Therapeutic approaches

Selective inhibition of inflammatory cytokines is also an attractive approach. In animal models, antibodies to TNFa prevent lung fibrosis when given prior to injury from silica, bleomycin or antigen-induced extrinsic allergic alveolitis (Piguet etal., 1989, 1990 Denis et al., 1991). This approach may be an option in humans since TNFa antibodies have been used successfully as a therapy in patients with rheumatoid arthritis (Elliot etal., 1993). 

Inhibition of increased release of IL-1 may be equally useful in preventing lung damage (Girardin et al., 1988 Shalaby etal., 1991). The identification of IL-lRa (Eisen-berg et al., 1990 Dinarello, 1991) raises the possibility that this may have therapeutic benefit. 

Relatively non-specific T cell immunosuppression has been successful in animal models. Treatment of hypersensitivity pneumonitis in mice with cyclosporin A led to improvement of the disease as seen by an abrogation of the increase in lung index, lack of IL-1 and TNFa release in BAL (Denis etal., 1992). However, this drug has not proven to be useful in clinical lung fibrosis in humans. 

The protective effects of liposome-entrapped superoxide dismutase and catalase have also been studied on bleomycin-induced collagen deposition in the lungs of mice (Ledwozyn, 1991). It has been suggested that liposomes might be good vectors for drugs in the treatment of bleomycin-induced fibrosis. 

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Topical Application. Azelastine (11) and levocabastine (13) have been developed for topical appHcation (45). The topical antihistamines address the preference of some patients for a local treatment and allow adrninistration of dmg directly to the site requited. The advantage of this therapeutic approach is likely to be in the speed of onset of symptom rehef. In contrast to earlier reports of sensitization with older antihistamines locally apphed to the skin (46), sensitization has not been reported with local appHcation to the nose or eyes. 

Cytokines, eg, interferons, interleukins, tumor necrosis factor (TNF), and certain growth factors, could have antitumor activity directiy, or may modulate cellular mechanisms of antitumor activity (2). Cytokines may be used to influence the proliferation and differentiation of T-ceUs, B-ceUs, macrophage—monocyte, myeloid, or other hematopoietic cells. Alternatively, the induction of interferon release may represent an important approach for synthetic—medicinal chemistry, to search for effective antiinflammatory and antifibrotic agents. Inducers of interferon release may also be useful for lepromatous leprosy and chronic granulomatous disease. The potential cytokine and cytokine-related therapeutic approaches to treatment of disease are summarized in Table 4. A combination of cytokines is a feasible modaUty for treatment of immunologically related diseases however, there are dangers inherent in such an approach, as shown by the induction of lethal disserninated intravascular coagulation in mice adrninistered TNF-a and IFN-y. 

Table 4. Cytokine and Cytokine-Related Therapeutic Approaches to Disease ...

Tumors derived from hormone sensitive tissues may remain hormone dependent and are then amenable to therapeutic approaches with hormonal agents. These include hormones with opposing (apoptotic) action, hormone antagonists, and agents that inhibit hormone synthesis. 

However, despite its enormous importance to human physiology, no pharmacological compounds targeting the components of the circadian clock system have been identified to date. There are, nevertheless, two therapeutic approaches that are currently used for treatment of circadian-related disorders - full-spectrum and bright light therapy and melatonin therapy. Melatonin is a hormone that is produced by the pineal gland in... 

If 50% of Europeans with essential hypertension are affected by this disease because of an elevated secretion of endogenous ouabain, then there might be a chance to block its interaction at the cardiac glycoside binding site of Na+/K+-ATPase and thus lower blood pressure. This therapeutic approach seems to be successfiil. Recent studies provide evidence that the cardenolide analogue Rostafuroxin (PST 2238 Fig. 4) at very low concentrations can overcome the ouabain-induced tise of hypertension in experimental animals [6]. This compound has recently entered the phase I of clinical trials and is certainly a prototype of a new class of antihypertensive drugs. 

The PAR family represents a novel target for drug therapy. Therapeutic approaches with most clinical benefit may rely upon the development of both agonists and antagonists, either of which could be utilised dqiending upon the disease condition [3]. 

Basic Gene Therapeutic Approaches for Viral Diseases.267... 

There are three principal gene therapeutic approaches for viral diseases. First, several genes that inhibit virus replication have been developed. This approach has been termed intracellular immunization (Baltimore 1988). Second, genetic approaches... 

De Swert LF, Bullens D, Raes M. Dermaux AM Anaphylaxis in referred pediatric patients demographic and chnical features, triggers, and therapeutic approach. Eur J Pediatr 2008 167 1251-1261. Brockow K, Jofer C, Behrendt H, Ring J Anaphylaxis in patients with mastocytosis a study on history chnical features and risk factors in 120 patients. AUergy 2008 63 226-232. 

Pauza CD. Streblow D.N. (1995) Therapeutic approaches to HIV infection based on vims stmcture and host-pathogen interaction. Curr Topics Microbiol Immunol, 202, 117-132. 

Staphylococcus aureus is responsible for a variety of skin infections which require therapeutic approaches different from those of streptococcal infections. Staphylococcal celluhtis is indistinguishable clinically from streptococcal cellulitis and responds to cloxacillin or flucloxacillin, but generally fails to respond to penicillin owing to penicillinase (/3-lactamase) production. Staphylococcus aureus is an important cause of superficial, localized skin sepsis which varies ftom small pustules to boils and occasionally to a more deeply invasive, suppurative skin abscess known as a carbuncle. Antibiotics are generally not indicated for these conditions. Pustules and boils settle with antiseptic soaps or creams and often discharge spontaneously, whereas carbuncles frequently require surgical drainage. Staphylococcus aureus may also cause... 

In humans, poor sleep correlates with low plasma melatonin and can be improved by melatonin administration. This therapeutic approach has been tried especially in individuals whose sleep rhythms are disrupted by shift-work, blindness or jet-lag but its benefits are as yet unconfirmed and, in any case, the mechanisms by which it might reset sleep patterns are unclear. Of course, it must be remembered that other body... 

RODAN G A and MARTIN T I (2000) Therapeutic approaches to bone diseases, Science 289, 1508-14. 

Hearse, D.J. and Yellon, D.M. (1984). Therapeutic Approaches to Myocardial In rct Size Limitation . Raven Press, New York. 

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