丙氨瑞林对大鼠,兔异位内膜的抑制作用

采用异位内膜模型大鼠和兔，以那法瑞林、达那唑、双侧卵巢切除（ＯＶＸ）作为阳性对照，观察了丙氨瑞林（１）对异位内膜的抑制作用。结果表明皮下或肌肉注射１１０～１００μｇ／ｋｇ有明显抑制作用，且具一定的剂量相关性。该作用较达那唑强，可达ＯＶＸ水平。但较那法瑞林为弱。这一作用是１的药物性去势作用的结果。     

子宫内膜异位症腹腔镜术后联合应用亮丙瑞林、达那唑对比性临床研究

目的 研究子宫内膜异位症患者术后联合亮丙瑞林、达那唑治疗前后的血清CA125及骨密度的变化及疗效.方法 经腹腔镜手术确诊后随机分为亮丙瑞林组和达那唑组药物治疗,所有患者子治疗前后3个月测定血清CA125、骨密度（BMD）值及疼痛VRS评分.结果 亮丙瑞林治疗组患者CA125水平低于达那唑组,骨密度值、疼痛VRS评分明显高于达那唑组.结论 ①亮丙瑞林和达那唑均能有效治疗子宫内膜异位症,并控制其复发.②亮丙瑞林对患者骨密度的影响小于达那唑.     

小柴胡汤对子宫内膜异位症大鼠异位内膜形态结构的影响

目的:探讨小柴胡汤治疗大鼠子宫内膜异位症对其异位内膜形态结构的影响。方法:采用实验性大鼠子宫内膜异位症动物模型,分 5组,小柴胡汤组分别给小柴胡汤 5, 10, 15g·kg-1·d-1,达那唑组给达那唑0. 1g·kg-1,对照组给蒸馏水 20mL·kg-1,均ig,qd。从大体、光镜、电镜等形态学水平,观察小柴胡汤对子宫内膜异位症大鼠异位内膜形态结构的影响。结果:给予小柴胡汤 5, 10, 15g·kg-1·d-1 4wk后,子宫内膜异位症大鼠均可见异位内膜体积缩小、萎缩;在光镜和电镜下观察到子宫内膜异位症大鼠异位内膜生长明显受抑制。结论:小柴胡汤对实验性大鼠子宫内膜异位症具有治疗作用。     

丙氨瑞林对大鼠、兔异位内膜的抑制作用

丙氨瑞林对大鼠、兔异位内膜的抑制作用Δ表１丙氨瑞林对大鼠异位内膜的抑制作用分组剂量（μｇ／ｋｇ）抑制率（％）（ｘ±ｓ）Δ肌注皮下注射丙氨瑞林１０６２±４＊（５）７４±７＊（５）３０７０±５＊（５）８８±８＊（５）１００８６±４＊（５）１００＊（５）那...     

戈舍瑞林联合腹腔镜治疗中重度子宫内膜异位症44例

目的 观察腹腔镜手术联合戈舍瑞林治疗中重度子宫内膜异位症的疗效.方法 选择经腹腔镜手术诊断并治疗的中重度子宫内膜异位症患者124例,术后随机分为3组.戈舍瑞林组44例,术后第3天开始皮下注射戈舍瑞林3.6 mg,此后每月1次,连用3～6个月;达那唑组加例,术后第3天开始口服达那唑0.2 g,2次/d,连用3～6个月;对照组40例未用药.所有患者均随访12个月并观察疗效.结果 戈舍瑞林组、达那唑组、对照组总有效率分别为86.36%,85.00%,55.00%,复发率分别为9.09%,15.00%,45.00%,术后1年妊娠率分别为36.36%,35.00%,5.00%.两用药组与未用药组比较,差异均有显著性(P＜0.05),但用药组之间比较差异无显著性(P＞0.05).戈舍瑞林组、达那唑组肝损害率分别为15.65%,50.00%,差异有显著性(P＜0.05).结论 腹腔镜联合药物治疗中重度子宫内膜异位症疗效确切,能降低复发率、提高妊娠率.且戈舍瑞林较达那唑不良反应小、使用方便.     

