复方小柴胡汤对肝纤维化大鼠基质金属蛋白酶抑制剂-1的影响

目的:观察复方小柴胡汤对肝纤维化大鼠基质金属蛋白酶抑制剂-1(TIMP-1)的影响及其抗纤维化作用,探讨其临床应用的理论依据。方法:以SD大鼠为实验材料,运用四氯化碳诱导大鼠肝硬化模型,试验第13周处死动物进行血清学及肝组织学检查,观察治疗前后TIMP-1变化;同时观察血清肝纤维化指标(HA、LN、PCⅢ)及肝组织羟脯氨酸(HYP)含量。结果:复方小柴胡汤组大鼠血清TIMP-1、肝纤维化指标(HA、LN、PCⅢ)及肝组织HYP含量明显低于0.9%氯化钠溶液组(P<0.01),而与正常组相近(P>0.05);复方小柴胡汤组与秋水仙碱组比较,TIMP-1、HA、LN、PCⅢ显著降低(P<0.05、P<0.01),HYP含量有统计学差异(P<0.01)。结论:复方小柴胡汤能显著降低肝纤维化大鼠TIMP-1、HA、LN、PCⅢ的水平,从而有效减轻和抑制肝纤维化进程。     

脱氧核苷酸钠注射液联合甘草酸二铵胶囊对人血白蛋白所致免疫性肝纤维化大鼠的影响

目的观察脱氧核苷酸钠注射液(DNA注射液)联合甘草酸二铵胶囊(甘利欣)对人血白蛋白(HSA)诱导的大鼠肝纤维化形成的影响。方法采用HSA诱导大鼠肝纤维化并随机分为DNA注射液联合甘利欣组、甘利欣组、秋水仙碱组、模型组和对照组5组。观察血清丙氨酸氨基转移酶(ALT)和天门冬氨酸氨基转移酶(AST)活性、总蛋白(TP)、白蛋白(Alb)含量、白蛋白和球蛋白比值(A/G),放射免疫分析法测定层连蛋白(LN)、透明质酸(HA)、fnⅣ型胶原(Ⅳ-C)的含量,化学法测定肝脏羟脯氨酸(HyP)的含量。光镜观察肝细胞结构和肝纤维化程度。结果 DNA注射液联合甘利欣能明显降低HSA诱导的肝纤维化大鼠ALT,AST活性(P<0.05,P<0.01),提高Alb、TP含量及A/G比值(P<0.05,P<0.01),降低血清LN、HA、Ⅳ-C含量(P<0.05,P<0.01)。DNA注射液联合甘利欣能使大鼠胶原纤维沉积明显减轻,假小叶结构显著减少。结论 DNA注射液联合甘利欣方可抑制HSA诱导的大鼠肝纤维化形成和发展,改善肝功能。     

吲哚-3-原醇对猪血清诱导大鼠肝纤维化的治疗作用

研究吲哚-3-原醇(I3C)对猪血清诱导大鼠肝纤维化的治疗作用及其机制。腹腔注射猪血清制备大鼠肝纤维化模型,造模成功后用I3C治疗17天。采用HE和Masson三色染色法分别观察肝脏病理学和胶原含量改变;生化比色法测定肝组织羟脯氨酸(Hyp)含量;免疫组织化学法观察肝脏中α-平滑肌肌动蛋白(α-SMA)的表达。进一步培养大鼠肝星状细胞株HSC-T6,用13C处理24 h后,FITC-Annexin V/PI双重染色法检测细胞凋亡;实时荧光定量PCR法检测细胞凋亡相关蛋白Bax和Bcl-2的mRNA表达。结果显示,与模型对照组比较,各I3C治疗组的肝组织Hyp含量不同程度降低,肝细胞损伤减轻,胶原纤维沉积减少(P<0.01),α-SMA表达降低(P<0.01)。细胞实验显示,I3C可明显增加HSC-T6细胞凋亡率,升高Bax/Bcl-2的mRNA表达(P<0.05)。以上结果说明,I3C对猪血清诱导大鼠肝纤维化有一定治疗作用,可能与其诱导活化HSC凋亡继而促进基质胶原降解有关。     

