抗结核药物对乙肝病毒感染肺结核患者发生肝损害的临床分析

目的：分析抗结核药物对乙肝病毒感染的肺结核患者发生肝损害的临床情况。方法61例乙肝病毒标记物阳性的肺结核患者（观察组）和64例乙肝病毒标记物阴性的肺结核患者（对照组）均采取相同抗结核药物治疗,比较两组患者肝功能损害发生率、治疗前后肝功能指标（ALT、AST、TBIL）变化和肝功能损害出现时间及恢复时间。结果观察组肝功能损害发生率明显高于对照组（P<0.05）;观察组治疗后肝功能指标（ALT、AST、TBIL）较对照组明显升高（P<0.05）;观察组肝功能损害出现时间较早,而恢复时间较对照组晚（P<0.05）。结论抗结核药物对乙肝病毒感染的肺结核患者造成明显的肝损害,所以抗结核药物治疗前应检查乙肝病毒标记物,治疗过程中应用保肝药物,并要经常检查肝功能,做到早发现、早诊断、早治疗,提高肺结核的治愈率。     

胸腺肽α1预防乙型肝炎病毒再激活临床研究

目的观察胸腺肽仪α1（Tα1）在预防肺结核合并乙型肝炎患者抗结核治疗后乙型肝炎病毒（HBV）再激活中的作用。方法将72例肺结核合并乙型肝炎病毒感染患者按入院先后分为治疗组（36例）和对照组（36例）。治疗组除给予常规抗结核治疗外,给予胸腺肽α1．6mg皮下注射,每周2次。对照组仅给予常规抗结核治疗。抗结核治疗后1、2、3个月检测肝功能及HBV-DNA,观察两组患者HBV再激活发生例数。结果治疗组36例患者中发生HBV再激活者12例,发生率为33．33％（12／36）。对照组36例患者中发生HBV再激活者20例,发生率为55．56％（20／36）。经统计学处理,P〈0．05。结论肺结核合并乙型肝炎患者,在抗结核治疗期间,给予胸腺肽α1治疗,可以起到预防发生乙型肝炎病毒再激活的作用。     

抗结核药物性肝炎与乙型肝炎病毒感染的相关性研究

目的探讨抗结核药物性肝炎与乙型肝炎病毒（HBV）感染的相关性，了解HBsAg阳性患者发生抗结核药物性肝炎的临床特点。方法观察81例抗结核药物性肝炎及其中14例急性、亚急性暴发型肝炎患者中HBsAg阳性率，比较HBsAg阳性和HBsAg阴性两组抗结核药物性肝炎患者的临床特点。结果在结核病化学治疗过程中出现肝功能损害的患者，HBsAg阳性者占48％（39／81）；急性、亚急性暴发型肝炎患者中，HBsAg阳性者占64％（9／14）。肝功能指标凝血酶原活动度（PTA）比较，HBsAg阳性组明显低于阴性组。结论HBV感染或携带者肝脏更易受到抗结核药物的损害，甚至可引发致死性肝衰竭。     

恩替卡韦对肺结核伴慢性乙型肝炎病毒携带者抗结核治疗致肝损伤的疗效及其对肝功能改善的影响

目的:评价恩替卡韦对肺结核并慢性乙型肝炎病毒(HBV)携带者抗结核治疗致肝损伤的临床疗效及其对肝功能改善的影响。方法:选取2015年3月—2017年2月间收治的肺结核伴HBV携带患者108例资料,根据用药方法的不同将其分为对照组和观察组,每组54例;其中对照组患者给予常规抗结核药物治疗,观察组患者在对照组基础上加用恩替卡韦治疗,比较两组患者治疗后的总有效率、肝损伤的发生率和肝损伤发生时间的差异,以及治疗前后肝功能各指标水平测得值的变化情况。结果:观察组患者治疗后总有效率明显优于对照组(94.45%vs 79.62%()χ~2=5.252,P<0.05),肝功能各指标(ALT、AST、TBIL)水平测得值显著低于对照组(P<0.05);观察组患者导致肝损伤出现时间明显晚于对照组(P<0.05),肝损伤的发生率明显低于对照组(χ~2=8.185,P<0.05)。结论:恩替卡韦对肺结核伴HBV携带者抗结核治疗致肝损伤的预防效果较为确切,有效加快肝功能的恢复,延缓了肝损伤出现时间,降低了肝损伤发生的风险。     

2HL_2S/4HL_2方案治疗合并HBV感染肺结核的临床效果

既往研究表明，合并乙型肝炎病毒（HBV）感染的肺结核患者化疗期间更易出现肝脏损害犤１犦。发生肝脏损害后常使化疗中断，甚至导致急性或亚急性肝坏死，影响预后。因此探讨合并HBV感染的肺结核患者的合理化疗方案，减少肝脏损害的发生具有重要的意义。我们近年来应用异烟肼（H）、利福喷丁（L）及链霉素（S）药物（２HL２S／４HL２方案）对此进行了观察，现报道如下。１材料与方法１．１病例选择肺结核患者９０例，均为初治菌阳性浸润性肺结核，未曾用过抗结核药物治疗，痰镜检抗酸杆菌阳性；年龄１６～６２岁；无严重心、肾等疾患及…     

