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Search Results: 1 - 10 of 297808 matches for " Kieran J Killian "
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Airway smooth muscle as a target of asthma therapy: history and new directions
Luke J Janssen, Kieran Killian
Respiratory Research , 2006, DOI: 10.1186/1465-9921-7-123
Abstract: Asthma is experienced during the life span of approximately 10% of the population, resulting in morbidity and mortality costing a substantial economic burden on society [1]. The predominant feature of asthma is the discomfort experienced upon breathing in the presence of excessive and inappropriate constriction of the airway smooth muscle (ASM). Although airway inflammation may play an important role in asthma, it is benign in the absence of airway narrowing. The patient is thus predominantly concerned with narrowing of their airways, contributing to an unpleasant increase in the effort required to breathe; in the extreme, this increased effort fails to allow sufficient ventilation, leading to morbidity and even mortality. As such, ASM is ultimately a major target in any management of asthma.The earliest recorded treatments of asthma included tobacco, indian hemp, sedation (using low doses of chloroform, ether, or opium), ipecacuana, coffee, tea, stramonium lobelia and other less effective agents. These agents express the pharmacological properties of the xanthines, cholinergic blockade, sympathetic stimulation, sedation and direct smooth muscle relaxation. Direct approaches using anti-cholinergics, anti-histamines, anti-leukotrienes, and functional antagonists modulating intracellular signalling pathways (β-agonists and phosphodiesterase inhibitors) followed (section 3.2). These have been used for decades with reasonable success, but patients continue to suffer exacerbations of asthma. Research energies were poured into developing new therapies to treat airway inflammation to prevent rather than treat the active disease. Asthma therapies using immune modulation and anti-inflammatory therapies proved to be so successful that targeting the ASM receded. Better understanding of the mechanisms underlying contraction of ASM is still essential to the management of the active disease. In this manuscript, basic excitation-contraction coupling in ASM is summarized and severa
Roflumilast attenuates allergen-induced inflammation in mild asthmatic subjects
Gail M Gauvreau, Louis-Philippe Boulet, Christine Schmid-Wirlitsch, Johanne C?té, MyLinh Duong, Kieran J Killian, Joanne Milot, Francine Deschesnes, Tara Strinich, Richard M Watson, Dirk Bredenbr?ker, Paul M O'Byrne
Respiratory Research , 2011, DOI: 10.1186/1465-9921-12-140
Abstract: 25 subjects with mild allergic asthma were randomized to oral roflumilast 500 mcg or placebo, once daily for 14 days in a double-blind, placebo-controlled, crossover study. Allergen challenge was performed on Day 14, and FEV1 was measured until 7 h post challenge. Methacholine challenge was performed on Days 1 (pre-dose), 13 (24 h pre-allergen), and 15 (24 h post-allergen), and sputum induction was performed on Days 1, 13, 14 (7 h post-allergen), and 15.Roflumilast inhibited the allergen-induced late phase response compared to placebo; maximum % fall in FEV1 (p = 0.02) and the area under the curve (p = 0.01). Roflumilast had a more impressive effect inhibiting allergen-induced sputum eosinophils, neutrophils, and eosinophil cationic protein (ECP) at 7 h post-allergen (all p = 0.02), and sputum neutrophils (p = 0.04), ECP (p = 0.02), neutrophil elastase (p = 0.0001) and AHR (p = 0.004) at 24 h post-allergen.This study demonstrates a protective effect of roflumilast on allergen-induced airway inflammation. The observed attenuation of sputum eosinophils and neutrophils demonstrates the anti-inflammatory properties of PDE4 inhibition and supports the roles of both cell types in the development of late phase bronchoconstriction and AHR.ClinicalTrials.gov: NCT01365533Asthma is characterized by the presence of cough, wheeze, dyspnea, reversible airway obstruction and airway hyperresponsiveness. Eosinophils are cells recognized to be a key feature of allergic asthma [1], however patients with severe asthma have increases in both eosinophils and neutrophils in their sputum [2]. Furthermore, severe asthma exacerbations are associated with bronchial mucosal eosinophilia and neutrophilia, as well as upregulation of CXC chemoattractants and their receptors [3]. Although current asthma therapies such as corticosteroids are effective in inhibiting eosinophilic inflammation through Th2 suppression, they may enhance neutrophil accumulation into the airways and until now therapies th
