防石合剂对实验性大鼠肾草酸钙结石形成的抑制作用

目的 研究防石合剂对大鼠肾草酸钙结石形成的抑制作用.方法 用1% 乙二醇和 2%氯化铵诱导大鼠肾草酸钙结石模型,灌胃给予不同剂量的防石合剂,实验结束后进行各组大鼠尿液、血清和肾组织中的多项生化指标[尿素氮(BUN)、肌酐(CR)、尿酸(UA)、无机磷(IP)、钙(Ca2+)]检测以及肾脏病理标本观察.结果 和成石模型组比较,防石合剂给药组能降低血清、肾组织和24 h尿中的UA、Ca2+含量,病理切片显示给药组草酸钙结晶明显减少.结论 防石合剂对于实验性大鼠肾草酸钙结石的形成有一定抑制作用.     

海金沙提取物对实验性大鼠肾草酸钙结石形成的影响

目的研究海金沙提取物对大鼠肾草酸钙结石形成的影响,并初步探讨其作用机制。方法采用1.25%乙二醇联合1%氯化铵1.5 mL灌胃诱导大鼠肾草酸钙结石模型,分别给予一定剂量的海金沙醇提物,并以结石通作为阳性对照。给药4周后,检测大鼠24 h尿量,尿钙（Ca）、镁（Mg）、磷（P）、尿酸（uric acid,UA）分泌量,血清尿素氮（blood urea nitrogen,BUN）、肌酐（creatinine,Cr）、肾组织超氧化物歧化酶（superoxide dismutase,SOD）和谷胱甘肽过氧化物酶（glutathione peroxidase,GSH Px）水平,肾组织草酸和钙含量。镜下观察肾组织切片草酸钙结晶及肾小管扩张情况。结果海金沙提取物能显著降低肾结石大鼠尿Ca、P、UA水平,提高尿Mg水平,并增加排尿量,能抑制肾组织草酸钙结晶的形成,降低肾组织草酸和钙含量。通过增加肾组织SOD和GSH Px活性,保护肾功能,降低BUN和Cr含量。给予海金沙提取物后,病理检测发现,肾组织内草酸钙明显减少,管腔未见明显扩张。结论海金沙提取物能有效防止大鼠肾草酸钙结石的形成。     

乙二醇和氯化铵灌胃建立大鼠肾草酸钙结石模型的探讨

目的 观察利用乙二醇和氯化铵灌胃建立大鼠肾草酸钙结石模型的优点,为今后研究抗肾草酸钙结石的药物提供可靠的模型.方法 以1%乙二醇＋2%氯化铵配成的造石液每天灌胃,连续28d,诱导大鼠草酸钙晶体形成,建立大鼠肾草酸钙结石模型,采用全自动生化分析仪测定大鼠尿生化、血生化,解剖取双肾,测定肾组织草酸、枸橼酸等指标.结果 模型组的尿生化、血生化、肾组织草酸均显著高于空白对照组（P＜0.001）.结论 以1%乙二醇＋2%氯化铵成功建立大鼠肾草酸钙结石模型,且效果显著.可应用此模型,对受试药物进行实验研究.     

尿石汤配方颗粒对大鼠草酸钙结石肾脏的保护作用

目的 探讨尿石汤配方颗粒对大鼠草酸钙结石肾脏的保护作用.方法 建立草酸钙大鼠肾结石模型,检测尿石汤不同剂量给药后大鼠血清中肌酐(CRE)、尿素氮(BUN)、Ca2+、Mg2+的变化以及肾脏组织病理变化和肾脏骨桥蛋白(OPN)的表达水平变化.结果 造模后大鼠血清CRE、BUN、Ca2+水平显著升高,Mg2+水平显著下降,...     

