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浙江大学学报（医学版） 2003年第4期32卷 300-303页

作者：许继德谢强敏陈季强卞如濂浙江大学医学院国家食品药品监督管理局浙江呼吸药物研究实验室

目的 :比较 RR-福莫特罗和 rac-福莫特罗对人支气管舒张作用。方法 :将内径 2～ 4 mm、长 15 mm的人支气管螺旋条置入持续供氧的浴槽内 ,静息张力为 1g,以蓄积给药法测定 RR-福莫特罗 (10 pmol·L-1～ 3.2 μmol·L-1)和 rac-... 详细信息

目的 :比较 RR-福莫特罗和 rac-福莫特罗对人支气管舒张作用。方法 :将内径 2～ 4 mm、长 15 mm的人支气管螺旋条置入持续供氧的浴槽内 ,静息张力为 1g,以蓄积给药法测定 RR-福莫特罗 (10 pmol·L-1～ 3.2 μmol·L-1)和 rac-福莫特罗 (10 pmol·L-1～ 3.2 μmol·L-1)在静息情况下 ,及氨甲酰胆碱 (10 μmol· L-1)或组胺 (10 0μmol·L-1)引起收缩情况下的张力改变。结果 :RR-福莫特罗在静息状况下支气管舒张作用强于 rac-福莫特罗 (P<0 .0 5 )。 RR-福莫特罗和 rac-福莫特罗对抗由氨甲酰胆碱和组胺引起的收缩 ,且 RR-福莫特罗的对抗作用强于rac-福莫特罗 (P<0 .0 5 )。结论 :RR-福莫特罗对人支气管的舒张作用强于 rac-福莫特罗。

关键词：支气管/药物作用卡巴胆碱组胺类药立体异构现象福莫特罗支气管舒张

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Effect of nitrogen dioxide on respiratory viral infection in airway epithelial cells

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ENVIRONMENTAL RESEARCH 1999年第2期81卷 159-166页

作者： Becker, S Soukup, JM US EPA Natl Hlth & Environm Effects Res Lab Res Triangle Pk NC 27711 USA

Nitrogen dioxide (NO2) is a common air pollutant outdoors and indoors in homes with unvented combustion sources. It is also a constituent of tobacco smoke. Epidemiological studies suggest that children exposed to NO2, or living with smoking parents, have an increased incidence of respiratory viral infections. The most common virus causing severe respiratory symptoms in infants and young children is respiratory syncytial virus (RSV), In the present study we investigated whether NO2 exposure affects RSV infection in airway epithelial cells, the host cells for viral replication and virus-induced cytokine production. Cultures of the bronchial epithelial cell line BEAS-2B exposed to 0.5, 1.0, and 1.5 ppm NO2 for 60 min were infected with RSV Viral replication, as well as RSV-induced interleukin (IL)-6 and IL-8, was assessed at various times postinfection, The NO2 doses used were not toxic to the BEAS-2B cells as measured by release of lactic dehydrogenase (LDH). The internalization of RSV was increased by exposure to 0.5 ppm NO2 and decreased by exposure to 1.5 ppm NO2, On the other hand, the release of infectious virus 48 h postexposure was not affected by the two lower doses of NO2, but was significantly reduced in cells exposed to 1.5 ppm NO2, Virus-induced cytokine production was also significantly reduced in cells exposed to 1.5 ppm NO2, and not affected by 0.5 and 1.0 ppm. It is likely that the decrease in cytokine production is related to the decrease in viral burden. These data suggest that possible increases in viral clinical symptoms associated with NO2 may not be caused by increased susceptibility of the epithelial cells to infection but may result from effects of NO2 on host defenses that prevent the spread of virus. (C) 1999 Academic Press.

