长期使用抗癫药物对发育期大鼠脑的影响

目的探讨长期使用抗癫药（AEDs）对发育期大鼠脑的影响,在细胞及分子水平上观察AEDs影响认知功能的机制。方法将生后7 d的Wistar大鼠234只任意分为13组：4种AEDs［苯巴比妥（PB）,丙戊酸（VPA）,拉莫三嗪（LTG）,托吡酯（TPM）］分别分为高、中、低剂量组和对照组,每组18只大鼠。PB 80、 40、20 mg·kg-1和VPA 200、100、50 mg·kg-1分别溶于超纯水腹腔注射每日1次共21 d,LTG 80、40、20 mg·kg-1和TPM 80、40、20 mg·kg-1分别溶于1％纤维素钠灌胃每日1次共21 d,对照组予相同体积1％纤维素钠灌胃每日1次共21 d。从第22天始每组6只大鼠断头取脑,用Annexin-V FITC/PI双标检测细胞凋亡,用实时定量PCR检测脑源性神经营养因子（BDNF）和神经营养物质-3（NT-3）mRNA的表达;余12只大鼠过量麻醉后灌注固定,分别用于BrdU染色和Timm's染色。 结果①4种AEDs均会造成幼鼠脑重减轻,其中VPA高、中、低剂量组大鼠脑重降低最明显,VPA高剂量组导致脑重降低15％。②4种AEDs均引起神经细胞凋亡的增加,其阈值分别为：PB 20 mg·kg-1, VPA 50mg·kg-1, LTG 80 mg·kg-1,TPM 40 mg·kg-1。③实时定量PCR结果显示,4种AEDs可导致海马区BDNF和NT-3 mRNA表达的减少,其阈值分别为PB 40 mg·kg-1、VPA 100 mg·kg-1、LTG 80 mg·kg-1、TPM 40 mg·kg-1。VPA和LTG低剂量组可引起海马齿状回和门区BrdU标记的细胞数增加。Timm's染色结果显示4种AEDs CA3区和颗粒细胞上层Timm评分与对照组比较差异均无统计学意义(P>0.05)。 结论长期使用AEDs会对发育期大脑造成损害,不同AEDs可引起大脑细胞凋亡增加和海马区神经营养物质表达减少,其阈值有所不同,这可能是造成认知损害的机制之一。VPA和LTG会造成神经发生增加,但不伴有明显的苔藓纤维发芽。     

An Overview on Biologic Medications and Their Possible Role in Apical Periodontitis

Introduction

Apical periodontitis (AP) is the expression of a deficient balance between infection and the host immune response.

Methods

If reducing the bacterial load from the root canal and preventing its reinfection may lead to clinical success, then the integrity of the nonspecific immune system has a relevant influence on the outcome of endodontic treatment.

Results

Compromised immune systems and/or genetic alterations of the host's response may as well play an important role on the development, progression, and healing of AP. Thus, immunomodulatory drugs might have the potential to influence both the severity of AP and the outcome of endodontic treatment. Biologic medications are a new class of drugs of monoclonal antibodies or fusion proteins that include fragments of a peculiar cytokine receptor. Specific inflammatory molecules or cells, such as tumor necrosis factor, interleukins, and T or B cells, are the selective targets of these drugs. They modulate the altered immune response and perform an important role in the short-term treatment of chronic inflammatory diseases such as rheumatoid arthritis, refractory Crohn disease, or ulcerative colitis. Despite the clinical positive outcomes and their widespread use, the consequences of administering biologic medications on the development of the dental diseases have not been adequately investigated.

Conclusions

The aim of this review was to give an overview of biologic medications, their composition, their mechanisms of action, and their possible implications on endodontic and other dental diseases.     

Perianesthesia Implications and Considerations for Drug-Induced QT Interval Prolongation

Prolongation of the QT interval can predispose patients to fatal arrhythmias such as torsade de pointes. While arrhythmias can occur spontaneously in patients with a genetic predisposition, drugs such as ondansetron and droperidol, which are frequently used in the perioperative period, have been implicated in the prolongation of the QT interval. As the list of medications that cause QT prolongation grows, anesthesia providers and perioperative nurses must be informed regarding the importance of the QT interval. This article reviews the physiology and measurement of the QT interval, the risk factors of QT prolongation, the mechanism of drug-induced QT prolongation, and perioperative considerations for patient care.     

不同疗程左氧氟沙星联合常规四联抗结核药物治疗结核性胸膜炎患者的临床效果

目的探讨不同疗程左氧氟沙星联合常规抗四联结核药物治疗结核性胸膜炎患者的临床效果。方法将96例结核性胸膜炎患者随机分为观察组(49例)和对照组(47例),两组患者均进行左氧氟沙星联合常规四联抗结核药物治疗,对照组疗程为1个月,观察组疗程为1周。比较两组患者的临床疗效、胸腔积液消失时间以及不良反应发生情况。结果两组患者的治疗总有效率、胸腔积液消失时间比较,差异无统计学意义(P>0.05)。观察组不良反应总发生率低于对照组(P<0.05)。结论左氧氟沙星联合常规四联抗结核药物短疗程治疗,可在保证结核性胸膜炎临床疗效的同时,有效降低不良反应的发生率,临床安全性高。     

