Subcutaneous Pancreatic Transplantation Shows Success In The Treatment Of Experimentally Induced Diabetes Mellitus In Golden Hamsters

Background: to evaluate subcutaneous pancreatic transplantation in an experimentally induced diabetes mellitus in golden hamsters. Methods - many indexes (histological /using two stains, histochemical /using three enzymes, morphometrical and biochemical /blood glucose level) were employed in this assessment. Alloxan was used as ß-cytotoxic therapy (to induce diabetes mellitus), and cyclophosphamide was employed as immunosuppressive agent. Results - high rate of success of transplantation (clearly evident by microscopical features of viable endocrine and exocrine tissue of transplanted pancreas and great tissue vascularization, normal enzymatic activities and significant lowering of blood glucose level) were elicited. Conclusion – subcutaneous pancreatic transplantation should be thank about in treatment of diabetes mellitus

Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach

Background: Cancer-associated fibroblasts (CAFs) of ovarian cancer (OvC) are the most prevalent element of the tumor microenvironment (TM). By promoting angiogenesis, immunological suppression, and invasion, CAFs speed up the growth of tumors by changing the extracellular matrix’s structure and composition and/or initiating the epithelial cells (EPT). IL-33/ST2 signaling has drawn a lot of attention since it acts as a pro-tumor alarmin and encourages spread by altering TM.Methods: Differentially expressed genes (DEGs) of the OvC tumor microenvironment were found in the GEO database, qRT-PCR, western blotting, and immunohistochemistry, and their presence and changes in healthy and tumor tissue content were examined. Primary cultures of healthy fibroblasts and CAFs obtained from healthy and tumor tissues retrieved from OvC samples were used for in vitro and in vivo investigations. Cultured primary human CAFs were utilized to investigate the regulation and the IL-33/ST2 axis role in the inflammation reactions.Results: Although ST2 and IL-33 expression was detected in both epithelial (EPT) and fibroblast cells of ovarian cancer, they are more abundant in CAFs. Lipopolysaccharides, serum amyloid A1, and IL-1β, the inflammatory mediators, could all induce IL-33 expression through NF-κB activation in human CAFs. In turn, via the ST2 receptor, IL-33 affected the production of IL-6, IL-1β, and PTGS2 in human CAFs via the MAPKs-NF-κB pathway.Conclusion: Our findings suggest that IL-33/ST2 is affected by the interaction of CAFs and epithelial cells inside the tumor microenvironment. Activation of this axis leads to increased expression of inflammatory factors in tumor CAFs and EPT cells. Therefore, targeting the IL-33/ST2 axis could have potential value in the prevention of OvC progression

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Occupational health risk assessment and control of fugitive emissions in chemical processes

Fugitive emissions are unavoidable and unanticipated releases can occur throughout a process plant wherever there are discontinuities or seals between the process fluids and the external environment. Despite being small in comparison to stack emissions, fugitive emissions can pose a significant hazard as it involves thousands of sources in a chemical plant (mostly from piping equipment and fittings) and the emissions occur continuously. Efforts to address the problem of fugitive emissions have mostly been driven by environmental concerns since emissions such as volatile organic compounds are an important source of greenhouse gases (GHGs). Besides the environmental impact, fugitive emissions are also considered as the main source of background exposure of workers to harmful chemical substances in chemical plants. Continuous, daily exposure to such emissions may pose a serious threat to the health of the workers. Therefore, this study focuses on dealing with fugitive emissions from the occupational health risk perspective. The main aim of this study is to develop a hybrid framework for assessing fugitive emissions health risk by integrating the concepts of Layers of Protection, Source-Path-Receptor and Hierarchy of Control. To achieve this purpose, this project proposes a new approach of adopting the Layer of Protection (LoP) technique together with the concept of Source-Pathway-Receptor (SPR) for assessing and controlling the occupational health risk due to emissions in chemical plants. This paper presents the concept of the proposed approach that has been developed during the initial stage of this study

Hybrid tool for occupational health risk assessment and fugitive emissions control in chemical processes based on the source, path and receptor concept

Fugitive emissions are unavoidable releases that occur continuously throughout a process plant or wherever there are connections or seals between the process fluids and the external environment. The daily exposure of workers to such emissions, typically spread across an entire chemical plant, poses a serious threat to their health and safety. Previous works have focused on assessing the occupational health risks in chemical plants through indexes such as the inherent occupational health index and the integrated inherent safety index. The indexes serve as good proxy indicators for potential sources of occupational hazards (chemicals, process conditions) and process equipment. However, by considering the Source-Path-Receptor (SPR) model, the eventual health risk is also dependent on the path and receptor, where a potential leakage and exposure can occur, respectively. Typically, chemical plants are fitted with controls and mitigation measures known as protection layers (PL) to control hazards. Hence, the occupational health risks in chemical plants due to fugitive emissions require a more holistic methodology for assessment and evaluation. Therefore, a hybrid framework for assessing the occupational health risks from fugitive emissions was developed by adopting and integrating the concepts of source-path-receptor, layers of protection and hierarchy of control. The generic protection layers identified were classified according to the traditional hierarchy of controls. At the source, the protection layers identified were hazard elimination/substitution, inherently safer design, and engineering controls. Next, the maintenance and equipment reliability were identified as PL along the exposure path. Finally, at the receptor, worker-exposure was linked to management systems, procedural safety behaviour and culture. Therefore, the proposed methodology can be used for benchmarking and performance tracking of occupational health risk in a chemical plant over time, as the methodology includes the time-varying parameters of plant maintenance, management system compliance, safety behaviour and culture