analysis of exhaled breath fingerprints and volatile organic compounds in copd

Exhaled air contains many volatile organic compounds (VOCs) produced during human metabolic processes, in both healthy and pathological conditions. Analysis of breath allows studying the modifications of the profile of the exhaled VOCs due to different disease states, including chronic obstructive pulmonary disease (COPD). The early diagnosis of COPD is complicated and the identification of specific metabolic profiles of exhaled air may provide useful indication to better identify the disease. The aim of our study was to characterize the specific exhaled VOCs by means of the electronic nose and by solid phase micro-extraction associated to gas chromatography–mass spectrometry (SPME GC-MS). Exhaled air was collected and measured in 34 subjects, 7 healthy and 27 former smokers affected by COPD (GOLD 1–4). The signals of the electronic nose sensors were higher in COPD patients with respect to controls, and allowed to accurately classify the studied subjects in healthy or COPD. GC-MS analysis identified 37 VOCs, nine of which were significantly correlated with COPD. In particular the concentration of two of these were positively correlated whereas seven were negatively correlated with COPD. The partial least squares discriminant analysis (PLS-DA) carried out with these nine VOCs produced a significant predictive model of disease. This study shows that COPD patients exhibit qualitative and quantitative differences in the chemical compositions of exhale. These differences are detectable both by the GC-MS and the six-sensor e-nose. The use of electronic nose may represent a suitable, non-invasive diagnostic tool for characterization of COPD

Indolyl aryl sulphones as HIV-1 non-nucleoside reverse transcriptase inhibitors: synthesis, biological evaluation and binding mode studies of new derivatives at indole-2-carboxamide.

New non-nucleoside reverse transcriptase inhibitors (NNRTIs) that are active against the commonly occurring mutations of HIV are urgently needed for the treatment of AIDS. We synthesized new NNRTIs of the indolyl aryl sulphone (IAS) family, which are endowed with high antiviral potency against HIV-1 wt (wild-type), and the Y181C and K103N-Y181C drug resistant mutant strains. Several new compounds were highly active in lymphocytes infected with primary isolates carrying the K103N-V108I-M184V and L100I-V108I mutations. The design of new IASs was based on three-dimensional quantitative structure-activity relationship (3D QSAR) studies and docking simulations. A cross-docking study was also undertaken to gain some insights in to the binding mode of the newly synthesized IASs in the wt and mutated isoforms of reverse transcriptase

The Time Course of Pulmonary Function Tests in COPD Patients with Different Levels of Blood Eosinophils

Only very few studies have investigated the influence of eosinophils on the functional progression of COPD. We aimed at retrospectively analyzing the trend of pulmonary function tests over time in patients with COPD according to two baseline blood eosinophil cell count strata (<2% [EOS−] and ≥2% [EOS+]). We used the last 9-year data present in the database of our outpatient clinic and selected only those who had two blood counts that would guarantee the stability of the value of eosinophils and serial spirometry for 4 consecutive years. The analysis of the time course of the spirometric variables analysed showed differences in FEV1 and FVC decline between the subjects of the EOS− group and those of the EOS+ group. The integrated evaluation of our results suggests that the different level of blood eosinophils in the two groups may have influenced independently the time course of the pulmonary function tests and identify two subgroups of subjects with specific disease characteristics: the hyperinflator and the rapid decliner, respectively

Downregulation of CD40 Ligand Response in Monocytes from Sepsis Patients▿

It has been suggested that a defective adaptive immune response contributes to septic immunosuppression. Here, the response of monocytes to CD40 ligand (CD40L) for patients with sepsis due to infection with gram-negative organisms has been analyzed. Compared to cells from controls, monocytes from septic patients showed significantly reduced production of tumor necrosis factor alpha, interleukin-1β (IL-1β), and IL-12 and were unable to acquire high levels of CD80 and CD86 molecules. These alterations were observed at the onset of sepsis and persisted at day 7. However, the ability of monocytes to respond to CD40L stimulation was partially but significantly restored in cells from patients who recovered from sepsis. In addition, costimulation of autologous CD4+ T lymphocytes by CD40L-activated monocytes from septic patients failed to induce cell proliferation and gamma interferon production. Finally, the ability of CD40L to rescue monocytes from apoptosis was severely impaired. We conclude that downregulation of the CD40L response may be an appropriate model for the monocyte alteration observed during septic immunosuppression and may help in the development of novel therapeutic strategies