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Falls are the leading cause of injury-related deaths among older adults and affect women at disproportionate rates. Dance has been used to improve postural stability, balance confidence and strength of older adults, but in-person classes are often inaccessible. This quasi-experimental pre-mid-post design study investigates whether 12 weeks of online dance classes can improve postural stability, dynamic balance and strength of women aged 65 plus. 16 participants (median=74 years, IQR=6) recruited via convenience sampling completed 12 weeks of twice weekly 75-minute online dance classes. In-person pre, mid and post assessments used 30-second trials of quiet standing, Star Excursion Balance Test, 30-second Sitto-Stand and Calf-Raise-Senior. Significance was evaluated using Friedman's test with Wilcoxon Signed-Rank test post-hoc (p≤.05). Participants demonstrated a high attendance rate (median=87.5, IQR=4.2%). Decreased mediolateral sway was observed pre-mid in eyes closed (p=.003, r=.76) and foam (p=.02, r=.60) conditions, where the latter also produced decreased sway area (p=.015, r=.63). Greater dynamic balance was demonstrated when reaching laterally (pre-mid p=.008, r=.68; pre-post p=.008, r=.69) and posterior-laterally (pre-post p=.009, r=.75). Participants significantly improved their number of repetitions on the Calf-Raise Senior (mid-post p=.02, r=.60; prepost p=.015, r=.63). Online dance classes are engaging, accessible and effective in decreasing older women's risk of falls and maintaining their independence.
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PURPOSE: Peripheral responses might be important in handcycling, given the involvement of small muscles compared to other exercise modalities. Therefore, the goal of this study was to compare changes in muscle oxygen saturation (∆SmO2) and deoxyhemoglobin level (∆[HHb]) between different efforts and muscles. METHODS: Handcyclists participated in a Wingate, a maximal incremental test and a 20-min time-trial (TT). Oxygen uptake (VO2) as well as ∆SmO2, ∆[HHb], deoxygenation and reoxygenation rates in the triceps brachii (TB), biceps brachii (BB), anterior deltoid (AD) and extensor carpi radialis brevis (ER) were measured. RESULTS: ER ∆[HHb]max was 37% greater in the incremental test than in the Wingate (ES = 0.392, P = 0.031). TT mean power (W/kg) was associated with BB ∆SmO2min measured in the incremental test (r = -0.998 [-1.190, -0.806], P = 0.002) and in the Wingate (r = -0.994 [-1.327, -0.661], P = 0.006). MAP (W/kg) was associated with Wingate BB ∆SmO2min (r = -0.983 [-0.999, -0.839], P = 0.003), and Wingate peak (r = 0.649 [0.379, 0.895], P = 0.008) and mean power (W/kg) (r = 0.925 [0.752, 0.972], P = 0.003) was associated with right handgrip force. The strongest physiological predictor for TT performance was BB ∆SmO2min in the incremental test (P = 0.002, r2 = 0.993, SEE 0.016 W/kg), Wingate BB ∆SmO2min for MAP (P = 0.003, r2 = 0.956, SEE 0.058 W/kg) and right handgrip force for Wingate peak power (P = 0.005, r2 = 0.856, SEE 0.551 W/kg). CONCLUSION: Peripheral aerobic responses (muscle oxygenation) were predictive of handcycling performance.
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Cranberries are rich in polyphenols, have a high antioxidant capacity, and may protect against exercise-induced free radical production. Mitochondria are known producers of free radical in skeletal muscle, and preventing overproduction of radicals may be a viable approach to improve muscle health. This study aimed to investigate the effect of a polyphenol-rich cranberry extract (CE) on muscle oxidative capacity and oxygenation metrics in healthy active adults. 17 participants (9 males and 8 females) were tested at: (i) baseline, (ii) 2 h following an acute CE dose (0.7 g/kg of body mass), and (iii) after 4 weeks of daily supplement consumption (0.3 g/kg of body mass). At each time point, muscle oxidative capacity was determined using near-infrared spectroscopy to measure the recovery kinetics of muscle oxygen consumption following a 15-20 s contraction of the vastus lateralis. Cranberry supplementation over 28 days significantly improved muscle oxidative capacity (k-constant, 2.8 ± 1.8 vs. 3.9 ± 2.2; p = 0.02). This was supported by a greater rate of oxygen depletion during a sustained cuff occlusion (-0.04 ± 0.02 vs. -0.07 ± 0.03; p = 0.02). Resting muscle oxygen consumption was not affected by cranberry consumption. Our results suggest that cranberry supplementation may play a role in improving mitochondrial health, which could lead to better muscle oxidative capacity in healthy active adult populations.
