An oral vaccine for type 1 diabetes based on live attenuated Salmonella

Type 1 diabetes (T1D) is a metabolic disease that is initiated by the autoimmune destruction of pancreatic insulin-producing beta cells that is accompanied by the development of antigen-specific antibodies and cytotoxic T lymphocytes (CTLs). Several studies have shown that vaccination with diabetic autoantigens provides some protection against this process. In this report we describe a new oral vaccine that utilizes live attenuated Salmonella for simultaneous delivery of autoantigens in conjunction with immunomodulatory cytokine genes to immune cells in the gut mucosa. Recent data showed that live attenuated Salmonella is a safe, simple and effective vector for expression of antigens and cytokines by antigen-presenting cells (APCs) of gut-associated lymphatic tissue (GALT). This novel strategy was tested by fusion of the diabetic autoantigen preproinsulin with Salmonella secretory effector protein (SseF) of pathogenicity island-2 (SPI2). In this way the autoantigen is only expressed inside the host immune cells and translocated to the host cell cytosol. In addition Salmonella was used to deliver the gene for the immunomodulatory cytokine transforming growth factor beta (TGFβ) for host cell expression. Oral co-vaccination of 8 week-old non-obese diabetic (NOD) mice with three weekly doses of both the autoantigen and cytokine significantly reduced the development of diabetes, improved the response to glucose challenge, preserved beta cell mass, and reduced the severity of insulitis compared with controls and autoantigen alone. Combination therapy also resulted in increased circulating levels of IL10 four weeks post-vaccination and IL2 for 12 weeks post-vaccination, but without effect on proinflammatory cytokines IL6, IL12(p70), IL17 and IFNγ. However, in non-responders there was a significant rise in IL12 compared with responders. Future studies will examine the mechanism of this vaccination strategy in more detail. In conclusion, Salmonella-based oral vaccines expressing autoantigens combined with imunomodulatory cytokines appears to be a promising therapy for prevention of T1D.     

Efficacy of zinc oxide nanoparticles in attenuating pancreatic damage in a rat model of streptozotocin-induced diabetes

Zinc oxide nanoparticles (ZnO NPs) therapy is a promising strategy for treatment of several diseases. We aimed to investigate the therapeutic potential of ZnO NPs in ameliorating the histopathological and functional alterations in the pancreas of a rat model of streptozotocin-induced diabetes. Rats were randomized into control, diabetic and ZnO NPs-treated diabetic groups. Biochemical assays of blood glucose and serum insulin were performed. Pancreas specimens were processed for light and electron microscope examinations. ZnO NPs effectively reversed diabetes-induced pancreatic injury, as evidenced by the structural and ultrastructural improvement and confirmed by biochemical normalization of blood glucose and serum insulin.     

Overview of injection practices in two governorates in Egypt

OBJECTIVE: To describe the extent and characteristics of injection use and injection providers in Egypt, given that unsafe injections are associated with blood-borne pathogen transmission. METHODS: Household surveys of a population-based sample of residents in the Nile Delta and in Upper Egypt; focus group discussions and in-depth interviews with community target groups, formal and informal medical providers. RESULTS: Of 4197 persons interviewed, 26.2% reported receiving an injection in the past 3 months. Of these, 77% reported it was for therapeutic indications. The age-sex specific prevalence of injections was highest among children 0-2 years of age and among older adults. Women were more likely to report having an injection than men, particularly at the age above 20 years. Overall, respondents reported receiving on average 4.2 injections per year, indicating that up to 281 million injections are provided per year in Egypt. Injection administrators were public and private sector physicians, pharmacists, barbers, doctor assistants, housekeepers, relatives and friends. Injection prescribers were mostly private and public sector physicians. Of the 1101 respondents who received an injection in the past 3 months, 92 (8.4%) reported that the provider did not use a syringe taken from a closed sealed packet. CONCLUSION: The frequency of therapeutic injection use is high in Egypt and may contribute to blood-borne pathogen transmission. The Ministry of Health and Population (MOHP) is developing interventions targeted towards promotion of injection safety and reduction of injection overuse on community basis as part of a comprehensive strategy to prevent blood-borne pathogen transmission in Egypt.     

