Cytotoxic Activity, Topoisomerase I Inhibition and In Silico Studies of New Sesquiterpene-aryl Ester Derivatives of (-) Drimenol.

In this study, we aimed to evaluate two sets of sesquiterpene-aryl derivatives linked by an ester bond, their cytotoxic activities, and their capacity to activate caspases 3/7 and inhibit human topoisomerase I (TOP1). A total of 13 compounds were synthesized from the natural sesquiterpene (-)-drimenol and their cytotoxic activity was evaluated in vitro against three cancer cell lines: PC-3 (prostate cancer), HT-29 (colon cancer), MCF-7 (breast cancer), and an immortalized non-tumoral cell line (MCF-10). From the results, it was observed that 6a was the most promising compound due to its cytotoxic effect on three cancer cell lines and its selectivity, 6a was 100-fold more selective than 5-FU in MCF-7 and 20-fold in PC-3. It was observed that 6a also induced apoptosis by caspases 3/7 activity using a Capsase-Glo-3/7 assay kit and inhibited TOP1. A possible binding mode of 6a in a complex with TOP1-DNA was proposed by docking and molecular dynamics studies. In addition, 6a was predicted to have a good pharmacokinetic profile for oral administration. Therefore, through this study, it was demonstrated that the drimane scaffold should be considered in the search of new antitumoral agents.

Recomendaciones de actividad física y ejercicio en el paciente adulto sometido a cirugía bariátrica. Documento de Consenso / Exercise and physical activity in adults who underwent bariatric surgery. Consensus document

Physical exercise is useful in people who underwent bariatric surgery. However, the right dosage is still a topic for discussion. The aim of this article is to consolidate the prescription criteria for physical activity and exercise in bariatric patients. A panel of experts to whom the topics were previously assigned for review, met to reach a consensus. Each topic was presented and subjected to discussion and voting by the participants and attendants who were exercise professionals from different obesity treatment centers. We report the conclusions reached for aerobic exercise, strength training, protein supplementation and physical activity for weight maintenance in bariatric patients.

[Exercise and physical activity in adults who underwent bariatric surgery. Consensus document]. / Recomendaciones de actividad física y ejercicio en el paciente adulto sometido a cirugía bariátrica. Documento de Consenso.

Physical exercise is useful in people who underwent bariatric surgery. However, the right dosage is still a topic for discussion. The aim of this article is to consolidate the prescription criteria for physical activity and exercise in bariatric patients. A panel of experts to whom the topics were previously assigned for review, met to reach a consensus. Each topic was presented and subjected to discussion and voting by the participants and attendants who were exercise professionals from different obesity treatment centers. We report the conclusions reached for aerobic exercise, strength training, protein supplementation and physical activity for weight maintenance in bariatric patients.

Oxygen pulse as a protective factor of insulin resistance in sedentary women with overweight or obesity.

BACKGROUND: obesity is associated with insulin resistance (IR). Through exercise, insulin resistant obese patients can effectively improve theircardiorespiratory fitness (CRF). The effect of exercise on patients CRF can be determined by oxygen pulse (PO2) analysis. Despite its usefulness, there is limited literature on PO2 analysis in patients with obesity and insulin resistance. OBJECTIVE: the goal of the present study is to evaluate the relation between PO2 and IR in sedentary obese women. METHODS: fifty-five women were submitted to a maximal exercise test for evaluation of maximal oxygen consumption and PO2. The subjects with a homeostatic model assessment of IR index greater or equal to 2.5 were considered as insulin-resistant (IR). Participants were divided into two groups, IR group (n = 35) and non-IR group (n = 20). RESULTS: the IR group had lower values of PO2 relative to body weight (11.0 ± 1.7 versus 12.6 ± 1.4 ml∙kg∙beats-1, p = 0.001) and relative to lean mass (21.7 ± 2.9 versus 23.2 ± 2.8 ml∙kg∙beats-1, p = 0.038) than non-IR group. No statistical differences were found in maximal oxygen consumption between the groups (non-IR = 1.53 ± 0.27 l∙min-1, IR = 1.51 ± 0.28 l∙min-1; p = 0.386). PO2 relative to body weight and HOMA-IR was inversely correlated (p < 0.001; r = -0.465). Logistic regression analysis showed an association between PO2 relative to weight (p = 0.001, OR = 0.47) and fat free mass (p = 0.01, OR = 0.73), both models adjusted by age. CONCLUSIONS: this study demonstrates a relation between HOMA-IR and PO2. Our results suggest that PO2 could be a protective factor against insulin resistance.

