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1.
Sports (Basel) ; 11(9)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37755860

RESUMO

Coconut water is used as an alternative to conventional sports drinks for hydration during endurance cycling; however, evidence supporting its use is limited. This study determined if drinking coconut water compared to a sports drink altered cycling performance and physiology. In a randomized crossover trial, 19 experienced male (n = 15) and female (n = 4) cyclists (age 30 ± 9 years, body mass 79 ± 11 kg, V̇O2 peak 55 ± 8 mL·kg-1·min-1) completed two experimental trials, consuming either a commercially available sports drink or iso-calorific coconut water during 90 min of sub-maximal cycling at 70% of their peak power output, followed by a simulated, variable gradient, 20 km time trial. Blood glucose, lactate, sweat loss, and heart rate were monitored throughout the 90 min of sub-maximal cycling, as well as the time trial performance (seconds) and average power (watts). A repeated measures analysis of variance and effect sizes (Cohen's d) analysis were applied. There were no significant differences (p ≥ 0.05) between the treatments for any of the measured physiological or performance variables. Additionally, the effect size analysis showed only trivial (d ≤ 0.2) differences between the treatments for all the measured variables, except blood glucose, which was lower in the coconut water trial compared to the sports drink trial (d = 0.31). Consuming coconut water had a similar effect on the cycling time trial performance and the physiological responses to consuming a commercially available sports drink.

2.
J Sci Med Sport ; 26(10): 561-563, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37643931

RESUMO

The proportion of individuals whose cardio-respiratory fitness change after endurance training does not exceed the test's measurement error can be 40 %. We determined if progressively increasing treadmill run intensity compared to maintaining the same run intensity, improved the responder proportion to a 6-week 20-minute treadmill training regimen. The intervention response standard deviation method estimated the proportion of responders attributable to progressively increasing run intensity. The mixed-effects model demonstrated V̇O2 peak improved significantly more in the progressive versus constant run intensity group. The proportion of V̇O2 peak responses above the smallest worthwhile change attributable to progressively increasing run intensity was 63.6 %.


Assuntos
Aptidão Cardiorrespiratória , Treino Aeróbico , Humanos , Consumo de Oxigênio , Exercício Físico/fisiologia , Teste de Esforço , Coração , Aptidão Física
4.
Sports (Basel) ; 10(6)2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35736835

RESUMO

There is a wide variance in the magnitude of physiological adaptations after resistance or endurance training. The incidence of "non" or "poor" responders to training has been reported to represent as high as 40% of the project's sample. However, the incidence of poor responders to training can be ameliorated with manipulation of either the training frequency, intensity, type and duration. Additionally, global non-response to cardio-respiratory fitness training is eliminated when evaluating several health measures beyond just the target variables as at least one or more measure improves. More research is required to determine if altering resistance training variables results in a more favourable response in individuals with an initial poor response to resistance training. Moreover, we recommend abandoning the term "poor" responders, as ultimately the magnitude of change in cardiorespiratory fitness in response to endurance training is similar in "poor" and "high" responders if the training frequency is subsequently increased. Therefore, we propose "stubborn" responders as a more appropriate term. Future research should focus on developing viable physiological and lifestyle screening tests that identify likely stubborn responders to conventional exercise training guidelines before the individual engages with training. Exerkines, DNA damage, metabolomic responses in blood, saliva and breath, gene sequence, gene expression and epigenetics are candidate biomarkers that warrant investigation into their relationship with trainability. Crucially, viable biomarker screening tests should show good construct validity to distinguish between different exercise loads, and possess excellent sensitivity and reliability. Furthermore "red flag" tests of likely poor responders to training should be practical to assess in clinical settings and be affordable and non-invasive. Early identification of stubborn responders would enable optimization of training programs from the onset of training to maintain exercise motivation and optimize the impact on training adaptations and health.

