氟伐他汀对充血性心力衰竭患者血清sICAM-1和sVCAM-1的影响

目的:探讨氟伐他汀短期治疗对充血性心力衰竭(CHF)患者血清中可溶性细胞间黏附分子-1(sICAM-1)、可溶性血管细胞黏附分子-1(sVCAM-1)和肿瘤坏死因子α(TNF-α)水平的影响。方法:将97例CHF患者随机分为对照组(常规治疗组)和试药组(氟伐他汀组)。采用ELISA测定治疗前及治疗两周后血清中sICAM-1、sVCAM-1和TNF-α水平。结果:两种方法都可以明显降低血清sICAM-1、sVCAM-1和TNF-α水平(P0.05);试药组血清TNF-α水平降低更为显著(P0.05),但血清sICAM-1和sVCAM-1降低水平与对照组无显著差别。结论:在常规治疗基础上短期加用氟伐他汀治疗不能进一步降低CHF患者血清sICAM-1和sVCAM-1水平。     

急性冠状动脉综合征患者血清sICAM-1、sVCAM-1、sP-选择素表达及意义

采用ELISA法测定40例急性冠脉综合征患者（AC组）、30例稳定型心绞痛患者（SAP组）及28例正常人（对照组）血清可溶性细胞间黏附分子-1（sICAM-1）、血管细胞间黏附分子-1（sVCAM-1）、P-选择素（sP-selectin）水平。结果ACS组血清sICAM-1、sVCAM-1、sP-selectin水平显著高于SAP组和对照组（P均〈0.01）,SAP组与对照组无显著性差异（P〉0.05）。ACS组血清sICAM-1、sVCAM-1与sP-selectin呈显著正相关（r=0.516、0.521,P均〈0.05）。提示ACS患者血清sICAM-1、sVCAM-1、sP-selectin水平均明显升高,并共同作用促进ACS的发生、发展。     

原发性胆汁性肝硬化患者血清可溶性血管细胞黏附分子-1和可溶性细胞间黏附分子-1的表达及其临床意义

目的 检测原发性胆汁性肝硬化(PBC)患者血清中可溶性血管细胞黏附分子-1(sVCAM-1)及可溶性细胞间黏附分子-1(sICAM-1)的表达,并探讨其临床意义.方法用酶联免疫吸附法(ELISA)测定27例PBC患者及20例对照组血清sVCAM-1、sICAM-1的含量,分别比较PBC患者child-pugh分级各级别上述因子表达水平.结果 PBC患者血清sVCAM-1和sICAM-1水平明显高于对照组(P<0.05);child-pugh分级B、C级患者血清sVCAM-1和sICAM-1水平高于A级(P<0.05).结论sVCAM-1、sICAM-1参与了PBC的病理生理过程,与疾病分级相关,血清8VCAM-1、sICAM-1含量增高可作为原发性胆汁性肝硬化肝损害的判断指标.     

妊娠期糖尿病患者血清sICAM-1、sVCAM-1和TNF-α水平检测及意义

采用ELISA法测定29例妊娠期糖尿病（GDM）患者（GDM组）及30例正常妊娠妇女（对照组）血清可溶性细胞间黏附分子-1（sICAM-1）、血管内皮细胞黏附分子-1（sVCAM-1）和肿瘤坏死因子-α（TNF—d）水平；分析其与血清空腹胰岛素（INS）、血浆葡萄糖浓度（FBG）及胰岛素抵抗的关系。结果GDM组血清TNF-α、sICAM-1、sVCAM-1均明显高于对照组IGDM组血清TNF-α水平与胰岛素敏感指数（ISI）、sICAM-1及sVCAM-1呈正相关（P均〈0．01）,GDM组血清TNF-α与sICAM-1及sVCAM-1存在协同表达作用。认为联合检测血清TNF-α、sICAM-1和sVCAM-1对控制GDM患者妊娠过程中血管内皮细胞的黏附、减少GDM发生有重要意义。     

