基质金属蛋白酶-9基因多态性与2型糖尿病大血管并发症的相关性研究

目的 探讨基质金属蛋白酶-9(MMP-9)基因启动子区C-1562-T基因多态性与2型糖尿病大血管并发症的相关性.方法 利用PCR-RFLP方法 对288例2型糖尿病患者及120名健康对照者MMP-9基因启动子区C-1562-T位点等位基因和基因型进行测定.结果 实验组和正常对照组间C、T两种等位基因和CC、CT、TT三种基因型分布无差异:实验组中,2型糖尿病无大血管病变组与合并大血管病变组比较CC基因型与C等位基因显著增加.结论 2型糖尿病患者与正常人群中MMP-9基因启动子区C-1562-T基因位点CT和,TT基因型与C、T等位基因频率分布相同;在2型糖尿病人群中,CC基因型与C等位基因在糖尿病无大血管病变者中显著升高,提示其可能是糖尿病大血管病变的保护型基因.     

回、汉两民族2型糖尿病视网膜病醛糖还原酶基因启动子区C（-106）T多态性的比较

目的：探讨甘肃地区回族及汉族人群醛糖还原酶基因启动子区C（-106）T多态性与糖尿病视网膜病的关系以及该多态性在两民族间的差异。方法：应用PCR-RFLP技术检测81例汉族2型糖尿病患者和83例健康汉族对照者ALR的基因型,分别以氧化酶法、放免法、比色法测定空腹血糖、空腹胰岛素、糖化血红蛋白水平。结果：①ALR基因C（-106）T多态各基因型及等位基因分布频率在对照组和2型糖尿病组间差异无统计学意义;糖尿病视网膜病组CT/TT基因型及T等位基因频率较无糖尿病视网膜病组均高,但差异无统计学意义;糖尿病视网膜病组T等位基因及CT/TT基因型分布频率明显高于正常对照组,差异有统计学意义。相对危险度分析发现,CT/TT基因型患糖尿病视网膜病的风险是CC基因型的2.127倍;携带T等位基因患糖尿病视网膜病的风险是C等位基因的1.962倍。②在回、汉两民族2型糖尿病患者中进行比较,回族CT/TT基因型及T等位基因均高于汉族,但是差异无统计学意义。结论：在甘肃地区回、汉两民族人群中都存在ALR基因启动子区C（-106）T多态性,且该位点多态性在两民族间无显著性差异。CT/TT基因型和T等位基因可能与回、汉两民族糖尿病视网膜病的发生相关。     

肾移植中环孢素的血药浓度与多药耐药基因多态性的关系

目的 探讨肾移植术后患者的MDR1C3435T、G2677T/A和C1236T位点的基因多态性对环孢素(CsA)血药浓度的影响.方法 使用荧光偏振免疫分析法(AxsYM)测定65例肾移植患者在术后1 wk和1 mo时的CsA血药浓度(包括峰浓度ρ2和谷浓度ρ0),使用等位基因特异扩增法(ASA-PCR)对患者进行MDR1基因分型,比较不同基因型之间CsA浓度剂量比的差异.结果 在65例患者中,C3435T,CC型25例(38.5%),CT型35例(53.8%),TT型5例(7.7%);G2677T/A,GG型15例(23.1%),GT型21例(32.3%),TT型10例(15.4%),GA型12例(18.5%),AT型6例(9.2%),AA型1例(1.5%);C1236T,CC型10例(15.4%),CT型32例(49.2%),TT型23例(35.4%).C3435T的CT型患者的CsA浓度剂量比略大于CC型和TT型;G2677T/A的从型患者的CsA浓度剂量比略大于其他基因型;C1236T的TT型患者的谷浓度剂量比略大于CC型和CT型,CC型患者的峰浓度剂量比略大于CT型和TT型,但差异均无统计学意义(P＞0.05).结论 在肾移植患者中,MDR1多态性与CsA血药浓度无明显相关性,有待进一步确认.     

