Mulheres com síndrome do ovário policísticos que desenvolveram diabetes melitus 2 antes dos 35 anos: ansiedade, má qualidade do sono e não controle glicêmico / Women with polycystic ovarian syndrome who developed diabetes mellitus 2 before the age of 35: anxiety, poor sleep quality and lack of glycemic control / Mujeres con síndrome de ovario poliquístico que desarrollaron diabetes melitus 2 antes de los 35 años: ansiedad, mala calidad del sueño y sin control glucémico

Introdução: A síndrome dos ovários policísticos (SOP) consiste em uma desordem de origem endocrinológica de grande prevalência nas mulheres em idade fértil, sendo acometidas por ela aproximadamente de 6 a 16% da população feminina - em consonância com diversos critérios diagnósticos 1-4. Essa síndrome é associada ao hiperandrogenismo e à resistência insulínica (RI), com manifestações clínicas relacionadas a alterações reprodutivas 4, desenvolvimento de diabetes mellitus (DM2) e obesidade. Esta pesquisa objetiva compreender o perfil das mulheres com DM 2 antes dos 35 anos e os fatores que podem levar a esta condição. Metodologia: Este estudo se deu por meio de inquérito on-line feito a mulheres diagnosticadas com SOP, e com menos de 35 anos de idade. Foi desenvolvido de maneira virtualizada via plataforma GoogleForms® em função da pandemia do COVID-19. Tratou-se de um levantamento sobre presença de fatores de risco para DM 2, como sobrepeso e alimentação, sedentarismo e qualidade do sono; em grupos de mulheres com SOP diabéticas e não diabéticas, para efeito de comparação. Resultados e discussão: Um total de 198 mulheres responderam ao questionário, sendo divididas em Diabéticas (DM) e não diabéticas (NDM). O grupo DM foi o que mais apresentou IMC elevado (acima de 30), e o que mais se declarou seguir orientações nutricionais. Atividade física não diferenciou entre os grupos. O grupo DM foi o que declarou dormir mais tarde (pós 23:00) quando comparado com o grupo NDM. O sobrepeso indica ser um fator importante para o advento da DM 2 neste grupo, sendo as orientações nutricionais não tão efetivas, devido muito a dificuldade de aderir às orientações. O hábito de dormir tarde implica em alterações que levam a aumento da RI via estresse oxidativo, contribuindo para obesidade e DM 2. Conclusões: A obesidade é um fator decisivo para a precocidade da DM 2 em mulheres com SOP, e sua condição é multifatorial, associada a seguimento de orientações nutricionais, atividade física e qualidade do sono. O evitar da precocidade da DM 2 neste grupo passa por esta compreensão.

Introduction: Polycystic ovary syndrome (PCOS) is an endocrinological disorder with high prevalence in women of childbearing age, affected by approximately 6 to 16% of the female population - in line with several diagnostic criteria 1-4. This syndrome is associated with hyperandrogenism and insulin resistance (IR), with clinical manifestations related to reproductive changes 4, development of diabetes mellitus (DM2) and obesity. This research aims to understand the profile of women with DM 2 before the age of 35 and the factors that can lead to this condition. Methodology: This study was carried out through an online survey made to women diagnosed with PCOS, and under 35 years of age. It was developed in a virtualized way via the GoogleForms® platform due to the COVID-19 pandemic. This was a survey on the presence of risk factors for DM 2, such as overweight and diet, sedentary lifestyle and sleep quality; in groups of women with diabetic and non-diabetic PCOS for comparison purposes. Results and discussion: A total of 198 women answered the questionnaire, divided into Diabetic (DM) and non-diabetic (NDM). The DM group was the one with the highest BMI (above 30), and the one that most declared to follow nutritional guidelines. Physical activity did not differ between groups. The DM group was the one who reported sleeping later (after 11 pm) when compared to the NDM group. Overweight is an important factor for the advent of DM 2 in this group, and nutritional guidelines are not so effective, due to the difficulty in adhering to the guidelines. The habit of sleeping late implies changes that lead to increased IR via oxidative stress, contributing to obesity and DM 2. Conclusions: Obesity is a decisive factor for the precocity of DM 2 in women with PCOS, and its condition is multifactorial, associated with following nutritional guidelines, physical activity and sleep quality. Avoiding the precocity of DM 2 in this group involves this understanding.

Introducción: El síndrome de ovario poliquístico (SOP) es un trastorno de origen endocrinológico de alta prevalencia en mujeres en edad fértil, afectando aproximadamente entre el 6 y el 16% de la población femenina, de acuerdo con diversos criterios diagnósticos 1- 4 . Este síndrome se asocia con hiperandrogenismo y resistencia a la insulina (RI), con manifestaciones clínicas relacionadas con cambios reproductivos 4, desarrollo de diabetes mellitus (DM2) y obesidad. Esta investigación tiene como objetivo conocer el perfil de las mujeres con DM 2 antes de los 35 años y los factores que pueden conducir a esta condición. Metodología: Este estudio se realizó a través de una encuesta online realizada entre mujeres diagnosticadas con SOP y menores de 35 años. Fue desarrollado de manera virtualizada a través de la plataforma GoogleForms® debido a la pandemia de COVID-19. Se realizó una encuesta sobre la presencia de factores de riesgo para DM 2, como sobrepeso y alimentación, sedentarismo y calidad del sueño; en grupos de mujeres diabéticas y no diabéticas con síndrome de ovario poliquístico, con fines de comparación. Resultados y discusión: Respondieron al cuestionario un total de 198 mujeres, divididas en diabéticas (DM) y no diabéticas (NDM). El grupo DM fue el que presentó un IMC más elevado (superior a 30), y el que más declaró seguir las pautas nutricionales. La actividad física no difirió entre los grupos. El grupo DM fue el que reportó dormir más tarde (después de las 11:00 pm) en comparación con el grupo NDM. El sobrepeso indica que es un factor importante en la aparición de DM 2 en este grupo, siendo las pautas nutricionales no tan efectivas, en gran parte por la dificultad para cumplirlas. El hábito de dormir tarde implica cambios que conducen a un aumento de la RI vía estrés oxidativo, contribuyendo a la obesidad y la DM 2. Conclusiones: La obesidad es un factor decisivo en la aparición temprana de la DM 2 en mujeres con SOP, y su condición es multifactorial, asociado con el seguimiento de pautas nutricionales, actividad física y calidad del sueño. Evitar la precocidad de la DM 2 en este grupo requiere esta comprensión.

