Allergen tachyphylaxis of guinea pigs in vivo: A prostaglandin E mediated phenomenon?

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)]     

左甲状腺素替代治疗对绝经后亚临床甲减患者心室结构和功能的影响

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。     

左甲状腺素钠片溶出度检测方法的改进

目的:改进左甲状腺素钠片的溶出度检测方法.方法:通过改变左甲状腺素钠片溶出度检查中片的投放量,采用HPLC法,色谱柱为Kromasoil ODS C18柱,流动相为甲醇:水:磷酸(600:400:1);检测波长:225 nm;流速:1.0 ml·min-1;进样量:200 μl,外标法计算.结果:左甲状腺素在0.05～2.00 μg·ml-1范围内,呈良好线性关系,r=0.999 9;平均回收率为97.3%,脚为0.79%(n:9).结论:本法简便,准确,重现性好.     

Tonic immobility in guinea pigs: a behavioural response for detecting an anxiolytic-like effect?

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.     

Unlabeled hemoglobin adducts of 4,4′-methylenebis (2-chloroaniline) in rats and guinea pigs

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.     

Decreases of voltage-dependent K^＋ currents densities in ventricular myocytes of guinea pigs by chronic oxidant stress

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…     

The study of dorsal hippocampal potential and neuronal activity during the spatial discrimination cognition in awaked guinea pigs

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 ）.     

Ascorbic acid suppresses endotoxemia and NF-κB signaling cascade in alcoholic liver fibrosis in guinea pigs: A mechanistic approach

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.     

Effects of berberine on L-and T-type calcium channels in guinea pig ventricular myocytes

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＜００５），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－２７８ｍＶ变为－３４２ｍＶ，斜率因子由９２２变为１３０３，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＜００５）．结论：Ｂｅｒ对Ｌ和Ｔ型钙通道均有抑制作用．     

左甲状腺素在弥漫性甲状腺肿伴甲亢患者临床治疗中的应用效果

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。     

小剂量左甲状腺素治疗良性甲状腺结节的临床效果观察

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。     

Effects of metallothionein on action potentials of anoxic and reoxygenated papillary muscles of guinea pigs

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，ｐＨ６８）和ＭＴ．结果：ＭＴ（００２ｍｍｏｌ·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（００２ｍｍｏｌ·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．     

Extensive skin sensitization with minimal antibody production in guinea pigs as a result of exposure to dicyclohexylmethane-4,4′-diisocyanate

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.     

塞治联合左甲状腺素治疗桥本氏甲亢的疗效观察

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。     

抗组胺药的药物相互作用

介绍了抗组胺药物和其他临床常用药物的相互作用,为患者安全用药提供参考.第一、二代抗组胺药易与多种药物发生相互作用而致心脏毒性等不良反应,第三代抗组胺药联用时不会导致严重的不良反应.所以抗组胺药作为临床和OTC常用抗过敏药,应对其药物相互作用及产生的不良反应引起注意.     

High-dose supplementation with natural α-tocopherol does neither alter the pharmacodynamics of atorvastatin nor its phase I metabolism in guinea pigs

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.