奥利司他对肥胖高血压患者非内皮依赖性血管舒张功能的影响

目的：观察肥胖高血压患者服用奥利司他治疗前后血压和硝酸甘油介导的肱动脉非内皮依赖性血管舒张功能的变化。方法：30例肥胖合并轻度高血压患者（肥胖高血压组）奥利司他120 mg,3次/d,共12周,服药前后诊所测量身高、体重、腰围及血压,计算BMI。并行肱动脉高解像度超声检查,舌下含服硝酸甘油0.3 mg,测定硝酸甘油介导的血管舒张（NMD）程度的变化。15例非肥胖的高血压患者作为对照组。结果：两组基线的特征具有可比性。肥胖高血压组患者治疗前与非肥胖高血压患者的NMD无差别,但BMI及腰围明显增加（P均〈0.01）。奥利司他治疗12周后BMI、腰围、血压均有显著下降（P〈0.05或P〈0.01）;NMD较治疗前无明显改善（16.2%vs15.5%,P〉0.05）。结论：奥利司他短期治疗能降低肥胖高血压患者的体重及血压,但对硝酸甘油介导的肱动脉非内皮依赖性血管舒张功能无作用。     

尿酸对超重高血压内皮依赖性血管舒张影响

目的观察尿酸对超重合并高血压患者内皮依赖性血管舒张功能的影响。方法81例超重合并高血压患者、检测尿酸,分为高尿酸组（男≥390umol/L,女性≥310umol/L）、低尿酸组,测定二组患者低密度脂蛋白胆固醇（LDL）,空腹血糖,空腹胰岛素、计算HOMA-IR,并行肱动脉超声检查,测定血流介导的血管舒张功能。结果高尿酸组LDL高于低尿酸组,与低尿酸组对比有显著性差异（P〈0.05）,高尿酸组空腹胰岛素与胰岛素抵抗指数高于低尿酸组,两组对比呈显著性差异（P〈0.01）,高尿酸组加压反应性充血后肱动脉内径平均增加（9.5±1.5）%低于低尿酸组（12.1±2.2）%（P〈0.01）。结论高尿酸血症与超重合并高血压患者内皮依赖性血管舒张功能的障碍关系密切。     

老年高血压患者血管内皮依赖性舒张功能探讨

目的　探讨老年高血压患者的内皮依赖性舒张功能及其影响因素。方法　用高分辨 2D和多谱勒超声测定 6 0例老年高血压患者及 6 0例正常血压的老年对照组的肱动脉。在袖带加压开放4.5min后 ,血流增加引起的肱动脉扩张反应的增量结果。结果　老年高血压组血流介导的血管扩张百分率 ( 5 .18± 3 .40 )明显低于对照组 ( 8.0 5± 5 .0 6 ,P <0 .0 5 ) ,两组硝酸甘油介导的血管扩张率无统计学差别。单因素分析发现除高血压外 ,血清总胆固醇水平、冠心病史、吸烟史是内皮依赖性舒张功能的影响因素。结论　老年高血压患者的血管内皮依赖性舒张功能比对照组明显降低 ,除高血压外 ,冠心病及其危险因素可能是其损害因素之一     

曲美他嗪对冠心病心力衰竭患者血管内皮依赖性舒张功能的影响

目的探讨曲美他嗪（TMZ）对冠心病心力衰竭（CHF）患者的治疗作用及其对血管内皮依赖性舒张功能的影响。方法80例冠心病CHF患者随机分为治疗组和对照组，每组40例，对照组给予洋地黄类、利尿剂、血管扩张剂、血管紧张素转化酶抑制剂、B受体阻滞剂常规治疗；治疗组在常规治疗基础上加用TMZ治疗，两组均连续用药6个月。治疗前后进行多普勒超声心动图检查，评定心功能及血管内皮依赖性舒张功能的变化。结果治疗组心功能改善的临床显效率（45．0％）和总有效率（92．5％）均较对照组（25．0％和67．5％）显著提高（P〈0．01），且无不良反应发生。治疗后治疗组患者左室射血分数、左室舒张末期容积、左室收缩末期容积、心排血量与血管内皮依赖性舒张功能指标均明显改善（P〈0．01或〈0．05），与对照组比较差异有统计学意义（P〈0．01或〈0．05）。结论TMZ有改善左心功能及血管内皮依赖性舒张功能的作用，是辅助治疗CHF的一种有效安全的药物。     

