麦考酚酸酯及其临床应用进展

目的:麦考酚酸酯(MMF)是一种新型的免疫抑制剂.在临床应用中,MMF的使用也越来越广泛,已不仅仅局限于器官移植,还涉及到系统性红斑狼疮(SLE)、自体免疫风湿性疾病的治疗,以及在糖尿病,肺部血管高压的辅助治疗等诸多方面.肠包衣麦考酚酸钠,是一种新的可抵抗胃溶作用的麦考酚酸肠包衣剂型,药物在肠内释放,可以降低胃肠道(GI)不良反应的发生.     

Anthracycline-induced cardiotoxicity: Overview of studies examining the roles of oxidative stress and free cellular iron

The risk of cardiotoxicity is the most serious drawback to the clinical usefulness of anthracycline antineoplastic antibiotics, which include doxorubicin (adriamycin), daunorubicin or epirubicin. Nevertheless, these compounds remain among the most widely used anticancer drugs. The molecular pathogenesis of anthracycline cardiotoxicity remains highly controversial, although the oxidative stress-based hypothesis involving intramyocardial production of reactive oxygen species (ROS) has gained the widest acceptance. Anthracyclines may promote the formation of ROS through redox cycling of their aglycones as well as their anthracycline-iron complexes. This proposed mechanism has become particularly popular in light of the high cardioprotective efficacy of dexrazoxane (ICRF-187). The mechanism of action of this drug has been attributed to its hydrolytic transformation into the iron-chelating metabolite ADR-925, which may act by displacing iron from anthracycline-iron complexes or by chelating free or loosely bound cellular iron, thus preventing site-specific iron-catalyzed ROS damage. However, during the last decade, calls for the critical reassessment of this “ROS and iron” hypothesis have emerged. Numerous antioxidants, although efficient in cellular or acute animal experiments, have failed to alleviate anthracycline cardiotoxicity in clinically relevant chronic animal models or clinical trials. In addition, studies with chelators that are stronger and more selective for iron than ADR-925 have also yielded negative or, at best, mixed outcomes. Hence, several lines of evidence suggest that mechanisms other than the traditionally emphasized “ROS and iron” hypothesis are involved in anthracycline-induced cardiotoxicity and that these alternative mechanisms may be better bases for designing approaches to achieve efficient and safe cardioprotection.     

选择性5-HT1A受体拮抗剂WAY-100635抑制帕金森病模型大鼠腹内侧前额叶皮质的神经活动

目的腹内侧前额叶皮质在随意运动的起始和控制、情感以及认知中具有重要作用。然而,黑质-纹状体通路变性后腹内侧前额叶皮质的神经活动和5-HT_(1A)受体的作用仍不清楚。本研究观察了6-羟基多巴胺(6- hydroxydopamine,6-OHDA)损毁黑质致密部(substantia nigra pars compacta,SNc)后大鼠腹内侧前额叶皮质神经活动的变化和体循环给予选择性5-HT_(1A)受体拮抗剂WAY-100635后神经元活动的改变。方法采用在体玻璃微电极细胞外记录方法,记录正常大鼠和SNc单侧损毁大鼠的腹内侧前额叶皮质神经元的活动。结果6-OHDA损毁SNc大鼠的腹内侧前额叶皮质神经元放电频率显著增加,放电形式没有明显改变。体循环给予WAY-100635 (0.1 mg/kg,i.v.)不改变正常大鼠腹内侧前额叶皮质神经元的平均放电频率和放电形式,而显著降低了SNc损毁大鼠前额叶皮质神经元的平均放电频率。结论黑质-纹状体通路的变性可导致腹内侧前额叶皮质神经活动增强,5-HT_(1A)受体拮抗剂WAY-100635可以抑制这种活动增强,提示可能存在腹内侧前额叶皮质5-HT_(1A)受体功能失调。     

MACS检测胃癌腹腔冲洗液游离癌细胞的研究

目的 探讨胃癌腹腔微转移情况的检测方法及意义。方法 手术中切除肿瘤前收集腹腔冲洗液，采用磁激活细胞分离术（MACS）对不同病理分期胃癌患者腹腔冲洗液中癌细胞进行富集并检测。分别标记带磁珠的细胞角蛋白（CK）抗体，经磁柱富集CK^＋上皮细胞，用流式细胞仪检测其含量，并比较胃癌组与胃平滑肌瘤组（对照组）以及胃癌不同分期之间、磁富集前后CK^＋上皮细胞含量的差异。结果 在未经MACS富集的标本中较少发现CK^＋ CD45^-细胞；在富集后的标本中其含量在胃癌组与对照组有显著差异（41／50，1／10，P〈0．001）；pTNMⅠ～Ⅱ期与Ⅲ～Ⅳ期之间（0．67％，3．42％，P〈0．001）差异有非常显著性。结论 MACS能有效地富集上皮来源细胞，提高上皮源细胞的检出率，并能反映腹腔游离癌细胞数量；上皮细胞数量与胃癌的存在及临床病理分期有关，其有利于判断肿瘤转移和预后并指导治疗。     

