不同血液净化方式对维持性血液透析患者炎性因子清除的疗效观察

目的观察常规血液透析(HD)、高通量血液透析(HFD)、血液灌流(HP)对终末期肾病(ESRD)维持性血液透析(MHD)患者体内炎性因子清除的疗效。方法选择透析龄3个月以上稳定的MHD患者60例,随机分为HD组、HFD组、HD+HP组,每组20例。3组患者分别在首次治疗前后及治疗3个月后透析前,测定患者C-反应蛋白(CRP)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、β2微球蛋白(β2-MG)血清含量,同时测定20例健康志愿者(对照组)CRP、IL-6、TNF-α、β2-MG血清含量。结果 MHD患者治疗前的CRP、IL-6、TNF-α、β2-MG水平均高于对照组(P<0.01),透析3组间差异无统计学意义(P>0.05)。HD组首次治疗后及治疗3个月后CRP、IL-6、β2-MG及TNF-α均升高,与治疗前比较差异无统计学意义(P>0.05)。HFD组合首次治疗后CRP、IL-6、β2-MG及TNF-α均下降,但与治疗前比较差异无统计学意义(P>0.05);治疗3个月后CRP、IL-6、β2-MG及TNF-α下降(P<0.05)。HD+HP组首次治疗后及治疗3个月后CRP、IL-6、β2-MG及TNF-α均下降(P<0.05)。治疗3个月后,HD+HP组的CRP、IL-6、β2-MG及TNF-α值低于HFD组(P<0.05),HD+HP组下降百分比高于HFD组(P<0.01)。结论 MHD患者存在微炎症状态,HFD和HP可以降低CRP、IL-6、β2-MG及TNF-ɑ水平,改善患者的微炎症状态,HP可能优于HFD。     

大黄减轻维持性血液透析患者静脉铁剂诱导的氧化应激和微炎症反应

目的探讨大黄对维持性血液透析（MHD）患者静脉铁剂诱导的氧化应激和微炎症反应的影响。方法选取在该院血液净化中心行MHD治疗的患者80例,随机分为对照组（A组）和大黄治疗组（B组）。B组给予大黄泡水服用8周。分别于治疗前后检测丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-px）、C反应蛋白（CRP）、肿瘤坏死因子（TNF）-α、白介素（IL）-1β、IL-10等。结果治疗后,两组的SOD和GSH-px较治疗前下降,MDA、CRP、TNF-α、IL-1β均较治疗前升高（P〈0.05或0.01）;B组SOD和GSH-px均较A组升高（P〈0.05或0.01）,MDA、CRP、TNF-α、IL-1β均较A组降低（P〈0.05或0.01）,两组间IL-10差异无统计学意义。结论大黄可以减轻静脉铁剂诱导的氧化应激和微炎症反应。     

维持性血液透析患者氧化应激和炎症状态与骨质疏松的关系

目的探讨维持性血液透析(MHD)患者氧化应激和炎症状态与骨质疏松(OP)的关系,为临床MHD患者防治OP提供理论依据。方法选取2016年1月至2018年12月在南部战区空军医院接受维持性血透的180例患者作为研究对象。检测患者骨密度(BMD)进行OP诊断。酶联免疫吸附测定法(ELISA)检测血清中超氧化物歧化酶(SOD)、丙二醛(MDA)和总抗氧化力(T-AOC)、C-反应蛋白(CRP)、白细胞介素-1(IL-1)和白细胞介素-6(IL-6)浓度值。Pearson相关性分析氧化应激指标与炎症介质与MHD患者发生OP的相关性。结果根据骨密度仪检测结果,将180例MHD患者分为OP组(n=92)和non-OP组(n=88)。OP组患者血清SOD和T-AOC浓度值均较non-OP组低,而MDA浓度值则高于non-OP组;OP组患者血清IL-1、IL-6和CRP浓度值均高于non-OP组(P 0.05)。Pearson相关性分析结果显示,MHD患者BMD值与血清SOD和T-AOC呈明显正相关,与血清IL-1、IL-6、CRP和MDA存在明显负相关(P 0.05)。结论 MHD患者中氧化应激和炎症状态与OP的发生有关,早期开展抗氧化应激和炎症反应治疗有利于防治OP的发生。     