5.
FASEB J ; 35(4): e21437, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33749880

RESUMO

Ca2+ /calmodulin-dependent protein kinase II (CaMKII) is a ubiquitous serine threonine kinase with established roles in physiological and pathophysiological vascular remodeling. Based on our previous study demonstrating that CaMKIIδ promotes thrombin-induced endothelial permeability and recent reports that CaMKII may contribute to inflammatory remodeling in the heart, we investigated CaMKIIδ-dependent regulation of endothelial function downstream of an interleukin-6 (IL-6)/JAK/STAT3 signaling axis. Upon treatment with IL-6 and its soluble receptor (sIL-6r), CaMKIIδ expression is significantly induced in HUVEC. Using pharmacological inhibitors of JAK and siRNA targeting STAT3, we demonstrated that activation of STAT3 is sufficient to induce CaMKIIδ expression. Under these conditions, rather than promoting IL-6-induced permeability, we found that CaMKIIδ promotes endothelial cell migration as measured by live cell imaging of scratch wound closure and single-cell motility analysis. In a similar manner, endothelial cell proliferation was attenuated upon knockdown of CaMKIIδ as determined by growth curves, cell cycle analysis, and capacitance of cell-covered electrodes as measured by ECIS. Using inducible endothelial-specific STAT3 knockout mice, we demonstrate that STAT3 signaling promotes developmental angiogenesis in the neonatal mouse retina assessed at postnatal day 6. CaMKIIδ expression in retinal endothelium was attenuated in these animals as measured by qPCR. STAT3's effects on angiogenesis were phenocopied by the endothelial-specific knockout of CaMKIIδ, with significantly reduced vascular outgrowth and number of junctions in the developing P6 retina. For the first time, we demonstrate that transcriptional regulation of CaMKIIδ by STAT3 promotes endothelial motility, proliferation, and in vivo angiogenesis.


Assuntos
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Interleucina-6/metabolismo , Janus Quinases/metabolismo , Vasos Retinianos/fisiologia , Fator de Transcrição STAT3/metabolismo , Animais , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/genética , Movimento Celular , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Interleucina-6/genética , Janus Quinases/genética , Camundongos , Neovascularização Fisiológica , Isoformas de Proteínas , Interferência de RNA , Retina , Fator de Transcrição STAT3/genética , Regulação para Cima
6.
Sci Rep ; 11(1): 4056, 2021 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-33603000

RESUMO

Amongst other immune cells, neutrophils play a key role in systemic inflammation leading to cardiovascular disease and can release inflammatory factors, including lipocalin-2 (LCN2). LCN2 drives cardiac hypertrophy and plays a role in maladaptive remodelling of the heart and has been associated with renal injury. While lifestyle factors such as diet and exercise are known to attenuate low-grade inflammation, their ability to modulate plasma LCN2 levels is unknown. Forty-eight endurance athletes and 52 controls (18-55 years) underwent measurement for various cardiovascular health indicators, along with plasma LCN2 concentration. No significant difference in LCN2 concentration was seen between the two groups. LCN2 was a very weak predictor or absent from models describing blood pressures or predicting athlete status. In another cohort, 57 non-diabetic overweight or obese men and post-menopausal women who fulfilled Adult Treatment Panel III metabolic syndrome criteria were randomly allocated into either a control, modified Dietary Approaches to Stop Hypertension (DASH) diet, or DASH and exercise group. Pre- and post-intervention demographic, cardiovascular health indicators, and plasma LCN2 expression were measured in each individual. While BMI fell in intervention groups, LCN2 levels remained unchanged within and between all groups, as illustrated by strong correlations between LCN2 concentrations pre- and 12 weeks post-intervention (r = 0.743, P < 0.0001). This suggests that circulating LCN2 expression are stable over a period of at least 12 weeks and is not modifiable by diet and exercise.


Assuntos
Dieta Redutora , Exercício Físico/fisiologia , Lipocalina-2/sangue , Adulto , Atletas , Feminino , Humanos , Lipocalina-2/metabolismo , Masculino
7.
J Strength Cond Res ; 34(9): 2596-2607, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30741863

