scholarly journals Stimulating the sir2-pgc-1α axis rescues exercise capacity and mitochondrial respiration in Drosophila tafazzin mutants.

2022 ◽  
Author(s):  
Deena Damschroder ◽  
Rubén Zapata-Pérez ◽  
Riekelt H. Houtkooper ◽  
Robert Wessells
Keyword(s):  
Exercise Capacity ◽  
Mitochondrial Respiration ◽  
Mitochondrial Diseases ◽  
Barth Syndrome ◽  
Exercise Intolerance ◽  
Nicotinamide Riboside ◽  
Beneficial Effects ◽  
Severe Exercise ◽  
First Time

Cardiolipin (CL) is a phospholipid required for proper mitochondrial function. Tafazzin remodels CL to create highly unsaturated fatty acid chains. However, when tafazzin is mutated, CL remodeling is impeded, leading to mitochondrial dysfunction and the disease Barth syndrome. Patients with Barth syndrome often have severe exercise intolerance, which negatively impacts their overall quality of life. Boosting NAD+ levels can improve symptoms of other mitochondrial diseases, but its effect in the context of Barth syndrome has not been examined. We demonstrate for the first time that nicotinamide riboside (NR) can rescue exercise tolerance and mitochondrial respiration in a Drosophila tafazzin mutant and that the beneficial effects are dependent on sir2 and pgc-1α . Overexpressing pgc-1α increased the total abundance of cardiolipin in mutants. In addition, muscles and neurons were identified as key targets for future therapies because sir2 or pgc-1α overexpression in either of these tissues is sufficient to restore the exercise capacity of Drosophila tafazzin mutants.

scholarly journals 2477 Targeting pulsatile load to increase exercise capacity and quality of life after TAVR for severe aortic stenosis

2018 ◽  
Vol 2 (S1) ◽  
pp. 48-48
Author(s):  
Anupam Kumar ◽  
Julio Chirinos
Keyword(s):  
Quality Of Life ◽  
Aortic Stenosis ◽  
Exercise Capacity ◽  
Severe Aortic Stenosis ◽  
Myocardial Strain ◽  
Study Drug ◽  
Potassium Nitrate ◽  
Exercise Intolerance ◽  
Double Blind

OBJECTIVES/SPECIFIC AIMS: The objective of the study is to test the effect of oral inorganic nitrate on the primary outcomes of exercise capacity and quality of life in patients who have undergone TAVR for severe aortic stenosis. We will also test the effect of the study drug on various physiology endpoints, including systemic vasodilator response to exercise, LV diastolic function and myocardial strain, late systolic LV load and pulsatile arterial wave reflections. METHODS/STUDY POPULATION: This is a randomized double-blind crossover clinical trial, in which 24 subjects who underwent TAVR for severe AS 3 or more months before enrollment will receive the following 2 interventions, in randomized order: (1) Potassium nitrate (KNO3), at a dose of 12–18 mmol/day by mouth for ~4 weeks, or (2) Potassium chloride (KCl), at a dose of 12–18 mmol/day by mouth for ~4 weeks. A 1-week washout period will be introduced between the 2 interventions. RESULTS/ANTICIPATED RESULTS: We hypothesize that sustained oral administration of potassium nitrate will lead to improvement of exercise capacity and quality of life in this population.DISCUSSION/SIGNIFICANCE OF IMPACT: His study will have a significant impact on assessment and management of patients after TAVR. We will gain a better understanding of physiologic abnormalities leading to exercise intolerance after TAVR. In addition, there are currently no proven therapies that improve exercise capacity in this population.

Exercise rehabilitation in heart failure

ESC CardioMed ◽  
2018 ◽  
pp. 1905-1908
Author(s):  
Florence Beauvais ◽  
Alain Cohen-Solal
Keyword(s):  
Heart Failure ◽  
Heart Transplantation ◽  
Exercise Capacity ◽  
Exercise Intolerance ◽  
Shortness Of Breath ◽  
Exercise Rehabilitation ◽  
Beneficial Effects ◽  
Poor Outcome ◽  
Patients With Heart Failure ◽  
Current Therapies

