RESUMEN
Cytochromes P450 (P450s) are involved in the oxidative metabolism of a plethora of structurally unrelated compounds, including therapeutic drugs. Two orphan members of the nuclear receptor superfamily, the pregnane X receptor (PXR; NR1I2) and constitutive androstane receptor (CAR; NR1I3) have been implicated in this phenomenon. In the present study, we examined the transcriptional regulation of the human CYP2B6 gene. In primary cultures of human hepatocytes, CYP2B6 was highly inducible by a number of compounds known to be human PXR ligands, including rifampicin and hyperforin. PXR was shown to be capable of activating the phenobarbital-responsive enhancer module (PBREM) region of the CYP2B6 gene, a 51-base-pair enhancer element that mediates induction of CYP2B6 expression by CAR. The two nuclear receptor-binding motifs within the PBREM effectively bound PXR as a heterodimer with the 9-cis retinoic acid receptor alpha (NR2B1). Taken together, these observations demonstrate that the CYP2B6 gene is directly regulated by PXR and further establish this receptor as a key regulator of drug-metabolizing P450s.
Asunto(s)
Hidrocarburo de Aril Hidroxilasas , Sistema Enzimático del Citocromo P-450/genética , Regulación Enzimológica de la Expresión Génica , Hepatocitos/enzimología , Oxidorreductasas N-Desmetilantes/genética , Receptores Citoplasmáticos y Nucleares/fisiología , Receptores de Esteroides/fisiología , Secuencias de Aminoácidos , Núcleo Celular/fisiología , Células Cultivadas , Receptor de Androstano Constitutivo , Citocromo P-450 CYP2B6 , Sistema Enzimático del Citocromo P-450/biosíntesis , Dimerización , Inducción Enzimática , Humanos , Oxidorreductasas N-Desmetilantes/biosíntesis , Receptor X de Pregnano , ARN Mensajero/biosíntesis , ARN Mensajero/efectos de los fármacos , Receptores Citoplasmáticos y Nucleares/química , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/metabolismo , Receptores de Ácido Retinoico/genética , Receptores de Ácido Retinoico/metabolismo , Receptores de Esteroides/química , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo , Receptores X Retinoide , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
PURPOSE: To determine the amount and type of training U.S. internal medicine residents receive in providing home care to patients. METHOD: A four-item questionnaire was developed and sent to the program directors of all accredited internal medicine residencies in the United States (n = 397) to assess the amounts and types of training (didactic sessions or lectures, house calls, or both) internal medicine residents receive in providing home care. Demographic information about the residency programs was also collected and analyzed. RESULTS: A total of 312 (78.6%) of the program directors responded. Sixty-eight percent of their programs included instruction in home care consisting of house calls, lectures, or both. Fewer than half of the responding programs offered any lecture in home care in their curricula, and only 25% of them included a mandatory house-call experience for trainees. Residency programs that had primary care tracks were more likely than were other programs to include either of these experiences in their curricula. CONCLUSIONS: Most internal medicine residents receive limited training in home care. As a consequence, future internists may be inadequately prepared to meet the needs of their patients, particularly as the population ages.
Asunto(s)
Servicios de Atención de Salud a Domicilio , Medicina Interna/educación , Internado y Residencia , Curriculum , Servicios de Atención de Salud a Domicilio/normas , Visita Domiciliaria , Encuestas y Cuestionarios , Estados UnidosRESUMEN
Depression is commonly seen in patients with chronic disease, including rheumatologic disease. Because of ongoing contact with their patients, rheumatologists are uniquely poised to recognize depressive disorders and formulate a treatment plan. Recent advances in pharmacotherapy have simplified management and increased the likelihood of successful treatment. Through heightened awareness, rheumatologists can feel more comfortable in diagnosing and initiating therapy for depression.