Effects of nepicastat upon dopamine-ß-hydroxylase activity and dopamine and norepinephrine levels in the rat left ventricle, kidney, and adrenal gland.

Background and Objective: Evaluate the activity of dopamine-ß-hydroxylase (DßH) as well as the effect of the DßH inhibitor nepicastat upon enzyme activity and levels of dopamine (DA) and norepinephrine (NE) in the rat left ventricle, kidney, and adrenal glands.Methods: DßH assay consisted of the enzymatic hydroxylation of tyramine into octopamine, and DA and NE tissues levels were quantified by HPLC-ED.Results: Nepicastat (30 mg/kg, p.o.) reduced DßH activity by 93% and 80% in the adrenals at 4 h and 8 h postdrug administration, accompanied by significant reductions in NE and epinephrine tissue levels and an increase in DA levels and of DA/NE tissue ratios, with similar findings for NE, DA and of DA/NE tissue ratios in left ventricle and kidney. DßH activity in the left ventricle and kidney showed a high degree of variability, which does not allow corroboration of the effects of nepicastat upon catecholamine tissue levels.Conclusion: The assay of DßH activity in heart and kidney lacks the necessary robustness, but DßH activity in the adrenals appears to be an appropriate marker. However, the effect size upon DA/NE tissue ratios (an indirect measure of DßH activity) as induced by nepicastat was very similar in sympathetically innervated tissues, left ventricle and kidney, and the adrenal medulla.

Malignant "triton" tumor of the lower extremity with a history of fracture.

INTRODUCTION: Malignant triton tumor (MTT) is a rare and aggressive subtype of malignant peripheral nerve sheath tumor consisting of a neurogenic tumor with rhabdomyoblastic differentiation. Only 170 cases have been reported to date, two-thirds occurring in young patients with neurofibromatosis type 1 and the remaining third presenting as a sporadic tumor. CASE PRESENTATION: We present the case of a 49-year-old man with a sporadic grade 2 MTT of the lower limb which had had a previous tibial fracture. The patient underwent an above-knee amputation. Five months post-operatively metastases were present in the liver and vertebral column causing compression of the spinal cord, so decompressive radiotherapy and palliative chemotherapy were initiated. CONCLUSION: Due to the precocious spread of the disease, we would suggest that adjuvant chemotherapy be considered for the eradication of micrometastases. To our knowledge, this is only the second reported case of an MTT arising in a site with a history of previous severe trauma.