CYP3A4,CYP3A5和MDR1基因多态性对环孢素处置的影响

环孢素是一个广泛用于器官移植患者的免疫抑制剂,具有治疗指数窄,不同个体间药代动力学差异较大的特点。它主要通过肝脏和小肠的CYP3A4和CYP3A5代谢;同时它又是药物转运体的底物。不同个体间药物代谢酶和转运体活性的差异可能是造成不同器官移植患者环孢素药代动力学差异的主要原因。而遗传因素即编码药物代谢酶和转运体基因序列的差异可能是其产生活性差异的分子机制。因此,从编码药物代谢酶和转运体的基因入手,可能会为器官移植患者提供最优的治疗方案。     

杭州地区抗排异药物在器官移植中的应用分析

目的：评估杭州地区抗排异药物的临床应用状况、药物的效果与费用间的关系。方法：应用金额分析法和DDDs分析法。结果：2004—2006年杭州地区抗排异药的消耗增一矢率为71％和10．1％。环孢素、霉酚酸酯和他克莫司的消耗较大；医院之间的用量非常不平衡，抗排异药的消耗量集中在器官移植的重点医院。DDDs排序前列的是霉酚酸酯和环孢素，DDDs增长最快的是他克莫司；DDC最高的是他克莫司。结论：杭州地区抗排异药的应用与国内外新药的发展基本一致；进口产品垄断市场的局面已发生改变；随着器官移植术的进一步推广，本类药物的消耗仍会快速增长；但抗排异药价格高、费用大，应该考虑降低药价，减轻患者经济负担。     

器官移植受者体内他克莫司膜转运体的遗传药理学研究进展

他克莫司作为一种新型免疫抑制剂,广泛应用于各类器官移植的治疗中,效果显著.他克莫司具有很强的个体代谢差异性,治疗窗窄,给药剂量难以在合理的范围内,引起术后移植功能不全,不良反应多发,严重降低了移植器官的生存率.代谢酶是影响他克莫司代谢的重要遗传因素,此外,转运体也与他克莫司代谢密切相关,对转运体的基因多态性进行研究,对...     

相关基因多态性与肾移植术后他克莫司疗效的关系研究进展

摘要：他克莫司是临床常用的免疫抑制药之一,其在器官移植术后的抗排斥治疗中的疗效显著,能够有效减少患者急性排斥反应的发生率,对提高患者器官移植术的成功率有着至关重要的意义。但据临床研究发现,不同人群中他克莫司的疗效存在差异,药物在人体内吸收、代谢和分布的过程可能受遗传因素的影响。目前临床对于他克莫司疗效相关基因的研究主要为药物代谢酶CYP450酶(CYP3A4、CYP3A5)、转运蛋白基因(MDR1、SLCO1B3)及调控基因(PXR、FOXP3)等,但国内外研究结果不尽相同。本文将进一步系统分析基因多态性与肾移植患者他克莫司疗效的相关性,旨在为器官移植患者提供更加合理和个体化的治疗方案,减少急性排斥反应及术后感染等情况的发生,提高患者的生存率及生活质量。     

抗真菌抗生素和免疫抑制剂

微生物来源的具免疫抑制活性的抗真菌抗生素如环孢素、他克莫司(FK506)、雷帕霉素和霉酚酸已被开发为器官移植抗排斥药物和自身免疫性疾病的治疗药物.笔者介绍了这些药物的抗真菌和免疫抑制活性以及作用机制等,还介绍了一些从抗真菌抗生素中开发的和从微生物中分郭得到的具有抗真菌活性的新免疫抑制剂.抗真菌抗生素和免疫抑制剂之间似乎有存在着一定的关系,对发现新的抗真菌抗生素和免疫抑制剂具有一定的意义.     

