238 research outputs found
Receptionen af Søren Ulrik Thomsens forfatterskab 1981-2000
No full textInternational audienceA presentation of the reception and interpretations of the Danish author Søren Ulrik Thomsen's work from his first collection of poems and app 20 years o
Receptionen af Søren Ulrik Thomsens forfatterskab 1981-2000
No full textInternational audienceA presentation of the reception and interpretations of the Danish author Søren Ulrik Thomsen's work from his first collection of poems and app 20 years o
The effect of exercise training on transverse tubules in normal, remodeled, and reverse remodeled hearts
No full textThe response of transverse (T)-tubules to exercise training in health and disease remains unclear. Therefore, we studied the effect of exercise training on the density and spacing of left ventricle cardiomyocyte T-tubules in normal and remodeled hearts that associate with detubulation, by confocal laser scanning microscopy. First, exercise training in normal rats increased cardiomyocyte volume by 16% (P < 0.01), with preserved T-tubule density. Thus, the T-tubules adapted to the physiologic hypertrophy. Next, we studied T-tubules in a rat model of metabolic syndrome with pressure overload-induced concentric left ventricle hypertrophy, evidenced by 15% (P < 0.01) increased cardiomyocyte size. These rats had only 85% (P < 0.01) of the T-tubule density of control rats. Exercise training further increased cardiomyocyte volume by 8% (P < 0.01); half to that in control rats, but the T-tubule density remained unchanged. Finally, post-myocardial infarction heart failure induced severe cardiac pathology, with a 70% (P < 0.01) increased cardiomyocyte volume that included both eccentric and concentric hypertrophy and 55% (P < 0.01) reduced T-tubule density. Exercise training reversed 50% (P < 0.01) of the pathologic hypertrophy, whereas the T-tubule density increased by 40% (P < 0.05) compared to sedentary heart failure, but remained at 60% of normal hearts (P < 0.01). Physiologic hypertrophy associated with conserved T-tubule spacing (similar to 1.8-1.9 mu m), whereas in pathologic hypertrophy, T-tubules appeared disorganized without regular spacing. In conclusion, cardiomyocytes maintain the relative T-tubule density during physiologic hypertrophy and after mild concentric pathologic hypertrophy, whereas after severe pathologic remodeling with a substantial loss of T-tubules; exercise training reverses the remodeling and partly corrects the T-tubule density
Exercise training corrects control of spontaneous calcium waves in hearts from myocardial infarction heart failure rats
No full textImpaired cardiac control of intracellular diastolic Ca<sup>2+</sup> gives rise to arrhythmias. Whereas exercise training corrects abnormal cyclic Ca<sup>2+</sup> handling in heart failure, the effect on diastolic Ca<sup>2+</sup> remains unstudied. Here, we studied the effect of exercise training on the generation and propagation of spontaneous diastolic Ca<sup>2+</sup> waves in failing cardiomyocytes. Post-myocardial infarction heart failure was induced in Sprague–Dawley rats by coronary artery ligation. Echocardiography confirmed left ventricular infarctions of 40 ± 5%, whereas heart failure was indicated by increased left ventricular end-diastolic pressures, decreased contraction-relaxation rates, and pathological hypertrophy. Spontaneous Ca<sup>2+</sup> waves were imaged by laser linescanning confocal microscopy (488 nm excitation/505–530 nm emission) in 2 μM Fluo-3-loaded cardiomyocytes at 37°C and extracellular Ca<sup>2+</sup> of 1.2 and 5.0 mM. These studies showed that spontaneous Ca<sup>2+</sup> wave frequency was higher at 5.0 mM than 1.2 mM extracellular Ca<sup>2+</sup> in all rats, but failing cardiomyocytes generated 50% (P < 0.01) more waves compared to sham-operated controls at Ca<sup>2+</sup> 1.2 and 5.0 mM. Exercise training reduced the frequency of spontaneous waves at both 1.2 and 5.0 mM Ca2+ (P< 0.05), although complete normalization was not achieved. Exercise training also increased the aborted/completed ratio of waves at 1.2 mM Ca<sup>2+</sup> (P < 0.01), but not 5.0 mM. Finally, we repeated these studies after inhibiting the nitric oxide synthase with L-NAME. No differential effects were found; thus, mediation did not involve the nitric oxide synthase. In conclusion, exercise training improved the cardiomyocyte control of diastolic Ca<sup>2+</sup> by reducing the Ca<sup>2+</sup> wave frequency and by improving the ability to abort spontaneous Ca<sup>2+</sup> waves after their generation, but before cell-wide propagation
Exercise training reverses myocardial dysfunction induced by CaMKIIδC overexpression by restoring Ca2+-homeostasis
No full textSeveral conditions of heart disease, including heart failure and diabetic cardiomyopathy, are associated with upregulation of cytosolic Ca2+/calmodulin-dependent protein kinase II (CaMKIIδC) activity. In the heart, CaMKIIδC isoform targets several proteins involved in intracellular Ca2+ homeostasis. We hypothesized that high-intensity endurance training activates mechanisms that enable a rescue of dysfunctional cardiomyocyte Ca2+ handling and thereby ameliorate cardiac dysfunction despite continuous and chronic elevated levels of CaMKIIδC. CaMKIIδC transgenic (TG) and wild-type (WT) mice performed aerobic interval exercise training over 6 wk. Cardiac function was measured by echocardiography in vivo, and cardiomyocyte shortening and intracellular Ca2+ handling were measured in vitro. TG mice had reduced global cardiac function, cardiomyocyte shortening (47% reduced compared with WT, P < 0.01), and impaired Ca2+ homeostasis. Despite no change in the chronic elevated levels of CaMKIIδC, exercise improved global cardiac function, restored cardiomyocyte shortening, and reestablished Ca2+ homeostasis to values not different from WT. The key features to explain restored Ca2+ homeostasis after exercise training were increased L-type Ca2+ current density and flux by 79 and 85%, respectively (P < 0.01), increased sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) function by 50% (P < 0.01), and reduced diastolic SR Ca2+ leak by 73% (P < 0.01), compared with sedentary TG mice. In conclusion, exercise training improves global cardiac function as well as cardiomyocyte function in the presence of a maintained high CaMKII activity. The main mechanisms of exercise-induced improvements in TG CaMKIIδC mice are mediated via increased L-type Ca2+ channel currents and improved SR Ca2+ handling by restoration of SERCA2a function in addition to reduced diastolic SR Ca2+ leak
