Inflammation suppression

Inflammation Anti-inflammation (suppression of NF-kB activity by activating Ikk 3) [34, 39,40,41,46]... 

The alkaloid erythraline (103), isolated from several Erythrina species which are used as Brazilian medicine plants for the treatment of inflammation, suppressed nitric oxide production and induction of inducible nitric oxide synthase expression in RAW264.7 cells stimulated by lipopolysaccharide. Erythraline also inhibits phosphorylation of mitogen -activated protein kinases. These results suggested that erythraline might inhibit the kinase activity of TAKl [69]. 

The predominant clinical use of corticosteroids is a result of their associated antiinflammatory properties. These are commonly used as topicals for the suppression of symptoms, including inflammation, occurring in a particular disease state these compounds are rarely considered curative in their usage. Many other disease states do, however, respond well symptomatically to treatment with corticosteroid therapy. Some of these (11) are Hsted below. 

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. 

Glucocorticoids have been shown to inhibit gene transcription of other proteins involved in the inflammatory process, including the key inflammation mediators called cytokines (IL-1, IL3—6, IL8, GM-CSF, TNFa) (10,58,63—65). Steroids have been also shown to suppress the formation of cytokine receptors (10) dexamethasone, in particular, downregulates gene transcription of angiotensin II type 2 receptors (66). 

Atropiae (41), isolated from the deadly nightshade Airopa belladonna L.) is the racemic form, as isolated, of (—)-hyoscyamine [which is not isolated, of course, from the same plant but is typically found ia solanaceous plants such as henbane (HyosQiamus mgerl. )]. Atropiae is used to dilate the pupil of the eye ia ocular inflammations and is available both as a parasympatholytic agent for relaxation of the intestinal tract and to suppress secretions of the saUvary, gastric, and respiratory tracts. In conjunction with other agents it is used as part of an antidote mixture for organophosphorus poisons (see Chemicals in war). 

These steioids aie capable of preventing or suppressing the development of the sweUing, redness, local heat, and tenderness which characterize inflammation. They inhibit not only the acute symptoms of the inflammatory process, such as edema, fibrin deposition, and capillary dilatation, but also the chronic manifestations. There is evidence that glucocorticoids induce the synthesis of a protein that inhibits phosphoHpase A 2 (60), diminishing the release of arachidonic acid from phosphoHpids (Fig. 2), thereby reducing chemotaxis and inflammation. 

Unfortunately steroids merely suppress the inflammation while the underlying cause of the disease remains. Another serious concern about steroids is that of toxicity. The abmpt withdrawal of glucocorticoid steroids results in acute adrenal insufficiency. Long term use may induce osteoporosis, peptidic ulcers, the retention of fluid, or an increased susceptibiUty to infections. Because of these problems, steroids are rarely the first line of treatment for any inflammatory condition, and their use in rheumatoid arthritis begins after more conservative therapies have failed. 

Theophylline s predominant mode of action appears to be bronchocHlation. However, it has also been shown that prophylactic acHriinistration of theophylline provides some protection from asthma attacks and suppresses the late-phase response (67,68). Some researchers beHeve that at therapeutic semm concentrations theophylline may inhibit the development of airway inflammation (69). There are conflicting reports on the effect of theophylline on allergen-induced bronchial hyperresponsiveness some clinical stucHes report a reduction in hyper-responsiveness, others do not (69,70). Theophylline clearly does not reverse the general bronchial hyperresponsiveness over the course of long-term therapy (71). Because of the relationship between... 

Insulin resistance occurs when the normal response to a given amount of insulin is reduced. Resistance of liver to the effects of insulin results in inadequate suppression of hepatic glucose production insulin resistance of skeletal muscle reduces the amount of glucose taken out of the circulation into skeletal muscle for storage and insulin resistance of adipose tissue results in impaired suppression of lipolysis and increased levels of free fatty acids. Therefore, insulin resistance is associated with a cluster of metabolic abnormalities including elevated blood glucose levels, abnormal blood lipid profile (dyslipidemia), hypertension, and increased expression of inflammatory markers (inflammation). Insulin resistance and this cluster of metabolic abnormalities is strongly associated with obesity, predominantly abdominal (visceral) obesity, and physical inactivity and increased risk for type 2 diabetes, cardiovascular and renal disease, as well as some forms of cancer. In addition to obesity, other situations in which insulin resistance occurs includes... 

The ghicocorticoids are used as replacement therapy for adrenocortical insufficiency, to treat allergic reactions, collagen diseases (eg, systemic lupus erythematosus), dermatologic conditions, rheumatic disorders, shock, and other conditions (see Display 50-1). The anti-inflammatory activity of these hormones make them valuable as anti-inflammatories and as immunosuppressants to suppress inflammation and modify the immune response... 

Systemic antibiotics are indicated for moderate-severe inflammatory acne not responding to topical treatments. Systemic antibiotics act on 1) suppression of P. acnes growth 2) inhibition of bacterial lipases 3) reduction of free fatty acids and 4) reduction of inflammation. Oxytetracycline and its derivatives are the most commonly used oral antibiotics. Second-generation tetracyclines such as minocycline, doxy-cycline and lymecycline present longer half-lives, enhanced bacterial activity and lower... 

A distinct population of effector T cells that promote tissue inflammation has been described without suppressive functions [9]. This population is termed as Th9 cells and exerts IL-9 and IL-10 secretion capacities. IL-4 and TGF-(I promotes an IL-9-producing subset, Th9 cells, which have roles in mucus production and tissue inflammation [100,101]. 

Iwamura and Ueda [386] described compound (611) as a CB2 selective inverse agonist in a patent application. The potential therapeutic roles of CB2 antagonists are not clearly defined at the moment, although roles in regulation of the immune system and inflammation have been widely proposed. This patent application describes that activity of compound (611) in a mouse model of asthma, in which the compound suppressed immediate and late-phase asthmatic response and airway hyper-responsiveness. 

Corticosteroids are the most potent anti-inflammatory agents available for the treatment of asthma. The efficacy of corticosteroids is due to their ability to affect multiple inflammatory pathways, resulting in the suppression of inflammatory cell activation and function, prevention of microvascular leakage, decreased mucus production, and upregulation of P2-adrenergic receptors.10,18 Clinically, corticosteroids decrease airway inflammation, decrease AHR, decrease mucus production and secretion, and improve the response to P2-agonists.18 Corticosteroids for the treatment of asthma are available in inhaled, oral, and injectable dosage forms. 

Gastric outlet obstruction occurs in approximately 2% of patients with PUD and is usually caused by ulcer-related inflammation or scar formation near the peripyloric region. Signs and symptoms of outlet obstruction include early satiety after meals, nausea, vomiting, abdominal pain, and weight loss. Ulcer healing with conventional acid-suppressive therapy is the primary treatment, but if this is unsuccessful then an endoscopic procedure (e.g., balloon dilation) is required. 

Major treatment goals for patients with IBD include alleviation of signs and symptoms and suppression of inflammation during acute episodes and maintenance of remission thereafter. 

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