The polymorphism T1470A of the SLC16A1 gene is associated with the lactate and ventilatory thresholds but not with fat oxidation capacity in young men.

PURPOSE: To examine the association of the single nucleotide polymorphism A1470T in the SLC16A1 gene with blood lactate accumulation during a graded exercise test and its associated metaboreflex. METHODS: Forty-six Latin-American men (Age: 27 ± 6 years; Body fat: 17.5 ± 4.7%) performed a graded exercise test on a treadmill for the assessment of maximal oxygen uptake (VO2max), lactate threshold (LT), ventilatory threshold (VT) and the exercise intensity corresponding to maximal fat oxidation rate (FATmax), via capillary blood samples and indirect calorimetry. Genomic DNA was extracted from a peripheral blood sample. Genotyping assay was carried out by real-time polymerase chain reaction to identify the A1470T polymorphism (rs1049434). RESULTS: Genotypes distribution were in Hardy-Weinberg equilibrium (X2 = 5.6, p > 0.05), observing allele frequencies of 0.47 and 0.53 for the A and T alleles, respectively. No difference in VO2max, body composition nor FATmax were observed across genotypes, whereas carriers of the TT genotype showed a higher LT (24.5 ± 2.2 vs. 15.6 ± 1.7 mL kg-1 min-1, p < 0.01) and VT in comparison to carriers of the AA + AT genotypes (32.5 ± 3.3 vs. 21.7 ± 1.5 mL kg-1 min-1, p < 0.01). Both, VO2max and the A1470T polymorphism were positively associated to the LT (R2 = 0.50, p < 0.01) and VT (R2 = 0.55, p < 0.01). Only VO2max was associated to FATmax (R2 = 0.39, p < 0.01). CONCLUSION: Independently of cardiorespiratory fitness, the A1470T polymorphism is associated to blood lactate accumulation and its associated ventilatory response during submaximal intensity exercise. However, the A1470 polymorphism does not influence fat oxidation capacity during exercise in young men.

Metabolic Biomarkers in Adults with Type 2 Diabetes: The Role of PPAR-γ2 and PPAR-ß/δ Polymorphisms.

Glucose and lipid metabolism regulation by the peroxisome proliferator-activated receptors (PPARs) has been extensively reported. However, the role of their polymorphisms remains unclear. OBJECTIVE: To determine the relation between PPAR-γ2 rs1801282 (Pro12Ala) and PPAR-ß/δ rs2016520 (+294T/C) polymorphisms and metabolic biomarkers in adults with type 2 diabetes (T2D). MATERIALS AND METHODS: We included 314 patients with T2D. Information on anthropometric, fasting plasma glucose (FPG), HbA1c and lipid profile measurements was taken from clinical records. Genomic DNA was obtained from peripheral blood. End-point PCR was used for PPAR-γ2 rs1801282, while for PPAR-ß/δ rs2016520 the PCR product was digested with Bsl-I enzyme. Data were compared with parametric or non-parametric tests. Multivariate models were used to adjust for covariates and interaction effects. RESULTS: minor allele frequency was 12.42% for PPAR-γ2 rs1801282-G and 13.85% for PPAR-ß/δ rs2016520-C. Both polymorphisms were related to waist circumference; they showed independent effects on HbA1c, while they interacted for FPG; carriers of both PPAR minor alleles had the highest values. Interactions between FPG and polymorphisms were identified in their relation to triglyceride level. CONCLUSIONS: PPAR-γ2 rs1801282 and PPAR-ß/δ rs2016520 polymorphisms are associated with anthropometric, glucose, and lipid metabolism biomarkers in T2D patients. Further research is required on the molecular mechanisms involved.

Early-Life Metabolic Traits and Physical Fitness in Tarahumara, Mennonite, and Mestizo Adolescents from Northern Mexico.

The WHO identifies high BMI, high blood pressure, and high fasting plasma glucose as chronic disease risk factors, whereas physical fitness is identified as a protective behavioral factor. This study responds to the rising interest in assessing metabolic factors and physical activity within young populations of Mestizo, Tarahumara, and Mennonite from Chihuahua Mexico, due to its strong relationship with disease development and low well-being. A cross-sectional study was conducted with 201 teenagers from rural towns in Northern Mexico, and relationships between physical fitness and cardio-metabolic risk related to anthropometric, glycolipid, and vascular function factors were assessed. ANOVA-tested differences among ethnic groups using physical fitness as a grouping variable and measures of cardio-metabolic risks were used as dependent variables. A stepwise regression analysis allowed us to identify the best predictors for physical fitness. Clinical risk factors were analyzed by ethnic group and sex. No differences were found among ethnic groups in physical fitness and cardio-metabolic health risks; sex differentiated higher health risks related to behavioral factors, since young women showed lower physical fitness across ethnicities. Clinically, the Mestizo sample showed higher numbers of individuals with one risk factor. Mennonites showed a high frequency of anthropometric and fitness health risks with low glycolipid and vascular risks. Tarahumara had fewer risk factors as compared with both Mestizo and Mennonite. Rural populations are harder to reach, both for health assessment and intervention; health professionals must work close to local community organizations to gain access.

