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O crescimento do mercado cervejeiro tem incitado buscas por inovação na forma de produzir cerveja para proporcionar produtos diferenciados. A produção de cervejas com leveduras não convencionais tem sido uma alternativa interessante para a geração de sabores e aromas diferenciados. A literatura demonstra a utilização de algumas novas espécies de leveduras para produção de cervejas com características únicas, entretanto, carece uma revisão sistemática que apresente as principais leveduras com potencial cervejeiro. O objetivo desta revisão sistemática é reunir artigos que investigaram a utilização de leveduras com o propósito de produzir cervejas e destacar as principais características observadas. Para isso, foram pesquisados das principais bases de dados (Science Direct e PubMed) e selecionados 17 artigos que descreviam a utilização de 19 espécies de leveduras e 2 bactérias na fermentação de cervejas. As informações de cada espécie foram reunidas e descritas separadamente, evidenciando os potenciais individuais de cada uma. O estudo revelou características específicas e únicas produzidas pelas leveduras não convencionais que impactam de maneira interessante na cerveja. Deste modo, foi possível concluir que as leveduras não convencionais proporcionam cervejas com perfil de sabor e aroma aprimorados e distintos das tradicionais Saccharomyces cerevisiae.

Hypertension is the most important and well-known risk factor for cardiovascular disease (CVD). Recently, acute organophosphate (OP) poisoning has also been pointed as a CVD risk factor. Despite these evidence, no studies have contrasted the cardiovascular (CV) effects of OP poisoning under conditions of normotension and hypertension. We hypothesized that hypertensive rats would have a greater impairment of CV function after acute exposure to chlorpyrifos (CPF), an OP compound. 12-14 week-old male normotensive Wistar and Spontaneously Hypertensive rats (SHRs) were intraperitoneally (i.p.) injected with saline (NaCl 0.9%) or 20 mg.kg-1 of CPF, a previously shown sublethal dose in normotensive rats. 24-hour survival was recorded and through cannulation of the femoral artery and vein, we assessed blood pressure (BP) and heart rate (HR) recordings and chemically activated the Bezold-Jarisch Reflex (BJR), the Chemoreflex (CR), as well as assessed the cardiac autonomic tone (AUT). BJR was activated by phenylbiguanide (PBG; 1.5; 3; 6; 12; 24 μg/kg; i.v.) and the CR by potassium cyanide (KCN, 10, 20, 40 and 80 μg/ rat; i.v.) injections, while the AUT was assessed by pharmacological blockade with atenolol (4mg.kg-1, i.v) and atropine (2mg.kg-1, i.v). CPF acute exposure induced 33% mortality in SHR without leading to lethality in Wistar rats. CPF poisoning impaired the BJR hypotensive response in Wistar rats for all PBG doses tested (ΔDBP: - 33.83±4.88 vs. -14.16±2.68; -44.58±3.48 vs. -30.58±2.16; -66.16±2.50 vs. -36.16±2.54; -72.66±2.66 vs. -47.91±2.50; -78.66±2.35 vs.-61.58±2.40; p Aitken AV, was recipeint of Fapes Foundation scholarship. Minassa VS, Batista TJ were recipients of Capes Foundation scholarship. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Purpose: Oral mucositis is a painful condition that occurs in patients who undergo chemotherapy. Due to the worsening of oral mucositis, the patient may progress to a worse clinical condition and interrupt antineoplastic treatment. There is little literature on low-power laser therapy in chemotherapy for other solid tumors. The purpose of this study was to investigate whether low-level laser therapy (LLLT) applied before chemotherapy could prevent oral mucositis in patients with solid tumors. Methods: Laser therapy was applied at a frequency of 630nm, with a dose of 2J / cm2, for the prevention of oral mucositis induced by chemotherapy specifically for non-hematological tumors. Epidemiological data, total neutrophils, general side effects, development of oral mucositis and degree, and the performance of low-power laser therapy to prevent oral mucositis were collected. The involvement of oxidative stress was evaluated by the enzyme superoxide dismutase (SOD) through blood samples, before and after chemotherapy treatments. Results: LLLT in the proposed protocol is efficient in reducing the development of oral mucositis (only at grade I/II) in patients under chemotherapy and able to reduce the severity of oral mucosal lesions, in patients who developed mucositis after the use of the laser for prevention. All individuals who underwent LLLT protocol did not show a significant reduction of SOD activity after the last chemotherapy cycle. Conclusions: The prophylactic laser therapy protocol proposed by the study, defined at a frequency of 630nm, a dose of 2J / cm2, demonstrated the ability to decrease the occurrence of oral mucositis in patients undergoing chemotherapy protocols to solid tumors. This effect could be related to preserved SOD activity, as it was observed that oral mucositis is related to leukopenia and reduced SOD activity and LLLT protocol prevented the decrease of SOD activity.

Endothelial mechanisms underlying the vascular effects of estrogen modulated by the G protein-coupled estrogen receptor (GPER) are not well understood, especially in gonadal sex hormone deprivation. Thus, we investigated vascular function and endothelial signaling pathways involved in the selective activation of GPER in resistance arteries of gonadectomized rats.Gonadectomy was performed in Wistar rats of both sexes. After 21 days, the animals were euthanized. Concentration-response curves were obtained by cumulative additions of G-1 in third-order mesenteric arteries. The vasodilatory effects of G-1 were evaluated before and after endothelium removal or incubation with pharmacological inhibitors. Tissue protein expression was measured by western blotting. Assays with 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate (DAF-FM) and 2',7' dichlorodihydrofluorescein-diacetate (H2DCF-DA) were performed in the arteries investigated. Immunolocalization was assessed by immunofluorescence.G-1 induced partially endothelium-dependent relaxation in both sexes. The three isoforms of the enzyme nitric oxide synthase contributed to the production and release of nitric oxide in both gonadectomized groups, but the role of inducible nitric oxide synthase is more expressive in males. The mechanistic pathway by which endothelial nitric oxide synthase is phosphorylated appears to differ between sexes, with the rapid signaling pathway phosphatidylinositol-3-kinase/protein kinase B/endothelial nitric oxide synthase (PI3k-Akt-eNOS) being identified for males and mitogen-activated protein kinase/extracellular signal-regulated kinase/endothelial nitric oxide synthase (MEK-ERK-eNOS) for females. The contribution of hydrogen peroxide as an endothelial relaxation mediator seems to be greater in females.These results provide new insights into the effects of estrogen-induced responses via GPER on vascular function in gonadal sex hormone deprivation.