N5,N10-亚甲基四氢叶酸还原酶基因多态性与青年脑梗死的关系

目的 研究N5,N10 -亚甲基四氢叶酸还原酶(MTHFR)基因多态性与青年脑梗死的关系.方法 将67例青年脑梗死患者作为病例组,同期71例健康体检者作为对照组,用聚合酶链反应-限制性内切酶片段长度多态性分析(PCR-RFLP)的方法来观察MTHFR 677和1298位点基因型.结果 MTHFR 677位点基因型病例组中TT型为20例,占29.8％;CT型32例,占47.8％;CC型15例,占22.4％;T等位基因频率为53.7％.对照组中TT型30例,占42.2％;CT型34例,占47.9％;CC型7例,占9.9％;T等位基因频率为66.2％.对照组中TT型及T等位基因频率明显高于病例组,2组差异有统计学意义(P＜0.05).MTHFR1298位点基因型病例组中AC型29例,占43.3％;AA型38例,占56.7％;C等位基因频率为21.6％.对照组中AC型14例,占19.7％,AA型57例,占80.3％,C等位基因为9.9％,病例组中AC型及C等位基因频率明显高于对照组,2组差异有统计学意义(P＜0.05).结论 本组人群中MTHFR基因677及1298位点多态性与青年脑梗死都有相关性.     

载脂蛋白C-Ⅲ基因多态性与血脂水平的关系

目的探讨载脂蛋白C-Ⅲ(ApoC-Ⅲ)C-482T基因多态性与血浆脂质的关系.方法用聚合酶链反应-限制性片段长度多态性方法(PCR- RFLP)检测172例心内科住院病人ApoC-Ⅲ基因多态性,同时检测血脂水平.结果ApoC-ⅢC-482T基因型以CT型最多,占57.54%,CC型及TT型分别占33.72%及14.53%,C等位基因频率为59.59%,T等位基因频率为40.41%.各基因型间血脂水平比较,总胆固醇(TC),低密度脂蛋白胆固醇(LDL-C)有显著性差异,P<0.05.进一步两两比较显示,CT型TC较TT型高,P<0.05;CT型LDL-C较CC型、TT型高,P<0.05.结论ApoC-Ⅲ-482T多态性位点与血TC、LDL-C水平关系密切.     

广东汉族人N5,N10-亚甲基四氢叶酸还原酶基因多态性与冠心病的关系初探

目的研究N5,N10-亚甲基四氢叶酸还原酶基因多态性及其与冠心病的关系.方法运用多聚酶链反应-限制片段长度多态性技术检测143例广东汉族正常人和47例冠心病患者N5,N10-亚甲基四氢叶酸还原酶基因C677T多态性.结果N5,N10-亚甲基四氢叶酸还原酶有三种基因型,即纯合子突变型(TT)、杂合子突变型(TC)和正常型(CC).正常组TT型频率为3%,TC型频率为36.5%,CC型频率为60.5%,T等位基因频率为19.6%,C等位基因频率为80.4%;冠心病组TT型频率为4.2%,TC型频率为23.4%,CC型频率为72.4%,T等位基因频率为13.9%,C等位基因频率为86.1%.两组等位基因频率经χ2检验差异无显著意义(P＞0.05).结论C677T可能不是广东汉族人冠心病的危险因素,但结果仍有待研究.     

妊娠期合并心脏病病人血清中 MTHFR基因 C677T位点多态性与母婴结局关系

目的 探讨妊娠期合并心脏病病人血清中MTHFR基因C677T位点多态性与母婴结局关系.方法 选取2018年2月至2019年10月德州市妇女儿童医院就诊的妊娠期合并心脏病病人88例(妊娠期心脏病组)及同期健康孕妇92例(对照组),通过聚合酶链式反应-限制性片段长度多态性(PCR-RELP)法检测受试者血清MTHFR基因C677T位点多态性分布频率,并分析MTHFR基因单核苷酸各基因型与符合妊娠结局的关系.结果 MTHFR基因C677T位基因型有CC野生型、CT杂合子型、TT纯合子型;对照组与妊娠期合并心脏病组MTHFR基因C677T位点各基因型符合Hardy-Weinberg平衡定律;与对照组相比,妊娠期心脏病组MTHFR基因C677T位点CT、TT基因型及T等位基因频率分布显著升高(P<0.05);妊娠期心脏病组孕妇CT型、TT型病人巨大儿、新生儿低血糖、新生儿窒息、早产儿发生率均高于CC型;TT型病人巨大儿、新生儿低血糖、新生儿窒息、早产儿发生率均高于杂合子CT型(P<0.05);二元logistic回归分析显示,MTHFR基因C677T位点杂合子CT型、纯合子突变TT型是妊娠期合并心脏病病人不良妊娠结局发生的危险因素(P<0.05).结论 血清中MTHFR基因C677T位点多态性与妊娠期心脏病母婴结局关系密切.     

