自身免疫性肝病的药物治疗

自身免疫性肝病(autoimmune liver disease,AILD)是一组由自身免疫介导的、以肝脏病理损害和肝功能异常为主要表现的慢性肝病.其病因和发病机制尚未完全阐明,目前认为细胞免疫损伤以及自身抗体参与的体液免疫损伤是AILD发病的重要病理生理机制之一.AILD主要包括以肝细胞损害为主的自身免疫性肝炎(autoimmune hepatitis,AIH)以及以胆系损害为主的原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)和原发性硬化性胆管炎(primary sclerosing cholangitis,PSC).此外,部分AILD患者同时具有其中两种疾病的临床和病理表现,临床上称之为重叠综合征(overlap syndrome).     

自身免疫性肝病的组织病理学

自身免疫性肝病(AILD)组织病理学改变,主要探讨自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)和原发性硬化性胆管炎(PSC)。AIH、PBC和     

自身免疫性肝病158例临床分析

目的分析比较自身免疫性肝病患者的临床表现、血清学等指标,以提高该病的诊断率以及对ALD的认识。方法回顾性分析笔者所在医院近3年来收治的自身免疫性肝病158例患者临床资料,其中自身免疫性肝炎(AIH)25例,原发性胆汁性胆硬化(PBC)110例,自身免疫性肝炎-原发性胆汁性肝硬化重叠综合征(AIH/PBC)23例患者的血清血指标的差异,并分析临床并发症及病理学特点。结果 AIH、AIH/PBC组中ALT、AST与PBC组比较差异有统计学意义,PBC、AIH/PBC组中GGT、ALP与AIH组比较,差异有统计学意义。AIH组中IgG与PBC组比较差异有统计学意义,PBC、AIH/PBC组中IgM与AIH组比较差异有统计学意义,上述指标比较差异均有统计学意义(P<0.05)。AIH组以ANA阳性为主,PBC组AMA、AMA-M2的阳性率较高而具有特异性,AIH/PBC兼有AIH及PBC的血清抗体特点。AIH、PBC、AIH/PBC最终均可进展为肝硬化失代偿期。结论 ALD临床表现多样化,起病隐匿,肝穿刺病理检查结合血清学指标阳性使诊断更为准确。     

自身免疫性肝病患者43例的临床观察

<正>自身免疫性肝病(AILD)是一组由自身免疫介导的以肝脏为靶器官的慢性进展性炎症疾病,主要包括自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)和原发性硬化性胆管炎(PSC)以及这3种疾病中任意两者之间的重叠综合征(OS)[1]。随着免疫学监测方法技术的不断提高,AILD患者的早期诊断率不断提高,自身抗体的监测在其早期诊断中起到了至关重要的作用,已成为AILD早期诊断的重要实验室指     

自身免疫性肝病218例临床分析

目的:分析比较三种自身免疫性肝病(autoimmune liver disease,ALD)患者的临床表现、血清学、自身抗体特点及治疗方案和疗效,为临床诊断及治疗提供帮助.方法:对我院2004年1月～2009年8月收治的自身免疫性肝病218例,其中自身免疫性肝炎(autoimmune hepatitis,AIH)164例,原发性胆汁性胆硬化(primary biliary cirrhosis,PBC)31例,自身免疫性肝炎-原发性胆汁性肝硬化重叠综合征(autoimmune hepatitis-primary biliary cirrhosis overlap syndrome,AIH+PBC)23例的临床表现、相关实验室检查及治疗方案进行回顾性分析.结果:AIH肝功中ALT与PBC、AIH/PBC,及γ-GIb与PBC比较(t9<0.05)有统计学意义,PBC肝功中GGT、ALP明显升高,与AIH、AIH/PBC比较(P<0.05)有统计学意义.AIH以ANA阳性为主(87.80%),SMA阳性占7.93%,PBC AMA(90.32%)、AMA-M2(80.65%)阳性率较高而具有特异性,AIH/PBC兼ANA(95.65%)、AMA(82.61%)阳性,AMA-M2(65.22%)阳性.AIH激素组治疗在生化指标与非激素组比较,出院复查AST指标有统计学意义(P<0.05).PBC、AIH/PBC主要给予熊去氧胆酸(UDCA)等治疗.结论:ALD主要为绝经期女性患者,临床表现具有多样性,肝穿刺病理检查对其诊断较为准确,但需结合肝功生化指标、特异型自身抗体等协助诊断.AIH治疗在无禁忌证情况下选择免疫抑制剂,PBC、AIH/PBC主要为UDCA.     

自身免疫性肝病的药物治疗研究与进展

自身免疫性肝病(autoimmune liver disease,AILD)主要是指由自身免疫介导的肝脏炎症性病变,传统临床上将其分为三种类型:自身免疫性肝炎(autoimmune hepatitis,AIH)、原发性胆汁性胆管炎(primary biliary cholangitis,PBC)和原发性硬化性胆管炎(primary sclerosing cholangitis,PSC)。近年来的研究发现,兼具以上任意两种疾病特征的重叠综合征(overlap syndrome,OS)和免疫球蛋白G(immunoglobulin G,IgG)4相关性肝胆疾病亦可归为AILD的范畴。不同类型的肝病其相应的治疗药物方案存在一定差异,大量关于AILD的理论和临床研究工作也取得了新进展。本文就AILD五种类型的药物治疗方案进行综述,为AILD的临床治疗提供建议,以提高患者生活质量。     

