皮肤晚期糖基化终末产物与2型糖尿病周围神经病变的相关性研究

目的 分析2型糖尿病(T2DM)伴周围神经病变(DPN)患者皮肤晚期糖基化终末产物(AGEs)水平变化及其临床意义.方法 选择99例T2DM患者,依据神经缺陷评分(NDS)将其分为DPN组和非DPN组,同时选取正常对照组(NC组)35例,测定各组皮肤AGEs和糖化血红蛋白(HbA1c)水平并进行比较.结果 与NC组相比,T2DM患者皮肤AGEs水平明显升高(P<0.05);与非DPN组相比,DPN组患者皮肤AGEs水平明显增(P<0.05),两组HbA1c水平差异无统计学意义(P>0.05).结论 T2DM患者皮肤AGEs水平升高可能参与糖尿病周围神经病变的发生.     

2型糖尿病患者踝肱指数与脑梗死的相关性分析

目的 测定2型糖尿病（T2DM）患者合并与非合并脑梗死患者的踝肱指数（ABI），探讨ABI与T2DM合并脑梗死的相关性。方法 选取2016年1月至2017年1月在安徽医科大学第一附属医院内分泌科住院的358例T2DM患者为研究对象。按是否合并脑梗死将患者分为T2DM组182例和T2DM合并脑梗死（T2DM+CI）组176例，测定两组患者的ABI，记录和收集患者一般情况、血糖及生化常规等相关资料。采用Pearson相关分析、多元线性回归分析以及logistic回归分析进行临床资料以及脑梗死与ABI的相关性分析。结果 T2DM组与T2DM+CI组ABI分级差异有统计学意义，且T2DM+CI组中ABI分级B组和C组比例显著高于T2DM组（P均<0.05）。Pearson相关分析显示，ABI与年龄、糖尿病病程、收缩压、空腹血糖、HbA1c呈负相关（r值分别为-0.230、-0.152、-0.108、-0.120、-0.143，P均<0.05）；多元线性回归分析显示，年龄、糖尿病病程、收缩压是ABI的独立危险因素；logistic回归分析显示，与正常ABI患者相比，轻度梗阻患者、中-重度梗阻患者脑梗死的患病风险均增加（OR值分别为1.34、2.23，P均<0.05）。结论 T2DM患者脑梗死的发病风险与ABI降低密切相关。     

2型糖尿病合并冠心病患者血vaspin IL-6水平与其心功能和胰岛素抵抗的相关性

目的 探讨血清内脏脂肪组织丝氨酸蛋白酶抑制因子（vaspin）、白介素-6（IL-6）与2型糖尿病（T2DM）合并冠心病患者心功能等级及胰岛素抵抗（IR）的关系。方法 选择2014年2月至2017年6月河南理工大学第一附属医院收治的T2DM患者89例,按是否合并冠心病分为T2DM组（n=55）与T2DM合并冠心病组（n=34）,并选择30例正常健康人为对照组,均留取外周血标本,采用酶联免疫吸附法测定血清vaspin、IL-6水平,分析上述指标与T2DM合并冠心病患者心功能等级及IR的关系。结果 ①vaspin水平对照组 > T2DM组 > T2DM合并冠心病组,IL-6水平T2DM合并冠心病组 > T2DM组 > 对照组（P<0.05）;②T2DM组与T2DM合并冠心病组空腹血糖（FPG）、餐后2 h血糖（2 h PG）、空腹胰岛素（FINS）、胰岛素抵抗指数（HOMA-IR）均高于对照组（P<0.05）,T2DM合并冠心病组上述指标高于T2DM组（P<0.05）;③Ⅱ级、Ⅲ级、Ⅳ级T2DM合并冠心病患者vaspin低于Ⅰ级者,IL-6、HOMA-IR高于Ⅰ级者（P<0.05）,Ⅲ级、Ⅳ级患者vaspin低于Ⅱ级者,IL-6、HOMA-IR高于Ⅱ级者,Ⅳ级患者vaspin低于Ⅲ级者,IL-6、HOMA-IR高于Ⅲ级者（P<0.05）;④vaspin与T2DM合并冠心病患者心功能等级、HOMA-IR呈负相关,IL-6与其心功能等级、HOMA-IR均呈正相关（P<0.05）。结论 T2DM合并冠心病患者血清vaspin降低、IL-6上升,均可引起胰岛素抵抗,促进冠心病进展。     

