Triptolide inhibits TGF-ß1 induced proliferation and migration of rat airway smooth muscle cells by suppressing NF-κB but not ERK1/2.

BACKGROUND: Airway remodeling contributes to increased mortality in asthma. We have reported that triptolide can inhibit airway remodeling in a mouse asthma model. In this study, we aimed to investigate the effect of triptolide on airway smooth muscle cells (ASMCs) proliferation, migration and the possible mechanism. METHODS: Rat airway smooth muscle cells were cultured and made synchronized, then pretreated with different concentrations of triptolide before stimulated by TGF-ß1. Cell proliferation was evaluated by cell counting and MTT assay. Flow cytometry was used to study the influence of triptolide on cell cycle. Migration was measured by Transwell analysis. Signal proteins (NF-κB p65 and ERK1/2) were detected by western blotting analysis. LDH releasing test and flow cytometry analysis of apoptosis were also performed to explore the potential cytotoxic or pro-apoptotic effects of triptolide. RESULTS: Triptolide significantly inhibited TGF-ß1 induced ASMC proliferation and migration (p<0.05). The cell cycle was blocked at G1/S-interphase by triptolide dose dependently. Western blotting analysis showed TGF-ß1 induced NF-κB p65 phosphorylation was inhibited by triptolide pretreatment, but ERK1/2 was not affected. No cytotoxic or pro-apoptotic effects were detected under the concentration of triptolide we used. CONCLUSIONS: Triptolide may function as an inhibitor of asthma airway remodeling by suppressing ASMCs proliferation and migration through inactivation of NF-κB pathway. This article is protected by copyright. All rights reserved.

Magnesium affects the cytokine secretion of CD4⁺ T lymphocytes in acute asthma.

INTRODUCTION: Magnesium (Mg) administration has been shown to promote bronchodilation and to improve lung function in asthma. It also plays an additional role in modulating the immune responses. This study was initiated to explore if Mg supplementation could affect the secretion of cytokines in acute asthmatic CD4⁺ T cells. METHODS: Total serum Mg concentrations of the acute asthmatic patients and healthy controls were determined. CD4⁺ T cells were isolated from the blood of the acute asthmatic patients. They were cultured in various concentrations of Mg-supplemented (0.8, 5, 10, 15, and 20 mmol/l) medium. Cytokine (IL-5, IL-13, and IFN-γ) levels were determined by Enzyme-Linked Immunosorbnent Assay (ELISA). RESULTS: Serum Mg concentration was lower in the acute asthmatic patients than that in the healthy controls (p < .05). The secretion of IL-5 and IL-13 was decreased, while the acute asthmatic CD4⁺ T cells were cultured in 10 and 15 mmol/l Mg-supplemented medium, respectively, as compared to the 0.8 mmol/l Mg group (p < .05). The secretion of IFN-γ increased in the 10 mmol/l Mg group (p < .05). CONCLUSION: Mg supplementation was able to modulate the immune responses of acute asthmatic CD4⁺ T cells and decrease the secretion of type 2 CD4⁺ T lymphocytes cytokines.

2-Aminoethoxydiphenyl borate reduces degranulation and release of cytokines in a rat mast cell line.

BACKGROUND AND OBJECTIVE: 2-aminoethoxydiphenyl borate (2-APB) has been reported to be a useful pharmacological tool in the study of calcium signaling. It is used either as a membrane-permeable inhibitor for inositol 1,4,5-trisphosphate (IP3) receptors or a store-operated calcium (Ca2+) entry (SOCE) inhibitor. The present study aimed to evaluate the effects of 2-APB on degranulation and cytokine production after antigen activation in a rat mast cell line, RBL-2H3 cells. MATERIALS AND METHODS: Degranulation levels were analyzed by beta-hexosaminidase assay. Intracellular calcium concentrations were measured by Fluo-3 assay. The mRNA expression of interleukin-4 (IL-4) and tumor necrosis factor (TNF)-alfa were analyzed by Real-time PCR. RESULTS: The intracellular Ca2+ levels were greatly suppressed in the absence or presence of 2 mmol/L Ca2+ in the extracellular medium when RBL-2H3 cells were pretreated with 100 micromol/L 2-APB for 15 min. The beta-hexosaminidase activity as well as the mRNA expression of IL-4 and TNF-alfa levels were significantly decreased after application of 2-APB. CONCLUSION: This study indicates that the application of 2-APB may be a useful method to inhibit mast cell activation.

[The role of medical antireflux in asthmatics with gastroesophageal reflux:a systematic review].