Ocorrência de indicações farmacológicas não recomendadas por estágios na endometriose e impacto no quadro de ansiedade por persistência de sintomas / Occurrence of pharmacological indications not recommended by stages in endometriosis and impact on anxiety due to persistence of symptoms / Presencia de indicaciones farmacológicas no recomendadas por etapas en la endometriosis e impacto en la ansiedad por la persistencia de los síntomas

Introdução: Endometriose é uma patologia pélvica crônica de caráter inflamatório e estrogênio-dependente. Manifesta-se em quatro tipos de estágio (EI, EII, EIII e EIV), caracterizados pelos números de lesões. Tem indicações farmacológicas recomendadas se baseadas nos estágios, sendo EI/EII sintomático com AINES e/ou uso de anticonceptivos de uso contínuo; e EIII/EIV com fármacos análogos de GnRH. O estilo de vida dessas mulheres é impactado pela dor, que altera a rotina e vida afetivo/sexual contribuindo para quadros de ansiedade. O presente estudo se norteia pela questão "qual impacto na ansiedade de mulheres com endometriose, quando não ocorrem indicações farmacológicas recomendadas para os estágios que se encontra? Logo, o objetivo deste estudo é avaliar os efeitos do tratamento medicamentoso não recomendado e risco de ansiedade. Metodologia: Levantamento de pacientes com diagnóstico de Endometriose, cadastradas no Banco de Dados do Projeto agrupadas em estágios de tratamentos farmacológicos similares (EI/EII e EIII/EIV). O relato de ansiedade, com diagnóstico médico e pós endometriose foi a variável dependente em estudo. As variáveis independentes (ou influenciadoras) foram [1] Estágio da doença, [2] Farmacoterapia recomendada (FR) ou não (FNR) e [3] esquema medicamentoso empregado (classes e combinações). Estatística feitas por chi quadrado e Fischer. Resultados: Do total de 375 mulheres, 274 apresentavam ansiedade. Destas, 170 estavam no grupo IFR; sendo 141 no agrupamento EI/EII, e 29 mulheres no EIII/EIV. No que se refere ao grupo IFNR, teve se um n=104 mulheres, sendo apenas 1 nos EI/EII e 103 nos EIII/EIV. Os casos de FNR estão mais presentes em EIII/EIV, com 90% dos casos (IC 95%, p<0,05). O esquema terapêutico mais presente foi AINEs em monoterapia, sendo 65% (IC 95%, p<0,05) em Estágio inadequado. Notou-se uma correlação positiva entre FNR e quadros de ansiedade, principalmente quando se empregava a monoterapia com AINEs (IC 95%, p<0,05). Conclusão: Dificuldades de acesso a especialistas para diagnóstico e aos medicamentos do EIII/EIV podem ser as causas, que serão investigadas em estudos futuros.

Introduction: Endometriosis is a chronic pelvic pathology with an inflammatory and estrogen-dependent nature. It manifests itself in four types of stages (EI, EII, EIII and EIV), characterized by the number of lesions. It has recommended pharmacological indications based on the stages, being symptomatic EI/EII with NSAIDs and/or use of continuous contraceptives; and EIII/EIV with GnRH analogue drugs. The lifestyle of these women is impacted by pain, which alters their routine and emotional/sexual life, contributing to anxiety. The present study is guided by the question "what impact on the anxiety of women with endometriosis, when there are no recommended pharmacological indications for the stage they are in?" Therefore, the objective of this study is to evaluate the effects of non-recommended drug treatment and the risk of anxiety. Methodology: Survey of patients diagnosed with Endometriosis, registered in the Project Database grouped into stages of similar pharmacological treatments (EI/EII and EIII/EIV). The report of anxiety, with medical diagnosis and post-endometriosis was the dependent variable under study. The independent (or influencing) variables were [1] Stage of the disease, [2] Pharmacotherapy recommended (FR) or not (FNR) and [3] medication regimen used (classes and combinations). Statistics made by chi square and Fischer. Results: Of the total of 375 women, 274 had anxiety. Of these, 170 were in the IFR group; 141 in the EI/EII group, and 29 women in the EIII/EIV group. Regarding the IFNR group, there were n=104 women, with only 1 in EI/EII and 103 in EIII/EIV. FNR cases are more present in EIII/EIV, with 90% of cases (95% CI, p<0.05). The most common therapeutic regimen was NSAIDs as monotherapy, with 65% (95% CI, p<0.05) in an inadequate stage. A positive correlation was noted between FNR and anxiety, especially when using monotherapy with NSAIDs (95% CI, p<0.05). Conclusion: Difficulties in accessing specialists for diagnosis and EIII/EIV medications may be the causes, which will be investigated in future studies.