RESUMO

Feros, SA, Young, WB, and O'Brien, BJ. Efficacy of combined general, special, and specific resistance training on pace bowling skill in club-standard cricketers. J Strength Cond Res 34(9): 2596-2607, 2020-This study investigated the efficacy of combined "general," "special," and "specific" resistance training on pace bowling skill. Twelve male, club-standard pace bowlers were randomly allocated to a combined resistance training (CRT) program or traditional cricket training (TCT) program for 8 weeks. The CRT group (n = 6) trained with 300, 250-g, and standard cricket balls; performed 20-m sprints with +20% and +15% body mass resistance (but also unresisted); and completed chin-up and pull-up training. The TCT group (n = 6) trained with standard balls and performed unresisted 20-m sprints. No statistically significant GROUP × TIME interactions were identified. The CRT group demonstrated a "clear moderate" enhancement in peak ball release speed (mean ±95% confidence limits [CLs]: 1.2 ± 1.5 m·s, d = 0.66 ± 0.83), a "clear large" increase in mean radial error (mean ±95% CLs: 7.1 ± 6.5 cm, d = 0.94 ± 0.87), and a "clear large" rise in bivariate variable error (mean ±95% CLs: 7.2 ± 7.8 cm, d = 0.97 ± 1.05). The TCT group exhibited "unclear" changes across all pace bowling skill measures. Both groups displayed "unclear" changes in approach speed, 20-m sprint time, and 1 repetition maximum pull-up strength. In 8 weeks, the CRT program improved peak ball release speed, but at the cost of poorer bowling accuracy and consistency of bowling accuracy. These findings could be attributed to bowling with the heavier balls. The inclusion of "specific" resistance training does not seem to be effective in enhancing all-round pace bowling skill in club-standard cricketers.


Assuntos
Treinamento Resistido/métodos , Esportes/fisiologia , Adolescente , Adulto , Humanos , Masculino , Padrões de Referência , Corrida/fisiologia , Adulto Jovem
8.
Bioresour Technol ; 285: 121312, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30978584

RESUMO

State-level policies in the New England region of the United States require diversion of organic materials away from landfills. One management option for food waste is anaerobic co-digestion with dairy manure. In addition to biogas, anaerobic digestion produces separated solid and liquid digestates. Solid digestates in the region are typically recycled as animal bedding before returning to the digester and liquids are used to fertilize local soils. Repeated land application of nutrients can contribute to eutrophication risk over time and alternative models are needed to convert digestates into valuable export products. We tested solid digestates derived from dairy manure and food waste as substrate ingredients in the cultivation of Pleurotus ostreatus. We show these materials can be used to offset non-local substrate ingredients while achieving mushroom yields comparable to commercial recipes. This strategy could help divert nutrients away from land adjacent to digesters and into safe, protein-rich food, while producing useful spent mushroom substrate.


Assuntos
Agaricales , Esterco , Anaerobiose , Animais , Biocombustíveis , Nutrientes
9.
Int J Sports Physiol Perform ; 13(7): 830-838, 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-28952840

RESUMO

OBJECTIVES: To evaluate the current evidence regarding the quantification of cricket fast-bowling skill. METHODS: Studies that assessed fast-bowling skill (bowling speed and accuracy) were identified from searches in SPORTDiscus (EBSCO) in June 2017. The reference lists of identified papers were also examined for relevant investigations. RESULTS: A total of 16 papers matched the inclusion criteria, and discrepancies in assessment procedures were evident. Differences in test environment, pitch, and cricket ball characteristics; the warm-up prior to test; test familiarization procedures; permitted run-up lengths; bowling spell length; delivery sequence; test instructions; collection of bowling speed data; and collection and reportage of bowling accuracy data were apparent throughout the literature. The reliability and sensitivity of fast-bowling skill measures have rarely been reported across the literature. Only 1 study has attempted to assess the construct validity of its skill measures. CONCLUSIONS: There are several discrepancies in how fast-bowling skill has been assessed and subsequently quantified in the literature to date. This is a problem, because comparisons between studies are often difficult. Therefore, a strong rationale exists for the creation of match-specific standardized fast-bowling assessments that offer greater ecological validity while maintaining acceptable reliability and sensitivity of the skill measures. If prospective research can act on the proposed recommendations from this review, then coaches will be able to make more informed decisions surrounding player selection, talent identification, return to skill following injury, and the efficacy of short- and long-term training interventions for fast bowlers.


