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.

Olodaterol + tiotropium bromide for the treatment of COPD.

Patients suffering from COPD not controlled by a single bronchodilator should be given two bronchodilators with different mechanisms of action. Addition of a LABA to a LAMA induces a larger bronchodilation than that obtained with the LAMA as monotherapy and also improves many patient-reported outcomes. Since the clinical-functional sign regarding simultaneous use of tiotropium, which is still the dominant LAMA, and olodaterol was very strong, the combination of these two bronchodilators has been developed as FDC delivered via a single inhaler (Respimat) with the aim of simplifying the treatment regimen and improving patient adherence to treatment.

Effect of indacaterol on arterial blood gases in patients suffering from acute exacerbation of COPD.

Aim: The administration of β2-agonists to patients with airways obstruction often results in transient decrease in PaO2 despite concomitant bronchodilation. This effect is potentially dangerous for patients suffering from acute exacerbation of COPD (AECOPD). In this study, we investigated the effect of indacaterol 150 μg and 300 μg on the arterial blood gas tensions of hospitalised patients with AECOPD.

Proinflammatory modulation of the surface and cytokine phenotype of monocytes in patients with acute Charcot foot.

Objective: Despite increased information on the importance of an inappropriate inflammatory response in the acute Charcot process, there has been no previous attempt to define the specific pathways that mediate its pathogenesis. Here, the role played by monocytes was analyzed.

Research Design And Methods: The immune phenotype of peripheral monocytes was studied by fluorescence-activated cell sorter analysis comparing patients with acute Charcot (n = 10) in both the active and recovered phase, diabetic patients with neuropathy (with or without osteomyelitis), and normal control subjects.

A pilot comparison of helium dilution and plethysmographic lung volumes to assess the impact of a long-acting bronchodilator on lung hyperinflation in COPD.

Background: Currently, two methods for measuring TLC, RV, and FRC are used in clinical pulmonary function laboratories: body plethysmography and helium dilution. However, these methods are not interchangeable. In moderate-to-severe airflow obstruction, dilution method tends to underestimate and body plethysmography tends to overestimate RV.

1Alpha,25-dihydroxyvitamin D3 inhibits CD40L-induced pro-inflammatory and immunomodulatory activity in human monocytes.

CD40 ligand (CD40L) stimulation induces proinflammatory and immunomodulatory activity in monocytes. Here, we report on the effects of the steroid hormone 1alpha,25-dihydroxyvitamin D3 (1,25D3) on human blood monocytes that have been stimulated with the CD40L ligand. Co-treatment of CD40L-stimulated monocytes with 1,25D3 resulted in reduced production and secretion of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, as well as in reduced expression of the surface co-stimulatory molecules CD80 and CD86.

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-1beta (IL-1beta), and IL-12 and were unable to acquire high levels of CD80 and CD86 molecules.

Targeting systemic inflammation: novel therapies for the treatment of chronic obstructive pulmonary disease.

The increasing evidence that inflammation in the lungs leads to the structural changes observed in chronic obstructive pulmonary disease, whereas extrapulmonary symptoms and comorbidities may be systemic manifestations of these inflammatory processes, highlights an urgent need to discover novel, effective anti-inflammatory treatments for this disease. Some studies are suggesting that, by decreasing dynamic hyperinflation, bronchodilators might reduce systemic inflammation; inhaled corticosteroids and their combination with long-acting beta2-agonists might contribute to this goal. Even so, the opinion that suppression of the inflammatory response might improve systemic complications is stimulating a search for novel anti-inflammatory therapies.

Lipopolysaccharide desensitizes monocytes-macrophages to CD40 ligand stimulation.

Polymicrobial sepsis induces the suppression of macrophage function as determined by a reduction of pro-inflammatory cytokine production upon re-exposure to lipopolysaccharide (LPS) in vitro. Here, we examined whether macrophages were refractory to only LPS or if they were unable to respond to other stimuli such as CD40 ligand (CD40L). Monocytic cells exposed in vitro to LPS showed a dose-dependent reduction of their ability to produce interleukin-12 and tumour necrosis factor-alpha upon subsequent CD40L stimulation, as compared to cells stimulated with CD40L alone.

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-V1081-M184V and L1001-V1081 mutations.

Design, molecular modeling, synthesis, and anti-HIV-1 activity of new indolyl aryl sulfones. Novel derivatives of the indole-2-carboxamide.

Molecular modeling studies and an updated highly predictive 3-D QSAR model led to the discovery of exceptionally potent indolyl aryl sulfones (IASs) characterized by the presence of either a pyrrolidyn-2-one nucleus at the indole-2-carboxamide or some substituents at the indole-2-carbohydrazide. Compounds 7 and 9 were found active in the sub-nanomolar range of concentration in both MT-4 and C8166 cell-based anti-HIV assays. These compounds, and in particular compound 9, also showed excellent inhibitory activity against both HIV-112 and HIV-AB1 primary isolates in lymphocytes and against HIV WT in macrophages.

Novel 1-[2-(diarylmethoxy)ethyl]-2-methyl-5-nitroimidazoles as HIV-1 non-nucleoside reverse transcriptase inhibitors. A structure-activity relationship investigation.

1-[2-(Diarylmethoxy)ethyl]-2-methyl-5-nitroimidazoles (DAMNIs) is a novel family of HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) active at submicromolar concentration. Replacement of one phenyl ring of 1-[2-(diphenylmethoxy)ethyl]-2-methyl-5-nitroimidazole (4) with heterocyclic rings, such as 2-thienyl or 3-pyridinyl, led to novel DAMNIs with increased activity. In HIV-1 WT cell-based assay the racemic 1-{2-[alpha-(thiophen-2-yl)phenylmethoxy]ethyl}-2-methyl-5-nitroimidazole (7) (EC(50) = 0.