Effects of vitamin D supplementation on neuroplasticity in older adults: a double-blinded, placebo-controlled randomised trial

Summary - Vitamin D can improve muscle function and reduce falls, but whether it can strengthen neural connections within the brain and nervous system is not known. This 10-week randomised controlled trial indicates that treatment with 2,000 IU/day vitamin D3 does not significantly alter neuroplasticity relative to placebo in older adults.
Introduction - The purpose of this study was to examine the effects of vitamin D supplementation on neuroplasticity, serum brain-derived neurotrophic factor (BDNF) and muscle strength and function in older adults.
Methods - This was a 10-week double-blinded, placebo-controlled randomised trial in which 26 older adults with 25-hydroxyvitamin D [25OHD] concentrations 25–60 nmol/L were randomised to 2,000 IU/day vitamin D3 or matched placebo. Single- and paired-pulse transcranial magnetic stimulation applied over the motor cortex was used to assess changes in motor-evoked potentials (MEPs) and short-interval intracortical inhibition (SICI), as measures of corticospinal excitability and inhibition respectively, by recording electromyography (EMG) responses to stimulation from the wrist extensors. Changes in muscle strength, stair climbing power, gait (timed-up-and-go), dynamic balance (four square step test), serum 25(OH)D and BDNF concentrations were also measured.
Results - After 10 weeks, mean 25(OH)D levels increased from 46 to 81 nmol/L in the vitamin D group with no change in the placebo group. The vitamin D group experienced a significant 8–11 % increase in muscle strength and a reduction in cortical excitability (MEP amplitude) and SICI relative to baseline (all P < 0.05), but these changes were not significantly different from placebo. There was no effect of vitamin D on muscle power, function or BDNF.
Conclusions - Daily supplementation with 2,000 IU vitamin D3 for 10 weeks had no significant effect on neuroplasticity compared to placebo, but the finding that vitamin D treatment alone was associated with a decrease in corticospinal excitability and intracortical inhibition warrants further investigation as this suggests that it may improve the efficacy of neural transmission within the corticospinal pathway.

G-CSF treatment can attenuate dexamethasone-induced reduction in C2C12 myotube protein synthesis

Granulocyte-colony stimulating factor (G-CSF) has been demonstrated to enhance skeletal muscle recovery following injury and increases muscle function in the context of neuromuscular disease in rodent models. However, understanding of the underlying mechanisms used by G-CSF to mediate these functions remains poor. G-CSF acts on responsive cells through binding to a specific membrane spanning receptor, G-CSFR. Recently identified, the G-CSFR is expressed in myoblasts, myotubes and mature skeletal muscle tissue. Therefore, elucidating the actions of G-CSF in skeletal muscle represents an important prerequisite to consider G-CSF as a therapeutic agent to treat skeletal muscle. Here we show for the first time that treatment with moderate doses (4 and 40ng/ml) of G-CSF attenuates the effects of dexamethasone in reducing protein synthesis in C2C12 myotubes. However, a higher dose (100ng/ml) of G-CSF exacerbates the dexamethasone-induced reduction in protein synthesis. In contrast, G-CSF had no effect on basal or dexamethasone-induced protein degradation, nor did G-CSF influence the phosphorylation of Akt, STAT3, Erk1/2, Src, Lyn and Erk5 in C2C12 myotubes. In conclusion, physiologically relevant doses of G-CSF may attenuate reduced skeletal muscle protein synthesis during catabolic conditions, thereby improving recovery.

Effectiveness of dual-task functional power training for preventing falls in older people: study protocol for a cluster randomised controlled trial