血管内皮依赖性舒张功能障碍

内皮细胞是人体大血管壁的第一道屏障,在动脉粥样硬化病变的发生上有重要意义。血管内皮细胞可分泌一氧化氮(NO)、内皮素-1(ET-1)、前列环素(PGI2)、血管紧张素(Ang)、血管假性血友病因子(vWF)、黏附分子(如ICAM-1、VCAM-1)等活性物质,这些活性物质之间的相互作用,维持着血管的舒缩     

超声检测高血压病患者内皮依赖性血管舒张功能障碍的研究进展

血管内皮及内皮释放的介质是目前心血管领域研究的热点,逆转失调的内皮功能是心血管疾病治疗的一个新趋势。内皮细胞对维持正常的血管功能起着很重要的作用,内皮本身是一个有生理活性的器官,它调节着动脉壁的平衡,在调节血管的舒张及收缩方面具有重要作用,内皮功能的临床诊断对于高血压病、冠心病等常见病的早期诊断、治疗效果判定和估计预后有重要意义。近年来越来越多的研究证实,内皮依赖性血管舒张功能障碍是形成高血压     

咪达普利对高血压合并糖耐量减低患者血管内皮依赖性舒张功能的影响

目的 探讨咪达普利对高血压合并糖耐量减低(impaired glucose tolerance,IGT)患者血管内皮依赖性舒张功能的影响.方法 咪达普利5～10 mg/d治疗高血压合并IGT患者50例,疗程3个月,分析治疗前后血压、空腹血糖(fasting plasma glucose,FPG)、糖负荷后2h血糖(2-hour plasma glucose,2hPG)、空腹胰岛素(fasting insulin,FINS)、胰岛素抵抗指数(HOMA-insulin resistance index,HOMA-IR)、血浆一氧化氮(NO)的变化,利用高频超声血管技术检测咪达普利治疗前后肱动脉内皮依赖性舒张(endothelium-dependent diastolic,EDD)功能,计算其舒张内径的变化率(flow mediated dilation,FMD).结果 与治疗前比较,治疗后患者的收缩压显著下降(P＜0.01),舒张压、FINS、HOMA-IR均下降(P＜0.05),血浆NO水平、FMD升高(P＜0.05).治疗前后FMD变化值(ΔD)分别与FINS、HOMA-IR、NO及其相应变化值ΔFINS、ΔHOMA-IR、ΔNO相关.结论 咪达普利对高血压合并IGT患者在有效降压的同时,能明显改善内皮依赖性舒张功能.     

依那普利对高血压患者内皮依赖性舒张功能的影响

目的评价依那普利对高血压患者内皮依赖性舒张功能的影响。方法30例高血压患者应用依那普利治疗前后分别用高分辨率超声,测量右肱动脉在静息时、反应性充血(流量介导血管舒张)、舌下含服硝酸甘油(硝酸甘油介导舒张)时的舒张末期内径,取25例健康人对比分析。结果高血压病组流量介导血管舒张(FMD),较对照组明显减弱(P<0.01),而硝酸甘介导血管舒张(NCD)两组无显著性差异(P>0.05)。经治疗,收缩压、舒张压均显著降低(P<0.01),FMD较治疗前显著提高,NCD无改变。结论依那普利可显著改善高血压患者内皮依赖性舒张功能。     

