High-performance liquid chromatographic isolation and fast atom bombardment mass spectrometric identification of Di-N-desethylamiodarone, a new metabolite of amiodarone in the dog

Amiodarone is an antiarrhythmic drug which has received considerable attention in recent years. It has been suggested that the unusual pharmacodynamic characteristics of this drug may be due in part to the influence of active metabolites. Using fast atom bombardment (FAB) mass spectrometry we have identified a new metabolite of amiodarone, the di-N-desethyl analog (DDEA). This metabolite was present in the blood of dogs treated with the parent drug, and showed a greater affinity for myocardium than did the parent drug. The unique features of FAB mass spectrometry over electron impact mass spectrometry was an essential element in facilitating the identification of this new metabolite. Whether or not this metabolite has pharmacologic activity or is responsible for some of the side effects occurring during amiodarone administration is not known.     

Chronobiology of blood pressure in childhood: implications for tracking

Chronobiology, in its methodological evolution, developed data series analyses paying particular attention to blood pressure (BP), because of the importance of this biorhythmic variable for assessing the risk of developing hypertension. An example of the potentiality of the chronobiologic procedures is given in the present report which deals with the inferential analysis of the BP 24-h patterns in 3-12 year-old children. By using the chronobiologic methodology, time-qualified standards for BP are calculated. Rhythmometric parameters for circadian rhythm of systolic and diastolic components of BP are also computed. Data presented are a tangible outcome for emphasizing the introduction of chronobiology in epidemiology and pediatrics in order to optimize the primary prevention and care of hypertension taking as reference the chronobiologic standards of BP.     

Numerous proteins phosphorylated on tyrosine and enhanced tyrosine kinase activities in vanadate-treated NIH 3T3 fibroblasts

A monoclonal antibody that can immunoprecipitate proteins containing phosphotyrosine has been isolated and characterized. To identify proteins that can act as substrates for tyrosine kinases in intact cells, extracts of phosphate-labeled NIH cells that had been treated with the phosphotyrosyl phosphatase inhibitor, vanadate, were precipitated with the antibody, and the immunoprecipitates were analyzed by two-dimensional gel electrophoresis. Numerous proteins were specifically precipitated from vanadate-treated NIH 3T3 cells by the antibody. The high level of phosphotyrosine detected in vanadate-treated cells is presumably primarily due to phosphatase inhibition, but approx. 2-fold increased tyrosine kinase activities were also detected in extracts of the cells after treatment with vanadate. The enhanced tyrosine kinase activity may contribute to the generation of the transformed phenotype seen in response to treatment with vanadate.