RESUMEN
Fish oil supplements have become a popular means of increasing one's dietary intake of essential polyunsaturated fatty acids. However, there is growing concern that the levels and potential health effects of lipophilic organic contaminants such as polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) may diminish some of the health benefits associated with the daily consumption of fish oil supplements. In this study, ten over-the-counter fish oil supplements available in the United States were analysed for PCBs and PBDEs and daily exposures calculated. Based on manufacturers' recommended dosages, daily intakes of PCBs and PBDEs ranged from 5 to 686 ng day(-1) and from 1 to 13 ng day(-1), respectively. Daily consumption of fish oil supplements expose consumers to PCBs and PBDEs. However, in comparison with fish ingestion, fish supplements may decrease daily PCB exposure and provide a safer pathway for individuals seeking to maintain daily recommended levels of polyunsaturated fatty acids.
Asunto(s)
Suplementos Dietéticos/análisis , Contaminantes Ambientales/administración & dosificación , Aceites de Pescado/administración & dosificación , Aceites de Pescado/química , Éteres Difenilos Halogenados/administración & dosificación , Bifenilos Policlorados/administración & dosificación , Animales , Suplementos Dietéticos/efectos adversos , Contaminantes Ambientales/química , Ácidos Grasos Esenciales/administración & dosificación , Peces , Cromatografía de Gases y Espectrometría de Masas , Éteres Difenilos Halogenados/química , Bifenilos Policlorados/química , Reproducibilidad de los Resultados , Alimentos Marinos/efectos adversos , Alimentos Marinos/análisis , Estados UnidosRESUMEN
Muscarinic agonists were tested in two models indicative of clinical antipsychotic activity: conditioned avoidance responding (CAR) in rats and inhibition of apomorphine-induced climbing in mice. The standard muscarinic agonists oxotremorine and pilocarpine were both active in these tests but showed little separation between efficacy and cholinergic side effects. Structure-activity relationships of the alkylthio-1,2,5-thiadiazole azacyclic type muscarinic partial agonists are shown, revealing the exo-6-(3-propyl/butylthio-1,2, 5-thiadiazol-4-yl)-1-azabicyclo[3.2.1]octane analogues (4a,b and 9a, b) to be the most potent antipsychotic agents with large separation between efficacy and cholinergic side effects. The lack of enantiomeric selectivity suggests the pharmacophoric elements are in the mirror plane of the compounds. A model explaining the potency differences of closely related compounds is offered. The data suggest that muscarinic agonists act as functional dopamine antagonists and that they could become a novel treatment of psychotic patients.
Asunto(s)
Antipsicóticos/síntesis química , Antagonistas de Dopamina/síntesis química , Agonistas Muscarínicos/síntesis química , Tiadiazoles/síntesis química , Animales , Antipsicóticos/química , Antipsicóticos/farmacología , Antipsicóticos/toxicidad , Reacción de Prevención/efectos de los fármacos , Encéfalo/metabolismo , Antagonistas de Dopamina/química , Antagonistas de Dopamina/farmacología , Antagonistas de Dopamina/toxicidad , Evaluación Preclínica de Medicamentos , Técnicas In Vitro , Inyecciones Subcutáneas , Masculino , Ratones , Modelos Moleculares , Conformación Molecular , Actividad Motora/efectos de los fármacos , Agonistas Muscarínicos/química , Agonistas Muscarínicos/farmacología , Agonistas Muscarínicos/toxicidad , Ratas , Ratas Sprague-Dawley , Salivación/efectos de los fármacos , Estereoisomerismo , Relación Estructura-Actividad , Tiadiazoles/química , Tiadiazoles/farmacología , Tiadiazoles/toxicidad , Temblor/inducido químicamenteRESUMEN
PURPOSE: To improve gadolinium-enhanced magnetic resonance (MR) angiogram quality by automatically synchronizing acquisition of central k-space image data with the arterial phase of contrast material bolus infusion. MATERIALS AND METHODS: A spin-echo pulse sequence with orthogonal 90 degrees and 180 degrees pulses was used to monitor signal in a single 4 x 4 x 12-cm voxel that encompassed a segment of aorta. An increase in signal that corresponded to the arrival of gadolinium was used to trigger three-dimensional, spoiled gradient-echo abdominal MR angiography in 50 adult patients. RESULTS: Arterial signal intensity increased 28-fold with automatic compared to 19-fold with manual triggering (P < .05) at an approximate dose of 0.3 mmol/kg. Automatic triggering with a lower dose (approximately 0.2 mmol/kg) resulted in 20-fold arterial enhancement, which is comparable with enhancement after manual triggering at the high dose. In addition, venous enhancement was less (1.5-fold) with automatic than with manual (3.5-fold) triggering at the same dose (P < .05). CONCLUSION: Automatic triggering results in improved arterial-tovenous contrast. It increases arterial enhancement or enables MR angiograms to be obtained with less contrast material. The authors now routinely use this technique for aortorenal imaging with a gadolinium-based contrast material dose of 20 mmol (40 mL) in patients who weigh more than 50 kg and 10 mmol (20 mL) in patients who weigh less than 50 kg.