卡马西平血清药物浓度对部分性癫痫患者疗效的影响

目的:研究不同卡马西平(CBZ)血清药物浓度对治疗部分性癫痫患者疗效的影响,为相关治疗提供参考依据。方法:按预期血药浓度控制水平将124例部分性癫痫患者随机分为高血药组即A组(卡马西平血药浓度:9～12μg/ml)和低血药组即B组(卡马西平血药浓度:4～8μg/ml),定期进行血药浓度监测,分析两组患者脑电图特征与临床疗效的差异。结果:在有效血药浓度范围内,卡马西平血药浓度增高不能提高临床疗效,对控制脑电图痫样放电也没有明显改善,且可导致背景活动异常。非线性动力学分析结果显示高血药浓度组脑电活动系统稳定性差。结论:卡马西平血药浓度以能控制症状的最低有效浓度即可,增加血药浓度对患者无益。     

通光散汤对小鼠哮喘模型气道高反应性和气道炎症的影响

目的观察通光散对小鼠哮喘模型气道反应和气道炎症的影响。方法35只6周龄BALB／c小鼠随机分为哮喘模型组、正常对照组和药物实验组。模型组和药物组以鸡卵白蛋白（OVA）致敏、激发;药物组在最后一次致敏后每天灌胃给予通光散汤0．72mL（相当于0．04g生药）;对照组以等体积的Ns代替OVA致敏、激发。末次激发48h后处理小鼠：无创法测定小鼠的气道高反应性,观察气道阻力变化;支气管肺泡灌洗液（BALF）行细胞学分类;观察肺组织的病理变化。结果①药物组小鼠气道阻力的变化与模型组相比明显下降,差异显著（P＜0．05）;②药物组BALF白细胞总数和Eos（％）与模型组相比明显降低（P＜0．05）。③模型组小鼠肺脏组织支气管、血管黏膜下和周围肺组织有明显的炎症细胞浸润,大量炎症细胞向支气管和血管迁移,上皮细胞部分有脱落,部分可见黏液栓,血管壁明显水肿;治疗组小鼠肺组织炎性细胞浸润和管腔黏液分泌情况较模型组明显减轻,气道粘液的分泌量得到明显的控制。结论通光散汤对小鼠哮喘模型气道高反应性和气道炎症有显著抑制作用。     

二室模型药物先静注后静滴的一种给药方案设计

静脉滴注(静滴)是临床上广泛使用的一种给药方法,只要选取适当的静滴速率,就能使稳态血药浓度等于治疗所需要的最佳有效血药浓度c_b,但对于半衰期较长的药物,静滴后血药浓度达到稳态值需很长时间,为了克服这一缺点,有同时快速静脉注射(静注)的方法。这一方法,对于一室模型药物,适当地选择静注剂量x_o和静滴速率k_o,可以使血药浓度在用药期间保持任一恒定值,从而有可能使血药浓度在用药期间保持最佳有效血药     

一种药物动力学模型控制问题的研究

生物的生长方程能够演变为Mitscherljch方程、Brody方程、Bertalanffy方程、Gompertz和Logistic等生长方程．此外它还能准确描述它们之间的过渡类型,在研究自然界中的生物物种方面被广泛应用,本文对一种生物控制模型进行分析,实现了对其控制模型的最优开发．在此基础上,将此模型的一种特例应用在药物动力学模型中,为模型研究提供了应用。     

用于药物评价的体外心脏组织模型研究进展

候选药物对心脏的毒副作用是其在开发过程中被淘汰的重要原因之一.传统药物评价所采用的动物模型存在种属差异、成本高、效率低等缺陷.因此,近年来随着干细胞和生物打印等技术的快速发展,体外心脏组织模型的构建受到了越来越多地关注.本文追踪体外心脏模型构建的起源与发展,综述模型所利用的心肌细胞来源以及二维、三维模型构建的相关技术与方法,着重阐述心肌组织模型血管化的重要性及研究进展,并对该领域未来的发展方向进行展望,以期为体外心肌组织模型在药物评价方面的研究和应用提供新思路.     

