Un examen actualizado de la percepción de las barreras para la implementación de la farmacogenómica y la utilidad de los pares fármaco/gen en América Latina y el Caribe

La farmacogenómica (PGx) se considera un campo emergente en los países en desarrollo. La investigación sobre PGx en la región de América Latina y el Caribe (ALC) sigue siendo escasa, con información limitada en algunas poblaciones. Por lo tanto, las extrapolaciones son complicadas, especialmente en poblaciones mixtas. En este trabajo, revisamos y analizamos el conocimiento farmacogenómico entre la comunidad científica y clínica de ALC y examinamos las barreras para la aplicación clínica. Realizamos una búsqueda de publicaciones y ensayos clínicos en este campo en todo el mundo y evaluamos la contribución de ALC. A continuación, realizamos una encuesta regional estructurada que evaluó una lista de 14 barreras potenciales para la aplicación clínica de biomarcadores en función de su importancia. Además, se analizó una lista emparejada de 54 genes/fármacos para determinar una asociación entre los biomarcadores y la respuesta a la medicina genómica. Esta encuesta se comparó con una encuesta anterior realizada en 2014 para evaluar el progreso en la región. Los resultados de la búsqueda indicaron que los países de América Latina y el Caribe han contribuido con el 3,44% del total de publicaciones y el 2,45% de los ensayos clínicos relacionados con PGx en todo el mundo hasta el momento. Un total de 106 profesionales de 17 países respondieron a la encuesta. Se identificaron seis grandes grupos de obstáculos. A pesar de los continuos esfuerzos de la región en la última década, la principal barrera para la implementación de PGx en ALC sigue siendo la misma, la "necesidad de directrices, procesos y protocolos para la aplicación clínica de la farmacogenética/farmacogenómica". Las cuestiones de coste-eficacia se consideran factores críticos en la región. Los puntos relacionados con la reticencia de los clínicos son actualmente menos relevantes. Según los resultados de la encuesta, los pares gen/fármaco mejor clasificados (96%-99%) y percibidos como importantes fueron CYP2D6/tamoxifeno, CYP3A5/tacrolimus, CYP2D6/opioides, DPYD/fluoropirimidinas, TMPT/tiopurinas, CYP2D6/antidepresivos tricíclicos, CYP2C19/antidepresivos tricíclicos, NUDT15/tiopurinas, CYP2B6/efavirenz y CYP2C19/clopidogrel. En conclusión, aunque la contribución global de los países de ALC sigue siendo baja en el campo del PGx, se ha observado una mejora relevante en la región. La percepción de la utilidad de las pruebas PGx en la comunidad biomédica ha cambiado drásticamente, aumentando la concienciación entre los médicos, lo que sugiere un futuro prometedor en las aplicaciones clínicas de PGx en ALC.Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region’s continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the “need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics”. Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%–99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC

Evaluación de la Capacidad Cognitiva y su Modificación Mediante Estimulación Cognitiva y Ácido Fólico.

4to Foro de Investigación Educativ

Congenital palmar polyonychia with postaxial limb defects may be the same as the ulnar-mammary syndrome [4] (multiple letters)

[No abstract available

Morbilidad y mortalidad por cáncer: experiencia del Centro Estatal de Cancerología de la SSA del Estado de Durango, México Morbidity and mortality from cancer: experience of the State Center of Cancer from the SSA of Durango State, Mexico