Introducción: La endometriosis es una patología pélvica crónica de naturaleza inflamatoria y estrógeno-dependiente. Se manifiesta en cuatro tipos de estadios (EI, EII, EIII y EIV), caracterizados por el número de lesiones. Tiene indicaciones farmacológicas recomendadas según los estadios, siendo EI/EII sintomática con AINE y/o uso de anticonceptivos continuos; y EIII/EIV con fármacos análogos de GnRH. El estilo de vida de estas mujeres se ve impactado por el dolor, lo que altera su rutina y su vida emocional/sexual, contribuyendo a la ansiedad. El presente estudio se guía por la pregunta "¿qué impacto tiene en la ansiedad de las mujeres con endometriosis, cuando no existen indicaciones farmacológicas recomendadas para las etapas en las que se encuentra? Por tanto, el objetivo de este estudio es evaluar los efectos del tratamiento farmacológico no recomendado y el riesgo de ansiedad. Metodología: Encuesta a pacientes diagnosticadas de Endometriosis, registradas en la Base de Datos del Proyecto agrupadas en etapas de tratamientos farmacológicos similares (EI/EII y EIII/EIV). El reporte de ansiedad, con diagnóstico médico y post-endometriosis fue la variable dependiente en estudio. Las variables independientes (o influyentes) fueron [1] Estadio de la enfermedad, [2] Farmacoterapia recomendada (FR) o no (FNR) y [3] régimen de medicación utilizado (clases y combinaciones). Estadística realizada por chi cuadrado y Fischer. Resultados: Del total de 375 mujeres, 274 presentaron ansiedad. De ellos, 170 estaban en el grupo IFR; 141 en el grupo EI/EII y 29 mujeres en el grupo EIII/EIV. En cuanto al grupo IFNR, hubo n=104 mujeres, siendo sólo 1 en EI/EII y 103 en EIII/EIV. Los casos de FNR están más presentes en EIII/EIV, con un 90% de los casos (IC 95%, p<0,05). El régimen terapéutico más común fue el de AINE en monoterapia, con un 65% (IC 95%, p<0,05) en estadio inadecuado. Se observó una correlación positiva entre la FNR y la ansiedad, especialmente cuando se utilizaba monoterapia con AINE (IC del 95%, p<0,05). Conclusión: Las dificultades para acceder a especialistas para el diagnóstico y a los medicamentos EIII/EIV pueden ser las causas, que serán investigadas en futuros estudios.

Schizophyllan from Schizophyllum commune BRM 060008: Potential application as an inhibitor of lipase.

ß-D-glucan has significant implications in regulating lipid metabolism and preventing diseases associated with lipid accumulation. Schizophyllan (SPG) from Schizophyllum commune fungus is a commercially important ß-glucan with applications in the health food industry, pharmacy, and cosmetics. However, SPG was obtained by submerged culture of the wood-rotting and filamentous fungus S. commune BRM 060008, which may have been isolated from the Cerrado Biome of Brazil. In this study, to confirm that the polysaccharide produced by BRM 060008 strain fermentation was indeed (1→3)(1→6)-ß-D-glucan, it was purified and characterized using Fourier transform infrared spectroscopy, thermogravimetric analysis, high-performance size exclusion chromatography, nuclear magnetic resonance, and methylation analysis. The polysaccharide produced was identified as the ß-D-glucan expected with a high molecular weight (1.093 × 106 g/mol) and the thermogravimetric analysis indicated a maximum degradation temperature of ~324 °C and a 60 % residual weight, lower than commercial SPG. The molecular structure and thermal properties of the ß-D-glucan were similar to the commercial sample. Additionally, the in vitro pancreatic lipase inhibitory activity was evaluated, investigating anti-obesity and anti-lipidemic properties. The results showed unprecedented lipase inhibition activity to SPG prepared using the S. commune strain BRM 060008, making it promising for food and pharmaceutical applications.

Neuroinflammation and neuroprogression produced by oxidative stress in euthymic bipolar patients with different onset disease times.

Bipolar disorder (BD) is associated with systemic toxicity, represented by changes in biomarkers associated with mood episodes, leading to neurological damage, which may reflect cognitive functions and functionality and the progression of the disease. We aimed to analyze the effect of four biomarkers, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and thiobarbituric acid reactive substances (TBA-RS), related to oxidative stress in BD and to correlate them with cognitive functions and functionality. We studied 50 bipolar types I/II patients in the euthymic phase, which was divided into two subgroups with 25 patients each (≤ 3 years and ≥ 10 years of diagnosis, from the first episode of mania) and 25 control patients. To analyze frontal cognitive functions and functionality, we used the Frontal Assessment Battery (FAB) and Functioning Assessment Short Test (FAST) tests, respectively. The scores of the FAST and FAB tests showed an increase and decrease respectively, in both bipolar groups, when compared to the control group, demonstrating impairment in cognitive functions and functionality since the disease onset. In addition, changes occurred in all six domains of the FAST test, and in four domains of the FAB test in bipolar patients when compared to the control group. Regarding oxidative stress biomarkers, we did not find changes in SOD and GSH-Px activities; however, a significant increase in CAT activity and lipid peroxidation was observed in both groups, although the patients were euthymic and medicated. These results allow us to raise the hypothesis that since the beginning of the disease, the euthymic bipolar patient has presented a level of oxidative stress, which gets worse with the evolution of the disease, promoting impairments in the frontal cognitive functions and functionality gradually.

Protective effect of Myrcia pubipetala Miq. against the alterations in oxidative stress parameters in an animal model of depression induced by corticosterone.

