RESUMEN

Purpose: Type 2 diabetic (T2D) patients have liver and adipose tissue microcirculation disturbances associated with metabolic dysfunction and disease progression. However, the potential role of aerobic training on hepatic and white adipose tissue (WAT) microcirculation and the underlying mechanisms have not been elucidated to date. Therefore, we investigated the role of aerobic training on liver and WAT microcirculation and AGE-RAGE modulation in T2D mice. Methods: The control group (CTL) was fed standard chow, and T2D was induced by feeding male C57BL/6 a high-fat, high-carbohydrate diet for 24 weeks. In the following 12 weeks, mice underwent aerobic training (CTL EX and T2D EX groups), or were kept sedentary (CTL and T2D groups). We assessed metabolic parameters, biochemical markers, oxidative damage, the AGE-RAGE axis, hepatic steatosis, hepatic stellate cells activation (HSC) and liver and WAT microcirculation. Results: Hepatic microcirculation was improved in T2D EX mice which were associated with improvements in body, liver and fat mass, blood pressure, hepatic steatosis and fibrosis, and decreased HSC and AGE-RAGE activation. In contrast, improvement in WAT microcirculation, that is, decreased leukocyte recruitment and increased perfusion, was associated with increased catalase antioxidant activity. Conclusion: Physical training improves hepatic and adipose tissue microcirculatory dysfunction associated with T2D, likely due to downregulation of AGE-RAGE axis, decreased HSC activation and increased antioxidant activity.

RESUMEN

Dengue is a mosquito-borne viral disease caused by the dengue virus (DENV1-4). The clinical manifestations range from asymptomatic to life-threatening dengue hemorrhagic fever (DHF) and/or Dengue Shock Syndrome (DSS). Viral and host factors are related to the clinical outcome of dengue, although the disease pathogenesis remains uncertain. The innate antiviral response to DENV is implemented by a variety of immune cells and inflammatory mediators. Blood monocytes, dendritic cells (DCs) and tissue macrophages are the main target cells of DENV infection. These cells recognize pathogen-associated molecular patterns (PAMPs) through pattern recognition receptors (PRRs). Pathogen recognition is a critical step in eliciting the innate immune response. Toll-like receptors (TLRs) are responsible for the innate recognition of pathogens and represent an essential component of the innate and adaptive immune response. Ten different TLRs are described in humans, which are expressed in many different immune cells. The engagement of TLRs with viral PAMPs triggers downstream signaling pathways leading to the production of inflammatory cytokines, interferons (IFNs) and other molecules essential for the prevention of viral replication. Here, we summarize the crucial TLRs' roles in the antiviral innate immune response to DENV and their association with viral pathogenesis.

Asunto(s)

Dengue , Inmunidad Innata , Moléculas de Patrón Molecular Asociado a Patógenos , Receptores Toll-Like , Dengue/inmunología , Virus del Dengue , Humanos , Moléculas de Patrón Molecular Asociado a Patógenos/inmunología , Receptores Toll-Like/inmunología

RESUMEN

Chikungunya virus (CHIKV) infection causes intense cytokine/chemokine inflammatory responses and debilitating joint pain. Indoleamine2,3-dioxygenase 1 (IDO-1) is an enzyme that initiates the tryptophan degradation that is important in initial host innate immune defense against infectious pathogens. Besides that, IDO-1 activation acts as a regulatory mechanism to prevent overactive host immune responses. In this study, we evaluated IDO-1 activity and cytokine/chemokine patterns in CHIKV patients. Higher IDO-1 (Kyn/Trp ratio) activation was observed during the early acute phase of CHIKV infection and declined in the chronic phase. Importantly, increased concentrations of Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), Interferon γ (IFN-γ), C-C motif chemokine ligand 2/Monocyte Chemoattractant Protein-1 (CCL2/MCP-1) and C-X-C motif chemokine ligand 10/Interferon Protein-10 (CXCL10/IP-10) were found in the acute phase of infection, while C-C motif chemokine ligand 4/Macrophage Inflammatory Protein 1 ß (CCL4/MIP-1ß) was found at increased concentrations in the chronic phase. Likewise, CHIKV patients with arthritis had significantly higher concentrations of CCL4/MIP-1ß compared to patients without arthritis. Taken together, these data demonstrated increased IDO-1 activity, possibly exerting both antiviral effects and regulating exacerbated inflammatory responses. CCL4/MIP-1ß may have an important role in the persistent inflammation and arthritic symptoms following chikungunya infection.