Assuntos
Teste de Esforço/normas , Destreza Motora/fisiologia , Esportes/fisiologia , Desempenho Atlético/fisiologia , Humanos , Reprodutibilidade dos Testes , Análise e Desempenho de Tarefas
10.
Int J Sports Physiol Perform ; 13(2): 151-155, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-28530507

RESUMO

OBJECTIVES: To evaluate the reliability and sensitivity of performance measures in a novel pace-bowling test. METHODS: Thirteen male amateur-club fast bowlers completed a novel pace-bowling test on 2 separate occasions, 4-7 d apart. Participants delivered 48 balls (8 overs) at 5 targets on a suspended sheet situated behind a live batter, who stood in a right-handed and left-handed stance for an equal number of deliveries. Delivery instruction was frequently changed, with all deliveries executed in a preplanned sequence. Data on ball-release speed were captured by radar gun. A high-speed camera captured the moment of ball impact on the target sheet for assessment of radial error and bivariate variable error. Delivery rating of perceived exertion (0-100%) was collected as a measure of intensity. RESULTS: Intraclass correlation coefficients and coefficients of variation revealed excellent reliability for peak and mean ball-release speed, acceptable reliability for delivery rating of perceived exertion, and poor reliability for mean radial error, bivariate variable error, and variability of ball-release speed. The smallest worthwhile change indicated high sensitivity with peak and mean ball-release speed and lower sensitivity with mean radial error and bivariate variable error. CONCLUSIONS: The novel pace-bowling test incorporates improvements in ecological validity compared with its predecessors and can be used to provide a more comprehensive evaluation of pace-bowling performance. Data on the smallest worthwhile change can improve interpretation of pace-bowling research findings and may therefore influence recommendations for applied practice.


Assuntos
Desempenho Atlético/fisiologia , Teste de Esforço/métodos , Esportes/fisiologia , Fenômenos Biomecânicos , Humanos , Masculino , Percepção/fisiologia , Esforço Físico/fisiologia , Reprodutibilidade dos Testes , Análise e Desempenho de Tarefas , Adulto Jovem
11.
Eur J Appl Physiol ; 116(8): 1537-44, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27278522

RESUMO

PURPOSE: Endurance exercise improves cardiovascular health and reduces mortality risk. Augmentation index (AIx) reflects adverse loading exerted on the heart and large arteries and predicts future cardiovascular disease. The purpose of this study was to establish whether endurance athletes possess lower AIx and aortic blood pressure compared to healthy controls, and to determine the association between AIx and cardiorespiratory fitness. METHODS: Forty-six endurance athletes and 43 healthy controls underwent central BP and AIx measurements by non-invasive applanation tonometry before a maximal exercise test. Peak oxygen uptake ([Formula: see text]) was assessed by pulmonary analysis. RESULTS: Relative to controls, athletes had significantly lower brachial diastolic blood pressure (BP, -4.8 mmHg, p < 0.01), central systolic BP (-3.5 mmHg, p = 0.07), and AIx at a heart rate of 75 beats min(-1) (AIx@75, -11.9 %, p < 0.001). No AIx@75 differences were observed between athletes and controls when adjusted for age and [Formula: see text] [athletes vs controls mean (%) ± SE: -6.9 ± 2.2 vs -5.7 ± 2.3, p = 0.76]. Relative to men with low [Formula: see text], those with moderate and high [Formula: see text] had lower age-adjusted AIx@75 (p < 0.001). In women, those with high [Formula: see text] had lower AIx@75 than those with low and moderate [Formula: see text] (p < 0.01). CONCLUSIONS: The lower AIx@75 in endurance athletes is partly mediated by [Formula: see text]. While an inverse relationship between AIx@75 and [Formula: see text] was found in men, women with the highest [Formula: see text] possessed lowest AIx@75 compared to females with moderate or poor cardiorespiratory fitness. We recommend aerobic training aimed at achieving a minimum [Formula: see text] of 45 ml kg(-1) min(-1) to decrease the risk of future cardiovascular events and all-cause mortality.


Assuntos
Aorta/fisiologia , Pressão Arterial/fisiologia , Aptidão Cardiorrespiratória/fisiologia , Resistência Física/fisiologia , Esportes/fisiologia , Rigidez Vascular/fisiologia , Adolescente , Adulto , Desempenho Atlético/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto Jovem
12.
Eur J Appl Physiol ; 116(6): 1245-53, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27155847

