加味生脉饮注射液对内毒素休克大鼠肺组织肿瘤坏死因子-α、白细胞介素-１β和核转录因子-κB 含量的影响

目的:观察加味生脉饮注射液对内毒素休克肺组织TNF-α、IL-1β和NF-κB表达的影响。方法:静脉注射脂多糖(LPS,8.00mg·kg^-1)造成内毒素休克模型,用加味生脉饮注射液作干预治疗,酶联免疫吸附法检测上述因子在假手术组、模型组、加味生脉饮组、阳性对照组等各组大鼠肺组织内的表达。结果:模型组肺损伤较重,TNF-α、IL-1β和NF-κB含量明显升高（P<0.05）;加味生脉饮组和阳性对照组肺损伤较轻,TNF-α、IL-1β和NF-κB含量明显降低（P<0.05）。结论:加味生脉饮注射液能减轻内毒素休克时肺损伤和TNF-α、IL-1β和NF-κB表达,提示该药对内毒素休克肺损伤的保护作用可能是通过调控NF-κB通路过度激活而实现。     

ICU急性呼吸窘迫综合征采用大剂量乌司他丁治疗的疗效分析

目的:分析ICU急性呼吸窘迫综合征采用大剂量乌司他丁的临床治疗效果.方法:选择2013年1月～2015年5月我院ICU收治的74例急性呼吸窘迫综合征患者作为研究对象,根据随机数字表法把74例患者分成对照组与观察组,各37例.对照组应用甲基泼尼松龙治疗,观察组在对照组治疗基础上增加大剂量乌司他丁治疗,对比两组ICU住院时间、机械通气时间和APACHEⅡ评分、肺泡灌洗液TNF-α和IL-10等情况.结果:经过治疗,观察组ICU住院时间、机械通气时间明显比对照组短,观察组A-PACHEⅡ评分明显比对照组低,观察组肺泡灌洗液TNF-α和IL-10改善情况明显优于对照组,两组对比差异显著(P＜0.05).结论:ICU急性呼吸窘迫综合征在甲基泼尼松龙治疗基础上,联合大剂量乌司他丁治疗疗效理想,可以明显缩短患者ICU住院时间和机械通气时间,改善肺泡灌洗液TNF-α和IL-10,降低APACHEⅡ评分,提高临床治疗效果,值得推广.     

乌司他丁联合甲基泼尼松龙治疗急性呼吸窘迫综合征的效果分析

目的探讨乌司他丁联合小剂量甲基泼尼松龙治疗急性呼吸窘迫综合征的临床效果。方法选取本院收治的62例急性呼吸窘迫综合征患者,随机均分为对照组（甲基泼尼松龙）和观察组（乌司他丁联合小剂量甲基泼尼松龙）,比较两组治疗前后的肺泡灌洗液TNF-α和IL-10、机械通气时间、ICU住院时间、急性肺损伤评分和APACHEⅡ评分。结果治疗后,观察组的肺泡灌洗液TNF-α和IL-10改善情况显著优于对照组,机械通气时间、ICU住院时间短于对照组,APACHEⅡ评分低于对照组（P〈0.05）;两组的急性肺损伤评分比较差异无统计学意义（P〉0.05）。结论乌司他丁联合小剂量甲基泼尼松龙治疗急性呼吸窘迫综合征能取得更好的效果。     

不同剂量乌司他丁与还原型谷胱甘肽对脓毒血症患者伴感染性休克的临床疗效及其对症状改善的影响

目的:探究不同剂量乌司他丁与注射用还原型谷胱甘肽联用对脓毒血症患者伴感染性休克的临床疗效及其对炎症因子水平与症状改善的影响。方法:选取2016年2月—2018年12月间收治的脓毒血症合并感染性休克患者80例资料,按治疗方法的不同将其分为对照组和观察组患者,每组40例;对照组患者给予20万U乌司他丁与注射用还原型谷胱甘肽治疗,观察组患者则给予30万U乌司他丁与注射用还原型谷胱甘肽治疗;比较两组患者治疗后的总有效率差异,以及治疗前后的急性生理学及慢性健康症状(APACHEⅡ)评分值和炎症因子如血清肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)水平测得值的变化情况。结果:观察组患者治疗后的总有效率(95.00%)高于对照组(80.00%()P<0.05);两组患者治疗前APACHEⅡ评分值、血清TNF-α、IL-6水平测得值经组间比较其差异无统计学意义(P>0.05),治疗7 d后APACHEⅡ评分值、血清TNF-α、IL-6水平值均低于治疗前(P<0.05);观察组患者治疗后的APACHEⅡ评分值、血清TNF-α、IL-6水平值均低于对(P<0.05)。结论:采用30万U乌司他丁与还原型谷胱甘肽联用治疗脓毒血症伴感染性休克患者的疗效确切,有效改善了炎症反应,缓解了其病情。     