溶石颗粒剂对结石模型大鼠肾骨桥蛋白mRNA表达的影响

目的通过测定用药前后肾脏骨桥蛋白(osteopontin,OPN)mRNA含量的变化,阐明民间验方溶石颗粒剂治疗肾结石的作用机制。方法采用乙二醇、氯化胺法致大鼠肾结石,同时每天一次ig给予溶石颗粒剂5.8,11.6,17.4g.kg-1,实验全程21d。每7d做以下测定:血标本测定尿素氮(BUN)、肌酐(Cr)、钙和磷含量;尿标本以EDTA法测定钙含量,比色法测定草酸含量;肾组织HE染色,逆转录聚合酶链式反应(RT-PCR)技术检测大鼠肾骨桥蛋白mRNA的表达。结果模型组大鼠肾OPN mRNA的表达明显增加,与溶剂对照组相比(P<0.01),其中21d模型组OPN mRNA的表达最高,为溶剂对照组的4倍;溶石颗粒剂各剂量组均能明显抑制大鼠肾结石模型OPN mRNA的表达(P<0.05),且呈现明显的量效关系;溶石颗粒剂各剂量组能减轻大鼠肾脏草酸钙结晶程度,显著降低大鼠尿钙和草酸含量(P<0.01)。结论溶石颗粒剂可以抑制大鼠肾结石模型中OPN mRNA的表达。     

倒心盾翅藤提取物对大鼠肾草酸钙结石形成的抑制作用

目的:研究傣药倒心盾翅藤不同溶剂提取物对大鼠肾草酸钙结石形成的抑制作用。方法:取Wistar健康雄性大鼠90只,随机分为空白(等容蒸馏水)组,模型(等容蒸馏水)组,水提液高、低剂量[20、10 g(生药)/kg]组,50%醇提液高、低剂量[20、10 g(生药)/kg]组,95%醇提液高、低剂量组[20、10 g(生药)/kg]组,肾石通颗粒(5 g/kg)组,每组10只。除空白组外其余各组大鼠ig给予1%乙二醇+2%氯化铵以复制肾结石模型,复制模型给药5 h后各组大鼠ig给予相应药物,每天1次,持续4周。末次给药后检测各组大鼠血清肌酐(Cr)、尿素氮(BUN)、钙离子、磷含量,观察肾组织病理切片和草酸钙结晶情况,测定肾组织钙离子、镁离子含量。结果:与空白组比较,模型组大鼠血清Cr、BUN和肾组织中钙离子含量均增加、肾组织中镁离子含量减少,差异有统计学意义(P<0.01或P<0.05)。与模型组比较,水提液高剂量组和95%醇提液高剂量组大鼠血清Cr、BUN和肾组织中钙离子含量均明显减少,95%醇提液低剂量组和肾石通颗粒组大鼠血清Cr含量明显减少,水提液高剂量组大鼠肾组织中镁离子含量增加,差异有统计学意义(P<0.01或P<0.05);其余组间比较差异无统计学意义(P>0.05)。镜下观察,模型组大鼠肾皮质和髓质交界处有多数结晶沉积,且晶体主要存在于肾小管内壁,管腔扩张明显;水提液高剂量组和95%醇提液高剂量组大鼠肾组织中草酸钙晶体明显减少(P<0.05),结晶大多散在分布,肾小管管腔扩张程度明显减轻。结论:傣药倒心盾翅藤对肾有一定的保护作用,能抑制大鼠肾草酸钙晶体的形成,具有预防肾结石的功效,其中95%醇提取液效果最好。     

尿石汤配方颗粒改善肾草酸钙结石大鼠肾功能效果及其机制

目的:探讨尿石汤配方颗粒改善肾草酸钙结石(CaXO)大鼠肾功能效果及其机制.方法:建立草酸钙肾结石大鼠模型,检测大鼠造模前后体质量变化,肾脏质量、脏器系数变化,排尿量、尿液pH、尿液Ca2+、尿液结晶数量及类型,观察肾结石模型在大鼠机体上的宏观变化.采用He染色和Von-Kossa'S染色,观察尿石汤配方颗粒对肾结石模...     

