Mediators, inflammatory asthma

The TP receptor requires the G/G protein to activate the Src-Ras-ERKl/2 (extracellular signal-regulated kinase 1 and 2) cascade to induce the proliferative response, which in turn promotes the rapid nuclear translocation of activated ERKl/2 (201). Because TP receptor may be activated by many inflammatory mediators (202-204), these findings suggest new therapeutic strategies that alter the ASM hypertrophy or hyperplasia observed in the chronic airflow obstruction and airway inflammation that characterizes asthma, chronic bronchitis, bronchiolitis obliterans, and chronic obstructive pulmonary disease. 

Glucose is a simple sugar and is the sole provider of energy to the brain. It is stored in the body as glucagon. Bradykinin, histamine, lymphokines and lysosomal enzymes are all different inflammatory mediators that play a significant role in precipitating asthma and other inflammatory conditions. 

Smooth muscle relaxation, central nervous system (CNS) excitation, and cardiac stimulation are the principal pharmacological effects observed in patients treated with theophylline. The action of theophylline on the respiratory system is easily seen in the asthmatic by the resolution of obstruction and improvement in pulmonary function. Other mechanisms that may contribute to the action of theophylline in asthma include antagonism of adenosine, inhibition of mediator release, increased sympathetic activity, alteration in immune cell function, and reduction in respiratory muscle fatigue. Theophylline also may exert an antiinflammatory effect through its ability to modulate inflammatory mediator release and immune cell function. 

Acerola contains vitamin C, which is associated with lower risk of asthma,19 20 and a regular use of vitamin C has been shown to reduce concentrations of histamine, a major allergic reaction and inflammatory mediator.2122... 

In addition to the use in the synthesis of potential hepatitis C drugs, microwave-assisted chemistry has also been used in the synthesis of mast cell tryptase inhibitors, thrombin inhibitors, and Factor Xa inhibitors. The trypsin-like serine protease tryptase is the major secretory product of human mast cells and has been implicated as an inflammatory mediator in a number of conditions, especially asthma. Once released upon mast cell activation, the tryptase cleaves substrates that otherwise cause smooth muscle relaxation and thereby bronchi- and vasodilation. It is therefore not surprising that numerous reports on low molecular weight tryptase inhibitors have appeared. 

Asthma is a chronic inflammatory disease affecting the airways. Inflammatory mediators such as prostaglandins and histamines cause inflammatory cells to damage the bronchial epithelium and cause bronchial constriction. 

As discussed in Section 3.3, few histopathological studies of asthma have focused specifically on the microvasculature. Nonetheless, there is evidence that neovascularization is one of the changes in the airways of asthmatics (Kuwano et al., 1991). This observation in potentially important because newly formed blood vessels may be abnormally leaky (Schoefl, 1967) or abnormally responsive to inflammatory mediators (McDonald, 1992). The plasma leakage that occurs in the airway mucosa of asthmatics could result from the heightened response of the mucosal blood vessels to inflammatory mediators. 

Selective 182-adrenergic receptor agonists (ft agonists) are widely used in the treatment of airway diseases such as asthma because of their bronchodilating action. In addition, ft agonists have anti-inflammatory effects, in that they can inhibit the release of inflammatory mediators and can decrease plasma leakage (Svensjo et al., 1977 Tomioka etal., 1981 Erjefalt and Persson, 1986 Barnes,... 

The second group of antiasthmatics are ANTIINFLAMMATORY Or ANTIALLERGIC AGENTS. SUCh aS the CORTICOSTEROIDS and sodium cromoglycate. These drugs prevent the release of local inflammatory mediators, which contribute to attacks, so preventing asthma attacks, and also provide symptomatic relief. 

To explore this scenario, five virtual patients were developed to explore the uncertainty surrounding the pathophysiology of moderate asthma, that is, the simulations were designed to plumb the space of how one became a moderate asthmatic in the first place. While the array of inflammatory mediators underlying the pathophysiology of asthma have been identified, for the most part, and are fairly well understood, the contribution of each to the disease process is not yet known in detail. Though all five virtual patients have similar clinical behaviors consistent with moderate asthma (i.e., a forced expiratory volume in one second [FEV1] between 65 and 80%), each virtual patient was created to explore a different combination of these mediators. 

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