关键词：空气污染物/毒性支气管/药物作用支气管/免疫学支气管/病毒学细胞系细胞因子类/生物合成剂量效应关系药物上皮细胞/药物作用上皮细胞/免疫学上皮细胞/病毒学二氧化氮/毒性呼吸道合胞病毒/药物作用病毒复制/药物作用人类

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Immune organs and haemopoietic system under modelling of the mission factors

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ACTA ASTRONAUTICA 1997年第1期41卷 57-62页

作者： Sapin, MR Grigoriev, AI Erofeeva, LM Grigorenko, DE Fedorenko, BS Moscow Med Sechenov Acad Moscow 103904 Russia

Literary and experimental data on the character of changes in immune organs and lymphoid tissue of respiratory system and digestive system in laboratory animals during the mission factors model are given. Inhibition of reproductive function in bone marrow, thymus and spleen under irradiation of gamma-rays and accelerated carbon ions, tensity of immune response in the lymphoid structures of larynx, trachea and bronchi under the influence of acetaldehyde vapors and decrease of lymphoid tissue square on histological series in spleen and small intestine with an increase of concentration of microbial bodies in the drinking water were estimated. (C) 1998 Elsevier Science Ltd. All rights reserved.

关键词：骨髓细胞/辐射效应支气管/药物作用支气管/病理学宇宙辐射红细胞计数/辐射效应 γ射线吸入暴露小肠/免疫学小肠/病理学喉/药物作用喉/病理学淋巴组织/免疫学淋巴组织/病理学淋巴组织/辐射效应小鼠近交BALBC 大鼠 Wistar 脾/免疫学脾/病理学脾/辐射效应胸腺/免疫学胸腺/病理学胸腺/辐射效应气管/药物作用气管/病理学水微生物学给水动物男(雄)性小鼠大鼠

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Role of peptidase and cyclooxygenase inhibitors in the guinea-pig bronchial response to the synthetic endothelin ET_B agonist IRL 1620 and antagonist BQ-788

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JOURNAL OF AUTONOMIC PHARMACOLOGY 1999年第4期19卷 201-207页

作者： Lazzeri, N Nieri, P Lenzi, P Ratti, C Breschi, MC Univ Pisa Dept Psychiat Neurobiol Pharmacol & Biotechnol I-56126 Pisa Italy Univ Pisa Dept Human Morphol & Appl Biol I-56126 Pisa Italy

1 In isolated guinea-pig bronchial preparations the selective endothelin ETB agonist, IRL 1620 caused a concentration-dependent contraction. The pD(2) value (7.16 +/- 0.09, n = 6) was significantly increased in the presence of peptidase inhibitors (thiorfan 1 mu M, captopril 1 mu M, bestatin 1 mu M) (pD(2) = 7.75 +/- 0.09, n = 6). Indomethacin (5 mu M) did not appear to influence the ETB-agonist pD(2) value (6.92 + 0.11, n = 6) but potentiated its maximal response significantly (67.23 +/- 4.81% vs. 53.37 +/- 4.80%). 2 The concentration-response curve for the contractile response to IRL 1620 (pD(2) = 7.83 +/- 0.01, (n) under bar = 16);was reproducible, although not completely, since the second curve to this selective ETB agonist was shifted significantly to the right (pD(2) = 7.34 +/- 0.09, n = 16) and a decrease in the maximal response was observed (20.0 +/- 2.0%). 3 BQ 788, a selective antagonist for ETB receptors, employed in concentrations ranging from 1.5 to 150 nM, caused a dose-dependent shift to the right of the concentration-response curve to IRL 1620, with a pIC(50) value of 8.11 +/- 0.03;this action was not influenced by adding enzyme inhibitors (pIC(50) = 8.17 +/- 0.29). 4 Our data show that IRL 1620 undergoes a hydrolytic metabolism in guinea-pig bronchial preparations, which could influence the calculation of the pD(2). Pretreatment of the tissue with peptidase inhibitors and indomethacin is consequently significant in the evaluation of IRL 1620 activity, while it does not influence the action of the antagonist, BQ 788.

关键词：支气管/药物作用环加氧酶抑制药/药理学剂量效应关系药物内皮缩血管肽类/药理学吲哚美辛/药理学寡肽类/药理学肽碎片/药理学哌啶类/药理学氯化钾/药理学蛋白酶抑制药/药理学受体内皮素B 受体内皮缩血管肽/激动剂受体内皮缩血管肽/拮抗剂和抑制剂动物豚鼠男(雄)性

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Cyclin D1 proteolysis: A retinoid chemoprevention signal in normal, immortalized, and transformed human bronchial epithelial cells

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JOURNAL OF THE NATIONAL CANCER INSTITUTE 1999年第4期91卷 373-379页

