克罗恩病并发瘘管形成的循证决策

目的探讨采用循证医学原则决策克罗恩病并发瘘管形成的治疗方案。方法采用循证医学实践的原则,对克罗恩病并发瘘管形成患者,通过检索医学文献,评价文献,并最终选择治疗方案。结果从经验的证据、文献的证据及循证医学的证据等方面总结克罗恩病并发瘘管形成的治疗方案,从而选择最佳方案。结论采用循证医学方法对临床疑难病例进行分析,是临床药师参与药物治疗决策的有效途径。     

炎性肠病药物治疗的演进

随着对IBD的临床表现及其发病机制认识的深入、药物开发的进展、对IBD药物治疗临床证据的积累,IBD药物治疗所使用的品种、方案和策略逐渐演进。遵循循证医学证据的临床指南的推荐意见仍然推荐"上阶梯"的药物治疗策略。     

维得利珠单抗治疗炎症性肠病的快速卫生技术评估

目的:评价维得利珠单抗(VDZ)治疗炎症性肠病(IBD)的有效性、安全性和经济性,为临床用药决策提供循证医学证据。方法:系统检索PubMed、the Cochrane Library、Embase、中国知网、万方等数据库和卫生技术评估(HTA)网站。根据纳排标准筛选文献、提取资料,并对文献进行质量评价与定性合成分析。结果:共纳入文献31篇,其中HTA报告2篇,系统评价/Meta分析17篇,经济学研究12篇。在有效性方面,VDZ有效提高IBD患者的临床应答率、临床缓解率、无类固醇缓解率、黏膜愈合率。安全性方面,VDZ的一般不良事件、严重不良事件、因不良事件停药、严重感染、输注反应发生率与安慰剂相当,优于其他IBD生物制剂,发生率低且为轻中度,其中鼻咽炎发生率较高。经济性方面,基于中国医疗保健体系,对于既往未接受过抗TNF-α治疗或抗TNF-α治疗失败的克罗恩病患者,VDZ比传统药物经济;对于既往未接受过抗TNF-α治疗的中重度活动性溃疡性结肠炎患者,VDZ比英夫利昔单抗经济。结论:VDZ治疗IBD具有良好的安全性、有效性、经济性。     

抗生素在炎症性肠病中的作用

炎症性肠病(IBD)主要包括克罗恩病(CD)和溃疡性结肠炎(UC)。虽然临床上普遍使用抗生素治疗IBD,但是迄今尚无确凿的证据表明抗生素在CD、UC和储袋炎中可以获得良好的疗效[1,2]。临床上使用抗生素治疗IBD是基     

克罗恩病并发瘘管形成的循证决策

目的 探讨采用循证医学原则决策克罗恩病并发瘘管形成的治疗方案.方法　采用循证医学实践的原则,对克罗恩病并发瘘管形成患者,通过检索医学文献,评价文献,并最终选择治疗方案.结果 从经验的证据、文献的证据及循证医学的证据等方面总结克罗恩病并发瘘管形成的治疗方案,从而选择最佳方案.结论 采用循证医学方法对临床疑难病例进行分析,...     

布地奈德治疗炎性肠病的机制与疗效

炎性肠病(inflammatory bowel disease,IBD)主要包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn's disease,CD),近年来在我国的发病率均呈明显的上升趋势。目前IBD发病机制不明,虽然治疗方法众多,但尚无特效治疗方法。布地奈德是一种新型激素制剂,安全性好,全身不良反应小,作为炎性肠病的治疗用药应用前景广阔,应当引起临床医生的足够重视。     

调节性T细胞与炎性肠病研究进展

炎性肠病(Inflammatory bowel disease,IBD)为非特异性炎症性肠病,主要包括溃疡性结肠炎(Ul-cerative colitis,UC)和克罗恩病(Crohn’s disease,CD)。其病因和发病机制尚未完全明确。已知肠道粘膜免疫系统异常反应所导致的炎症反应在IBD中发挥着重要作用。笔者对调节性T细胞在肠道免疫系统中的作用与IBD的发病机制相关性的研究进展做一综述,为临床治疗IBD的新药研究提供可能性的途径。     

炎性肠病的基因疗法

炎性肠病(inflammatory bowel disease,IBD)包括溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn's disease,CD),其致病原因尚不清楚。目前常用的药物治疗伴有明显不良反应而且无法完全治愈疾病。最近几年IBD基因治疗引起关注。通过抑制炎症因子基因以及上调免疫调节因子基因表达来恢复肠道细胞因子的平衡是一种有前途的治疗IBD的方法。本文简要介绍几个可以用于IBD基因治疗的分子(如TNF-α、IL-10、NF-κB和IL-22等)以及它们相应的动物临床试验结果和未来展望。     

克罗恩病的临床维持缓解治疗

<正> 炎症性肠病(IBD)包括克罗恩病(Crohn’sDisease;CD)和溃疡性结肠炎(UC)。IBD药物治疗的客观疗效目标是提高患者生活质量,降低相关并发症的危险和避免外科手术。CD是慢性、难治性、反复发作性疾病,临床治疗缓解后如何维持缓解,获得持久、长期疗效,是CD治疗的重要研究     

促生素治疗克罗恩病的循证研究

目的 通过复习文献从流行病学和循证医学的角度研究促生素治疗克罗恩病的效果.方法 检索近年来研究促生素治疗克罗恩病的临床证据的文献,进行评价.结果 促生素治疗克罗恩病的作用不太明显,但提示促生素在克罗恩病的治疗方面有较好的前景.结论 从循证医学的角度对过去的研究文献进行质量评价,具有较高质量级别的文献(设计良好的RCT的Meta分析)目前尚未有,大样本多中心质量较高的临床试验也非常有限.因此,仍然需要一些高质量的随机对照实验进一步明确促生素在克罗恩病预防和治疗方面的作用.     

Pharmacological treatment of COVID-19: an opinion paper

The precocity and efficacy of the vaccines developed so far against COVID-19 has been the most significant and saving advance against the pandemic. The development of vaccines has not prevented, during the whole period of the pandemic, the constant search for therapeutic medicines, both among existing drugs with different indications and in the development of new drugs. The Scientific Committee of the COVID-19 of the Illustrious College of Physicians of Madrid wanted to offer an early, simplified and critical approach to these new drugs, to new developments in immunotherapy and to what has been learned from the immune response modulators already known and which have proven effective against the virus, in order to help understand the current situation.     

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.

     

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.     

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.