Search

Objectives Acute lung injury (ALI) is a critical complication subsequent to hemorrhage shock and resuscitation (HSR) that frequently leads to multiple organ failure. Collective evidence suggested that the activation of pulmonary nicotinamide adenine dinucleotide-dependent deacetylase sirtuin-1 (SIRT1) plays a critical role in inhibiting the production of reactive oxygen species (ROS) and tumor necrosis factor (TNF)-α, as well as the protection against ALI. Curcumin is a potent activator of SIRT1 and possesses antioxidative and anti-inflammatory effects. In this study, we aim to investigate the dose-dependent protective effectiveness of curcumin pretreatment against HSR-induced ALI. Methods Studies were conducted on Sprague-Dawley male rats in 5 groups: sham-operated, HSR, and HSR pretreated with 50, 200, or 400 mg/kg of curcumin. Curcumin was treated orally for 4 days and 1 hour before HSR induction. HSR was induced by decreasing the mean aortic pressure (MAP) to 40 mm Hg for 60 min through drawing blood from the left femoral artery, followed by blood replenish and leaving for another 120 min. At the end of HSR, the severity of ALI was assessed by pulmonary barrier function, via pulmonary filtration coefficient (Kfc) evaluated using isolated a perfused lung model, lung weight-to-body weight ratio (LW/BW), lung wet-to-dry weight ratio (W/D), and lavage protein concentration (PCBAL). We also examined the level of lung inflammation by lavage TNF-α and differential neutrophil count, and oxidative stress by lavage malondialdehyde (MDA). Results HSR significantly increased Kfc, LW/BW, W/D, and PCBAL; decreased pulmonary SIRT1; and increased lavage TNF-α and MDA contents and differential neutrophil count (P Conclusions Curcumin pretreatment protects against HSR-induced pulmonary function impairment by increasing tissue SIRT1, which reduced lavage MDA and TNF-α and differential neutrophil count in a dose-dependent fashion.

Background The capability of bronchoscopy in the diagnosis of peripheral pulmonary nodules (PPNs) remains limited. Despite decades of effort, evidence suggests that the diagnostic accuracy for electromagnetic navigational bronchoscopy (EMN) and radial endobronchial ultrasound (EBUS) approach only 50%. New developments in robotic bronchoscopy (RB) may offer improvements in the assessment of PPNs. Methods A prospective single-blinded randomized controlled comparative study to assess success in localization and puncture of PPNs, using an ultrathin bronchoscope with radial EBUS (UTB-rEBUS) vs EMN vs RB in a human cadaver model of PPNs Results Sixty procedures were performed to target 20 PPNs over the study period. Implanted PPNs were distributed across all lobes, with 80% located within the lung periphery. The target PPN mean diameter was 16.5 ± 1.5 mm, with 50% noted to have a CT bronchus sign. The rate of successful PPN localization and puncture was superior when using RB, compared with EMN (80% vs 45%; P = .02). Among unsuccessful needle passes, the median needle to target “miss” distance was significantly different when comparing UTB-rEBUS, EMN, and RB (P = .0014). Conclusions In a cadaver model, use of RB significantly increased the ability to localize and successfully puncture small PPNs when compared with existing technologies. This study demonstrates the potential of RB to precisely reach, localize, and puncture small nodules in the periphery of the lung.