OBJECTIVE: to evaluate the effect of antireflux treatment in asthma patients with gastroesophageal reflux disease (GERD). METHODS: prospective randomized trials of antireflux treatment in asthma patients with gastroesophageal reflux were all included. Antireflux treatment should be double-blinded. Sample size and matching ways were not restricted. The study subjects were defined as asthmatic patients with gastroesophageal reflux aged 13 or older. Computer searching included The Cochrane Central Register of Controlled Trials, PubMed, Embase, OVID database, Chinese Biological Medicine database (CBMdisc), China National Knowledge Infrastructure (CNKI), and Wanfang Data. Manual searching included Chinese Journal of Tuberculosis and Respiratory Diseases, Chinese Journal of Digestion, Chinese Journal of Internal Medicine, CHEST and the references of trails included. The search ended on November of 2009. Trials with subjects using antireflux drugs in 3 days before entry, trials repeatly or mutiply published, and trials with methodology quality under grade B were excluded. With the method of Cochrane systematic review, 2 reviewers assessed the quality of the studies, extracted data independently and cross checked the data. Data were combined and analyzed with RevMan 4.3.2 to evaluate the effect of antireflux treatment on asthmatic patients with gastroesophageal reflux disease. RESULTS: fourteen randomized controlled studies met inclusion criteria, including 1555 cases. Meta-analyses demonstrated that antireflux treatment improved the pulmonary function in asthmatics with gastroesophageal reflux. Compared to the placebo group, FEV(1) improved [WMD 0.11 L; 95%CI (0.02 - 0.20); Z = 2.49, P = 0.010]; and PEF also improved, including daytime PEF [WMD 42.33 L/min; 95%CI (3.39 - 81.28), Z = 2.13, P = 0.030], morning PEF [WMD 16.16 L/min; 95%CI (5.91 - 26.41); Z = 3.09, P = 0.002], and nighttime PEF [WMD 18.35 L/min; 95%CI (6.77 - 29.92); Z = 3.11, P = 0.002]. However, no significant difference was found in the decrease of provocative concentration of acetylcholine causing a 20% decrease in FEV(1) (PC20-FEV(1)) [WMD -0.07 mg/L; 95%CI (-0.33 -0.19); Z = 0.55, P = 0.590]. Eight out of 14 studies showed improvement in asthma symptoms after antireflux treatment, but neither daytime symptoms nor nighttime symptoms showed significant improvement in this Meta-analysis. CONCLUSION: antireflux treatment in asthmatics with gastroesophageal reflux could improve pulmonary function, but showed no significant effect on airway hyper-responsiveness or asthma symptoms.

Dermatomyositis and malignancy: a retrospective study of 115 cases.

UNLABELLED: Aim of this study was to identify the association between dermatomyositis and malignancy in China. METHODS: We retrospectively analyzed the clinical data of 115 cases of dermatomyositis associated with malignancy. RESULTS: From 1974 to 2008, there were 678 cases of dermatomyositis collected from the Second Affiliated Hospital, Sun Yat-Sen University, China. Among them, 115 cases (17.0%) were associated with malignancy. 7.4% (22/297) of patients under 40 years old were diagnosed with malignant tumor, while 24.4% (93/381) of patients aged 40 years or above were associated with malignancy. Malignancy preceded dermatomyositis in 14 cases. Dermatomyositis and malignancy were diagnosed at the same time in 22 patients. Another 79 patients were found to have cancer within 3 years after the dermatomyositis was diagnosed. Among them, cancer was detected in 66 patients in the first year, 11 patients in the second year and only 2 patients in the third year. Nasopharyngeal cancer made up 51.3% (59/115) of the associated malignancies, while lung cancer accounted for 17.4% (20/115). Other malignancies associated with dermatomyositis included liver cancer, ovarian cancer, cervical lymph node metastases of unknown origin, cholangial cancer, esophageal cancer, colon cancer, laryngeal cancer, renal cancer, tongue cancer and lymphoma. CONCLUSIONS: Dermatomyositis associated with malignancy was more common in patients aged 40 years or above. Malignancy was often detected within the first year after the onset of dermatomyositis. The most common malignancy associated with dermatomyositis was nasopharyngeal cancer, followed by lung cancer in Guangdong, China.

The risk of pulmonary complication after surgery for gallstone disease.

