白细胞介素、肿瘤坏死因子-α与椎间盘退变的相关性研究

目的通过测定白细胞介素-1（IL-1）、白细胞介素-8（IL-8）及肿瘤坏死因子-α（TNF-α）在退变椎间盘组织中的水平,探讨其在椎间盘退变中的作用。方法用放免法测量椎间盘退变组（观察组）和对照组椎间盘组织中IL-1、IL-8及TNF-α的含量,并进行统计学分析。结果观察组中IL-1、IL-8及TNF-α含量分别为（71．35±11．23）μg/L、（7．33±2．45）μg/L、（6．54±2．67）μg/L;对照组分别为（28．58±12．25）μg/L、（2．35±1．15）μg/L、（3．33±1．45）μg/L。观察组IL-1、IL-8及TNF-α水平显著高于对照组。结论椎问盘组织中细胞因子IL-1、IL-8及TNF—α水平与椎间盘退变有关,可能是导致椎间盘组织退变的重要原因之一。     

丙氨酰-谷氨酰胺对AECOPD患者CD4＋、CD8＋淋巴细胞及IL-8、TNF-α的影响

目的 观察静脉补充丙氨酰-谷氨酰胺（AG）对慢性阻塞性肺疾病急性加重（acuteexacerbation of chronic obstructive pulmonary disease,AECOPD）患者CD4＋/CD8＋T细胞及IL-8、TNF-α的影响.方法 通过静脉对AECOPD患者补充丙氨酰-谷氨酰胺,ELISA法检测IL-8、TNF-α表达水平,流式细胞仪检测CD4＋、CD8＋、CD3＋淋巴细胞变化.结果 与对照组比较,丙氨酰-谷氨酰胺治疗组（AG组）临床缓解率高于对照组（93.33％vs 73.33％）;治疗后AG组IL-8[（102.11±13.57） ng/ml]、TNF-α[（0.83±0.26）μg/L]水平低于对照组[（137.46±12.9） ng/ml、（1.34±0.42）μg/L],两组比较差异有统计学意义（P＜0.05）;治疗后,两组CD4＋/CD8＋比值比较差异无统计学意义,但AG组CD3＋淋巴细胞绝对值（0.69×109/L）高于对照组（0.50×109/L） （P＜0.05）.结论 谷氨酰胺可促进AECOPD患者T淋巴细胞的增殖,并同时减少IL-8、TNF-α的表达,从而可能对AECOPD起到治疗作用.     

沙美特罗/氟替卡松对慢性阻塞性肺疾病患者急性加重期气道炎症的影响

目的 探讨沙美特罗/氟替卡松对慢性阻塞性肺疾病（COPD）患者气道炎症的影响.方法 选择40例COPD急性加重期患者,随机分成沙美特罗/氟替卡松治疗组（A组）和对照组（B组）,并选择18例健康人作为健康对照组（C组）.观察其支气管肺泡灌洗液（BALF）中自细胞介素8（IL-8）和肿瘤坏死因子α（TNF-α）的变化.结果 A组和B组患者BAL中[IL-8（10.60±1.42）μg/L,（10.77±1.98）μg/L]及TNF-α含量[（14.80±2.05）μg/L,（14.70±2.03）μg/L]均高于C组[（3.40±0.65）μg/L,（4.67±1.01）μg/L]（均P〈0.01） 治疗前BALF中IL-8与TNF-α含量,A组[（10.60±1.42）μg/L,（14.80±2.05）μg/L]和B组[（10.77±1.98）μg/L,（14.70±2.03）μg/L]差异均无统计学意义（均P〉0.05）,但治疗两周后,A组BALF中IL-8及TNF-α含量[（4.39±0.92）μg/L,（5.84±1.26）μg/L]较B组[（9.69±1.43）μg/L,（12.88±2.51）μg/L]均明显下降（均P〈0.01）.结论 沙美特罗/氟替卡松可以有效控制COPD患者的气道炎症.     

不同通气策略对老年患者腹部手术支气管肺泡灌洗液中肿瘤坏死因子α和白细胞介素8浓度的影响

目的 探讨不同通气策略对老年患者腹部手术支气管肺泡灌洗液（BALF）中肿瘤坏死因子α（TNF-α）和白细胞介素8（IL-8）浓度的影响.方法 选择温州医科大学附属第一医院择期行腹部择期手术的老年患者90例,根据机械通气方式不同,完全随机分为Ⅰ组（常规潮气量组）、Ⅱ组（低潮气量组）和Ⅲ组（低潮气量±呼气末正压）,每组30例于插管后3 min、麻醉机械通气3h收集BALF,检测BALF中TNF-α、IL-8水平.结果 3组患者插管后3h的TNF-α、IL-8与插管后3 min比较,差异均有统计学意义[Ⅰ组：（62±4） μg/L比（24±5） μg/L,（97±5）μg/L比（42±5）μg/L;Ⅱ组：（38±4）μg/L比（23±3）μg/L,（61±4） μg/L比（44±5）μg/L;Ⅲ组：（39±4）μg/L比（24 ±4） μg/L,（69±5） μg/L比（4l±6）μg/L]（均P＜0.05）.Ⅱ组和Ⅲ组插管后3 h的TNF-α、IL-8低于Ⅰ组,差异均有统计学意义（均P＜0.05）结论 在老年患者腹部手术中,低潮气量、低潮气量加小呼气末正压、常规潮气量均可引起老年患者BALF中TNF-α和IL-8水平升高,但常规潮气量更为显著.     