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Suplementos Nutricionais , Músculo Esquelético , Consumo de Oxigênio , Extratos Vegetais , Polifenóis , Vaccinium macrocarpon , Humanos , Vaccinium macrocarpon/química , Masculino , Feminino , Polifenóis/farmacologia , Polifenóis/administração & dosagem , Adulto , Consumo de Oxigênio/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Adulto Jovem , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Antioxidantes/farmacologiaRESUMO
Insulin deficiency in type 1 diabetes (T1D) leads to an impairment of glucose metabolism and mitochondrial function. Actovegin is a hemodialysate of calf blood, which has been shown to enhance glucose uptake and cell metabolism in healthy human skeletal muscle. The objectives of this study were to determine the effects of Actovegin on skeletal muscle mitochondrial respiration and functional aerobic capacity in a T1D mouse model. Effects on the expression of mitochondrial proteins, body mass, and food and water consumption were also investigated. Streptozotocin-induced T1D male C57B1/6 mice (aged 3-4 months) were randomized to an Actovegin group and a control group. Every third day, the Actovegin and control groups were injected intraperitoneally with (0.1 mL) Actovegin and (0.1 mL) physiological salt solution, respectively. Oxidative phosphorylation (OXPHOS) capacity of the vastus lateralis muscle was measured by high resolution respirometry in addition to the expression levels of the mitochondrial complexes as well as voltage-dependent anion channel. Functional aerobic capacity was measured using a rodent treadmill protocol. Body mass and food and water consumption were also measured. After 13 days, in comparison to the control group, the Actovegin group demonstrated a significantly higher skeletal muscle mitochondrial respiratory capacity in an ADP-restricted and ADP-stimulated environment. The Actovegin group displayed a significantly lesser decline in functional aerobic capacity and baseline body mass after 13 days. There were no significant differences in food or water consumption between groups. Actovegin could act as an effective agent for facilitating glucose metabolism and improving OXPHOS capacity and functional aerobic capacity in T1D. Further investigation is warranted to establish Actovegin's potential as an alternative therapeutic drug for T1D.
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Diabetes Mellitus Tipo 1 , Heme/análogos & derivados , Masculino , Camundongos , Humanos , Animais , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Modelos Animais de Doenças , Músculo Esquelético/metabolismo , Mitocôndrias/metabolismo , Respiração , Glucose/metabolismo , Mitocôndrias Musculares/metabolismo , Consumo de Oxigênio/fisiologiaRESUMO
BACKGROUND: The oxidative stress (OS) theory of disease stipulates that a chronic imbalance in the ratio of oxidants to antioxidants in the cellular environment leads to a variety of debilitating conditions, including type 2 diabetes, cardiovascular and liver diseases. Metabolites in the gut microbiome have been associated with increases in reactive oxygen species (ROS). Many randomized controlled trials (RCTs) have thus investigated the potential of probiotics as a nutraceutical intervention to improve parameters of OS. AIM: The objective of this paper is to review relevant human RCTs exploring the potential of probiotic supplementation to prevent OS in metabolically healthy individuals. METHODS: This systematic review and meta-analysis was registered on PROSPERO (CRD42021297210). The PubMed database was searched using keywords related to probiotics and OS. In total, out of the 652 studies were screened, 9 respected the inclusion criteria. RESULTS: Total antioxidant capacity (TAC) (SMD: 0.83 mmol/L, 95% CI: 0.25-1.40, p = 0.005) and glutathione (GSH) (SMD: 0.45, 95% CI: 0.13-0.77, p = 0.006) are improved with probiotic ingestion, although there are no alterations in superoxide dismutase (SOD) (SMD: 0.33, 95% CI: -0.27-0.93, p = 0.28). Decreases in plasma concentrations of the OS biomarker malondialdehyde (MDA) (SMD: -0.55, 95% CI: -1.11-0.00, p = 0.05) are also detected. CONCLUSION: Probiotics improve AS and OS in metabolically healthy individuals. However, more studies are needed to address the moderate to high degree of heterogeneity in methodology.