BACKGROUND: Falls are a major public health concern with at least one third of people aged 65 years and over falling at least once per year, and half of these will fall repeatedly, which can lead to injury, pain, loss of function and independence, reduced quality of life and even death. Although the causes of falls are varied and complex, the age-related loss in muscle power has emerged as a useful predictor of disability and falls in older people. In this population, the requirements to produce explosive and rapid movements often occurs whilst simultaneously performing other attention-demanding cognitive or motor tasks, such as walking while talking or carrying an object. The primary aim of this study is to determine whether dual-task functional power training (DT-FPT) can reduce the rate of falls in community-dwelling older people. METHODS/DESIGN: The study design is an 18-month cluster randomised controlled trial in which 280 adults aged ≥65 years residing in retirement villages, who are at increased risk of falling, will be randomly allocated to: 1) an exercise programme involving DT-FPT, or 2) a usual care control group. The intervention is divided into 3 distinct phases: 6 months of supervised DT-FPT, a 6-month 'step down' maintenance programme, and a 6-month follow-up. The primary outcome will be the number of falls after 6, 12 and 18 months. Secondary outcomes will include: lower extremity muscle power and strength, grip strength, functional assessments of gait, reaction time and dynamic balance under single- and dual-task conditions, activities of daily living, quality of life, cognitive function and falls-related self-efficacy. We will also evaluate the cost-effectiveness of the programme for preventing falls. DISCUSSION: The study offers a novel approach that may guide the development and implementation of future community-based falls prevention programmes that specifically focus on optimising muscle power and dual-task performance to reduce falls risk under 'real life' conditions in older adults. In addition, the 'step down' programme will provide new information about the efficacy of a less intensive maintenance programme for reducing the risk of falls over an extended period. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ACTRN12613001161718 . Date registered 23 October 2013.

Fall and fracture risk in sarcopenia and dynapenia with and without obesity: the role of lifestyle interventions

Due to their differing etiologies and consequences, it has been proposed that the term "sarcopenia" should revert to its original definition of age-related muscle mass declines, with a separate term, "dynapenia", describing muscle strength and function declines. There is increasing interest in the interactions of sarcopenia and dynapenia with obesity. Despite an apparent protective effect of obesity on fracture, increased adiposity may compromise bone health, and the presence of sarcopenia and/or dynapenia ("sarcopenic obesity" and "dynapenic obesity") may exacerbate the risk of falls and fracture in obese older adults. Weight loss interventions are likely to be beneficial for older adults with sarcopenic and dynapenic obesity but may result in further reductions in muscle and bone health. The addition of exercise including progressive resistance training and nutritional strategies, including protein and vitamin D supplementation, may optimise body composition and muscle function outcomes thereby reducing falls and fracture risk in this population.

Enhanced physiological tremor deteriorates plantar flexor torque steadiness after bed rest

This study evaluated the effectiveness of resistance training to preserve submaximal plantar flexor (PF) torque steadiness following 60 days of bed rest (BR). Twenty-two healthy male subjects underwent either BR only (CTR, n=8), or BR plus resistance training (RT, n=14). The magnitude of torque fluctuations during steady submaximal isometric PF contractions (20%, 40%, 60% and 80% of maximum) were assessed before and after BR. Across contraction intensities, torque fluctuations (coefficient of variation, CV) increased more (P<0.05) after BR for CTR (from 0.31±0.10 to 0.92±0.63; P<0.001), than for RT (from 0.30±0.09 to 0.54±0.27; P<0.01). A shift in the spectral content of torque fluctuations towards increased rhythmic activity between 6.5 and 20Hz was observed in CTR only (P<0.05). H-reflex amplitude (H(max)/M(max) ratio) declined across groups from 0.57±0.18 before BR to 0.44±0.14 following BR (P<0.01) without correlation to CV. The present study showed that increased torque fluctuation after BR resulted from enhanced physiological tremor. Resistance training prevented the spectral shift in isometric PF torque fluctuation and offset ∼50% of the decline in performance associated with long-term BR.

Estimation of changes in volume of individual lower-limb muscles using magnetic resonance imaging (during bed-rest)

Muscle size in the lower limb is commonly assessed in neuromuscular research as it correlates with muscle function and some approaches have been assessed for their ability to provide valid estimates of muscle volume. Work to date has not examined the ability of different measurement approaches (such as cross-sectional area (CSA) measures on magnetic resonance (MR) imaging) to accurately track changes in muscle volume as a result of an intervention, such as exercise, injury or disuse. Here we assess whether (a) the percentage change in muscle CSA in 17 lower-limb muscles during 56 days bed-rest, as assessed by five different algorithms, lies within 0.5% of the muscle volume change and (b) the variability of the outcome measure is comparable to that of muscle volume. We find that an approach selecting the MR image with the highest muscle CSA and then a series of CSA measures, the number of which depended upon the muscle considered, immediately distal and proximal, provided an acceptable estimate of the muscle volume change. In the vastii, peroneal, sartorius and anterior tibial muscle groups, accurate results can be attained by increasing the spacing between CSA measures, thus reducing the total number of MR images and hence the measurement time. In the two heads of biceps femoris, semimembranosus and gracilis, it is not possible to reduce the number of CSA measures and the entire muscle volume must be evaluated. Using these approaches one can reduce the number of CSA measures required to estimate changes in muscle volume by ~60%. These findings help to attain more efficient means to track muscle volume changes in interventional studies.

