Inflammation initiation

Rabbit Eye Irritation. Instillation of the chlorodibenzodioxins into the conjunctival sac caused slight, transient pain and conjunctival inflammation, initially. Treatment with 2,3,7,8-TCDD was associated with delayed conjunctival chemosis 13-22 days later. By day 27, the chemosis had subsided, but the rim of the eyelid was thickened and encrusted. 

The clinical aspects of asbestosis are well defined and predictable. First, the lung tissue changes to scar tissue as inflammation, initiated by the cells normally in the tissue or air spaces, is expressed as an increase of inelastic collagen. The fibrosed or scar tissue renders the lung tissue stiff and narrows the airways. Mechanical constraints become obvious as the patient expends more effort to breathe. 

The effects of ozone appear to be cumulative for initial exposures followed by adaptation. Five of six subjects exposed to 0.5 ppm ozone 2 hours/day for 4 days showed cumulative effects of symptoms and lung function tests for the first 3 days, followed by a return to near control values on day 4." In animals exposure to 0.3-3 ppm for up to 1 hour permits the animals to withstand multilethal doses for months afterwards. However, repeated exposures impart protection from all forms of lung injury (e.g., susceptibility to infectious agents, enzyme activities, inflammation). Initial ozone exposure may act to reduce cell sensitivity and/or increase mucus thickness, factors which may modify the accessibility and action of the gas. It is not known how variations in the length, frequency, or magnitude of exposure modify the time course for tolerance. 

The most common side effects of IFN (3-1 a (Avonex) involve flu-like symptoms including headache, fever, chills, muscle or joint ache, fatigue, pain or injection site inflammation. Initiation of therapy in a step-wise increase in dose and use of pain medications usually alleviate or substantially decrease these side effects. Less common side effects include nausea, stomach upset, diarrhea, a lower red blood cell count, sleep disturbances, dizziness, and infection. As with other IFN(3... 

Information derived from a variety of experimental animal models suggests that a number of cytokines play a role in the initiation, maintenance, and resolution of chronic interstitial pulmonary inflammation. However, the mechanism by which each cytokine is involved in the evolution of the inflammatory response is not clear. For example, in vivo studies assessing the development of interstitial lung granulomas induced by a mycobacterial antigen, purified protein derivative (PPD), have demonstrated that IFN-y and TNF were necessary cytokines for lesion progression (52). In contrast, pulmonary inflammation initiated by either the... 

Rather than being a maladaptive response, the inflammation initiated and coordinated by arachidonic acid products and cytokines after exposure to mineral oxides is absolutely essential for the survival of the host. The iron was initially complexed to the dust with a labile or reactive coordination site available. Consequently, the metal was capable of oxidant generation and injury to host tissues. After reduction by superoxide produced by NADPH oxidoreductase in the neutrophil, reaction with lactoferrin released by the neutrophil (108), and deposition in ferritin of the reticuloendothelial system (109), the iron is rendered catalytically less active. 

Transactivation. Protein synthesis is initiated or inhibited by the action of the activated GR on DNA. The use of glucocorticoids leads to antiinflammatory effects by first controlling gene expression, which subsequentiy leads to the synthesis and/or suppression of inflammation regulatory proteins. 

Horie and coworkers synthesized a series of flavones that showed promising inhibitory activity against archidonate 5-lipooxygenase. This enzyme is responsible for the initiation of bioactive leukotrienes that are chemical mediators of anaphylaxis and inflammation. Under standard K-R conditions o-hydroxyarylketone 66 and anhydride 67 in presence of the corresponding anhydride 68 delivered flavones 69 in yields of 42-65%. Subsequent hydrogenation of 69 afforded the flavone inhibitors 70. 

For the pathogenesis of multiple sklerosis, autoimmune T-lymphocy tes play a predominant role, which are directed against components of the neural myelin sheath. T-lymphocy tes by secreting cytokines such as interferon y maintain the chronic inflammation which destructs the myelin sheath. Also cytotoxic T-lymphocytes may participate directly. The cause of multiple sklerosis is unknown. Significantly increased antibody titers against several vitusses, mostly the measles virus, point to a (latent) virus infection initiating the disease. 

The activation of mast cells by allergen initiates the asthma symptoms within minutes after allergen contact, the early allergic response (EAR), within horns the late allergic response (LAR), and within years and after rqDeated asthma episodes, chronic airway inflammation, airway remodeling, and airway hyperresponsiveness. 

These disorders are all acquired conditions with no evidence of an hereditary basis. Most of them involve inflammation of the skeletal muscle itself (myositis) (Figure 17), though this may sometimes occur because of initial targeting of the muscle vasculature or connective tissue. Many instances of myositis are classed as idiopathic disorders, in that the precise mechanisms of muscle degeneration are not known, but is widely accepted that these syndromes are associated with abnormal function of the immune system. The syndromes of polymyositis (PM) and derma-... 

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