Association of CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T Polymorphisms with Tacrolimus Dose, Serum Concentration, and Biochemical Parameters in Mexican Patients with Kidney Transplant.

Tacrolimus (TAC) is an immunosuppressant drug that prevents organ rejection after transplantation. This drug is transported from cells via P-glycoprotein (ABCB1) and is a metabolic substrate for cytochrome P450 (CYP) 3A enzymes, particularly CYP3A4 and CYP3A5. Several single-nucleotide polymorphisms (SNPs) have been identified in the genes encoding CYP3A4, CYP3A5, and ABCB1, including CYP3A4-392A/G (rs2740574), CYP3A5 6986A/G (rs776746), and ABCB1 3435C/T (rs1045642). This study aims to evaluate the association among CYP3A4-392A/G, CYP3A5-6986A/G, and ABCB1-3435C/T polymorphisms and TAC, serum concentration, and biochemical parameters that may affect TAC pharmacokinetics in Mexican kidney transplant (KT) patients. METHODS: Forty-six kidney transplant recipients (KTR) receiving immunosuppressive treatment with TAC in different combinations were included. CYP3A4, CYP3A5, and ABCB1 gene polymorphisms were genotyped using qPCR TaqMan. Serum TAC concentration (as measured) and intervening variables were assessed. Logistic regression analyses were performed at baseline and after one month to assess the extent of the association between the polymorphisms, intervening variables, and TAC concentration. RESULTS: The GG genotype of CYP3A5-6986 A/G polymorphism is associated with TAC pharmacokinetic variability OR 4.35 (95%CI: 1.13-21.9; p = 0.0458) at one month of evolution; in multivariate logistic regression, CYP3A5-6986GG genotype OR 9.32 (95%CI: 1.54-93.08; p = 0.028) and the use of medications or drugs that increase serum TAC concentration OR 9.52 (95%CI: 1.79-88.23; p = 0.018) were strongly associated with TAC pharmacokinetic variability. CONCLUSION: The findings of this study of the Mexican population showed that CYP3A5-6986 A/G GG genotype is associated with a four-fold increase in the likelihood of encountering a TAC concentration of more than 15 ng/dL. The co-occurrence of the CYP3A5-6986GG genotype and the use of drugs that increase TAC concentration correlates with a nine-fold increased risk of experiencing a TAC at a level above 15 ng/mL. Therefore, these patients have an increased susceptibility to TAC-associated toxicity.

Efecto de un plan de estudios de Medicina sobre las competencias para la promoción de la salud y la participación social / Effect of a medical curriculum on the competencies for promotion of health and social participation

OBJETIVO: Evaluar el efecto del plan de estudios de la Licenciatura en Medicina de la Universidad Guadalajara LAMAR sobre las competencias profesionales para la promoción de la salud y la participación social. MATERIAL Y MÉTODOS: Estudio cuasiexperimental de tipo preexperimental de comparación con un grupo estático. Emplazamiento: Campus Vallarta. Temporalidad: septiembre-diciembre de 2017. Universo: 182 estudiantes de Medicina. Muestra: no probabilística, n = 114 estudiantes de Medicina, 62 de primer semestre (G1, intervención momento «A») y 52 de sexto semestre (G2, intervención momento «B»), más 50 estudiantes de primer semestre de licenciatura no relacionada con salud (G0, control). Muestreo: propositivo. Criterios de selección: cualquier edad y sexo, y responder instrumentos. VARIABLES: edad, sexo y competencias profesionales para la promoción de la salud y la participación social. Instrumentos: Instrumento en Español para Evaluar Prácticas de Salud Pública. Procedimientos: las evaluaciones se realizaron al término del semestre 2017B. Análisis: comparación mediante estadística inferencial no paramétrica (p ≤ 0,05). RESULTADOS: Niveles de competencias profesionales para la promoción de la salud y participación social: G0 100% poco o nada competentes, G1 64,5% poco o nada competentes y 35,5% medianamente competentes, G2 11,5% poco o nada competentes y 88,5% medianamente competentes. El nivel de competencia fue mayor al estar expuestos al plan de estudios, y aumentó a mayor tiempo de exposición (Chi2, p ≤ 0,05 en todos los casos). CONCLUSIONES: El plan de estudios de Medicina evaluado desarrolla en sus estudiantes competencias profesionales para la promoción de la salud y la participación social, pero es susceptible de ser mejorado

OBJECTIVE: To evaluate the effect of medical curriculum from Universidad Guadalajara LAMAR over professional competencies for promotion of health and social participation in medical students. MATERIAL AND METHODS: Quasi-experimental study type pre-experimental of comparison with static group. Emplacement: Vallarta's Campus. Temporality: September-December 2017. Universe: 182 medical students. Sample: non-randomized, n = 114 medical students, 62 from first semester (G1, intervention's moment "A") and 52 from sixth semester (G2, intervention's moment "B"), and additionally 50 from first semester of bachelor not related with health (G0, control). Sampling: propositive. Selection criteria: any age and gender, and to answer instruments. VARIABLES: age, gender and professional competencies for promotion of health and social participation. Instruments: Instrument in Spanish for to Evaluate Public Health Practices. Procedures: the evaluation it achieved to term of 2017B scholar cycle. Analysis: comparison by mean of non-parametric inferential statistics (P ≤ 0.05). RESULTS: Professional competencies level for promotion of health and social participation: G0 100% little or nothing competent, G1 64.5% little or nothing competent and 35.5% fairly competent, G2 11.5% little or nothing competent and 88.5% fairly competent. The competency level was higher in exposed to medical curriculum and increased to a longer exposure time (Chi2, P ≤ 0.05 in all cases). CONCLUSIONS: The medical curriculum from Universidad Guadalajara LAMAR develop professional competencies for promotion of health and social participation in your students, but this can be improved because nobody was highly competent

Role and New Insights of Pirfenidone in Fibrotic Diseases.

Pirfenidone (PFD) is a non-peptide synthetic molecule issued as a broad-spectrum anti-fibrotic drug with the ability to decrease TGF-ß1, TNF-α, PDGF and COL1A1 expression, which is highly related to prevent or remove excessive deposition of scar tissue in several organs. Basic and clinical evidence suggests that PFD may safely slow or inhibit the progressive fibrosis swelling after tissue injuries. Furthermore, a number of evidence suggests that this molecule will have positive effects in the treatment of other inflammatory diseases. This review contains current research in which PFD has been used as the treatment of several diseases, and focus mainly in the outcomes related to improve inflammation and fibrogenesis. Therefore, the main goal of this review is to focus on the novel findings of PFD efficacy rather than deepen in the chemical aspects of the molecule.