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1.
Child Care Health Dev ; 50(1): e13153, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37460209

RESUMO

BACKGROUND: This study aims to determine the extent to which preschool teachers and childcare workers are aware of the presence of developmental problems among children and to what extent they share information with parents about their concerns regarding a child's development or diagnosis of neurodevelopmental disorders (NDDs). METHODS: We wrote to all 924 preschools and childcare centres in Japan's Nagano and Yamanashi prefectures to request participants. We then sent survey forms to the preschools and childcare centres that agreed to cooperate for three grades comprising 3-, 4- and 5-year-olds in the school year 2020. We asked the staff member in charge of each child to complete the survey. The survey included questions about the teacher's concerns regarding the possibility of an NDD and whether the matter had been shared with the children's parents. RESULTS: We obtained data for 10 354 children from 206 preschools and childcare centres (response rate = 22.3%). Among these children, 457 (4.4%) had an NDD diagnosis that their parents shared with the teachers. However, the teachers of 1274 children (12.3%) had concerns regarding their development but were not informed by the parents about the diagnosis, if any. These 1274 children included 775 (60.8%) cases where the teachers failed to share their concerns with parents because (1) the teachers could not communicate with parents (n = 119), (2) the teachers were not sure if there was a neurodevelopmental problem (n = 360) and (3) the parents were not aware of the problem (n = 296). CONCLUSIONS: Preschool teachers and childcare workers had concerns about the development of a substantial proportion of children in their charge. However, teachers and childcare workers did not share their concerns regarding many children's developmental problems with their parents. The findings suggest that there are challenges in information-sharing between teachers/childcare workers and parents.


Assuntos
Cuidado da Criança , Professores Escolares , Criança , Humanos , Pré-Escolar , Japão , Instituições Acadêmicas , Pais
2.
Drug Metab Dispos ; 32(12): 1383-91, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15345660

RESUMO

The Ministry of Health and Welfare, Japan banned coadministration of carbapenems, such as panipenem/betamipron (PAPM), meropenem (MEPM), and valproic acid (VPA) because clinical reports have indicated that the coadministration caused seizures in epileptic patients due to lowered plasma levels of VPA. In this study, we have clarified the mechanism of the drug-drug interaction using PAPM, MEPM, and doripenem [S-4661; (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[[(3S,5S)-5-[(sulfamoylamino)methyl]-3-pyrrolidinyl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-caboxylic acid monohydrate], a newly synthesized carbapenem. In vitro experiments using monkey liver slices suggested that the apparent synthetic rate of VPA glucuronide (VPA-G) increased in the presence of carbapenems. However, no such increase was observed in the experiment using monkey liver microsomes. Although no increase of uridine 5'-diphosphate D-glucuronic acid was found in monkey liver slices in the presence of carbapenems, potent inhibitory activity of carbapenems for the hydrolysis of VPA-G was found in monkey and rat liver homogenate. In vivo hydrolysis of VPA-G was clearly shown by the existence of VPA in plasma after dosing of VPA-G to rats, and its inhibition by carbapenems was also clearly shown by the negligible levels of VPA in rat plasma after coadministration of carbapenems and VPA-G. These results clearly indicate one of the important causes of drug interaction as follows: carbapenems would inhibit the hydrolytic enzyme, which is involved in the hydrolysis of VPA-G to VPA, resulting in a decrease of plasma concentration of VPA.


Assuntos
Anticonvulsivantes/farmacologia , Carbapenêmicos/farmacologia , Ácido Valproico/farmacologia , Animais , Anticonvulsivantes/farmacocinética , Bile/metabolismo , Carbapenêmicos/farmacocinética , Interações Medicamentosas , Feminino , Meia-Vida , Hidrólise , Técnicas In Vitro , Injeções Intravenosas , Rim/metabolismo , Fígado/metabolismo , Macaca fascicularis , Masculino , Microssomos Hepáticos/metabolismo , Ratos , Ratos Sprague-Dawley , Frações Subcelulares/metabolismo , Ácido Valproico/farmacocinética
3.
Steroids ; 67(11): 907-15, 2002 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12234626