OBJETIVO: En este estudio evaluamos el primer reporte de las estadísticas del cáncer en el Centro Estatal de Cancerología (CEC-Durango), México. MÉTODOS: Se realizó un estudio longitudinal retrospectivo, del período comprendido de enero de 2001 a diciembre de 2003, para conocer la morbimortalidad por cáncer de acuerdo con el sexo y edad, identificando sus características y tendencias. RESULTADOS: Desde la niñez hasta los 64 años de edad se observó un incremento en el número de casos, para disminuir en las últimas etapas de la vida. Durante la etapa pediátrica existe una alta tasa de casos de leucemia para niños y niñas, seguidas de tumores del sistema nervioso central (SNC) en niños y de osteosarcomas en las niñas. En los adultos, la mayoría de casos se observaron entre los 55 y 64 años de edad, para disminuir en la senescencia. Existen más casos en mujeres que en hombres; el cáncer cervicouterino (CaCu) y el cáncer de mama ocupan el primer lugar en las mujeres, y los tumores del SNC y el cáncer de pulmón en los hombres. El número total de casos disminuye conforme aumenta la edad de los sujetos. CONCLUSIONES: Hay diferencias en la morbilidad y la mortalidad por cáncer de acuerdo con la etapa de crecimiento y desarrollo de los individuos. La tasa de mortalidad general fue de 10 % del total de casos. La mortalidad se vio incrementada exponencialmente a medida que se incrementa la edad de los sujetos. La mayoría de las muertes correspondió a grupos entre 15 a 24 años de edad y de 45 a 64 años en los hombres, y en las mujeres de 35 a 44 años, y después de los 65 años en ambos grupos.PURPOSE: In this study, we evaluate the first report of cancer statistics of the Oncology State Center-Durango Mexico. METHODS: This is a retrospective longitudinal analysis of morbidity and mortality from cancer according to chronological age. RESULTS: From childhood to 64 years it was observed an increase in the number of cases to decrease in latter stages. On pediatrics age, there is a high rate of cases of leukemia for boys and girls, followed by Central Nervous System (CNS) tumors in boys and osteosarcomas in girls. For adults, most of cases were observed between 55 and 64 years to decrease in senescent. There are more cases in women than in men; cervical intraepithelial neoplasia (CIN) and breast cancer, for the former and CNS tumors and lung cancer for the last. The whole number of cases decreases as age increases. CONCLUSIONS: There are differences in morbidity and mortality from cancer according to stage of growth and development of the individuals. The general mortality rate was 10 % of total cases. The mortality was increased exponentially as age increases. The majority of deaths corresponded to groups between 15 to 24 years and 45 to 64 years in men, 35 to 44 years and after 65 years in women

Farmacoepidemiologia de psicoformccos empleados en 10 proctico pediotrico en el Servicio de Psiquiotrio Infantil del Hospital General de Durango, Mexico

Artículo de Investigació

Mitochondrial Dysfunction Induced by Zinc Oxide Nanoparticles

The constant evolution and applications of metallic nanoparticles (NPs) make living organisms more susceptible to being exposed to them. Among the most used are zinc oxide nanoparticles (ZnO-NPs). Therefore, understanding the molecular effects of ZnO-NPs in biological systems is extremely important. This review compiles the main mechanisms that induce cell toxicity by exposure to ZnO-NPs and reported in vitro research models, with special attention to mitochondrial damage. Scientific evidence indicates that in vitro ZnO-NPs have a cytotoxic effect that depends on the size, shape and method of synthesis of ZnO-NPs, as well as the function of the cells to which they are exposed. ZnO-NPs come into contact with the extracellular region, leading to an increase in intracellular [Zn2+] levels. The mechanism by which intracellular ZnO-NPs come into contact with organelles such as mitochondria is still unclear. The mitochondrion is a unique organelle considered the “power station” in the cells, participates in numerous cellular processes, such as cell survival/death, multiple biochemical and metabolic processes, and holds genetic material. ZnO-NPs increase intracellular levels of reactive oxygen species (ROS) and, in particular, superoxide levels; they also decrease mitochondrial membrane potential (MMP), which affects membrane permeability and leads to cell death. ZnO-NPs also induced cell death through caspases, which involve the intrinsic apoptotic pathway. The expression of pro-apoptotic genes after exposure to ZnO-NPs can be affected by multiple factors, including the size and morphology of the NPs, the type of cell exposed (healthy or tumor), stage of development (embryonic or differentiated), energy demand, exposure time and, no less relevant, the dose. To prevent the release of pro-apoptotic proteins, the damaged mitochondrion is eliminated by mitophagy. To replace those mitochondria that underwent mitophagy, the processes of mitochondrial biogenesis ensure the maintenance of adequate levels of ATP and cellular homeostasis

Mitochondrial Dysfunction Induced by Zinc Oxide Nanoparticles

The constant evolution and applications of metallic nanoparticles (NPs) make living organisms more susceptible to being exposed to them. Among the most used are zinc oxide nanoparticles (ZnO-NPs). Therefore, understanding the molecular effects of ZnO-NPs in biological systems is extremely important. This review compiles the main mechanisms that induce cell toxicity by exposure to ZnO-NPs and reported in vitro research models, with special attention to mitochondrial damage. Scientific evidence indicates that in vitro ZnO-NPs have a cytotoxic effect that depends on the size, shape and method of synthesis of ZnO-NPs, as well as the function of the cells to which they are exposed. ZnO-NPs come into contact with the extracellular region, leading to an increase in intracellular [Zn2+] levels. The mechanism by which intracellular ZnO-NPs come into contact with organelles such as mitochondria is still unclear. The mitochondrion is a unique organelle considered the “power station” in the cells, participates in numerous cellular processes, such as cell survival/death, multiple biochemical and metabolic processes, and holds genetic material. ZnO-NPs increase intracellular levels of reactive oxygen species (ROS) and, in particular, superoxide levels; they also decrease mitochondrial membrane potential (MMP), which affects membrane permeability and leads to cell death. ZnO-NPs also induced cell death through caspases, which involve the intrinsic apoptotic pathway. The expression of pro-apoptotic genes after exposure to ZnO-NPs can be affected by multiple factors, including the size and morphology of the NPs, the type of cell exposed (healthy or tumor), stage of development (embryonic or differentiated), energy demand, exposure time and, no less relevant, the dose. To prevent the release of pro-apoptotic proteins, the damaged mitochondrion is eliminated by mitophagy. To replace those mitochondria that underwent mitophagy, the processes of mitochondrial biogenesis ensure the maintenance of adequate levels of ATP and cellular homeostasis

