Extrafine beclomethasone/formoterol in severe COPD patients with history of exacerbations

The FORWARD study is a randomised, double-blind trial that compares the efficacy and safety of 48 weeks treatment with extrafine beclomethasone dipropionate/formoterol fumarate (BDP/FOR), 100/6 μg pMDI, 2 inhalations BID, vs. FOR 12 μg pMDI, 1 inhalation BID, in severe COPD patients with a history of exacerbations. Co-primary endpoints were exacerbation rate over 48 weeks and pre-dose morning FEV1 at 12 weeks. The ITT population included 1186 patients (69% males, mean age 64 years) with severe airflow limitation (mean post-bronchodilator FEV1 42% predicted). Salbutamol as rescue therapy, theophylline and tiotropium (if stable regimen prior to screening) were allowed. Compared to FOR, BDP/FOR: (1) reduced the exacerbation rate (rate ratio: 0.72 [95% confidence interval 0.62–0.84], p < 0.001); (2) improved pre-dose morning FEV1 (mean difference: 0.069 L [0.043–0.095] p < 0.001); (3) prolonged the time to first exacerbation; (4) improved the SGRQ total score. The percentage of patients with adverse events was similar (52.1% with BDP/FOR and 49.2% with FOR). Pneumonia incidence was low, slightly higher with BDP/FOR (3.8%) than with FOR (1.8%). No difference for laboratory values, ECG or vital signs. Extrafine BDP/FOR significantly reduces the exacerbation rate and improves lung function of patients with severe COPD and history of exacerbations as compared to FOR alone

Iron entry route in horse spleen apoferritin Involvement of the three-fold channels as probed by selective reaction of cysteine-126 with the spin label 4-maleimido-tempo

AbstractApoferritin has been selectively labeled with a maleimide nitroxide derivative at Cys-126, located in the hydrophilic 3-fold channels. Titration of this derivative with Fe(II), which gives rise to the initial Fe(III)-apoferritin complex, produces, at low metal-to-protein ratios, a decrease of the intensity of the label EPR signal due to the occurrence of a magnetic dipolar interaction. A label-metal distance ranging between 8–12 Å can be estimated from titrations performed with VO(IV), which is known to bind in the 3-fold channels, and likewise produces a decrease in the label EPR signal. The present findings indicate that iron binds in the hydrophilic channels in its higher oxidation slate and that these channels represent the metal entry route at least at low metal-to-protein ratios

Respiratory inhibition of isolated mammalian mitochondria by salivary antifungal peptide histatin-5

Histatin-5 is a peptide secreted in the human saliva, which possesses powerful antifungal activity. Previous studies have shown that this peptide exerts its candidacidal activity, through the inhibition of both mitochondrial respiration and the formation of reactive oxygen species. The purpose of the present study was to investigate the biological consequences of histatin-5 action on mammalian mitochondria to verify if the toxic mechanism exerted on mitochondria from Candida albicans is an exclusive for fungal cells. Moreover, hypothesising that the damage exerted on mitochondria may induce programmed cellular death pathways, we evaluated two main markers of apoptosis: the mitochondrial membrane potential (DeltaPsi) and the release of cytochrome c. The results obtained show that exposure of isolated mammalian mitochondria to histatin-5 determines: (i) a large inhibition of the respiratory chain at the level of complex 1, (ii) a slight decrease in the mitochondrial membrane potential, and (iii) no release of cytochrome c. (C) 2003 Elsevier Inc. All rights reserved

MOLECULAR IDENTIFICATION AND GENOTYPING OF CIAUSCOLO AUTOCHTHONOUS MICROFLORA: PRELIMINARY STUDY

The present study reports the results of a preliminary characterization of the bacterial population of Ciauscolo, a typical Italian fermented sausage, traditionally manufactured in Marche region. The bacterial community involved in Ciauscolo fermentation was investigated using both molecular and culturebased methods. The estimation of genotypic intra-species variation of the autochthonous bacteria isolated was also evaluated by using randomly amplified polymorphic DNA (RAPD) analysis and unweighted pairgroup method with arithmetic averages (UPGMA) cluster analysis. Our findings revealed an high diversity of the autochthonous bacterial population investigated, both at species and strain level

Carcinogen metabolism in human lung tissues and the effect of tobacco smoking: results from a case--control multicenter study on lung cancer patients.