Depression is a debilitating disorder in humans that significantly affects quality of life. As such, alternative therapies are highly sought after by patients seeking treatment for depression. Experimentally, the chronic administration of corticosterone (CORT) in rodents has been reported to promote depressive-like behaviors. Herein, animals received saline or CORT for 21 days and, during the last 7 days, they were treated with the crude hydroalcoholic extract (CHE) of Myrcia pubipetala Miq (50, 100 or 150 mg/Kg), or vehicle (distilled water), by oral route. After 24 h, animals were subjected to the open field (OFT) and forced swimming tests (FST), and then sacrificed for the removal of the hippocampus and cerebral cortex for biochemical analysis. Results showed enhanced catalase (CAT) and superoxide dismutase (SOD) activities, as well as an elevated formation of thiobarbituric acid reactive substances (TBARS), in the cerebral cortex of CORT-treated mice. The chronic administration of the CHE (100 and 150 mg/Kg) reduced TBARS and the increased total sulfhydryl content, and also reversed the increase in TBARS induced by CORT. In the hippocampus, CORT increased CAT and SOD activities and reduced glutathione peroxidase (GSH-Px) (C) activity, while Myrcia pubipetala Miq. CHE (100 and 150 mg/Kg) increased GSH-Px activity when administered alone and reversed decreased GSH-Px (100 and 150 mg/Kg) activity when given during CORT administration. Neither CORT administration nor CHE treatment significantly altered the immobility time of the animals in FST and no changes were observed in the locomotor activity of the animals in the OFT. Findings indicate that the CHE of Myrcia pubipetala Miq. exerts antioxidant effects in the cerebral cortex and hippocampus of mice induced to depression by CORT. Since phenolic compounds are reported to have antioxidant effects in this species, the effects of the CHE may be, at least in part, mediated by the presence of these compounds in Myrcia extract.

Prevalência de aneurismas cerebrais incidentais entre homens e mulheres / Prevalence of incidental brain aneurysms be¬tween men and women

Verificar a prevalência de aneurisma cerebral incidental, diagnosticados por meio de ressonância magnética entre homens e mulheres. Trata-se de um estudo de coorte retrospectivo descritivo, baseado em banco de dados. A amostra é composta por 1.545 pacientes. Foram feitas tabulações cruzadas considerando as frequências absoluta e relativa. Utilizou-se o teste U de Mann-Whitney para comparar resultados entre sexos. Os aneurismas incidentais têm maior frequência relativa em mulheres. A idade de maior incidência é de 51 a 60 anos para ambos os sexos. Os fatores de risco presentes em ambos os sexos são hipertensão arterial, dislipidemia, tabagismo, diabetes e rins policísticos. As mulheres apresentam maior prevalência de aneurismas nas artérias comunicante posterior e artéria carótida interna. Os homens nas artérias comunicante anterior e artéria basilar. Os fatores de risco modificáveis são responsáveis em grande medida pelo crescimento e desenvolvimento de aneurismas. Em suma, a prevalência de aneurismas cerebrais incidentais em mulheres ocorre na proporção 3:1 em relação aos homens, porém está prevalência variou de 2:1 a 9:1 entre os anos pesquisados.

Verifying the prevalence of incidental cerebral aneurysm diagnosed by magnetic resonance imaging (MRI) between men and women. This research is a descriptive retrospective, database-based cohort study. The sample is composed of 1,545 patients. We use cross-tabulations to perform the absolute and relative frequencies. The Mann-Whitney U-Test was used to compare results between sexes. Incidental aneurysms have a higher relative frequency in women. The age of the highest incidence is 51 to 60 years for both genders. The risk factors present in both sexes are hypertension, dyslipidemia, smoking, diabetes, and polycystic kidneys. The women present a higher incidence of aneurysms in the posterior communicating arteries and internal carotid artery. For the men, there is a higher incidence of aneurysms in the anterior communicating arteries and the basilar artery. Modifiable risk factors are mostly responsible for the growth and development of aneurysms. In sum, the prevalence of incidental cerebral aneurysms in women occurs in a 3: 1 ratio to men, but this prevalence ranged from 2:1 to 9:1 among the years surveyed.

Effects of aerobic exercise training on oxidative stress in the skeletal muscles of obese rats / Efeitos do treinamento aeróbico sobre o estresse oxidativo em músculos esqueléticos de ratos obesos / Efectos del entrenamiento aeróbico sobre el estrés oxidativo en músculos esqueléticos de ratones obesos

ABSTRACT Introduction Obesity is a complex and multifactorial metabolic disorder characterized by the accumulation of body fat; physical exercise increases energy expenditure and promotes a reparative effect through modulation of endogenous antioxidant defenses. Objective To evaluate the effects of the high-fat diet (HFD) on oxidative stress parameters in skeletal muscles of rats using aerobic exercise training protocols (AETP), moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT). Methods The study was quantitative and experimental. Animals received 8 weeks of HFD or normal diet (ND), followed by 9 weeks of HFD or ND and the two AETPs. Results HFD did not alter the formation of thiobarbituric acid reactive substances (TBA-RS), total sulfhydryl and protein carbonyl content in the soleus and plantaris muscles; in contrast, the protocols caused a decrease in TBA-RS levels in the plantaris muscle and increased the sulfhydryl content in the soleus muscle, while MICT increased the sulfhydryl content in the plantaris muscle and reduced protein carbonyl content in both muscles. HFD reduced SOD activity in the plantaris muscle while the MICT protocol enhanced SOD in the soleus muscle and both protocols reversed the decrease in SOD in the plantaris muscle. HFD increased CAT activity in the soleus muscle, the HIIT protocol prevented this alteration and both protocols increased CAT in the plantaris muscle. HFD reduced GSH-Px activity in both muscles, and the MICT protocol prevented this reduction in the soleus muscle, while the HIIT protocol partially prevented this decrease. The MICT protocol did not prevent the reduction of GSH-Px and the HIIT protocol partially prevented this decrease in the plantaris muscle. Conclusions HFD elicited oxidative stress in the skeletal muscle of rats, and both protocols were able to prevent most of the alterations in oxidative stress parameters caused by the HFD. Level of evidence IV; Investigation of treatment outcomes.