丙氨瑞林缓释微球注射剂对大鼠异位子宫内膜抑制作用

目的：观察丙氨瑞林缓释微球注射剂（LHRH-Ams）对异位内膜的抑制作用。方法：用外科自体移植术建立大鼠子宫内膜异位症动物模型,随机分组给药,同时在给药后不同时间采集血样,测定血清E₂水平。结果：LHRH-Ams作用相似于LHRH-Alp,剂量为100 μg.kg^-1.d^-1时,对大鼠异位内膜明显抑制,可达“药物性去卵巢”作用,增加剂量,作用并未相应增加。给药后1周,血清E2可降低至间情期水平,6周后开始恢复。结论：LHRH-Ams对大鼠异位子宫内膜有明显的抑制,可达“药物性去卵巢”作用,为临床应用提供实验依据。     

缓释醋酸亮丙瑞林微球对大鼠子宫异位内膜的抑制作用

目的 :观察国内研制的醋酸亮丙瑞林微球(LE ms)对异位子宫内膜的抑制作用 ,并初步探讨原料药的作用机制。方法 :以手术方法制备子宫内膜异位症 (endometriosis ,EMT)模型SD大鼠 6 0只 ,随机分组给药 ,并计算各用药组对异位内膜的抑制率。另取SD大鼠 30只 ,随机分为假手术组、EMT模型组、用药组。 3周后 ,测血清E2 水平 ;异位内膜体积 ;子宫、卵巢、胸腺和脾脏重量 ;NK细胞活性。结果 :醋酸亮丙瑞林 (LE) 2 0 μg·kg-1、进口LE ms2 0 μg·kg-1·d-1,抑制率依次为 87.2 %和 78.3%。国产LE ms 2、2 0、2 0 0 μg·kg-1·d-1对大鼠异位内膜抑制率依次为 5 7.3%、89.0 %和 94 .7%。LE可使EMT大鼠动情周期消失 ;血清E2 水平降低 ;子宫重量明显减轻 ;胸腺重量明显增加和NK细胞活性明显提高。结论 :国内研制的醋酸亮丙瑞林微球疗效与相同剂量的进口同类产品及原料药的作用相当 ,其作用机制可能是抑制大鼠性腺轴系并通过拮抗雌激素作用来提高EMT大鼠的免疫功能。     

缓释醋酸亮丙瑞林微球对大鼠子宫异位内膜的抑制作用

目的观察国内研制的醋酸亮丙瑞林(LE)微球对异位子宫内膜的抑制作用,并与进口醋酸亮丙瑞林微球(enanton)及醋酸亮丙瑞林(LE)注射溶液进行疗效比较.方法以手术方法制备大鼠子宫内膜异位症模型,将动物分为辅料组、原料药组(LE,20μg·kg-1·d-1×28d,sc)、进口微球组(enanton20μg·kg-1·d-1,sc)、国产微球组(国产LE微球2、20、200μg·kg-1·d-1,sc).结果辅料组异位内膜体积呈增长趋势,阳性对照药LE20μg·kg-1(sc×28d)、enanton20μg·kg-1·d-1,及国产LE微球2、20、200μg·kg-1·d-1对异位内膜均有明显抑制作用,且后者具有一定的剂量相关性.结论国产醋酸亮丙瑞林微球20μg·kg-1·     

GnRH拮抗剂对子宫内膜异位症模型大鼠的实验研究

目的观察促性腺激素释放激素(GnRH)拮抗剂阿巴瑞克(Abarelix)对大鼠移植性异位子宫内膜的抑制作用及其对子宫内膜异位症模型大鼠血清CA125、E_2、FSH、LH水平的影响。方法用外科自体移植术建立大鼠子宫内膜异位症动物模型,分为4组:对照组、去势组、GnRH激动剂丙氨瑞林组和阿巴瑞克组。分别测定给药前及给药4周后,各组模型大鼠异位子宫内膜体积及血清CA125、E_2、FSH、LH水平,观察给药前后各组模型大鼠异位子宫内膜体积及血清CA125、E_2、FSH、LH水平变化。结果给药4周后,阿巴瑞克组模型大鼠异位子宫内膜体积明显缩小,血清CA125、E_2、FSH、LH水平明显降低。结论阿巴瑞克对异位子宫内膜有抑制作用,对子宫内膜异位症有治疗作用,具有良好的临床应用前景。     

不同促性腺激素释放激素激动剂治疗子宫内膜异位症的应用情况和疗效分析

目的探讨促性腺激素释放激素激动剂(gonadotropin-releasing hormone agonist,GnRHa)在子宫内膜异位症的应用情况,并比较不同GnRHa的疗效。方法利用医院计算机处方管理系统提取2018年1月1日-2019年1月1日门诊药房调配含有GnRHa的处方信息,分析和讨论亮丙瑞林、戈舍瑞林、曲普瑞林用于治疗子宫内膜异位症的比例,并研究不同GnRHa对子宫异常出血、内膜厚度及CA125的影响。结果亮丙瑞林、戈舍瑞林、曲普瑞林在子宫内膜异位症的使用比例分别为29.45%,46.52%,24.03%;不同GnRHa用药前后子宫内膜厚度、子宫体积和CA125无显著性差异;子宫不规则出血病例数曲普瑞林最多,亮丙瑞林最少。结论不同GnRHa疗效无明显差异,使用比例不同可能与药物的安全性、经济性,医师的地域性、使用习惯有关。     

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.