Vasoactive intestinal peptide in human nasal mucosa

Vasoactive intestinal peptide (VIP), which is present with acetylcholine in parasympathetic nerve fibers, may have important regulatory functions in mucous membranes. The potential roles for VIP in human nasal mucosa were studied using an integrated approach. The VIP content of human nasal mucosa was determined to be 2.84 +/- 0.47 pmol/g wet weight (n = 8) by RIA. VIP-immunoreactive nerve fibers were found to be most concentrated in submucosal glands adjacent to serous and mucous cells. 125I-VIP binding sites were located on submucosal glands, epithelial cells, and arterioles. In short-term explant culture, VIP stimulated lactoferrin release from serous cells but did not stimulate [3H]glucosamine-labeled respiratory glycoconjugate secretion. Methacholine was more potent than VIP, and methacholine stimulated both lactoferrin and respiratory glycoconjugate release. The addition of VIP plus methacholine to explants resulted in additive increases in lactoferrin release. Based upon the autoradiographic distribution of 125I-VIP binding sites and the effects on explants, VIP derived from parasympathetic nerve fibers may function in the regulation of serous cell secretion in human nasal mucosa. VIP may also participate in the regulation of vasomotor tone

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Concentration-Dependent Noncysteinyl Leukotriene Type 1 Receptor-Mediated Inhibitory Activity of Leukotriene Receptor Antagonists

BACKGROUND: The use of leukotriene antagonists (LTRAs) for asthma therapy has been associated with a significant degree of inter-patient variability in response to treatment. Some of that variability may be attributable to non-cysteinyl leukotriene type 1 receptor (CysLT(1)) mediated inhibitory mechanisms that have been demonstrated for this group of drugs. OBJECTIVE: We have used a model of CysLT(1) signaling in human monocytes to characterize CysLT(1)-dependent and CysLT(1)-independent anti-inflammatory activity of two chemically different, clinically relevant, LTRAs (montelukast and zafirlukast). RESULTS: Using receptor desensitization experiments in monocytes and CysLT(1) transfected HEK293 cells, and IL-10 and CysLT(1) siRNA induced downregulation of CysLT(1) expression, we showed that reported CysLT(1) agonists, LTD(4) and uridine diphosphate (UDP), signal through calcium mobilization, acting on separate receptors and that both pathways were inhibited by montelukast and zafirlukast. However, 3 logs higher concentrations of LTRAs were required for inhibition of UDP induced signaling. In monocytes, UDP, but not LTD(4), induced IL-8 production that was significantly inhibited by both drugs at micromolar concentrations. Both LTRAs, at low micromolar concentrations, also inhibited calcium ionophore induced leukotriene (LTB(4) and LTC(4)) production, indicating 5-lipoxygenase inhibitory activities. CONCLUSION: We report here that montelukast and zafirlukast, acting in a concentration dependent manner, can inhibit non-CysLT(1) mediated, proinflammatory reactions, suggesting activities potentially relevant for inter-patient variability in response to treatment. Higher doses of currently known LTRAs or new compounds derived from this class of drugs may represent a new strategy for finding more efficient therapy for bronchial asthma