小肠脂酸结合蛋白基因多态性与2型糖尿病合并冠心病的关系

为了解小肠脂酸结合蛋白基因（ＦＡＢＰ２）多态性与２型糖尿病合并冠心病（ＣＨＤ）的关系。方法２型糖尿病无冠心病组（ＤＭ－１）６４型糖尿病合并冠心病组（ＤＭ－２）８２例,非糖尿病冠心病组６２例,正常对照组６０例。应用聚合链酶反应（ＰＣＲ）技术检测２６８例对象ＦＡＢＰ２ＨｈａⅠ位点的限制性片段长度多态性（ＲＦＬＰｓ）。结果（１）武汉地区汉族人存在ＰＡＢＰ２ＨｈａＩ多态性位点,可产生Ｔｈｒ５４（－）和Ｔｈ     

载脂蛋白B基因多态性与I型糖尿病并冠心病关系的研究

应用聚合酶链反应（ＰＣＲ）技术对非胰岛素依赖型糖尿病（ＮＩＤＤＭ）４１例、ＮＩＤＤＭ合并冠心病５１例和正常对照组６０例进行载脂蛋白Ｂ基因ＥｃｏＲＩ和ＸｂａＩ酶切位点限制性片段长度多态性（ＲＦＬＰ）研究。结果显示少见等位基因频率在ＮＩＤＤＭ组及ＮＩＤＤＭ并冠心病组均升高。与对照组比较，Ｅ－等位基因频率在糖尿病患者显著升高。ｘ＋等位基因频率升高与ＮＩＤＤＭ并发冠心病明显相关     

2型糖尿病合并冠心病AT1A／C多态性研究

目的　ＡＴ１的Ａｌｌ６６Ｃ基因多态性与２型糖尿病、２型糖尿病合并冠心病的关联。方法用聚合酶链反应－限制性片段长度多态性分析法（ＰＣＲ－ＲＦＬＰ）探查ＡＴ１的Ａｌｌ６６Ｃ 基因多态在正常对照组（７３例）、单纯２型糖尿病组（简称糖尿病组８０例）、２型糖尿病合并冠心病组（简称合并冠心病组４３例）中的基因频率分布,并分析其对以上疾病发病因素的影响。结果 ２型糖尿病合并冠心病组 ＡＴ１的 １１６６Ｃ等位基因频率明显高于对照组（Ｘ２＝６． ０２,Ｐ＜０． ０５）和单纯糖尿病组（Ｘ２＝５．７１,Ｐ＜０．０５）。结论我们的结果提示携带ＡＴ１１１６６Ｃ等位基因的２型糖尿病患者比携带Ａ等位基因更易罹患冠心病。     

醛糖还原酶基因5‘端（AC）n多态性对2型糖尿病患者红细 …

目的 探讨醛糖还原酶（ＡＲ）基因５’端（ＡＣ）ｎ的多态性对２型糖尿病（ＤＭ）红细胞ＡＲ活性的影响。方法 １６３例２型ＭＤ分为无微血管病变（ＮＤＣ）组（６６例）和微血管病变（ＤＭＡＰ）组（９７组），正常对照（ＣＯＮ）组４２例；另按ＡＲ基因５’端（ＡＣ）ｎ的等位基因类型分为ＤＭ携带Ｚ＋２等位基因（ＤＺ＋２）组（５４例）、ＤＭ携带Ｚ－２等位基因（ＤＺ－２）组（３５例）、ＤＭ同时携带Ｚ＋２和Ｚ－２等位基因     

Ⅰ型血管紧张素Ⅱ受体基因A1166C多态性与糖尿病合并冠 …

目的 血管紧张素Ⅱ的Ⅰ型受体基因Ａ１１６６Ｃ多态性与２型糖尿 病及合并冠心病的关系。方法 用聚合酶链反应＝－限制性片段长度多态性（ＰＣＲ－ＲＦＬＰ）分析法探查Ⅰ型ＡＴＲ基因Ａ１１６６Ｃ多性在正常对照组、单纯２型糖尿病缓刑不病合并冠心病组中的基因频率分布。结果 ２糖尿病合并冠心病组Ⅰ型ＡＴＲ的Ｃ等位基因频率明显高于正常对照组和单纯２型糖尿病组，且与甘 油三酯和脂蛋白相关。结论 携带Ｃ等位基因的２型糖     