RESUMO

PURPOSE: Regular engagement in resistance exercise training elicits many health benefits including improvement to muscular strength, hypertrophy and insulin sensitivity, though the underpinning molecular mechanisms are poorly understood. The purpose of this study was to determine the influence 8 weeks of resistance exercise training has on leukocyte genome-wide DNA methylation and gene expression in healthy young men. METHODS: Eight young (21.1 ± 2.2 years) men completed one repetition maximum (1RM) testing before completing 8 weeks of supervised, thrice-weekly resistance exercise training comprising three sets of 8-12 repetitions with a load equivalent to 80 % of 1RM. Blood samples were collected at rest before and after the 8-week training intervention. Genome-wide DNA methylation and gene expression were assessed on isolated leukocyte DNA and RNA using the 450K BeadChip and HumanHT-12 v4 Expression BeadChip (Illumina), respectively. RESULTS: Resistance exercise training significantly improved upper and lower body strength concurrently with diverse genome-wide DNA methylation and gene expression changes (p ≤ 0. 01). DNA methylation changes occurred at multiple regions throughout the genome in context with genes and CpG islands, and in genes relating to axon guidance, diabetes and immune pathways. There were multiple genes with increased expression that were enriched for RNA processing and developmental proteins. Growth factor genes-GHRH and FGF1-showed differential methylation and mRNA expression changes after resistance training. CONCLUSIONS: Our findings indicate that resistance exercise training improves muscular strength and is associated with reprogramming of the leukocyte DNA methylome and transcriptome.


Assuntos
DNA/genética , Epigênese Genética/fisiologia , Leucócitos/fisiologia , Força Muscular/genética , Treinamento Resistido/métodos , Transcriptoma/genética , Adaptação Fisiológica/genética , Metilação de DNA/genética , Regulação da Expressão Gênica/genética , Humanos , Masculino , Adulto Jovem
13.
Sports Med ; 46(9): 1213-37, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26914269

RESUMO

Telomeres are tandem repeat DNA sequences located at distal ends of chromosomes that protect against genomic DNA degradation and chromosomal instability. Excessive telomere shortening leads to cellular senescence and for this reason telomere length is a marker of biological age. Abnormally short telomeres may culminate in the manifestation of a number of cardio-metabolic diseases. Age-related cardio-metabolic diseases attributable to an inactive lifestyle, such as obesity, type 2 diabetes mellitus and cardiovascular disease, are associated with short leukocyte telomeres. Exercise training prevents and manages the symptoms of many cardio-metabolic diseases whilst concurrently maintaining telomere length. The positive relationship between exercise training, physical fitness and telomere length raises the possibility of a mediating role of telomeres in chronic disease prevention via exercise. Further elucidation of the underpinning molecular mechanisms of how exercise maintains telomere length should provide crucial information on how physical activity can be best structured to combat the chronic disease epidemic and improve the human health span. Here, we synthesise and discuss the current evidence on the impact of physical activity and cardiorespiratory fitness on telomere dynamics. We provide the molecular mechanisms with a known role in exercise-induced telomere length maintenance and highlight unexplored, alternative pathways ripe for future investigations.


Assuntos
Aptidão Cardiorrespiratória , Doenças Cardiovasculares/prevenção & controle , Exercício Físico/fisiologia , Doenças Metabólicas/prevenção & controle , Homeostase do Telômero/fisiologia , Envelhecimento/fisiologia , Humanos , Resistência Física/fisiologia , Complexo Shelterina , Telomerase/metabolismo , Proteínas de Ligação a Telômeros/metabolismo
14.
J Appl Physiol (1985) ; 120(2): 148-58, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26586905

RESUMO

Leukocyte telomeres shorten with age, and excessive shortening is associated with age-related cardiometabolic diseases. Exercise training may prevent disease through telomere length maintenance although the optimal amount of exercise that attenuates telomere attrition is unknown. Furthermore, the underlying molecular mechanisms responsible for the enhanced telomere maintenance observed in endurance athletes is poorly understood. We quantified the leukocyte telomere length and analyzed the expression of telomere-regulating genes in endurance athletes and healthy controls (both n = 61), using quantitative PCR. We found endurance athletes have significantly longer (7.1%, 208-416 nt) leukocyte telomeres and upregulated TERT (2.0-fold) and TPP1 (1.3-fold) mRNA expression compared with controls in age-adjusted analysis. The telomere length and telomere-regulating gene expression differences were no longer statistically significant after adjustment for resting heart rate and relative V̇O(2 max) (all P > 0.05). Resting heart rate emerged as an independent predictor of leukocyte telomere length and TERT and TPP1 mRNA expression in stepwise regression models. To gauge whether volume of exercise was associated with leukocyte telomere length, we divided subjects into running and cycling tertiles (distance covered per week) and found individuals in the middle and highest tertiles had longer telomeres than individuals in the lowest tertile. These data emphasize the importance of cardiorespiratory fitness and exercise training in the prevention of biological aging. They also support the concept that moderate amounts of exercise training protects against biological aging, while higher amounts may not elicit additional benefits.