抗结核药物对乙肝病毒携带者合并肺结核患者肝功能的影响

目的：探讨抗结核药物对乙肝病毒携带者合并肺结核患者肝功能的影响。方法：对比分析乙肝病毒携带者大三阳、小三阳合并肺结核患者和乙肝病毒阴性肺结核患者,经过抗结核治疗后肝功能损害情况。结果：270例病例中,肝功能损害总的发生率为23．7％（64／270）,乙肝病毒携带者发生肝功能损害的比率明显高于对照组,大三阳组和小三阳组发生肝功能损害的情况在统计学上无差异,乙肝病毒携带者肝损害发生的时间早,程度较严重。结论：乙肝病毒携带者在服用抗结核药物后更易引发肝损伤,在临床上应注意观察,保护患者肝功能。     

抗结核药物肝损害与血清HBV DNA定量水平的关系

异烟肼（H）与利福平（R）等抗结核药物具有肝脏损害等不良反应。既往研究表明。合并乙型肝炎病毒（HBV）感染肺结核患者化疗期间更易出现肝脏损害。发生肝脏损害后常使化疗中断。甚至导致急性或亚急性肝坏死，影响预后。因此探讨合并HBV感染的肺结核患者肝脏损害与HBV感染的关系。对防治此类患者肝脏损害的发生具有重要的意义。我们近年来应用的荧光定量聚合酶链反应（FQ—PCR）技术对此进行了回顾性研究，报告如下。     

肺结核合并丙肝抗体阳性患者肝功能的检测

目的：探讨抗结核药物对肺结核合并丙肝抗体阳性患者肝功能的影响。方法：对比分析丙肝抗体阳性患者合并肺结核和丙肝抗体阴性肺结核患者经过抗结核治疗后肝功能损害情况。结果：137例患者中,肝功能损害总发生率为24.1%（33/137）,丙肝抗体阳性患者发生肝功能损害的比例明显高于对照组,丙肝抗体阳性患者肝损害发生的时间早,程度较严重。结论：丙肝抗体阳性患者在服用抗结核药物后更易引发肝损伤,在临床上应注意观察,保护患者肝功能。     

双环醇预防抗结核药所致肝损害近期疗效观察

目的评价双环醇预防抗结核药物所致药物性肝功能损害的临床疗效。方法将124例初治肺结核病人随机分为观察组与对照组,观察组62例,采用双环醇和抗结核药物联合治疗;对照组62例,采用抗结核药物治疗。比较两组治疗前后肝功能指标变化情况。结果观察组经治疗3个月后无肝功能损害人数60例,占96．77％;对照组元肝功能损害人数43例,占69．35％。结果表明,观察组预防抗结核药物所致肝功能损害疗效显著,差异有显著性意义（P〈0．05）。结论双环醇可显著降低肺结核患者抗结核药物所致肝功能损害的发生率,同时治疗过程中不良反应发生率降低,安全性好,有利于患者顺利完成抗结核治疗。     

抗结核同时给予替比夫定治疗肺结核合并HBV携带者的疗效观察

目的探讨抗结核的同时对肺结核合并HBV携带者给予替比夫定治疗的临床效果,方法选择我院2009年5月至2011年5月收治的肺结核合并HBV携带者的患者60例,随机分为两组,对照组30例采用常规抗结核方案治疗,观察组30例在此基础上加用替比呋定治疗,对两组临床结果进行回顾性分析。结果观察组30例患者中,肝功能损害4例,占13.3%;对照组30例中,肝功能损害12例,占40%。两组比较差异有统计学意义(P<0.05)。两组患者在治疗后第2-4w为肝功能集中损害的时间,对AST、ALT、HBV DNATBIL指标在治疗过程中进行检测,病毒载量及肝功能损害程度在治疗后半年的情况观察组好转情况均优于对照组,差异有统计学意义(P<0.05)。结论采用替比夫定在抗结核治疗的同时对肺结核合并HBV携带者进行治疗,具有较高安全性,降低了肝内炎症反应等肝损害的并发症发生率,患者有较好耐受性,效果满意,在临床应用上有较高的推广价值。     

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.

     

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.     

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.     

2-(Acetoxyphenyl)-(Z)-styryl sulfides as cyclooxygenase inhibitors

2-(Acetoxyphenyl)-(Z)-styryl sulfides are described as selective cyclooxygenase-2 (COX-2) inhibitors, useful for treating inflammation and COX-2-mediated disorders including neoplasia. 2-(Acetoxyphenyl)-(Z)-styryl sulfide is claimed to be the most potent COX inhibitor in the series with a COX-2 selectivity ratio of 33. This compound is also claimed to be superior to celecoxib (Celebrex^®, Pfizer) in inhibiting cell growth of colorectal carcinoma cells. In this evaluation, the COX inhibitory activity of this compound is compared to that previously disclosed for diarylheterocycles and 2-(acetoxyphenyl)alkyl sulfides. The validity of the DLD-1 cell line in the growth inhibition studies is questioned based on recent literature reports indicating the lack of COX-2 expression in this cell line.     

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ～ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.     

Drug targets for cognitive enhancement in neuropsychiatric disorders

The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA_A α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.