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Estresse Oxidativo , Probióticos , Adulto , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Suplementos Nutricionais , Antioxidantes/farmacologia , Probióticos/farmacologiaRESUMO
Cardiolipin (CL) is a phospholipid molecule found in the inner mitochondrial membrane, where it normally associates with and activates the respiratory complexes. Following myocardial infarction, CL gets released from necrotic cells, consequently affecting neighboring tissues. We have previously demonstrated that physiological concentrations of up to 100 µM CL diminish endothelial cell migration and angiogenic sprouting. Since CL is vital to cellular life, we hypothesized that this molecule may have considerable implications on vascular smooth muscle cells bioenergetics, a key phase in atherogenesis. We examined the acute effects of physiological concentrations of CL on oxidative phosphorylation in permeabilized mice aorta using high-resolution respirometry and a substrate-inhibitor titration protocol. We found that CL significantly lowers LEAK and maximal State 3 respiration. In addition, we found that the acceptor control ratio, representing the coupling between oxidation and phosphorylation, was significantly upregulated by CL. Our findings demonstrate that in situ mitochondrial respiration in permeabilized smooth muscle cells is attenuated when physiological concentrations of CL are applied acutely. This could provide a novel therapy to reduce their dedifferentiation and consequently atherogenesis.
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PURPOSE: Cranberries have the highest polyphenol and antioxidant capacity among fruits and vegetables and may protect against exercise-induced free radical production, consequently improving performance. This study aimed to investigate the effect of polyphenol-rich cranberry extract (CE) on time-trial performance and lactate response following exercise. METHODS: A total of 14 trained runners were tested at i) baseline, ii) 2 h following an acute CE dose (0.7 g/kg of body mass), and iii) 4 weeks after daily supplement consumption (0.3 g/kg of body mass). At each time point, runners performed a 1500-m race followed by a 400-m race where the live vastus lateralis oxygenation changes were determined by near-infrared spectroscopy and blood lactate was measured at rest and 1 and 3 min after each trial. The Shapiro-Wilk test and repeated-measures analysis of variance were used to establish significance (P <0.05). RESULTS: Cranberry supplementation over 28 d improved aerobic performance during the 1500-m time trial, whereas the acute dose had no effect. More specifically, muscle reoxygenation rates were significantly faster after 28 d compared to baseline (P = 0.04; η² = 0.29), and a trend towards slower deoxygenation rate was observed (P = 0.13; η² = 0.20). Chronic CE consumption also buffered the post-exercise lactate response for the 400-m race (P = 0.01; η² = 0.27), while no effects were seen for the longer race. CONCLUSION: Our results suggest that cranberry supplementation may have ergogenic effects, as it improves physiological markers of performance during short- and long-distance running.
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Increasing evidence suggests that mitochondrial dysfunction and aberrant release of mitochondrial reactive oxygen species (ROS) play crucial roles in early synaptic perturbations and neuropathology that drive memory deficits in Alzheimer's disease (AD). We recently showed that solubilized human amyloid beta peptide 1-42 (hAß1-42) causes rapid alterations at glutamatergic synapses in the entorhinal cortex (EC) through the activation of both GluN2A- and GluN2B-containing NMDA receptors. However, whether disruption of mitochondrial dynamics and increased ROS contributes to mechanisms mediating hAß1-42-induced synaptic perturbations in the EC is unknown. Here we assessed the impact of hAß1-42 on mitochondrial respiratory functions, and the expression of key mitochondrial and synaptic proteins in the EC. Measurements of mitochondrial respiratory function in wild-type EC slices exposed to 1 µM hAß1-42 revealed marked reductions in tissue oxygen consumption and energy production efficiency relative to control. hAß1-42 also markedly reduced the immunoexpression of both mitochondrial superoxide dismutase (SOD2) and mitochondrial-cytochrome c protein but had no significant impact on cytosolic-cytochrome c expression, voltage-dependent anion channel protein (a marker for mitochondrial density/integrity), and the immunoexpression of protein markers for all five mitochondrial complexes. The rapid impairments in mitochondrial functions induced by hAß1-42 were accompanied by reductions in the presynaptic marker synaptophysin, postsynaptic density protein (PSD95), and the vesicular acetylcholine transporter, with no significant changes in the degradative enzyme acetylcholinesterase. We then assessed whether reducing hAß1-42-induced increases in ROS could prevent dysregulation of entorhinal synaptic proteins, and found that synaptic impairments induced by hAß1-42 were prevented by the mitochondria-targeted antioxidant drug mitoquinone mesylate, and by the SOD and catalase mimetic EUK134. These findings indicate that hAß1-2 can rapidly disrupt mitochondrial functions and increase ROS in the entorhinal, and that this may contribute to synaptic dysfunctions that may promote early AD-related neuropathology.