RESUMO Introdução Obesidade é uma desordem metabólica complexa e multifatorial, caracterizada pelo acúmulo de gordura corporal. O exercício físico tem a capacidade de aumentar o gasto energético e promover efeito reparador por meio da modulação das defesas antioxidantes endógenas. Objetivo Avaliar os efeitos da dieta hiperlipídica (DHL) sobre parâmetros de estresse oxidativo em músculos esqueléticos de ratos, por protocolos de treinamento físico aeróbico (TFA), treinamento contínuo de intensidade moderada (TCIM) e treinamento intervalo de alta intensidade (HIIT). Métodos O estudo foi quantitativo e experimental. Animais receberam 8 semanas de DHL ou dieta normal (DN), seguidas por 9 semanas de DHL ou DN e os dois TFA. Resultados A DHL não alterou a formação de substâncias reativas ao ácido tiobarbitúrico (TBA-RS), conteúdo total de sulfidrilas e de proteínas carboniladas nos músculos sóleo e plantar. Em contraste, os protocolos diminuíram TBA-RS no músculo plantar e aumentaram o conteúdo de sulfidrilas no músculo sóleo. TCIM aumentou o conteúdo de sulfidrilas no músculo plantar e reduziu o conteúdo de proteínas carboniladas em ambos os músculos. A DHL reduziu a atividade da SOD no músculo plantar; o TCIM aumentou a SOD no músculo sóleo e ambos os protocolos reverteram a diminuição da SOD no músculo plantar. A DHL aumentou a CAT no músculo sóleo, o HIIT preveniu essa alteração e ambos os protocolos aumentaram a CAT no músculo plantar. A DHL diminuiu a atividade da GSH-Px em ambos os músculos, e o TCIM preveniu esta diminuição no músculo sóleo, enquanto que o HIIT preveniu parcialmente esta diminuição. O TCIM não preveniu a redução da GSH-Px, e o HIIT preveniu parcialmente esta diminuição no músculo plantar. Conclusão A DHL causou estresse oxidativo nos músculos esqueléticos de ratos, e ambos os protocolos foram capazes de prevenir a maioria das alterações nos parâmetros de estresse oxidativo causadas pela DHL. Nível de evidência IV; Investigação dos resultados do tratamento.

RESUMEN Introducción La obesidad es un desorden metabólico complejo y multifactorial caracterizado por la acumulación de grasa corporal. El ejercicio físico tiene la capacidad de aumentar el gasto energético y promover efecto reparador por medio de la modulación de las defensas antioxidantes endógenas. Objetivos Evaluar los efectos de la dieta hiperlipídica (DHL) sobre parámetros de estrés oxidativo en los músculos esqueléticos de las ratas, por protocolos de entrenamiento físico aeróbico (TFA), entrenamiento continuo de intensidad moderada (TCIM) y entrenamiento de intervalo de alta intensidad (HIIT). Métodos El estudio fue cuantitativo y experimental. Los animales recibieron ocho semanas de DHL o dieta normal (DN), seguidas por nueve semanas de DHL o DN y los dos TFA. Resultados La DHL no alteró la formación de sustancias reactivas al ácido tiobarbitúrico (TBA-RS), contenido total de sulfhidrilos y de proteínas carboniladas en los músculos sóleo y plantar. En contraste, los protocolos disminuyeron TBA-RS en el músculo plantar y aumentaron el contenido de sulfhidrilos en el músculo sóleo. TCIM aumentó el contenido de sulfhidrilos en el músculo plantar y redujo el contenido de proteínas carboniladas en ambos músculos. La DHL redujo la actividad de la SOD en el músculo plantar, el TCIM aumentó la SOD en el músculo sóleo y ambos protocolos revirtieron la disminución de la SOD en el músculo plantar. La DHL aumentó la CAT en el músculo sóleo, el HIIT previno esa alteración y ambos protocolos aumentaron la CAT en el músculo plantar. La DHL disminuyó la actividad de GSH-Px en ambos músculos, y el TCIM previno esta disminución en el músculo sóleo, mientras que el HIIT previno parcialmente esta disminución. El TCIM no previno la reducción de la GSH-Px y el HIIT previno parcialmente esta disminución en el músculo plantar. Conclusión La DHL causó estrés oxidativo en los músculos esqueléticos de ratones y ambos protocolos fueron capaces de prevenir la mayoría de las alteraciones en los parámetros de estrés oxidativo causados por DHL. Nivel de evidencia IV; Investigación de los resultados del tratamiento.

Simvastatin treatment reduces the cholesterol content of membrane/lipid rafts, implicating the N -methyl-D-aspartate receptor in anxiety: a literature review

ABSTRACT Membrane/lipid rafts (MLRs) are plasmalemmal microdomains that are essential for neuronal signaling and synaptic development/stabilization. Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase (statins) can disable the N-methyl-D-aspartate (NMDA) receptor through disruption of MLRs and, in turn, decrease NMDA-mediated anxiety. This hypothesis will contribute to understanding the critical roles of simvastatin in treating anxiety via the NMDA receptor.

Acute Administration of Diazepam Provokes Redox Homeostasis Imbalance in the Rat Brain: Prevention by Simvastatin.

We investigated the effects of acute diazepam (DZP) administration on thiobarbituric acid-reactive substance (TBARS) levels, protein carbonyl content, and on the activities of the antioxidant enzymes catalase, glutathione peroxidase, and superoxide dismutase in the brain of rats. Additionally, we investigated the antioxidant role of chronic pretreatment with simvastatin on the effects provoked by DZP. Simvastatin was administered (1 or 10 mg/kg by oral gavage) for 30 days. On the 30th day of treatment, groups were randomized and DZP was administered (0.5 or 1.0 mg/kg by intraperitoneal injection). Control groups received saline. Results showed that DZP enhanced TBARS levels and protein carbonyl content and altered enzymatic activity in the brain of rats. Simvastatin prevented most of the alterations caused by DZP on the oxidative stress parameters. Data indicate that DZP administration causes an oxidative imbalance in the brain areas studied; however, in the presence of simvastatin, some of these alterations in oxidative stress were prevented.

