Joan Martin

Creatine monohydrate increases strength in patients with neuromuscular disease.

Article abstract Creatine monohydrate has been shown to increase strength in studies of young healthy subjects and in a few studies with patients. Creatine monohydrate (10 g daily for 5 days to 5 g daily for 5 days) was administered to patients with neuromuscular disease in a pilot study (Study 1; n = 81), followed by a single-blinded study (Study 2; n = 21). Body weight, handgrip, dorsiflexion, and knee extensor strength were measured before and after treatment. Creatine administration increased all measured indices in both studies. Short-term creatine monohydrate increased high-intensity strength significantly in patients with neuromuscular disease.

Hypertrophy without increased isometric strength after weight training

SummaryEight men (20–23 years) weight trained 3 days week−1 for 19 weeks. Training sessions consisted of six sets of a leg press exercise (simultaneous hip and knee extension and ankle plantar flexion) on a weight machine, the last three sets with the heaviest weight that could be used for 7–20 repetitions. In comparison to a control group (n = 6) only the trained group increased (P<0.01) weight lifting performance (heaviest weight lifted for one repetition, 29%), and left and right knee extensor cross-sectional area (CAT scanning and computerized planimetry, 11%, P<0.05). In contrast, training caused no increase in maximal voluntary isometric knee extension strength, electrically evoked knee extensor peak twitch torque, and knee extensor motor unit activation (interpolated twitch method). These data indicate that a moderate but significant amount of hypertrophy induced by weight training does not necessarily increase performance in an isometric strength task different from the training task but involving the same muscle group. The failure of evoked twitch torque to increase despite hypertrophy may further indicate that moderate hypertrophy in the early stage of strength training may not necessarily cause an increase in intrinsic muscle force generating capacity.

A randomized trial of coenzyme Q10 in mitochondrial disorders

Case reports and open‐label studies suggest that coenzyme Q10 (CoQ10) treatment may have beneficial effects in mitochondrial disease patients; however, controlled trials are warranted to clinically prove its effectiveness. Thirty patients with mitochondrial cytopathy received 1200 mg/day CoQ10 for 60 days in a randomized, double‐blind, cross‐over trial. Blood lactate, urinary markers of oxidative stress, body composition, activities of daily living, quality of life, forearm handgrip strength and oxygen desaturation, cycle exercise cardiorespiratory variables, and brain metabolites were measured. CoQ10 treatment attenuated the rise in lactate after cycle ergometry, increased (∽1.93 ml) VO2/kg lean mass after 5 minutes of cycling (P < 0.005), and decreased gray matter choline‐containing compounds (P < 0.05). Sixty days of moderate‐ to high‐dose CoQ10 treatment had minor effects on cycle exercise aerobic capacity and post‐exercise lactate but did not affect other clinically relevant variables such as strength or resting lactate. Muscle Nerve, 2010

Neuromuscular fatigue during repetitive stimulation in elderly and young adults.

SummaryThe purpose of this investigation was to examine the integrity of neuromuscular transmission and impulse propagation during fatigue by examining the muscle compound action potential (M wave) in elderly and young adults. The tibialis anterior muscle of nine elderly [{ie567-1}=67.7 (SE 1.7) years] and nine young [{ie567-2}=26.7 (SE 1.2) years] adults was maximally stimulated repetitively at frequencies of 20, 30 or 40 Hz for 60 s on separate occasions. There was a significantly smaller resting M wave amplitude [7.9 (SE 0.4) mV versus 9.9 (SE 0.6) mV] and M wave area [0.038 (SE 0.005) mV s versus 0.06 (SE 0.004) mV · s] in the elderly versus the young adults respectively. Measurement of the evoked muscle contractile properties revealed significantly (P<0.05) longer twitch durations and a significantly (P<0.05) greater peak twitch torque [4.6 (SE 0.4) Nm versus 3.2 (SE 0.5) Nm] in the elderly versus the young adults, respectively. The elderly adults had a significantly greater torque decline during the 20-Hz trial; however, the decline in torque during the 30-Hz and 40-Hz trials was similar in the elderly and the young adults (30 Hz: 40%; 40 Hz: 56%). Throughout each of the stimulation trials, the decline in torque was accompanied by a significant reduction in M wave amplitude (20 Hz: 14%; 30 Hz: 53%; 40 Hz: 67%); M wave area also declined significantly during the 30-Hz (31%) and 40-Hz (53%) trials. There was no significant difference between the elderly and the young adults in the reduction in the M wave amplitude or area during each trial. The similar electrical responses of the tibialis anterior between the elderly and the young adults suggest that any age-associated changes that occur in the neuromuscular apparatus do not appear to affect the integrity of neuromuscular propagation of the development of fatigue during repetitive stimulation at these frequencies.

