RESUMEN
Atopic dermatitis is a common, chronic inflammatory skin disorder, present in about 12% of children worldwide. Optimizing management of severe atopic dermatitis in pediatric patients is critical to reduce signs of inflammation, alleviate pruritus and sleep disturbance, minimize the development and/or impact of comorbidities, and improve the patient and caregiver's quality of life. Evaluating the longitudinal severity of pediatric atopic dermatitis is an important component of measuring therapeutic response and long-term management, and is different in clinical practice versus clinical trials. This article describes when and how to use different treatments for pediatric patients with severe atopic dermatitis, including topical medications, phototherapy, and systemic medical therapies (traditional immunosuppressants, biologics, and small molecule inhibitors). It also provides recommendations useful in clinical practice for nonpharmacologic interventions for pediatric patients with severe atopic dermatitis.
Asunto(s)
Dermatitis Atópica , Eccema , Niño , Dermatitis Atópica/epidemiología , Dermatitis Atópica/terapia , Humanos , Inmunosupresores , Prurito/terapia , Calidad de VidaRESUMEN
Natural compounds containing vanilloid and Michael acceptor moieties appear to possess anti-cancer and chemopreventive properties. The ginger constituent shogaol represents one such compound. In this study, the anti-cancer potential of a synthetic novel shogaol analog 3-phenyl-3-shogaol (3-Ph-3-SG) was assessed by evaluating its effects on signaling pathways. At non-toxic concentrations, 3-Ph-3-SG suppressed cancer cell invasion in MDA-MB-231 and MCF-7 breast carcinoma cells through inhibition of PMA-activated MMP-9 expression. At similar concentrations, 3-Ph-3-SG reduced expression of the inflammatory mediators nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and prostanglandin-E2 (PGE2) in RAW 264.7 macrophage-like cells. Inhibition of cancer cell invasion and inflammation by 3-Ph-3-SG were mediated through suppression of the nuclear factor-kappaB (NF-κB) signaling pathway. The 3-Ph-3-SG also demonstrated cytoprotective effects by inducing the antioxidant response element (ARE)-driven genes NAD(P)H quinone oxidoreductase-1 (NQO1) and heme oxygenase-1 (HO-1). Cytoprotection by 3-Ph-3-SG was achieved at least partly through modification of cysteine residues in the E3 ubiquitin ligase substrate adaptor Kelch-like ECH-associated protein 1 (Keap1), which resulted in accumulation of transcription factor NF-E2 p45-related factor 2 (Nrf2). The activities of 3-Ph-3-SG were comparable to those of 6-shogaol, the most abundant naturally-occurring shogaol, and stronger than those of 4-hydroxyl-null deshydroxy-3-phenyl-3-shogaol, which attested the importance of the 4-hydroxy substituent in the vanilloid moiety for bioactivity. In summary, 3-Ph-3-SG is shown to possess activities that modulate stress-associated pathways relevant to multiple steps in carcinogenesis. Therefore, it warrants further investigation of this compound as a promising candidate for use in chemotherapeutic and chemopreventive strategies.