Background: Juçara açaí is a Brazilian berry with high anthocyanidin content and high antioxidant properties. A correlation between oxidative stress, hypertension and baroreflex impairment is known, however, no previous studies investigate the effect of juçara fruit pulp on hypertension. Aim: The aim of this study was to investigate antihypertensive effect of juçara (Euterpe edulis) fruit pulp in SHR animals, its antioxidant capacity and influence on baroreflex sensitivity. Methods: Chemical profile was obtained by ESI(-)-FT-ICR-MS. For biological analysis, male SHR were separated into groups: control (S), which received water; captopril (SC), which received captopril (30 mg/kg), and juçara (SJ), which received juçara pulp (4.4mL/kg). Treatments were daily performed by gavage and remained for 8 weeks. Baroreflex evaluation was made by in bolus injection of phenylephrine and sodium nitroprusside, after the analysis the heart was frozen (-80ºC) for biomolecular evaluations (AOPP, TBARS, SOD and catalase activity and protein expression). Results: The treatments promoted decrease in arterial pressure (S: 163.3±2.2; SC: 154.0±0.6; SJ: 149.0±3.8 mmHg) and improved the baroreflex sensitivity after nitroprusside activation. In addition, it promoted a decrease in AOPP and an increase in the activity of antioxidant enzymes. However, no changes were observed in protein expression. Conclusion: It was shown that juçara can promote cardiovascular benefits and its consume should be stimulated for prevention of hypertension. Introducción: Juçara açaí es una fruta brasileña con alta concentración de antocianidinas y excelentes propiedades antioxidantes. La correlación entre el estrés oxidativo, la hipertensión y el daño barorreflejo es conocido, sin embargo, los estudios previos que investigan el efecto de la pulpa de juçara en la hipertensión son escasos. Objetivo: El objetivo del presente estudio es investigar el efecto antihipertensivo de la pulpa del fruto de juçara (Euterpe edulis) en animales SHR, su capacidad antioxidante y la influencia del tratamiento en la sensibilidad barorrefleja. Metodología: El perfil químico se obtuvo por ESI(-)-FT-ICR-MS. Para los análisis biológicos, las ratas macho SHR se separaron en grupos: control (S) que recibió agua; captopril (SC) que recibió captopril (30 mg/kg) y el grupo juçara (SJ) que recibió pulpa de juçara (4,4 mL/kg). Todos los tratamientos se realizaron diariamente por vía oral (gavage) y se mantuvieron durante 8 semanas. La evaluación del barorreflejo se realizó mediante inyección en bolo de fenilefrina y nitroprusiato de sodio, y después del análisis hemodinámico, los corazones se recolectaron y congelaron (-80ºC) para análisis biomolecular (AOPP, TBARS, SOD y actividad de catalasa y expresión de proteínas). Resultados: Los tratamientos promovieron una reducción de la presión arterial (S: 163,3±2,2; SC: 154,0±0,6; SJ: 149,0±3,8 mmHg) y mejoraron la sensibilidad barorrefleja después de la activación con nitroprusiato de sodio. Además, se observó una reducción en los niveles de AOPP y un aumento en la actividad de las enzimas antioxidantes. Sin embargo, no se observaron cambios en la expresión de proteínas. Conclusión: Nuestros datos demuestran que la juçara puede promover beneficios cardiovasculares y se debe fomentar su consumo para prevenir la hipertensión arterial. Introdução: O açaí juçara é uma fruta brasileira com alta concentração de antocianidinas e excelente propriedade antioxidante. A correlação entre estresse oxidativo, hipertensão e prejuízo no barorreflexo é conhecida, porém, estudos prévios investigando o efeito da polpa de juçara na hipertensão são escassos. Objetivo: O objetivo do presente estudo é investigar o efeito anti-hipertensivo da polpa do fruto de juçara (Euterpe edulis) em animais SHR, sua capacidade antioxidante e a influência do tratamento na sensibilidade do barorreflexo. Metodologia: O perfil químico foi obtido por ESI(-)-FT-ICR-MS. Para as análises biológicas, os ratos SHR machos foram separados em grupos: controle (S) que recebeu água; captopril (SC) que recebeu captopril (30 mg/kg) e o grupo juçara (SJ) que recebeu a polpa de juçara (4,4 mL/kg). Todos os tratamentos foram realizados diariamente por via oral (gavagem) e mantidos por 8 semanas. A avaliação do barorreflexo foi feita pela injeção in bolus de fenilefrina e nitroprussiato de sódio, e após as análises hemodinâmicas, os corações foram coletados e congelados (-80ºC) para as análises biomoleculares (AOPP, TBARS, atividade da SOD e catalase e expressão proteica). Resultados: Os tratamentos promoveram redução na pressão arterial (S: 163,3±2,2; SC: 154,0±0,6; SJ: 149,0±3,8 mmHg) e melhoraram a sensibilidade do barorreflexo após a ativação com o nitroprussiato de sódio. Adicionalmente, foi observado redução nos níveis de AOPP e aumento da atividade das enzimas antioxidantes. Entretanto, não foram observadas mudanças na expressão proteica. Conclusão: Nossos dados demonstram que a juçara pode promover benefícios cardiovasculares e o seu consumo deve ser estimulado para a prevenção da hipertensão arterial.

Stanozolol is a steroid that causes lipid deposition in LDLr-/- mice, although the mechanism by which this dyslipidemia results in cardiac dysfunction is little understood. The aim of this study was to evaluate the effect of stanozolol on cardiac contractility and the participation of myocardial phospholamban (pPLB) phosphorylation in an atherosclerosis mouse model. LDL receptor knockout mice (LDLr-/-) were fed a standard chow diet and received weekly subcutaneous injections of either saline (control, C group) or 20 mg/kg stanozolol (S group). After 8 weeks, hemodynamic parameters were assessed in the left ventricle. The heart was collected, weighted for hypertrophy evaluation, and kept in formalin buffer for morphometric analysis (H&E) and collagen quantification (Picrossirius). Protein expression of PLB and its phosphorylated form (p-PLB) in the left ventricle was determined by western blot. We observed that stanozolol treatment favored cardiac hypertrophy and collagen deposition in heart tissue. Also, stanozolol induced left ventricle dysfunction, increasing PBL expression and decreasing the p-PLB/PLB ratio. Altogether, our data showed that stanozolol causes cardiac remodeling and ventricular dysfunction by decreasing PLB phosphorylation in the left ventricle of LDLr-/- mice. El estanozolol es un esteroide que promueve el depósito de lípidos en las arterias de ratones LDLr-/-, sin embargo, el mecanismo por el cual la dislipidemia promueve la disfunción cardíaca en estos animales aún no se conoce bien. Por lo tanto, el objetivo del presente estudio es evaluar el efecto del estanozolol sobre la contractilidad cardíaca y la participación de la fosforilación de la proteína fosfolambano miocárdico (pPBL) en el modelo animal de aterosclerosis. Se alimentó a ratones sin receptor de LDL (LDLr-/-) con una dieta estándar de casa de animales y recibieron inyecciones subcutáneas semanales de solución salina (grupo de control, C) o 20 mg/kg de estanozolol (grupo S). Después de ocho semanas de tratamiento, se evaluaron los parámetros hemodinámicos en el ventrículo izquierdo. Luego se recolectó el corazón, se pesó para determinar la hipertrofia y se almacenó en tampón de formalina para análisis morfométrico (H&E) y cuantificación de colágeno (picrosirius). La expresión de la proteína fosfolambano (PBL) y su forma fosforilada (p-PBL) en el ventrículo izquierdo se determinó por western blot. Observamos que el tratamiento con estanozolol favorecía la hipertrofia y el depósito de colágeno en el tejido cardíaco. Además, el estanozolol indujo disfunción ventricular izquierda, aumentó la expresión de PBL y redujo la relación p-PBL/PBL. En conjunto, nuestros datos muestran que el estanozolol promueve la remodelación cardíaca y la disfunción ventricular al reducir la fosforilación del fosfolambano del ventrículo izquierdo en ratones LDLr-/-. O stanozolol é um esteroide que promove deposição lipídica nas artérias de camundongos LDLr-/-, entretanto, o mecanismo pelo qual a dislipidemia promove disfunção cardíaca nesses animais, ainda é pouco entendida. Deste modo, o objetivo do presente estudo é avaliar o efeito do stanozolol na contratilidade cardíaca e a participação da fosforilação da proteína fosfolambam (pPBL) miocárdica no modelo animal de aterosclerose. Os camundongos knock-out para receptor de LDL (LDLr-/-) foram alimentados com dieta padrão para biotérios e receberam semanalmente injeções subcutâneas com salina (grupo controle, C) ou 20 mg/kg de stanozolol (grupo S). Depois de oito semanas de tratamento, os parâmetros hemodinâmicos foram avaliados no ventrículo esquerdo. O coração foi então coletado, pesado para determinação da hipertrofia e armazenado em tampão formalina para a determinação das análises morfométrica (H&E) e da quantificação de colágeno (picrossirius). A expressão da proteína fosfolambam (PBL) e da sua forma fosforilada (p-PBL) no ventrículo esquerdo foi determinado por western blot. Nós observamos que o tratamento com stanozolol favoreceu a hipertrofia e a deposição de colágeno no tecido cardíaco. Além disso, o stanozolol induziu a disfunção do ventrículo esquerdo, aumento da expressão do PBL e a redução da razão p-PBL/PBL. Em conjunto, nossos dados mostram que o stanozolol promove remodelamento cardíaco e disfunção ventricular pela redução da fosforilação do fosfolambam no ventrículo esquerdo em camundongos LDLr-/-.

