Comparison of intravenous oxytocin and prostaglandin E2 for accelerating labour.

In a prospective study of 52 consecutive women who required acceleration of labour intravenous prostaglandin E2 (PGE2) was used as the oxytocic agent. These mothers were matched for age, parity, height, gestational age, initial cervical dilatation, and station and position of the fetal head with 52 women whose labours were accelerated with oxytocin; both drugs were equally effective. Acceleration to delivery intervals, second-stage durations, the number of assisted deliveries, and Apgar scores were similar regardless of the oxytocic used. Although PGE2 compares well with oxytocin, it offers no further advantages and is more expensive and less well tried than oxytocin.     

Comparative interactions of withanolides and sterols with two members of sterol glycosyltransferases from Withania somnifera

Background

Sterol glycosyltransferases (SGTs) are ubiquitous but one of the most diverse group of enzymes of glycosyltransferases family. Members of this family modulate physical and chemical properties of secondary plant products important for various physiological processes. The role of SGTs has been demonstrated in the biosynthesis of pharmaceutically important molecules of medicinal plants like Withania somnifera.

Results

Analysis suggested conserved behaviour and high similarity in active sites of WsSGTs with other plant GTs. Substrate specificity of WsSGTs were analysed through docking performance of WsSGTs with different substrates (sterols and withanolides). Best docking results of WsSGTL1 in the form of stable enzyme-substrate complex having lowest binding energies were obtained with brassicasterol, transandrosteron and WsSGTL4 with solasodine, stigmasterol and 24-methylene cholesterol.

Conclusion

This study reveals topological characters and conserved nature of two SGTs from W. somnifera (WsSGTs) i.e. WsSGTL1 and WsSGTL4. However, besides being ubiquitous in nature and with broad substrate specificity, difference between WsSGTL1 and WsSGTL4 is briefly described by difference in stability (binding energy) of enzyme-substrate complexes through comparative docking.

Electronic supplementary material

The online version of this article (doi:10.1186/s12859-015-0563-7) contains supplementary material, which is available to authorized users.     

Expression of nodal signalling components in cycling human endometrium and in endometrial cancer

Background  

The human endometrium is unique in its capacity to remodel constantly throughout adult reproductive life. Although the processes of tissue damage and breakdown in the endometrium have been well studied, little is known of how endometrial regeneration is achieved after menstruation. Nodal, a member of the transforming growth factor-beta superfamily, regulates the processes of pattern formation and differentiation that occur during early embryo development.     

CC chemokine receptor 2 expression in donor cells serves an essential role in graft-versus-host-disease

The complete repertoire of cellular and molecular determinants that influence graft-vs-host disease (GVHD) is not known. Using a well-established murine model of GVHD (B6-->bm12 mice), we sought to elucidate the role of the donor non-T cell compartment and molecular determinants therein in the pathogenesis of GVHD. In this model the acute GVHD-inducing effects of purified B6 wild-type (wt) CD4(+) T cells was inhibited by wt non-T cells in a dose-dependent manner. Paradoxically, unlike the chronic GVHD phenotype observed in bm12 mice transplanted with B6wt unfractionated splenocytes, bm12 recipients of B6ccr2-null unfractionated splenocytes developed acute GVHD and died of IFN-gamma-mediated bone marrow aplasia. This switch from chronic to acute GVHD was associated with increased target organ infiltration of activated CD4(+) T cells as well as enhanced expression of Th1/Th2 cytokines, chemokines, and the antiapoptotic factor bfl1. In vitro, ccr2(-/-) CD4(+) T cells in unfractionated splenocytes underwent significantly less activation-induced cell death than B6wt CD4(+) T cells, providing another potential mechanistic basis along with enhanced expression of bfl1 for the increased numbers of activated T cells in target organs of B6ccr2(-/-) splenocyte-->bm12 mice. Collectively, these findings have important clinical implications, as they implicate the donor non-T cell compartment as a critical regulator of GVHD and suggest that ccr2 expression in this cellular compartment may be an important molecular determinant of activation-induced cell death and GVHD pathogenesis.     

Potent knockdown of the X RNA of hepatitis B by a novel chimeric siRNA-ribozyme construct and modulation of intracellular target RNA by selectively disabled mutants

A multitarget approach is needed for effective gene silencing that combines more than one antiviral strategy. With this in mind, we designed a wild-type (wt) and selectively disabled chimeric mutant (mt) constructs that consisted of small hairpin siRNA joined by a short intracellular cleavable linker to a known hammerhead ribozyme, both targeted against the full-length X RNA of hepatitis B. These chimeric RNAs possessed the ability to cleave the target RNA under in vitro conditions and were efficiently processed at the cleavable site. When this wt chimeric RNA construct was introduced into a liver-specific mammalian cell line, HepG2, along with the HBx substrate encoding DNA, very significant (approximately 70%) intracellular downregulation in the levels of target RNA was observed. When the siRNA portion of this chimeric construct was mutated, keeping the ribozyme (Rz) region unchanged, it caused only approximately 25% intracellular reduction. On the contrary, when only the Rz was made catalytically inactive, about 55% reduction in the target RNA was observed. Construct possessing mt Rz and mt siRNA caused only 10% reduction. This wt chimeric construct also resulted in almost complete knockdown of intracellular HBx protein production, and the mt versions were less effective. The intracellular reduction of target RNA with either wt or mt constructs also interfered with the known functions of HBx protein with varying efficiencies. Thus, in this proof of concept study we show that the levels of the target RNA were reduced potently by the wt chimeric siRNA-Rz construct, which could be modulated with mt versions of the same.     