FAT/CD36 Participation in Human Skeletal Muscle Lipid Metabolism: A Systematic Review.

Fatty acid translocase/cluster of differentiation 36 (FAT/CD36) is a multifunctional membrane protein activated by a high-fat diet, physical exercise, fatty acids (FAs), leptin, and insulin. The principal function of FAT/CD36 is to facilitate the transport of long-chain fatty acids through cell membranes such as myocytes, adipocytes, heart, and liver. Under high-energy expenditure, the different isoforms of FAT/CD36 in the plasma membrane and mitochondria bind to the mobilization and oxidation of FAs. Furthermore, FAT/CD36 is released in its soluble form and becomes a marker of metabolic dysfunction. Studies with healthy animals and humans show that physical exercise and a high-lipid diet increase FAT/CD36 expression and caloric expenditure. However, several aspects such as obesity, diabetes, Single Nucleotide polymorphisms (SNPs), and oxidative stress affect the normal FAs metabolism and function of FAT/CD36, inducing metabolic disease. Through a comprehensive systematic review of primary studies, this work aimed to document molecular mechanisms related to FAT/CD36 in FAs oxidation and trafficking in skeletal muscle under basal conditions, physical exercise, and diet in healthy individuals.

Efeito Cardioprotetor da Suplementação Materna com Resveratrol sobre a Toxicidade Induzida por Doxorrubicina em Cardiomiócitos de Neonatos / Cardioprotective Effect of Maternal Supplementation with Resveratrol on Toxicity Induced by Doxorubicin in Offspring Cardiomyocytes

Resumo Fundamento A doxorrubicina (DOX) é frequentemente usada para tratar muitos tipos de cânceres, apesar da cardiotoxicidade dose-dependente. Como alternativa, o resveratrol é um polifenol que tem demonstrado efeitos cardioprotetores em vários modelos de disfunção cardíaca. Objetivo Este estudo investigou se o tratamento com resveratrol em ratas gestantes protege contra toxicidade induzida por doxorrubicina em cardiomiócitos da ninhada. Métodos Ratas Wistar (n-8) receberam sresveratrol como suplemento alimentar durante a gestação. No nascimento da ninhada, os corações (9-11) foram usados para se obter a cultura primária de cardiomiócitos. A cardiotoxicidade induzida por DOX e os efeitos da suplementação com resveratrol foram avaliados por marcadores de stress oxidativo, tais como oxidação da diclorofluoresceína diacetato, diminuição da atividade de enzimas antioxidantes, e oxidação do teor total de grupos sulfidrila, além da avaliação da viabilidade celular, geração de danos ao DNA, bem como a resposta de reparo aos danos ao DNA. Um valor de p <0,05 foi considerado estatisticamente significativo. Resultados Os cardiomiócitos de neonatos de ratas que receberam suplemento resveratrol apresentaram um aumento (p <0,01) na viabilidade das células, e diminuição (p <0,0001) de células apoptóticas/necróticas após o tratamento com DOX, o que está correlacionado às atividades de enzimas antioxidantes e produção de diclorofluoresceína. Além disso, o resveratrol protegeu os cardiomiócitos de danos ao DNA induzidos por DOX, apresentando uma diminuição (p <0,05) nas quebras de DNA induzidas por stress oxidativo, avaliadas pela atividade de enzimas reparadoras do DNA endonuclease III e formamidopirimidina glicosilase. A suplementação com resveratrol aumentou (p <0,05) a expressão da proteína reparadora Sirt6 nos cardiomiócitos dos filhotes. Conclusão Essa pesquisa indica que a suplementação com resveratrol durante o período gestacional tem um efeito cardioprotetor no coração da ninhada contra a toxicidade induzida por DOX, o que pode se dever a sua função antioxidante, e o aumento na resposta de danos ao DNA.