ACS患者血清sICAM-1、sVCAM-1、可溶性P选择素的水平变化及意义

目的探讨血清可溶性细胞间黏附分子1（sICAM-1）、可溶性血管细胞间黏附分子1（sVCAM-1）、可溶性P选择素（sP选择素）在急性冠脉综合征（ACS）发生、发展中的作用。方法采用ELISA法测定50例ACS患者（ACS组）、40例稳定型心绞痛（SAP）患者（SAP组）及26例正常人（对照组）sICAM-1、sVCAM-1、sP选择素水平。结果ACS组血清sICAM-1、sVCAM-1、sP选择素水平显著高于SAP组和对照组（P均〈0．01）。ACS组血清sICAM-1、sVCAM-1与sP选择素呈显著正相关（r=0．432、0．501,P均〈0．05）。结论ACS患者血清sICAM-1、sVCAM-1和sP选择素共同作用促进ACS的发生、发展。     

sICAM-1、sVCAM-1在急性动脉硬化性脑梗死中的临床意义

目的:探讨可溶性细胞间黏附分子-1(sICAM-1)及可溶性血管细胞间黏附分子-1(sVCAM-1)在急性动脉硬化性脑梗死中的临床意义。方法:研究对象分为急性脑梗死组(n=60例)及对照组(n=28例),检测所有受试者血清sICAM-1、sVCAM-1水平,分析二者与脑梗死面积及临床转归之间的关系。结果:急性脑梗死患者血清sICAM-1、sVCAM-1水平显著高于对照组(P<0.01),二者与梗死面积大小呈正相关;而不同转归组之间二者含量无显著差别。结论:sICAM-1、sVCAM-1参与脑梗死炎症过程,可预示脑梗死严重程度。     

急性冠脉综合征患者血清炎性标志物浓度变化及其临床意义

目的探讨血清炎性标志物与急性冠脉综合征(ACS)的关系。方法检测48例ACS患者血清C-反应蛋白(CRP)、可溶性血管内皮细胞黏附分子-1(sVCAM-1)和可溶性细胞间黏附分子-1(sICAM-1)等炎性因子变化,与冠脉造影结果和临床预后进行对比分析。结果1ACS组血清CRP与sICAM-1、sVCAM-1水平均高于稳定性心绞痛(SA)组和正常对照组;2sVCAM-1≥870ng/ml者3个月内主要冠脉不良事件(MACE)发生率明显高于<870ng/ml者;3血清肌钙蛋白阳性者CRP、sICAM-1、sVCAM-1浓度均明显高于阴性者;4冠脉狭窄程度在ACS组与SA组无统计学差异;冠脉狭窄程度积分与TC水平呈正相关,而与血清CRP、sICAM-1、sV-CAM-1及血浆纤维蛋白原(Fig)水平均无相关性;5sVCAM-1、Fig和肌钙蛋白预测3个月内MACE发生的敏感性分别为67.5%、82.4%、57.1%;特异性分别为54.8%、58.1%、81.5%。结论血清炎性标志物对ACS患者临床危险分层和判断预后有重要意义。     

活动性幼年特发性关节炎患者sICAM-1 sVCAM-1的表达及意义

目的测定各型活动性幼年特发性关节炎(JIA)患儿血清中可溶性细胞间黏附分子-1(sICAM-1)、可溶性血管间黏附分子-1(sVCAM-1)、白细胞介素(IL)-1、IL-4、肿瘤坏死因子(TNF)-α水平,探讨sICAM-1、sVCAM-1与疾病活动、疾病分型以及疾病严重程度的关系。方法用酶联免疫吸附试验(ELISA)检测30例活动性JIA患儿与8名健康对照儿童sICAM-1、sVCAM-1水平;用放射免疫法(RIA)检测IL-1、IL-4、TNF-α水平。结果30例JIA患者血清中sICAM-1、sVCAM-1、IL-1、IL-4、TNF-α水平明显高于健康对照组(P<0.01);在各型JIA中sVCAM-1与血沉(ESR)、C反应蛋白(CRP)呈正相关(P<0.05或0.01);而sICAM-1仅在全身型及多关节型JIA患儿中与关节肿胀指数、夜间痛呈正相关(P<0.01),与炎性指标ESR、CRP等无关。结论JIA患者血清中sICAM-1、sVCAM-1、IL-1、IL-4、TNF-α水平显著升高,可能参与了JIA的发病过程,sVCAM-1、sICAM-1可与ESR、CRP一起作为判断病情严重性的指标,且可能与JIA分型有关。     