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The expression of circadian clock genes, either centrally or in the periphery, has been shown to play an integral role in the control of behavior. Brain region-specific downregulation of clock genes revealed behavioral phenotypes associated with neuropsychiatric disorders and neurodegenerative disease. The specific function of the clock genes as well as the underlying mechanisms that contribute to the observed phenotypes, however, are not yet fully understood. We assessed anxiety- and depressive-like behavior and motor functions in male and female mice with a conditional ablation of Bmal1 or Per2 from medium spiny neurons (MSNs) of the striatum as well as mice lacking one copy of Gpr88. Whereas the conditional knockout of Bmal1 and Per2 had mild effects on affective behaviors, a pronounced effect on motor functions was found in Bmal1 knockout mice. Subsequent investigation revealed an attenuated response of Bmal1 knockout mice to dopamine receptor type 1 agonist treatment, independently of the expression of targets of the dopamine signaling pathway or mitochondrial respiration in MSNs. The study thus suggests a potential interaction of Bmal1 within the direct dopamine signaling pathway, which may provide the link to a shared, MSN-dependent mechanism regulating affective behavior and motor function in mice.
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Oxidative stress represents an impaired metabolic system that promotes damage to cells and tissues. This is the predominant factor that leads to the development and progression of diabetes and diabetic complications. Research has indicated that zinc plays a consequential mechanistic role in the protection against oxidative stress as zinc is required for the proper functioning of the antioxidant system, the suppression of inflammatory mediators, and the modulation of zinc transporters. Recently, the mechanisms surrounding ZnT8, ZIP7, and metallothionein have shown to be of particular pathogenic importance and are considered as potential therapeutic targets in disease management. The literature has shown that zinc dysregulation is associated with diabetes and may be considered as a leading contributor to the deleterious vascular alterations exhibited by the disease. Although further investigation is required, studies have indicated the favorable use of zinc supplementation in the protection against and prevention of oxidative stress and its consequences over the course of the condition. This review aims to provide a comprehensive account of zinc homeostasis, the oxidative mechanisms governed by zinc status, current therapeutic targets, and the impact of zinc supplementation in the prevention of disease onset and in mitigating vascular complications.
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In this work, a novel technique for real-time clutter rejection in ultrasound Color Flow Imaging (CFI) is proposed. Suppressing undesired clutter signal is important because clutter prohibits an unambiguous view of the vascular network. Although conventional eigen-based filters are potentially efficient in suppressing clutter signal, their performance is highly dependent on proper selection of a clutter to blood boundary which is done manually. Herein, we resolve this limitation by formulating the clutter suppression problem as a foreground-background separation problem to extract the moving blood component. To that end, we adapt the fast Robust Matrix Completion (fRMC) algorithm, and utilize the in-face extended Frank-Wolfe method to minimize the rank of the matrix of ultrasound frames. Our method automates the clutter suppression process, which is critical for clinical use. We name the method RAPID (Robust mAtrix decomPosition for suppressIng clutter in ultrasounD) since the automation step can substantially streamline clutter suppression. The technique is validated with simulation, flow phantom and two sets of in-vivo data. RAPID code as well as most of the data in this paper can be downloaded from RAPID.sonography.ai.