模拟加速度对肾草酸钙结石模型大鼠氧化应激的影响

目的 探讨加速度暴露对肾草酸钙结石模型大鼠氧化应激的影响.方法 采用乙二醇饮水和氯化铵灌胃法诱导建立大鼠草酸钙结石模型,将40只8周龄Wistar健康雄性大鼠随机分为4组(每组10只):空白对照组(A组)、单纯诱石组(B组)、加速度并诱石组(C组)和单纯加速度组(D组).其中A组采用自来水饮水+生理盐水2 mL/d灌胃,B组采用1％乙二醇+2％氯化铵溶液2 mL/d灌胃,C组在B组的基础上给予加速度(+6G)暴露,D组单纯给予+6G暴露.各组大鼠在相同条件下饲养28 d后收集血液及双肾标本,左肾组织做石蜡切片HE染色,光镜下观察草酸钙结晶情况;右肾组织制成组织匀浆,测定血液和右肾组织匀浆中丙二醛(MDA)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、还原性谷胱甘肽(GSH)和谷胱甘肽过氧化物酶(GSH-Px)含量,以了解氧化应激情况.结果 单纯诱石组和加速度并诱石组肾组织草酸钙结晶评分较空白对照组和单纯加速度组均显著增高(P＜0.01),加速度并诱石组结晶评分亦较单纯诱石组增高(P＜0.01).单纯诱石组和加速度并诱石组与空白对照组比较,大鼠血、肾组织MDA浓度显著升高(P＜0.01),血、肾组织SOD、CAT、GSH-Px浓度显著降低(p＜0.01).结论 加速度暴露可能是泌尿系结石形成的危险因素之一,其机制可能与加速度暴露引起大鼠肾脏组织氧化应激损伤有关.     

表没食子儿茶素没食子酸酯对肾缺血再灌注损伤的保护作用

目的　探讨表没食子儿茶素没食子酸酯 (EGCG)对大鼠肾缺血再灌注损伤的影响。方法　通过结扎肾动脉 60min后再灌注 ,建立大鼠肾缺血再灌注损伤模型 ,给药组于结扎前后分别静脉给予 10mg·kg-1和 40mg·kg-1EGCG。化学法观察大鼠血清肌酐 (Scr)、尿素氮 (Bun)、丙二醛(MDA)含量 ,肾组织内MDA、活性氧 (ROS)含量和超氧化物歧化酶 (SOD)、Ca2 + ATP酶活性的变化 ,并观察肾组织的病理变化。结果　与模型对照组比较 ,40mg·kg-1的EGCG组可抑制由肾缺血再灌注引起的血清Bun、Scr、MDA含量和组织MDA、ROS含量的变化 ,增强SOD和Ca2 + ATP酶活性 ,减轻肾组织病理改变。结论　EGCG有保护大鼠肾缺血再灌注损伤的作用 ,其机制可能与抗自由基损伤和减少细胞内钙有关     

肾茶提取物防治大鼠慢性肾功能衰竭的实验研究

目的研究肾茶提取物对慢性肾功能衰竭(CRF)大鼠肾功能的影响。方法采用腺嘌呤致大鼠慢性肾功能衰竭动物模型,将SD大鼠随机分成5组:1组为正常组、2组为模型组、3组为肾茶提取物高剂量组、4组为肾茶提取物低剂量组、5组为尿毒清对照组。将2～5组实验动物腺嘌呤灌胃,18d后收集1组、2组24h尿液,并眼底采血测24h尿蛋白定量(UTP)、血清尿素氮(BUN)、血肌酐(Cr)、尿酸(UA)、血红蛋白(Hb)、尿微量白蛋白(UMA)及肿瘤坏死因子-α(TNF-α),验证造模成功。19d后3、4组给予肾茶提取物,5组给予尿毒清,1、2组给予生理盐水。49d后收集全部大鼠24h尿液,然后处死大鼠,采血及取肾、称肾重、体重。检测UTP、BUN、Cr、Hb、UMA、UA、TNF-α、Ca、P等指标。HE染色观察肾脏病理结构。结果实验前后肾茶高、低剂量组大鼠的肾功能指标与模型组相比较,均具有显著性,与对照组相比,效果亦显著;明显降低CRF大鼠体内TNF-α,明显抑制肾小球系膜细胞及基质增生,减轻肾小管-间质损害。结论肾茶提取物能够降低CRF大鼠UTP、Cr、BUN、UA、P、UMA、TNF-α水平、升高血中Hb、Ca等水平,从而有效改善CRF大鼠的肾功能及免疫功能。     

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.