Propylthiouracil-induced organizing pneumonia: A case report.

RATIONALE: Propylthiouracil (PTU) is a common antithyroid drug which can treat hyperthyroidism effectively. PTU is, however, associated to multiple adverse effects. In rare case, PTU can cause interstitial pneumonia. PATIENT CONCERNS: A 40-year-old woman presented with dyspnea and was diagnosed with pulmonary infection at the first time. After the treatment with moxifloxacin, her symptoms still got worse. DIAGNOSIS: The lung tissues biopsy confirmed the diagnosis of organizing pneumonia (OP) and the administration of PTU suggested the diagnosis of PTU-induced OP. INTERVENTION: Withdrawal of PTU and the administration of methylprednisolone. OUTCOMES: The patient's symptoms relieved significantly 1 month later and lung computed tomography (CT) scan also demonstrated significant reduction of lung lesions. LESSONS: Here we report the first case of histologically confirmed OP induced by PTU and conduct a literature review of the cases of PTU-induced interstitial pneumonia. The awareness of PTU-induced OP can help physicians reduce the possibility of misdiagnosis.

MS-275 potentiates the effect of YM-155 in lung adenocarcinoma via survivin downregulation induced by miR-138 and miR-195.

BACKGROUND: YM-155 has been proven to be an efficient antitumor suppressor in non-small cell lung cancer (NSCLC) cells. However, the suppressive effect of YM-155 on the expression of survivin is not sufficient and has a short half-life. MS-275, a histone deacetylase inhibitor, has significant antitumor capacity with a relatively long half-life. Our study explored whether MS-275 could enhance the inhibitory effect of YM-155 on LUAD proliferation. METHODS: To investigate the synergistic effect of MS-275 and YM-155, we employed methyl thiazolyl tetrazolium and colony formation assays to access the inhibition effect of MS-275, YM-155, or a combination in A549 and HCC827 cell lines. We then detected the effect of MS-275 and YM-155 on the expression of survivin and pro-apoptotic proteins by Western blot and miR-138 or miR-195 expression by quantitative PCR. We also analyzed the methylation level of microRNAs (miRNAs) using methylation-sensitive quantitative PCR. Finally, we investigated the interaction between miRNAs and survivin by luciferase reporter assay. RESULTS: MS-275 facilitated an inhibitory effect of YM-155 on lung adenocarcinoma cell proliferation. MS-275 can upregulate the level of acetylated H3, promote the degradation of DNA methyltransferases, and inhibit the methylation of miR-138 and miR-195 genes to elevate the expression of miR-138 and miR-195. Moreover, miR-138 and miR-195 showed a synergistic effect with YM-155 by directly binding to the 3 untranslated region of survivin to attenuate its expression. CONCLUSION: For the first time, we report the synergistic effective of MS-275 and YM-155 and suggest a new direction for the future application of YM-155.

Multinodule abnormalities of the tracheobronchus: bronchoscopy findings and clinical diagnosis.

BACKGROUND AND AIMS: Bronchoscopy is an important method for diagnosing respiratory disease. Multiple tracheobronchial nodules are rarely reported and their causes remain unclear. OBJECTIVES: The aim of this study was to describe the clinical characteristics of multiple nodule tracheobronchial abnormalities found under bronchoscopy caused by different diseases. METHODS: Eighty-seven patients with multiple tracheobronchial nodules were enrolled in this study. The characteristics of the multinodule lesions and the patient were diagnosed based on the pathology findings in our hospital. Chest computed tomography images were retrospectively reviewed by pulmonologists and radiologist. RESULTS: In 55 patients with definite pathological diagnosis, 16 (29%) patients were diagnosed as tuberculosis (TB) granuloma; 23 (41.8%) cases were diagnosed as malignant disease; 12 (21.8%) cases were diagnosed as tracheobronchopathia osteochondroplastica; 2 (3.6%) cases were diagnosed as sarcoidosis; and one case (1.8%) was diagnosed as lymphoma and one case (1.8%) as fungal infection. There were 32 cases of chronic inflammation. There was no relationship between nodule distribution and the pathological diagnosis. Malignant nodules usually smaller with a pale outlook, while nodules with larger size and smooth and intact mucosa usually turn out to be granuloma of unknown reason. CONCLUSION: The major causes of mutinodule lesions observed using bronchoscopy are tumor and TB. The presence of multiple endotracheobronchial nodules suggest that pulmonary lesion is present, and biopsy should be performed. Malignant nodules can be diagnosed by appearance and biopsy. Pathology results of TB, sarcoidosis and fungal infection can turn out to be granuloma of unknown reason. Further diagnosis needs other clinical materials.