Objectives To examine the prognostic significance of pre-treatment C-reactive protein (CRP), N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) levels on all-cause mortality three years after head and neck squamous cell carcinoma (HNSCC) diagnosis. Subjects and methods Data from 118 consecutive HNSCC patients, treated between 2012 and 2015, were evaluated prospectively. The impact of CRP, high-sensitive (hs)-cTnT and NT-proBNP levels on the 3-year overall survival was estimated using the Kaplan-Meier method and Cox proportional hazard models. Results During the 36-month follow-up, 37 patients (31.35%) died. Multivariate analysis revealed that elevated CRP (Hazard ratio: 3.71, 95% CI: 1.44 - 9.53, P = 0.007) and NT-proBNP levels (Hazard ratio: 5.04, 95% CI: 2.02 - 12.55, P = 0.001) were associated to negative prognosis, independent on age, sex, smoking and alcohol status, TNM classification, tumor site, body mass index (BMI), systolic blood pressure (SBP), and treatment modality (except for radiotherapy). hs-cTnT had no influence over the prognosis, but it was correlated with TNM classification and SBP. CRP was significantly correlated with BMI and TNM classification, and NT-proBNP with SBP and hs-cTnT. Conclusions Pre-treatment CRP and NT-proBNP levels were identified as independent prognostic markers for poor clinical outcome three years after HNSCC diagnosis.

Cardiovascular effects induced by snake venoms, in spite of having a crucial role in the outcome of the envenomation, have been less studied than other toxic activities displayed by these venoms. In this study we evaluated acute cardiovascular responses to Bothrops leucurus venom - Bl-V - both in vivo, in anesthetized rats, and in vitro, in isolated rat mesenteric resistance arteries. Bl-V (10–100 μg protein/kg) caused dose-dependent hypotension, followed by gradual recovery (2–20 min) to basal levels, and induced dose-dependent (1–20 μg/mL) vasodilation in pre-contracted arteries, what was more pronounced when the endothelium remained intact. These effects were partially counteracted by pre-treatment with indomethacin (cyclooxygenase inhibitor). Prior incubation of Bl-V with commercial pentavalent Bothrops antivenom also attenuated the cardiovascular effects induced by the venom, in spite of it not being among the venoms used for the development of the bothropic antivenom. Through an approach based on two chromatographic steps and mass spectrometry (MALDI-ToF and MALDI-ISD), a component with acute cardiovascular effects was isolated and identified as the basic phospholipase blD-PLA2, previously purified from the venom of B. leucurus. Taken together, our results show that, at low doses, the venom of B. leucurus induces transient, acute hypotension in anesthetized rats following systemic vasodilation in a dose-dependent way. In addition, we provide clear evidence of the involvement of the enzymatic activity of blD-PLA2 in this cardiovascular response, acting via the production of vasodilating prostanoids.

Background Adipose tissue is involved in several metabolic changes. This study investigated the association between the fatty acid (FA) composition of subcutaneous (SAT) and visceral (VAT) adipose tissue pre-surgery and the postsurgical response regarding the evolution of weight and concentrations of tumour necrosis factor alpha (TNF) and interleukin 6 (IL-6) in adult women who underwent Roux-en-Y gastric bypass (RYGB, n = 14) or sleeve gastrectomy (SG, n = 19) at one (T1), three (T3) and six (T6) years after surgery. Methods Blood samples were collected to obtain plasma for the measurement of IL-6 and TNF. Anthropometric measurements were performed, collecting samples of VAT and SAT during surgery to assess the FA profiles. Results Weight loss had a positive correlation with the percentage of VAT-C17:0 (T1, T3) and SAT-C18:2 (T1, T3, T6), and it had a negative correlation with SAT-C22:0 (T1, T3) and VAT-C22:0 (T3). Regarding the inflammatory response, SAT-C14:0 (T6), VAT-C14:0 (T6), SAT-C14:1 (baseline), SAT-C15:0 (T6), SAT-C16:1 (T6), VAT-C16:1 (baseline), SAT-C17:1 (T6), VAT-C17:1 (baseline), VAT-C18:1 (T6), and VAT-C20:1 (T6) exhibited positive correlations with the concentration of IL-6, which were different from the correlations of IL-6 concentrations with SAT-C18:2, VAT-C18:2 (T6), and VAT-C18:3 (T6). The FA SAT-C18:0 (T1) was negatively correlated with TNF concentrations. Conclusions Saturated FAs were predominantly proinflammatory, primarily in the late postoperative period. Alternately, the polyunsaturated FAs exhibited anti-inflammatory potential and predicted weight loss. Thus, the FA profile of the adipose tissue of obese adult women may be a predictor of the ponderal and inflammatory response 6 years after bariatric surgery. Trial registration This study was approved by the ethics committee of Federal University of Viçosa; Registration n. 17287913.2.0000.5153; Date: 07/05/2013.

Background and aims Metformin has been known to promote cardiovascular benefits in humans and animal models, even in non-diabetic subjects. However, its chronic effects on hypertension-related autonomic dysfunction remain poorly understood. Therefore, we evaluate the cardiac autonomic effects of chronic metformin in hypertensive rats. Methods and results Twelve-week-old male SHR and Wistar rats were separated into 3 groups: WN (Wistar normotensive); SC (SHR hypertensive control); and SM (SHR: Metformin 300 mg/kg/day for 30 days). Spontaneous and induced (by phenylephrine and sodium nitroprusside) baroreflexes were analysed in catheterised rats. Next, cardiac autonomic tone was evaluated through heart rate shift by atropine (parasympathetic) or atenolol (sympathetic). Plasma TNFα was assessed by ELISA. Western blot analyses of inflammatory, oxidant and antioxidant proteins were performed. Cardiac parasympathetic tone and baroreflex function were lower in SC than in WN, whereas cardiac sympathetic tone was higher. Metformin treatment in non-diabetic hypertensive rats reduced the resting heart rate, attenuated the cardiac sympathetic tone and improved baroreflex (especially in the offsetting of rising BP), while blood pressure and glycaemia remained unchanged. Cardiac sympathetic tone correlated negatively with spontaneous baroreflex. Metformin reduced plasma TNFα levels and decreased tissue expression of COX2 and NOX2 (which were positively correlated), without affecting SOD1 and SOD2. Conclusion Chronic metformin presented anti-inflammatory and antioxidant effects and, independently of alterations in glycaemia, it improved cardiac autonomic parameters that are impaired in hypertension, being related to end-organ damage and mortality. These findings open up perspectives for future innovative uses of metformin in cardiovascular diseases, especially in hypertension.