生理房室药动学模型

生理药动学模型较ｎ房室模型能更准确地描述药物在体内的处置过程,但在实际应用中由于其计算结果有较大的误差而限制其应用和推广．在生理模型中,某一组织器官中血液分布容积相对于单位时间的血流量来说,如果太大,就去给计算结果带来较大的误差．本文提出的生理房室模型可以减小这种误差,从而更准确地模拟药物在体内的处置过程．文中对一组模拟的生理和生化参数分别求出了生理房室模型和生理模型的数值解．通过两组解的比较,说明生理房室模型可以描述药物在体内处置过程中的细微变化．     

吸入麻醉诱导阶段药物动力学模型的定量分析

考虑了给药浓度、氧流量对吸入麻醉诱导阶段的影响,建立了诱导期药物动力学模型.利用非线性拟合的方法给出了诱导阶段的麻醉药血药浓度的拟合曲线;讨论了给药浓度相同的情况下,氧流量对诱导阶段所需时间的影响,得到了诱导阶段的氧流量分别与吸入肺部的药物浓度和体内消除系数的关系式,利用这两个关系式和诱导阶段的一般解可确定在此阶段体内血药浓度和完成诱导的时间.     

海马脑片抗癫痫药物研究的离体模型

目的：建立离体海马脑片癫痫样放电模型并用于抗癫痫药物研究。方法：在豚鼠海马脑片上灌流青霉素建立颠阗痫样放电的离体模型。并用此模型对抗癫痫药物苯巴比妥钠和苯妥英钠两种药物在不同浓度下对癫痫样放电的对抗作用进行了定量分析,结果：在海马脑片上灌流致痫药物可建立一个较好的离体组织癫痫样放电模型,苯的对抗作用进行了定量分析,结果：在海马脑片上灌流致痫药物可建立一个较好的离体组织癫痫样放电模型。苯巴比妥和苯妥英钠在一定浓度下均有显著对抗癫痫样放电的作用,且与整体实验的结果相一致。结论：本实验建立有离体脑片模型具有实验手段简单,方法灵活,易于建立药物量效关系等优点,可用于抗癫痫药物筛选和研究。     

马尔可夫药物动力学模型B

本文建立的Markov模型B适于计算肾、心、脑、皮肤、脂肪、肌肉中的血药浓度,它具有生理药动学模型的优点,即动力学参数具有解剖学和生理学意义,又能象房室模型一样用简单、优美的形式表示模型的解.     

亚胺培南/西司他丁钠与丙戊酸钠相互作用1例分析

男患,70岁,因"间断发热、咳嗽、伴黄痰半个月"入院,确诊为社区获得性肺炎(CAP)后结合患者基础疾病及高危因素,给予亚胺培南/西司他丁钠抗感染治疗。入院后补充诊断为继发性癫痫,给予丙戊酸钠(VPA)治疗。临床药师重点关注亚胺培南/西司他丁钠与VPA的药物相互作用,密切监测VPA血药浓度,发现两种药物联用时,患者VPA血药浓度明显低于正常值,导致癫痫再发作,停用亚胺培南/西司他丁钠后,VPA血药浓度显著上升,癫痫症状得到有效控制。临床药师分析亚胺培南/西司他丁钠与VPA联用会产生相互作用,前者可明显降低VPA的血药浓度,建议在药物治疗过程中密切监测VPA血药浓度,避免亚胺培南/西司他丁钠与VPA联用。     

Modulating effect of anticonvulsive agents on Ca2+ dependent membrane fusion in cell-free model of neurosecretion

The effect of antiepileptic drug ethosuximide and sodium valproat on fusion of synaptic vesicles with synaptosomal plasma membranes was studied in cell-free system. It was shown that ethosuximide and sodium valproat increases the rate of Ca(2+)-dependent fusion reaction in vitro. We have found that convulsant drugs pentylenetetrazol and picrotoxin did not fuse membrane components of the model system. Ethosuximide- and sodium valproat-provoked fusion of synaptic vesicles and plasma membranes of synaptosomes were suppressed by convulsant drugs pentylenetetrazol and picrotoxin.     

