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1.
Am J Physiol Heart Circ Physiol ; 326(6): H1462-H1468, 2024 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-38639741

RESUMO

It is unclear whether muscle blood flow (MBF) is altered in long-term Hodgkin lymphoma (HL) survivors. We tested the hypothesis that 1) MBF response during mental stress (MS) is impaired in long-term HL survivors and 2) aerobic exercise training combined with local strength exercise (ET) restores MBF responses during MS in these survivors. Eighteen 5-year HL survivors and 10 aged-paired healthy subjects (HC) were studied. Twenty HL survivors were randomly divided into two groups: exercise-trained (HLT, n = 10) and untrained (HLUT, n = 10). Maximal aerobic capacity was evaluated by a cardiopulmonary exercise test and forearm blood flow (FBF) by venous occlusion plethysmography. MS was elicited by Stroop color and word test. ET was conducted for 4 mo, 3/wk for 60 min each session. The aerobic exercise intensity corresponded to anaerobic threshold up to 10% below the respiratory compensation point. The strength exercises consisted of two to three sets of chest press, pulley and squat exercises, 12-15 repetitions each exercise at 30-50% of the maximal voluntary contraction. Baseline was similar in HL survivors and HC, except peak oxygen consumption (peak V̇o2, P = 0.013) and FBF (P = 0.006) that were lower in the HL survivors. FBF responses during MS were lower in HL survivors (P < 0.001). ET increased peak V̇o2 (11.59 ± 3.07%, P = 0.002) and FBF at rest (33.74 ± 5.13%, P < 0.001) and during MS (24 ± 5.31%, P = 0.001). Further analysis showed correlation between the changes in peak V̇o2 and the changes in FBF during MS (r = 0.711, P = 0.001). In conclusion, long-term HL survivors have impaired MBF responses during MS. ET restores MBF responses during MS.NEW & NOTEWORTHY Long-term Hodgkin lymphoma (HL) survivors have impaired muscle blood flow responses during mental stress and decreased maximal aerobic capacity. Supervised aerobic exercise training combined with local strength exercises restores muscle blood flow responses during mental stress and maximal aerobic capacity in these survivors. These findings provide evidence of safety and effectiveness of exercise training in HL survivors. Moreover, they highlight the importance of exercise training in the treatment of this set of patients.


Assuntos
Sobreviventes de Câncer , Tolerância ao Exercício , Doença de Hodgkin , Músculo Esquelético , Consumo de Oxigênio , Fluxo Sanguíneo Regional , Treinamento Resistido , Humanos , Doença de Hodgkin/fisiopatologia , Doença de Hodgkin/terapia , Masculino , Feminino , Adulto , Músculo Esquelético/irrigação sanguínea , Músculo Esquelético/fisiopatologia , Pessoa de Meia-Idade , Exercício Físico , Fatores de Tempo , Antebraço/irrigação sanguínea , Terapia por Exercício/métodos , Aptidão Cardiorrespiratória
2.
Lasers Med Sci ; 32(2): 317-325, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27909917

RESUMO

We evaluated whether strength training (ST) performed prior to skeletal muscle cryolesion would act as a preconditioning, improving skeletal muscle regeneration and responsiveness to low-level laser therapy (LLLT). Wistar rats were randomly assigned into non-exercised (NE), NE plus muscle lesion (NE + LE), NE + LE plus LLLT (NE + LE + LLLT), strength training (ST), ST + LE, and ST + LE + LLLT. The animals performed 10 weeks of ST (climbing ladder; 3× week; 80% overload). Forty-eight hours after the last ST session, tibialis anterior (TA) cryolesion was induced and LLLT (InGaAlP, 660 nm, 0.035 W, 4.9 J/cm2/point, 3 points, spot light 0.028 cm2, 14 J/cm2) initiated and conducted daily for 14 consecutive days. The difference between intergroups was assessed using Student's t test and intragroups by two-way analysis of variance. Cryolesion induced massive muscle degeneration associated with inflammatory infiltrate. Prior ST improved skeletal regeneration 14-days after cryolesion and potentiated the regenerative response to LLLT. Cryolesion induced increased TNF-α levels in both NE + LE and ST + LE groups. Both isolated ST and LLLT reduced TNF-α to control group levels; however, prior ST potentiated LLLT response. Both isolated ST and LLLT increased IL-10 levels with no additional effect. In contrast, increased TA IL-6 levels were restricted to ST and ST + LE + LLLT groups. TA myogenin mRNA levels were not changed by neither prior ST or ST + LLLT. Both prior ST and LLLT therapies increased MyoD mRNA levels and, interestingly, combined therapies potentiated this response. Myf5 mRNA levels were increased only in ST groups. Taken together, our data provides evidences for prior ST potentiating LLLT efficacy in promoting skeletal muscle regeneration.