Forbidden in some countries due to its proven toxicity to humans, chlorpyrifos (CPF) still stands as an organophosphate pesticide (OP) highly used worldwide. Cardiotoxicity assessment is an unmet need in pesticide regulation and should be deeply studied through different approaches to better inform and generate an appropriate regulatory response to OP use. In the present study, we used our 4-week intermittent OP exposure model in rats to address the CPF effects on cardiac morphology allied with cardiovascular functional and biomolecular evaluation. Rats were intermittently treated with CPF at doses of 7 mg/kg and 10 mg/kg or saline (i.p.) and assessed for cardiac morphology (cardiomyocyte diameter and collagen content), cardiopulmonary Bezold-Jarisch reflex (BJR) function, cardiac autonomic tone, left ventricle (LV) contractility, cardiac expression of NADPH oxidase (Nox2), catalase (CAT), superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2) and cardiac levels of advanced oxidation protein products (AOPP) and thiobarbituric acid reactive substances (TBARS). Plasma butyrylcholinesterase (BuChE) and brainstem acetylcholinesterase (AChE) were also measured. Intermittent exposure to CPF induced cardiac hypertrophy, increasing cardiomyocyte diameter and collagen content. An impairment of cardioinhibitory BJR responses and an increase in cardiac vagal tone were also observed in CPF-treated animals without changes in LV contractility. CPF exposure increased cardiac Nox-2, CAT, SOD1, and TBARS levels and inhibited plasma BuChE and brainstem AChE activities. Our data showed that intermittent exposure to CPF induces cardiac hypertrophy together with cardiovascular reflex impairment, imbalance of autonomic tone and oxidative stress, which may bring significant cardiovascular risk to individuals exposed to OP compounds seasonally.

Atherosclerosis is among the major cardiovascular diseases that cause death in the world. Men who are deficient in androgen hormones are more susceptible to this disease. The aim of this study was to evaluate the influence of reduced levels of testosterone on the lipid profile, pro and anti-inflammatory cytokines, apoptosis of peritoneal macrophages and the development of atherosclerosis in LDLr-/-mice, as well as on the levels of OxLDL in healthy male humans. Tissues and organs of the experimental animals were used to evaluate lipid deposition in aorta and apoptosis of peritoneal macrophages. In humans the levels of testosterone and OxLDL were analyzed in blood samples from healthy male subjects, who were divided into two groups: low level and high level of testosterone. Animals with decreased testosterone did not present changes in the lipid profile or the levels of IL-6 and TNF-α. However, a decrease in IL-10 and an increase in the IL-6/IL-10 and TNF-α/IL-10 ratios were observed. An increase in the aorta lipid deposition was observed and a decrease in macrophage apoptosis was also demonstrated. In humans, there was an increase of OxLDL in the group with lower levels of testosterone. The findings suggest that decreasing endogenous testosterone levels may induce the development of atherosclerosis, with participation of inflammatory response and macrophage apoptosis. This is reinforced by our human studies, where individuals with low testosterone levels had higher LDL oxidation, which may predict a high atherosclerotic risk for these men.

Cardiovascular diseases rank the top causes of death worldwide, with a substantial increase in women compared to men. Such increase can beexplained by the drastic decrease in 17-β-estradiol hormone during menopause and associated with endothelium-dependent vascular dysfunction. The current treatments for cardiovascular diseases (e.g., hypertension), are only palliative and therefore, feasible, non-invasive options for preventing further vascular damage are needed. The polyphenol ellagic acid (EA) has risen as a candidate with possible vascular protection properties. This study evaluated the effects of EA in small mesenteric arteries of ovariectomized spontaneously hypertensive rats. Our findings showed that EA oral treatment for 4 weeks preserved vasodilation endothelial-dependent in acetylcholine pre-constricted arteries of spontaneously hypertensive rats to the same extent as 17-β-estradiol treatment, an effect that was abolished in the presence of the nitric oxide synthase inhibitor L-Nitro

The present study aimed to investigate the beneficial role of AT1 receptor blockade and PPAR-γ activation in preventing cardiac contractile changes in hypertensive animals (SHR) with testosterone deficiency. Rats were divided into a control group (sham), orchiectomized (OCT), orchiectomized that received telmisartan (OCT + Tel) or telmisartan plus PPAR-γ antagonist (OCT + Tel + BADGE). After 8 weeks, contractility of isolated papillary muscles was evaluated. The OCT group showed a reduction in the contraction force, avoided in the OCT + Tel and Tel + BADGE groups. Post-pause potentiation (PPP) was similar in the Sham, OCT and OCT + Tel group, suggesting prevention of sarcoplasmic reticulum activity. In contrast, PPP in the OCT + Tel + BADGE group decreased. The reduction in response to calcium or isoproterenol in the OCT group was prevented in the OCT + Tel and Tel + BADGE group. The influx of calcium, assessed indirectly, although it was similar in the OCT and Sham groups, increased both in the OCT + Tel groups and in the OCT + Tel + BADGE groups. SERCA2a protein expression was increased in the OCT group, which was avoided in the OCT + Tel and Tel + BADGE group. NCX expression was increased in the Tel + BADGE group compared to OCT + Tel and sham. Our results suggest that AT1 receptor blockade with telmisartan prevents compromised papillary muscle contractility in SHR. Moreover, it has been shown that the activation of PPAR-γ adds benefits to the inhibition of renin-angiotensin system with telmisartan in preventing harmful effects on the contractility of hypertensive rats with testosterone deficiency.

Oxandrolone (OXA) used in clinical practice, however, its misuse is frequent, including by adolescents pursuing an aesthetic goal. However, the impacts of noxious doses on the cardiovascular system remain unknown. Aim To investigate cardiac effects of OXA in low (LD) and high (HD) doses. Methods Male Wistar prepubescent rats were separated into 3 experimental groups: control (CON), LD, and HD. Only the CON group received the carrier (carboxymethylcellulose, 0.5%), while the LD and HD groups received, respectively, 2.5 and 37.5 mg/kg/day of OXA via gavage for 4 weeks. The hemodynamic parameters (+dP/dtmax, −dP/dtmin, and Tau) and cardiac autonomic tonus were assessed. Hearts were retrieved for histological analyses and oxidative stress evaluation. Expression levels of calcium-handling proteins were measured by western blot. Results The OXA treatment changed neither the cardiac contractility nor the cardiac autonomic tonus. However, cardiac hypertrophy, collagen deposition, and increased angiotensin-converting enzyme (ACE) expression were observed in a dose-dependent way. Also, the p-phospholamban (p-PLB)/PLB ratio was observed to decrease and increase, respectively, in the LD and HD groups; the sarcoplasmic/endoplasmic reticulum calcium ATPase 2a (SERCA2a)/PLB ratio being higher in both groups. OXA increased SOD1 expression and decreased catalase expression only in the LD group, and protein oxidation was increased in HD. Conclusion Both doses of OXA could promote pathological cardiac remodeling, probably via increased ACE, and these effects were exacerbated in the HD treatment, but cardiac contractility was not affected regardless of the dose.

Aims Hypertension is a relevant sex and sex hormones-dependent risk factor where the cardiovascular and renal health of the population are concerned. Men experience greater losses of renal function (RF) than women, but the mechanisms remain somewhat unclear. Our goal was to evaluate the relationship between oxidative stress (OS), angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) activities and RF in male and female SHR. Main methods Twelve-week-old spontaneously hypertensive rats (SHR) were submitted to either castration or SHAM surgery and divided into 4 groups, SHAM or Castrated (CAST) males or females. After 51 days we evaluated RF (inulin and sodium para-aminohippurate), ACE and ACE2 activities (fluorimetry), OS (flow cytometry), collagen deposition (picrosirius red) and protein expression (western blot). Key findings Males presented lower RF than females and castration impaired this parameter in both groups. Sexual dimorphism was not observed regarding OS and inflammation; however, castration increased this parameter more severely in males than in females. SHAM males exhibited higher collagen deposition than females, though castration increased it in both sexes, eliminating the difference. We found sexual dimorphism regarding renal ACE and ACE2 activities, which were lower in males than in females. Although castration did not alter ACE activity, it reduced ACE2 activity in females and increased it in males. Significance These results indicate that sex hormones affect RF in SHR. As alterations in the oxidative system were capable of promoting podocyte injury, inflammation, and collagen deposition, we put forward that these effects are differently modulated by ACE and ACE2.

