亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性与血压变化的相关性研究

高血压和高同型半胱氨酸血症是冠状动脉粥样硬化性心脏病(简称冠心病CVD)的独立危险因素。同型半胱氨酸浓度主要受亚甲基四氢叶酸还原酶(MTHFR)C677T基因多态性的影响,尤其受纯合子(即TT基因型)的影响。本综述旨在研究MTHFR C677T基因多态性与血压变化的关系。     

新疆维汉民族胱硫醚-β-合成酶基因多态性及血浆同型半胱氨酸与冠状动脉粥样硬化性心脏病的关系

目的:分析新疆维汉民族胱硫醚-β-合成酶基因T833C多态性及其与同型半胱氨酸水平、冠状动脉粥样硬性心病之间的关系,探讨胱硫醚-β-合成酶基因T833C基因突变是否增加维汉民族冠状动脉粥样硬化性心脏病的危险。方法:选择2004-09/2005-10在新疆医科大学第一附属医院心内科住院并行冠状动脉造影术的320例维汉民族患者,按冠状动脉造影结果分为冠状动脉粥样硬化性心脏病组189例与对照组131例。冠状动脉粥样硬化性心脏病组冠状动脉造影显示,左冠状动脉主干、左前降支、左回旋支或右冠状动脉中至少1支血管狭窄程度≥50%,维吾尔族75例,汉族114例,(56.0±10.5)岁。对照组冠状动脉造影未发现任何可辨认的斑块和狭窄,维吾尔族48例,汉族83例,(53.6±10.8)岁。纳入对象对实验目的均知情同意。应用扩增阻滞突变体系方法分析胱硫醚-β-合成酶基因T833C多态性,用荧光偏振免疫分析法测定血浆同型半胱氨酸水平,并分析同型半胱氨酸及胱硫醚-β-合成酶基因T833C多态性与冠状动脉粥样硬化性心脏病的关联性。结果:320例患者全部进入结果分析。①维汉民族冠状动脉粥样硬化性心脏病组和对照组胱硫醚-β-合成酶基因T833CTT,TC,CC三种基因型分布和等位基因频率分布,以及组内维汉不同民族基因型分布和等位基因频率分布差异均无统计学意义。②维汉民族冠状动脉粥样硬化性心脏病组和对照组中,CC基因型的血浆同型半胱氨酸水平高于同组同民族TC和TT型者[对照组:汉族:(15.52±6.77),(11.01±5.00),(11.05±6.13)μmol/L,维吾尔族:(14.59±5.24),(11.05±1.92),(9.76±3.20)μmol/L;冠状动脉粥样硬化性心脏病组:汉族:(22.92±17.84),(16.06±8.27),(14.67±8.92)μmol/L,维吾尔族:(17.77±8.61),(12.82±6.34),(12.21±5.60)μmol/L,P<0.05];TC和TT基因型之间血浆同型半胱氨酸水平的差异不显著。结论:①同型半胱氨酸代谢关键酶基因胱硫醚-β-合成酶基因T833C存在多态性,维汉民族间略有差异,但不显著。②胱硫醚-β-合成酶基因T833C基因突变可导致血浆同型半胱氨酸明显增高。③胱硫醚-β-合成酶基因T833C基因多态性与新疆维汉民族冠状动脉粥样硬化性心脏病发病无相关性。     

亚甲基四氢叶酸还原酶基因C677T多态性与高血压患者动脉粥样斑块形成的相关性

目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因C677T的多态性以及与高血压患者动脉粥样斑块形成的相关性。方法应用PCR-金磁微粒层析法检测246例高血压患者C677T基因的多态性,循环酶法检测高血压患者血清同型半胱氨酸水平,采用彩色超声仪进行颈动脉以及冠状动脉粥样斑块的检测。结果 246例高血压患者中有斑块178例,无斑块68例。有斑块组TT基因型频率和T等位基因频率显著高于无斑块组(47.3%vs.15.9%,P0.01;43.5%vs.30.1%,P0.01),有斑块组血浆中Hcy水平[(21.13±8.22)μmol/L]高于无斑块[(12.58±7.21)μmol/L],差异有统计学意义(P0.05)。TT纯合子患者的颈动脉内膜及冠状动脉厚度高于CT型和CC型者,差异有统计学意义(P0.05)。高Hcy血症(OR=2.48,95%CI:1.42~3.71,P=0.03)为动脉粥样硬化斑块形成的独立危险因素中。结论亚甲基四氢叶酸还原酶基因C677基因中位点C突变为T明显增加了高血压患者动脉粥样斑块形成的风险。     

