Metabolic mitochondrial alterations prevail in the female rat heart 8 weeks after exercise cessation.

BACKGROUND: The consumption of high-caloric diets strongly contributes to the development of non-communicable diseases (NCDs), including cardiovascular disease, the leading cause of mortality worldwide. Exercise (along with diet intervention) is one of the primary non-pharmacological approaches to promote a healthier lifestyle and counteract the rampant prevalence of NCDs. The present study evaluated the effects of exercise cessation after a short period training on the cardiac metabolic and mitochondrial function of female rats. METHODS: Seven-week-old female Sprague-Dawley rats were fed a control or a high-fat, high-sugar (HFHS) diet and, after 7 weeks, the animals were kept on a sedentary lifestyle or submitted to endurance exercise for 3 weeks (6 days per week, 20-60 min/day). The cardiac samples were analysed 8 weeks after exercise cessation. RESULTS: The consumption of the HFHS diet triggered impaired glucose tolerance, whereas the HFHS diet and physical exercise resulted in different responses in plasma adiponectin and leptin levels. Cardiac mitochondrial respiration efficiency was decreased by the HFHS diet consumption, which led to reduced ATP and increased NAD(P)H mitochondrial levels, which remained prevented by exercise 8 weeks after cessation. Exercise training-induced cardiac adaptations in redox balance, namely increased relative expression of Nrf2 and downstream antioxidant enzymes persist after an eight-week exercise cessation period. CONCLUSIONS: Endurance exercise modulated cardiac redox balance and mitochondrial efficiency in female rats fed a HFHS diet. These findings suggest that exercise may elicit cardiac adaptations crucial for its role as a non-pharmacological intervention for individuals at risk of developing NCDs.

Stretch Harmonizes Sarcomere Strain Across the Cardiomyocyte.

BACKGROUND: Increasing cardiomyocyte contraction during myocardial stretch serves as the basis for the Frank-Starling mechanism in the heart. However, it remains unclear how this phenomenon occurs regionally within cardiomyocytes, at the level of individual sarcomeres. We investigated sarcomere contractile synchrony and how intersarcomere dynamics contribute to increasing contractility during cell lengthening. METHODS: Sarcomere strain and Ca2+ were simultaneously recorded in isolated left ventricular cardiomyocytes during 1 Hz field stimulation at 37 °C, at resting length and following stepwise stretch. RESULTS: We observed that in unstretched rat cardiomyocytes, differential sarcomere deformation occurred during each beat. Specifically, while most sarcomeres shortened during the stimulus, ≈10% to 20% of sarcomeres were stretched or remained stationary. This nonuniform strain was not traced to regional Ca2+ disparities but rather shorter resting lengths and lower force production in systolically stretched sarcomeres. Lengthening of the cell recruited additional shortening sarcomeres, which increased contractile efficiency as less negative, wasted work was performed by stretched sarcomeres. Given the known role of titin in setting sarcomere dimensions, we next hypothesized that modulating titin expression would alter intersarcomere dynamics. Indeed, in cardiomyocytes from mice with titin haploinsufficiency, we observed greater variability in resting sarcomere length, lower recruitment of shortening sarcomeres, and impaired work performance during cell lengthening. CONCLUSIONS: Graded sarcomere recruitment directs cardiomyocyte work performance, and harmonization of sarcomere strain increases contractility during cell stretch. By setting sarcomere dimensions, titin controls sarcomere recruitment, and its lowered expression in haploinsufficiency mutations impairs cardiomyocyte contractility.

Exercise reduces intramuscular stress and counteracts muscle weakness in mice with breast cancer.

BACKGROUND: Patients with breast cancer exhibit muscle weakness, which is associated with increased mortality risk and reduced quality of life. Muscle weakness is experienced even in the absence of loss of muscle mass in breast cancer patients, indicating intrinsic muscle dysfunction. Physical activity is correlated with reduced cancer mortality and disease recurrence. However, the molecular processes underlying breast cancer-induced muscle weakness and the beneficial effect of exercise are largely unknown. METHODS: Eight-week-old breast cancer (MMTV-PyMT, PyMT) and control (WT) mice had access to active or inactive in-cage voluntary running wheels for 4 weeks. Mice were also subjected to a treadmill test. Muscle force was measured ex vivo. Tumour markers were determined with immunohistochemistry. Mitochondrial biogenesis and function were assessed with transcriptional analyses of PGC-1α, the electron transport chain (ETC) and antioxidants superoxide dismutase (Sod) and catalase (Cat), combined with activity measurements of SOD, citrate synthase (CS) and ß-hydroxyacyl-CoA-dehydrogenase (ßHAD). Serum and intramuscular stress levels were evaluated by enzymatic assays, immunoblotting, and transcriptional analyses of, for example, tumour necrosis factor-α (TNF-α) and p38 mitogen-activated protein kinase (MAPK) signalling. RESULTS: PyMT mice endured shorter time and distance during the treadmill test (~30%, P < 0.05) and ex vivo force measurements revealed ~25% weaker slow-twitch soleus muscle (P < 0.001). This was independent of cancer-induced alteration of muscle size or fibre type. Inflammatory stressors in serum and muscle, including TNF-α and p38 MAPK, were higher in PyMT than in WT mice (P < 0.05). Cancer-induced decreases in ETC (P < 0.05, P < 0.01) and antioxidant gene expression were observed (P < 0.05). The exercise intervention counteracted the cancer-induced muscle weakness and was accompanied by a less aggressive, differentiated tumour phenotype, determined by increased CK8 and reduced CK14 expression (P < 0.05). In PyMT mice, the exercise intervention led to higher CS activity (P = 0.23), enhanced ß-HAD and SOD activities (P < 0.05), and reduced levels of intramuscular stressors together with a normalization of the expression signature of TNFα-targets and ETC genes (P < 0.05, P < 0.01). At the same time, the exercise-induced PGC-1α expression, and CS and ß-HAD activity was blunted in muscle from the PyMT mice as compared with WT mice, indicative that breast cancer interfere with transcriptional programming of mitochondria and that the molecular adaptation to exercise differs between healthy mice and those afflicted by disease. CONCLUSIONS: Four-week voluntary wheel running counteracted muscle weakness in PyMT mice which was accompanied by reduced intrinsic stress and improved mitochondrial and antioxidant profiles and activities that aligned with muscles of healthy mice.

