吉安市结核分枝杆菌耐药状况分析

目的 探讨吉安市结核分枝杆菌的耐药状况，为结核病疫情防控提供可靠的参考依据。方法 回顾性分析2014年至2019年吉安市365例结核分枝杆菌培养结果显示阳性并具有药敏试验结果的病例，分析结核分枝杆菌对异烟肼(INH)、利福平(RFP)、氧氟沙星(OFX)、卡那霉素(KM)四种抗结核药物的耐药情况。结果 365例结核分枝杆菌感染患者中，初治患者278例(76.16%)，复治患者87例(23.84%)，株结核分枝菌总耐药率为24.66%，耐多药率为9.59%,广泛耐药率为0.55%;复治患者的耐药率(49.43%)高于初治患者(16.91%)，两者耐药差异有统计学意义(χ²=140.35,P<0.05)。耐药结核病在不同性别患者中分布的差异无统计学意义，在不同年龄患者中分布差异有统计学意义，以51～70岁年龄组耐药率最高。结论 吉安市结核分枝杆菌耐药情况比较严重,应加强抗结核药物的耐药性监测，并加强对结核病患者特别是复治患者的治疗管理，同时根据药敏结果选择科学有效的治疗方案。     

护肝片预防抗结核药物性肝炎的临床研究

目的：探讨护肝片预防抗结核药物对肝损害的临床作用。观察其疗效及安全性、可靠性。方法 观察组在使用抗结核药物的同时加用护肝片。结果 观察组抗结核药物性肝炎发病率低于对照组。对照组间抗结核药物性肝炎发病率相似。观察组与对照组间，统计学处理有显著性差异。结论 护肝片与抗结核药物联用，可有效预防抗结核药物性肝炎的发生，明显优于常规单纯抗结核药物治疗，效果是肯定的。可保证抗结核疗程的完成，对预防耐药结核病的发生有重要意义。     

基因芯片与液体快速培养技术诊断耐药结核病的对比研究

目的 对比研究基因芯片与液体快速培养技术诊断耐药结核病的效果。方法 1156例疑似肺结核及肺结核患者的同一痰样本,同时应用基因芯片技术(芯片组)与液体快速培养技术(快培组)进行结核菌耐药检测,对两组检测结果进行对比分析。结果 对两组实验检测结果进行对比分析,结核菌检出率:芯片组270例,阳性率为23.36%,快培组237例,阳性率为20.50%。结核菌耐药结果 :芯片组46例,耐药率为17.04%,快培组43例,耐药率为18.14%,比较差异无统计学意义(P>0.05)。芯片组与快培组同时检出结核菌阳性时,二者耐药符合率达80%。结论 基因芯片检测结合聚合酶链式反应(PCR)技术和反向杂交技术(RDB)诊断结核病及耐药结核病,具有简便、快速、灵敏、准确的特点,及时检出结核病及耐药结核病,指导临床针对性制定个性化抗结核方案,避免盲目制定抗结核方案而导致医源性耐药结核病的出现,真正有效控制结核病及耐药结核病。     

耐药肺结核患者结核分枝杆菌菌型分布及耐药研究

目的 研究肺结核耐药患者结核分枝杆菌菌型分布及耐药情况。方法 收集2011年4月至2012年7月肺结核患者痰液标本,分离培养后进行菌种鉴定和药敏试验。结果 人结核分枝杆菌约占83.91%,牛结核分枝杆菌约占15.70%;患者对一线抗结核药物耐药率显著高于对二线抗结核药物耐压率,差异有统计学意义(P<0.05);一类抗结核药物单一耐药率显著高于二类抗结核药物(χ²=4.281,P<0.05)。结论 肺结核耐药患者菌型以人结核分枝杆菌最多,对一线抗结核药物的耐药率显著高于对二线抗结核药物的耐药率。     

厦门地区2016年—2020年结核病患者对4种常用一线抗结核药物的耐药情况分析

目的：分析厦门地区结核病患者对异烟肼（isoniazid,INH）、利福平（rifampin,RFP）、链霉素（streptomycin,SM）、乙胺丁醇（ethambutol,EMB）4种常用一线抗结核药物的耐药情况,为结核病患者的抗结核治疗提供参考。方法：选取2016年1月—2020年12月厦门大学附属第一医院收治的2 126例结核病患者作为研究对象,采集患者的性别、年龄,以及对INH、RFP、SM、EMB 4种一线抗结核药物的耐药情况等临床资料,分析结核病患者的耐药现状和耐药特点。结果：2016年—2020年的2 126例结核病患者中,对一线抗结核药物存在耐药的有531例（耐药率为24.98%）,其间各年度耐药率的波动不大（P>0.05）;2 126例结核病患者中,男性患者对一线抗结核药物的耐药率高于女性（26.32%vs 21.62,P<0.05）;经比较,不同年龄段结核病患者对一线抗结核药物的耐药率存在显著差异（P<0.05）,其中>40～60岁患者的耐药率最高（28.21%）,而≤20岁患者的耐药率最低（18.99%）;531例耐药结核病患者中,患者...     

