RESUMEN
AIM: The present study evaluated whether topiramate (TPM) treatment during the peripubertal period affects vascular parameters of male rats and whether oxidative stress plays a role in these changes. MAIN METHODS: Rats were treated with TPM (41 mg/kg/day, gavage) or vehicle (CTR group) from the postnatal day (PND) 28 to 50. At PND 51 and 120 the rats were evaluated for: thoracic aorta reactivity to phenylephrine, in the presence (Endo+) or absence of endothelium (Endo-), to acetylcholine and to sodium nitroprusside (SNP), aortic thickness and endothelial nitric oxide synthase (eNOS) expression. In serum were analyzed: the antioxidant capacity by ferric reducing antioxidant power assay; endogenous antioxidant reduced glutathione, and superoxide anion. Results were expressed as mean ± s.e.m., differences when p < 0.05. STATISTICS: Two-way ANOVA (and Tukey's) or Student t-test. KEY FINDINGS: At PND 51, the contraction induced by phenylephrine in Endo+ ring was higher in TPM when compared to CTR. At PND 120, the aortic sensitivity to acetylcholine in TPM rats was reduced in comparison with CTR. The aortic eNOs expression and the aortic thickness were similar between the groups. At PND 51 and 120, TPM group presented a decrease in antioxidants when compared to CTR groups and at PND 120, in TPM group the superoxide anion was increased. SIGNIFICANCE: Taken together, the treatment of rats with TPM during peripubertal period promoted permanent impairment of endothelial function probably mediated by oxidative stress.
Asunto(s)
Acetilcolina , Antioxidantes , Ratas , Animales , Masculino , Antioxidantes/farmacología , Antioxidantes/metabolismo , Topiramato/farmacología , Acetilcolina/metabolismo , Superóxidos/metabolismo , Endotelio Vascular/metabolismo , Óxido Nítrico Sintasa de Tipo III/metabolismo , Estrés Oxidativo , Aorta Torácica/metabolismo , Fenilefrina/farmacología , Óxido Nítrico/metabolismoRESUMEN
Clinical studies have shown a correlation between thyroid disorders and cardiac diseases. High levels of triiodothyronine (T3) induce cardiac hypertrophy, a risk factor for cardiac complications and heart failure. Previous results have demonstrated that angiotensin-(1-7) is able to block T3-induced cardiac hypertrophy; however, the molecular mechanisms involved in this event have not been fully elucidated. Here, we evidenced the contribution of FOXO3 signaling to angiotensin-(1-7) effects. Angiotensin-(1-7) treatment increased nuclear FOXO3 levels and reduced p-FOXO3 levels (inactive form) in isolated cardiomyocytes. Knockdown of FOXO3 by RNA silencing abrogated the antihypertrophic effect of angiotensin-(1-7). Increased expression of antioxidant enzymes superoxide dismutase 1 (SOD1 and catalase) and lower levels of reactive oxygen species and nuclear factor-κB (NF-κB) were observed after angiotensin-(1-7) treatment in vitro. Consistent with these results, transgenic rats overexpressing angiotensin-(1-7) displayed increased nuclear FOXO3 and SOD1 levels and reduced NF-κB levels in the heart. These results provide a new molecular mechanism responsible for the antihypertrophic effect of angiotensin-(1-7), which may contribute to future therapeutic targets.
Asunto(s)
Angiotensina I/farmacología , Catalasa/metabolismo , Proteína Forkhead Box O3/metabolismo , Miocitos Cardíacos/patología , FN-kappa B/metabolismo , Fragmentos de Péptidos/farmacología , Superóxido Dismutasa-1/metabolismo , Triyodotironina/efectos adversos , Regulación hacia Arriba , Animales , Antioxidantes/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Hipertrofia , Masculino , Modelos Biológicos , Miocitos Cardíacos/efectos de los fármacos , Proto-Oncogenes Mas , Proteínas Proto-Oncogénicas/metabolismo , Ratas Sprague-Dawley , Ratas Transgénicas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Objective: The aim was to evaluate if maternal treatment with metformin (MET) during pregnancy and lactation could be safe for metabolic and cardiovascular parameters of adult male and female offspring.Materials and methods: Wistar female rats were treated with MET (293 mg/kg/d) or tap water, by gavage during gestation (METG or CTRG) or gestation and lactation (METGL or CTRGL).Results: At 75 days of life, male and female MET offspring presented similar blood pressure when compared with their CTR. The heart rate of female METGL was higher than in the CTRGL. The insulin sensitivity, basal glycaemia, body weight, Lee index of obesity, plasmatic concentration of triglycerides, total cholesterol and fat acid of male and female MET were similar to CTR groups. Lower fat pad deposition was observed in female METG and METGL.Conclusion: MET exposure during gestational and lactation does not program cardiovascular and metabolic alterations in adult offspring life.