Metabolism of anabolic androgenic steroids is important for its physiological effects. The aim was to investigate the effects of finasteride (a 5α-reductase inhibitor - 5αR) on cardiac and mutagenic effects promoted by ND. Male Wistar rats were separated into three groups: CONT, received the vehicles of ND and finasteride (Peanut oil+Saline); DECA group, received ND (20 mg.kg.week-1, i.m.), and DECAF received ND and finasteride (100 µg.kg-1, i.p.), for four weeks. After, hypertrophy, cytokines and Angiotensin Converting Enzyme (ACE) activity was determined in heart. Bone marrow was used for micronucleus evaluation. Treatment with ND promotes increase in cardiac hypertrophy, ACE activity and disbalance among pro- and anti-inflammatory cytokines, and combination with finasteride worsened those effects. Association with finasteride ameliorates the toxic effects of ND on bone marrow cells, as was observed by a normalization of the number of micronucleate polychromatic erythrocytes and the mitotic index. Our data demonstrates that deleterious effects promoted by ND are depend, at least in part, of its metabolization. Also, inhibition of 5αR by finasteride present variated effects dependent on organ studied. It can promote increase on cardiac damage and a reduction on mutagenic effects of ND, which demonstrated that dehydronandrolone has diverse role on ND effects..

Aim An imbalance between antioxidant and pro-oxidant factors, with a predominance of the latter, characterises oxidative stress and is indicative of a loss of vascular function. The beneficial vascular effects of oestrogen may be related to its ability to stimulate the G protein-coupled oestrogen receptor (GPER) and produce antioxidant activity. This study evaluated the GPER-dependent relaxation response in the mesenteric resistance arteries of female and male rats and measured the contributions of pro-oxidant and antioxidant enzymes in this response. Main methods The relaxation response was characterised in third-order mesenteric arteries using concentration-response curves of the selective GPER agonist G-1 (1 nM–10 μM), target protein levels were measured using Western blots, and vascular superoxide anion (O2 −) and hydrogen peroxide (H2O2) levels were measured using dihydroethidium (DHE) and dichlorofluorescein (DCF) staining, respectively. Key findings The GPER agonist induced concentration-dependent vasorelaxation without showing differences between sexes. However, GPER expression was greater in male rats. No sex differences were detected in the expression of antioxidant proteins (catalase, SOD-1, and SOD-2). The basal vascular production of O2 − and H2O2 was similar in the studied groups, and stimulation with G-1 maintained this response. Significance Together, our results show that the expression of GPER is greater in male mesenteric arteries, despite of the lack of a difference in vascular response. Nevertheless, antioxidant enzyme expression levels and the generation rates of pro-oxidants were similar between the studied groups. These results offer a new perspective for understanding GPER expression and functionality in resistance arteries.

Aims Hypertension is a highly prevalent disease that has been correlated to severe organ damage and mortality. However, the role of androgens in hypertension is controversial. The aim of this study was to evaluate the cardiac effects of the nandrolone decanoate (NDL) in male SHR. Main methods At 12 weeks of age, male SHR rats were separated into three groups: Control (CON), Nandrolone 10 mg/kg twice weekly (NDL), and NDL plus Enalapril 10 mg/kg/day (NDL-E) groups. The animals were treated for 4 weeks. Haemodynamic parameters were acquired through ventricular catheter implantation. The left ventricle was stained with haematoxylin/eosin or picrosirius red. Western blot analysis of TNF-α, ACE, AT1R, β1-AR, PLB, p-PLBser16 and SERCA2a was performed. Key findings Nandrolone increased hypertension in SHR rats and enalapril reduced blood pressure to values below those of the control. NDL increased +dP/dtmax, −dP/dtmax and cardiac hypertrophy, which were prevented in the NDL-E group. Cardiac collagen deposition was increased in the NDL group, with this effect being attenuated by enalapril in NDL-E animals. TNF-α, ACE, AT1R and β1-AR proteins were increased in the NDL, and enalapril decreased them, except for TNF-α. The ratio p-PLBser16/PLB revealed an increase after nandrolone, which was prevented in the NDL-E group. The SERCA2a expression protein and SERCA2a/PLB were increased in NDL animals, which did not occur in the NDL-E group. Significance Nandrolone has distinct effects on cardiac function and remodelling in male SHR, altering the hypertension development process in the heart through modulation of calcium handling proteins and the renin-angiotensin system.

Background:Endothelial dysfunction is commonly present in estrogen-deficient states, e.g., after menopause. In the search for alternatives to hormone replacement therapy (HRT), treatments based on phytoestrogens or in non-hormonal mechanisms have been under evaluation.Objective:Here we aim to present an overview of innovative potential treatments for endothelial dysfunction in estrogen-deficient states, introducing our own preliminary data about the probiotic kefir.Methods:We conducted a review based on a PubMed database search for keywords of interest (Menopause, Ovariectomy, Vascular dysfunction, Hot flashes, Metformin, Statins, Phytoestrogens, Omega-3, Vitamin D, Probiotics).Results:Vascular parameters were found to be improved by both metformin and statins through pleiotropic effects, being related to a decrease in oxidative stress and restoration of the nitric oxide pathway. Phytoestrogens such as genistein and resveratrol have also been shown to improve vascular dysfunction, which seems to involve their estrogenic-like actions. Omega-3, vitamin D and its analogues, as well as probiotics, have shown similar vascular beneficial effects in both postmenopausal women and an animal model of ovariectomy (OVX), which could be related to antioxidant and/or anti-inflammatory effects. Moreover, our preliminary data on the probiotic kefir treatment in OVX rats suggested a vascular antioxidant effect. In particular, some evidence points to statins and vitamin D having anti-atherogenic effects.Conclusion:Pleiotropic effects of common medications and natural compounds could have therapeutic potential for endothelial dysfunction in estrogen-deficient states. They could, therefore, work as future complementary or alternative treatments to HRT.

Objectives We aimed to evaluate whether long-term treatment with the soluble non-bacterial fraction of kefir affects mean arterial pressure (MAP) and cardiac hypertrophy through the modulation of baroreflex sensitivity, ACE activity, and the inflammatory-to-anti-inflammatory cytokine ratio in spontaneously hypertensive rats (SHRs). Methods SHRs were treated with the soluble non-bacterial kefir fraction (SHR-kefir) or with kefir vehicle (SHR-soluble fraction of milk). Normotensive control Wistar Kyoto animals received the soluble fraction of milk. All treatments were administered by gavage (0.3 mL/100g/body weight), once daily for eight weeks. At the end, after basal MAP and Heart Rate (HT) measurement, barorreflex sensitivity was evaluated through in bolus administrations of sodium nitroprusside and phenylephrine (AP50 [arterial pressure 50%], the lower plateau, and HR range were measured). ACE activity and cytokines (TNF-α and IL-10) were evaluated by ELISA. Cardiac hypertrophy was analysed morphometrically. Results Compared to SHR control, SHR-kefir exhibited a significant decrease in both MAP (SHR: 184 ± 5; SHR-Kefir: 142 ± 8 mmHg), and HR (SHR: 360 ± 10; SHR-kefir: 310 ± 14 bpm). The non-bacterial fraction of kefir also reduced cardiac hypertrophy, TNF-α-to-IL10 ratio, and ACE activity in SHRs. SHR-kefir baroreflex sensitivity, resulted in a partial but significant recovery of baroreflex gain, as demonstrated by improvements in AP50, the lower plateau, and HR range. Conclusion In summary, our results indicate that long-term administration of the non-bacterial fraction of kefir promotes a significant decrease in both MAP and HR, by improving baroreflex, and reduces cardiac hypertrophy in SHRs, likely via ACE inhibition, and reduction of the TNF-α-to-IL10 ratio.

