Inhibition therapeutic implications

R. C. Moellering, /3-Lactamase Inhibition Therapeutic Implications in infectious Diseases -An Overview , Rev. Infect. Dis. 1991, 13, S723-S726. 

Anandamide is rapidly hydrolysed enzymatically to arachidonic acid and ethanol-amine by a fatty acid amide hydrolase (FAAH) [50], The molecular characterization, cloning and expression of FAAH have been reported in a recent study [51]. FAAH can be blocked with either the general serine protease inhibitor phenyl methy(sulphonyl fluoride [38] or with the highly efficient methyl arachidonyl fluorophsphonate [52], The non-steroidal antiinflammatory ibuprofen in therapeutic doses, but not aspirin, sulindac or acetaminophen, also inhibits anandamide metabolism [53], This observation may have therapeutic implications. 

A number of studies have examined the anti-inflammatory aetivities of CO (Abraham et al, 1988 Mannaioni et al, 2006). An activation of the heme oxygenase system and exposure to CO in vitro (Chauveau et al, 2005 Gibbons and Farrugia, 2004 Otterbein et al, 1999, 2000 Pae et al, 2004 Sethi et al, 2002) and in vivo (Dolinay et al, 2004 Nakao et al, 2003 Neto et al, 2004 Otterbein et al, 1999) revealed anti-inflainmatory activity in animal models but not in humans (Mayr et al, 2005). CO can inhibit apoptosis of endothelial cells (Soares et al, 2002). There is some evidence that upregulation of HO-1 might be beneficial in inflammatory diseases (Willis et al, 1996). In any case, the ability of CO to inhibit platelet aggregation and inflammation has important therapeutic implications and needs to be explored. 

Vij N, Fang S, Zeitlin PL. Selective inhibition of endoplasmic reticulum-associated degradation rescues DeltaF508-cystic fibrosis transmembrane regulator and suppresses interleukin-8 levels therapeutic implications. J. Biol. Chem. 2006 281 17369-17378. 

The polybrominated diphenyl ether derivatives have also been reported to inhibit enzymes implicated in tumor development and artherosclerotic plague which indicates their potential as promising candidates for therapeutic agents [186]. It was previously shown that the symbiotic cyanobacterium, Oscillatoria spongeliae produces the polybrominated diphenyl ether [187, 188]. The marine sponge Dysidea herbacea collected from Indonesia, yielded a series of polybrominated diphenyl ether congeners [189, 190]. D. herbacea occurs in two chemotypes [188] - one chemotype contains both polychlorinated amino acid derivatives [191, 192] and sesquiterpenes [193, 194], while the second chemotype contains... 

Inhibition of aromatase may have therapeutic implications in diseases that are estrogen-dependent, such as some types of breast and endometrial cancer in women " " and possibly in benign prostatic hyperplasia in men Several steroidal and nonsteroidal com-... 

Phan, T.T., Sun, L., Bay, B.H., Chan, S.Y., and Lee, S.T., Dietary compounds inhibit proliferation and contraction of keloid and hypertrophic scar-derived fibroblasts in vitro therapeutic implication for excessive scarring, J. Trauma, 54 (6), 1212-1224, 2003. 

Mabley J, Viidg L, Szab6 C. Role of PARP activation in the pathogenesis of diabetes and diabetic vascular dysfunction. In Zhang J, ed. Therapeutic Implications of PARP Inhibition. Boca Raton CRC Press, 2002 277-319. 

McGinn CJ, Miller EM, Lindstrom MJ, et al (1994) The role of cell cycle redistribution in radiosensitization implications regarding the mechanism of fluorodeoxyuridine radiosensitization. Int J Radiat Oncol Biol Phys 30 851-859 McGinn CJ, Shewach DS, Lawrence TS (1996) Radiosensitiz-ing nucleosides. J Natl Cancer Inst 88 1193-1203 Milas L, Hunter NR, Mason KA, et al (1994) Enhancement of tumor radioresponse of a murine mammary carcinoma by paclitaxel. Cancer Res 54 3506-3510 Milas L, Hunter NR, Mason KA, et al (1995) Role of reoxygenation in induction of enhancement of tumor radioresponse by paclitaxel. Cancer Res 55 3564-3568 Miller EM, Kinsella TJ (1992) Radiosensitization by fluorodeoxyuridine effects of thymidylate synthase inhibition and cell synchronization. Cancer Res 52 1687-1694 Miller SJ, Lavker RM, Sun TT (2005) Interpreting epithelial cancer biology in the context of stem cells tumor properties and therapeutic implications. Biochem Biophys Acta 1756 25-52... 

The accumulation of evidence implicating a role for adenosine in the pathogenesis of airway inflammation has led to investigations into all adenosine receptor subtypes as potential therapeutic targets for the treatment of asthma and COPD. To this end, the efficacy of A3AR in the clinical setting has been inconclusive. However, inhibition of Aj and A2B receptors and/or activation of the A2A pathway may serve as an alternative therapeutic approach (Brown et al. 2008b). 

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