Mitochondrial NDUFA4L2 is a novel regulator of skeletal muscle mass and force.

The hypoxia-inducible nuclear-encoded mitochondrial protein NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 (NDUFA4L2) has been demonstrated to decrease oxidative phosphorylation and production of reactive oxygen species in neonatal cardiomyocytes, brain tissue and hypoxic domains of cancer cells. Prolonged local hypoxia can negatively affect skeletal muscle size and tissue oxidative capacity. Although skeletal muscle is a mitochondrial rich, oxygen sensitive tissue, the role of NDUFA4L2 in skeletal muscle has not previously been investigated. Here we ectopically expressed NDUFA4L2 in mouse skeletal muscles using adenovirus-mediated expression and in vivo electroporation. Moreover, femoral artery ligation (FAL) was used as a model of peripheral vascular disease to induce hind limb ischemia and muscle damage. Ectopic NDUFA4L2 expression resulted in reduced mitochondrial respiration and reactive oxygen species followed by lowered AMP, ADP, ATP, and NAD+ levels without affecting the overall protein content of the mitochondrial electron transport chain. Furthermore, ectopically expressed NDUFA4L2 caused a ~20% reduction in muscle mass that resulted in weaker muscles. The loss of muscle mass was associated with increased gene expression of atrogenes MurF1 and Mul1, and apoptotic genes caspase 3 and Bax. Finally, we showed that NDUFA4L2 was induced by FAL and that the Ndufa4l2 mRNA expression correlated with the reduced capacity of the muscle to generate force after the ischemic insult. These results show, for the first time, that mitochondrial NDUFA4L2 is a novel regulator of skeletal muscle mass and force. Specifically, induced NDUFA4L2 reduces mitochondrial activity leading to lower levels of important intramuscular metabolites, including adenine nucleotides and NAD+ , which are hallmarks of mitochondrial dysfunction and hence shows that dysfunctional mitochondrial activity may drive muscle wasting.

Body composition, but not insulin resistance, influences postprandial lipemia in patients with Turner's syndrome.

OBJECTIVE: The aim of the present study was to examine the influence of body composition and insulin resistance on the magnitude of postprandial lipemia in patients with Turner's syndrome receiving oral versus transdermal estrogen replacement. METHODS: Twenty-five patients with Turner's syndrome receiving oral or transdermal estrogen replacement were evaluated for body mass index, waist-to-hip and waist-to-height ratios, fasting glycemia, insulin, body composition (dual-energy X-ray absorptiometry), and postprandial lipid metabolism. For statistical analysis, we used parametric tests to compare numeric variables between the two subgroups. RESULTS: We observed no difference in postprandial triglyceride levels between patients receiving oral versus transdermal hormone replacement therapy. The postprandial triglycerides increment correlated positively with the percentage of total fat mass (p=0.02) and android fat mass (p=0.02) in the transdermal group. In the oral estrogen group, a positive correlation was observed between the increment in postprandial triglycerides and waist-to-hip (p=0.15) and waist-to-height (p=0.009) ratios. No association was observed between the estrogen replacement route and insulin resistance evaluated by the homeostatic model assessment-insulin resistance (HOMA-IR) index (p=0.19 and p=0.65 for the oral and transdermal groups, respectively). CONCLUSION: We concluded that body composition and anthropometric characteristics possibly affect the extent of postprandial lipemia independently from the route of estrogen replacement.

Body composition, but not insulin resistance, influences postprandial lipemia in patients with Turner's syndrome

ABSTRACT Objective: The aim of the present study was to examine the influence of body composition and insulin resistance on the magnitude of postprandial lipemia in patients with Turner's syndrome receiving oral versus transdermal estrogen replacement. Subjects and methods: Twenty-five patients with Turner's syndrome receiving oral or transdermal estrogen replacement were evaluated for body mass index, waist-to-hip and waist-to-height ratios, fasting glycemia, insulin, body composition (dual-energy X-ray absorptiometry), and postprandial lipid metabolism. For statistical analysis, we used parametric tests to compare numeric variables between the two subgroups. Results: We observed no difference in postprandial triglyceride levels between patients receiving oral versus transdermal hormone replacement therapy. The postprandial triglycerides increment correlated positively with the percentage of total fat mass (p=0.02) and android fat mass (p=0.02) in the transdermal group. In the oral estrogen group, a positive correlation was observed between the increment in postprandial triglycerides and waist-to-hip (p=0.15) and waist-to-height (p=0.009) ratios. No association was observed between the estrogen replacement route and insulin resistance evaluated by the homeostatic model assessment-insulin resistance (HOMA-IR) index (p=0.19 and p=0.65 for the oral and transdermal groups, respectively). Conclusion: We concluded that body composition and anthropometric characteristics possibly affect the extent of postprandial lipemia independently from the route of estrogen replacement.