Ferulic acid chronic treatment exerts antidepressant-like effect: role of antioxidant defense system.

Oxidative stress has been claimed a place in pathophysiology of depression; however, the details of the neurobiology of this condition remains incompletely understood. Recently, treatments employing antioxidants have been thoroughly researched. Ferulic acid (FA) is a phenolic compound with antioxidant and antidepressant-like effects. Herein, we investigated the involvement of the antioxidant activity of chronic oral FA treatment in its antidepressant-like effect using the tail suspension test (TST) and the forced swimming test (FST) in mice. The modulation of antioxidant system in blood, hippocampus and cerebral cortex was assessed after stress induction through TST and FST. Our results show that FA at the dose of 1 mg/kg has antidepressant-like effect without affecting locomotor activity. The stress induced by despair tests was able to decrease significantly the activities of superoxide dismutase (SOD) in the blood, catalase (CAT) in the blood and cerebral cortex and glutathione peroxidase (GSH-Px) in the cerebral cortex. Thiobarbituric acid-reactive substances (TBA-RS) levels were increased significantly in the cerebral cortex. Furthermore, the results show that FA was capable to increase SOD, CAT and GSH-Px activities and decrease TBA-RS levels in the blood, hippocampus and cerebral cortex. These findings demonstrated that FA treatment in low doses is capable to exert antidepressant-like effect with the involvement of the antioxidant defense system modulation.

Differential in vitro effects of homoarginine on oxidative stress in plasma, erythrocytes, kidney and liver of rats in the absence and in the presence α-tocopherol, ascorbic acid or L-NAME.

In the present study, we evaluated the in vitro effects of homoarginine (hArg) at 1, 10 and 20 µM on thiobarbituric acid-reactive substances (TBA-RS), total sulfhydryl content and on the activity of the antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in plasma, erythrocytes, kidney and liver of rats (60 days old). We also investigated the influence of the antioxidants (each at 1 mM) α-tocopherol and ascorbic acid, as well as of the nitric oxide synthase inhibitor N (G)-nitro-L-arginine methyl ester (L-NAME) at 1 mM, on the effects elicited by hArg on the parameters tested. In plasma, hArg at concentrations of 10 and 20 µM decreased moderately the total sulfhydryl content. At 20 µM, hArg enhanced moderately TBA-RS in the plasma. In plasma, the effects of hArg (20 µM) on TBA-RS and total thiol content were abolished by α-tocopherol, ascorbic acid and L-NAME. At all concentrations tested, hArg did not exert any effect on CAT, SOD or GSH-Px activity in the erythrocytes. In the kidney, hArg exerted effects only at 20 µM and in a different manner: TBA-RS levels increased and total thiol content and CAT activity decreased, while SOD and GSH-Px activity increased. In the renal medulla, α-tocopherol and ascorbic acid but not L-NAME abolished the effects of hArg (20 µM) on TBA-RS, while all agents inhibited the hArg-induced increase in SOD activity. In the renal cortex, α-tocopherol, ascorbic acid and L-NAME abolished the effects of hArg (20 µM) on the total sulfhydryl content and GSH-Px activity, but L-NAME did not reverse the inhibitory effects of hArg on CAT activity. In the liver, no effects of hArg were observed of all biomarkers measured. At the pathologically high concentration of 20 µM, as it may occur in plasma in hyperargininemia, hArg may enhance lipid peroxidation and thiol oxidation and inhibit CAT activity, but may increase SOD and GSH-Px activity predominantly in the kidney.

Efeitos da fração acetato de etila de Tabernaemontana catharinensis sobre respostas glicêmicas e estresse oxidativo de Rattus norvegicus diabéticos / Effects of tabernaemontana catharinensis ethyl acetate fraction on glycemic responses and oxidative stress

OBJECTIVE: To evaluate the Tabernaemontana catharinensis ethyl acetate fraction hypoglycemic and antioxidant activity through the peripheral glycemic dosage and enzymatic tests. Methods: Male rats were divided into 6 groups: control, diabetic control, control extract 50, diabetic extract 50, control extract 80, diabetic extract 80. In diabetic group animals alloxan (150mg/Kg) was administered to induce Diabetes Mellitus. The animals were beheaded following 15 days of treatment with extract or distilled water and the blood was collected in order to perform oxidative stress tests. Results: The diabetic control group showed high levels of glucose, increased levels of thiobarbituric acid and superoxide dismutase activity, and decreased activity of catalase and glutathione peroxidase enzymes. The diabetic animals that received 50mg/Kg and 80mg/Kg of extract showed a decrease in thiobarbituric acid levels and an increase of glutathione peroxidase activity when compared to the diabetic control group. It was observed that only animals treated with 80mg/Kg of extract had positive results regarding superoxide dismutase. Conclusions: The Tabernaemontana catharinensis ethyl acetate fraction when orally administered for 14 consecutive days at doses of 50mg/Kg and 80mg/Kg reduces the oxidative stress induced by alloxan administration

OBJETIVO: Avaliar a ação hipoglicemiante e antioxidante da fração acetato de etila do extrato de Tabernaemontana catharinensis através da dosagem glicêmica periférica e testes enzimáticos. MÉTODOS: Ratos machos foram divididos em seis grupos: controle, controle diabético, controle extrato 50, diabético extrato 50, controle extrato 80, diabético extrato 80. Nos animais dos grupos diabéticos foi induzida Diabetes Mellitus pela administração de 150mg/Kg de aloxana. Após 15 dias de tratamento com a fração acetato de etila de Tabernaemontana catharinensis ou água destilada, os animais foram decapitados e o sangue foi coletado para realização dos testes de estresse oxidativo. RESULTADOS: O grupo controle diabético apresentou níveis elevados de glicose, aumento dos níveis de ácido tiobarbitúrico e atividade da superóxido dismutase, e diminuição da atividade das enzimas catalase e glutationa peroxidase. Os animais dos grupos diabéticos tratados com 50 e 80mg/Kg do extrato apresentaram redução nos níveis de ácido tiobarbitúrico e aumento da atividade de glutationa peroxidase quando comparado ao grupo controle diabético. Apenas os animais que receberam o extrato na dose de 80mg/Kg obtiveram resultados positivos em relação ao superóxido dismutase. CONCLUSÕES: A fração acetato de etila de Tabernaemontana catharinensis, quando administrada por 14 dias consecutivos, via oral, nas doses de 50 e 80mg/Kg, promove redução nos níveis de estresse oxidativo gerado pela administração de aloxana