Assuntos
Terapia com Luz de Baixa Intensidade , Músculo Esquelético/lesões , Músculo Esquelético/efeitos da radiação , Condicionamento Físico Animal , Regeneração/efeitos da radiação , Animais , Citocinas/genética , Citocinas/metabolismo , Masculino , Modelos Biológicos , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Wistar , Cicatrização/efeitos da radiação
3.
Am J Physiol Heart Circ Physiol ; 311(5): H1180-H1188, 2016 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-27591218

RESUMO

Heart failure (HF) is characterized by decreased exercise capacity, attributable to neurocirculatory and skeletal muscle factors. Cardiac resynchronization therapy (CRT) and exercise training have each been shown to decrease muscle sympathetic nerve activity (MSNA) and increase exercise capacity in patients with HF. We hypothesized that exercise training in the setting of CRT would further reduce MSNA and vasoconstriction and would increase Ca2+-handling gene expression in skeletal muscle in patients with chronic systolic HF. Thirty patients with HF, ejection fraction <35% and CRT for 1 mo, were randomized into two groups: exercise-trained (ET, n = 14) and untrained (NoET, n = 16) groups. The following parameters were compared at baseline and after 4 mo in each group: V̇o2 peak, MSNA (microneurography), forearm blood flow, and Ca2+-handling gene expression in vastus lateralis muscle. After 4 mo, exercise duration and V̇o2 peak were significantly increased in the ET group (P = 0.04 and P = 0.01, respectively), but not in the NoET group. MSNA was significantly reduced in the ET (P = 0.001), but not in NoET, group. Similarly, forearm vascular conductance significantly increased in the ET (P = 0.0004), but not in the NoET, group. The expression of the Na+/Ca2+ exchanger (P = 0.01) was increased, and ryanodine receptor expression was preserved in ET compared with NoET. In conclusion, the exercise training in the setting of CRT improves exercise tolerance and neurovascular control and alters Ca2+-handling gene expression in the skeletal muscle of patients with systolic HF. These findings highlight the importance of including exercise training in the treatment of patients with HF even following CRT.


Assuntos
Cálcio/metabolismo , Terapia de Ressincronização Cardíaca , Terapia por Exercício , Exercício Físico , Insuficiência Cardíaca/terapia , Acoplamento Neurovascular , Músculo Quadríceps/metabolismo , Sistema Nervoso Simpático/metabolismo , Ecocardiografia , Teste de Esforço , Tolerância ao Exercício , Feminino , Antebraço/irrigação sanguínea , Expressão Gênica , Insuficiência Cardíaca/genética , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/inervação , Músculo Esquelético/metabolismo , Consumo de Oxigênio , Músculo Quadríceps/inervação , RNA Mensageiro/metabolismo , Fluxo Sanguíneo Regional , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Trocador de Sódio e Cálcio/genética
4.
J Neurooncol ; 119(1): 59-70, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24797829

RESUMO

In the present study, we searched for genes highly expressed in placenta and that could contribute to the establishment and maintenance of a malignant phenotype in different types of tumours, and in astrocytomas in particular. We employed a strategy based on the integration of in silico data from previously generated massively parallel signature sequencing and public serial analysis of gene expression databases. Among 12 selected genes, CD99 exhibited the highest relative mRNA expression in GBM compared to non-neoplastic brain tissues. In a larger cohort of astrocytic tumours, we further demonstrated increased CD99 expression in all malignant grades, with GBMs showing the highest values. These findings were confirmed at the protein level by Western blotting and immunohistochemistry. Additionally, we demonstrated the CD99 localisation profile in astrocytic tumours. Interestingly, CD99 expression was confined to the cytoplasm or membrane in more malignant astrocytomas, in contrast to non-neoplastic brain tissue or non-infiltrative pilocytic astrocytoma, which showed no obvious staining in these structures. Comparison of three GBM cell lines revealed higher CD99 expression at the membrane and higher migratory capacity in the A172 and U87MG lines, but lower CD99 expression and no migratory ability in the T98 line. Knocking down CD99 expression by siRNA decreased significantly the migration of both cell lines. These integrated CD99 gene and protein expression results suggest that CD99 expression in astrocytomas of different malignant grades might contribute to the infiltrative ability and support the importance of CD99 as a potential target to reduce infiltrative astrocytoma capacity in migration and invasion.