Patients with heart failure exhibit exercise intolerance and their symptoms, such as fatigue and shortness of breath among others, mainly appear during exercise. This reduced exercise capacity has consistently been associated with poor outcome. Indeed, a peak VO2 of less than 11–12 mL/min/kg has generally been accepted as a criterion for heart transplantation. Many therapeutics have improved the prognosis of these patients, as well as their symptoms; their effects on exercise capacity have generally been mild. In recent years, numerous studies have shown the importance of peripheral abnormalities in heart failure, which are usually not targeted by current therapies, and the beneficial effects of exercise rehabilitation.

scholarly journals A Study on the Quality and Identity of Brazilian Pampa Biome Honey: Evidences for Its Beneficial Effects against Oxidative Stress and Hyperglycemia

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
L. C. Cruz ◽  
J. E. S. Batista ◽  
A. P. P. Zemolin ◽  
M. E. M. Nunes ◽  
D. B. Lippert ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Antioxidant Properties ◽  
High Concentration ◽  
Beneficial Effects ◽  
Pampa Biome ◽  
First Time

We characterized, for the first time, the quality and identity of Brazilian Pampa biome honey and its antioxidant propertiesin vitro(FRAP, DDPH and ABTS). The potential protective effect of honey against oxidative stress induced by iron (Fe) and paraquat, (PQ) in aDrosophila melanogastermodel (in vivo) was also tested. The results indicated that all honey samples tested showed antioxidant activityin vitro. Flies treated with honey showed increased lifespan and were protected against oxidative stress induced by Fe and PQ. Despite the high concentration of sugars in honey (approximately 70–80%), our results demonstrate a hypoglycemic-like effect of honey inDrosophila. Thus, this study demonstrates the high quality of Brazilian Pampa biome honey as well as its significant antioxidant activityin vitroandin vivo, pointing to the potential use of this natural product as an alternative in the therapy of oxidative stress-associated diseases.

scholarly journals Aerobic Exercise and Pharmacological Therapies for Skeletal Myopathy in Heart Failure: Similarities and Differences

2016 ◽  
Vol 2016 ◽  
pp. 1-16 ◽  
Author(s):  
Aline V. Bacurau ◽  
Telma F. Cunha ◽  
Rodrigo W. Souza ◽  
Vanessa A. Voltarelli ◽  
Daniele Gabriel-Costa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Aerobic Exercise ◽  
Pharmacological Therapy ◽  
Aerobic Exercise Training ◽  
Exercise Intolerance ◽  
Therapeutic Approaches ◽  
Beneficial Effects ◽  
Skeletal Myopathy ◽  
Ambulatory Patients

Skeletal myopathy has been identified as a major comorbidity of heart failure (HF) affecting up to 20% of ambulatory patients leading to shortness of breath, early fatigue, and exercise intolerance. Neurohumoral blockade, through the inhibition of renin angiotensin aldosterone system (RAS) andβ-adrenergic receptor blockade (β-blockers), is a mandatory pharmacological therapy of HF since it reduces symptoms, mortality, and sudden death. However, the effect of these drugs on skeletal myopathy needs to be clarified, since exercise intolerance remains in HF patients optimized withβ-blockers and inhibitors of RAS. Aerobic exercise training (AET) is efficient in counteracting skeletal myopathy and in improving functional capacity and quality of life. Indeed, AET has beneficial effects on failing heart itself despite being of less magnitude compared with neurohumoral blockade. In this way, AET should be implemented in the care standards, together with pharmacological therapies. Since both neurohumoral inhibition and AET have a direct and/or indirect impact on skeletal muscle, this review aims to provide an overview of the isolated effects of these therapeutic approaches in counteracting skeletal myopathy in HF. The similarities and dissimilarities of neurohumoral inhibition and AET therapies are also discussed to identify potential advantageous effects of these combined therapies for treating HF.