连续性血液净化治疗对脓毒症患者外周血炎性因子的影响

目的：探讨连续性血液净化（ CBP ）治疗对脓毒症患者外周血炎性因子的影响。方法选择132例脓毒症患者为研究对象,按照其接受的具体治疗方案分为观察组（66例）和对照组（66例）。对照组接受常规的方法治疗,观察组在接受常规治疗的基础上加用CBP治疗。比较两种治疗方法的疗效,观察血液净化治疗前后观察组患者外周血炎性因子的水平变化。结果观察组治疗前血清CRP、IL-6、IL-10、TNF-α分别为（102．84±14．57）mg/L、（183．41±27．53）μg/L、（37．13±5．28）μg/L、（212．45±29．23）mg/L,治疗后分别为（53．59±7．56）mg/L、（126．37±18．08）μg/L、（35．24±5．03）μg/L、（111．57±15．43）mg/L,治疗前后CRP、IL-6、IL-10和TNF-α水平差异均有统计学意义（ t＝24．375、14．070、2．106、27．699,均P＜0．05）;且观察组CRP、IL-6和TNF-α低于接受常规治疗后对照组[CRP（50．71±7．16）mg/L、IL-6（137．19±20．24）μg/L和TNF-α（132．33±18．18）μg/L],差异均有统计学意义（t＝2．247、3．239、7．073,均P＜0．05）,治疗后两组IL-10差异无统计学意义。结论 CBP治疗可以降低脓毒症患者外周血炎性因子水平,清除血浆细胞因子。     

妊娠期高血压疾病患者血清肿瘤坏死因子α白细胞介素6水平的变化及意义

目的 观察妊娠期高血压疾病（HDIP）患者血清肿瘤坏死因子α（TNF-α）和白细胞介素6（IL-6）水平的变化,探讨其在HDIP发病中的意义.方法 测定30例HDIP（11例妊娠期高血压、11例轻度子痫前期、8例重度子痫前期）和18例健康孕妇的血清TNF-α和IL-6水平.结果 HDIP患者血清TNF-α水平分别为（1.88±0.48）μg/L、（2.32±0.40） μg/L、（2.35±0.42） μg/L,血清IL-6水平分别是（99.54±31.62）ng/L、（ 120.53±26.42） ng/L、（ 140.83±22.13） ng/L,健康孕妇血清TNF-α水平为（1.63±0.32）μg/L,血清IL-6水平为（95.82±30.65） ng/L,组间差异均有统计学意义（均P＜0.05）.结论 HDIP患者血清TNF-α和IL-6水平明显增高,血管内皮细胞损伤在HDIP的发生发展过程中起到重要作用.     

胸腺法新联合抗生素用于恶性肿瘤并发肺部感染疗效观察

目的 观察胸腺法新联合抗生素用于ICU恶性肿瘤并发肺部感染患者的临床疗效.方法 将68例恶性肿瘤并发肺部感染患者按数字表法随机分为观察组（A组）34例和对照组（B组）34例,A组在使用抗生素治疗肺部感染的基础上皮下注射胸腺法新.记录并比较两组患者治疗前、治疗14 d后T细胞亚群、WBC、IL-6、TNF-α、CRP的变化及总有效率.结果 治疗14 d后,A组CD3^＋、CD4^＋、CD4^＋/CD8^＋较B组明显上升[CD3^＋：（63.54±8.61）比（56.97±8.10）;CD4＋：（48.73±5.36）比（35.32±5.62）; CD4^＋/CD8^＋：（1.47±0.43）比（0.96±0.90）,t=3.24、4.64、3.12,均P＜0.05],WBC：（×10^9/L）、IL-6（μg/L）、TNF-α（μg/L）、CRP（μg/mL）下降均较B组更显著（[WBC：（8.4±2.8）比（12.5±5.0）;IL-6：（0.15±0.06）比（0.38±0.14）;TNF-α：（3.54±0.90）比（7.80±1.76）; CRP：（81.72±29.93）比（107.08±28.96）,t=4.11、8.50、12.52、3.55,均P＜0.01],且治疗总有效率明显增高（91.2%比61.8%,χ^2=8.173,P=0.004）.结论 胸腺法新联合抗生素用于ICU恶性肿瘤并发肺部感染患者,能更有效改善恶性肿瘤患者免疫功能,有助于严重肺部感染的控制.     