Treinamento muscular inspiratório para asma: revisão sistemática com metanálise

In asthmatic, the lung hyperinflation leaves the inspiratory muscle at a suboptimal position in length-tension relationship, reducing the capacity of to generate tension. The increase in transversal section area of the inspiratory muscles could reverse or delay the deterioration of inspiratory muscle function. Objective: To evaluate the evidence for the efficacy of inspiratory muscle training (IMT) with an external resistive device in patients with asthma. Methods: A systematic review with meta-analysis was carried out. The sources researched were the Cochrane Airways Group Specialised Register of trials, Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 11 of 12, 2012), MEDLINE, EMBASE, PsycINFO, CINAHL, AMED, ClinicalTrials.gov and reference lists of articles. All databases were searched from their inception up to November 2012 and there was no restriction on the language of publication. Randomised controlled trials that involved the use of an external inspiratory muscle training device versus a control (sham or no inspiratory training device) were considered for inclusion. Two reviewers independently selected articles for inclusion, evaluated risk of bias in studies and extracted data. Results: A total of five studies involving 113 asthmatic patients were included. Three clinical trials were produced by the same group. The included studies showed a significant increase in maximal inspiratory pressure (MD 13.34 cmH2O, 95% CI 4.70 to 21.98), although the confidence intervals were wide. There was no statistically significant difference between the IMT group and the control group for maximal expiratory pressure, peak expiratory flow rate, forced expiratory volume in one second, forced vital capacity, sensation of dyspnea and use of beta2-agonist. There were no studies describing exacerbation events that required a course of oral and inhaled corticosteroids or emergency department visits, inspiratory muscle endurance, hospital admissions and days of work or school. Conclusions: There is no conclusive evidence in this review to support or refute inspiratory muscle training for asthma, once the evidence was limited by the small number of studies included, number of participants in them together with the risk of bias. More well conducted randomized controlled trials are needed, such trials should investigate respiratory muscle strength, exacerbation rate, lung function, symptoms, hospital admissions, use of medications and days off work or school. IMT should also be assessed in the context of more severe asthma

Comparação e mobilidade, equilíbrio corporal e desempenho muscular segundo a auto-eficácia para quedas em idosas

The aging process modifies various systems in the body, leading to changes in mobility, balance and muscle strength. This can cause a drop in the elderly, or not changing the perceived self-efficacy in preventing falls. Objective: To compare the mobility, body balance and muscle performance according to self-efficacy for falls in community-dwelling elderly. Methods: A cross-sectional comparative study with 63 older (65-80 years) community. Were evaluated for identification data and sociodemographic, cognitive screening using the Mini Mental State Examination (MMSE), effective for the fall of Falls Efficacy Scale International Brazil (FES-I-BRAZIL), Mobility through the Timed Up and Go Test , the balance Berg Balance Scale (BBS) and the Modified Clinical Test tests of Sensory Interaction on Balance (mCTSIB), tandem walk (TW) and Sit to Stand (STS) of the Balance Master® System. Finally, muscle performance by using isokinetic dynamometry. Statistical analysis was performed Student t test for comparison between groups, with p value ≤ 0.05. Results: Comparing the elderly with low-efficacy for falls with high-efficacy for falls, we found significant differences only for the variable Timed Up and Go Test (p = 0.04). With regard to data on balance tests were significant differences in the speed of oscillation firm surface eyes open modified Clinical Test of Sensory Interaction on Test of Balance (p = 0.01). Variables to isokinetic dynamometry were no significant differences in movement knee extension, as regards the variables peak torque (p = 0.04) and power (p = 0.03). Conclusion: The results suggest that, compared to older community with low-and high-efficacy for falls, we observed differences in variables related to mobility, balance and muscle function

Effect of unsaturated fatty acids on myocardial performance, metabolism and morphology

