Testosterone deficiency impairs cardiac interfibrillar mitochondrial function and myocardial contractility while inducing oxidative stress.

Introduction: Clinical studies have shown that low levels of endogenous testosterone are associated with cardiovascular diseases. Considering the intimate connection between oxidative metabolism and myocardial contractility, we determined the effects of testosterone deficiency on the two spatially distinct subpopulations of cardiac mitochondria, subsarcolemmal (SSM) and interfibrillar (IFM). Methods: We assessed cardiac function and cardiac mitochondria structure of SSM and IFM after 12 weeks of testosterone deficiency in male Wistar rats. Results and Discussion: Results show that low testosterone reduced myocardial contractility. Orchidectomy increased total left ventricular mitochondrial protein in the SSM, but not in IFM. The membrane potential, size and internal complexity in the IFM after orchidectomy were higher compared to the SHAM group. However, the rate of oxidative phosphorylation with all substrates in the IFM after orchidectomy was lower compared to the SHAM group. Testosterone replacement restored these changes. In the testosterone-deficient SSM group, oxidative phosphorylation was decreased with palmitoyl-L-carnitine as substrate; however, the mitochondrial calcium retention capacity in IFM was increased. There was no difference in swelling of the mitochondria in either group. These changes in IFM were followed by a reduction in phosphorylated form of AMP-activated protein kinase (p-AMPK-α), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) translocation to mitochondria and decreased mitochondrial transcription factor A (TFAM). Testosterone deficiency increased NADPH oxidase (NOX), angiotensin converting enzyme (ACE) protein expression and reduced mitochondrial antioxidant proteins such as manganese superoxide dismutase (Mn-SOD) and catalase in the IFM. Treatment with apocynin (1.5 mM in drinking water) normalized myocardial contractility and interfibrillar mitochondrial function in the testosterone depleted animals. In conclusion, our findings demonstrate that testosterone deficiency leads to reduced myocardial contractility and impaired cardiac interfibrillar mitochondrial function. Our data suggest the involvement of reactive oxygen species, with a possibility of NOX as an enzymatic source.

Instrumentos de avaliação do ajuste psicossocial à amputação, uso e satisfação com a prótese: uma revisão sistemática da literatura / Instruments for evaluation of psychosocial adjustment to amputation, use and satisfaction with the prosthesis: a systematic review of literature

O ajuste à amputação envolve tanto questões físicas quanto psicossociais e a satisfação com o membro artificial. Objetivo: Revisar sistematicamente a literatura acerca dos instrumentos que avaliam o ajuste psicossocial à amputação e uso da prótese e a satisfação com a prótese em pessoas com amputação de membro inferior. Métodos: Fonte de dados: Medline via Pubmed, Web of Science e Scopus. Critérios de elegibilidade: estudos originais que utilizaram questionários para avaliar o ajustamento psicossocial a amputação e uso da prótese e a satisfação com a prótese. Participantes: pessoas com amputação de membro inferior. Métodos de avaliação e síntese dos estudos: todas as análises foram realizadas por três avaliadores, de forma independente, sendo os resultados apresentados de forma descritiva, em tabelas. Resultados: Foram encontrados 239 artigos na busca inicial, sendo incluídos 12 artigos ao final da revisão. Nestes, foram identificados 14 questionários que avaliam o ajuste psicossocial e a satisfação com a prótese, porém, somente 5 são validados especificamente para a população amputada. Conclusão: A Trinity Amputation and Prosthesis Experience Scale (TAPES) e o Prosthesis Evaluation Questionnaire (PEQ) são os instrumentos mais utilizados, sendo sempre importante uma seleção criteriosa dos instrumentos a serem utilizados nas pesquisas e intervenções a fim de se obter dados válidos, confiáveis e comparáveis. Número de registro da revisão sistemática: CRD42019097279