Assuntos
Antígenos CD/metabolismo , Astrocitoma/metabolismo , Neoplasias Encefálicas/metabolismo , Encéfalo/metabolismo , Moléculas de Adesão Celular/metabolismo , Movimento Celular/genética , Placenta/metabolismo , Regulação para Cima , Antígeno 12E7 , Antígenos CD/genética , Astrocitoma/genética , Astrocitoma/patologia , Encéfalo/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Gradação de Tumores , Gravidez
5.
J Am Heart Assoc ; 10(5): e018076, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33619982

RESUMO

Background Patients treated for breast cancer have a high incidence of cardiovascular complications. In this study, we evaluated the impact of breast cancer on cardiac function and cardiomyocyte Ca2+-handling protein expression. We also investigated whether exercise training (ET) would prevent these potential alterations. Methods and Results Transgenic mice with spontaneous breast cancer (mouse mammary tumor virus-polyomavirus middle T antigen [MMTV-PyMT+], n=15) and littermate mice with no cancer (MMTV-PyMT-, n=14) were studied. For the ET analysis, MMTV-PyMT+ were divided into sedentary (n=10) and exercise-trained (n=12) groups. Cardiac function was evaluated by echocardiography with speckle-tracking imaging. Exercise tolerance test was conducted on a treadmill. Both studies were performed when the tumor became palpable and when it reached 1 cm3. After euthanasia, Ca2+-handling protein expression (Western blot) was evaluated. Exercise capacity was reduced in MMTV-PyMT+ compared with MMTV-PyMT- (Pinteraction=0.031). Longitudinal strain (Pgroup <0.001) and strain rate (Pgroup=0.030) were impaired. Cardiomyocyte phospholamban was increased (P=0.011), whereas phospho-phospholamban and sodium/calcium exchanger were decreased (P=0.038 and P=0.017, respectively) in MMTV-PyMT+. No significant difference in sarcoplasmic or endoplasmic reticulum calcium 2 ATPase (SERCA2a) was found. SERCA2a/phospholamban ratio was reduced (P=0.007). ET was not associated with increased exercise capacity. ET decreased left ventricular end-systolic diameter (Pgroup=0.038) and end-diastolic volume (Pgroup=0.026). Other morphological and functional cardiac parameters were not improved by ET in MMTV-PyMT+. ET did not improve cardiomyocyte Ca2+-handling protein expression. Conclusions Breast cancer is associated with decreased exercise capacity and subclinical left ventricular dysfunction in MMTV-PyMT+, which is at least partly associated with dysregulation of cardiomyocyte Ca2+ handling. ET did not prevent or reverse these changes.


Assuntos
Neoplasias da Mama/complicações , Cálcio/metabolismo , Doenças Cardiovasculares/etiologia , Ventrículos do Coração/fisiopatologia , Miócitos Cardíacos/metabolismo , Condicionamento Físico Animal/métodos , Função Ventricular Esquerda/fisiologia , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/metabolismo , Ecocardiografia Doppler , Feminino , Ventrículos do Coração/diagnóstico por imagem , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Miócitos Cardíacos/patologia , Neoplasias Experimentais , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/metabolismo
6.
J Cachexia Sarcopenia Muscle ; 11(1): 89-102, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31743617