Abstract Background Doxorubicin (DOX) is frequently used to treat many types of cancers, despite its dose-dependent cardiotoxicity. Alternatively, resveratrol is a polyphenol that has shown useful cardioprotective effects in many heart dysfunction models. Objective This study investigated whether resveratrol treatment in pregnant rats protects against doxorubicin-induced toxicity in offspring cardiomyocytes. Methods Wistar rats (n=8) were supplemented with dietary resveratrol during pregnancy. Upon the offspring's birth, hearts (9-11) were used to obtain the primary culture of cardiomyocytes. DOX-induced cardiotoxicity and the effects of resveratrol supplementation were evaluated by oxidative stress markers, such as dichlorofluorescein diacetate oxidation, decrease in the activity of antioxidant enzymes, and oxidation of total sulfhydryl content, in addition to cell viability evaluation, DNA damage generation, and DNA damage repair response. A value of p<0.05 was considered statistically significant. Results Neonatal cardiomyocytes from resveratrol supplemented rats exhibiting an increase (p<0.01) in cell viability and lower (p<0.0001) apoptotic/necrotic cells after DOX treatment, which correlates with the activities of antioxidant enzymes and dichlorofluorescein production. Moreover, resveratrol protected cardiomyocytes from DOX-induced DNA damage, showing a decrease (p<0.05) in DNA breaks induced by oxidative stress, evaluated by the activity of DNA-repair enzymes endonuclease III and formamidopyrimidine glycosylase. Supplementation with resveratrol increased (p<0.05) the expression of the repair protein Sirt6 in the cardiomyocytes of the pups. Conclusion This research indicates that supplementation with resveratrol during the gestational period has a notable cardioprotective effect on the offspring's heart against DOX-induced toxicity, which may well be due to its antioxidant function, and the increase in the DNA damage repair response.

Aspectos epidemiológicos da COVID-19 sobre a enfermagem: uma análise retrospectiva / Epidemiological aspects of COVID-19 on nursing: a retrospective analysis

Resumo Objetivo: Analisar os aspectos epidemiológicos da COVID-19 nos profissionais de enfermagem brasileiros. Metodologia: Estudo transversal e quantitativo, com base em dados secundários de domínio público, do Observatório de Enfermagem do Conselho Federal de Enfermagem. Os dados foram coletados em novembro de 2020 e importados para a versão STATA 12.0. Foi realizada uma análise estatística descritiva, com números absolutos e medidas de freqüência. Resultados e discussão: 38.628 profissionais de enfermagem com suspeita de COVID-19 foram relatados, 52,4% com diagnóstico confirmado e predominantemente técnicos (62,9%). A faixa etária predominante entre os mortos era mais alta (41 a 60 anos) do que entre os infectados (31 a 40 anos), enquanto o sexo feminino era quantitativamente dominante em ambos, apesar da maior taxa de casos fatais entre os homens (4,5%). A mortalidade / 1.000 profissionais era alta no Amapá, Acre, Mato Grosso e Rondônia. O pico no número diário de casos novos (525) ocorreu em julho de 2020, enquanto que o número de mortes (18) ocorreu em setembro, mês em que houve uma tendência de queda na variação da taxa de crescimento da média móvel entre os casos novos, o que não é evidente na variável da média móvel entre as mortes. Este cenário tem uma forte relação com as condições precárias de trabalho, falta de EPI, sobrecarga física e emocional e os resultados da rápida contratação e qualificação para a gestão de pacientes com COVID-19. Conclusão: A compreensão da situação de vulnerabilidade experimentada por esses trabalhadores no contexto da pandemia revela a necessidade de concentrar ações de saúde eficazes voltadas para esse grupo.

Abstract Objective: To analyze the epidemiological aspects of COVID-19 in Brazilian nursing professionals. Methodology: Cross-sectional and quantitative study, based on secondary data in the public domain, from the Nursing Observatory of the Federal Nursing Council. Data were collected in November 2020 and imported into the STATA version 12.0 program. Descriptive statistical analysis was performed, with absolute numbers and frequency measures. Results and discussion: 38,628 Nursing professionals with suspected COVID-19 were notified, 52.4% with confirmed diagnosis and a predominance of technicians (62.9%). The prevalent age group among deaths was higher (41 to 60 years) than among those infected (31 to 40 years), while the female gender was quantitatively dominant in both, despite the higher lethality rate among men (4.5%). Mortality / 1,000 professionals was high in Amapá, Acre, Mato Grosso and Rondônia. The peak in the daily number of new cases (525) occurred in July 2020, while the number of deaths (18) in September, a month in which there was a downward trend in the variation in the growth rate of the moving average between the new cases, the which is not evident in the variable of the moving average between deaths. This scenario has a strong relationship with the precarious working conditions, lack of PPE, physical and emotional overload and the outcomes of the fast hiring and qualification for the management of patients with COVID-19. Conclusion: Understanding the situation of vulnerability experienced by these workers in the pandemic context reveals the need to target effective health actions aimed at this group.

