RESUMEN
While an excess of glucocorticoids is associated with hippocampal pathology in mood disorders, lithium exerts robust neuroprotective and neurotrophic effects. Here, 21 stably remitted bipolar I patients who had been on chronic lithium maintenance therapy, on average, for more than a decade, and 19 carefully matched healthy controls were studied using 3 T (1)H-magnetic resonance spectroscopy of left and right hippocampus. Salivary cortisol samples were obtained to assess activity of the hypothalamus-pituitary-adrenal system. Absolute concentrations of N-acetylaspartate (NAA), choline-containing compounds and total creatine were similar in euthymic bipolar patients and healthy controls. Hippocampal glutamate concentrations were significantly increased as an effect of patient status (patients>controls) and laterality (left hippocampus>right hippocampus). Hippocampal glutamate content (Glu) was strongly correlated with NAA. Across groups and within the patient group, diurnal saliva cortisol levels showed a significant inverse relationship with both Glu and NAA. Taken together, these results add to the concept of bipolar disorder as an illness involving disturbed hippocampal structural plasticity under the opposing influences of lithium and glucocorticoids.
Asunto(s)
Trastorno Bipolar , Ritmo Circadiano/fisiología , Ácido Glutámico/metabolismo , Hipocampo/patología , Hidrocortisona/metabolismo , Cloruro de Litio/uso terapéutico , Plasticidad Neuronal/fisiología , Adulto , Anciano , Antimaníacos/farmacología , Antimaníacos/uso terapéutico , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Trastorno Bipolar/tratamiento farmacológico , Trastorno Bipolar/patología , Estudios de Casos y Controles , Colina/metabolismo , Ritmo Circadiano/efectos de los fármacos , Creatina/metabolismo , Femenino , Humanos , Modelos Lineales , Cloruro de Litio/farmacología , Espectroscopía de Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Plasticidad Neuronal/efectos de los fármacos , Saliva/metabolismoRESUMEN
Carbon-13 cross-polarization magic-angle spinning nuclear magnetic resonance spectroscopy ((13)C-CP/MAS-NMR) was applied to study the chemical modification process of humic acids (HA) with diazomethane and the subsequent alkaline hydrolysis of the methylated HA. This modification process results in HA with selectively blocked phenolic OH groups, which can be used for metal ion binding studies with humic substances. Different chemically modified and unmodified natural and synthetic HA with carbon-13 of natural abundance were investigated. In addition, carbon-13 labeled modified synthetic HA, that were synthesized with [(13)C]diazomethane as methylation reagent, were studied to confirm the assumed modification process and to determine the type of functional groups that have the highest affinity for methylation with diazomethane. The results of the NMR studies with carbon-13 labeled modified HA show that predominantly carboxyl and phenolic OH groups are methylated with diazomethane resulting in methyl ester and methyl ether groups, respectively. Due to the alkaline treatment of the methylated HA, the methyl esters of carboxyl groups are hydrolyzed, whereas methyl ethers of phenolic OH groups remain unchanged, which results in modified HA with blocked phenolic OH groups. From the spectra of the modified and unmodified HA with carbon-13 of natural abundance it can be concluded that the applied preparative modification procedure causes only the desired structural changes in HA.
RESUMEN
[1,2-14C]TCA of a high specific activity (3.7 GBq/mmol) and appropriate radioindicator techniques were used, to study the effect of trichloroacetic acid (TCA) on conifers. Easy uptake of TCA from soil through spruce roots and its further translocation by the transpiration stream up to the needles (where damage of the photosynthetic apparatus occurs) has been proved. During the growth period, after one-shot load of TCA, the uptake was most intensive in current-year needles at first; over an extended period a decrease in the level of [1,2-14C]TCA-derived radioactivity was found in the current-year needles while in older needles (C + 2), the level rose. Symptoms of TCA biodegradation and/or metabolism were found in the plant/soil system under study. During an eight-week exposure significant losses of radioactivity into the atmosphere were noticed, at least a part of them in the form of carbondioxide. The results of these more or less preliminary experiments demonstrated the suitability and advantages of the radioisotopic technique used.
Asunto(s)
Cáusticos/farmacocinética , Picea/fisiología , Contaminantes del Suelo/farmacocinética , Ácido Tricloroacético/farmacocinética , Radioisótopos de Carbono/farmacocinética , Monitoreo del AmbienteRESUMEN
In this study, the influence of different stages and transplantation routes of the experimentally widely used solid tumor melanoma B16 on the pharmacokinetics of the antineoplastic agent mitoguazone was investigated in B6D2F1 mice. It could be shown that changes of the pharmacokinetic parameters as well as the distribution pattern of this drug were clearly influenced and dependent on the tumor stage but not by the tumor inoculation route. Advanced melanoma (d16) led to a sharp decrease in the terminal elimination half-life as well as to decreased spleen levels and increased initial liver concentrations of the drug. With respect to the results obtained in leukemia P388-bearing mice it can be concluded that the tumor stage as well as the tumor model are to be considered as important factors in which way and to which extent a tumor may alter the pharmacokinetics of antineoplastic agents.
Asunto(s)
Melanoma Experimental/metabolismo , Mitoguazona/farmacocinética , Animales , Femenino , Inyecciones Intravenosas , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos , Mitoguazona/administración & dosificación , Trasplante de Neoplasias , Distribución Tisular , Trasplante HomólogoRESUMEN
The aim of the present study was to investigate the influence of different stages of leukemia P388 on the pharmacokinetics of the antineoplastic agent mitoguazone in mice. It could be shown that, independent of the tumor stage investigated, the total clearance of mitoguazone is slightly reduced reflecting a moderate increase of AUC in the serum of leukemia-bearing animals. Furthermore, in an advanced tumor stage the drug levels in kidneys, liver, spleen and serum were found to be elevated to some extent in comparison to tumor-free controls in contrast to an earlier stage of leukemia. In conclusion, the tumor stage has to be considered as an important factor to which extent a neoplasia may alter the pharmacokinetics of drugs used for anticancer chemotherapy.