汉防己甲素对硫唑嘌呤致大鼠肝损伤的保护作用

目的 研究汉防己甲素（Tet)对硫唑嘌呤（Aza)致大鼠肝损伤的保护作用。方法 大鼠分为三组：①对照组；②Aza组；③Aza Tet组。给药量分别为Aza 25mg/kg·d。Tet 30mg/kg·d,测定用药1wk和2wk时大鼠血清谷丙转氨酶（ALT）、碱性磷酸酶（AKP）、总蛋白（TP）和白蛋白（Alb）等肝功能指标以及血清中丙二醛（MDA）、超氧化物歧化酶（SOD）和全血谷胱甘肽含量（GSH），并作病理观察。结果 用药1wk及2wk后，Aza组大鼠血清ALT、AKP、MDA含量均显升高，TP、Alb、SOD、GSH含量均显降低；合用Tet组则上述变化不明显，与对照组比较无显性差异。病理学检查发现合用Tet组病理改变较轻微。结论 Tex对Aza致大鼠肝损伤有保护作用，推测此作用与其抗脂质过氧化物、增加内源性解毒物质有关。     

番茄红素对异烟肼和利福平致大鼠肝损伤的保护作用

目的观察番茄红素对异烟肼(INH)和利福平(RFP)合用致大鼠肝损伤的保护作用并探讨其作用机制。方法给予异烟肼和利福平(各75mg.kg-1)用药4wk制备肝损伤动物模型,分别给予低、中、高剂量番茄红素(10、20、30mg.kg-1),4wk后测定大鼠血清中AST和ALT含量、肝脏指数,以及肝组织匀浆中的MDA、GSH的含量和SOD的活性,并作肝组织病理学检测。结果番茄红素能降低肝脏指数(P<0.05)、降低大鼠血清AST和ALT的含量、降低大鼠肝匀浆中的MDA、增加肝匀浆中GSH、升高SOD(P<0.05或P<0.01),减轻肝组织变性、坏死程度,缓解肝组织的病理改变。结论番茄红素对INH和RFP合用所致的大鼠肝损伤具有保护作用,其作用机制可能与番茄红素的抗脂质过氧化作用有关。     

硒对硫唑嘌呤引起小鼠肝损伤的保护作用

小鼠灌胃给予Aza 10mg·kg~(-1)·d~(-1)及合用Selmg·kg~(-1)·d~(-1),连续用药1wk和2wk时观察血浆ALT,全血GSH,肝组织匀浆中MDA含量和GSH-Px活力变化.结果1wk和2wk时Aza组小鼠ALT、MDA均明显高于正常对照组,GSH、GSH-Px则明显低于对照组;加Se组则与之相反,ALT、MDA均降到正常,GSH、GSH-Px也明显升高,接近正常.光镜下见Aza组肝细胞明显变性坏死,加Se组则损害很轻微,接近正常.表明Se对Aza的肝损伤有保护作用.     

虫草菌丝提取物对大鼠脂肪性肝炎与肝纤维化的影响

目的探讨虫草菌丝提取物对大鼠脂肪性肝炎与盱纤维化的作用。方法Wistar雄性大鼠,随机分为3 wk和6 wk的正常组、模型组和虫草菌丝组。造模后3 wk和6 wk分别观察肝组织脂肪变性、炎症与胶原沉积;分析血清ALT、AST水平与TBil、Alb、TG、TC含量;肝组织TG、MDA、GSH含量与SOD、γ-GT活性、羟脯氯酸(Hyp)含量及肝组织α-SMA表达。结果3 wk、6 wk模型大鼠血清ALT、AST、γ-GT活性与TBil含量均升高(P<0.05),Alb、TG含量下降(P<0.01),肝组织Hyp、TG、MDA含量明显增加(P<0.01),α-SMA表达增加。3 wk虫草菌丝组改善模型大鼠肝组织脂肪变性与炎症;降低血清TBil含量,提高血清Alb含量;降低肝组织TG、MDA含量(P<0.01),提高肝组织GSH含量与SOD活性(P<0.05)。6 wk虫草菌丝组减轻模型大鼠肝纤维化;降低血清ALT、AST水平(P<0.05);降低肝组织TG、MDA含量和γ-GT活性(P<0.05),提高SOD活性。虫草菌丝3 wk和6 wk组均明显减少α-SMA表达(P<0.05),且6 wk作用较3 wk更为明显。结论虫草菌丝提取物显著改善大鼠脂肪性肝炎、抑制脂肪性肝纤维化,其作用机制与抗肝脂质过氧化、抑制肝星状细胞活化有关。     

槲皮黄酮对酒精性肝损伤大鼠高同型半胱氨酸血症及氧化应激的作用

目的探讨槲皮黄酮对酒精性肝损伤大鼠高同型半胱氨酸血症(HHcy)及氧化应激的作用。方法将30只大鼠随机分为正常对照组、模型组、低剂量槲皮黄酮治疗组、中剂量槲皮黄酮治疗组、高剂量槲皮黄酮治疗组,每组6只。用酒精+0.5 mL鱼油灌胃诱导酒精性肝损伤模型,造模3周后,治疗组大鼠分别给予4、2、1 g/kg槲皮黄酮灌胃,7周后麻醉处死大鼠,测定血浆总同型半胱氨酸(tHcy)浓度及血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、白蛋白(Alb)、白/球蛋白比值(A/G)、肝匀浆丙二醛(MDA)、超氧化物歧化酶(SOD)和还原型谷胱甘肽(GSH)表达水平,并对肝脏病理组织进行检测。结果模型组大鼠tHcy、ALT、AST、MDA的表达水平高于正常对照组,而SOD、GSH含量低于对照组,差异均有统计学意义(P<0.05);治疗后,槲皮黄酮治疗组大鼠tHcy、ALT、AST、MDA均低于模型组(P<0.05),而SOD、GSH含量高于模型组(P<0.05),并呈浓度依赖性。组织病理学检测显示,模型大鼠出现肝细胞脂肪变性、点状坏死,伴随炎性细胞浸润,槲皮黄酮治疗后,点状坏死和炎性细胞浸润消失。结论槲皮黄酮可改善酒精性肝损伤,其作用机制可能与降低高同型半胱氨酸水平及氧化应激有关。     