Ruxolitinib add-on in corticosteroid-refractory graft-vs-host disease after allogeneic stem cell transplantation: Results from a retrospective study on 38 Chinese patients

BACKGROUND Graft-vs-host disease (GVHD) is a major cause of mortality after allogeneic hematopoietic stem cell transplantation.Some patients have steroid-refractory(SR) GVHD.AIM To evaluate the effect and safety of ruxolitinib add-on in the treatment of patients with SR acute (a) and chronic (c) GVHD.METHODS We retrospectively analyzed 38 patients administered ruxolitinib add-on to standard immunosuppressive therapy for SR-aGVHD or SR-cGVHD following allogeneic hematopoietic stem cell transplantation.Ruxolitinib was administered5-10 mg/d depending on disease severity,patient status,and the use of antifungal drugs.Overall response rate,time to best response,malignancy relapse rate,infection rate,and treatment-related adverse events were assessed.RESULTS The analysis included 10 patients with SR-aGVHD (gradeⅢ/Ⅳ,n=9) and 28patients with SR-cGVHD (moderate/severe,n=24).For the SR-aGVHD and SRcGVHD groups,respectively:Median number of previous GVHD therapies was 2(range:1-3) and 2 (1-4);median follow-up was 2.5 (1.5-4) and 5 (1.5-10) mo;median time to best response was 1 (0.5-2.5) and 3 (1-9.5) mo;and overall response rate was 100%(complete response:80%) and 82.1%(complete response:10.7%) with a response observed in all GVHD-affected organs.The malignancy relapse rates for the SR-aGVHD and SR-cGVHD groups were 10.0%and 10.7%,respectively.Reactivation rates for cytomegalovirus,Epstein-Barr virus,and varicella-zoster virus,respectively,were 30.0%,10.0%,and 0%for the SR-aGVHD group and 0%,14.3%,and 7.1%for the SR-cGVHD group.CONCLUSION Ruxolitinib add-on was effective and safe as salvage therapy for SR-GVHD.     

2013-2018年西安市各级医院第一批国家重点监控药品不良反应/不良事件分析

目的 总结、分析西安市各级医院第一批国家重点监控药品(以下简称重点监控药品)不良反应/事件(ADR/ADE)发生的情况,以促进重点监控药品合理化使用.方法 对西安市各级医院2013-2018年上报的重点监控药品ADR/ADE报告进行统计分析,包括患者性别、年龄、ADR/ADE发生的时间、产生ADR/ADE的重点监控药品...     

基于全周期管理的中美日仿制药替代促进政策对比研究

目的:基于全周期管理理念,从仿制药研发注册、市场准入、临床使用和上市后再评价多个环节为我国仿制药替代促进政策的制定和完善提供建议。方法:采用文献研究法和对比分析法,对我国和美日的仿制药替代促进政策现状进行对比分析。结论:仿制药替代是涉及多个环节的系统工程,美国和日本通过在研发注册环节不断完善技术标准和数据指南,在市场准入环节合理定价和医保激励,在临床使用环节管理医师药师处方行为、加强宣传教育,在上市后再评价环节对仿制药进行再评价和替代效果评估,构建了全周期的仿制药替代促进政策体系,实现了仿制药替代目标。     

创新药价值评估的国际经验比较及启示

随着我国医药卫生体制改革的不断深入,以价值为导向的创新药医保谈判准入模式已经逐步确立,如何科学开展创新药的价值评估已成为政府决策部门和社会各界关注的重要问题。本文对英国、德国、法国、加拿大四个国家的创新药价值评估体系与评估流程进行了系统梳理与对比,总结了英国关于药物经济学评价以及德国、法国、加拿大关于附加临床收益评估的过往经验;在此基础上,针对我国的创新药价值评估流程,在构建创新药附加临床收益评估体系、完善创新药医保准入的谈判规则、完善创新药医保准入的决策依据三个方面提出了相关建议。     

国谈抗肿瘤药配备机构的空间可达性评价研究——以武汉市为例

目的：本研究旨在评估武汉市中心城区国谈抗肿瘤药配备机构的空间可达性水平,为优化药物供应与配置提供经验证据。方法：以武汉市为例,采用基于高斯衰减函数的两步移动搜索法(2-Step Floating Catchment Area, 2SFCA)评估研究区域内各个需求单元在不同交通出行方式下的国谈抗肿瘤药配备机构的可达性,同时运用空间自相关分析和K-means聚类分析识别需求单元可达性的分布态势和分类模式。结果：在驾车或公交出行的情况下,武汉市中心城区各需求单元的配药定点机构的可达性呈现出明显的空间分异特征。江汉区、汉阳区等可达性水平较高且均衡,而青山区和洪山区可达性水平较低且内部存在明显分层。此外,各需求单元呈现显著正相关空间分布,区域内高值集聚与分区内部分化现象并存。结论：武汉市中心城区配药机构可达性整体较高,但存在从核心城区向边缘城区递减的趋势;多数辖区的可达性良好且较为均衡,但少数辖区的可达性较差且存在明显的内部等级分层。