Valproic acid (VPA) enhances cisplatin sensitivity of non-small cell lung cancer cells via HDAC2 mediated down regulation of ABCA1.

Valproic acid (VPA) has been suggested to be a histone deacetylase inhibitor (HDACI). Our present study revealed that VPA at 1 mm, which had no effect on cell proliferation, can significantly increase the sensitivity of non-small cell lung cancer (NSCLC) cells to cisplatin (DDP). VPA treatment markedly decreased the mRNA and protein levels of ABCA1, while had no significant effect on ABCA3, ABCA7 or ABCB10. Luciferase reporter assays showed that VPA can decrease the ABCA1 promoter activity in both A549 and H358 cells. VPA treatment also decreased the phosphorylation of SP1, which can bind to -100 and -166 bp in the promoter of ABCA1. While the phosphorylation of c-Fos and c-Jun were not changed in VPA treated NSCLC cells. Over expression of HDAC2 attenuated VPA induced down regulation of ABCA1 mRNA expression and promoter activities. Over expression of HDAC2 also attenuated VPA induced DDP sensitivity of NSCLC cells. These data revealed that VPA can increase the DDP sensitivity of NSCLC cells via down regulation of ABCA1 through HDAC2/SP1 signals. It suggested that combination of VPA and anticancer drugs such as DDP might be great helpful for treatment of NSCLC patients.

IL-17 protein levels in both induced sputum and plasma are increased in stable but not acute asthma individuals with obesity.

BACKGROUND: Obesity worsens asthma control partly through enhanced airway neutrophilia, altered lung mechanics and comorbidities, including obstructive sleep apnea syndrome, gastroesophageal reflux disease and depression. Although controversial, obesity may also cause poorer outcomes in acute asthma. IL-17 is associated with neutrophilic inflammation, steroid resistance and severe asthma, but its importance in the association between asthma and obesity is unknown. OBJECTIVE: To investigate the role of IL-17 in obese asthma in both acute and stable settings. METHODS: Both stable (n = 177) and acute (n = 78) asthmatics were recruited and categorized into lean (n = 77 and 39 respectively), overweight (n = 41 and 17 respectively) and obese (n = 59 and 22 respectively) groups and compared for clinical characteristics, including sputum and plasma IL-17 protein concentrations, sputum cellularity, spirometry and comorbidities. Correlations of IL-17 expression with other measures were explored. RESULTS: In stable subjects, airway neutrophilia and IL-17 concentrations were most prominent in the obese, and correlated positively with each other. Significant increase in plasma IL-17 levels was also noted and associated with elevated depressive symptoms in obesity. In acute asthma, IL-17 expression, like most other clinical measures, was similar among lean, overweight and obese groups, but was higher in acute versus stable asthma subjects, with sputum IL-17 correlating positively with sputum neutrophils and negatively with FEV1 and plasma IL-17 showing a positive connection to airway eosinophilia during exacerbation. CONCLUSIONS: IL-17 contributes to worse disease control in obese asthma through enhancing airway neutrophilia and depression, and may implicate in asthma exacerbations. Effects of adiposity on acute asthma remain uncertain.

Utility of uric acid as a risk marker of extubation success in chronic obstructive pulmonary disease.

