Does intracellular metabolite diffusion limit post-contractile recovery in burst locomotor muscle?

Post-metamorphic growth in the blue crab entails an increase in body mass that spans several orders of magnitude. The muscles that power burst swimming in these animals grow hypertrophically, such that small crabs have fiber diameters that are typical of most cells (<60 microm) while in adult animals the fibers are giant (>600 microm). Thus, as the animals grow, their muscle fibers cross and greatly exceed the surface area to volume ratio (SA:V) and intracellular diffusion distance threshold that is adhered to by most cells. Large fiber size should not impact burst contractile function, but post-contractile recovery may be limited by low SA:V and excessive intracellular diffusion distances. A number of changes occur in muscle structure, metabolic organization and metabolic flux during development to compensate for the effects of increasing fiber size. In the present study, we examined the impact of intracellular metabolite diffusive flux on the rate of post-contractile arginine phosphate (AP) resynthesis in burst locomotor muscle from small and large animals. AP recovery was measured following burst exercise, and these data were compared to a mathematical reaction-diffusion model of aerobic metabolism. The measured rates of AP resynthesis were independent of fiber size, while simulations of aerobic AP resynthesis yielded lower rates in large fibers. These contradictory findings are consistent with previous observations that there is an increased reliance on anaerobic metabolism for post-contractile metabolic recovery in large fibers. However, the model results suggest that the interaction between mitochondrial ATP production rates, ATP consumption rates and diffusion distances yield a system that is not particularly close to being limited by intracellular metabolite diffusion. We conclude that fiber SA:V and O2 flux exert more control than intracellular metabolite diffusive flux over the developmental changes in metabolic organization and metabolic fluxes that characterize these muscles.

Australian and New Zealand clinical practice guidelines for the treatment of anorexia nervosa.

BACKGROUND: The Royal Australian and New Zealand College of Psychiatrists is co-ordinating the development of clinical practice guidelines (CPGs) in psychiatry, funded under the National Mental Health Strategy (Australia) and the New Zealand Ministry of Health. This CPG covers anorexia nervosa (AN). METHOD: The CGP team consulted with scientists, clinicians, carers and consumer groups in meetings of over 200 participants and conducted a systematic review of meta-analyses, randomized controlled trials and other studies. TREATMENT RECOMMENDATIONS: It is extremely difficult to draw general conclusions about the efficacy of specific treatment options for AN. There are few controlled clinical trials and their quality is generally poor. These guidelines necessarily rely largely upon expert opinion and uncontrolled trials. A multidimensional approach is recommended. Medical manifestations of the illness need to be addressed and any physical harm halted and reversed. Weight restoration is essential in treatment, but insufficient evidence is available for any single approach. A lenient approach is likely to be more acceptable to patients than a punitive one and less likely to impair self-esteem. Dealing with the psychiatric problems is not simple and much controversy remains. For patients with less severe AN who do not require in-patient treatment, out-patient or day-patient treatment may be suitable, but this decision will depend on availability of such services. Family therapy is a valuable part of treatment, particularly for children and adolescents, but no particular approach emerges as superior to any other. Dietary advice should be included in all treatment programs. Cognitive behaviour therapy or other psychotherapies are likely to be helpful. Antidepressants have a role in patients with depressive symptoms and olanzapine may be useful in attenuating hyperactivity.