谷胱甘肽复方注射液治疗猪血清致大鼠肝纤维化的药效研究

 目的：研究谷胱甘肽复方注射液（CGII）治疗猪血清致大鼠免疫性肝纤维化的药效作用。方法：建立猪血清诱导免疫性肝纤维化模型,全自动生化仪检测血清中丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、白蛋白（A）及球蛋白（G）水平;酶免法检测血清中透明质酸（HA）的含量;称取肝脏湿重,计算肝脏指数;消化法检测肝组织羟脯氨酸（Hyp）含量;苏木素-伊红（HE）及Masson染色处理肝脏组织切片;光镜观察病理学改变。结果：在猪血清诱导的大鼠肝纤维化模型中,所有剂量水平的CGII（2.7,5.4,10.8 mg?kg-1,im）能显著降低大鼠血清ALT,AST,A/G值和HA水平;中、高剂量CGII（5.4,10.8 mg?kg-1,im）能显著降低大鼠肝组织Hyp含量,明显改善肝脏病理组织状况;高剂量CGII（10.8 mg?kg-1,im）能显著降低大鼠肝脏指数。结论：CGII对猪血清致大鼠肝纤维化有治疗作用。     

抗肝纤饮对实验性肝纤维化大鼠TGF-β1的影响

目的:观察抗肝纤饮对实验性肝纤维化大鼠的防治作用,并探讨其作用机制。方法:48只雄性 SD 大鼠被随机分为正常组、模型组、抗肝纤饮及秋水仙碱组,采用 ih40% CCl_4花生油溶液诱导大鼠肝纤维化模型。造模同时,各组分别灌胃给予抗肝纤饮、秋水仙碱及0.9%氯化钠溶液治疗。于11周末检测大鼠血清透明质酸(HA)、Ⅳ型胶原(CⅣ)、层粘蛋白(LN)、血清转化生长因子β_1(TGF-β_1)的水平,检测肝组织 TGF-β_1阳性面积及 TGF-β_1 mRNA 的表达水平。结果:与模型组比较,抗肝纤饮组血清 HA、CⅣ及 TGF-β_1水平显著下降(P<0.01或 P<0.05),肝组织内 TGF-β_1阳性面积及 TGF-β_1 mRNA 的含量明显下降(P<0.01或 P<0.05)。结论:抗肝纤饮对实验性肝纤维化大鼠有较好的防治作用,其作用机制与降低血清及肝组织内 TGF-β_1有关。     

肝康乐抗免疫损伤性肝纤维化的实验研究

目的探讨肝康乐抗免疫损伤性肝纤维化的作用及其作用机制。方法腹腔注射无菌猪血清制造免疫损伤性肝纤维化模型,以复方鳖甲软肝片作为对照,经肝康乐药物防治后,检测血清酶学、肝纤维化指标、肝组织羟脯氨酸含量、脾指数、胸腺指数、血清循环免疫复合物。结果与模型组比较,肝康乐治疗组大鼠血清ALT、AST、HA、Ⅳ型胶原含量及肝脏Hyp含量均显著降低;同时肝康乐治疗组大鼠脾指数明显降低,胸腺指数明显升高,血清循环免疫复合物明显减少。结论肝康乐对免疫损伤性肝纤维化有一定的防治作用,其机理可能与其保护肝细胞,影响胶原代谢,调节免疫有关。     