Tumour necrosis factor-α stimulates human neutrophils to release preformed activin A

Activin A, a member of the transforming growth factor-β superfamily, is a critical early mediator of acute inflammation. Activin A release coincides with the release of tumour necrosis factor-α (TNF-α) in models of lipopolysaccharide (LPS)-induced inflammation. The source of circulating activin A during acute inflammation has not been identified and the potential contribution of leukocyte subsets was examined in the following study. Human leukocytes from healthy volunteers were fractionated using Ficoll gradients and cultured under serum-free conditions. Freshly isolated human neutrophils contained 20-fold more activin A than blood mononuclear cells as measured by enzyme-linked immunosorbent assay (ELISA), and both dimeric and monomeric forms of activin A were detected in these cells by western blotting. Activin A was predominantly immunolocalized in the neutrophil cytoplasm. Purified neutrophils secreted activin A in culture when stimulated by TNF-α, but were unable to respond to LPS directly. Although TNF-α stimulated activin A release from neutrophils within 1 h, activin subunit mRNA expression did not increase until 12 h of culture, and the amount of activin A released following TNF-α stimulation did not change between 1 and 12 h. Specific inhibition of the p38 MAP kinase signalling pathway blocked TNF-α-induced activin release, and the secretion of activin A was not due to TNF-α-induced neutrophil apoptosis. These data provide the first evidence that neutrophils are a significant source of mature, stored activin A. Stimulation of the release of neutrophil activin A by TNF-α may contribute to the early peak in circulating activin A levels during acute inflammation.     

Barriers to Malaria Control among Marginalized Tribal Communities: A Qualitative Study

Background

Malaria infection accounts for over one million deaths worldwide annually. India has the highest number of malaria deaths outside Africa, with half among Indian tribal communities. Our study sought to identify barriers to malaria control within tribal populations in malaria-endemic Gadchiroli district, Maharashtra.

Methods and Findings

This qualitative study was conducted via focus groups and interviews with 84 participants, and included tribal villagers, traditional healers, community health workers (CHWs), medical officers, and district officials. Questions assessed knowledge about malaria, behavior during early stages of infection, and experiences with prevention among tribal villagers and traditional healers. CHWs, medical officers, and district officials were asked about barriers to treating and preventing malaria among tribal populations. Data were inductively analyzed and assembled into broader explanation linking barriers to geographical, cultural and social factors. Findings indicate lack of knowledge regarding malaria symptoms and transmission. Fever cases initially present to traditional healers or informal providers who have little knowledge of malaria or high-risk groups such as children and pregnant women. Tribal adherence with antimalarial medications is poor. Malaria prevention is inadequate, with low-density and inconsistent use of insecticide-treated nets (ITNs). Malaria educational materials are culturally inappropriate, relying on dominant language literacy. Remote villages and lack of transport complicate surveillance by CHWs. Costs of treating malaria outside the village are high.

Conclusions

Geographic, cultural, and social factors create barriers to malaria control among tribal communities in India. Efforts to decrease malaria burden among these populations must consider such realities. Our results suggest improving community-level knowledge about malaria using culturally-appropriate health education materials; making traditional healers partners in malaria control; promoting within-village rapid diagnosis and treatment; increasing ITN distribution and promoting their use as potential strategies to decrease infection rates in these communities. These insights may be used to shape malaria control programs among marginalized populations.     

In vitro plantlet production system for Kaempferia galanga,a rare Indian medicinal herb

A rapid clonal propagation system for Kaempferia galanga (Zingiberaceae), a rare folk medicinal herb has been developed. Various concentrations of 6-benzyladenine (BA) and a range of auxins have been investigated for in vitro plantlet production, using rhizomes as explants. In vitro plantlet production has been achieved on 0.75 × Murashige and Skoog (MS) medium supplemented with 12 μM BA, 3 μM ∝-naphthaleneacetic acid (NAA) and 3% sucrose. The procedure ensures 13-fold rate of plantlet production every 4 weeks. Hardened plantlets produced normal storage roots as the parent plants. Around 1,000 plantlets have been produced successfully for field transfer. This revised version was published online in August 2006 with corrections to the Cover Date.     

SMEDDS of Glyburide: Formulation, In Vitro Evaluation, and Stability Studies

The objective of the present investigation was to develop and evaluate self-microemulsifying drug delivery system (SMEDDS) for improving the delivery of a BCS class II antidiabetic agent, glyburide (GLY). The solubility of GLY in oils, cosurfactants, and surfactants was evaluated to identify the components of the microemulsion. The ternary diagram was plotted to identify the area of microemulsion existence. The in vitro dissolution profile of GLY SMEDDS was evaluated in comparison to the marketed GLY tablet and pure drug in pH 1.2 and pH 7.4 buffers. The chemical stability of GLY in SMEDDS was determined as per the International Conference on Harmonisation guidelines. The area of microemulsion existence increased with the increase in the cosurfactant (Transcutol P) concentration. The GLY microemulsion exhibited globule size of 133.5 nm and polydispersity index of 0.94. The stability studies indicated that GLY undergoes significant degradation in the developed SMEDDS. This observation was totally unexpected and has been noticed for the first time. Further investigations indicated that the rate of GLY degradation was highest in Transcutol P.