BACKGROUND: The objective of this observational study was to determine whether there is an association between extubation success and uric acid in chronic obstructive pulmonary disease patients with mechanical ventilation admitted to the intensive care units, and identify the risk markers for extubation success in COPD patients with mechanical ventilation. METHODS: Consecutive COPD patients with intubation were screened at baseline. The study included patients on mechanical ventilation (MV) for over 12 hours and who, in the process of weaning, were subjected to low-level pressure support. Exclusion criteria were age under 18 years, ventilation via tracheotomy, and patients failing to cooperate for different reasons. The final study population consisted of 106 patients. Demographic, clinical, laboratory, and mechanical ventilation parameters were carefully recorded. Logistic regression was used for the multivariate analysis of independent risk factors. RESULTS: Uric acid on admission, duration of mechanical ventilation, pressure support ventilation, and APACHE II score on admission were significantly higher in COPD patients with extubation failure than in those with extubation success (p < 0.05), but lower tidal volume before weaning was observed in COPD patients with extubation failure. Among these patients, multiple logistic analyses indicated the independent risk factors for extubation success in the COPD subjects included serum uric acid level, APACHE II score on admission, and duration of mechanical ventilation. The diagnosis analysis showed that higher uric acid level and APACHE II score on admission and longer duration of mechanical ventilation had a significant ability to reflect extubation success in the COPD patients with respiratory failure. CONCLUSIONS: The novel finding of this study is that the extubation failure in COPD patients with respiratory failure is strongly related to serum uric acid level, APACHE II score on admission, and duration of mechanical ventilation. These results might be helpful for selecting the best time to remove the tracheal intubation and improving extubation success rate in COPD patients with respiratory failure.

Azithromycin attenuates pulmonary inflammation and emphysema in smoking-induced COPD model in rats.

INTRODUCTION: The role of inflammation and immunity in COPD treatment is increasingly being recognized. The relationship between anti-inflammation/immunoregulation and emphysema in COPD lungs remains to be elucidated. The aim of this study was to investigate the effects of azithromycin (Azm) on the development of emphysema in smoking-induced COPD in rats. METHODS: Sprague-Dawley rats (n = 50) were randomly assigned to normal, COPD, saline-treated, Azm-treated, and levofloxacin-treated (Lev) groups. The effects of treatment were assessed by measuring the levels of vascular endothelial growth factor (VEGF) by enzyme-linked immunosorbent assay and measuring the numbers of neutrophil and macrophage in bronchoalveolar lavage fluid, vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR2) protein expression by western blotting. Lung function measurements and histopathological evaluations (mean linear intercept and destructive index) were performed. RESULTS: FEV0.3/FVC and peak expiratory flow were lower in the COPD group than in the normal group. Mean linear intercept and destructive index were lower in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. The numbers of neutrophil and macrophage in bronchoalveolar lavage fluid were lower in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. As confirmed by western blotting, the levels of VEGF in lung homogenates were higher in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. VEGFR2 protein expression was higher in the Azm-treated group than in the COPD, saline-treated, and Lev-treated groups. CONCLUSIONS: Azm attenuates pulmonary emphysema by partly reversing the decrease in the numbers of inflammatory cells (neutrophil and macrophage) and VEGF secretion and VEGFR2 protein expression in smoking-induced COPD in rats.

Uric acid levels in obstructive sleep apnea patients with atrial fibrillation.

BACKGROUND AND AIMS: The objective of this observational study was to determine whether there is an association between atrial fibrillation (AF) and uric acid and to identify the risk markers for AF in obstructive sleep apnea (OSA). METHODS: Consecutive patients with newly diagnosed OSA were screened at baseline. The final study population consisted of 516 patients. One hundred and eight patients had AF. Demographic, clinical, laboratory, and echocardiographic characteristics were carefully recorded. Logistic regression was used for the multivariate analysis of independent risk factors. RESULTS: Uric acid, triglyceride, high-density lipoprotein, C-reactive protein (CRP), left atrial diameter, interventricular septum thickness, apnea hypopnea index, and Epworth sleepiness scale were significantly higher in OSA patients with AF than in those without AF (p <0.05). Among these patients, multiple logistic analyses indicated the independent risk factors for AF occurrence in the OSA subjects included serum uric acid level, left atrial diameter, percentage of time with SaO2 <90%, CRP. The diagnosis analysis showed that higher uric acid, CRP, left atrial diameter and percentage of time with SaO2 <90% had a significant ability to reflect the presence of AF occurrence. CONCLUSIONS: The novel finding of this study is that the occurrence of AF in OSA patients is strongly related to serum uric acid level, left atrial diameter, percentage of time with SaO2 <90% and CRP level. These results may be helpful for monitoring AF occurrence in OSA patients.

