对氧磷酸酯酶-1Glu-Arg192位多态性与冠心病关系的研究

目的探讨对氧磷酸酯酶-1(PON-1)基因Glu-Arg192位多态性、血清PON-1活性与冠心病的关系。 方法用多聚酶链限制片段多态性反应技术对123例冠心病(CHD)患者(CHD组)及110例正常人(正常对照组)的PON-1192位进行基因分型，用酚乙酸酯为底物测定血清PON-1活性。 结果重庆居民PON-1基因192A、B等位基因频率在正常对照组为0.43、0.57，CHD组为0.40、0.60。CHD组的PON-1AA、AB、BB基因型的构成比与正常对照组无显著性差异(P＞0.05)，正常对照组3种基因型之间血脂无显著相关(P＞0.05)，CHD组的PON-1活性(75.6±23.5KU/L)比正常对照组(108.4±18.3KU/L)显著下降(P＜0.01)。 结论重庆居民PON-1192B等位基因与CHD无关，血清PON-1活性与CHD有一定的关系。     

血清对氧磷酶-1水平及其基因L55M位点多态性与冠心病的关系研究

目的探讨血清对氧磷酶(PON)-1水平及其基因L55M位点多态性与冠心病的关系。方法选取2013—2015年在广东医学院附属深圳市福田人民医院心内科住院的患者252例,根据冠状动脉造影检查结果分为冠心病组160例和非冠心病组92例。采用酶联免疫吸附试验(ELISA)测定血清PON-1水平,应用Mass ARRAY时间飞行质谱技术分析PON-1基因L55M位点多态性。结果冠心病组患者血清PON-1水平低于非冠心病组(P0.05)。冠状动脉多支病变及双支病变患者血清PON-1水平低于单支病变患者(P0.05)。两组患者PON-1基因L55M位点基因型、等位基因分布频率比较,差异均无统计学意义(P0.05)。冠心病组LL基因型患者血清PON-1水平低于非冠心病组(P0.05),而两组ML基因型患者血清PON-1水平比较,差异均无统计学意义(P0.05)。结论冠心病患者血清PON-1水平明显降低,而PON-1基因L55M位点多态性与冠心病无关。     

血管紧张素原基因M235T多态性与冠状动脉病变的关系

目的研究我国山西及周边地区人群血管紧张素原基因M235T多态性与冠状动脉病变的关系。方法选择152名行冠状动脉造影的住院患者为研究对象,根据冠状动脉病变支数和积分分组,应用聚合酶链反应结合限制片长多态性对患者的基因型和等位基因进行分析并比较。结果冠状动脉病变支数和积分不同者,其TT基因型分布和T等位基因频率不同,该差异有显著性(χ2分别为29.537、28.560、31.970和31.771,均P<0.01)。病变支数和积分与T等位基因频率均呈正相关关系(r分别为0.396和0.395,均P<0.01)。结论血管紧张素原基因变异与冠状动脉病变支数和冠状动脉积分均具有相关性。T等位基因频率越高,冠状动脉病变支数越多,冠状动脉积分越高。     

载脂蛋白M基因rs707921位点多态性与冠心病易感性的关系

目的检测载脂蛋白M(ApoM)基因rs707921位点的基因多态性,探讨其与冠心病(CHD)的相关性。方法采用单荧光标记探针技术检测111例CHD患者及248例对照组的ApoM rs707921位点单核苷酸多态性,分析其基因型和等位基因频率的分布情况。结果 ApoM rs707921位点3种基因型(AA型、AC型和CC型)在CHD组中分布频率为1.8%、13.5%和84.7%,在对照组中分布频率为2.0%、25.4%和72.6%,两组差异有统计学意义(P=0.039);ApoM rs707921位点A、C等位基因的频率在CHD组和对照组中分布频率分别为8.6%、91.4%和14.7%、85.3%,两组比较差异有统计学意义(P=0.023)。CHD组中AC+AA基因型者甘油三酯水平显著低于CC基因型者(P=0.043)。CHD组rs707921位点多态性不同基因型间冠状动脉病变严重程度差异无统计学意义(P0.05)。结论ApoM基因rs707921位点A等位基因可能降低CHD的发病风险,但与CHD的严重程度无关。     