Mitochondrial Reversible Changes Determine Diastolic Function Adaptations During Myocardial (Reverse) Remodeling.

BACKGROUND: Often, pressure overload-induced myocardial remodeling does not undergo complete reverse remodeling after decreasing afterload. Recently, mitochondrial abnormalities and oxidative stress have been successively implicated in the pathogenesis of several chronic pressure overload cardiac diseases. Therefore, we aim to clarify the myocardial energetic dysregulation in (reverse) remodeling, mainly focusing on the mitochondria. METHODS: Thirty-five Wistar Han male rats randomly underwent sham or ascending (supravalvular) aortic banding procedure. Echocardiography revealed that banding induced concentric hypertrophy and diastolic dysfunction (early diastolic transmitral flow velocity to peak early-diastolic annular velocity ratio, E/E': sham, 13.6±2.1, banding, 18.5±4.1, P=0.014) accompanied by increased oxidative stress (dihydroethidium fluorescence: sham, 1.6×108±6.1×107, banding, 2.6×108±4.5×107, P<0.001) and augmented mitochondrial function. After 8 to 9 weeks, half of the banding animals underwent overload relief by an aortic debanding surgery (n=10). RESULTS: Two weeks later, hypertrophy decreased with the decline of oxidative stress (dihydroethidium fluorescence: banding, 2.6×108±4.5×107, debanding, 1.96×108±6.8×107, P<0.001) and diastolic dysfunction improved simultaneously (E/E': banding, 18.5±4.1, debanding, 15.1±1.8, P=0.029). The reduction of energetic demands imposed by overload relief allowed the mitochondria to reduce its activity and myocardial levels of phosphocreatine, phosphocreatine/ATP, and ATP/ADP to normalize in debanding towards sham values (phosphocreatine: sham, 38.4±7.4, debanding, 35.6±8.7, P=0.71; phosphocreatine/ATP: sham, 1.22±0.23 debanding, 1.11±0.24, P=0.59; ATP/ADP: sham, 6.2±0.9, debanding, 5.6±1.6, P=0.66). Despite the decreased mitochondrial area, complex III and V expression increased in debanding compared with sham or banding. Autophagy and mitophagy-related markers increased in banding and remained higher in debanding rats. CONCLUSIONS: During compensatory and maladaptive hypertrophy, mitochondria become more active. However, as the disease progresses, the myocardial energetic demands increase and the myocardium becomes energy deficient. During reverse remodeling, the concomitant attenuation of cardiac hypertrophy and oxidative stress allowed myocardial energetics, left ventricle hypertrophy, and diastolic dysfunction to recover. Autophagy and mitophagy are probably involved in the myocardial adaptation to overload and to unload. We conclude that these mitochondrial reversible changes underlie diastolic function adaptations during myocardial (reverse) remodeling.

Skeletal muscle redox signaling in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovitis and the presence of serum autoantibodies. In addition, skeletal muscle weakness is a common comorbidity that contributes to inability to work and reduced quality of life. Loss in muscle mass cannot alone account for the muscle weakness induced by RA, but instead intramuscular dysfunction appears as a critical factor underlying the decreased force generating capacity for patients afflicted by arthritis. Oxidative stress and associated oxidative post-translational modifications have been shown to contribute to RA-induced muscle weakness in animal models of arthritis and patients with RA. However, it is still unclear how and which sources of reactive oxygen and nitrogen species (ROS/RNS) that are involved in the oxidative stress that drives the progression toward decreased muscle function in RA. Nevertheless, mitochondria, NADPH oxidases (NOX), nitric oxide synthases (NOS) and phospholipases (PLA) have all been associated with increased ROS/RNS production in RA-induced muscle weakness. In this review, we aim to cover potential ROS sources and underlying mechanisms of oxidative stress and loss of force production in RA. We also addressed the use of antioxidants and exercise as potential tools to counteract oxidative stress and skeletal muscle weakness.

Physical exercise mitigates behavioral impairments in a rat model of sporadic Alzheimer's disease.

Physical exercise has proven to be beneficial to mitigate several deleterious effects associated with neurodegenerative diseases, including Alzheimer's Disease (AD). Here, we investigated the role of long-term exercise as a preventive and therapeutic tool against AD cognitive and behavioral impairments using a sporadic AD-like rat model, established through the administration of streptozotocin (STZ) inside both cerebral ventricles (icv). Six-weeks-old Wistar male rats (56) were divided into groups (either saline or STZ): sedentary (Sed), voluntary physical activity (VPA), VPA + endurance treadmill training (VPA + ET) and VPA + ET only after the injection (VPA + ET-post). Surgeries occurred at 16wks and the animals were sacrificed at 28 wks. VPA, VPA + ET, and VPA + ET-post had continuous access to the running wheels during the entire experimental protocol. VPA + ET (entire protocol) and VPA + ET-post (only after surgical procedure) ran 60 min/d, 25 m/min, 5d/wk in a treadmill. Both ET regimens led to significant improvements in the compromised spatial learning and long-term memory of STZ-infused animals that were not observed neither in the saline Sed nor in VPA STZ groups. General activity patterns and exploration habits were also ameliorated with chronic-exercise in STZ treated animals, while freezing patterns were decreased in these groups. these results were further. Positive alterations were seen in mitochondrial oxygen consumption endpoints (synaptosomal and non-synaptosomal brain mitochondria) that might underlie the neurobehavioral improvements observed. Data suggest that VPA alone was not able to counteract the AD-related deleterious consequences, although when accompanied by endurance training (either lifelong or later-life) may be able to prevent and reverse cognitive and phenotypic impairments associated with AD.

