高效液相色谱法测定消糖灵胶囊中格列本脲的含量

目的探讨用高效液相色谱(HPLC)法测定消糖灵胶囊中格列本脲的含量。方法采用HP ODS-Hypersil色谱柱(4.6 mm×200 mm,5μm),柱温:20℃,流动相为甲醇-0.005 mol/L磷酸二氢胺(pH3.5,70∶30),流速0.8 ml/min,检测波长300 nm。结果格列本脲在0.141~2.25μg范围内呈较好的线性关系(r=0.999 9,n=5),平均回收率为99.18%,RSD为1.72%(n=3)。结论高效液相色谱法测定格列本脲简便、快捷、灵敏,可以作为消糖灵胶囊含量的测定方法。     

心肌缺血预适应引起的ATP敏感性钾电流变化

许多研究证实三磷酸腺苷敏感性钾电流 (KATP)在心肌保护的机制中起重要作用 ,但尚未有缺血预适应 (IPC)期间KATP电流变化的直接报道。本实验用全细胞膜片钳技术在豚鼠心室肌细胞上观察了多次模拟缺血 (低氧、去能量 )和再灌注期间KATP电流的变化情况。结果 :对照组 (n =9)和IPC组 (n =12 )的KATP电流分别由实验开始时的- 97± 14和 - 94± 16pA开放至第 3次短暂缺血结束时的 - 5 7± 10和 - 16± 2 0pA(P <0 .0 5 ) ,以及持续缺血 5min时的 35± 2 3和 472± 310pA(P均 <0 .0 1) ;然而在持续缺血晚期和再灌注过程中KATP通道的开放程度在两组之间无显著差异。以上这些效应可被优降糖阻断。结论 :本文首次直接观察到IPC可导致KATP通道在预适应末及随后长时间缺血早期的适度激活 ,但不影响长时间缺血晚期和再灌注过程中的开放程度 ,为进一步研究IPC的发生机制和开发KATP开放剂作为新型抗缺血性心脏病药物提供了理论基础     

Graft-versus-Host Disease-like Syndrome in Malignant Thymoma

Allogenic transfusion of immunocompetent T lymphocytes into an immunodeficient recipient is necessary for the development of graft-versus-host-disease (GVHD). The gastrointestinal tract is one of the most involved organs in human GVHD, and single-cell necrosis with apoptotic change and crypt abscess are characteristic histopathologic features. The thymus is important in immune regulation, and dysregulation of the immune system can be expected once its microenvironment is disrupted. We report the case of a 38-year-old woman with malignant thymoma without transplantation or transfusion history who initially presented with myasthenia gravis and clinically developed a GVHD-like syndrome with characteristic GVHD-like colitis on colonoscopy. We propose that disruption of the thymic microenvironment caused a dysregulated immune system and development of a GVHD-like syndrome.     

Molecular and biochemical monitoring of the possible herb-drug interaction between Momordica charantia extract and glibenclamide in diabetic rats

Momordica charantia is used in folk medicine to manage diabetes mellitus. In this study, we investigated the possible herb-drug interaction between M. charantia fruit extract (MCFE) and glibenclamide (GLB) in streptozotocin-diabetic rats. Rats were divided into 7 groups. The 1st group received 3% Tween 80. The 2nd–5th groups were diabetic rats received vehicle, GLB (5 mg/kg), MCFE (250 and 500 mg/kg), respectively. The 6th–7th groups administered GLB plus MCFE (250 and 500 mg/kg), respectively. After 8 weeks, fasting blood glucose (FBG), insulin and glycosylated hemoglobin (HbA1c) levels were assessed. Histopathological and immunohistochemical examinations of the pancreases were done. Quantitative RT-PCR was used to analyze hepatic mRNA expression of insulin receptor (INR), glucose transporter 2 (Slc2a2) and peroxisome proliferator-activated receptor α (PPAR-α) genes. All medicaments greatly reduced FBG in diabetic rats when compared with diabetic control group. GLB plus MCFE combination was better than GLB alone in improving levels of insulin and HbA1c. All medicaments restored insulin content of pancreatic β-cells and reduced glucagon and somatostatin of alpha and delta endocrine cells. Moreover, GLB plus MCFE-500 was the most efficient in restoring INR, Slc2a2 and PPAR-α mRNA expression to their normal levels. In conclusion, MCFE in combination with GLB gives greater glycemic improvement than GLB monotherapy.     

