Examinando por Autor "Miranda, C."

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    Farmacogenómica como herramienta fundamental para la medicina personalizada: aplicaciones en la práctica clínica
    (Sociedad Médica de Santiago, 2017-04) Quiñones, L.; Roco, Á.; Cayún, J.P.; Escalante, P.; Miranda, C.; Varela, N.; Meneses, F.; Gallegos, B.; Zaruma-Torres, F.; Lares-Asseff, I.
    Pharmacogenomics is an emergent field aimed at tailoring pharmacological therapy. Genetic polymorphisms can modify the expression and function of enzymes and proteins involved in drug metabolism, affecting absorption, distribution, biotransformation and excretion as well as the drug-target interaction. Therefore, the presence of allelic variants will classify people as poor, extensive or rapid/ultra rapid metabolizers, modifying drug efficacy and safety. In this work, the state of art in relation to this discipline is presented and the genetic variants of enzymes that are involved in drug pharmacokinetics or pharmacodynamics are described. The effects of these variants on the therapeutic response to drugs used in our country are also discussed.
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    Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the chilean population: Comparison with caucasian and asian populations
    (Frontiers Media S.A., 2012-11) Roco, A.; Quiñones, L.; Agúndez, J.; García-Martín, E.; Squicciarini, V.; Miranda, C.; Garay, J.; Farfán, N.; Saavedra, I.; Cáceres, D.; Ibarra, C.; Varela, N.
    Cancer is a leading cause of death worldwide. The cancer incidence rate in Chile is 133.7/100,000 inhabitants and it is the second cause of death, after cardiovascular diseases. Most of the antineoplastic drugs are metabolized to be detoxified, and some of them to be activated. Genetic polymorphisms of drug-metabolizing enzymes can induce deep changes in enzyme activity, leading to individual variability in drug efficacy and/or toxic-ity. The present research describes the presence of genetic polymorphisms in the Chilean population, which might be useful in public health programs for personalized treatment of cancer, and compares these frequencies with those reported for Asian and Caucasian populations, as a contribution to the evaluation of ethnic differences in the response to chemotherapy. We analyzed 23 polymorphisms in a group of 253 unrelated Chilean volunteers from the general population. The results showed that CYP2A6*2, CYP2A6*3, CYP2D6*3, CYP2C19*3, and CYP3A4* 17 variant alleles are virtually absent in Chileans. CYP1A1*2A allele frequency (0.37) is similar to that of Caucasians and higher than that reported for Japanese people. Allele frequencies for CYP3A5* 3(0.76) and CYP2C9* 3(0.04) are similar to those observed in Japanese people. CYP1A1*2C(O.32), CYP1A2* 1F(0.77), CYP3A4* 1B(0.06), CYP2D6*2(0.4V, and MTHFRT(0.52) allele frequencies are higher than the observed either in Caucasian or in Japanese populations. Conversely, CYP2C19* 2 allelic frequency (0.12), and genotype frequencies for GSTT1 null (0.11) and GSTM1 null (0.36) are lower than those observed in both populations. Finally, allele frequencies for CYP2A6* 4(0.04), CYP2C8*3(0.06), CYP2C9* 2(0.06), CYP2D6*4(0.12), CYP2EV5B(0.14), CYP2E1* 6(0.19), and UGT2B7* 2(0.40) are intermediate in relation to those described in Caucasian and in Japanese populations, as expected according to the ethnic origin of the Chilean population. In conclusion, our findings support the idea that ethnic variability must be considered in the pharmacogenomic assessment of cancer pharmacotherapy, especially in mixed populations and for drugs with a narrow safety range. © 2012 Roco, Quiñones, Agúndez, García-Martín, Squicciarini, Miranda, Garay, Farfán, Saavedra, Cáceres, Ibarra and Varela. © 2012 Roco, Quiñones, Agúndez, García-Martín, Squicciarini, Miranda, Garay, Farfán, Saavedra, Cáceres, Ibarra and Varela.
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    Uso de la cinética del consumo de oxígeno para la evaluación de la capacidad cardiorrespiratoria en pacientes con obesidad
    (Sociedad Medica de Santiago, 2018-01) Miranda, C.; Ibacache, P.; Opazo, E.; Rojas, J.; Cano, M.
    Background: The evaluation of cardiorespiratory fitness (RCC) using maximal or peak oxygen consumption (VO2), requires a high level of effort in obese patients. We propose a method to evaluate RCC using constant and moderate loads, called VO2 kinetics (tau). Aim: To determine the relationship between tau and peak VO2 in patients with obesity. Material and Methods: Forty patients (87% females) aged 37 ± 12 years and with a body mass index (BMI) of 34.6 ± 4.0 kg/m2, were divided into two groups according to the applied workload (0.5 and 0.8 Watts/kg body mass) using a cycle ergometer and Cortex Metalyzer 3b equipment. The protocol was started with 6 minutes at constant load and then increments of 20-25 Watts every two min were made until determination of the peak VO2. Results: The tau value was 51.8 ± 17.6 s, the absolute peak VO2 was 2.0 ± 0.7 L/min and the relative peak VO2 was 26.6 ± 30.0 ml/kg/min. There was a significant difference of tau medians between the group that used 0.5 and 0.8 Watts/kg (p = 0.002) and a significant inverse correlation between the absolute peak VO2 and the tau value for a load of 0.5 Watts/kg (rho = -0.415, p = 0.0327). Conclusions: The higher tau value, the lower the peak VO2 of an obese patient. It is suggested to apply loads of 0.5 Watts/kg for a VO2 kinetics test in obese patients or in subjects who do not wish to carry out higher physiological demands with a non-invasive and low risk procedure.