虫草多糖对庆大霉素诱发的急性肾衰的预防作用

目的：探讨虫草多糖对庆大霉素诱发的急性肾衰的防治作用。方法：将实验动物分为阳性地塞米松磷酸钠组,虫草多糖高、中、低剂量组以及正常对照组、模型组;采用腹腔注射庆大霉素的方法复制大鼠急性肾衰（ARF）模型,造模过程中预防给药。观察大鼠的血液生化指标、肾功能、肾病理、肾指数等指标的变化。结果：预防给药后,阳性对照组和虫草多糖3个剂量组大鼠的血清尿素氮、肌酐的含量,以及尿蛋白和尿量降低,与模型组比较有显著差异（P〈0．01或P〈0．05）,高剂量和中剂量虫草多糖的作用优于阳性对照组。病理切片可见阳性对照组和虫草多糖高剂量组大鼠肾脏病理损伤明显好转,优于中、低剂量组。结论：虫草多糖能够预防大鼠庆大霉素诱发的急性肾衰,改善肾功能。     

健脾益气方对化疗性胃肠功能紊乱大鼠血清GAS、EGF水平的影响

目的探讨健脾益气方（JPYQ）防治大鼠化疗性胃肠功能紊乱的效果及作用机制。方法将48只大鼠按随机原则分为6组：空白对照组、化疗模型组、枸橼酸莫沙必利组（阳性药对照组）、化疗＋JPYQ高剂量组（高剂量组）、化疗＋JPYQ中剂量组（中剂量组）、化疗＋JPYQ低剂量组（低剂量组）,每组8只。采用环磷酰胺制备大鼠化疗模型,在实验的第1、3、5天,空白对照组给予生理盐水腹腔注射,其余5组给予环磷酰胺注射液腹腔注射,造模后每组给予相应的药物灌胃。检测各组大鼠血清胃泌素（GAS）与表皮生长因子（EGF）的水平。结果与空白对照组比较,化疗模型组大鼠血清EGF水平明显降低,GAS含量则明显升高,差异有统计学意义（P〈0．05）;与模型组比较,JPYQ高剂量组和阳性药对照组大鼠血清EGF含量显著升高（P〈0．05）,而中、低剂量组大鼠血清EGF含量差异无统计学意义（P〉0．05）;各给药组大鼠血清GAS水平与模型组及与空白对照组比较,差异无统计学意义（P〉0．05）。结论JPYQ防治化疗性胃肠功能紊乱的效果明显,其作用机制主要与影响血清EGF水平相关。     

海带多糖对应激小鼠肾组织抗氧化能力的影响

目的：研究海带多糖对实验性应激小鼠肾组织抗氧化能力的影响。方法：随机将40只小鼠分为正常组、对照组、低剂量给药组和高剂量给药组，每组10只。采用皮下注射肾上腺素加耐力游泳法复制应激小鼠模型，测定小鼠肾组织丙二醛（MDA）、一氧化氮（NO）含量和超氧化物歧化酶（SOD）、一氧化氮合成酶（NOS）活性。结果：与对照组比较，高低剂量组海带多糖均能降低MDA的含量（P〈0．05），增加NO的含量（P〈0．05），并能提高SOD和NOS的活性（P〈0．05）。结论：海带多糖能够提高肾组织抗氧化能力。     