Physical exercise positively modulates DOX-induced hepatic oxidative stress, mitochondrial dysfunction and quality control signaling.

Doxorubicin (DOX), a widely used and efficient antineoplastic agent, is mainly limited by cardiotoxicity, although other tissues including liver are also affected. The effects of exercise to cope with DOX side-effects has already been studied in the heart and brain, demonstrating successful results. However, the benefits of this non-pharmacological strategy have not been so extensively checked in the liver. We here aimed to ascertain whether exercise could mitigate DOX-induced liver harmful effects using mitochondria as a model for evaluating toxicity. Twenty-four male rats were divided into four groups: SED + SAL (sedentary with saline administration), SED + DOX (sedentary with DOX administration), ET + DOX (endurance-trained with DOX administration) and VPA + DOX (voluntary physical activity with DOX administration). Isolated liver mitochondria were obtained for evaluation of their respiratory activity and transmembrane electrical potential endpoints. Molecular markers of oxidative damage (carbonyls, MDA, aconitase, MnSOD), mitochondrial dynamics (PGC-1α, TFAM, OPA1, DRP1, MFN1) and auto(mito)phagy signaling (p62, LC3, Beclin1, Bcl-2, PINK, Parkin) were measured. Transmission electron microscopy evaluation was used to analyze mitochondrial morphological alterations. When compared to SED + SAL, respiratory function of SED + DOX was compromised. Decreased SOD and aconitase activities and increased MDA content, decreases in PGC-1α, TFAM, OPA1 and MFN1 expressions, and increases in DRP1 and LC3II/LC3I ratio were also observed after DOX administration. However, these alterations were reverted or mitigated in the ET + DOX group. Semi-quantitative and qualitative analyses from microphotographs showed that liver mitochondria of SED + DOX animals were more circular and had lower density, whereas the animals with exercise showed a tendency to revert this phenotype and increase the mitochondrial density. Taken together, our results suggest that physical exercise, particularly ET, positively reversed the deleterious effects caused by DOX administration, such as oxidative damage, mitochondrial dysfunction, and altered mitochondrial dynamics toward fission, thus contributing to increase liver resistance against DOX administration.

Self-Paced Free-Running Wheel Mimics High-Intensity Interval Training Impact on Rats' Functional, Physiological, Biochemical, and Morphological Features.

Free-running wheel (FRW) is an animal exercise model that relies on high-intensity interval moments interspersed with low-intensity or pauses apparently similar to those performed in high-intensity interval training (HIIT). Therefore, this study, conducted over a 12-weeks period, aimed to compare functional, thermographic, biochemical and morphological skeletal and cardiac muscle adaptations induced by FRW and HIIT. Twenty-four male Wistar rats were assigned into three groups: sedentary rats (SED), rats that voluntarily exercise in free wheels (FRW) and rats submitted to a daily HIIT. Functional tests revealed that compared to SED both FRW and HIIT increased the ability to perform maximal workload tests (MWT-cm/s) (45 ± 1 vs. 55 ± 2 and vs. 65 ± 2). Regarding thermographic assays, FRW and HIIT increased the ability to lose heat through the tail during MWT. Histochemical analyzes performed in tibialis anterior (TA) and soleus (SOL) muscles showed a general adaptation toward a more oxidative phenotype in both FRW and HIIT. Exercise increased the percentage of fast oxidative glycolytic (FOG) in medial fields of TA (29.7 ± 2.3 vs. 44.9 ± 4.4 and vs. 45.2 ± 5.3) and slow oxidative (SO) in SOL (73.4 ± 5.7 vs. 99.5 ± 0.5 and vs. 96.4 ± 1.2). HITT decreased fiber cross-sectional area (FCSA-µm2) of SO (4350 ± 286.9 vs. 4893 ± 325 and vs. 3621 ± 237.3) in SOL. Fast glycolytic fibers were bigger across all the TA muscle in FRW and HIIT groups. The FCSA decrease in FOG fibers was accompanied by a circularity decrease of SO from SOL fibers (0.840 ± 0.005 vs. 0.783 ± 0.016 and vs. 0.788 ± 0.010), and a fiber and global field capillarization increase in both FRW and HIIT protocols. Moreover, FRW and HIIT animals exhibited increased cardiac mitochondrial respiratory control ratio with complex I-driven substrates (3.89 ± 0.14 vs. 5.20 ± 0.25 and vs. 5.42 ± 0.37). Data suggest that FRW induces significant functional, physiological, and biochemical adaptations similar to those obtained under an intermittent forced exercise regimen, such as HIIT.

Can exercise training counteract doxorubicin-induced oxidative damage of testis proteome?