黏附分子ICAM-1基因C469T多态性与冠心病的关系

目的:探讨中国湖北地区汉族人群黏附分子ICAM-1基因外显子6,469编码处碱基C/T多态性与冠心病(CHD)的关系,以了解CHD发生、发展的遗传机制,通过黏附分子ICAM-1基因型筛选冠状动脉粥样硬化易患人群和CHD患者中高危人群的可能性。方法:①共入选CHD患者145例,其中73例为急性冠状动脉综合征(ACS),72例为稳定型CHD(SCHD),同时入选心电图检查无异常或冠状动脉造影正常者144例为对照组。所有CHD患者均经冠状动脉造影证实。②采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,分析CHD患者和对照组的ICAM-1基因型。结果:CHD组与对照组及CHD组中ACS者与SCHD者ICAM-1基因C469T编码处T等位基因频率的差异均有统计学意义(CHD组比对照组χ2=20·254,P<0·01;ACS比SCHD者χ2=3·981,P<0·05)。基因型频率的相对风险分析发现,TT加CT基因型患CHD的风险是CC基因型的5·288倍(OR=5·288,95%,CI:2·977~9·395)。结论:ICAM-1基因C469T多态性与CHD密切相关,T等位基因可能是CHD发病的遗传易感基因。     

内皮素-1基因Taq I多态性与冠心病的关系

目的探讨内皮素-1(ET-1)基因Taq I多态性与中国汉族人群冠心病(CHD)的关系。方法应用聚合酶链反应(PCR)、限制性片段长度多态性分析(RFLP),对138例中国汉族CHD患者和112例对照组进行ET-1基因Taq I多态性分析。结果CHD组ET-1基因Taq I多态性TT、TC、CC基因型频率与对照组比较,TC和CC基因型频率显着高于对照组,差异有极显着性(X~2=17.5,P<0.01)。T、C等位基因频率与对照组比较,C等位基因频率显着高于对照组,差异有极显着性(X~2= 15.56,P<0.01)。经Logistic回归分析CHD的危险因素显示,ET-1基因Taq I多态性(C等位基因)为CHD的一个独立危险因素。结论ET-1基因Taq I多态性与中国汉族人群CHD的发生具有相关性,C等位基因可能是CHD的易感性标志。     

对氧磷酯酶-1与老年人2型糖尿病关系的研究

目的 探讨血清对氧磷酯酶-1(PON-1)活性、基因Glu-Arg192位多态性与老年人2型糖尿病(DM)及并发症的关系。方法 用酚乙酸酯为底物测定血清PON-1活性;用多聚酶链限制片段多态件反应技术对老年2型DM各组及健康老年人的PON-1基因192位进行基因分型。结果 老年单纯2型DM组PON-1活性为(98.32±21.68)kU/L,比健康对照组显著降低〔(13.29±19.74)kU/L,P<0.01〕,老年2型DM合并大、微血管病变组PON-1活性分别为(73.18±13.00)和(74.02±15.13)kU/L,比老年单纯2型DM组显著降低对(P<0.01)。重庆市老年居民PON-1基因192位A、B等位基因频率在健康对照组为0.44、0.56,老年人单纯2型DM组及大、微血管病变组为0.43、0.57,0.33、0.67和0.38、0.62,老年人2型DM各组与健康对照组比较PON-1、AA、AB、BB基因到分布差异无显著性。结论 PON-1活性在老年2型DM及共发血管病变患者中均显著降低,提示PON-1活性的降低参与了DM血管并发症的发生。重庆市老年居民PON-1基因192位B等位基因与老年人2型DM及2型DM并发血管病变无明显关系。     

中国西北地区汉族人群三磷酸腺苷结合盒转运体A1-V771M与血浆高密度脂蛋白胆固醇水平及冠心病的相关性

目的:探讨中国西北地区汉族人群三磷酸腺苷结合盒转运体A1(ABCA1)的V771 M单核苷酸多态性(SNPs)与血浆HDL水平和冠心病(CHD)的关系。方法:采用病例对照研究,选择经选择性冠状动脉造影(CAG)的中国西北地区汉族人群292例,其中CHD患者176例,正常对照组111例,被剔除5例,聚合酶链反应-限制性片段长度多态性法检测ABCA1-V771 M多态性的基因型,计算V771 M各基因型及等位基因频率分布,分别比较V771 M不同基因型组间临床及血脂生化等指标,分析V771 M多态性对HDL-C水平和CHD的影响。结果:中国西北地区汉族人群的ABCA1-V771 M多态性分布符合Hardy-Weinberg平衡规律,V、M等位基因频率分别为33.91%和66.09%。MM型的HDL-C水平明显低于VV加VM型(P<0.01),但其余血脂成分水平与V771 M各基因型均无相关性(P>0.05)。M等位基因在CHD组的分布频率明显高于V等位基因(P<0.05),M等位基因相关的冠状动脉病变程度显著高于V等位基因(P<0.05),ABCA1-V771 M3种基因型的急性心肌梗死发生率差异无统计学意义(P>0.05)。结论:在中国西北地区汉族人群中,ABCA1-V771 M多态性不仅与血浆HDL-C水平明显相关,而且与CHD易感性及冠状动脉病变严重程度明显相关,V771 M的M等位基因具有致冠状动脉粥样硬化和CHD的遗传学功能。     