The adjustment to amputation involves physical and psychosocial issues and the satisfaction with the artificial limb. Objective: To systematically review the literature about the instruments that assess psychosocial adjustment to amputation and use of the prosthesis and satisfaction with the prosthesis in people with lower limb amputation. Methods: Data sources: Medline via Pubmed, Web of Science and Scopus. Study eligibility criteria: Original studies that using questionnaires to evaluated the psychosocial adjustment to amputation and prosthesis use and about prosthesis satisfaction. Participants: people with lower limb amputation. Study appraisal and synthesis methods: all analyzes were performed independently by three evaluators, and the results were presented descriptively, in tables. Results: Were found 239 articles in the initial search, with 12 articles included at the end of the review. In these, 16 questionnaires were identified that assess the psychosocial adjustment and satisfaction with the prosthesis, however, only five are validated specifically for the amputated population. Conclusion: The Trinity Amputation and Prosthesis Experience Scale (TAPES) and the Prosthesis Evaluation Questionnaire (PEQ) are the most used instruments, being always important to carefully select the instruments to be used in research and interventions in order to obtain valid, reliable and comparable data. Systematic review registration number: CRD42019097279

Endurance training restores spatially distinct cardiac mitochondrial function and myocardial contractility in ovariectomized rats.

We previously demonstrated that the loss of female hormones induces cardiac and mitochondrial dysfunction in the female heart. Here, we show the impact of endurance training for twelve weeks, a nonpharmacological therapy against cardiovascular disease caused by ovariectomy and its contribution to cardiac contractility, mitochondrial quality control, bioenergetics and oxidative damage. We found that ovariectomy induced cardiac hypertrophy and dysfunction by decreasing SERCA2 and increasing phospholamban protein expression. Endurance training restored myocardial contractility, SERCA2 levels, increased calcium transient in ovariectomized rats but did not change phospholamban protein expression or cardiac hypertrophy. Additionally, ovariectomy decreased the amount of intermyofibrillar mitochondria and induced mitochondrial fragmentation that were accompanied by decreased levels of mitofusin 1, PGC-1α, NRF-1, total AMPK-α and mitochondrial Tfam. Endurance training prevented all these features except for mitofusin 1. Ovariectomy reduced O2 consumption, elevated O2.- release and increased Ca2+-induced mitochondrial permeability transition pore opening in both mitochondrial subpopulations. Ovariectomy also increased NOX-4 protein expression in the heart, reduced mitochondrial Mn-SOD, catalase protein expression and increased protein carbonylation in both mitochondrial subpopulations, which were prevented by endurance training. Taken together, our findings show that endurance training prevented cardiac contractile dysfunction and mitochondrial quality control in ovariectomized rats.

Estrogen regulates spatially distinct cardiac mitochondrial subpopulations.

Increased susceptibility to permeability transition pore (mPTP) is a significant concern to decreased cardiac performance in postmenopausal females. The goal of this study was to assess the effects of estrogen deficiency on the two spatially distinct mitochondrial subpopulations from left ventricle: subsarcolemmal mitochondria (SSM) and intermyofibrillar mitochondria (IFM) based on: morphology, membrane potential, oxidative phosphorylation, mPTP and reactive oxygen species production. Female rats (8weeks old) that underwent bilateral ovariectomy were randomly assigned to receive daily treatment with placebo (OVX), estrogen replacement (OVX+E2) and Sham for 60days. The yield for IFM was found higher in the OVX group and lower in the SSM. SSM internal complexity and size were higher in the OVX group, although membrane potential was not different. The maximal rate of mitochondrial respiration, states 3 and 4, using glutamate+malate as substrate, were higher in IFM and SSM from the OVX group. The respiratory control ratio (RCR - state3/state 4), was not different in both SSM and IFM with glutamate+malate. The ADP:O ratio was found lower in IFM and SSM from OVX compared to Sham. When pyruvate was used, state 3 was found unchanged in both IFM and SSM, state 4 was greater in IFM from OVX rats compared to Sham and the ADP/O ratio was decreased. The RCR was unchanged in both subpopulations. The IFM from OVX rats presented a lower Ca2+retention capacity compared to Sham, however, the SSM remained unchanged. Hydrogen peroxide formation was found increased in the IFM from OVX animals with glutamate+malate and rotenone+succinate as substrates. The SSM showed increased ROS production only with rotenone+succinate. Western blot analyzes showed decreased levels of PGC-1α and NRF-1 in the OVX group. Estrogen replacement was able to restore most of the alterations induced by ovariectomy. In conclusion, our data shows that estrogen deficiency has distinct effects on the two spatially distinct mitochondrial subpopulations in oxidative phosphorylation, morphology, calcium retention capacity and ROS production.

Tributyltin chloride increases phenylephrine-induced contraction and vascular stiffness in mesenteric resistance arteries from female rats.