The use of the chemotherapeutic drug doxorubicin (DOX) is limited by its toxicity in several organs such as testes. So, we analyzed the effect of endurance treadmill exercise training (EX) performed before sub-chronic DOX treatment on sperm count and motility, testes markers of oxidative damage and apoptosis. Tissue profiling of proteins more susceptible to oxidation was made to identify the molecular pathways regulated by oxidative modifications, as nitration and carbonylation. Twenty-four adult male rats were divided into four groups (n=6/group): sedentary saline (SED+SAL), sedentary sub-chronically injected with DOX (2mg-kg-1 per week, during 7 weeks; SED+DOX), 12 weeks trained saline (EX+SAL) and trained treated with DOX (EX+DOX). DOX treatment started 5 weeks after the beginning of the exercise program. Testes caspase-3, -8 and -9, as well as aconitase activities, the content of malondialdehyde (MDA), sulfhydryl groups (-SH), carbonyl and nitrotyrosine derivatives were determined. Modified proteins were identified by 2D-Western blot followed by MALDI-TOF/TOF mass spectrometry, and bioinformatic analysis was performed to assess the biological processes regulated by these chemical modifications. The decreased sperm motility induced by DOX was not modified by exercise. Significant increases in MDA content in SED+DOX and in caspase-3 and -9 activities in EX+DOX were found. Despite no significant differences in the levels of carbonylated and nitrated proteins, exercise modulated testis proteome susceptibility to oxidation in DOX-treated group, with less modified proteins identified. Zinc finger Ran-binding domain-containing protein 2 (ZRAB2) and AN1-type zinc finger protein 3 (ZFAN3) were among the proteins found oxidativelly modified. Although no marked alterations in testes oxidative damage were noticed, proteomic analysis of oxidativelly modified proteins highlighted the protective role of exercise against oxidative damage of some proteins involved in metabolism and stress response against DOX.

Modulation of mitochondrial biomarkers by intermittent hypobaric hypoxia and aerobic exercise after eccentric exercise in trained rats.

Unaccustomed eccentric contractions induce muscle damage, calcium homeostasis disruption, and mitochondrial alterations. Since exercise and hypoxia are known to modulate mitochondrial function, we aimed to analyze the effects on eccentric exercise-induced muscle damage (EEIMD) in trained rats using 2 recovery protocols based on: (i) intermittent hypobaric hypoxia (IHH) and (ii) IHH followed by exercise. The expression of biomarkers related to mitochondrial biogenesis, dynamics, oxidative stress, and bioenergetics was evaluated. Soleus muscles were excised before (CTRL) and 1, 3, 7, and 14 days after an EEIMD protocol. The following treatments were applied 1 day after the EEIMD: passive normobaric recovery (PNR), 4 h daily exposure to passive IHH at 4000 m (PHR) or IHH exposure followed by aerobic exercise (AHR). Citrate synthase activity was reduced at 7 and 14 days after application of the EEIMD protocol. However, this reduction was attenuated in AHR rats at day 14. PGC-1α and Sirt3 and TOM20 levels had decreased after 1 and 3 days, but the AHR group exhibited increased expression of these proteins, as well as of Tfam, by the end of the protocol. Mfn2 greatly reduced during the first 72 h, but returned to basal levels passively. At day 14, AHR rats had higher levels of Mfn2, OPA1, and Drp1 than PNR animals. Both groups exposed to IHH showed a lower p66shc(ser36)/p66shc ratio than PNR animals, as well as higher complex IV subunit I and ANT levels. These results suggest that IHH positively modulates key mitochondrial aspects after EEIMD, especially when combined with aerobic exercise.

Terapia comunitária integrativa e mulheres vivenciando o climatério: uma pesquisa ação- intervenção / Integrative Community Therapy and women experiencing climacteric: an action-research-intervention

A Terapia Comunitária Integrativa (TCI)se constitui em um espaço de acolhimento, partilha de sabedoria de vida e de sofrimentos vivenciados no cotidiano das pessoas, onde elas se tornam terapeutas de si mesmas, permitindo encontrar soluções para seus conflitospessoais e familiares. O estudo teve como objetivo avaliar a eficácia da TCI, como tecnologia do cuidado, capaz de aumentar a autoestima e reduzir os sinais e sintomas da depressão, de mulheres vivenciando o climatério. Trata-se de uma pesquisa-ação-intervençãocom 06 mulheres no climatérioque apresentavam sinais e sintomas de depressão e,que participaram de no mínimo de 06 rodas de TCI, em uma Unidade Integrada de Saúde da Família, de João Pessoa, PB, Brasil.Como instrumentos, foram utilizados o Inventário de Depressão de Beck e a Escala de Autoestima de Rosenberg-versão UNIFESP-EPM e, como intervenção, foram realizadas 12 rodasde TCI, no período de 19 semanas. Para a produção do material empírico foram utilizados as videogravações das rodas, caderno de campo eentrevistas semiestruturadas, sendo analisados, por meio da análise de conteúdo temática de Bardin. O estudoobedeceu aos preceitos éticos, sendo deferidasob o protocolo: CAAE 50926615.7.0000.5188. Como resultados, as mulheres melhoraram a autoestima e reduziram os sinais e sintomas de depressão. Percebeu-se que a TCI representou para elas, uma possibilidade de descobrir um jeito novo de ver a vida, despertando a necessidade de mudança, mediante a autorreflexão e desenvolvimento das competências pessoais, como autonomia, emancipação, empoderamento e resgate da autoestima.Conclui-se que a TCI é uma tecnologia do cuidado potente, capaz de ampliar o olhar das participantes, as motivando a saírem da estagnação da qual suas vidas se encontravam, adotando novas posturas e jeito de conduzir a vida, encorajando-as a refletirem e buscaremrespostas para suas necessidades subjetivas, provocando mudanças importantes em suas vidas. (AU)

