This report is the first description of dosing procedures, pharmacokinetics, biochemical action, and general tolerability of the antiaging drug rapamycin in the common marmoset, a small and short-lived monkey. Eudragit-encapsulated rapamycin was given orally to trained marmosets in a short-term (3 weeks) and a long-term (14 months) study. Circulating trough rapamycin levels (mean = 5.2 ng/mL; 1.93-10.73 ng/mL) achieved at roughly 1.0 mg/kg/day was comparable to those reported in studies of rodents and within the therapeutic range for humans. Long-term treated animals (6/8) indicated a reduction in mammalian target of rapamycin complex 1 signaling as noted by a decrease in the phospho rpS6 to total rpS6 ratio after 2 weeks of treatment. All long-term treated subjects had detectable concentrations of rapamycin in liver (4.7-19.9 pg/mg) and adipose tissue (2.2-32.8 pg/mg) with reduced mammalian target of rapamycin signaling in these tissues. There was no evidence of clinical anemia, fibrotic lung changes, or mouth ulcers. The observed death rate in the long-term study was as expected given the animals' ages. The ability to rapidly and reliably dose socially housed marmosets with an oral form of rapamycin that is well tolerated and that demonstrates a suppression of the mammalian target of rapamycin pathway leads us to conclude that this species offers a viable model for rapamycin testing to establish safety and efficacy for long-term antiaging intervention.
A 14 year old girl presented with an 8 month history of increasing weight loss, peaking at approximately 10%; and disordered eating, increasing pallor, intermittent fevers and lethargy on the background of a complex social situation, anxiety issues and known congenital heart disease. This occurred on the background of known previous issues regarding desire for thinness in her mother. An outpatient referral had already been made by the GP for concerns of weight loss and food restriction. At presentation she was a pale, sick, emaciated and frail looking adolescent girl. She was afebrile with tachycardia (140 bpm), tachypnoiec (RR 40 breath per min), normotensive with no significant postural drop. Further careful physical examination revealed a cardiac murmur with hyperkinetic apex beat, tender hepatosplenomegaly, red splinter haemorrhages and red macular lesions on her neck, arms and abdomen. Echocardiogram confirmed extensive vegetative lesions consistent with infective endocarditis and she was transferred for cardiac surgery. As her acute issues were being managed, the aetiology of her weight loss was explored and the possible co-existence of an eating disorder was thoroughly assessed but found not to be implicated in this case.
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