a second dose on day 14.

Result

The vaccine did not elicit any diarrhea related adverse events. Other adverse events were rare, mild and similar in two groups. One subject in the vaccine group excreted the vaccine strain on the second day after first dose. The proportion of participants who seroconverted (i.e. had 4-folds or higher rise in reciprocal titre) in the vaccine group were 65.9% (95% CI: 50.1%–79.5%) at both 7 days (i.e. after 1^st dose) and 21 days (i.e. after 2^nd dose). None of the placebo recipients seroconverted. Anti-cholera toxin antibody was detected in very few recipients of the vaccine.

Conclusion

This study demonstrates that VA 1.4 at a single dose of 1.9×10⁹ is safe and immunogenic in adults from a cholera endemic region. No additional benefit after two doses was seen.

Trial Registration

Clinical Trials Registry-India, National Institute of Medical Statistics (Indian Council of Medical Research) CTRI/2012/04/002582     

23S rRNA assisted folding of cytoplasmic malate dehydrogenase is distinctly different from its self-folding

The role of the 50S particle of Escherichia coli ribosome and its 23S rRNA in the refolding and subunit association of dimeric porcine heart cytoplasmic malate dehydrogenase (s-MDH) has been investigated. The self-reconstitution of s-MDH is governed by two parallel pathways representing the folding of the inactive monomeric and the dimeric intermediates. However, in the presence of these folding modulators, only one first order kinetics was observed. To understand whether this involved the folding of the monomers or the dimers, subunit association of s-MDH was studied using fluorescein-5-isothiocyanate–rhodamine-isothiocyanate (FITC–RITC) fluorescence energy transfer and chemical cross-linking with gluteraldehyde. The observation suggests that during refolding the interaction of the unstructured monomers of s-MDH with these ribosomal folding modulators leads to very fast formation of structured monomers that immediately dimerise. These inactive dimers then fold to the native ones, which is the rate limiting step in 23S or 50S assisted refolding of s-MDH. Furthermore, the sequential action of the two fragments of domain V of 23S rRNA has been investigated in order to elucidate the mechanism. The central loop of domain V of 23S rRNA (RNA1) traps the monomeric intermediates, and when they are released by the upper stem–loop region of the domain V of 23S rRNA (RNA2) they are already structured enough to form dimeric intermediates which are directed towards the proper folding pathway.     

Impact of rapid urbanization on the rates of infection by Vibrio cholerae O1 and enterotoxigenic Escherichia coli in Dhaka, Bangladesh

Background

In Bangladesh, increases in cholera epidemics are being documented with a greater incidence and severity. The aim of this prospective study was to identify the prevalence and importance of V. cholerae O1 and enterotoxigenic Escherichia coli (ETEC) as causal agents of severe diarrhea in a high diarrhea prone urban area in Dhaka city.

Methodology

Systematic surveillance was carried out on all diarrheal patients admitted from Mirpur between March 2008 to February 2010 at the ICDDR, B hospital. Stool or rectal swabs were collected from every third diarrheal patient for microbiological evaluation.

Principal Findings

Of diarrheal patients attending the hospital from Mirpur, 41% suffered from severe dehydration with 39% requiring intravenous rehydration therapy. More diarrheal patients were above five years of age (64%) than those below five years of age (36%). About 60% of the patients above five years of age had severe dehydration compared with only 9% of patients under five years of age. The most prevalent pathogen isolated was Vibrio cholerae O1 (23%) followed by ETEC (11%). About 8% of cholera infection was seen in infants with the youngest children being one month of age while in the case of ETEC the rate was 11%. Of the isolated ETEC strains, the enterotoxin type were almost equally distributed; ST accounted for 31% of strains; LT/ST for 38% and LT for 31%.

Conclusion

V. cholerae O1 is the major bacterial pathogen and a cause of severe cholera disease in 23% of patients from Mirpur. This represents a socioeconomic group that best reflects the major areas of high cholera burden in the country. Vaccines that can target such high risk groups in the country and the region will hopefully be able to reduce the disease morbidity and the transmission of pathogens that impact the life and health of people.     