Integrative Community Therapy (ICT) is a space for welcoming and sharing of life wisdom and suffering experienced in people's daily lives, where they become therapists of themselves, which enables them to find solutions to their personal and family conflicts. The study was intended to assess the effectiveness of ICT as a health care technology capable of improving self-esteem and mitigating the depression signs and symptoms in women experiencing climacteric. This is an action-research-intervention with 06 women in climacteric who showed depression signs and symptoms and who took part in at least 06 ICT rounds in an Integrated Family Health Unit in João Pessoa-PB, Brazil. Beck's Depression Inventory and Rosenberg's Self-esteem Scale ­ UNIFESP-EPM version were used as instruments, whilst 12 ICT rounds were held as interventions in a 19-week period. In order to produce the empirical material, we used the video-recordings of the rounds, field notebook and semi-structured interviews, which were analyzed through the Bardin thematic content analysis. The study complied with the ethical precepts, and then accepted under the CAAE protocol: 50926615.7.0000.5188. As a result, women have improved self-esteem and mitigated the depression signs and symptoms. We have realized that ICT represented for them a possibility of discovering a new way of seeing life, thus awakening the need for change, through the self-reflection and development of personal skills, such as autonomy, emancipation, empowerment and rescue of self-esteem. We can conclude that ICT is a powerful health care technology capable of enhancing the participants' standpoint, thus motivating them to leave the stagnation of their lives, by adopting new stances and ways of driving life, as well as encouraging them to reflect and seek answers to their subjective needs, which may entail important changes in their lives. (AU)

Stress among nursing students at a public university / Estresse entre graduandos de enfermagem de uma universidade pública / Estrés entre graduandos de enfermería de una universidad pública

OBJECTIVE: To estimate the level of stress and symptomatology reported in nursing students from a public university. METHOD: This is a transversal and quantitative study involving 151 nursing students selected from a draw based on the list of students enrolled. The adult version of the Lipp’s inventory of symptoms of stress was used. Data were analyzed and descriptively presented by absolute and percentage distributions using the statistical software R. RESULTS: 49.7% of students showed symptoms of stress, and most students were attending the 8th and 9th periods. Psychological symptoms were more present (50.7%). CONCLUSION: Implementing lightweight care technology tools is recommended, at low cost and high resolute power, to better combat stress.

OBJETIVO: Estimar o nível de estresse e a sintomatologia apresentada em acadêmicos de enfermagem de uma universidade pública. MÉTODO: Estudo transversal e quantitativo envolvendo 151 graduandos de enfermagem selecionados a partir de um sorteio baseado na lista de alunos matriculados. Foi utilizado o inventário de sintomas do stress de Lipp versão para adultos. Os dados foram analisados e apresentados descritivamente por meio de distribuições absolutas e percentuais, utilizando software estatístico R. RESULTADOS: 49,7% dos alunos apresentaram sintomas de estresse, com a maioria de indivíduos cursando o 8º e 9º períodos. Os sintomas psicológicos foram mais presentes (50,7%). CONCLUSÃO: Recomenda-se implementação de ferramentas de tecnologia leve do cuidado que apresentam baixo custo e alto poder resolutivo, para melhor combate ao estresse.

OBJETIVO: Estimar el nivel de estrés y la sintomatología presentada en académicos de enfermería de una universidad pública. MÉTODO: Estudio transversal y cuantitativo envolviendo 151 graduandos de enfermería seleccionados desde un sorteo basado en la lista de alumnos matriculados. Fue utilizado el inventario de síntomas del estrés de Lipp versión para adultos. Los datos fueron analizados y presentados descriptivamente por medio de distribuciones absolutas y porcentuales, utilizando software estadístico R. RESULTADOS: 49,7% de los alumnos presentaron síntomas de estrés, con la mayoría de individuos cursando el 8º y 9º períodos. Los síntomas psicológicos fueron más presentes (50,7%). CONCLUSIÓN: Se recomienda implementación de herramientas de tecnología lleve del cuidado que presentan bajo coste y alto poder resolutivo, para mejor combate al estrés.

Exercise mitigates mitochondrial permeability transition pore and quality control mechanisms alterations in nonalcoholic steatohepatitis.

Mitochondrial quality control and apoptosis have been described as key components in the pathogenesis of nonalcoholic steatohepatitis (NASH); exercise is recognized as a nonpharmacological strategy to counteract NASH-associated consequences. We aimed to analyze the effect of voluntary physical activity (VPA) and endurance training (ET) against NASH-induced mitochondrial permeability transition pore (mPTP) opening and mitochondrial and cellular quality control deleterious alterations. Forty-eight male Sprague-Dawley rats were divided into standard-diet sedentary (SS, n = 16), standard-diet VPA (n = 8), high-fat diet sedentary (HS, n = 16), and high-fat diet VPA (n = 8). After 9 weeks of diet treatment, half of the SS and HS groups were engaged in an ET program for 8 weeks, 5 days/week, 1 h/day. Liver mPTP susceptibility through osmotic swelling, mPTP-related proteins (cyclophilin D, Sirtuin3, Cofilin-1), markers of mitochondrial biogenesis ((mitochondrial transcription factor A (Tfam) and peroxisome proliferator-activated receptor gamma co-activator protein (PGC-1α)), dynamics (Mitofusin 1 (Mfn1), Mitofusin 2 (Mfn2), Dynamin related protein 1, and Optic atrophy 1)), auto/mitophagy (Beclin-1, microtubule-associated protein 1 light chain 3, p62, PINK1, and Parkin), and apoptotic signaling (Bax, Bcl-2) and caspases-like activities were assessed. HS animals showed an increased susceptibility to mPTP, compromised expression of Tfam, Mfn1, PINK1, and Parkin and an increase in Bax content (HS vs. SS). ET and VPA improved biogenesis-related proteins (PGC-1α) and autophagy signaling (Beclin-1 and Beclin-1/Bcl-2 ratio) and decreased apoptotic signaling (caspases 8 activity, Bax content, and Bax/Bcl-2 ratio). However, only ET decreased mPTP susceptibility and positively modulated Bcl-2, Tfam, Mfn1, Mfn2, PINK1, and Parkin content. In conclusion, exercise reduces the increased susceptibility to mPTP induced by NASH and promotes the increase of auto/mitophagy and mitochondrial fusion towards a protective phenotype.

