Association of ß-2 adrenergic agonist and corticosteroid injection in the treatment of lipomas.

AIM: The aim of this study was to evaluate the efficacy of isoproterenol and prednisolone in the treatment of subcutaneous lipomas. METHODS: The first experiment evaluated in vitro lipolysis induced by isoproterenol 10(-6) M alone and across a range of prednisolone concentrations to determine the optimal dose to maximize lipolysis. The second experiment evaluated lipolysis in a lipoma and subcutaneous fat by in vivo microdialysis in five subjects to isoproterenol 10(-6) M with and without prednisolone 10(-6) M. These five subjects and five additional subjects had a lipoma treated five times a week for 4 weeks in a 4-cm grid with 0.2 ml injections of 10(-6) M isoproterenol and 10(-6) M prednisolone. Lipoma size was followed monthly for 1 year or until surgical removal. RESULTS: Prednisolone increased in vitro lipolysis to isoproterenol and 10(-6) M was the optimal concentration of both drugs. Lipomas responded with less lipolysis to isoproterenol than subcutaneous fat during microdialysis, and prednisolone treatment increased lipolysis in both lipomas and subcutaneous fat. Injection treatment of the lipomas decreased their volume 50%. All but one lipoma grew after treatment. Eight of the 10 subjects elected for surgical treatment, and the histology of the lipomas was normal fat tissue. CONCLUSIONS: Prednisolone and isoproterenol in combination increased lipolysis, and injections of the combination into lipomas decreased their volume 50% over 4 weeks. Eight of the 10 subjects elected for surgical removal.

PACAP38 increases vesicular monoamine transporter 2 (VMAT2) expression and attenuates methamphetamine toxicity.

Pituitary adenylyl cyclase activating polypeptide, 38 amino acids (PACAP38) is a brain-gut peptide with diverse physiological functions and is neuroprotective in several models of neurological disease. In this study, we show that systemic administration of PACAP38, which is transported across the blood-brain barrier, greatly reduces the neurotoxicity of methamphetamine (METH). Mice treated with PACAP38 exhibited an attenuation of striatal dopamine loss after METH exposure as well as greatly reduced markers of oxidative stress. PACAP38 treatment also prevented striatal neuroinflammation after METH administration as measured by overexpression of glial fibrillary acidic protein (GFAP), an indicator of astrogliosis, and glucose transporter 5 (GLUT5), a marker of microgliosis. In PACAP38 treated mice, the observed protective effects were not due to an altered thermal response to METH. Since the mice were not challenged with METH until 28 days after PACAP38 treatment, this suggests the neuroprotective effects are mediated by regulation of gene expression. At the time of METH administration, PACAP38 treated animals exhibited a preferential increase in the expression and function of the vesicular monoamine transporter (VMAT2). Genetic reduction of VMAT2 has been shown to increase the neurotoxicity of METH, thus we propose that the increased expression of VMAT2 may underlie the protective actions of PACAP38 against METH. The ability of PACAP38 to increase VMAT2 expression suggests that PACAP38 signaling pathways may constitute a novel therapeutic approach to treat and prevent disorders of dopamine storage.