醛糖还原酶5’端两种基因多态性与2型糖尿病肾病的相关性研究

目的探讨醛糖还原酶(AR)基因启动子区C(-106)T单核苷酸多态性和2.1Kb处(AC)n二核苷酸微卫星多态性与2型糖尿病肾病(DN)的关系。方法用聚合酶链反应(PCR)、测序及琼脂糖凝胶电泳技术检测AR基因两多态位点的基因型及等位基因,比较各组分布频率。结果在DM组和CON组均发现AR基因C(-106)T多态位点存在C、T两种等位基因和CC、CT、TT三种基因型,(AC)n序列的7种等位基因(Z-6~Z+6);T、Z-2等位基因及CT+TT及含有Z-2的基因型在DN组明显高于NDN和CON组,但在DM组和CON组之间无显著性差异。结论 AR基因C(-106)T多态位点的T等位基因及(AC)n多态位点的Z-2等位基因可能是DN的易感基因。     

彝族高血压患者MTHFR C677T基因多态性及其与血压、同型半胱氨酸水平的关系

目的探讨彝族居民MTHFR C677T基因位点的分布特征及其与血压、同型半胱氨酸(HCY)水平的关联性。方法于2018年10月对122例彝族高血压患者(高血压组),检测收缩压,舒张压,HCY和MTHFR C677T基因位点,并与110例彝族非高血压居民(对照组)比较。结果高血压组MTHFR C677T基因位点TT型频率高于对照组,差异有统计学意义(P 0.05),高血压组MTHFR C677T位点T等位基因频率高于对照组,差异有统计学意义(P 0.05)。高血压组CC、CT和TT三组收缩压,舒张压和HCY平均水平均高于对照组(P 0.01)。在高血压组中,TT型患者收缩压平均水平高于CC型,也高于CT型,差异有统计学意义(P 0.05);TT型患者舒张压平均水平高于CC型,也高于CT型,差异有统计学意义(P 0.05)。在对照组中,CC、CT和TT三组收缩压和舒张压平均水平,差异无统计学意义(P 0.05)。在高血压组中,TT型的HCY平均水平高于CC型,也高于CT型,差异有统计学意义(P 0.05)。在对照组中TT型的HCY平均水平高于CC型,差异有统计学意义(P 0.05)。对照组CT与CC比较差异无统计学意义(P 0.05)。结论彝族高血压患者MTHFR C677T基因位点TT纯合子突变携带者其收缩压,舒张压和HCY水平高于CC和CT基因型。彝族非高血压者MTHFR C677T基因位点TT纯合子突变携带者HCY水平高于CC基因型。提示MTHFR C677T基因位点TT纯合子突变与血浆HCY高水平有关联。     

ABCA1启动子区基因多态性与血脂水平及冠心病的关系

目的：检测三磷酸腺苷结合盒转运子A1(ATP binding cassette transporter 1,ABCA1)基因启动子-14bp单核酸多态性(single nucleotide polymorphism,SNP) 位点与天津市汉族人群冠心病发生(coronary heart disease,CHD)及血脂水平的关系。方法：采用病例对照研究,聚合酶链反应-限制性片段长度多态性(Polymerase Chain Reaction-Restriction Fragment Length Polymorphism)方法,对228例经冠状动脉造影确诊的冠心病患者和同一地区造影排除冠心病正常对照200例,进行ABCA1基因-14bp位点SNP分析检测,比较不同基因型与血脂水平和冠心病的关系。结果：ABCA1基因-14bp位点多态性有三种：CC、CT和TT型。全部检测人群中CC型占42.99%,CT型占51.64%,TT型占5.31%。冠心病组与对照组中CC、CT、TT三种基因型频率差异无统计学意义（p＞0.05）;冠心病患者与正常人等位基因频率差异无显著性（p＞0.05）;T等位基因携带者HDL-C水平低于非携带者（p＜0.05）。结论：ABCA1基因-14bp位点多态性与冠心病发生无相关性;T等位基因携带者血浆HDL-C水平低下。     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Nachweis einiger Heilmittel in der Kniegelenksynovialflüssigkeit

Zusammenfassung Mittels Gaschromatographie und Dünschichtchromatographie wiesen die Autoren 11 Substanzen nach, welche durch Injektion oder nach Verabreichung per os in die Kniegelenksynovialflüssigkeit eindrangen. In ihrer Aufstellung konnten sie eine direkte Beziehung zwischen Struktur sowie chemischphysikalischen Eigenschaften der Substanz und ihrer Fähigkeit, aus dem Blut in die Kniegelenksynovialflüssigkeit einzudringen, nicht nachweisen, außer der Tatsache, daß Substanzen mit starker Affinität zu Eiweißstoffen erst in höheren Dosen nachweisbar waren.     

