Upregulation of mGlu2 receptors via NF-kB p65 acetylation is involved in the proneurogenic and antidepressant effects of acetyl-L-carnitine

Acetyl-L-carnitine (ALC) is a naturally occurring molecule with an important role in cellular bioenergetics and as donor of acetyl groups to proteins, including NF-kappa B p65. In humans, exogenously administered ALC has been shown to be effective in mood disturbances, with a good tolerability profile. No current information is available on the antidepressant effect of ALC in animal models of depression and on the putative mechanism involved in such effect. Here we report that ALC is a proneurogenic molecule, whose effect on neuronal differentiation of adult hippocampal neural progenitors is independent of its neuroprotective activity. The in vitro proneurogenic effects of ALC appear to be mediated by activation of the NF-kappa B pathway, and in particular by p65 acetylation, and subsequent NF-kappa B-mediated upregulation of metabotropic glutamate receptor 2 (mGlu2) expression. When tested in vivo, chronic ALC treatment could revert depressive-like behavior caused by unpredictable chronic mild stress, a rodent model of depression with high face validity and predictivity, and its behavioral effect correlated with upregulated expression of mGlu2 receptor in hippocampi of stressed mice. Moreover, chronic, but not acute or subchronic, drug treatment significantly increased adult born neurons in hippocampi of stressed and unstressed mice. We now propose that this mechanism could be potentially involved in the antidepressant effect of ALC in humans. These results are potentially relevant from a clinical perspective, as for its high tolerability profile ALC may be ideally employed in patient subpopulations who are sensitive to the side effects associated with classical antidepressant

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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Concentraciones plasmáticas y hepáticas de los principales elementos minerales en cerdos en crecimiento y engorda provenientes de criaderos industriales

Se evaluó el estado nutricional mineral de 242 cerdos, 114 hembras y 128 machos castrados pro­venientes de criaderos industriales de la zona cen­tral de Chile, con manejo alimentario a discre­ción y dietas por etapa productiva ajustadas a NRC 1973 -1979. Se determinaron los valores plasmá­ticos de Ca, P, Mg, Na, K, Cu y Zn y a nivel hepá­tico las concentraciones de Fe, Cu y Zn, mediante técnicas de espectrofotometría de absorción ató­mica, a excepción del P y Na los cuales fueron determinados por fotocolorimetría y emisión de llama, respectivamente. Los resultados fueron con­trastados con valores considerados normales en la li­teratura. La variable sexo se estudió por análisis de varianza (método de mínimos cuadrados).El análisis mostró diferencias según sexo para P y Cu plasmáticos, 9,1 y 9,5 mg/dl (p 0,10) y 204,6 y 197,2 Mg/dl (p 0,05) para machos castra­dos y hembras, respectivamente. A nivel hepá­tico sólo se determinaron diferencias por sexo para Zn (187,1 y 158,8 μg/g MS, machos cas­trados y hembras, respectivamente). Entre los macrominerales analizados sólo las concentracio­nes de Na y K fueron consideradas normales, sien­do los valores de Ca, P y Mg, y en especial este último, superiores a lo reportado por la literatura como normales. Los valores de Cu y Zn plasmáti­cos oscilaron entre 142 - 291 y 36,6 - 192,6 μg/dl, respectivamente, rangos considerados como nor­males y presentando CV de 13,5% y 23,8%, res­pectivamente. Los valores hepáticos, en general, se pueden considerar como elevados (518,1, 32,1 y 178,5 μg/g MS), para Fe, Cu y Zn, respectivamen­te y con altos CV. Se concluye que para la mayo­ría de los elementos existiría un aporte dietario excesivo, debido al uso de insumos no tradiciona­les ricos en estos minerales y al uso de una suple­mentación mineral que excede los requerimientos de las etapas de crecimiento y engorda.AbstractAn evaluation of the mineral nutritional status of 242 pigs, 114 sows and 128 barrowas, proceeding from industrial piggeries of Chile's Central Zone was made. These animals were raised by ad libitum alimentary management and their diets were adjusted by the 1973-1979 NRC recommendations according to the productive stage. Plasma concentra­tions of Ca, Mg, K, Cu and Zn, and hepatic levels of Fe, Cu and Zn were determined by atomic absorption spectrophotometry; plasmatic concentrations of Pand Na were deter­mined by photocolorimetry and (lame emision, resp. ectively. The results obtained were statistically evaluated and compared with normal values reported in the literature. The variable sex was studied throuhg analysis of variance (minimum square method).The analysis showed differences according to sex for plasmatic Pand Cu (9.1 and 9.5 μg/dl) (p  0,10) and 204.6 and 197.2 µg/dl (p  0,05) for barrocas and sows, respecti­vely. At hepatic level, sex differences were only observed for Zn (187.1 and 158.8 pglg DM, in barrocas and socas, respectively). Among the macrominerals analyzed only the concentrations of Na and K were considered normal; the values of Ca, P and Mg, specially the last one, were higher than those reported as normal in the literatures. The values of plasmatic Cu and Zn fuctuated between 142.0 - 291.0 and 36.6 - 192.6 μg/dl, respecti­vely, ranges considered as normal. In general, the hepatic values can be considered high (518.1; 31.1 and 178.5 μg/g DM, f for Fe, Cu and Zn, respectively), and with high VC. It is concluded that for the majority of the elements there would be al] excessive dietary contribution, due to the use of underutilized resources rich in these minerals as well as the use of minerals supplementation which exceeds the requirements of growing and finishing period