Diets rich in saturated fatty acids are one of the most important causes of atherosclerosis in men, and have been replaced with diets rich in unsaturated fatty acids (UFA) for the prevention of this disorder. However, the effect of UFA on myocardial performance, metabolism and morphology has not been completely characterized. The objective of the present investigation was to evaluate the effects of a UFA-rich diet on cardiac muscle function, oxidative stress, and morphology. Sixty-day-old male Wistar rats were fed a control (N = 8) or a UFA-rich diet (N = 8) for 60 days. Myocardial performance was studied in isolated papillary muscle by isometric and isotonic contractions under basal conditions after calcium chloride (5.2 mM) and ss-adrenergic stimulation with 1.0 mu M isoproterenol. Fragments of the left ventricle free wall were used to study oxidative stress and were analyzed by light microscopy, and the myocardial ultrastructure was examined in left ventricle papillary muscle. After 60 days the UFA-rich diet did not change myocardial function. However, it caused high lipid hydroperoxide (176 +/- 5 vs 158 +/- 5, P < 0.0005) and low catalase (7 +/- 1 vs 9 +/- 1, P < 0.005) and superoxide-dismutase (18 +/- 2 vs 27 +/- 5, P < 0.005) levels, and discrete morphological changes in UFA-rich diet hearts such as lipid deposits and mitochondrial membrane alterations compared to control rats. These data show that a UFA-rich diet caused myocardial oxidative stress and mild structural alterations, but did not change mechanical function.

Mechanical, biochemical, and morphological changes in the heart from chronic food-restricted rats

Food restriction (FR) has been shown to induce important morphological changes in rat myocardium. However, its influence on myocardial performance is not completely defined. We examined the effects of chronic FR on cardiac muscle function and morphology. Sixty-day-old Wistar-Kyoto rats were fed a control (C) or a restricted diet (daily intake reduced to 50% of the amount of food consumed by the control group) for 90 days. Myocardial performance was studied in isolated left ventricular (LV) papillary muscle. Fragments of the LV free wall were analysed by light microscopy, and the ultrastructure of the myocardium was examined in the LV papillary muscle. The myocardial collagen concentration was also evaluated. FR decreased body weight (BW) and LV weight (LVW); the LVW/BW ratio was higher in the restricted group (C, 1.86 +/- 0.17 mg/g; FR, 2.19 +/- 0.31 mg/g; p < 0.01). In the FR animals, the cardiac fibers were polymorphic, some of them were of small diameter and others presented lateral infoldings; the ultrastructural alterations were focal and included reduction of sarcoplasmic content, absence and (or) disorganization of myofilaments and Z line, numerous electron dense and polymorphic mitochondria, and deep infoldings of the plasma membrane. The hydroxyproline concentration was higher in the FR animals (p < 0.01). FR prolonged the contraction and relaxation time of the papillary muscle and did not change its ability to contract and shorten. In conclusion, although a 90-day period of FR caused striking myocardial ultrastructural alterations and increased the collagen concentration, it only minimally affected the mechanical function.

Quantidade de gordura no músculo levantador da pálpebra de portadores de ptose congênita

OBJETIVO: Quantificar a gordura presente no músculo levantador da pálpebra de portadores de ptose congênita, correlacionando este achado com fatores clínico-epidemiológicos desta afecção. MÉTODOS: Vinte e duas amostras de músculo levantador da pálpebra superior, provenientes de portadores de ptose congênita, foram avaliadas morfometricamente, com o intuito de quantificar a gordura presente nos espécimes e correlacionar este achado com características como idade, sexo, grau de ptose e função do músculo levantador. RESULTADOS: Não houve correlação entre a quantidade de gordura encontrada no músculo levantador de portadores de ptose congênita e os dados clínicos dos pacientes estudados. CONCLUSÃO: A quantidade de gordura presente no músculo levantador da pálpebra superior, nas condições do presente estudo, não está associada com idade, sexo, grau de ptose ou função do músculo levantador. Novos estudos serão necessários para avaliar a real alteração que ocorre no músculo levantador da pálpebra de indivíduos com ptose palpebral.

Myocardial dysfunction induced by food restriction is related to calcium cycling and beta-adrenergic system changes

Food restriction (FR) has been shown to promote myocardial dysfunction in rats. The aim of this study was to verify the participation of calcium and beta-adrenergic system on myocardial mechanical alteration in rats submitted to FR. Myocardial performance was studied in isolated left ventricular papillar muscle from young Wistar-Kyoto rats (WKY) submitted to FR or to control diet. The groups subjected to FR were fed 50% less food than the control group for 90 days. Mechanical function was studied in isometric contraction at post-rest contraction of 30 seconds (PRC), calcium chloride concentration 5.20 mM, and beta-adrenergic stimulation with isoproterenol 10(-6) M. FR decreased the body weight, and left and right ventricular weight. In basal condition (1.25 MM of calcium) time to peak tension (TPT) and time from peak tension to 50% relaxation (RT50) were greater in the FR group. Muscle function was. The same in both PRC groups. TPT decrease in both high calcium groups, more in FR rats; RT50 dropped only in FR animals. TPT decreased in both Isoproterenol groups, more intensely in the FR group. This result suggests that food restriction impairs myocardial performance and these changes may be attributed to alterations in the intracellular calcium cycling and beta-adrenergic system. (C) 2003 Elsevier B.V. All rights reserved.