他克莫司给药后个体代谢差异与CYP3A基因型的相关性研究进展

他克莫司是近年来兴起的临床常用抗生素类免疫抑制剂,对于接受器官移植的患者具有明显的免疫抑制改善作用。他克莫司体内代谢个体差异较大,治疗窗和安全范围小,有研究表明可能由于编码细胞色素P450酶系基因的相关作用导致他克莫司药物代谢动力学个体间变异。本文通过总结最新研究内容,对影响他克莫司代谢的相关基因进行概述。     

免疫抑制剂的应用分析与临床评价

目的：免疫抑制剂在器官移植和自身免疫系统疾病方面疗效显著。目前市场上免疫抑制剂种类繁多,作用机制多样。本文阐述免疫抑制剂的应用分析与临床评价。方法：采用国内、外文献综述方法。结果与结论：由3年数量份额上分析,销售数量和销售金额最多的排序前3位品种为霉酚酸酯、环孢素、他克莫司。而他克莫司有望成为器官移植的首选药物。     

药物基因组学与抗排异药物个体化用药

目的探讨药物基因组学在抗排异药物个体化用药的进展与前景。方法对临床常用的抗排异药物的作用机理和特点进行比较,介绍药物基因组学的概念与应用范围,重点介绍药物基因组学在他克莫司、环孢素及霉酚酸酯个体化用药中的研究实例。结果MDR1与CYP3A5基因多态性与环孢素和他克莫司在移植病人体内的药动学与用药剂量之间存在着明显的基因剂量效应;而UGT1A8、UGT1A9、UGT2B7和ABCC2基因多态性与霉酚酸酯代谢物MPA、MAPG和AcMPAG的体内消除和蛋白表达密切相关。结论药物基因组学在抗排异药物个体化用药中的应用,可以在改善药物疗效的同时,减少药物不良反应的发生。     

他克莫司的药物基因组学研究进展

他克莫司（tacrolimus,FK506）是从链霉菌属中分离出的一种新型强效免疫抑制药,它与环孢素（cyclosporine,CsA）同属于钙调磷酸酶抑制药（calcineurin inhibitors,CNIs）家族,由于其具有更好的免疫抑制作用和肝肾安全性,FK506正逐渐取代CsA成为器官移植患者术后的首选免疫抑制药。然而同CsA一样,FK506治疗窗窄、药动学个体差异大一直是困扰该药临床应用的难题,而编码药物代谢酶、     

免疫抑制剂的进展与临床和市场评价

目的：免疫抑制剂在器官移植和自身免疫系统疾病方面疗效显著。目前市场上免疫抑制剂种类繁多，作用机制多样。本文阐述免疫抑制剂的进展与市场态势。方法：采用国内外文献综述方法，并应用国内权威信息网的数据，进行分析。结果及结论：由3年数量份额上分析，销售数量和销售金额排序前3位品种为霉酚酸酯、环孢素、他克莫司。而他克莫司有望成为器官移植的首选药。     

Role of the liver in the disposition of intravenous nitroglycerin in the rat

Previous studies have indicated that the liver is the main site of nitroglycerin (NTG) elimination when the drug is systematically infused. To examine this hypothesis, we measured the apparent systemic clearance (Cls) of nitroglycerin in anesthesized rats receiving a constant intravenous infusion at a dose of 100 micrograms per kg per min. Animals were divided into shunt and sham groups; the former had undergone a portal vein ligation 10 days prior to the study, while the latter was subjected to a sham operation. On the study day, half of the animals of each group also received probenecid at 200 mg/kg, i.v., a drug previously reported to inhibit organic nitrate ester reductase (ONER) activity in rat liver. Arterial NTG samples were obtained at 41, 43 and 45 min of infusion in all four experimental groups; Cls was 439 +/- 32 ml per kg per min (mean +/- S.E.) in sham, 460 +/- 44 in sham and probenecid, 477 +/- 39 in shunt, and 461 +/- 34 in shunt and probenecid animals. During NTG infusion, hepatic blood flow (measured with a constant infusion of indocyanine green) was decreased markedly in shunted rats as was liver/body weight, indicating hepatic atrophy. The specific activity of hepatic ONER was similar in all four groups. In spite of marked differences in hepatic blood flow and hepatic mass, the Cls was similar in all four groups. The liver does not appear to be a major site for the elimination of systemic nitroglycerin as hitherto assumed.     

