Maria Jesús Caballero

Comparative cytochrome p450 in vitro inhibition by atypical antipsychotic drugs.

The goal of this study was to assess in human liver microsomes the inhibitory capacity of commonly used antipsychotics on the most prominent CYP450 drug metabolizing enzymes (CYP1A2, CYP2C9, CYP2D6, and CYP3A). Chlorpromazine was the only antipsychotic that inhibited CYP1A2 activity (IC50 = 9.5 μM), whilst levomepromazine, chlorpromazine, and thioridazine significantly decreased CYP2D6-mediated formation of 1′-hydroxybufuralol (IC50 range, 3.5–25.5 μM). Olanzapine inhibited CYP3A-catalyzed production of 1′, and 4′-hydroxymidazolam (IC50 = 14.65 and 42.20 μM, resp.). In contrast, risperidone (IC50 = 20.7 μM) and levomepromazine (IC50 = 30 μM) showed selectivity towards the inhibition of midazolam 1′-hydroxylation reaction, and haloperidol did so towards 4′-hydroxylation (IC50 of 2.76 μM). Thioridazine displayed a K i of 1.75 μM and an inhibitory potency of 1.57 on CYP2D6, suggesting a potential to induce in vivo interactions. However, with this exception, and given the observed K i values, the potential of the assayed antipsychotics to produce clinically significant inhibitions of CYP450 isoforms in vivo seems limited.

Determination of urine steroid profile in untrained men to evaluate recovery after a strength training session.

Timon, R, Olcina, G, Muñoz, D, Maynar, JI, Caballero, MJ, and Maynar, M. Determination of urine steroid profile in untrained men to evaluate recovery after a strength training session. J Strength Cond Res 22: 1087-1093, 2008-Intense physical exercise is an important modifier of hormone metabolism. The aim of this study was to evaluate the variations in the urine profile of glucuroconjugated steroids (androgens, estrogens, and corticosteroids) as a consequence of a session of strength exercises. The subjects were a group (N = 20) of untrained male university students. They performed 3 sets of 10 repetitions, with a 3-minute recovery time between sets, at 70-75% of 1 repetition maximum (1RM). Four urine samples were collected per subject: before the session, immediately after, 3 hours after, and 48 hours after the session. They were assayed using a gas chromatograph coupled with a mass spectrometer. The concentrations of the different hormones were determined according to the urine creatinine level (ng steroid per mg creatinine). The substances assayed were testosterone, epitestosterone (Epit), androstenedione, dehydroepiandrosterone (DHEA), androsterone, etiocholanolone, β-estradiol, estrone, tetrahydrocortisone (THE), and tetrahydrocortisol (THF). The results showed a significant decline after exercise with respect to the rested state in the urinary excretion of testosterone, Epit, DHEA, androsterone, and etiocholanolone. At 48 hours, there was a significant increase in the urinary excretion of Epit, androstenedione, androsterone, etiocholanolone, estrone, and THE. The androsterone + etiocholanolone/THE + THF ratio decreased after exercise, increased significantly (p < 0.05) at 3 hours, and returned to near resting levels at 48 hours. The data suggest that the performing a strength session at 70-75% of maximum strength provoked a state of fatigue in the subjects, from which they recovered 48 hours after the exercise.

Plasma total fatty acid responses to exercise following caffeine ingestion

Abstract Aerobic exercise is associated with changes in the blood profile of fatty acids. Caffeine is known to be a potential lipolytic agent. Hence, caffeine ingestion in addition to exercise might have an influence on fatty acids, with positive effects on health and performance. The aim of the present study, therefore, was to assess the effect of caffeine (5 mg · kg body mass−1) ingested before aerobic exercise on the total plasma fatty acid profile. In a crossover, double-blind, randomized study involving 20 untrained males ( 43.57±6.48 ml · kg−1 · min−1), blood lactate concentration, plasma caffeine values, and plasma fatty acid profile were examined using chromatographic techniques before and after 30 min of steady-state cycle exercise at 75% under placebo and caffeine conditions. Ventilatory responses and substrate oxidation rates were determined during exercise and recovery. Ventilatory responses, lactate concentrations, and fat and carbohydrate oxidation rates were not affected by caffeine ingestion. Carbohydrate was the main substrate oxidized during steady-state trials under both conditions, although exercise increased blood saturated fatty acids (placebo: 28.30±5.90% vs. 31.09±4.59, P<0.05; caffeine: 28.88±4.12% vs. 29.60±4.56%). Unsaturated blood concentrations of oleic fatty acid trans (C18:1t) increased due to caffeine (placebo: 2.22±2.81% vs. 2.61±3.86%; caffeine 1.53±0.19% vs. 1.70±0.49%, P<0.05). In conclusion, the ingestion of caffeine prior to moderate-to-high aerobic exercise may not have a clear metabolic advantage under the conditions of the present study in untrained individuals, although it might influence some individual unsaturated fatty acids (C18:1t) despite low fat oxidation rates.