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Background: Persons with Multiple Sclerosis have elevated resting serum lactate concentrations compared to healthy controls (HC)., Objective: To evaluate lactate concentrations during acute exercise and/or following training in MS compared to HC., Methods: In this retrospective study, blood lactate concentrations (mmol/l) originating from two previous studies were analyzed. Lactate concentrations originated from acute submaximal (MSsubmax; HC, n = 11; MS, n = 32) or maximal (MSmax; HC, n = 20; MS, n = 24) exercise tests and following a 24-week mild to moderate intensity (MSsubmax, n = 12) or 12-week high intensity interval (MSmax, n = 13) exercise intervention., Results: Under submaximal conditions in MS and compared to HC, lactaterest (MS: 2.7±0.6 vs HC: 2.3±0.7 was significantly (p < 0.05) elevated. After 24 weeks of mild-to-moderate-intensity exercise training and compared to PRE-values, lactatebout2 (2.5±0.7 vs 3.4±1.1) significantly (p < 0.05) decreased during submaximal testing in MSsubmax. Under maximal conditions, lactatestart (2.3±1.0 vs 1.7±0.9) was significantly (p > 0.05) elevated in MS. Twelve weeks of high intensity interval training did not improve this (p > 0.05)., Conclusions: Under the conditions of this retrospective analysis we conclude that lactate concentrations during acute submaximal and maximal exercise in persons with MS are similar compared to healthy controls. Moderate intensity exercise therapy appeared to improve lactate accumulation but high intensity exercise therapy did not.

Obesity-related adipose tissue (AT) dysfunction, in particular subcutaneous AT (SCAT) lipolysis, is characterized by catecholamine resistance and impaired atrial natriuretic peptide (ANP) responsiveness. It remains unknown whether exercise training improves (non-)adrenergically mediated lipolysis in metabolically compromised conditions. We investigated the effects of local combined α-/β-adrenoceptor blockade on abdominal SCAT lipolysis in lean insulin sensitive (IS) ( n =10), obese IS ( n =10), and obese insulin resistant (IR) ( n =10) men. Obese men participated in a 12-week exercise training intervention to determine the effects on SCAT lipolysis. Abdominal SCAT extracellular glycerol concentration and blood flow (ATBF) were investigated using microdialysis, with/without locally combined α-/β-adrenoceptor blockade at rest, during low-intensity endurance-type exercise and post-exercise recovery. In obese IR men, microdialysis was repeated after exercise intervention. The exercise-induced increase in SCAT extracellular glycerol was more pronounced in obese IS compared with lean IS men, possibly resulting from lower ATBF in obese IS men. The exercise-induced increase in extracellular glycerol was blunted in obese IR compared with obese IS men, despite comparable local ATBF. Abdominal SCAT extracellular glycerol was markedly reduced (remaining ~60% of exercise-induced SCAT extracellular glycerol) following the local α-/β-adrenoceptor blockade in obese IS but not in IR men, suggesting reduced catecholamine-mediated lipolysis during exercise in obese IR men. Exercise training did not affect (non-)adrenergically mediated lipolysis in obese IR men. Our findings showed a major contribution of non-adrenergically-mediated lipolysis during exercise in male abdominal SCAT. Furthermore, catecholamine-mediated lipolysis may be blunted during exercise in obese IR men but could not be improved by exercise intervention, despite an improved metabolic profile and body composition., (© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Despite frequent muscle strength or muscle oxidative capacity (based on exercise-onset oxygen uptake [VO2] kinetics) assessments in patients with multiple sclerosis, the impact of time of day on these parameters is often not taken into account. Based on observations in healthy subjects, it remains to be studied whether muscle strength, and/or exercise-onset VO2 kinetics, varies between the morning and the afternoon in patients with multiple sclerosis. In this prospective observational pilot study, walking capacity, exercise-onset VO2 kinetics, isometric knee extension/flexion strength (dynamometry), and self-reported fatigue were measured in 11 patients with multiple sclerosis (age, 51.8 ± 9.3 yrs; body mass index, 24.7 ± 5.1 kg/m; Expanded Disability Status Scale, 3.5 ± 1.4; 3 men) in the morning and 5 hrs later (afternoon). In the afternoon, self-reported fatigue (1.9 ± 0.9 cm) and muscle strength (knee extension peak torque at 45 degrees, 84 ± 26 Nm) were significantly different (P < 0.05), than in the morning (self-reported fatigue, 1.2 ± 0.9 cm; knee extension peak torque at 45 degrees, 93 ± 32 Nm), but walking capacity and exercise-onset VO2 kinetics were similar at these two time points (P > 0.05). Consistent with observations in healthy subjects, muscle strength varies between the morning and the afternoon in patients with multiple sclerosis, under the conditions of the present study. These findings suggest that muscle strength assessments should be conducted at similar or nearly similar times of the day to minimize diurnal variation in these measures and hence insure correct interpretation.

