Evaluation of antiarthritic activity of Strychnos potatorum Linn seeds in Freund's adjuvant induced arthritic rat model

<p>Abstract</p> <p>Background</p> <p><it>Strychnos potatorum </it>Linn (Loganiaceae) is a moderate sized tree found in southern and central parts of India, Sri Lanka and Burma. In traditional system of medicine, <it>Strychnos potatorum </it>Linn seeds were used for various ailments including inflammation, diabetes etc. To investigate the folkloric use of the seeds the present study was carried out on Freund's adjuvant induced arthritic rats.</p> <p>Methods</p> <p>The present study states the effect of the aqueous extract (SPE) and the whole seed powder (SPP) of <it>Strychnos potatorum </it>Linn seeds on the Freund's complete adjuvant (FCA) induced arthritic rat paw edema, body weight changes and alterations in haematological and biochemical parameters in both developing and developed phases of arthritis. Histopathology of proximal interphalangeal joints and radiology of hind legs were studied.</p> <p>Results</p> <p>In FCA induced arthritic rats, there was significant increase in rat paw volume and decrease in body weight increment, whereas SPP and SPE treated groups, showed significant reduction in paw volume and normal gain in body weight. The altered haematological parameters (Hb, RBC, WBC and ESR) and biochemical parameters (blood urea, serum creatinine, total proteins and acute phase proteins) in the arthritic rats were significantly brought back to near normal by the SPP and SPE treatment at the dose of 200 mg/kg/p.o in both developing and developed phases of arthritis. Further the histopathological and radiological studies revealed the antiarthritic activity of SPP and SPE by indicating fewer abnormalities in these groups when compared to the arthritic control group.</p> <p>Conclusion</p> <p>In conclusion, both SPP and SPE at the specified dose level of 200 mg/kg, p.o. showed reduction in rat paw edema volume and it could significantly normalize the haematological and biochemical abnormalities in adjuvant induced arthritic rats in both developing and developed phases of FCA induced arthritis. Further the histopathological and radiological studies confirmed the antiarthritic activity of SPP and SPE.</p

Study of FoxA Pioneer Factor at Silent Genes Reveals Rfx-Repressed Enhancer at Cdx2 and a Potential Indicator of Esophageal Adenocarcinoma Development

Understanding how silent genes can be competent for activation provides insight into development as well as cellular reprogramming and pathogenesis. We performed genomic location analysis of the pioneer transcription factor FoxA in the adult mouse liver and found that about one-third of the FoxA bound sites are near silent genes, including genes without detectable RNA polymerase II. Virtually all of the FoxA-bound silent sites are within conserved sequences, suggesting possible function. Such sites are enriched in motifs for transcriptional repressors, including for Rfx1 and type II nuclear hormone receptors. We found one such target site at a cryptic “shadow” enhancer 7 kilobases (kb) downstream of the Cdx2 gene, where Rfx1 restricts transcriptional activation by FoxA. The Cdx2 shadow enhancer exhibits a subset of regulatory properties of the upstream Cdx2 promoter region. While Cdx2 is ectopically induced in the early metaplastic condition of Barrett's esophagus, its expression is not necessarily present in progressive Barrett's with dysplasia or adenocarcinoma. By contrast, we find that Rfx1 expression in the esophageal epithelium becomes gradually extinguished during progression to cancer, i.e, expression of Rfx1 decreased markedly in dysplasia and adenocarcinoma. We propose that this decreased expression of Rfx1 could be an indicator of progression from Barrett's esophagus to adenocarcinoma and that similar analyses of other transcription factors bound to silent genes can reveal unanticipated regulatory insights into oncogenic progression and cellular reprogramming

Blocking and its response to climate change

Purpose of review: Atmospheric blocking events represent some of the most high-impact weather patterns in the mid-latitudes, yet they have often been a cause for concern in future climate projections. There has been low confidence in predicted future changes in blocking, despite relatively good agreement between climate models on a decline in blocking. This is due to the lack of a comprehensive theory of blocking and a pervasive underestimation of blocking occurrence by models. This paper reviews the state of knowledge regarding blocking under climate change, with the aim of providing an overview for those working in related fields. Recent Findings: Several avenues have been identified by which blocking can be improved in numerical models, though a fully reliable simulation remains elusive (at least, beyond a few days lead time). Models are therefore starting to provide some useful information on how blocking and its impacts may change in the future, although deeper understanding of the processes at play will be needed to increase confidence in model projections. There are still major uncertainties regarding the processes most important to the onset, maintenance and decay of blocking and advances in our understanding of atmospheric dynamics, for example in the role of diabatic processes, continue to inform the modelling and prediction efforts. Summary: The term ‘blocking’ covers a diverse array of synoptic patterns, and hence a bewildering range of indices has been developed to identify events. Results are hence not considered fully trustworthy until they have been found using several different methods. Examples of such robust results are the underestimation of blocking by models, and an overall decline in future occurrence, albeit with a complex regional and seasonal variation. In contrast, hemispheric trends in blocking over the recent historical period are not supported by different methods, and natural variability will likely dominate regional variations over the next few decades

ANCA-associated vasculitis.

The anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAVs) are a group of disorders involving severe, systemic, small-vessel vasculitis and are characterized by the development of autoantibodies to the neutrophil proteins leukocyte proteinase 3 (PR3-ANCA) or myeloperoxidase (MPO-ANCA). The three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis and eosinophilic GPA (EGPA), are defined according to clinical features. However, genetic and other clinical findings suggest that these clinical syndromes may be better classified as PR3-positive AAV (PR3-AAV), MPO-positive AAV (MPO-AAV) and, for EGPA, by the presence or absence of ANCA (ANCA+ or ANCA-, respectively). Although any tissue can be involved in AAV, the upper and lower respiratory tract and kidneys are most commonly and severely affected. AAVs have a complex and unique pathogenesis, with evidence for a loss of tolerance to neutrophil proteins, which leads to ANCA-mediated neutrophil activation, recruitment and injury, with effector T cells also involved. Without therapy, prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. Meeting these challenges requires a more detailed knowledge of the fundamental biology of AAV as well as cooperative international research and clinical trials with meaningful input from patients