Resumen Objetivo: Analizar los aspectos epidemiológicos del COVID-19 en profesionales de enfermería brasileños. Metodología: Estudio transversal y cuantitativo, basado en datos secundarios de dominio público, del Observatorio de Enfermería del Consejo Federal de Enfermería. Los datos se recopilaron en noviembre de 2020 y se importaron al programa STATA versión 12.0. Se realizó análisis estadístico descriptivo, con números absolutos y medidas de frecuencia. Resultados y discusión: Se notificaron 38.628 profesionales de enfermería con sospecha de COVID-19, 52,4% con diagnóstico confirmado y predominio de técnicos (62,9%). El grupo de edad prevalente entre las muertes fue mayor (41 a 60 años) que entre los infectados (31 a 40 años), mientras que el género femenino fue cuantitativamente dominante en ambos, a pesar de la mayor tasa de letalidad entre los hombres (4,5%). La mortalidad / 1.000 profesionales fue alta en Amapá, Acre, Mato Grosso y Rondônia. El pico en el número diario de nuevos casos (525) se produjo en julio de 2020, mientras que el número de defunciones (18) en septiembre, mes en el que hubo una tendencia a la baja en la variación de la tasa de crecimiento de la media móvil entre los nuevos casos, el lo cual no se evidencia en la variable del promedio móvil entre defunciones. Este escenario tiene una fuerte relación con las precarias condiciones laborales, la falta de EPP, la sobrecarga física y emocional y los resultados de la rápida contratación y calificación para el manejo de pacientes con COVID-19. Conclusión: Comprender la situación de vulnerabilidad que viven estos trabajadores en el contexto de la pandemia revela la necesidad de focalizar acciones de salud efectivas dirigidas a este colectivo.

Cardioprotective Effect of Maternal Supplementation with Resveratrol on Toxicity Induced by Doxorubicin in Offspring Cardiomyocytes. / Efeito Cardioprotetor da Suplementação Materna com Resveratrol sobre a Toxicidade Induzida por Doxorrubicina em Cardiomiócitos de Neonatos.

BACKGROUND: Doxorubicin (DOX) is frequently used to treat many types of cancers, despite its dose-dependent cardiotoxicity. Alternatively, resveratrol is a polyphenol that has shown useful cardioprotective effects in many heart dysfunction models. OBJECTIVE: This study investigated whether resveratrol treatment in pregnant rats protects against doxorubicin-induced toxicity in offspring cardiomyocytes. METHODS: Wistar rats (n=8) were supplemented with dietary resveratrol during pregnancy. Upon the offspring's birth, hearts (9-11) were used to obtain the primary culture of cardiomyocytes. DOX-induced cardiotoxicity and the effects of resveratrol supplementation were evaluated by oxidative stress markers, such as dichlorofluorescein diacetate oxidation, decrease in the activity of antioxidant enzymes, and oxidation of total sulfhydryl content, in addition to cell viability evaluation, DNA damage generation, and DNA damage repair response. A value of p<0.05 was considered statistically significant. RESULTS: Neonatal cardiomyocytes from resveratrol supplemented rats exhibiting an increase (p<0.01) in cell viability and lower (p<0.0001) apoptotic/necrotic cells after DOX treatment, which correlates with the activities of antioxidant enzymes and dichlorofluorescein production. Moreover, resveratrol protected cardiomyocytes from DOX-induced DNA damage, showing a decrease (p<0.05) in DNA breaks induced by oxidative stress, evaluated by the activity of DNA-repair enzymes endonuclease III and formamidopyrimidine glycosylase. Supplementation with resveratrol increased (p<0.05) the expression of the repair protein Sirt6 in the cardiomyocytes of the pups. CONCLUSION: This research indicates that supplementation with resveratrol during the gestational period has a notable cardioprotective effect on the offspring's heart against DOX-induced toxicity, which may well be due to its antioxidant function, and the increase in the DNA damage repair response.

