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Ovalbumin (OA) sensitized guinea pigs were repeatedly challenged with 1% OA in saline nebulized ultrasonically at the 0, 10, 20, 60 and 70th min. The intensity of bronchial obstruction was measured by body plethysmography. The first three challenges (0, 10, 20 min) caused strong asthmatic reactions in all animals, the last two (60, 70 min) only mild ones in 10 out of 15 animals. The development of this tachyphylaxis was markedly reduced by pretreatment of the animals with cyclooxygenase inhibitors (indomethacin 10 mg/kg intraperitoneally resp. acetylsalicylic acid 10 mg/kg orally 2h before test). The effect of both inhibitors (i.e. inhibition of tachyphylaxis) was abolished by supplementing prostaglandin E2 as aerosol simultaneously to the allergen (100–200 ng per inhalation). The results suggest that allergen tachyphylaxis we have observed in vivo might be due to synthesis of cyclooxygenase products, e.g. prostaglandin E.Supported by Deutsche Forschungsgemeinschaft (grant Do 240) in part presented at the 17th workshop on pediatric research [Göttingen 1981, Eur. J. Pediatr. 135: 336 (1981)] 相似文献
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目的探讨长期口服左甲状腺素片对绝经后亚临床甲减女性患者心室结构、功能的影响。方法随机选择50例确诊且未经治疗的患亚临床甲减的绝经后女性(研究组),给予左甲状腺素片替代治疗。以血清TSH达到正常水平为观察起点,治疗后1年为观察终点,检测血清FT3、FT4、TSH,并使用二维超声心动图检测心脏结构和功能相关指标。同时选择45例与研究组患者年龄相匹配的绝经后健康女性作为对照。结果研究组患者接受左甲状腺素替代治疗前后,左心室质量指数均高于对照组。治疗前,与对照组比较,研究组左心室舒张功能、收缩功能及左心功能受损,右心室室壁厚度、舒张功能及右心功能受损。上述指标在左甲状腺素有效替代治疗后1年均有改善。结论亚临床甲减对绝经后女性患者的左右心室的结构、收缩及舒张、心功能均有影响。左甲状腺素替代治疗能够改善心脏结构和功能。 相似文献
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Tonic immobility (TI) is considered to be an innate fear response characterized by a temporary state of profound and reversible motor inhibition. TI occurs in a wide range of species in a predator-prey confrontation and is hypothesized to be a terminal defence response occurring when there is physical contact between prey and predator. The objective of the present study was to investigate the validity of the TI model in guinea pigs for detection of anxiolytic and/or antidepressant drug activity. Compounds that reduced TI include the serotonin (5-HT) releaser fenfluramine, the 5-HT(1A) receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and buspirone, the 5-HT(2C/2B) receptor antagonist SB206553, the 5-HT(2A) receptor antagonist MDL 100.151 -- but only at doses thought also to inhibit 5-HT(2C) receptors--the noradrenaline (NA) reuptake inhibitor desipramine, the benzodiazepine inverse agonist FG-7142, the alpha(2)-adrenergic receptor antagonist yohimbine, the neurokinin (NK)(1) receptor antagonist L-733.060, and the NK(2) receptor antagonist SR-48968. Compounds that increased TI include the benzodiazepine agonists diazepam and alprazolam, and the alpha(2)-adrenergic receptor agonist clonidine. The selective 5-HT reuptake inhibitors citalopram, paroxetine and fluoxetine, the 5-HT(1A) receptor antagonist WAY100.635, the 5-HT(2C) receptor agonist MK-212, the 5-HT/NA reuptake inhibitor imipramine, the NA reuptake inhibitor talopram, the benzodiazepine antagonist flumazenil, the alpha(2)-adrenergic receptor antagonist idazoxan and the psychostimulant amphetamine did not have any effect. These findings indicate that the serotonergic, noradrenergic and neurokinin systems are involved in mediating or modulating TI behaviour in guinea pigs. The potential of TI as a behaviour for detecting anxiolytic-like effect may be questioned due to the contradictory effect of the benzodiazepine ligands, which may be attributed to the sedative and/or ataxic effects of the compounds. Nevertheless, there is preclinical evidence suggesting that 5-HT(1A) receptor agonists, 5-HT(2C) receptor antagonists and NK(1) and NK(2) receptor antagonists possess anxiolytic potential. Only when results of clinical investigations of the anxiolytic potential of non-benzodiazepine ligands (for example the NK receptor antagonists) are available, will it be possible to determine fully the predictive validity of the TI model. 相似文献
