噻托溴铵对慢性阻塞性肺疾病的支气管扩张作用

支气管扩张剂可扩张支气管、缓解气流受限及改善肺通气功能,是控制慢性阻塞性肺疾病(COPD)的主要治疗措施.噻托溴铵是新型抗胆碱能药物,具有较强的支气管扩张作用,其对COPD患者的肺功能改善作用如何,目前尚不十分清楚.本研究观察了应用噻托溴铵前后患者肺功能变化,旨在探讨噻托溴铵对肺功能的改善作用,现将报告如下.     

噻托溴铵对慢性阻塞性肺疾病患者肺功能的影响

目的 评价噻托溴铵治疗慢性阻塞性肺疾病(COPD)的疗效和安全性.方法 采用随机、双盲、平行对照方法,对轻、中度稳定期COPD患者吸入噻托溴铵(20例)与异丙托溴铵(20例)治疗4周,通过检测肺功能,观察其临床疗效.结果 用药后,噻托溴铵组患者第1秒用力呼气容积(FEV1)和用力肺活量(FVC)均显著增加(P<0.01);4周时,FEV1的增加较异丙托溴铵组差异有统计学意义(P<0.05);两组应急药物应用情况及药物不良反应发生率差异无统计学意义(P<0.05).结论 噻托溴铵是治疗COPD患者有效和安全的支气管扩张药物,疗效显著而且安全可靠.     

噻托溴铵治疗慢性阻塞性肺疾病随机双盲双模拟对照临床试验

目的 评价噻托溴铵治疗慢性阻塞性肺疾病（COPD）的疗效和安全性。方法 用双盲双模拟随机对照方法，观察了COPD病人吸人噻托溴铵（21例，18μg，qd）与异丙托溴铵（23例，40μg q6h）的支气管扩张作用及安全性。结果 用药后，噻托溴铵组病人第1秒用力呼气容积（FEV1）和用力肺活量（FVC）均显著增加（P〈0．001）；2，3h时，FEV1的增加较异丙托溴铵组有显著性差异（P〈0．05）；治疗2，4周时，噻托溴铵组病人FEV，谷值明显上升（P〈0.01），较异丙托溴铵组分别高0．14，0．05L。2组药物不良反应发生率无统计学差异。结论 噻托溴铵是治疗COPD病人有效和安全的支气管扩张药物，疗效和用法均优于异丙托溴铵。     

噻托溴铵粉吸入剂在治疗支气管扩张症中的应用进展

从噻托溴铵粉吸入剂的作用机制,目前临床中的应用,支气管扩张症的发病机理及噻托溴铵的不良反应等多方面进行详细的阐述,着重介绍噻托溴铵粉吸入剂在支气管扩张症治疗中的作用,这也是目前支气管扩张症治疗的一个新突破、新进展,值得进一步的研究和探讨。     

抗胆碱药物在哮喘治疗中的地位

作为支气管扩张药,抗胆碱药物在治疗阻塞性气道疾病(包括哮喘和慢性阻塞性肺疾病)方面有重要地位。本文就短效和长效抗胆碱药物治疗哮喘的有效性和不良反应进行综述。异丙托溴铵和速效β受体激动药合用可有效控制不同年龄哮喘的急性发作。噻托溴铵是长效支气管扩张药,它与M1、M2、M3受体竞争结合,与异丙托溴铵相比噻托溴铵从M1、M3胆碱能受体复合物上解离的速度要比从M2胆碱能受体复合物上解离的速度慢。噻托溴铵能减少Th2细胞因子和气道炎症,降低气道重塑和气道高反应性。噻托溴铵与吸入激素联合用药能有效控制未完全缓解的哮喘患者的症状并改善其肺功能。吸入抗胆碱药物不易吸收入血,因而全身不良反应小。     