Asunto(s)
Enfermedades Cardiovasculares/inducido químicamente , Lactancia , Exposición Materna , Enfermedades Metabólicas/inducido químicamente , Metformina/efectos adversos , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Tejido Adiposo/metabolismo , Animales , Animales Recién Nacidos , Glucemia/metabolismo , Peso Corporal , Femenino , Resistencia a la Insulina , Masculino , Metformina/administración & dosificación , Obesidad/metabolismo , Embarazo , Preñez , Ratas , Ratas Wistar , Factores de Tiempo , Triglicéridos/metabolismoRESUMEN
Selective serotonin reuptake inhibitors are the most widely prescribed antidepressants to women during pregnancy. Maternal treatment with fluoxetine can expose fetuses and neonates to higher levels of serotonin that plays a role in stress response. Thus, the aim of the study was to evaluate whether maternal treatment with fluoxetine interferes with aorta reactivity of adult male offspring after acute restraint stress. Wistar rats were gavaged with fluoxetine (5mg/kg/day) or water (control) during pregnancy and lactation. The experiments were performed in adult male offspring, treated or not with reserpine (4mg/Kg, ip, 28h before the experimental protocol). Fluoxetine and control rats were submitted to a single restraint stress session (ST) for 1h. Curves to phenylephrine were performed in thoracic aorta with endothelium. Aortic nitric oxide (NOx) were evaluated by the Griess method. The aortic contraction induced by phenylephrine was similar between control and fluoxetine rats. The acute stress reduced contraction in aorta of control ST compared to control, and L-NAME equaled this response. In fluoxetine rats, ST did not change the aortic constriction. Reserpine treatment restored the vasoconstriction in control ST, but did not interfere with aortic contraction in control, fluoxetine or fluoxetine ST. The NOx concentration was higher in aortas from control ST than control rats, and reserpine reduced NOx levels of control ST. The NOx concentration was similar between fluoxetine and fluoxetine ST rats, treated or not with reserpine. In conclusion, maternal treatment with fluoxetine blunted acute restraint stress-induced NO system activation and aortic adaptation in adult offspring.
Asunto(s)
Aorta/fisiopatología , Fluoxetina/farmacología , Lactancia , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Estrés Psicológico/fisiopatología , Útero/efectos de los fármacos , Útero/fisiopatología , Adaptación Fisiológica/efectos de los fármacos , Animales , Aorta/efectos de los fármacos , Femenino , Masculino , Óxido Nítrico/metabolismo , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Ratas , Ratas Wistar , Restricción Física/psicología , Estrés Psicológico/metabolismo , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/metabolismo , Vasoconstricción/efectos de los fármacosRESUMEN
OBJECTIVES: To identify the most cited articles in general surgery published by Brazilian authors. INTRODUCTION: There are several ways for the international community to recognize the quality of a scientific article. Although controversial, the most widely used and reliable methodology to identify the importance of an article is citation analysis. METHODS: A search using the Institute for Scientific Information citation database (Science Citation Index Expanded) was performed to identify highly cited Brazilian papers published in twenty-six highly cited general surgery journals, selected based on their elevated impact factors, from 1970 to 2009. Further analysis was done on the 65 most-cited papers. RESULTS: We identified 1,713 Brazilian articles, from which nine papers emerged as classics (more than 100 citations received). For the Brazilian contributions, a total increase of about 21-fold was evident between 1970 and 2009. Although several topics were covered, articles covering trauma, oncology and organ transplantation were the most cited. The majority of classic studies were done with international cooperation. CONCLUSIONS: This study identified the most influential Brazilian articles published in internationally renowned general surgery journals.
Asunto(s)
Bibliometría , Cirugía General/estadística & datos numéricos , Publicaciones Periódicas como Asunto/estadística & datos numéricos , Investigación Biomédica/estadística & datos numéricos , Brasil , Cirugía General/clasificación , Humanos , Factor de Impacto de la RevistaRESUMEN
OBJECTIVES: To identify the most cited articles in general surgery published by Brazilian authors. INTRODUCTION: There are several ways for the international community to recognize the quality of a scientific article. Although controversial, the most widely used and reliable methodology to identify the importance of an article is citation analysis. METHODS: A search using the Institute for Scientific Information citation database (Science Citation Index Expanded) was performed to identify highly cited Brazilian papers published in twenty-six highly cited general surgery journals, selected based on their elevated impact factors, from 1970 to 2009. Further analysis was done on the 65 most-cited papers. RESULTS: We identified 1,713 Brazilian articles, from which nine papers emerged as classics (more than 100 citations received). For the Brazilian contributions, a total increase of about 21-fold was evident between 1970 and 2009. Although several topics were covered, articles covering trauma, oncology and organ transplantation were the most cited. The majority of classic studies were done with international cooperation. CONCLUSIONS: This study identified the most influential Brazilian articles published in internationally renowned general surgery journals.