RESUMEN
Medical radiation exposure is a significant concern for interventional cardiologists (IC). This study was aimed at estimating the radiation exposure of IC operators and assistants in real clinical practice. The radiation exposure of the operator and assistant was evaluated by conducting two types of procedures via coronary angiography (CAG) and percutaneous coronary intervention (PCI) on 1090 patients in 11-cardiovascular centers in Korea. Radiation exposure was measured using an electronic personal dosimeter (EPD). EPD were attached at 3 points on each participant: on the apron on the left anterior chest (A1), under the apron on the sternum (A2), and on the thyroid shield (T). Average radiation exposure (ARE) of operators at A1, A2, and T was 19.219 uSv, 4.398 uSv, and 16.949 uSv during CAG and 68.618 uSv, 15.213 uSv, and 51.197 uSv during PCI, respectively. ARE of assistants at A1, A2, and T was 4.941 uSv, 0.860 uSv, and 5.232 uSv during CAG and 20.517 uSv, 4.455 uSv, and 16.109 uSv during PCI, respectively. AED of operator was 3.4 times greater during PCI than during CAG.
Asunto(s)
Angiografía Coronaria , Arteria Femoral/diagnóstico por imagen , Exposición Profesional , Intervención Coronaria Percutánea , Arteria Radial/diagnóstico por imagen , Dosis de Radiación , Exposición a la Radiación , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Since the discovery of the 2,4 (1H,3H)-pyrimidinediones as potent non-nucleoside inhibitors of the HIV-1 reverse transcriptase (RT) this class of compounds has yielded a number of N-1 acyclic substituted pyrimidinediones with substantial antiviral activity, which is highly dependent upon their molecular fit into the binding pocket common to this inhibitory class. We have specifically examined the structure activity relationships of compounds with chemical modification made by substituting homocyclic rather than acyclic moieties at N-1 of the pyrimidinedione. Seventy-four compounds were synthesized and evaluated for antiviral activity against HIV-1 and HIV-2. The homocyclic modifications resulted in compounds with significant activity against both HIV-1 and HIV-2, suggesting these compounds represent a new class of non-nucleoside RT inhibitors. The structure-activity relationship (SAR) evaluations indicated that cyclopropyl, phenyl and 1- or 3-cyclopenten-1-yl substitutions at the N-1 of the pyrimidinedione, the addition of a methyl linker between the cyclic moiety and the N-1 and the addition of a benzoyl group at the C-6 of the pyrimidinedione had the greatest contribution to antiviral activity. Five pyrimidinedione analogues with therapeutic indexes (TIs) > 450,000 and a specific analogue (1-cyclopropylmethyl-5-isopropyl-6-(3,5-dimethylbenzoyl)-2,4(1H,3H)-pyrimidinedione), which exhibited a TI of > 2,000,000, were identified. None of the analogues were cytotoxic to target cells at the highest in vitro test concentration, which is the upper limit of compound solubility of the analogues in aqueous solution. Thus, we have identified a series of pyrimidinediones with substantially improved antiviral efficacy and range of action and with significantly reduced cellular cytotoxicity.
Asunto(s)
Fármacos Anti-VIH/farmacología , VIH-1/efectos de los fármacos , VIH-2/efectos de los fármacos , Uracilo/análogos & derivados , Fármacos Anti-VIH/síntesis química , Fármacos Anti-VIH/química , Línea Celular , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Estereoisomerismo , Relación Estructura-Actividad , Uracilo/síntesis química , Uracilo/química , Uracilo/farmacologíaRESUMEN
A new piperazine derivative, SJ-8026, is a synthetic anti-cancer agent which exhibits topoisomerase II-inhibiting activities. In this study, we investigated the possibility that this compound inhibits angiogenesis and induces tumor-cell apoptosis using bovine aortic endothelial cells (BAECs) and human hepatocellular carcinoma cells (HepG2) as a model system. in vivo, SJ-8026 decreased the neovascularization of chick embryos and the basic fibroblast growth factor-induced angiogenesis in the chorioallantoic membrane and the mouse Matrigel implants. in vitro, SJ-8026 treatment resulted in the inhibition of proliferation, migration, invasion and tube formation in BAECs. In addition, the treatment of SJ-8026 in HepG2 cells reduced the cell viability, and caused the production of fragmented DNA and the morphological changes corresponding to apoptosis including condensed and fragmented DNA. SJ-8026 also elicited the release of cytochrome c and the activation of caspase-3. Therefore, it is possible that SJ-8026 functions as both angiogenesis inhibitor and apoptosis inducer. Taken together, these results suggest that SJ-8026 may be a candidate for strong anti-cancer agent with the ability to inhibit the angiogenesis of endothelial cells and to induce the apoptosis of tumor cells.
Asunto(s)
Acridinas/farmacología , Inhibidores de la Angiogénesis/farmacología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Inhibidores de Topoisomerasa II , Animales , Caspasa 3 , Caspasas/metabolismo , Bovinos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Citocromos c/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
A new piperazine derivative, SJ-8002, is a synthetic anti-cancer agent which exhibits microtubule-inhibiting activities. In this study, we investigated the possibility that this compound inhibits angiogenesis and induces tumor-cell apoptosis using bovine aortic endothelial cells (BAECs) and human hepatocellular carcinoma cells (HepG2) as a model system, respectively. In vivo, SJ-8002 decreased the neovascularization of chick embryos and the basic fibroblast growth factor (bFGF)-induced angiogenesis in the chorioallantoic membrane (CAM) and the mouse Matrigel implants, respectively. In vitro, SJ-8002 treatment resulted in the inhibition of proliferation, migration, invasion and tube formation, and of matrix metalloproteinase-2 (MMP-2) expression in BAECs. In addition, the SJ-8002 treatment in HepG2 cells reduced cell viability, and caused the production of fragmented DNA and the morphological changes corresponding to apoptosis including condensed and fragmented DNA in a concentration-dependent manner. SJ-8002 also elicited the release of cytochrome c and the activation of caspase-3. Therefore, it is possible that SJ-8002 functions as both angiogenesis inhibitor and apoptosis inducer. Taken together, these results suggest that SJ-8002 may be a candidate for strong anti-cancer agent with the ability to inhibit the angiogenesis of endothelial cells and to induce the apoptosis of tumor cells.