充血性心力衰竭患者血清VCAM-1、ICAM-1含量的变化

目的:观察充血性心力衰竭(CHF)患者血清中血管细胞粘附分子-1(VCAM-1)、细胞间粘附分子-1(ICAM-1)浓度变化。方法:应用酶联免疫吸附分析法测定56例CHF患者和55名健康对照者血清中VCAM-1、ICAM-1浓度。结果:CHF患者组血清ICAM-1浓度和VCAM-1浓度均明显高于正常对照组(P<0.05),而且与心功能状态有关。冠心病所致CHF患者与扩张型心肌病所致CHF患者血清ICAM-1与VCAM-1无显著性差别(P>0.05)。结论:CHF患者血清VCAM-1和ICAM-1浓度升高,而且VCAM-1浓度与心力衰竭的程度有关。提示炎症有可能在充血性心力衰竭发病机制中起作用。     

慢性充血性心力衰竭患者血清sICAM-1与血管紧张素Ⅱ相关性研究

目的　研究慢性充血性心力衰竭 (CHF)患者血清可溶性细胞间粘附分子 - 1(s ICAM- 1)和血管紧张素 (Ang )的变化 ,并探讨两者之间的关系。方法　分别采用酶联免疫吸附法和放射免疫法测定 6 0例 CHF患者 (CHF组 )及 2 0例健康人 (正常对照组 )血清 s ICAM- 1及血浆 Ang 水平 ,进行比较和相关分析。结果　 CHF组血清 s ICAM-1及血浆 Ang 水平均较正常对照组明显增高 (P<0 .0 1) ,其增高程度与心功能状态有关。血清 s ICAM- 1与血浆Ang 水平呈正相关 (r=0 .4 91,P<0 .0 1)。结论　 CHF患者血清 s ICAM- 1和血浆 Ang 均增加 ,两者共同作用促进 CHF的发生和发展。     

心力衰竭患者血清胱抑素-C、血管细胞间黏附分子-1和细胞间黏附分子-1水平的表达及意义

目的观察心力衰竭患者血清胱抑素(Cys)-C、血管细胞间黏附分子(VCAM)-1、细胞间黏附分子(ICAM)-1的水平及意义。方法确诊为心力衰竭患者58例作为观察组,25例经体检证实为无明显器质性病变的成人血清标本作为对照组。检测两组血清中Cys-C、VCAM-1和ICAM-1的表达。结果观察组血清中Cys-C、VCAM-1和ICAM-1的表达明显高于对照组(均P<0.05),观察组血清中Cys-C、VCAM-1和ICAM-1的表达与心力衰竭的分级相关,相关性分析显示VCAM-1和ICAM-1呈正相关,其他指标间未见明显相关性。结论心力衰竭患者血清中Cys-C、VCAM-1和ICAM-1高表达对病变的发生和进展有一定的促进作用;VCAM-1和ICAM-1有协同作用。     

糖尿病患者血清可溶性细胞间粘附分子-1和可溶性血管细胞粘附分子-1变化的研究

目的　研究糖尿病患者血清可溶性细胞间粘附分子 - 1(s ICAM- 1)和可溶性血管细胞粘附分子 - 1(s VCAM- 1)水平的变化。方法　应用酶联免疫吸附法 (EL ISA)检测了 18例 1型糖尿病和 47例 2型糖尿病患者及 2 0例健康对照者的血清 s ICAM- 1、s VCAM- 1以及甘油三酯 (TG)水平。结果　 1血清 s ICAM- 1和 s VCAM- 1水平 ,1型、2型糖尿病患者组均显著高于健康对照组 (P<0 .0 5～ 0 .0 1) ,2型糖尿病有微血管病变组又高于无微血管病变组 (P<0 .0 5～ 0 .0 1) ,1型糖尿病与 2型糖尿病组之间无显著性差异 ;2血清 s VCAM- 1水平 ,2型糖尿病的高甘油三酯血症组 (A组 )、高甘油三酯血症合并高血压组 (B组 )高于单纯高血压组 (C组 )和甘油三酯、血压正常组 (D组 ) (P均 <0 .0 5 ) ;3 1型糖尿病和 2型糖尿病患者血清 s ICAM- 1和 s VCAM- 1之间均呈正相关关系 (r=0 .83、0 .5 3,P均 <0 .0 1)。结论　 12型糖尿病患者血清 s VCAM- 1升高与高甘油三酯血症有关 ;2血清 s ICAM- 1和 s VCAM- 1参与了糖尿病微血管病变的发病过程 ,并可作为糖尿病病情变化的监测指标     

