Creatine Fails to Augment the Benefits from Resistance Training in Patients with HIV Infection: A Randomized, Double-Blind, Placebo-Controlled Study

Progressive resistance exercise training (PRT) improves physical functioning in patients with HIV infection. Creatine supplementation can augment the benefits derived from training in athletes and improve muscle function in patients with muscle wasting. The objective of this study was to determine whether creatine supplementation augments the effects of PRT on muscle strength, energetics, and body composition in HIV-infected patients.This is a randomized, double blind, placebo-controlled, clinical research center-based, outpatient study in San Francisco. 40 HIV-positive men (20 creatine, 20 placebo) enrolled in a 14-week study. Subjects were randomly assigned to receive creatine monohydrate or placebo for 14 weeks. Treatment began with a loading dose of 20 g/day or an equivalent number of placebo capsules for 5 days, followed by maintenance dosing of 4.8 g/day or placebo. Beginning at week 2 and continuing to week 14, all subjects underwent thrice-weekly supervised resistance exercise while continuing on the assigned study medication (with repeated 6-week cycles of loading and maintenance). The main outcome measurements included muscle strength (one repetition maximum), energetics ((31)P magnetic resonance spectroscopy), composition and size (magnetic resonance imaging), as well as total body composition (dual-energy X-ray absorptiometry). Thirty-three subjects completed the study (17 creatine, 16 placebo). Strength increased in all 8 muscle groups studied following PRT, but this increase was not augmented by creatine supplementation (average increase 44 vs. 42%, difference 2%, 95% CI -9.5% to 13.9%) in creatine and placebo, respectively). There were no differences between groups in changes in muscle energetics. Thigh muscle cross-sectional area increased following resistance exercise, with no additive effect of creatine. Lean body mass (LBM) increased to a significantly greater extent with creatine. CONCLUSIONS / SIGNIFICANCE: Resistance exercise improved muscle size, strength and function in HIV-infected men. While creatine supplementation produced a greater increase in LBM, it did not augment the robust increase in strength derived from PRT.ClinicalTrials.gov NCT00484627

A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

Skeletal muscle contractile and noncontractile components in young and older women and men

Trabalho final de mestrado integrado em Medicina (Geriatria), apresentado á Faculdade de Medicina da Universidade de CoimbraA doença demencial tem alcançado proporções epidémicas, atingindo 4,6 milhões de indivíduos por ano no mundo. Com uma população cada vez mais envelhecida, a prevalência da demência irá aumentar dramaticamente nas próximas décadas. Embora a idade possa estar fortemente relacionada com o desenvolvimento de demência, essa doença não é uma parte inevitável do envelhecimento, mas uma doença com os seus fatores de risco genéticos e não genéticos. A prevenção será então possível quando forem identificados os fatores de risco não genéticos. Alguns fatores de risco já foram sugeridos, mas ainda não foram todos comprovados por estudos de investigação. As baixas concentrações de vitaminas B (folatos, vitamina B12 e vitamina B6) são um possível fator de risco no desenvolvimento de demência vascular e de doença de Alzheimer. Objetivo: Realizar uma revisão da literatura sobre o declínio cognitivo associado aos níveis de vitamina B Métodos: Foram pesquisados artigos na língua inglesa, portuguesa, francesa e espanhola através das bases de dado PubMed e Google académico. Todos os estudos prospetivos, avaliando a associação entre os níveis de vitamina B12 ou seus biomarcadores e cognição, foram incluídos. Resultados: Foram identificados e avaliados trinta e cinco estudos de coorte. Vinte e um estudos de qualidade positiva não confirmaram o papel dos níveis de vitamina B12 na etiologia de demência ou na deterioração cognitiva. Apenas sete estudos de 5 qualidade positiva, demonstraram a associação entre os níveis de vitamina B12 e o declínio cognitivo, demência ou doença de Alzheimer. Conclusão: No geral, os estudos foram de qualidade razoável mas com duração de seguimento e número de amostra inadequados para determinar se existe realmente uma relação entre o nível de vitamina B12 sérico e a cognição ou demênciaDementia has reached epidemic proportions, with an estimated 4.6 million new cases worldwide each year. With an aging world population, the prevalence of dementia will increase dramatically in the next few decades. Although strongly age-related, dementia is not an inevitable part of aging but is a true disease, caused by exposure to several genetic and nongenetic risk factors. Prevention will be possible when the nongenetic risk factors have been identified. Some risk factors have been postulated, but very few have been established by studies. Low concentrations of B vitamins (folate, vitamin B12 and vitamin B6) are candidate risk factors for both Alzheimer’s disease and vascular dementia. Objective: To conduct a literature review, about the cognitive decline associated with vitamin B status. Methods: Articles were search in English, Portuguese, French and Spanish in PubMed and Google academy databases. All prospective cohort studies assessing the association of serum vitamin B12 or biomarkers with cognition were included. Results: Thirty-five cohort studies were identified and evaluated. The twenty-one studies of positive quality, does not support a role for the association of serum vitamin B12 concentrations in the etiology of cognitive impairment or dementia. Seven studies of positive quality, found significant association between vitamin B12 status and cognitive decline, dementia or Alzheimer’s disease. 7 Conclusion: In general, the studies were of reasonable quality but of short duration and inadequate subject number to determine whether an effect exists between serum vitamin B12 and cognition or dementia