Risk factors and mortality of patients with nosocomial carbapenem-resistant Acinetobacter baumannii pneumonia.

BACKGROUND: Acinetobacter baumannii is characterized by strictly aerobic, gram-negative, nonmotile, nonlactose-fermenting, oxidase-negative, catalase-positive coccobacilli, and the combination of its environmental resilience and its rapid development of resistance to multiple classes of antimicrobials renders it a successful nosocomial pathogen. OBJECTIVES: The aim of this study was to identify specific risk factors and outcome of nosocomial pneumonia because of carbapenem-resistant Acinetobacter baumannii (CRAB). METHODS: The retrospective study, set in a 1,500-bed referral and tertiary care hospital, was conducted to analyze the clinical and microbiologic data of patients with nosocomial pneumonia because of Acinetobacter baumannii (A baumannii) from January 2006 to December 2011. Comparisons were made between patients with CRAB pneumonia and patients with carbapenem-susceptible A baumannii (CSAB) pneumonia. Only the first isolation of A baumannii was considered. RESULTS: A total of 145 patients with CSAB pneumonia and 97 patients with CRAB pneumonia was included. Among these patients, the independent risk factors for acquiring CRAB pneumonia were Acute Physiology and Chronic Health Evaluation II (APACHE II) score (>20) at admission, systemic illnesses (chronic respiratory disease and cerebrovascular accident), presence of excess noninvasive or invasive devices (mechanical ventilation), and ever used antibiotics within 28 days (carbapenem and cefepime). The patients with CRAB pneumonia had higher mortality rate than CSAB pneumonia. Multivariate analysis showed that, among patients with A baumannii pneumonia, APACHE II score (>20) at pneumonia onset, infections with other microorganisms, and inappropriate therapy were independently associated with 28-day mortality. CONCLUSION: Patients with CRAB pneumonia have a higher mortality rate than those with CSAB pneumonia. The nosocomial occurrence of CRAB pneumonia is strongly related to systemic illnesses, APACHE II score, mechanical ventilation, and ever used antibiotics within 28 days.

Citric acid reduces the decline in P300 amplitude induced by acute alcohol consumption in healthy adults.

Event-related potential (ERP) is a reliable neuroelectric measure of brain activity that helps to confirm the assessment of mental status and cognitive impairment. Many studies have reported that alcoholics show a significantly lower ERP P300 amplitude than the norm. In the present study, ERP P300 waves were measured to evaluate the effect of citric acid on cognitive function during excessive alcohol consumption in healthy adults. Five volunteers were selected through clinical interview, physical examination, and psychiatric assessment for participation in this study. In a double-blind placebo-controlled before-after design, each subject was treated with 5 ml/kg body weight alcohol, 5 ml/kg body weight alcohol and 1 mg citric acid, or a placebo on three separate occasions, one week apart. ERP P300, blood biochemical indicators, blood alcohol concentrations (BACs) and acetaldehyde concentrations were assessed. Repeated measure analysis of variance (ANOVA) with a within-subjects factor was used to evaluate differences in blood biochemical indicators, BACs, blood acetaldehyde concentrations, and ERP P300 in the three sessions of assessments. Several blood biochemical indicators showed significant differences between treatments, including the levels of cholinesterase (CHE), total bile acid (TBA), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and glycylproline dipeptidyl aminopeptidase (GPDA). BACs after consumption of alcohol alone or citric acid with alcohol were significantly higher compared to those after placebo treatment (P<0.05). There were no significant differences in blood acetaldehyde concentrations between the treatments. The P300 amplitudes on the frontal (Fz), central (Cz), and parietal (Pz) regions of the scalp after consumption of alcohol were significantly lower than those after consumption of the placebo or citric acid with alcohol (P<0.05), while there were no significant differences between the latter two treatments. The results of this study suggest that citric acid could reduce the decline in ERP P300 amplitude and cognitive ability induced by acute alcohol consumption. It may also affect some blood biochemical indicators, but the specific mechanisms need further research.