The effect of tai chi on chronic obstructive pulmonary disease: a pilot randomised study of lung function, exercise capacity and diaphragm strength.

BACKGROUND: Although the benefits of exercise on the health of patients with chronic obstructive pulmonary disease (COPD) have been widely reported, the effect of Tai Chi as an alternative exercise has not been thoroughly evaluated in patients with COPD. This study reported a randomised controlled trial, which investigated the effects of Tai Chi on lung function, exercise capacity, and diaphragm strength in patients with COPD. TRIAL DESIGN: Single blind randomised controlled study. SETTING: Department of Respiratory Medicine, Xiangya Hospital, Central South University. METHODS: Forty patients with COPD were randomised into either a control group or Tai Chi intervention group. Participants in the control group received only routine care, while participants in the Tai Chi group received routine care and completed a six-month Tai Chi exercise program. OUTCOMES: Lung function parameters, blood gas parameters, 6-min walking distance (6MWD), and diaphragm strength parameters. RESULTS: Lung function parameters (FEV1: 1.43 ± 0.08 and FEV1 (%) predicted: 47.6 ± 4.76), 6MWD (476 ± 15) and diaphragm strength parameters (TwPes: 1.17 ± 0.07, TwPga: -1.12 ± 0.06, and TwPdi: 1.81 ± 0.09) were found to be significantly increased in participants who successfully completed the six-month Tai Chi program compared to participants in the control group who only received routine care (p<0.05). These parameters were also found to be significantly increased in participants who completed the Tai Chi exercise program compared to the baseline (p<0.05). In contrast, no significant differences in PaO2 and PaCO2 were observed in participants before or after completing a Tai Chi program or between Tai Chi group and control group (p>0.05). CONCLUSIONS: Tai Chi enhances lung function, exercise capacity, and diaphragm strength. However, this is only preliminary research data and a larger trial is needed for more detailed results.

Salubrinal protects against cigarette smoke extract-induced HBEpC apoptosis likely via regulating the activity of PERK-eIF2α signaling pathway.

BACKGROUND AND AIMS: Endoplasmic reticulum (ER) stress plays an important role in cigarette smoke extract (CSE)-induced apoptotic cell death, which is an important pathogenic factor of chronic obstructive pulmonary disease (COPD). The aim of this study was to explore the role of the PERK-eIF2 pathway in CSE-induced human bronchial epithelial (HBE) cell apoptosis and to evaluate the protective effects and possible mechanism of salubrinal (Sal) on CSE-induced HBE cell apoptosis. METHODS: Normal human bronchial epithelial cells (HBEpC) were cultured and then treated with CSE alone or together with Sal or preincubated with or without PERK siRNA. Expressions of p-PERK/PERK, p-eIF2α/eIF2α, and caspase 3 and 4 were detected with PCR, Western blot, and immunofluorescence. Apoptosis was detected using AnnexinV-PI flow cytometry. RESULTS: CSE induced apoptotic cell death and caused a dynamic change in PERK-eIF2α pathway activity following the course of CSE exposure. The knockdown of PERK suppressed the expression of both PERK and p-eIF2a and caused a great increase in cell apoptosis. Sal could eliminate the effects of PERK knockdown, protecting the cells against the CSE insult, and this protection was accomplished through maintaining the homeostasis of PERK- eIF2α pathway. CONCLUSIONS: PERK-eIF2α pathway mediates the CSE-induced HBE cell apoptosis. The intactness of PERK-eIF2α pathway is crucial for HBE cell survival under CSE insult. Sal can protect against CSE-induced HBE cell apoptosis, and this effect is likely achieved through maintaining the homeostasis of PERK- eIF2α pathway.

Analysis of two cases with bronchopulmonary neurofibromatosis.

Neurogenic tumor of lung is very rare. Only few cases have been reported in the literature. We present here two cases of bronchopulmonary neurofibromatosis in two adults. In both cases, attempts at imaging failed to diagnose the case, and it was the histological study that ensured the diagnosis of neurofibromatosis. Biopsy specimens showed bundles of spindle-shaped cells mixed with collagen, and on immunohistochemistry some cells were positive for S-100 protein.

