Drugs exhibiting anti-inflammatory and analgesic properties have been clinically used in the management of pain and impairment of joint functions in arthritis. In view of available studies on the beneficial effect of artesunate in various inflammatory conditions, the present study was carried out to evaluate its efficacy in ameliorating functional limitations of arthritis and to understand the underlying mechanisms. The study was carried out in rat model of Freund's complete adjuvant-induced monoarthritis where artesunate was found to produce a dose-dependent reduction in joint inflammation, improvement in functional parameters like stair climbing ability, motility, and suppression of mechanical allodynia at the doses of 50 and 150 mg/kg. Our study shows that protection afforded by artesunate was brought about by decreasing the levels of nitric oxide, influx of neutrophils, maintenance of oxidative homeostasis, inhibition of COX-2 expression, and apoptosis. Further, histological analysis of the arthritic joints also substantiated the anti-inflammatory property of artesunate. Thus, our study shows that artesunate has a potential for use in the treatment of arthritis.

Arthritis is a joint disorder where the joint damage is associated with elevated levels of inflammatory mediators and reactive oxygen species (ROS). The inflammatory hyperalgesia associated with arthritis has been shown to be attenuated by anti-hyperlipidemic drug, atorvastatin. The present study was carried out to evaluate the effect of atorvastatin on joint inflammation and associated oxidative stress markers in a rat model where arthritis was induced by intra-articular injection of 0.1 ml of 0.1% Freund's Complete Adjuvant (FCA). Atorvastatin (10 mg and 50 mg/kg) and diclofenac (5 mg/kg) were administered orally, daily during the study period of 4 days and their effect on joint inflammation was evaluated by measuring joint diameter, levels of glutathione (GSH), thiobarbituric acid reactive substances (TBARS), activity of super oxide dismutase (SOD) and tissue histology. Atorvastatin produced a dose-dependent reduction in joint inflammation that was associated with normalization of levels of oxidative stress markers and tissue histology and its effect was found to be comparable to that of diclofenac.

The non-dialysable proteins present in the latex of plant Calotropis procera possess anti-inflammatory and analgesic properties. The aim of this study was to evaluate the effect of latex proteins (LP) on the level of inflammatory mediators, oxidative stress markers and tissue histology in the rat model of carrageenan-induced acute inflammation. This study also aimed at evaluating the anti-inflammatory efficacy of LP against different mediators and comparing it with their respective antagonists. Paw inflammation was induced by subplantar injection of carrageenan, and the effect of LP was evaluated on oedema volume, level of TNF-α, PGE(2), myeloperoxidase, nitric oxide, reduced glutathione, thiobarbituric acid-reactive substances and tissue histology at the time of peak inflammation. Paw inflammation was also induced by histamine, serotonin, bradykinin and PGE(2), and the inhibitory effect of LP against these mediators was compared with their respective antagonists at the time of peak effect. Treatment with LP produced a dose-dependent inhibition of oedema formation, and its anti-inflammatory effect against carrageenan-induced paw inflammation was accompanied by reduction in the levels of inflammatory mediators, oxidative stress markers and normalization of tissue architecture. LP also produced a dose-dependent inhibition of oedema formation induced by different inflammatory mediators, and its efficacy was comparable to their respective antagonists and more pronounced than that of diclofenac. Thus, our study shows that LP has a potential to be used for the treatment of various inflammatory conditions where the role of these mediators is well established.

Organic solvents enhance intracellular oxidative stress and induce various physiological responses in bacteria. The study shows the morphological changes in Paracoccus sp. SKG when exposed to higher concentrations of acetonitrile, which alter the composition of the membrane fatty acid that accompanies the increase in K(+) efflux. This enhances the oxidative stress with greater activities of catalase and super oxide dismutase (SOD). The increased oxidative stress results in the generation of free radicals, which was confirmed by electron paramagnetic resonance (EPR) studies. The free radical scavenging activities were measured by ABTS and DPPH to understand the non-enzymatic defensive system during oxidative stress. The studies demonstrate the increase in free radicals in association with enzymatic and non-enzymatic defense systems under solvent stress.

Background: Most clinical trials of sepsis treatment modalities fail at their primary objective of establishing superiority over placebo when added to background standard of care. While there is no definitive explanation for the high failure rate, it might be stated that our attempts to insert a new therapeutic agent into standard of care encounters severe problems with definition of exactly what stage is ongoing, and what are the criteria for progression or resolution from that time point onwards. Clearly there is need for a means of defining steps in the septic process that would apply to individuals, and to better define the course of sepsis in each patient after they are enrolled in a trial. Methods: For core model development, 30 septic patients were studied for time-related progression in relation to biomarkers, employing a Load Model in a neural net algorithm in MatLab. Causative bacterial infections were linked to primary infection sites. In order to minimize overparameterization, the model was allowed to estimate outputs using the best three input parameters. Bacterial load was tracked from origin using clinical and microbiologic data to provide an estimate at the start of sepsis. The bacterial load as well as clinical and laboratory parameters were model inputs with the output parameter being organ failures and/ or mortality. Results: At onset of sepsis, human bacterial load estimates ranged from between 10 8 and 10 11 CFU, which is consistent with inocula in animal models of sepsis. Sepsis proceeds to organ failures and mortality in a series of steps that are initially linked to bacterial load and inflammatory response, followed by coagulopathy, ischemia, oxygen deprivation in organs and tissues, and culminating in organ failures. The later stages of sepsis are all driven by metabolic parameters, and there seems to be little benefit to blocking inflammation at later stages. Substrate and oxygen deficiencies must be addressed first. Conclusion: Neural net progression models based on biomarkers and physiological markers are able to describe the evolution of sepsis to septic shock, organ failures, and provide some evidence that mortality may be a consequence of the stages of sepsis. Overall, these models appear useful to the task of sorting out organ failure endpoints and mechanisms in individual patients with sepsis progression across sepsis to septic shock. P2 Extracellular matrix turnover, angiogenesis and endothelial function in acute lung injury: relationship to pulmonary dysfunction and outcome