Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents - Current Issue

Type 2 diabetes mellitus is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. Type 2 diabetic individuals are also characterized by reduced β-cell mass likely due to increased cellular apoptosis. Traditional strategies to treat diabetes have been developed with the main purpose of reducing hyperglycemia, and include insulin sensitizers, α-glucosidase inhibitors, and β-cell se Read More

Insulin analogs have largely replaced conventional insulin preparations and extensive clinical studies have confirmed the beneficial action profile of these artificial insulin molecules. Tight blood sugar control is a major goal of intensified insulin therapy and this can be obtained much more efficiently when using insulin analogs. Currently, three rapidacting insulin analogs are in clinical use based on either a change of the ami Read More

The incretin hormone glucagon-like peptide 1 (GLP-1) is produced by post-translational processing of the proglucagon gene in intestinal L-cells. Owing to its glucose-dependent insulinotropic effect, a potential in the treatment of type 2 diabetes has been suggested already 20 years ago. However, rapid enzymatic inactivation of GLP-1 in vivo and the need for parenteral administration have obviated its earlier therapeutic a Read More

During the past 10 years a multitude of clinical and observational studies have confirmed the efficacy of the antidiabetic drug, glimepiride, in lowering fasting and postprandial blood glucose in lean and obese type 2 diabetic patients even after a single administration per day, only, as well as its high safety and patient's compliance. Additional findings obtained in these studies suggested a number of clinical advantages com Read More

The prevalence of Type 2 diabetes (Non-Insulin-Dependent Diabetes Mellitus) increases at an alarming rate in the world's population, reaching an epidemic proportion. Moreover, impaired glucose tolerance and insulin resistance are being diagnosed nowadays in a growing subpopulation of obese children and adolescents, mostly in Western societies. This adds to the concern that not only the number of NIDDM patients will in Read More

Protein phosphorylation is the most common mechanism of protein function regulation. Protein kinases are key signaling enzymes that participate in the regulation of multiple cellular responses. Insulin regulates whole-body glucose homeostasis by modulating the activities of protein kinases in its target tissues: muscle, liver and fat. Defects in insulin's ability to modulate protein kinase activity lead to 'insulin resistance' or impaire Read More

Graft-versus-host disease (GVHD) is a devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT). Although significant progress in the treatment of GVHD has been made, several obstacles remain in overcoming this complication. Animal models have been critical to our understanding of the pathophysiology of GVHD, and multiple clinical approaches have been taken, based on experimental animal m Read More

The pathophysiology of acute graft versus host disease (GVHD) can be considered as a three-step process where the innate and adaptive immune systems interact (Fig. 1). The three steps are: 1) tissue damage to the recipient by the radiation/chemotherapy pre-transplant conditioning regimen, 2) donor T cell activation and clonal expansion, and 3) cellular and inflammatory factors. This schema underscores the importance of m Read More

A new bone marrow transplantation (BMT) method, "intra-bone marrow (IBM)-BMT" has recently been developed. This method was found to prevent not only graft-versus-host (GvH) reaction but also host-versus-graft (HvG) reaction, since IBM-BMT can efficiently recruit donor-derived stromal cells (including mesenchymal stem cells: MSCs), which produce immunosuppressive cytokines. This paper shows that IBM-BMT p Read More

An ability to modulate three distinct yet inter-related immune processes is required for successful allogeneic hematopoietic stem cell transplantation (HSCT): reduction in graft-versus-host reactivity that initiates graft-versus-hostdisease (GVHD), inhibition of host-versus-graft reactivity that causes allograft rejection, and enhancement of graftversus- leukemia (GVL) and graft-versus-tumor (GVT) effects that pri Read More

Graft-versus-host disease (GVHD) has been the primary limitation to the wide application of allogeneic hematopoietic stem cell transplantation (HSCT). GVHD is initiated by activation of donor T cells recognizing host tissue antigens, with subsequent dysregulated inflammatory cytokine production by monocytes and macrophages. These inflammatory cytokines are crucial for the pathogenesis of acute GVHD and these in Read More

Since its description roughly 30 years ago, the parent-into-F1 model of graft-vs.-host disease has provided insights into the mechanisms of in vivo T cell activation and the pathogenesis of autoimmune conditions. A new and emerging role for the P→F1 model is one of identifying agents with immunomodulatory activity and defining in vivo mechanisms that promote cell mediated or antibody mediated immune responses. Bec Read More

Graft vs. host disease (GVHD) represents the major obstacle to more widespread clinical application of allogeneic hematopoietic cell transplants and experimentally provides perhaps the most important model for immunologists to study the significance and regulation of allogeneic T cell responses in situ. The sensitivity of induction to donor T cell numbers, the target tissues 'attacked' in the host and the clinical sequelae a Read More