Guanidinoacetate alters antioxidant defenses and butyrylcholinesterase activity in the blood of rats

Deficiency of guanidinoacetate methyltransferase, the first described creatine biosynthesis defect, leads to depletion of creatine and phosphocreatine, and accumulation of guanidinoacetate (GAA) in brain and body fluids. The present study aimed to investigate the influence of GAA on the activities of antioxidant enzymes, as well as on thiobarbituric acid-reactive substances (TBARS) and butyrylcholinesterase (BuChE) activity in the blood of rats. We also evaluated the effect of trolox (6-hydr oxy-2,5,7,8-tetramethylchroman-2-carboxylic acid), GSH (glutathione) and L-NAME (NG-nitro-L-arginine methyl ester) on the alterations elicited by GAA. Methods: The rats were randomly divided into 8 groups: (1) control; (2) GAA (10, 30, 50, 100 mM/kg); (3) trolox (1 mM/kg) + control; (4) trolox (1 mM/kg) + GAA (100 mM/kg); (5) GSH (1 mM/kg) + control; (6) GSH (1 mM/kg) + GAA (100 mM/kg); (7) L-NAME (1 mM/kg) + control; (8) L-NAME + GAA (100 mM/kg). After the addition of compounds, erythrocytes and plasma were pre-incubated at 37°C for 1h and tested immediately. Results: GAA enhanced the activities of catalase (CAT) and glutathione peroxidase (GSH-Px) in the erythrocytes and BuChE activity. In addition, GAA enhanced TBARS levels in the plasma. Trolox, GSH and L-NAME addition prevented the majority of alterations in oxidative stress parameters and the increase of BuChE activity that were caused by GAA. Data suggest that GAA alters antioxidant defenses and induces lipid peroxidation in the blood, as well altering BuChE activity. However, in the presence of trolox, GSH and L-NAME some of these alterations in oxidative stress and BuChE activity were prevented. Conclusions: Our findings lend support to a potential therapeutic strategy for this condition, which may include the use of appropriate antioxidants for ameliorating the damage caused by GAA...

Hypoxanthine induces oxidative stress in kidney of rats: protective effect of vitamins E plus C and allopurinol.

In the present study, we investigated the in vitro effect of hypoxanthine on the activities of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase, as well as on thiobarbituric-acid-reactive substances (TBA-RS), in the renal cortex and medulla of rats. Results showed that hypoxanthine, at a concentration of 10.0 µM, enhanced the activities of CAT and SOD in the renal cortex of 15-, 30- and 60-day-old rats, enhanced SOD activity in the renal medulla of 60-day-old rats and enhanced TBA-RS levels in the renal medulla of 30-day-old rats, as compared with controls. Furthermore, we also verified the influence of allopurinol (an inhibitor of xanthine oxidase), as well as of the antioxidants, trolox and ascorbic acid on the effects elicited by hypoxanthine on the parameters tested. Allopurinol and/or administration of antioxidants prevented most alterations caused by hypoxanthine in the oxidative stress parameters evaluated. Data suggest that hypoxanthine alters antioxidant defences and induces lipid peroxidation in the kidney of rats; however, in the presence of allopurinol and antioxidants, some of these alterations in oxidative stress were prevented. Our findings lend support to a potential therapeutic strategy for this condition, which may include the use of appropriate antioxidants for ameliorating the damage caused by hypoxanthine.

Adjuvant effects of classical music on simvastatin induced reduction of anxiety but not object recognition memory in rats

Simvastatin is one of many hydroxymethylglutaryl-coenzyme-A reductase inhibitors that are prescribed to lower cholesterol. Some emerging evidence indicates that classical music can serve as an effective adjuvant in rats treated with simvastatin. Moreover, simvastatin and classical music have been shown to influence some cognitive functions. To further understand the mechanisms of action, we exposed rats to classical music for 1 month, and then treated them orally with simvastatin. The behavioral experiments suggested that exposure to subchronic simvastatin (1 or 10 mg/kg/day) reduced anxiety levels in the elevated plus-maze and open-field test in rats exposed to Mozart music. The recognition object test results indicated that simvastatin altered non-spatial working memory only at the 1 mg/kg/day dose and improved both short- and long-term object recognition. No significant differences were found between Mozart music and silence in the object recognition test, suggesting that music did not significant affect learning and memory in adult rats. We hypothesize that the anxiolytic, but not object-recognition memory, effects of simvastatin and classical music occur through similar mechanisms, providing an important foundation for future preclinical and clinical research...

In vitro stimulation of oxidative stress by hypoxanthine in blood of rats: prevention by vitamins e plus C and allopurinol.