Oxygen pulse as a protective factor of insulin resistance in sedentary women with overweight or obesity / Pulso de oxígeno como factor protector de resistencia a la insulina en mujeres sedentarias con sobrepeso u obesidad

Background: obesity is associated with insulin resistance (IR). Through exercise, insulin resistant obese patients can effectively improve their cardiorespiratory fitness (CRF). The effect of exercise on patients CRF can be determined by oxygen pulse (PO2) analysis. Despite its usefulness, there is limited literature on PO2 analysis in patients with obesity and insulin resistance. Objective: the goal of the present study is to evaluate the relation between PO2 and IR in sedentary obese women. Methods: fifty-five women were submitted to a maximal exercise test for evaluation of maximal oxygen consumption and PO2. The subjects with a homeostatic model assessment of IR index greater or equal to 2.5 were considered as insulin-resistant (IR). Participants were divided into two groups, IR group (n = 35) and non-IR group (n = 20). Results: the IR group had lower values of PO2 relative to body weight (11.0 ± 1.7 versus 12.6 ± 1.4 ml∙kg∙beats-1, p = 0.001) and relative to lean mass (21.7 ± 2.9 versus 23.2 ± 2.8 ml∙kg∙beats-1, p = 0.038) than non-IR group. No statistical differences were found in maximal oxygen consumption between the groups (non-IR = 1.53 ± 0.27 l∙min-1, IR = 1.51 ± 0.28 l∙min-1; p = 0.386). PO2 relative to body weight and HOMA-IR was inversely correlated (p < 0.001; r = -0.465). Logistic regression analysis showed an association between PO2 relative to weight (p = 0.001, OR = 0.47) and fat free mass (p = 0.01, OR = 0.73), both models adjusted by age. Conclusions: this study demonstrates a relation between HOMA-IR and PO2. Our results suggest that PO2 could be a protective factor against insulin resistance

Introducción: la sensibilidad a la insulina ha sido ampliamente relacionada con el fitness cardiorrespiratorio (FCR), el cual puede ser evaluado a través del pulso de oxígeno (PO2). Este corresponde al producto entre el volumen sistólico y la diferencia arteriovenosa de oxígeno y en sujetos sin alteraciones cardiovasculares podría ser un indicador de alteraciones del metabolismo a nivel periférico como la resistencia a la insulina (RI). Objetivo: el objetivo del presente estudio es evaluar la relación entre el PO2 y la RI en mujeres sedentarias con obesidad. Métodos: cincuenta y cinco mujeres fueron sometidas a una prueba de ejercicio maximal para la evaluación del consumo máximo de oxígeno (VO2max) y del PO2. Los sujetos con un índice HOMA-IR mayor o igual a 2,5 fueron considerados con resistencia a la insulina. Los participantes fueron divididos en dos grupos, RI (n = 35) y no-RI (n = 20). Resultados: el grupo RI presentó valores menores de PO2 relativo al peso corporal (11,0 ± 1,7 versus 12,6 ± 1,4 ml∙kg∙latidos-1, p = 0,001) y relativo a la masa libre de grasa (21,7 ± 2,9 versus 23,2 ± 2,8 ml∙kg∙latidos-1, p = 0,038) respecto al grupo no-RI. No se encontraron diferencias estadísticamente significativas en el VO2max entre ambos grupos (no-RI = 1.53 ± 0.27 l∙min-1, RI = 1,51 ± 0,28 l∙min-1; p = 0,386). Se encontró una correlación inversa entre el PO2 relativo al peso y el índice HOMA-IR (p < 0,001; r = -0,465). El análisis de regresión logística mostró una asociación entre el PO2 relativo al peso (p = 0,001, OR = 0,47) y la masa libre de grasa (p = 0,01, OR = 0,73), ambos modelos ajustados por edad. Conclusiones: este estudio demuestra que existe una relación entre el índice HOMA-IR y el PO2. Estos resultados sugieren que el PO2 podría ser un factor protector de RI

Cardiorespiratory fitness and fat oxidation during exercise as protective factors for insulin resistance in sedentary women with overweight or obesity.