Mutation m.3395A > G in MT-ND1 leads to variable pathologic manifestations

2020 ◽  
Vol 29 (6) ◽  
pp. 980-989
Author(s):  
Nicolás Gutiérrez Cortés ◽  
Claire Pertuiset ◽  
Elodie Dumon ◽  
Marine Börlin ◽  
Barbara Da Costa ◽  
...  
Keyword(s):  
Complex I ◽  
Mitochondrial Diseases ◽  
Mitochondrial Respiratory Chain ◽  
Functional Study ◽  
Mtdna Mutation ◽  
Wide Range ◽  
Complex I Assembly ◽  
First Time ◽  
Do So

Abstract A non-synonymous mtDNA mutation, m.3395A > G, which changes tyrosine in position 30 to cysteine in p.MT-ND1, was found in several patients with a wide range of clinical phenotypes such as deafness, diabetes and cerebellar syndrome but no Leber’s hereditary optic neuropathy. Although this mutation has already been described, its pathogenicity has not been demonstrated. Here, it was found isolated for the first time, allowing a study to investigate its pathogenicity. To do so, we constructed cybrid cell lines and carried out a functional study to assess the possible consequences of the mutation on mitochondrial bioenergetics. Results obtained demonstrated that this mutation causes an important dysfunction of the mitochondrial respiratory chain with a decrease in both activity and quantity of complex I due to a diminution of p.MT-ND1 quantity. However, no subcomplexes were found in cybrids carrying the mutation, indicating that the quality of the complex I assembly is not affected. Moreover, based on the crystal structure of p.MT-ND1 and the data found in the literature, we propose a hypothesis for the mechanism of the degradation of p.MT-ND1. Our study provides new insights into the pathophysiology of mitochondrial diseases and in particular of MT-ND1 mutations.

scholarly journals Pulmonary rehabilitation for cystic fibrosis: A narrative review of current literature

2021 ◽  
Vol 91 (2) ◽  
Author(s):  
Evgenia I. Kalamara ◽  
Evangelos T. Ballas ◽  
Georgia Pitsiou ◽  
Guergana Petrova
Keyword(s):  
Cystic Fibrosis ◽  
Exercise Training ◽  
Exercise Capacity ◽  
Pulmonary Rehabilitation ◽  
Beneficial Effects ◽  
The Past ◽  
Airway Clearance ◽  
Questions And Answers ◽  
Lung Health

Pulmonary rehabilitation is a key component in cystic fibrosis care.  This review summarizes the recent evidence in the area of pulmonary rehabilitation for cystic fibrosis in the form of questions and answers regarding interventions, indications, benefits and risks of pulmonary rehabilitation. Pulmonary rehabilitation includes airway clearance techniques, exercise training, education and behaviour change and can improve patients’ exercise capacity, muscle strength, quality of life and nutritional status. Airway clearance techniques have beneficial effects for clearing mucous. Over the past years, evidence for the beneficial effects of exercise training on exercise capacity and overall lung health is growing. In cystic fibrosis, multiple factors result in reduced exercise capacity. All modalities of pulmonary rehabilitation should be offered to patients with cystic fibrosis, as the benefits in most cases outweigh the risks, though the optimal regimens need to be yet defined.

scholarly journals Higher Circulating miR-199a-5p Indicates Poor Aerobic Exercise Capacity and Associates With Cardiovascular Dysfunction During Chronic Exposure to High Altitude

2021 ◽  
Vol 12 ◽  
Author(s):  
He Huang ◽  
Shenwei Xie ◽  
Xiaolan Gu ◽  
Bin Xiang ◽  
Zhifeng Zhong ◽  
...  
Keyword(s):  
High Altitude ◽  
Exercise Capacity ◽  
Step Test ◽  
Cardiovascular Dysfunction ◽  
High Altitudes ◽  
Aerobic Exercise Capacity ◽  
Important Regulator ◽  
Run Test ◽  
First Time

