Experimental lung research
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American guidelines, unlike European guidelines, support the use of antihistamines as a first line of treatment for some causes of chronic cough. Transient receptor potential vanilloid-1 (TRPV1) is an ion channel activated by the tussive agents capsaicin, resiniferatoxin, and protons. It is predominantly expressed by C-fiber and some Adelta -fiber sensory neurons and is thought to be a cough receptor. ⋯ Dexbrompheniramine also inhibited activation of rat TRPV1 expressed in HEK and Pro5 cells, without interfering with TRPA1 and proteinase-activated receptor-2 (PAR(2)) activation. Finally, in rat dorsal root ganglia neuron preparations, dexbrompheniramine dose-dependently inhibited capsaicin-evoked calcium responses. Thus, the inhibition of TRPV1 activation by dexbrompheniramine may provide one potential mechanism whereby this antihistamine exerts its therapeutic effect in chronic cough.
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Several strategies have been developed to treat atelectasis, including positive end-expiratory pressure and deep inspirations. However, in some patients these recruitment strategies fail to improve lung function. Therefore, the authors studied whether recruitment maneuvers could resolve atelectasis following either passive airway closure or active bronchconstriction. ⋯ Following methacholine, aerated lung areas were also significantly reduced; however, deep inspirations had no significant effect. Passive atelectasis was easily resolved by deep inspirations. In contrast, active airway constriction that leads to atelectasis could not be overcome with recruitment maneuvers.
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The continuous exposure of the epithelial surface of the conducting airways to inhaled pathogens requires the presence of an efficient innate immune system to prevent infections. The innate immune system of the lung provides protection against a broad spectrum of microbial threats through a variety of effector mechanisms. The antimicrobial peptides and proteins form important elements of this defence system in the lung. ⋯ More recently, also active vitamin D(3) has been implicated as a major regulator of AMPs expression. AMPs contribute to host defence through direct antimicrobial activity, as well as by modulating innate and adaptive immunity, and wound repair. Novel insight into the mechanism of action of these peptides and the regulation of their expression may lead to innovative approaches for treatment of infectious and inflammatory lung disorders.
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Respiratory syncytial virus (RSV) bronchiolitis is a serious and distressing illness, which occurs almost exclusively in infants under one year of age. Although the majority of all children will have experienced an infection with RSV by the time they reach their second birthday, only a minority develop bronchiolitis. It is unclear why some otherwise healthy infants develop this severe illness and many studies have investigated whether or not this relates to an over-exuberant immunological response to the infection. It is increasingly being recognized that the innate immune response may play a key role.
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The authors compared the ability of a single dose of the proenzyme single-chain urokinase (scuPA), low-molecular-weight urokinase, tissue plasminogen activator (tPA), or a mutant site-inactive scuPA to resolve intrapleural loculations at 72 to 96 hours after tetracycline-induced pleural injury in rabbits. Both scuPA and tPA reversed loculations at 96 hours after injury P < or = .001, whereas low-molecular-weight urokinase and the scuPA mutant were ineffective. scuPA and tPA generated inhibitor complexes, induced fibrinolytic activity, and quenched plasminogen activator-1 activity in pleural fluids. The authors conclude that scuPA reverses loculations as effectively as tPA at clinically applied intrapleural doses, whereas low-molecular-weight urokinase was ineffective.