载脂蛋白B基因多态性与Ⅱ型糖尿病并冠心病关系的研究

应用聚合酶链反应（ＰＣＲ）技术对非胰岛屿纱依赖型糖尿病（ＮＩＤＤＭ）４１例、ＮＩＤＤＭ合并冠心病５１例和正常对照组６０例进行载脂蛋白Ｂ基因ＥｃｏＲ和ＸｂａＩ酶切位点限制性片段长度多态性（ＲＦＬＰ）研究。结果显示少见等位基因频率在ＮＩＤＤＭ组及ＮＩＤＤＭ并冠心病均升高。与对照组比较，Ｅ等位基因频率在糖尿病患者显著升高，等位基因频率升高与ＮＩＤＤＭ并发冠心病明显相关。     

载脂蛋白E基因多态性与Alzheimer病的相关性研究

目的：研究中国老龄人群ＡｐｏＥ等位基因与Ａｌｚｈｅｉｍｅｒ病（ＡＤ）发病危险性的关系。方法选取２２例散发性ＡＤ患者和６４例正常老年人做为研究对象,采用聚合酶链式反应（ＰＣＲ）和限制性片段长度多态性（ＲＦＬＰ）方法鉴定载脂蛋白Ｅ（ＡｐｏＥ）基因型,分析ＡｐｏＥ等位基因及ε４基因剂量与ＡＤ发病的关系。结果ＡｐｏＥε４等位基因与ＡＤ发病关系密切,ＡＤ患者中ε４基因频率较正常对照明显增高,且随着ε４基因剂     

血管紧张素Ⅱ-1型受体基因A1166/C多态性与原发性高血压及血脂水平关系

目的：探讨血管紧张素Ⅱ－１型受体（ＡＴ_１Ｒ）基因 Ａ１１６６／Ｃ多态性与国人原发性高血压的关系,并探讨原发性高血压的发病机制。方法：应用限制性内切酶酶解聚合酶链式反应（ＰＣＲ－ＲＦＬＰ）的方法检测７０例健康人和１１２例高血压患者的ＡＴ_１Ｒ基因型,生化技术测定血脂水平。结果：原发性高血压组的ＡＣ基因型频率２５．７％,Ｃ等位基因频率１２．９％,分别显著高于正常对照组的７．１％和３．６％（Ｐ＜０． ０５）;原发性高血压组的 ＡＴ_１Ｒ基因与血浆 ＬＰ（ａ）水平正相关。结论：提示ＡＴ_１Ｒ基因Ａ１１６６／Ｃ多态性可能是原发性高血压的遗传因素,ＡＴ_１Ｒ基因可能参与脂质的调节。     

ApoAI基因多态性与NIDDM关系的研究

采用限制性片段长度多态性（ＲＦＬＰ）技术，对９０例中国汉族人进行分析，发现载脂蛋白ＡＩ（ＡｐｏＡＩ）Ｍ１等位基因频率在体重指数（ＢＭＩ）≥２４的ＮＩＤＤＭ与ＢＭＩ〈２４的ＮＩＤＤＭ之间、在动脉硬化（ＡＳ）与正常对照组之间均存在显著性差异。此外，ＮＩＤＤＭ件ＡＳ（ＮＡ）的等位基因频率分布与ＮＩＤＤＭ相似，与ＡＳ不同。根据上述结果，认为：ＡｐｏＡＩ基因与ＢＭＩ≥２４的ＮＩＤＤＭ相关联：ＢＭＩ≥２４的Ｎ     

中国汉族系统性红斑狼疮某些易感基因的研究

为了探索我国北方汉族人群人类白细胞抗原－ＤＲ（ＨＬＡ－ＤＲ）及肿瘤坏死因子Ｂ（ＴＮＦＢ）等位基因多态性与系统性红斑狼疮（ＳＬＥ）的易感性关系，对１０６例健康人和４５例ＳＬＥ患者的ＨＬＡ－ＤＲ和对８０例健康人及４５例ＳＬＥ患者的ＴＮＦＢ等位基因，采用多聚酶链反应－限制性酶切片段长度多态性（ＰＣＲ－ＲＦＬＰ）法进行分析。结果显示：ＳＬＥ患者中频率显著升高的等位基因有ＤＲ２［Ｐ＜０．０５，相对危险性（ＲＲ）＝１．５６］及ＤＲ３（Ｐ＜０．０１，ＲＲ＝２．６９）。而ＤＲ５和对照相比呈相反结果（Ｐ＜０．０５，ＲＲ＝０．４３）。ＳＬＥ患者ＴＮＦＢ＊２等位基因频率显著增高（Ｐ＜０．０５，ＲＲ＝１．８４）。提示ＤＲ２、ＤＲ３、ＴＮＦＢ＊２可能是易感等位基因或易感等位基因标记，而ＤＲ５是一拮抗等位基因或拮抗等位基因标记。并研究了ＨＬＡ－ＤＲ、ＴＮＦＢ等位基因与患者血浆中Ｓ蛋白和补体５ｂ－９结合物的复合物（ＳＣ５ｂ－９）的水平和多种自身抗体及狼疮肾炎、狼疮肺炎、狼疮脑病等狼疮并发症之间的相关性，发现ＨＬＡ－ＤＲ２基因与狼疮肾炎的发生存在正相关（Ｐ＜０．０５，ＲＲ＝１．３２）。     

Monoamine oxidase inhibitors and atypical antidepressants.