硝苯地平对老年高血压患者内皮分泌及依赖性舒张功能的影响

目的:观察硝苯地平对老年高血压患者内皮分泌及依赖性舒张功能的影响.方法:选取我院2010年5月～2011年5月70例高血压脑出血患者为研究对象,将患者随机分为观察组与对照组,每组35例;另选健康体检者35例为正常组.观察组给予硝苯地平干预,对照组给予清脑降压片干预,观察并记录两组内皮素(ET)、一氧化氮(NO)水平,收缩压(SBP)、舒张压(DBP)及不良反应发生率.结果:观察组治疗后ET水平(51.69±5.21)pg/m、SBP(146.62±11.35)mmHg、BBP(82.34±4.96)mmHg低于对照组(59.36±5.06)pg/m、(162.35±12.64)mmHg、(89.60±4.58)mmHg,观察组NO水平(69.64±6.52) μmol/L高于对照组(61.35±8.83) μmol/L,差异有统计学意义(P＜0.05).两组总不良反应发生率比较差异无统计学意义(P＞0.05).结论:硝苯地平降压作用较好,能改善老年高血压患者内皮依赖性舒张功能,调节血管内皮分泌功能不良反应较少.     

Long-term inhibition of intestinal lipase by orlistat improves release of gut hormones increasing satiety in obese women

BackgroundReduced postprandial secretion of peptide YY (PYY), glucagon-like peptide-1 (GLP-1), cholecystokinin, and increased hunger was reported after a single dose of orlistat, an inhibitor of intestinal lipase. As yet, the influence of long-term therapy with orlistat on PYYand GLP-1 release has not been studied. Our study was aimed at assessing the influence of 8-week therapy with orlistat as a component of a weight loss program on pre-prandial circulating PYY and GLP-1 levels.MethodsForty obese women, without concomitant diseases, were randomly allocated to groups receiving orlistat or placebo during an 8-week weight management program. Body mass, body composition and plasma levels of PYY, GLP-1 and insulin (for QUICKI calculation) were determined prior to and at the end of therapy.ResultsWomen treated with orlistat obtained significantly greater body and fat mass loss than those receiving placebo (9.0 ± 3.1 vs. 5.9 ± 3.2% and 21.9 ± 10.9 vs. 7.4 ± 15.6%, respectively). Only in those treated with orlistat a slight, but significant increase of the QUICKI was found (8.0 ± 16.5 vs. –0.1 ± 12.7%, respectively).Weight loss was followed by a significant increase of plasma levels of PYY and GLP-1 in group treated with orlistat, and was about 2-times greater than receiving placebo. The increase was independent of body mass changes.ConclusionThe long-term inhibition of intestinal lipase by orlistat increases the pre-prandial levels of GLP-1 and PYY, independent of body mass changes. Therefore, it seems that long-term treatment with orlistat may exert hunger suppressing and insulin sensitizing incretin effect beyond weight reduction.     

Comparison of orlistat treatment and placebo in obese type 2 diabetic patients

Aim: To evaluate the effects of 1-year treatment with orlistat compared with placebo on different inflammatory parameters in type 2 obese diabetic patients.

Materials and methods: Two hundred and fifty-four type 2 diabetic patients were randomized to take orlistat 120 mg three times a day or placebo for 12 months. We evaluated at baseline and after 3, 6, 9 and 12 months: leptin, tumor necrosis factor (TNF)-α, adiponectin (ADN), vaspin and high-sensitivity C-reactive protein (HS-CRP), body weight, waist circumference, body mass index (BMI), lipid profile, glycemic profile, fasting plasma insulin (FPI) and homeostasis model assessment insulin resistance index (HOMA-IR).

Results: Regarding inflammatory parameters, there was a significant improvement of ADN and TNF-α, and a faster decrease of leptin and HS-CRP in the orlistat group compared with the control group. We also recorded a significant reduction of body weight and BMI with orlistat, but not with placebo. A faster improvement of glycemic profile and FPI was obtained with orlistat compared with the controls. Also, there was a significant reduction of lipid profile with orlistat, not reached with placebo.

Conclusions: Orlistat was more effective than placebo in ameliorating inflammatory parameters such as ADN and TNF-α, and anthropometric parameters.     