RESUMEN

Advances in knowledge of the pathophysiology of COVID-19 have been acquired; however, the host factors that could explain the mild and severe forms of the disease are not fully understood. Thus, we proposed to evaluate anti-SARS-CoV-2 antibodies and the inflammatory response of different groups of individuals, including healthcare workers (HCW), sick and dead COVID-19 patients and also recovered patients to contribute to this knowledge gap. Our objective is to relate the clinical evolution of these individuals with the level of detection and functionality of specific antibodies and with the production of inflammatory mediators. As main findings, IgA and IgG anti-SARS-CoV-2 were detected in asymptomatic HCW. IFN-γ and TNF-α levels were higher in symptomatic HCWs than patients with COVID-19 and those who died. Patients who died had higher levels of IL-6, IL-10, and CCL2/MCP-1. We found an imbalance between antiviral and pro-inflammatory mediators in the groups, in which IFN-γ and TNF-α seem to be more associated with protection and IL-6 and CCL2/MCP-1 with pathology. Our work is pioneering the Brazilian population and corroborates data from people from other countries.

Asunto(s)

COVID-19 , SARS-CoV-2 , Anticuerpos Antivirales , Personal de Salud , Humanos , Mediadores de Inflamación

RESUMEN

Increased reactive oxidative stress, lipid peroxidation, inflammation, and fibrosis, which contribute to tissue damage and development and progression of nonalcoholic liver disease (NAFLD), play important roles in microcirculatory disorders. We investigated the effect of the modulatory properties of simvastatin (SV) on the liver and adipose tissue microcirculation as well as metabolic and oxidative stress parameters, including the advanced lipoxidation end product-receptors of advanced glycation end products (ALE-RAGE) pathway. SV was administered to an NAFLD model constructed using a high-fat-high-carbohydrate diet (HFHC). HFHC caused metabolic changes indicative of nonalcoholic steatohepatitis; treatment with SV protected the mice from developing NAFLD. SV prevented microcirculatory dysfunction in HFHC-fed mice, as evidenced by decreased leukocyte recruitment to hepatic and fat microcirculation, decreased hepatic stellate cell activation, and improved hepatic capillary network architecture and density. SV restored basal microvascular blood flow in the liver and adipose tissue and restored the endothelium-dependent vasodilatory response of adipose tissue to acetylcholine. SV treatment restored antioxidant enzyme activity and decreased lipid peroxidation, ALE-RAGE pathway activation, steatosis, fibrosis, and inflammatory parameters. Thus, SV may improve microcirculatory function in NAFLD by downregulating oxidative and ALE-RAGE stress and improving steatosis, fibrosis, and inflammatory parameters.

Asunto(s)

Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Microcirculación , Enfermedad del Hígado Graso no Alcohólico/etiología , Estrés Oxidativo/fisiología , Simvastatina/farmacología , Simvastatina/uso terapéutico

RESUMEN

Obesity is recognized as an independent risk factor for cardiovascular diseases and is an important contributor to cardiac mortality. Açaí seed extract (ASE), rich in proanthocyanidins, has been shown to have potential anti-obesity effects. This study aimed to investigate the therapeutic effect of ASE in cardiovascular remodeling associated with obesity and compare it with that of rosuvastatin. Male C57BL/6 mice were fed a high-fat diet or a standard diet for 12 weeks. The ASE (300 mg/kg/day) and rosuvastatin (20 mg/kg/day) treatments started in the 8th week until the 12th week, totaling 4 weeks of treatment. Our data showed that treatment with ASE and rosuvastatin reduced body weight, ameliorated lipid profile, and improved cardiovascular remodeling. Treatment with ASE but not rosuvastatin reduced hyperglycemia and oxidative stress by reducing immunostaining of 8-isoprostane and increasing SOD-1 and GPx expression in HFD mice. ASE and rosuvastatin reduced NOX4 expression, increased SIRT-1 and Nrf2 expression and catalase and GPx activities, and improved vascular and cardiac remodeling in HFD mice. The therapeutic effect of ASE was similar to that of rosuvastatin in reducing dyslipidemia and cardiovascular remodeling but was superior in reducing oxidative damage and hyperglycemia, suggesting that ASE was a promising natural product for the treatment of cardiovascular alterations associated with obesity.

Asunto(s)

Antioxidantes/uso terapéutico , Cardiomegalia/tratamiento farmacológico , Obesidad/metabolismo , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Remodelación Ventricular/efectos de los fármacos , Animales , Cardiomegalia/etiología , Dieta Alta en Grasa , Euterpe/química , Masculino , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/complicaciones , Proantocianidinas/uso terapéutico , Semillas/química