Concentraciones plasmáticas y hepáticas de los principales elementos minerales en cerdos en crecimiento y engorda provenientes de criaderos industriales

Se evaluó el estado nutricional mineral de 242 cerdos, 114 hembras y 128 machos castrados pro­venientes de criaderos industriales de la zona cen­tral de Chile, con manejo alimentario a discre­ción y dietas por etapa productiva ajustadas a NRC 1973 -1979. Se determinaron los valores plasmá­ticos de Ca, P, Mg, Na, K, Cu y Zn y a nivel hepá­tico las concentraciones de Fe, Cu y Zn, mediante técnicas de espectrofotometría de absorción ató­mica, a excepción del P y Na los cuales fueron determinados por fotocolorimetría y emisión de llama, respectivamente. Los resultados fueron con­trastados con valores considerados normales en la li­teratura. La variable sexo se estudió por análisis de varianza (método de mínimos cuadrados).El análisis mostró diferencias según sexo para P y Cu plasmáticos, 9,1 y 9,5 mg/dl (p 0,10) y 204,6 y 197,2 Mg/dl (p 0,05) para machos castra­dos y hembras, respectivamente. A nivel hepá­tico sólo se determinaron diferencias por sexo para Zn (187,1 y 158,8 μg/g MS, machos cas­trados y hembras, respectivamente). Entre los macrominerales analizados sólo las concentracio­nes de Na y K fueron consideradas normales, sien­do los valores de Ca, P y Mg, y en especial este último, superiores a lo reportado por la literatura como normales. Los valores de Cu y Zn plasmáti­cos oscilaron entre 142 - 291 y 36,6 - 192,6 μg/dl, respectivamente, rangos considerados como nor­males y presentando CV de 13,5% y 23,8%, res­pectivamente. Los valores hepáticos, en general, se pueden considerar como elevados (518,1, 32,1 y 178,5 μg/g MS), para Fe, Cu y Zn, respectivamen­te y con altos CV. Se concluye que para la mayo­ría de los elementos existiría un aporte dietario excesivo, debido al uso de insumos no tradiciona­les ricos en estos minerales y al uso de una suple­mentación mineral que excede los requerimientos de las etapas de crecimiento y engorda.AbstractAn evaluation of the mineral nutritional status of 242 pigs, 114 sows and 128 barrowas, proceeding from industrial piggeries of Chile's Central Zone was made. These animals were raised by ad libitum alimentary management and their diets were adjusted by the 1973-1979 NRC recommendations according to the productive stage. Plasma concentra­tions of Ca, Mg, K, Cu and Zn, and hepatic levels of Fe, Cu and Zn were determined by atomic absorption spectrophotometry; plasmatic concentrations of Pand Na were deter­mined by photocolorimetry and (lame emision, resp. ectively. The results obtained were statistically evaluated and compared with normal values reported in the literature. The variable sex was studied throuhg analysis of variance (minimum square method).The analysis showed differences according to sex for plasmatic Pand Cu (9.1 and 9.5 μg/dl) (p  0,10) and 204.6 and 197.2 µg/dl (p  0,05) for barrocas and sows, respecti­vely. At hepatic level, sex differences were only observed for Zn (187.1 and 158.8 pglg DM, in barrocas and socas, respectively). Among the macrominerals analyzed only the concentrations of Na and K were considered normal; the values of Ca, P and Mg, specially the last one, were higher than those reported as normal in the literatures. The values of plasmatic Cu and Zn fuctuated between 142.0 - 291.0 and 36.6 - 192.6 μg/dl, respecti­vely, ranges considered as normal. In general, the hepatic values can be considered high (518.1; 31.1 and 178.5 μg/g DM, f for Fe, Cu and Zn, respectively), and with high VC. It is concluded that for the majority of the elements there would be al] excessive dietary contribution, due to the use of underutilized resources rich in these minerals as well as the use of minerals supplementation which exceeds the requirements of growing and finishing period