老年人不同类型脑梗死与血浆氧化型低密度脂蛋白、血糖、C-反应蛋白及白细胞介素6的关系

目的 探讨老年人急性脑梗死患者血浆氧化型低密度脂蛋白(OX-LDL)、血糖、C-反应蛋白(CRP)和白细胞介素6(IL-6)水平变化及与不同类型急性脑梗死的关系.方法 100例急性脑梗死患者(A组)及30例同期住院的非脑梗死健康患者(B组)行血浆OX-LDL、血糖、CRP、IL-6和颈动脉超声检查.并按低分子肝素试验TOAST病因分型标准分型,对不同类型脑梗死相关危险因素进行分析.结果 A组OXLDL、血糖、CRP和IL-6分别为(627.2±174.7) μg/L、(8.8±1.7) mmol/L、(107.5±19.4) mg/L、(79.5±12.1)ng/L,均高于B组的(506.1±152.4) μg/L、(6.9±1.5) mmol/L、(87.2±13.6)mg/L、(58.5±10.3) ng/L(t=2.74,3.18,2.61,2.91,均P＜0.05).结论 老年人急性脑梗死与血浆OX-LDL、血糖、CRP和IL-6含量升高有关,且血浆OX-LDL增高易发大动脉粥样硬化型脑梗死,血糖增高发生小动脉闭塞型脑梗死的可能性大.     

松杉灵芝菌丝体多糖(FI_0-c)对人组织瘤细胞和人外周血白细胞产生炎症性细胞因子的影响(Ⅱ)(英文)

目的:比较研究水溶性多糖(FI_0-c)及其氯磺酸修饰产物(FI_0-c-S)对人炎症性细胞因子产生的影响.方法:应用氯磺酸修饰法对多糖进行化学修饰.用放射免疫分析法(RIA)及逆转录聚合酶链反应(RT-PCR)测FI_0-c和FI_0-c-S对人组织瘤细胞(THP-1)和人外周血单核细胞(PBMC)分泌各种与炎症有关的细胞因子,白介素-1(IL-1α)和肿瘤坏死因子α(TNFα)的影响及对mRNA表达的影响.结果:FI_0-c和FI_0-c-S(浓度分别为4,40,400 mg/L)显著提高 低剂量组LPS 10 mg/L协同PMA 200 nmol/L诱导的THP-1细胞产生TNFα的量,然而,这些多糖明显地抑制高剂量组LPS 100 mg/L协同PMA诱导的THP-1细胞产生TNFα.在无刺激的条件下FI_0-c能够诱导比较多量的IL-1α产生,但是FI_0-c或FI_0-c-S却都明显抑制高剂量或低剂量LPS和PMA诱导的THP-1细胞产生IL-1α.低浓度FI_0-c 4 mg/L显著抑制高剂量组LPS 100 mg/L协同PMA诱导的THP-1细胞产生IL-1或TNFα mRNA及蛋白质的量.结论:松杉灵芝菌丝体水溶性多糖在不同的刺激条件下具有双向免疫调节作用.化学修饰的多糖可改变原多糖对细胞因子产生的调节方向.     

葛根素对巨噬细胞基质金属蛋白酶9及其组织抑制物1表达的影响

目的 观察葛根素对巨噬细胞分泌和表达基质金属蛋白酶9(MMP-9)及其组织抑制因子1(TIMP-1)的影响.方法 将人单核细胞系THP-1来源的巨噬细胞与不同浓度的葛根素进行培养,采用RT-PCR和ELISA方法 分别检测巨噬细胞的MMP-9、TIMP-1的基凶和蛋白质表达.结果 葛根素对氧化低密度脂蛋白(ox-LDL)诱导THP-1细胞MMP-9 mRNA及其蛋白质表达作用呈浓度依赖性地减少MMP-9 mRNA及其蛋白的表达,但对TIMP-1的表达无影响.结论 葛根素可以通过调节巨噬细胞分泌MMP-9途径发挥稳定动脉粥样硬化斑块的作用.     

人参皂苷Rg_1的肠内菌代谢Ⅱ 人参皂苷Rg_1和Rh_1免疫活性(英文)

目的:比较人参皂苷Rg_1及其代谢产物Rh_1对细胞因子及其mRNA表达的影响.方法:将Rg_1及Rh_1加入正常人外周血单核细胞(PBMC)培养24小时后,计数细胞,观察其对正常细胞增殖的影响.用放射免疫法(RIA)观察Rg_1及Rh_1对人组织瘤细胞(THP-1)分泌与炎症有关的细胞因子(IL-1α,TNFα,IL-8)产生的影响,用逆转录酶链式聚合反应(RT-PCR)方法,检测Rg_1及Rh_1对TNFα的mRNA表达的影响.结果:Rg_1及Rh_1(0.1,1,10,100 mg/L)对PBMC增殖无明显影响.但在脂多糖10 mg/L和PMA 200 nmol/L存在下,Rh_1的低浓度(1 mg/L)能促进THP-1细胞产生TNFα与IL-8.而Rg_1在LPS 100 mg/L时抑制TNFα的产生.Rg_1 1 mg/L及Rh_1 100 mg/L均能促进IL-1α的产生.RT-PCR实验结果表明,Rh_1能显著促进TNFα mRNA的表达.结论:Rg_1与Rh_1的免疫活性有所不同,在有些方面甚至相反.     

