Isosojagol,a coumestan from Phaseolus coccineus

A novel coumestan isolated from Phaseolus coccineus has been characterized as 3,9-dihydroxy-10-(γ,γ-dimethylallyl)-coumestan and named isosojagol.     

Studies on the anti-inflammatory and toxic effects of the stem bark of Khaya ivorensis (Meliaceae) on rats.

Khaya ivorensis A. Chev. (Meliaceae) is a common feature in anti-malarial recipe prescribed by African traditional medical practitioners. Investigations have proved that Khaya species possesses some level of anti-plasmodial activity. Anti-inflammatory and toxicity studies were carried out on this plant using the Ugo Basile model 7140 and routine toxicity study methods, respectively, on adult wistar rats. The brain, spleen, heart, liver and kidneys were examined for dismorphological features, following oral administration of the ethanolic extract of K. ivorensis at the daily dose levels of 1000, 500 or 125 mg/kg for 7, 14 and 7 days after cessation of drug administration. The study showed that tissue toxicity, especially neurotoxicity was dose dependent, similarly the anti-inflammatory effect. The toxicity appeared to be reversible at lower doses. The wide margin between the therapeutic and toxic dosages makes the extract a possible safe drug in the management of malaria.     

Transplantation of placenta‐derived mesenchymal stem cells enhances angiogenesis after ischemic limb injury in mice

Mesenchymal stem cell‐based therapy has emerged as a promising approach for the treatment of peripheral arterial disease. The purpose of this study was to examine the potential effects of human placenta‐derived mesenchymal stem cells (PMSCs) on mouse hindlimb ischemia. PMSCs were isolated from human placenta tissue and characterized by flow cytometry. An in vivo surgical ligation‐induced murine limb ischemia model was generated with fluorescent dye (CM‐DiI) labelled PMSCs delivered via intramuscular injection. Our data show that PMSCs treatment significantly enhanced microvessel density, improved blood perfusion and diminished pathologies in ischemic mouse hindlimbs as compared to those in the control group. Further immunostaining studies suggested that injected PMSCs can incorporate into the vasculature and differentiate into endothelial and smooth muscle cells to enhance angiogenesis in ischemic hind limbs. This may in part explain the beneficial effects of PMSCs treatment. Taken together, we found that PMSCs treatment might be an effective treatment modality for treatment of ischemia‐induced injury to mouse hind limbs by enhancement of angiogenesis.     

The effects of insulin,glucose and anti-insulin upon the activity of uridine diphosphate glucose glycogen α-4-glucosyl-transferase EC2.4.1.11 in the rat placenta

Summary The enzyme uridine diphosphate glucose glycogen -4-glyoosyl-transferase EC2.4.1.11 was found to be active in the rat placenta. The total activity of the enzyme, present from the earliest day investigated, day 12, increased significantly between days 14 and 16 and days 18 and 20. The enzyme was observed to be present in both the active and the inactive forms. In in vivo studies of the effects of insulin, glucose and anti-insulin serum it was observed that insulin and glucose produced an increase in the activity of the enzyme while anti-insulin serum inhibited its activity. Insulin was observed to exert its stimulatory effect also in vitro.The activity of the enzyme was observed to be localized strongly in the decidua basalis, the spongy zone, the labyrinth as well as in the yolk sac. There was a shift in the activity of the enzyme from the decidua basalis and the visceral layer of the yolk sac where it was strongest in the younger placentae (14 or 16 days) to the spongy layer where it was stronger towards the end of gestation. The activity of the enzyme was very weak, at 12 days, in all areas of the placenta.     

A fluorescent histochemical method for the detection of tissue disulphide groups

Summary Bennett and Yphantis (1948) introduced into histochemistry the use of organic mercurials for the detection of sulphydryl groups. The new fluorescent method which is now reported is similarly based upon the reaction of mercaptans with an organic mercurial, fluorescein mercuric acetate (FMA). This method is sensitive; moreover it is not as elaborate as the dihydroxy-dinaphthyl-disulphide (DDD) technique of Barrnett and Seligman (1952).     

