桑黄多糖对小鼠精子和睾丸细胞染色体畸变研究

目的 通过小鼠精子畸变和睾丸细胞染色体畸变试验,探讨桑黄多糖对雄性小鼠的生殖毒性.方法 试验设三个剂量组为2.5g·kg-1、5.0g·kg-、10.0g· kg-1 BW,经口灌胃进行试验,取小鼠睾丸制备标本,分别观察并计算各剂量组小鼠的精子畸变和睾丸细胞染色体畸变率.结果 桑黄多糖各剂量组小鼠的精子和睾丸细胞染色体畸变率与空白对照均无显著性差异(P＞0.05),而环磷酰胺与空白对照组比较有显著性差异(P＜0.01).结论 桑黄多糖各剂量组对雄性小鼠无生殖毒性作用.     

蜂王浆软胶囊对小鼠精子和睾丸细胞染色体畸变研究

目的通过小鼠小鼠精子畸变和睾丸细胞染色体畸变试验,探讨蜂王浆软胶囊对雄性小鼠的生殖毒性。方法试验设3个剂量组为2.5g.kg-1、5.0g.kg-1、10.0g.kg-1BW,经口灌胃进行试验,取小鼠睾丸制备标本,分别观察并计算各剂量组小鼠的精子畸变和睾丸细胞染色体畸变率。结果蜂王浆软胶囊各剂量组小鼠的精子和睾丸细胞染色体畸变率与空白对照均无显著性差异(P>0.05),而阳性对照组环磷酰胺与空白对照组比较有显著性差异(P<0.01)。结论蜂王浆软胶囊各剂量组对雄性小鼠无生殖毒性作用。     

乙体氯氰菊酯对雄性大鼠睾丸的损伤作用

目的　探讨乙体氯氰菊酯 (β CP)对雄性大鼠的睾丸毒性。 方法　成年Wistar雄性大鼠 ,分别以 0、2 0、40和80mg kg剂量的 β CP连续 8周灌胃染毒 ,按常规方法对染毒大鼠进行精子数、精子活动度和精子畸形检测 ,并对睾丸进行组织病理学检查。结果　 80mg kg剂量组大鼠活精率 (60 5 % )及精子活动度 (56 55 % )明显低于对照组 (分别为78 75 %和 72 2 0 % ) ,差异有显著性 (P <0 0 5) ,睾丸支持细胞和各级生精细胞发生病理改变。 2 0和 40mg kg剂量组均未见异常。结论　高剂量的 β CP对雄性大鼠睾丸有损伤作用     

苦豆子总碱对小鼠的抗突变作用

目的探讨苦豆子总碱对亚慢性受照小鼠的抗突变作用。方法昆明种近交系雄性小鼠腹腔注射高、中、低剂量的苦豆子总碱,采用60Coγ射线全身均匀低剂量间断照射小鼠106 d,累计吸收剂量为3.25 Gy,以小鼠睾丸精原细胞染色体畸变率、精子畸形率和骨髓嗜多染红细胞微核率为检测指标,对苦豆子总碱高、中、低3个剂量组进行观察。结果辐射损伤后小鼠染色体畸变率、精子畸形率和骨髓嗜多染红细胞微核率均增加,苦豆子总碱对受照小鼠上述受损指标具有一定的促进恢复作用。结论苦豆子总碱对亚慢性受照小鼠具有保护作用。     