中国西北地区人群高同型半胱氨酸血症、亚甲基四氢叶酸还原酶多态性与缺血性脑卒中的关系

背景血浆中总同型半胱氨酸水平增高是缺血性脑卒中的一项危险因素,5,10-亚甲基四氢叶酸还原酶是同型半胱氨酸代谢途径中的关键酶.关于5,10-亚甲基四氢叶酸还原酶与缺血性脑卒中的关系还存在争议.目的通过检测中国西北地区汉族人群中缺血性脑卒中患者血浆中总同型半胱氨酸水平和5,10-亚甲基四氢叶酸还原酶基因两个位点C677T和A1298C的基因表型,探讨三者之间的关联性.设计病例-对照实验.单位吉林大学第一附属医院神经内科,解放军第四军医大学西京医院神经内科.对象病例组随机选取2001-11/2002-05解放军第四军医大学西京医院神经内科经CT或磁共振确诊的缺血性脑卒中患者97例,男71例,女26例.对照组94例,无脑卒中病史,其中男58例,女36例.以上两组受试者有脑出血,癌症,肾功能障碍及服用维生素和雌激素的排除在外.方法血浆总同型半胱氨酸水平用全自动荧光偏振免疫分析法检测,5,10-亚甲基四氢叶酸还原酶基因两个位点C677T和A1298C的基因表型用聚合酶链式反应-限制性片段多态性分析法检测.主要观察指标脑卒中患者C677T和A1298C的基因型频率,血浆总同型半胱氨酸水平.结果677T等位基因在病例组的分布明显高于对照组(59.3%,44.7%,P=0.006),但是1298C等位基因的频率在两组间较接近(22.7%,19.7%,P＞0.05).677TT纯合子与高同型半胱氨酸血症显著相关(P＜0.01).Logistic分析表明,C677T突变及高同型半胱氨酸血症者患缺血性脑卒中的OR值分别是1.87和1.03(P＜0.05).结论高同型半胱氨酸血症是缺血性脑卒中的危险因素.C677T基因突变与缺血性脑卒中的发生相关,显著影响血浆总同型半胱氨酸水平,可能是缺血性脑卒中的一个独立的遗传危险因素.     

新疆哈萨克族人群同型半胱氨酸及其代谢酶基因多态性与原发性高血压的关系

背景:新疆哈萨克族人群高血压的发病率居全国前列,但其发病机制至今未明.有报道证实同型半胱氨酸与许多心血管疾病的发病有关,但同型半胱氨酸水平及代谢酶基因多态性与新疆哈萨克族人群原发性高血压是否存在关系尚无报道.目的:探讨同型半胱氨酸水平及亚甲基四氢叶酸还原酶A1298C、甲硫氨酸合酶A2756G多态性与新疆哈萨克族人群原发性高血压的关系.方法:纳入408例哈萨克族受试者,分成两组,高血压组195例,其中男性93例,女性102例,平均年龄(49.44±9.71)岁;对照组213例,其中男性95例,女性118例,平均年龄(40.82±8.87)岁.应用特异引物PCR及聚合酶链反应限制性片断长度多态性(PCR-RFLP)方法,检测两组亚甲基四氢叶酸还原酶基因A1298C、甲硫氨酸合酶A2756G多态位点的基因型;采用酶标免疫吸附法检测血浆同型半胱氨酸水平.结果与结论:高血压组血浆同型半胱氨酸水平明显高于正常对照组(P＜0.05),且血浆同型半胱氨酸水平有性别差异,男性血浆同型半胱氨酸水平明显高于女性(P＜0.05).两组间亚甲基四氢叶酸还原酶A1298C、甲硫氨酸合酶A2756G各多态位点及联合基因的基因型和等位基因频率分布无明显差异(P＞0.05).亚甲基四氢叶酸还原酶A1298C、甲硫氨酸合酶A2756G各基因型和各联合基因型之间的血浆同型半胱氨酸水平比较无明显差异(P＞0.05).结果表明新疆哈萨克族人群亚甲基四氢叶酸还原酶基因A1298C、甲硫氨酸合酶基因A2756G位点多态性与新疆哈萨克族人群原发性高血压的发生无明显的相关性.血浆同型半胱氨酸水平可能是新疆哈萨克族人群高血压发生的危险因素,但不是独立的危险因素.     

