宁心红杞胶囊对围绝经期综合征的治疗作用

目的：观察长期服用纯中药制剂宁心红杞胶囊，对围绝经期妇女症状、子宫内膜、性激素水平的影响。方法：绝经未逾5年妇女26例，未绝经妇女14例，持续服用宁心红杞胶囊3个月以上，观察其临床症状、阴道脱落细胞、血清中女性激素含量、阴道流血及子宫内膜厚度等的变化。结果：长期服药后，临床症状好转，阴道脱落细胞伊红指数上升，女性激素稳定在一定水平，无阴道不规则流血现象，子宫内膜增值在正常范围内。结论：纯中药制剂宁心红杞胶囊治疗围绝经期综合征疗效确切且安全、无毒副作用。     

长期应用吗啡对雌性大鼠性腺轴功能的影响

目的探讨长期应用吗啡的雌性大鼠,当动情周期发生改变后,其下丘脑-垂体-卵巢轴功能的变化。方法选取30只成年雌性大鼠,采用剂量递增法皮下注射盐酸吗啡,定期进行阴道细胞学观察直至大鼠动情周期紊乱。放射免疫分析测定血清卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)、孕酮(P),免疫组织化学测下丘脑、垂体、卵巢和子宫雌激素受体(ER)的表达。结果①维持吗啡用药7周时,60%(18/30)大鼠发生动情周期紊乱,用药10周,76.7%(23/30)动情周期被抑制;②长期应用吗啡,造成动情周期紊乱时,FSH、LH、E2、P基础分泌较对照组均显著降低(P<0.05,P<0.05,P<0.01,P<0.05);若长期应用吗啡后未出现动情周期紊乱,各激素水平较对照组有下降趋势;③长期应用吗啡后,无论大鼠动情周期是否被抑制,非动情期及动情期大鼠性腺轴各组织中ER平均吸光度(A)值均显著降低(P<0.01,P<0.001)。结论长期使用吗啡对下丘脑-垂体-卵巢轴有不同程度的损伤。     

胸腺因子D对老龄大鼠垂体-性腺轴内分泌激素的影响

目的　探讨胸腺因子 D对垂体 -性腺轴内分泌衰老的延缓作用。 方法 　雌、雄 2 1月老龄 SD大鼠各随机分成两组 ,一组隔日背部皮下注射胸腺因子 D2 mg· kg- 1 ,另一组及 6月青龄雌、雄对照注射等量生理盐水 ,连续处理 3个月后 ,用放射免疫法测定腺垂体组织、血清 FSF、L H和血清 E2 、T。结果 　与雄性青龄对照组相比 ,雄性老年血清 L H升高 ,血清 T和 E2 下降 ,给药后 ,这些老年性改变可部分得到改善 ,而腺垂体组织FSH和血清 FSH、L H、E2 、T在各雌性大鼠间无差异。结论 　胸腺因子 D可逆转老龄雄性大鼠垂体 -性腺轴内分泌激素的老龄性改变 ,从而延缓衰老     

赛庚啶对大鼠垂体-性腺轴功能的影响

目的　研究赛庚啶对大鼠垂体 性腺轴内分泌功能的影响。方法　用放射免疫分析法(RIA)和电镜,观察赛庚啶对大鼠垂体性腺轴内分泌功能及垂体促性腺细胞、卵巢、睾丸细胞超微结构的影响。结果　赛庚啶2.3mg·kg^-1·d^-1,ig ,连续用药14d ,可明显降低雌性大鼠血清卵泡刺激素(FSH)、孕酮(P)的含量(P<0.01) ,而升高黄体生成素(LH)的水平(P<0.05)。4 .6mg·kg^-1·d^-1赛庚啶不但可引起雌性大鼠血清FSH、雌二醇(E2 )、P的水平显著降低,升高LH的含量(P<0.05及P<0.01) ,而且使雄性大鼠血清LH、T的含量明显升高(P<0.05)。组织形态电镜观察,该药亦可引起大鼠卵巢细胞超微结构的退行性改变,睾丸支持细胞呈分泌状态,而垂体促性腺分泌细胞则无明显变化。结论　赛庚啶可抑制雌性大鼠FSH、E₂、P的分泌,促进雌、雄大鼠LH及雄性大鼠T的分泌,其机制可能与赛庚啶直接影响靶器官的分泌细胞有关。     

食源性肥胖致不孕大鼠下丘脑弓状核内GnRH的表达下调

目的探讨食源性肥胖致不孕大鼠中枢性激素表达变化以及对性腺轴的影响。方法将100只刚断乳雌性SD大鼠分2组。正常组20只,给予普通饲料。高能饲料组80只,饲高能饲料,根据Lee's指数及阴道涂片检查筛选出肥胖不孕大鼠22只,作为实验组。检测E2、T、leptin、FSH、LH的水平;观察卵巢的形态学变化以及促性腺激素释放激素在下丘脑弓状核的表达情况。结果实验组较正常组大鼠血清E2、T、leptin水平明显升高,FSH、LH水平明显降低;下丘脑弓状核GnRH表达明显减弱;实验组大鼠卵巢体积明显减小,卵巢中未见接近成熟的卵泡及黄体。结论肥胖导致大鼠的神经内分泌代谢紊乱,致使下丘脑-垂体-卵巢轴功能失调性无排卵而引起不孕。     