[The effect of erythromycin on transforming growth factor-ß(1) and secretory leukocyte proteinase inhibitor in a rat model of chronic obstructive pulmonary disease].

OBJECTIVE: To study the protective mechanism of erythromycin in the process of COPD. METHODS: Thirty-six male Wistar rats, grade SPF, weight (220 ± 20) g, were randomly divided into 3 groups, 12 each: a control group, a COPD model group and an erythromycin treated group. Measurement of rat pulmonary function and the pathological changes were performed, and the expression of transforming growth factor-ß(1) (TGF-ß(1)) and secretory leukocyte proteinase inhibitor (SLPI) in the lung of rats were evaluated by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Analysis of variance, pairwise comparison between groups using SNK-q test, Pearson linear correlation analysis were carried out for statistical analysis. RESULTS: The rats in the COPD model group showed sign of less activity, loss of appetite and weight, dry and yellow hair, and sometimes wheezing, which were less or milder in the group treated with erythromycin. FEV(0.3)/FVC [(58 ± 7)%] and Cdyn [(0.16 ± 0.07) L/cm H2O, 1 cm H2O = 0.098 kPa] were significantly lower in the model group as compared to the control group [(83 ± 7)% and (0.33 ± 0.16) L/cm H2O], RI [(0.69 ± 0.14) cm H2O×L(-1)×s(-1)], but was significantly higher than the control group [(0.33 ± 0.11) cm H2O×L(-1)×s(-1)]. FEV(0.3)/FVC [(65 ± 9)%] and Cdyn [(0.23 ± 0.08) L/cm H2O] were significantly higher in the erythromycin treated group as compared to the model group [(58 ± 7)% and (0.16 ± 0.07) L/cm H2O], RI [(0.50 ± 0.13) cm H2O×L(-1)×s(-1)], but was significantly lower than the model group [(0.69 ± 0.14) cm H2O×L(-1)×s(-1)]. The expression of TGF-ß(1)protein (integral optical density value) and mRNA (absorbance value) (6.7 ± 1.5 and 0.45 ± 0.13) were lower in the erythromycin treated group as compared to the model group (10.7 ± 1.9 and 0.66 ± 0.18), but the expression of SLPI protein (integral optical density value) and mRNA (absorbance value) (9.9 ± 1.7 and 0.69 ± 0.34) were higher than those of the model group (8.1 ± 1.7 and 0.41 ± 0.27). The expressions of TGF-ß(1)and SLPI were negatively associated (r = -0.686, P < 0.05). CONCLUSIONS: The expression of SLPI was decreased but the expression of TGF-ß(1)was increased significantly in the bronchial and lung tissues of rats with COPD. Airway inflammation was inhibited by erythromycin which was able to reduce the inhibitory effect of TGF-ß(1)to SLPI, indicating a partial protective effect of erythromycin.

[Endoplasmic reticulum stress and related apoptosis in the lungs of a chronic obstructive pulmonary disease rat model].

OBJECTIVE: To study the endoplasmic reticulum stress (ERS) and the apoptosis of alveolar epithelial cells in a COPD rat model. METHODS: Twenty-four Wistar rats were divided into a control group and a COPD group at random. The COPD rat model was established by intratracheal instillation of lipopolysaccharide (LPS) twice and exposure to cigarette smoke daily. The spirometry was conducted and the pathological changes were observed after the model was established. The levels of glucose regulated protein 78 (GRP78) and CCAAT/enhancer binding protein homologous protein (CHOP) mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR). The protein expression of GRP78, CHOP and caspase-12 was detected by Western blot. TdT-mediated dUTP nick end labeling (TUNEL) was used to analyze alveolar epithelial cell apoptosis. Comparisons between the two groups were performed by t-test. RESULTS: Significant decrease of FEV(0.3)/FVC [(60 ± 6)%] and dynamic compliance of lung (CLdyn) [(0.17 ± 0.02) cm H2O×ml(-1)×s(-1)], and increase of airway resistance [(0.64 ± 0.07) ml/cm H2O] were found in the COPD group compared with the control group [(83 ± 7)%, (0.31 ± 0.03) cm H2O×ml(-1)×s(-1), (0.32 ± 0.03) ml/cm H2O] (t = -14.532 - 11.619, P < 0.05). GRP78 mRNA and CHOP mRNA densitometry [(0.65 ± 0.07), (0.79 ± 0.06)] were significantly increased in the COPD group compared with the control group [(0.21 ± 0.04), (0.07 ± 0.04), respectively] (t = -19.102 and -32.573, P < 0.05). GRP78, CHOP, and active caspase-12 protein densitometry (0.83 ± 0.06, 0.82 ± 0.06 and 0.81 ± 0.07) were significantly increased in the COPD group compared with the control group [(0.33 ± 0.05, 0.05 ± 0.03 and 0.24 ± 0.06), respectively] (t = -40.866 - -22.070, P < 0.05). More apoptotic alveolar epithelial cells were found in the COPD group [(32.4 ± 3.7)%] than in the control group [(6.2 ± 0.9)%] (t = -23.852, P < 0.05). CONCLUSIONS: ERS was triggered in the lung tissues of COPD rats, especially in the alveolar epithelial cells. Alveolar epithelial cell apoptosis was increased in the COPD group. The ERS mediated apoptosis pathway may participate in the alveolar epithelial cell apoptosis in COPD.