辛伐他汀对维持性血液透析患者氧化应激及微炎症状态的影响

目的：探讨辛伐他汀对维持性血液透析（MHD）患者氧化应激及微炎症状态的影响。方法选择80例尿毒症血透患者分为两组,单纯血透组和辛伐他汀治疗组患者各40例,观察治疗前后血清中丙二醛（MDA）,超氧化物歧化酶（SOD）和血清总抗氧化物能力（T-AOC）等氧化指标以及血清C-反应蛋白、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）等炎症指标的变化。结果研究组给予辛伐他汀治疗后,患者MDA、CRP、IL-6和TNF-α较治疗前和对照组明显降低（P〈0.05）,SOD活性、T-AOC活性较治疗前升高（P〈0.05）,而对照组治疗前后各项指标差异无统计学意义（P〉0.05）。结论辛伐他汀能在一定程度上改善MHD患者的氧化应激和微炎症状态,且不良反应少,具有广泛的临床应用潜能。     

血液灌流联合血液透析对慢性肾衰竭患者微炎症状态的影响

目的观察血液灌流联合血液透析对慢性肾衰竭患者微炎症状态的影响。方法选择2012年1月至2012年12月在我院治疗的92例慢性肾衰竭尿毒症患者,随机均分成血液灌流联合血液透析治疗组（观察组）或血液透析治疗组（对照组）,分别于治疗前、后测患者白细胞介素-1（IL-1）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）及C反应蛋白（CRP）水平。结果两组患者在治疗前IL-1、IL-6、TNF-α和CRP都没有显著性差异（P〉0.05）,观察组患者在治疗后的IL-1、IL-6、TNF-α和CRP都显著低于对照组患者（P〈0.05）。结论慢性肾衰竭患者存在微炎症状态,血液灌流联合血液透析可显著改善患者的慢性炎症状态,值得在临床推广应用。     

尼莫地平对蛛网膜下腔出血后坐骨神经炎性因子表达的影响

目的 探讨尼莫地平对蛛网膜下腔出血(SAH)后坐骨神经肿瘤坏死因子(TNF-α)、白细胞介素(IL)-1β和IL-6表达的干预作用.方法 SD大鼠分成对照组(n=10),SAH组(n=15),尼莫地平干预组(n=15).尼莫地平干预纰从第1天开始通过尾静脉注射尼莫地平至第14天;第3、7和14天取各组坐骨神经进行TNF-α、IL-1β和IL-6免疫组化与荧光染色,并对结果进行数据分析.结果 第3、7和14天SAH组坐骨神经的TNF-α、IL-1β和IL-6表达较对照组明显增高(P<0.05);第3、7天干预组坐骨神经TNF-α、IL-1β和IL-6表达较SAH组明显减少(P<0.05);第14天,IL-1β和IL-6表达与SAH组的差异仍有统计学意义(P<0.05).结论 蛛网膜下腔出血后,坐骨神经上TNF-α、IL-1β和IL-6表达明显升高,尼莫地平能降低其表达.     

厄贝沙坦对维持性血液透析患者微炎症状态的影响

目的:探讨厄贝沙坦对维持性血液透析(MHD)患者微炎症状态的影响.方法:选择52例行MHD治疗的慢性肾衰患者,随机分为厄贝沙坦治疗组27例和非厄贝沙坦治疗组25例,并设28例健康对照组作为比较,检测治疗前及治疗6个月后血清C-反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α).结果:尿毒症MHD组CRP,IL-6,TNF-α显著高于健康对照组(P<0.01),治疗6个月后,厄贝沙坦治疗组CRP,IL-6,TNF.d的水平均有所下降,厄贝沙坦治疗组CRP,IL-6,TNF-α下降的水平与治疗前及非厄贝沙坦治疗组相比,差异具有显著性(P<0.05);非厄贝沙坦治疗组CRP,IL-6,TNF-α的水平较治疗前有所上升(P<0.05).结论:尿毒症患者体内存在微炎症状态,厄贝沙坦可改善MHD患者的微炎症状态.     