FUNDAMENTO: A doxorrubicina (DOX) é frequentemente usada para tratar muitos tipos de cânceres, apesar da cardiotoxicidade dose-dependente. Como alternativa, o resveratrol é um polifenol que tem demonstrado efeitos cardioprotetores em vários modelos de disfunção cardíaca. OBJETIVO: Este estudo investigou se o tratamento com resveratrol em ratas gestantes protege contra toxicidade induzida por doxorrubicina em cardiomiócitos da ninhada. MÉTODOS: Ratas Wistar (n-8) receberam sresveratrol como suplemento alimentar durante a gestação. No nascimento da ninhada, os corações (9-11) foram usados para se obter a cultura primária de cardiomiócitos. A cardiotoxicidade induzida por DOX e os efeitos da suplementação com resveratrol foram avaliados por marcadores de stress oxidativo, tais como oxidação da diclorofluoresceína diacetato, diminuição da atividade de enzimas antioxidantes, e oxidação do teor total de grupos sulfidrila, além da avaliação da viabilidade celular, geração de danos ao DNA, bem como a resposta de reparo aos danos ao DNA. Um valor de p <0,05 foi considerado estatisticamente significativo. RESULTADOS: Os cardiomiócitos de neonatos de ratas que receberam suplemento resveratrol apresentaram um aumento (p <0,01) na viabilidade das células, e diminuição (p <0,0001) de células apoptóticas/necróticas após o tratamento com DOX, o que está correlacionado às atividades de enzimas antioxidantes e produção de diclorofluoresceína. Além disso, o resveratrol protegeu os cardiomiócitos de danos ao DNA induzidos por DOX, apresentando uma diminuição (p <0,05) nas quebras de DNA induzidas por stress oxidativo, avaliadas pela atividade de enzimas reparadoras do DNA endonuclease III e formamidopirimidina glicosilase. A suplementação com resveratrol aumentou (p <0,05) a expressão da proteína reparadora Sirt6 nos cardiomiócitos dos filhotes. CONCLUSÃO: Essa pesquisa indica que a suplementação com resveratrol durante o período gestacional tem um efeito cardioprotetor no coração da ninhada contra a toxicidade induzida por DOX, o que pode se dever a sua função antioxidante, e o aumento na resposta de danos ao DNA.

Exercise Fat Oxidation Is Positively Associated with Body Fatness in Men with Obesity: Defying the Metabolic Flexibility Paradigm.

Obesity is thought to be associated with a reduced capacity to increase fat oxidation in response to physical exercise; however, scientific evidence supporting this paradigm remains scarce. This study aimed to determine the interrelationship of different submaximal exercise metabolic flexibility (Metflex) markers and define its association with body fatness on subjects with obesity. Twenty-one male subjects with obesity performed a graded-intensity exercise protocol (Test 1) during which cardiorespiratory fitness (CRF), maximal fat oxidation (MFO) and its corresponding exercise intensity (FATmax) were recorded. A week afterward, each subject performed a 60-min walk (treadmill) at FATmax (Test 2), and the resulting fat oxidation area under the curve (TFO) and maximum respiratory exchange ratio (RERpeak) were recorded. Blood lactate (LAb) levels was measured during both exercise protocols. Linear regression analysis was used to study the interrelationship of exercise Metflex markers. Pearson's correlation was used to evaluate all possible linear relationships between Metflex and anthropometric measurement, controlling for CRF). The MFO explained 38% and 46% of RERpeak and TFO's associated variance (p < 0.01) while TFO and RERpeak were inversely related (R2 = 0.54, p < 0.01). Body fatness positively correlated with MFO (r = 0.64, p < 0.01) and TFO (r = 0.63, p < 0.01) but inversely related with RERpeak (r = -0.67, p < 0.01). This study shows that MFO and RERpeak are valid indicators of TFO during steady-state exercise at FATmax. The fat oxidation capacity is directly associated with body fatness in males with obesity.

L-carnitine protects DNA oxidative damage induced by phenylalanine and its keto acid derivatives in neural cells: a possible pathomechanism and adjuvant therapy for brain injury in phenylketonuria.

Although phenylalanine (Phe) is known to be neurotoxic in phenylketonuria (PKU), its exact pathogenetic mechanisms of brain damage are still poorly known. Furthermore, much less is known about the role of the Phe derivatives phenylacetic (PAA), phenyllactic (PLA) and phenylpyruvic (PPA) acids that also accumulate in this this disorder on PKU neuropathology. Previous in vitro and in vivo studies have shown that Phe elicits oxidative stress in brain of rodents and that this deleterious process also occurs in peripheral tissues of phenylketonuric patients. In the present study, we investigated whether Phe and its derivatives PAA, PLA and PPA separately or in combination could induce reactive oxygen species (ROS) formation and provoke DNA damage in C6 glial cells. We also tested the role of L-carnitine (L-car), which has been recently considered an antioxidant agent and easily cross the blood brain barrier on the alterations of C6 redox status provoked by Phe and its metabolites. We first observed that cell viability was not changed by Phe and its metabolites. Furthermore, Phe, PAA, PLA and PPA, at concentrations found in plasma of PKU patients, provoked marked DNA damage in the glial cells separately and when combined. Of note, these effects were totally prevented (Phe, PAA and PPA) or attenuated (PLA) by L-car pre-treatment. In addition, a potent ROS formation also induced by Phe and PAA, whereas only moderate increases of ROS were caused by PPA and PLA. Pre-treatment with L-car also prevented Phe- and PAA-induced ROS generation, but not that provoked by PLA and PPA. Thus, our data show that Phe and its major metabolites accumulated in PKU provoke extensive DNA damage in glial cells probably by ROS formation and that L-car may potentially represent an adjuvant therapeutic agent in PKU treatment.

