The cysteinyl leukotrienes (LTC 4 , LTD 4 and LTE 4 ) are lipid mediators produced from an arachidonic acid precursor following a series of enzymatic steps. Arachidonic acid is firstly released from the phospholipid bilayer by phospholipase A 2 and may be metabolized by either the cyclooxygenase (COX) or 5-lipoxygenase pathway. Once the unstable precursor LTA 4 has been produced, it may be converted in neutrophils or monocytes to the noncysteinyl LTB 4 by LTA 4 hydrolase. In mast cells, eosinophils, macrophages, and basophils, LTA 4 may alternatively be converted into LTC 4 by LTC 4 synthase and subsequently into LTD 4 and LTE 4. (more…)
The prevalence of aspirin-sensitive asthma is uncertain although it may exist in up to 20% of all asthmatics patients. The char ...
Some features seem to be common to severe asthma and Chronic Obstructive Pulmonary Disease with reversibility of airflow limita ...
A variety of proinflammatory cells, mediators, and cytokines orchestrate the development of airway hyperresponsiveness, which r ...
Leukotrienes are present in increased amounts in exhaled breath condensate (EBC) in patients with asthma. So far, no data have ...
Two main strategies have been developed to block the effects of cysteinyl leukotrienes in the airway. One method is to use drug ...
With the exception of complement protein C3, most soluble mediators of innate immunity are found in relatively small amounts in the serum under normal conditions. The concentrations of several of these proteins, however, can increase as much as 1000-fold during serious infections or other crises, as part of a coordinated protective reaction called the acute-phase response. In this response, the liver temporarily increases its synthesis of more than 30 different serum proteins, often called acute-phase proteins (Table bellow). Many of these, such as complement factors C3 and B, MBL, LBP, C-reactive protein, and serum amyloid protein P, participate in antimicrobial defense. (more…)
Acute phase proteins are plasma proteins, the synthesis and the circulating concentrations of which are adaptively regulated in res ...
Most acute phase proteins are synthesized in the liver, although the genes for some are also expressed in cells and tissues els ...
There is considerable diversity among acute phase proteins with respect to the concentrations attained, their structures, and their ...
Acute phase proteins and the acute phase response in general arc stably conserved in evolution and are universal within each specie ...
An especially elaborate and important type of innate antimicrobial enzymes defense is provided by a group of serum proteins tha ...
In asthma, the secretory phospholipases A2 (sPLA2) have been implicated in the release of arachidonic acid from cellular membranes, the generation of lysophospholipids, the sPLA2-mediated activation of cellular PLA2 (cPLA2) with increased Leukotriene Receptor Antagonist synthesis, and the breakdown of surfactant. In this double-blind, placebo-controlled, random-order crossover study, a potent inhibitor of sPLA2, LY333013, was assessed. (more…)
Marimastat is a synthetic broad-spectrum matrix metalloproteinase (MMP) inhibitor. This study assessed the anti-inflammatory effect ...
Asthma is a common condition among pregnant women and the use of inhaled corticosteroids has been associated with an increased ...
Roflumilast is an oral, once-daily inhibitor of phosphodiesterase type 4 (PDE4) that prevents the breakdown of cyclic adenosine ...
Roflumilast is an oral, once-daily PDE4 inhibitor with antiinflammatory activity in development for the treatment of asthma. Ro ...
Tumour Necrosis Factor is a pro-inflammatory cytokine implicated in the pathogenesis of asthmatic airway inflammation, hyper-react ...
Adenosine is a nucleoside and consists of adenine in glycosidic linkage with ribose. Most adenosine is derived from cleavage of adenosine 5′-monophosphate (AMP) by membrane- associated 5′-nucleotidase. However, the majority of AMP is phosphorylated to ADP or ATP during the process of energy generation. All cells contain adenosine. Indeed, adenosine was shown to cause airway obstruction in patients with asthma. (more…)
Roflumilast is an oral, once-daily inhibitor of phosphodiesterase type 4 (PDE4) that prevents the breakdown of cyclic adenosine ...
Current internationally recognized guidelines indicate that symptomatic asthmatics using a low to medium inhaled corticosteroid ...
A role for Leukotriene B4 in the induction of airway hyper-responsiveness was explored through the use of transgenic mice defic ...
The overlapping functions of cytokines largely reflect the properties of the cell surface receptors to which they bind. All cyt ...
Treating allergic rhinitis may have a downstream effect on concomitant asthma and this may be due to attenuation of the underlying ...