Objective To assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship.Methods A total of 100 ...Objective To assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship.Methods A total of 100 Sprague-Dawley rats (equal numbers of male and female) were randomly divided into five groups (20 rats in each group):four groups were treated with rhG-CSFa at 500,100,10,1 μg/kg,respectively,and one group was treated with vehicle only to serve as the control.The rats were received subcutaneous injections of rhG-CSFa or vehicle daily for 13 weeks.During the course of the chronic toxicity study,the physical status,body weight,and food consumption were monitored.Half of the rats in each group (n=10) were sacrificed after the last rhG-CSFa administration,and the other half were sacrificed at five weeks after the last rhG-CSFa administration.Urinalyses,blood biochemistry,hematological analysis,histopathological examination,and immunological tests were performed for each of the rats.Results The hematological analyses revealed that the mean white blood cells count,neutrophils count,and neutrophils percentage were increased in male rats at the dose of 10 μg/kg or higher,and these were related with the biological activity of rhG-CSFa.Some small abnormalities were observed in the spleen of a few rats when used highest dose (500 μg/kg,a dosage of 200 folds higher than the normal clinical dosage),but these abnormalities were recovered within 5-week recovery period.No other rhG-CSFa-related abnormalities were observed in this chronic toxicity study.Conclusion No significant toxicity and immunogenicity are observed with rhG-CSFa administration to rats in the chronic toxicity studies.展开更多
Objective To assess the spectrum of causes, clinical features, differences between disease phases, and prognosis of extrinsic allergic alveolitis （EAA）. Methods Patients with EAA diagnosed at Peking Union Medical C...Objective To assess the spectrum of causes, clinical features, differences between disease phases, and prognosis of extrinsic allergic alveolitis （EAA）. Methods Patients with EAA diagnosed at Peking Union Medical College Hospital from August 1983 to May 2007 were analyzed retrospectively. Their medical records were examined to gather clinical, laboratorial, radiological, and histopathological data. Patients were divided to three phases （acute, subacute, and chronic） according to clinical presentations. Follow-up data regarding treatment response, subsequent radio- logical and pulmonary function studies, and clinical outcomes were collected. Results A total of 21 cases were enrolled. Among them, 11 were subacute, 10 were chronic. The most common exposure was pet birds （6 cases, 28.6%）. The primary abnormality of pulmonary function was restriction and/or reduction in diffusing capacity （12 cases, 63.2%）. The most common findings on high-resolution computed tomography （HRCT） were ground-glass opacities （13 cases, 68.4%） and centri- lobular nodules （8 cases, 42.1%）. Airway obstruction in pulmonary function test, emphysema, hmg cysts, and fibrosis on HRCT were more frequently seen in chronic than in subacute patients, though the differences were not statistically significant. Bronchoalveolar lavage fluid （BALF） showed lymphocytosis. The total＇cell count and the percentage of neutrophils were significantly higher in subacute than in chronic patients （P〈0.05）. Nonnecrotizing granulomas were seen in 8 （47.1%） cases. Improvement or normalization in symptoms, radiography, and pulmonary function test after treatment were seen in all 18 patients with avail- able follow-up data. Five patients recurred. Conclusions The characteristic abnormalities of pulmonary function, findings on HRCT, and pa- thology are essential for all phases of EAA, and the atypical manifestations such as obstruction and fibrosis can also be present frequently, particularly in chronic cases. Differential cell counts of BALF are related to the phase of the disease. The treatment response and prognosis of EAA are good.展开更多
基金Supported by State Scientific Key Projects for New Drug Research and Development (2009ZX09102-250)High-tech Research Project for Medicine and Pharmacology of Jiangsu Province (BG20070605)
文摘Objective To assess the severity and reversibility of the chronic toxicity of a novel recombinant human granulocyte colony-stimulating factor (rhG-CSFa) in rats and the dose-effect relationship.Methods A total of 100 Sprague-Dawley rats (equal numbers of male and female) were randomly divided into five groups (20 rats in each group):four groups were treated with rhG-CSFa at 500,100,10,1 μg/kg,respectively,and one group was treated with vehicle only to serve as the control.The rats were received subcutaneous injections of rhG-CSFa or vehicle daily for 13 weeks.During the course of the chronic toxicity study,the physical status,body weight,and food consumption were monitored.Half of the rats in each group (n=10) were sacrificed after the last rhG-CSFa administration,and the other half were sacrificed at five weeks after the last rhG-CSFa administration.Urinalyses,blood biochemistry,hematological analysis,histopathological examination,and immunological tests were performed for each of the rats.Results The hematological analyses revealed that the mean white blood cells count,neutrophils count,and neutrophils percentage were increased in male rats at the dose of 10 μg/kg or higher,and these were related with the biological activity of rhG-CSFa.Some small abnormalities were observed in the spleen of a few rats when used highest dose (500 μg/kg,a dosage of 200 folds higher than the normal clinical dosage),but these abnormalities were recovered within 5-week recovery period.No other rhG-CSFa-related abnormalities were observed in this chronic toxicity study.Conclusion No significant toxicity and immunogenicity are observed with rhG-CSFa administration to rats in the chronic toxicity studies.
文摘Objective To assess the spectrum of causes, clinical features, differences between disease phases, and prognosis of extrinsic allergic alveolitis （EAA）. Methods Patients with EAA diagnosed at Peking Union Medical College Hospital from August 1983 to May 2007 were analyzed retrospectively. Their medical records were examined to gather clinical, laboratorial, radiological, and histopathological data. Patients were divided to three phases （acute, subacute, and chronic） according to clinical presentations. Follow-up data regarding treatment response, subsequent radio- logical and pulmonary function studies, and clinical outcomes were collected. Results A total of 21 cases were enrolled. Among them, 11 were subacute, 10 were chronic. The most common exposure was pet birds （6 cases, 28.6%）. The primary abnormality of pulmonary function was restriction and/or reduction in diffusing capacity （12 cases, 63.2%）. The most common findings on high-resolution computed tomography （HRCT） were ground-glass opacities （13 cases, 68.4%） and centri- lobular nodules （8 cases, 42.1%）. Airway obstruction in pulmonary function test, emphysema, hmg cysts, and fibrosis on HRCT were more frequently seen in chronic than in subacute patients, though the differences were not statistically significant. Bronchoalveolar lavage fluid （BALF） showed lymphocytosis. The total＇cell count and the percentage of neutrophils were significantly higher in subacute than in chronic patients （P〈0.05）. Nonnecrotizing granulomas were seen in 8 （47.1%） cases. Improvement or normalization in symptoms, radiography, and pulmonary function test after treatment were seen in all 18 patients with avail- able follow-up data. Five patients recurred. Conclusions The characteristic abnormalities of pulmonary function, findings on HRCT, and pa- thology are essential for all phases of EAA, and the atypical manifestations such as obstruction and fibrosis can also be present frequently, particularly in chronic cases. Differential cell counts of BALF are related to the phase of the disease. The treatment response and prognosis of EAA are good.