降钙素原检测对于耐药结核病的预测价值

目的观察血清降钙素原（PCT）在抗结核治疗时的动态变化,及早发现耐药患者。方法选择300例初治接受正规抗结核药物治疗的涂阳培阳肺结核患者,治疗前均做罗氏比例法药敏试验和血清PCT检测,并于抗结核治疗期间每个月做血清PCT检测,分析结核分枝杆菌耐药和敏感患者PCT动态变化规律,以便及早发现耐药患者。结果耐药组和敏感组肺结核患者治疗前血清PCT差异无统计学意义（P〉0.05）,治疗后1个月、2个月时2组血清PCT均降低,但组间差异无统计学意义（P〉0.05）,治疗3、4和6个月时耐药组无下降,与敏感组相比差异显著（P〈0.01）。结论血清PCT可作为肺结核患者抗结核治疗疗效评估指标,并对耐药结核有预测作用。     

住院痰阳老年肺结核患者耐药特点分析

目的分析安徽省胸科医院71例痰阳老年肺结核患者的耐药情况,为老年肺结核患者的抗结核方案制定提供依据。方法收集2016年1-12月收治的痰抗酸染色阳性的老年肺结核患者,经痰分离培养并进行9种抗结核药物(异烟肼、利福平、链霉素、乙胺丁醇、左氧氟沙星、阿米卡星、卷曲霉素、丙硫异烟胺、对氨基水杨酸钠)的药物敏感性试验,对其结果进行分析。结果对一线药物的耐药情况:异烟肼(18.31%)=链霉素(18.31%)>利福平(12.68%)>乙胺丁醇(1.41%)。对二线药物的耐药情况:丙硫异烟胺(12.68%)>左氧氟沙星(11.27%)>阿米卡星(4.23%)>对氨基水杨酸钠(2.82%)>卷曲霉素(1.41%)。初治患者与复治患者比较,对异烟肼、利福平、链霉素以及多耐药差异有统计学意义。60～69岁老年患者耐药情况最为严重,75～79岁年龄段出现一次小高峰。结论老年结核病的耐药情况应引起重视,乙胺丁醇、卷曲霉素、阿米卡星的耐药率较低,可考虑在耐药老年患者中首选应用,应注意早期进行药敏检测,并合理制定抗结核方案,遏制耐药结核病流行。     

氟喹诺酮：一类重要的抗结核药物

从上世纪80年代开始,随着耐药结核病（尤其是耐多药结核病）发病率的不断上升以及结核病与AIDS病的相互结合,结核病疫情再度上升,成为全球重大公共卫生问题和社会问题。WHO于1996年推出的耐药结核病治疗指南明确把氟喹诺酮类药物作为二线抗结核病药物,与其他抗结核药物联合使用治疗耐多药结核病以及对不能耐受一线抗结核药物的患者使用。但由于伦理学等原因,这类药物同传统抗结核药物一样也无法进行单药的现代临床试验,因此,其抗结核作用的基础研究在指导临床医师合理用药等方面显得尤为重要。本文从氟喹诺酮单独使用及其与其他抗结核药物联合使用时对细胞外和巨噬细胞内分枝杆菌的体外活性方面比较全面地评价了这类药物的抗结核作用。     

某市结核病涂阳患者耐药情况的调查分析

目的了解并研究广东省惠州市辖区内结核病对一线抗结核药物的耐药情况,为今后惠州市结核病控制工作提供参考依据。方法对2003~2012在惠州市结核病防治研究所结核科门诊就诊的肺结核痰涂片阳性患者进行结核菌培养及药敏试验。结果总体耐药率为50.60%、初始耐药率为42.31%,获得性耐药率为56.85%。耐多药(MDR)率为22.09%。结论惠州地区结核分枝杆菌总耐药率和耐多药率均高于全国平均水平。需更严格执行结核病控制策略,防止耐药患者及耐药菌株的产生和传播。     

利奈唑胺治疗结核病的临床疗效及安全性

目的评价利奈唑胺治疗耐药结核病的临床疗效及安全性。方法将我院收治的42例耐药结核病患者随机分为观察组25例和对照组17例,对照组给予常规化疗,观察组在对照组基础上加用利奈唑胺;对比两组患者临床疗效,并分析不良反应发生情况。结果观察组患者临床病症改善情况、影像学改变情况以及痰菌变化情况均优于对照组,两组比较差异有统计学意义(P<0.05);观察组不良反应发生率与对照组比较差异无统计学意义(P>0.05)。结论利奈唑胺治疗耐药结核病临床疗效显著,不良反应可控,可以用于耐药结核病的治疗。     

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.

     

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.     

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.     

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.     

Gender-related symptoms and correlates of alcohol dependence among men and women with a lifetime diagnosis of alcohol use disorders

This study explored gender-related symptoms and correlates of alcohol dependence in a crosssectional study of 150 men and 150 women with a lifetime diagnosis of alcohol use disorders (AUD). Participants were recruited in equal numbers from treatment settings, correctional centres and the general community. Standardized measures were used to determine participants' use of substances, history of psychiatric disorders and psychosocial stress, their sensation seeking and family history of substance use and mental health disorders. Multivariate analyses were used to detect patterns of variables associated with gender and the lifetime severity of AUD. Men had a longer history of severe AUD than women. Women had similar levels of alcohol dependence and medical and psychological sequelae as men, despite 6 fewer years of AUD. More women than men had a history of severe psychosocial stress, severe dependence on other substances and antecedent mental health problems, especially mood and anxiety disorders. There were differences in family history of alcohol-related problems approximating same-gender aggregation. The severity of a lifetime AUD was predicted by its earlier age at onset and the occurrence of other disorders, especially anxiety, among both men and women. The limitations in the generalizability of these findings due to sample idiosyncrasies are discussed.