Objective Acute lung injury (ALI) is one of the most common extra-pancreatic complications of acute pancreatitis. In this study, we examined the protective effect of protease inhibitor aprotinin and a matrix metalloproteinase inhibitor (MMPi) on pulmonary inflammation in rats with severe pancreatitis-associated ALI. Method A rat model of acute pancreatitis (AP) was established by injecting sodium glycodeoxycholate (GDOC) into the pancreatic duct. Pharmacological interventions included pretreatment with a protease inhibitor aprotinin (10 mg/kg) and a matrix metalloproteinase inhibitor (MMPi, 100 g/kg). The extent of pancreatic and lung injury and systemic inflammation was assessed by examinations of blood, bronchoalveolar lavage (BAL), and lung tissue. Pancreatic or lung tissue edema was evaluated by tissue water content. Pulmonary arterial pressure and alveolar-capillary membrane permeability were evaluated post-injury via a catheter inserted into the pulmonary artery in an isolated, perfused lung model. Results Pre-treatment with aprotinin or MMPi significantly decreased amylase and lactate dehydrogenase (LDH), and the wet/dry weight ratio of the lung and pancreas in AP rats. Compared to the GDOC alone group, administration of aprotinin or MMPi prevented pancreatitis-induced IL-6 increases in the lung. Similarly, treatment with aprotinin or MMPi significantly decreased the accumulation of white blood cells, oxygen radicals, nitrite/nitrates in both blood and BAL, and markedly reduced lung permeability. Conclusion Pretreatment with either aprotinin or MMPi attenuated the systemic inflammation and reduced the severity of lung and pancreas injuries. In short, our study demonstrated that inhibition of protease may be therapeutic to pulmonary inflammation in this GDOC-induced AP model.

Background For marginally operable stage IIIA non–small-cell lung cancer (NSCLC), surgery might not be done as planned after neoadjuvant concurrent chemoradiotherapy (CCRT) for reasons (unresectable or medically inoperable conditions, or patient refusal). This study aims to investigate the outcomes of a phased CCRT protocol established to maximize the operability of marginally operable stage IIIA NSCLC and to care for reassessed inoperable patients, in comparison with continuous-course definitive CCRT. Materials and Methods Forty-seven patients with marginally operable stage IIIA NSCLC receiving CCRT were included. Twenty-eight patients were treated with our phased CCRT protocol, including neoadjuvant CCRT followed by surgery (group A, n = 16) or, for reassessed inoperable patients, maintenance chemotherapy and split-course CCRT boost (group B, n = 12). The other 19 were treated with continuous-course definitive CCRT (group C). Overall survival (OS) and progression-free survival (PFS) were analyzed. Results Among all, median OS and PFS were 35.6 and 12.8 months, respectively (median follow-up, 22.3 months). The median OS of group A (not reached) was better than that of group B (34.4 months) and group C (15.2 months) ( P = .009). On multivariate analysis, performance status 0 to 1 (hazard ratio [HR], 0.026; P P = .003), and group A (HR, 0.199; P = .033) were independent prognostic factors. The OS of group B (HR, 0.450; 95% confidence interval, 0.118-1.717; P = .243) was not statistically different from that of group C. Conclusions For marginally operable stage IIIA NSCLC, our phased CCRT strategy may optimize survival by maximizing operability and maintain an acceptable survival for reassessed inoperable patients by split-course CCRT boost following maintenance chemotherapy.

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) is the standard therapy for advanced lung adenocarcinomas with common EGFR mutations. Preclinical studies have suggested that uncommon G719X, L861Q, and S768I mutations are also sensitive to EGFR-TKIs. However, the efficacy of EGFR-TKIs in patients with these uncommon mutations remains unclear.A nationwide survey was performed to collect data from gefitinib and erlotinib treatment outcomes of patients with stage IIIB/IV lung adenocarcinoma bearing EGFR G719X/L861Q/S768I mutations. The results were compared with those regarding patients with exon 19 deletions or L858R mutations.One hundred and sixty-one patients with uncommon EGFR mutations were enrolled from 18 institutes throughout Taiwan. Mutations of G719X, L861Q, S768I, G719X + L861Q, and G719X + S768I were observed in 78, 57, 7, 9, and 10 patients, respectively. After receiving EGFR-TKI treatment, patients with uncommon mutations exhibited a significantly inferior tumor response rate (41.6% vs. 66.5%; p0.001) and progression-free survival (median, 7.7 vs. 11.4 months; p0.001) than patients with common mutations. Among the patients who used EGFR-TKIs as first-line treatment, there was a significant difference in overall survival between these two groups of patients (median, 24.0 vs. 29.7 months; p = 0.005).Gefitinib and erlotinib are active in patients with G719X/L861Q/S768I mutations; however, less effective than in those with common mutations.