Pharmacological comparison between tolbutamide and two second generation hypoglycemic sulfonylureas (Glibenclamide and glisoxepide)

Summary The authors conclude that administered i.v. in the normal conscious dog, glibenclamide and glisoxepide are considerably more active on glycemia than tolbutamide. Administered p.o., glibenclamide acts less rapidly on the glycemia than tolbutamide and glisoxepide. Thedynamic study of the insulin secretion shows that the secretion of insulin begins more slowly and lasts longer with glibenclamide than with the two other products. On the isolated and perfused rat pancreas, glisoxepide and tolbutamide more rapidly stimulate the secretion of insulin than glibenclamide; with the latter substance the duration of the secretion of insulin is longer and the total quantity of insulin secreted is greater. As far as thebeta-cytotrophic action is concerned, all three sulfonamides stimulate the neogenesis of the islets of Langerhans in Swiss mice. Traduzione a cura di G. U.     

Slowly Progressing Type 1 Diabetes: Persistence of Islet Cell Autoantibodies is Related to Glibenclamide Treatment

Background: Several experimental studies in rats have demonstrated that sulfonylurea treatment increases autoantigen expression in B-cells. This phenomenon may be deleterious for the preservation of residual beta cell function in patients with slowly progressing type 1 diabetes or latent autoimmune diabetes of adult (LADA). Aim/hypothesis: The aim of the present study was to evaluate whether the exclusion of glibenclamide in the treatment of ICA positive type 2 diabetic patients may diminish or halt the humoral autoimmune response against B-cells as well as improve metabolic control and insulin secretion. Subjects and methods: Fourteen type 2 diabetic patients with pancreatic autoimmunity (ICA+ and GABA+) and treated with insulin and glibenclamide (duration of disease 2.0 &#45 2.2, range 0.1-7 years and age 53 &#45 12.5, range 36-75 years) were studied. Patients were randomly assigned to two treatment groups, Group 1: insulin monotherapy (n = 8, age 53 &#45 6.4 years) (Exclusion of glibenclamide) and, Group 2: insulin plus glibenclamide (n = 6, age 53.5 &#45 16.9 ) (Unmodified treatment). Both groups were investigated at the beginning of the study and after one year for the following parameters: ICA and anti-GAD65 antibodies, fasting glucose and fasting C-peptide. Results: In group 1, six out of eight patients became ICA negative while all patients in group 2 remained ICA positive (p = 0.0097). Fasting glucose concentrations improved in group 1 (4.6 &#45 2.8) in relation to group 2 (11.5 &#45 5.5, p = 0.0023) after one year of treatment. No differences were found for anti-GAD antibodies and fasting C-Peptide between the groups. Conclusions: These data show that exclusion of glibenclamide in the treatment of ICA+ type 2 diabetic patients partially decreases specific autoimmunity against endocrine pancreatic cells and improves metabolic control. This may reflect decreased expression of B-cell autoantigens suggesting that insulin monotherapy is a better choice for the treatment of LADA.     

格列本脲在糖尿病大鼠体内药动学评价

目的 从格列本脲的药动学考察链脲佐菌素诱导糖尿病模型大鼠的适宜性.方法 腹腔注射链脲佐菌素60 mg/kg诱发糖尿病大鼠模型,与正常大鼠灌胃给予10 mg/kg格列本脲,采用高效液相色谱法分析其血药浓度.用DAS 2.0软件处理数据,计算药动学参数.结果 格列本脲在正常大鼠和模型大鼠体内的药动学参数为:Tmax分别是84.784 min,255.427 min;Cmax分别是0.259 mg/L,0.910 mg/L;CL分别是0.092 L/min/kg,0.019 L/min/kg;AUC(0-720min)分别是509.523 mg/L·min,1528.280 mg/L·min.结论 格列本脲在正常大鼠与糖尿病大鼠体内的药动学过程有显著性差异,但此结果与文献不一致,此模型可能不适合考察药物在Ⅱ型糖尿病病态下的药动学研究.     