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Processamento de Imagem Assistida por Computador/métodos , Processamento de Sinais Assistido por Computador , Ultrassonografia Doppler em Cores/métodos , Algoritmos , Animais , Aorta Abdominal/diagnóstico por imagem , Velocidade do Fluxo Sanguíneo/fisiologia , Humanos , Joelho/irrigação sanguínea , Joelho/diagnóstico por imagem , Masculino , Imagens de Fantasmas , Ratos , Ratos Sprague-DawleyRESUMO
Low-carbohydrate diets are considered to be an effective approach to weight loss and have, subsequently, grown in popularity. Despite the apparent health benefits that these diets may provide for insulin resistance, hypertension, and dyslipidemia, their implications on cardiomyocyte oxidative capacity have yet to be investigated. To evaluate the adaptations induced by a 6-week low-carbohydrate, high-fat (LCHF) diet on mitochondrial respiration, two groups of male mice were investigated: Apolipoprotein E-deficient mice on a LCHF diet (L-DIET) and apolipoprotein E-deficient mice on a regular rodent diet (CON). Heart tissue was extracted and used for high-resolution respirometry (HRR), while immunoblotting was performed to quantify mitochondrial density and complexes. The results demonstrate increased expression of all five mitochondrial subunits in the L-DIET group compared to control condition. Furthermore, HRR revealed increased efficiency of substrate consumption, implying augmented oxidative capacity in the L-DIET group. These findings further support the notion that cardiomyocytes prefer lipids as a primary fuel source, by demonstrating that the shift in metabolism caused by a LCHF diet facilitates such an environment. This provides important information regarding the effects of a LCHF on cardiomyocytes, especially when considering free radical production and heart dysfunction.
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Apolipoproteínas E/genética , Carboidratos da Dieta/farmacologia , Gorduras na Dieta/farmacologia , Complexo de Proteínas da Cadeia de Transporte de Elétrons/genética , Mitocôndrias/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Animais , Apolipoproteínas E/deficiência , Dieta com Restrição de Carboidratos/métodos , Dieta Hiperlipídica/métodos , Carboidratos da Dieta/metabolismo , Gorduras na Dieta/metabolismo , Complexo de Proteínas da Cadeia de Transporte de Elétrons/agonistas , Complexo de Proteínas da Cadeia de Transporte de Elétrons/metabolismo , Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Camundongos Knockout , Mitocôndrias/metabolismo , Miocárdio/citologia , Miocárdio/metabolismo , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Fosforilação Oxidativa/efeitos dos fármacosRESUMO
PURPOSE: Multimodal prehabilitation programs (exercise, nutrition, and anxiety reduction) have been shown to be successful for enhancing patients' physical function prior to surgery, although adherence remains a challenge. Given the short pre-operative period, maintaining adherence is critical to maximize program effectiveness. This study was designed to better understand patients' perspectives of prehabilitation and to identify factors related to program adherence. METHODS: A qualitative descriptive study was conducted based on 52 cancer patients enrolled in a prehabilitation program at the Montreal General Hospital, Montreal, Canada. Data was collected with a structured questionnaire designed to evaluate the program. RESULTS: Patients enjoyed their experience in prehabilitation, especially the exercise program and training sessions. The primary motivating factor for participation was to be physically prepared for the surgery. The most challenging exercise component was resistance training, while the most enjoyed was the aerobic training. Approximately 50% of patients were interested in group fitness classes as opposed to supervised individual training sessions for reasons related to social support. The preferred methods for exercise program delivery were home-based and one supervised exercise session per week. The biggest barrier to participation was related to transportation. CONCLUSIONS: These findings highlight the need to make prehabilitation programs more patient-centered. This is critical when designing more effective therapeutic strategies tailored to meet patients' specific needs while overcoming program non-adherence.
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Exercício Físico/psicologia , Neoplasias/reabilitação , Cooperação do Paciente/psicologia , Cuidados Pré-Operatórios/métodos , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Preferência do Paciente , Cuidados Pré-Operatórios/psicologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Prehabilitation has been previously shown to be more effective in enhancing postoperative functional capacity than rehabilitation alone. The purpose of this study was to determine whether a weekly supervised exercise session could provide further benefit to our current prehabilition program, when comparing to standard post-surgical rehabilitation. METHODS: A parallel-arm single-blind randomized control trial was conducted in patients scheduled for non-metastatic colorectal cancer resection. Patients were assigned to either a once weekly supervised prehabilitation (PREHAB+, n = 41) or standard rehabilitation (REHAB, n = 39) program. Both multimodal programs were home-based program and consisted of moderate intensity aerobic and resistance exercise, nutrition counseling with daily whey protein supplementation and anxiety-reduction strategies. Perioperative care was standardized for both groups as per enhanced recovery after surgery (ERAS®) guidelines. Functional exercise capacity, as determined by the 6-minute walk test distance (6MWD), was the primary outcome. Exercise quantity, intensity and energy expenditure was determined by the CHAMPS questionnaire. RESULTS: Both groups were comparable for baseline walking capacity (PREHAB+: 448 m [IQR 375-525] vs. REHAB: 461 m [419-556], p=.775) and included a similar proportion of patients who improved walking capacity (>20 m) during the preoperative period (PREHAB+: 54% vs. REHAB: 38%, p = .222). After surgery, changes in 6MWD were also similar in both groups. In PREHAB+, however, there was a significant association between physical activity energy expenditure and 6MWD (p < .01). Previously inactive patients were more likely to improve functional capacity due to PREHAB+ (OR 7.07 [95% CI 1.10-45.51]). CONCLUSIONS: The addition of a weekly supervised exercise session to our current prehabilitation program did not further enhance postoperative walking capacity when compared to standard REHAB care. Sedentary patients, however, seemed more likely to benefit from PREHAB+. An association was found between energy spent in physical activity and 6MWD. This information is important to consider when designing cost-effective prehabilitation programs.