Phase 1 Safety and Immunogenicity Evaluation of ADMVA,a Multigenic,Modified Vaccinia Ankara-HIV-1 B'/C Candidate Vaccine

Background

We conducted a Phase I dose-escalation trial of ADMVA, a Clade-B''/C-based HIV-1 candidate vaccine expressing env, gag, pol, nef, and tat in a modified vaccinia Ankara viral vector. Sequences were derived from a prevalent circulating HIV-1 recombinant form in Yunnan, China, an area of high HIV incidence. The objective was to evaluate the safety and immunogenicity of ADMVA in human volunteers.

Methodology/Principal Findings

ADMVA or placebo was administered intramuscularly at months 0, 1 and 6 to 50 healthy adult volunteers not at high risk for HIV-1. In each dosage group [1×10⁷ (low), 5×10⁷ (mid), or 2.5×10⁸ pfu (high)] volunteers were randomized in a 3∶1 ratio to receive ADMVA or placebo in a double-blinded design. Subjects were followed for local and systemic reactogenicity, adverse events including cardiac adverse events, and clinical laboratory parameters. Study follow up was 18 months. Humoral immunogenicity was evaluated by anti-gp120 binding ELISA, immunoflourescent staining, and HIV-1 neutralization. Cellular immunogenicity was assessed by a validated IFNγ ELISpot assay and intracellular cytokine staining. Anti-vaccinia binding titers were measured by ELISA.ADMVA was generally well-tolerated, with no vaccine-related serious adverse events or cardiac adverse events. Local or systemic reactogenicity events were reported by 77% and 78% of volunteers, respectively. The majority of events were of mild intensity. The IFNγ ELISpot response rate to any HIV antigen was 0/12 (0%) in the placebo group, 3/12 (25%) in the low dosage group, 6/12 (50%) in the mid dosage group, and 8/13 (62%) in the high dosage group. Responses were often multigenic and occasionally persisted up to one year post vaccination. Antibodies to gp120 were detected in 0/12 (0%), 8/13 (62%), 6/12 (50%) and 10/13 (77%) in the placebo, low, mid, and high dosage groups, respectively. Antibodies persisted up to 12 months after vaccination, with a trend toward agreement with the ability to neutralize HIV-1 SF162 in vitro. Two volunteers mounted antibodies that were able to neutralize clade-matched viruses.

Conclusions/Significance

ADMVA was well-tolerated and elicited durable humoral and cellular immune responses.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00252148","term_id":"NCT00252148"}}NCT00252148     

The JAX Synteny Browser for mouse-human comparative genomics

Visualizing regions of conserved synteny between two genomes is supported by numerous software applications. However, none of the current applications allow researchers to select genome features to display or highlight in blocks of synteny based on the annotated biological properties of the features (e.g., type, function, and/or phenotype association). To address this usability gap, we developed an interactive web-based conserved synteny browser, The Jackson Laboratory (JAX) Synteny Browser. The browser allows researchers to highlight or selectively display genome features in the reference and/or the comparison genome according to the biological attributes of the features. Although the current implementation for the browser is limited to the reference genomes for the laboratory mouse and human, the software platform is intentionally genome agnostic. The JAX Synteny Browser software can be deployed for any two genomes where genome coordinates for syntenic blocks are defined and for which biological attributes of the features in one or both genomes are available in widely used standard bioinformatics file formats. The JAX Synteny Browser is available at: http://syntenybrowser.jax.org/. The code base is available from GitHub: https://github.com/TheJacksonLaboratory/syntenybrowser and is distributed under the Creative Commons Attribution license (CC BY).

     

A contribution to the study of the fixation of glycogen in embryonic tissues

Summary In chick embryos the best preservation of glycogen by conventional fixation methods was obtained withRossman's fixative. Although quenching methods give even better results, they are unsuitable for large pieces of tissues such as whole embryos. For this type of material a technique of intraventricular perfusion withRossman's fixative was devised. This method gave excellent preservation of glycogen and good cytological detail; most important of all, it made it possible to study the distribution of glycogen throughout a whole embryo in serial sections.