G蛋白β3亚单位基因和α-内收蛋白基因多态性与早发冠心病的相关性研究

目的 观察G蛋白β3亚单位基因(GNB3)C825T和α-内收蛋白基因(ADD1)CA60W多态性在中国早发冠心病(coronary heart disease,CHD)患者中的分布情况及特点,探讨CHD发生的遗传学机制。方法 采用聚合酶链反应和限制性片段内切酶的方法检测了342例早发CHD患者(冠状动脉造影证实,其中男性275例,年龄<55岁,女性67例,年龄<65岁)及133例对照(冠状动脉造影阴性)的GNB3基因C825T和ADDl基因G460W多态性。结果 GNB3基因C825T多态性在两组人群中的分布差异有显著性,CHD组T等位基因和TT基因型频率显著高于对照组(P<0.05),ADD1基因CA60W的等位基因和基因型频率两组比较差异均无显著性(P>0.05)。Logistic回归分析结果显示:在调整了其他危险因素后,T等位基因携带者和具有TT基因型者早发CHD的相对危险度增加(T等位基因:OR=1.8,95％CI为1.117～3.040,P=0.017;TT 基因型:OR=2.4,95％CI为1.312～4.254,P=0.004)。进一步的联合基因型分析显示:同时具有GNB3 825TF基因型和ADD1 460WW基因型者比单独有825TT基因型者有较高的早发CHD的危险(OR=6.1;95％CI 1.316～27.945,P=0.021)。结论 GNB3基因C825T多态性的825T等位基因和TT基因型可能是CHD早期发病的遗传因素之一。在早发CHD患者中GNB3 825TT基因型和ADD1 460WW基因型相互有一定影     

内皮素-1基因Taq Ⅰ多态性与冠心病的关系

目的 探讨内皮素-1（ET-1）基因Taq Ⅰ多态性与中国汉族人群冠心病（CHD）的关系.方法 应用聚合酶链反应（PCR）、限制性片段长度多态性分析（RFLP）,对138例中国汉族CHD患者和112例对照组进行ET-1基因Taq Ⅰ多态性分析.结果 CHD组ET-1基因Taq Ⅰ多态性TT、TC、CC基因型频率与对照组比较,TC和CC基因型频率显着高于对照组,差异有极显着性（χ2=17.5,P＜0.01）.T、C等位基因频率与对照组比较,C等位基因频率显着高于对照组,差异有极显着性（χ2=15.56,P＜0.01）.经Logistic回归分析CHD的危险因素显示,ET-1基因Taq Ⅰ多态性（C等位基因）为CHD的一个独立危险因素.结论 ET-1基因Taq Ⅰ多态性与中国汉族人群CHD的发生具有相关性,C等位基因可能是CHD的易感性标志.     

Oxaceprol is as Effective as Diclofenac in the Therapy of Osteoarthritis of the Knee and Hip

In this multicentre (five centres in Germany), randomised, double-blind, comparative study, 150 patients with painful degenerative joint disease according to EULAR criteria received either oxaceprol (200 mg three times daily) or diclofenac (25 mg three times daily) for 20 days. Joint function, the primary variable, assessed according to Lequesne’s indices, improved equally in both treatment groups to a clinically relevant degree. Joint mobility improved by approximately 60% in both groups. By the end of therapy in both groups, the period of pain-free walking time had more than doubled and subjectively evaluated pain perception (VAS) was reduced by almost 50% without any significant differences between the treatments. The incidence of adverse drug reactions was similar in both groups but oxaceprol induced milder symptoms. Oxaceprol is as effective and better tolerated than diclofenac in the treatment of osteoarthritis. Received: 13 November 1997 / Accepted: 19 June 1998     

Advances in the immunopathophysiology of the idiopathic inflammatory myopathies: Not as simple as suspected

In the past three decades, not much has changed in the pathophysiologic concepts of dermatomyositis and polymyositis. However, in the past couple of years, many changes have occurred reflecting the extremely complex nature of the immune response in general. New pathophysiologic models are needed, but at present, none of them encompasses all the recent findings. The changing concepts of dermatomyositis and polymyositis offer new opportunities for unraveling these diseases and developing better strategies for prevention and treatment. This article discusses the most important developments and their methodologic short-comings.     