大剂量氟伐他汀短期治疗对老年不稳定性心绞痛患者血清可溶性细胞黏附分子和肿瘤坏死因子-α水平的影响

目的探讨大剂量氟伐他汀短期治疗对老年不稳定性心绞痛患者血清中可溶性细胞间黏附分子-1（sICAM-1）、可溶性血管细胞黏附分子-1（sVCAM-1）和肿瘤坏死因子-α（TNF-α）水平的影响。方法将56例老年不稳定性心绞痛患者随机分为常规治疗组和大剂量治疗组,两组患者均给予抗心绞痛常规治疗,常规治疗组给予氟伐他汀40mg／d,大剂量治疗组给予氟伐他汀80mg／d,入院当日和治疗1个月时检测患者血清中sICAM-1、sVCAM-1和TNF-α水平。结果两组患者治疗后血清sICAM-1、sVCAM-1和TNF-α水平均较治疗前明显降低（P〈0．05）,但组间比较差异无统计学意义（P〉0．05）。结论大剂量氟伐他汀短期治疗不能进一步降低老年不稳定性心绞痛患者血清sICAM-1、sVCAM-1和TNF-α水平。     

舒冠滴丸对动脉粥样硬化兔CD40通路调节作用研究

目的观察舒冠滴丸对动脉粥样硬化斑块CD40通路的调节作用。方法运用高脂高胆固醇饲料造成兔动脉粥样硬化模型,随机分成模型组、舒冠滴丸组、辛伐他汀组,另设空白对照组。采用酶联免疫吸附法测定血浆可溶性CD40L(sCD40L)、可溶性细胞间黏附分子-1(sICAM-1)和血管细胞黏附分子-1(sVCAM-1)浓度。然后,提取AS兔主动脉和心脏进行病理组织形态学观察。结果舒冠滴丸组血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平显著低于模型组(P<0.01),舒冠滴丸组血浆sCD40L,sICAM-1水平明显降低,与模型组比较有统计学意义(P<0.01),而血浆sVCAM-1水平无统计学意义;病理组织形态学观察,舒冠滴丸组主动脉AS斑块明显少于模型组(P<0.05),冠状动脉AS斑块各组差异无统计学意义(P>0.05);舒冠滴丸组内膜病变较模型组明显减轻,其内膜厚度、内膜/中膜厚度比、内膜/中膜面积比亦较模型组显著减少(P<0.01)。结论舒冠滴丸具有调节血脂紊乱,减少动脉内膜斑块数量,消退和稳定AS斑块,降低血浆sCD40L,sICAM-1水平,其作用可能与抑制AS斑块炎症反应有关。     

1-Naphthyl isocyanate and 1-naphthylamine as metabolites of 1-naphthylisothiocyanate

Abstract: The importance of the bioactivation of 1-naphthylisothiocyanate was studied. Forty minutes after 1-naphthylisothiocyanate administration to rats, bile was collected over a 2.5-h period; the liver was then excised and homogenized. 1-naphthylisothiocyanate and its metabolites in bile and liver of rats were identified and quantified using coupled gas chromatography-mass spectrometry. Three main compounds were found in all 1-naphthylisothiocyanate-treated animals. They were identified as 1-naphthyl isocyanate, 1-naphthylamine and the parent compound, 1-naphthylisothiocyanate. When rats were given cycloheximide, which attenuates 1-naphthylisothiocyanate toxicity, 30 min before 1-naphthylisothiocyanate (300 mg/kg), 1-naphthyl isocyanate concentration was significantly lower than in rats receiving only 1-naphthylisothiocyanate. The appearance of 1-naphthylamine was also inhibited by cycloheximide, although not to the same extent as 1-naphthyl isocyanate. On the other hand, phenobarbital, which potentiates 1-naphthylisothiocyanate hepatotoxicity, enhanced 1-naphthyl isocyanate and 1-naphthylamine formation. It is suggested that 1-naphthyl isocyanate, 1-naphthylamine and the highly reactive sulfur released from 1-naphthylisothiocyanate might be involved in the hepatotoxic effect of 1-naphthylisothiocyanate.     

Genetic link with cholelithiasis among pediatric SCA Tunisian patients: Examples of UGT1A1, SLCO1A2 and SLCO1B1

Aims and background: Hyperbilirubinemia is often observed in chronic hemolysis and results in the formation of pigment cholelithiasis that could be increased by the presence of defected enzymes involved in the bilirubin metabolism. Indeed, this is the first report that interested in the study of polymorphisms in genes encoded for enzymes involved in the bilirubin metabolism: rs 4149056 of SLCO1B1 and rs4149000 of SLCO1A2 in combination with rs8175347 and rs887829 of UGT1A1 in order to find a correlation between the polymorphisms studied and the presence of gallstones in a population of sickle cell anemia (SCA) pediatric Tunisians.