血栓弹力图参数指标与MTHFR基因多态性在胎儿不良妊娠结局中的诊断价值

目的通过血栓弹力图参数及亚甲基四氢叶酸还原酶(MTHFR)基因多态性指标回顾性分析胎儿不良结局患者情况,为不良妊娠结局患者提供分子生物学层面诊断依据,并对MTHFR基因多态性的育龄妇女进行早期预防、早期治疗提供诊疗新方案。方法选择符合胎儿不良妊娠结局女性患者病例100例作为不良妊娠组,选取身体健康,有正常妊娠史的育龄妇女病例100例作为对照组,亚甲基四氢叶酸还原酶基因C677T,A1298C多态性应用聚合酶链式反应技术进行限制性片段长度多态性检测;实验组进行血栓弹力图检测及凝血4项检测。结果 A1298C基因多态性(基因型AA、CC、AC;等位基因A、C)在胎儿不良妊娠结局中不良妊娠组与对照组对比无明显差异,P0.05;亚甲基四氢叶酸还原酶基因C677T等位基因C,T频数分布对比差异有统计学意义(χ~2=4.60,P0.05,OR值=1.645,95%CI:1.042~2.595);不良妊娠结局中死胎因素分析,TT型与CT+CC型两组对比,χ~2值为7.49,P0.05,差异显著。血栓弹力图MA值指标对不良妊娠结局患者中,32例亚甲基四氢叶酸还原酶基C677T基因型TT型诊断价值分析,MA值AUC曲线下面积为0.795。结论亚甲基四氢叶酸还原酶C677T多态性TT型伴血栓弹力图参数高凝状态是不良妊娠结局中发生妊娠期死胎的重要因素。     

中国西北地区人群高同型半胱氨酸血症、亚甲基四氢叶酸还原酶多态性与缺血性脑卒中的关系

背景：血浆中总同型半胱氨酸水平增高是缺血性脑卒中的一项危险因素，5，10-亚甲基四氢叶酸还原酶是同型半胱氨酸代谢途径中的关键酶。关于5，10-亚甲基四氢叶酸还原酶与缺血性脑卒中的关系还存在争议。 目的：通过检测中国西北地区汉族人群中缺血性脑卒中患者血浆中总同型半胱氨酸水平和5，10-亚甲基四氢叶酸还原酶基因两个位点C677T和A1298C的基因表型，探讨三者之间的关联性。 设计：病例一对照实验。 单位：吉林大学第一附属医院神经内科，解放军第四军医大学西京医院神经内科。 对象：病例组：随机选取2001-11／2002-05解放军第四军医大学西京医院神经内科经CT或磁共振确诊的缺血性脑卒中患者97例，男71例，女26例。对照组：94例，无脑卒中病史，其中男58例，女36例。以上两组受试者有脑出血，癌症，肾功能障碍及服用维生素和雌激素的排除在外。 方法：血浆总同型半胱氨酸水平用全自动荧光偏振免疫分析法检测，5，10-亚甲基四氢叶酸还原酶基因两个位点C677T和A1298C的基因表型用聚合酶链式反应-限制性片段多态性分析法检测。 主要观察指标：脑卒中患者C677T和A1298C的基因型频率，血浆总同型半胱氨酸水平。 结果：677T等位基因在病例组的分布明显高于对照组（59．3％，44．7％，P=0．006），但是1298C等位基因的频率在两组间较接近（22．7％，19．7％，P〉0．05）。6777T纯合子与高同型半胱氨酸血症显著相关（P〈0．01）。Logistic分析表明，C677T突变及高同型半胱氨酸血症者患缺血性脑卒中的OR值分别是1．87和1．03（P〈0．05）。 结论：高同型半胱氨酸血症是缺血性脑卒中的危险因素。C677T基因突变与缺血性脑卒中的发生相关，显著影响血浆总同型半胱氨酸水平，可能是缺血性脑卒中的一个独立的遗传危险因素。     

Ⅱb型高血脂症患者MTHFR C677T基因多态性研究

目的探讨亚甲基四氢叶酸还原酶C677T基因多态性与Ⅱb型高血脂症的相关性。方法采用TaqMan探针法检测101例Ⅱb型高血脂症患者和150健康体检者MTHFR C677T基因多态性,同时检测血脂和同型半胱氨酸水平。结果Ⅱb型高血脂症组TC、TG、LDL-C、HCY水平均高于健康对照组,差异有统计学意义(P<0.01);同时Ⅱb型高血脂症组CT、TT基因型频率明显高于健康对照组,差异有统计学意义(χ2=6.597,P=0.01)。携带CT、TT基因型个体发病风险是CC基因型的2.4倍(95%CI:1.2161～4.685)。结论 MTHFR C677T基因多态性与Ⅱb型高血脂症发病风险相关联。     

