Duchenne muscular dystrophy: focus on pharmaceutical and nutritional interventions.

Duchenne muscular dystrophy is a lethal X-linked muscle disease resulting from a defect in the muscle membrane protein dystrophin. The absence of dystrophin leads to muscle membrane fragility, muscle death (necrosis) and eventual replacement of skeletal muscle by fat and fibrous connective tissue. Extensive muscle wasting and respiratory failure results in premature death often by the early 20s. This short review evaluates drug and nutritional interventions designed to reduce the severity of muscular dystrophy, while awaiting the outcome of research into therapies to correct the fundamental gene defect. Combinations of dietary supplementation with amino-acids such as creatine, specific anti-inflammatory drugs and perhaps drugs that target ion channels might have immediate realistic clinical benefits although rigorous research is required to determine optimal combinations of such interventions.

Therapies for improving muscle function in neuromuscular disorders.

Muscle atrophy or wasting is a loss of muscle tissue resulting from disease or lack of use. This review examines recent pharmacologic or nutrition interventions for ameliorating wasting and improving muscle function in neuromuscular disorders. The information has application for treating the muscular dystrophies, cancer cachexia, weightlessness, immobilization, denervation, and disuse atrophy.

Hyperbaric oxygen modulates antioxidant enzyme activity in rat skeletal muscles.

In skeletal muscle the activity of the enzymatic antioxidants superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) is regulated in response to generation of reactive oxygen species (ROS). Increased activity of these enzymes is observed after repeated bouts of aerobic exercise, a potent stimulus for intracellular ROS production. Hyperbaric oxygen (HBO) inhalation also stimulates intracellular ROS production although the effects of HBO on skeletal muscle SOD, GPx and CAT activity have not been studied. We tested the hypothesis that SOD, GPx and CAT activity is modulated in skeletal muscles in response to acute and repeated HBO administration. In adult male rats acute HBO inhalation (60 mm at 3 atmospheres absolute) reduced catalase activity by approximately 51% in slow-twitch soleus muscles. Additionally, repeated HBO inhalation (twice daily for 28 days) increased Mn2+-superoxide dismutase activity by approximately 241% in fast-twitch extensor digitorum longus muscles. We conclude that both acute and repeated HBO inhalation can alter enzymatic antioxidant activity in skeletal muscles.

Hyperbaric oxygen improves contractile function of regenerating rat skeletal muscle after myotoxic injury.

There is growing interest in hyperbaric oxygen (HBO) as an adjunctive treatment for muscle injuries. This experiment tested the hypothesis that periodic inhalation of HBO hastens the functional recovery and myofiber regeneration of skeletal muscle after myotoxic injury. Injection of the rat extensor digitorum longus (EDL) muscle with bupivacaine hydrochloride causes muscle degeneration. After injection, rats breathed air with or without periodic HBO [100% O(2) at either 2 or 3 atmospheres absolute (ATA)]. In vitro maximum isometric tetanic force of injured EDL muscles and regenerating myofiber size were unchanged between 2 ATA HBO-treated and untreated rats at 14 days postinjury but were approximately 11 and approximately 19% greater, respectively, in HBO-treated rats at 25 days postinjury. Maximum isometric tetanic force of injured muscles was approximately 27% greater, and regenerating myofibers were approximately 41% larger, in 3 ATA HBO-treated rats compared with untreated rats at 14 days postinjury. These findings demonstrate that periodic HBO inhalation increases maximum force-producing capacity and enhances myofiber growth in regenerating skeletal muscle after myotoxic injury with greater effect at 3 than at 2 ATA.

Reciprocal anatomical connections between hippocampus and subiculum in the rabbit evidence for subicular innervation of regio superior.

Anatomical connections between the dorsal hippocampus and subiculum were examined in the rabbit, using horseradish peroxidase (HRP) and autoradiographic methods. A previously undescribed pathway was found to project from the dorsal prosubicular-subicular region to dorsal hippocampal cell fields CA1 and CA2. Autoradiographic findings showed that subicular afferents travel via two routes. One pathway projected through the alveus and stratum oriens, with results suggesting collateral input to the basal dendritic pyramidal cell region. The other projection coursed through the stratum lacunosum-moleculare with apparent termination onto CA1 and CA2 apical dendrites. Regions of subiculum providing afferents to hippocampus were compared with subicular areas receiving efferent terminations from hippocampal CA1 and CA3 cell zones. Distribution of hippocampal-subicular terminations were regionally distinct from subicular retrograde cell fields in rostral areas of the subicular complex, extended over a much wider area of subiculum than was seen for retrograde-labeled cells, and was cytoarchitectonically organized. In total, findings indicated that a reciprocal anatomical relationship exists between dorsal hippocampus and subiculum in the rabbit.