Tributyltin chloride (TBT) is an organotin compound that reduces estrogen levels in female rats. We aimed to investigate the effects of TBT exposure on vascular tonus and vascular remodelling in the resistance arteries of female rats. Rats were treated daily with TBT (500 ng/kg) for 15 days. TBT did not change arterial blood pressure but did modify some morpho-physiological parameters of third-order mesenteric resistance arteries in the following ways: (1) decreased lumen and external diameters; (2) increased wall/lm ratio and wall thickness; (3) decreased distensibility and increased stiffness; (4) increased collagen deposition; and (5) increased pulse wave velocity. TBT exposure increased the phenylephrine-induced contractile response in mesenteric resistance arteries. However, vasodilatation responses induced by acetylcholine and sodium nitroprusside were not modified by TBT. It is suggested that TBT exposure reduces vascular nitric oxide (NO) production, because:(1) L-NAME incubation did not cause a leftward shift in the concentration-response curve for phenylephrine; (2) both eNOS protein expression; (3) in situ NO production were reduced. Incubation with L-NAME; and (4) SOD shifted the phenylephrine response curve to the left in TBT rats. Tiron, catalase, ML-171 and VAS2870 decreased vascular reactivity to phenylephrine only in TBT rats. Moreover, increased superoxide anion production was observed in the mesenteric resistance arteries of TBT rats accompanied by an increase in gp91phox, catalase, AT1 receptor and total ERK1/2 protein expression. In conclusion, these findings show that TBT induced alterations are most likely due to a reduction of NO production combined with increased O2(-) production derived from NADPH oxidase and ERK1/2 activation. These findings offer further evidence that TBT is an environmental risk factor for cardiovascular disease.

Prevalence of postural alterations in students of Basic Education in the city of Vila Velha, Espírito Santo state, Brazil / Prevalência de alterações posturais em escolares de Ensino Fundamental de Vila Velha (ES)

Introduction Human posture goes through a series of changes in the course of body growth and development, i.e., in childhood and adolescence. Moreover, during these phases, individuals are subject to risk behaviors for spinal problems, especially those related to the use of backpacks and to poor sitting posture. Objective This study aimed to detect the prevalence of postural alterations in school children enrolled in the UMEF Vila Olímpica, Vila Velha, Espírito Santo. Methods We evaluated 513 schoolchildren in the orthostatic position and in the anterior, posterior and side view. The following structures were analyzed: head, shoulder, the cervical, thoracic and lumbar spine, pelvis and lower limbs. Results There was a high prevalence of postural deviations: rotated or tilted head, elevated shoulder and pelvis, valgus or varus knee, head protraction, alterations of the thoracic spine, anteriorized shoulders, pelvis in anteversion, knees semiflexion or hyperextension and cavus or planus feet. Conclusion Our results suggest that there is a high prevalence of postural alterations in students in the school network of Vila Velha (ES). This could be detected through public health policies, such as the federal government´s Health at School Program (PSE). .

Introdução A postura do ser humano apresenta uma série de mudanças no decorrer do crescimento e desenvolvimento corporais, ou seja, na infância e na adolescência. Além disso, durante essas fases, os indivíduos estão sujeitos a comportamentos de risco para a coluna, principalmente aqueles relacionados à utilização de mochilas e à postura sentada. Objetivo A finalidade desse trabalho foi verificar a prevalência de alterações posturais em escolares da UMEF Vila Olímpica, Vila Velha, Espírito Santo. Métodos Foram avaliados 513 escolares na posição ortostática, em vista anterior, posterior e perfil, no qual foram analisadas as seguintes estruturas: cabeça, ombro, colunas cervical, torácica e lombar, pelve e membros inferiores. Resultados Os resultados apresentaram uma grande prevalência de desvios posturais: cabeça rodada ou inclinada, elevação do ombro e da pelve, joelho valgo ou varo, além de cabeça em prostração, alterações da coluna torácica, ombros anteriorizados, pelve em anteroversão, joelhos em semiflexão ou hiperextensão, e pés cavos ou planos. Conclusão Os resultados sugerem que há uma alta prevalência de alterações posturais em escolares na rede de ensino do município, o que poderia ser identificado através de políticas públicas de saúde, como o Programa Saúde na Escola (PSE) do governo federal. .