MTHFR C677T/MS A2756G基因多态性及血浆Hcy水平与阿尔茨海默病的关系

目的:探讨亚甲基四氢叶酸还原酶(MTHFR) C677T、蛋氨酸合成酶(MS) A2756G基因多态性及血浆同型半胱氨酸(Hcy)水平与阿尔茨海默病(AD)的关系.方法:用多聚酶链反应技术分析75例AD患者(AD组)及71例健康老人(对照组)的MTHFR C677T、MS A2756G基因多态性及测定血浆Hcy、叶酸和VitB12水平.结果:(1)两组MTHFR C677T、MS A2756G的基因型频率及等位基因频率分布差异无统计学意义(P＞0.05);(2)对照组携带MTHFR T等位基因者血浆Hcv水平升高(P＜0.05);两组血浆Hcy水平与MS基因A2756G基因型不相关(P＞0.05) 结论:MTHFR基因C677T及MS基因A2756G多态性与AD发生不相关,AD患者血浆Hcy水平升高可能主要与体内叶酸、VitB12不足有关     

PCR熔解曲线法检测MTHFR 677T基因多态性在H型高血压诊治中的应用

高同型半胱氨酸血症是指血浆同型半胱氨酸（homocysteine,Hcy）水平的异常升高（Hcy≥10μmol/L）。亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase,MTHFR）是同型半胱氨酸代谢过程中较为重要的关键酶,MTHFR677C/T多态性可引起血浆Hcy水平的增高,研究发现MTHFR677C/T突变是中国人患有高同型半胱氨酸血症的重要原因之一。     

Measurement of L-carnitine and acylcarnitines in body fluids and tissues in children and in adults

We have developed a reliable and validated radio-enzymatic method for the assay of L-carnitine and acylcarnitines, using a modification of existing methods. The sensitivity of the assay is 10 mumol/l using 10 microliters of plasma or urine. It is also suitable for measurements of carnitine in a 10 mg sample of liver or muscle obtained by percutaneous biopsy. The use of N-ethylmaleimide in the reaction mixture together with an excess of [1-14C]acetyl CoA ensures that the reaction proceeds to completion and a linear response is obtained. Using this method control ranges have been established for plasma and urine carnitine concentrations in healthy children and adults, and for the carnitine content of liver and muscle in adults. No significant difference was found between fasting and post-prandial plasma carnitine levels. An age-related increase was found in urinary total carnitine and acylcarnitine concentration throughout childhood. These data provide a reliable basis for studies of patients with abnormal carnitine and acylcarnitine metabolism, distribution and excretion.     

Activity of amikacin and ampicillin in succession and in combination

One strain each of Escherichia coli and Streptococcus faecalis were exposed to amikacin and ampicillin in combination as well as in succession. Exposure to ampicillin for 1 hr followed by amikacin for 3 or 4 hr had the greatest antibacterial activity when the antibiotics were applied in succession. The least effective exposures for both organisms were 1 hr to amikacin followed by 3 or 4 hr to ampicillin. Exposure to the antibiotics in combination each at 1 MIC had the overall greatest antibacterial activity. Simultaneous exposure to the antibiotic combination does not necessarily mean simultaneous activity of both ampicillin and amikacin on the E. coli. The cell wall autolytic activities produced by ampicillin are triggered within 10 min after physical contact with the bacteria. In contrast, amikacin requires at least 30 min after physical contact to manifest its activity on the ribosome. Although physical exposure to both antibiotics in the combination is simultaneous, the specific activity of each is in fact sequential, with ampicillin acting first. This explains the synergistic effect of the combination. It appears, therefore, that the synergistic or antagonistic affect of a drug combination is determined by the sequence and timing of the antibacterial manifestations of its components.     

