慢性肾功能衰竭的非透析疗法

慢性肾功能不全（CRF）是各种慢性肾脏疾病持续不愈并呈进行性发展的最后结局。从肾脏受损发展到慢性肾功能不全的过程中，肾脏形态学的主要表现为肾小球内细胞外基质大量堆积、广泛的肾小球硬化、肾小球周围和间质的纤维化及间质中不同程度的单核一巨噬细胞及淋巴细胞的浸润和慢性炎症、肾小管萎缩等。     

Bax/Bcl-2在淋巴回流障碍大鼠肾组织中的表达

目的：探讨阻断肾淋巴循环对大鼠肾脏细胞Bax、Bcl-2表达的影响及与大鼠肾脏功能的关系。方法选取雄性Wistar大鼠48只,将其随机分为模型组和对照组,各24只。各组大鼠分别于术后第1、7、14、28天各处死6只,留取肾组织标本提取组织蛋白、mRNA和制作石蜡切片。运用Real-time PCR、Western blot和免疫组织化学检测Bax、Bcl-2在肾组织中的表达,并测定24 h尿蛋白和血肌酐水平。结果模型组大鼠的肾功能逐渐减退,随着术后时间的延长,肾功能损害逐渐加重。模型组大鼠的Bax表达明显强于对照组,免疫组织化学显示,Bax的表达主要在肾小管及肾间质,远端小管的表达尤其明显,相反,模型组大鼠的Bcl-2的表达明显减弱。结论阻断肾淋巴循环可导致大鼠肾功能及肾小管间质的损害,并随时间延长而加重,肾细胞凋亡与此密切相关,其中Bax/Bcl-2途径发挥了积极作用。     

肾脏纤维化治疗的研究进展

肾脏纤维化是各种肾脏疾病进展到慢性肾衰竭的共同途径和主要病理基础,包括。肾小球硬化、肾小管萎缩、细胞外基质异常增多和过度沉积及肾间质纤维化的病理过程。近年来的研究发现,一些细胞途径,包括系膜细胞和成纤维细胞活化,肾小管上皮-间充质细胞转分化（EMT）,单核、淋巴细胞浸润,细胞凋亡等被认为参与了肾脏纤维化的发生发展过程。     

伊贝沙坦抑制大鼠单侧输尿管梗阻模型肾间质纤维化

目的探讨伊贝沙坦对单侧输尿管梗阻大鼠模型肾间质纤维化的影响。方法制作大鼠肾间质纤维化模型,随机分为假手术组(A组)、模型组(B组)和伊贝沙坦治疗组(C组),术后第7、14天分别处死各组中6只大鼠,用免疫组化方法测定肾间质中血小板衍生生长因子(PDGF-BB)、α-平滑肌肌动蛋白(α-SMA)表达和CD68(巨噬细胞标记物)阳性细胞浸润,观察肾脏病理变化。结果与B组相比,C组肾间质纤维化明显减轻,肾间质中α-SMA、PDGF-BB表达明显减少(P<0.05),CD68阳性细胞浸润无明显减少(P>0.05)。结论伊贝沙坦可通过下调肾间质PDGF-BB表达减轻肾间质纤维化。     

来氟米特对肾大部切除大鼠肾皮质α-平滑肌肌动蛋白的影响

目的探讨来氟米特对肾大部切除大鼠肾脏功能的影响。方法将大鼠随机分为假手术组和手术组,术后3d再将手术组大鼠随机分为来氟米特组和模型组。8周后测尿蛋白和血肌酐;取肾组织做病理检查;用免疫组织化学检查肌成纤维细胞标志抗原———α-平滑肌肌动蛋白(α-SMA)。结果模型组大鼠肾脏出现肾小球硬化和肾间质纤维化;和假手术组相比α-SMA表达明显升高;来氟米特组肾脏纤维化明显减轻,α-SMA表达比模型组明显下降。结论来氟米特可抑制肌成纤维细胞增生和浸润,减轻肾脏纤维化从而保护肾功能。     

急性间质性肾炎21例的临床与病理

急性间质性肾炎（AIN）是由多种病因引起的突然发生的以肾间质炎症水肿、炎症细胞浸润、肾小管呈不同程度退行性变伴肾功能不全的临床综合征,表现为急性肾功能衰竭（ARF）、肾间质水肿和炎性细胞浸润,肾小球和肾血管多正常或轻度病变。为了提高对AIN的诊治水平,现对本院近年来肾活检确诊的21例急性间质性肾炎患者的病因、临床表现、肾脏病理改变进行分析报告如下。     

肾安胶囊对5/6肾大部切除大鼠肾脏的保护作用

目的探讨肾安胶囊对肾大部切除大鼠肾脏功能的影响。方法将大鼠随机分为假手术组和手术组,术后3天再将手术组大鼠随机分为肾安胶囊组和Nx组。8周后测尿蛋白和血肌酐;取肾组织做病理检查;用免疫组织化学检查肌成纤维细胞标志抗原(α-平滑肌肌动蛋白α-SMA)。结果Nx组大鼠肾脏出现肾小球硬化和肾间质纤维化;和Sham组相比α-SMA表达明显升高;肾安胶囊组肾脏纤维化明显减轻(P<0.05),α-SMA表达比Nx组明显下降。结论肾安胶囊可抑制肌成纤维细胞增殖和浸润,减轻肾脏纤维化从而保护肾功能。     