The following conclusions may be drawn from this article: 1. The age at which subjects are considered "elderly" or "geriatric" varies from study to study. By convention, age 65 is usually taken as the minimum age, yet virtually all studies cited included subjects below 65. Indeed, in a majority of studies, most of the subjects were below the conventional age of 65. Defining the minimum age for geriatric psychopharmacology studies is particularly important because there may be considerable pharmacodynamic and pharmacokinetic heterogeneity in people aged 65 and older. Clinical experience suggests that patients below age 80 tend to respond to medications like late middle-age adults, whereas those above age 80, as a group, are more sensitive to drugs. Because people 80 and above constitute the fastest growing group of Americans, it is essential to conduct more therapeutic clinical trials using them as research subjects. Information gathered from persons aged 60 to 79 may not be relevant to this older age group. 2. The total number of individuals studied in carefully controlled, double-blind research studies of MAOIs, atypical antidepressants, or psychomotor stimulants are relatively few when compared with the number of individuals studied with tricyclic antidepressants, or the number of nonelderly subjects studied. 3. Although many older persons are included in mixed-age research populations, the number of studies specifically designed in the elderly is also remarkably few. 4. In those studies that did focus on older patients, the definition of elderly was extended "downward" to include patients at age 55, or even 50. Whether or not this was done in order to enhance research subject recruitment, the net result is to vitiate any overall conclusion regarding the efficacy of drugs in patients over age 65, the usual lower cutoff for "elderly" or "geriatric" definition. 5. With the exception of a handful of patients receiving fluoxetine and methylphenidate, virtually no research patient above the age of 80 has been studied using any of the compounds discussed in this article. 6. Some of the double-blind studies reviewed are more than a decade old and techniques in research design have changed substantially since those studies were conducted. Many of the earlier studies would not be acceptable according to contemporary research design criteria because of inappropriate or inadequate inclusion criteria, inappropriate or inadequate outcome criteria, and inappropriate or inaccurate diagnostic criteria.(ABSTRACT TRUNCATED AT 400 WORDS)     

Central Monoamine Systems and New Antihypertensive Agents

This review describes the relationship between central monoamine pathways and centrally acting antihypertensive agents. By using antagonists with affinity for α₂-adrenoceptors and also imidazoline receptors we have found that the first generation agents clonidine and α-methyldopa activate α₂-adrenoceptors while the newer second generation antihypertensive agents rilmenidine and moxonidine activate imidazoline receptors. Despite the difference in receptors activated, the hypotension produced by central administration of all agents was attenuated after chemical lesioning of the brainstem noradrenergic or serotonergic pathways suggesting a similar dependence on central monoamine pathways. Since the acute 6-hydroxydopamine-induced release of noradrenaline in the brainstem produces hypotension it suggests that these agents normally mimic brainstem noradrenergic function. By contrast the pressor response shortly following 5,6-dihydroxytryptamine suggests serotonergic neurones in the brainstem are pressor and that part of the anti-hypertensive action of centrally acting antihypertensive agents is mediated by inhibition of bulbar serotonergic pathways. We suggest that the similar haemodynamic and baroreflex effects of the two generations of agents can be explained by the α₂-adrenoceptors and the imidazoline receptors being in series along the noradrenergic and serotonergic pathways.     

Monoamine oxidase inhibitors in hypertension

1. 1. A survey of the literature reveals that the monoamine oxidase inhibitors, 1-isonicotinyl-2-isopropyl hydrazine (iproniazid, Marsilid), betaphenylisopropyl-hydrazine hydrochloride (JB 516, Catron®) and DL-serine-N²-isopropyl hydrazide monohydrochloride (RO4–1038)have antihypertensive effects in man.

2. 2. The monoamine oxidase inhibitors cause primarily postural hypotension and in general are potentiated by the simultaneous administration of chlorothiazide. Their cumulative action permits continuous control of hypertension with infrequent dosage but also creates the danger of prolonged hypotension following overdosage.

