Abstract:
:Phosphodiesterase (PDE)-5 degrades guanosine 3',5'cyclic monophosphate (cGMP) and its inhibitor sildenafil citrate (Viagra) treats erectile dysfunction by smooth muscle relaxation through elevated cGMP. Sildenafil was examined in two guinea pig models of airways disease: guinea pigs exposed to LPS or sensitized guinea pigs with atopy exposed to ovalbumen. Ovalbumen exposure caused early- and late-phase bronchoconstrictor responses, measured in conscious animals by whole-body plethysmography. Twenty-four hours after ovalbumen exposure there was airway hyperreactivity (AHR) to inhaled histamine and significantly elevated macrophages, eosinophils, and nitric oxide (NO) metabolites in bronchoalveolar lavage fluid. Sildenafil treatment (1 mg/kg, intraperitoneally) failed to affect the early and late responses but significantly reduced AHR, leukocyte influx, and elevated NO. LPS exposure (30 microg/ml) caused AHR to histamine at 1 hour and macrophage, eosinophil, and neutrophil influx at 24 hours with raised NO. Sildenafil pretreatment inhibited LPS-induced AHR, leukocyte influx, and NO generation. The effectiveness of sildenafil was not dependent on endogenous NO because inhibition of NO synthase with Nomega-nitro-L-arginine methyl ester did not prevent its action. Inhibition of PDE5 by sildenafil was confirmed by elevated S-nitroso-N-acetylpenicillamine-induced cGMP generation in isolated lungs. These antiinflammatory actions of sildenafil in guinea pig models suggest that PDE5 inhibitors may have potential in treating airways disease.
journal_name
Am J Respir Crit Care Medauthors
Toward TJ,Smith N,Broadley KJdoi
10.1164/rccm.200211-1372OCkeywords:
subject
Has Abstractpub_date
2004-01-15 00:00:00pages
227-34issue
2eissn
1073-449Xissn
1535-4970pii
200211-1372OCjournal_volume
169pub_type
杂志文章abstract::Noninvasive and invasive diagnostic techniques have been shown to achieve comparable performances in the evaluation of suspected ventilator-associated pneumonia (VAP). We studied the impact of both approaches on outcome in a prospective, open, and randomized study in three intensive care units (ICUs) of a 1,000-bed te...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.162.1.9907090
更新日期:2000-07-01 00:00:00
abstract::Although skeletal muscle abnormalities have been described in association with human immunodeficiency virus (HIV), the effects of HIV infection on respiratory muscle function have not been well characterized. We hypothesized that HIV+ individuals may develop respiratory muscle weakness and that respiratory muscle dysf...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.155.3.9116990
更新日期:1997-03-01 00:00:00
abstract::During Operation Everest III (Comex '97), to assess the consequences of altitude-induced hypoxia, eight volunteers were decompressed in a hypobaric chamber, with a decompression profile simulating the climb of Mount Everest. Cardiac function was assessed using a combination of M-mode and two-dimensional echocardiograp...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.161.1.9902096
更新日期:2000-01-01 00:00:00
abstract:RATIONALE:The promise of newborn screening (NBS) for cystic fibrosis (CF) has not been fully realized, and the extent of improvement in respiratory outcomes is unclear. We hypothesized that significant lung disease was present at diagnosis. OBJECTIVES:To determine the extent of lung disease in a geographically defined...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200901-0069OC
更新日期:2009-07-15 00:00:00
abstract::We investigated the relationship between the extent of pulmonary emphysema, assessed by quantitative high-resolution computed tomography (HRCT), and lung mechanics in 24 patients with chronic obstructive pulmonary disease (COPD). The extent of emphysema was quantified as the relative lung area with CT numbers < -950 H...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.4.2010066
更新日期:2001-08-15 00:00:00
abstract::In unilateral lung injury, application of global positive end-expiratory pressure (PEEP) may cause overdistension of normal alveoli and redistribution of blood flow to diseased lung areas, thereby worsening oxygenation. We hypothesized that selective application of tracheal gas insufflation (TGI) will recruit the inju...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.4.2005127
更新日期:2001-08-15 00:00:00
abstract::Superoxide dismutase (SOD) is a ubiquitous metalloenzyme in aerobic organisms that catalyzes the conversion of superoxide anion to hydrogen peroxide. Mycobacterium tuberculosis is unusual in that it secretes large quantities of iron-cofactored SOD. To determine the role of SOD in pathogenesis, we constructed mutants o...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.12.2106093
更新日期:2001-12-15 00:00:00