连翘苷元对大鼠免疫性肝纤维化的影响

目的 研究连翘苷元对牛血清白蛋白诱导的大鼠免疫性肝纤维化的影响。方法 动物按照体质量随机分为对照组、模型组、连翘苷元低、中、高剂量(0.1、0.3、1.0 mg/kg)组和水飞蓟宾葡甲胺组(50 mg/kg), 利用牛血清白蛋白建立大鼠免疫性肝纤维化模型。全自动生化分析仪检测血清蛋白水平;Elisa试剂盒检测血清透明质酸(HA)、层黏蛋白(LN)、Ⅳ型胶原(Ⅳ-C)和Ⅲ型前胶原(PCⅢ)水平;分光光度计法检测肝脏组织羟脯氨酸(Hyp);取肝左叶固定、HE染色, 显微镜下观察肝纤维化程度。结果 连翘苷元能够显著降低肝纤维化大鼠血清HA、LN、Ⅳ-C和PCⅢ的量, 减少肝脏质量和肝脏系数, 降低肝脏Hyp水平, 减轻肝纤维化程度。结论 连翘苷元对免疫性大鼠肝纤维化有较好的治疗作用。     

中药"乙肝散"抑制免疫性肝纤维化的实验研究

目的探讨中药"乙肝散"抗免疫性肝纤维化的作用,为临床应用乙肝散抗肝纤维化提供了理论依据.方法雄性Wistar大鼠尾静脉注射白蛋白建立实验性免疫性肝纤维化模型,分组加用不同浓度的乙肝散颗粒饲料,实验结束宰杀动物,检测血清HA、AST、ALT、ALB指标以及肝组织病理、肝组织化学染色、Ⅳ胶原免疫组化、a-SMA免疫组化、肝匀浆Hyp、和流式细胞仪a-SMA阳性细胞定量分析.结果高浓度组(B组)、低浓度组(C组)和正常对照组(D组)血清AST、ALT和肝组织匀浆Hyp水平,a-SMA阳性细胞定量分析,B组和D组血清HA均明显低于模型组(A组)(P<0.01),A组大鼠肝组织肝细胞普遍变性坏死,汇管区大量胶原纤维、网状纤维和Ⅳ胶原沉积,相互连接形成纤维隔,重新分割肝小叶,部分假小叶形成.B组和C组肝细胞坏死及胶原纤维、网状纤维和Ⅳ胶原纤维组织增生程度明显减轻.结论中药乙肝散抑制肝细胞坏死,改善肝脏功能,抑制HSC活化,抑制胶原纤维、网状纤维、Ⅳ型胶原的合成,具有抗免疫性肝纤维化作用.     

鸡骨草胶囊对大鼠免疫性肝纤维化的治疗作用

目的探讨鸡骨草胶囊对免疫性肝纤维化的治疗作用。方法采用腹腔注射猪血清法建立大鼠免疫性肝纤维化模型,纤维化大鼠灌胃给予不同浓度的鸡骨草胶囊,观察给药后血清酶的活性及肝脏病理变化。结果鸡骨草胶囊可降低免疫性肝纤维化大鼠血清中ALT、AST、MDA的含量,升高ALB、TP、SOD的含量,减轻肝脏组织病理损伤程度。结论鸡骨草胶囊对大鼠免疫性肝纤维化具有明显的保护作用,能明显减轻肝纤维化程度。     

地顶胞霉菌丝体对免疫性肝纤维化大鼠的保护作用

目的研究地顶胞霉菌丝体(AMM)对猪血清致大鼠免疫性肝纤维化的保护作用。方法采用猪血清腹腔注射造成大鼠免疫性肝纤维化模型,用试剂盒测定血清丙氨酸氨基转移酶(ALT)、血清天门冬氨酸氨基转移酶(AST)的活性和肝脏匀浆中超氧化物歧化酶(SOD)的活性、丙二醛(MDA)的含量;HE染色观察AMM对免疫性肝纤维化大鼠肝脏形态学影响。结果 AMM(350、700 mg.kg-1)不同程度增加大鼠的体重,降低大鼠的肝脾指数及血清中的ALT、AST的含量,减少肝组织匀浆中MDA的含量,升高肝组织中SOD的活性,明显减轻病理损伤。结论 AMM对猪血清所致大鼠免疫性肝纤维化有一定的保护作用。     

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.