细胞药代动力学研究进展

经典的药物代谢动力学理论是建立在血浆药物浓度测定的基础上,常难以真实有效地预测体内药物的药效。很多药物必须穿透多重生物屏障,与细胞内的靶点相结合才能发挥药效。因此药代动力学研究迫切需要从“宏观”的血浆药物浓度深入到“微观”的细胞/ 亚细胞水平。综述细胞药代动力学研究领域取得的进展,重点介绍细胞药代动力学理论的提出、技术体系的建立及其在药物研发、筛选、临床方面的应用。     

Efficacy of different antidiabetic drugs based on metformin in the treatment of type 2 diabetes mellitus: A network meta-analysis involving eight eligible randomized-controlled trials

Diabetes mellitus is one of the most prevalent metabolic diseases globally and it is increasing in prevalence. It is one of the most expensive diseases with respect to total health care costs per patient as a result of its chronic nature and its severe complications. To provide a more effective treatment of type 2 diabetes mellitus (T2DM), this study aims to compare different efficacies of six kinds of hypoglycemic drugs based on metformin, including glimepiride, pioglitazone, exenatide, glibenclamide, rosiglitazone, and vildagliptin, in T2DM by a network meta-analysis that were verified by randomized-controlled trials (RCTs). Eight eligible RCT in consistency with the aforementioned six hypoglycemic drugs for T2DM were included. The results of network meta-analysis demonstrated that the exenatide + metformin and vildagliptin + metformin regimens presented with better efficacy. Patients with T2DM with unsatisfactory blood glucose control based on diet control, proper exercise, and metformin treatment were included. The original regimen and dose of medication were unchanged, followed by the addition of glimepiride, pioglitazone, exenatide, glibenclamide, rosiglitazone, and vildagliptin. The results of RCTs showed that all these six kinds of drugs reduced the HbA1c level. Compared with other regimens, exenatide + metformin reduced fasting plasma glucose (FPG), fasting plasma insulin (FPI), total cholesterol (TC), and homeostasis model assessment insulin resistance index (HOMA-IR) levels, but increased the high-density lipoprotein (HDL) level; vildagliptin + metformin decreased FPI and low-density lipoprotein (LDL) levels; glibenclamide + metformin decreased the FPG level, but promoted HDL; and glimepiride + metformin decreased the TC level and rosiglitazone + metformin reduced the LDL level. Our findings indicated that exenatide + metformin and vildagliptin + metformin have better efficacy in T2DM since they can improve insulin sensitivity.     

卡托普利单次和多次给药对自发性高血压大鼠模型的作用

目的探讨自发性高血压大鼠（SHR）是否同时适用抗高血压药物单次给药的快速评价和连续给药的降压效果评价。方法SHR大鼠分组给药后,用Powlab/16sp测量单次和多次给药后不同时间点SHR大鼠SAP、DAP、BMP和HR的变化。结果卡托普利单次给药1~2 h内对收缩压和舒张压有明显的降压作用（P〈0.05）,而连续给药随着给药时间延长给药28 d降压作用更为明显（P〈0.01）。结论自发性高血压大鼠既可用于降压药连续给药的药效学评价,也适用于单次给药的降压药快速筛选。     

Intervention effect of total flavonoids of ilex pubesceus on tolerant rat models under cerebral anoxia

Objective: To observe the intervention effect of total flavonoid of ilex pubesceus on animal models of cerebral ischemic tolerance. Methods: A rat model of global-focal cerebral ischemic tolerance was established by blocking bilateral common carotid artery blood flow and occluding left middle cerebral artery using thread-occlusion method. After the first operation, the Ginaton group and large-dosage, medium-dosage and small-dosage groups of total flavonoid of ilex pubesceus were given intragastric administration of corresponding drugs. The sham-operated group, pretreatment model group and ischemia-reperfusion group were given intragastric administration of the same volume of normal saline, 1 time a day, and administrated for 4d. At 24 h after the second operation, the neurological deficit was assessed, the whole blood viscosity, plasma viscosity, iNOS activity as well as NO level, IL-1β content and TNF-α content in the brain tissue of the rats were determined, and the morphological changes of brain tissue of the rats were observed by HE staining. Results: All the rat models of cerebral ischemic tolerance were established successfully. The total flavonoid of ilex pubesceus can obviously or significantly reduce the neurological deficit score, whole blood viscosity and plasma viscosity, obviously or significantly increase the NO level in the brain tissue of the rats, and significantly reduce the pathological damage of brain tissue of the rats. But compared with the ischemia-reperfusion group, the total flavonoid of ilex pubesceus can significantly or obviously increase the iNOS activity, IL-1β content and TNF-α content in the brain tissue of the rats.     