Clinical analysis of 68 patients with pulmonary mycosis in China.

BACKGROUND: Due to the lack of specific clinical manifestations and imaging features, the diagnosis of pulmonary mycosis is difficult. This study aimed to investigate the pathogens, clinical manifestations, imaging features, diagnosis and management of pulmonary mycosis. METHODS: Data on 68 patients diagnosed as pulmonary mycosis in Xiang Ya hospital from January 2001 to December 2010 were collected and their clinical manifestations, radiographic characterization, diagnostic methods and management were analyzed. RESULTS: All patients were diagnosed by pathological examination. Of the 68 cases, 38 (55.9%) had pulmonary aspergillosis and 19 (27.9%) pulmonary cryptococcosis. Open-lung surgery was performed in 38 patients (55.9%), transbronchial biopsy in 15 (22.0%), and computerized tomography (CT) guided percutaneous needle biopsy in 11 (16.2%). Main symptoms were as follows: cough in 51 cases (75.0%), expectoration in 38 (55.9%), hemoptysis in 25 (37.8%), fever in 20 (29.4%), while 6 cases (11.1%) were asymptomatic. X-ray and chest CT showed masses or nodular lesions in 52 cases (76.5%), patchy lesions in 10 (14.7%), cavity formation in 15 (22.0%), and diffuse miliary nodules in 1 case. In 51 cases (75.0%) misdiagnosis before pathological examination occurred. Surgical resection was performed in 38 patients (55.9%). In 25 patients (36.7%) systemic antifungal therapy was administered, and 20 patients (29.4%) experienced complete responses or partial responses. CONCLUSION: The main pathogens of pulmonary mycosis are Aspergillus, followed by cryptococcosis. Final diagnosis of pulmonary mycosis mainly depends on pathological examination. The clinical manifestations, imaging features, diagnostic methods and management differ depending on the pathogens. Satisfactory therapy can be obtained by both antifungal and surgical treatment.

[The function of nuclear factor-erythroid 2-related factor 2 and its association with I-kappa B kinases alpha/beta in a rat model of chronic obstructive pulmonary disease.].