乌司他丁对创伤失血性休克兔细胞因子和黏附分子的影响

目的通过测定创伤失血性休克兔血清细胞因子(TNF-α、IL-8)和可溶性细胞间黏附分子-1(sICAM-1),以及肺组织病理学改变,评价乌司他丁对创伤失血性休克的疗效及对缺血再灌注损伤的保护作用。方法将新西兰白兔30只随机分为3组:对照组、创伤失血性休克生理盐水组和创伤失血性休克乌司他丁组。分别在休克前、休克末、复苏后2h、4h各时相点静脉采血测定细胞因子(TNF-α、IL-8)及可溶性细胞间黏附分子-1(sICAM-1)。复苏后4h空气栓塞处死动物,取右下肺叶组织观察病理变化。结果对照组TNF-α、IL-8在各时点变化不明显。另外2组在TNF-α水平变化明显升高,且生理盐水组高于乌司他丁组(P<0.05)。而生理盐水组IL-8在复苏后4h才较对照组明显增高(P<0.05),而且辐度大于乌司他丁组(P<0.05)。肺组织病理学观察显示乌司他丁对缺血再灌注损伤肺具有保护作用。结论乌司他丁可能通过抑制TNF-α、IL-8和sICAM-1的释放,对创伤失血性休克及其引起的缺血再灌注肺损伤产生保护作用。     

干细胞动员对ALI大鼠TNF-α、IL-1β及肺泡表面活性物质保护作用分析

目的 探讨骨髓干细胞动员对急性肺损伤(ALI)大鼠肿瘤坏死因子α(TNF-α)、白介素1β(IL-1β)及肺泡表面活性物质的影响.方法 选取清洁级健康雄性SD大鼠60只,随机分为观察组和对照组,每组30只.2组大鼠建立ALI模型,其中观察组模型建立后皮下注射重组人粒细胞刺激因子(rhG-CSF),对照组皮下注射等量0.9%氯化钠溶液.在干预后3 d、7 d和14 d每组处死10只,采用HE染色观察各期辐射状肺泡计数(RAC)值和湿/干重比,酶联免疫吸附法(ELISA)检测支气管肺泡灌洗液(BALF)TNF-α、IL-1β水平,双重免疫荧光染色检测BrdU和肺泡表面活性物质结合蛋白A(SP-A)表达.结果 观察组伤后3 d、7 d和14 d肺组织湿/干重比、IL-1β和TNF-α均低于对照组,差异有统计学意义(P<0.05);观察组伤后3 d、7 d和14 d RAC值明显多于对照组,差异有统计学意义(P<0.05);观察组伤后3 d、7 d、14 d BrdU和SP-A双标阳性细胞标记率分别为(0.74±0.13)%、(1.40±0.23)%和(2.33±0.31)%,明显多于对照组,差异有统计学意义(P<0.05).结论 骨髓干细胞动员对ALI起保护作用,其保护作用涉及多种机制.     