HACCP在学校集体食堂卫生管理中的应用研究

目的 通过HACCP在学校集体食堂管理中的应用,提高食品卫生水平,保障学生的身体健康。方法 HACCP原则。结果 食品卫生达到较高水平,极大地减少了食物中毒的发生。结论 提示HACCP原则可在学校集体食堂的卫生管理中发挥有效作用。     

半导体激光治疗老年人压疮疗效观察

目的探讨半导体激光局部照射治疗老年人压疮疗效.方法:收集2012年1月-2015年6月48例压疮患者,分为半导体组和常规组各24例.常规组采用常规治疗,半导体组采用半导体激光加常规治疗,10 d为1个疗程,不超过3个疗程.疗程结束后比较两组疗效.结果:半导体组压疮愈显率为83.33％,创面愈合时间为(12.75±5.51)d,常规组分别为54.17％和(19.63±8.65)d,组间差异有统计学意义(P＜0.05),两组均未见不良反应.结论:半导体激光加常规治疗压疮效果肯定,无明显不良反应,且操作简便.     

脑卒中恢复期患者社区综合康复的疗效观察

目的：探讨社区开展康复活动对于脑卒中患者肢体功能康复的影响。方法：选取2014年4至10月参与社区“陈睿健康工作室”康复活动的脑卒中恢复期患者50例作为观察组,选取同期延吉社区卫生服务中心门诊的50例脑卒中恢复期患者作为对照组（进行门诊随访、服药、自我康复）。采用知识、信念、行为（KAP）量表对观察组患者进行问卷调查。采用简化Fugl-Meyer肢体运动功能评分表（Fugl-Meyer assessment of motor function,FAM）比较两组患者入组时和入组6个月时的肢体功能恢复情况及对家庭医生（门诊医师）的满意度。结果：入组6个月时,两组患者的FAM均有所改善,观察组FAM得分[上肢（50.92±7.05）分,下肢（33.01±1.37）分]较对照组[上肢（34.85±6.55）分,下肢（25.20±4.88）分]更高,差异有统计学意义（t上肢=11.8215,t下肢=10.8595,P均＜0.01）。观察组患者的满意率为92%（46/50）,明显高于对照组的30%（15/50,P＜0.05）。结论：在社区开展康复活动可以促进脑卒中患者肢体功能的康复,提高患者的满意度。     

Evaluation of the safety of enalapril in the treatment of heart failure in the very old

Summary We have introduced enalapril, in doses equal to or less than the 2.5 mg currently recommended, as an adjuvant to digoxin and diuretics in 17 patients of mean (SD) age 83 (5) years with severe heart failure. Only eleven patients tolerated its introduction. Unlike those reported in younger patients, all but one of the adverse drug reactions occurred 8 h or more after the first dose. Aged patients started on ACE inhibitors should be observed in hospital until stabilized on a maintenance dose. Three patients had an adverse reaction which differed in nature from those previously reported: acute confusional state, ataxia and mesenteric ischaemia.Ten patients were discharged on 5 mg or 10 mg maintenance doses of enalapril. In nine of them improvement on triple therapy was sustained for a minimum of three months. ACE inhibition was lost in the other patient when her compliance with enalapril therapy fell to around 75%: monitoring compliance is essential when ACE inhibitors are used in low dosages.Enalapril was withdrawn during follow up in three patients because of symptoms of mesenteric ischaemia and in four because of dramatic deterioration of renal function. One of the latter was found subsequently to have severe bilateral atheromatous renal artery stenosis. When isosorbide dinitrate was substituted for enalapril, symptoms of mesenteric ischaemia resolved and renal function returned to baseline. Continuing surveillance for adverse effects is essential in patients of this age group with severe heart failure, and the risk of occult renal artery stenosis requires regular biochemical screening during follow up.The benefit to cost ratio of ACE inhibitors might be improved in aged patients by their use at an earlier stage in the natural history of heart failure, when perfusion of essential organs is not grossly impaired, but carefully monitored trials would be necessary to establish this.     