α-硫辛酸对糖尿病小鼠血糖和氧化应激水平的影响

目的：探讨抗氧化剂α-硫辛酸对糖尿病小鼠的治疗作用。方法：25只小鼠随机分成正常对照组，糖尿病组．α-硫辛酸治疗低剂量组、中剂量组、高剂量组（分别15mg／kg、30mg／kg、60mg／kg腹腔注射共14d）。单次尾静脉注射四氧嘧啶诱发糖尿病小鼠模型．采用TBA法检测骨骼肌丙二醛（MDA）含量．葡萄氧化酶生物传感器测定尾静脉随机血糖。结果：糖尿病组血清、骨骼肌组织中MDA含量高于对照组及α-硫辛酸治疗各组（P〈0．01）：正常对照组与高剂量组、中剂量组血清MDA含量差异无统计学意义（P〉0．05），低剂量组高于正常对照组（P〈0．05）：低、中、高剂量3组小鼠骨骼肌组织中MDA含量随α-硫辛酸用量的增加而减少，高剂量组与正常对照组未见差异（P〉0．05）；高、中、低剂量组小鼠给药后血糖较给药前下降（P〈0．05或P〈0．01）。结论：α-硫辛酸通过清除氧自由基．抑制氧化应激．调整糖尿病小鼠的血糖．     

黄芪对大鼠肾脏缺血再灌注损伤的保护作用及其对细胞凋亡影响的研究

目的探讨黄芪对大鼠肾脏缺血再灌注损伤的保护作用及其对细胞凋亡影响的可能机制。方法采用无创伤动脉夹夹闭双侧肾动脉建立肾脏缺血再灌注损伤大鼠模型方法,将大鼠分为A组（缺血再灌注组）、B组（黄芪治疗组）和C组（正常对照组）,观察三组大鼠肾脏缺血再灌注损伤后血肌酐（cr）、尿素氮（BUN）、血浆超氧化物歧化酶（SOD）、血清丙二醛（MDA）、凋亡调控基因Bcl-2、Bax的表达及肾脏细胞凋亡指数（AI）的变化。结果黄芪治疗组SOD水平显著性高于缺血再灌注组（P〈0．05）,MDA、BUN和cr指标与缺血再灌注组比较,显著降低（P〈0．05）。正常对照组Bcl-2、Bax表达极少,缺血再灌注组Bcl-2、Bax表达均明显增强（Bcl-2：P〈0．05、Bax：P〈0．01）;黄芪治疗组较缺血再灌注组Bax表达明显下降（P〈0．05）,Bcl-2表达显著增强（P〈0．01）。黄芪治疗组凋亡指数显著低于缺血再灌注组（P〈0．05）。结论黄芪对肾脏缺血再灌注损伤具有保护作用,可能是通过影响凋亡调控基因Bcl-2、Bax的表达以降低肾脏细胞凋亡指数实现的。     

丹参酮ⅡA对术后肠黏连大鼠模型防治作用研究

目的研究丹参酮ⅡA对大鼠腹腔术后肠黏连的防治作用并测定大鼠血清中IL-1β、tPA、PAI含量的变化。方法构建大鼠肠黏连模型。70只大鼠随机分为假手术组、模型对照组、丹参酮ⅡA高、中、低剂量组、空白溶剂组、阳性对照药组,每组10只;地塞米松组腹腔注射地塞米松5mg／kg,假手术组及模型组给予等量生理盐水,空白溶剂组给予等量不含丹参酮ⅡA的溶剂。各组大鼠于术前1d、术后1、3、5、7d测定血清中IL-1β、tPA和PAI含量。结果高、中、低剂量组、阳性对照药组血清中IL-1β含量显著低于模型对照组、空白溶剂组与假手术组（P〈0．05）;血清中tPA含量显著高于模型对照组、空白溶剂组与假手术组（P〈0．05）,PAI含量显著低于模型组和空白溶剂组（P〈0．05）,与假手术组相比无显著性差异;高、中、低剂量组、阳性对照药组与模型对照组、空白溶剂组相比,肠黏连程度亦显著性降低（P〈0．001）。结论大鼠腹腔术后腹腔注射丹参酮ⅡA对肠黏连发生有防治作用,其防治作用可能与降低血清中IL-1β、PA1,升高血清中tPA有关。     

