丙氨酰谷氨酰胺对ALI患者肺保护机制的研究

目的 观察丙氨酰谷氨酰胺(Ala-Gln)对急性肺损伤(ALI)患者血清热休克蛋白-70(HSP-70)及肿瘤坏死因子-α(TNF-α)、白介素-8(IL-8)水平的影响及对ALI患者预后的影响,进一步探讨其对ALI患者肺保护作用的内在机制.方法 110例ALI患者随机分为对照组50例和Gln组60例,2组常规治疗一致,Gln组给予Ala-Gln 0.4 g·kg-1·d-1共7d.比较2组患者治疗前后血清HSP-70、TNF-α、IL-8浓度及APACHEⅡ评分的变化及机械通气时间.结果 与本组治疗前及对照组治疗后比较,Gln组治疗后血清HSP-70水平显著升高(P＜0.05),TNF-α水平明显下降(P＜0.05或＜0.01),IL-8水平显著下降(P ＜0.05或＜0.01),APACHEⅡ评分显著降低(P＜0.05或＜0.01),与对照组比较,Gln组机械通气时间缩短(P＜0.05).结论 ALI患者给予Ala-Gln治疗,比常规治疗更有利于促进肺功能恢复,改善患者预后.其机制可能与Gln提高患者血清HSP-70的水平,从而降低TNF-α、IL-8的血清浓度,调控细胞因子的产生和释放,减轻了过度的炎性反应有关.     

乌司他丁对急性肺损伤患者的疗效观察

目的 探讨乌司他丁对急性肺损伤患者的疗效.方法 将65例急性肺损伤患者应用数字表法随机分为观察组(35例)和对照组(30例).对照组行常规治疗方法,观察组在常规治疗方法基础上加用乌司他丁进行治疗.治疗后对两组患者的肺功能以及炎性因子等进行检测.结果 两组治疗前后PaO2 、PaO2、PaCO2水平,氧合指数及呼吸频率均明显改善(均P＜0.05),且观察组改善程度均优于对照组(均P＜0.05);观察组治疗后24 h以及48 h后其肿瘤坏死因子α、白细胞介素6、白细胞介素8等炎性因子水平明显低于对照组(均P ＜0.05);观察组患者转化为急性呼吸窘迫综合征、使用呼吸机以及死亡例数分别为9例、11例、3例,均低于对照组的14例、19例、9例(均P＜0.05);观察组患者治疗后胸片结果均优于对照组(均P＜0.05).结论 乌司他丁治疗急性肺损伤可明显改善患者肺功能和预后.     

地塞米松对大鼠急性肺损伤中性粒细胞凋亡的影响

目的 Dex)在大鼠急性肺损伤(ALI)中对中性粒细胞(PMN)凋亡的影响.方法 雄性SD大鼠66只,随机分为3组.正常对照组(N组)6只,静注生理盐水后采集标本.内毒素致伤组(LPS组)30只,静注脂多糖制成ALI模型;地塞米松干预组(DEX组)30只,静注脂多糖的同时静注地塞米松.两组分别于给药后2、4、6、8、16h采集标本.观察肺组织病理切片、肺水含量测定(W/D)、肺泡灌洗液(BALF)中PMN凋亡测定.结果 LPS组注射内毒素2h后光镜可见肺泡腔狭窄,中性粒细胞渗出等ALI表现,且随时程延长病变加重;DEX组ALI表现较LPS组好转.LPS组和DEX组肺W/D均比N组明显增加(P＜0.05).但DEX组与LPS组比较,2、6、16h显著减少(P＜0.05),BALF中PMN凋亡率比N组明显降低(P＜0.01).DEX组PMN凋亡率比N组显著降低(P＜0.01);与LPS组相比,DEX组PMN凋亡率增加,4、6、8及16h与对应的LPS组比较有显著差异(P＜0.05).结论 ALI时PMN在肺泡内的凋亡延迟,DEX减轻ALI时肺组织损伤可能与DEX促进PMN在肺泡内的凋亡有关.     