Aims Oxandrolone (OXA) is a synthetic steroid used for the treatment of clinical conditions associated with catabolic states in humans, including children. However, its behavioral effects are not well known. Our goal was to evaluate the anxiety-like behavior induced in young adult rats after the treatment of juvenile animals with OXA. Methods Four-week-old male rats were separated into three groups: Control (CON), therapeutic-like OXA dose (TD), and excessive OXA dose (ED), in which 2.5 and 37.5 mg/kg/day of OXA were administered via gavage for four weeks for TD and ED, respectively. Behavior was evaluated through the elevated plus maze (EPM) and open field (OF) tests. Protein expression of catalase (CAT), superoxide dismutase (SOD), Tumor necrosis factor-α (TNF-α), and dopamine receptor 2 (DrD2) were analyzed in tissue samples of the hippocampus, amygdala, and prefrontal cortex by Western Blot. Results OXA induced anxiety-like behaviors in both TD and ED animals; it decreased the time spent in the open arms of the EPM in both groups and reduced the time spent in the central zone of the OF in the TD group. In the hippocampus, CAT expression was higher in TD compared with both control and ED animals. No differences were found in the amygdala and prefrontal cortex. TNF-α, SOD, and DrD2 levels were not altered in any of the assessed areas. Conclusions Treatment of juvenile rats with OXA led to anxiety-like behavior in young adult animals regardless of the dose used, with minor changes in the antioxidant machinery located in the hippocampus.

Background Metabolic syndrome (MS) occurs when different metabolic and hemodynamic components change simultaneously, being one of the factors related to high mortality rates in patients with cardiovascular diseases. This study investigated the effects of the probiotic kefir on anthropometric and physiological parameters in human subjects with MS. Methods forty-eight patients diagnosed with MS were assigned into two groups in this randomized, double-blind, placebo-controlled clinical trial. Kefir group (KG) and control group (CG) drank kefir beverage and curd (1.6 mL/kg for men or 1.9 mL/kg for women) for 12 weeks, respectively. Blood pressure, anthropometric, and biochemical parameters (fasting glycemia, glycated hemoglobin (HA1c), total cholesterol (TC), high density lipoprotein (HDLc), triglycerides (Tg), oxidized LDL cholesterol (oxLDL), high-sensitivity C-reactive protein (hs-CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinophosphokinase (CPK), γ-Glutamyl Transferase (γ-GT), urea nitrogen, urea, and creatinine were evaluated before and after treatment. The risk of cardiovascular events for the next ten years was calculated through the Framingham Score method. Results Kefir intake decreased blood pressure, fasting glycemia, LDLc, non-HDLc, Tg, and oxLDL, and increased HDLc levels in women. Kefir also reduced the risk of cardiovascular events for the next ten years, although anthropometric parameters remained unchanged. Conclusions Kefir intake improved blood pressure, fasting glucose, and lipid levels, reducing oxLDL and the risk of developing cardiovascular events in the next ten years. These results suggest regular kefir intake may have positive effects on MS treatment.

Chronic fructose intake induces major cardiovascular and metabolic disturbances and is associated with the development of hypertension due to changes in vascular function. We hypothesized that high fructose intake for 6 weeks would cause metabolic syndrome and lead to initial vascular dysfunction. Male Wistar rats were assigned to receive fructose (FRU, 10%) or drinking water (CON) for 6 weeks. Systolic blood pressure was evaluated by tail plethysmography. Fasting glucose, insulin and glucose tolerance were measured at the end of the follow-up. Mesenteric vascular bed reactivity was tested before and after pharmacological blockade. Western blot analysis was performed for iNOS, eNOS, Nox2 and COX-2. DHE staining was used for vascular superoxide anion detection. Vessel structure was evaluated by optical and electronic microscopy. Fructose intake did not alter blood pressure, but did increase visceral fat deposition and fasting glucose as well as impair insulin and glucose tolerance. Fructose increased NE-induced vasoconstriction compared with CON, and this difference was abrogated by indomethacin perfusion as well as endothelium removal. ACh-induced relaxation was preserved, and the NO modulation tested after L-NAME perfusion was similar between groups. SNP-induced relaxation was not altered. Inducible NOS was increased; however, there were no changes in eNOS, Nox2 or COX-2 protein expression. Basal or stimulated superoxide anion production was not changed by fructose intake. In conclusion, high fructose intake increased NE-induced vasoconstriction through the endothelial prostanoids even in the presence of a preserved endothelium-mediated relaxation. No major changes in vessel structure were detected.

Nandrolone Decanoate (ND) is an Anabolic Androgenic Steroid (AAS) that under abusive regimen can lead to multiple physiological adverse effects. Studies of AAS-mediated cardiovascular (CV) alterations were mostly taken from male subjects, even though women are also susceptible to the effects of AAS and gender-specific differences in susceptibility to vascular diseases exist. Here we investigate ND-induced vascular reactivity alterations in both sedentary and exercised female rats and whether these alterations depend on endothelium-derived factors. We show that chronic exposure of female Wistar rats to ND (20 mg/Kg/week for 4 weeks) impaired the vascular mesenteric bed (MVB) reactivity to vasodilator (acetylcholine) agonist. The endothelium-dependent Nitric Oxide (NO) component was reduced in ND-treated rats, whereas neither the endothelium-derived hyperpolarizing factor (EDHF) component nor prostanoids were altered in the MVBs. Endothelial dysfunction observed in ND-treated rats was associated with decreased eNOS (Ser1177) and Akt (Ser473) phosphorylation sites and upregulation of iNOS and NADPH oxidase expression. Exercise training by weight lifting in water did not improve the vascular alterations induced by ND treatment. ND treatment also significantly reduced the serum levels of estradiol in females, overriding its CV protective effect. These results help uncover the role of ND modulating endothelial function in the setting of CV disease caused by the abuse of AAS in females. If this translates to humans, young women abusing AAS can potentially lose the cardio protective effect rendered by estrogen and be more susceptible to CV alterations.

The renin-angiotensin-system is an important component of cardiovascular control and is up-regulated under various conditions, including hypertension and menopause. The aim of this study was to evaluate the effects of swimming training and estrogen therapy (ET) on angiotensin-II (ANG II)-induced vasoconstriction and angiotensin-(1-7) [ANG-(1-7)]-induced vasorelaxation in aortic rings from ovariectomized spontaneously hypertensive rats. Animals were divided into Sham (SH), Ovariectomized (OVX), Ovariectomized treated with E2 (OE2), Ovariectomized plus swimming (OSW) and Ovariectomized treated with E2 plus swimming (OE2+SW) groups. ET entailed the administration of 5μg of 17β-Estradiol three times per week. Swimming was undertaken for sixty minutes each day, five times per week. Both, training and ET were initiated seven days following ovariectomy. Forty-eight hours after the last treatment or training session, the animals' systolic blood pressures were measured, and blood samples were collected to measure plasma ANG II and ANG-(1-7) levels via radioimmunoassay. In aortic rings, the vascular reactivity to ANG II and ANG-(1-7) was assessed. Expression of ANG-(1-7) in aortic wall was analyzed by immunohistochemistry. The results showed that both exercise and ET increased plasma ANG II levels despite attenuating systolic blood pressure. Ovariectomy increased constrictor responses to ANG II and decreased dilatory responses to ANG-(1-7), which were reversed by swimming independently of ET. Moreover, it was observed an apparent increase in ANG-(1-7) content in the aorta of the groups subjected to training and ET. Exercise training may play a cardioprotective role independently of ET and may be an alternative to ET in hypertensive postmenopausal women.