OBJECTIVES: To identify the risk factors of postoperative pulmonary complications (PPC) after surgery for gallstone disease. METHODS: A total of 544 patients undergoing open surgery for gallstone disease were retrospectively studied. Univariate and multivariate logistic regression were used to analyze each factor. RESULTS: There were 24 factors relating to PPC in univariate logistic analysis. And multivariate logistic analysis identified 5 independent risk factors associated with PPC, including perioperative aerosol therapy (OR = 5.906), duration of postoperative antacids therapy (OR = 1.145), duration of operation (OR = 1.011), preoperative serum albumin (OR = 0.689), postoperative analgesia (OR = 0.059), Logistic regression equation for predicting the risk of PPC was P(1) = 1/[1 + e-(- 9.803 + 1.776 x A + 0.135 x B + 0.011 x C - 0.372 x D - 2.835 x E)]. CONCLUSION: Perioperative aerosol therapy, duration of postoperative antacids therapy, duration of operation, preoperative serum albumin and postoperative analgesia were independent risk factors associated with PPC in patients undergoing surgery for gallstone disease.

[Risk factors for postoperative pulmonary complications after gastroduodenal operation].

OBJECTIVE: To investigate the risk factors for postoperative pulmonary complications (PPC) after gastroduodenal operation. METHODS: From December 1999 to December 2003, clinical data of 508 patients undergoing gastroduodenal operation were analyzed retrospectively. Risk factors for PPC were screened. RESULTS: The complication rate of PPC was 25.8% (131/508). Multivariate logistic regression analysis revealed that age (OR=1.052), history of respiratory diseases (OR=2.915), serum albumin level (OR=0.995), length of intratracheal intubation (OR=1.005), length of nasogastric intubation (OR=1.059) and length of postoperative mechanical ventilation (OR=1.367) were risk factors for PPC. CONCLUSION: Patients with old age, lower serum albumin level, intraoperative or postoperative nasogastric intubation, intratracheal intubation or long-term mechanical ventilation were more prone to develop PPC.

Multivariate analysis of the risk for pulmonary complication after gastrointestinal surgery.

AIM: To identify the risk factors for postoperative pulmonary complications (PPC) after gastrointestinal surgery. METHODS: A total of 1 002 patients undergoing gastrointestinal surgery in the Second Affiliated Hospital, Sun Yat-Sen University, during December 1999 and December 2003, were retrospectively studied. RESULTS: The overall incidence of PPC was 22.8% (228/1,002). Multivariate logistic analysis identified nine risk factors associated with PPC, including age odds ratio (OR = 1.040) history of respiratory diseases (OR = 2.976), serum albumin (OR = 0.954), chemotherapy 2 wk before operation (OR = 3.214), volume of preoperative erythrocyte transfusion (OR = 1.002), length of preoperative antibiotic therapy (OR=1.072), intraoperative intratracheal intubation (OR = 1.002), nasogastric intubation (OR = 1.050) and postoperative mechanical ventilation (OR = 1.878). Logistic regression equation for predicting the risk of PPC was P(1) = 1/[1+e(-(-3.488+0.039 x Y+1.090 x Rd+0.001 x Rbc-0.047 x Alb+0.002 x Lii+0.049 x Lni+0.630 x Lmv+0.070 x Dat+1.168 x Ct))]. CONCLUSION: Old patients are easier to develop PPC.

[Comparison of clinical features of severe acute respiratory syndrome among different transmission generations].

OBJECTIVE: To investigate the differences among various transmission generation of severe acute respiratory syndrome (SARS) by comparing the corresponding clinical data. METHODS: The clinical data of 84 patients with SARS were retrospectively studied, 66 women and 18 men, mean age (29.2 +/- 10.3) years old, 96.4% of whom were health care workers. All subjects had exposure to a source patient and the epidemic progressively propagated in a short time. For the infectious chain, we defined these patients who had exposure to a source patient as the primary cases, which included 35 patients (41.7%). Patients who got the disease by exposure to the primary cases were defined as secondary cases, which included 34 patients (40.5%). Similarly, the tertiary cases included 15 patients (17.9%). RESULTS: (1) No statistical differences in age, sex ratio, incubation period and hospitalization duration among various infectious generations were found (P > 0.05). (2) With descending in infectious generations, the initial temperature lowered, and cases with cough decreased (P < 0.05) with no statistical differences in the peak temperature, other accompanying symptoms and leukopenia (P > 0.05). (3) With descending in infectious generations, the course from the appearance of pulmonary lesions to their resolution shortened (P < 0.05). No differences were found in the maximal involved pulmonary fields, duration from initial fever to appearance of pulmonary lesions and course from the initial pulmonary lesions to their peak among the above three generations (P > 0.05). (4) No statistical differences were found in ways of oxygen therapy and classes of antibiotics prescribed (P > 0.05). With descending in infectious generation, cases treated with methylprednisolone, human gamma-immunoglobulin, interferon-alpha, and antiviral drugs (oral ribavirin or oseltamivir) increased (P < 0.05) and the duration of their use also increased (P < 0.05). CONCLUSIONS: With descending in infectious generations, the clinical features of SARS may become ameliorated.