Oxidative Stress and DNA Damage of Zebrafish Sperm at Different Stages of the Cryopreservation Process.

Although gamete cryopreservation has facilitated advancement of reproduction research by allowing the storage of cells over prolonged periods of time, during freezing-thawing cycles, cells inevitably suffer from cryoinjuries. Here, we evaluate oxidative stress and DNA damage of zebrafish sperm at different stages of the cryopreservation process. It was generally observed that the freezing and thawing of the samples led to an increase in the generation of reactive oxygen species and the activity of the catalase enzyme and a reduction in the generation of sulfhydryl groups and superoxide dismutase activity. The alkaline comet assay demonstrated that DNA damage increased after equilibration time, with an even greater increase after freezing and thawing. The comet assay modified with the enzyme formamidopyrimidine glycosylase, and Endonuclease III demonstrated greater DNA damage than the standard comet assay, demonstrating a high degree of oxidation of purines and pyrimidines at all stages of cryopreservation. Our results show that the freeze and thaw processes cause greater oxidative stress and DNA damage than cryoprotectant toxicity during exposure at the equilibrium stage.

Lacosamide improves biochemical, genotoxic, and mitochondrial parameters after PTZ-kindling model in mice.

This study evaluated the effect of lacosamide (LCM) on biochemical and mitochondrial parameters after PTZ kindling in mice. Male mice were treated on alternative days for a period of 11 days with LCM (20, 30, or 40 mg/kg), saline, or diazepam (2 mg/kg), before PTZ administration (50 mg/kg). The hippocampi were collected to evaluate free radicals, the activities of superoxide dismutase (SOD), catalase (CAT), and the mitochondrial complexes I-III, II, and II-III, as well as Bcl-2 and cyclo-oxygenase-2 (COX-2) expressions. Hippocampi, blood, and bone marrow were collected for genotoxic and mutagenic evaluations. LCM 40 mg/kg increased latency and decreased percentage of seizures, only on the 3rd day of observation. The dose of 30 mg/kg only showed positive effects on the percentage of seizures on the 2nd day of observation. LCM decreased free radicals and SOD activity and the dose of 40 mg/kg were able to increase CAT activity. LCM 30 and 40 mg/kg improved the enzymatic mitochondrial activity of the complex I-III and LCM 30 mg/kg improved the activity of the complex II. In the comet assay, the damage induced by PTZ administration was reduced by LCM 20 and 30 mg/kg. The dose of 20 mg/kg increased COX-2 expression while the highest dose used, 40 mg/kg, was able to reduce this expression when compared to the group treated with LCM 20 mg/kg. Although LCM did not produce the antiepileptogenic effect in vivo, it showed the neuroprotective effect against oxidative stress, bioenergetic dysfunction, and DNA damage induced by the repeated PTZ administration.

Protective effect of N-acetyl-L-cysteine and rosuvastatin against oxidative stress in fibroblasts from asymptomatic patients with X-ALD: a preliminary study

Introduction: Several studies in the literature have evaluated the role of oxidative stress and adjuvant therapies for X-linked adrenoleukodystrophy (X-ALD). Here, we investigated whether n-acetyl-L-cysteine (NAC) and rosuvastatin (RSV) could influence the generation of reactive species, redox status and nitrative stress in fibroblasts from asymptomatic patients with X-ALD. Methods: Skin biopsy samples were cultured and treated for 2 hours (37 °C) with NAC and RSV. Results: X-ALD fibroblasts generated high levels of reactive oxygen species. These levels were significantly lower in fibroblasts treated with NAC and RSV relative to untreated samples. The X-ALD fibroblasts from asymptomatic patients also had higher catalase activity, and only NAC was able to increase enzyme activity in the samples. Conclusions: Our results indicated that NAC and RSV were able to improve oxidative stress parameters in fibroblasts from asymptomatic patients with X-ALD, showing that adjuvant antioxidant therapy may be a promising treatment strategy for asymptomatic patients with this disease. (AU)

Chronic Effect of Fatmax Training on Body Weight, Fat Mass, and Cardiorespiratory Fitness in Obese Subjects: A Meta-Analysis of Randomized Clinical Trials.