RESUMEN

Early weaning can predispose the offspring to greater risk of developing chronic diseases in adulthood. It is believed that the consumption of functional foods is able to prevent these effects. The aim of this study is to evaluate the effects of maternal and postnatal cocoa powder supplementation on body mass, metabolism, and morphology of the prostate of early weaned Wistar rats. The animals were divided into four experimental groups according to lactation time (21 or 18 days, n=6, each) as follows: control group (C), cocoa control group (CCa), early weaning group (EW), and cocoa early weaning group (EWCa). The animals were euthanized at 90 days of age. Serum biochemical analysis and prostate histomorphometric evaluation were performed. The animals supplemented with cocoa powder were heavier than their respective controls (p <0.05), although with no difference in food intake among the groups. Likewise, these same groups showed a reduction in the serum glucose in relation to C and EW groups (p <0.0001). With respect to the prostate, there was no difference in smooth muscle and lumen area densities, while the EW group had a lower epithelial height and a higher percentage of mast cells than the C group (p <0.05). On the other hand, the EWCa group managed to reverse these parameters, leveling with the controls. Early weaning resulted in hyperglycemia and important morphological changes in the prostate. In contrast, dietary supplementation with cocoa powder attenuated these effects on the metabolism and prostatic histoarchitecture, proving to be a good nutritional treatment strategy.

Asunto(s)

Chocolate , Obesidad , Animales , Suplementos Dietéticos , Femenino , Masculino , Ratas , Ratas Wistar , Destete

RESUMEN

Background: Zika virus (ZIKV) infection causes for mild and self-limiting disease in healthy adults. In newborns, it can occasionally lead to a spectrum of malformations, the congenital Zika syndrome (CZS). Thus, little is known if mothers and babies with a history of ZIKV infection were able to develop long-lasting T-cell immunity. To these issues, we measure the prevalence of ZIKV T-cell immunity in a cohort of mothers infected to the ZIKV during pregnancy in the 2016-2017 Zika outbreak, who gave birth to infants affected by neurological complications or asymptomatic ones. Results: Twenty-one mothers and 18 children were tested for IFN-γ ELISpot and T-cell responses for flow cytometry assays in response to CD4 ZIKV and CD8 ZIKV megapools (CD4 ZIKV MP and CD8 ZIKV MP). IFN-γ ELISpot responses to ZIKV MPs showed an increased CD4 and CD8 T-cell responses in mothers compared to children. The degranulation activity and IFN-γ-producing CD4 T cells were detected in most mothers, and children, while in CD8 T-cells, low responses were detected in these study groups. The total Temra T cell subset is enriched for IFN-γ+ CD4 T cells after stimulation of CD4 ZIKV MP. Conclusion: Donors with a history of ZIKV infection demonstrated long-term CD4 T cell immunity to ZIKV CD4 MP. However, the same was not observed in CD8 T cells with the ZIKV CD8 MP. One possibility is that the cytotoxic and pro-inflammatory activities of CD8 T cells are markedly demonstrated in the early stages of infection, but less detected in the disease resolution phase, when the virus has already been eliminated. The responses of mothers' T cells to ZIKV MPs do not appear to be related to their children's clinical outcome. There was also no marked difference in the T cell responses to ZIKV MP between children affected or not with CZS. These data still need to be investigated, including the evaluation of the response of CD8 T cells to other ZIKV peptides.

Asunto(s)

Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Memoria Inmunológica , Infección por el Virus Zika/inmunología , Virus Zika/inmunología , Adulto , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Linfocitos T CD8-positivos/metabolismo , Reacciones Cruzadas/inmunología , Estudios Transversales , Femenino , Humanos , Inmunidad Materno-Adquirida , Inmunofenotipificación , Pruebas de Neutralización , Embarazo , Complicaciones Infecciosas del Embarazo , Adulto Joven , Infección por el Virus Zika/sangre , Infección por el Virus Zika/epidemiología

RESUMEN

NEW FINDINGS: What is the central question of this study? What are the mechanisms underlying the cardiac protective effect of aerobic training in the progression of a high fructose-induced cardiometabolic disease in Wistar rats? What is the main finding and its importance? At the onset of cardiovascular disease, aerobic training activates the p-p70S6K, ERK and IRß-PI3K-AKT pathways, without changing the miR-126 and miR-195 levels, thereby providing evidence that aerobic training modulates the insulin signalling pathway. These data contribute to the understanding of the molecular cardiac changes that are associated with physiological left ventricular hypertrophy during the development of a cardiovascular disease. ABSTRACT: During the onset of cardiovascular disease (CVD), disturbances in myocardial vascularization, cell proliferation and protein expression are observed. Aerobic training prevents CVD, but the underlying mechanisms behind left ventricle (LV) hypertrophy are not fully elucidated. The aim of this study was to investigate the mechanisms by which aerobic training protects the heart from LV hypertrophy during the onset of fructose-induced cardiometabolic disease. Male Wistar rats were allocated to four groups (n = 8/group): control sedentary (C), control training (CT), fructose sedentary (F) and fructose training (FT). The C and CT groups received drinking water, and the F and FT groups received d-fructose (10% in water). After 2 weeks, the CT and FT rats were assigned to a treadmill training protocol at moderate intensity for 8 weeks (60 min/day, 4 days/week). After 10 weeks, LV morphological remodelling, cardiomyocyte apoptosis, microRNAs and the insulin signalling pathway were investigated. The F group had systemic cardiometabolic alterations, which were normalised by aerobic training. The LV weight increased in the FT group, myocardium vascularisation decreased in the F group, and the cardiomyocyte area increased in the CT, F and FT groups. Regarding protein expression, total insulin receptor ß-subunit (IRß) decreased in the F group; phospho (p)-IRß and phosphoinositide 3-kinase (PI3K) increased in the FT group; total-AKT and p-AKT increased in all of the groups; p-p70S6 kinase (p70S6K) protein was higher in the CT group; and p-extracellular signal-regulated kinase (ERK) increased in the CT and FT groups. MiR-126, miR-195 and cardiomyocyte apoptosis did not differ among the groups. Aerobic training activates p-p70S6K and p-ERK, and during the onset of a CVD, it can activate the IRß-PI3K-AKT pathway.

