Antiinflammatory effects

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. 

There are hundreds of topical steroid preparations that are available for the treatment of skin diseases. In addition to their aforementioned antiinflammatory effects, topical steroids also exert their effects by vasoconstriction of the capillaries in the superficial dermis and by reduction of cellular mitosis and cell proliferation especially in the basal cell layer of the skin. In addition to the aforementioned systemic side effects, topical steroids can have adverse local effects. Chronic treatment with topical corticosteroids may increase the risk of bacterial and fungal infections. A combination steroid and antibacterial agent can be used to combat this problem. Additional local side effects that can be caused by extended use of topical steroids are epidermal atrophy, acne, glaucoma and cataracts (thus the weakest concentrations should be used in and around the eyes), pigmentation problems, hypertrichosis, allergic contact dermatitis, perioral dermatitis, and granuloma gluteale infantum (251). 

Leukotriene B5 can be biosynthesized in the body from eicosapentaenoic acid, which is ingested in the form of dietary fish lipid. Synthetic LTB5 was synthesized as outlined below and found to have only 20% of the neutrophil chemotactic activity of LTB4, a fact which may be relevant to the antiinflammatory effect of dietary marine lipid. 

Di-tert-butyl-4-hydroxyphenyl)-7//-triazolo [3,2-b][l, 2,4]triazin-7-one (HWA-131)is anon-immunosuppressive drug that effectively inhibited carrageenan-induced paw edema, attenuated the active Arthus reaction, and demonstrated antierythema as well as antipyretic activity. Part of the antiinflammatory effect of this new compound is most probably related to its antioxidative activity as well as inhibition of lipoxygenase... 

The antiinflammatory effects of statins likely result from their ability to inhibit the formation of mevalonic acid. Downstream products of this molecule include not only the end product, cholesterol, but also several isoprenoid intermediates that covalently modify ( pre-nylate ) certain key intracellular signaling molecules. Statin treatment reduces leukocyte adhesion, accumulation of macrophages, MMPs, tissue factor, and other proinflammatory mediators. By acting on the MHC class II transactivator (CIITA), statins also interfere with antigen presentation and subsequent T-cell activation. Statin treatment can also limit platelet activation in some assays as well. All these results support the concept that in addition to their favorable effect on the lipid profile, statins can also exert an array of antiinflammatory and immunomodulatory actions. 

Perricone NV (1993) The photoprotective and antiinflammatory effects of topical ascorbyl palmitate. J Ger Dermatol 1 5-10... 

Ajulemic acid (CT3, 8.9) is the dimethylheptyl homolog of the main metabo-hte of A8-THC. It has no psychotropic activity, but has analgesic and antiinflammatory effects. 

Aruoma, O.I., Wasil, M., HaUiweU, B., Hoey, B.M. and Butler, J. (1987). The scavenging of oxidants by sulphasala-zine and its metabolites. A possible contribution to their antiinflammatory effects Biochem. Pharm. 36, 3739-3742. 

The purported prophylactic use of Japanese herbal medicines to combat neuronal ageing has been related to their free-radical scavenging activity (Hiramatsu a al., 1992). Inhibition of the pro-inflammatory effects of cytokine interleukin-1 by recombinant endogenous interleukin-1 receptor antagonist in experimental rats is associated with alleviation of excitotoxic neuronal damage, an action which has also been related to the antiinflammatory effect of lipocortin 1 (Relton and Roth well, 1992). 

Retinoids, which are highly effective in the treatment of acne, stimulate epithelial cell turnover and aid in unclogging blocked pores. Retinoids also exhibit anti-inflammatory properties through the inhibition of neutrophil and monocyte chemotaxis.8 Because of these comedolytic and antiinflammatory effects, topical retinoids are recommended as first-line treatment for mild to moderate comedonal and inflammatory acne.3 While success is seen with monotherapy, using a retinoid in combination with benzoyl peroxide or topical antibacterials is also an appropriate and effective therapeutic treatment option.3 Tretinoin, adapalene, and tazarotene are topical retinoids available for use in the treatment of acne. Table 62-2 describes the strengths and formulations of these agents. 

Ozaki Y, Sekita S, Soedigdo S, Harada M. Antiinflammatory effect of Graptophyllum pictum (L.) Griff. Chem Pharm Bull (Tokyo) 1989 37 2799-2802. 