Crack users’ perceptions of factors that influence use and addiction / Concepções dos usuários de crack sobre os fatores que influenciam o uso e a dependência / Concepciones de los usuários de crack sobre los factores que influencian su uso y su dependencia

The aim of this study was to identify factors that influence and facilitate crack use and factors that make it difficult to give up. This was a piece of qualitative research involving 20 crack users in João Pessoa, PB, in 2012. The data were collected using a semi-structured questionnaire and analyzed using the Discourse of the Collective Subject technique. Easy access, curiosity, peer pressure and alcohol/marihuana use were all shown to be factors that influenced crack use and made it difficult to give up. It is suggested that the views and actions taken of the phenomenon of drug addiction be broadened and more comprehensive nursing care provided based on the factors uncovered in this study.(AU)

Neste estudo objetivou-se identificar fatores influenciadores e facilitadores no uso do crack e os fatores que dificultam seu abandono. Trata-se de pesquisa qualitativa, envolvendo 20 usuários de crack, desenvolvida em João Pessoa, PB, em 2012. Os dados foram coletados através de formulário semiestruturado e analisados conforme a técnica do Discurso do Sujeito Coletivo. A facilidade de acesso, curiosidade, influência de pessoas e uso do álcool/maconha se mostraram fatores que influenciam o uso do crack e dificultam seu abandono. Sugere-se ampliamento das ações e do olhar para o fenômeno da drogadição e espera-se contribuir para assistência mais integral, prestada pelo enfermeiro, através dos fatores explicitados neste estudo.(AU)

El objetivo de este estudio es identificar los factores que influencian y facilitan el uso del crack, como también los factores que dificultan su abandono. Este estudio es una investigación cualitativa, participaron 20 usuarios de crack y fue realizada en la ciudad João Pessoa, estado de Paraiba, 2012. Los datos fueron recolectados por medio de un formulario semiestruturado, y analizados de acuerdo a la técnica de Discurso del Sujeto Colectivo. La facilidad del acceso, la curiosidad, influencia de otras personas y el uso de alcohol y mariguana fueron los factores que influyen en el uso del crack y que también dificultaran su abandono. Se sugiere una ampliación de las acciones y dela mirada frente al fenómeno de la drogadicción, se espera contribuir para generar una asistencia mas integral, prestada por el enfermero, de acuerdo a los factores explicados en este estudio.(AU)

Crack users’ perceptions of factors that influence use and addiction / Concepções dos usuários de crack sobre os fatores que influenciam o uso e a dependência / Concepciones de los usuários de crack sobre los factores que influencian su uso y su dependencia

The aim of this study was to identify factors that influence and facilitate crack use and factors that make it difficult to give up. This was a piece of qualitative research involving 20 crack users in João Pessoa, PB, in 2012. The data were collected using a semi-structured questionnaire and analyzed using the Discourse of the Collective Subject technique. Easy access, curiosity, peer pressure and alcohol/marihuana use were all shown to be factors that influenced crack use and made it difficult to give up. It is suggested that the views and actions taken of the phenomenon of drug addiction be broadened and more comprehensive nursing care provided based on the factors uncovered in this study...

Neste estudo objetivou-se identificar fatores influenciadores e facilitadores no uso do crack e os fatores que dificultam seu abandono. Trata-se de pesquisa qualitativa, envolvendo 20 usuários de crack, desenvolvida em João Pessoa, PB, em 2012. Os dados foram coletados através de formulário semiestruturado e analisados conforme a técnica do Discurso do Sujeito Coletivo. A facilidade de acesso, curiosidade, influência de pessoas e uso do álcool/maconha se mostraram fatores que influenciam o uso do crack e dificultam seu abandono. Sugere-se ampliamento das ações e do olhar para o fenômeno da drogadição e espera-se contribuir para assistência mais integral, prestada pelo enfermeiro, através dos fatores explicitados neste estudo...

El objetivo de este estudio es identificar los factores que influencian y facilitan el uso del crack, como también los factores que dificultan su abandono. Este estudio es una investigación cualitativa, participaron 20 usuarios de crack y fue realizada en la ciudad João Pessoa, estado de Paraiba, 2012. Los datos fueron recolectados por medio de un formulario semiestruturado, y analizados de acuerdo a la técnica de Discurso del Sujeto Colectivo. La facilidad del acceso, la curiosidad, influencia de otras personas y el uso de alcohol y mariguana fueron los factores que influyen en el uso del crack y que también dificultaran su abandono. Se sugiere una ampliación de las acciones y dela mirada frente al fenómeno de la drogadicción, se espera contribuir para generar una asistencia mas integral, prestada por el enfermero, de acuerdo a los factores explicados en este estudio...

