RESUMEN
Serum kinetics, tissue distribution, and excretion of citrate-coated silver nanoparticles (AgNPs) were investigated in rabbits (n = 4) up to 28 days after a single intravenous injection. Following a single injection of AgNPs, the AUC(last) was reported to be 3.65 ± 0.68 µg·day/ml in 5 mg/kg-treated group and 0.90 ± 0.16 µg·day/ml in 0.5 mg/kg-treated group, respectively. The accumulation of silver was observed in all the tested organs including liver, kidney, spleen, lung, brain, testis, and thymus at 1 day, 7 day, and 28 day of measurement. The liver and spleen seemed to be the major targets because of high accumulation of silver. Excretion via feces and urine was also monitored during the entire experimental period. Unexpectedly, much more excretion of silver occurred via feces than through urine after an intravenous injection, which suggests biliary excretion of AgNPs. General toxicity was analyzed and histopathological changes were also evaluated.
Asunto(s)
Nanopartículas/metabolismo , Plata/farmacocinética , Animales , Área Bajo la Curva , Relación Dosis-Respuesta a Droga , Heces/química , Inyecciones Intravenosas , Nanopartículas/química , Conejos , Plata/sangre , Plata/química , Plata/metabolismo , Plata/orina , Organismos Libres de Patógenos Específicos , Distribución Tisular , Pruebas de ToxicidadRESUMEN
The present study was carried out to examine the toxicity and target organs of oral cholera vaccine (OCV) after repeated oral administration in Sprague-Dawley rats for 6 weeks (3 administrations, once every 2 weeks). OCV is an inactivated oral cholera vaccine that contains Vibrio cholerae and confers protection against cholera caused by V. cholera serogroups O1 (Inaba and Ogawa serotypes) and O139 (strain 4260B). The animals were orally administered either OCV placebo (negative control) or OCV at a dose equivalent to 240 times the anticipated human dose. Throughout the administration period, no significant change was detected in clinical signs, body weight, food or water consumption, urinalysis results, hematological and clinical biochemistry test results, organ weights, necropsy, or histopathological examination results. Minor changes were found in hematological and clinical biochemistry tests; however, these changes were within normal ranges. The above results suggest that oral administration of OCV in rats did not induce any toxicologically meaningful changes, and the target organs could not be determined. This study was conducted in accordance with the guidelines established by Good Laboratory Practice (2009-183, KFDA, December 22, 2009) and the OECD Principles of Good Laboratory Practice (1997).
RESUMEN
Cyclical hormonal changes during an ovarian cycle may affect immune responses, which is crucial for the embryonic implantation. We aim to investigate whether the levels and activity of T, B, and NK cells change during a menstrual cycle. Twenty-two normally cycling women were enrolled and peripheral blood was drawn serially during a menstrual cycle. Intracellular cytokine expression of CD3(+)CD4(+) and CD3(+)CD8(+) cells, and Th1/Th2 cytokine-producing T cell ratios were determined using flow cytometric analysis. NK cell cytotoxicity was measured by flow cytometric analysis at E:T ratios of 50:1, 25:1, and 12.5:1 and also using LU at 20%. Proportions (percentage) of CD3(+) (p = 0.046) and CD3(+)CD4(+) (p = 0.002) T cells were increased in the follicular phase compared with the luteal phase. The levels of CD3(-)CD56(+) (p = 0.010) and CD3(-)CD56(dim) (p = 0.012) NK cells and NK cytotoxicity at E:T ratio of 50:1, 25:1, and 12.5:1 and LU at 20% were significantly increased in the luteal phase compared with the follicular phase. Even though IL-10-producing CD3(+)CD4(+) T cells were significantly lower in the midluteal phase as compared with the early follicular phase, proportions of CD19(+) B cells, CD3(+)CD56(+) NKT cells, Th1 cytokine-producing T cell subsets, and ratios of Th1/Th2 cytokine-producing T cells were not significantly changed during a menstrual cycle. We conclude that peripheral blood NK and T cell levels as well as NK cytotoxicity are changed during a menstrual cycle. Neuroendocrine regulation on immune responses is suggested during an ovarian cycle, which may be critical for embryonic implantation and pregnancy.