Associations of HLA and drug-metabolizing enzyme genes in co-trimoxazole-induced severe cutaneous adverse reactions

Co-trimoxazole is mainly used as a first-line drug for treatment and prophylaxis against Pneumocystis jiroveci pneumonia. This drug, however, has been reported as the most common causative drug for severe cutaneous adverse reactions (SCARs). This study aimed to extensively elucidate the associations between genetic polymorphisms of HLA class I and genes involved in bioactivation and detoxification of co-trimoxazole on co-trimoxazole-induced SCARS in a large sample size and well-defined Thai SCARs patients. A total of 67 patients with co-trimoxazole-induced SCARs, consisting of 51 SJS/TEN patients and 16 DRESS patients, and 91 co-trimoxazole tolerant controls were enrolled in the study. The results clearly demonstrated that the HLA-B¹13:01 allele was significantly associated with co-trimoxazole-induced SCARs, especially with DRESS (OR = 8.44, 95% CI = 2.66–26.77, P = 2.94 × 10⁻⁴, Pc = 0.0126). Moreover, the HLA-C¹08:01 allele was significantly associated with co-trimoxazole-induced SJS/TEN in the HIV/AIDS patients with an OR of 8.51 (95% CI = 2.18–33.14, P = 8.60 × 10⁻⁴, Pc = 0.0241). None of the genes involved in the bioactivation and detoxification of co-trimoxazole investigated in this study play any major role in the development of all phenotypes of SCARs.     

我院药物代谢酶和药物作用靶点基因检测与精准药学服务实践与总结

目的回顾我院药物代谢酶和药物作用靶点相关基因检测与精准药学服务实践过程,总结经验,与同行分享。方法从准备工作、相关检测项目的确定,学术推广、项目优化和开展情况等方面详细阐述我院基因检测开展过程与精准药学服务情况。结果根据临床需求,我院已开展了以心脑血管药和抗精神病药为主的27种药物,26项检测,2018年全年位1587名患者提供个体化用药建议,受到临床医生和患者欢迎。结论基于代谢酶和药物作用靶点相关基因检测的个体化用药建议是临床药师参与精准治疗的重要途径,有助于医生和药师之间的沟通,有利于提高药学服务水平。     

L-丙酰肉碱对再灌注心肌损伤的保护及体外抗自由基作用

目的:观察L－丙酰肉碱对缺血再灌注心肌的保护作用，并探讨其机理。方法：采用大鼠在体心脏冠状动脉前降支阻断5min造成缺血再灌注模型，持续心电监护，观察心律失常与心功能指标；应用电子顺磁共振观察L－丙酰肉碱对Fenton体系及二甲基亚砜（DMSO）碱性有氧体系产生自由基的作用。结果：L－丙酰肉碱静脉给药明显减少再灌注时室性心动过速、室性纤维颤动的发生（P＜0．05），促进再灌注后左室收缩压、左室压最大上升速率、左室压最大下降速率、心力环面积的恢复，与对照组相比，各参数均明显增高（P＜0．05）；静脉注射L－丙酰肉碱100mmol／L时促进Fenton体系OH的产生，而500mmol／L时产生明显抑制作用，L－丙酰肉碱明显抑制DMSO碱性有氧体系OS的产生。结论：L－丙酰肉碱明显减少再灌注心律失常的发生，促进再灌注后心功能的恢复。推测它对自由基的作用可能是再灌注损伤保护机理之一。     

MISE AU POINT D'UNE TECHNIQUE D'ADMINISTRATION IN VIVO DES VECTEURS GENETIQUES DANS LEMUSCLE CARDIAQUE

Objective In order to improve the in vivo gene transfer into the heart muscle, we have designed a ECG-synchronized microinjection system that allows sequential gene delivery to the myocardium.Methods A cannula was introduced into the right carotid artery of the Wistar rat under general anesthesia.With the ECG-synchronized injection during diastole, the genetic vector (Ad CMV lacZ ) infusion was performed with various concentrations( l07 ～ l010pfu ) and different frequency ( the ratio of heart beats per injection from 1: 1 to 4: 1 ). The hearts of the rats were removed after 7 days for histological examination. Results Best results were obtained with a total vector amount of l09 pfu and a good ratio 3: 1 between heart frequency and injection frequency. The transfection efficiency was increased by use of vasodilators and by an increase of vascular permeability. No signs of myocardial ischemia or ventricular arrythmia were observed. Conclusion We have established a novel and safe method for in vivo gene transfer into the heart. Transgene expression suggests that this method may be useful technique to study cardiac function of treat cardiac diseases by means of gene theratpy.     

