A5024460960- Asthma and respiratory diseases
- Respiratory and Cough-Related Research
- Neuroscience of respiration and sleep
- Neuropeptides and Animal Physiology
- Receptor Mechanisms and Signaling
- Allergic Rhinitis and Sensitization
- Pulmonary Hypertension Research and Treatments
- Mast cells and histamine
- Pharmacological Receptor Mechanisms and Effects
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Nicotinic Acetylcholine Receptors Study
- Ion channel regulation and function
- Respiratory Support and Mechanisms
- Inhalation and Respiratory Drug Delivery
- Nitric Oxide and Endothelin Effects
- Phosphodiesterase function and regulation
- Neonatal Respiratory Health Research
- Neuroendocrine regulation and behavior
- Olfactory and Sensory Function Studies
- Eicosanoids and Hypertension Pharmacology
- IL-33, ST2, and ILC Pathways
- Chemical Synthesis and Analysis
- Eosinophilic Esophagitis
- Phenothiazines and Benzothiazines Synthesis and Activities
- Cytokine Signaling Pathways and Interactions
Insmed (United States)
2017-2024
Theratechnologies (Canada)
2017
Lovelace Respiratory Research Institute
2017
Merck & Co., Inc., Rahway, NJ, USA (United States)
2010-2013
University of Wisconsin–Madison
2000
Mayo Clinic
1998
ENT and Allergy
1991
Pennsylvania State University
1987
Rutgers, The State University of New Jersey
1978-1980
University of North Texas
1976
Abstract We have biologically characterized two new members of the IL-17 cytokine family: IL-17F and IL-25. In contrast to conventional in vitro screening approaches, we activity these molecules by direct vivo analysis compared their function that other family members. Intranasal administration adenovirus expressing IL-17, IL-17C, or resulted bronchoalveolar lavage neutrophilia inflammatory gene expression lung. contrast, intranasal IL-25-expressing IL-25 protein production IL-4, IL-5,...
To investigate the role of interleukin-5 (IL-5) on airway hyperreactivity and pulmonary inflammation in nonhuman primate airways, effect a neutralizing monoclonal antibody to murine IL-5 (TRFK-5) was investigated cynomolgus monkey model allergic asthma. Anesthetized Ascaris-sensitive monkeys underwent bronchoalveolar lavage (BAL) assess granulocyte content this fluid before 24 h after aerosolized Ascaris suum extract inhalation. Airway reactivity assessed by concentration inhaled histamine...
Interleukin-5 (IL-5) is important in the control of differentiation, migration, and activation eosinophils. In order to study role IL-5 development eosinophilic inflammation airways, we have used a monoclonal antibody murine (TRFK-5) model allergic pulmonary inflammation. B6D2F1 mice were sensitized with alum-precipitated ovalbumin challenged aerosolized on day 12 after sensitization. Samples bronchoalveolar lavage (BAL) fluid, lung tissue, blood, bone marrow aspirate collected at different...
It has been hypothesized that the destruction of lung tissue observed in smokers with chronic obstructive pulmonary disease and emphysema is mediated by neutrophils recruited to lungs smoke exposure. This study investigated role chemokine receptor CXCR2 mediating neutrophilic inflammation mice acutely exposed cigarette smoke. Exposure dilute mainstream for 1 h, twice per day 3 days, induced acute C57BL/6 mice, increased neutrophil chemotactic CXC chemokines macrophage inflammatory protein...
Mast cells are important effector in IgE-mediated acute allergic reactions. also produce cytokines such as interleukin (IL)-3, IL-4, IL-5, tumor necrosis factor (TNF), and granulocyte-macrophage colony-stimulating (GM-CSF) that regulate the function of eosinophils development a late-phase inflammatory response to antigen challenge. To evaluate role mast on pulmonary eosinophilia vivo, we compared eosinophil infiltration into lungs cell deficient mice (WBB6F1/J-W/Wv) with their congenic...
Sch527123 [2-hydroxy-<i>N</i>,<i>N</i>-dimethyl-3-[[2-[[1(<i>R</i>)-(5-methyl-2-furanyl)propyl]amino]-3,4-dioxo-1-cyclobuten-1-yl]amino]ben-zamide] is a potent, selective antagonist of the human CXCR1 and CXCR2 receptors (Gonsiorek et al., 2007). Here we describe its pharmacologic properties at rodent in cynomolgus monkey, as well vivo activity models demonstrating prominent pulmonary neutrophilia, goblet cell hyperplasia, mucus production. bound with high affinity to mouse...
This report describes the development and biology of Sch 55700, a humanized monoclonal antibody to human IL-5 (hIL-5). 55700 was synthesized using CDR (complementarity determining regions) grafting technology by incorporating antigen recognition sites for hIL-5 onto consensus regions IgG4 framework. In vitro, displays high affinity (Kd = 20 pmol/l) binding hIL-5, inhibits Ba/F3 cells (IC50 0.5 nmol/l) blocks mediated proliferation erythroleukemic TF-1 cells. allergic mice, (0.1-10 mg/kg,...
