龙牡壮骨颗粒对小鼠性激素水平的影响

目的：探讨龙牡壮骨颗粒对性激素水平的影响.方法：昆明小鼠雌雄各30只,以该制剂溶于水制成溶液剂为供试药,以双蒸水为空白对照.受试小鼠按性别随机分为龙牡壮骨颗粒雌性高、等效剂量组和龙牡壮骨颗粒雄性高、等效剂量组,给药14 d,观察对血清睾酮、雌二醇含量和骨指标的影响.结果：龙牡壮骨颗粒能显著提高小鼠骨干重、骨密度、骨量,等效剂量龙牡壮骨颗粒组还能明显提高雄性小鼠骨湿重（P=0.022）,等效剂量龙牡壮骨颗粒对小鼠性激素水平无影响（P=0.855）.高剂量龙牡壮骨颗粒显著降低雄性小鼠雌二醇水平（P=0.048）.结论：与临床剂量等效的龙牡壮骨颗粒对小鼠骨质有增强作用,同时对小鼠性激素水平无影响.     

白假丝酵母菌阴道炎小鼠模型的构建

摘 要 目的：构建白假丝酵母菌阴道炎小鼠模型,探索最佳成模条件,以提供经济实用的白假丝醇母菌性阴道炎动物模型。方法: 采用昆明雌性小鼠,预先连续灌胃给予低、中、高剂量（0.001 5,0.015,0.15 mg/10 g）的戊酸雌二醇7 d后接种白假丝酵母菌建立阴道炎模型,并进行阴道灌洗液真菌载量和阴道组织病理观察。结果: 戊酸雌二醇低、中、高剂量组阴道灌洗液的菌落计数分别为124.67±19.01、217.67±22.50、282.00±27.87,高剂量组与中、低剂量组比较差异有统计学意义（P<0.05或P<0.01）。HE染色和PAS染色结果显示,戊酸雌二醇高剂量组有较多多形核粒细胞（PMNs）浸润及紫红色线状菌丝。结论: 戊酸雌二醇高剂量组造模方式为昆明小鼠白假丝酵母菌阴道炎模型的最佳造模条件。     

芪防鼻敏颗粒抗炎、抗过敏作用研究

摘 要 目的：初步探讨中药复方芪防鼻敏颗粒的抗炎、抗过敏作用。方法: 采用二甲苯致小鼠耳廓肿胀法和大鼠棉球肉芽组织形成法观察芪防鼻敏颗粒的抗炎作用,采用大鼠同种被动皮肤过敏反应实验和小鼠耳异种被动皮肤过敏反应观察芪防鼻敏感颗粒的抗过敏作用。结果: 与空白组比较,芪防鼻敏颗粒各剂量组可显著降低二甲苯所致小鼠耳廓肿胀度（P<0.01或0.05）,对大鼠棉球肉芽组织增生无明显抑制作用。与空白组比较,芪防鼻敏颗粒各剂量组可明显降低卵蛋白所致大鼠皮肤蓝斑A值（P<0.01或0.05）,芪防鼻敏颗粒高剂量组可显著降低小鼠耳廓蓝染程度（P<0.05）。结论:芪防鼻敏颗粒具有一定抗炎、抗过敏作用。     

芪防鼻敏颗粒对变应性鼻炎大鼠炎性因子表达的影响研究

摘 要 目的：观察芪防鼻敏颗粒对变应性鼻炎（AR）大鼠血清白介素 4(IL 4),白介素 17(IL 17）,肿瘤坏死因子（TNF α）及鼻黏膜γ干扰素（IFN γ）、白介素 6（IL 6）、TNF α表达的影响。方法: SD大鼠随机分为正常组,模型组,氯雷他定组（1.17 mg·kg^-1）,鼻炎康组（0.6 g·kg^-1）,芪防鼻敏颗粒高（26.48 g·kg^-1）、中（13.24 g·kg^-1）、低（6.62 g·kg^-1）剂量组。采用卵蛋白（OVA）建立AR大鼠模型。造模成功后分别灌胃给药,连续14 d。酶联免疫吸附法（ELISA）检测AR大鼠血清IL 4、IL 17、TNF α水平,免疫组化染色法（IHC）检测鼻黏膜IFN γ、IL 6、TNF α表达。结果:与正常组相比,模型组大鼠血清IL 4、IL 17水平明显上升（P<0.01）;鼻黏膜IFN γ阳性表达明显降低（P<0.05）,IL 6、TNF α阳性表达显著升高（P<0.01）。与模型组相比,氯雷他定组、芪防鼻敏颗粒中剂量组大鼠血清IL 4水平显著下降（P<0.05）,芪防鼻敏颗粒低剂量组大鼠血清IL 17水平明显下降（P<0.05）,氯雷他定组、鼻炎康组、芪防鼻敏颗粒高、中剂量组大鼠血清TNF α水平显著下降（P<0.05或P<0.01）;高、低剂量组大鼠鼻黏膜IFN γ阳性表达显著升高（P<0.05或P<0.01）,高、中剂量组IL 6阳性表达显著降低（P<0.01）,高剂量组TNF α阳性表达显著降低（P<0.01）。与氯雷他定组相比,鼻炎康组、芪防鼻敏颗粒高剂量组大鼠血清IL 17水平明显上升（P<0.05）,鼻炎康组、芪防鼻敏颗粒低剂量组大鼠血清IL 4水平明显上升（P<0.05）,芪防鼻敏颗粒高、中、低剂量组TNF α阳性表达显著升高（P<0.05）;与鼻炎康组比较,芪防鼻敏颗粒中剂量组大鼠血清IL 4水平明显下降（P<0.05）;与芪防鼻敏颗粒低剂量组相比,芪防鼻敏颗粒高剂量组大鼠血清IL 17水平明显上升（P<0.05）,芪防鼻敏颗粒中剂量组大鼠血清IL 4水平明显下降（P<0.05）。结论:芪防鼻敏颗粒可增加AR鼻黏膜IFN γ表达,降低血清IL 4、TNF α、IL 17水平及鼻黏膜TNF α、IL 6表达。     

