黄芪总苷的抑瘤作用及其作用机制

目的　探讨黄芪总苷的抗肿瘤作用及其作用机制。方法　采用小鼠肝癌 (HepA)和肉瘤 (S1 80 )两种小鼠移植瘤的动物模型 ,以瘤重抑制率作指标。体外采用人宫颈癌细胞株HeLa细胞 ,用MTT法测肿瘤细胞的生长 ,流式细胞术及TUNEL法检测细胞周期及细胞凋亡。结果　黄芪总苷显著抑制小鼠肝癌 (HepA)和肉瘤 (S1 80 )的生长 ;体外可显著抑制HeLa细胞的生长 ,使细胞周期阻滞于G0 /G1 期 ,并诱导其凋亡。结论　黄芪总苷对小鼠肝癌 (HepA)与肉瘤(S1 80 )具有抑瘤作用。对HeLa细胞的生长有直接抑制作用。其抗肿瘤作用可能与细胞周期阻滞于G0 /G1 期和诱导细胞凋亡有关     

猴头多糖抗肿瘤及对免疫功能的影响

目的　研究猴头多糖 ( HEPS)对小鼠 S1 80 肉瘤及免疫功能的影响。方法　 H EPS按 10 0、2 0 0、40 0m g/ kg体重连续灌胃 15 d,测定荷瘤小鼠瘤重 ,通过检测小鼠抗体生成细胞、迟发性变态反应、NK细胞活性 ,荷瘤小鼠免疫器官分别检测 HEPS对体液免疫、细胞免疫、非特异免疫及异常免疫的调节作用。结果　 HEPS可显著抑制 S1 80 肉瘤的生长 ,提高荷瘤小鼠胸腺和脾重 ,增强正常小鼠抗体形成细胞溶解绵羊红细胞能力、迟发型变态反应能力、NK细胞活性。结论　 HEPS具有抗肿瘤及免疫调节作用     

姜黄素对S180肉瘤小鼠的抗肿瘤作用及对血清IL-2和IL-12水平影响的研究

目的研究姜黄素(curcumin)对S180肉瘤小鼠的作用及机制。方法建立S180肉瘤小鼠模型,给予姜黄素治疗后,观察其抗肿瘤作用及其对小鼠血清IL-2和IL-12水平的影响。结果姜黄素对S180肉瘤有显著抑制作用,可提高肉瘤小鼠的脾脏指数及胸腺指数;能显著提高血清IL-2和IL-12水平。结论姜黄素对S180肉瘤有显著抑制作用,其作用机制可能与升高机体细胞因子,调节小鼠免疫功能有关。     

姜黄素对S180肉瘤小鼠的抗肿瘤作用及对血清IL-2和IL-12水平影响的研究

目的 研究姜黄素( curcumin)对S180肉瘤小鼠的作用及机制.方法 建立S180肉瘤小鼠模型,给予姜黄素治疗后,观察其抗肿瘤作用及其对小鼠血清IL-2和IL-12水平的影响.结果 姜黄素对S180肉瘤有显著抑制作用,可提高肉瘤小鼠的脾脏指数及胸腺指数;能显著提高血清IL-2和IL-12水平.结论 姜黄素...     

壳寡糖对S180肉瘤小鼠抗肿瘤作用的研究

目的研究壳寡糖在S180肉瘤小鼠体内抑制肿瘤的作用机制。方法制造小鼠移植性肿瘤模型观察壳寡糖对肿瘤生长的影响,采用ELISA法检测对荷瘤小鼠外周血血清中IL-2和免疫组化法检测肉瘤组织中VEGF、b FGF表达含量的影响。结果壳寡糖对S180肉瘤生长的抑制率以中剂量为佳;能够提高S180肉瘤小鼠外周血血清中IL-2的含量,降低肉瘤组织中VEGF、b FGF表达,但中剂量效果较为显著(P<0.01,有统计学意义)。结论壳寡糖在小鼠体内具有抑制S180肉瘤生长和转移的作用。     

二氢卟吩e6的合成及其光敏化力和肿瘤光生物活性

由蚕沙叶绿素粗品,经酸碱降解反应制得二氢卟吩ｅ６（Ｉ）;并测定了１在Ｄ２Ｏ中对ＮＡＤＰＨ光氧化作用的敏化效应和对小鼠Ｓ１８０肉瘤的光动力损伤作用。初步试验结果表明：１在非细胞体系内的光敏化力和对小鼠Ｓ１８０肉瘤的光动力疗效均优于参比药物血卟啉衍生物（ＨＰＤ）。     