罗格列酮对人单核巨噬细胞THP-1中胆固醇代谢的影响机制研究

目的:研究罗格列酮(RG)对氧化低密度脂蛋白(oxLDL)诱导的人单核巨噬细胞THP-1源性泡沫细胞中胆固醇代谢的影响机制。方法:将THP-1巨噬细胞分为空白对照组、oxLDL(100 mg.L-1)组和oxLDL(100 mg.L-1)+RG(10μmol.L-1)组,后2组先加oxLDL培养48 h,最后1组再加RG培养48 h,采用高效液相色谱法检测每组细胞内游离胆固醇(FC)和胆固醇酯(CE)的含量,逆转录-聚合酶链式反应(RT-PCR)、蛋白质印迹法分别检测每组细胞中三磷酸腺苷结合盒转运蛋白(ABC)A1、ABCG1 mRNA及蛋白的表达情况。结果:与空白对照组比较,oxLDL组FC、CE含量明显升高,ABCA1、ABCG1 mRNA及蛋白表达均明显降低(P<0.01);与oxLDL组比较,oxLDL+RG组FC、CE含量明显降低,ABCA1、ABCG1 mRNA及蛋白表达均明显升高(P<0.01)。结论:RG可能通过上调THP-1巨噬细胞ABCA1、ABCG1的表达,减少FC在细胞内的蓄积,促进细胞内胆固醇代谢,进而抑制动脉粥样硬化的形成。     

阿托伐他汀对oxLDL诱导泡沫细胞Lkn-1表达的影响

目的观察阿托伐他汀对OX-LDL诱导U937细胞形成泡沫细胞过程中Lkn-1表达的影响,探讨阿托伐他汀抗AS的作用机制。方法在由O．1μmol／L佛波脂（PMA）诱导分化人U937巨噬细胞中加入100mg／Lox—LDL及不同浓度（0．1、1、10μmol／L）的阿托伐他汀共同孵育24h,分别用酶联免疫吸附试验（ELISA）和RT-PCR方法检测培养细胞上清中Lkn-1的表达变化。结果OX-LDL组较正常对照组Lkn-1的表达明显增加（P〈0．05）。给药各组较OX-LDL组Lkn-1明显减少（P〈0．05）。且随阿托伐他汀浓度的增加Lkn-1表达呈逐渐减少的趋势（P〈0．05）。结论阿托伐他汀能抑制ox—LDL诱导U937细胞系形成泡沫细胞过程炎症因子Lkn-1的表达和分泌,可能为其抗动脉粥样硬化的重要机制之一。     

CRRT辅助治疗脓毒性休克患者的临床疗效及其对血清PCT与CRP的影响

目的 评价分析连续性肾脏替代疗法(CRRT)辅助治疗脓毒性休克患者的临床疗效及其对血清降钙素原(PCT)与C反应蛋白(CRP)的影响。方法 68例脓毒性休克患者,采取随机数字表法分为对照组和观察组,每组34例。对照组患者采取常规方法治疗,观察组患者在对照组基础上采取CRRT辅助治疗。比较两组患者的临床疗效及治疗前后血清PCT和CRP水平。结果 观察组患者的治疗总有效率为94.12%,显著高于对照组的67.65%,差异具有统计学意义(P<0.05)。观察组患者治疗前血清PCT水平为(84.56±3.98)μg/L、CRP水平为(181.36±32.87)mg/L,治疗后分别为(37.36±3.07)μg/L、(12.31±3.79)mg/L;对照组患者治疗前血清PCT水平为(84.54±3.96)μg/L、CRP水平为(179.25±35.91)mg/L,治疗后分别为(67.34±3.25)μg/L、(26.34±5.12)mg/L;治疗前,两组患者的血清PCT、CRP水平比较,差异无统计学意义(P>0.05);治疗后,两组患者的血清PCT、CRP水平均低于治疗前,且观察组显著低于对照组,差异均具有统计学意义(P<0.05)。结论 对于脓毒性休克患者,给予CRRT辅助治疗具有显著的疗效,且有助于患者血清PCT与CRP水平的改善,值得采纳及应用。     

