RESUMEN
Among the eight forms of vitamin E, the liver preferentially releases α-tocopherol into the circulation and it is distributed to the non-liver tissues. In the hepatocytes, alpha tocopherol transfer protein (TTPA) specifically recognizes α-tocopherol with 2R-configuration and facilitates its intracellular transfer. The identification and characterization of TTPA expression have not been demonstrated in avian species. Therefore, the objectives of this study were to identify avian TTPAs, to compare the sequence conservation, phylogenetic relationship, protein interactions, and disease associations of chicken TTPA with those of human and vertebrate TTPA, and to characterize the tissue expression of the TTPA gene in chickens fed diets supplemented with different amounts of α-tocopherol. Our results suggest that the chicken TTPA was highly conserved with the human and vertebrate TTPA, and consisted of a cellular retinaldehyde binding protein and TRIO guanine exchange factor (CRAL_TRIO) domain. Feeding diets supplemented with increasing amounts of α-tocopherol (25â¯IU/Kg, 50â¯IU/Kg, or 100â¯IU/Kg) to broiler chickens had no effects on growth performance compared with feeding basal diets containing no supplemental α-tocopherol. The expression of TTPA gene was detected high in the liver of chickens in response to dietary α-tocopherol concentrations, whereas its expression was very low or undetectable in the non-liver tissues. In conclusion, the chicken TTPA protein sequence is highly conserved with other avian and vertebrate TTPA protein sequences. The higher expression of TTPA gene in the chicken liver in response to dietary α-tocopherol concentrations may suggest its crucial role in transporting α-tocopherol in the chicken liver.
Asunto(s)
Alimentación Animal/análisis , Proteínas Portadoras/metabolismo , Pollos/metabolismo , Dieta/veterinaria , alfa-Tocoferol/administración & dosificación , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Transporte Biológico , Proteínas Portadoras/genética , Suplementos Dietéticos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Hígado/metabolismo , Filogenia , Vitamina E , alfa-Tocoferol/metabolismoRESUMEN
BACKGROUND AND OBJECTIVES: Synthetic cannabinoids (SC) have become widely abused as recreational drugs, and are now known to carry risk of severe mental and physical health effects. Catatonia, spanning the gamut from motor retardation to agitation, can constitute a psychiatric emergency for which benzodiazepines are the mainstay of treatment. The purpose of this paper is to report on an unusual occurrence of catatonia in the context of synthetic cannabinoid use, and a discussion of treatment options that have been helpful as adjuncts to benzodiazepines. METHODS: We present two cases of catatonia occurring in context of SC use. The first patient was using SC quasi-daily for 18 months. The second patient used a large quantity over a two-week period. Both patients were admitted to our emergency center with catatonia and no overt psychosis or mood symptoms. RESULTS: The absence of pre-existing mood or psychotic disorder and the severity of catatonic symptoms separates these cases from other cases reported in the literature. Additionally, pharmacological management targeting gamma-aminobutyric acid (GABA) and serotonin neurotransmitter systems were used, specifically aripiprazole and valproic acid, supplementing benzodiazepine administration; these were needed for optimal symptom control. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The above-reported cases are highly significant because of the severity of catatonic symptoms requiring inpatient hospitalization, the potential for rapid and severe decompensation with catatonia, and the atypical/unexpected development of catatonia with SC use.
Asunto(s)
Benzodiazepinas/uso terapéutico , Cannabinoides/efectos adversos , Catatonia/inducido químicamente , Catatonia/tratamiento farmacológico , Adolescente , Antipsicóticos/uso terapéutico , Aripiprazol/uso terapéutico , Quimioterapia Combinada , GABAérgicos/uso terapéutico , Humanos , Masculino , Ácido Valproico/uso terapéutico , Adulto JovenRESUMEN
The structure-activity relationship (SAR) of a novel, potent and metabolically stable series of sulfonamide-pyrazoles that attenuate ß-amyloid peptide synthesis via γ-secretase inhibition is detailed herein. Sulfonamide-pyrazoles that are efficacious in reducing the cortical Aßx-40 levels in FVB mice via a single PO dose, as well as sulfonamide-pyrazoles that exhibit selectivity for inhibition of APP versus Notch processing by γ-secretase, are highlighted.