SIGMOISIDE E: A NEW ANTIBACTERIAL TRITERPENOID SAPONIN FROM ERYTHRINA SIGMOIDEA (HUA)

Chemical analysis of the stem bark of Erythrina sigmoidea (Leguminoseae) yielded two known isoflavones, 6,8-diprenylgenisteine (3) and warangalone (4) as well as a new triterpenoid saponin designated sigmoiside E (1). Its structure was established by chemical and spectroscopic means as 16-O-β-D-galactopyranosyl maniladiol (1). Sigmoiside E exhibited antibacterial activity against gram-negative bacteria. KEY WORDS: Erythrina sigmoidea, Stem bark, Triterpenoid, Saponin, Isoflavone, Leguminoseae Bull. Chem. Soc. Ethiop. 2007, 21(3), 373-378

The epidemiology of injuries across the weight-training sports

Background: Weight-training sports, including weightlifting, powerlifting, bodybuilding, strongman, Highland Games, and CrossFit, are weight-training sports that have separate divisions for males and females of a variety of ages, competitive standards, and bodyweight classes. These sports may be considered dangerous because of the heavy loads commonly used in training and competition. Objectives: Our objective was to systematically review the injury epidemiology of these weight-training sports, and, where possible, gain some insight into whether this may be affected by age, sex, competitive standard, and bodyweight class. Methods: We performed an electronic search using PubMed, SPORTDiscus, CINAHL, and Embase for injury epidemiology studies involving competitive athletes in these weight-training sports. Eligible studies included peer-reviewed journal articles only, with no limit placed on date or language of publication. We assessed the risk of bias in all studies using an adaption of the musculoskeletal injury review method. Results: Only five of the 20 eligible studies had a risk of bias score ≥75 %, meaning the risk of bias in these five studies was considered low. While 14 of the studies had sample sizes >100 participants, only four studies utilized a prospective design. Bodybuilding had the lowest injury rates (0.12–0.7 injuries per lifter per year; 0.24–1 injury per 1000 h), with strongman (4.5–6.1 injuries per 1000 h) and Highland Games (7.5 injuries per 1000 h) reporting the highest rates. The shoulder, lower back, knee, elbow, and wrist/hand were generally the most commonly injured anatomical locations; strains, tendinitis, and sprains were the most common injury type. Very few significant differences in any of the injury outcomes were observed as a function of age, sex, competitive standard, or bodyweight class. Conclusion: While the majority of the research we reviewed utilized retrospective designs, the weight-training sports appear to have relatively low rates of injury compared with common team sports. Future weight-training sport injury epidemiology research needs to be improved, particularly in terms of the use of prospective designs, diagnosis of injury, and changes in risk exposure

Effects of Combined CCR5/Integrase Inhibitors-Based Regimen on Mucosal Immunity in HIV-Infected Patients Naïve to Antiretroviral Therapy: A Pilot Randomized Trial

Whether initiation of antiretroviral therapy (ART) regimens aimed at achieving greater concentrations within gut associated lymphoid tissue (GALT) impacts the level of mucosal immune reconstitution, inflammatory markers and the viral reservoir remains unknown. We included 12 HIV- controls and 32 ART-naïve HIV patients who were randomized to efavirenz, maraviroc or maraviroc+raltegravir, each with fixed-dose tenofovir disoproxil fumarate/emtricitabine. Rectal and duodenal biopsies were obtained at baseline and at 9 months of ART. We performed a comprehensive assay of T-cell subsets by flow cytometry, T-cell density in intestinal biopsies, plasma and tissue concentrations of antiretroviral drugs by high-performance liquid chromatography/mass spectroscopy, and plasma interleukin-6 (IL-6), lipoteichoic acid (LTA), soluble CD14 (sCD14) and zonulin-1 each measured by ELISA. Total cell-associated HIV DNA was measured in PBMC and rectal and duodenal mononuclear cells. Twenty-six HIV-infected patients completed the follow-up. In the duodenum, the quadruple regimen resulted in greater CD8+ T-cell density decline, greater normalization of mucosal CCR5+CD4+ T-cells and increase of the naïve/memory CD8+ T-cell ratio, and a greater decline of sCD14 levels and duodenal HIV DNA levels (P = 0.004 and P = 0.067, respectively), with no changes in HIV RNA in plasma or tissue. Maraviroc showed the highest drug distribution to the gut tissue, and duodenal concentrations correlated well with other T-cell markers in duodenum, i.e., the CD4/CD8 ratio, %CD4+ and %CD8+ HLA-DR+CD38+ T-cells. Maraviroc use elicited greater activation of the mucosal naïve CD8+ T-cell subset, ameliorated the distribution of the CD8+ T-cell maturational subsets and induced higher improvement of zonulin-1 levels. These data suggest that combined CCR5 and integrase inhibitor based combination therapy in ART treatment naïve patients might more effectively reconstitute duodenal immunity, decrease inflammatory markers and impact on HIV persistence by cell-dependent mechanisms, and show unique effects of MVC in duodenal immunity driven by higher drug tissue penetration and possibly by class-dependent effects

