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排序方式: 共有293条查询结果,搜索用时 125 毫秒
81.
Defect of hepatocyte growth factor secretion by fibroblasts in idiopathic pulmonary fibrosis 总被引:8,自引:0,他引:8
Marchand-Adam S Marchal J Cohen M Soler P Gerard B Castier Y Lesèche G Valeyre D Mal H Aubier M Dehoux M Crestani B 《American journal of respiratory and critical care medicine》2003,168(10):1156-1161
Hepatocyte growth factor (HGF) is a growth factor that protects alveolar epithelial cells from pulmonary fibrosis in various animal models. We compared in vitro HGF production by human lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF, n = 8) and from control subjects (n = 6). Basal HGF secretion by IPF fibroblasts was decreased by 50% when compared with control fibroblasts (p < 0.05). HGF was secreted mainly in the cleaved mature form, both in IPF and control fibroblasts. HGF messenger RNA levels were reduced in IPF fibroblasts. Prostaglandin (PG) E2 secretion by IPF fibroblasts was low when compared with control subjects (p < 0.05). After the addition of PGE2 (10-6 M) or dibutyryl cyclic AMP (10-3 M), HGF secretion by IPF fibroblasts reached the level of control subjects. Inhibition of PGE2 synthesis with indomethacin reduced HGF secretion by control fibroblasts but had no effect on IPF fibroblasts. HGF secretion by control fibroblasts was also slightly inhibited by transforming growth factor (TGF)-beta1 and stimulated by anti-TGF-beta antibody, whereas both agents had no effect on IPF fibroblasts. Our results demonstrate a defect in HGF production by IPF fibroblasts that seems secondary to a defect in PGE2 secretion. 相似文献
82.
Crestani E Guerra S Wright AL Halonen M Martinez FD 《The Journal of allergy and clinical immunology》2004,113(2):284-290
BACKGROUND: Recent epidemiologic evidence has challenged the paradigm suggesting a direct causal relationship between allergic sensitization and asthma. OBJECTIVE: We sought to investigate the role of a familial predisposition for asthma in the development of atopy in children. METHODS: Subjects were participants in the Tucson Children's Respiratory Study. Skin tests to aeroallergens were performed in parents and in children at ages 6, 11, and 16 years. Parents were considered asthmatic if they reported physician-confirmed asthma. Parents were divided into 4 phenotypes on the basis of skin sensitization (Skt+ or Skt-) and asthma status (As+ or As-): Skt-/As-, Skt-/As+, Skt+/As-, and Skt+/As+. RESULTS: Children's allergic sensitization differed among parental phenotypes at all ages (P <.0001). Children in the Skt+/As- and Skt+/As+ groups were significantly more likely to be allergic than children in the Skt-/As- group at all ages. Among children with allergic parents, those with at least one parent with asthma were significantly more likely to have positive skin test responses than those with nonasthmatic parents at age 6 years (52.4% vs 37.4%, P <.005) and 11 years (70.1% vs 55.6%, P <.005) but not at age 16 years (82.3% vs 75.1%, P =.180). Results were independent of wheezing in the child and of the characteristics of atopy in parents. The Skt-/As+ group had too few subjects for meaningful comparisons. CONCLUSION: Among children of atopic parents, parental asthma is a risk factor for allergic sensitization in early childhood. The strong association between allergic sensitization and asthma is at least in part explained by an increased susceptibility to allergen sensitization in subjects predisposed to asthma. 相似文献
83.
BACKGROUND: Asthma control and prevention of exacerbations are primary objectives for asthma care. However there is a lack of universal definition of these notions which may therefore have a different meaning according to the physician's practice. METHODS: In the present survey, 1805 general practitioners, 551 pulmonologists, 176 allergologists and 470 resuscitation/emergency care physicians were randomly selected in fall 2001 and asked to answer one question on asthma control and three questions on asthma exacerbation. RESULTS: Regarding asthma control, the presence of minimum symptoms was the primary criterion for asthma specialists (pulmonologists and allergologists), while a normal respiratory function was first considered by nonspecialist physicians (general practitioners and emergency care physicians). The first criterion of mild exacerbation for asthma specialists was the occurrence during at least 2 days of an increase in the frequency of dyspnoea and/or the use of short-acting bronchodilators. For nonspecialist physicians, dyspnoea affecting daily activities and/or sleeping was the preferred notion. Hospitalization was unanimously recognized as the first criterion for severe exacerbations. A decrease in peak expiratory flow of more than 30% below the baseline value on two consecutive days and an episode requiring systemic corticosteroids were the next criteria. CONCLUSIONS: This survey emphasizes the complexity of the notions of asthma control and exacerbation and provides novel informations to orient continuing education programmes. 相似文献
84.