Comparison of clinical course of patients with severe acute respiratory syndrome among the multiple generations of nosocomial transmission.

BACKGROUND: Severe acute respiratory syndrome (SARS) is characterized by both an atypical pneumonia and efficient nosocomial transmission. However, it remains unknown whether the infectivity and the virulence of the pathogen will change throughout the successive transmission. This study was conducted to compare the clinical features and management regimens of patients with SARS among the multiple generations from nosocomial transmission initiated by a super-spreader. METHODS: The clinical data of 84 epidemiologically-linked SARS patients from a hospital outbreak were retrospectively studied. All patients, in whom a clear-cut transmission generation could be noted, had a direct or indirect exposure to the index patient and the epidemic successively propagated through the multiple generations of cases within a short period of time. RESULTS: There were 66 women and 18 men with mean age of (29.2 +/- 10.3) years in this cluster; and 96.4% of whom were health care workers. Detailed contact tracing identified 35 (41.7%) first-generation cases, 34 (40.5%) second-generation cases, and 15 (17.8%) third-generation cases. No statistical differences among the multiple generations of transmission were found in terms of age, gender, incubation period and length of hospital stay. With the advanced transmission generations, the initial temperature lowered, the number of cases with dry cough decreased. There were no statistical differences in the peak temperature and duration of fever, other accompanying symptoms, leucopenia; however, the time from initial pulmonary infiltrates to radiographic recovery shortened (P < 0.05). No differences were found in maximum number of lung fields involved, duration from the onset of fever to the occurrence of pulmonary infiltrates and time from the initial pulmonary infiltrate to its peak among the multiple transmission generations (P > 0.05). No statistical differences were found in modes of oxygen therapy and sorts of antibiotics prescribed among the various transmission generations (P > 0.05); however, as with the advanced transmission generations, the number of cases prescribed with methylprednisolone, human gamma-globulin, interferon-alpha, antiviral drugs (oral ribavirin or oseltamivir) increased (P < 0.05) and time from admission to starting these medication shortened (P < 0.05). CONCLUSIONS: There is no evidence that SARS infection will evolve or transmit within a fashion that permits it to become less powerful throughout the successive transmission within a short time.

[A study of the architectural factors and the infection rates of healthcare workers in isolation units for severe acute respiratory syndrome].

OBJECTIVE: To investigate measures to prevent the outbreak of severe acute respiratory syndrome (SARS) in healthcare workers in isolation units. METHODS: The architectural factors and the infection of healthcare workers in different wards in our hospital between 30 January 2003 and 30 March 2003 were analyzed. RESULTS: Four kinds of isolation wards were evaluated, including the ward where the thirty-first bed lied in on the twelfth floor, the laminar flow ward in the intensive care unit (ICU) where the tenth bed lied in on the fifteenth floor, the ward where the twenty-seventh bed lied in on the thirteenth floor of Building A, and thirty wards on the fourteenth to eighteenth floors of Building B. The ratios (m2/m3) of the area of the ventilation windows to the volume of the room were 0, 0, 1:95 and 1:40, respectively. Numbers of SARS cases in the wards mentioned above were 1, 1, 1 and 96, respectively. The total lengths (hour) of hospitalization were 43, 168, 110 and 1,272, respectively. The infection rates of the healthcare workers in the areas mentioned above were 73%, 32%, 28% and 2%, respectively. The difference of the infection rates was of statistical significance. CONCLUSION: In addition to strict personal protective measures, isolation of SARS cases in wards with high ratio of the area of ventilation windows to the volume of the room and good ventilation may be the key to preventing the outbreak of SARS in healthcare workers in isolation units.

[Clinical features of 96 patients with severe acute respiratory syndrome from a hospital outbreak].