龙须菜多糖抑瘤活性及对荷瘤小鼠抗氧化作用的研究

目的 探讨龙须菜多糖(PGL)抗肿瘤作用及对荷瘤小鼠抗氧化能力的影响.方法 以S180荷瘤小鼠为模型,研究龙须莱热水提取的多糖对S180肉瘤生长的影响,通过测定S180荷瘤小鼠血液红细胞中超氧化物歧化酶(SOD)活性和肝匀浆中脂质过氧化物(LPO)含量评价PGL对小鼠抗氧化能力的作用.结果 PGL可显著抑制小鼠S180肉瘤的生长,当灌胃剂量为150mg·kg-1时,抑瘤率达63.56%,并能明显降低荷瘤小鼠体内LPO含量.结论 PGL能提高荷瘤小鼠抗氧化能力,PGL具有的抗氧化作用可能是实现其抗肿瘤活性的机制之一.     

聚乙二醇修饰对羟喜树碱隐形纳米囊泡的肿瘤靶向和抑瘤作用的影响

目的探讨聚乙二醇相对分子质量对载羟喜树碱(HCPT)的聚乙二醇化聚十六烷基氰基丙烯酸酯纳米囊泡(PEG-PHDCA)在S180肉瘤小鼠体内的肿瘤靶向性及抗肿瘤作用的影响。方法选用司盘60和PEG-PHDCA为载体材料,制备HCPT的PEG-PHDCA隐形纳米囊泡,进行S180肉瘤小鼠瘤内药动学试验和抑瘤试验。结果PEG相对分子质量为2 000、5 000、10 000的PEG-PHDCA纳米囊泡在S180肉瘤小鼠肿瘤中125I-HCPT的AUC分别为HCPT的9.21、13.82、9.48倍;对S180肉瘤小鼠抑瘤率分别为88%、97.1%、80.8%,普通纳米粒PHDCA组抑瘤率为41.8,而原药组抑瘤率仅为17.3%。结论PEG修饰纳米囊泡明显优于原药和未经PEG修饰纳米囊泡,PEG相对分子质量为5 000,粒径为80 nm左右时,载HCPT的隐形纳米囊泡具有最佳肿瘤靶向作用。     

桦木酸的抗肿瘤作用及其诱导KB细胞凋亡的研究

目的研究桦木酸(betulinic acid,BetA)体内对S180肉瘤的抑制作用和体外对人口腔上皮癌(KB)细胞系凋亡的诱导活性。方法建立小鼠体内荷S180肉瘤模型,测定BetA的体内抑瘤率;采用MTT分析、细胞形态学观察、原位末端标记和流式细胞仪检测等方法检测BetA对KB细胞生长状态和细胞周期的影响以及诱导细胞凋亡的作用。结果BetA 800和1 200 mg.kg-1给荷瘤小鼠灌胃,对S180肉瘤有显著的抑制作用;体外对KB细胞生长呈剂量依赖性抑制作用(其IC50为11.60μmol.L-1),并出现大量凋亡细胞。结论BetA体内对S180肉瘤、体外对KB细胞增殖均有抑制作用,诱导肿瘤细胞死亡的主要途径可能是凋亡。     

枸杞子糖缀合物对荷瘤小鼠的抑瘤作用

目的:研究枸杞子糖缀合物对S180荷瘤小鼠的肿瘤抑制作用.方法:选择Balb/c小鼠50只,体重(20～25)g,随机分为5组.利用接种肉瘤S180诱导的小鼠肿瘤模型,检测对S180肉瘤的抑制率.结果:枸杞子糖缀合物可抑制小鼠S180肉瘤的生长.结论:枸杞子糖缀合物具有肿瘤抑制活性.     