小檗碱对兔颈动脉损伤后白介素-6等的影响

目的观察兔颈动脉损伤后炎性因子IL-6、TNF-α、ICAM-1及CRP的动态变化以及小檗碱对其的影响,探讨小檗碱在兔颈动脉血管损伤后对IL-6等炎性因子的作用及其机制。方法30只日本大耳白兔随机分成假手术组(n=6)、模型组(n=6)、小檗碱组(n=9)、辛伐他汀组(n=9),制备兔颈动脉球囊扩张模型。假手术组不用药物,模型组给予生理盐水腹腔注射,小檗碱组2.5?/(kg.d)每日腹腔注射,辛伐他汀组3.3mg/(kg.d)灌胃。于术后第3、6、10d自耳缘静脉取血4m l/只,分离血清,用放射免疫法测定IL-6,TNF-α,用酶联免疫吸附法(ELISA)测定ICAM-1及CRP。结果术后10d,模型组IL-6的浓度明显高于假手术组(P<0.01),也高于辛伐他汀组及小檗碱组(P<0.01);术后3d,模型组TNF-α浓度高于假手术组(P<0.05)及小檗碱组(P<0.01);术后6d模型组TNF-α浓度高于假手术组(P<0.05);术后10d模型组TNF-α高于假手术组(P<0.01)及小檗碱组和辛伐他汀组(P<0.05)。术后6d模型组ICAM-1浓度高于假手术组(P<0.05)、小檗碱组(P<0.01)及辛伐他汀(P<0.05);术后10d模型组ICAM-1高于小檗碱组(P<0.05)。术后3~10d模型组CRP的浓度高于假手术组及小檗碱组(P<0.01,P<0.05)。结论小檗碱对兔颈动脉损伤后IL-6等炎症因子有影响,对动脉损伤后炎症反应有作用。     

淫羊藿苷对大鼠创伤性脑损伤后白细胞介素1β和肿瘤坏死因子α的作用

目的观察淫羊藿苷(Ica)对大鼠创伤性脑损伤(TBI)后炎症因子白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)的影响。方法 SD雄性大鼠60只,随机分为空白组、模型组、Ica低剂量(10 mg·kg~(-1))组和Ica高剂量(40 mg·kg-1)组,均n=15。造模前一周连续预防性灌胃给药,每日2次,空白组和模型组灌胃给予等体积生理盐水。采用Feeney法建立大鼠TBI模型,造模24 h后取材,取材前先进行神经行为学功能评分;HE染色法观察脑组织病理形态学变化;Real-Time PCR法检测损伤区皮质中IL-1β和TNF-αm RNA的表达;免疫组化法观察损伤区皮质中IL-1β和TNF-α表达情况;Western blot检测损伤区皮质中IL-1β和TNF-α蛋白表达。结果与空白组相比,模型组大鼠神经行为学功能评分明显升高(P<0.01),损伤区能观察到明显的病理学损伤,损伤区皮质中IL-1β和TNF-αm RNA和蛋白的表达均明显上调(P<0.05或P<0.01)。与模型组相比,Ica低、高剂量组大鼠神经行为学功能评分显著降低(P<0.01),且损伤区组织的病理学损伤减轻;Ica低剂量组损伤区皮质中IL-1β和TNF-αm RNA表达显著下调(P<0.05),但Ica高剂量组TNF-αm RNA表达无显著改变(P>0.05);Ica低、高剂量组IL-1β和TNF-α蛋白的表达均显著下调(P<0.05或P<0.01)。结论 Ica对TBI具有改善作用,其中一个重要的原因可能与抑制炎症因子IL-1β、TNF-α的表达有关。     

高通量血液透析对血清β2微球蛋白和C反应蛋白的影响

目的 探讨高通量血液透析(HFHD)对中分子毒素及炎症因子的影响.方法 36名维持性血液透析患者,随机分成HFHD组(n=18)和常规血液透析(LFHD)组(n=18),比较治疗前(0个月)、后(3个月)β2微球蛋白(β2-MG)、C反应蛋白(CRP)水平.结果 治疗前,两组间血清差异无统计学意义(P>0.05);与治疗前比较,治疗3月后HFHD组血清β2-MG和CRP浓度均显著降低(P<0.05),而LFHD组血清β2-MG和CRP差异无统计学意义(P>0.05).结论 HFHD能有效清除β2-MG,改善患者慢性炎症状态,提高患者生活质量.     

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.

     

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.     

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.     

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.