Intestinal dendritic cells in the pathogenesis of inflammatory bowel disease

The gastrointestinal tract harbors a large number and diverse array of commensal bacteria and is an important entry site for pathogens.For these reasons,the intestinal immune system is uniquely dedicated to protect against infections,while avoiding the development of destructive inflammatory responses to the microbiota.Several models have been proposed to explain how the immune system discriminates between,and appropriately responds to,commensal and pathogenic microorganisms.Dendritic cells(DCs)and regulatory T cells(Treg)are instrumental in maintaining immune homeostasis and tolerance in the gut.DCs are virtually omnipresent and are remarkably plastic,having the ability to adapt to the influences of the microenvironment.Different DC populations with partially overlapping phenotypic and functional properties have been described in different anatomical locations.DCs in the draining mesenteric lymph nodes,in the intestinal lamina propria and in Peyer's patches partake both in the control of intestinal inflammation and in the maintenance of gut tolerance.In this respect,gutresident DCs and macrophages exert tolerogenic functions as they regularly encounter and sense commensal bacteria.In contrast,migrating DC subsets that are recruited to the gut as a result of pathogenic insults initiate immune responses.Importantly,tolerogenic DCs act by promoting the differentiation and expansion of Treg cells that efficiently modulate gut inflammation,as shown both in preclinical models of colitis and in patients with inflammatory bowel disease(IBD).This article reviews the phenotypic and functional features of gut DC subsets and discusses the current evidence underpinning the DC contribution to the pathogenesis of the major clinical subtypes of human IBD.It also addresses the potential clinical benefit derived from DC targeting either in vivo or in vitro.

Electromyographic evaluation of functional electrical stimulation to injured oculomotor nerve

Functional electrical stimulation delivered early after injury to the proximal nerve stump has been proposed as a therapeutic approach for enhancing the speed and specificity of axonal regeneration following nerve injury. In this study, the injured oculomotor nerve was stimulated functionally by an implantable electrode. Electromyographic monitoring of the motor unit potential of the inferior oblique muscle was conducted for 12 weeks in two injury groups, one with and one without electric stimulation. The results revealed that, at 2, 4, 6, 8 weeks after functional electric stimulation of the injured oculomotor nerve, motor unit potentials significantly increased, such that amplitude was longer and spike duration gradually shortened. These findings indicate that the injured oculomotor nerve has the potential for regeneration and repair, but this ability is not sufficient for full functional recovery to occur. Importantly, the current results indicated that recovery and regeneration of the injured oculomotor nerve can be promoted with functional electrical stimulation.

Pioneering drugs for overactive bladder and detrusor overactivity: Ongoing research and future directions

The ongoing research on pioneering drug candidates for the overactive bladder （OAB） aimed to overcome the limitations of currently licensed pharmacotherapies, such as antimuscarinics, β3-adrenergic agents, and botulinum neurotoxin, has been reviewed performing a systematic literature review and web search. The review covers the exploratory agents alternative to available medications for OAB and that may ultimately prove to be therapeutically useful in the future mana-gement of OAB patients based on preclinical and early clinical data. It emerges that many alternative pharmacological strategies have been discovered or are under investigation in disease-oriented studies. Several potential therapeutics are known for years but still fnd obstacles to pass the clinical stages of development, while other completely novel compounds, targeting new pharmacological targets, have been recently discovered and show potential to translate into clinical therapeutic agents for idiopathic and neurogenic OAB syndrome. The global scenario of investigational drugs for OAB gives promise for the development of innovative thera-peutics that may ultimately prove effective as first, combined or second-line treatments within a realistic timescale of ten years.

Impact of living with bipolar patients: Making sense of caregivers' burden

The aim of the present review was to examine objective and subjective burdens in primary caregivers(usually family members) of patients with bipolar disorder(BD) and to list which symptoms of the patients are considered more burdensome by the caregivers. In order to provide a critical review about caregiver's burden in patients with bipolar disorder, we performed a detailed Pub Med, Bio Med Central, ISI Web of Science, Psyc INFO, Elsevier Science Direct and Cochrane Library search to identify all papers and book chapters in English published during the period between 1963 and November 2011. The highest levels of distress were caused by the patient's behavior and the patient's role dysfunction(work, education and social relationships). Furthermore, the caregiving role compromises other social roles occupied by the caregiver, becoming part of the heavy social cost of bipolar affective disorder. There is a need to better understand caregivers' views and personal perceptions of the stresses and demands arising from caring for someone with BD in order to develop practical appropriate interventions and to improve the training of caregivers.

应用背向散射和二次发射扫描电镜观察未脱钙未染色组织块关节软骨形态：一项描述性研究(英文)

背景:在与关节软骨有关的组织工程研究中,应用未脱钙和未染色的样本对于保留关节软骨的三维结构十分有利。当分析大量样本时,应用未脱钙的组织块将减少实验时间和复杂性。目的:检验在未脱钙、未染色的组织块上研究关节软骨形态的可能性,这样可以避免切割并染色薄切片。方法:取新西兰白兔和Sardinian绵羊的股骨髁,在多聚甲醛溶液中固定,乙醇中脱水,包埋于多异丁烯酸甲酯中,切成组织块,并染色。将金钯溅镀于标本上,然后用Jeol JSM 6310电子显微镜进行观察。将背向散射和二次发射扫描电镜对组织块相同部位的观察结果进行合并分析。结果与结论:在兔的关节软骨组织块上,可明显区分未钙化与钙化软骨的传代,但较难辨认位于Ⅱ区和Ⅲ区的小软骨陷窝。在绵羊的软骨组织块中,则能较为容易地区分关节软骨各区和细胞结构。应用背向散射电镜能容易分辨出钙化软骨结构和潮标。合并二次发射扫描电镜和背向散射电镜,可在样本上观察到大的腔道。这些腔道穿过软骨下骨和钙化软骨,终止于未钙化的软骨。结果表明,应用背向散射和二次发射扫描电镜能在未脱钙和未染色的包埋组织块上观察到关节软骨的三维结构。

Mirabegron, a novel, non-antimuscarinic drug for the overactive bladder: An up-to-dated review

Mirabegron opened a new era in the treatment of overactive bladder(OAB). For the fi rst time physicians dealing with OAB have an effective alternative to the pharmacological mainstay of the therapy for this disorder, the antimuscarinic drugs. This fi rst-in-class, potent β3-adrenoceptors agonist has recently received approval by regulatory authorities in Japan, United States and Europe, based on the favourable efficacy-tolerability profile demonstrated in multiple randomized, multinational, controlled trials, both short and long-term. There is substantial consistency through the studies in reporting the cardiovascular safety of treatment with mirabegron. The main advantage of mirabegron is the placebo-like incidence of classic adverse effects caused by antimuscarinics, dry mouth and constipation, that is expected to improve long-term adherence of patients to treatment. Mirabegron can be used in patients with contraindications to antimuscarinics and in those who discontinued previous antimuscarinic therapy. Herein, we reviewed the published literature on mirabegron, focusing on the rationale of β3-agonism for OAB treatment and on the preclinical and clinical evidence of effi cacy and safety available on this new pharmacological principle.

恶性骨肿瘤接受照射后的异体骨移植的临床研究

为减少并发症,提高术后功能,有很多方法应用于异体骨.为将感染降低到最低限度,许多组织库应用了放射线照射的方法.但随着本方法的应用,随之而来的问题也显现出来,包括:组织的机械强度和并发症的发生.研究的目的是:(1)回顾并发症在应用照射方法处理和非照射方法处理过的异体骨之间的区别;(2)研究移植骨与宿主骨之间的连接情况及术后功能.