Addition of a low dose of rimonabant to orlistat therapy decreases weight gain and reduces adiposity in dietary obese rats

1. The aim of the present study was to determine whether the addition of a subeffective dose of rimonabant (1 mg/kg) to orlistat would be beneficial in the treatment of diet-induced obesity in rats compared with orlistat monotherapy. 2. Male rats were divided into five groups: (i) rats fed a low-fat diet for 4 months; (ii) rats fed a high-fat diet (HFD) for 4 months and treated daily with vehicle (0.2% Tween-80 solution); (iii) orlistat (10 mg/kg per day)-treated HFD-fed rats; (iv) rimonabant (1 mg/kg per day)-treated HFD-fed rats; and (v) HFD-fed rats treated with a combination of orlistat plus rimonabant. Fasting blood glucose, serum insulin, leptin and adiponectin levels were measured. Liver and adiposity indices were calculated and liver and adipose tissues were processed for histological examination. 3. Over the 4 months of the study, vehicle-treated HFD-fed rats exhibited increased cumulative food intake, bodyweight and liver and adiposity indices. Moreover, vehicle-treated HFD-fed rats exhibited a deterioration in liver function and an abnormal lipid profile. Insulin resistance and serum leptin were increased in this group, whereas serum adiponectin levels were decreased. Orlistat monotherapy or combination therapy with orlistat plus rimonabant improved all these parameters. 4. The addition of the low subeffective dose of rimonabant to orlistat therapy ameliorated HFD-induced obesity to a much greater extent than orlistat monotherapy. This combination showed better weight control and metabolic profile compared with orlistat alone. Therefore, the results of the present study encourage reassessment of the use of a low dose of rimonabant to potentiate the effect of orlistat in the clinical management of obesity if proper clinical safety data are available.     

Safety assessment of FDA-approved (orlistat and lorcaserin) anti-obesity medications

Introduction: Options for treating obesity remain limited despite it being a chronic, recurrent and morbid condition. New drugs that are proposed for its treatment encounter strong reluctance by regulatory agencies and many doctors.

Areas covered: This review will focus on the safety of an older drug, orlistat (the only one still approved in the European Union) and a newer recently FDA-approved one, lorcaserin. Both are approved as long-term monotherapy for obesity in the United States of America and they have demonstrated median weight loss of nearly 3% over placebo.

Expert opinion: Research, development and approval of new anti-obesity drugs are necessary for improved management of this chronic condition. Orlistat and lorcaserin are two FDA-approved drugs with limited overall efficacy. Nevertheless they are useful weapons for at least some obese individuals. Orlistat has a long and solid safety profile, whereas the safety of lorcaserin is still a matter of debate, mainly due to a lack of long-term data. However, lorcaserin’s selective agonism on 5HT2c serotonin receptors diminishes concerns about valvulopathy associated with other serotonin agonists, such as fenfluramine.     

The effectiveness of pharmaceutical interventions for obesity: weight loss with orlistat and sibutramine in a United Kingdom population-based cohort

Aims

Drug treatments for obesity have proven efficacy from randomized trials, but their effectiveness in routine clinical practice is unknown. We assessed the effects on weight and body mass index (BMI) of orlistat and sibutramine when delivered in routine primary care.

Methods

We used United Kingdom data from the Clinical Practice Research Datalink to estimate the effects of orlistat or sibutramine on weight and BMI over 3 years following treatment initiation. For comparison, we matched each patient with up to five obese patients receiving neither drug. Mixed effects linear regression with splines was used to model change in weight and BMI. Mean change with 95% confidence intervals (CI) was estimated.

Results

We identified 100 701 patients receiving orlistat, 15 355 receiving sibutramine and 508 140 non-intervention patients, with body mass index of 37.2, 36.6 and 33.2 kg m⁻², respectively. Patients receiving orlistat lost, on average, 0.94 kg month⁻¹ (0.93 to 0.95) over the first 4 months. Weight gain then occurred, although weight remained slightly below baseline at 3 years. Patients receiving sibutramine lost, 1.28 kg month⁻¹ (1.26 to 1.30) over the first 4 months, but by 3 years had exceeded baseline weight. Non-intervention patients had slight increases in weight throughout the 3 year period, with gains ranging between 0.01 and 0.06 kg month⁻¹.