Vascular risk factors correlate to the extent as well as the severity of coronary atherosclerosis

BACKGROUND: Because most acute coronary events result from thrombosis at sites of minor plaque, the extent of non-obstructive coronary artery disease (CAD), rather than simply the number of severe stenoses, might be clinically relevant. OBJECTIVE: To examine the relationship between vascular risk factors and a novel extent score for CAD that measures the percentage of the coronary tree involved with atheromatous plaque, as judged by coronary angiography. METHODS: We assessed the extent and severity of CAD and the presence of vascular risk factors of 429 consecutive eligible patients (296 men, aged 61 +/- 11 years) who presented for elective coronary angiography. Detailed analyses of lipid levels were performed for 126 subjects. RESULTS: The mean extent score was 54 (range 0-100). The presence of diabetes (P < 0.001), current or former smoking (P < 0.005) and a history of hypertension (P < 0.001) were all strongly associated with the CAD extent score, as was severity of disease. For the 283 patients with one or no severe stenosis, diabetes was associated with a greater extent score (57 versus 41%, P < 0.005), as was smoking (49 versus 34%, P < 0.005). For the 126 patients with detailed data on lipid levels, extent of coronary artery disease was independently correlated to age (P < 0.005), male sex (P < 0.05), presence of diabetes (P < 0.05), hypertension (P < 0.05), level of lipoprotein (a) (P < 0.005) and low-density:high-density lipoprotein ratio (P < 0.01) in multivariable analysis. CONCLUSIONS: Extent of CAD, as well as its severity, is significantly associated with traditional vascular risk factors. Because most acute coronary events occur at sites of minor plaque, this might explain the mechanism whereby risk factors confer adverse prognostic significance.     

Motility of Lyme disease spirochetes in fluids as viscous as the extracellular matrix

When properties of extracellular fluids that might regulate the ability of the Lyme disease spirochete to locomote were investigated, the rate of progression correlated with viscoelasticity. Such spirochetes flexed and rotated but did not progress in relatively nonviscous fluids and migrated increasingly rapidly as the viscous characteristics of the medium increased. The viscoelastic properties of various kinds of hyaluronic acid resembled those of a methylcellulose standard. The maximum velocity that spirochetes achieved in such solutions related directly to viscoelasticity rather than to chemical composition. Spirochetes remained motile during 3 h of observation despite 100-fold dilution of the standard nutrient medium. The immobility of Lyme disease spirochetes in media less viscous in character than fixed tissue suggests dissemination via the intercellular ground substance of skin.     

Orlistat is as beneficial as metformin in the treatment of polycystic ovarian syndrome

The objective of this study was to evaluate and compare the effect of treatment with orlistat vs. metformin on the hormonal and biochemical features of patients with polycystic ovarian syndrome (PCOS). Twenty-one Caucasian women with PCOS [mean (+/-SEM) age 27 +/- 0.9 yr and body mass index 36.7 +/- 3.3 kg/m(2)] participated in this prospective, randomized, open-labeled study. All subjects had an 8-wk run-in period of dietary modification and then randomized to receive either metformin (500 mg three times daily) or orlistat (120 mg three times daily) for 3 months. Weight, blood pressure, and fasting blood samples were taken at screening, randomization, and on completion. Insulin resistance (IR) was calculated using the homeostasis model of assessment (HOMA)-IR method [HOMA-IR = (insulin x glucose)/22.5]. The results are expressed as mean +/- SEM. When compared with baseline, treatment with both orlistat [93.5 +/- 11.5 ng/dl (3.24 +/- 0.4 nmol/liter) vs. 114.5 +/- 11.5 ng/dl (3.97 +/- 0.4 nmol/liter), P = 0.039] and metformin [97.2 +/- 11.5 ng/dl (3.37 +/- 0.4 nmol/liter) vs. 120.0 +/- 8.7 ng/dl (4.16 +/- 0.3 nmol/liter), P = 0.048] produced a significant reduction in total testosterone. Treatment with orlistat produced a 4.69% reduction in weight (99.0 +/- 6.0 vs. 94.6 +/- 6.1 kg, P = 0.002), and this reduction was more significant than the reduction produced by metformin (4.69 vs. 1.02%, P = 0.006). There was no significant reduction seen after either treatment group for fasting insulin, HOMA-IR, SHBG, or any of the lipid parameters studied. In this study, orlistat produced a significant reduction in weight and total testosterone. The reduction in total testosterone was similar to that seen after treatment with metformin. Therefore, orlistat may prove to be a useful adjunct in the treatment of PCOS.