钙池操纵的Ca2+通道的激活机制研究进展

钙池操纵的Ca~(2 )通道(store-operated Ca~(2 ) channels,SOC)是非兴奋细胞Ca~(2 )内流的主要通道之一,参与多种病理和生理过程,在钙信号通路的研究中,SOC的激活机制一直是人们关注的焦点之一,迄今为止,钙内流因子模型(Ca~(2 ) innux factor model,CIF model)和构象耦联模型fconformational coupling model)受到广泛关注.部分学者已经从很多不同类型的细胞中提取出CIF,并证实钙非依赖性的磷脂酶A_2(Ca~(2 )-independent phospholipase A_2,iPLA_2)作为CIF的底物,在某些类型细胞的SOC激活过程中发挥重要作用,并进一步提出了ER- CIF-iPLA_2-CaM-LysoPLs-SOC通路模型.瞬时受体电位(transient receptor potential,TRP)通道蛋白与1.4,5-磷酸肌醇受体(inositol 1,4,5 trisphosphate receptor,IP_3R)的结构连接作为构象耦联模型的基础已被广泛证实,随着对IP_3R,Ryanodine受体、肌动蛋白等在钙信号通路中所发挥作用的深入研究,构象耦联模型将得到不断补充和完善.SOC激活机制的破解,将对进一步完善非兴奋细胞的钙通道特性及其调节机制理论带来重大突破.     

不同方法治疗压褥的临床效果比较

目的探讨不同方法治疗压疮的临床效果。方法将65例患者计Ⅱ～Ⅲ度溃疡84处按基本条件相当原则随机分成A、B、C三组，A组21例28处，伤口采用清创冲洗后，给予康惠尔水胶体敷料；B组23例30处，伤口采用湿润烧伤膏；C组21例26处，清创冲洗后，给予自制凡士林油纱敷料外敷溃疡面处。结果B组愈合率最高，且平均显效时间和愈合时间均较A、C两组明显缩短，且A、B组明显高于C组。结论采用清创冲洗后用湿润烧伤膏是治疗压疮较好的方法之一。     

聚γ-谷氨酸高产突变株的选育及摇瓶发酵条件

对地衣芽孢杆菌(Bacilluslicheniformis)进行亚硝基胍和60Co诱变,获得一株γ PGA的高产菌株C9.γ PGA质量浓度由9.44g/L提高到19.76g/L,提高了109%.突变株传代10次,质量浓度保持基本稳定.通过正交试验和单因素试验对发酵培养基及发酵条件进行了优化.当发酵培养基中含柠檬酸12g/L、甘油80g/L、L 谷氨酸23g/L、氯化铵7g/L,pH7.0,装液量为50mL/250mL三角瓶,接种体积分数为5%时,37℃摇瓶发酵72h,γ PGA达到23.32g/L.     

Impact of gastrointestinal endoscopy on HIV‐infected children

Objective: To evaluate the role of gastrointestinal (GI) endoscopy in human immunodeficiency virus (HIV)‐infected children with GI problems. Methods: From 1998 to 2002, we retrospectively reviewed all cases of HIV‐infected children presenting with GI problems in which an upper or lower GI endoscopy was indicated. The initial diagnostic endoscopic examination and any repeat endoscopic session leading to a new diagnosis were used in the data analysis. Tissue biopsies were obtained from all abnormal lesions and representative sites of normal‐appearancing GI mucosa. Results: Fourteen patients (median age: 22.5 months) underwent 23 sessions of GI endoscopy, including 10 esophagogastroduodenoscopy, nine colonoscopy and four flexible sigmoidoscopy. Chronic diarrhea was the most common indication, followed by lower GI bleeding, abdominal/retrosternal pain, dysphagia/odynophagia, and upper GI bleeding. Gross endoscopic abnormalities were observed in 78.3%; whereas histological inflammation and opportunistic pathogens were identified in 87% and 43.5%, respectively. Cytomegalovirus was the most common identified pathogen. Abnormal gross findings were significantly associated with histological inflammation and identification of pathogens (P = 0.006 and 0.046, respectively). Specific changes in medical management were made in 50% of cases as a result of endoscopic investigation. Conclusion: If non‐invasive investigations for HIV‐infected children with GI symptoms fail to establish a diagnosis, gastrointestinal endoscopy should be performed and often yields a positive result leading to changes in medical management.     

595nm激光对兔耳瘢痕成纤维细胞增殖与凋亡的影响

目的：探讨595nmVbeam激光照射对增生性瘢痕动物模型伤口愈合过程中成纤维细胞增殖与凋亡的影响。方法：成年大耳白兔20只,建立兔耳腹侧面增生性瘢痕模型,对比研究在瘢痕形成过程中595nmVbeam激光照射对兔耳瘢痕成纤维细胞的影响,采用免疫组化方法检测增殖细胞核抗原（PCNA）蛋白表达和细胞凋亡的原位检测。结果：兔耳增生性瘢痕经595nmVbeam激光照射后,按不同时间段取材进行免疫组化染色并与对照组比较,高倍镜下观察结果,显示PCNA蛋白表达明显减弱,细胞凋亡增加。结论：595nmVbeam激光照射可抑制兔耳增生性瘢痕成纤维细胞的增殖过程,诱导细胞凋亡。应用595nmVbeam激光预防和治疗瘢痕是可行的。     

Empfehlungen für die Anwendung der Immunapherese bei der Therapie bullöser Autoimmundermatosen

The etiology of epidermolysis bullosa acquisita (EBA) is unknown. EBA may be associated with other autoim‐mune systemic diseases; it also has been described in connection with different malignant tumors, showing complete remission after successful treatment of the tumor.In such cases, EBA may be regarded as a paraneo‐plastic dermatosis. We detected a highly differentiated neuroendocrine pancreatic cancer in a 78‐year‐old woman with EBA. Even thought her tumor was completely removed and the patient has been disease‐free for over seven years, a complete regression of her autoimmune bullous dermatosis could not be induced. By using intravenous immunoglobulins in combination with mycophenolate mofetil, further blister formation could be ameliorated.