Assuntos
Exercício Físico/fisiologia , Expressão Gênica/genética , Leucócitos/metabolismo , Resistência Física/genética , Complexo Shelterina/genética , Proteínas de Ligação a Telômeros/genética , Telômero/genética , Adulto , Envelhecimento/genética , Atletas , Feminino , Humanos , Masculino , Resistência Física/fisiologia , RNA Mensageiro/genética , Corrida/fisiologia , Regulação para Cima/genética
15.
Epigenomics ; 7(5): 717-31, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25864559

RESUMO

AIM: DNA methylation programs gene expression and is involved in numerous biological processes. Accumulating evidence supports transgenerational inheritance of DNA methylation changes in mammals via germ cells. Our aim was to determine the effect of exercise on sperm DNA methylation. MATERIALS & METHODS: Twenty-four men were recruited and assigned to an exercise intervention or control group. Clinical parameters were measured and sperm samples were donated by subjects before and after the 3-month time-period. Mature sperm global and genome-wide DNA methylation was assessed using an ELISA assay and the 450K BeadChip (Illumina). RESULTS: Global and genome-wide sperm DNA methylation was altered after 3 months of exercise training. DNA methylation changes occurred in genes related to numerous diseases such as schizophrenia and Parkinson's disease. CONCLUSIONS: Our study provides the first evidence showing exercise training reprograms the sperm methylome. Whether these DNA methylation changes are inherited to future generations warrants attention.


Assuntos
Metilação de DNA , Epigenômica/métodos , Exercício Físico/fisiologia , Genoma Humano/genética , Espermatozoides/metabolismo , Adolescente , Adulto , Análise por Conglomerados , Ilhas de CpG/genética , Regulação da Expressão Gênica , Impressão Genômica/genética , Frequência Cardíaca/fisiologia , Humanos , Masculino , Fatores de Tempo , Adulto Jovem
16.
Am J Physiol Cell Physiol ; 308(9): C737-49, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25696811

RESUMO

Vinpocetine protects against a range of degenerative conditions and insults of the central nervous system via multiple modes of action. Little is known, however, of its effects on metabolism. This may be highly relevant, as vinpocetine is highly protective against ischemia, a process that inhibits normal metabolic function. This study uses the ischemic retina as a model to characterize vinpocetine's effects on metabolism. Vinpocetine reduced the metabolic demand of the retina following ex vivo hypoxia and ischemia to normal levels based on lactate dehydrogenase activity. Vinpocetine delivered similar effects in an in vivo model of retinal ischemia-reperfusion, possibly through increasing glucose availability. Vinpocetine's effects on glucose also appeared to improve glutamate homeostasis in ischemic Müller cells. Other actions of vinpocetine following ischemia-reperfusion, such as reduced cell death and improved retinal function, were possibly a combination of the drug's actions on metabolism and other retinal pathways. Vinpocetine's metabolic effects appeared independent of its other known actions in ischemia, as it recovered retinal function in a separate metabolic model where the glutamate-to-glutamine metabolic pathway was inhibited in Müller cells. The results of this study indicate that vinpocetine mediates ischemic damage partly through altered metabolism and has potential beneficial effects as a treatment for ischemia of neuronal tissues.