Skeletal Muscle Fatigue

Skeletal muscle fatigue is defined as the fall of force or power in response to contractile activity. Both the mechanisms of fatigue and the modes used to elicit it vary tremendously. Conceptual and technological advances allow the examination of fatigue from the level of the single molecule to the intact organism. Evaluation of muscle fatigue in a wide range of disease states builds on our understanding of basic function by revealing the sources of dysfunction in response to disease

High-intensity interval training alters ATP pathway flux during maximal muscle contractions in humans

AIM: High-intensity interval training (HIT) results in potent metabolic adaptations in skeletal muscle, however little is known about the influence of these adaptations on energetics in vivo. We used magnetic resonance spectroscopy to examine the effects of HIT on ATP synthesis from net PCr breakdown (ATP(CK)), oxidative phosphorylation (ATP(OX)) and non-oxidative glycolysis (ATP(GLY)) in vivo in vastus lateralis during a 24-s maximal voluntary contraction (MVC). METHODS: Eight young men performed 6 sessions of repeated, 30-s “all-out” sprints on a cycle ergometer; measures of muscle energetics were obtained at baseline, and after the first and sixth sessions. RESULTS: Training increased peak oxygen consumption (35.8±1.4 to 39.3±1.6 ml·min(−1)·kg(−1), p=0.01) and exercise capacity (217.0±11.0 to 230.5±11.7 W, p=0.04) on the ergometer, with no effects on total ATP production or force-time integral during the MVC. While ATP production by each pathway was unchanged after the first session, 6 sessions increased the relative contribution of ATP(OX) (from 31±2 to 39±2% of total ATP turnover, p<0.001), and lowered the relative contribution from both ATP(CK) (49±2 to 44±1%, p=0.004) and ATP(GLY) (20±2 to 17±1%, p=0.03). CONCLUSION: These alterations to muscle ATP production in vivo indicate that brief, maximal contractions are performed with increased support of oxidative ATP synthesis, and relatively less contribution from anaerobic ATP production following training. These results extend previous reports of molecular and cellular adaptations to HIT and show that 6 training sessions are sufficient to alter in vivo muscle energetics, which likely contributes to increased exercise capacity after short-term HIT

A Computational Model of Torque Generation: Neural, Contractile, Metabolic and Musculoskeletal Components

Abstract The pathway of voluntary joint torque production includes motor neuron recruitment and rate-coding, sarcolemmal depolarization and calcium release by the sarcoplasmic reticulum, force generation by motor proteins within skeletal muscle, and force transmission by tendon across the joint. The direct source of energetic support for this process is ATP hydrolysis. It is possible to examine portions of this physiologic pathway using various in vivo and in vitro techniques, but an integrated view of the multiple processes that ultimately impact joint torque remains elusive. To address this gap, we present a comprehensive computational model of the combined neuromuscular and musculoskeletal systems that includes novel components related to intracellular bioenergetics function. Components representing excitatory drive, muscle activation, force generation, metabolic perturbations, and torque production during voluntary human ankle dorsiflexion were constructed, using a combination of experimentally-derived data and literature values. Simulation results were validated by comparison with torque and metabolic data obtained in vivo. The model successfully predicted peak and submaximal voluntary and electrically-elicited torque output, and accurately simulated the metabolic perturbations associated with voluntary contractions. This novel, comprehensive model could be used to better understand impact of global effectors such as age and disease on various components of the neuromuscular system, and ultimately, voluntary torque output