Differential effects of halothane and thiopental on surfactant protein C messenger RNA in vivo and in vitro in rats 总被引:4,自引:0,他引:4
Paugam-Burtz C Molliex S Lardeux B Rolland C Aubier M Desmonts JM Crestani B 《Anesthesiology》2000,93(3):805-810
BACKGROUND: Pulmonary surfactant is a complex mixture of proteins and phospholipids synthetized by alveolar type II cells. Volatile anesthetics have been shown to reduce surfactant phospholipid biosynthesis by rat alveolar type II cells. Surfactant-associated protein C (SP-C) is critical for the alveolar surfactant functions. Our goal was to evaluate the effects of halothane and thiopental on SP-C messenger RNA (mRNA) expression in vitro in rat alveolar type II cells and in vivo in mechanically ventilated rats. METHODS: In vitro, freshly isolated alveolar type II cells were exposed to halothane during 4 h (1, 2, 4%) and 8 h (1%), and to thiopental during 4 h (10, 100 micrometer) and 8 h (100 micrometer). In vivo, rats were anesthetized with intraperitoneal thiopental or inhaled 1% halothane and mechanically ventilated for 4 or 8 h. SP-C mRNA expression was evaluated by ribonuclease protection assay. RESULTS: In vitro, 4-h exposure of alveolar type II cells to thiopental 10 and 100 micrometer increased their SP-C mRNA content to 145 and 197%, respectively, of the control values. In alveolar type II cells exposed for 4 h to halothane 1, 2, and 4%, the SP-C mRNA content increased dose-dependently to 160, 235, and 275%, respectively, of the control values. In vivo, in mechanically ventilated rats, 4 h of halothane anesthesia decreased the lung SP-C mRNA content to 53% of the value obtained in control (nonanesthetized, nonventilated) animals; thiopental anesthesia increased to 150% the lung SP-C mRNA content. CONCLUSIONS: These findings indicate that halothane and thiopental used at clinically relevant concentrations modulate the pulmonary SP-C mRNA content in rats. In vivo, the additive role of mechanical ventilation is suggested. 相似文献
85.
G. L. Piacentini D. Peroni E. Crestani F. Zardini A. Bodini S. Costella A. L. Boner 《Clinical and experimental allergy》2007,37(3):415-419
BACKGROUND: Exhaled breath temperature has been proposed as a surrogate marker for the evaluation of airway inflammation in asthmatic patients. OBJECTIVE: The aim of the present study was to extend the investigation of exhaled air temperature as a means for the evaluation of airway inflammation using a professionally developed instrument. METHODS: Fifty-seven children, 41 allergic mild asthmatics and 16 healthy controls have been evaluated. They underwent exhaled air temperature and lung function measurement. The asthmatic children also underwent exhaled nitric oxide measurement, and hypertonic saline sputum induction for the evaluation of eosinophil (EOS) percentage. RESULTS: The level of exhaled temperature was significantly higher in asthmatics than in controls, being 30.18+/-0.14 degrees C vs. 27.47+/-0.24 degrees C (P<0.001). In asthmatic children, a positive relationship was observed between exhaled air temperature and both exhaled nitric oxide (r=0.39; P=0.01) and EOS percentage in samples from induced sputum (rho=0.53; P=0.04). CONCLUSION: The data from the present study support the hypotheses that exhaled breath temperature is related to the degree of airway inflammation in asthma. 相似文献
86.
Synthesis, biological evaluation, and molecular modeling investigation of new chiral fibrates with PPARalpha and PPARgamma agonist activity 总被引:2,自引:0,他引:2
87.