2型糖尿病患者血清C反应蛋白与可溶性细胞粘附分子水平变化的临床意义

目的　探讨 2型糖尿病患者血清 C反应蛋白 (CRP)、可溶性细胞粘附分子水平变化及其与血管并发症的关系。方法　采用 EL ISA法检测 12 7例 2型糖尿病患者 (糖尿病组 )血清 CRP、可溶性血管细胞间粘附分子 - 1(s VCAM- 1)和可溶性细胞间粘附分子 - 1(s ICAM- 1)水平 ,并与 6 4例健康人 (对照组 )进行比较。结果　糖尿病组血清 CRP、s ICAM- 1、s VCAM- 1均明显高于对照组 ,有极显著性差异 (P <0 .0 1) ;有血管并发症者CRP、s ICAM- 1、s VCAM- 1明显高于无血管并发症者 (P<0 .0 1) ,大血管并发症、微血管并发症和大血管与微血管并发症并存者各指标比较差异均有显著性 (P <0 .0 1)。糖尿病组血清 CRP水平与 s ICAM- 1、s VCAM- 1水平变化呈正相关 (r =0 .5 76～ 0 .6 2 4 ,P <0 .0 1)。结论　血清 CRP、 s ICAM- 1、 s VCAM- 1相互作用、可能参与了糖尿病的发生与发展 ,并与血管并发症的发生与发展有密切关系     

2型糖尿病患者外周血粘附分子变化及甘糖酯干预治疗的初步研究

为研究 2型糖尿病患者血清中可溶性细胞间粘附分子 - 1( s ICAM- 1)、血管细胞粘附分子 - 1( s VCAM-1)及单个核细胞表面细胞间粘附分子 - 1( ICAM- 1)、血小板表面颗粒膜蛋白 - 14 0 ( GMP- 14 0 )与大血管病变间的关系 ,并观察甘糖酯的疗效 ,对 4 5例 2型糖尿病患者及 2 0例正常对照者用 EL ISA法测定其 s ICAM- 1及 s VCAM-1,流式细胞仪测定 ICAM- 1及 GMP- 14 0。 2型糖尿病患者分为有大血管病变组 ( 19例 )和无大血管病变组 ( 2 6例 ) ,部分患者经胰岛素或胰岛素 甘糖酯治疗 2周后复查。结果显示 ,2型糖尿病患者 s ICAM- 1、s VCAM- 1、I-CAM- 1、GMP- 14 0显著高于正常对照组 ,其中 s ICAM- 1、s VCAM- 1、ICAM- 1有大血管病变组显著高于无大血管病变组。胰岛素治疗后上述粘附分子无明显变化 ,胰岛素 甘糖酯治疗能够显著降低 s VCAM- 1、ICAM- 1、GMP-14 0 ( P<0 .0 5 )     