双酚A对小鼠睾丸组织氧化损伤及生殖细胞凋亡的影响

目的研究双酚A(bisphenolA,BPA)对雄性小鼠睾丸组织氧化损伤及其对生殖细胞凋亡的影响。方法将52只健康成年雄性昆明种小鼠随机分为溶剂对照组(玉米油)和低(75 mg/kg·bw)、中(150 mg/kg·bw)、高(300 mg/kg·bw)剂量组,每组13只,连续经口染毒8周。处死小鼠后,解剖取材,称量睾丸的重量并计算脏器系数;取附睾,制成精子混悬液于镜下观察精子活动率、统计精子畸形率;采用酶标仪检测睾丸组织匀浆中超氧化歧化酶(SOD)、乳酸脱氢酶(LDH)活力及丙二醛(MDA)含量;采用qPCR方法检测凋亡相关基因CytC、Caspase-3及Bcl-2 mRNA表达量。结果各染毒剂量组较对照组睾丸脏器系数升高,精子活力随剂量升高明显降低(P0.05);精子畸形数及精子畸形率均随剂量升高明显升高(P0.05);各染毒剂量组睾丸组织SOD、LDH酶活力及MDA含量均升高,差异有统计学意义(P0.05);各染毒剂量组睾丸组织中CytC及Caspase-3 mRNA表达量较对照组均升高,Bcl-2 mRNA表达量较对照组降低,差异有统计学意义(P0.05)。结论 BPA引起雄性小鼠睾丸组织的氧化损伤及生殖细胞凋亡。     

螺旋藻片对小鼠睾丸染色体致畸变实验研究

目的探讨螺旋藻片的毒性作用。方法以4.0、2.0、1.0g.kg-1BW（体重Body Weight）剂量的螺旋藻片连续给小鼠灌胃5d,取小鼠两侧睾丸,制备小鼠睾丸生殖细胞染色体标本。结果各剂量组小鼠睾丸染色体断片、易位、畸变细胞率、常染色体单价体、性染色体单价体与溶剂对照组比较无显著性差异（P〉0.05）,而阳性对照组断片、畸变细胞率、常染色体单价体、性染色体单价体与溶剂对照组比较有极显著性差异（P〈0.01）。结论螺旋藻片各剂量组对小鼠睾丸生殖细胞无染色体畸变作用。     

农药克菌丹对小鼠生精上皮细胞超微结构的影响

农药克菌丹对小鼠体细胞及生殖细胞的诱变性问题,国外曾有争论,本室也相继有报道.有的报道对小鼠睾丸初级精母细胞染色体畸变及精子形态畸形,作了较细的论述,为进一步研究克菌丹对雄性生殖细胞的损伤类型,本实验利用     

益母草对小鼠雄性生殖细胞遗传损伤的防护作用

目的　观察中草药益母草对醋酸铅引起的小鼠雄性生殖细胞遗传损伤作用。方法　采用小鼠精子畸形试验、精原细胞姐妹染色单体互换试验和小鼠精子非程序DNA合成试验。结果　在 2 0～ 8 0g kg剂量范围 ,益母草对醋酸铅所诱发的小鼠精子畸形、精原细胞姐妹染色单体互换和小鼠精子非程序DNA合成有明显的抑制作用 (P <0 0 1) ,并且随着益母草浓度的增加 ,其抑制作用逐渐增强。结论　益母草对小鼠雄性生殖细胞遗传损伤具有防护作用     

人精子染色体分析方法及其在遗传和毒理学中的应用

环境化学物质对人类生殖细胞的诱变作用研究甚少,但其意义重大,因为生殖细胞的遗传损伤有可能对下一代产生不良影响。1978年Rudak等人利用去透明带金黄地鼠卵与人精子在体外异种受精,获得人精子染色体中期相标未,建立了人精子染色体分析方法。十年来共分析100多位正常人21390组精子染色体核型,平均结构染色体畸变率为11.5％;非整倍体率为1.4%。人精子在体外经辐射线(X线等)照射后,染色体畸变率明显升高,与剂量呈线性关系。martin等人观察了18名经放疗/化疗以及经化疗后的肿瘤患者,治疗后精子染色体畸变率亦明显升高,且在数年至十多年后仍高于正常人。人精子染色体分析方法可用于环境化学物质对人类生殖细胞(精子)诱变作用的监测。     

环丙沙星对雄性小鼠生殖细胞作用的研究

环丙沙星为含氟新型喹诺酮类抗菌药物,是在临床上应用的此类药物中具有代表性的药物,其急性毒性属低毒类,且抗菌谱、抗菌作用,抗菌速度和药代动力学都有显著特点。据文献报道一些氟喹酮类药物对睾丸生殖细胞有一定影响,为了解环丙沙星对睾丸生殖细胞有无诱变作用,本文采用雄性小鼠精于畸形试验和睾丸生殖细胞染色体畸变试验,观察了环丙沙星对雄性小鼠生殖细胞     

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.