2型糖尿病患者腰髋部骨密度水平与骨质疏松相关性分析

目的 研究2型糖尿病患者腰髋部骨密度水平,并分析其与骨质疏松的相关性。方法 选取2013年1月至2014年确诊的2型糖尿病患者127例作为2型糖尿病(T2DM)组,同期选取体检健康者134例作为健康对照组,对两组患者腰髋部骨密度水平,骨质疏松发病率进行比较,研究其相关性。结果 与健康组相比较,T2DM组的L₁,L₂,L₃,L₄,股骨颈,大转子及Ward区的股骨密度均显著下降,差异均有统计学意义(P < 0.05),骨质疏松发病率显著上升,差异有统计学意义(P < 0.05)。结论 T2DM患者腰髋部骨密度水平与骨质疏松发病率呈负相关。     

骨钙素β胶原特殊序列对2型糖尿病患者糖脂代谢的影响

目的 探讨2型糖尿病（T2DM）患者骨钙素（BGP）和β胶原特殊序列（β-CTX）对糖、脂代谢的影响。方法 选取2017年11月至2018年10月在河南省驻马店市中心医院内分泌科住院的T2DM患者376例为研究对象（T2DM组），另选取同期体检健康人群100例作为对照（对照组），比较两组研究对象糖、脂代谢指标及BGP、β-CTX水平差异，分析T2DM患者BGP、β-CTX水平与糖、脂代谢指标的关系。结果 T2DM组空腹血糖（FBG）、糖化血红蛋白（HbAlc）、三酰甘油（TG）、总胆固醇（TC）和β-CTX水平均高于对照组，BGP水平低于对照组，差异均有统计学意义（P<0.05）；T2DM患者BGP水平与FBG、HbAlc呈负相关（r=-0.524、-0.362，P均<0.05），与TG和TC无关（r=-0.125、-0.056，P均>0.05），β-CTX水平与以上指标均无相关性（r=0.094、0.164、-0.031、0.042，P均>0.05）；高水平和低水平BGP（以7 ng/L界限）的T2DM患者间FBG、HbAlc比较，差异有统计学意义（P<0.05）。以HbAlc为因变量进行多因素分析，结果显示BGP是影响HbAlc的独立相关因素（P<0.05），β-CTX与HbAlc无关（P>0.05）；以FBG为因变量进行多因素分析，结果显示BGP和β-CTX均不是影响HbAlc的独立相关因素（P>0.05）。结论 T2DM患者BGP水平与HbAlc呈负相关，且是影响HbAlc水平的独立相关因素。     

血尿酸与2型糖尿病患者颈动脉粥样硬化的关系

目的探讨2型糖尿病(T2DM)患者血尿酸(BUA)与颈动脉粥样硬化的关系,探讨其在2型糖尿病颈动脉粥样硬化及大血管病变中的作用。方法 110例2型糖尿病患者,根据颈动脉内中膜厚度(IMT)分为动脉粥样硬化(AS)组和非AS组,同期选择我院健康体检50例作为正常对照组(NC组),采用ELISA测定BUA水平,并分析BUA与IMT、BMI、血糖血脂血压、HOMA-IR等相关代谢指标的关系。结果 AS组、非AS组BUA水平均高于NC组(P<0.01);AS组BUA水平显著高于非AS组(P<0.01)。2型糖尿病患者BUA与WHR、BMI、IMT、FBG、HOMA-IR和HbA1c呈负相关,与HDL-C呈正相关(P<0.01或<0.05)。HOMA-IR、BMI和IMT为影响T2DM患者BUA的独立相关因素。HOMA-IR和BUA是影响T2DM患者颈动脉IMT的独立相关因素。结论 BUA与T2DM患者早期动脉粥样硬化密切相关,可能在T2DM颈动脉粥样硬化及大血管病变的发生发展中起着重要作用。     

2型糖尿病患者血尿酸及同型半胱氨酸与颈动脉粥样硬化的关系

目的 探讨2型糖尿病（T2DM）患者血尿酸（SUA）及同型半胱氨酸（Hcy）水平与颈动脉粥样硬化（CAS）的关系。方法 选择2017年6月至2018年5月在合肥市第二人民医院内分泌科住院治疗符合入组条件的T2DM患者147例,根据颈动脉内膜中层厚度将患者分为颈动脉粥样硬化（CAS）组（40例）和非CAS组（107例）。分析T2DM患者CAS发生的危险因素。结果 CAS组患者的年龄、收缩压、脉压、血肌酐、SUA、Hcy均高于非CAS组,差异有统计学意义（P<0.05）。多因素logistic回归分析结果显示：年龄（OR=1.304）、SUA （OR=41.313）、Hcy （OR=5.134）为CAS的危险因素（P<0.05）。结论 T2DM患者的年龄、SUA及Hcy与CAS的发生呈明显相关性,对预测T2DM患者CAS的发生有重要意义。     