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The capacity of N-oxidized metabolites of 4,4-methylenebis(2-chloroaniline) (MBOCA) to form hemoglobin (Hb) adducts was determined in vitro, and the formation of Hb adducts following in vivo administration of MBOCA was assessed with or without prior induction of cytochrome P-450 enzymes with phenobarbital or -naphthoflavone. Hb adduct formation was determined by electron-capture GLC of MBOCA as the heptafluorobutyryl derivative following mild acid hydrolysis of protein-bound MBOCA. The method was confirmed by gas chromatography-mass spectrometry with selected ion monitoring. N-hydroxy- and mononitroso-MBOCA, but not MBOCA itself, formed adducts to rat and human Hb in vitro in a dose-related manner. Binding was inhibited by cysteine and glutathione but not oxidized glutathione or methionine. Intravenous administration of as little as 0.04 mol/kg N-hydroxy-MBOCA to rats resulted in measurable formation of MBOCA-Hb adducts (0.9 ng/50 mg Hb). Intraperitoneal administration of 0.5–50 mg/kg MBOCA to rats, and subcutaneous administration of 5–500 mg/kg MBOCA to rats and 4–100 mg/kg to guinea pigs resulted in dose-related formation of Hb adducts. MBOCA-Hb remained elevated in blood for greater than 10 weeks following a single subcutaneous dose in guinea pigs. Pretreatment of rats with phenobarbital induced microsomal benzphetamine N-demethylase (BND) activity and resulted in a small increase in in vitro N- andortho- hydroxylation of MBOCA, but did not increase in vivo Hb adducts. Pretreatment of rats with -naphthoflavone induced microsomal aryl hydrocarbon hydroxylase as well as ethoxyresorufin-O-deethylase, and increased in vitro N- but notortho-hydroxylation of MBOCA. -Naphthoflavone pretreatment increased the formation of MBOCA-Hb adducts when rats were dosed with MBOCA at 100 and 500 mg/kg, but not 20 mg/kg subcutaneously. 相似文献
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Decreases of voltage-dependent K^+ currents densities in ventricular myocytes of guinea pigs by chronic oxidant stress 总被引:1,自引:0,他引:1
INTRODUCTION Intracellular K concentration plays an importantrole in the regulation of apoptosis process[1]. ExcessiveK efflux and intracellular K depletion may be respon-sible for the cell shrinkage and apoptotic death[2,3]. Cel-lular K homeostasis is maintained by K efflux and K uptake mechanism. Voltage-dependent K currents arethe major pathways for the K efflux, which indicatesthat voltage-dependent K currents are involved in theapoptosis. Several studies reported th… 相似文献
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Huang Wei Sui Jian - feng 《中国药理通讯》2005,22(4):53-54
Abstract:This research is designed to study the characteristic changes of different hippocampal neural firing and potential during the spatial discrimination cognition in awaked guinea pigs, combining the linear and nonlinear analytical methods, so as to discuss the role of hippocampus during the spatial information encoding and spatial learning. The main results are as follows: 1. In the cognition state, the study reveals that there is significant difference between the active cognition group and passive cognition group in the firing frequency and complexity ( P 〈 0. 05 ), but there is no significant difference between them in the spontaneous state (P 〉 0. 05 ). 相似文献
