Liver X receptor modulators: a review of recently patented compounds (2009 – 2012)

Introduction: The development of small molecule agonists of the liver X receptors (LXRs) has been an area of interest for over a decade, given the critical role of those receptors in cholesterol metabolism, glucose homeostasis, inflammation, innate immunity and lipogenesis. Many potential indications have been characterized over time including atherosclerosis, diabetes, inflammation, Alzheimer's disease and cancer. However, concerns about the lipogenic effects of full LXRα/β agonists have required extensive efforts aimed at identifying LXRβ agonist with limited activity on the LXRα receptor to increase the safety margins.

Areas covered: This review includes a summary of the LXR agonists that have reached the clinic and summarizes the patent applications for LXR modulators from September 2009 to December 2012 with emphasis on chemical matters, biological data associated with selected analogs and therapeutic indications.

Expert opinion: As LXR agonists have the potential to be useful for many indications, the scientific community, despite setbacks due to on-target side effects, has maintained interest and devised strategies to overcome safety hurdles. While a clinical proof of concept still remains elusive, the recent advancement of compounds into the clinic highlights that acceptable safety margins in preclinical species have been achieved.     

Exercise in neuromuscular disease

In this review, we present an overview of the role of exercise in neuromuscular disease (NMD). We demonstrate that despite the different pathologies in NMDs, exercise is beneficial, whether aerobic/endurance or strength/resistive training, and we explore whether this benefit has a similar mechanism to that of healthy subjects. We discuss further areas for study, incorporating imaginative and novel approaches to training and its assessment in NMD. We conclude by suggesting ways to improve future trials by avoiding previous methodological flaws and drawbacks in this field. Muscle Nerve, 2013     

Identification of the critical attribute(s) of EBV gp350 antigen required for elicitation of a neutralizing antibody response in vivo

Vaccine prophylaxis with EBV glycoprotein 350 (gp350) subunit plus adjuvant has been demonstrated clinically to protect individuals against infectious mononucleosis (IM), but the specifications of the antigen required to elicit this protection has remained largely theoretical. Previous studies have shown that antibodies to gp350 comprise the principle component of EBV-neutralizing sera. Further, a murine monoclonal antibody against gp350 (clone 72A1) is able to prevent infection by the virus both in vitro and in vivo. In the present study, we identify the 72A1 epitope on recombinant gp350 antigen as the site required for binding to CD21 on human B cells. We also identify the need for conformational-dependence of the antigen to generate EBV-neutralizing antibodies in vivo. Further, we have characterized the glycosylation status and antigenicity profiles of both native and denatured CHO-produced soluble gp350 as well as non-glycosylated protein produced in Escherichia coli. Collectively our in vitro and in vivo data demonstrate the requirement for a conformationally accessible 72A1 epitope on gp350 to elicit EBV-neutralizing responses, and establish this as a critical attribute of this vaccine antigen. These data provide direction for commercial vaccine development, as the absence of this epitope on either E. coli-expressed or denatured gp350, may limit production and purification options for the antigen.     

An overview of travel-associated central nervous system infectious diseases: risk assessment,general considerations and future directions

Nervous system infections are among the most important diseases in travellers. Healthy travellers might be exposed to infectious agents of central nervous system, which may require in-patient care. Progressive course is not uncommon in this family of disorders and requires swift diagnosis. An overview of the available evidence in the field is, therefore, urgent to pave the way to increase the awareness of travel-medicine practitioners and highlights dark areas for future research. In November 2013, data were collected from PubMed, Scopus, and Web of Knowledge (1980 to 2013) including books, reviews, and peer-reviewed literature. Works pertained to pre-travel care, interventions, vaccinations related neurological infections were retrieved. Here we provide information on pre-travel care, vaccination, chronic nervous system disorders, and post-travel complications. Recommendations with regard to knowledge gaps, and state-of-the-art research are made. Given an increasing number of international travellers, novel dynamic ways are available for physicians to monitor spread of central nervous system infections. Newer research has made great progresses in developing newer medications, detecting the spread of infections and the public awareness. Despite an ongoing scientific discussion in the field of travel medicine, further research is required for vaccine development, state-of-the-art laboratory tests, and genetic engineering of vectors.     

The role of immune mechanisms in alcoholic and nonalcoholic steatohepatitis: a 2015 update

So far, innate immune mechanisms have been recognized as the main responsible for the evolution of both alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH). However, increasing evidence points toward the possible role of adaptive immune responses, as an additional factor in promoting hepatic inflammation in steatohepatitis. In this article, we discuss recent data involving circulating antibodies and lymphocyte-mediated responses in sustaining the progression of ASH and NASH to fibrosis, as well as the possible mechanisms implicated in favoring the onset of adaptive immunity in the setting of steatohepatitis.     

清代名医陈念祖“重视气血”治疗月经病用药规律及特点研究

[目的] 探讨研究陈念祖治疗月经病的用药规律及特点。[方法] 收集陈氏《女科要旨》《南雅堂医案》《医学从众录》中治疗月经病的处方81首，构建处方数据库。运用Excel 2010与SPSS Statistics 26.0软件对高频药物进行频数和聚类分析，并结合理论分析，提炼出陈氏治疗月经病的用药规律及特点。[结果] 收集的81首处方中，涉及药物共121味。≥6次的高频药物共32味，使用频数排前3位的是当归、白芍、茯苓。高频药物种类以补血药、补气药为主；四气以温性为首；五味以甘、苦、辛为主；归经以脾经为首，肝经次之，心经再次。聚类分析得出5组核心药组，涉及归脾汤、六君子汤、越鞠丸等方剂。用药特点:使气血化生而调和脾胃，畅气血运行而疏理心肝，守气血循经而调理冲任。[结论] 陈氏治疗月经病以气血为核心，调和脾胃气血、调畅心肝气机、调理冲任气血，多运用补血药、补气药、理气药。     

注射用依那西普联合骨痹汤治疗幼年脊柱关节病的临床观察

目的观察注射用依那西普联合骨痹汤治疗幼年脊柱关节病(JSp A)的临床疗效。方法将77例JSp A患者随机分为2组,治疗组40例应用注射用依那西普联合骨痹汤治疗,对照组37例单纯应用柳氮磺吡啶肠溶片治疗。2组均治疗12周,观察2组治疗前、治疗2周后及治疗12周后红细胞沉降率(ESR)、C反应蛋白(CRP)、血小板计数(PLT)及视觉模拟评分(VAS)变化,比较2组疗效。结果 2组治疗过程中ESR、CRP、PLT及VAS评分均逐步降低,治疗2周后比较差异无统计学意义(P0.05),但治疗12周后,2组均较本组治疗前降低(P0.05),且治疗组各项观察指标较对照组降低更明显(P0.05)。治疗组缓解率55.0%、总有效率97.5%,对照组缓解率27.0%、总有效率81.1%,2组缓解率、总有效率比较差异均有统计学意义(P0.05),治疗组疗效优于对照组。结论注射用依那西普联合骨痹汤治疗JSp A,疗效显著,安全性好。