OBJECTIVE: Insulin resistance is characterized by the failure of target cells to respond to normal levels of circulating insulin, and this condition is related to cardiovascular disease. This study sought to evaluate the prevalence of insulin resistance and its association with markers of metabolic abnormalities and metabolic syndrome in bank employees. METHODS: A cross-sectional study was performed on 498 working men and women aged ≥20 years old. The Homeostasis Model Assessment (HOMA-IR) was used to determine the presence of insulin resistance based on cut-off values of ≤2.71 for normal insulin levels and >;2.71 for insulin resistance, as established for the adult Brazilian population. RESULTS: It was observed that the 52 (10.4%) overweight individuals with insulin resistance were 4.97 times (95%CI 1.31-18.83) more likely to have high HOMA-IR values than the normal-weight participants; among those who were obese, the likelihood increased to 17.87 (95%CI 4.36-73.21). Individuals with large waist circumferences were 3.27 times (95%CI 1.03-10.38) more likely to develop insulin resistance than those who were within normal parameters. The HOMA-IR values differed between subjects with and without metabolic syndrome, with values of 2.83±2.5 and 1.10±0.81 (p=0.001), respectively. The levels of insulin, ultrasensitive C-reactive protein and uric acid were also associated with insulin resistance. CONCLUSION: The prevalence of insulin resistance among bank employees is high, and insulin resistance is associated with and serves as a marker of metabolic syndrome. Cardiovascular disease and metabolic syndrome-associated metabolic abnormalities were observed, and insulin resistance may be a risk factor in this group of professionals.

Introduction Misuse of AAS is emergent among both genders, however, few studies were performed evaluating AAS effects on female body and none evaluate the impact of nandrolone decanoate (ND) in renal function. Aim Determine the effects of chronic treatment with ND on kidney function of female rats and evaluate the influence of oxidative stress on it. Material and methods Female rats were separated into two groups (n = 8 each), the treated group (DECA), which received ND at a dose of 20 mg/kg/week (i.m), and the control group (C), which was treated with the vehicle (peanut oil, i.m.). All treatments were performed during eight weeks. After this period, 24 h urine, blood and organs (heart, gastrocnemius muscle, liver and kidney) were collected. Organ hypertrophy was calculated, and kidney collagen content was evaluated. AOPP, TBARS, SOD and catalase activity were determined in the kidney. Moreover, proteinuria and creatinine clearance were also investigated. Key-findings Hypertrophy was observed in the liver, gastrocnemius muscle, heart and kidney. Kidney hypertrophy was followed by a reduced organ function and an increase in collagen deposition. Oxidative stress upsurge occurred in both proteins and lipids, followed by a reduction in SOD activity. Significance Administration of DN in rats was followed by renal damage and kidney fibrosis due to increased oxidative stress on that organ.

Aims Telmisartan (TEL), an angiotensin II type I receptor blocker and PPARγ partial agonist, has been used for to treat hypertension. It is known that PPARγ activation induces bone loss. Therefore, we evaluate the effects of telmisartan on PPARγ protein expression, biomechanics, density and bone microarchitecture of femurs and lumbar vertebrae in SHR ovariectomized animals, a model of hypertension in which preexisting bone impairment has been demonstrated. Main methods SHR females (3 months old) were distributed into four groups: sham (S), sham + TEL (ST), OVX (C) and OVX + TEL (CT). TEL (5 mg/kg/day) or vehicle were administered according to the groups. After the protocol, blood pressure was measured and density, microarchitecture and biomechanics of bone were analyzed. Western blotting analysis was performed to evaluate PPARγ protein expression in the bones. Key findings Castration induced a deleterious effect on mineral density and trabecular parameters, with telmisartan enhancing such effects. Telmisartan increased PPARγ levels, which were at their highest when the treatment was combined with castration. As to biomechanical properties, telmisartan reduced the stiffness in the castration group (CT vs. S or C group), as well as resilience and failure load in ST group (vs. all others groups). Significance These results demonstrated that telmisartan compromised bone density and microarchitecture in animals that shows preexisting osteoporotic bone disorders, probably via mechanisms associated with increased PPARγ. If this translates to humans, a need for greater caution in the use of telmisartan by patients that have preexisting bone problems, as in the postmenopausal period, may be in order.

This work evaluated the effects of long-term kefir treatment in cardiac function (cardiac contractility and calcium-handling proteins) and the central nervous system (CNS) control of the sympathetic signaling in spontaneously hypertensive rats (SHR). Male normotensive rats [Wistar Kyoto rats (WKYs)] and SHRs were divided into three groups: WKYs and SHRs treated with vehicle, and SHRs treated with milk fermented by the grains of kefir (5%; SHR-Kefir; oral gavage, 0.3 ml/100 g daily/9 weeks). At the end of treatment, mean arterial pressure (MAP) and heart rate (HR) were measured by direct arterial catheterization. Hemodynamic parameters (left ventricular systolic pressure, left ventricular isovolumetric relaxation time constant, maximal and minimal pressure decay) were acquired through a left ventricular catheter implantation. Left ventricle protein expressions of phospholamban (PLB), its phosphorylated form (p-PLB) and sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) were determined by Western blot. Tyrosine hydroxylase (TH) protein expression was evaluated via immunofluorescence within the paraventricular nucleus (PVN) of the hypothalamus and the rostral ventrolateral medulla (RVLM). SHR-Kefir group presented lower MAP and HR compared to SHRs. Kefir treatment ameliorated cardiac hypertrophy and promoted reduced expression of PLB, p-PLB and SERCA2a contractile proteins. Within the PVN and RVML, TH protein overexpression observed in SHRs was reduced by probiotic treatment. In addition, kefir improved cardiac hemodynamic parameters in SHR-treated animals. Altogether, the data show that long-term kefir treatment reduced blood pressure by mechanisms involving reduction of cardiac hypertrophy, improvement of cardiac contractility and calcium-handling proteins, and reduction in the CNS regulation of the sympathetic activity.

Renovascular hypertension is characterized by increased angiotensin II and oxidative stress, and by endothelial dysfunction. The purpose of this study was to test whether the administration of aliskiren (ALSK) and l-arginine (l-ARG) would restore impaired baroreflex sensitivity and reduce oxidative stress in a rat renovascular hypertension model. Hypertension was induced by clipping the left renal artery, and the following five groups were created: SHAM; two-kidney, 1-clip (2K1C); 2K1C plus ALSK (ALSK); 2K1C plus l-ARG (l-ARG); and 2K1C plus ALSK+l-ARG (ALSK+l-ARG). After 21 days of treatment, only the ALSK+l-ARG group was effective in normalizing the arterial pressure (108.8±2.8 mm Hg). The l-ARG and ALSK+l-ARG groups did not show hypertrophy of the left ventricle. All the treatments restored the depressed baroreflex sensitivity to values found in the SHAM group. Acute administration of TEMPOL restored the depressed baroreflex sensitivity in the 2K1C group to values that resembled those presented by the other groups. All treatments were effective for an increase in the antioxidant pathway and reduction in the oxidative pathway. In conclusion, the treatment with ALSK or l-ARG reduced oxidative stress and restored reduced baroreflex sensitivity in renovascular hypertension. In addition, the treatments were able to normalize blood pressure and reverse left ventricular hypertrophy when used in combination.