Material and methods: Our study involved 102 unrelated Tunisian subjects. All SCA patients are children (less than 16 years old) and were characterized by hyperbilirubinemia and 52 of them have cholelithiasis. The polymorphisms of the candidate genes were analyzed for all subjects by PCR/sequencing. Genotype and allele frequencies between cases and controls were compared using Pearson's chi-square test with a significance threshold of P?<?0.05 (compare 2, version 1.02).

Results: The novelty of this report is that children carrying the combined genotype of the rs studied: (TA7TA7)/TT/TC/GA have a higher risk to develop gallstones (P?=?0.0027, RR?=?18.27 (20.0061–915.28)).

Conclusion: Altogether our data provide the implication of UGT1A1 and SLCO1A2 in sickle cell anemia-related cholelithiasis.     

甲型H1N1与季节性H1N1流感病毒血凝素基因比较分析

目的分析泰安市2008～2009年度季节性流感与2009年度甲型H1N1流感病原学检测结果 ,比较季节性H1N1与甲型H1N1血凝素基因变异情况。方法选择国家级流感监测哨点医院以及暴发疫情的疫点,采集流感样病例的鼻咽拭子标本,通过RealtimePCR进行病毒检测,用MDCK细胞进行病毒分离,通过RT-PCR扩增血凝素HA1片段的基因并测序,利用生物信息学进行序列分析。结果 2008～2009年共检测鼻咽拭子标本283份,分离出流感病毒33株,分离阳性率为11.67%,其中季节性H1N1亚型31株。2009年5月1日～12月31日,检测鼻咽拭子标本996份,流感核酸检测阳性417份,阳性率为41.86%,其中甲型H1N1337份,季节性H1N1亚型1份。6株季节性H1N1病毒均在多个氨基酸位点上发生变异,与疫苗株A/Brisbane/59/2007(H1N1)比较,有11个位点发生了突变,其中5个位点位于抗原决定簇上;测序成功的6株甲型H1N1病毒在多个氨基酸位点发生变异,与疫苗株A/California/07/2009(H1N1)比较,有6个位点发生突变,其中1个位点位于抗原决定簇的B区。结论 2008～2009年度季节性H1N1为优势株,甲流暴发后,甲型H1N1成为绝对优势毒株。季节性H1N1分离株有多处氨基酸替换,抗原决定簇B区变异频繁;甲型H1N1病毒分离株的基因有变异,但关键位点第222位仍为D(天冬氨酸),与疫苗株相比抗原决定簇的关键位点变化不大。     

Cytochrome 1A1 and 1B1 gene diversity in the Zanzibar islands

Amodiaquine (AQ) is a 4‐aminoquinoline widely used in the treatment of malaria as part of the artemisinin combination therapy (ACT). AQ is metabolised towards its main metabolite desethylamodiaquine mainly by cytochrome P450 2C8 (CYP2C8). CYP1A1 and CYP1B1 play a minor role in the metabolism but they seem to be significantly involved in the formation of the short‐lived quinine‐imine. To complete the genetic variation picture of the main genes involved in AQ metabolism in the Zanzibar population, previously characterised for CYP2C8, we analysed in this study CYP1A1 and CYP1B1 main genetic polymorphisms. The results obtained show a low frequency of the CYP1A1*2B/C allele (2.4%) and a high frequency of CYP1B1*6 (approximately 42%) followed by CYP1B1*2 (approximately 27%) in Zanzibar islands. Genotype data for CYP1A1 and CYP1B1 show a low incidence of fast metabolisers, revealing a relatively safe genetic background in Zanzibar’s population regarding the appearance of adverse effects.     

甲型H1N1流感合并肺炎的临床特点分析

目的通过对甲型H1N1流感合并肺炎的临床特点的分析。方法分析2009年月10月-2010年3月在我院入住的29例甲型H1N1流感合并肺炎患者的临床表现、实验室检查及胸部CT等资料。结果本组病例男性16例,女性13例。3例妊娠,13例合并有基础疾病。所有病例均有流感样前驱症状,呼吸道主要症状为发热、干咳少痰,严重者气短、呼吸困难、咯血。合并细菌感染时咯脓痰。肺部听诊无啰音或少啰音,合并哮喘时有哮鸣音,合并细菌感染时可有湿啰音。实验室检查65%白细胞不高或降低,41%心肌酶升高,58.6%存在低氧血症,35%呼吸衰竭。影像学表现多种多样：65.5%主要为单侧或双侧棉团样、团片样边界模糊高密度渗出影伴肺实变,其内见充气支气管征,病变沿支气管血管束分布。轻症及早期较局限,重症者及晚期病变融合呈双肺多发弥漫性改变。少数呈大叶及小叶性肺炎表现。预后大多良好,病死率6.9%。主要死亡原因为呼吸衰竭及大咯血。结论甲型H1N1流感合并肺炎是以甲型H1N1流感病毒肺炎为主要疾病的多种肺炎构成。甲型H1N1流感病毒肺炎临床表现具有流感病毒肺炎共性特点,其影像学表现有一定特征性。     