RESUMO

BACKGROUND: The exercise intolerance in chronic heart failure with reduced ejection fraction (HFrEF) is mostly attributed to alterations in skeletal muscle. However, the mechanisms underlying the skeletal myopathy in patients with HFrEF are not completely understood. We hypothesized that (i) aerobic exercise training (AET) and inspiratory muscle training (IMT) would change skeletal muscle microRNA-1 expression and downstream-associated pathways in patients with HFrEF and (ii) AET and IMT would increase leg blood flow (LBF), functional capacity, and quality of life in these patients. METHODS: Patients age 35 to 70 years, left ventricular ejection fraction (LVEF) ≤40%, New York Heart Association functional classes II-III, were randomized into control, IMT, and AET groups. Skeletal muscle changes were examined by vastus lateralis biopsy. LBF was measured by venous occlusion plethysmography, functional capacity by cardiopulmonary exercise test, and quality of life by Minnesota Living with Heart Failure Questionnaire. All patients were evaluated at baseline and after 4 months. RESULTS: Thirty-three patients finished the study protocol: control (n = 10; LVEF = 25 ± 1%; six males), IMT (n = 11; LVEF = 31 ± 2%; three males), and AET (n = 12; LVEF = 26 ± 2%; seven males). AET, but not IMT, increased the expression of microRNA-1 (P = 0.02; percent changes = 53 ± 17%), decreased the expression of PTEN (P = 0.003; percent changes = -15 ± 0.03%), and tended to increase the p-AKTser473 /AKT ratio (P = 0.06). In addition, AET decreased HDAC4 expression (P = 0.03; percent changes = -40 ± 19%) and upregulated follistatin (P = 0.01; percent changes = 174 ± 58%), MEF2C (P = 0.05; percent changes = 34 ± 15%), and MyoD expression (P = 0.05; percent changes = 47 ± 18%). AET also increased muscle cross-sectional area (P = 0.01). AET and IMT increased LBF, functional capacity, and quality of life. Further analyses showed a significant correlation between percent changes in microRNA-1 and percent changes in follistatin mRNA (P = 0.001, rho = 0.58) and between percent changes in follistatin mRNA and percent changes in peak VO2 (P = 0.004, rho = 0.51). CONCLUSIONS: AET upregulates microRNA-1 levels and decreases the protein expression of PTEN, which reduces the inhibitory action on the PI3K-AKT pathway that regulates the skeletal muscle tropism. The increased levels of microRNA-1 also decreased HDAC4 and increased MEF2c, MyoD, and follistatin expression, improving skeletal muscle regeneration. These changes associated with the increase in muscle cross-sectional area and LBF contribute to the attenuation in skeletal myopathy, and the improvement in functional capacity and quality of life in patients with HFrEF. IMT caused no changes in microRNA-1 and in the downstream-associated pathway. The increased functional capacity provoked by IMT seems to be associated with amelioration in the respiratory function instead of changes in skeletal muscle. ClinicalTrials.gov (Identifier: NCT01747395).


Assuntos
Insuficiência Cardíaca/terapia , Inalação/fisiologia , MicroRNAs/metabolismo , Qualidade de Vida/psicologia , Volume Sistólico/fisiologia , Adulto , Idoso , Exercício Físico/fisiologia , Feminino , Insuficiência Cardíaca/genética , Humanos , Masculino , Pessoa de Meia-Idade
7.
Med Sci Sports Exerc ; 51(1): 84-93, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30113523

RESUMO

INTRODUCTION: Low-intensity endurance training (ET) performed with blood flow restriction (BFR) can improve muscle strength, cross-sectional area (CSA) and cardiorespiratory capacity. Whether muscle strength and CSA as well as cardiorespiratory capacity (i.e., V˙O2max) and underlying molecular processes regulating such respective muscle adaptations are comparable to resistance and ET is unknown. PURPOSE: To determine the respective chronic (i.e., 8 wk) functional, morphological, and molecular responses of ET-BFR training compared with conventional, unrestricted resistance training (RT) and ET. METHODS: Thirty healthy young men were randomly assigned to one of three experimental groups: ET-BFR (n = 10, 4 d·wk, 30-min cycling at 40% of V˙O2max), RT (n = 10, 4 d·wk, 4 sets of 10 repetitions leg press at 70% of one repetition maximum with 60 s rest) or ET (n = 10, 4 d·wk, 30-min cycling at 70% of V˙O2max) for 8 wk. Measures of quadriceps CSA, leg press one repetition maximum, and V˙O2max as well as muscle biopsies were obtained before and after intervention. RESULTS: Both RT and ET-BFR increased muscle strength and hypertrophy responses. ET-BFR also increased V˙O2max, total cytochrome c oxidase subunit 4 isoform 1 abundance and vascular endothelial growth factor mRNA abundance despite the lower work load compared to ET. CONCLUSIONS: Eight weeks of ET-BFR can increase muscle strength and induce similar muscle hypertrophy responses to RT while V˙O2max responses also increased postintervention even with a significantly lower work load compared with ET. Our findings provide new insight to some of the molecular mechanisms mediating adaptation responses with ET-BFR and the potential for this training protocol to improve muscle and cardiorespiratory capacity.