Anabolic-androgenic steroids are misused, including by women, but little is known about the cardiovascular effects of these drugs on women. Aim: To evaluated the effects of nandrolone decanoate (ND) and resistive physical exercise on cardiac contractility in young female rats. Main methods: Female Wistar rats were separated into 4 groups: C (untrained animals); E (animals were submitted to resistance exercise by jumping in water 5 times per week); ND (animals were treated with ND, 20 mg/kg/week for 4 weeks); and NDE (trained and treated). The haemodynamic parameters (+ dP/dt max , − dP/dt min and Tau) were assessed in the left ventricle. The heart was collected for histological analyses and collagen deposition. The gastrocnemius muscle was weighed, and hypertrophy was assessed by the ratio of their weights to gastrocnemius/tibia length. The expression of calcium handling proteins was measured by western blot analysis. Results: ND treatment and physical exercise increased cardiac contractility and relaxation. In addition, ND promoted increases in phospholamban phosphorylated (p-PLB) and isoforms of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a) expression, while resistance exercise increased the phosphorylation of PLB and expression of Na + /Ca 2 + exchangers (NCX). Cardiac hypertrophy and collagen deposition were observed after ND treatment. Conclusion: Regulatory components of cytosolic calcium, such as SERCA2a and p-PLB, play important roles in modulating the contractility and relaxation effects of ND in females.

The negative relationship between androgens and the Bezold–Jarisch reflex (BJR) has been demonstrated, but no studies evaluated the physiological influence of testosterone on this reflex. We evaluated the influence of male rat castration on the BJR, cardiac morphometric parameters, and the plasmatic and the cardiac angiotensin converting enzyme (ACE) activity. After castration (CAS), the rats were divided into 24 and 72 h (CAS24H, CAS72H), and 7 and 21 days (CAS7D, CAS21D) groups. The BJR was studied by administering increasing doses of phenylbiguanide (PBG; 1.5–24 μg/kg) at different times after castration. Castration results in the following: (i) reduction in testosterone levels (SHAM: 238.7 ± 15.1; CAS24H: 9.0 ± 0.5; CAS72H: 6.7 ± 0.4; CAS7D: 5.2 ± 0.2; and CAS21D: 2.2 ± 0.3 ng/dL; p < 0.05); (ii) no changes in 17β-estradiol; (iii) a reduced BJR sensitivity (PBG 6 μg/kg; SHAM: 77 ± 7; CAS24H: 63 ± 10; CAS72H: 55 ± 6; CAS7D: 54 ± 4; and CAS21D: 35 ± 2%; p < 0.01); (iv) a decrease in cardiac (SHAM: 107 ± 6; CAS24H: 92 ± 2; CAS72H: 82 ± 3; CAS7D: 54 ± 3; and CAS21D: 43 ± 4%; p < 0.05) and plasmatic (SHAM: 135 ± 8; CAS24H: 102 ± 5; CAS72H: 99 ± 3; CAS7D: 89 ± 4; and CAS21D: 56 ± 6%; p < 0.05) ACE activity. No changes were observed in cardiac morphometry and hemodynamic parameters. Therefore, castration leads to decrease in testosterone levels as early as 24 h, reduction in ACE activity and loss of BJR sensitivity 7 days after castration. The loss of BJR sensitivity was not related to cardiac morphometric changes and cardiovascular hemodynamics.

This study evaluated the effects of nandrolone associated with resistance training (RT) on cardiac cytokines, angiotensin-converting enzyme activity (ACEA), and the sensitivity of the Bezold-Jarisch reflex (BJR). Male Wistar rats were divided into 3 groups: CONT (received vehicle, no training); EXERC (RT: after one week of water adaptation, rats were exercised by jumping into water twice a week for 4 weeks), and ND+EXERC (received nandrolone decanoate 10 mg/kg, twice/week, i.m, associated with RT). The BJR was analysed by measuring bradycardic and hypotensive responses elicited by serotonin administration. Myocyte hypertrophy and matrix collagen deposition were determined by morphometric analysis of H&E and picrosirius red-stained samples, respectively. TNF-α and ACEA were also studied. RT promoted physiological myocyte hyrpertrophy but did not cause changes in the other parameters. The association of ND with RT increased myocyte hypertrophy, deposition of matrix type I collagen, TNF-α and ACEA; decreased IL-10, and impairment in the BJR were observed in ND+EXERC compared with CONT and EXERC. ND is associated with alterations in cardiac structure and function as a result of the development of pathological cardiac hypertrophy (cardiac cytokine imbalance, elevation of ACEA) and cardiac injury, even when combined with resistance training.

O objetivo deste trabalho foi verificar como trabalhadores bancários avaliam seu estado de saúde e os principais fatores associados a esse indicador nessa população. Trata-se de um estudo transversal com 525 funcionários de uma rede bancária do Estado do Espírito Santo, Brasil. A magnitude das associações foi avaliada através de regressão logística hierarquizada em níveis. Verificou-se que 17% (n = 87) dos bancários autoavaliaram seu estado de saúde como regular ou ruim. Estiveram associados à pior autoavaliação de saúde o reduzido nível socioeconômico (OR = 1,80; IC95%: 1,06-3,05), o estilo de vida sedentário (OR = 2,64; IC95%: 1,42-4,89), o excesso de peso (OR = 3,18; IC95%: 1,79-5,65), o baixo apoio social (OR = 3,71; IC95%: 2,10-6,58) e a presença de doenças crônicas (OR = 5,49; IC95%: 2,46-12,27). Concluiu-se que, comparado com outras localidades, houve um expressivo número de bancários que autoavaliaram seu estado de saúde como regular ou ruim, e que a presença de doenças crônicas apresentou-se como o fator de maior impacto sobre a forma como o indivíduo avalia sua própria saúde. The aim of this study was to determine how bank employees assess their health status and risk factors associated with this indicator in this population. This is a cross-sectional study involving 525 workers of a banking system in the State of Espírito Santo, Brazil. The magnitude of the associations was assessed using logistic regression hierquizada in levels. It was found that 17% (n = 87) of bank self-rated their health status as fair or poor. Were associated with worse self-assessed health of the low socioeconomic level (OR = 1.80; 95%CI: 1.06-3.05), the sedentary lifestyle (OR = 2.64; 95%CI: 1.42-4.89), the excess weight (OR = 3.18; 95%CI: 1.79-5.65), low social support (OR = 3.71; 95%CI: 2.10-6.58), and the presence of chronic diseases (OR = 5,49; 95%CI: 2.46-12.27). It is concluded that, compared with other locations, there was a significant number of banking that self-rated their health status as fair or poor, and that the presence of chronic diseases was presented as the factor with the greatest impact on how the individual evaluates their own health. El objetivo de este estudio fue investigar cómo los empleados del banco a evaluar su estado de salud y factores de riesgo asociados a este indicador en esta población. Se trata de un estudio transversal con 525 trabajadores de un sistema bancario en el estado de Espírito Santo, Brasil. La magnitud de las asociaciones se evaluó mediante regresión logística hierquizada en niveles. Se encontró que 17% (n = 87) de los trabajadores del banco auto-calificaron su estado de salud como regular o mala. Se asociaron con la salud autopercibida peor del bajo nivel socio-económico (OR = 1,80; IC95%: 1,06-3,05), el sedentarismo (OR = 2,64; IC95%: 1,42-4,89), el exceso de peso (OR = 3,18; IC95%: 1,79-5,65), el baja apoyo social (OR = 3,71; IC95%: 2,10-6,58), y la presencia de enfermedades crónicas (OR = 5,49; IC95%: 2,46-12,27). Se concluye que, en comparación con otros lugares, hubo un número significativo de la banca que la auto-calificaron su estado de salud como regular o mala, y que la presencia de enfermedades crónicas se presenta como el factor de mayor impacto en cómo los evalúa individuales su propia salud.