Previously, we reported that patients with multiple sclerosis (MS) demonstrate improved muscle strength, exercise tolerance, and lean tissue mass following a combined endurance and resistance exercise program. However, the effect of exercise on the underlying disease pathogenesis remains elusive. Since recent evidence supports a crucial role of dendritic cells (DC) in the pathogenesis of MS, we investigated the effect of a 12-week combined exercise program in MS patients on the number and function of DC. We demonstrate an increased number of plasmacytoid DC (pDC) following the exercise program. These pDC display an activated phenotype, as evidenced by increased numbers of circulating CD62L(+) and CD80(+) pDC. Interestingly, the number of CD80(+) pDC positively correlates with the presence of IL-10-producing regulatory type 1 cells (Tr1), an important cell type for maintaining peripheral tolerance to self-antigens. In addition, decreased production of the inflammatory mediators, TNF-α and MMP-9, upon Toll-like receptor (TLR) stimulation was found at the end of the exercise program. Overall, our findings suggest that the 12-week exercise program reduces the secretion of inflammatory mediators upon TLR stimulation and promotes the immunoregulatory function of circulating pDC, suggestive for a favorable impact of exercise on the underlying immunopathogenesis of MS.

Introduction: Low-to-moderate intensity exercise improves muscle contractile properties and endurance capacity in multiple sclerosis (MS). The impact of high intensity exercise remains unknown., Methods: Thirty-four MS patients were randomized into a sedentary control group (SED, n = 11) and 2 exercise groups that performed 12 weeks of a high intensity interval (HITR, n = 12) or high intensity continuous cardiovascular training (HCTR, n = 11), both in combination with resistance training. M.vastus lateralis fiber cross sectional area (CSA) and proportion, knee-flexor/extensor strength, body composition, maximal endurance capacity and self-reported physical activity levels were assessed before and after 12 weeks., Results: Compared to SED, 12 weeks of high intensity exercise increased mean fiber CSA (HITR: +21 ± 7%, HCTR: +23 ± 5%). Furthermore, fiber type I CSA increased in HCTR (+29 ± 6%), whereas type II (+23 ± 7%) and IIa (+23 ± 6%,) CSA increased in HITR. Muscle strength improved in HITR and HCTR (between +13 ± 7% and +45 ± 20%) and body fat percentage tended to decrease (HITR: -3.9 ± 2.0% and HCTR: -2.5 ± 1.2%). Furthermore, endurance capacity (Wmax +21 ± 4%, time to exhaustion +24 ± 5%, VO2max +17 ± 5%) and lean tissue mass (+1.4 ± 0.5%) only increased in HITR. Finally self-reported physical activity levels increased 73 ± 19% and 86 ± 27% in HCTR and HITR, respectively., Conclusion: High intensity cardiovascular exercise combined with resistance training was safe, well tolerated and improved muscle contractile characteristics and endurance capacity in MS., Trial Registration: ClinicalTrials.gov NCT01845896.

In healthy individuals, one exercise bout induces a substantial increase in the number of circulating leukocytes, while their function is transiently suppressed. The effect of one exercise bout in multiple sclerosis (MS) is less studied. Since recent evidence suggests a role of dendritic cells (DC) in the pathogenesis of MS, we investigated the effect of one combined endurance/resistance exercise bout on the number and function of DC in MS patients and healthy controls. Our results show a rapid increase in the number of DC in response to physical exercise in both MS patients and controls. Further investigation revealed that in particular DC expressing the migratory molecules CCR5 and CD62L were increased upon acute physical activity. This may be mediated by Flt3L- and MMP-9-dependent mobilization of DC, as demonstrated by increased circulating levels of Flt3L and MMP-9 following one exercise bout. Circulating DC display reduced TLR responsiveness after acute exercise, as evidenced by a less pronounced upregulation of activation markers, HLA-DR and CD86, on plasmacytoid DC and conventional DC, respectively. Our results indicate mobilization of DC, which may be less prone to drive inflammatory processes, following exercise. This may present a negative feedback mechanism for exercise-induced tissue damage and inflammation.