Cigarette smoking is the strongest risk factor for lung cancer, but genetically determined variations in the activities of pulmonary enzyme that metabolize tobacco-derived carcinogens may affect individual risk. To investigate whether these enzymes (e.g., CYP1A-related) can serve as markers for carcinogen-DNA damage, lung tissue specimens were taken during surgery from middle-aged men with either lung cancer or non-neoplastic lung disease. Phase I [aryl hydrocarbon hydroxylase (AHH), ethoxycoumarin O-deethylase (ECOD)] and phase II (epoxide hydrolase, UDP-glucuronosyltransferase, glutathione S-transferase) enzyme activities, glutathione and malondialdehyde contents were determined in lung parenchyma and/or bronchial tissues; some samples were also analyzed for DNA adducts, using 32P-postlabeling. The data were then analyzed for the following: a) differences in metabolic profiles between bronchial and parenchymal lung tissue; b) the effect of recent exposure to tobacco smoke on enzyme inducibility and benzo[a]pyrene metabolism; c) differences in enzyme inducibility between lung cancer and non-lung cancer patients; d) the effect of smoking on metabolism of mutagens in vitro; e) pulmonary DNA adduct levels and AHH activity in lung parenchyma of smokers and ex-smokers; f) lipid peroxidation products in lung tissue from lung cancer and non-lung cancer patients, as related to smoking habits and degree of airway obstruction; and g) prognostic value of AHH pulmonary activity in lung cancer patients. The results demonstrate a pronounced effect of tobacco smoke on pulmonary metabolism of xenobiotics and prooxidant state and suggest the existence of a metabolic phenotype at higher risk for tobacco-associated lung cancer

Multi-level analysis of on-chip optical wireless links

Networks-on-chip are being regarded as a promising solution to meet the on-going requirement for higher and higher computation capacity. In view of future kilo-cores architectures, electrical wired connections are likely to become inefficient and alternative technologies are being widely investigated. Wireless communications on chip may be therefore leveraged to overcome the bottleneck of physical interconnections. This work deals with wireless networks-on-chip at optical frequencies, which can simplify the network layout and reduce the communication latency, easing the antenna on-chip integration process at the same time. On the other end, optical wireless communication on-chip can be limited by the heavy propagation losses and the possible cross-link interference. Assessment of the optical wireless network in terms of bit error probability and maximum communication range is here investigated through a multi-level approach. Manifold aspects, concurring to the final system performance, are simultaneously taken into account, like the antenna radiation properties, the data-rate of the core-to core communication, the geometrical and electromagnetic layout of the chip and the noise and interference level. Simulations results suggest that communication up to some hundreds of μm can be pursued provided that the antenna design and/or the target data-rate are carefully tailored to the actual layout of the chip

Metallo-Dielectric Multilayer Structure for Lactose Malabsorption Diagnosis through H2 Breath Test

A metallo-dielectric multilayer structure is proposed as a novel approach to the analysis of lactose malabsorption. When lactose intolerance occurs, the bacterial overgrowth in the intestine causes an increased spontaneous emission of H2 in the human breath. By monitoring the changes in the optical properties of a multilayer palladium-polymeric structure, one is able to detect the patient's disease and the level of lactose malabsorption with high sensitivity and rapid response

Bdellovibrio bacteriovorus to control Escherichia coli on meat matrices

Bdellovibrio bacteriovorus is a predator micro-organism towards other Gram-negative bacteria. We tested B.&nbsp;bacteriovorus to control Escherichia coli growth on chicken slices and canned beef. Moreover, we analysed B.&nbsp;bacteriovorus's lytic ability on eight toxigenic or multidrug-resistant E.&nbsp;coli strains. In chicken slices, the predator induced the highest prey reduction (4.3 log) respect to control at 6&nbsp;h. In canned beef, the predator induced the highest prey reduction (2.1 log) respect to control at 6&nbsp;h. Moreover, B.&nbsp;bacteriovorus showed lytic ability towards all tested E.&nbsp;coli strains. B.&nbsp;bacteriovorus could control E.&nbsp;coli and other pathogenic and spoilage bacteria in those meat-based foods that have a shelf life &lt;10&nbsp;days. It could integrate modified atmosphere packaging (MAP) to prolong the shelf life and improve the safety of pre-packed fresh meat, meat preparations and meat products. In future applications on meat-based foods, B.&nbsp;bacteriovorus could also minimise the use of additives