RESUMEN
The intestinal mucosa plays a capital role in dictating the bioavailability of a large array of orally ingested drugs and toxicants. The activity and the expression of several xenobiotic metabolizing enzymes were measured in subcellular fractions from the duodenal mucosa of male veal calves and beef cattle displaying a functional rumen but differing in both age (about 8 months vs. 18 to 24 months) and dietary regimens (i.e., milk replacer plus hay and straw vs. corn and concentrated meal). Intestinal microsomes showed cytochrome P450 (CYP) 2B, 2C- and 3A-mediated activities and the presence of the corresponding immunorelated proteins, but no proof of CYP1A expression and/or functions could be provided. Intestinal microsomes were also active in performing reactions typically mediated by carboxylesterases (indophenylacetate hydrolysis), flavin-containing monooxygenases (methimazole S-oxidation), and uridindiphosphoglucuronyltransferases (1-naphthol glucuronidation), respectively. Cytosolic fractions displayed the glutathione S-transferase (GST)-dependent conjugation of 1-chloro-2,4-dinitrobenzene; besides, the GST-mediated conjugation of ethacrinic acid (GSTpi) or cumene hydroperoxide (GSTalpha) was matched by the presence of the corresponding immunorelated proteins. Conversely, despite the lack of measurable activity with 3,4-dichloronitrobenzene, a protein cross reacting with anti-rat GSTmu antibodies could be clearly detected. Although, as detected by densitometry, CYPs and GST isoenzymes tended to be more expressed in beef cattle than in veal calf preparations, there was a general poor correlation with the rate of the in vitro metabolism of the selected diagnostic probes.
Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Mucosa Intestinal/enzimología , Intestino Delgado/enzimología , Factores de Edad , Animales , Benzfetamina/metabolismo , Biotransformación , Western Blotting , Bovinos , Clorfeniramina/metabolismo , Dieta/veterinaria , Duodeno/enzimología , Electroforesis en Gel de Poliacrilamida , Etilmorfina/metabolismo , Glutatión Transferasa/metabolismo , Masculino , Microsomas/enzimologíaRESUMEN
We present multi-wavelength observations of SN 2014C during the first 500 days. These observations represent the first solid detection of a young extragalactic stripped-envelope SN out to high-energy X-rays ~40 keV. SN 2014C shows ordinary explosion parameters (Ek ~ 1.8 × 1051 erg and Mej ~ 1.7 Mâ). However, over an ~1 year timescale, SN 2014C evolved from an ordinary hydrogen-poor supernova into a strongly interacting, hydrogen-rich supernova, violating the traditional classification scheme of type-I versus type-II SNe. Signatures of the SN shock interaction with a dense medium are observed across the spectrum, from radio to hard X-rays, and revealed the presence of a massive shell of ~1 Mâof hydrogen-rich material at ~6 × 1016 cm. The shell was ejected by the progenitor star in the decades to centuries before collapse. This result challenges current theories of massive star evolution, as it requires a physical mechanism responsible for the ejection of the deepest hydrogen layer of H-poor SN progenitors synchronized with the onset of stellar collapse. Theoretical investigations point at binary interactions and/or instabilities during the last nuclear burning stages as potential triggers of the highly time-dependent mass loss. We constrain these scenarios utilizing the sample of 183 SNe Ib/c with public radio observations. Our analysis identifies SN 2014C-like signatures in ~10% of SNe. This fraction is reasonably consistent with the expectation from the theory of recent envelope ejection due to binary evolution if the ejected material can survive in the close environment for 103-104 years. Alternatively, nuclear burning instabilities extending to core C-burning might play a critical role.
Asunto(s)
Hidrocarburo de Aril Hidroxilasas/metabolismo , Diterpenos/farmacología , Hígado/enzimología , Oxidorreductasas N-Desmetilantes/metabolismo , Espiramicina/farmacología , Animales , Hidrocarburo de Aril Hidroxilasas/efectos de los fármacos , Hidrocarburo de Aril Hidroxilasas/genética , Citocromo P-450 CYP3A , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Hígado/efectos de los fármacos , Oxidorreductasas N-Desmetilantes/efectos de los fármacos , Oxidorreductasas N-Desmetilantes/genética , ConejosRESUMEN
Glucocorticoids are often illegally used in association with anabolic steroids as growth promoters in veal calves and beef production. An experimental administration of dexamethasone was carried out in veal calves in order to assess the role of low doses of exogenous glucocorticoids on induction of thymus atrophy and on the immune response. Three groups of five veal calves each were included in this study: group D was administered 0.4 mg/day of dexamethasone-21-phosphate per os for 25 days; group V was administered 2 mg of dexamethasone-21-isonicotinate i.m. at days 14 and 21, and group K served as control. At slaughter, the weight of the thymus was severely reduced in group D and in group V, compared with control animals. Lesions included severe lymphoid depletion and hyperplasia of adipose tissue. In situ evaluation of apoptosis in thymus, showed a reduction of the percentage of positive nuclear areas of animals belonging to group V in comparison with control animals. An overall decrease of lymphocyte proliferative response was detected after treatment with short acting dexamethasone, while antibody response was not affected by treatments.