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Neoplasias Colorretais/reabilitação , Neoplasias Colorretais/cirurgia , Terapia por Exercício/métodos , Idoso , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Método Simples-CegoRESUMO
Atherosclerosis is one of the leading causes of morbidity and mortality in the Western world. Although the clinical manifestations of this disease are well documented, the etiology and progression remain to be fully understood. Recently, the mitochondria have been implicated in important cellular processes involved in development of atherosclerosis. Despite the link between mitochondria and atherosclerosis, early-phase mechanisms of the disease have yet to be elucidated. The aim of this project was to explore the role of mitochondria in vascular smooth muscle (VSMC) dedifferentiation. A murine in vitro model, involving organ culture of aortic tissue in serum-free media, was used. Mitochondrial function was measured by high-resolution respirometry. Proteins associated with the VSMC phenotype switch, as well as mitochondrial density, were assessed by immunoblotting. The findings show that intrinsic mitochondrial Complex I activity is significantly upregulated during VSMC dedifferentiation. Diminished coupling between phosphorylation and oxidation was also found, indicating a greater ADP:ATP ratio. This data suggests increased leak in the electron transport chain and altered mitochondrial function specifically at Complex I. This project provides important information regarding the role of mitochondria in the early atherosclerotic process and that detectable changes in mitochondrial function and expression are related to VSMC dedifferentiation.
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Trifosfato de Adenosina/biossíntese , Desdiferenciação Celular , Complexo I de Transporte de Elétrons/metabolismo , Regulação Enzimológica da Expressão Gênica , Mitocôndrias/metabolismo , Músculo Liso Vascular/citologia , Animais , Respiração Celular , Masculino , Camundongos , Consumo de Oxigênio , FenótipoRESUMO
KEY POINTS: Pre-ischaemic administration of aminooxiacetate (AOA), an inhibitor of the malate-aspartate shuttle (MAS), provides cardioprotection against ischaemia-reperfusion injury. The underlying mechanism remains unknown. We examined whether transient inhibition of the MAS during ischaemia and early reperfusion by AOA treatment could prevent mitochondrial damage at later reperfusion. The AOA treatment preserved mitochondrial respiratory capacity with reduced mitochondrial oxidative stress during late reperfusion to the same extent as ischaemic preconditioning (IPC). However, AOA treatment, but not IPC, reduced the myocardial interstitial concentration of tricarboxylic acid cycle intermediates at the onset of reperfusion. The results obtained in the present study demonstrate that metabolic regulation by inhibition of the MAS at the onset of reperfusion may be beneficial for the preservation of mitochondrial function during late reperfusion in an IR-injured heart. ABSTRACT: Mitochondrial dysfunction plays a central role in ischaemia-reperfusion (IR) injury. Pre-ischaemic administration of aminooxyacetate (AOA), an inhibitor of the malate-aspartate shuttle (MAS), provides cardioprotection against IR injury, although the underlying mechanism remains unknown. We hypothesized that a transient inhibition of the MAS during ischaemia and early reperfusion could preserve mitochondrial function at later phase of reperfusion in the IR-injured heart to the same extent as ischaemic preconditioning (IPC), which is a well-validated cardioprotective strategy against IR injury. In the present study, we show that pre-ischaemic administration of AOA preserved mitochondrial complex I-linked state 3 respiration and fatty acid oxidation during late reperfusion in IR-injured isolated rat hearts. AOA treatment also attenuated the excessive emission of mitochondrial reactive oxygen species during state 3 with complex I-linked substrates during late reperfusion, which was consistent with reduced oxidative damage in the IR-injured heart. As a result, AOA treatment reduced infarct size after reperfusion. These protective effects of MAS inhibition on the mitochondria were similar to those of IPC. Intriguingly, the protection of mitochondrial function by AOA treatment appears to be different from that of IPC because AOA treatment, but not IPC, downregulated myocardial tricarboxilic acid (TCA)-cycle intermediates at the onset of reperfusion. MAS inhibition thus preserved mitochondrial respiratory capacity and decreased mitochondrial oxidative stress during late reperfusion in the IR-injured heart, at least in part, via metabolic regulation of TCA cycle intermediates in the mitochondria at the onset of reperfusion.
