糖尿病口服药物研究进展

糖尿病是以高血糖为主要特征的代谢性内分泌疾病,系因胰岛素绝对或相对不足,或靶细胞对胰岛素敏感性减低所致。可分为胰岛素依赖型和非胰岛素依赖型。其中1型糖尿病为胰岛素分泌绝对不足,需外源性胰岛素治疗,口服降糖药无效;2型糖尿病为胰岛素相对分泌不足,大多数可使用口服降血糖药治疗。本资料对目前治疗糖尿病各种类型的口服药物的作用机制、临床应用及主要不良反应做一概述。     

糖尿病药物治疗及机制研究进展

糖尿病可分为两型:1型--胰岛素依赖性糖尿病(insulin-dependent diabetes meilitus,IDDM),是由于胰岛B细胞破坏,胰岛素分泌缺乏而致高血糖;2型--非胰岛素依赖性糖尿病(non-insulin-dependent diabetes mellitus,NIDDM),是B细胞功能低下,胰岛素相对缺乏及胰岛素作用环节不健全而致血糖水平升高.     

糖尿病治疗药物的研究进展

糖尿病是由于胰岛素绝对或相对不足而引起的、以高血糖和多发并发症并存等为特点的内分泌代谢性疾病,是最常见的慢性病之一。临床上主要有胰岛素依赖型（IDDM,1型）和非胰岛素依赖型（NIDDM,2型）。     

α-葡萄糖苷酶抑制剂的研究进展

糖尿病是一种多病因引起、以高血糖为特征的内分泌代谢紊乱性疾病。高血糖是由胰岛素分泌不足、胰岛素抵抗,或二者共同存在而引起。世界上,糖尿病患者已超过1．7亿,已成为继心血管疾病和肿瘤之后第三大严重威胁人类健康的非传染性疾病^[1]。临床上,根据糖尿病发病机制不同,主要分为1型糖尿病（胰岛素依赖型）和2型糖尿病（非胰岛素依赖型）,我国以2型居多。治疗2型糖尿病的药物主要分为：（1）胰岛素及类似物：如赖脯胰岛素等;（2）促胰岛素分泌剂：如磺酰脲类;（3）胰岛素增敏剂：如噻唑烷类衍生物;     

胰岛素泵治疗早期2型糖尿病的疗效观察

胰岛B细胞分泌功能异常及胰岛素抵抗是2型糖尿病发病的基本环节，持续高血糖可直接损伤B细胞功能及胰岛素敏感性，致血糖进一步升高而形成恶性循环，故积极控制血糖对B细胞功能及胰岛素敏感性将产生有利影响。2型糖尿病胰岛B细胞功能缺陷在早期主要表现为胰岛素分泌第一时相消失。随着病程延长，B细胞功能逐渐衰竭，胰岛素分泌第二时相也越来越低平。本研究在于观察外源性胰岛素快速控制血糖后，对早期2型糖尿病B细胞功能的变化。     

糖尿病药物治疗进展

糖尿病[1](diabotes mellitus,DM)是一种糖、蛋白和脂肪代谢障碍性疾病,原因众多,主要是胰岛素分泌或生成异常,分为胰岛素依赖型(又称1型)及非胰岛素依赖型糖尿病(又称2型)。1型DM患者内源性胰岛素分泌不足,需用胰岛素治疗。     

糖尿病微血管病变胰岛β细胞功能研究

目的　探讨 2型糖尿病微血管病变患者胰岛 β细胞分泌功能及相关因素。 方法　应用馒头餐胰岛素释放试验 ,对 15 6例 2型糖尿病患者 (其中微血管并发症 77例、无微血管并发症者 79例 )进行血糖、胰岛素测定 ,计算血糖、胰岛素曲线下面积、胰岛素敏感性指数、胰岛素分泌指数 ,并进行比较。结果　糖尿病微血管病变组各时相血糖值、血糖曲线下面积显著高于无微血管病变组 (P <0 .0 1) ,各时相胰岛素值、胰岛素曲线下面积均低于无微血管病变组 (P <0 .0 1)胰岛素分泌指数显著低于无微血管病变组 (P <0 .0 1)。多元Logistic逐步回归分析显示 ,微血管病变与糖尿病病程呈显著正相关 ,与胰岛素分泌指数呈显著负相关。结论　 2型糖尿病微血管病变患者存在严重的持续性高血糖。糖尿病病程的延长、严重的胰岛 β细胞分泌功能障碍为 2型糖尿病微血管病变的主要危险因素     

Ⅱ型糖尿病的口服药物治疗

2型糖尿病(或称非胰岛素依赖型糖尿病,NIDDM)是一种因胰岛素分泌和作用异常所引起的慢性代谢障碍。它是以胰岛素抵和高血糖为特征,并常伴有高血压,脂质代谢紊乱和肥胖。2型糖尿病是最为常见的糖尿病类型,约占糖尿病总发病率的90％。2型糖尿病的主要病理变化是胰岛β细胞功能低下,而胰岛素抵可能是β细胞衰竭的主要原因。     

去胰高血糖素样肽1受体激动剂成为2型糖尿病治疗新热点

1．传统2型糖尿病治疗观念面临严峻挑战 糖尿病（Diabetes mellitus,DM）是一组病因和发病机理尚未完全明确的内分泌-代谢综合征,其特点是慢性高血糖,伴随因胰岛素（Insulin）分泌及／或作用缺陷所引起的糖、脂肪和蛋白质代谢紊乱。糖尿病可分为4型：胰岛素依赖型糖尿病（1型糖尿病,IDDM）、非胰岛素依赖型糖尿病（2型糖尿病,NIDDM）、其他类型糖尿病、妊娠期糖尿病。主要分为1型和2型,后者占患者群体的90％以上。目前,     

1,5脱水葡萄糖醇与2型糖尿病相关研究进展

糖尿病为一类以复杂病因导致的代谢性疾病,其主要特征为慢性长期高血糖.高血糖主要由胰岛素的分泌释放功能受损或胰岛素的利用在机体的特异性器官或组织上产生抑制作用.糖尿病导致的长期高血糖状态会引起以心血管系统、神经系统、视网膜以及肾脏等组织或器官病变为特征的多种并发疾病的产生.高血糖状态主要包括波动性高血糖以及持续性高血糖,它们是损伤糖尿病患者的血管,尤其是微血管最主要的因素.波动性高血糖对糖尿病患者的危害较大,会增加慢性并发症的风险;特别是餐后高血糖,是大血管病变的重要影响因素.目前,临床上常见的血糖检测指标为糖化血红蛋白(Glycated Hemoglobin,HbA1c)和糖化血清白蛋白(Glycated Albumin,GA)等.血清l,5脱水葡萄糖醇(1,5-Anhydroglucitol,1,5-AG)又称1,5脱水山梨醇,是吡喃糖环状结构第一位碳脱氧所形成的多元醇,其含量在多元醇糖类物质中仅次于葡萄糖.1,5-AG已经成为诊断和监控糖尿病高血糖的一项新的重要指标.目前,1,5-AG主要用于辅助糖化血红蛋白反映近期(1~2周)血糖水平变化及餐后血糖波动.     

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.     

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.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

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.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

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.