Exercise training performed at the maximal fat oxidation intensity (FMT) stands out as a potential treatment of overweight and obesity. This work is a meta-analysis of randomized clinical trials of studies about the effect of FMT on fat mass and maximal oxygen consumption using PubMed, SCOPUS, EBSCOhost, and ScienceDirect as databases. Two independent reviewers selected 11 trials from 356 publications identified by the following keywords: fatmax, lipoxmax, maximal fat oxidation, peak of fat oxidation, physical training, physical exercise, body fat (BF), fat mass, overweight, and obesity. The risk of bias was assessed following the Cochrane Guidelines. The pooled mean difference was computed for each outcome with the random-effects model and the inverse-variance method. The meta-analysis was performed with the RevMan software v 5.3, and the heterogeneity across studies by the I2. The statistical significance was accepted at p < 0.05. Results showed that the FMT reduced body weight (MD = -4.30 kg, p < 0.01, I2 = 0%), fat mass (MD = -4.03 kg, p < 0.01, I2 = 0%), and waist circumference (MD = -3.34 cm, p < 0.01). Fat-free mass remains unchanged (MD = 0.08 kg, p = 0.85), but maximal oxygen consumption increased (MD = 2.96 mL∙kg-1∙min-1, p < 0.01, I2 = 0%). We conclude that FMT at short and medium-term (eight to twenty weeks) reduces body weight and BF, increasing cardiovascular fitness in low physical fitness people with obesity.

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.

Nanoparticles containing ß-cyclodextrin potentially useful for the treatment of Niemann-Pick C.

ß-Cyclodextrin (ß-CD) is being considered a promising therapy for Niemann-Pick C (NPC) disease because of its ability to mobilise the entrapped cholesterol from lysosomes, however, a major limitation is its inability to cross the blood-brain barrier (BBB) and address the central nervous system (CNS) manifestations of the disease. Considering this, we aimed to design nanoparticles able to cross the BBB and deliver ß-CD into the CNS lysosomes. The physicochemical characteristics of ß-CD-loaded nanoparticles were evaluated by dynamic light scattering, small-angle X-ray scattering, and cryogenic transmission electron microscopy. The in vitro analyses were performed with NPC dermal fibroblasts and the ß-CD-loaded nanoparticles were tracked in vivo. The nanoparticles showed a mean diameter around 120 nm with a disordered bicontinuous inner structure. The nanoparticles did not cause decrease in cell viability, impairment in the antioxidant enzymes activity, damage to biomolecules or release of reactive species in NPC dermal fibroblasts; also, they did not induce genotoxicity or alter the mitochondrial function in healthy fibroblasts. The ß-CD-loaded nanoparticles were taken up by lysosomes reducing the cholesterol accumulated in NPC fibroblasts and reached the CNS of mice more intensely than other organs, demonstrating advantages compared to the free ß-CD. The results demonstrated the potential of the ß-CD-loaded nanoparticles in reducing the brain impairment of NPC.

Intradialytic neuromuscular electrical stimulation reduces DNA damage in chronic kidney failure patients: a randomized controlled trial.

BACKGROUND: Chronic kidney failure (CKF) patients on renal replacement therapies exhibit elevated levels of DNA lesions and this is directly related to high mortality. OBJECTIVE: This study aimed to evaluate the effect of neuromuscular electrical stimulation (NMES) on genomic damage in CKF patients on conventional haemodialysis (HD). METHODS: Twenty-one patients with CKF on HD were randomized into control (CG =10) or neuromuscular electrical stimulation (NMESG = 11) groups. NMES was applied on the quadriceps muscle during the HD session, three times a week, for 8 weeks in NMESG. DNA damage in blood was evaluated by the alkaline comet assay prior to follow-up, after 4 and 8 weeks of intervention. RESULTS: Intradialytic NMES in CKF patients induced a significant decrease in DNA damage after four [49.9 (3.68) vs 101.5 (6.53); p = 0.000] than eight [19.9 (2.07) vs 101.5 (6.53); p = 0.000] weeks compared to baseline. Genomic damage was also significantly less after four [NMESG: 49.9 (3.68) vs CG: 92.9 (12.61); p = 0.001] than after eight [NMESG: 19.9 (2.07) vs CG: 76.4 (11.15); p = 0.000] weeks compared to CG. CONCLUSIONS: This study demonstrates for the first time that intradialytic NMES is able to reduce DNA damage in blood of CKF patients.

GSTT1 and GSTM1 null variants in Mestizo and Amerindian populations from northwestern Mexico and a literature review

Abstract The GSTT1 and GSTM1 genes are key molecules in cellular detoxification. Null variants in these genes are associated with increase susceptibility to developing different types of cancers. The aim of this study was to determine the prevalence of GSTT1 and GSTM1 null genotypes in Mestizo and Amerindian individuals from the Northwestern region of Mexico, and to compare them with those reported worldwide. GSTT1 and GSTM1 null variants were genotyped by multiplex PCR in 211 Mestizos and 211 Amerindian individuals. Studies reporting on frequency of GSTT1 and GSTM1 null variants worldwide were identified by a PubMed search and their geographic distribution were analyzed. We found no significant differences in the frequency of the null genotype for GSTT1 and GSM1 genes between Mestizo and Amerindian individuals. Worldwide frequencies of the GSTT1 and GSTM1 null genotypes ranges from 0.10 to 0.51, and from 0.11 to 0.67, respectively. Interestingly, in most countries the frequency of the GSTT1 null genotype is common or frequent (76%), whereas the frequency of the GSMT1 null genotype is very frequent or extremely frequent (86%). Thus, ethnic-dependent differences in the prevalence of GSTT1 and GSTM1 null variants may influence the effect of environmental carcinogens in cancer risk.

