Objective To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 （ TGF-β1...Objective To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 （ TGF-β1 ）, tissue inhibitor of metalloproteinase-1 （ TIMP-1 ）, and matrix metalloproteinase-13 （ MMP-13 ） in lung tissue. Methods Male Wistar rats were endotracheally instilled with bleomycin or normal saline. Pirfenidone （25-800 mg · kg^-l · d^-1 ）, dexamethasone （3 mg/kg）, or 1% carboxymethylcellulose sodium were given daily by feed 2 days before instillation of bleomycin. Groups T7 and T14 were fed pirfenidone 50 mg · kg^-1 · d^-1 at 7 days or 14 daYs after bleomycin instillation. Lungs were harvested at 28 days after bleomycin instillation. Patholological changes in luffg tissues were evaluated with HE staining. Lung collagen was stained by sirius red and measured by content of hydroxypro- line. Expression of proteins of TGF-β1 TIMP-1, and MMP-13 were detected by Western blotting. Results At doses of 25, 50, and 100 mg· kg^- 1 · d ^- 1, pirfenidone had significant anti-fibrotic effects for bleomy- cin-induced rat pulmonary fibrosis, and these effects were most significantly attenuated at the dosage of 50 mg · kg^-1 ·d^ -1（ HE： P 〈 0. 01, P 〈 0.01, and P = 0.064; sirius red： P 〈0.05, P 〈 0.01, and P 〈 0.05 ; hydroxyproline： P = 0.595, P 〈 0.01, and P = 0.976）. Pirfenidone at a dosage of 50 mg · kg^- l · d^-1 inhibited protein expression of TGF-131 and TIMP-1 in lung tissue in the early phase （0.79 and 0.75 times of control group）, but had no effect on ex- nr^eelnn nf MMP-13. Conclusion Low dose pirfenidone, especially at dosage of 50 mg · kg^-1 · d^-1, has significant anti-fibrotic effects on bleomycin-induced rat pulmonary fibrosis. Pirfenidone partially inhibits the enhancement of the expression of TGF-131 and TIMP-β1 in lung tissue.展开更多
This was a comparative cross-sectional study of eclamptic and normal healthy pregnant women conducted in kaduna State, Nigeria to determine Pregnancy Specific beta-1 Glycoprotein (PSG-1) levels in the peripheral blood...This was a comparative cross-sectional study of eclamptic and normal healthy pregnant women conducted in kaduna State, Nigeria to determine Pregnancy Specific beta-1 Glycoprotein (PSG-1) levels in the peripheral blood of third trimester women with eclampsia (EC;n = 38), normal healthy pregnant and non pregnant women controls (PC;n = 25 and NPC;n = 25 respectively), age and parity matched, attending labour rooms/wards and Antenatal Clinics (ANC) of Ahmadu Bello University Teaching Hospital Shika, Zaria and four other Hospitals in Kaduna state, Nigeria. Participants with smear positive malaria, seropositive for human immunodeficiency virus (HIV) or any other known clinical infection were excluded from this study. Pregnancy specific beta-1 glycoprotein levels were estimated using Quantikine ELISA kits. Data obtained were analyzed using SPSS version 20.0 (Chicago, USA) and Graph pad Prism 6.0. Results were expressed as mean ± standard deviation while Kruskal Wallis test was used to determine the significant differences. A p-value of less than 0.05 was considered to be significant. The mean serum level of PSG-1 in EC was 2.53 ± 0.11 pg/ml, PC;2.56 ± 0.03 pg/ml) and NPC;0.62 ± 0.20 pg/ml. There was no significant difference between EC and PC (P > 0.05). Pregnant women (with and without EC) had significantly higher mean serum values compared to NPC p < 0.05. While pregnancy was associated with high levels of PSG-1, the study did not support the hypothesis of low PSG-1 level in EC. A longitudinal study to capture changes in PSG-I levels in the course of pregnancy as they manifest is recommended.展开更多
基金Supported by National Ministry of Education Doctor Foundation of China(20020023045)
文摘Objective To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 （ TGF-β1 ）, tissue inhibitor of metalloproteinase-1 （ TIMP-1 ）, and matrix metalloproteinase-13 （ MMP-13 ） in lung tissue. Methods Male Wistar rats were endotracheally instilled with bleomycin or normal saline. Pirfenidone （25-800 mg · kg^-l · d^-1 ）, dexamethasone （3 mg/kg）, or 1% carboxymethylcellulose sodium were given daily by feed 2 days before instillation of bleomycin. Groups T7 and T14 were fed pirfenidone 50 mg · kg^-1 · d^-1 at 7 days or 14 daYs after bleomycin instillation. Lungs were harvested at 28 days after bleomycin instillation. Patholological changes in luffg tissues were evaluated with HE staining. Lung collagen was stained by sirius red and measured by content of hydroxypro- line. Expression of proteins of TGF-β1 TIMP-1, and MMP-13 were detected by Western blotting. Results At doses of 25, 50, and 100 mg· kg^- 1 · d ^- 1, pirfenidone had significant anti-fibrotic effects for bleomy- cin-induced rat pulmonary fibrosis, and these effects were most significantly attenuated at the dosage of 50 mg · kg^-1 ·d^ -1（ HE： P 〈 0. 01, P 〈 0.01, and P = 0.064; sirius red： P 〈0.05, P 〈 0.01, and P 〈 0.05 ; hydroxyproline： P = 0.595, P 〈 0.01, and P = 0.976）. Pirfenidone at a dosage of 50 mg · kg^- l · d^-1 inhibited protein expression of TGF-131 and TIMP-1 in lung tissue in the early phase （0.79 and 0.75 times of control group）, but had no effect on ex- nr^eelnn nf MMP-13. Conclusion Low dose pirfenidone, especially at dosage of 50 mg · kg^-1 · d^-1, has significant anti-fibrotic effects on bleomycin-induced rat pulmonary fibrosis. Pirfenidone partially inhibits the enhancement of the expression of TGF-131 and TIMP-β1 in lung tissue.
文摘This was a comparative cross-sectional study of eclamptic and normal healthy pregnant women conducted in kaduna State, Nigeria to determine Pregnancy Specific beta-1 Glycoprotein (PSG-1) levels in the peripheral blood of third trimester women with eclampsia (EC;n = 38), normal healthy pregnant and non pregnant women controls (PC;n = 25 and NPC;n = 25 respectively), age and parity matched, attending labour rooms/wards and Antenatal Clinics (ANC) of Ahmadu Bello University Teaching Hospital Shika, Zaria and four other Hospitals in Kaduna state, Nigeria. Participants with smear positive malaria, seropositive for human immunodeficiency virus (HIV) or any other known clinical infection were excluded from this study. Pregnancy specific beta-1 glycoprotein levels were estimated using Quantikine ELISA kits. Data obtained were analyzed using SPSS version 20.0 (Chicago, USA) and Graph pad Prism 6.0. Results were expressed as mean ± standard deviation while Kruskal Wallis test was used to determine the significant differences. A p-value of less than 0.05 was considered to be significant. The mean serum level of PSG-1 in EC was 2.53 ± 0.11 pg/ml, PC;2.56 ± 0.03 pg/ml) and NPC;0.62 ± 0.20 pg/ml. There was no significant difference between EC and PC (P > 0.05). Pregnant women (with and without EC) had significantly higher mean serum values compared to NPC p < 0.05. While pregnancy was associated with high levels of PSG-1, the study did not support the hypothesis of low PSG-1 level in EC. A longitudinal study to capture changes in PSG-I levels in the course of pregnancy as they manifest is recommended.