盐酸纳美芬对急性创伤性颅脑损伤疗效及脑保护作用观察

目的 探讨盐酸纳美芬治疗急性创伤性颅脑损伤的临床效果,并分析其脑保护作用.方法 选取解放军252医院于2013年1月-2016年5月收治的92例急性创伤性颅脑损伤患者作为研究对象,按照治疗方法将其分成两组,每组46例.两组均给予常规治疗,观察组在此基础上给予盐酸纳美芬治疗,比较两组近期疗效、预后以及治疗前、治疗第1、3、7和14天血清β-内咖肽、S100B蛋白、神经特异性烯醇化酶(NSE)水平.结果 观察组治疗第1、3、7和14天血清β-内咖肽、S100B蛋白、NSE水平逐渐下降,且明显低于治疗前(P＜0.01);对照组治疗第7和14天血清β-内咖肽水平逐渐下降,明显低于治疗前(P＜0.01),治疗第3、7和14天血清S100B蛋白、NSE水平逐渐下降,均明显低于治疗前(P＜0.01);观察组治疗后同时间点血清β-内咖肽、S100B蛋白、NSE水平均明显低于对照组(P＜0.01).观察组呼吸异常和心率异常发生率均明显低于对照组(P＜0.05),颅内压控制效果明显优于对照组(P＜0.05),预后良好率明显高于对照组(P＜0.05).两组不良反应发生率比较差异无统计学意义(P＞0.05).结论 在常规治疗基础上联合使用盐酸纳美芬治疗急性创伤性颅脑损伤可有效提高临床效果,减轻继发性脑损害,脑保护作用明显.     

乌司他丁在急性肺损伤肺保护性机械通气中的疗效观察

目的 探讨乌司他丁在急性肺损伤(ALI)肺保护性机械通气中的疗效.方法 将90例ALI患者分为观察组与对照组各45例,所有患者均给予一般治疗与保护性机械通气,观察组另给予乌司他丁治疗,5d后对比两组的疗效.结果 治疗前两组动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)、氧合指数(PaO2/FiO2)、白细胞计数(WBC)差异无统计学意义(P＞0.05),治疗后观察组PaO2、PaO2/FiO2高于对照组(P＜0.05),PaCO2、WBC低于对照组(P＜0.05).观察组总有效率高于对照组(P＜0.01).结论 乌司他丁对保护性机械通气的ALI患者可有效抑制炎症反应,改善肺组织换气功能,改善预后.     

阿魏酸钠联合厄贝沙坦对慢性肾功能衰竭患者血清炎性因子、Hcy、PTH及β_2-MG的影响

目的探讨阿魏酸钠联合厄贝沙坦对慢性肾功能衰竭患者血清炎性因子、Hcy、PTH及β_2-MG的影响。方法选取2016年3月～2017年5月我院收治的慢性肾功能衰竭患者100例,随机分为两组,对照组给予口服厄贝沙坦,研究组在对照组基础上加用阿魏酸钠静脉滴注进行治疗。观察并比较治疗1个月后两组患者治疗前后各项血清炎性因子、同型半胱氨酸(Hcy)、甲状旁腺素(PTH)及β2微球蛋白(β2-MG)等指标情况,观察并比较两组患者治疗过程中不良反应的发生情况。结果经治疗1个月后,研究组治疗后各项血清炎性因子含量明显低于对照组治疗后和本组治疗前含量(P 0.05),同时研究组治疗后Hcy、PTH及β_2-MG含量明显低于对照组治疗后和本组治疗前含量(P 0.05),研究组治疗过程中并发症发生率明显低于对照组(P 0.05)。结论阿魏酸钠联合厄贝沙坦对慢性肾功能衰竭患者具有显著疗效,可以有效减少慢性肾功能衰竭患者血清内炎性因子,可有效减少患者血清中Hcy、β_2-MG及PTH等含量,可有效改善患者肾功能,减少患者的痛苦,在临床上应当进行进一步的推广与应用。     

微创血肿穿刺术后联合依达拉奉对高血压脑出血疗效和认知功能及血清炎性因子水平的影响

目的 探讨微创血肿穿刺术后联合依达拉奉对高血压脑出血疗效和认知功能及血清炎性因子水平的影响.方法 选取雅安市人民医院于2014年6月-2016年6月收治的90例高血压脑出血.按照治疗方法分为对照组与观察组,每组45例,对照组给予微创血肿穿刺术与常规治疗,观察组在对照组基础上联合依达拉奉治疗.对比两组临床疗效、中国脑卒中临床神经功能缺损程度评分量表(CSS)评分、蒙特利尔认知评估量表(MoCA)评分、血清超敏C反应蛋白(hs-CRP)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平.结果 观察组临床总有效率明显高于对照组(P＜0.05).治疗后14 d和28 d,两组CSS评分、hs-CRP、TNF-α和IL-6水平均低于治疗前(P＜0.05),且观察组上述指标低于对照组(P＜0.05).治疗后14 d和28 d,两组MoCA评分均高于治疗前(P＜0.05),且观察组MoCA评分高于对照组(P＜0.05).结论 微创血肿穿刺术联合依达拉奉治疗高血压脑出血可获得显著效果,促进神经功能的恢复,降低血清炎性因子水平.     