Conclusions

Orlistat and sibutramine had early effects on weight loss, not sustained over 3 years. As new treatments for obesity are approved, their effectiveness should be measured in routine clinical practice, as effectiveness may be considerably less than seen in randomized trials.     

临界高血压患者经卡托普利治疗前后血管内皮功能的超声对比研究

目的 :研究卡托普利对临界原发性高血压患者血管内皮功能的影响。方法 :利用高分辨超声技术 ,观察了 2 3例临界原发性高血压患者和 2 0例正常人的肱动脉血管内皮依赖性舒张功能。结果 :虽然两组受检者对硝酸甘油的反应性无显著性差异(% :2 6.0 2± 5 .5 9vs 2 8.0 2± 6.0 4 ,P >0 .0 5 ) ,但临界高血压患者肱动脉血流介导性较正常组明显减弱(% :6.34± 2 .4 3vs 2 4 .38± 5 .87,P <0 .0 5 )。经服用卡托普利治疗血压控制 3mon后 ,肱动脉内皮性舒张较治疗前明显改善 (% :2 2 .5 0± 5 .4 5vs 6.34±2 .4 3,P <0 .0 5 ) ,且基本恢复至正常。结论 :临界高血压患者存在血管内皮依赖性舒张功能障碍 ,经卡托普利治疗后 ,受损的血管内皮依赖性舒张功能能恢复致正常水平。     

The use of orlistat in the treatment of obesity,dyslipidaemia and Type 2 diabetes

Orlistat (tetrahydrolipstatin) is an inhibitor of gastrointestinal lipases, especially pancreatic lipase. It is used as an adjunct to diet and exercise in order to achieve weight loss in obese individuals (body mass index > 30 kg/m²) or in overweight individuals (body mass index > 27 kg/m²) with other risk factors for atherosclerotic vascular disease, such as hypertension, dyslipidaemia or diabetes. Short- and long-term studies of up to 4 years duration have shown the drug to have significant benefits in weight loss, as well as in the reduction in lipids, glucose and haemoglobin A1c, and in time to onset of Type 2 diabetes compared with diet alone or placebo groups. The incremental amount of weight loss that orlistat produces is modest, but sufficient to result in improvement in obesity comorbidities such as elevated blood pressure, dyslipidaemia and hyperglycaemia compared with diet and exercise alone. Orlistat should only be prescribed for individuals who are motivated to adhere to lifestyle modifications, especially dietary fat restriction.     

UPLC在奥利司他制备液相纯化过程中的应用

目的研究建立奥利司他超高效液相色谱快速检测方法。方法以ACQUITY UPLC BEH C18柱(Φ100mm×2.1mm,1.7μm)为固定相,以81%乙腈水溶液为流动相,流速0.4mL.min-1,进样0.8μL,在195nm检测,采集信号并分析。结果在此色谱条件下,可有效地对奥利司他样品进行快速检测。结论该超高效液相色谱法可快速、有效地完成对奥利司他的分析检测。     

二甲双胍治疗肥胖型顽固性高血压病人的临床观察

目的 :观察二甲双胍对肥胖型、顽固性高血压病人的相关参数的影响。 方法 :将 34名肥胖型、顽固性高血压病人随机分为试验组和对照组 ,前者服用二甲双胍 85 0 m g,bid,后者服用谷维素 10 m g,bid,治疗开始前及 3个月后观察空腹血糖、三酸甘油酯、胰岛素、胰岛素敏感性参数及血压的变化。 结果 :治疗 3个月后试验组的空腹胰岛素、三酰甘油、胰岛素敏感性参数及血压均有下降 (P<0 .0 5 ) ;试验组及对照组降压疗效有效率分别为 5 2 .9%、11.8% ,两组相比有显著差异 (P<0 .0 1)。 结论 :二甲双胍可明显改善肥胖型、顽固性高血压病人的胰岛素敏感性 ,并可能通过此降低血压水平