异丙酚与安氟醚或七氟醚静吸复合麻醉对心肌酶的影响

目的:观察异丙酚与安氟醚或七氟醚静吸复合麻醉对心肌酶的影响.方法:32例择期非心脏手术的全麻病人,随机分为4组(每组8例),分别给予安氟醚麻醉(A组)、七氟醚麻醉(B组)、异丙酚-安氟醚麻醉(C组)、异丙酚-七氟醚麻醉(D组).其中A、B组为对照组,C、D组为观察组.分别于麻醉前、麻醉诱导后2 h和术后3 d采集静脉血测血清磷酸肌酸激酶(CK)及其同功酶(CK-MB)、天门冬氨酸氨基转移酶(AST)、乳酸脱氢酶(LDH)、α-羟丁酸脱氢酶(HBDH).结果:麻醉诱导后2 h,A组CK、CK-MB值、LDH及HBDH值升高,与麻醉前比较差异有显著性(P<0.01或P<0.05);B组CK和CK-MB值升高,与麻醉前比较差异有显著性(P<0.05或P<0.01).术后3 d,A、B两组CK值升高,与麻醉前和麻醉诱导后2 h比较差异有显著性(P<0.01或P<0.05),AST值升高,与麻醉前比较差异有显著性(P<0.01或P<0.05).而且A、B两组相比较,A组的CK、LDH值升高幅度明显大于B组(P<0.05).C、D两组仅CK值在术后3 d与麻醉前比较差异均有显著性(P<0.01),但其升高幅度均明显低于A、B两组的同时值(P<0.01),其余各项心肌酶的变化在麻醉诱导后2 h及术后3 d差异均无显著性(P>0.05).与C组比较,A组在麻醉诱导后2 h CK、CK-MB、HBDH值升高(P<0.01),LDH值升高(P<0.05);在术后3 d CK值升高(P<0.01).与D组比较,B组CK值在麻醉诱导后2 h及术后3 d升高(P<0.01),CK-MB值在麻醉诱导后2 h升高(P<0.05).结论:安氟醚和七氟醚两者均能使心肌酶升高,但安氟醚所致的心肌酶升高幅度更明显;临床麻醉剂量的异丙酚能有效地防止安氟醚和七氟醚麻醉时心肌酶的升高.     

Extracellular Enzyme Activities by Basidiobolus and Conidiobolus Isolates on Solid Media./Extrazelluläre Enzymaktivitäten bei Basidiobolus- und Condiobolus-Isólaten auf festen Medien

Summary: Fifty-seven isolates of Basidiobolus from reptiles and amphibians, and 7 other obtained from the American Type Culture Collection (ATCC) in Maryland were studied for their extracellular enzyme activities on solid media. The Conidiobolus isolates studied included 4 recovered from Nigerian soil and additional 4 obtained from the ATCC All these isolates produced active extracellular lipase and protease and failed to exhibit amylase, deoxyribonuclease and ribonuclease activities. The significance of the findings is discussed.
Zusammenfassung: Fünfundsiebzig Basidiobolus-Isolate aus Reptilien und Amphibien und sieben weitere aus der American Type Culture Collection (ATCC) in Maryland wurden auf Aktivtäten extrazellulärer Enzyme auf festen Medien untersucht Die untersuchten Conidiobolus-Isolate schlossen vier aus nigerianischen Böden und vier weitere aus der ATCC ein. Alle Isolate zeigten extrazellulär Lipase- und Proteaseaktivität Amylase-, Desoxyribonuclease- und Ribonucleaseaktivität war jedoch nicht nachzuweisen. Die Bedeutung dieser Befunde wird diskutiert.     