abstract::A histologic feature of usual interstitial pneumonia is the presence of fibroblastic foci. As some patients with usual interstitial pneumonia and an underlying collagen vascular disease have a better prognosis, we hypothesized that they would have fewer fibroblastic foci. Pathologists reviewed surgical lung biopsies f...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200204-373OC
更新日期:2003-05-15 00:00:00
abstract::Epidemiologic investigation has established an association between exposure to particulate matter (PM) and human health in the Utah Valley. Reduction of particle mass during the temporary closure of a local steel mill was associated with diminished morbidity and mortality. We tested the hypothesis that the biologic ef...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.164.4.2011089
更新日期:2001-08-15 00:00:00
abstract:RATIONALE:There is conflicting information about the development and resolution of airway inflammation and airway hyperresponsiveness (AHR) after repeated airway exposure to allergen in sensitized mice. METHODS:Sensitized BALB/c and C57BL/6 mice were exposed to repeated allergen challenge on 3, 7, or 11 occasions. Air...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200505-783OC
更新日期:2006-01-01 00:00:00
abstract:RATIONALE:It is hypothesized that the affective dimension of dyspnea (unpleasantness, emotional response) is not strictly dependent on the intensity of dyspnea. OBJECTIVES:We tested the hypothesis that the ratio of immediate unpleasantness (A(1)) to sensory intensity (SI) varies depending on the type of dyspnea. METH...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,随机对照试验
doi:10.1164/rccm.200711-1675OC
更新日期:2008-06-15 00:00:00
abstract::This prospective and controlled pilot study evaluates the long-term effects of nocturnal oxygen therapy (NOT) on exercise endurance, hematology variables, quality of life, and survival of 23 adult patients (mean age, 32 +/- 6 yr) with post-tricuspid congenital heart defects (ventricular septal defect = 10; patent duct...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.164.9.2106076
更新日期:2001-11-01 00:00:00
abstract::To determine the usefulness of positron emission tomography with fluoro-2-deoxyglucose (PET-FDG) in assessing mediastinal disease in patients with non-small-cell lung cancer (NSCLC) and to compare its yield to that of computed tomography (CT), we performed a prospective consecutive sample investigation in a university...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.152.6.8520780
更新日期:1995-12-01 00:00:00
abstract::This study aimed to compare O2 consumption (VO2) determination by the gas-exchange (VO2GE) and Fick (VO2F) methods in cardiac surgical patients. A total of 10 mechanically ventilated postoperative patients were studied prospectively. Thermodilution was performed using three randomly applied techniques: room temperatur...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.149.5.8173750
更新日期:1994-05-01 00:00:00
abstract::Historically, infections caused by Mycobacterium tuberculosis have been treated simultaneously with isoniazid and rifampin. As a consequence of this combined therapy, strains resistant only to rifampin were rarely recovered. However, recently there has been an increasing number of reports describing HIV-positive patie...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.153.2.8564140
更新日期:1996-02-01 00:00:00
abstract:RATIONALE:Although current resuscitation guidelines are rescuer focused, the opportunity exists to develop patient-centered resuscitation strategies that optimize the hemodynamic response of the individual in the hopes to improve survival. OBJECTIVES:To determine if titrating cardiopulmonary resuscitation (CPR) to blo...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201407-1343OC
更新日期:2014-12-01 00:00:00
abstract::Salbutamol inhibits neutropenia, increased airway resistance, and gas exchange abnormalities provoked by platelet-activating factor (PAF) challenge in normal persons. To further explore the intriguing dissociation between spirometric abnormalities and gas exchange defects shown in patients with asthma, we investigated...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.156.1.9610100
更新日期:1997-07-01 00:00:00
abstract:RATIONALE:Platelets are essential for pulmonary leukocyte recruitment, airway hyperresponsiveness, and bronchial remodeling in animals with allergic inflammation and can be found in bronchoalveolar lavage of sensitized animals. No studies, however, have explored the direct migration of platelets to lungs. OBJECTIVES:T...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200702-214OC
更新日期:2008-03-15 00:00:00
abstract:RATIONALE:Cytokine receptors can be markers defining different T-cell subsets and considered as therapeutic targets. The association of IL-6 and IL-6 receptor α (IL-6Rα) with asthma was reported, suggesting their involvement in asthma. OBJECTIVES:To determine whether and how IL-6Rα defines a distinct effector memory (...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201403-0601OC