Inhibition of procarcinogen-bioactivating human CYP1A1, CYP1A2 and CYP1B1 enzymes by melatonin

Abstract:  Administration of melatonin to rodents decreases the incidence of tumorigenesis initiated by benzo[ a ]pyrene or 7,12-dimethylbenz[ a ]anthracene, which requires bioactivation by cytochrome P450 enzymes, such as CYP1A1, CYP1A2 and CYP1B1, to produce carcinogenic metabolites. The present study tested the hypothesis that melatonin is a modulator of human CYP1 catalytic activity and gene expression. As a comparison, we also investigated the effect of melatonin on the catalytic activity of CYP2A6, which is also a procarcinogen-bioactivating enzyme. Melatonin (3–300 μ m ) decreased 7-ethoxyresorufin O -dealkylation catalyzed by human hepatic microsomes and recombinant CYP1A1, CYP1A2 and CYP1B1, whereas it did not affect coumarin 7-hydroxylation catalyzed by hepatic microsomes or recombinant CYP2A6. Melatonin inhibited CYP1 enzymes by mixed inhibition, with apparent K _i values (mean ± S.E.M.) of 59 ± 1 (CYP1A1), 12 ± 1 (CYP1A2), 14 ± 2 (CYP1B1) and 46 ± 8 μ m (hepatic microsomes). Additional experiments indicated that melatonin decreased benzo[ a ]pyrene hydroxylation catalyzed by hepatic microsomes and CYP1A2 but not by CYP1A1 or CYP1B1. Treatment of MCF-10A human mammary epithelial cells with melatonin (up to 300 μ m ) did not affect basal or benzo[ a ]pyrene-inducible CYP1A1 or CYP1B1 gene expression. Consistent with this finding, melatonin did not influence reporter activity in aryl hydrocarbon receptor-dependent pGudluc6.1-transfected MCF-10A cells treated with or without benzo[ a ]pyrene, as assessed in an in vitro cell-based luciferase reporter gene assay. Overall, melatonin is an in vitro inhibitor of human CYP1 catalytic activity, and it may be useful to develop potent analogues of melatonin as potential cancer chemopreventive agents that block CYP1-mediated chemical carcinogenesis.     

Role of CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 genes in the susceptibility to acute leukemias

Acute leukemias (ALs) are heterogeneous diseases. Functional polymorphisms in the genes encoding detoxification enzymes cause inter-individual differences, which contribute to leukemia susceptibility. The CYP2D6, CYP1A1, CYP2E1, GSTT1, and GSTM1 polymorphisms in ALL (n = 156) and AML (n = 94) patients and 140 healthy controls were genotyped by PCR and/or PCR-RFLP using blood or bone marrow samples. No association was observed between the GSTT1 gene deletion and patients (OR = 0.8, 95% CI = 0.4-1.7 for AMLs and OR = 0.9, 95% CI = 0.5-1.6 for ALLs). Patients with ALL and AML had a higher prevalence of the GSTM1 deletions compared to controls but only the difference among adult AML patients (OR = 2.1, 95% CI = 1.0-4.2) was statistically significant. The CYP2D6*3 variant allele frequency was lower in the overall acute leukemia patients (0.6%) compared to controls (P = 0.03). CYP2D6*1/*3 genotype frequency also showed a protective association in AML patients (OR = 0.09, 95% CI = 0.01-1.7; P = 0.04). We also found a risk association for CYP2E1*5 in ALL and AML (OR = 3.6, 95% CI = 1.4-9.4 and OR = 3.9, 95% CI = 1.4-10.5, respectively). No association was found for the studied CYP2D6*4, CYP1A1*2A, and GSTT1"null" variants and the risk of acute leuke-mia (ALL or AML). This case-control study suggests a contribution of CYP2E1, CYP2D6, and GSTM1 "null" variants to the development of acute leukemias.