GSTT1 and GSTM1 null variants in Mestizo and Amerindian populations from northwestern Mexico and a literature review.

The GSTT1 and GSTM1 genes are key molecules in cellular detoxification. Null variants in these genes are associated with increase susceptibility to developing different types of cancers. The aim of this study was to determine the prevalence of GSTT1 and GSTM1 null genotypes in Mestizo and Amerindian individuals from the Northwestern region of Mexico, and to compare them with those reported worldwide. GSTT1 and GSTM1 null variants were genotyped by multiplex PCR in 211 Mestizos and 211 Amerindian individuals. Studies reporting on frequency of GSTT1 and GSTM1 null variants worldwide were identified by a PubMed search and their geographic distribution were analyzed. We found no significant differences in the frequency of the null genotype for GSTT1 and GSM1 genes between Mestizo and Amerindian individuals. Worldwide frequencies of the GSTT1 and GSTM1 null genotypes ranges from 0.10 to 0.51, and from 0.11 to 0.67, respectively. Interestingly, in most countries the frequency of the GSTT1 null genotype is common or frequent (76%), whereas the frequency of the GSMT1 null genotype is very frequent or extremely frequent (86%). Thus, ethnic-dependent differences in the prevalence of GSTT1 and GSTM1 null variants may influence the effect of environmental carcinogens in cancer risk.

Low maternal care is associated with increased oxidative stress in the brain of lactating rats.

Maternal care is crucial for offspring development and licking/grooming patterns can be induced by sensorial, neuroendocrine, and metabolic variations in the CNS. Important brain functions, such as learning and memory, can be influenced by oxidative stress, which can also modulate pathophysiological processes (e.g., depression, anxiety, and other psychiatric disorders). This study evaluated oxidative stress in the hippocampus (HP), olfactory bulb (OB), and plasma in Low-Licking (LL) and High-Licking (HL) lactating rats through superoxide dismutase (SOD) and catalase (CAT) activities, DNA damage (comet assay), and dihydrodichlorofluorescein (DCF) oxidation assay. Results demonstrate that in the HP of LL, the activities of SOD and CAT were increased compared to HL. In the OB, the activities of SOD and CAT were also increased in LL. The comet assay in the HP showed that LL had higher levels of basal damage and increased levels of DNA breaks than HL. In the OB, LL also had higher levels of DNA damage. In the plasma, no difference was observed in either SOD or CAT activities, but the DCF oxidation assay revealed that LL had higher levels of ROS production than HL. In conclusion, we observed that LL mothers showed evidence of increased oxidative stress when compared to HL, suggesting that variations in maternal behavior might be related to these biochemical parameters.

Exercise during pregnancy decreases doxorubicin-induced cardiotoxic effects on neonatal hearts.

Cancer treatment with Doxorubicin (DOX) is limited due its dose-dependent cardiotoxicity, mainly related to the oxidative stress production. In experimental models of DOX treatment exercise can be used as a beneficial adjuvant therapy. This work aimed to investigate the effects of exercise during pregnancy on DOX-induced cardiotoxicity in cardiomyocytes of progeny, examining the possible intergenerational cardioprotective effects of maternal exercise. For this purpose pregnant rats were divided in control and exercise groups and pre-treated during gestational days. Hearts of newborns were used to obtain a culture of cardiomyocytes to be treated with DOX for analyses of cell viability, apoptosis and necrosis; ROS production; DNA damage; SOD and CAT activities; and Sirt6 protein expression. The results showed that exercise during pregnancy induced an increase in the viability of neonatal cardiomyocytes and a decrease in DOX-induced apoptotic and necrotic death which were correlated to the decrease in ROS production and an increase in antioxidant defenses. Exercise also protected neonatal cardiomyocytes from DOX-induced DNA damage, demonstrating a reduction in the oxidative DNA breaks. Likewise, exercise induced an increase in expression of Sirt6 in neonatal cardiomyocytes. Therefore, these results demonstrate for the first time that exercise performed by mothers protects the neonatal heart against DOX-induced toxicity. Our data demonstrate the intergenerational effect of exercise in cardiomyocytes of progeny, where the modulation of oxidative stress through antioxidant enzymes, and DNA integrity via Sirt6, were induced due to exercise in mothers, increasing the resistance of the neonatal heart against DOX toxicity.