作者： Boyle, JO Langenfeld, J Lonardo, F Sekula, D Reczek, P Rusch, V Dawson, MI Dmitrovsky, E Mem Sloan Kettering Canc Ctr Sloan Kettering Inst Head & Neck Serv New York NY 10021 USA Mem Sloan Kettering Canc Ctr Sloan Kettering Inst Mol Med Lab New York NY 10021 USA Mem Sloan Kettering Canc Ctr Sloan Ketting Inst Thorac Surg Serv New York NY 10021 USA Mem Sloan Kettering Canc Ctr Sloan Kettering Inst Mol Pharmacol & Therapeut Program New York NY 10021 USA Mem Sloan Kettering Canc Ctr Sloan Kettering Inst Dept Pathol New York NY 10021 USA Bristol Myers Squibb Pharmaceut Res Inst Buffalo NY USA SRI Int Retinoid Program Menlo Park CA 94025 USA

Background: Retinoids (derivatives of vitamin A) are reported to reduce the occurrence of some second primary cancers, including aerodigestive tract tumors. In contrast, beta-carotene does not reduce the occurrence of primary aerodigestive tract cancers. Mechanisms explaining these effective retinoid and ineffective carotenoid chemoprevention results are poorly defined. Recently, the all-trans-retinoic acid (RA)-induced proteolysis of cyclin D1 that leads to the arrest of cells in G(1), phase of the cell cycle was described in human bronchial epithelial cells and is a promising candidate for such a mechanism. In this study, we have investigated this proteolysis as a common signal used by carotenoids or receptor-selective and receptor-nonselective retinoids, Methods: We treated cultured normal human bronchial epithelial cells, immortalized human bronchial epithelial cells (BEAS-2B), and transformed human bronchial epithelial cells (BEAS-2B(NNK)) with receptor-selective or receptor-nonselective retinoids or with carotenoids and studied the effects on cell proliferation by means of tritiated thymidine incorporation and on cyclin D1 expression by means of immunoblot analysis. We also examined whether calpain inhibitor I, an inhibitor of the 26S proteasome degradation pathway, affected the decline (i,e., proteolysis) of cyclin D1, Results: Receptor-nonselective retinoids were superior to the carotenoids studied in mediating the decline in cyclin D1 expression and in suppressing the growth of bronchial epithelial cells. Retinoids that activated retinoic acid receptor beta or retinoid X receptor pathways preferentially led to a decrease in the amount of cyclin D1 protein and a corresponding decline in growth. The retinoid-mediated degradation of cyclin D1 was blocked by cotreatment with calpain inhibitor I. Conclusions: Retinoid-dependent cyclin D1 proteolysis is a common chemoprevention signal in normal and neoplastic human bronchial epithelial cells. In contrast, caroten

关键词：抗致癌药/药理学支气管/药物作用支气管/代谢支气管肿瘤/代谢支气管肿瘤/预防和控制卡配因/拮抗剂和抑制剂类胡萝卜素类/药理学细胞培养的细胞周期蛋白D1/代谢上皮细胞/药物作用上皮细胞/代谢维生素A酸类/药理学人类

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USE OF EPHEDRINE IN BRONCHODILATOR THERAPY

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PEDIATRIC CLINICS OF NORTH AMERICA 1975年第1期22卷 121-127页

作者： WEINBERGER, MM UNIV COLORADO MED CTRDIV CLIN PHARMACOL 2253PEDIAT ALLERGY CLIN4200 E 9TH AVEDENVERCO 80220 NATL JEWISH HOSP & RES CTR DENVERCO

New data regarding theophylline have enhanced its importance as an oral bronchodilator. Ephedrine has thus become the oral bronchodilator of second choice for other than mild intermittent asthma. The introduction of newer, more potent oral sympathomimetic agents may further decrease even the currently limited indications for this drug.

