Methamphetamine accelerates cellular senescence through stimulation of de novo ceramide biosynthesis.

Methamphetamine is a highly addictive psychostimulant that causes profound damage to the brain and other body organs. Post mortem studies of human tissues have linked the use of this drug to diseases associated with aging, such as coronary atherosclerosis and pulmonary fibrosis, but the molecular mechanism underlying these findings remains unknown. Here we used functional lipidomics and transcriptomics experiments to study abnormalities in lipid metabolism in select regions of the brain and, to a greater extent, peripheral organs and tissues of rats that self-administered methamphetamine. Experiments in various cellular models (primary mouse fibroblasts and myotubes) allowed us to investigate the molecular mechanisms of systemic inflammation and cellular aging related to methamphetamine abuse. We report now that methamphetamine accelerates cellular senescence and activates transcription of genes involved in cell-cycle control and inflammation by stimulating production of the sphingolipid messenger ceramide. This pathogenic cascade is triggered by reactive oxygen species, likely generated through methamphetamine metabolism via cytochrome P450, and involves the recruitment of nuclear factor-κB (NF-κB) to induce expression of enzymes in the de novo pathway of ceramide biosynthesis. Inhibitors of NF-κB signaling and ceramide formation prevent methamphetamine-induced senescence and systemic inflammation in rats self-administering the drug, attenuating their health deterioration. The results suggest new therapeutic strategies to reduce the adverse consequences of methamphetamine abuse and improve effectiveness of abstinence treatments.

The effect of structured training on breast self-examination search behaviors as measured using biomedical instrumentation.

BACKGROUND: Although breast self-examination (BSE) has long been recommended by health care practitioners as a complement to mammography and clinical breast examination, only a small percentage of U.S. women report doing monthly BSE, and an even smaller number of women perform this procedure proficiently. OBJECTIVES: To measure the effect of a structured training protocol on improving two dimensions of BSE technique (depth of palpation and search time) in each of two search patterns (vertical strip and concentric circle) using biomedical instrumentation. METHODS: For this study, 41 young women participated in a structured training protocol for BSE instruction. The dependent variable was thoroughness of search, for which there were two measures: depth of palpation (displacement of the sensors) and duration of the examination. An instrumented breast model designed by the investigator provided quantitative measurements of examination behaviors and was used to test outcomes of the instruction. RESULTS: Multivariate analyses demonstrated an overall difference across examinations (F = 28.03; p = 0.0001). Univariate tests showed treatment effects for both dependent variables: depth of palpation and duration of examination. CONCLUSIONS: Individual training in BSE with guided practice improved two measures of thoroughness of search: depth of palpation and duration of search time. Biomedical instrumentation represented a novel approach to the collection of quantitative performance data.