Assuntos
Metabolismo Energético/efeitos dos fármacos , Células Ependimogliais/efeitos dos fármacos , Isquemia/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Doenças Retinianas/tratamento farmacológico , Alcaloides de Vinca/farmacologia , Animais , Morte Celular/efeitos dos fármacos , Citoproteção , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Eletrorretinografia , Células Ependimogliais/metabolismo , Células Ependimogliais/patologia , Potenciais Evocados , Glucose/metabolismo , Ácido Glutâmico/metabolismo , Isquemia/metabolismo , Isquemia/patologia , Isquemia/fisiopatologia , L-Lactato Desidrogenase/metabolismo , Ratos Sprague-Dawley , Doenças Retinianas/metabolismo , Doenças Retinianas/patologia , Doenças Retinianas/fisiopatologia , Técnicas de Cultura de Tecidos
17.
J Appl Physiol (1985) ; 118(4): 475-88, 2015 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-25539938

RESUMO

Physical exercise has proven cardiovascular benefits, yet there is no clear understanding of the related molecular mechanisms leading to this. Here we determined the beneficial epigenetic effects of exercise after sprint interval training, a form of exercise known to improve cardiometabolic health. We quantified genome-wide leukocyte DNA methylation of 12 healthy young (18-24 yr) men before and after 4 wk (thrice weekly) of sprint interval training using the 450K BeadChip (Illumina) and validated gene expression changes in an extra seven subjects. Exercise increased subjects' cardiorespiratory fitness and maximal running performance, and decreased low-density lipoprotein cholesterol concentration in conjunction with genome-wide DNA methylation changes. Notably, many CpG island and gene promoter regions were demethylated after exercise, indicating increased genome-wide transcriptional changes. Among genes with DNA methylation changes, epidermal growth factor (EGF), a ligand of the epidermal growth factor receptor known to be involved in cardiovascular disease, was demethylated and showed decreased mRNA expression. Additionally, we found that in microRNAs miR-21 and miR-210, gene DNA methylation was altered by exercise causing a cascade effect on the expression of the mature microRNA involved in cardiovascular function. Our findings demonstrate that exercise alters DNA methylation in circulating blood cells in microRNA and protein-coding genes associated with cardiovascular physiology.


Assuntos
Sistema Cardiovascular/metabolismo , Metilação de DNA/genética , Exercício Físico/fisiologia , Expressão Gênica/genética , Leucócitos/metabolismo , Adulto , Ilhas de CpG/genética , Fator de Crescimento Epidérmico/metabolismo , Epigênese Genética/genética , Receptores ErbB/metabolismo , Humanos , Lipoproteínas LDL/metabolismo , Masculino , MicroRNAs/genética , Regiões Promotoras Genéticas/genética , Adulto Jovem
18.
PLoS One ; 9(12): e115308, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25521824

RESUMO

OBJECTIVES: Competitive endurance athletes commonly undertake periods of overload training in the weeks prior to major competitions. This investigation examined the effects of two seven-day high-intensity overload training regimes (HIT) on performance and physiological characteristics of competitive cyclists. DESIGN: The study was a matched groups, controlled trial. METHODS: Twenty-eight male cyclists (mean ± SD, Age: 33±10 years, Mass 74±7 kg, VO2 peak 4.7±0.5 L·min-1) were assigned to a control group or one of two training groups for seven consecutive days of HIT. Before and after training cyclists completed an ergometer based incremental exercise test and a 20-km time-trial. The HIT sessions were ∼120 minutes in duration and consisted of matched volumes of 5, 10 and 20 second (short) or 15, 30 and 45 second (long) maximal intensity efforts. RESULTS: Both the short and long HIT regimes led to significant (p<0.05) gains in time trial performance compared to the control group. Relative to the control group, the mean changes (±90% confidence limits) in time-trial power were 8.2%±3.8% and 10.4%±4.3% for the short and long HIT regimes respectively; corresponding increases in peak power in the incremental test were 5.5%±2.7% and 9.5%±2.5%. Both HIT (short vs long) interventions led to non-significant (p>0.05) increases (mean ± SD) in VO2 peak (2.3%±4.7% vs 3.5%±6.2%), lactate threshold power (3.6%±3.5% vs 2.9%±5.3%) and gross efficiency (3.2%±2.4% vs 5.1%±3.9%) with only small differences between HIT regimes. CONCLUSIONS: Seven days of overload HIT induces substantial enhancements in time-trial performance despite non-significant increases in physiological measures with competitive cyclists.