Pro12Ala PPAR-γ2 and +294T/C PPAR-δ Polymorphisms and Association with Metabolic Traits in Teenagers from Northern Mexico

Peroxisome proliferator-activated receptors (PPARs) play roles in glucose and lipid metabolism regulation. Pro12Ala PPAR-γ2 and +294T/C PPAR-δ have been associated with dyslipidemia, hyperglycemia and high body mass index (BMI). We compared metabolic traits and determined associations with Pro12Ala PPAR-γ2 or +294T/C PPAR-δ polymorphism among teenagers from different ethnicity. Four hundred and twelve samples with previous biochemical and biometric measurements were used. Genomic DNA from peripheral blood was extracted and analyzed by end-point PCR for Pro12Ala PPAR-γ2. The +294T/C PPAR-δ PCR product was also digested with Bsl I. Two genotype groups were formed: major allele homozygous and minor allele carriers. Pro12Ala PPAR-γ2 G minor allele frequencies were: 10% in Mestizo-1, 19% in Mestizo-2, 23% in Tarahumara, 12% in Mennonite, and 17% in the total studied population. The +294T/C PPAR-δ C minor allele frequencies were: 18% in Mestizo-1, 20% in Mestizo-2, 6% in Tarahumara, 13% in Mennonite, and 12% in the total studied population. Teenagers with PPAR-γ2 G allele showed a greater risk for either high waist/height ratio or low high-density lipoprotein; and, also had lower total cholesterol. Whereas, PPAR-γ2 G allele showed lower overweight/obesity phenotype (BMI Z-score) frequency, PPAR-δ C allele was a risk factor for it. Metabolic traits were associated with both PPAR polymorphisms

Genetic Polymorphisms Associated to Folate Transport as Predictors of Increased Risk for Acute Lymphoblastic Leukemia in Mexican Children

Acute lymphoblastic leukemia (ALL) is a frequent neoplasia occurring in children. The most commonly used drug for the treatment of ALL is methotrexate (MTX), an anti-folate agent. Previous studies suggest that folate transporters play a role in ALL prognosis and that genetic polymorphism of genes encoding folate transporters may increase the risk of ALL. Therefore, the main goal of this study was to determine the associations among six genetic polymorphisms in four genes related with the folate transporter pathway to determine a relationship with the occurrence of ALL in Mexican children. A case-control study was performed in 73 ALL children and 133 healthy children from Northern and Northwestern Mexico. COL (rs2274808), SLC19A1 (rs2838956), ABCB1 (rs1045642 and rs1128503), and ABCC5 (rs9838667 and rs3792585). Polymorphisms were assayed through qPCR. Our results showed an increased ALL risk in children carrying CT genotype (OR = 2.55, Cl 95% 1.11-5.83, p = 0.0001) and I I genotype (OR = 21.05, Cl 95% 5.62-78.87, p 0.0001) of COL18A1 rs2274808; in SLC19A1 rs2838956 AG carriers (OR = 44.69, Cl 95% 10.42-191.63, p = 0.0001); in ABCB1 rs1045642 H carriers (OR = 13.76, Cl 95% 5.94-31.88, p = 0.0001); in ABCC5 rs9838667 AC carriers (OR = 2.61, Cl 95% 1.05-6.48, p 0.05); and in ABCC5 rs3792585 CC carriers (OR = 9.99, Cl 95% 3.19-31.28, p = 0.004). Moreover, several combinations of genetic polymorphisms were found to be significantly associated with a risk for ALL. Finally, two combinations of ABCC5 polymorphisms resulted in protection from this neoplasia. In conclusion, certain genetic polymorphisms related to the folate transport pathway, particularly COL18A1 rs2274808, SLC19A1 rs2838956, ABCB1 rs1045642, and ABCC5 rs3792585, were associated with an increased risk for ALL in Mexican children