Asunto(s)

Enfermedades Cardiovasculares , MicroARNs , Condicionamiento Físico Animal , Animales , Enfermedades Cardiovasculares/metabolismo , Fructosa/metabolismo , Masculino , Redes y Vías Metabólicas , MicroARNs/metabolismo , Miocitos Cardíacos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Condicionamiento Físico Animal/fisiología , Ratas , Ratas Wistar

RESUMEN

Early weaning can lead to changes in the morphology of organs in adulthood, and the consumption of functional foods during lactation and postnatal life is believed to prevent these changes. However, it is not known if early weaning affects testicular morphology and if the use of cocoa can prevent that. We studied the effects of maternal and postnatal supplementation of cocoa powder on the testicular morphology of early weaned adult rats. The animals were divided into four groups (n = 6 each), control group, cocoa control group, early weaning (EW) group, and cocoa early weaning (EWCa) group, and were analyzed for 90 d, after which they were euthanized. The animals from the EW group showed a reduction in the tubular diameter and height of the seminiferous epithelium, a decrease in epithelial surface density (Sv), and an increase in the lumen and proper tunic. However, the animals from the EWCa group showed an increase in the diameter and height of the epithelium, an increase in the epithelium Sv, and a decrease in the lumen and the proper tunic. The early weaning promotes morphological changes in the testicles; however, supplementation with cocoa powder can preserve the testicular histoarchitecture.

Asunto(s)

Chocolate , Fenómenos Fisiologicos Nutricionales Maternos , Testículo/crecimiento & desarrollo , Destete , Animales , Suplementos Dietéticos , Femenino , Masculino , Embarazo , Ratas Wistar

RESUMEN

Animal models are widely used to study the physiopathology of human diseases. However, the influence of gender on modern society diet style-induced cardiovascular disease has not thus far been explored in these models. Thus, this study investigated cardiovascular remodelling in C57BL/6J mice fed a diet rich in saturated fat, sucrose and salt, evaluating gender effect on this process. Male and female C57BL/6J mice were fed AIN93M diet or a modified AIN93M rich in fat, sucrose and salt (HFSS) for 12 weeks. Body mass, water and food intake and cardiovascular remodelling were assessed. The HFSS diet did not lead to body mass gain or glucose metabolism disturbance as assessed by serum glucose, insulin and oral glucose tolerance test. However, female mice on a HFSS diet had increased visceral and subcutaneous adiposity. Only male mice displayed heart hypertrophy. The left ventricle was not hypertrophied in either male or female mice, but its lumen was dilated. Intramyocardial arteries and the thoracic aorta showed media thickening in male mice, but in the female it was only observed in the thoracic aorta. Finally, intramyocardial artery dilation was present in both genders, but not in the aorta. Therefore changes in LV dimensions and arterial remodelling were influenced by both gender and the HFSS diet. In conclusion, male and female C57BL/6J mice suffered cardiovascular remodelling after 12 weeks of HFSS feeding, although they did not develop obesity or diabetes. Sexual dimorphism occurred in response to diet for body adiposity, heart hypertrophy and intramyocardial artery remodelling.

Asunto(s)

Dieta Alta en Grasa , Obesidad/metabolismo , Sacarosa/metabolismo , Animales , Grasas de la Dieta/farmacología , Ratones Endogámicos C57BL , Modelos Animales , Caracteres Sexuales

RESUMEN

MiRNA (or microRNA) is a subclass of non-coding RNAs that is responsible for post-transcriptional gene regulation. It has approximately 22 nucleotides and regulates gene expression in plants and animals at the post-transcriptional level, by the cleavage of a target mRNA or by suppression of its translation. Although many of the processes and mechanisms have not yet been fully elucidated, there is a strong association between miRNA expression and several diseases. It is known that miRNAs are expressed in the cardiovascular system, but their role in cardiovascular diseases (CVDs) has not been clearly established. In this non-systematic review of the literature, we first present the definition of miRNAs and their action at the cellular level. Afterward, we discuss the role of miRNAs as circulating biomarkers of CVDs, and then their role in cardiac remodeling and atherosclerosis. Despite the complexity and challenges, it is crucial to identify deregulated miRNAs in CVDs, as it allows a better understanding of underlying cellular and molecular mechanisms and helps in the development of more accurate diagnostic and prognostic circulating biomarkers, and new therapeutic strategies for different stages of CVDs.

