Gastrointestinal stasis during sepsis may be associated with gastrointestinal smooth muscle dysfunction. Endotoxin [lipopolysaccharide (LPS)] impairs smooth muscle contraction, in part through inducible nitric oxide synthase (NOS II) and enhanced nitric oxide production. We studied the roles of tumor necrosis factor-α (TNF) and interleukin-1 (IL-1) in this process by using TNF binding protein (TNFbp) and IL-1 receptor antagonist (IL-1ra). Rats were treated with TNFbp and IL-1ra, or their vehicles, 1 h before receiving LPS or saline. At 5 h after LPS, contractility was measured in strips of ileal longitudinal smooth muscle, and NOS II activity was measured in full-thickness segments of ileum. LPS decreased maximum stress (mean ± SE) from 508 ± 55 (control) to 355 ± 33 g/cm2( P < 0.05). Pretreatment with TNFbp plus IL-1ra prevented the LPS-induced decrease. Separate studies of TNFbp alone or IL-1ra alone indicated that, at the doses and timing used, TNFbp was more effective. LPS also increased NOS II activity by >10-fold ( P < 0.01) over control. This increase was prevented by TNFbp plus IL-1ra ( P = not significant vs. control). We conclude that the LPS-induced increase in NOS II activity and the decrease in ileal muscle contractility are mediated by TNF and IL-1.

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SummaryThe marked improvement of several immune-mediated inflammatory diseases during pregnancy has drawn attention to pregnancy hormones as potential therapeutics for such disorders. Low molecular weight fractions derived from the pregnancy hormone human chorionic gonadotrophin (hCG) have remarkable potent immunosuppressive effects in mouse models of diabetes and septic shock. Based on these data we have designed a set of oligopeptides related to the primary structure of hCG and tested these in models of septic shock in mice and rhesus monkeys. We demonstrate that mice exposed to lipopolysaccharide (LPS) and treated subsequently with selected tri-, tetra-, penta-and hepta-meric oligopeptides (i.e. MTR, VVC, MTRV, LQGV, AQGV, VLPALP, VLPALPQ) are protected against fatal LPS-induced septic shock. Moreover, administration of a cocktail of three selected oligopeptides (LQGV, AQGV and VLPALP) improved the pathological features markedly and nearly improved haemodynamic parameters associated with intravenous Escherichia coli-induced septic shock in rhesus monkeys. These data indicate that the designed hCG-related oligopeptides may present a potential treatment for the initial hyperdynamic phase of septic shock in humans.

Background: Against a background of interest in rates of diabetes in schizophrenia and related psychoses and claims that data from historical periods demonstrate a link that antedates modern antipsychotics, we sought to establish the rate of diabetes in first onset psychosis and subsequent prevalence in historical and contemporary cohorts.

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Background: Organisations in the contemporary workplace lack meaningful work and life, resulting in psychological and physical pain for workers. Employees seek organisations that align their daily work activities with society. Partially limited research exists on the relationship between corporate social responsibility (CSR) and employee work-related attitudes, especially with the mediating mechanism of employee work meaningfulness (EWM) and organisation identification (OID) in developing country contexts such as Pakistan. This study has used Social Learning Theory (SLT) and Social Identification Theory (SIT). Methods: Data were collected through a sample of 154 employees in two waves from multiple sectors in Karachi, Pakistan, using non-probability, purposive sampling. The PLS-SEM, along with IBM-SPSS, was run for data analysis. Results: The results demonstrated that Corporate social responsibility (CSR) has a significant positive relationship with employee work-related attitudes. CSR affects organisational citizenship behaviour (OCB) and pro-environmental behaviours (PEB) through the mediation mechanism of employee work meaningfulness (EWM) and organisational identification (OID). Conclusion: This study contributes to the nascent literature by establishing that EWM and OID mediate the effect of CSR on OCB and PEB. Furthermore, this study utilizes two primary theoretical lenses and provides a novel contribution to the current literature. Finally, this study provides valuable insights to policymakers, businesses, and society.

Mood disorders such as depression are the most ubiquitous disease amongst psychiatric disorders. According to the estimations of the World Health Organisation, depression will be the second leading cause of disability in 2020. Psychiatric disorders are the foremost problems in the world since relic. In Unani system of medicine, there is no any direct description of depression but it is described in detail under the heading of "Amraze nafsaniya". This system has a gem of valuable single and compound formulations for psychiatric disorders as there are several mufrad (Single) drugs used to treat psychiatric disorders such as Aftimoon (Cuscuta reflexa), Badranjboya (Nepeta hindostana), Nilofar (Nymphaea alba), Gule surkh (Rosa damascena), Bisfaij (Polypodium vulgare) etc. Sharbat Ahmad Shahi is one of the polyherbal Unani preparations and it has been conventionally used in Malankholia (Melancholia), Insanity, Mania and for saudavi amraaz. It has been reported for its antidepressant potential in recent years.