Assuntos
Ciclismo/fisiologia , Aptidão Cardiorrespiratória/fisiologia , Força Muscular/fisiologia , Resistência Física/fisiologia , Músculo Quadríceps/irrigação sanguínea , Fluxo Sanguíneo Regional , Treinamento Resistido/métodos , Adaptação Fisiológica , Biópsia , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Humanos , Masculino , Consumo de Oxigênio , Músculo Quadríceps/anatomia & histologia , Músculo Quadríceps/diagnóstico por imagem , Músculo Quadríceps/fisiologia , RNA Mensageiro/metabolismo , Fluxo Sanguíneo Regional/fisiologia , Ultrassonografia , Fator A de Crescimento do Endotélio Vascular/metabolismo
8.
Int J Parasitol ; 36(2): 157-63, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16373069

RESUMO

The role of amino acids in trypanosomatids goes beyond protein synthesis, involving processes such as differentiation, osmoregulation and energy metabolism. The availability of the amino acids involved in those functions depends, among other things, on their transport into the cell. Here we characterize a glutamate transporter from the human protozoan parasite Trypanosoma cruzi. Kinetic data show a single saturable system with a Km of 0.30 mM and a maximum velocity of 98.34 pmoles min(-1) per 2 x 10(7) cells for epimastigotes and 20 pmoles min(-1) per 2 x 10(7) cells for trypomastigotes. Transport was not affected by parasite nutrient starvation for up to 3h. Aspartate, alanine, glutamine, asparagine, methionine, oxaloacetate and alpha-ketoglutarate competed with the substrate in 10-fold excess concentrations. Glutamate uptake was strongly dependent on pH, but not on Na+ or K+ concentrations in the extracellular medium. These data were consistent with the sensitivity of the system to the H+ ionophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone, suggesting that transport is driven by H+ concentration gradient across the cytoplasmic membrane. The glutamate transport increased linearly with temperature in a range from 15 to 40 degrees C, allowing the calculation of an activation energy of 52.38 kJ/mol.


Assuntos
Sistema X-AG de Transporte de Aminoácidos/metabolismo , Ácido Glutâmico/metabolismo , Trypanosoma cruzi/metabolismo , Aminoácidos/metabolismo , Animais , Transporte Biológico , Membrana Celular/metabolismo , Doença de Chagas/parasitologia , Ácido Glutâmico/análise , Concentração de Íons de Hidrogênio , Parasitologia/métodos , Proteínas de Protozoários/metabolismo
9.
FEMS Microbiol Lett ; 247(1): 65-71, 2005 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-15927749

RESUMO

Aspartate is one of the compounds that induce the differentiation process of the non-infective epimastigote stage to the infective trypomastigote stage of the protozoan parasite Trypanosoma cruzi. l-aspartate is transported by both epimastigote and trypomastigote cells at the same rate, about 3.4 pmolmin(-1) per 10(7) cells. Aspartate transport is only competed by glutamate suggesting that this transport system is specific for anionic amino acids. Aspartate uptake rates increase along the parasite growth curve, by amino acids starvation or pH decrease. The metabolic fate of the transported aspartate was predicted in silico by identification of seven putative genes coding for enzymes involved in aspartate metabolism that could be related to the differentiation process.


Assuntos
Ácido Aspártico/metabolismo , Trypanosoma cruzi/metabolismo , Adenilossuccinato Sintase/genética , Adenilossuccinato Sintase/metabolismo , Animais , Asparaginase/genética , Asparaginase/metabolismo , Aspartato Aminotransferases/genética , Aspartato Aminotransferases/metabolismo , Aspartato-Amônia Ligase/genética , Aspartato-Amônia Ligase/metabolismo , Transporte Biológico , Catálise , Biologia Computacional , Cinética , Dados de Sequência Molecular , Trypanosoma cruzi/enzimologia , Trypanosoma cruzi/genética
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