RESUMO
Applications of ultrasound for noninvasive drug and gene delivery have been limited by associated cell death as a result of sonication. In this study, we sought to quantify the distribution of cellular bioeffects caused by low-frequency ultrasound (24 kHz) and test the hypothesis that Ca(2+) chelation after sonication can shift this distribution by saving cells from death by apoptosis. Using flow cytometry, we quantitatively categorized sonicated cells among four populations: (i) cells that appear largely unaffected, (ii) cells reversibly permeabilized, (iii) cells rendered nonviable during sonication and (iv) cells that appear to be viable shortly after sonication, but later undergo apoptosis and die. By monitoring cells for 6 h after ultrasound exposure, we found that up to 15% of intact cells fell into this final category. Those apoptotic cells initially had the highest levels of uptake of a marker compound, calcein; also had highly elevated levels of intracellular Ca(2+); and contained an estimated plasma membrane wound radius of 100-300 nm. Finally, we showed that chelation of intracellular Ca(2+) after sonication reduced apoptosis by up to 44%, thereby providing a strategy to save cells. We conclude that cells can be saved from ultrasound-induced death by appropriate selection of ultrasound conditions and Ca(2+) chelation after sonication.
Assuntos
Apoptose , Cálcio/metabolismo , Quelantes/farmacologia , Próstata/diagnóstico por imagem , Ultrassonografia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Citometria de Fluxo , Humanos , Masculino , SonicaçãoRESUMO
In an attempt to identify attitudinal orientations that might be used as indicators of attrition, demographic, academic performance, and attitudinal data on 261 students enrolled in the Woodruff School of Nursing at Emory University, Atlanta, between 1968 and 1972, were studied. Traditional measures of scholastic aptitude were not found to be good indicators. The higher the father's educational attainment, the more likely attrition was to occur. The higher the mother's occupational status, the less likely attrition was to occur. Attitudinal measures used in the study seemed to have little direct impact on attrition.