硼替佐米对大鼠肾移植AMR的保护作用及机制研究

目的研究硼替佐米对肾移植抗体介导排斥反应(AMR)的保护作用及机制。方法采用输血致敏法构建大鼠肾移植AMR模型。在此模型基础上,静脉注射硼替佐米,研究其对移植肾功能和病理损害的保护作用。流式细胞仪检测供体特异性抗体(DSA)的水平,免疫组织化学检测移植肾C4d表达,免疫荧光法检测CD68表达以反映巨噬细胞的浸润。结果硼替佐米可以明显改善肾移植AMR大鼠移植肾功能(P<0.05),减轻移植肾病理损害。硼替佐米显著降低大鼠肾移植AMR模型血清中IgM、IgG 2b和IgG 2c等DSA亚型的水平(P<0.05),同时抑制移植肾组织中C4d的表达和巨噬细胞浸润。结论硼替佐米对肾移植AMR具有明显的保护作用,其机制可能与抑制受体DSA产生及减少移植肾组织中巨噬细胞浸润有关。     

N-乙酰基-L-谷氨酰基-泼尼松龙肾靶向前体药物研究

目的通过研究N-乙酰基-L-谷氨酰基-泼尼松龙的体内分布,考察该前体药物的肾靶向性.方法小鼠iv后,采用高效液相法,在规定时间段测定各组织脏器的泼尼松龙浓度, 并采用大鼠骨密度的测定仪确证前体药物的副作用.结果小鼠给药后15 min,前体药物组肾脏中泼尼松龙浓度为(86±8) μg*g-1,泼尼松龙组为(57±4) μg*g-1,60 min后前体药物组肾脏药物浓度为 (67±5) μg*g-1;泼尼松龙组(42±4) μg*g-1.大鼠给药30 d后,股骨的骨密度分别为(0.08±0.03) g*cm-2 (泼尼松龙)和(0.14±0.06) g*cm-2(前体药物组).结论前体药物具有肾靶向性, 并能降低致骨质疏松的副作用.     

肾移植术后早期蛋白尿对移植肾功能影响的回顾分析

目的 探讨肾移植术后早期蛋白尿对移植肾功能的影响。方法 选取50例术后出现蛋白尿的肾移植患者,同时选取一般情况无差异的50例肾移植患者设立对照组。观察血肌酐变化情况,以及移植肾存活情况。结果 尿蛋白阳性组的血肌酐升高情况明显高于对照组,移植肾存活率明显少于对照组,数据比较具有统计学意义(P<0.05)。结论 肾移植术后早期蛋白尿是移植肾功能的重要影响因子。     

大鼠心脏移植中常山酮对树突状细胞的抑制作用及对血清IL-17的影响

目的：观察大鼠移植心脏中常山酮( halofuginone, HF)对树突状细胞( dendritic cell, DC)的抑制作用及对IL-17的影响。方法将30只Wistar大鼠和30只SD大鼠分别随机分为HF-DC组、DC组和对照组,供体为Wistar大鼠,受体为SD大鼠。各组在术前及术后1 d对应注射经HF处理过的DC溶液、经生理盐水处理过的DC溶液及生理盐水;观察大鼠心脏移植术后存活时间、移植心脏排斥反应病理学分级及受体大鼠血清中IL-17的含量。结果HF-DC组和对照组大鼠的存活时间均显著高于DC组(P<0．05),且HF-DC组大鼠的存活时间显著高于对照组(P<0．05)。术后第5天,HF-DC组大鼠未见明显的炎性细胞浸润和血管炎症出现,术后第7天可见少量散在的淋巴细胞浸润,分级为Ⅱ级。术后第5天,DC组大鼠移植心脏发生了广泛的炎性浸润,分级为ⅢB级;对照组有多灶性侵袭性淋巴细胞浸润或伴有心肌细胞损害,分级为ⅡA级。在各时间点,DC组和HF-DC组大鼠血清IL-17含量显著高于对照组(P<0．05);HF-DC组大鼠血清IL-17含量显著低于DC组(P<0．05)。结论经HF处理的DC诱导免疫排斥反应的能力下降,HF通过降低T细胞增殖能力抑制IL-17的表达。     

外源性胆红素对大鼠肾缺血再灌注损伤的作用

目的探索外源性胆红素在大鼠肾缺血再灌注过程中的作用及其机制。方法60只健康雄性Wistar大鼠随机分为假手术组、IRI模型组、胆红素(BR)处理组,观察各组动物在手术及静脉注射不同剂量胆红素干预后的肾功能改变,并测定肾组织超氧化物歧化酶(SOD)、丙二醛(MDA)含量和总抗氧化能力(T-AOC),同时观察肾组织形态学改变。结果与假手术组相比,IRI模型组SOD、T-AOC含量显著降低(P<0.05),MDA显著升高(P<0.05),肾功能损伤严重。与模型组比较,2.5、5BR处理组能不同程度地增强SOD、T-AOC的活力(P<0.05),显著降低MDA含量,减轻肾功能的损伤,但10BR处理组此作用不显著。结论①外源性胆红素可能通过增强组织T-AOC和SOD活性提高大鼠肾组织的抗氧化应激的能力,减轻肾组织的炎性损伤,从而减轻大鼠肾IRI,保护肾功能;②胆红素的作用与其剂量有关,一定剂量的胆红素可以减轻大鼠肾IRI,保护肾功能。     

大黄酸对大鼠慢性移植肾肾病的影响

目的 探讨大黄酸对大鼠慢性移植肾肾病(CAN)模型移植肾的治疗作用.方法 建立30只大鼠CAN模型,分成模型对照组(A组)16只,大黄酸治疗组(B组)14只.于移植后1、2、4个月分别收集大鼠的血和尿样,检测肾功能及尿蛋白含量.并于移植后2、4个月宰杀大鼠,观察A、B组大鼠移植肾组织病理学变化,并检测肾结缔组织生长因子(CTGF)的表达.结果 与A组比较,B组大鼠肾功能明显改善,肾组织病理检查示肾间质纤维化及间质炎症明显减轻,肾组织CTGF表达降低(P＜0.05).结论 大黄酸可通过降低CTGF表达改善CAN大鼠肾功能及肾脏慢性病变.     