熊果酸抑制HepG2中C-反应蛋白的异常表达及其对HUVECs的损伤

目的:研究不同剂量的熊果酸(UA)对IL-6诱导的HepG2细胞中C-反应蛋白(CRP)异常表达的抑制作用以及对CRP所致人脐静脉血管内皮细胞(HUVECs)损伤的保护作用.方法:IL-6(30 ng/mL)、UA(6.5、12.5、25μmol/L)与IL-6(30 ng/mL)共同作用于HepG2细胞48 h,分别用MTT法、Western blot法及RT-PCR法检测各组细胞活力、CRP蛋白及mRNA表达情况.CRP(25 μg/mL)、UA(5,10,20 μmol/L)与CRP(25 μg/mL)共同作用于HUVECs 24 h,分别用MTT法、Western blot法及RT-PCR法检测各组细胞增殖、VCAM-1和LOX-1的蛋白及mRNA表达.结果:UA能显著抑制IL-6诱导的HUVECs细胞活力下降及细胞中CRP蛋白与mRNA的表达升高;UA显著抑制CRP引起的内皮细胞增殖,并且在mRNA及蛋白水平均能显著抑制CRP诱导的HUVECs异常高表达VCAM-1及LOX-1.结论:UA可通过抑制肝脏合成炎症因子CRP而降低血液中CRP浓度,并降低CRP等炎症因子对内皮细胞的损伤等途径从而发挥抗心肌缺血及动脉粥样硬化等心血管疾病的作用.     

小剂量利多卡因对丙泊酚麻醉诱导和维持效应的影响

目的:探讨小剂量利多卡因对丙泊酚麻醉诱导和维持效应的影响。方法:年龄18～65岁、按美国麻醉医师协会标准病情为Ⅰ～Ⅱ级、择期行全麻开胸手术的患者共40例纳入研究,用抽签法随机分为2组:利多卡因组和对照组,每组20例。麻醉诱导期和维持期2组患者给药顺序如下:(1)静脉滴注马来酸咪达唑仑0.03 mg/kg;(2)利多卡因组静脉滴注利多卡因1 mg/kg,之后持续滴注33μg.kg-1.min-1,对照组等速给予等量0.9%氯化钠注射液;(3)静脉滴注瑞芬太尼1μg/kg,之后持续滴注0.2μg.kg-1.min-1;(4)静脉滴注丙泊酚,起始血浆靶浓度为1 mg/L,每次以0.3 mg/L上调,使脑电双频指数(BIS)稳定在40～60;(5)意识消失后静脉注射罗库溴铵0.6 mg/kg。监测和比较2组患者围术期不同时间点的BIS、心率、有创动脉血压(IAP)、丙泊酚血浆靶浓度和效应室浓度、鼻咽温、阿托品或麻黄碱和硝酸甘油用量,以及不良反应和术后合并症发生率的差异。监测利多卡因组患者利多卡因血药浓度。结果:利多卡因组男13例,女7例,平均年龄(54±9)岁;对照组男13例,女7例,平均年龄(51±1)岁。2组患者的基本特征、麻黄碱或阿托品和硝酸甘油用量、BIS、IAP、鼻咽温及不良反应发生率差异均无统计学意义。2组均未发生严重不良反应与合并症。利多卡因组和对照组各时间点丙泊酚血浆靶浓度和效应室浓度分别比较如下:气管插管时,(1.9±0.4)mg/L比(2.4±0.4)mg/L,(1.2±0.4)mg/L比(1.6±0.4)mg/L;器官切除时,(2.0±0.5)mg/L比(2.7±0.7)mg/L,(2.0±0.5)mg/L比(2.7±0.7)mg/L;关胸时,(1.7±0.4)mg/L比(2.2±0.7)mg/L,(1.8±0.4)mg/L比(2.3±0.7)mg/L;拔管时(0.8±0.2)mg/L比(0.9±0.2)mg/L,(0.9±0.2)mg/L比(1.0±0.3)mg/L。差异均有统计学意义(均P<0.05)。利多卡因组患者在麻醉诱导后30、120、240 min和手术结束时血清利多卡因浓度分别为(2.24±0.53)、(2.20±0.42)、(2.45±0.73)和(2.31±0.75)mg/L,均低于中毒浓度(8 mg/L)。结论:小剂量利多卡因可增加丙泊酚诱导和维持的效应。     

维持性血液透析患者C-反应蛋白变化的临床分析

目的探讨维持性血液透析患者C-反应蛋白(CRP)的改变及其临床意义。方法用凝集试验和比色法分别对22例维持性血液透析患者进行CRP、血红蛋白(Hb)、血清白蛋白(ALB)、血肌酐(SCr)动态检测。结果维持性血液透析患者CRP、Hb、ALB、SCr表达水平分别为(11.08±1.62)mg/L、(87.17±11.84)g/L、(35.40±3.27)g/L、(711.22±213.37)μmol/L,与正常对照相比,差异有显着性(P<0.05-P<0.01)。其中13例CRP异常患者治疗前后CRP、Hb、ALB、SCr表达水平分别为(13.78±2.38)mg/L、(16.16±4.19)mg/L和(83.54±12.31)g/L、(82.68±12.36)g/L和(33.45±3.45)g/L、(32.94±3.19)g/L和(724.15±222.32)μmol/L、(367.43±152.76)μmol/L,与CRP正常组相比,CRP水平增高,ALB水平下降,差异有显着性(P<0.05-P<0.01)。结论血液透析治疗可显着降低患者外周血中SCr水平,但可诱导CRP增高;CRP增高与Hb、ALB呈负相关。     

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.

---

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.     

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.     

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.