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Rheumatoid arthritis (RA) is a systemic autoimmune disease that causes chronic inflammation of the joints and several extra-articular manifestations that account for increased morbimortality of these patients. The involvement of B cells in RA pathophysiology was recognized early, with the discovery of rheumatoid factor antibody. Recently, a number of autoantibodies against citrullinated proteins have been described, of which anti-cyclic citrullinated peptide (anti-CCP) is the most specific for RA. A cohort of 937 patients with RA was studied to determine the clinical correlates of anti-CCP antibodies. The presence of anti-CCP antibodies correlated with worse joint involvement and several extra-articular manifestations, i.e., higher incidence of ischemic heart disease independent of classic cardiovascular factors and higher mortality rate. A multivariate logistic regression model showed that only anti-CCP antibodies were independently associated with the development of ischemic heart disease in patients with RA. The clinical value of anti-citrullinated protein antibodies and the relevance of anti-CCP antibodies in daily clinical practice are reviewed.

Animal experiments and clinical studies have indicated that propofol pretreatment significantly improves post-resuscitation recovery of neuronal functions. However, current theories on how propofol enhances the inhibitory effects of gamma-aminobutyric acid (GABA) cannot fully explain its protective action on the brain. Recent studies have suggested that during the process of resuscitation, the effect of GABA is converted from inhibitory to excitatory, via a mechanism that is closely associated with activation of microglia and downregulation of the K(+)-Cl(-) cotransporter 2 (KCC2). We propose a hypothesis that propofol protects the brain through inhibiting the conversion of GABAergic inhibition into excitation during resuscitation. Activation of microglia, downregulation of KCC2, and correlations between these effects and the protective actions of propofol, may reveal the molecular mechanisms of propofol-mediated brain protection. Further investigations into the protective mechanisms of general anesthetics on the brain represented by propofol will help to guide rational clinical drug use, and will contribute to the discovery and development of novel brain-protective drugs to prevent perioperative cardiopulmonary resuscitation-associated brain injury.

Type 2 diabetes (T2D) is associated with a greatly increased risk of cardiovascular disease. An increasing need for glucose-lowering treatments is emphasized by the almost inevitable failure of monotherapy and occurrence of weight gain. Recently, novel classes of drugs derived from the incretin system have been introduced into the management of T2D. Recent advances in the field of incretin-based therapies in the management of T2D were discussed at the 45th Annual Meeting of the European Association for the Study of Diabetes, held from September 29 until October 2, 2009, in Vienna, Austria.

Histone deacetylases (HDACs) are a family of proteins that play an important role in regulating transcription as well as the function of a variety of cellular proteins. While these proteins are expressed abundantly in the brain, little is known about their roles in brain function. A growing body of evidence suggests that HDACs regulate neuronal survival. Results from studies conducted in vertebrate and mammalian experimental systems indicate that while some of these proteins are involved in promoting neuronal death, a majority of the HDACs studied thus far protect against neurodegeneration. Here we review the research performed on the role played by individual members of the HDAC family in the regulation of neuronal death. Chemical inhibitors of HDACs have been used in a variety of models of neurodegenerative disorders. We summarize the results from these studies, which indicate that HDAC inhibitors show great promise as therapeutic agents for human neurodegenerative disorders.

In the United States, preeclampsia (PreE) affects 5-7% of all pregnancies, yet represents 15% of all maternal-fetal morbidity and mortality. PreE causes fetal growth restriction, oligohydramnios, fetal death, and maternal seizures, stroke, cerebrovascular hemorrhage and death. It has immediate and potentially long-term effects on both the fetus and mother. To date, the molecular pathogenesis of PreE is largely unknown. Multiple pathways, including dysfunctional angiogenesis, inappropriate placentation, oxidative stress and an altered immunological milieu have been proposed as key players in the development of PreE. In addition, genetic factors in all of these pathways are essential components in the etiology of this disease. This review introduces the clinical presentation of PreE and its particular disease phenotype that has prompted some of the molecular investigations of its etiology. Evidence of the many molecular pathways involved in the pathogenesis of PreE, as well as the therapeutic investigations targeting these pathways, is presented.

Dendritic cells (DCs) have a central role in the immune system, as they control the adaptive immune response and mediate both protective immunity and the maintenance of immune tolerance to self antigens. In this review, we will summarize the recent advances regarding the subsets of DCs and how they regulate the differentiation of naive CD4(+) T cells towards different populations of T helper cells. We will particularly describe the role of DCs in the development and regulation of allergic diseases and asthma, and discuss the capacity of DCs to induce proallergenic Th2 cells versus regulatory T cells. Undoubtedly, tolerogenic DCs play a crucial role in the induction of regulatory cells. Understanding the biology of these cells will help us design novel strategies to cure or prevent allergic diseases and asthma.

Bispecific antibodies are capable of interacting with two different antigens and when selected properly, can redirect cytotoxic effector cells to tumor cells for effective killing. These antibodies are therefore of great interest in the research and development of cancer treatment. Over the last two decades, many different bispecific antibody-derived molecular formats have been described, among which diabodies represent an important class of engineered molecules that possess tumor-targeting function. Since diabodies were first introduced in the early 1990s, extensive efforts have been made to optimize their physicochemical and key functional properties, as well as to provide in vivo proof of concept of their antitumor efficacy in animal models. With the clinical validation of the T-cell-retargeting mechanism for cancer therapy currently in place, there is renewed interest in this bispecific class of biologic molecules, with additional novel formats being described in recent years. Even with the remaining challenges of the manufacturing yields and drug-like properties, diabodies and their derivatives remain viable therapeutic modalities that warrant further consideration and development.