雌激素类药物对去卵巢大鼠认知功能的影响

目的 研究雌激素类药物对去卵巢大鼠认知功能的影响.方法 48只3～5个月龄雌性SD大鼠(清洁级)随机分为8组:假手术组、去卵巢(OVX)组、去卵巢后7-甲基异炔诺酮治疗组、去卵巢后雷洛昔芬治疗组、去卵巢后戊酸雌二醇治疗组、去卵巢后大豆异黄酮治疗组、去卵巢后半量戊酸雌二醇+半量大豆异黄酮治疗组、去卵巢后半量戊酸雌二醇+全量大豆异黄酮治疗组,每组6只,用药3个月.做Morris水迷宫实验测定大鼠逃避潜伏期及运动策略以判断认知功能的变化,同时用RT-PCR方法检测大鼠脑部海马淀粉样蛋白前体(APP)mRNA水平.结果 OVX组逃避潜伏期明显长于假手术组.所有用药组逃避潜伏期时间明显短于OVX组;且用药组高级运动策略次数明显多于OVX组.大鼠去卵巢后.海马APP mRNA表达量明显增高,用药组及假手术组APPmRNA表达低于OVX组.结论 雌激素类药物能抵抗去卵巢大鼠认知功能的损害,且可能是通过下调去卵巢大鼠海马APP mRNA表达水平发挥作用的.     

重组特立帕肽注射液对去卵巢所致大鼠骨质疏松模型的药效学观察

目的观察重组特立帕肽注射液对去卵巢大鼠骨质疏松治疗作用,并对市售原研产品复泰奥进行比较。方法选择60只雌性SD大鼠,依据动物的体质量、骨密度分为Sham组和双侧去卵巢(OVX)组,OVX组动物切除双侧卵巢;手术8周后,对OVX组再随机分为6组,分别接受赋形剂或不同剂量受试药及复泰奥治疗,连续治疗8周;取各组动物第L1~L4截段进行BMD检测,取L4腰椎和左股骨进行生物力学评价。结果治疗结束时赋形剂亚组BMD显著低于假手术组及受试药和复泰奥各组,相同剂量的受试药物和复泰奥均无显著性差异。结论重组特立帕肽注射液可显著改善去卵巢动物的BMD及腰椎最大荷载,受试药和复泰奥的药效表现相似。     

人胎盘埋植疗法对去卵巢大鼠雌二醇水平和脑胆碱酯酶活性的影响

目的探讨人胎盘埋植疗法对去卵巢大鼠雌二醇及脑内乙酰胆碱酯酶的影响。方法测定和比较以下四组3个月龄SD雌性大鼠的雌二醇、脑胆碱酯酶含量;(1)实验组摘除双侧卵巢,不同剂量胎盘皮下包埋;(2)阴性对照组去除卵巢,无治疗;(3)阳性对照组去除卵巢,用雌激素治疗;(4)假手术组不摘除卵巢。结果高、中剂量人胎盘组的雌二醇水平高于阴性对照组(P<0.01);脑胆碱酯酶活性低于阴性对照组(P<0.01)。低剂量组与阴性对照组比较无差异(P>0.05)。结论高、中剂量人胎盘能提高去卵巢大鼠的雌激素水平,并能抑制其脑内胆碱酯酶的活性。     

雌激素水平对肾血管性高血压大鼠肾功能及氧化应激的影响

目的研究雌激素水平对肾血管性高血压大鼠肾功能及氧化应激的影响。方法取10周龄雌性Sprague-Dawley (SD)大鼠,狭窄一侧肾动脉建立肾血管性高血压模型,雌性高血压大鼠切除双侧卵巢建立雌激素低下模型,去势高血压大鼠补充雌二醇建立雌激素治疗组。将其随机分为雌性假手术组、雌性手术组、雌性手术去势组和雌激素治疗组。手术32周后进行颈动脉插管测定收缩压,全自动生化仪测定血清中的尿素氮(BUN)和血肌酐(Scr)水平;WST-1法测定肾脏组织中的超氧化物歧化酶(SOD)水平;TBA法测定肾脏组织中的丙二醛(MDA)水平。结果雌激素治疗组Scr水平明显高于假手术组、雌性手术组和雌性手术去势组(P<0.05);与假手术组和雌性手术去势组比较,雌激素治疗组BUN水平显著升高(P<0.01)。雌激素治疗组SOD水平明显低于假手术组和雌性手术去势组(P<0.05,P<0.01),MDA水平明显升高(P<0.05)。结论雌性肾血管性高血压大鼠切除双侧卵巢致雌激素水平低下后,补充雌激素治疗可加重肾血管性高血压大鼠肾功能损伤程度和氧化应激水平。     