Addictive agents and intracranial stimulation (ICS): novel antagonists and agonists of morphine and pressing for ICS

Rats fixed with chronically indwelling bipolar electrodes pressed for intracranial stimulation (ICS) of the lateral hypothalamus during daily sessions. The effects of two antagonists of morphine (Win 44,441 and naloxone) were then assessed. Naloxone (10 mg/kg) produced its characteristic reduction in pressing. Win 44, 441 produced a reliable increase in pressing at doses as small as 1 mg/kg. Large doses of morphine (10 mg/kg) produced its characteristic effects: depression in pressing when given 1 hr before the test session and facilitation when given 3 hr before the test session. Win 44,441 antagonized morphine's depressive effects. Other compounds (Win 44,156, Win 42,156), having similar structure to Win 44,441 but having agonist and mixed agonist-antagonist activity with respect to analgesia, also facilitated pressing for ICS. All three compounds' effects on pressing for ICS were antagonized by naloxone. It is inferred that opioids' facilitatory effects on pressing for ICS are separable from opioids' other capabilities such as production of analgesia.     

Anorexigenic effects of GLP-1 and its analogues

GLP-1 receptors are expressed in the brain, especially in the regions responsible for the regulation of food intake, and intracerebroventricular injection of GLP-1 results in inhibition of food intake. Peripheral administration of GLP-1 dose-dependently enhances satiety and reduces food intake in normal and obese subjects as well as in type 2 diabetic patients. So far, the mechanisms by which GLP-1 exerts its effects are not completely clear. Interactions with neurons in the gastrointestinal tract or possibly direct access to the brain through the blood-brain barrier as observed in rats are possible and discussed in this chapter as well as a novel hypothesis based on the finding that GLP-1 is also expressed in taste cells. Finally, the role of GLP-1 receptor agonists as a possible treatment option in obesity is discussed as well as the role of GLP-1 in the effects of bariatric surgery on adiposity and glucose homeostasis.     

Cyclooxygenase isoenzymes and newer therapeutic potential for selective COX-2 inhibitors

Cyclooxygenase (COX), also known as prostaglandin G/H synthase, is a membrane-bound enzyme responsible for the oxidation of arachidonic acid to prostaglandins that was first identified over 20 years ago. In the past decade, however, more progress has been made in understanding the role of cyclooxygenase enzymes in various pathophysiological conditions. Two cyclooxygenase isoforms have been identified and are referred to as COX-1 and COX-2. COX-1 enzyme is constitutively expressed and regulates a number of housekeeping functions such as vascular hemostasis and gastroprotection, whereas COX-2 is inducible (i.e., sites of inflammation) by number of mediators such as growth factors, cytokines and endotoxins. Nonsteroidal antiinflammatory drugs (NSAIDs) produce their therapeutic effects through inhibition of COX, the enzyme that makes prostaglandins. Nonselective inhibition of COX isoenzyme leads to not only beneficial therapeutic effects but also a number of detrimental effects. Beneficial effects are due to inhibition of COX-2 and detrimental effects are due to inhibition of physiological COX-1. The present review discusses the biology as well as the role of these COX isoenzymes in various pathophysiological conditions.     

Effects of acute and chronic buspirone on impulsive choice and efflux of 5-HT and dopamine in hippocampus, nucleus accumbens and prefrontal cortex

Rationale Reduced central serotonin (5-HT) activity has been associated with impulsive choice behaviour, but there is no consensus about the precise nature of these effects. Behavioural and neurochemical effects of 5-HT_1A agonists such as buspirone depend critically on the dose and the duration of treatment. We thus undertook a parametric study of the effects of acute and chronic buspirone on the performance on a test of delayed gratification, as well as on the efflux of serotonin and dopamine (DA) in cortical and subcortical regions in rats.Objectives Three experiments examined (i) the effects of acute buspirone on impulsive choice and how such effects were modified by prior chronic exposure to buspirone; (ii) the effects of chronic buspirone on impulsive choice; (iii) the effects on impulsive choice of a selective 5-HT_1A antagonist, WAY-100635 tested alone and in combination with buspirone; (iv) the effects of chronic and acute buspirone on 5-HT and DA efflux in anaesthetised rats.Methods In experiment 1, rats previously trained on the delayed gratification task were tested with acute buspirone (0.5, 1 and 2 mg/kg). The same rats were then treated with chronic buspirone (1 mg/kg/day) over the next 65 days, and the effects of acute buspirone (1 mg/kg) re-determined at 20, 45 and 65 days of chronic treatment. In experiment 2, two groups of rats trained on the delayed gratification task were treated either with saline or buspirone (1 mg/kg/day) continually for 65 days before being tested with acute buspirone (1 mg/kg), WAY-100635 (0.08 mg/kg), or a combination of the two drugs. In experiment 3, rats received the same regimen of buspirone dosing as in experiment 2, before receiving in-vivo microdialysis for 5-HT and DA in the ventral hippocampus, nucleus accumbens and medial prefrontal cortex.Results Acute buspirone dose dependently increased the choice for the small, immediate reinforcer (impulsive choice) but the effects of 1 mg/kg were reversed on chronic administration of buspirone. This increased choice of the large, delayed reinforcer, which was not accompanied by any changes in baseline (non-drugged) performance, was blocked by the 5-HT_1A receptor antagonist WAY-100635. The chronic buspirone regimen did not alter buspirone-evoked reductions in 5-HT efflux in hippocampus but did lead to a differential effect of acute buspirone in medial prefrontal cortex, with the chronic buspirone and saline groups exhibiting decreases and increases in efflux, respectively. There were no systematic changes in DA efflux under any condition.Conclusions These findings show that the effects of acute buspirone on impulsive choice are reversed following chronic treatment and are mediated by 5-HT_1A receptors, and suggest, in addition, that the behavioural effects may involve changes in 5-HT functioning in medial prefrontal cortex.     