灯盏乙素对异烟肼和利福平合用致小鼠肝损伤的保护作用

目的:观察灯盏乙素对异烟肼(INH)和利福平(RFP)合用致小鼠肝损伤的保护作用.方法:小鼠每天同时灌胃RFP和INH各100 mg·kg-1,2 h后灌胃灯盏乙素50,100,200 mg·kg-1,qd,连续给药10 d,末次给药16 h后,取血和各器官组织,测定肝、脾和胸腺指数、血清丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)的活性、肝匀浆中超氧化物歧化酶(SOD)、脂质过氧化物丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-PX)以及一氧化氮(NO)的含量.结果:灯盏乙素能显著降低RFP和INH合用致肝损伤小鼠的肝指数、血清ALT和AST活性、肝匀浆中的MDA和NO含量,并能显著提高肝匀浆中的SOD和GSH-Px活性.结论:灯盏乙素对RFP和INH合用致小鼠肝损伤具有明显的保护作用,可能与其抗脂质过氧化及调节体内NO水平有关.     

彩虹明樱蛤多糖对小鼠急性化学性肝损伤的保护作用

目的研究彩虹明樱蛤多糖(MIP)对CCl4致小鼠急性化学性肝损伤的保护作用。方法 MIP对小鼠连续腹腔注射7 d,以0.1%CCl4橄榄油溶液经腹腔注射,建立小鼠急性化学性肝损伤模型,测定给药后模型小鼠肝指数,检测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)活性,测定肝组织匀浆中丙二醛(MDA)含量和超氧化物歧化酶(SOD)、谷胱甘肽(GSH)的活性及观察肝脏病理学变化。结果 MIP中、高剂量组(80,160 mg/kg)均能显著降低CCl4致急性肝损伤小鼠血清ALT、AST活性(P<0.01),降低肝脏MDA含量(P<0.01),增强SOD和GSH活力(P<0.01或0.05),并能明显改善肝组织的病理学损伤,但对肝指数无明显影响。结论 MIP对CCl4致小鼠急性化学性肝损伤有保护作用。     

扛板归对CCl_4致大鼠肝损伤的保护作用研究

目的:研究扛板归醇提物对CCl4致大鼠肝损伤的保护作用。方法:复制CCl4致大鼠化学性肝损伤模型,测定血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、超氧化物歧化酶(SOD)活性及丙二醛(MDA)的含量。结果:扛板归能不同程度降低肝损伤大鼠血清中ALT、AST活性,升高SOD活性,降低MDA含量;并能减轻肝组织变形、坏死等病理改变。结论:扛板归具有一定的保肝作用,其机制可能与抗脂质过氧化作用有关。     

雷竹笋汁对四氯化碳致大鼠急性肝损伤的防治作用

目的 :探讨雷竹笋汁对肝损伤的防治作用。方法 :分别对健康大鼠和预先用四氯化碳制作的肝损伤模型大鼠用不同剂量的雷竹笋汁 (Ⅰ组 2 0 5.70mg·kg 1,Ⅱ组 43 6.40mg·kg 1)灌胃 7d ,然后将健康大鼠亦用四氯化碳制备肝损伤模型 ,并另取健康大鼠作空白对照 ,测定各组大鼠血清丙氨酸氨基转移酶 (ALT)、天冬氨酸氨基转移酶 (AST)和超氧化物歧化酶 (SOD)活性及丙二醛 (MDA)含量。结果 :雷竹笋汁显著降低实验大鼠血清ALT和AST的活性 ,升高SOD活性及降低MDA含量 ,且呈量效关系。结论 :雷竹笋汁对四氯化碳致大鼠急性肝损伤有明显的防治作用 ,其机制可能与抗氧化反应有关     

连翘苷元对四氯化碳大鼠急性肝损伤的保护作用

目的探讨连翘苷元对四氯化碳(CCl4)所致急性肝损伤的保护作用。方法用CCl4诱导化学性急性肝损伤模型,测定血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBIL)水平;肝脏组织切片,苏木精-伊红(HE)染色,光镜观察病理学改变;用试剂盒测定肝组织中SOD、GSH-Px和GSH的活性及脂质过氧化产物MDA含量。ELISA法检测血清中TNF-α、IL-8含量。结果在CCl4诱导的大鼠急性肝损伤模型中,连翘苷元(0.05、0.15、0.5mg·kg-1,sc)明显降低血清ALT、AST和TBIL水平;明显改善肝脏病理组织状况;连翘苷元(0.05、0.15、0.5 mg·kg-1,sc)明显降低CCl4诱导的急性肝损伤大鼠的肝组织匀浆中MDA的含量,明显增加SOD、GSH-Px和GSH的活性。连翘苷元(0.15、0.5 mg·kg-1,sc)明显降低TNF-α、IL-8含量。结论连翘苷元对CCl4诱导大鼠急性肝损伤具有保护作用,该作用与其增加肝组织中抗氧化酶的活性、降低脂质过氧化水平、降低TNF-α、IL-8等促炎因子水平有关。     

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.