高能肠内营养乳剂对重症心力衰竭患者N末端B型利钠肽原及炎性因子的影响

目的 探讨高能肠内营养对重症心力衰竭患者N末端B型利钠肽原(NT-proBNP)及血清炎性因子的影响.方法 选择我科2016年2-8月收治的重症心力衰竭患者60例,随机分为两组.两组在常规治疗心衰同时,常规饮食组自由饮食,高能肠内营养组经口进食高能肠内营养乳剂瑞先.治疗前后检测营养指标及血清炎性因子白介素-6、C-反应蛋白及心功能指标血浆氨基末端脑钠肽前体变化.结果 常规饮食组患者治疗前后各项营养指标无改善,心功能及血清炎性因子水平较前改善,差异有统计学意义(P＜0.05).高能肠内营养组患者治疗前后各项营养指标明显改善,心功能及血清炎性因子水平较前明显改善,差异有统计学意义(P＜0.05),与常规饮食组比较改善更加明显,差异有统计学意义(P＜0.05).结论 重症心力衰竭常规治疗心衰的同时加强肠内营养的支持,可以改善患者的营养状况,降低炎性因子水平,进一步改善心功能.     

根管填充环氧树脂类糊剂治疗根尖周炎的疗效及对患者炎性因子的影响

目的:分析在根尖周炎患者治疗中采用根管填充环氧树脂类糊剂的疗效及对患者炎性因子的影响.方法:选取我院收治的70例根尖周炎患者作为本次研究对象,基于治疗方式的差异分为观察组与对照组,两组各有患者35例.对比两组患者的治疗效果和治疗前后患者炎性因子的变化情况.结果:治疗结束后,观察组的治疗总有效率明显优于对照组患者,组间差异明显(P＜0.05);两组患者治疗后静息和咬合VAS评分对比中,观察组患者VAS评分情况明显低于对照组,组间差异明显(P＜0.05),而在炎性因子方面,观察组患者的血清c反应蛋白、白介素-6、肿瘤坏死因子-α炎性因子下降水平明显高于对照组患者,组间差异明显(P＜0.05).结论:在根尖周炎患者治疗中采用根管填充环氧树脂类糊剂能够有效的改善患者的治疗效果与炎症情况,缓解患者的疼痛.     

早期肠内营养对ICU重型颅脑损伤患者的免疫功能和监护时间的影响

目的探讨早期肠内营养(ENN)对ICU重症颅脑损伤患者的免疫功能、炎症因子水平以及监护时间的影响。方法选取2016年1月～2018年6月在我院ICU住院治疗的80例重症颅脑损伤患者,随机分为对照组和观察组,每组40例。对照组患者给予延迟肠内营养治疗,观察组患者给予早期肠内营养,分别在治疗前及治疗后10d观察两组患者的细胞免疫指标、体液免疫指标、炎症因子水平以及ICU监护时间及预后情况。结果入住ICU时,两组患者的T淋巴细胞亚群CD4~+、CD8~+及CD4~+/CD8~+,体液免疫指标IgA、IgG及IgM水平,以及血清IL-6、IL-8及TNF-α水平均无明显差异(P 0.05),早期肠内营养10d后,两组患者的T淋巴细胞亚群指标、体液免疫指标指标均明显升高(P 0.05),且观察组患者的各项指标水平均高于对照组(P 0.05);两组患者血清IL-6、IL-8及TNF-α均较治疗前明显降低(P 0.05),且观察组患者各炎性因子指标水平均明显低于对照组(P 0.05);观察组患者的并发症发生率22.50%明显低于对照组的52.50%(P 0.05),观察组患者的ICU住院时间明显少于对照组(P 0.05)。结论早期肠内营养治疗可有效提高重症颅脑外伤患者的免疫功能,降低炎性因子水平,缩短ICU监护时间,改善患者预后状况。     

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.