Microbial mineralization of organic phosphate in soil

Summary Phosphate-dissolving microorganisms were isolated from non-rhizosphere and rhizosphere of plants. These isolates included bacteria, fungi and actinomycetes. In broth cultures, Gram-negative short rod,Bacillus andStreptomyces species were found to be more active in solubilizing phosphate thanAspergillus, Penicillium, Proteus, Serratia, Pseudomonas andMicrococcus spp. The sterile soils mixed with isolated pure culture showed slower mineralization of organic phosphate than that of non-sterile soil samples at all incubation periods. Maximum amount of phosphate mineralization by isolated microorganisms were obtained at the 60th and the 75th day of incubation in sterile and non-sterile soils respectively. The mixed cultures were most effective in mineralizing organic phosphate and individuallyBacillus sp. could be ranked next to mixed cultures. Species ofPseudomonas andMicrococcus were almost the same as that of the control under both sterile and non-sterile conditions.     

The coenzyme b12 analog 5'-deoxyadenosylcobinamide-gdp supports catalysis by methylmalonyl-coa mutase in the absence of trans-ligand coordination

Methylmalonyl-CoA mutase is an 5'-adenosylcobalamin (AdoCbl)-dependent enzyme that catalyzes the rearrangement of methylmalonyl-CoA to succinyl-CoA. The crystal structure of this protein revealed that binding of the cofactor is accompanied by a significant conformational change in which dimethylbenzimidazole, the lower axial ligand to cobalt in solution, is replaced by His(610) donated by the active site. The role of the lower axial ligand in the trillion-fold labilization of the upper axial cobalt-carbon bond has been the subject of enduring debate in the model inorganic literature. In this study, we have used a cofactor analog, 5'deoxyadenosylcobinamide GDP (AdoCbi-GDP), which reconstitutes the enzyme in a "histidine-off" form and which allows us to evaluate the contribution of the lower axial ligand to catalysis. The k(cat) for the enzyme in the presence of AdoCbi-GDP is reduced by a factor of 4 compared with the native cofactor AdoCbl. The overall deuterium isotope effect in the presence of AdoCbi-GDP ((D)V = 7.2 +/- 0.8) is comparable with that observed in the presence of AdoCbl (5.0 +/- 0.6) and indicates that the hydrogen transfer steps in this reaction are not significantly affected by the change in coordination state of the bound cofactor. These surprising results are in marked contrast to the effects ascribed to the corresponding lower axial histidine ligands in the cobalamin-dependent enzymes glutamate mutase and methionine synthase.     

Accumulation of Trace Metals by Mangrove Plants in Indian Sundarban Wetland: Prospects for Phytoremediation

The work investigates on the potential of ten mangrove species for absorption, accumulation and partitioning of trace metal(loid)s in individual plant tissues (leaves, bark and root/pneumatophore) at two study sites of Indian Sundarban Wetland. The metal(loid) concentration in host sediments and their geochemical characteristics were also considered. Mangrove sediments showed unique potential in many- fold increase for most metal(loid)s than plant tissues due to their inherent physicochemical properties. The ranges of concentration of trace metal(loid)s for As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Ni, Pb and Zn in plant tissue were 0.006–0.31, 0.02–2.97, 0.10–4.80, 0.13–6.49, 4.46–48.30, 9.2–938.1, 0.02–0.13, 9.8–1726, 11–5.41, 0.04–7.64, 3.81–52.20 μg g ^?1respectively. The bio- concentration factor (BCF) showed its maximum value (15.5) in Excoecaria agallocha for Cd, suggesting that it can be considered as a high-efficient plant for heavy metal bioaccumulation. Among all metals, Cd and Zn were highly bioaccumulated in E. agallocha (2.97 and 52.2 μg g ^?1 respectively. Our findings suggest that the species may be classified as efficient metal trap for Cd in aerial parts, as indicated by higher metal accumulation in the leaves combined with BCF and translocation factor (TF) values.     

A determinant of polyomavirus virulence enhances virus growth in cells of renal origin.

We have identified a strain of polyomavirus, Py(L), which is unusual in causing acute morbidity and early death after inoculation of newborn mice. We determined that these animals died of kidney failure associated with extensive, virus-mediated destruction of renal tissue. Interestingly, the Py(L) strain infects baby mouse kidney cell cultures more efficiently than do other strains.