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Zusammenfassung Die Glykogenerhaltung in Hühnerembryonen wurde durch die üblichen Fixierungsmethoden mittelsRossmans Flüssigkeit erreicht. Obgleich man mit Kaltfixierung (quenching) noch bessere Resultate erhält, ist diese Methode für große Gewebsstücke (z. B. ganze Embryonen) unpassend. Für solches Material haben wir eine intra-ventrikuläre Perfusionstechnik unter Anwendung vonRossmans Gemisch entwickelt, welche sich ausgezeichnet für die Glykogenerhaltung eignet und zytologische Details gut zum Vorschein bringt. Am wichtigsten jedoch erachten wir, daß man auf diese Weise die wahre Glykogenverbreitung in ganzen Embryonen an Hand von Serienschnitten beurteilen kann.

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With 4 Figures in the Text     

Effect of Metabolic Syndrome on Mitsugumin 53 Expression and Function

Metabolic syndrome is a cluster of risk factors, such as obesity, insulin resistance, and hyperlipidemia that increases the individual’s likelihood of developing cardiovascular diseases. Patients inflicted with metabolic disorders also suffer from tissue repair defect. Mitsugumin 53 (MG53) is a protein essential to cellular membrane repair. It facilitates the nucleation of intracellular vesicles to sites of membrane disruption to create repair patches, contributing to the regenerative capacity of skeletal and cardiac muscle tissues upon injury. Since individuals suffering from metabolic syndrome possess tissue regeneration deficiency and MG53 plays a crucial role in restoring membrane integrity, we studied MG53 activity in mice models exhibiting metabolic disorders induced by a 6 month high-fat diet (HFD) feeding. Western blotting showed that MG53 expression is not altered within the skeletal and cardiac muscles of mice with metabolic syndrome. Rather, we found that MG53 levels in blood circulation were actually reduced. This data directly contradicts findings presented by Song et. al that indict MG53 as a causative factor for metabolic syndrome (Nature 494, 375-379). The diminished MG53 serum level observed may contribute to the inadequate tissue repair aptitude exhibited by diabetic patients. Furthermore, immunohistochemical analyses reveal that skeletal muscle fibers of mice with metabolic disorders experience localization of subcellular MG53 around mitochondria. This clustering may represent an adaptive response to oxidative stress resulting from HFD feeding and may implicate MG53 as a guardian to protect damaged mitochondria. Therapeutic approaches that elevate MG53 expression in serum circulation may be a novel method to treat the degenerative tissue repair function of diabetic patients.     

An Evaluation of the Quality of IMCI Assessments among IMCI Trained Health Workers in South Africa

Background

Integrated Management of Childhood Illness (IMCI) is a strategy to reduce mortality and morbidity in children under 5 years by improving case management of common and serious illnesses at primary health care level, and was adopted in South Africa in 1997. We report an evaluation of IMCI implementation in two provinces of South Africa.

Methodology/Principal Findings

Seventy-seven IMCI trained health workers were randomly selected and observed in 74 health facilities; 1357 consultations were observed between May 2006 and January 2007. Each health worker was observed for up to 20 consultations with sick children presenting consecutively to the facility, each child was then reassessed by an IMCI expert to determine the correct findings. Observed health workers had been trained in IMCI for an average of 32.2 months, and were observed for a mean of 17.7 consultations; 50/77(65%) HW''s had received a follow up visit after training. In most cases health workers used IMCI to assess presenting symptoms but did not implement IMCI comprehensively. All but one health worker referred to IMCI guidelines during the period of observation. 9(12%) observed health workers checked general danger signs in every child, and 14(18%) assessed all the main symptoms in every child. 51/109(46.8%) children with severe classifications were correctly identified. Nutritional status was not classified in 567/1357(47.5%) children.

Conclusion/Significance

Health workers are implementing IMCI, but assessments were frequently incomplete, and children requiring urgent referral were missed. If coverage of key child survival interventions is to be improved, interventions are required to ensure competency in identifying specific signs and to encourage comprehensive assessments of children by IMCI practitioners. The role of supervision in maintaining health worker skills needs further investigation.