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Alcohol consumption increases the small intestinal bacterial overgrowth (SIBO) and intestinal permeability of endotoxin. The endotoxin mediated inflammatory signaling plays a major role in alcoholic liver fibrosis. We evaluated the effect of ascorbic acid (AA), silymarin and alcohol abstention on the alcohol induced endotoxemia and NF-κB activation cascade pathway in guinea pigs (Cavia porcellus). Guinea pigs were administered ethanol at a daily dose of 4 g/kg b.wt for 90 days. After 90 days, ethanol administration was stopped. The ethanol treated animals were divided into abstention, silymarin (250 mg/kg b.wt) and AA (250 mg/kg b.wt) supplemented groups and maintained for 30 days. The SIBO, intestinal permeability and endotoxin were significantly increased in the ethanol group. The mRNA expressions of intestinal proteins claudin, occludin and zona occludens-1 were significantly decreased in ethanol group. The mRNA levels of inflammatory receptors, activity of IKKβ and the protein expressions of phospho-IκBα, NF-κB, TNF-α, TGF-β1 and IL-6 were also altered in ethanol group. The expressions of fibrosis markers α-SMA, α1 (I) collagen and sirius red staining in the liver revealed the induction of fibrosis. But the supplementation of AA could induce greater reduction of ethanol induced SIBO, intestinal barrier defects, NF-κB activation and liver fibrosis than silymarin. The possible mechanism may be the inhibitory effect of AA on SIBO, intestinal barrier defect and IKKβ, which decreased the activation of NF-κB and synthesis of cytokines. This might have led to suppression of HSCs activation and liver fibrosis. 相似文献
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Effects of berberine on L-and T-type calcium channels in guinea pig ventricular myocytes 总被引:10,自引:2,他引:8
目的:研究小檗碱(Ber)对心室肌细胞钙通道的影响.方法:全细胞膜片箝技术.结果:Ber(10,30μmol·L-1)使豚鼠心室肌细胞L型钙流由1400±247pA分别减至978±204pA及617±23pA(n=5,P<005),抑制效应呈浓度依赖及非频率依赖,其电流-电压曲线的峰值下降.Ber(10μmol·L-1)使L型钙流失活曲线的最大半激活电压由-278mV变为-342mV,斜率因子由922变为1303,对激活曲线无影响.Ber(10,30μmol·L-1)使T型钙流峰值由加药前的154±80pA降至101±78pA及48±45pA(n=8,P<005).结论:Ber对L和T型钙通道均有抑制作用. 相似文献
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《中国医药指南》2019,(19)
目的分析弥漫性甲状腺肿伴甲亢患者经左甲状腺素治疗后临床效果。方法根据随机均等分组法划分2016年1月至2017年4诊治90例弥漫性甲状腺肿伴甲亢患者为对照组和观察组,两组分别采用他巴唑治疗及左甲状腺素治疗,对比两组不同治疗效果。结果两组治疗3个月甲状腺体积、TSH浓度、Tg含量、TR-ab情况、T3含量及T4含量比较,差异无统计学意义(P>0.05)。观察组治疗6个月甲状腺体积、TSH浓度、Tg含量、TR-ab情况明显较低(P<0.05);T4含量明显较高(P<0.05)。结论左甲状腺素应用在弥漫性甲状腺肿伴甲亢患者临床治疗当中,临床治疗价值较高,营造良好的Tg及TR-ab水平、缩小甲状腺体积,促使患者临床症状改善。 相似文献
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《中国医药指南》2020,(3)
目的探究小剂量左甲状腺素治疗良性甲状腺结节的临床效果。方法选取2016年1月至2017年1月在我院进行治疗的50例良性甲状腺结节患者,给予其小剂量左甲状腺素进行治疗,比较其治疗前后甲状腺体积及积极大小改变情况,并对治疗前后TC、TG、TSH、FT_4、HDL及LDL水平进行比较,同时记录其不良反应发生情况。结果患者甲状腺体积及结节直径在治疗前分别为(12.88±2.07)cm~3及(1.72±0.49)cm,经治疗,其水平分别降低至(9.06±1.25)cm~3及(1.29±0.38)cm,与治疗前相比差异显著(P <0.05),且患者治疗后,其TC及TSH分别由治疗前的(3.19±0.56)mmol/L及(2.63±0.75)mU/L降低至(2.71±0.23)mmol/L及(0.03±0.11)mU/L,差异显著(P <0.05),而TG、FT_4、LDL及HDL等指标,在治疗前后无显著改变(P> 0.05),另外,不良反应发生率为8.00%。结论对良性甲状腺结节患者采用小剂量左甲状腺素进行治疗,能够有效降低甲状腺体积及结节直径,对改善患者相应症状具有重要意义。 相似文献
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目的:研究金属硫蛋白(MT)对缺氧和复氧豚鼠乳头状肌动作电位的影响.方法:利用标准的玻璃微电极技术,将标本暴露于缺氧液(低氧,高钾,无糖,pH68)和MT.结果:MT(002mmol·L-1)对正常豚鼠乳头状肌的动作电位无影响;单纯将标本暴露于缺氧液,明显使APD20,APD50和APD90缩短,增高RP水平,降低APA及Vmax;缺氧液加入MT(002mmol·L-1)后,则使缺氧期间的RP,APA和Vmax的改变恢复正常,但APD进一步缩短;同时发现MT减少复氧期间导致的自律性的发生率.结论:MT具有钙调节剂的特征. 相似文献