唑来膦酸联合特立帕肽治疗绝经后骨质疏松症对骨密度影响的临床观察

目的 观察唑来膦酸联合特立帕肽治疗绝经后骨质疏松症对骨密度(BMD)的影响.方法 60例绝经后骨质疏松症患者随机分成唑来膦酸组、特立帕肽组和特立帕肽+唑来膦酸组,观察各组用药后13、26和52周时腰椎、髋部和股骨颈BMD相对于基线的变化.结果 特立帕肽+唑来膦酸组用药后13和26周的腰椎BMD增长百分比与唑来膦酸组、特立帕肽组相比存在显著差异(P＜0.01).用药后52周,特立帕肽+唑来膦酸组与特立帕肽组腰椎BMD无统计学差异,但显著高于唑来膦酸组(P＜0.01).唑来膦酸组、特立帕肽+唑来膦酸组用药后13、26和52周的髋部和股骨颈BMD增长百分比与特立帕肽组相比,差异有统计学意义(P＜0.05),特立帕肽+唑来膦酸组用药后13周的髋部BMD增长百分比与唑来膦酸组相比,差异有统计学意义(P＜0.05).结论 唑来膦酸和特立帕肽联合治疗对提高绝经后骨质疏松症患者的BMD有益.     

17β-雌二醇和运动对去卵巢大鼠后肢骨组织PPARγ蛋白表达的影响

目的观察17β-雌二醇(E2)和运动对去卵巢大鼠后肢骨组织过氧化物酶体增殖物激活受体γ(PPARγ)蛋白表达和骨髓脂肪细胞的影响。方法3mon成年♀性未经产SD大鼠40只,经双侧卵巢切除手术或假手术1wk后,按体重随机分为假手术、去卵巢、去卵巢运动和雌激素4个组。运动组每周进行4次45min、速度18m.min-1、坡度5°的跑台训练。雌激素组每周颈部皮下注射3次,剂量为25μg.kg-1E2。实验结束后,HE染色观察股骨和胫骨形态学变化,Westernblot检测骨组织PPARγ蛋白的表达量。结果去卵巢组股骨远端和胫骨近端的骨髓腔脂肪空泡数目以及股骨PPARγ蛋白表达高于假手术组、去卵巢运动组和雌激素组。结论E2与运动能改善去卵巢大鼠的骨组织学结构,其机制可能部分是与抑制去卵巢大鼠骨组织PPARγ蛋白的表达和抑制骨髓脂肪分化有关。     

卵巢切除大鼠降钙素基因相关肽、乙酰胆碱和去甲肾上腺素血管效应的变化(英文)

目的　研究雌性大鼠卵巢切除和雌激素替代治疗 4个月后 ,血管活性物质对离体动脉作用的改变。方法　采用双侧卵巢切除的雌性大鼠 ,分为假手术组、去卵巢组 (8周龄切除双侧卵巢 )和雌激素替代组 (苯甲雌二醇 40 μg,sc ,每日 1次 ,卵巢切除后 1 4d开始给药至切除后 4个月 )。于给药结束时取升主动脉、胸主动脉及尾动脉 ,进行离体血管功能实验 ,观察对降钙素基因相关肽 (CGRP)、乙酰胆碱(ACh)及去甲肾上腺素 (NE)的反应。结果　卵巢切除 4个月使CGRP引起的大鼠升主动脉舒张最大效应明显降低 ,而对胸主动脉无影响 ;同时ACh对胸主动脉的舒张效应曲线明显右移 ,而对升主动脉无影响。雌激素替代治疗使上述变化反转。去卵巢组的各类动脉对NE的反应性无变化 ,而雌激素替代组的升主动脉和胸主动脉对NE引起的最大收缩效应明显降低。在尾动脉 ,去卵巢组和雌激素替代组的CGRP和NE反应性均无改变。结论　内源性雌激素可以通过多种途径调节血管反应性 ,发挥其心血管保护作用。本研究进一步提示对绝经期妇女进行激素替代治疗的重要性     

卵巢去势引起神经细胞凋亡及凋亡相关蛋白改变与UPAN的作用

目的　通过观察去卵巢大鼠海马组织神经元凋亡相关蛋白的表达及用TUNEL试剂盒检测 ,研究缺乏雌激素是否引起神经元凋亡 ;评估UPAN是否能改善雌激素缺乏引起的凋亡 ,探讨雌激素缺乏引起神经细胞凋亡的机制与UP AN神经保护作用机制。方法　♂Wistar大鼠随机分 3组 :假手术组 (C组 ) ,卵巢去势对照组 (OVX组 ) ,UPAN治疗组(UPAN +OVX组 )。C组做假手术 ,OVX组和UPAN +OVX组做双侧卵巢切除术。UPAN +OVX组从卵巢去势第7wk开始用UPAN治疗 6wk ,用免疫组化和Westernblot观察AIF、Bax、Bcl 2的表达 ,并用TUNEL试剂盒检测。结果　免疫组化和Westernblot结果表明去卵巢大鼠海马组织AIF、Bax表达增加 ,Bcl 2表达减少 ,UPAN治疗组这些蛋白表达恢复到接近正常。在去卵巢大鼠海马组织和皮层存在大量的TUNEL阳性细胞 ,UPAN治疗组TUNEL阳性细胞比卵巢去势对照组明显减少。结论　去卵巢大鼠因雌激素缺乏引起神经细胞凋亡及凋亡相关蛋白改变 ,UP AN具有明显的治疗作用     