OBJECTIVE: To study the expression of nuclear factor-erythroid 2-related factor 2 (Nrf2) in the bronchial and lung tissues of chronic obstructive pulmonary disease (COPD) rat models and its association with I-kappa B kinases (IKKs). METHODS: Rat COPD models were established by intratracheal instillation of lipopolysaccharide (LPS) twice and exposure to cigarette smoke daily. The drug intervention group received 15-deoxy-Delta2, 14-prostaglandin J2 (15d-PGJ2) 0.3 mg/kg twice via tail venous injection. Spirometry was conducted and the pathological changes were observed. Antioxidation activities were measured and the expressions of Nrf2, IKKalpha/beta and NF-kappaB p65 were detected by immunohistochemistry and RT-PCR. The differences among groups were calculated by one-way ANOVA, and comparison between groups was made by LSD-t test. RESULTS: FEV(0.3)/FVC, Cdyn values and antioxidation capacity including total anti-oxidation competence and superoxidase dismutase in the COPD group [(58.8 +/- 2.6)%, (0.14 +/- 0.02) ml/cm H2O (1 cm H2O = 0.098 kPa), (0.20 +/- 0.03) U/ml and (19.6 +/- 2.4) U/ml, respectively] were significantly lower than those in the normal control group [(86.3 +/- 2.5)%, (0.38 +/- 0.02) ml/cm H2O, (3.16 +/- 0.31) U/ml and (56.1 +/- 2.2) U/ml, respectively]. RI values (0.69 +/- 0.17) cm H2Oxml(-1)xs(-1) were significantly higher than that of the normal control group (0.34 +/- 0.06) cm H2Oxml(-1)xs(-1). The above measurements of the drug intervention group [(74.5 +/- 3.9)%, (0.30 +/- 0.04) ml/cm H2O, (1.90 +/- 0.24) U/ml, (39.7 +/- 1.9) U/ml and (0.43 +/- 0.05) cm H2Oxml(-1)xs(-1), respectively] were between the COPD and the control groups, with airflow limitation and pulmonary ventilation improved significantly. Immunohistochemistry showed that, the positive coefficient of Nrf2, IKKalpha/beta and NF-kappaB p65 were increased significantly in the COPD models (3.23 +/- 0.31, 3.80 +/- 0.16 and 3.85 +/- 0.18, respectively), as compared with the control group (0.91 +/- 0.45, 1.17 +/- 0.42 and 1.30 +/- 0.34, respectively). The expression of IKKalpha/beta (2.10 +/- 0.46) and NF-kappaB p65 (2.53 +/- 0.36) in the lungs of the intervention group was between the COPD group and the control group, but the expression of Nrf2 (3.78 +/- 0.22) increased as compared to the COPD group. The results of RT-PCR showed that, the mRNA IOD value of Nrf2, IKKbeta and NF-kappaB p65 increased significantly in the COPD group (0.61 +/- 0.08, 0.89 +/- 0.05 and 0.91 +/- 0.02, respectively), as compared with the control group (0.29 +/- 0.07, 0.30 +/- 0.07, 0.30 +/- 0.07, respectively), while the expression of IKKbeta (0.67 +/- 0.04) and NF-kappaB p65 (0.69 +/- 0.04) in the lungs of the drug intervention group were between the above two groups, and the expression of Nrf2 (0.90 +/- 0.05) increased as compared to the COPD group. CONCLUSIONS: 15d-PGJ2 was shown to have anti-oxidation and anti-inflammation effects in this COPD model, which may be related to the increase of Nrf2. Nrf2 inhibited the expression of NF-kappaB p65 possibly through the down-regulation of IKKbeta.

[Expression of secretory leukocyte proteinase inhibitor in human bronchial epithelial cell is downregulated by transforming growth factor-beta1/Smads pathway].

OBJECTIVE: To study the relationship between the downregulated expression of secretory leukocyte proteinase inhibitor (SLPI) in human bronchial epithelial cells and transforming growth factor (TGF)-beta1/Smads pathway. METHODS: Normal human bronchial epithelial cells of the line HBE were cultured and divided into 4 groups: TGF-beta1 stimulation group stimulated by TGF-beta1, interference group preincubated with Smad4 siRNA and then stimulated by TGF-beta1, interference control group preincubated with negative siRNA and then stimulated by TGF-beta1, and normal control group. Forty-eight hours later immunocytochemistry was used to observe the SLPI positive staining in the cells, and the protein and mRNA expression levels of Smad4 and SLPI were detected by Western blotting and RT-PCR respectively. RESULTS: Immunocytochemistry showed that the Smad4 staining was strongly positive in the TGF-beta1 stimulation group and interference control group, and the SLPI staining was strongly positive in the normal control group, positive in the interference group, and only weakly positive in the TGF-beta1 stimulation and interference control groups. The protein and mRNA expression levels of Smad4 in the HBE cells of the TGF-beta1 stimulation group were 1.18 +/- 0.17 and 1.33 +/- 0.16 respectively, both significantly higher than those of the normal control group (0.29 +/- 0.06 and 0.31 +/- 0.07 respectively, both P < 0.01) and interference group (0.27 +/- 0.08 and 0.34 +/- 0.09 respectively, both P < 0.01). The protein and mRNA expression levels of SLPI in the HBE cells of the TGF-beta1 stimulation group were 0.17 +/- 0.10 and 0.11 +/- 0.05 respectively, both significantly lower than those of the normal control group (1.29 +/- 0.21 and 0.83 +/- 0.13 respectively, both P < 0.01), and those of the interference group (1.22 +/- 0.18 and 0.81 +/- 0.11 respectively, both P < 0.01). There were no significant differences in the expression levels of Smad4 and SLPI between the TGF-beta1 stimulation group and interference control group. CONCLUSION: TGF-beta1 downregulates the SLPI expression in human bronchial epithelial cell via Smads pathway.

