高山红景天对实验性大鼠肝纤维化的抑制作用

目的：观察单方生药高山红号天对大鼠实验性肝纤维化的治疗效果,并探讨其作用机制。方法：用四氯化碳诱导大鼠肝纤维化模型,将实验动物随机分为正常对照组（A）、模型组（B）、秋水仙碱组（C）、红景天高剂量组（D）、红景天低剂量组（E）。除正常对照组外,其余4组均用四氯化碳诱发肝纤维化。各组于造模第8周末处死动物,分别用放射免疫法检测血清层粘连蛋白（LN）,Ⅲ型前肢原（PCⅢ）,透明质酸（HA）及Ⅳ型胶原（CⅣ）;检测ALT、AST、ALB、STP;作HE染色。结果：与模型组大鼠比较．经该中药治疗．大鼠血清中LN、PCⅢ、HA、CⅣ和ALT、AST水平明显降低（P〈0．01）;ALB水平显著升高（P〈0．01）;大鼠肝组织病理学检测改善显著。结论：单方生药高山红景天能有效地减轻肝纤维化大鼠的肝脏损伤和抑制肝纤维化的作用,其机制是通过抑制肝HSC增殖,降低ECM的分泌．促进胶原纤维降解而达到的。     

中药虎杖水煎液对CCL4诱导肝纤维化的保护作用

目的 观察虎杖水煎液对四氯化碳(CCL4)诱导肝纤维化的作用.方法 40只大鼠随机均分为正常对照(A)组、肝纤维化模型(B)组、虎杖水煎液低剂量3 g/kg(C)组和高剂量6 g/kg(D)组.10周后,检测血清ALT、AST以及肝纤维化血清标志物透明质酸(HA)与Ⅵ型胶原(C-Ⅳ)水平,测定肝组织匀浆中超氧化物歧化酶(SOD)活性与丙二醛(MDA)含量,并取肝组织做病理形态学检查.结果 与B组相比,C、D组血清ALT、AST、HA和C-Ⅳ水平降低,肝组织中MDA含量减少,而SOD活性增加(P＜0.05或P＜0.01),肝纤维化的组织学改变亦减轻.结论 虎杖水煎液对CCL4诱导的肝纤维化具有一定保护作用.     

四氯化碳诱导大鼠肝纤维化进展期和恢复期模型的建立

目的确定肝纤维化进展期和恢复期。方法采用50%四氯化碳(carbon tetrachloride,CCl4)皮下注射建立大鼠肝纤维化和自然恢复模型。检测血清中丙氨酸氨基转氨酶(alanine aminotransferase,ALT)、天冬氨酸氨基转移酶(as-partate aminotransferase,AST)、透明质酸(hyaluronic acid,HA)、层粘连蛋白(laminin,LN)、Ⅳ-C型胶原(collagenⅣ,Ⅳ-C)和Ⅲ型前胶原(procollagenⅢ,PCⅢ)含量及肝组织羟脯氨酸(hydroxyproline,Hyp)水平;HE染色和Masson胶原染色观察肝脏病理组织学改变。结果 CCl4注射8周,大鼠肝组织己出现慢性肝炎的病理变化,注射12～16周出现了典型的从肝纤维化—肝硬化的病理改变,同时大鼠血清中ALT、AST、HA、LN、Ⅳ-C和PCⅢ含量及肝组织Hyp水平逐渐上升。而随着恢复期的延长,血清中ALT、AST、HA、LN、Ⅳ-C和PCⅢ含量及肝组织Hyp水平逐渐下降。结论成功建立CCl4诱导的大鼠自愈性肝纤维化模型,并确定进展期和恢复期。     

齐墩果酸对四氯化碳所致大鼠肝纤维损伤的保护作用

目的：研究齐墩果酸对四氯化碳所致大鼠肝纤维损伤的保护作用.方法：取健康雄性SD大鼠,随机分成4组,A组正常对照组,B组模型对照组,C组齐墩果酸低剂量组（30 mg·kg-1OA溶液）,D组齐墩果酸高剂量组（60 mg·kg-1OA溶液）.除正常对照组灌胃给予花生油外,其余各组都灌胃给予40%四氯化碳花生油溶液,进行肝纤维化的造模.造模同时,正常对照组和模型对照组灌胃等容0.25%CMC-Na溶液,齐墩果酸组按分组灌胃齐墩果酸0.25%CMC-Na溶液.每日一次,连续5周.末次给药后禁食24 h,取大鼠血和肝脏,进行血清肝功能指标检测（ALT、AST、ALB、TP、HA、LN、C-Ⅳ、PC-Ⅲ）和组织病理学观察.结果：齐墩果酸各剂量治疗组大鼠血清中ALT和AST含量明显低于模型对照组（P＜0.01）,Alb含量则显著高于模型组（P＜0.01）,而TP值两组间差异无统计学意义（P＞0.05）;模型组大鼠肝纤维化指标HA、LN、C-Ⅳ、PC-Ⅲ水平明显高于空白组（P＜0.01）,而齐墩果酸各剂量治疗组大鼠血清中这四个参数水平则明显低于模型对照组（P＜0.01）.病理组织学检查表明,用药各组肝纤维病理变化明显减轻.结论：齐墩果酸对实验性肝纤维化大鼠肝细胞有保护作用及抗肝纤维化作用.     