乳癖消颗粒不同提取物对小鼠原发性痛经模型的影响

摘 要 目的： 研究乳癖消颗粒各提取部位的抗痛经作用。方法: 采用缩宫素致小鼠扭体实验观察乳癖消颗粒各提取部位的抗痛经作用。结果: 与模型组相比,乳癖消颗粒的各提取部位均能显著减少缩宫素引起的小鼠扭体反应次数（P <0.05,P<0.01或P<0.001）;其中,水溶性部位效果最好（P<0.001）,且与阳性对照组相比差异无统计学意义（P＞0.05）。结论:乳癖消颗粒的水溶性部位具有显著抗痛经作用。     

阿那曲唑对绝经后乳腺癌患者性激素水平的影响及人乳腺癌细胞的抑制作用

摘 要 目的：探讨阿那曲唑对绝经后乳腺癌患者性激素水平的影响及对人乳腺癌细胞（MCF 7）的抑制作用。方法: 收集80例女性乳腺癌病例,将接受常规管理与他莫昔芬治疗的40例患者纳入对照组;将接受常规管理与阿那曲唑治疗的40例患者纳入观察组。比较两组患者治疗前、治疗3个月后性激素水平变化、疗效及药品不良反应发生率,以及两种药物对MCF 7细胞的抑制作用。结果: 治疗后,两组患者雌二醇、孕酮、黄体生成素水平均较治疗前降低,睾酮水平则较治疗前升高（P＜0.01）;且他莫昔芬组患者雌二醇、孕酮、黄体生成素水平均高于阿那曲唑组,睾酮水平低于阿那曲唑组（P＜0.01）。两种药物作用72 h的MCF 7细胞抑制率均高于作用48 h（P＜0.05）;阿那曲唑不同时点的MCF 7细胞抑制率均优于他莫昔芬（P＜0.05）。对照组患者治疗总有效率（45.0%）低于观察组（70.0%）（P＜0.05）;两组药品不良反应总发生率比较,差异无统计学意义（P＞0.05）。结论: 给予绝经后乳腺癌患者阿那曲唑疗效显著,安全性高,对MCF 7细胞有较强的抑制作用,能有效调节患者性激素水平,减少乳腺癌复发及转移风险。     

晕吐宁颗粒抗眩晕作用研究

摘 要 目的： 晕吐宁颗粒对小鼠及豚鼠抗眩晕作用及初步机制探讨,为该药临床应用提供实验支持。方法: 机械旋转使小鼠产生眩晕后,通过迷宫实验与跳台实验测定正常组,模型组,阳性对照组(盐酸地芬尼多片,10 mg·kg^-1·d^{-1),晕吐宁颗粒低、中、高剂量三组 (3,6,12 g·kg-1·d-1)小鼠逃避电击所用时间,并观察各组眩晕小鼠的进食量;观察外耳道注入三氯甲烷的眩晕模型豚鼠摇头和眼球震颤次数,观察晕吐宁颗粒的抗眩晕作用。结果: 晕吐宁颗粒各剂量组能够显著缩短眩晕小鼠逃避电击所用时间(P＜0.01或0.05),增加眩晕小鼠进食量;降低眩晕豚鼠的摆头和眼球震颤次数(P＜0.01, P＜0.05)。结论: 晕吐宁颗粒对眩晕具有显著的治疗效果。}     