Supplemental digital content is available in the text. Introduction: This study examines the role of nutritional status during exercise training in patients with type 2 diabetes mellitus by investigating the effect of endurance-type exercise training in the fasted versus the fed state on clinical outcome measures, glycemic control, and skeletal muscle characteristics in male type 2 diabetes patients. Methods: Twenty-five male patients (glycated hemoglobin (HbA1c), 57 ± 3 mmol·mol−1 (7.4% ± 0.3%)) participated in a randomized 12-wk supervised endurance-type exercise intervention, with exercise being performed in an overnight-fasted state (n = 13) or after consuming breakfast (n = 12). Patients were evaluated for glycemic control, blood lipid profiles, body composition and physical fitness, and skeletal muscle gene expression. Results: Exercise training was well tolerated without any incident of hypoglycemia. Exercise training significantly decreased whole-body fat mass (−1.6 kg) and increased high-density lipoprotein concentrations (+2 mg·dL−1), physical fitness (+1.7 mL·min−1·kg−1), and fat oxidation during exercise in both groups (P TIME < 0.05), with no between-group differences (P TIME × GROUP > 0.05). HbA1c concentrations significantly decreased after exercise training (P TIME < 0.001), with a significant greater reduction after consuming breakfast (−0.30% ± 0.06%) compared with fasted state (−0.08% ± 0.06%; mean difference, 0.21%; P TIME × GROUP = 0.016). No interaction effects were observed for skeletal muscle genes related to lipid metabolism or oxidative capacity. Conclusions: Endurance-type exercise training in the fasted or fed state do not differ in their efficacy to reduce fat mass, increase fat oxidation capacity, and increase cardiorespiratory fitness and high-density lipoprotein concentrations or their risk of hypoglycemia in male patients with type 2 diabetes. HbA1c seems to be improved more with exercise performed in the postprandial compared with the postabsorptive state. [ABSTRACT FROM AUTHOR]

Background: Exercise therapy studies in persons with multiple sclerosis (pwMS) primarily focused on motor outcomes in mid disease stage, while cognitive function and neural correlates were only limitedly addressed. Objectives: This pragmatic randomized controlled study investigated the effects of a remotely supervised community-located "start-to-run" program on physical and cognitive function, fatigue, quality of life, brain volume, and connectivity. Method: In all, 42 pwMS were randomized to either experimental (EXP) or waiting list control (WLC) group. The EXP group received individualized training instructions during 12 weeks (3×/week), to be performed in their community aiming to participate in a running event. Measures were physical (VO2max, sit-to-stand test, Six-Minute Walk Test (6MWT), Multiple Sclerosis Walking Scale-12 (MSWS-12)) and cognitive function (Rao's Brief Repeatable Battery (BRB), Paced Auditory Serial Attention Test (PASAT)), fatigue (Fatigue Scale for Motor and Cognitive Function (FSMC)), quality of life (Multiple Sclerosis Impact Scale-29 (MSIS-29)), and imaging. Brain volumes and diffusion tensor imaging (DTI) were quantified using FSL-SIENA/FIRST and FSL-TBSS. Results: In all, 35 pwMS completed the trial. Interaction effects in favor of the EXP group were found for VO2max, sit-to-stand test, MSWS-12, Spatial Recall Test, FSMC, MSIS-29, and pallidum volume. VO2max improved by 1.5 mL/kg/min, MSWS-12 by 4, FSMC by 11, and MSIS-29 by 14 points. The Spatial Recall Test improved by more than 10%. Conclusion: Community-located run training improved aerobic capacity, functional mobility, visuospatial memory, fatigue, and quality of life and pallidum volume in pwMS. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To explore the etiology of exercise intolerance in patients with MS, it is analyzed whether a disturbed cardiac autonomic control could be observed during exercise testing in patients with MS, and is related to exercise tolerance. PATIENTS AND METHOD: From 26 MS patients and 15 healthy subjects, exercise-onset (first 20 and 60 seconds) and -offset (1-minute recovery) HR change was determined during a 6-minute constant-load exercise bout on bike. Blood lactate, HR, oxygen uptake, expiratory volume and perceived exertion were assessed during exercise, and compared between groups. In 15 MS patients, a 6-min walking test was executed. RESULT: Twenty-second exercise-onset HR increase was significantly smaller in MS patients (14 ± 7 bts/min) vs. healthy subjects (20 ± 8 bts/min, p < 0.05), and independently related to MS and age in total group (p < 0.05). Sixty-second exercise-onset and -offset HR changes were not different between groups, nor independently related to MS presence (p > 0.05). A significant correlation was found between 20-second exercise-onset HR increase and walking capacity in MS patients (r = 0.64, p < 0.01). CONCLUSION: In MS patients, the early increase in heart rate during endurance exercise is significantly slowed, indicating a disturbed cardiac autonomic control, and is related to exercise tolerance. [ABSTRACT FROM AUTHOR]