泼尼松龙新型靶向脂质体制剂对嘌呤霉素氨基核苷肾病的疗效

目的 :观察肾小球向性泼尼松龙新型靶向脂质体制剂对嘌呤霉素氨基核苷性肾病的治疗作用。方法 :选用雄性Wistar大鼠 ,按照嘌呤霉素氨基核苷 ( puromycinaminoneucleoside ,PAN) 4 .0mg/ 10 0 g体重的剂量建立大鼠PAN模型 ,以泼尼松龙 ( prednisolone ,PRED) 2mg/ 10 0 g体重及泼尼松龙新型靶向脂质体制剂(liposome prednisolone ,Lipo PRED) 1.5mg/ 10 0 g体重的剂量进行治疗 ,观察尿蛋白的排出量、肾组织白细胞浸润等。结果 :泼尼松龙新型靶向脂质体制剂治疗组尿蛋白排泄量显著性降低 ,肾组织中白细胞浸润减少 ,其作用优于泼尼松龙治疗组结论 :泼尼松龙新型靶向脂质体制剂可显著性抑制PAN模型的尿蛋白排泄量和急性期肾间质白细胞浸润。     

致敏受者肾移植围手术期处理

目的探讨致敏受者肾移植围手术期处理方法。方法将84例致敏受者和同期108例非致敏受者分为两组,两组患者在年龄、性别、透析时间、HLA匹配、供肾冷热缺血时间等方面无明显差别。致敏组术前诱导治疗,术后预防性抗排斥及加大常规药物用量;非致敏组常规治疗。观察两组患者术后急性排斥(AR)、移植肾功能延迟恢复(DGF)发生情况和人/肾存活,感染及肝肾损害情况。结果术后两组患者在AR、DGF的发生率、人/肾存活上无显著性差异(P>0.05),但致敏受肾组术后感染及肝肾功损害发生率高(P<0.05)。结论致敏受者术前诱导用药、术后预防性抗排斥治疗、加大术后免疫抑制剂用量、对出现并发症的综合处理是致敏受者肾移植成功的关键。     

移植肾功能延迟恢复患者早期应用前列地尔临床观察

目的 评估前列地尔在肾移植术后移植肾功能延迟恢复(DGF)患者早期应用对促进移植肾功能恢复的效果.方法 回顾性分析肾移植术后发生移植肾功能延迟恢复应用前列地尔患者16例,与同期未使用前列地尔的DGF患者14例进行比较,比较两组间术后尿量、血肌酐(SCr)、移植肾血流阻力指数、急性排斥反应的发生率及1年人/肾生存率.结果 应用前列地尔的患者术后尿量明显大于对照组(P ＜0.05);SCr浓度、移植肾血流阻力指数均明显低于对照组(均P ＜0.05);两组急性排斥反应发生率差异无统计学意义(P＞0.05).结论 肾移植受者术后DGF患者早期应用前列地尔有利于促进移植肾功能的恢复.     

水药金耳环多糖对实验性2型糖尿病模型大鼠糖脂代谢、肾功能及氧化应激的影响

目的:研究水药金耳环多糖对实验性2型糖尿病模型大鼠糖脂代谢、肾功能及氧化应激的影响,为金耳环多糖的开发利用提供参考。方法:将60只SD大鼠随机分为正常对照组、模型对照组、阳性对照组(厄贝沙坦片,0.02 g/kg)和金耳环多糖低、中、高剂量组(以生药计分别为2、4、8 g/kg),每组10只。除正常对照组外,其余各组大鼠均ip链脲佐菌素75 mg/(kg·d)复制糖尿病大鼠模型。成模后,各给药组大鼠ig相应药物,正常对照组和模型对照组大鼠ig等体积5%羧甲基纤维素钠溶液,每天2次,连续42d。给药结束后,采用紫外分光光度计检测肝组织中肝糖原含量;采用全自动生化分析仪检测大鼠24 h尿量、24 h尿蛋白含量,血清中三酰甘油(TG)、胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、肌酐(Cr)、尿素氮(BUN)水平,以及肾组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、超氧化物歧化酶(ROS)、丙二醛(MDA)水平。结果:与正常对照组比较,模型对照组大鼠肝组织中肝糖原含量减少(P<0.05);24 h尿量、24 h尿蛋白量增加(P<0.05);血清中TG、TC、LDL-C水平升高(P<0.05),HDL-C水平降低(P<0.05);肾组织中SOD、CAT、GSH-Px水平降低(P<0.05),ROS、MDA水平升高(P<0.05)。与模型组比较,除肝组织中肝糖原含量、血清中HDL-C水平以及金耳环多糖低剂量组大鼠24 h尿量改善不显著外,其余各给药组大鼠上述指标均得到明显改善(P<0.05)。结论:金耳环多糖可调节实验性2型糖尿病模型大鼠的血脂代谢紊乱、改善大鼠肾功能和提高肾抗氧化能力。     

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.     

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.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.     

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.