Direct and indirect effects of pollutants on algae and algivorous ciliates in an aquatic indoor microcosm

An aquatic indoor microcosm was used to study effects of the pesticides parathion-methyl and prometryn on phototrophic flagellates (Cryptomonas sp.) and predatory ciliates (Urotricha furcata). Parathion-methyl caused effects to flagellates and ciliates at the range of low mg L(-1), regardless of whether the organisms were exposed separately or combined in the multi-species test system. Prometryn caused effects on the flagellates at low microg L(-1) concentrations, resulting in a NOEC of 6.9 microg L(-1) in the single-species test and a NOEC of 15.2 microg L(-1) in the multi-species microcosm. For ciliates the NOEC decreased by factor 145 in the multi-species test compared to the NOEC of 2.2 mg L(-1) in the single-species test when exposed to prometryn. The lower NOEC for ciliates exposed to prometryn in the microcosm was most likely caused by an indirect effect due to reduced availability of flagellates as food. The measurement of nutrient concentrations in the test media and organisms facilitated the modelling of effects. The presented aquatic indoor microcosm is considered as a tool which could be standardised and applied as an instrument to provide data for higher tier risk assessment.     

5-Hydroxytryptamine1A receptors and behavioral responses

The special role of behavioral studies in attempting to understand the substrates for the psychotherapeutic actions of 5-hydroxytryptamine1A (5-HT1A)-selective agents, such as buspirone and other azapirones, is reviewed. The effects of buspirone and related drugs is discussed in three different types of behavioral studies: (1) unconditioned behaviors elicited by 5-HT agonists; (2) drug discrimination studies; and (3) conditioned behaviors that predict clinical drug effects. These studies have helped define important neuropharmacologic actions on 5-HT receptors that may contribute to therapeutic effects in anxiety and depression. Finally, critical problems for advancing our understanding of the association between 5-HT receptor subtypes and behavior are discussed.     

Chronic fluoxetine-induced desensitization of 5-HT1A and 5-HT1B autoreceptors: regional differences and effects of WAY-100635

Desensitization of 5-HT(1A) and 5-HT(1B) autoreceptors is thought to be the mechanism underlying the therapeutic effects of fluoxetine and other selective serotonin reuptake inhibitors when these are administered chronically. The blockade of 5-HT(1A) autoreceptors occurring on administration of a selective serotonin reuptake inhibitor together with a 5-HT(1A) autoreceptor antagonist is responsible for the acute increase in 5-hydroxytryptamine (serotonin, 5-HT) levels observed under these circumstances. The effects of repeated administration of selective serotonin reuptake inhibitors together with 5-HT(1A) receptor antagonists have not been widely studied. In this work, we found that the effects of fluoxetine (5 mg/kg, i.p., daily for 12 days) to desensitize 5-HT(1B) autoreceptors in the frontal cortex, as measured by the effect of the locally administered 5-HT(1B) receptor agonist, 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (CP 93129), and to desensitize 5-HT(1A) autoreceptors as measured by the action of the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT; 50 microg/kg, s.c.) to reduce 5-HT levels in cortex, were prevented by concomitant administration of the 5-HT(1A) receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexanecarboxamide (WAY-100635; 0.3 mg/kg, s.c.). 5-HT(1B) receptor activity in the hypothalamus, as measured by the effects of locally administered CP 93129, and 5-HT(1A) autoreceptor activity, as determined by the effects of subcutaneous 8-OH-DPAT to reduce 5-HT levels in hypothalamus, were not altered either by fluoxetine alone or by fluoxetine in the presence of WAY-100635. The data suggest that the regulation of extracellular levels of 5-HT in the cortex and hypothalamus is subject to different autoregulatory mechanisms.     