Inhibition of p38 mitogen-activated protein kinase protects human islets from cryoinjury and improves the yield, viability, and quality of frozen-thawed islets

The development of an optimal islet cryopreservation method will permit transplantation of islets from multiple donors in a single procedure and contribute to alleviation of the islet shortage. In this study, we have improved human islet cryopreservation methods under serum-free conditions using an intracellular-based islet cryopreservation solution (ICS), especially supplemented with a p38 pathway inhibitor (p38IH) to suppress p38 mitogen-activated protein kinase (MAPK) activation. Three different solutions were compared for freezing and thawing of human islets (1) conventional RPMI1640 medium, (2) ICS, and (3) ICS supplemented with a p38IH, SD-282 (ICS-p38IH). Islet cryopreservation with ICS-p38IH significantly improved islet recovery, viability, and quality after thawing of cryopreserved islets. This improvement may allow the use of cryopreserved islets in clinical islet transplantation.     

Evaluation of Chronic Urticaria in Patients with Hashimoto Thyroiditis

The coincidence of Hashimoto thyroiditis (HT) and chronic idiopathic urticaria (CIU) is a commonly observed phenomenon in western New York. Previous literature suggested that there may be a direct relationship between them. We undertook these studies to determine whether humoral or cell-mediated mechanisms might link HT and CIU.Skin biopsies from patients with CIU, with or without HT, were indistinguishable by light microscopy. No immune complex deposition was observed, although only the skin from patients with CIU and HT contained perivascular fibrin deposits. Similarly, immunohistochemical studies evaluating cellular expression of CD3, CD4, CD8, CD20, and CD68 failed to differentiate between CIU with or without HT. Analysis of V restriction in thyroid tissue of patients with HT and the skin of patients with CIU and HT by in situ polymerase chain reaction failed to reveal any oligoclonal T-lymphocyte subpopulations. In contrast, only patients with CIU and HT had anti-FcRI antibodies in their sera that could induce degranulation of normal basophils. Some sera from patients with CIU and HT caused degranulation of normal basophils in the absence of anti-FceRI. The factor causing basophil degranulation in these sera was not determined. Patients with CIU and HT failed to improve clinically with thyroid replacement therapy. All CIU patients were equally well managed with symptomatic therapies.In conclusion, HT likely represents a marker of other autoimmunity, rather than being a direct causative agent in CIU. Management of CIU, with or without HT and with or without anti-FceRI antibodies, should be the same. Future studies will have to examine whether cell-mediated responses participate in CIU, especially in association with HT.     

Posttransplant oxygen inhalation improves the outcome of subcutaneous islet transplantation: A promising clinical alternative to the conventional intrahepatic site

Subcutaneous tissue is a promising site for islet transplantation, due to its large area and accessibility, which allows minimally invasive procedures for transplantation, graft monitoring, and removal of malignancies as needed. However, relative to the conventional intrahepatic transplantation site, the subcutaneous site requires a large number of islets to achieve engraftment success and diabetes reversal, due to hypoxia and low vascularity. We report that the efficiency of subcutaneous islet transplantation in a Lewis rat model is significantly improved by treating recipients with inhaled 50% oxygen, in conjunction with prevascularization of the graft bed by agarose–basic fibroblast growth factor. Administration of 50% oxygen increased oxygen tension in the subcutaneous site to 140 mm Hg, compared to 45 mm Hg under ambient air. In vitro, islets cultured under 140 mm Hg oxygen showed reduced central necrosis and increased insulin release, compared to those maintained in 45 mm Hg oxygen. Six hundred syngeneic islets subcutaneously transplanted into the prevascularized graft bed reversed diabetes when combined with postoperative 50% oxygen inhalation for 3 days, a number comparable to that required for intrahepatic transplantation; in the absence of oxygen treatment, diabetes was not reversed. Thus, we show oxygen inhalation to be a simple and promising approach to successfully establishing subcutaneous islet transplantation.     

Rotational thormboelastolmetry guided transfusion practice in living donor liver transplantation,A retrospective comparative study

Introduction

Living donor liver transplantation (LDLT) is a complex surgery with high risk for massive bleeding and blood component transfusion. This retrospective study investigated the effect of adopting ROTEM based transfusion algorithm on blood products transfusion practice among LDLT recipients and the effect of this change on patient outcome.