Sites of in vivo extraction and interconversion of testosterone and androstenedione in dogs

The interconversion and extraction of testosterone and androstenedione across and within different tissues or areas have been studied by the constant infusion technique. The results were calculated using the (3)H/(14)C ratios and radioactive concentrations of testosterone and androstenedione obtained from afferent and efferent blood and tissues at equilibrium. In each tissue studied, the interconversion between testosterone and androstenedione inside the tissue was significantly higher than the corresponding interconversion across the tissue. The pulmonary contribution to the total interconversion between testosterone and androstenedione was far more important than that of any of the other tissues studied. The hepatic metabolic clearance rates of testosterone and androstenedione were not different from their metabolic clearance rates in the mesenteric area. The extraction of each of these compounds, although not negligible, was lower in the kidney and the femoral bed compared with the extraction in the liver and the mesenteric area. Finally, with the possible exception of the liver, testosterone and androstenedione were more completely metabolized when they originated from the cells than from afferent blood.The evaluation of these different tissue transfer constants provides more precise information concerning the relative importance of different sites in the metabolism of these interconverting hormones.     

Role of oxidants and antioxidants in atherosclerosis: results of in vitro and in vivo investigations

Both in vitro and in vivo studies have shown that oxidants are central in the development of atherosclerosis. Consequently, additional studies evaluated the protective effects of various natural and synthetic antioxidants, alone and in combination, with most studies focusing on alpha-tocopherol (vitamin E). Here, we summarize the role of oxidants in the pathomechanism of atherosclerosis. We also discuss epidemiological studies and others focused on the protective effect of vitamin E against atherosclerosis. Other antioxidants are also considered if they were included in studies involving vitamin E. The protective effect of antioxidants on atherosclerotic pathomechanisms has been confirmed in vitro, but only in some animal studies. Various epidemiological and observational studies have produced conflicting results on the protective effect of antioxidants. Most studies of primary or secondary prevention failed to show a protective effect. These conflicting results are biased by a number of factors, including differences between the study groups. Therefore, we describe these studies in detail.     

纤维支气管镜在儿童咯血诊断与治疗中的应用

目的 评价纤维支气管镜术在儿童咯血病因诊断及治疗中的价值以及安全性.方法 应用用日本产Olympus BF 3c-40纤维支气管镜(最小外径3.6 mm)给58名咯血原因不明的患者行纤维支气管镜检查,并予镜下局部止血治疗.判断出血部位、观察病变情况和出血的原因、临床表现、其他辅助检查、治疗及转归等进行综合分析.结果 引起咯血的主要疾病为气管支气管、肺部的炎症24例(41.3%)、支气管内膜结核12例(20.7%)、支气管异物8例(13.7%)、特发性肺含铁血黄素沉着症7例(12.1%)、支气管扩张4例(6.9%)、心肺血管发育异常1例,原因不明2例.诊断阳性率为96.5%.镜下发现有活动性出血18例,镜下局部止血治疗后显效者10例,有效者8例,有效率为100%.术中并发短暂低氧血症(SaO2＜85%,＜20 s)15例,加大吸氧流量后均改善;术后发热3例均为低热,24 h后热退.结论 纤维支气管镜检查可明确出血部位及原因并可进行局部治疗,且安全的有效.     

Pharmacokinetics and tolerance of flunitrazepam in neonates and in infants.

OBJECTIVE: To study the pharmacokinetics of flunitrazepam (used for sedation in neonates and infants), to determine the influence of both gestational and postnatal age on the pharmacokinetic parameters, and to analyze the relationship between the hemodynamic parameters and flunitrazepam plasma concentration. METHODS: Flunitrazepam was infused for 20 minutes as a single dose (0.2 mg x kg(-1)) and as multiple doses (0.1 mg x kg(-1)). Six to eight 1-mL blood samples were collected per patient. Flunitrazepam plasma concentration was measured by gas chromatography-mass spectrometry. RESULTS: Thirty-one patients (25 neonates and six infants) were included in the study. Only three of them received multiple doses. After the single dose (n = 28), half-life was 22.6 +/- 7.3 hours, clearance was 0.15 +/- 0.14 L x kg x h(-1), and volume of distribution was 4.6 +/- 4.1 L x kg(-1) (mean +/- SD). Plasma clearance and volume of distribution significantly increased with postnatal age (P < .05), but no pharmacokinetic parameter varied significantly with gestational age. Diastolic blood pressure significantly decreased with increasing flunitrazepam plasma concentrations (P < .05). CONCLUSION: Postnatal age but not gestational age influenced flunitrazepam pharmacokinetic parameters in neonates and infants. Diastolic blood pressure was inversely correlated to flunitrazepam plasma concentration.