他克莫司对炎症反应血清TNF-α、IL-1β含量的影响

目的:探讨他克莫司(FK506)预处理对炎症反应血清肿瘤坏死因子(TNF-α)、白细胞介素-1β(IL-1β)含量的影响.方法:以内毒素休克和重症急性胰腺炎造成的急性肺损伤动物作为研究对象.脂多糖(LPS)腹腔注射法诱导内毒素休克小鼠模型,牛磺胆酸钠胰胆管逆行注射法建立大鼠重症急性胰腺炎(SAP)模型.实验动物随机分为AII组、AII+FK506组,实验前2 d开始,AII+FK506组动物给予他克莫司20 mL*kg-1,sc,每12 h给予相同剂量维持;AII组以0.9%氯化钠注射液替代他克莫司.分别测定0,3,6,9 h两组血清TNF-α、IL-1β含量并观察肺湿重/干重(W/D)比值,肺组织病理学改变.结果:两组血清TNF-α、IL-1β含量均呈先升后降趋势,TNF-α于3 h达峰值, IL-1β于6 h达峰值,各时间AII+FK506组TNF-α、IL-1β含量均较AII组低,均差异有极显著性(均P＜0.01);各时间点AII、AII+FK506组大、小鼠W/D比值均较0 h相显著升高,AII+FK506组升高幅度低于AII组,均差异有极显著性(均P＜0.01).肺组织病理显示:AII组大小鼠肺实质及间质广泛性损害,肺间隔明显水肿、增厚,肺泡结构紊乱伴大量炎性渗出及PMN浸润;AII+FK506组肺组织损伤程度减轻.结论:他克莫司干预可减少炎症反应时血清TNF-α、IL-1β含量,减轻由炎性递质引发的急性炎症损害.     

支气管肺泡灌洗对兔肺泡内TNF-α的影响

目的 观察生理盐水、亚胺培南、氟康唑支气管肺泡灌洗后对兔肺泡内炎症因子的影响.方法 新西兰白兔34只气管插管后分为四组:A组(3只)作为空白对照;B组(11只)用生理盐水支气管肺泡灌洗;C组(8只)用亚胺培南灌洗;D组(12只)用氟康唑灌洗.2 h后处死动物,ELISA法比较肺泡灌洗液及肺组织匀浆中肿瘤坏死因子α(TNF-α)含量.结果 四组肺泡灌洗液的TNF-α水平各组间差异无统计学意义(P>0.05).C组肺组织匀浆TNF-α水平低于A、B、D组(P<0.05).结论 生理盐水、亚胺培南、氟康唑支气管肺泡灌洗并未增加局部TNF-α的释放.     

早期应用乌司他丁治疗COPD机械通气患者的呼吸机相关性肺损伤

目的探讨乌司他丁治疗呼吸机相关性肺损伤的临床疗效。方法选择40例呼吸机相关性肺损伤患者,随机分为乌司他丁治疗组(n=21)和对照组(n=19),两组患者均在常规积极治疗原发病的基础上采用肺保护性机械通气,乌司他丁治疗组在常规治疗基础上静脉滴注乌司他丁20万U,1次/8h,观察两组的临床疗效,血气分析指标及炎性因子水平的变化。结果治疗组与对照组在治疗前各项指标无差异。治疗后治疗组的氧合指数/呼吸指数及总有效率高于对照组(P<0.05),而IL-6,IL-8及TNF-α水平较对照组低,IL-10水平较对照组高(P<0.05)。结论乌司他丁可抑制机体炎症介质的产生,早期应用治疗效果明显。     

氨溴索对家兔单肺通气肺内炎性因子的影响

目的通过家兔单肺通气(OLV)模型,评价静脉注射氨溴索对家兔OLV时肺内炎性因子的影响。方法健康家兔30只,采用随机数字表法分为3组(每组10只):双肺通气组(C组)、单肺通气组(OLV组)、静脉注射氨溴索组(A组)。C组行双肺通气2h,其余2组行右侧肺通气2h。A组在右肺通气前10min静脉注射氨溴索15mg/kg。比较各组通气后右肺支气管肺泡灌洗液中肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β、IL-8、IL-10浓度的变化,并行组织病理形态学检查。结果与C组比较,其余2组右肺灌洗液TNF-α、IL-1β、IL-8浓度明显升高,IL-10浓度明显降低(P<0.01)。与OLV组比较:A组右肺灌洗液TNF-α、IL-1β、IL-8浓度明显降低,IL-10浓度明显升高(P<0.01)。与C组比较,其余2组病理形态学肺损伤评分明显升高(P<0.01)。与OLV组比较,A组肺损伤评分明显降低(P<0.01)。结论静脉注射氨溴索,可有效抑制家兔OLV肺内炎性反应。     

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.     

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.     

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.