Asunto(s)

Enfermedades Cardiovasculares/fisiopatología , MicroARNs/fisiología , Aterosclerosis/genética , Aterosclerosis/metabolismo , Aterosclerosis/fisiopatología , Biomarcadores , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/metabolismo , Regulación de la Expresión Génica/genética , Humanos , MicroARNs/genética , Remodelación Ventricular/genética

RESUMEN

Abstract MiRNA (or microRNA) is a subclass of non-coding RNAs that is responsible for post-transcriptional gene regulation. It has approximately 22 nucleotides and regulates gene expression in plants and animals at the post-transcriptional level, by the cleavage of a target mRNA or by suppression of its translation. Although many of the processes and mechanisms have not yet been fully elucidated, there is a strong association between miRNA expression and several diseases. It is known that miRNAs are expressed in the cardiovascular system, but their role in cardiovascular diseases (CVDs) has not been clearly established. In this non-systematic review of the literature, we first present the definition of miRNAs and their action at the cellular level. Afterward, we discuss the role of miRNAs as circulating biomarkers of CVDs, and then their role in cardiac remodeling and atherosclerosis. Despite the complexity and challenges, it is crucial to identify deregulated miRNAs in CVDs, as it allows a better understanding of underlying cellular and molecular mechanisms and helps in the development of more accurate diagnostic and prognostic circulating biomarkers, and new therapeutic strategies for different stages of CVDs.

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Resumo O miRNA (ou microRNA) constitui uma subclasse de RNAs não codificantes responsáveis pela regulação gênica pós-transcricional. Ele possui aproximadamente 22 nucleotídeos e regula a expressão gênica em plantas e animais ao nível pós-transcricional, pela clivagem de um mRNA alvo ou da repressão de sua tradução. Embora muitos processos e mecanismos ainda não estejam completamente elucidados, existe uma forte associação entre a expressão de miRNAs e diversas doenças que acometem o organismo. Os miRNAs são expressos no sistema cardiovascular, contudo o seu papel no desenvolvimento das doenças cardiovasculares (DCVs) ainda não está totalmente elucidado. Diante disso, realizou-se uma revisão não sistemática da literatura a fim de se discutir a relação entre os miRNAs e as DCVs. Nesta revisão, primeiramente é discutido o que são os miRNAs e a sua ação a nível celular. Após, é discutido o papel dos miRNAs como biomarcadores circulantes de DCVs e então o seu papel no remodelamento cardíaco e na aterosclerose. Apesar da complexidade e dos desafios, a identificação dos miRNAs desregulados nas DCVs é crucial, uma vez que possibilita uma melhor compressão dos mecanismos celulares e moleculares envolvidos, assim como auxilia o desenvolvimento de marcadores circulantes de diagnóstico e prognóstico mais acurados e de novas estratégias terapêuticas para os diferentes estágios da DCV.

Asunto(s)

Humanos , Enfermedades Cardiovasculares/fisiopatología , MicroARNs/fisiología , Biomarcadores , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/metabolismo , Regulación de la Expresión Génica/genética , Remodelación Ventricular/genética , MicroARNs/genética , Aterosclerosis/fisiopatología , Aterosclerosis/genética , Aterosclerosis/metabolismo

RESUMEN

Endothelial function is a key mechanism in the development of CVD. Arginine and exercise are important non-pharmacological strategies for mitigating the impact of metabolic changes in the metabolic syndrome, but the effect of their combined administration is unknown. Thus, the aim of this study was to investigate the isolated and combined effects of aerobic training and arginine supplementation on metabolic variables and vascular reactivity in rats at high risk for developing the metabolic syndrome. Wistar rats were divided into two groups: control and fructose (F - water with 10 % fructose). After 2 weeks, the F group was divided into four groups: F, fructose+arginine (FA, 880 mg/kg per d of l-arginine), fructose+training (FT) and fructose+arginine+training (FTA); treatments lasted for 8 weeks, and no difference was observed in body mass gain. Arginine did not improve the body protein content, and both the FA and FT groups show a reversal of the increase in adipose tissue. Insulin increase was prevented by training and arginine, without additive effect, and the increase in serum TAG was prevented only by training. The F group showed impaired endothelium-dependent vasodilation and hyperreactivity to phenylephrine, but arginine and training were capable of preventing these effects, even separately. Higher nitric oxide level was observed in the FA and FT groups, and no potentiating effect was detected. Thus, only training was able to prevent the increase in TAG and improve the protein mass, and training and arginine exert similar effects on fat content, insulin and endothelial function, but these effects are not additive.