DADLE对急性全脑缺血再灌注大鼠心肺肾损伤保护作用的研究

目的通过二血管阻断加低血压法建立大鼠急性全脑缺血再灌注模型,探讨在脑缺血再灌注情况下DADLE对于心肺肾的保护作用。方法将50只SD大鼠随机分为5组:假手术组(Sham)、模型组(I/R)、DADLE处理组(根据不同剂量可分为2 mg/kg[A]、3 mg/kg[B]、5 mg/kg[C])。采用改良的二血管阻断加低血压法建立全脑缺血再灌注模型。手术后立即取心肺肾,常规HE染色观察其形态学改变。结果 I/R组心肌细胞间有出血现象,心肌细胞有轻度萎缩,少量炎性细胞浸润;肺脏表现为肺泡间隔增宽,毛细血管扩张充血,肺胞腔内及血管周围中性粒细胞浸润,气管壁部分上皮脱落,肺胞腔及气管腔均有浆液渗出,肺大泡形成越来越多;肾脏表现为肾小球与肾间质有少量充血,肾小球毛细血管未见明显扩张。DADLE处理组心肌出血减少并逐渐被吸收(P<0.05);肺脏充血减轻,中性粒细胞浸润有所减少(P<0.05);肾脏可见肾小球无明显充血肿胀,间质亦无明显瘀血。DADLE处理组组间差异无统计学意义(P>0.05)。结论改良的二血管阻断加低血压法建立大鼠全脑缺血再灌注模型对心肺均有不同程度的损伤,但对肾脏影响较小,并且DADLE对全脑缺血再灌注大鼠心肺损伤有一定的保护作用,但与剂量无明显相关。     

姜黄素对肾毒血清肾炎大鼠肾组织超微结构及细胞增殖的影响

目的　探讨姜黄素对实验性肾炎组织病理以及增殖细胞核抗原 (PCNA)的影响。方法雄性SD大鼠 72只随机分成 3组 ,正常对照组 :注射生理盐水 ;模型组 :尾静脉注射兔抗鼠肾毒血清0 5ml/d ,连用 2d ,腹腔注射二甲亚砜 0 5ml·kg 1·d 1;姜黄素组 :尾静脉注射兔抗鼠肾毒血清 0 5ml/d ,连用d ,同时腹腔注射姜黄素 5 0mg·kg 1·d 1。分别于第 3、7、14、2 8d处死大鼠 ,取肾组织分送常规病理、免疫组化及透射电子显微镜检查。结果　姜黄素组肾小球细胞数明显少于模型组 ;间质炎细胞浸润亦较模型组明显减少 ;14d后小管间质损伤指数也低于模型组。电镜显示 ,姜黄素可明显阻止肾小球上皮细胞足突融合以及基膜增厚 ,抑制系膜细胞、内皮细胞增殖 ,减少肾组织内炎细胞浸润 ,尤其是对间质单核样细胞浸润的减少作用更为明显 ;免疫组化也证实姜黄素应用 7d后即可降低PCNA表达。结论　姜黄素能明显改善肾炎时肾小球超微结构的改变 ,并抑制系膜细胞、内皮细胞增殖 ,减轻小管间质损伤及肾组织内炎性细胞的浸润。     

黄芪当归合剂对慢性肾病鼠肾脏细胞表型及MAPK信号转导通路的影响

目的　在慢性嘌呤霉素肾病 (PAN)大鼠模型中观察黄芪当归合剂 (A&A)对肾脏固有细胞表型及MAPK信号通路各亚类激酶 (ERK、JNK和p38)表达与活性的影响 ,初步探讨A&A治疗作用的细胞生物学机制。方法　肾组织标本来源于对照组、PAN组、A&A组和ACEI组大鼠。采用常规病理染色和免疫组化技术 ,观察各组肾组织不同部位的病理改变、细胞数量、细胞外基质积聚程度、不同部位α SMA表达变化及肾组织内MAPK表达及活化情况。结果　PAN大鼠肾小球内的α SMA表达量与肾小球系膜细胞增殖、细胞外基质的积聚程度密切相关 ;肾小管间质区的α SMA表达量与肾间质浸润细胞数相关 ,同时伴有肾小管上皮变性、萎缩和扩张。A&A治疗可使PAN大鼠上述部位的α SMA表达和病理变化明显减轻。在本实验条件下 ,PAN组与对照组肾组织内JNK、ERK、p38的蛋白表达量及表达部位无差别 ,肾组织内ERK、p38亦未被激活 ;PAN大鼠肾小球、肾小管及肾间质细胞的JNK均明显活化 ,A&A可明显抑制上述部位的JNK活化。结论　黄芪当归合剂可显著减轻嘌呤霉素肾病的肾脏损伤 ,它对肾脏固有细胞 (尤其是系膜细胞 )表型转化的抑制作用可能是其作用的主要环节之一 ,该作用可能与其下调JNK信号通路活化有关     

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.

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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.     

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.