Autocrine Regulation of Pulmonary Inflammation by Effector T-Cell Derived IL-10 during Infection with Respiratory Syncytial Virus

Respiratory syncytial virus (RSV) infection is the leading viral cause of severe lower respiratory tract illness in young infants. Clinical studies have documented that certain polymorphisms in the gene encoding the regulatory cytokine IL-10 are associated with the development of severe bronchiolitis in RSV infected infants. Here, we examined the role of IL-10 in a murine model of primary RSV infection and found that high levels of IL-10 are produced in the respiratory tract by anti-viral effector T cells at the onset of the adaptive immune response. We demonstrated that the function of the effector T cell -derived IL-10 in vivo is to limit the excess pulmonary inflammation and thereby to maintain critical lung function. We further identify a novel mechanism by which effector T cell-derived IL-10 controls excess inflammation by feedback inhibition through engagement of the IL-10 receptor on the antiviral effector T cells. Our findings suggest a potentially critical role of effector T cell-derived IL-10 in controlling disease severity in clinical RSV infection

Analysis of humanized antibody diversification in rabbits and mice using transgenic Immunoglobulin heavy chain (IgH) mini-loci.

Somatic mutation of rearranged immunoglobulin genes (IgH and IgL) is a key process because it leads to the diversification of the antibody chains, a vital progression in the affinity maturation process whereby antibody-antigen binding is enhanced. Two different mechanisms of somatic mutation have been described and attributed to different species: somatic hypermutaion (in man and mouse) occurs by fixation of individual non-templated nucleotide substitutions, whereas gene conversion (in rabbits, sheep, birds and cattle) occurs by templated substitutions with sequences donated by upstream pseudogenes to the rearranged IgV gene segment. These two processes have been described to be alternative methods employed in revamping a lesion caused by the protein Activation Induced Deanimase (AID) in the rearranged IgV gene segment. The decision which method is thereby used depends on interplay of cis (Ig promoter and enhancer) and trans (genes involved in homologous recombination) elements. In this work a transgenic vector is created using a novel approach, whereby the coding sequences of a rabbit IgH locus are substituted with their human counterparts. In the first part of the study, this transgenic vector is used to generated transgenic mice, and somatic diversification of the humanized antibodies investigated; the question posed being what would be the result of the interaction between rabbit ( a gene converting animal) cis regulatory elements (on the transgenic vector) and the trans elements of the mouse host ( a hypermutating animal)? The results advocate a species specific activity of the Ig cis and trans elements as no somatic hypermutation was observed, albeit successful rearrangement and employment of the translocus. In the second part of the work, a second humanized rabbit transgenic vector was used to generate transgenic rabbits and mice and the somatic diversification of the humanized antibodies investigated. Mice and rabbits transgenic for the same locus proffer a much comprehensible comparison of somatic hypermutation in these animals. The question to be answered in this second part was would the humanized antibodies undergo somatic hypermutation in the transgenic mice and gene conversion in the transgenic rabbits? The results give credit to the hypothesis from the first part: the humanized antibodies from the transgenic mice showed no somatic hypermutation, while those from the transgenic rabbits did undergo effective gene conversion. In total these results argue for a species specific interaction of Ig cis and trans regulatory elements in determining the method of somatic mutation employed