关键词：哮喘/药物疗法支气管/药物作用中枢神经系统疾病/化学诱导药物疗法联合麻黄碱/副作用麻黄碱/治疗应用胃肠疾病/化学诱导入睡和睡眠障碍/化学诱导茶碱/治疗应用人类

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Genistein inhibits constitutive and inducible NFκB activation and decreases IL-8 production by human cystic fibrosis bronchial gland cells

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AMERICAN JOURNAL OF PATHOLOGY 1999年第2期155卷 473-481页

作者： Tabary, O Escotte, S Couetil, JP Hubert, D Dusser, D Puchelle, E Jacquot, J INSERM U514 F-51092 Reims France Hop Broussais Dept Chirurg Cardiovasc F-75674 Paris France Hop Cochin Serv Pneumol F-75674 Paris France

The inflammatory pathogenesis in airways of patients with cystic fibrosis (CF) is still unresolved. We demonstrate here that in in situ human Delta F508 homozygous CF bronchial tissues, submucosal gland cells exhibit an absence of inhibitor factor kappa B alpha (I kappa B alpha) and high levels of chemokine interleukin-8 (IL-8) expression. These results were confirmed by cultured human CF bronchial gland cells in which a lack of cytosolic I kappa B alpha and high levels of constitutively activated nuclear factor kappa B (NF kappa B) associated with an up-regulation of IL-8 production (13-fold increase) were found when compared to non-CF (control) disease bronchial gland cells. We also demonstrated that the isoflavone genistein, a well known CFTR mutant Cl- channel stimulator, significantly reduces the endogenous and Pseudomonas aeruginosa lipopolysaccharide-induced IL-8 production in cultured CF bronchial gland cells by increasing cytosolic I kappa B alpha protein levels. Overall, results show that genistein is a potent inhibitor of the activated NF kappa B identified in CF gland cells. This strong inhibition of constitutively activated NF kappa B and the resulting down-regulation of IL-8 production by genistein in the CF gland cells highlights the key role played by cytosolic I kappa B alpha in the regulation of inflammatory processes in CF human airway cells.

关键词：支气管/药物作用支气管/代谢细胞核/代谢细胞培养的囊性纤维化/代谢剂量效应关系药物酶抑制剂/药理学酶联免疫吸附测定染料木黄酮/药理学免疫组织化学白细胞介素8/生物合成脂多糖类/药理学肺移植 NF-κB/分析 NF-κB/拮抗剂和抑制剂 NF-κB/代谢铜绿假单胞菌/代谢时间因素青少年成年人老年人儿童女(雌)性人类男(雄)性中年人

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In vivo and in vitro correlation of pulmonary map kinase activation following metallic exposure

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INHALATION TOXICOLOGY 2000年第6期12卷 453-468页

作者： Silbajoris, R Ghio, AJ Samet, JM Jaskot, R Dreher, KL Brighten, LE US EPA Human Studies Div Natl Hlth & Environm Effects Res Lab Res Triangle Pk NC 27711 USA US EPA Expt Toxicol Div Natl Hlth & Environm Effects Res Lab Res Triangle Pk NC 27711 USA Univ N Carolina Ctr Environm Med & Lung Biol Chapel Hill NC USA

Residual oil fly ash (ROFA) is a particulate pollutant produced in the combustion of fuel oil. Exposure to ROFA is associated with adverse respiratory effects in humans, induces lung inflammation in animals, and induces inflammatory mediator expression in cultured human airway epithelial cells (HAEC). ROFA has a high content of transition metals, including vanadium, a potent tyrosine phosphatase inhibitor that we have previously shown to disregulate phosphotyrosine metabolism and activate mitogen-activated protein kinase (MAPK) signaling cascades in HAEC. In order to study MAPK activation in response to in vivo metal exposure, we used immunohistochemical methods to detect levels of phosphorylated protein tyrosines (P-Tyr) and the MAPKs ERK1/2, JNK, and P38 in lung sections from rats intratracheally exposed to ROFA. After a 1-h exposure to 500 mu g ROFA, rat lungs showed no histological changes and no significant increases in immunostaining for either P-Tyr or phospho-(P-) MAPKs compared to saline-instilled controls. At 4 h of exposure, there was mild and variable inflammation in the lung, which was accompanied by an increase in specific immunostaining for P-Tyr and P-MAPKs in airway and alveolar epithelial cells and resident macrophages. By 24 h of exposure, there was a pronounced inflammatory response to ROFA instillation and a marked increase in levels of P-Tyr and P-MAPKs present within the alveolar epithelium and in the inflammatory cells, while the airway epithelium showed a continued increase in the expression of P-ERK1/2. By comparison, HAEC cultures exposed to 100 mu g/ml ROFA for 20 min resulted in marked increases in P-Tyr and P-MAPKs, which persisted after 24 h of exposure. P-Tyr levels continued to accumulate for up to 24 h in HAEC exposed to ROFA. These results demonstrate in vivo activation in cell signaling pathways in response to pulmonary exposure to particulate matter, and support the relevance of in vitro studies in the identification of mechanism