Systemic Inflammatory Markers and Disease Severity in Chronic Obstructive Pulmonary Disease—The Effect of Acute Exercise and Pulmonary Rehabilitation  [PDF]
Amani I. El Gammal, Rob O’Farrell, Liam O’Mahony, Fergus Shanahan, Kieran Killian, Terence M. O’Connor
Open Journal of Respiratory Diseases (OJRD) , 2015, DOI: 10.4236/ojrd.2015.51003
Abstract: Background: Decreased physical capacity and increased systemic inflammatory response are frequently observed in patients with chronic obstructive pulmonary disease (COPD). The relationship between the inflammatory response and disease severity and the immunological response to exercise were addressed in COPD. Objective: The first objective was to identify systemic biomarkers and their relationship with COPD severity. The second objective was to examine the effect of both acute exercise and pulmonary rehabilitation on these biomarkers. Methods: Forty subjects participated in the study. Thirty-two patients with moderate or severe COPD and 8 healthy non-smokers completed the study. Spirometry was preformed. Physical capacity was determined by a progressive symptom-limited cycle ergo meter (incremental) test. Blood samples were analyzed for C-reactive protein (CRP), pro-inflammatory cytokines (IL-6, TNF-α), pro-fibrotic cytokines (TGF-β) and oxidative burst in circulating leukocytes before and after exercise, and before and after pulmonary rehabilitation. Results: IL-6, CRP, WCC and TGF-β were higher in COPD (p < 0.05) than eight healthy controls. WCC, IL-6, TNF-α, CRP and TGF-β were negatively related to forced expiratory volume in 1 s (FEV1) (r = 0.4054, 0.3221, 0.1528, 0.1846 and 0.1187, respectively). Acute exercise increased circulating leucocytes and oxidative stress in both groups (p = 0.000, 0.0049 respectively), while IL-6 was increased in COPD group ((p = 0.0115) and circulating TNF-α in healthy control (p = 0.0369). Pulmonary rehabilitation didn’t modify the levels of inflammatory mediators. Conclusions: Reduced lung function is associated with increased levels of systemic inflammatory markers and acute exercise can further increase this inflammatory response. However pulmonary rehabilitation is unlikely to exacerbate systemic inflammation in COPD.
How Polymers Behave as Viscosity Index Improvers in Lubricating Oils  [PDF]
Michael J. Covitch, Kieran J. Trickett
Advances in Chemical Engineering and Science (ACES) , 2015, DOI: 10.4236/aces.2015.52015
Abstract: One of the requirements of engine lubricating oil is that it must have a low enough viscosity at low temperatures to assist in cold starting and a high enough viscosity at high temperatures to maintain its load-bearing characteristics. Viscosity Index (VI) is one approach used widely in the lubricating field to assess the variation of viscosity with temperature. The VI of both mineral and synthetic base oils can be improved by the addition of polymeric viscosity modifiers (VMs). VI improvement by VMs is widely attributed to the polymer coil size expanding with increasing temperature. However, there is very little physical data supporting this generally accepted mechanism. To address this issue, intrinsic viscosity measurements and Small-Angle Neutron Scattering (SANS) have been used to study the variation of polymer coil size with changing temperature and concentration in a selection of solvents. The results will show that coil size expansion with temperature is not necessary to achieve significant elevation of viscosity index.
Primary Cutaneous Diffuse Large B-Cell Lymphoma (Leg Type) Presenting as Necrotising Fasciitis  [PDF]
Niall M. McInerney, Kieran T. Power, Alan J. Hussey
Modern Plastic Surgery (MPS) , 2012, DOI: 10.4236/mps.2012.24024
Abstract: Necrotising fasciitis is a rare rapidly progressive, life threatening, soft tissue infection which spreads along fascial planes. We present a patient who was diagnosed with a primary cutaneous Diffuse Large B-Cell Lymphoma (leg type) following initial presentation as probable necrotising fasciitis. Presentation was of a painful swollen leg, septic shock and MRI findings consistent with the clinical signs. Diagnosis of necrotising fasciitis remains challenging and it is often missed in the early stages. Early fascial biopsy and histopathological analysis is useful in cases where the diagnosis is unclear. We feel that this case highlights these important issues and will benefit others in their management of similar cases in the future.
