RESUMO
Although many chemical agents induce supernumerary ribs (SNR), few efforts have been published examining the induction of SNR in the presence or absence of maternal toxicity and the effect of dose on SNR length. A single administration of sodium salicylate on Day 9 of pregnancy at different dose levels (120, 180, 240, and 300 mg/kg) was used to induce SNR in the thoracolumbar region. At 180, 240, and 300 mg/kg, body weight loss was observed for dams following the administration, associated with reduced food consumption. The mean litter incidence of SNR in the control groups ranged between 0 and 17.1% and in the treated groups (from 180 to 300 mg/kg) between 50.5 and 88.6%. At 120 mg/kg, no adverse effects were noted in dams and the incidence of SNR was in the range of the control groups. Furthermore, in the three highest dose groups, increased incidences of 27 presacral vertebrae (PSV) were noted. In most instances, fetuses with 27 PSV had extra ribs whereas fetuses with 26 PSV tended to have rudimentary ribs. The distinction of SNR between rudimentary and extra ribs is usually based on a ratio of the length of 14th to 13th rib of 0.50. However, this value does not reflect the separation of the apparent bimodal distribution of SNR induced by sodium salicylate. A ratio of 0.35, which corresponds to the superior limit of the SNR of control fetuses, seemed to better define the two populations of SNR.
Assuntos
Anormalidades Induzidas por Medicamentos/etiologia , Feto/efeitos dos fármacos , Costelas/anormalidades , Salicilato de Sódio/toxicidade , Teratogênicos/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Feto/anormalidades , Vértebras Lombares/anormalidades , Vértebras Lombares/efeitos dos fármacos , Masculino , Gravidez , Ratos , Ratos Sprague-Dawley , Costelas/efeitos dos fármacosRESUMO
A method has been developed for the separation and measurement of haloperidol and hydroxy haloperidol in human plasma through high performance liquid chromatography. The method uses chlorohaloperidol as an internal standard and provides a limit of detection of about 0.7 nmol/l for haloperidol and 0.67 nmol/l for hydroxy haloperidol. HPLC and RIA radioimmunoassay methods are compared.
Assuntos
Cromatografia Líquida de Alta Pressão , Haloperidol/sangue , Haloperidol/análogos & derivados , Humanos , Hidroxilação , Radioimunoensaio , Valores de ReferênciaRESUMO
Radiographs were used to follow the postnatal evolution of 14th ribs in rat pups. Initially, 30 pregnant female rats were randomly distributed into two groups receiving 0 or 300 mg kg(-1) sodium salicylate on day 9 of pregnancy. In the treated group, adverse effects were noted on body weight changes and food consumption during the 2 days following dosing. At birth, a high majority of pups had extra ribs at the 300 mg kg(-1) dose. Radiographs done on postnatal days 1, 6, 14, 28 and 54 showed a reduction in the incidence of rudimentary ribs only, whereas extra ribs, often associated with 27 presacral vertebrae, had the same incidence from birth to adult stage. Furthermore, extra ribs seemed to exhibit similar growth evolution to the other thoracic ribs. This work helps to clarify the postnatal evolution of supernumerary ribs because it was performed on the same animals from birth to adult stage, showing that the reversibility was related to rib length and, in consequence, concerned the rudimentary ribs only. The coexistence of additional presacral vertebrae primarily with extra ribs suggests that both kinds of supernumerary ribs (rudimentary and extra) might be different phenomena and could be considered separately in developmental toxicology studies.
Assuntos
Anormalidades Induzidas por Medicamentos/patologia , Anti-Inflamatórios não Esteroides/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Costelas/anormalidades , Costelas/crescimento & desenvolvimento , Salicilato de Sódio/toxicidade , Anormalidades Induzidas por Medicamentos/diagnóstico por imagem , Animais , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Masculino , Tamanho do Órgão/efeitos dos fármacos , Gravidez , Radiografia , Ratos , Costelas/diagnóstico por imagemRESUMO
The concentrations of dopamine (DA) and its metabolites and the levels of 5-hydroxyindoleacetic acid (5-HIAA), the metabolite of serotonin, were determined in discrete cerebral areas of rats 3 hr after (neutron-gamma) irradiation at 4 and 7 Gy. After the 7 Gy irradiation, no significant effect was observed. After the 4 Gy exposure, the most marked difference between irradiated and control rats was in the levels of DA and its metabolites in the striatum. We observed a decrease of DA, HVA, and DOPAC levels in the striatum and an opposite pattern in the substantia nigra. Whatever the brain area observed, an increase of 5-HIAA levels was noted.