Assuntos
Desempenho Atlético/fisiologia , Ciclismo/fisiologia , Exercício Físico , Consumo de Oxigênio , Adulto , Estudos de Casos e Controles , Comportamento Competitivo , Humanos , Masculino
19.
PLoS One ; 9(4): e92088, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24752326

RESUMO

Telomeres are specialized nucleoprotein structures that protect chromosomal ends from degradation. These structures progressively shorten during cellular division and can signal replicative senescence below a critical length. Telomere length is predominantly maintained by the enzyme telomerase. Significant decreases in telomere length and telomerase activity are associated with a host of chronic diseases; conversely their maintenance underpins the optimal function of the adaptive immune system. Habitual physical activity is associated with longer leukocyte telomere length; however, the precise mechanisms are unclear. Potential hypotheses include regulation of telomeric gene transcription and/or microRNAs (miRNAs). We investigated the acute exercise-induced response of telomeric genes and miRNAs in twenty-two healthy males (mean age = 24.1±1.55 years). Participants undertook 30 minutes of treadmill running at 80% of peak oxygen uptake. Blood samples were taken before exercise, immediately post-exercise and 60 minutes post-exercise. Total RNA from white blood cells was submitted to miRNA arrays and telomere extension mRNA array. Results were individually validated in white blood cells and sorted T cell lymphocyte subsets using quantitative real-time PCR (qPCR). Telomerase reverse transcriptase (TERT) mRNA (P = 0.001) and sirtuin-6 (SIRT6) (P<0.05) mRNA expression were upregulated in white blood cells after exercise. Fifty-six miRNAs were also differentially regulated post-exercise (FDR <0.05). In silico analysis identified four miRNAs (miR-186, miR-181, miR-15a and miR-96) that potentially targeted telomeric gene mRNA. The four miRNAs exhibited significant upregulation 60 minutes post-exercise (P<0.001). Telomeric repeat binding factor 2, interacting protein (TERF2IP) was identified as a potential binding target for miR-186 and miR-96 and demonstrated concomitant downregulation (P<0.01) at the corresponding time point. Intense cardiorespiratory exercise was sufficient to differentially regulate key telomeric genes and miRNAs in white blood cells. These results may provide a mechanistic insight into telomere homeostasis and improved immune function and physical health.


Assuntos
Exercício Físico/fisiologia , Regulação da Expressão Gênica , Sistema Imunitário/citologia , Leucócitos/metabolismo , MicroRNAs/genética , Telômero/genética , Adulto , Teste de Esforço , Genoma Humano/genética , Humanos , Masculino , MicroRNAs/metabolismo , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , Linfócitos T/citologia , Linfócitos T/metabolismo
20.
Neurochem Int ; 66: 1-14, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24412512

RESUMO

Vinpocetine is a natural drug which exerts neuroprotective effects in ischaemia of the brain through actions on cation channels, glutamate receptors and other pathways. This study investigated the effect of vinpocetine on cation channel permeability of inner retinal neurons after acute retinal metabolic insult. We focused on amacrine and ganglion cells immunoreactive for calretinin or parvalbumin due to their previously documented susceptibility to ischaemia. Using the probe, 1-amino-4-guanidobutane (AGB), we observed increased cation channel permeability across amacrine and ganglion cells under ischaemia and hypoglycaemia but not anoxia. Calretinin and parvalbumin immunoreactivity was also reduced during ischaemia and hypoglyacemia but not anoxia. Vinpocetine decreased AGB entry into ischaemic and hypoglycaemic ganglion cells indicating that the drug can modulate unregulated cation entry. In addition, vinpocetine prevented the loss of calretinin and parvalbumin immunoreactivity following ischaemia suggesting it may indirectly regulate intracellular calcium. Vinpocetine also reduced AGB permeability in selected amacrine and ganglion cell populations following N-methyl-D-aspartate (NMDA) but not kainate activation suggesting that vinpocetine's regulation of cation channel permeability may partly involve NMDA sensitive glutamate receptors.


Assuntos
Canais Iônicos/metabolismo , Isquemia/metabolismo , Neurônios Retinianos/efeitos dos fármacos , Neurônios Retinianos/metabolismo , Alcaloides de Vinca/farmacologia , Agmatina/metabolismo , Animais , Bloqueadores dos Canais de Cálcio/farmacologia , Bloqueadores dos Canais de Cálcio/uso terapêutico , Isquemia/tratamento farmacológico , Técnicas de Cultura de Órgãos , Permeabilidade/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Retina/efeitos dos fármacos , Retina/metabolismo , Alcaloides de Vinca/uso terapêutico
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