Lung disease and PKCs

The lung offers a rich opportunity for development of therapeutic strategies focused on isozymes of protein kinase C (PKCs). PKCs are important in many cellular responses in the lung, and existing therapies for pulmonary disorders are inadequate. The lung poses unique challenges as it interfaces with air and blood, contains a pulmonary and systemic circulation, and consists of many cell types. Key structures are bronchial and pulmonary vessels, branching airways, and distal air sacs defined by alveolar walls containing capillaries and interstitial space. The cellular composition of each vessel, airway, and alveolar wall is heterogeneous. Injurious environmental stimuli signal through PKCs and cause a variety of disorders. Edema formation and pulmonary hypertension (PHTN) result from derangements in endothelial, smooth muscle (SM), and/or adventitial fibroblast cell phenotype. Asthma, chronic obstructive pulmonary disease (COPD), and lung cancer are characterized by distinctive pathological changes in airway epithelial, SM, and mucous-generating cells. Acute and chronic pneumonitis and fibrosis occur in the alveolar space and interstitium with type 2 pneumocytes and interstitial fibroblasts/myofibroblasts playing a prominent role. At each site, inflammatory, immune, and vascular progenitor cells contribute to the injury and repair process. Many strategies have been used to investigate PKCs in lung injury. Isolated organ preparations and whole animal studies are powerful approaches especially when genetically engineered mice are used. More analysis of PKC isozymes in normal and diseased human lung tissue and cells is needed to complement this work. Since opposing or counter-regulatory effects of selected PKCs in the same cell or tissue have been found, it may be desirable to target more than one PKC isozyme and potentially in different directions. Because multiple signaling pathways contribute to the key cellular responses important in lung biology, therapeutic strategies targeting PKCs may be more effective if combined with inhibitors of other pathways for additive or synergistic effect. Mechanisms that regulate PKC activity, including phosphorylation and interaction with isozyme-specific binding proteins, are also potential therapeutic targets. Key isotypes of PKC involved in lung pathophysiology are summarized and current and evolving therapeutic approaches to target them are identified.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.     

Biochemical and molecular characterisation of cubozoan protein toxins

Class Cubozoa includes several species of box jellyfish that are harmful to humans. The venoms of box jellyfish are stored and discharged by nematocysts and contain a variety of bioactive proteins that are cytolytic, cytotoxic, inflammatory or lethal. Although cubozoan venoms generally share similar biological activities, the diverse range and severity of effects caused by different species indicate that their venoms vary in protein composition, activity and potency. To date, few individual venom proteins have been thoroughly characterised, however, accumulating evidence suggests that cubozoan jellyfish produce at least one group of homologous bioactive proteins that are labile, basic, haemolytic and similar in molecular mass (42-46 kDa). The novel box jellyfish toxins are also potentially lethal and the cause of cutaneous pain, inflammation and necrosis, similar to that observed in envenomed humans. Secondary structure analysis and remote protein homology predictions suggest that the box jellyfish toxins may act as α-pore-forming toxins. However, more research is required to elucidate their structures and investigate their mechanism(s) of action. The biological, biochemical and molecular characteristics of cubozoan venoms and their bioactive protein components are reviewed, with particular focus on cubozoan cytolysins and the newly emerging family of box jellyfish toxins.     

Dose tolerability of chronically inhaled voriconazole solution in rodents

Invasive pulmonary aspergillosis (IPA) is a fungal disease of the lung associated with high mortality rates in immunosuppressed patients despite treatment. Targeted drug delivery of aqueous voriconazole solutions has been shown in previous studies to produce high tissue and plasma drug concentrations as well as improved survival in a murine model of IPA. In the present study, rats were exposed to 20 min nebulizations of normal saline (control group) or aerosolized aqueous solutions of voriconazole at 15.625 mg (low dose group) or 31.25 mg (high dose group). Peak voriconazole concentrations in rat lung tissue and plasma after 3 days of twice daily dosing in the high dose group were 0.85 ± 0.63 μg/g wet lung weight and 0.58 ± 0.30 μg/mL, with low dose group lung and plasma concentrations of 0.38 ± 0.01 μg/g wet lung weight and 0.09 ± 0.06 μg/mL, respectively. Trough plasma concentrations were low but demonstrated some drug accumulation over 21 days of inhaled voriconazole administered twice daily. Following multiple inhaled doses, statistically significant but clinically irrelevant abnormalities in laboratory values were observed. Histopathology also revealed an increase in the number of alveolar macrophages but without inflammation or ulceration of the airway, interstitial changes, or edema. Inhaled voriconazole was well tolerated in a rat model of drug inhalation.