Sociodemographic characteristics of adolescents living with alcoholic families in the city of Jo‹o Pessoa, Para’ba / Características sociodemográficas de adolescentes que vivem com familiares alcoolistas no município de João Pessoa, Paraíba / Características sociodemográficas de adolescentes que viven con familiares alcohólicos en el municipio de João Pessoa, Paraíba

The aim of this study is to estimate the amount of teens that inhabit homes with alcoholic families in a representative sample of adolescents in the city of Jo‹o Pessoa, Para’ba; then characterize the demographic profiles of these adolescents and their alcoholic families. This is a cross-sectional population-based study, conducted with 715 teenagers between the ages of 14 to 19 years old. A sociodemographic questionnaire and CAGE-family instrument were used. For data analysis, descriptive statistics were used. According to the results, most of the teenagers were girls, age 17 years old, and within the alcoholic family, the father was most referenced. It is necessary to implement preventive measures for the health of teens with alcoholic family members, taking into account the risk for the development of biopsychosocial problems.(AU)

Tem-se como objetivo estimar o quantitativo de adolescentes que habitam lares com familiares alcoolistas em uma amostra representativa de adolescentes na cidade de Jo‹o Pessoa, Para’ba, e caracterizar os perfis sociodemogr‡ficos e familiares dos adolescentes que convivem com familiares alcoolistas. Estudo do tipo transversal de base populacional, realizado com 715 adolescentes entre 14 e 19 anos. Foram utilizados question‡rio sociodemogr‡fico e o CAGE-familiar. Para an‡lise dos resultados, foi utilizada estat’stica descritiva. De acordo com resultados, a maioria dos adolescentes eram meninas, com idade de 17 anos; entre os familiares alcoolistas, o pai foi mais referenciado. Torna-se necess‡rio implementar a›es de preven‹o para a saœde dos adolescentes com familiares alcoolistas, levando em considera‹o o risco para o desenvolvimento de problemas biopsicossociais.(AU)

Se tiene como objetivo estimar cuantitativamente los adolescentes que habitan en hogares con familiares alcoh—licos, en una muestra representativa de adolecentes en la ciudad de Jo‹o Pessoa, Para’ba, y caracterizar los perfiles sociodemogr‡ficos y familiares de los adolescentes que conviven con familiares alcoh—licos, es un estudio transversal de base poblacional realizado con 715 adolescentes entre los 14 y los 19 a–os. Fueron utilizados cuestionario sociodemogr‡fico y el CAGE-familiar. Para el an‡lisis de resultados se utiliz— la estad’stica descriptiva. De acuerdo con los resultados, la mayor’a de los adolecentes eran chicas de 17 a–os, ente los familiares alcoh—licos el padre fue el mas referenciado. Es necesario implementar acciones de prevenci—n para la salud de los adolescentes con familiares alcoh—licos, teniendo en cuenta el riesgo para desarrollar problemas biopsicosociales.(AU)

Produção cientifica sobre a sexualidade de mulheres no climatério: revisão integrativa / Producción científica acerca de la sexualidad de las mujeres en el climaterio: una revisión integradora / Scientific production about the sexuality of women in climacteric: an integrative review

Objective: analyzing the scientific production about sexuality in climacteric women. Method: an integrative review of bibliometric approach, held through consultation online, advanced and systematic, in the Virtual Health Library, using the technique of meta-searching. Results: the authors were linked to 20 institutions, 53,2% were doctors, 61,7% were doctorates. The country with the highest number of authors was Brazil. The issue most discussed was sexual function. Most publications were quantitative, occurred in 2008 and published in Brazilian Portuguese language. The level four of evidence was the most frequent. The Law enforcement of Bradford resulted in three areas of productivity. Conclusion: there is a need for more qualitative researches, especially in nursing, and studies with greater power of evidence, as well as more investment in other regions of Brazil.

Objetivo: analisar a produção científica publicada sobre a sexualidade de mulheres no climatério. Metódo: revisão integrativa de abordagem bibliométrica realizada através de consulta online, avançada e sistemática, na Biblioteca Virtual de Saúde, utilizando-se a técnica da metapesquisa. Resultados: os autores estavam vinculados a 20 instituições, 53,2% eram médicos, 61,7% eram doutores. O país com maior número de autores foi o Brasil. O tema mais abordado foi a função sexual. A maioria das publicações era quantitativa, e ocorreram em 2008, e foram publicados no idioma português brasileiro. O nível de evidência mais frequente foi o quarto. A aplicação da lei de Bradford resultou em três zonas de produtividade. Conclusão: observou-se a necessidade de mais pesquisas qualitativas, principalmente na área de enfermagem, além de estudos com maior poder de evidência, assim como mais investimentos em outras regiões do Brasil.

Objetivo: analizar la producción científica publicada acerca de la sexualidad en las mujeres en el climaterio. Método: una revisión integradora de enfoque bibliométrico, que se celebró a través de consultas en línea, avanzadas y sistemáticas, en la Biblioteca Virtual en Salud, utilizando la técnica de meta-búsqueda. Resultados: Los autores estaban vinculados a 20 instituciones, 53,2% eran médicos, 61,7% doctorados. El país con el mayor número de autores fue Brasil. El tema más abordado fue la función sexual. La mayoría de las publicaciones era cuantitativa, se produjo en 2008 y se publicó en idioma portugués de Brasil. El nivel de evidencia más frecuente fue el cuatro. La Aplicación de la ley Bradford dio lugar a tres áreas de productividad. Conclusión: hay una necesidad de más investigación cualitativa, especialmente en ancianos, y los estudios con un mayor poder de las pruebas, así como una mayor inversión en otras regiones de Brasil.