乳癖消颗粒对家兔乳腺增生的抑制作用

摘 要 目的：考察乳癖消颗粒对家兔乳腺增生的抑制作用,并探讨其抑制作用的可能机制,为该药临床应用提供理论依据。方法: 苯甲酸雌二醇联合黄体酮法构建家兔乳腺增生模型,以逍遥丸、三苯氧胺为阳性对照组,受试药乳癖消颗粒分为低、中、高（0.525,1.05,2.1 g·kg^-1）剂量组,按组别灌胃30 d,测定家兔血清中的雌二醇（E2）、孕酮（PROG）、催乳素（PRL）、促卵泡生成素（FSH）及促黄体生成素（LH）含量。并对乳腺组织进行病理组织学检查同时检测各组家兔乳腺组织中血管内皮增长因子（VEGF）的含量表达。结果: “保留卵巢 苯甲酸雌二醇联合黄体酮法” 可用于构建家兔乳腺增生模型。与模型组比较,乳癖消颗粒可使家兔血清E2及PRL含量明显下降（P<0.01）,PROG含量显著升高（P<0.01或P<0.001）。与模型组比较,乳癖消颗粒高剂量组可恢复到空白对照组家兔的乳腺结构的水平,抗乳腺增生作用优于逍遥丸和三苯氧胺。与模型组比较,各给药治疗组家兔乳腺组织中VEGF的表达均明显下降（P<0. 001）。结论: 乳癖消颗粒对家兔乳腺增生有较好的治疗作用。乳癖消颗粒对家兔乳腺增生的抑制作用可能与抑制家兔乳腺增生组织中VEGF的表达有关,其抑制水平与三苯氧胺和逍遥丸的抑制水平无差异。     

耳复康口服液对小鼠微循环障碍的影响

摘 要 目的：观察耳复康口服液对肾上腺素致急性血瘀症小鼠微循环障碍的影响。方法: 将小鼠随机分为模型组,脑得生片组（1.35 g·kg^-1）,高(30 ml·kg^-1)、中(15 ml·kg^-1)、低(7.5 ml·kg^-1)剂量耳复康口服液组,用微循环仪观察正常小鼠给药1 h后毛细血管开放数。尾静脉注射肾上腺素造成耳廓微循环障碍,观察造模后2 min小鼠的毛细血管开放数及血流情况。结果:和模型组相比,高、中、低剂量耳复康口服液对正常小鼠耳廓毛细血管开放数无明显影响(P＞0.05);与模型组相比,高、中剂量耳复康口服液可显著改善肾上腺素致小鼠耳壳微循环障碍模型微循环血流情况(P＜0.05或P<0.01),可明显对抗肾上腺素所致小鼠耳壳微循环障碍模型毛细血管网开放数的减少(P<0.05)。结论:耳复康口服液有改善微循环障碍的作用。     

健脾生血颗粒对气虚、脾虚型贫血模型小鼠的治疗效果

摘 要 目的： 探讨健脾生血颗粒对气虚、脾虚型贫血小鼠的治疗效果。方法: 昆明鼠（SPF级）随机分为模型对照组、正常对照组、健脾生血组、浸膏组、硫酸亚铁组等5组。除正常对照组外,其余受试动物均皮下注射利血平建立脾气虚症小鼠模型。分别考察健脾生血颗粒对小鼠单核吞噬细胞功能、小鼠血清溶血素的影响以及对小鼠疏肝和胃功效的影响。结果: 与其余各实验组相比,健脾生血组能显著提高小鼠的血清溶血素水平（P<0.05）;对廓清指数作用显著（P<0.05）,可提高吞噬活性（P<0.01）,显著改善疏肝和胃模型小鼠的体质量和进食量（P<0.01）。结论:健脾生血颗粒能提高免疫水平,对于气虚脾虚型贫血中医模型小鼠具有显著的治疗效果,这对于临床使用健脾生血颗粒具有一定的参考价值。     

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.

     

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.     

2-(Acetoxyphenyl)-(Z)-styryl sulfides as cyclooxygenase inhibitors

2-(Acetoxyphenyl)-(Z)-styryl sulfides are described as selective cyclooxygenase-2 (COX-2) inhibitors, useful for treating inflammation and COX-2-mediated disorders including neoplasia. 2-(Acetoxyphenyl)-(Z)-styryl sulfide is claimed to be the most potent COX inhibitor in the series with a COX-2 selectivity ratio of 33. This compound is also claimed to be superior to celecoxib (Celebrex^®, Pfizer) in inhibiting cell growth of colorectal carcinoma cells. In this evaluation, the COX inhibitory activity of this compound is compared to that previously disclosed for diarylheterocycles and 2-(acetoxyphenyl)alkyl sulfides. The validity of the DLD-1 cell line in the growth inhibition studies is questioned based on recent literature reports indicating the lack of COX-2 expression in this cell line.     

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ～ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.     

Drug targets for cognitive enhancement in neuropsychiatric disorders

The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA_A α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.