Asunto(s)

Arginina/farmacología , Endotelio Vascular/fisiología , Síndrome Metabólico/prevención & control , Condicionamiento Físico Animal/fisiología , Tejido Adiposo/metabolismo , Animales , Composición Corporal/efectos de los fármacos , Suplementos Dietéticos , Endotelio Vascular/efectos de los fármacos , Fructosa , Insulina/sangre , Masculino , Síndrome Metabólico/metabolismo , Óxido Nítrico/sangre , Fenilefrina/farmacología , Proteínas/metabolismo , Ratas Wistar , Triglicéridos/sangre

RESUMEN

NEW FINDINGS: What is the central question of this study? What are the effects of exercise training on the hepatic renin-angiotensin system and their contribution to damage resulting from fructose overload in rats? What is the main finding and its importance? Exercise training attenuated the deleterious actions of the angiotensin-converting enzyme/angiotensin II/angiotensin II type 1 receptor axis and increased expression of the counter-regulatory (angiotensin-converting enzyme 2/angiotensin (1-7)/Mas receptor) axis in the liver. Therefore, our study provides evidence that exercise training modulates the hepatic renin-angiotensin system, which contributes to reducing the progression of metabolic dysfunction and non-alcoholic fatty liver disease in fructose-fed rats. The renin-angiotensin system (RAS) has been implicated in the development of metabolic syndrome. We investigated whether the hepatic RAS is modulated by exercise training and whether this modulation improves the deleterious effects of fructose overload in rats. Male Wistar rats were divided into (n = 8 each) control (CT), exercise control (CT-Ex), high-fructose (HFr) and exercise high-fructose (HFr-Ex) groups. Fructose-drinking rats received d-fructose (100 g l-1 ). After 2 weeks, CT-Ex and HFr-Ex rats were assigned to a treadmill training protocol at moderate intensity for 8 weeks (60 min day-1 , 4 days per week). We assessed body mass, glucose and lipid metabolism, hepatic histopathology, angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activity, the angiotensin concentration and the expression profile of proteins affecting the hepatic RAS, gluconeogenesis and inflammation. Neither fructose overload nor exercise training influenced body mass gain and serum ACE and ACE2 activity. The HFr group showed hyperinsulinaemia, but exercise training normalized this parameter. Exercise training was effective in preventing hepatic steatosis and in preventing triacylglycerol and glycogen accumulation. Furthermore, exercise improved the response to the deleterious effects of HFr overload by normalizing the gluconeogenesis pathway and the protein levels of interleukin-6 and tumour necrosis factor-α. The HFr rats displayed increased hepatic ACE activity and protein expression and angiotensin II concentration, which were attenuated by exercise training. Exercise training restored the ACE2/angiotensin-(1-7)/Mas receptor axis. Exercise training may favour the counter-regulatory ACE2/angiotensin-(1-7)/Mas receptor axis over the classical RAS (ACE/angiotensin II/angiotensin II type 1 receptor axis), which could be responsible for the reduction of metabolic dysfunction and the prevention of non-alcoholic fatty liver disease.

Asunto(s)

Fructosa/metabolismo , Hígado/fisiología , Condicionamiento Físico Animal/fisiología , Sistema Renina-Angiotensina/fisiología , Angiotensina I/metabolismo , Angiotensina II/metabolismo , Enzima Convertidora de Angiotensina 2 , Animales , Hígado Graso/metabolismo , Hígado Graso/fisiopatología , Gluconeogénesis/fisiología , Interleucina-6/metabolismo , Metabolismo de los Lípidos/fisiología , Hígado/metabolismo , Masculino , Fragmentos de Péptidos/metabolismo , Peptidil-Dipeptidasa A/metabolismo , Ratas , Ratas Wistar , Receptor de Angiotensina Tipo 1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo

RESUMEN

Handmade anatomy models may be a complementary useful tool to dissection and prosection, since the student interacts with the body structure in a three-dimensional way. In this study homemade dough (biscuit) was used to create a brain model. Two anatomy trainees from the medical school of the Universidade Federal Fluminense (Niteroi Brazil) were challenged to model the gross anatomy of the lateral aspect of the brain. They prepared and handled homemade dough to produce a simple and low cost model of the cerebral hemisphere. Styrofoam balls fixed by pins were used to create a framework, and dough rolls were modeled in order to create the brain sulci and gyri. At the end, the model closely resembled three-dimensional features of the human brain. Also, brain lobes were easily identified, as well as some major gyri and sulci, such as the central and lateral sulci and the precentral and postcentral gyri. In conclusion, the three-dimensional spatial characteristics, the clear identification of sulci and gyri and the brain lobes, make this model a good tool for students who only require basic anatomy in their curriculum.