炭疽疫苗及治疗药物筛选和评价模型研究进展

炭疽疫苗和治疗药物的研究是近年来国际上研究热点之一,由于对它们的有效性研究不能在人体进行,因此实验模型的选择就特别重要.目前常用的细胞模型主要包括CHO细胞和J774A.1细胞.动物模型种类较多,包括小鼠、大鼠、豚鼠、兔和猴等都被作为炭疽的动物模型加以研究.由于模型选择的差异,实验结果常出现较大差异,甚至得到相反的结果.回顾了以往在细胞和动物模型上进行的炭疽实验,分析选择炭疽研究模型的原则和依据.同时,为探讨不同模型之间产生实验结果差异的原因,简要介绍了炭疽杆菌的致病机理,以及炭疽疫苗和治疗药物的研究进展.     

Polymer conjugates of acridine-type anticancer drugs with pH-controlled activation

Acridines are potent DNA-intercalating anticancer agents with high in vivo anticancer effectiveness, but also severe side effects. We synthesized five 9-anilinoacridine-type drugs and their conjugates with biocompatible water-soluble hydrazide polymer carrier. All of the synthesized acridine drugs retained their in vitro antiproliferative properties. Their polymer conjugates were sufficiently stable at pH 7.4 (model of pH in blood plasma) while releasing free drugs at pH 5.0 (model of pH in endosomes). After internalization of the conjugates, the free drugs were released and are visible in cell nuclei by fluorescence microscopy. Their intercalation ability was proven using a competitive ethidium bromide displacement assay.     

异麦芽低聚糖对衰老模型小鼠肠黏膜免疫功能调节作用的研究

目的探讨异麦芽低聚糖（Isomalto oligosaccharide,IMO）对衰老模型小鼠肠黏膜免疫功能的调节作用及可能机制。方法昆明纯系小鼠随机分为Young组、Aging组、IMO组和IMOLCM组。采用D-半乳糖造成衰老模型后,给予相应药物干预。采用细菌定量测定法检测肠道菌群、放射免疫法检测肠黏膜sIgA、免疫组化法检测肠黏膜IgA^＋浆细胞的表达。结果与Young组相比,Aging组小鼠存在肠道菌群失调、肠黏膜sIgA含量降低、IgA^＋浆细胞表达减少（P〈0．05）;与Aging组相比,IMO组肠道菌群失调状况有所改善,肠黏膜sIgA含量增加、IgA^＋浆细胞的表达增加（P〈0．05）;与IMO组相比,IMOLCM组肠道菌群失调再次出现,肠黏膜sIgA降低、IgA^＋浆细胞的表达降低（P〈0．05）。结论异麦芽低聚糖可改善衰老模型小鼠肠道菌群失调状态和提高肠黏膜免疫功能;异麦芽低聚糖提高肠黏膜免疫功能可能主要由增加益生菌数量间接实现的。     

Central Regulation of Adrenal Tyrosine Hydroxylase: Effect of Induction on Catecholamine Levels in the Adrenal Medulla and Plasma

The effect of induction of adrenal tyrosine hydroxylase (TH) by various centrally acting drugs on catecholamine levels in adrenal and plasma was investigated in rats. All the drugs tested, namely oxotremorine, Piribedil, B-HT 920, and HA-966, produced significant increases in adrenal dopamine content and plasma epinephrine level. Denervation of the adrenal abolished the increase in adrenal dopamine as it did the induction of tyrosine hydroxylase. The results suggest that the induced increase of adrenal TH activity, as mediated by certain drugs, results in an elevation of the plasma epinephrine level and that the adrenal dopamine content is a better indicator of the catecholamine-synthesizing capacity of the adrenal medulla than are the other catecholamines.     

Effect of drugs on urate binding to plasma proteins

The effect of various drugs on urate binding to plasma proteins was investigated in normal subjects. Whereas allopurinol, aspirin, phenylbutazone, probenecid, and sulphinpyrazone all significantly reduced plasma urate concentrations, only aspirin, phenylbutazone, and probenecid significantly impaired urate binding. Colchicine and indomethacin in the doses administered had no significant effect on plasma urate concentrations or binding. In the case of aspirin, urate binding was reduced to 25% of normal, and this effect was quickly abolished after cessation of therapy. Phenylbutazone reduced urate binding to 56% and probenecid to 46% of normal; this impairment was still detected four days after cessation of therapy. Drugs may impair urate binding by competition for plasma protein binding sites, with displacement of bound urate. Impairment of urate binding in vivo by administration of certain drugs may be relevant to the precipitation of acute gouty arthritis, to the formation of gouty tophi, and to the augmentation of uricosuria. Furthermore, the role of drugs must be seriously considered during all studies on urate binding in patients with gout.