No abstract

In bovine tracheal smooth muscle the presence of airway epithelium significantly reduced the sensitivity and maximum contractile response to histamine, 5‐hydroxytryptamine (5‐HT) or acetylcholine. Muscle contraction induced by K+ and electrical field stimulation was of similar magnitude both in the presence or absence of adherent epithelium. The effect of epithelium on smooth muscle contractility was unaffected by pretreatment with indomethacin (10−6 M) or mepacrine (5 × 10−5 M). The relaxant response to isoprenaline was enhanced in the presence of epithelium, although this was significant only in the case of precontraction with 5‐HT. It is concluded that the bronchial epithelium may produce a relaxant factor which is not a cyclo‐oxygenase or lipoxygenase product. The production of this factor may be reduced or lost following epithelial damage and this may be important in the pathogenesis of bronchial hyperresponsiveness in asthma.

No abstract

The results of six carefully designed and controlled studies suggest that an assumed H. pylori infection rate of approximately 95% may overestimate the actual rate of H. pylori infection in duodenal ulcer patients in the United States. Although H. pylori infection is an important factor in the etiology of noniatrogenic duodenal ulcer disease, other factors may predominate in some patients and should not be overlooked in determining an appropriate course of treatment. The empiric use of antibiotic therapy for ulcer patients without confirmation of the presence of H. pylori cannot be recommended.

Summary The Ecological Limits of Hydrologic Alteration (ELOHA) method described in Poff et al. (2010) was applied to streams and small rivers in a large central region of the Potomac River basin in the U.S.A. The area, which is topographically complex, has karst geology, is increasingly urban and has few flow‐altering impoundments, allows a test of the flexibility and applicability of the ELOHA method's four steps: build a hydrological foundation, calculate flow alteration, classify streams and develop flow alteration–ecology (FA‐E) relationships. A hydrological foundation of baseline (undisturbed) and current (existing) hydrographs was simulated for 747 catchments using the Chesapeake Bay Program Hydrologic Simulation Program‐FORTRAN (HSPF) model and the Virginia Department of Environmental Quality Online Object Oriented Meta‐Model (WOOOMM) routing module. The outlet of each catchment was associated with one, and sometimes two or more, stream macroinvertebrate sampling sites. Pairing each catchment's simulated current flow with its own simulated baseline flow produced estimates of flow alteration that reflect the combination of natural and anthropogenic factors controlling streamflow in individual catchments. Flow metrics from the baseline and current simulations were compared with observed values from gauged streams in undisturbed and disturbed catchments. The model may have failed to simulate streamflow well in small urbanised catchments on or near karst geology, but observed data were insufficient to fully evaluate model behaviour in these units. Elsewhere, simulated and observed values of 13 of the 15 tested flow metrics generally agreed well. A stream hydrological classification system to account for natural biological variability was not feasible in the study area for two reasons. First, the natural landscape features that most strongly govern undisturbed streamflows (catchment size and karst geology) do not greatly influence undisturbed macroinvertebrate communities. Second, the study area's complex topography ensures that many streams crossed physiographic boundaries or flowed through karst geology before reaching the macroinvertebrate sampling sites. Stream macroinvertebrates responded strongly to alteration in the duration and frequency of both high and low flow events, rise rate, flashiness and magnitude of high flow events. They did not respond to the alteration in middle‐ and low‐magnitude flow metrics, fall rate or extreme low flow frequency. Flow alteration–ecological relationships were developed for combinations of six flow metrics and seven macroinvertebrate metrics using quantile regression and conditional probability methods. Of the seven macroinvertebrate metrics, % scrapers, % clingers and the Chessie BIBI were most affected by flow alteration. Degraded habitat and water quality conditions modify and, if strong enough, conceal the flow alteration–ecological relationships. Water quality and habitat improvements can potentially ameliorate the impacts of flow alteration. Resource managers nee...

There is increasing evidence in many species that vasoactive intestinal peptide (VIP) may be a neurotransmitter in nonadrenergic inhibitory nerves. We have studied the effect of electrical field stimulation (EFS), exogenous VIP, and isoproterenol (Iso) on human airways in vitro. We have also studied a related peptide, peptide histidine methionine (PHM), which coexists with VIP in human airway nerves, and in separate experiments studied fragments of the VIP amino acid sequence (VIP1-10 and VIP16-28) for agonist and antagonist activity. Human airways were obtained at thoracotomy and studied in an organ bath. In bronchi EFS gave an inhibitory response that was unaltered by 10(-6) M propranolol but was blocked by tetrodotoxin, whereas in bronchioles there was little or no nonadrenergic inhibitory response. VIP, PHM, and Iso all caused dose-dependent relaxation of bronchi, VIP and PHM being approximately 50-fold more potent than Iso. VIP, but not Iso, mimicked the time course of nonadrenergic inhibitory nerve stimulation. In contrast bronchioles relaxed to Iso but not to VIP or PHM. Neither propranolol nor indomethacin altered the relaxant effects of VIP or PHM, suggesting a direct effect of these peptides on airway smooth muscle. Neither of the VIP fragments showed either agonist or antagonist activity. We conclude that VIP and PHM are more potent bronchodilators of human bronchi than Iso and that the association between the relaxant effects of these peptides and nonadrenergic inhibitory responses suggests that they may be possible neurotransmitters of nonadrenergic inhibitory nerves in human airways.

in the control of asthma over three months, and more effective than salbutamol (400,ufg twice daily) over a further nine months. Neither salmeterol nor salbutamol was associated with any worsening of control of asthma. (Thorax 1993;48:148-153) f2 Adrenoceptor agonists are established treatment for asthma for patients of all ages. They are effective bronchodilators and protect against various constrictor challenges such as exercise, cold air, methacholine, and histamine.lA The inhaled route is preferred as this delivers the drug directly to the lung and thus minimises potential systemic side effects.5 The major drawback of currently available inhaled drugs is their short duration of action-namely, less than six hours.6Salmeterol is a potent selective fl2 agonist that has a duration of action in excess of 12 hours in vitro and in vivo.8 In a four week parallel group study in 692 patients with mild to moderate asthma salmeterol increased morning and evening peak flow, reduced the variation in diurnal peak flow, reduced the requirement for additional salbutamol, and lessened symptoms by comparison with placebo.9This study was designed to investigate the safety and efficacy of salmeterol (50 ,ug) twice daily and salbutamol (400 ,ug)

1 In human airways synthetic human sequence calcitonin gene-related peptide (hCGRP), a novel peptide produced by alternative processing of mRNA from the calcitonin gene, caused concentrationdependent contraction of human bronchi (EC_, 4.9 x 10-' M) and was significantly more potent than substance P or carbachol. 3 CGRP was detected in human airways by radioimmunoassay with highest concentrations in cartilaginous airways. 4 CGRP was localised by immunocytochemistry to both nerves and ganglia in human airways. 5 CGRP, is a potent constrictor of human airways and may have important effects on airway function and be implicated in the pathogenesis of bronchial hyper-responsiveness and asthma.