葛根异黄酮对运动训练大鼠血液生化指标及抗氧化的影响

[摘目的探讨葛根异黄酮对运动训练大鼠血液生化指标及抗氧化的影响。方法将健康雄性sD大鼠分为安静组、训练组、训练组＋不同剂量的葛根异黄酮组。通过游泳运动训练比较各组大鼠血清中血液生化指标（谷草转氨酶、谷丙转氨酶、血糖、全血血红蛋白）及抗氧化能力（超氧化物歧化酶的活性、丙二醛的含量）。结果100．0、200．0mg／kg的葛根异黄酮能显著升高运动训练大鼠的血清超氧化物歧化酶活性、血糖、全血血红蛋白含量（P〈0．05）,并显著降低丙二醛含量和谷草转氨酶活性（P〈0．05）。结论葛根异黄酮对运动训练大鼠具有明显的抗氧化作用,可明显改善血液生化指标。     

缬沙坦对2型糖尿病大鼠肾脏抗氧化应激作用机制的研究

目的：观察缬沙坦对实验性2型糖尿病大鼠肾脏病变的保护作用及其机制。方法：链脲佐菌素（STZ）诱导的糖尿病肾病大鼠模型随机分为对照组糖尿病组及治疗组（缬沙坦10mg·kg^-1·d^-1），治疗6周后，比较各组大鼠肾组织中丙二醛（MDA）含量和超氧化物歧化酶（SOD）活性，同时检测各组大鼠血糖、血肌酐、尿素氮、24h尿蛋白定量等。采用RT-PCR方法检测P22phoxmRNA表达。结果：治疗组较非治疗组明显改善尿白蛋白、尿素氮水平和肾脏肥大指数。肾脏MDA含量明显下降（P〈0．05），SOD活性显著上升（P〈0．05）。p22phox的mRNA相对含量在糖尿病组为（0．875±0．94），明显高于单切对照组（0．297±0．067）（P〈0．01），在治疗组为（0．484±0．064），较糖尿病组显著降低（P〈0．01），但仍高于对照组（P〈0．05）。结论：缬沙坦对2型糖尿病肾脏病变有一定的保护作用，其机制可能是通过抑制氧化应激反应，下调糖尿病大鼠P22phoxmRNA的表达对2型糖尿病模型大鼠肾脏产生保护作用。     

肾衰康2号抗肾纤维化及其尿毒素清除作用的研究

目的观察肾衰康2号对5／6肾切除大鼠所致慢性肾衰肠道清除尿毒素及其延缓肾脏纤维化的作用。方法将5／6肾切除大鼠分为肾衰康治疗组和对照组，并设假手术组为正常对照。普通喂养10周后检测各组的血清及粪便尿素氮、肌酐，并留取肾组织作病理，免疫组化法检测肾组织内纤维连接蛋白（FN）的表达水平。结果肾衰康2号治疗组血清尿素氮、肌酐较对照组下降（P〈0．05），粪便尿素氮、肌酐水平较对照组升高（P〈0．05），病理切片显示治疗组残余肾小球体积、直径与对照组相比明显减小（P〈0．05），肾小球系膜细胞、基质的增生程度亦明显减轻（P〈0．05），免疫组化显示，治疗组肾小球内FN的沉积比对照组减少（P〈0．05）。结论肾衰康2号有延缓肾纤维化，促进尿毒素排泄的作用。     

氧化应激在燃煤污染型氟中毒大鼠中的作用

目的研究氧化应激在燃煤污染型氟中毒大鼠中的作用。方法选择SD大鼠随机分2组（每组11只，雌雄各半），设对照组、染氟组。染氟组以氟中毒病区煤烘玉米为主要饲料，复制氟中毒动物模型，检查氟斑牙、尿氟浓度及血清、肝、肾、脑组织中丙二醛（MDA）含量、超氧化物歧化酶（SOD）及谷胱甘肽还原酶（GR）活性，及血清中反映肝、肾功能的指标。结果染氟组大鼠血清、肝、肾、脑组织中MDA含量升高，SOD和GR活性明显降低（P〈0．05或P〈0．01）。同时大鼠肝、肾功能已有一定的改变。结论氟中毒大鼠机体内氧化系统与抗氧化系统失衡，氧化应激引起的氧化损伤作用在氟致大鼠肝、肾毒性中起着重要的作用。     

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.     

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.