INTRODUCTION: obesity is a global pandemic and it is the biggest risk factor for death worldwide nowadays. Studies suggest that both cardiorespiratory fitness and fat oxidation in exercise are related to insulin resistance and type 2 diabetes mellitus, and they could be used as metabolic fitness markers. OBJECTIVES: the aim of this study is to determine if cardiorespiratory fitness (VO2) and fat oxidation during exercise are protective factors of insulin resistance (IR) in sedentary women with obesity or overweight. METHODS: sixty women were selected for fat oxidation analysis and 55 for cardiorespiratory fitness analysis that fitted the inclusion and exclusion criteria. VO2, maximal fat oxidation (MFO) and the intensity where MFO is reached (FATmax) were determined through an incremental test on a cycle ergometer with gas analysis. The subjects with a Homeostatic model assessment of IR index greater or equal to 2.5 were considered as insulin-resistant. Participants were divided into 2 groups, IR group (n = 38) and Non-IR group (n = 22). RESULTS: VO2(%) and MFO were lower in the IR group (76.1% vs.83.2%; p = 0.015 and 1.08 mg × kg-1 × min-1 vs. 1.62 mg × kg-1 × min-1; p= 0.044, respectively) compared to the Non-IR group. There was an association between VO2(%) and IR (OR = 0.92, p = 0.017) and between MFO and IR (OR = 0.52, p = 0.035), both models adjusted for age and body mass index. CONCLUSIONS: VO2(%) and MFO are independent protective factors for IR. No association was found between FATmax and IR.

Cardiorespiratory fitness and fat oxidation during exercise as protective factors for insulin resistance in sedentary women with overweight or obesity / Fitness cardiorrespiratorio y oxidación de grasas durante el ejercicio como factores protectores de resistencia a la insulina en mujeres sedentarias con sobrepeso u obesidad

Introduction: obesity is a global pandemic and it is the biggest risk factor for death worldwide nowadays. Studies suggest that both cardiorespiratory fitness and fat oxidation in exercise are related to insulin resistance and type 2 diabetes mellitus, and they could be used as metabolic fitness markers. Objectives: the aim of this study is to determine if cardiorespiratory fitness (VO2) and fat oxidation during exercise are protective factors of insulin resistance (IR) in sedentary women with obesity or overweight. Methods: sixty women were selected for fat oxidation analysis and 55 for cardiorespiratory fitness analysis that fitted the inclusion and exclusion criteria. VO2, maximal fat oxidation (MFO) and the intensity where MFO is reached (FATmax) were determined through an incremental test on a cycle ergometer with gas analysis. The subjects with a Homeostatic model assessment of IR index greater or equal to 2.5 were considered as insulin-resistant. Participants were divided into 2 groups, IR group (n = 38) and Non-IR group (n = 22). Results: VO2(%) and MFO were lower in the IR group (76.1% vs. 83.2%; p = 0.015 and 1.08 mg × kg-1 × min-1 vs. 1.62 mg × kg-1 × min-1; p = 0.044, respectively) compared to the Non-IR group. There was an association between VO2(%) and IR (OR = 0.92, p = 0.017) and between MFO and IR (OR = 0.52, p = 0.035), both models adjusted for age and body mass index. Conclusions: VO2(%) and MFO are independent protective factors for IR. No association was found between FATmax and IR

Introducción: la obesidad es una pandemia global y actualmente es el mayor factor de riesgo de muerte a nivel mundial. Estudios sugieren que tanto el fitness cardiorrespiratorio (VO2) como la oxidación de grasas durante el ejercicio podrían ser utilizados como marcadores del fitness metabólico. Objetivos: el objetivo de este estudio es determinar si el VO2 y la oxidación de grasas durante el ejercicio son factores protectores de resistencia a la insulina en mujeres sedentarias con obesidad o sobrepeso. Métodos: fueron seleccionadas 60 mujeres para análisis de oxidación de grasas y 55 para análisis de VO2 que cumplieran con los criterios de inclusión y exclusión. El VO2, la máxima oxidación de grasas (MFO) y la intensidad donde se alcanza el MFO (FATmax) fueron determinados mediante un test incremental en cicloergómetro con análisis de gases. Los sujetos con un índice HOMA-IR mayor o igual a 2,5 fueron considerados con resistencia a la insulina. Los participantes fueron divididos en dos grupos, IR (n = 38) y No-IR (n = 22). Resultados: el VO2(%) y la MFO fueron menores en el grupo IR en comparación al grupo No-IR (76,1% versus 83,2%; p = 0,015 y 1,08 mg × kg-1 × min-1 versus 1,62 mg × kg-1 × min-1; p = 0,044, respectivamente). Mediante el análisis de regresión logística se encontró una asociación entre VO2(%) e IR (OR = 0,92; p = 0,017) y entre MFO e IR (OR = 0,52; p = 0,035), ambos modelos ajustados por edad e índice de masa corporal. Conclusión: el VO2(%) y la MFO son factores protectores independientes de IR. No se encontró asociación entre el FATmax y la IR