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Los modelos de anatomía elaborados a mano pueden ser una herramienta útil y complementaria a la disección y la prosección, debido a que el alumno interactúa con la estructura del cuerpo de manera tridimensional. En este estudio se utilizó una masa casera (bizcocho) para crear un modelo cerebral. Dos estudiantes de anatomía de la Facultad de Medicina de la Universidade Federal Fluminense (Niteroi, Brasil) fueron desafiados a modelar la anatomía macroscópica de la cara lateral del cerebro. Prepararon y manejaron masa casera para producir un modelo simple y de bajo costo del hemisferio cerebral. Bolas de espuma de poliestireno fijado por alfileres se utilizaron para crear un marco, y los rollos de masa fueron modelados con el fin de crear los surcos cerebrales y giros. Al final, el modelo resultó ser muy semejante a las características tridimensionales del cerebro humano. Además, los lóbulos cerebrales fueron fácilmente identificados, así como algunos giros y surcos mayores, tales como el surco central y lateral y el giro precentral y postcentral. En conclusión, las características espaciales tridimensionales, la identificación clara de los surcos y giros y los lóbulos cerebrales, hacen de este modelo una buena herramienta para los estudiantes que sólo requieren anatomía básica en su plan de estudios.

Asunto(s)

Humanos , Encéfalo/anatomía & histología , Modelos Anatómicos , Neuroanatomía/educación

RESUMEN

Fat storage changes throughout life and affects body metabolism. Ageing impact on brown (BAT) and white adipose tissue (WAT) deserves attention, especially in females, because they are less prone to age-induced weight gain. While in male mice the impact of ageing on adipose tissue remodelling is well characterized, the effects in female mice remain largely unclear. Thus, we investigated BAT and WAT remodelling during ageing in female C57BL/6 mice. At 3 months, body weight was 24 ± 0.3 g (mean±SD), and it increased from 6 to 9 months of age (+20%, P < 0.0001). Oral glucose tolerance test showed no disturbance of glucose metabolism. All WAT depots became heavier, and white adipocytes hypertrophied. The subcutaneous and visceral WAT had clusters of beige cells in younger mice, but they were progressively lost by ageing, indicating loss of WAT browning. Older mice had hypertrophied classic brown adipocytes that had larger cytoplasmic lipid droplets than younger mice. Pearson's correlation showed that WAT mass has a weak correlate with BAT mass, although white adipocyte diameter has a strong correlation with classic brown adipocyte size. In conclusion, our results indicate that female C57BL/6 mice have a progressive age-dependent loss of subcutaneous and visceral WAT browning, and this process runs in parallel with BAT morphological changes towards a fat storer phenotype, independent of cycling or disturbances in glucose metabolism.

Asunto(s)

Adipocitos Marrones/metabolismo , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Envejecimiento/metabolismo , Tejido Adiposo/metabolismo , Adiposidad , Animales , Peso Corporal , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/metabolismo

RESUMEN

Quantitative morphology is a reliable tool in developmental, clinical and aging biology. Quantitative data of histological improvement and/or impairment due to dietary manipulations or pharmacological interventions draws the attention of countless researchers worldwide. Morphometry allows a wide range of two-dimension analysis to be performed, whereas image segmentation allows the measurement of a single structure or the determination of the intensity of its color after adequate immunostaining or even the area occupied by a specific sort of cell. When it comes to unbiased analysis, consideration should be given to suitable tissue perfusion, fixation and embedding, avoiding artifacts. Furthermore, tissue shrinkage should be taken into account. In order to ensure reproducibility, one of the most important principles in scientific research, and to allow different groups to be compared, image acquisition and image segmentation emerge as crucial steps and should be standardized. This paper aims to approach some important care for appropriate tissue processing and evaluation, and shows some practical examples of how morphometry and image segmentation can be applied to your experiment.

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La morfología cuantitativa es una herramienta confiable en la biología del desarrollo, clínica y en el envejecimiento. Los innumerables datos cuantitativos de mejoras histológica y / o deterioro debido a las manipulaciones dietéticas o intervenciones farmacológicas atraen la atención de los investigadores en todo el mundo. La morfometría permite realizar una amplia gama de análisis en dos dimensiones, mientras que la segmentación de imágenes permite la medición de una única estructura o la determinación de la intensidad de su color después de una adecuada inmunotinción o incluso el área ocupada por un tipo específico de célula. Cuando se trata de un análisis imparcial, debe considerarse la posibilidad de la perfusión tisular adecuada, fijación e inclusión, evitando artefactos. Además, se debe considerar la contracción del tejido. Con el fin de asegurar la reproducibilidad, uno de los principios más importantes en la investigación científica, y para permitir que diferentes grupos se comparen, la adquisición y segmentación de la imagen aparecen como pasos cruciales y deben ser estandarizados. En este trabajo se abordan algunos cuidados importantes para el procesamiento de tejidos y evaluación apropiadas, y se muestran algunos ejemplos prácticos de cómo la segmentación morfométrica y la imagen se pueden aplicar a su experimento.