Marzo A Crestani S Fumagalli I Giusti A Lowenthal DT 《American journal of therapeutics》2004,11(2):98-102
This is an outcomes pharmacodynamic study using Nonsteroidal antiinflammatory agents, particularly acetylsalicylic acid (ASA), have been shown useful in various cardiovascular disorders, but they can be a major cause of iatrogenic gastrointestinal injury. Newer NSAIDs such as indobufen, an inhibitor of platelet aggregation that acts by reversibly inhibiting the platelet cyclooxygenase enzyme, have proven to be as effective as the older NSAIDs and appear to have a better gastrointestinal tolerability profile. When the gastroduodenal tolerability of 10 days of oral treatment with indobufen or ASA was assessed in healthy adult volunteers using endoscopic evaluation and the modified score scale of Lanza, only 1 of 18 (6%) volunteers who received indobufen had an increased erosion score at the completion of therapy, compared with 6 of 18 volunteers who received ASA (33%). Overall, both drugs were well tolerated. These results suggest that indobufen has a lower incidence of gastrointestinal effects than other NSAIDs and should be useful in the management of patients with cardiovascular disease. 相似文献
88.
Täuber M Calame-Droz E Prut L Rudolph U Crestani F 《The European journal of neuroscience》2003,18(9):2599-2604
Classical benzodiazepines such as diazepam are widely used tranquillisers and hypnotics in various neuropsychiatric diseases including alcohol-related disorders. One of the major drawbacks of benzodiazepine therapy, however, is an exacerbation of the sedative and hypnotic effects associated with alcohol intake, even at low doses. Even though the gamma-aminobutyric acid (GABA)A receptor complex is a common target for the actions of both classes of drugs, the molecular mechanisms underlying the enhanced pharmacological properties of the combined use of benzodiazepines and alcohol remain to be identified. The present experiments aimed at clarifying which of the GABAA receptor subtypes mediate the augmented hypnotic-like and sedative effects of combined diazepam and alcohol using the righting reflex and motor activity assays, respectively, in histidine-to-arginine point mutated mice that possess diazepam-insensitive alpha1-, alpha2-, alpha3- or alpha5-GABAA receptors. The combination of diazepam (2 or 3 mg/kg) and ethanol (3 g/kg) induced loss of righting reflex with a significantly dose-dependent increase of the latency to its full recovery in wild-type, alpha1(H101R), alpha3(H126R) and alpha5(H105R) but not in alpha2(H101R) mice. A combined treatment with diazepam (1 mg/kg) and ethanol (2.5 g/kg) precipitated motor inhibition similarly in wild-type and alpha2(H101R) mice. Responsiveness of the alpha2(H101R) mice to ethanol alone was similar to that of wild-type mice. These results demonstrate that induction of loss of righting reflex by combined diazepam and alcohol is closely dependent on the activation of the alpha2-GABAA receptors by the benzodiazepine whereas precipitation of sedation involves GABAA receptors other than the alpha2-GABAA receptors. 相似文献
89.
90.
Taïeb J Delarche C Paradis V Mathurin P Grenier A Crestani B Dehoux M Thabut D Gougerot-Pocidalo MA Poynard T Chollet-Martin S 《Journal of hepatology》2002,36(3):342-348
BACKGROUND/AIMS: Hepatocyte growth factor (HGF) is a pleiotropic cytokine involved in liver regeneration. Plasma HGF levels correlate with survival and hepatocyte proliferation in alcoholic hepatitis (AH). As AH is accompanied by inflammation, neutrophilia and polymorphonuclear neutrophil (PMN) infiltration of the liver, we postulated that PMN could be a source of HGF in such patients. METHODS: We studied 25 patients with severe AH in comparison with 20 alcoholic cirrhotic patients without AH and 20 healthy controls; the impact of a 28-day course of corticosteroids was evaluated in patients with AH. RESULTS: On day 0, HGF plasma and homogenized liver tissue levels were markedly increased in AH patients as compared to controls. The role of PMN in HGF production during AH was confirmed by a significantly higher ex-vivo HGF production capacity of lipopolysaccharide-stimulated blood PMN from AH patients relative to both control groups. Formyl-Methionyl-Leucyl-Phenylalanine-induced PMN release of HGF (degranulation conditions) was also higher in AH patients. In this setting, we found that HGF release by PMN ex vivo correlated strongly with HGF plasma levels, and that the degree of hepatic PMN correlated strongly with hepatic HGF levels. HGF plasma levels and ex-vivo HGF release by PMN were unaffected by steroid therapy. CONCLUSIONS: These findings suggest that, by releasing HGF, PMN could participate in liver regeneration during severe alcoholic hepatitis. 相似文献