Insulin receptor and glucose transporter-4 expression in the skeletal muscle of chronically stressed rats

Background: Stress defined as a disruption in the normal homeostatic functions of an organism caused by stressor (a physiological or psychological challenge) is an unavoidable normal component of life. Previous studies suggest that stress hormones have acute adverse effects on glycaemic control. The aim of this study was to assess the effect of chronic psychological and physical stress on the expression of insulin receptor and GLUT4 transporters in male Sprague-Dawley rats.Methods: Male rats (12 weeks old) were randomly distributed into 3 groups: control, water avoidance stress (WAS), forced swimming stress (FSS). The stress procedures were performed between 9:00 and 11:00 am to minimize the effect of circadian rhythm and lasted for 28 consecutive days. Levels of insulin and corticosterone in the blood were determined using enzyme-linked immunosorbent assay. Glucose metabolism was assessed by glucose tolerance test (GTT) and insulin tolerance test (ITT), and expression of insulin receptor (INSR) and glucose transporter-4 (GLUT4) in skeletal muscle.Results: The FSS rats had decreased food intake as well as final body weight and without adverse changes in GTT, stress worsened insulin sensitivity in FSS rats and increased insulin in the blood. Stress also increased corticosterone, decreased INSR and GLUT4 in the skeletal muscle of both groups.Conclusion: Chronic stress evokes insulin insensitivity and impairs glucose metabolism through the down-regulation of INSR and GLUT4 in skeletal muscles.Keywords: Chronic Stress, Glucose Tolerance, Glucose Transporter, Insulin Sensitivity, Corticosteron

Antioxidant Capacities and Phytoconstituents of Fractions of Ethanol Extract of Cymbopogon citratus (DC.) Stapf: Inhibition of Iron II (Fe2+) - Induced Lipid Peroxidation in Rat Colon Homogenate

Oxidative stress is associated with the generation of excess free radicals and reduction in the levels of antioxidant enzymes. It is also implicated in the initiation and progression of colorectal cancer. Cymbopogon citratus, commonly called ‘lemon grass,’ is widely distributed in the tropics and it is known for its therapeutic applications. In this study, the antioxidant activities of the crude ethanol extract of Cymbopogon citratus and its fractions were determined using total antioxidant capacity (TAC), 2-2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, Fe3+ reducing ability, total phenolic content (TPC) and total flavonoid content (TFC). The phytocomponents were determined through Gas Chromatography - Mass Spectrometry and lipid peroxidation was induced in rat colon homogenate. TFC and TPC were highest in the ethyl acetate fraction (EAF) > crude extract (CE) > ethanol fraction (EF) > chloroform fraction (CF). Both DPPH scavenging activity and Fe3+ reducing ability exhibited similar trend; EAF > EF > CF > CE. In addition, the ability to inhibit lipid peroxidation in rat colon is as follows; EAF> CF > CE > EF. The EAF and CF of the ethanol extract of C. citratus contain most of the compounds that could be responsible for its activity against reactive oxygen species

Carryover effect on carcass characteristics of growing rabbits from does subjected to feed restriction during pregnancy with or without vitamin E inclusion

Several studies have been carried out on quantitative feed restriction and its impact on carcass characteristics of growing rabbits and findings concluded that feed restriction helps in reducing carcass fat deposition in growing rabbits. Feed restriction during breeding periods have been carried out extensively in pregnant rabbit does, however, the carryover effect on the carcass characteristics of growing rabbits from does subjected to such feeding regimen have not been examined. A total of one hundred and eighty (180) weaned rabbits harvested from rabbit does subjected to maternal feed restriction (0% and 15% feed restriction) at three pregnancy periods (15-19 days, 20-24 days and 25-29 days) with or without (+/-) vitamin E were profiled for this study. Kits were randomly assigned to 12 treatments of 5 replicates, each consisting of 3 rabbits per replicate. Data obtained for carcass weight, dressed weight, chest, back, hindlimb, forelimbs, loin, back, kidney, liver, spleen, lungs and heart; these were arranged in a 2×3×2 factorial arrangement. Significantly (p<0.05) higher carcass weight and dressing percentage were obtained for growing rabbit from does fed ad libitum during pregnancy. However, significant influence recorded for carcass and dressing percentage cannot be attributed solely to the treatment during gestation since all results obtained were within acceptable or recommended ranges for healthy rabbits. Therefore, it can be concluded that maternal feed restriction during pregnancy positively influence carcass yield and dressing percentage of growing rabbits from does subjected to feed restriction between 20 – 24 days with or without Vitamin E was influenced (p<0.05)

Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Background: In this study, we aimed to evaluate the effects of tocilizumab in adult patients admitted to hospital with COVID-19 with both hypoxia and systemic inflammation. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. Those trial participants with hypoxia (oxygen saturation <92% on air or requiring oxygen therapy) and evidence of systemic inflammation (C-reactive protein ≥75 mg/L) were eligible for random assignment in a 1:1 ratio to usual standard of care alone versus usual standard of care plus tocilizumab at a dose of 400 mg–800 mg (depending on weight) given intravenously. A second dose could be given 12–24 h later if the patient's condition had not improved. The primary outcome was 28-day mortality, assessed in the intention-to-treat population. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings: Between April 23, 2020, and Jan 24, 2021, 4116 adults of 21 550 patients enrolled into the RECOVERY trial were included in the assessment of tocilizumab, including 3385 (82%) patients receiving systemic corticosteroids. Overall, 621 (31%) of the 2022 patients allocated tocilizumab and 729 (35%) of the 2094 patients allocated to usual care died within 28 days (rate ratio 0·85; 95% CI 0·76–0·94; p=0·0028). Consistent results were seen in all prespecified subgroups of patients, including those receiving systemic corticosteroids. Patients allocated to tocilizumab were more likely to be discharged from hospital within 28 days (57% vs 50%; rate ratio 1·22; 1·12–1·33; p<0·0001). Among those not receiving invasive mechanical ventilation at baseline, patients allocated tocilizumab were less likely to reach the composite endpoint of invasive mechanical ventilation or death (35% vs 42%; risk ratio 0·84; 95% CI 0·77–0·92; p<0·0001). Interpretation: In hospitalised COVID-19 patients with hypoxia and systemic inflammation, tocilizumab improved survival and other clinical outcomes. These benefits were seen regardless of the amount of respiratory support and were additional to the benefits of systemic corticosteroids. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

Background: Many patients with COVID-19 have been treated with plasma containing anti-SARS-CoV-2 antibodies. We aimed to evaluate the safety and efficacy of convalescent plasma therapy in patients admitted to hospital with COVID-19. Methods: This randomised, controlled, open-label, platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]) is assessing several possible treatments in patients hospitalised with COVID-19 in the UK. The trial is underway at 177 NHS hospitals from across the UK. Eligible and consenting patients were randomly assigned (1:1) to receive either usual care alone (usual care group) or usual care plus high-titre convalescent plasma (convalescent plasma group). The primary outcome was 28-day mortality, analysed on an intention-to-treat basis. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936. Findings: Between May 28, 2020, and Jan 15, 2021, 11558 (71%) of 16287 patients enrolled in RECOVERY were eligible to receive convalescent plasma and were assigned to either the convalescent plasma group or the usual care group. There was no significant difference in 28-day mortality between the two groups: 1399 (24%) of 5795 patients in the convalescent plasma group and 1408 (24%) of 5763 patients in the usual care group died within 28 days (rate ratio 1·00, 95% CI 0·93–1·07; p=0·95). The 28-day mortality rate ratio was similar in all prespecified subgroups of patients, including in those patients without detectable SARS-CoV-2 antibodies at randomisation. Allocation to convalescent plasma had no significant effect on the proportion of patients discharged from hospital within 28 days (3832 [66%] patients in the convalescent plasma group vs 3822 [66%] patients in the usual care group; rate ratio 0·99, 95% CI 0·94–1·03; p=0·57). Among those not on invasive mechanical ventilation at randomisation, there was no significant difference in the proportion of patients meeting the composite endpoint of progression to invasive mechanical ventilation or death (1568 [29%] of 5493 patients in the convalescent plasma group vs 1568 [29%] of 5448 patients in the usual care group; rate ratio 0·99, 95% CI 0·93–1·05; p=0·79). Interpretation: In patients hospitalised with COVID-19, high-titre convalescent plasma did not improve survival or other prespecified clinical outcomes. Funding: UK Research and Innovation (Medical Research Council) and National Institute of Health Research

A fully validated microbiological assay to evaluate the potency of ceftriaxone sodium

Ceftriaxone (CFTX) sodium is a third-generation, broad-spectrum cephalosporin that is resistant to beta-lactamases. An alternative bioassay for the assessment of the potency of this drug in pharmaceutical formulations has not been previously reported. Thus, this paper reports the development and full validation of a 3 x 3 agar diffusion bioassay using a cylinder-plate method to quantify CFTX sodium in pharmaceutical samples. The strain Staphylococcus aureus ATCC 6538P was used as the test microorganism, and the results of the proposed bioassay displayed high linearity, precision, accuracy, specificity and robustness. All potency results were statistically analyzed using an analysis of variance (ANOVA) and were found to be linear (r=0.99999) in the range of 16-64 µg/mL, accurate (100.5%), and precise [repeatability: relative standard deviation (RSD)=1.4%; intermediate precision: between-day RSD=2.1% and between-analyst RSD=2.5%]. The specificity of the bioassay was determined by evaluating a degraded sample (50 ºC) at 0, 24 and 48 hours as compared against the results from the pharmacopeial liquid chromatography method for CFTX. The results validated the proposed microbiological assay, which allows reliable quantitation of CFTX in pharmaceutical samples. Moreover, it is a useful, simple and low-cost alternative method for monitoring the quality of this medicine