Class I antiarrhythmic drugs alter the severity of myocardial stunning by modulating ATP-sensitive K+ channels in guinea pig ventricular muscles

The effects of various class I antiarrhythmic drugs and glibenclamide were examined on the recovery of contraction during reperfusion, in relation to the action potential duration (APD) seen during ischemia. Action potential and contractile tension were recorded from isolated guinea pig right ventricular muscles perfused with oxygenated Tyrode solution via the coronary artery. Ten minutes of no-flow ischemia shortened the APD at 90% of repolarization level (APD₉₀) to 58% of control (pre-ischemic values). The APD₉₀ was completely restored after 60 min of reperfusion. The developed tension was abolished during ischemia and recovered to 87% of control after 60 min of reperfusion. In the presence of Vaughan Williams class Ia drug cibenzoline (5 μM) or an ATP-sensitive potassium (K_ATP) channel blocker glibenclamide (10 μM), the shortening of the APD₉₀ during ischemia was significantly attenuated. However, the recovery of developed tension was significantly inhibited. Class Ic drug pilsicainide (10 μM) did not affect the ischemia-induced shortening of the APD₉₀ or the recovery of developed tension after reperfusion. In the presence of class Ib drug mexiletine (10 μM), the shortening of the APD₉₀ during ischemia was significantly facilitated. The recovery of developed tension in the presence of mexiletine tended to be improved, although the difference was not statistically significant. The developed tension measured after the 60 min reperfusion period following 20 min of no-flow ischemia was markedly depressed, indicating the presence of myocardial stunning. Mexiletine and pilsicainide significantly improved the recovery of developed tension and diminished the stunning. We conclude that cibenzoline and glibenclamide, which block cardiac K_ATP channels inhibit contractile recovery after reperfusion by attenuating the shortening of APD during ischemia. In contrast, mexiletine, which activates K_ATP channels (in addition to blockade of Na⁺ channels) improves contractile recovery by facilitating the shortening of APD during ischemia. Received: 21 July 1997 / Accepted: 3 December 1997     

血小板活化因子在缺血再灌注损伤中电生理作用的实验研究

目的　研究正常灌注、模拟缺血 /再灌注下血小板活化因子的电生理作用 ,初步探讨血小板活化因子的作用机制。方法　通过标准微电极技术 ,分析豚鼠左心室乳头肌在正常灌注、缺血 /再灌注时的血小板活化因子的电生理作用以及CV 6 2 0 9和格列本脲对其作用的影响。结果　血小板活化因子明显缩短了动作电位时相 ,灌注前后APD90 (90 %复极水平的动作电位时相 )分别为 (14 4 0± 5 8)ms和 (12 0 3±5 8)ms (n =8,P <0 0 0 1) ,CV 6 2 0 9(血小板活化因子受体阻断剂 )和格列本脲 (ATP敏感性K+ 通道阻断剂 )明显抑制了血小板活化因子诱发的动作电位持续时间缩短。CV 6 2 0 9组 (n =5 )、格列本脲组 (n =6 )和对照组相比较 ,血小板活化因子诱发的APD90 缩短率分别为 (5 8± 1 9) % ,(1 1± 1 9) %比 (16 4±1 8) % (P <0 0 5 ,P <0 0 0 1)。血小板活化因子引起了早期的动作电位持续时间的进一步缩短 ,相反 ,血小板活化因子引起再灌注早期的动作电位时相延长。结论　血小板活化因子明显缩短了动作电位时相 ,CV 6 2 0 9和格列本脲阻断血小板活化因子诱发的动作电位持续时间缩短 ,提示血小板活化因子受体和ATP敏感性K+ 通道 ,可能介入血小板活化因子电生理作用 ;血小板活化因子放大缺血 /再灌注时缺血区和