噻托溴铵联合沙美特罗/氟替卡松对老年支气管哮喘患者肺通气功能的改善

目的：探讨联合吸入噻托溴铵和沙美特罗/氟替卡松对老年支气管哮喘患者肺通气功能的影响。方法：将本院呼吸内科100例确诊为支气管哮喘的患者随机分为吸入噻托溴铵和沙美特罗/氟替卡松治疗组43例,沙美特罗/氟替卡松组29例,噻托溴铵组28例。治疗6个月后,观察治疗疗效、治疗前后肺功能变化及治疗后肺功能改善率。结果：联合吸入噻托溴铵和沙美特罗/氟替卡松组的总有效率为88.4%,明显高于噻托溴铵组的67.9%和沙美特罗/氟替卡松组的72.4%,差异具有统计学意义,P〈0.05。同时联合吸入噻托溴铵和沙美特罗/氟替卡松组的肺功能改善率高于其他两组,改善更显著,差异具有统计学意义。结论：噻托溴铵联合沙美特罗/氟替卡松能明显改善支气管哮喘患者肺通气功能,疗效显著。     

布地奈德、沙丁胺醇、噻托溴铵治疗68例老年支气管哮喘疗效观察

目的探讨布地奈德、沙丁胺醇、噻托溴铵雾化吸入治疗老年支气管哮喘疗效。方法将患者随机分成两组,均经常规抗感染、化痰、吸氧等治疗,治疗组予布地奈德、沙丁胺醇、噻托溴铵雾化吸入;对照组予喘定0.5~1.0g/天、地塞米松10~30mg/天静脉滴注。结果吸入药物后,症状及各项肺功能指标均有明显改善,两组疗效无明显差异。结论布地奈德、沙丁胺醇、噻托溴铵治疗老年支气管哮喘起效快、疗效稳定且毒副作用少,患者易接受。     

噻托溴铵治疗慢性阻塞性肺疾病的临床试验

噻托溴铵是新型的长效抗胆碱药，其扩张支气管的作用优于目前在临床作为治疗慢性阻塞性肺疾病（COPD）一线药物的异丙托溴铵，在2004年经美国FDA核准可作为COPD长期维持治疗用药。因此，我们首次采用国产噻托溴铵对稳定期COPD患者进行13周的随机、双盲、安慰剂平行对照临床试验，观察该药在国人COPD患者的疗效。     

噻托溴铵与异丙托溴铵在慢性阻塞性肺疾病治疗中的成本-效果评价分析

目的:开展对噻托溴铵与异丙托溴铵在临床治疗慢性阻塞性肺疾病(COPD)患者的药物经济学研究,为临床用药决策提供依据。方法:采用回顾性研究筛选某院COPD患者,建立马尔可夫(Markov)模型对接受噻托溴铵与异丙托溴铵的患者进行模拟,并参考相关随机对照试验研究成果以及中外公开发表的文献。结果:5年噻托溴铵组和异丙托溴铵组的效果值质量调整生命年(QALYs)分别为3.90和3.87,噻托溴胺组成本为5 792.55元,比对照组减少1 262.9元,增量成本-效果比为119 977.67元/QALY。结论:在治疗COPD过程中,5年内噻托溴铵组和异丙托溴铵组治疗方案疗效相当,但噻托溴铵组的成本更低,治疗更具有成本-效果性。     

噻托溴铵治疗慢性阻塞性肺疾病作用机制的研究进展

慢性阻塞性肺疾病(COPD)是呼吸系统疾病中常见的疾病,可引起呼吸衰竭、肺源性心脏病、心力衰竭等严重疾病。噻托溴铵作为长效的抗胆碱制剂,现为临床治疗慢性阻塞性肺炎的常用药物,其可通过扩张支气管、抑制炎症因子和抑制气道重塑的作用机制,进而有效缓解支气管痉挛、呼吸困难和降低炎症反应。主要对噻托溴铵治疗慢性阻塞性肺疾病的作用机制进行综述。     

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.