[Effects of secretory leukocyte protease inhibitor on expression of inflammation mediators in normal human bronchial epithelial cells induced by cigarette smoke extract].

OBJECTIVE: To study the effect of secretory leukocyte protease inhibitor (SLPI) on the expression of MMP-9 and IL-8 in normal human bronchial epithelial (NHBE) cells induced by cigarette smoke extract (CSE), and therefore to explore the mechanisms of SLPI for protecting the local airways of chronic inflammatory diseases. METHODS: The experiments of cultured airway epithelia cells in vivo were randomly divided into 4 groups, including a control group, a CSE group, a SLPI group, and a SLPI + CSE group. The expression level of IL-8 in NHBE cell supernatant was examined by ELISA. The expression level of MMP-9 protein in NHBE cells was evaluated by using immunocytochemical stain method. One way analysis of variance was employed in significance test of different groups, followed by SNK test with equal variances and Dunnett3 test with unequal variances. RESULTS: A small quantities of MMP-9 and IL-8 expression were observed in the control group NHBE cells. The mean integral expression of MMP-9 protein was (3.1 +/- 0.5), and the concentration of IL-8 in NHBE cell supernatant was (4.9 +/- 0.6) ng/L. After exposure to CSE for different times, the expression of MMP-9 and IL-8 in NHBE cells of the CSE group was higher than those of in control group. The expression levels of MMP-9 and IL-8 were dependent on CSE exposure time within certain limits. The highest expression was observed at the time of 24 h exposure to CSE. The mean integral expression of MMP-9 protein was 6.6 +/- 0.4, and the concentration of IL-8 in NHBE cell supernatant was (17.7 +/- 1.9) ng/L. But subsequently the levels decreased significantly in 36 h. When NHBE cells were exposed to 10 microg/L SLPI, the expression levels of MMP-9 and IL-8 were inhibited. The integral expression of MMP-9 protein was 0.8 +/- 0.5, and the concentration of IL-8 in NHBE cell supernatant was (0.7 +/- 0.6) ng/L. CONCLUSION: SLPI inhibited the expression of MMP-9 and IL-8 in NHBE cells induced by cigarette smoking extract.

Downregulation of secretory leukocyte proteinase inhibitor in chronic obstructive lung disease: the role of TGF-beta/Smads signaling pathways.

BACKGROUND: Secretory leukocyte proteinase inhibitor (SLPI) is an important antileukoprotease in airway. The aim of the present study was to explore the expression of SLPI in the bronchi and lung tissues of chronic obstructive pulmonary disease (COPD) models and the regulative mechanism by transforming growth factor (TGF)beta(1)/Smads signal pathway in bronchial epithelial cell. METHODS: COPD rat model was established and was treated with or without TGFbeta1 monoclonal antibody. Spirometry was conducted, and expressions of TGFbeta(1), Smad4 and SLPI were examined by immunohistochemistry and reverse-transcription polymerase chain reaction (RT-PCR), respectively. The normal human bronchial epithelial cell (NHBE) was cultured, preincubated with or without siRNA (Smad4), and then stimulated with TGFbeta(1). Expressions of Smad4 and SLPI were detected by immunocytochemistry, Western blot and RT-PCR, respectively. RESULTS: As compared with the model group, after treatment with TGFbeta(1) monoclonal antibody, peak expiratory flow (PEF), forced expiratory volume in 0.3 sec (FEV(0.3)) and FEV(0.3)/forced vital capacity (FVC) in the TGFbeta(1) monoclonal antibody intervention group were all significantly improved. Expression of SLPI was also improved, but expression of Smad4 was significantly decreased. Expression of SLPI in NHBE cells was inhibited by TGFbeta(1) both at the mRNA level and the protein level. Furthermore, effect of TGFbeta(1)-inhibited expression of SLPI in NHBE cells was disengaged by siRNA (Smad4) both at the mRNA level and the protein level. CONCLUSIONS: Decreased expression of SLPI in the COPD rat model may be mainly caused by the increased expression of TGFbeta(1), and this process is probably related to the activation of Smads signal pathway.