低血容量性休克大鼠心肌细胞Ca2+浓度及膜电位的变化

目的 旨在探讨低血容量性休克大鼠心肌细胞Ca2 浓度及其膜电位的变化.方法 选用Wistar大鼠84只,随机分成休克高渗复苏组(HES组)、生理盐水复苏组(NS组).建立休克模型,按7个时相(休克前、休克、复苏后5、15、30、60、90min)处死大鼠.取心室肌细胞培养传代,用Fluo-4/AM为游离钙荧光探针、JC-1荧光染色,流式细胞仪分别检测不同时相心肌细胞Ca2 浓度及线粒体膜电位.结果 HES组在休克、复苏后5、15、30min各时间点心肌细胞Ca2 浓度较休克前明显升高,其膜电位较休克前显著降低(P＜0.01);在复苏后60、90min心肌细胞Ca2 浓度及线粒体膜电位与休克时比较差异有显著性意义(P＜0.01);NS组在休克、复苏后各个时相与休克前比较心肌细胞Ca2 浓度均明显升高,其膜电位明显下降(P＜0.01);复苏后各时间点与休克时比较差异无显著性意义(P＞0.05);HSE组和NS组在休克后60、90min心肌细胞Ca2 浓度及其膜电位差异有显著性意义(P＜0.01).结论 低血容量性休克可诱发大鼠心肌细胞Ca2 浓度升高,线粒体膜电位下降,导致心肌细胞电生理活动障碍;高渗盐溶液不但可改善低血容量休克时心肌细胞Ca2 浓度,而且能有效地稳定其线粒体膜电位;而生理盐水对心肌细胞Ca2 浓度及其膜电位的作用不显著.     

幼兔缺血预处理在心肌保护第二窗期对未成熟心肌Bcl-2基因mRNA表达的影响

目的　观察幼兔心脏缺血预处理 2 4h对未成熟心肌缺血 /再灌注后Bcl -2mRNA表达的影响 ,探讨未成熟心肌保护第二窗形成的作用机理。方法　 18只 3～ 4周龄幼兔 ,随机分为 3组 ,每组 6只 :Ⅰ组 ,正常对照组 ;Ⅱ组 ,缺血 /再灌注损伤组 ;Ⅲ组 ,缺血预处理组。建立活体心脏缺血 /再灌注损伤模型 ,Maclab/8s系统监测左心室发展压 (LVDP)、左室压上升及下降最大速率 (+dp/dtmax,-dp/dtmax)变化 ,原位免疫杂交 (ISH)方法检测心肌细胞内Bcl-2mRNA的表达。结果　缺血再灌注前 ,各组间LVDP、±dp/dtmax无显著性差异 (P >0 .0 5) ;再灌注 1h后 ,Ⅱ组的LVDP、+dp/dtmax和 -dp/dtmax恢复率分别为 (42 .81± 12 .56) %、(3 0 .67± 16.2 2 ) %和 (2 9.49± 10 .13 ) % ;Ⅲ组LVDP、+dp/dtmax及 -dp/dtmax恢复率分别为 (84.15± 13 .56) %、(69.49± 10 .3 6) %和 (58.3 7± 12 .45) % ,两组间有显著性差异 (P <0 .0 1)。Ⅱ组、Ⅲ组Bcl -2mRNA表达阳性细胞面积百分数分别为 (8.3± 2 .5) %、(76.3±13 .5) % ,两组间有显著性差异 (P <0 .0 1)。结论　缺血预处理可上调Bcl -2mRNA表达 ,参与未成熟心肌保护第二窗的形成 ,促进未成熟心肌缺血 /再灌注后心室功能恢复     

应用门控SPECT测量左心室功能的方法学研究

目的：试用门控心肌显像测定左室功能并与心血池显像结果比较。材料和方法：61例受检者进行了Tc-99m—MIBI门控心肌显像及心血池显像．结果：门控断层心肌显像的短轴中间部左室功能结果与平衡法心血池显像有良好的相关性(r=0．82）。结论：门控心肌断层显像测定的左室功能结果方法简便可靠．能同时反映心肌直流及左室功能。