RESUMO

The metabolism of estradiol 17-sulfate (ES) by hepatic microsomes of female rats produced four new metabolites in addition to 2- and 4-hydroxyestradiol 17-sulfates (2- and 4-OH-ES), which were detected on an HPLC chromatogram. By comparison with synthetic specimens, three of these compounds were identified as 6alpha-, 6beta-, and 7beta-hydroxyestradiol 17-sulfates. To elucidate the structure of the remaining metabolite, a large-scale incubation of ES was carried out, followed by isolation using preparative HPLC to give the single material, which was assigned as 15beta-hydroxyestradiol 17-sulfate by instrumental analyses. On the other hand, when ES was incubated with the microsomes of male rats, 2-OH-ES was produced accompanied by two minor products: 4-OH-ES and a metabolite of unknown structure. The results show clearly that the metabolism of ES by rat hepatic microsomes is remarkably different between the sexes.


Assuntos
Estradiol/análogos & derivados , Estradiol/química , Estradiol/metabolismo , Microssomos Hepáticos/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Feminino , Hidroxilação , Espectroscopia de Ressonância Magnética , Masculino , Estrutura Molecular , Ratos , Ratos Wistar , Caracteres Sexuais
4.
Carcinogenesis ; 23(2): 245-56, 2002 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11872629

RESUMO

Expression of cyclooxygenase (COX)-2 protein during rat hepatocarcinogenesis associated with fatty change, fibrosis, cirrhosis and oxidative DNA damage, caused by a choline-deficient, L-amino acid-defined (CDAA) diet were investigated in F344 male rats, along with the chemopreventive efficacy of the specific COX-2 inhibitor, nimesulide (NIM). Nimesulide, which was administered in the diet at concentrations of 200, 400, 600 and 800 p.p.m. for 12 weeks, decreased the number and size of preneoplastic enzyme-altered liver foci, levels of oxidative DNA damage, and the grade and incidence of fibrosis in a dose-dependent manner. A preliminary long-term study of 65 weeks also revealed that 800 p.p.m. NIM decreased the multiplicity of neoplastic nodules and hepatocellular carcinomas and prevented the development of cirrhosis. Western blot analysis revealed that COX-2 protein was barely expressed in control livers and increased approximately 2.9-fold in the livers of rats fed on a CDAA diet for 12 weeks and approximately 4.5-5.4-fold in tumors, with a diameter larger than 5 mm, at 80 weeks. Immunohistochemically, COX-2 protein was positive in sinusoidal and stromal cells in fibrotic septa, which were identified by immunoelectron microscopy as Kupffer cells, macrophages, either activated Ito cells or fibroblasts, after exposure to the CDAA diet for 12 weeks, whereas it was only occasionally weakly positive in sinusoidal, probably Kupffer, cells in control livers. In neoplastic nodules in rats fed on a CDAA diet for 30 and 80 weeks, sinusoidal cells and cells with relatively large round nuclei and scanty cytoplasm were strongly positive for COX-2 protein, with the neoplastic hepatocytes in the minority of the nodules, but not the cancer cells, being moderately positive. These results clearly indicate that rat hepatocarcinogenesis, along with fatty change, fibrosis and cirrhosis, is associated with increased expression of COX-2 protein, and point to the chemopreventive efficacy of a selective COX-2 inhibitor against, at least, the early stages of hepatocarcinogenesis.


Assuntos
Aminoácidos/farmacologia , Colina/farmacologia , Inibidores de Ciclo-Oxigenase/farmacologia , Desoxiguanosina/análogos & derivados , Isoenzimas/biossíntese , Neoplasias Hepáticas/enzimologia , Prostaglandina-Endoperóxido Sintases/biossíntese , Sulfonamidas/farmacologia , 8-Hidroxi-2'-Desoxiguanosina , Fenômenos Fisiológicos da Nutrição Animal , Animais , Anticarcinógenos/farmacologia , Western Blotting , Células Cultivadas , Ciclo-Oxigenase 1 , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Dano ao DNA , Desoxiguanosina/farmacologia , Relação Dose-Resposta a Droga , Fibrose , Glutationa Transferase/metabolismo , Hepatócitos/metabolismo , Imuno-Histoquímica , Isoenzimas/antagonistas & inibidores , Células de Kupffer/ultraestrutura , Fígado/metabolismo , Masculino , Proteínas de Membrana , Microscopia Imunoeletrônica , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344 , Fatores de Tempo
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