赛庚啶对大鼠垂体-性腺轴功能的影响

目的　研究赛庚啶对大鼠垂体 性腺轴内分泌功能的影响。方法　用放射免疫分析法 (RIA)和电镜 ,观察赛庚啶对大鼠垂体 性腺轴内分泌功能及垂体促性腺细胞、卵巢、睾丸细胞超微结构的影响。结果　赛庚啶 2 .3mg·kg-1·d-1,ig ,连续用药14d ,可明显降低雌性大鼠血清卵泡刺激素 (FSH)、孕酮 (P)的含量 (P <0 .0 1) ,而升高黄体生成素 (LH)的水平 (P <0 .0 5 )。 4 .6mg·kg-1·d-1赛庚啶不但可引起雌性大鼠血清FSH、雌二醇 (E2 )、P的水平显著降低 ,升高LH的含量 (P <0 .0 5及 <0 .0 1) ,而且使雄性大鼠血清LH、T的含量明显升高 (P <0 .0 5 )。组织形态电镜观察 ,该药亦可引起大鼠卵巢细胞超微结构的退行性改变 ,睾丸支持细胞呈分泌状态 ,而垂体促性腺分泌细胞则无明显变化。结论　赛庚啶可抑制雌性大鼠FSH、E2 、P的分泌 ,促进雌、雄大鼠LH及雄性大鼠T的分泌 ,其机制可能与赛庚啶直接影响靶器官的分泌细胞有关。     

“三棱-莪术”组分配伍对子宫肌瘤大鼠下丘脑和垂体激素的影响（英文）

目的:研究"三棱-莪术"组分配伍对子宫肌瘤大鼠下丘脑和垂体相关激素的影响。方法:将未生孕的SD雌性大鼠随机分为6组:正常对照组(NC),模型组(UL),桂枝茯苓胶囊组(GZFLC),"三棱-莪术"组分配伍高剂量组(HCRSR)、中剂量组(MCRSR)及低剂量组(LCRSR)。经肌注孕酮和灌胃己烯雌酚来诱导建立子宫肌瘤大鼠模型。经过五周的造模和药物治疗后,收集大鼠股动脉血、下丘脑及垂体,通过ELISA法测定血清,下丘脑和垂体中促性腺激素释放激素(GnRH),促卵泡激素(FSH)和促黄体激素(LH)的水平。结果:该造模方法成功地建立了大鼠子宫肌瘤模型。各组血清中GnRH,FSH和LH的浓度,以及下丘脑中的GnRH水平均无统计学意义(P 0.05)。模型组垂体中FSH和LH的表达高于正常组(P 0.01)。治疗后,高剂量(HCRSR)和桂枝茯苓胶囊组(GZFLC)组中"三棱-莪术"组分配伍的FSH和LH水平显著降低(P 0.01)。结论:这些数据表明"三棱-莪术"组分配伍可以降低子宫平滑肌瘤大鼠垂体中FSH和LH的表达。     

大豆异黄酮对去卵巢大鼠血液生化指标的影响

目的　研究大豆异黄酮对去卵巢大鼠血液生化指标的影响。方法　将4月龄雌性SD大鼠摘除卵巢,按体重分成6组,分别给予不同剂量的大豆异黄酮或/和钙粉,连续灌胃饲养二个半月后,断头处死,收集血样并测定生化指标,采集右股骨、右胫骨、子宫并称重。结果　大豆异黄酮对大鼠体重和子宫重量均有影响,可抑制去卵巢大鼠的代偿性增重和促进子宫的生长。大豆异黄酮对去卵巢大鼠血清钙、磷和骨钙素的影响不大,碱性磷酸酶活性稍有降低,血清雌二醇和降钙素水平稍有提高,但这些实验给药组与模型B组的的大多未达到显著水平。结论　大豆异黄酮对去卵巢大鼠血液生化指标有一定的调节作用,所起的作用类似于弱雌激素活性,大豆异黄酮与钙剂联合使用时调节作用更明显。     

二甲双胍对大鼠垂体—性腺轴内分泌功能的影响

目的研究二甲双胍(Metformin,MF)对大鼠垂体-性腺轴内分泌功能的影响。方法采用放射免疫分析法和电子显微镜技术,系统研究MF对大鼠血清性激素含量及靶腺组织形态的影响。结果MF135mg·kg-1·d-1,ig,连续用药14d,可使♂大鼠睾酮(T)的含量及♀大鼠血清黄体生成素(LH)水平明显降低,而对♀大鼠卵泡刺激素(FSH)、雌二醇(E2)、孕酮(P)的含量和♂大鼠血清LH、FSH的含量均无影响。270mg·kg-1·d-1MF除明显降低♂大鼠血清T和♀大鼠血清LH的含量外,可使♀大鼠血清P、E2的含量升高(P<0.01)。电镜观察显示,大鼠睾丸内分泌细胞超微结构发生退行性改变,而卵巢细胞超微结构则呈现分泌旺盛的表现。结论MF对♀大鼠垂体-卵巢轴内分泌功能有促进作用,而对♂大鼠垂体-睾丸轴内分泌功能有抑制作用,且使靶腺内分泌细胞的超微结构出现相应的变化。     

大豆异黄酮对去卵巢大鼠血液生化指标的影响

目的研究大豆异黄酮对去卵巢大鼠血液生化指标的影响。方法将4月龄雌性SD大鼠摘除卵巢，按体重分成6组，分别给予不同剂量的大豆异黄酮或／和钙粉。连续灌胃饲养二个半月后，断头处死，收集血样并测定生化指标，采集右股骨、右胫骨、子宫并称重。结果大豆异黄酮对大鼠体重和子宫重量均有影响，可抑制去卵巢大鼠的代偿性增重和促进子宫的生长。大豆异黄酮对去卵巢大鼠血清钙、磷和骨钙素的影响不大，碱性磷酸酶活性稍有降低，血清雌二醇和降钙素水平稍有提高，但这些实验给药组与模型B组的的大多未达到显著水平。结论大豆异黄酮对去卵巢大鼠血液生化指标有一定的调节作用，所起的作用类似于弱雌激素活性，大豆异黄酮与钙剂联合使用时调节作用更明显。     

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.     

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.