Twitch potentiation during fatiguing exercise in the elderly: the effects of training

SummaryTwitch potentiation was studied during a fatigue paradigm involving intermittent maximum voluntary contractions (MVCs) of the tibialis anterior muscle in the elderly and in young adults. Resting twitch torques were similar between groups, but twitch potentiation was significantly greater (241% vs 166%) in the young; the recovery of the twitch after fatigue was similar between groups. Contraction time, time to peak torque and half-relaxation time were all significantly slower in the elderly. Following 12 weeks of resistance training in the elderly, there was no significant change in the twitch contractile properties at rest, but there was a significant main effect of training on the degree of twitch potentiation during the same fatigue protocol (peak potentiation 192% post-training vs 165% pre-training). These data suggest that the mechanism(s) responsible for twitch potentiation following MVCs may be influenced by both aging and training.

Cerebrospinal fluid from patients with amyotrophic lateral sclerosis inhibits sonic hedgehog function

Sonic hedgehog (Shh) is a morphogen essential to the developing nervous system that continues to play an important role in adult life by contributing to cell proliferation and differentiation, maintaining blood-brain barrier integrity, and being cytoprotective against oxidative and excitotoxic stress, all features of importance in amyotrophic lateral sclerosis (ALS). ALS is a fatal disease characterized by selective loss of motor neurons due to poorly understood mechanisms. Evidence indicates that Shh might play an important role in ALS, and that Shh signaling might be also adversely affected in ALS. Since little is known about the functional status of Shh pathway in patients with ALS, we therefore sought to determine whether Shh protein levels or biological activity in cerebrospinal fluid (CSF) was less in ALS patients than controls, and whether these measures could be correlated with ALS disease severity and disease progression, and with other CSF analytes of biological interest in ALS. Comparing Shh levels in the CSF of normal controls (n = 13), neurological controls (n = 12), and ALS patients (n = 9) measured by ELISA, we found that CSF Shh levels were not different between controls and ALS patients. However, when assessing Shh biological activity in CSF using in vitro cell-based assays, which measure Shh activity as inducible Gli-driven luminescence, we found that in the presence of exogenous recombinant Shh or the Shh agonist, purmorphamine, the inducible activity of CSF was significantly augmented in the control groups as expected, but not in the ALS group, suggesting the presence of an inhibitor of Shh signaling in ALS CSF samples. Since purmorphamine acts on Smoothened, downstream of Shh and its receptor Patched, the inhibitory action is downstream of Smoothened. Our results also demonstrated that while the inhibitory effect of ALS CSF on Shh signaling did not correlate significantly with ALS disease characteristics, the levels of IL-1β and TNF-α did. In addition to being significantly elevated in ALS CSF, these cytokines negatively correlated with the disease duration, whereas GDF11 was a favorable predictor of ALS clinical score. We also found that TNF-α significantly inhibited Shh biological activity in vitro, potentially suggesting a novel role of TNF-α in ALS pathogenesis. Collectively, this is the first report demonstrating that Shh signaling in CSF of ALS patients is compromised.

Body Composition and Bone Mass in Female Adolescents and Elderly Subjects Entering Exercise Programs

Osteoporosis is a disease in which the mass of mineral in the skeleton is reduced but is of normal composition. The result of the reduced bone mass is that bones are less able to resist normal compressive forces and the risk of bone fracture is greatly increased, particularly at sites such as the lumbar spine, the femoral neck and the distal radius. The incidence of bone fractures rises dramatically with age, particularly for women, and 1 in 3 women who live to the age of 80 will suffer a fractured hip. There is considerable morbidity associated with osteoporosis, and about 1 in 5 people will die within a few months of the surgical repair of a hip fracture. Osteoporosis is a major burden to the patient, to society and to the health care system’.