2型糖尿病患者血尿酸与蛋白尿的关系

目的 探讨2型糖尿病（T2DM）患者血尿酸（SUA）与蛋白尿的关系。方法 选择2016年5月至2017年9月安徽省立医院住院的T2DM患者791例,根据血尿酸（SUA）水平将患者分为正常尿酸（NUA）组656例和高尿酸（HUA）组135例,通过单因素分析比较两组患者尿白蛋白/肌酐（UACR）的差异;通过Pearson相关分析,比较UACR与其他生化指标的相关性,并将有统计学意义的指标纳入logistic回归分析中,了解SUA对蛋白尿发生的相对危险度。结果 ①HUA组患者UACR高于NUA组,差异有统计学意义（P<0.05）;HUA组患者蛋白尿的发生率（54.8%）高于NUA组（38.6%）,差异有统计学意义（P<0.05）;②Pearson相关分析显示,UACR与SUA呈正相关（P<0.05）;Logistic回归分析显示,血尿酸水平每增加1 mg/dL,发生蛋白尿的相对危险度为1.096（P=0.005）。结论 T2DM患者中,血尿酸水平升高可引起UACR升高,是蛋白尿发生的危险因素,在糖尿病的治疗中需监测血尿酸水平。     

老年2型糖尿病患者血清维生素D与T细胞亚群水平及胰岛素抵抗的关系

目的 探讨老年2型糖尿病（T2DM）血清维生素D（VitD）与T细胞亚群水平及胰岛素抵抗的关系。方法 根据VitD水平,将2013年11月至2018年7月中国科学技术大学附属第一医院老年医学科收治的128例T2DM患者根据VitD水平分为正常组（29例）、不足组（40例）、缺乏组（28例）与严重缺乏组（31例）。比较T细胞亚群水平,分析VitD与T细胞亚群水平及胰岛素抵抗的关系。结果 严重缺乏组HOMA-IR、CD3⁺T、CD8⁺T细胞水平均高于缺乏组、不足组和正常组,差异均有统计学意义（P<0.05）;缺乏组HOMA-IR、CD3⁺T、CD8⁺T细胞水平均高于不足组、正常组,差异均有统计学意义（P<0.05）;正常组HOMA-IR、CD3⁺T、CD8⁺T细胞水平最低,差异均有统计学意义（P<0.05）。lgHOMA-IR、CD3⁺T、CD8⁺T细胞水平与VitD呈负相关（P<0.05）。HOMA-IR的多元线性回归分析的回归方程为：Y_lgHOMA-IR=0.480X_CD8+T+0.605X_BMI-27.875（R²=15.103,P=0.006）。结论 老年T2DM血清VitD影响T细胞亚群水平导致胰岛素抵抗加重。     

2型糖尿病患者血清胆红素水平与视网膜病变的关系

目的 探讨2型糖尿病（T2DM）视网膜病变与血清胆红素水平之间的关系。方法 选择2017年4月至2018年4月安徽省立医院收治的T2DM患者203例,根据眼底检查结果分为糖尿病视网膜病变（DR）组（78例）与非糖尿病视网膜病变（NDR）组（125例）,比较两组患者之间血清胆红素水平的差异,并对DR的影响因素进行logistic回归分析。结果 DR组患者的总胆红素、直接胆红素和间接胆红素水平分别为（9.91±3.55）、（3.35±1.25）和（6.55±2.72）μmol/L,均低于NDR组,而病程、糖化血红蛋白、总胆固醇和低密度脂蛋白胆固醇分别为（10.77±4.85）年、（9.19±1.78）%、（4.25±0.72）和（2.61±0.66）mmol/L,均高于NDR组,差异有统计学意义（P<0.05）。logistic回归分析显示,总胆红素是DR的保护性因素（P<0.05）,而病程、低密度脂蛋白胆固醇是DR的独立危险因素（P<0.05）。结论 胆红素可能在DR的发生发展中起到保护性作用,应重视胆红素的抗氧化作用。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

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.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.     

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.