[Expression of secretory leukocyte proteinase inhibitor in the bronchi and lung tissues of chronic obstructive pulmonary disease rat models and the regulatory mechanism by transforming growth factor beta(1)].

OBJECTIVE: To study the expression of secretory leukocyte proteinase inhibitor (SLPI) in the bronchi and lung tissues of chronic obstructive pulmonary disease (COPD) rat models and the regulatory mechanism by transforming growth factor beta(1) (TGF-beta(1)). METHODS: Rat COPD models were established by intratracheal instillation of lipopolysaccharide (LPS) twice and exposure to cigarette smoke daily. The drug intervention group received TGF-beta(1) monoclonal antibody 0.5 mg twice via tail venous injection. Spirometry was conducted and the pathological changes were observed. The concentrations of SLPI in bronchoalveolar lavage fluid (BALF) was measured by enzyme-linked immunosorbent assay (ELISA), the expressions of TGF-beta(1), Smad4 and SLPI in the bronchi and lung tissues examined by immunohistochemistry, and the expressions of TGF-beta(1) mRNA, Smad4 mRNA and SLPI mRNA in the bronchi and lung tissues detected by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The SLPI positive coefficient, SLPI mRNA IOD value and the concentration of SLPI in BALF were significantly lower in the model group [(1.07), (0.17 +/- 0.01), (47 +/- 4) microg/L, respectively] as compared to the control group [(3.86), (0.84 +/- 0.10), (82 +/- 7) microg/L, respectively]. The TGF-beta(1) positive coefficient and the TGF-beta(1) mRNA IOD value were higher in the model group [(3.91), (0.71 +/- 0.09) respectively]than the control group [(1.12), (0.15 +/- 0.01), respectively]. After treated with TGF-beta(1) monoclonal antibody, the SLPI positive coefficient, SLPI mRNA IOD value and the concentration of SLPI in BALF were all significantly increased [(2.69), (0.59 +/- 0.05), (69 +/- 6) microg/L, respectively]. The PEF, FEV(0.3) and FEV(0.3)/FVC were all significantly improved in the drug intervention group [(28 +/- 6) ml/s, (4.4 +/- 1.3) ml, (80 +/- 10)%, respectively] as compared to the model group [(23 +/- 5) ml/s, (3.3 +/- 1.4) ml, (62 +/- 9)%, respectively]. CONCLUSION: The expression of SLPI in the COPD rat models significantly decreased, which may be caused by the increased expression of TGF-beta(1), and this process is probably related to the activation of Smads signal pathway.

[Experimental study on the mechanisms of regulating airway neurogenic inflammation in asthma by never growth factor and leukemia inhibitory factor].

OBJECTIVE: To study the mechanisms of regulating airway neurogenic inflammation in asthma by never growth factor (NGF) and leukemia inhibitory factor (LIF), and then to explore new targets in treating asthma. METHODS: Adult male SD rats (n 36) were divided into the normal group, the asthmatic group and the anti-NGF group at random. There were 12 rats in each group. The asthma models were established by sensitization and challenge with ovalbumin, and the asthma model was treated with anti-NGF. The expression of NGF, LIF and substance P (SP) in lung tissue or in doral root ganglion of each rat were detected by immunohistochemistry and hybridisation in situ. RESULTS: (1) The gray-levels of NGF protein/NGF mRNA, LIF protein/LIF mRNA in the lungs were 157 +/- 7, 138 +/- 8, 156 +/- 6, 141 +/- 10 for the asthmatic group respectively, 183 +/- 7, 190 +/- 7, 187 +/- 7, 181 +/- 8 for the normal control group respectively, and 177 +/- 6, 169 +/- 9, 178 +/- 7, 172 +/- 9 for the asthmatic group with anti-NGF treatment. There were significant differences in gray-level of NGF protein/NGF mRNA, LIF protein/LIF mRNA among those three groups (t = 19.40, 15.80, 20.38, [corrected] 14.79, all P < 0.01). (2) The gray-levels of NGF protein/LIF protein, SP protein/SP mRNA in the doral root ganglions were 136 +/- 8, 148 +/- 6, 140 +/- 8, 128 +/- 8 for the asthmatic group respectively, 185 +/- 7, 187 +/- 8, 174 +/- 7, 180 +/- 8 for the normal control group respectively, and 164 +/- 6, 170 +/- 8, 163 +/- 9, 157 +/- 7 for the asthmatic group with anti-NGF treatment. There were also significant differences in gray-level of NGF protein/LIF protein, SP protein/SP mRNA among those three groups (t = 29.50, 22.65, 23.12, 28.71, all P < 0.01). CONCLUSION: Enhancing the synthesis and release of SP in doral root ganglion may be one of the mechanisms by which NGF and LIF regulate airway neurogenic inflammation in asthmatic rats, and this mechanism can be depressed by the intervention of anti-NGF.