高尔基体蛋白73在自身免疫性肝病鉴别诊断及疗效评估中的价值

为了探讨高尔基体蛋白73(GP73)在自身免疫性肝病(AILD)鉴别诊断及疗效评估中的价值,选取2020年1月至2023年的7月在本院就诊的144例病毒性肝炎患者和55例AILD患者[自身免疫性肝炎(AIH)20例、原发性胆汁性胆管炎(PBC)19例及原发性硬化性胆管炎(PSC)16例]为研究对象,分别纳入病毒性肝炎组与AILD组。测定三组受试者GP73水平,并比较不同分型AILD患者GP73水平;AILD患者接受免疫抑制治疗1 w后,检测血清丙氨酸氨基转移酶(ALT)与GP73水平,根据ALT测定结果将AILD患者分成A组[ALT<2倍正常值上限(ULN)]与B组(ALT≥2×ULN),并对A组患者进行肝活检,评估纤维化分期,分析GP73水平与纤维化分期的相关性。结果发现,AILD组和病毒性肝炎组GP73水平均高于对照组(P<0.05),且AILD组和病毒性肝炎组GP73水平比较,差异无统计学意义(P>0.05);不同分型AILD患者GP73水平比较,差异无统计学意义(P>0.05);B组GP73水平高于A组(P<0.05),且A组纤维化分期≥S2期的患...     

自身抗体和免疫球蛋白检测对鉴别诊断原发性胆汁性肝硬化的价值

目的探讨抗线粒体抗体-M2亚型(AMA-M2)、抗核抗体(ANA)以及免疫球蛋白IgG、IgA、IgM对鉴别诊断原发性胆汁性肝硬化(PBC)与肝脏疾病、自身免疫性疾病的价值及临床意义。方法用酶联免疫法、免疫印迹法以及散色比浊法分别对12例PBC患者、27例病毒性肝炎患者、21例自身免疫性肝病患者、33例SLE患者、34例RF患者、26例SS患者和20例健康体检者同时检测抗AMA-M2抗体、ANA以及免疫球蛋白IgG、IgA、IgM。结果 PBC组阳性率与各组均有显著差异(P<0.01),PBC组阳性率与病毒性肝炎、AIH有显著差异(P<0.01)。体液免疫方面,PBC患者的IgG水平明显高于SLE、RF组(P<0.05,P<0.01),与病毒性肝炎、自身免疫性肝病无统计学意义;IgA水平与其它各组均无显著差异,IgM水平均显著高于其它各组(P<0.01)。结论抗AMA-M2抗体对诊断PBC具有较高的特异性和灵敏度,通过抗AMA-M2抗体、ANA检测对鉴别PBC与病毒性肝炎、AIH有较高的临床诊断价值;通过免疫球蛋白的检测,对鉴别PBC与SLE、RF、SS等自身免疫性疾病有较高的临床诊断价值。     

自身免疫性肝病测定血清Ⅲ型前胶原肽和透明质酸及甘胆酸测定的临床意义

目的:了解自身免疫性肝病肝纤维化指标测定的意义,比较自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(PBC)、原发性硬化性胆管炎(PSC)三者之间肝纤维化发生发展的规律,以探索其对早期肝硬化的临床诊断价值。方法:选择自身免疫性肝病的住院患者63例,PBC32例,AIH25例,PSC6例,所有病例均测定血清Ⅲ型前胶原肽(PⅢP)、透明质酸(HA)、甘胆酸(CG)、白蛋白及蛋白电泳。结果:各组病例血清PⅢP,HA,CG值均较正常对照组明显升高,有统计学意义(P<0.01)。PⅢP以AIH组为最高,与其他各组比较差异有统计学意义(P<0.01)。HA及CG均以PSC组为最高,与其他各组比较差异有统计学意义(P<0.01)。血清白蛋白仅在AIH组降低明显,与PBC组和PSC组比较差异有统计学意义(P<0.01)。蛋白电泳中A蛋白的降低和γ球蛋白的升高,也以PSC组为明显,而与AIH组和PBC组比较差异有统计学意义(P<0.05)。结论:PⅢP以AIH组为最高,AIH组纤维化较PBC组和PSC发生早、进展快。HA及CG对PSC最敏感,血清白蛋白AIH降低最明显,肝功能损害最严重,进展最快。     

肝抗原自身抗体测定在自身免疫性肝病的临床评价

目的 探讨肝抗原自身抗体在自身免疫性肝病患者血清中的阳性率。方法 155例患者分为三组：自身免疫性肝病组45例，包括自身免疫性肝炎（AIH）15例、原发性胆汁性肝硬化（PBC）20例、原发性硬化性胆管炎（PSC）10例；病毒性肝炎组50例；不明原因肝损伤组30例。分别用间接免疫荧光法、免疫印迹法检测肝抗原（SAL／LP、LKM，1、LC-1、LC-1）自身抗体。结果 抗SLP／LP抗体在AIH患者血清中阳性率为46．4％，明显高于LKM．1（13．3％）、LC-1（0％）及AMA-M2（13．3％）抗体，并且在病毒性肝炎患者血清中呈阴性反应。抗AMA-M2抗体在PBC患者血清中阳性率达95．0％。不明原因肝损伤组患者中有6．6％的AMA—M2抗体阳性。结论 抗SLA／LP抗体对AIH具有特异性，肝抗原自身抗体的检测将有助于自身免疫性肝病患者的诊断及治疗。     

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.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

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.     

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.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.