RESUMEN
OBJECTIVE: To investigate the risk and genetic association of oxcarbazepine-induced cutaneous adverse reactions (OXC-cADRs), including Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), in Asian populations (Chinese and Thai). METHODS: We prospectively enrolled patients with OXC-cADRs in Taiwan and Thailand from 2006 to 2014, and analyzed the clinical course, latent period, drug dosage, organ involvement, complications, and mortality. We also investigated the carrier rate of HLA-B*15:02 and HLA-A*31:01 of patients with OXC-cADRs and compared to OXC-tolerant controls. The incidence of OXC-SJS/TEN was compared with carbamazepine (CBZ)-induced SJS/TEN according to the nationwide population dataset from the Taiwan National Health Insurance Research Database. RESULTS: We enrolled 50 patients with OXC-cADRs, including 20 OXC-SJS/TEN and 6 drug reaction with eosinophilia and systemic symptoms, of Chinese patients from Taiwan and Thai patients from Thailand. OXC-cADRs presented with less clinical severity including limited skin detachment (all â¦5%) and no mortality. There was a significant association between HLA-B*15:02 and OXC-SJS (p = 1.87 × 10-10; odds ratio 27.90; 95% confidence interval [CI] 7.84-99.23) in Chinese and this significant association was also observed in Thai patients. The positive and negative predictive values of HLA-B*15:02 for OXC-SJS/TEN were 0.73% and 99.97%, respectively. HLA-A*31:01 was not associated with OXC-cADRs. The incidence and mortality of OXC-SJS/TEN was lower than CBZ-STS/TEN in new users (p = 0.003; relative risk 0.212; 95% CI 0.077-0.584). CONCLUSIONS: Our findings suggest that HLA-B*15:02 is significantly associated with OXC-SJS in Asian populations (Chinese and Thai). However, the severity and incidence of OXC-SJS/TEN are less than that of CBZ-SJS/TEN. The need for preemptive HLA-B*15:02 screening should be evaluated further.
Asunto(s)
Anticonvulsivantes/efectos adversos , Carbamazepina/análogos & derivados , Antígenos HLA-B/genética , Síndrome de Stevens-Johnson , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Carbamazepina/efectos adversos , Niño , Preescolar , Epilepsia/tratamiento farmacológico , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad/genética , Genotipo , Antígenos HLA-A/genética , Humanos , Incidencia , Masculino , Metaanálisis como Asunto , Persona de Mediana Edad , Programas Nacionales de Salud/estadística & datos numéricos , Oxcarbazepina , Estudios Prospectivos , Estudios Retrospectivos , Estadísticas no Paramétricas , Síndrome de Stevens-Johnson/epidemiología , Síndrome de Stevens-Johnson/etiología , Síndrome de Stevens-Johnson/genética , Taiwán , Tailandia , Adulto JovenAsunto(s)
Adenina/farmacología , Senescencia Celular/efectos de los fármacos , Dermis/citología , Folículo Piloso/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacología , División Celular/efectos de los fármacos , Células Cultivadas , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Folículo Piloso/citología , Folículo Piloso/enzimología , Humanos , NAD/metabolismo , Fosforilación/efectos de los fármacos , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Ribonucleótidos/farmacología , beta-Galactosidasa/análisisRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Soy has been used in traditional Chinese medicine for thousands of years for its health and nutritional benefits, as well as to treat and care for the skin. Advanced skin care research has shown that soy isoflavone and genistein are effective in reducing damage to the skin from the sun. AIM OF THE STUDY: To study the protective effects of isoflavone extract from soybean cake against the UVB-induced skin damage. MATERIALS AND METHODS: The in vitro effects and possible mechanisms of soybean extract on UVB protection were determined in HaCaT cells. In the in vivo study, ICR-Foxn/(nu) mice were irradiated with UVB. The epidermal thickness, catalase and the expressions of cyclooxygenase-2 (COX-2) and proliferating cell nuclear antigen (PCNA) were detected to evaluate the antioxidant and anti-inflammatory activities of the isoflavone extract. RESULTS: Our in vitro studies showed that UVB-induced HaCaT cell death and the phosphorylation of p38, JNK, and ERK1/2 decreased in the presence of isoflavone extract. In the in vivo studies, we found that the topical application of isoflavone extract before UVB irritation decreased the epidermal thickness and the expressions of COX-2 and PCNA and increased catalase concentration. These results showed anti-photoaging effect of isoflavone extract from soybean cake involved the inhibition of UVB-induced apoptosis and inflammation. CONCLUSIONS: It is shown that isoflavone extract from soybean cake may be functional cosmeceutical candidate for skin photoaging.