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It has been reported that workers exposed to dicyclohexylmethane-4,4′-diisocyanate (HMDI) developed dermal sensitization with little accompanying pulmonary sensitivity (E. A. Emmett, 1976, J. Occup. Med., 18, 802–804; R. Israeli, V. Smirnov, and M. Sculsky, 1981, Int. Arch. Occup. Environ. Health, 48, 179–184). Such findings contrast with those reported for workers sensitized to toluene diisocyanate (TDI) where pulmonary symptomatology has been frequently cited. An animal model recently developed for sensitization to TDI (M. H. Karol, 1981, In Inhalation Toxicology and Technology, (B. K. J. Leong, ed.), pp. 233–246, Ann Arbor Science, Ann Arbor, Mich.; M. H. Karol, C. Dixon, M. Brady, and Y. Alarie, 1980, Toxicol. Appl. Pharmacol., 53, 260–270; M. H. Karol, B. A. Hauth, E. J. Riley, and C. M. Magreni, 1981, Toxicol, Appl. Pharmacol., 58, 221–230.) was employed to investigate characteristics of sensitivity resulting from exposure to HMDI. Comparison was made between sensitization to HMDI and to TDI. Guinea pigs were exposed to HMDI by topical application, intradermal and intraperitoneal injection, as well as toepad inoculation of HMDI in Freund's complete adjuvant. Each method of HMDI administration resulted in development of dermal sensitivity. In contrast to findings with TDI, animals injected with HMDI produced little, if any, antibody, and no pulmonary sensitivity was detected in any of 12 animals sensitized by topical exposure to HMDI. Two of eleven animals injected with HMDI in adjuvant displayed respiratory sensitivity. With HMDI, as in previous studies with TDI, the pattern of sensitivity observed in the animal model paralleled that noted previously in workers. 相似文献
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目的:观察塞治联合左甲状腺素治疗桥本氏甲亢的疗效。方法:从2014年9月~2015年9月在我院接受治疗的桥本氏甲亢患者中随机抽选52例,作为本次的研究对象,分为两组,对照组采用塞治治疗,研究组在对照组治疗基础上加用左甲状腺素治疗,观察两组临床疗效。结果:采用塞治联合左甲状腺素治疗的研究组,各项甲状腺指标、治疗总有效率和不良反应发生率等与对照组比较,差异存在统计学意义(P<0.05)。结论:塞治联合左甲状腺素治疗桥本氏甲亢的疗效较为显著,能够有效改善患者症状,具有临床应用价值。 相似文献
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Maren C. Podszun Nadine Grebenstein Ute Hofmann Jan Frank 《Toxicology and applied pharmacology》2013,266(3):452-458
It has been hypothesized in the literature that intake of high-dosage vitamin E supplements might alter the expression of cytochrome P450 enzymes (CYP), particularly CYP3A4, which may lead to adverse nutrient–drug interactions. Because previously published studies reported conflicting findings, we investigated the pharmacodynamics of the lipid-lowering drug atorvastatin (ATV), a CYP3A4 substrate, in response to high-dose α-tocopherol (αT) feeding and determined protein expression and activities of relevant CYP. Groups of ten female Dunkin–Hartley guinea pigs were fed a control (5% fat) or a high-fat control diet (HFC; 21% fat, 0.15% cholesterol) or the HFC diet fortified with αT (250 mg/kg diet), ATV (300 mg/kg diet) or both ATV + αT for 6 weeks. Relative to control, HFC animals had increased serum cholesterol concentrations, which were significantly reduced by ATV. High-dose αT feeding in combination with ATV (ATV + αT), albeit not αT feeding alone (αT), significantly lowered serum cholesterol relative to HFC, but did not alter the cholesterol-lowering activity of the drug compared to the ATV treated guinea pigs. Protein expression of CYP3A4, CYP4F2, CYP20A1 and OATP C was similar in all groups. Accordingly, no differences in plasma concentrations of phase I metabolites of ATV were observed between the ATV and ATV + αT groups. In conclusion, feeding guinea pigs high-doses of αT for 6 weeks did neither alter the hepatic expression of CYP, nor the pharmacodynamics and metabolism of ATV. High-dose αT intake is thus unlikely to change the efficacy of drugs metabolized by CYP enzymes, particularly by CYP3A4. 相似文献