Ventricular remodeling induced by retinoic acid supplementation in adult rats

Retinoic acid (RA) plays a role in regulating cardiac geometry and function throughout life. The aim of this study was to analyze the cardiac effects of RA in adult rats. Wistar rats were randomly allocated to a control group (n = 18) receiving standard rat chow and a group treated with RA (n = 14) receiving standard rat chow supplemented with RA for 90 days. All animals were evaluated by echocardiography, isolated papillary muscle function, and morphological studies. Whereas the RA-treated group developed an increase in both left ventricular (LV) mass and LV end-diastolic diameter, the ratio of LV wall thickness to LV end-diastolic diameter remained unchanged when compared with the control group. In the isolated papillary muscle preparation, RA treatment decreased the time to peak developed tension and increased the maximum velocity of isometric relengthening, indicating that systolic and diastolic function was improved. Although RA treatment produced an increase in myocyte cross-sectional area, the myocardial collagen volume fraction was similar to controls. Thus our study demonstrates that small physiological doses of RA induce ventricular remodeling resembling compensated volume-overload hypertrophy in rats.

Participação do Estado Contrátil e do Relaxamento Miocárdico na Disfunção Ventricular durante a Transição Hipertrofia-Falência Cardíaca

Purpose - To investigate the participation of contractile state and relaxation in cardiac muscle dysfunction during the transition from stable hypertrophy to cardiac decompensation in aging spontaneously hypertensive rats (SHR). Methods - isolated left ventricular papillary muscle function was studied in SHR with heart failure (SHR-F), in age-matched SHR without evidence of heart failure (SHR-NF), and in nonhypertensive controls Wistar-Kyoto rats (WKY). Muscles were analised in isometric and isotonic contractions in Krebs-Henseleit solution with calcium concentration of 1.25mM at 28°C. Results - Papillary muscles from SHR-F and SHR-NF demonstrated decreased active tension development and shortening velocity relative to normotensive WKY (p<0.05). SHR-F and SHR-NF did not differ. Compared with SHR-NF and WKY, muscle passive stiffness was increased in the failing SHR (p<0.05 versus WKY and SHR-NF). This parameter did not differ between SHR-NF and WKY (p> 0.05). Conclusion - These data suggest that the progression from stable hypertrophy to heart failure is associated with changes in the passive stiffness and is not related to depression of myocardial contractile function.

Is chronic hypoxemia in patients with chronic obstructive pulmonary disease associated with more marked nutritional deficiency?: A study of the fat-free mass evaluated by anthropometry and bioelectrical impedance methods

In order to determine wheter blood gases abnormalities, specially hypoxemia, are associated with more marked changes in fat-free mass in patients with chronic obstructive pulmonary disease (CPOD), nutritional assessment was performed on 16 normoxemic (PaO 2 > 55 mm Hg) and 16 hypoxemic (PaO 2 < 55 mm Hg) COPD patients in stable clinical condition. Body weight was expressed as percentage of the ideal body weight. Fat-free mass was estimated by anthropometry (FFM-Anthr) and by bioelectrical impedance (FFM- BI). Handgrip-strength was assessed as a measure of peripheral skeletal muscle strength. Patients were age-matched and presented similar degree of airway obstruction. Malnutrition, defined as body weight less than 90% of the ideal, was observed in 19% of the normoxemic patients and in 25% of the hypoxemic patients (p>0,05). FFM values in hypoxemic patients, estimated by both methods, were not different from those observed in normoxemic patients. No significant difference was observed on handgrip values between the two groups. No correlation was found between nutritional indices and pulmonary function and gases exchange parameters. FFM correlated positively with values of peripheral muscle function in normoxemic and hypoxemic patients. These data add further evidence to the hypothesis that hypoxemia is not a primary cause of the nutritional deficiency observed in COPD patients.