The Inhibition of Ureteral Motility by Periureteral Adipose Tissue
Lyndsey M. Killian,Stuart J. Bund
ISRN Urology , 2012, DOI: 10.5402/2012/312487
Ion Acoustic Waves in Ultracold Neutral Plasmas
J. Castro,P. McQuillen,T. C. Killian
Physics , 2010, DOI: 10.1103/PhysRevLett.105.065004
Abstract: We photoionize laser-cooled atoms with a laser beam possessing spatially periodic intensity modulations to create ultracold neutral plasmas with controlled density perturbations. Laser-induced fluorescence imaging reveals that the density perturbations oscillate in space and time, and the dispersion relation of the oscillations matches that of ion acoustic waves, which are long-wavelength, electrostatic, density waves.
High Resolution Ionization of Ultracold Neutral Plasmas
P. McQuillen,J. Castro,T. C. Killian
Physics , 2011, DOI: 10.1088/0953-4075/44/18/184013
Abstract: Collective effects, such as waves and instabilities, are integral to our understanding of most plasma phenomena. We have been able to study these in ultracold neutral plasmas by shaping the initial density distribution through spatial modulation of the ionizing laser intensity. We describe a relay imaging system for the photoionization beam that allows us to create higher resolution features and its application to extend the observation of ion acoustic waves to shorter wavelengths. We also describe the formation of sculpted density profiles to create fast expansion of plasma into vacuum and streaming plasmas.
Health-information seeking on the Internet and current smoking status: Evidence from the national health interview survey  [PDF]
Timothy S. Killian
Open Journal of Preventive Medicine (OJPM) , 2012, DOI: 10.4236/ojpm.2012.23042
Abstract: Two research questions were addressed. First, what are the differences between internet searchers and non-searchers for health-related information among current and former smokers? Second, does searching the internet for health-related information predict current smoking status in a multivariate model that controls for variations in sociodemographic and family characteristics? Data collected from 10,929 current and former smokers who participated in the 2009 National Health Interview Survey showed significant differences in sociodemographic and family characteristics between searchers and non-searchers. Importantly, searching the internet for health-related information made an independent contribution to the prediction of current smoking status in a multinomial logistic regression model. This study is significant in that it utilized a nationally representative sample to examine the correlation between internet use and smoking behavior and supports ongoing efforts of public health advocates to continue their efforts in developing and delivering online smoking cessation programs.
Biophysical Investigation of the Membrane-Disrupting Mechanism of the Antimicrobial and Amyloid-Like Peptide Dermaseptin S9
Lucie Caillon, J. Antoinette Killian, Olivier Lequin, Lucie Khemtémourian
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0075528
Abstract: Dermaseptin S9 (Drs S9) is an atypical cationic antimicrobial peptide with a long hydrophobic core and with a propensity to form amyloid-like fibrils. Here we investigated its membrane interaction using a variety of biophysical techniques. Rather surprisingly, we found that Drs S9 induces efficient permeabilisation in zwitterionic phosphatidylcholine (PC) vesicles, but not in anionic phosphatidylglycerol (PG) vesicles. We also found that the peptide inserts more efficiently in PC than in PG monolayers. Therefore, electrostatic interactions between the cationic Drs S9 and anionic membranes cannot explain the selectivity of the peptide towards bacterial membranes. CD spectroscopy, electron microscopy and ThT fluorescence experiments showed that the peptide adopts slightly more β-sheet and has a higher tendency to form amyloid-like fibrils in the presence of PC membranes as compared to PG membranes. Thus, induction of leakage may be related to peptide aggregation. The use of a pre-incorporation protocol to reduce peptide/peptide interactions characteristic of aggregates in solution resulted in more α-helix formation and a more pronounced effect on the cooperativity of the gel-fluid lipid phase transition in all lipid systems tested. Calorimetric data together with 2H- and 31P-NMR experiments indicated that the peptide has a significant impact on the dynamic organization of lipid bilayers, albeit slightly less for zwitterionic than for anionic membranes. Taken together, our data suggest that in particular in membranes of zwitterionic lipids the peptide binds in an aggregated state resulting in membrane leakage. We propose that also the antimicrobial activity of Drs S9 may be a result of binding of the peptide in an aggregated state, but that specific binding and aggregation to bacterial membranes is regulated not by anionic lipids but by as yet unknown factors.
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