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Ácido Aspártico/metabolismo , Malatos/metabolismo , Mitocôndrias Cardíacas/metabolismo , Isquemia Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Miocárdio/metabolismo , Ácido Amino-Oxiacético/farmacologia , Animais , Cardiotônicos/farmacologia , Respiração Celular/efeitos dos fármacos , Ciclo do Ácido Cítrico/efeitos dos fármacos , Complexo I de Transporte de Elétrons/metabolismo , Coração/efeitos dos fármacos , Masculino , Mitocôndrias Cardíacas/efeitos dos fármacos , Infarto do Miocárdio/metabolismo , Oxirredução/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
PURPOSE: High complication rates following colorectal surgery render many patients unable to fully regain functional capacity, thus seriously compromising quality of life. The aim of this study was to assess whether a 4-week trimodal prehabilitation program (exercise, nutritional supplementation, and counseling on relaxation techniques), implemented during the preoperative period, is sufficient to modify exercise behaviors and improve functional capacity of elderly patients scheduled for colorectal cancer surgery. METHODS: Patients were assigned to either a prehabilitation (PREHAB; n = 57) or matched time control group (CTRL; n = 59). Over the 4-week period prior to surgery, patients in PREHAB participated in a trimodal prehabilitation program. Patients in CTRL received the same program but only postoperatively. The Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire was used to measure physical activity levels, while the 6-min walk test (6MWT) was used for assessment of functional walking capacity. Measurements were collected at baseline and at the time of surgery. RESULTS: Over the preoperative period, patients in PREHAB significantly increased the amount of moderate- and vigorous-intensity physical activities that they performed. PREHAB patients also demonstrated a greater improvement in 6MWT compared to CTRL. At the time of surgery, a greater proportion of patients in PREHAB met current physical activity guidelines, as compared to CTRL. CONCLUSIONS: These findings highlight the positive effects of a trimodal prehabilitation program on patients' physical activity levels and functional walking capacity and demonstrate that modifying exercise behaviors and improving physical function within the 4-week preoperative period are an achievable goal.
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Neoplasias Colorretais/reabilitação , Exercício Físico/fisiologia , Cuidados Pré-Operatórios/métodos , Qualidade de Vida/psicologia , Recuperação de Função Fisiológica , Idoso , Feminino , Humanos , Masculino , Resultado do Tratamento , CaminhadaRESUMO
Type I diabetes mellitus (T1DM) is a chronic disorder, characterized by an almost or complete insulin deficiency. Widespread tissue dysfunction and deleterious diabetes-complications are associated with long-term elevations of blood glucose. The aim of this study was to investigate the effects of type I diabetes, as induced by streptozotocin, on the mitochondria in skeletal muscles that predominantly consist of either slow or fast twitch fibers. Soleus (primarily slow twitch fiber type) and the plantaris muscle (mainly fast twitch fiber type) were removed in order to measure mitochondrial protein expression and integrated mitochondrial respiratory function. Mitochondrial capacity for oxidative phosphorylation (OXPHOS) was found to be higher in the slow (more oxidative) soleus muscle from STZ rats when evaluating lipid and complex I linked OXPHOS capacity, whereas no difference was detected between the groups when evaluating the more physiological complex I and II linked OXPHOS capacity. These findings indicate that chronic hyperglycemia results in an elevated intrinsic mitochondrial respiratory capacity in both soleus and, at varying degree, plantaris muscle, findings that are consistent with human T1DM patients.