充血性心力衰竭患者血清心肌营养素1、细胞间黏附分子1、N-末端脑钠肽原水平变化及与心功能关系

目的 观察充血性心力衰竭(CHF)患者血清心肌营养素1(CT-1)、细胞间黏附分子1(ICAM-1)及N-末端脑钠肽原(NT-proBNP)水平变化,并分析其与心功能关系。方法 选取山东省立第三医院2018年4月至2019年8月112例CHF患者为观察组,按照美国纽约心脏病学会(NYHA)心功能分级分为三个亚组(II级组、III级组、IV组),并取同期50例体检健康者作为对照组,检测各组血清CT-1、ICAM-1、NT-proBNP水平,并利用超声仪测定心功能指标[左心室射血分数(LVEF)、左心室收缩末内径(LVESD)与左心室舒张末内径(LVEDD)],进行相关性分析。结果 观察组血清CT-1、ICAM-1、NT-proBNP水平显著高于对照组(t=18.919、14.795、127.439,P 0.05);CHF患者不同心功能分级亚组血清CT-1、ICAM-1、NT-proBNP水平比较差异均有统计学意义(F=102.424、11.194、127.439,P 0.05),IV级组血清CT-1、ICAM-1、NT-proBNP水平明显高于II级组与III级组(P 0.05),III级组明显高于II级组(P 0.05)。CHF患者不同心功能分级亚组心功能指标比较差异均有统计学意义(F=84.148、30.930、21.158,P 0.05),IV级组患者LVEF明显低于II级组与III级组(P 0.05),LVESD、LVEDD明显大于II级组与III级组(P 0.05),III级组LVEF明显低于II级组(P 0.05),LVESD、LVEDD明显大于II级组(P 0.05)。Pearson分析显示血清CT-1、ICAM-1、NT-proBNP与LVEF呈负相关(r=-0.978、-0.989、-0.991,P 0.05)。结论 CHF患者血清CT-1、ICAM-1、NT-proBNP水平有异常升高改变,且心功能损伤越严重,升高程度越大,与LVEF呈显著负相关。     

老年骨折延迟愈合患者血清IGF-1、sICAM-1、sVCAM-1、β-CTX水平的表达及临床意义

目的探讨老年骨折延迟愈合患者血清胰岛素样生长因子(IGF)-1、人可溶性细胞间黏附分子(s ICAM)-1、血清可溶性血管细胞黏附分子(s VCAM)-1和I型胶原羧基端肽β特殊序列(β-CTX)水平及临床意义。方法老年骨折延迟愈合患者60例作为研究组,另选取同期收治的骨折正常愈合老年患者60例作为对照组。分别于骨折后1、6、12 w应用双抗体酶联免疫吸附试验检测血清IGF-1、s ICAM-1、s VCAM-1和β-CTX水平,并对比不同年龄、不同骨折类型骨折延迟愈合患者血清IGF-1、s ICAM-1、s VCAM-1和β-CTX水平,采用Pearson相关分析IGF-1、s ICAM-1、s VCAM-1和β-CTX水平与年龄、骨折类型的相关性。结果骨折后6 w、12 w两组患者血清IGF-1和β-CTX水平较骨折后1 w升高,s ICAM-1、s VCAM-1水平较骨折后1 w降低(P<0.05),研究组血清IGF-1和β-CTX水平低于对照组,s ICAM-1、s VCAM-1水平高于对照组(P<0.05)。骨折后6 w、12 w 60~70岁组血清IGF-1和β-CTX水平高于>70岁组,s ICAM-1、s VCAM-1水平低于>70岁组(P<0.05)。闭合性骨折、开放性骨折患者各时间段血清IGF-1、s ICAM-1、s VCAM-1和β-CTX水平比较无统计学意义(P>0.05)。骨折延迟愈合患者血清IGF-1和β-CTX与年龄呈负相关(r=-0.523,-0.571,P=0.018,0.015),血清s ICAM-1、s VCAM-1与年龄呈正相关(r=0.489,0.478,P=0.022,0.025),血清IGF-1、s ICAM-1、s VCAM-1和β-CTX与骨折类型无相关性(P>0.05)。结论老年骨折延迟愈合患者血清IGF-1、β-CTX明显降低,s ICAM-1、s VCAM-1明显升高,其水平与骨折延迟愈合密切相关,是反映骨折延迟愈合的良好指标。     