BackgroundHypoxia-induced decline in exercise capacity is ubiquitous among lowlanders who immigrated to high altitudes, which severely reduces their work efficiency and quality of life. Although studies have revealed that hypoxia-induced cardiovascular dysfunction limits exercise capacity at high altitudes, the mechanisms have not been well explored at the molecular level. miR-199a-5p is hypoxia-sensitive and serves as an important regulator in cardiovascular pathophysiology. However, whether miR-199a-5p is involved in cardiovascular dysfunction at high altitudes and contributes to subsequent reductions in exercise capacity remains unknown. Thus, this study aimed at exploring these relationships in a high altitude population.MethodsA total of 175 lowlanders who had immigrated to an altitude of 3,800 m 2 years previously participated in the present study. The level of plasma miR-199a-5p and the concentration of serum myocardial enzymes were detected by qRT-PCR and ELISA, respectively. Indices of cardiovascular function were examined by echocardiography. The exercise capacity was evaluated by Cooper’s 12-min run test and the Harvard Step Test. Furthermore, we explored the biological functions of miR-199a-5p with silico analysis and a biochemical test.ResultsThe level of miR-199a-5p was significantly higher in individuals with poor exercise capacity at 3,800 m, compared with those with good exercise capacity (p < 0.001). miR-199a-5p accurately identified individuals with poor exercise capacity (AUC = 0.752, p < 0.001). The level of miR-199a-5p was positively correlated with cardiovascular dysfunction indices (all, p < 0.001). Furthermore, miR-199a-5p was involved in the oxidative stress process.ConclusionIn this study, we reported for the first time that the level of circulating miR-199a-5p was positively associated with exercise capacity during chronic hypoxia at high altitudes. Moreover, higher miR-199a-5p was involved in hypoxia-induced cardiovascular dysfunctions, thus contributing to poorer exercise endurance at high altitudes.

scholarly journals AMPK activator O304 improves metabolic and cardiac function, and exercise capacity in aged mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Madelene Ericsson ◽  
Pär Steneberg ◽  
Rakel Nyrén ◽  
Helena Edlund
Keyword(s):  
Quality Of Life ◽  
Cardiac Function ◽  
Exercise Capacity ◽  
Vascular Function ◽  
Metabolic Dysfunction ◽  
Aged Mice ◽  
Beneficial Effects ◽  
Positive Effects ◽  
Age Related

AbstractAge is associated with progressively impaired, metabolic, cardiac and vascular function, as well as reduced work/exercise capacity, mobility, and hence quality of life. Exercise exhibit positive effects on age-related dysfunctions and diseases. However, for a variety of reasons many aged individuals are unable to engage in regular physical activity, making the development of pharmacological treatments that mimics the beneficial effects of exercise highly desirable. Here we show that the pan-AMPK activator O304, which is well tolerated in humans, prevented and reverted age-associated hyperinsulinemia and insulin resistance, and improved cardiac function and exercise capacity in aged mice. These results provide preclinical evidence that O304 mimics the beneficial effects of exercise. Thus, as an exercise mimetic in clinical development, AMPK activator O304 holds great potential to mitigate metabolic dysfunction, and to improve cardiac function and exercise capacity, and hence quality of life in aged individuals.

Communication Sciences and Disorders PhD Graduates' Perceptions of Their PhD Program

2020 ◽  
Vol 5 (2) ◽  
pp. 463-478
Author(s):  
Elizabeth Crais ◽  
Melody Harrison Savage
Keyword(s):  
Detailed Examination ◽  
Career Expectations ◽  
Doctoral Preparation ◽  
Creative Solutions ◽  
Phd Education ◽  
Doctor Of Philosophy ◽  
First Time ◽  
Students Success ◽  
Phd Program

Purpose The shortage of doctor of philosophy (PhD)–level applicants to fill academic and research positions in communication sciences and disorders (CSD) programs calls for a detailed examination of current CSD PhD educational practices and the generation of creative solutions. The intended purposes of the article are to encourage CSD faculty to examine their own PhD program practices and consider the perspectives of recent CSD PhD graduates in determining the need for possible modifications. Method The article describes the results of a survey of 240 CSD PhD graduates and their perceptions of the challenges and facilitators to completing a PhD degree; the quality of their preparation in research, teaching, and job readiness; and ways to improve PhD education. Results Two primary themes emerged from the data highlighting the need for “matchmaking.” The first time point of needed matchmaking is prior to entry among students, mentors, and expectations as well as between aspects of the program that can lead to students' success and graduation. The second important matchmaking need is between the actual PhD preparation and the realities of the graduates' career expectations, and those placed on graduates by their employers. Conclusions Within both themes, graduate's perspectives and suggestions to help guide future doctoral preparation are highlighted. The graduates' recommendations could be used by CSD PhD program faculty to enhance the quality of their program and the likelihood of student success and completion. Supplemental Material https://doi.org/10.23641/asha.11991480

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