更新日期:2014-12-15 00:00:00
abstract::Patients in whom acid-fast bacilli smear-positive pulmonary tuberculosis was newly diagnosed were randomized to receive 400 mg moxifloxacin, 300 mg isonaizid, or 600 mg rifampin daily for 5 days. Sixteen-hour overnight sputa collections were made for the 2 days before and for 5 days of monotherapy. Bactericidal activi...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/rccm.200305-682OC
更新日期:2003-12-01 00:00:00
abstract:RATIONALE:Airways obstruction with thick, adherent mucus is a pathophysiologic and clinical feature of muco-obstructive respiratory diseases, including chronic obstructive pulmonary disease, asthma, and cystic fibrosis (CF). Mucins, the dominant biopolymer in mucus, organize into complex polymeric networks via the form...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201802-0245OC
更新日期:2019-01-15 00:00:00
abstract::We used three-dimensional reconstructions obtained with spiral computed tomography to measure total diaphragm surface area (Adi), and the surface area of the dome (Ado) and of the zone of apposition (Aap) of the diaphragm in nine patients with single-lung transplantation (SLT) for emphysema and nine normal subjects ma...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/ajrccm.159.6.9812052
更新日期:1999-06-01 00:00:00
abstract:INTRODUCTION:Proteinases with a disintegrin and a metalloproteinase domain (ADAMs) have not been well studied in COPD. We investigated whether ADAM9 is linked to COPD in humans and mice. METHODS:ADAM9 blood and lung levels were measured in COPD patients versus controls, and air- versus cigarette smoke (CS)-exposed wil...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.201711-2300OC
更新日期:2018-06-04 00:00:00
abstract::The present prospective study was designed to determine the prevalence of pleural effusion at approximately 28 days after cardiac surgery and their subsequent course. This consecutive case study included 389 patients; 312 had only coronary artery bypass graft surgery (CABG) surgery, 37 had both valve and CABG surgery,...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200203-184OC
更新日期:2002-12-15 00:00:00
abstract:RATIONALE:Obstructive sleep apnea (OSA) has been associated with kidney function loss, which may be related to changes in the renin-angiotensin system (RAS). OBJECTIVES:We sought to determine the effect of continuous positive airway pressure (CPAP) of patients with OSA on renal hemodynamics at baseline and in response...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章
doi:10.1164/rccm.201403-0526OC
更新日期:2014-09-01 00:00:00
abstract:RATIONALE:The development of tuberculin skin test (TST) positivity following infection by Mycobacterium tuberculosis is not invariable and may depend on bacillary as well as host factors. OBJECTIVES:First, to compare the diagnostic performance of the TST and a form of in vitro IFN-gamma release assay (IFNGRA) in the c...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200509-1526OC
更新日期:2006-05-01 00:00:00
abstract::The relationship between asthma medication and the perception of asthma symptoms is of interest for daily practice. Poor perception of asthma symptoms might influence patients' health care behavior and subsequently might lead to undertreatment and deterioration of their disease. This study investigated the influence o...
journal_title:American journal of respiratory and critical care medicine
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1164/ajrccm.164.5.9910103
更新日期:2001-09-01 00:00:00
abstract:RATIONALE:Extensively drug-resistant (XDR) tuberculosis (TB) may arise in individuals on treatment for multidrug-resistant (MDR) TB. Preventing this amplification of resistance will likely improve clinical outcomes and delay the secondary spread of XDR-TB. OBJECTIVES:To measure the proportion of individuals that devel...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200911-1768OC
更新日期:2010-08-01 00:00:00
abstract:RATIONALE:There are few follow-up studies on long-term cardiopulmonary function after pulmonary endarterectomy (PEA), the operation of choice for chronic thromboembolic pulmonary hypertension (CTEPH). OBJECTIVES:To prospectively evaluate long-term outcome of patients with CTEPH treated with PEA. METHODS:Between 1994 ...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章
doi:10.1164/rccm.200801-101OC
更新日期:2008-08-15 00:00:00
abstract::Genetic susceptibility to asthma is due to multiple genes that interact with each other and the environment. There are many known environmental influences, such as viral and other respiratory infections and exposure to allergens, air pollutants, and active or passive cigarette smoke (1). Genome-wide screens for asthma...
journal_title:American journal of respiratory and critical care medicine
pub_type: 杂志文章,多中心研究,评审
doi:10.1164/ajrccm.156.4.12tac7
更新日期:1997-10-01 00:00:00