We report a case of "rectangular (quadrangular) heart" seen on the chest X-ray. Full evaluation showed massive enlargement of right-sided chambers shadowing the left-sided chambers. Primary etiology of the right-sided failure was attributed to severe mitral and tricuspid regurgitation for which the patient underwent surgery. Learning objective: To understand that a cardiac chamber enlargement can result in massive increase in cardiac silhouette on a chest X-ray. Predominant right atrial and ventricular enlargement in comparison to left-sided chambers can give rise to a peculiar shape (rectangular/quadrangular) in the chest X-ray.>

Silicas chemically modified with attached aminopropyl, imidazolyl, and trimethylsilyl groups, with adsorptive and coordinative grafted hemin were synthesized. Adsorption of some bile acids on the surface of hydroxylated silica, synthesized siliceous adsorbents and cholestyramine has been studied. It was found that the main contribution to the total adsorption is caused by electrostatic attraction between anions of bile acids and positively charged sites of the surface of modified silica and also by dispersion interactions between steroid skeleton of bile acids and functional groups of modified silicon dioxides. It was established that the kinetic parameters of adsorption and adsorptive capacity for all investigated siliceous adsorbents exceed similar characteristics for cholestyramine. The best of synthesized adsorbents is hemin-containing adsorbent IX, and the sequence of increase in its adsorptive capacity in relation to bile acids corresponds to the following series: I < III < II, IV < VI < V < VIII < VII < IX.

An all-aqueous sol-gel method for encapsulation of bacterial cells in porous silicate matrices towards the development of a biosensor is described. The sol-gel encapsulation of cells is achieved at room temperature and neutral pH. Furthermore, use of sodium silicate as precursor avoids generation of alcohol that can be detrimental to cells in contrast to the traditional alkoxide sol-gel encapsulation process. Moraxella spp. cells engineered to express recombinant organophosphorus hydrolase (OPH) on the cell surface were encapsulated and OPH enzymatic activity was measured for paraoxon hydrolysis. Kinetic parameters (Km and Vmax) as well as pH behavior of surface-expressed OPH were determined to evaluate the effect of encapsulation. Cells encapsulated by the sodium silicate method displayed higher activity retention compared to those by the traditional alkoxide process. Time-course studies over a 2-month period indicate that immobilization through the sodium silicate process led to a reduction in activity of approximately 5% as compared to approximately 30% activity reduction in case of free cells in buffer indicating that immobilization leads to stabilization, a key parameter in biosensor development.

Interaction of poly(1-vinyl-2-pyrrolidone) with the surface of highly dispersed silica and character of its thermal destruction were investigated by means of ad-desorption measurement, vibration and electron spectroscopy, and thermal gravimetric analysis with programmed heating. The correlation between the character of polymer keeping on the surface of silicon dioxide and its thermal decomposition was established.

The chemical modification of silica surfaces by nitrogen-containing organic reagents (γ-aminopropyltriethoxysilane, imidazole, or N-vinyl-2-pyrrolidone) and also with hexamethyl disilazane and hydrocarbon oligomers was proposed to enhance the adsorptive capacity of silica with respect to monocarboxylic and bile acids. The calculation of the content of protonated and deprotonated groups on the surfaces of synthesized organosilicas with distinguished basicity of functional groups was performed using the program GRFIT for the model of a diffuse layer. The contribution of hydrophobic and electrostatic interactions to the adsorption of organic acids was revealed. It has been established that the maximum of organic acid adsorption coincides with the pH at which the curve of increasing concentration of the anion of an organic acid and the curve of decreasing concentration of the protonated functional groups of aminopropyl silica are intercrossed.