充血性心力衰竭患者可溶性细胞间粘附分子-1检测的临床意义

目的 :探讨充血性心力衰竭 （CHF）患者血清可溶性细胞间粘附分子 - 1（s ICAM- 1）的水平与 CHF患者心功能状态的关系。方法 :采用酶联免疫吸附法 （EL ISA）检测 84例 CHF患者 s ICAM- 1水平并与 30例健康人作对照 ,通过彩色多普勒超声心动图测定 CHF患者左室射血分数 （L VEF值 ）。结果 :1CHF患者 s ICAM- 1水平 （5 88± 15 2μg· L- 1 ）较对照组 （16 7± 35μg· L- 1 ）明显升高 ,有显著性差异 （P<0 .0 1）。 2 s ICAM- 1水平随着心功能不全的加重而升高 ,心功能 级患者高于心功能 , 级患者 （P<0 .0 5 ） ,3L VEF值和 s ICAM- 1水平 ,两者呈显著的负相关（r=- 0 .5 5 ,P<0 .0 1）。结论 :s ICAM- 1在 CHF的发病机制中起重要作用 ,s ICAM- 1水平可能是 CHF患者心功能程度判定和疗效观察的有价值的检测指标     

慢性阻塞性肺疾病患者血清基质金属蛋白酶及其抑制因子与细胞黏附因子和血管内皮黏附因子的关系研究

目的探讨慢性阻塞性肺疾病(COPD)患者血清基质金属蛋白酶-9(MMP-9)及其抑制因子(TIMP-1)的变化与细胞黏附因子-1(ICAM-1)、血管内皮黏附因子-1(VCAM-1)之间的关系。方法应用酶联免疫吸附试验(ELISA)检测2005年1月至7月哈尔滨医科大学附属第一医院呼吸内科收治的58例COPD患者和同期来医院进行健康体检的30名正常人血清中MMP-9,TIMP-1、ICAM-1和VCAM-1的质量浓度,将MMP-9、TIMP-1和MMP-9/TIMP-1比值与ICAM-1、VCAM-1及第一秒用力呼气容积(FEV1)占预计值百分比(FEV1%)、1秒率(FEV1/FVC%)进行相关性分析。结果(1)COPD患者的MMP-9、TIMP-1、ICAM-1、VCAM-1血清质量浓度[(128.89±115.84),(228.28±107.13),(203.98±70.37),(352.98±117.73)μg/L]明显高于对照组[(30.65±18.43),(133.69±41.41),(148.35±23.77),(233.57±36.65)μg/L],差异均具有显著性意义(P均<0.01)。(2)COPD组血清MMP-9与ICAM-1、VCAM-1质量浓度呈正相关(P均<0.05);血清TIMP-1与ICAM-1、VCAM-1质量浓度呈正相关(P均<0.01);血清MMP-9、TIMP-1、ICAM-1、VCAM-1质量浓度与FEV1%及FEV1/FVC%均呈明显负相关(P均<0.01);MMP-9/TIMP-1比值与FEV1%及FEV1/FVC%均具有明显负相关(P均<0.05)。结论(1)COPD患者血中ICAM-1、VCAM-1增加与MMP-9、TIMP-1增加具有相关性,是COPD发病中基质金属蛋白酶降解细胞外基质的重要调节因素。(2)COPD患者血清MMP-9、TIMP-1明显增加,MMP-9/TIMP-1比值增加,与气流阻塞成负相关,MMP-9、TIMP-1是引起气流阻塞很重要的因素。     

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.     