[Effect of xinglong pingchuan recipe on interleukin-5 and the inflammagen related to oxygen free radical in asthmatic mice].

OBJECTIVE: To observe the effect of Xinglong Pingchuan recipe (XLPCR) on interleukin-5 (IL-5), superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA) in mouse asthma models, and to explore its mechanism in treating asthma. METHODS: The mouse asthma models were established by sensitization and challenge with ovalbumin (OVA). The asthma model was treated with XLPCR. At last, the number of white blood cells and eosinophil was counted, and the concentrations of inflammation factors such as IL-5, SOD, GPx, and MDA in the serum or the lung tissue of each mouse were detected. RESULTS: Compared with the asthmatic group, the number of eosinophil in the XLPCR group decreased significantly (P < 0.01); the concentration of IL-5 in the XLPCR group significantly decreased in the serum or the lung tissue (all P < 0.01); and the concentrations of SOD and GPx in the XLPCR group increased (P < 0.01 and P > 0.05, respectively). On the other hand, the concentration of MDA in the XLPCR group was significantly lower than that of the asthmatic group (P < 0.05). CONCLUSION: XLPCR might inhibit the airway inflammation by decreasing the IL-5 level and adjusting the balance of oxidants/antioxidants.

Effect of fenofibrate on LDL-induced endothelial dysfunction in rats.

Previous investigations have demonstrated that asymmetric dimethylarginine (ADMA) is an important factor contributing to endothelial dysfunction, and that fenofibrate has a protective effect on the endothelium in hyperlipidaemic patients. In the present study in rats treated with native low-density lipoprotein (nLDL), we addressed the question of whether the beneficial effect of fenofibrate on endothelial cells is related to reduction of the ADMA concentration. A single injection of nLDL (4 mg/kg, 48 h) markedly reduced endothelium-dependent relaxation in response to acetylcholine and the plasma level of nitrite/nitrate and increased the plasma concentrations of ADMA, malonyldialdehyde (MDA) and tumour necrosis factor-alpha (TNF-alpha). Treatment with fenofibrate (30 or 100 mg/kg) significantly reduced the inhibition of vasodilator responses to acetylcholine, decreased the elevated levels of ADMA, MDA and TNF-alpha, and enhanced the decreased level of nitrite/nitrate in the rats treated with LDL. These results suggest that the protective effect of fenofibrate on endothelial cells in rats treated with LDL may be related to the reduction of ADMA concentration.

[Pathogen variance and drug-sensibility analysis of lower-respiratory-tract bacterial infection in chronic pulmonary heart disease].

We contrastively analyzed pathogens and their drug sensibilities of lower-respiratory-tract infection in chronic pulmonary heart disease in two different periods. The results were that the Gram-positive cocci (GPC) was 43.8% and Gram-negative bacilli (GNB) was 56.2% in Group A (1985-1990); GPC was 24.6% and GNB was 75.4% in Group B (1995-2000). The predominant bacteria were in the following order: Preudomonas (21.9%), pneumococcal (18.8%), streptococcus (10.9%), acinetobacter (9.4%), staphylococcus epidermidis (7.8%), and klebsiella (7.8%) in Group A; and preudomonas (30.7%), acinetobacter (12.3%), staphylococcus epidermidis (12.3%), klebsiella (10.5%), enteric bacilli (7.0%), and staphylococcus aureus (7.0%) in Group B. The results suggest that GNB is the main pathogen in recent years; sensibility of most drugs in the 1990s fell in varying degrees compared with that in the 1980s, but antibacterial in common use is still available.