Asunto(s)

Procesamiento de Imagen Asistido por Computador , Anatomía/métodos , Programas Informáticos

RESUMEN

PURPOSE: To study the effects of a diet rich in salt and/or saturated fat on atrial natriuretic peptide (ANP)-granules, hypertension, renin expression, and cardiac structure in C57Bl/6 mice. METHODS: Young adult male mice were separated into four groups (n = 12) and fed one of the following for 9 weeks: standard chow/normal salt (SC-NS), high-fat chow/normal salt (HF-NS), standard chow/high salt (SC-HS) and high-fat chow/high salt (HF-HS). Alterations in the serum ANP, ultrastructural analysis of cardiomyocytes that produce ANP, structural analysis of the left ventricle, blood pressure, renin expression, glomerular filtration rate (GFR), feed efficiency, and lipid and glucose parameters were examined. RESULTS: The HF-NS diet showed a small increase in ANP production and left ventricular hypertrophy, increased food efficiency, and abnormal lipid and glucose parameters. The SC-HS diet showed a large increase in ANP granules in myocytes and corresponding elevation in ANP serum levels, left ventricular hypertrophy, hypertension, decrease in renin levels, and increase in GFR. The combination of the two diets (HF-HS) had an additive effect. CONCLUSION: The incorporation of a high-fat high-salt diet induced ultrastructural changes in cardiomyocytes, increased the production of ANP and increased its serum level, and reduced the amount of renin in the kidney.

Asunto(s)

Factor Natriurético Atrial/metabolismo , Dieta Alta en Grasa/efectos adversos , Riñón/metabolismo , Síndrome Metabólico/metabolismo , Miocitos Cardíacos/metabolismo , Renina/metabolismo , Cloruro de Sodio Dietético/efectos adversos , Animales , Factor Natriurético Atrial/sangre , Grasas de la Dieta/efectos adversos , Regulación hacia Abajo , Tasa de Filtración Glomerular , Hipertensión/etiología , Hipertrofia Ventricular Izquierda/etiología , Riñón/patología , Riñón/fisiopatología , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/patología , Síndrome Metabólico/fisiopatología , Ratones , Ratones Endogámicos C57BL , Miocitos Cardíacos/ultraestructura , Distribución Aleatoria , Vesículas Secretoras/metabolismo , Vesículas Secretoras/ultraestructura , Aceite de Soja/efectos adversos , Regulación hacia Arriba

RESUMEN

This work aimed to analyze the effect of low-intensity exercise training on ultrastructural and molecular aortic remodeling. Male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were allocated into four groups: sedentary WKY (SED-WKY), exercised WKY (EX-WKY, 1 h/day, 5 days/week treadmill exercise training), sedentary SHR (SED-SHR), and exercised SHR (EX-SHR). EX-SHR showed blood pressure reduction of 26% in comparison to SED-SHR after 1 month of exercise (P<0.05). At the 20th week, BP level was not different between EX-SHRs and WKYs. Circumferential wall tension (CWT) was higher by 77% in SED-SHRs than in SED-WKYs (P<0.001). Exercise training reduced CWT by 30% in EX- vs. SED-SHR (P<0.001). In SED-SHRs, endothelial cells showed large and numerous cytoplasmatic vacuoles, fragmented inner elastic lamina and scarce elastin and fibrillin, while exercise training ameliorated it in EX-SHR group. The highest eNOS immunodensity was observed in EX-SHR, which was 50% higher than EX-WKY (P<0.01) and 120% higher than SED-SHR (P<0.0001). In conclusion, present findings indicate beneficial effects of exercise training in hypertensive rats since it increased elastin, fibrillin and eNOS content in the aortic wall.

Asunto(s)

Aorta/metabolismo , Elastina/metabolismo , Hipertensión/metabolismo , Proteínas de Microfilamentos/metabolismo , Óxido Nítrico/metabolismo , Condicionamiento Físico Animal/fisiología , Animales , Aorta/química , Aorta/ultraestructura , Presión Sanguínea/fisiología , Elastina/ultraestructura , Fibrilinas , Hipertensión/rehabilitación , Immunoblotting , Inmunohistoquímica , Masculino , Proteínas de Microfilamentos/ultraestructura , Microscopía Electrónica de Transmisión , Óxido Nítrico Sintasa de Tipo III/metabolismo , Ratas , Ratas Endogámicas SHR , Ratas Endogámicas WKY , Resistencia a la Tracción