CYP1A1 , GSTM1 , GSTT1 and NQO1 polymorphisms and colorectal adenomas in Japanese men

AIM: To investigate the role of functional genetic poly-morphisms of metabolic enzymes of tobacco carcinogens in the development of colorectal adenomas. METHODS: The study subjects were 455 patients with colorectal adenomas and 1052 controls with no polyps who underwent total colonoscopy in a preretirement health examination at two Self Defense Forces hospitals. The genetic polymorphisms studied wereCYP1A1*2A (rs 4646903), CYP1A1*2C (rs 1048943), GSTM1 (null or non-null genotype), GSTT1 (null or non-null genotype) and NQO1 C609T (rs 1800566). Genotypes were determined by the polymerase chain reaction (PCR)-restriction fragment length polymorphism or PCR method using genomic DNA extracted from the buffy coat. Cigarette smoking and other life-style factors were ascertained by a self-administered questionnaire. The associations of the polymorphisms with colorectal adenomas were examined by means of OR and 95%CI, which were derived from logistic regression analysis. Statistical adjustment was made for smoking, alcohol use, body mass index and other factors. The gene-gene interaction and effect modification of smoking were evaluated by the likelihood ratio test. RESULTS: None of the five polymorphisms showed a significant association with colorectal adenomas, nor was the combination of GSTM1 and GSTT1 . A borderline significant interaction was observed for the combination of CYP1A1*2C and NQO1 (P = 0.051). The OR associated with CYP1A1*2C was significantly lower than unity among individuals with the NQO1 609CC genotype. The adjusted OR for the combination of the CYP1A1*2C allele and NQO1 609CC genotype was 0.61 (95%CI: 0.42-0.91). Although the interaction was not statistically significant (P = 0.24), the OR for individuals carrying the CYP1A1*2C allele and GSTT1 null genotype decreased significantly compared with those who had neither CYP1A1*2C allele nor GSTT1 null genotype (adjusted OR: 0.69, 95%CI: 0.49-0.97). Smoking did not modify the associations of the individual polymorphisms with colorectal adenomas. There w     

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.     

The target of ezetimibe is Niemann-Pick C1-Like 1 (NPC1L1)

Ezetimibe is a potent inhibitor of cholesterol absorption that has been approved for the treatment of hypercholesterolemia, but its molecular target has been elusive. Using a genetic approach, we recently identified Niemann-Pick C1-Like 1 (NPC1L1) as a critical mediator of cholesterol absorption and an essential component of the ezetimibe-sensitive pathway. To determine whether NPC1L1 is the direct molecular target of ezetimibe, we have developed a binding assay and shown that labeled ezetimibe glucuronide binds specifically to a single site in brush border membranes and to human embryonic kidney 293 cells expressing NPC1L1. Moreover, the binding affinities of ezetimibe and several key analogs to recombinant NPC1L1 are virtually identical to those observed for native enterocyte membranes. KD values of ezetimibe glucuronide for mouse, rat, rhesus monkey, and human NPC1L1 are 12,000, 540, 40, and 220 nM, respectively. Last, ezetimibe no longer binds to membranes from NPC1L1 knockout mice. These results unequivocally establish NPC1L1 as the direct target of ezetimibe and should facilitate efforts to identify the molecular mechanism of cholesterol transport.     

Interleukin 1 (IL 1)

Interleukin 1 is an essential factor of macrophage dependent T cell activation and has a large quantity of other biological activities. This paper gives a review of present knowledge of Interleukin 1. In addition to biochemical properties, the IL 1 production and IL 1 activities, methods for determining of IL 1 and inhibitory factors of IL 1 induced T cell proliferation are described.     

Pandemic H1N1 influenza

The 2009 H1N1 influenza A virus that has targeted not only those with chronic medical illness, the very young and old, but also a large segment of the patient population that has previously been afforded relative protection - those who are young, generally healthy, and immune naive. The illness is mild in most, but results in hospitalization and severe ARDS in an important minority. Among those who become critically ill, 20-40% will die, predominantly of severe hypoxic respiratory failure. However, and potentially in part due to the young age of those affected, intensive care with aggressive oxygenation support will allow most people to recover. The volume of patients infected and with critical illness placed substantial strain on the capacity of the health care system and critical care most specifically. Despite this, the 2009 pandemic has engaged our specialty and highlighted its importance like no other. Thus far, the national and global critical care response has been brisk, collaborative and helpful - not only for this pandemic, but for subsequent challenges in years ahead.