关键词：空气污染物印迹法蛋白质支气管/药物作用支气管/酶学支气管/病理学碳/投药和剂量碳/毒性细胞培养的酶激活/药物作用上皮细胞/药物作用上皮细胞/酶学免疫酶技术插管法气管内肺/药物作用肺/酶学肺/病理学丝裂原激活蛋白激酶类/代谢颗粒物磷酸酪氨酸/药物作用磷酸酪氨酸/代谢呼吸道黏膜/药物作用呼吸道黏膜/酶学人类

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DOUBLE-BLIND COMPARISON OF ACUTE BRONCHIAL AND CARDIOVASCULAR EFFECTS OF ORAL TERBUTALINE AND EPHEDRINE

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CHEST 1975年第2期68卷 155-159页

作者： TASHKIN, DP METH, R SIMMONS, DH LEE, YE UNIV CALIF SCH MEDDEPT MEDDIV PULM DISLOS ANGELESCA 90024 UNIV CALIF HOSP PULM FUNCTION LABLOS ANGELESCA

Acute effects of oral terbutaline (5 mg), ephedrine (25 mg) and placebo on bronchial dynamics, heart rate, systolic and diastolic pressure and arterial blood gases at rest were compared over a period of 7 hours in 20 subjects with bronchial asthma using a double-blind crossover technique. Both terbutaline and ephedrine caused significant bronchodilation, but the effect of terbutaline on specific airway conductance (SGA) was significantly greater (peak mean increase in SGA 0.069 vs 0.027 L/sec/cm H2O/L), had an earlier onset (30 minutes vs 1 hour) and lasted longer (7 hours vs 4 hours) than that of ephedrine. Slight but significant increases in arterial P02 were noted following institution of both ephedrine and terbutaline, suggesting improvement in ventilation-perfusion relationships. Both drugs caused modest but statistically significant increases in heart rate of 8.4-10.9 beats/min and the mean peak increase following terbutaline (8.4 beats/min) was comparable to that following ephedrine. In contrast to ephedrine, terbutaline caused significant, although slight, increases in systolic pressure and decreases in diastolic pressure, indicating that this drug, in the dose recommended for clinical use, is not free of cardiovascular effects.

关键词：气道阻力/药物作用哮喘/药物疗法哮喘/病理生理学血压/药物作用支气管/药物作用心血管系统/药物作用麻黄碱/药理学用力呼气量心率/药物作用安慰剂特普他林/药理学时间因素肺活量/药物作用青少年成年人老年人女(雌)性人类男(雄)性中年人

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BETA-ADRENERGIC BRONCHODILATORS

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PEDIATRIC CLINICS OF NORTH AMERICA 1975年第1期22卷 129-139页

作者： AVNER, SE NATL JEWISH HOSP & RES CTR 3800 E COLFAX AVE DENVER CO 80206 USA UNIV COLORADO MED CTR DENVER CO USA

There are many useful β -adrenergic bronchodilators available now or soon to be available. Better drugs will be developed as our understanding of mechanisms and methods for clinical study improve to allow for their proper use. Thoughtful utilization of the agents that are available can provide meaningful relief to a great number of patients.

关键词：投药口服气雾剂沙丁胺醇/投药和剂量沙丁胺醇/治疗应用茴香醚类/治疗应用哮喘/药物疗法支气管/药物作用支气管痉挛/药物疗法支气管扩张药/治疗应用儿茶酚类/治疗应用药物评价临床前乙醇胺类/治疗应用海索那林/治疗应用注射异丙肾上腺素/类似物和衍生物异喹啉类/投药和剂量异喹啉类/治疗应用甲醇/治疗应用哌啶类/治疗应用雷琐辛类/投药和剂量雷琐辛类/化学合成雷琐辛类/治疗应用呼吸疗法动物人类

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