3. 3. Their antihypertensive action could not be correlated with their relative potency as monoamine oxidase inhibitors.

4. 4. RO4–1038 appears to be the most effective hypotensive agent and from preliminary observations is without serious side effects or major toxicity in the doses used.

5. 5. The monoamine oxidase inhibitors will probably have an important place in the therapy of hypertension.

     

Monoamine Oxidase and Cerebral Uptake of Dopaminergic Drugs

The brain uptake of amines that do not enter the brain or enter it poorly was promoted by noncompetitive inhibitors of monoamine oxidase, as shown by behavioral and chemical criteria. Mice pretreated with water or enzyme inhibitors other than those mentioned were placid after receiving dopamine (3,4-dihydroxyphenethylamine). Mice pretreated with monoamine oxidase inhibitors (nialamide or iproniazid) showed upon treatment with dopamine the brisk motor responses characteristic of treatment with its precursor, L-dopa (3,4-dihydroxyphenylalanine). After receiving dopamine, intact nialamide-pretreated mice showed marked increases of brain dopamine, in contrast to water-pretreated test mice or water-treated controls. In unilaterally caudectomized, nialamide-pretreated mice, dopamine induced marked lateral curving of the body toward the lesion followed by running in that direction. Noradrenaline or adrenaline induced curving in caudectomized mice, whereas intact ones remained placid.These catecholamines are bound and inactivated by monoamine oxidase. The cerebral uptakes of chemicals that are bound but not inactivated by monoamine oxidase were thereafter tested. Nialamide induced increased behavioral responses to apomorphine and to N-propyl noraporphine, increased cerebral concentrations of both, and a deep coloration of the brain from methylene blue (bound by monoamine oxidase) but not Evans blue (bound by albumin). Even large doses of nialamide, however, failed to affect the behavioral responses to oxotremorine, which has cholinergic rather than adrenergic or dopaminergic properties. Mitochondrial monoamine oxidase seems therefore to play a specific regulatory role in the transport of substances that it binds, either to inactivate or to release them.     

Monoamine oxidase and catechol-o-methyltransferase activity in hamster and rat insulinomas

Hamster and rat insulinomas were assayed for norepinephrine, dopamine and serotonin concentration and for monoamine oxidase and catechol-o-ethyltransferase (COMT) activity. The concentration of norepinephrine (mean 0.55 mumol/kg, range less than 0.20 to 2.64 mumol/kg) and serotonin (mean 5.22 mucol/kg, rang less than 0.6 to 26.5 mumol/kg) in hamster insulinomas were comparable to previously reported concentrations. Dopamine conentration (mean 0.34 mumol/kg, range less than 0.20 to 0.95 mumol/kg) was only 2 to 2.5% of that reported previously. Monoamine oxidase activity of the hamster and rat insulinomas were comparable to those of normal hamster islets. In contrast, the COMT activity of both insulinomas was much greater than the COMT activity of normal pancreatic islets of both species and was greater than in several other tissues and tumours. The tumour COMT, which was predominantly in the cytosol, was Mg2+ dependent and had a comparable sensitivity to inhibition by tropolone as purified beef-liver COMT. Hamster insulinoma monoamine oxidase was more sensitive than rat insulinoma monoamine oxidase to inhibition by tranylcypromine and deprenyl, while rat insulinoma monoamine oxidase was more sensitive to inhibition by clorgyline and was more heat labile.     

Prevalence of Low Monoamine Oxidase Function in Alcoholism

Several studies have found a trend for low platelet monoamine oxidase activity (MAO) in alcoholism but with a great deal of overlap in MAO activity of alcoholics versus controls. The main objective of this study was to carry out a detailed assessment of MAO function that included the measurement of key kinetic parameters (i.e., K_m, V_max) in three groups of male subjects: (a) 51 hospitalized chronic alcoholics, (b) 16 recovering alcoholics with 2–10 years of abstinence, and (c) 21 controls. MAO activity was assayed radio-chemically with [14^C]tyramine as substrate (43–729 μM). The present study demonstrated that alcoholics had low platelet MAO activity (p < 0.05). Kinetic analysis revealed a substantial reduction (p < 0.01) in enzyme V_max values of chronic and recovering alcoholics. Greater than 95% of the alcoholics had V_max values lower than the smallest value of control subjects. Moreover, 100% of the alcoholics in both groups exhibited exceedingly low V_max values that were below the 25th percentile of controls. In summary, results of MAO V_max determinations provided us with a better separation of the alcoholics from controls. Measurements of platelet MAO function that include enzyme V_max may provide us a reliable biochemical marker for alcoholism.