Comparative cytotoxicity of naphthalene and its monomethyl- and mononitro-derivatives in the mouse lung

Male Swiss-Webster mice were exposed to naphthalene, 1-methyl-, 2-methyl-, 1-nitro- and 2-nitronaphthalene by intraperitoneal injection of peanut oil solutions over a dose range of 0.5-3.0 mmol kg-1 body weight. Treated mice were killed at times from 6 hours to 14 days post-treatment. Tissues were analyzed for cytotoxic effects by optical and electron microscopy, and for cell proliferation by autoradiography following in vitro labeling of lung slices with 3H-thymidine. The naphthalene derivatives varied widely in their cytotoxic effects. The most toxic was 1-nitronaphthalene with no mice surviving doses greater than 1 mmol kg-1. Naphthalene and 2-methylnaphthalene were about equally toxic, followed by 2-nitro- and 1-methylnaphthalene, in decreasing order of toxicity. In all cases the first evidence of cytotoxic effects was seen in the Clara cells of the bronchiolar epithelium, and, at the highest doses, toxic effects were found in the adjacent ciliated cells. Changes could be detected at the ultrastructural level at all doses, and within 6 hours after treatment. Only slight effects were seen in other cell types. Increased cell proliferation following chemical treatment was seen only in the bronchiolar epithelium, among cells tentatively identified as Clara cells or their precursors. Cytotoxic effects of naphthalene and its 1- and 2-methyl derivatives were confined to the lung, with minimal evidence of toxicity in the liver and kidney. The mononitronaphthalenes both produce small areas of centrizonal necrosis in the liver, but no discernible effects in the kidney. The experiments demonstrate the effect of small structural differences on the cytotoxicity of this group of environmental pollutants and also illustrate the sensitivity of the Clara cell as a target for xenobiotics.     

Effects of cytokines on contractile and dilator responses of airway smooth muscle

1. Increased bronchoconstrictor responses to contractile agonists and decreased dilator responses to beta-adrenoceptor agonists are characteristics of human asthma. One explanation for these features of asthma is that cytokines released in the asthmatic airway have direct effects on airway smooth muscle cells that alter their phenotype. 2. The present review summarizes data indicating that inflammatory cytokines, such as interleukin (IL)-1 beta and tumour necrosis factor-alpha, T helper (h) 1 cytokines, such as interferon-gamma, and Th2 cytokines, such as IL-13 and IL-5, have the capacity to enhance contractile responses and/or decrease relaxant responses of airway smooth muscle. These effects are observed in smooth muscle from human airways and airway smooth muscle of other species. 3. Understanding the mechanistic basis for the effects of these cytokines may prove to be an important step in improving the efficacy of beta-adrenoceptor agonists for the treatment of asthma.     

Pharmacological profile and clinical effect of zolpidem (Myslee tablets), a hypnotic agent

Zolpidem is a non-benzodiazepine hypnotic agent with a chemical structure of imidazopyridine. In vitro and in vivo binding studies, zolpidem exhibits selectivity to omega 1 receptors (GABAA-receptor subtypes containing alpha 1 subunits). Unlike benzodiazepines, zolpidem produces sedative effects in preference to anxiolytic, anticonvulsant and myorelaxant effects in behavioral experiments using mice. Double-blind comparative studies with reference drugs such as triazolam and zopiclone show that zolpidem is an effective and highly safe drug for the treatment of insomnia. In addition, zolpidem does not produce next-day residual effects, rebound insomnia and tolerance. This clinical profile of zolpidem may be related to its selectivity and high intrinsic activity for omega 1 receptors.