阿托伐他汀对急性冠脉综合征患者白细胞介素6和肿瘤坏死因子的影响

目的 探讨阿托伐他汀对急性冠脉综合征（ACS）患者血清白细胞介素6（IL-6）及肿瘤坏死因子α（TNF-α）水平变化的影响。方法将ACS患者48例随机分为阿托伐他汀组25例和常规治疗组23例,分别于治疗前及治疗4周后采用放射免疫分析方法行血清IL-6及TNF—α检测。结果ACS患者治疗前血清IL-6、TNF-α水平均明显高于对照组（均P〈0．01）。阿托伐他汀组治疗后血清IL-6（0．67±0．05）μg/L、TNF-μ（65．1±13．2）μg／L水平均明显低于治疗前,但仍高于对照组（均P〈0．05）。常规治疗组患者治疗后血清IL-6（0．74±0．08）μg／L、TNF—±（73．6±12．0）μg／L降低不明显（P〉0．05）。结论IL-6、TNF-α水平升高与ACS发病密切相关,阿托伐他汀可降低ACS患者血IL-6、TNF—α水平,具有减轻病变部位炎性反应和保护内皮细胞的作用。     

中介素通过激活AMPK信号通路对脂多糖诱导巨噬细胞极化的影响

目的探讨中介素(intermedin,IMD)对脂多糖(lipopolysaccharide,LPS)诱导小鼠单核巨噬细胞系RAW 264.7极化的影响及其作用机制。方法RAW 264.7细胞随机分为对照组、LPS组、LPS+IMD组、LPS+IMD+CC(AMPK抑制剂Compound C)组。Real time-PCR法检测TNF-α、CD86、iNOS、Arg^-1、CD206 mRNA表达,Western blot法检测p-AMPK、AMPK、TNF-α、IL-6和IL^-10蛋白表达,流式细胞术检测巨噬细胞亚型,ELISA法检测培养基上清IL-6和TNF-α浓度。结果与对照组及LPS组比较,IMD处理可增加AMPK磷酸化水平,增加p-AMPK/AMPK比值;与对照组相比,LPS诱导可导致巨噬细胞发生M1极化,M1型标志分子CD86、TNF-α及iNOS mRNA表达升高,M2型标志分子CD206、Arg^-1 mRNA表达降低,上调促炎因子TNF-α、IL-6表达,降低抑炎因子IL^-10表达,使M1型细胞数量增加,细胞上清中TNF-α、IL-6分泌增加;而IMD处理可抑制LPS诱导的M1极化,AMPK抑制剂Compound C组处理可在一定程度上拮抗这一作用。结论IMD通过激活AMPK信号通路抑制LPS诱导的巨噬细胞M1型极化。     

醒脑静对急性酒精中毒患者炎性因子含量的影响

目的 探讨急性酒精中毒患者血浆炎性因子含量的变化及醒脑静对其影响.方法 选取甘肃省兰州市第一人民医院严重急性酒精中毒患者50例,采用随机数字表法分为常规治疗组（对照组）和醒脑静＋常规治疗组（观察组）,各25例.分别检测2组患者治疗前后内皮素1、一氧化氮、肿瘤坏死因子α（TNF-α）和白细胞介素6（IL-6）含量的变化,并与20名体检者健康（正常组）进行对比分析.结果 对照组和观察组治疗前后的内皮素1、一氧化氮、TNF-α和IL-6[对照组：治疗前（77±7）ng/L、（34±10）μmol/L、（2.6±0.1）ng/L、（31.3±3.2）ng/L,治疗后（68±6）ng/L、（48±10）μmol/L、（2.2±0.2）ng/L、（26.3±3.1）ng/L;观察组：治疗前（78±7）ng/L、（35±11）μmol/L、（2.6±0.2）ng/ml、（32.4±3.1）ng/L,治疗后（62±7）ng/L、（57±9）μmol/L、（2.0±0.3）ng/ml、（22.6±3.2）ng/L]与正常组[（55±9）ng/L、（57±14）μmol/L、（2.0±0.4）ng/ml、（16.6±2.8）ng/L]相比,差异均有统计学意义（均P〈0.01）.观察组、对照组治疗后血浆内皮素1、一氧化氮、TNF-α、IL-6与治疗前比较,差异均有统计学意义（均P〈0.05）.观察组治疗后血浆内皮素1、TNF-α及IL-6显著低于对照组（P〈0.01）,一氧化氮明显高于对照组（P〈0.01）.结论 急性酒精中毒患者血中内皮素1、TNF-α和IL-6明显升高,一氧化氮水平降低,醒脑静治疗后可降低内皮素1、TNF-α和IL-6,提高一氧化氮水平,具有改善急性酒精中毒病理损害的作用.     

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.     

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.     

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.