OBJECTIVE: To describe a hospital outbreak of severe acute respiratory syndrome (SARS) and summarize the clinical features and therapeutic approaches. METHODS: Clinical data in this cohort were collected prospectively as they were identified. RESULTS: The outbreak started with a SARS patient from the community on 30 January 2003, followed by a total of 96 people [76 women and 20 men; mean age (29.5 +/- 10.3) years; 93.8% of whom were health care workers] infected in a short period of time after their exposure to this source patient. The incubation period ranged from 1 to 20 days, with a mean of (5.9 +/- 3.5) days. The initial temperature was (38.3 +/- 0.6) degrees C, while the highest was (39.2 +/- 0.6) degrees C (P < 0.001), with a mean fever duration of (9.0 +/- 4.2) days. Other common symptoms included fatigue, cough, mild sputum production, chills, headache, general malaise and myalgia. The radiographic changes were predominantly bilateral and in the middle or lower lung zones. Leukopenia was observed in 67.7% of this cohort. The mean lowest oxygen saturation was (94.8 +/- 3.1)% with supplementary oxygen through a nasal cannula. 68.8% of the patients were treated with methylprednisolone for a mean period l of (4.9 +/- 2.4) days. The initial dose was (67.3 +/- 28.2) mg/d and the maximal dose was (82.4 +/- 30.5) mg/d. Ninety-five patients (99.0%) had a complete clinical recovery, and 1 patient died of progressive acute respiratory distress syndrome. The mean hospitalized duration was (17.2 +/- 8.0) days. CONCLUSION: SARS appears to be highly contagious and potentially lethal among health care workers, characterized by acute onset and rapid progression. Corticosteroids, antibiotics, human gamma-globulin, interferon-alpha, and antiviral drugs, although used empirically, might be of some benefits in shortening the clinical course.

Effects of antireflux treatment on bronchial hyper-responsiveness and lung function in asthmatic patients with gastroesophageal reflux disease.

AIM: To investigate the effects of antireflux treatment on bronchial hyper-responsiveness and lung function in asthmatic patients with gastroesophageal reflux disease (GERD). METHODS: Thirty asthmatic patients with GERD were randomly divided into two groups (group A and group B). Patients in group A (n=15) only received asthma medication including inhaled salbutamol 200 microg four times a day and budesonide 400 microg twice a day for 6 weeks. Patients in Group B (n=15) received the same medication as group A, and also antireflux therapy including oral omeprazole 20 mg once a day and domperidone 10 mg three times a day for 6 weeks. Pulmonary function tests and histamine bronchoprovocation test were performed before and after the study. RESULTS: There was no significant difference in the baseline values of pulmonary function and histamine PC(20-FEV1) between the two groups. At the end of the study, the mean values for VC, VC%, FVC, FVC%, FEV(1), FEV(1)%, PEF, PEF%, PC(20-FEV1) were all significantly improved in group B, compared with group A. CONCLUSION: Antireflux therapy may improve pulmonary function and inhibit bronchial hyper-responsiveness in asthmatic patients with GERD.

[Expression of cyclin D1 and vascular endothelial growth factor(VEGF) in non-small cell lung carcinoma and their association with the prognosis].

BACKGROUND & OBJECTIVE: The occurrence and development of tumors are controled by oncogene, antioncogene and tumor metastasis-related gene. Cyclin D1 is the expressive product of CCND1(a kind of oncogen). Vascular endothelial growth factor (VEGF) regulates the growth of neoplastic angiogenesis, which plays a role in the invasion and metastasis of tumor. The objective of this study was to detect the expression of Cyclin D1 and VEGF in non-small cell lung cancer (NSCLC), and to explore their association with the prognosis of NSCLC. METHODS: Immunohistochemistry was used to detect the expression of Cyclin D1 and VEGF in pathological tissue sections of 55 cases of NSCLC and 10 cases of non-malignant tissue from lung lesions. The relationship between the expression of Cyclin D1 and VEGF in 55 NSCLC sections and the age, sex, smoke, size of tumor, histopathological type, differentiation, stage, lymph node metastasis and survival time were analyzed statistically. RESULTS: The expression rates of Cyclin D1 and VEGF in the 55 NSCLC tissue sections were 61.82% and 74.55%, respectively. In 10 cases of non-malignant tissue sections, cyclin D1 expression was not detected and VEGF expression (+/-) was only in 2 cases. The expression of Cyclin D1 and VEGF showed: (1) there was no significant difference among age, sex, histopathological type, stage, differentiation, tumor size and smoking level; (2) there were significant differences between the patients with and without lymph node metastasis; (3) there were significant differences of survival time between positive and negative expression groups. It meant Cyclin D1 and VEGF would be the poor prognostic factors. CONCLUSION: The expression of Cyclin D1 and VEGF occurred in more than 60% cases of NSCLC, which may play a role in the biologic behavior and prognosis of NSCLC.