Effect of the Immunomodulator Tilorone on the in Vivo Acetylation of Procainamide in the Rat

Interferon and interferon inducers have been found to inhibit cytochrome P-450-dependent metabolism in animals and man. The effect of these agents on the acetylation of drugs has not been previously reported. Since these agents stimulate the reticuloendothelial system, together with the abundance of N-acetyltransferase in the reticuloendothelial system, it was hypothesized that these immunomodulators may affect drug acetylation. To test this hypothesis, the effect of tilorone (a synthetic interferon inducer) on the in vivo acetylation of procainamide was examined in the rat. Pretreatment with tilorone hydrochloride (50 mg/kg) 48 hr prior to the administration of procainamide hydrochloride (50 mg/kg) resulted in a 32% increase in the urinary recovery of N-acetylprocainamide and a 35% increase in the metabolic clearance of procainamide to N-acetylprocainamide. These data indicate that interferon inducers increase the N-acetylation of drugs in vivo.     

药物经济学成本-效果分析应用的相关问题探讨

目的探讨药物经济学成本-效果分析(CEA)应用的相关问题。方法运用文献计量学方法、数学证明方法等。结果与结论在运用CEA进行药品的经济性评价时,尤其需要重视临床治疗指标的选择、成本的确定、增量分析的使用和与最小成本分析的比较。     

替普瑞酮治疗老年慢性浅表性胃炎的疗效分析

目的 分析替普瑞酮治疗老年慢性浅表性胃炎的疗效.方法 100例老年慢性浅表性胃炎患者,通过计算机随机表数字法分为对照组和实验组,每组50例.对照组患者选择西咪替丁作为本次治疗药物,实验组患者选择替普瑞酮作为本次治疗药物.比较两组患者临床疗效、不良反应发生情况以及生活质量.结果 实验组治疗总有效率92.00％高于对照组的...     

Adenosine mechanisms in the regulation of breathing in the rat

The central respiratory effects of various adenosine (A) analogues were studied in halothane-anesthetized rats. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) injections of the A analogues (2-Cla, L-PIA, CHA and NECA) reduced minute ventilation (VE) due to decreases in respiratory frequency (f) as well as tidal volume (VT). Dose-dependent effects were seen after i.c.v. L-PIA in both normal and vagotomized rats. Analysis of the A-induced changes using the occluded breath technique revealed an increase in expiratory time (TE) as well as a decrease in inspiratory drive. NECA, a relatively specific A2 agonist seemed to be somewhat more potent in eliciting respiratory depression than a relatively specific A1 agonist like L-PIA. Pretreatment with the methylxanthine theophylline completely antagonized the respiratory depression induced by L-PIA. It is concluded that central A receptors are involved in the central regulation of breathing and that A interacts with the respiratory control system mainly by decreasing inspiratory neural drive and prolonging expiratory time.     

Nifedipine in the treatment of hypertension in the elderly

The effect of nifedipine monotherapy, retard tablets, 20 mg bid, was evaluated in 23 hypertensive patients, mean age, 79 +/- 2 years. Twenty-one patients completed an eight-week study. Blood pressure (BP) decreased to 160/90 mm Hg in 15 patients; in four additional patients diastolic BP dropped by 15% to 28%. In a subset of five patients with isolated systolic hypertension, a significant reduction in systolic BP was noted. Side effects were relatively mild and only two patients discontinued the study. The results suggest that nifedipine monotherapy offers an alternative, logic, therapeutic approach to hypertension in the elderly.