还原型谷胱甘肽对慢性乙型肝炎患者血清肝纤维化指标和细胞因子的影响

目的:探讨还原型谷胱甘肽(GSH)对慢性乙型肝炎(CHB)患者血清肝纤维化指标及细胞因子的影响。方法:96例CHB患者随机分为对照组和治疗组(GSH组),治疗前后采用酶联免疫吸附试验(ELISA)双抗体夹心法和放射免疫分析法(RIA)测定血清转化生长因子-β1(TGF-β1)、肿瘤坏死因子-α(TNF-α)、玻璃酸(HA)、Ⅳ型胶原(C-Ⅳ)、层黏连蛋白(LN)以及丙氨酸氨基转移酶(ALT)、天门氡氨酸氨基转移酶(AST);另设30例健康体检者为健康组。结果:CHB患者血清ALT、AST、HA、C-Ⅳ、LN和TGF-β1、TNF-α水平较健康组显著升高(P<0.01)。采用GSH治疗8周后ALT、AST、HA、C-Ⅳ、LN和TGF-β1、TNF-α水平较治疗前及对照组均有显著降低(P<0.01)。结论:GSH能够降低CHB患者血清TGF-β1、TNF-α水平,具有抗炎及抗肝纤维化作用。     

软肝片抗肝纤维化作用的实验研究

目的探讨软肝片对四氯化碳中毒性肝纤维化的防治作用。方法用四氯化碳皮下注射造成大鼠肝纤维化模型 ,以联苯双酯作为阳性对照 ,测定血清丙氨酸氨基转移酶 (ALT)、天冬氨酸氨基转移酶 (AST)、玻璃酸(HA)、唾液酸及肝组织羟脯氨酸 (Hyp)、丙二醛 (MDA)、超氧化物歧化酶 (SOD)含量 ,以反映肝细胞损伤及肝纤维化程度。结果软肝片可明显降低肝纤维化大鼠血清ALT、AST、HA、唾液酸水平及肝组织Hyp和MDA水平 ,提高肝组织中SOD活力。结论软肝片具有一定的抗肝纤维化及抗脂质过氧化作用。     

复方熊去氧胆酸口服液对大鼠肝纤维化的防治作用

目的：观察复方熊去氧胆酸口服液（C-UDCA）对四氯化碳（CCl4）致大鼠肝纤维化的防治作用。方法：采用皮下注射40%CCl4-花生油溶液制备肝纤维化模型,检测经口给予C-UDCA后对大鼠肝功能指标、肝纤维化各项生化指标及肝组织病理形态学的影响。结果：C-UDCA各剂量组能显著减轻CCl4导致的肝脂肪变性、肝细胞损伤和纤维组织增生。与UDCA相比,C-UDCA-H能显著降低血清ALT、AST、HA、PCⅢ、CⅣ、LN及肝组织Hyp含量,显著升高血清Alb、A/G、肝组织GSH含量;C-UDCA-M亦能显著降低血清HA、LN 含量。结论：C-UDCA对CCl4致大鼠肝纤维化具有一定的防治作用,且C-UDCA-H、C-UDCA-M的作用优于UDCA。     

白饭树水提取物对肝纤维化大鼠血清学的影响

目的:研究白饭树水提取物对肝纤维化(HF)大鼠血清学的影响。方法:采用皮下注射(SC)四氯化碳(CCl4)油溶液造成HF模型,以秋水仙碱(colchicine)为阳性对照,观察白饭树水提取物对血清丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)、总蛋白(TP)、白蛋白(ALB)、球蛋白(GLO)、透明质酸(HA)、层粘连蛋白(LN)、Ⅲ型前胶原(PCⅢ)含量的影响。结果:白饭树水提取物能降低HF模型大鼠血清中ALT、AST含量,提升ALB含量,并且有效降低HF模型大鼠血清中HA、LN、PCⅢ的含量,高剂量组总体效果优于低剂量组。结论:白饭树水提取物对HF大鼠有保肝降酶、改善蛋白脂质、抗HF作用,值得深入研究。     

楤木皂苷抗四氯化碳致大鼠肝纤维化作用

目的观察楤木皂苷对四氯化碳致大鼠肝纤维化的保护作用。方法采用质量分数为40%的四氯化碳皮下注射诱导大鼠肝纤维化模型,MASSON染色观察肝组织病理学改变,采集血清检测肝功能及透明质酸(hyaluronic acid,HA)、层黏连蛋白(laminin,LN)、三型胶原蛋白(typesⅢ-collagen,COI-Ⅲ)含量的变化。结果楤木皂苷可抑制肝假小叶的形成和胶原纤维沉积,改善肝功能,降低血清中HA、LN、COI-Ⅲ的含量(P<0.05)。结论楤木皂苷有显著的抗肝纤维化的作用。     

黄芍颗粒抗大鼠肝纤维化作用研究

目的:研究黄芍颗粒对CCl4致大鼠肝纤维化的作用及其机制。方法:将60只大鼠随机分为6组,分别为空白组、模型组、大黄蟅虫丸组和黄芍颗粒高、中、低剂量组,除空白组外,其余各组采用CCl4复制大鼠肝纤维化模型,造模、给药结束后观察各组动物的肝组织病理学变化;并检测丙胺酸氨基转移酶(ALT)、天冬胺酸氨基转移酶(AST)的活性及白蛋白含量,检测血清玻璃酸(HA)、Ⅲ型前胶原(PCⅢ)、Ⅳ型胶原(ⅣC)及层粘连蛋白(LN)的含量。结果:与模型组比较,黄芍颗粒中、高剂量组以及大黄蟅虫丸组肝细胞结构显著改善,并可使大鼠血清ALT、AST的活性降低,白蛋白的含量升高,同时也可降低血清中HA、PCⅢ、ⅣC、LN的含量。结论:黄芍颗粒具有较好的抗模型大鼠肝纤维化的作用,值得进一步研究和开发。     

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.     

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.     

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.     

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.