We herein investigated the in vitro effect of hypoxanthine on the activities of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) in erythrocytes, as well as on thiobarbituric acid-reactive substances (TBA-RS), in the plasma of rats. Results showed that hypoxanthine, when added to the incubation medium, enhanced CAT (10.0 µM), GSH-Px and SOD (8.5 µM and 10.0 µM) activities in erythrocytes of 15-day-old rats, reduced CAT activity (10.0 µM) and enhanced GSH-Px activity (10.0 µM) in erythrocytes of 30-day-old rats, reduced CAT activity (10.0 µM) and enhanced GSH-Px activity (8.5 µM and 10.0 µM) in erythrocytes of 60-day-old rats, as compared to controls. In addition, hypoxanthine (10.0 µM) enhanced TBA-RS levels in the plasma of 30- and 60-day old rats. Furthermore, we also tested the influence of allopurinol, trolox, and ascorbic acid on the effects elicited by hypoxanthine on the antioxidant enzymes and TBA-RS. Allopurinol and/or administration of antioxidants prevented most alterations caused by hypoxanthine in the oxidative stress parameters evaluated. Findings suggest that hypoxanthine alters antioxidant defenses and induces lipid peroxidation in the blood of rats; however, in the presence of allopurinol and antioxidants, some of these alterations in oxidative stress caused are prevented. Data indicate that, in humans, antioxidant administration might serve as a potential adjuvant therapy for ameliorating the damage caused by hypoxanthine.

Adjuvant effects of classical music on simvastatin induced reduction of anxiety but not object recognition memory in rats

Simvastatin is one of many hydroxymethylglutaryl-coenzyme-A reductase inhibitors that are prescribed to lower cholesterol. Some emerging evidence indicates that classical music can serve as an effective adjuvant in rats treated with simvastatin. Moreover, simvastatin and classical music have been shown to influence some cognitive functions. To further understand the mechanisms of action, we exposed rats to classical music for 1 month, and then treated them orally with simvastatin. The behavioral experiments suggested that exposure to subchronic simvastatin (1 or 10 mg/kg/day) reduced anxiety levels in the elevated plus-maze and open-field test in rats exposed to Mozart music. The recognition object test results indicated that simvastatin altered non-spatial working memory only at the 1 mg/kg/day dose and improved both short- and long-term object recognition. No significant differences were found between Mozart music and silence in the object recognition test, suggesting that music did not significant affect learning and memory in adult rats. We hypothesize that the anxiolytic, but not object-recognition memory, effects of simvastatin and classical music occur through similar mechanisms, providing an important foundation for future preclinical and clinical research.(AU)

The effects of swimming exercise on recognition memory for objects and conditioned fear in rats / Os efeitos do exercício de natação sobre a memória para reconhecimento de objetos e de medo condicionados em ratos

Experiments conducted in animals have repeatedly demonstrated the ability of exercise to enhance cognitive function. This study examines the effects of chronic swimming exercise on non-spatial memory in adult rats after 12 weeks of swimming exercise in object recognition and elevated T-maze tests. In the object recognition test, repeated measures analysis of variance revealed a group effect (F1,42 = 26,093; p < 0.001), control rats had lower discrimination ratios than the exercise group. However, the swimming exercise did not affect the performance of inhibitory avoidance and escapes, when memory was tested in elevated T-maze. Analysis of variance showed a significant reduction in inhibitory avoidance 24h after the first training (F1,42 = 14,552; p < 0.001). Results indicated that regular swimming exercise significantly increased non-spatial memory in object recognition behavior, but did not affect the performance of inhibitory avoidance and escape on elevated T-maze test in adult rats. These findings suggest that the perirhinal cortex plays a role in memory consolidation and storage in addition to that of the amygdala, which could be regarded as the center of a second memory system, separate from those governed by the perirhinal cortex.

As experiências realizadas em animais mostram a capacidade do exercício em melhorar as funções cognitivas. Este estudo analisa os efeitos do exercício crônico de natação sobre a memória não-espacial em ratos adultos após 12 semanas de exercício de natação nos testes de reconhecimento de objetos e labirinto em T elevado. O teste de reconhecimento de objetos, pelas repetidas análises de variância revelaram um efeito de grupo (F1,42 = 26.093; p < 0,001), os ratos controles discriminaram uma razão inferior ao do grupo de exercício. Entretanto, o exercício de natação não afetou o desempenho de esquiva inibitória e escape, quando a memória foi testada no labirinto em T elevado. Análise de variância mostrou redução significativa na esquiva inibitória 24h após o primeiro treino (F1,42 = 14.552; p < 0,001). Os resultados indicam que o exercício regular de natação aumenta significativamente a memória não-espacial no comportamento de reconhecimento de objetos, mas não afeta o medo condicionado no teste do labirinto em T elevado em ratos adultos. Estes resultados sugerem que o córtex peririnal desempenha papel nos processos de consolidação e armazenamento de memória além da amígdala, podendo esta ser encarada como um segundo centro de sistema de memória, separada dos regidos pelo córtex peririnal.

Behavioral interactions of simvastatin and fluoxetine in tests of anxiety and depression.

Simvastatin inhibits 3-hydroxy-3-methylglutaryl CoA reductase, the rate-limiting enzyme in the cholesterol biosynthetic pathway, and is widely used to control plasma cholesterol levels and prevent cardiovascular disease. However, emerging evidence indicates that the beneficial effects of simvastatin extend to the central nervous system. The effects of simvastatin combined with fluoxetine provide an exciting and potential paradigm to decreased anxiety and depression. Thus, the present paper investigates the possibility of synergistic interactions between simvastatin and fluoxetine in models of anxiety and depression. We investigated the effects of subchronically administered simvastatin (1 or 10 mg/kg/day) combined with fluoxetine (2 or 10 mg/kg) at 24, 5, and 1 hour on adult rats before conducting behavioral tests. The results indicate that simvastatin and/or fluoxetine treatment reduces anxiety-like behaviors in the elevated plus-maze and open-field tests. Our results showed that simvastatin and/or fluoxetine induced a significant increase in the swimming activity during the forced swimming test (antidepressant effect), with a concomitant increase in climbing time in simvastatin-treated animals only (noradrenergic activation). We hypothesize that anxiolytic and antidepressant effects of simvastatin and/or fluoxetine produce their behavioral effects through similar mechanisms and provide an important foundation for future preclinical research.