雌激素替代治疗对去势大鼠阴道组织雌激素受体表达的影响

目的 研究雌激素对去势大鼠阴道组织ERα与ERβ表达的影响，探讨雌激素治疗老年性阴道炎的分子机制。方法将40只雌性SD大鼠随机分成对照组、假手术组、去势组和雌激素替代治疗组各10只。对照组为空白对照；假手术组去除卵巢周围与卵巢相同大小脂肪组织；去势组行双侧卵巢切除术；雌激素替代治疗组在去卵巢手术3周后行戊酸雌二醇800 μg&#8226;kg 1&#8226;d 1替代治疗8周。免疫组织化学染色检测大鼠阴道组织ERα与ERβ表达情况。结果去势组大鼠ERα、ERβ表达显著低于对照组（均P＜0.01），雌激素替代组ERα、ERβ表达上升，较去势组显著增强（均P＜0.01）。结论雌激素替代治疗可导致雌激素受体表达上升，可能导致雌激素受体效应增强，从而提高阴道局部抵抗力。     

骨金散对去卵巢大鼠Ⅰ型胶原交联N-端肽、Ⅰ型胶原mRNA表达的影响

目的：复制去卵巢大鼠骨质疏松动物模型,探讨中药骨金散对去卵巢雌性大鼠血清Ⅰ型胶原交联N-端肽（NTX）和骨组织Ⅰ型胶原mRNA表达的影响。方法：6月龄雌性SD大鼠40只,随机分为去势组和假手术组。去势组切除双侧卵巢,假手术组切除部分脂肪。大鼠去势后1个月,将去势组随机分为3组：模型组、雌激素组和骨金散组,雌激素组每日灌服己烯雌酚0.05m g/kg,骨金散组按1.8g/kg剂量灌服骨金散,其余各组灌服等量生理盐水。2个月后,酶联免疫吸附法测量血清碱性磷酸酶（ALP）、NTX水平,RT-PCR方法检测右侧股骨骨组织Ⅰ型胶原mRNA表达水平。结果：与假手术组比较,模型组血清ALP、NTX含量明显升高（P〈0.01）,Ⅰ型胶原mRNA水平显著下降（P〈0.01）。雌激素组和骨金散组大鼠体内的ALP、NTX水平显著低于模型组（P〈0.01）,骨金散组大鼠体内的ALP水平高于雌激素组（P〈0.05）。雌激素组和骨金散组实验大鼠骨组织中Ⅰ型胶原蛋白mRNA表达含量明显高于模型组（P〈0.01）。结论：骨金散可减轻去卵巢大鼠ALP、NTX水平的提高,上调骨组织Ⅰ型胶原mRNA的表达水平,这可能与其治疗骨质疏松的机制有关。     

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.

---

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.

     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

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.     

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.     

Glycofection: The Ubiquitous Roles of Sugar Bound on Glycoplexes

Glycofection (transfection by using sugar-substituted polylysine) was assessed in order to provide an alternative to viral vectors for the transfer of genes into vascular smooth muscle cells. A rabbit vascular smooth muscle cell line (Rb-1 cells) was selectively transfected by using glycoplexes (glycosylated polylysine/pSV2LUC complexes) in the presence of 10 mu M of the fusogenic peptide GALA. A sugar-specific transfection was obtained when the glycofection was conducted for 1 h with glycoplexes containing either alpha Gal, alpha -Glc, alpha -GalNAc, beta -GlcNAc, or beta -GalNAc residues. The gene expression was high after transfection, with glycoplexes bearing alpha Gal, alpha -GalNAc, or beta -GalNAc residues that were weakly internalized, and low with glycoplexes carrying Lact or Rha residues that were well taken up by cells. These results suggest that 1) glycofection can be a good approach for a selective transfer of genes intovascular smooth muscle cells, 2) an efficient uptake of the glycoplexes is not the unique limiting step for an efficient transfection, and 3) the sugar-dependent trafficking of the glycoplexes inside the cells may account for the transfection efficiency.     

直肠癌下切缘病理组织学分析

目的探讨直肠癌逆向浸润与下切缘的安全距离的关系。方法对36例直肠癌Miles手术和Dixon手术后标本的肿瘤下缘1.0cm、2.0cm、3.0cm的肠壁及对应的系膜病理组织学检查,观察直肠癌逆向浸润或转移的距离。结果36例直肠癌标本距癌肿下缘1.0 cm、2.0cm、3.0cm的肠壁及对应的系膜病理组织学检查均为阴性,结论直肠癌远恻逆向浸润或转移未见超过1.0cm,因此认为保肛手术时切除肿瘤远侧肠管(包括系膜)2.0cm是安全的。