Longitudinal study of the effect of a 5-year exercise intervention on structural brain complexity in older adults. A Generation 100 substudy
No full textPhysical inactivity has been identified as an important risk factor for dementia. High levels of cardiorespiratory fitness (CRF) have been shown to reduce the risk of dementia. However, the mechanism by which exercise affects brain health is still debated. Fractal dimension (FD) is an index that quantifies the structural complexity of the brain. The purpose of this study was to investigate the effects of a 5-year exercise intervention on the structural complexity of the brain, measured through the FD, in a subset of 105 healthy older adults participating in the randomized controlled trial Generation 100 Study. The subjects were randomized into control, moderate intensity continuous training, and high intensity interval training groups. Both brain MRI and CRF were acquired at baseline and at 1-, 3- and 5-years follow-ups. Cortical thickness and volume data were extracted with FreeSurfer, and FD of the cortical lobes, cerebral and cerebellar gray and white matter were computed. CRF was measured as peak oxygen uptake (VO2peak) using ergospirometry during graded maximal exercise testing. Linear mixed models were used to investigate exercise group differences and possible CRF effects on the brain's structural complexity. Associations between change over time in CRF and FD were performed if there was a significant association between CRF and FD. There were no effects of group membership on the structural complexity. However, we found a positive association between CRF and the cerebral gray matter FD (p < 0.001) and the temporal lobe gray matter FD (p < 0.001). This effect was not present for cortical thickness, suggesting that FD is a more sensitive index of structural changes. The change over time in CRF was associated with the change in temporal lobe gray matter FD from baseline to 5-year follow-up (p < 0.05). No association of the change was found between CRF and cerebral gray matter FD. These results demonstrated that entering old age with high and preserved CRF levels protected against loss of structural complexity in areas sensitive to aging and age-related pathology
: Eller hvordan man skriver sig igennem et forbillede
No full textWritten in collaboration with Svend Skriver.An interpretation of a poem by the Danish author Søren Ulrik Thomsen which sees the poem in the light of its relationship to a poem by the Swedish author Gunnar Ekelöf
: Eller hvordan man skriver sig igennem et forbillede
No full textWritten in collaboration with Svend Skriver.An interpretation of a poem by the Danish author Søren Ulrik Thomsen which sees the poem in the light of its relationship to a poem by the Swedish author Gunnar Ekelöf
Intermediate outcomes for clinical trials of multiple sclerosis rehabilitation interventions: Conceptual and practical considerations
No full textBackground:Rehabilitation is an essential health care service and a critical component of comprehensive multiple sclerosis (MS) care. Objective:As part of a 2-day meeting hosted by the International Advisory Committee on Clinical Trials in MS in December 2022, a panel initiated a discussion on the conceptual and practical issues related to selecting intermediate outcomes for clinical trials of MS rehabilitation interventions. Results:The overarching goal of rehabilitation - optimal functioning - was acknowledged as a complex biopsychosocial phenomenon that varies with patient priorities and environmental context. This complexity means that multiple causal pathways and potential intermediate outcomes must be carefully considered during the design of clinical trials in MS rehabilitation that aim to improve functioning. In addition, practical issues must be considered such as psychometric properties of outcome measures, measure type, and characteristics of the target population, including severity of dysfunction. Conclusion:This article uses the International Classification of Functioning, Disability and Health as a foundation for determining relevant intermediate outcomes for clinical trials of MS rehabilitation interventions.The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: The International Advisory Committee on Clinical Trials in Multiple Sclerosis and the International Conference on Innovations in Clinical Trial Design & Enhancing Inclusivity of Clinical Trial Populations were supported by the National Multiple Sclerosis Society and the European Committee for Treatment and Research in Multiple Sclerosis. There was no involvement of the sponsors in the design, collection, analysis or interpretation of data discussed at the Conference. The opinions expressed are those of the authors. Open access was made possible by the participation of Queen’s University in the Canadian Research Knowledge Network
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