Casellas F, Borruel N, Papo M, Guarner F, Antolin M, Videla S, Malagelada JR Antiinflammatory effects of enterically coated amoxicillin-clavulanic acid in ulcerative colitis. Inflamm Bowel Dis 1998 4 1-5. 

Low-potency products (e.g., hydrocortisone 1%) have a weak antiinflammatory effect and are safest for long-term application, for use on the face and intertriginous areas, for use with occlusion, and for use in infants and young children. 

Vitamin D and its analogs inhibit keratinocyte differentiation and proliferation and have antiinflammatory effects by reducing IL-8, IL-2, and other cytokines. Use of vitamin D itself is limited by its propensity to cause hypercalcemia. 

Cushman M, Costantino JP, Tracy RP, Song K, Buckley L, Roberts JD, Krag DN (2001) Tamoxifen and cardiac risk factors in healthy women suggestion of an antiinflammatory effect. Arterioscler Thromb Vase Biol 21 255-261... 

Isoflavonoid has been used as dietary biomarkers [103,104], It has been further established that isoflavonoids influence receptor expression [105] and induce immune changes [106,107], The individual variation in metabolism of isoflavones has also been extansively studied [108,109], It has been further demonstrated that flavonoids show antiinflammatory effects on adjuvant arthritis [110], and protect mice from two types of lethal shock caused by endotoxin [111],... 

Polygenic analyses of the MTX pathway genes have also been perfonned. This is particularly relevant in the case of MTX as the drug exerts its effects by influencing several different genes in the intracellular pathways. AIC AR transfonnylase (ATIC) converts AlCAR to 10-formyl AlCAR and is directly inhibited by MTX see Fig. 14.1). This leads to accumulation of AlCAR and adenosine, a purine with antiinflammatory properties. Adenosine may be an important mediator of the antiinflammatory effects of MTX (11). 

Acetylsalicylic acid (ASA) exerts an antiinflammatory effect, in addition to its analgesic and antipyretic actions. 

Conversely, certain drugs modify the effectiveness or side effects of aspirin. Phenobarbital, occasionally used for seizures, induces liver enzymes that increase the metabolism and excretion of aspirin, (3-adrenoceptorblocking drugs, such as propranolol, and decrease the antiinflammatory effects of aspirin, whereas reserpine decreases its analgesic effects. Antacids decrease the absorption of aspirin. Alcohol consumption in combination with aspirin increases the latter s ulcerogenic effects. 

The arylpropionic acid derivatives are useful for the treatment of rheumatoid arthritis and osteoarthritis, for reduction of mild to moderate pain and fever, and for pain associated with dysmenorrhea. Side effects of the drugs are similar to but less severe than those described for the salicylates. Those who are sensitive to salicylates also may be sensitive to and have adverse reactions when taking ibuprofen and related drugs. Acute hypersensitivity to ibuprofen has been reported in patients with lupus. The hypersensitivity reaction to sulindac can be fatal. The use of sulindac has also been linked to cases of acute pancreatitis. The use of dimethylsulfoxide (DMSO) topically in combination with sulindac has been reported to induce severe neuropathies. The concurrent use of ibuprofen with aspirin reduces the antiinflammatory effects of both drugs. Ibuprofen is contraindicated in patients with aspirin sensitivity leading to bronchiolar constriction and in patients with an-gioedema. As with all NSAIDs, renal and liver function should be normal for adequate clearance of the drugs. 

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. 

Clofazimine is given to treat sulfone-resistant leprosy or to patients who are intolerant to sulfones. It also exerts an antiinflammatory effect and prevents erythema nodosum leprosum, which can interrupt treatment with dapsone. This is a major advantage of clofazimine over other antileprosy drugs. Ulcerative lesions caused by Mycobacterium ulcerans respond well to clofazimine. It also has some activity against M. tuberculosis and can be used as last resort therapy for the treatment of MDR tuberculosis. 

In vitro antiinflammatory effects have been documented, and the herb has a long history of being used externally for wound healing, psoriasis, and the reduction of skin irritation. Although there are a few small positive studies, the available evidence is not yet conclusive in regard to clinical use. 

Saw palmetto extract can inhibit the enzyme 5-a-reductase in vitro. This enzyme converts testosterone into dihydrotestosterone (DHT), which in turn contributes to prostatic enlargement. Saw palmetto also appears to have an antiinflammatory effect and can reduce DHT binding to prostatic androgen receptors (antiandrogenic effect). Despite its proposed 5-a-reductase mechanism. 

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