The present study was conducted to determine the effects of administration centrally active antitussive drugs on cough motor pattern. Electromyograms diaphragm and rectus abdominis muscles were recorded in anesthetized, spontaneously breathing cats. Cough produced by mechanical stimulation intrathoracic trachea. Centrally acting administered included codeine, morphine, dextromethorphan, baclofen, CP-99,994, SR-48,968. Intravertebral artery all reduced number (number coughs per stimulus...
Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES
The GABA‐B receptor agonists baclofen and 3‐aminopropylphosphinic acid (3‐APPi) have antitussive activity in the cat guinea pig. purpose of this study was to investigate sites action these inhibit cough reflex. Single intracerebroventricular (i.e.v.) cannulas were placed lateral ventricles anaesthetized pigs. Approximately 1 week later, animals exposed aerosols capsaicin (0.3 μ m ) elicit coughing. Coughs detected with a microphone counted. Cough produced cats by mechanical stimulation...
SCH 34826 [(S)-N-[N-[1-[[(2,2-dimethyl-1,3-dioxolan-4yl) methoxy]carbonyl]-2-phenylethyl]-L-phenylalanine]-beta-alanine] was synthesized as a p.o. active prodrug enkephalinase inhibitor. In vivo, it is de-esterified to 32615 (N-[L-(-1-carboxy-2-phenyl)ethyl]-L-phenylalanyl-beta-alanine), the constituent. vitro, Ki for block degradation of Met5-enkephalin by isolated 19.5 +/- 0.9 nM. contrast, did not inhibit aminopeptidase or diaminopeptidase III up 10 microM and affect angiotensin...
Loratadine is a new non‐sedating antihistamine. The present studies compared loratadine and terfenadine, another antihistamine, for their ability to inhibit the bronchial response histamine other autacoids which have been implicated as contributing symptoms of an allergic reaction. In addition, two antihistamines were evaluated in models immunologically mediated reactions. more potent inhibitor histamine‐induced bronchospasm guinea pigs than terfenadine. Both exhibit marked antiserotonin...
Idiopathic pulmonary fibrosis is a progressive and lethal disease while there are now two approved drugs (Esbriet® Ofev®) additional effective treatments still needed. Recently, prostacyclin analogs such as iloprost treprostinil (TRE) have been shown to exert some protection against bleomycin-induced in mice when administered prophylactic regimen. In this study, we evaluated the effect of inhaled prodrug hexadecyl-treprostinil (C16TR) formulated lipid nanoparticle (INS1009) therapeutically...
Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES
Experiments were conducted to characterize the pharmacology of SCH 50911 ((+)-5,5-dimethyl-2-morpholineacetic acid hydrochloride), a structurally novel GABA-B receptor antagonist. Although more potent antagonists have been reported, in this study was compared with CGP 35348, moderately and selective antagonist acceptable vivo activity. inhibit binding GABA rat brain (IC50 = 1.1 microM) than 35348 62 microM). had no affinity for GABA-A, histamine H1, H3, dopamine D1, D2, serotonin 5-HT2, or...
Accumulation of eosinophils in the lung with concomitant tissue damage are defining histopathologic features human asthma. Through degranulation and release proinflammatory proteins such as major basic protein (MBP), may perpetuate this inflammatory response. We investigated extent eosinophil a murine model allergic pulmonary inflammation. In paradigm, mice develop eosinophilia, mucus hypersecretion, damage, airway edema hyperreactivity. To evaluate degree degranulation, we used polyclonal...
1. GABAB agonists inhibit neuronal processes which are important in the pathogenesis of airway disease, such as bronchospasm. Cough is a prominent symptom pulmonary but effects on this reflex unknown. Experiments were conducted to determine antitussive effect receptor comparison known agents, codeine and dextromethorphan. 2. Unanaesthetized guinea-pigs exposed aerosols 0.3 mM capsaicin elicit coughing, was detected with microphone counted. also produced anaesthetized cats by mechanical...
The effect of ( R )‐α‐methylhistamine, a selective H 3 ‐histamine receptor agonist, was examined on the neurogenic hypertension and tachycardia that is induced by stimulation areas in medulla oblongata guinea‐pigs. Electrical medullary (32 Hz, 3–5 s trains, 0.5–1.0 ms square pulse, 25–400 μA) produced intensity‐dependent increases blood pressure more variable tachycardia. )‐α‐methylhistamine inhibited due to submaximal CNS stimulation. inhibition dose‐dependent (10–300 μg kg −1 , i.v.) not...
We measured ventilatory responses to CO2 (delta VI/delta PCO2) and transient hypoxia SaO2) during reductions of brain blood flow (BBF) 70% 50% control in unanesthetized goats. Increase inspiratory volume per change tension was rebreathing with sampling both arterial cerebral venous blood; increase fall oxygen saturation assessed by the N2 inhalation method. Delta SaO2 did not significantly at BBF, but depressed BBF. PCO2 increased (0.94 +/- 0.18 1.29 0.24 l . min-1 Torr-1) BBF if were used...