RESUMO
In this study of atretic cephaloceles, the authors have considered the pedunculated or sessile type of cephalocele and also small nonpedunculated scalp defects developing in the vertex midline. Parietal cephaloceles were found in 15 infants (10 boys and five girls), and accounted for 37.5% of all cephaloceles. They consisted of four encephaloceles, six meningoceles, and five atretic cephaloceles. The clinical and morphological characteristics of parietal cephaloceles were investigated and compared with those arising at other locations. Parietal cephaloceles carried a much less favorable prognosis than those in the occipital region, regardless of the type of cephalocele; they were associated with cerebral malformations more frequently and were more severe than occipital cephaloceles. Grave congenital anomalies were found in 87% of patients with parietal cephalocele, and only two patients (neither of whom had any other malformation) attained normal development. Brain malformations were closely related to the site from which the cephalocele issued, and dorsal cyst malformation was found in eight patients with parietal cephalocele. Two types of atretic cephaloceles were found, each in a different location. The first type was an alopecic lesion occurring in the parietal midline; all five patients with this type had dorsal cyst malformations and none developed normally. The second type was a nodular lesion developing at the occipital midline, not associated with cerebral anomalies; all five patients with this type showed normal development. The pathogenesis of atretic cephaloceles and their associated intracranial malformations are discussed.
Assuntos
Encéfalo/anormalidades , Encefalocele/classificação , Lobo Parietal , Couro Cabeludo/anormalidades , Alopecia/complicações , Encefalopatias/complicações , Cistos/complicações , Encefalocele/complicações , Encefalocele/patologia , Feminino , Humanos , Hidrocefalia/complicações , Hidrocefalia/congênito , Lactente , Recém-Nascido , Masculino , PrognósticoRESUMO
The effects of theobromine, a xanthine derivative, on the testis were compared between rats dosed for 2 and 4 weeks to determine whether a 2-week dosing period is long enough to detect toxicity. Theobromine was administered orally to male Sprague-Dawley rats at dose levels of 250 and 500 mg/kg for 2 weeks starting at the age of 6 or 8 weeks, and for 4 weeks from the age of 6 weeks. Histopathological examination of reproductive organs revealed toxic findings in the testis at 500 mg/kg after 2 weeks of dosing at both ages, and at 250 and 500 mg/kg after 4 weeks of dosing. The primary findings were degeneration/necrosis and desquamation of spermatids and spermatocytes, vacuolization of seminiferous tubules, and multinucleated giant cell formation. These findings were present mainly in stages I-VI and XII-XIV. From these results, it is concluded that the toxic effects of theobromine on the testis can be detected by repeated dosing for 2 weeks as well as for 4 weeks.
Assuntos
Testículo/efeitos dos fármacos , Teobromina/toxicidade , Administração Oral , Animais , Atrofia/induzido quimicamente , Atrofia/patologia , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Epididimo/efeitos dos fármacos , Epididimo/patologia , Masculino , Tamanho do Órgão/efeitos dos fármacos , Próstata/efeitos dos fármacos , Próstata/patologia , Ratos , Ratos Sprague-Dawley , Glândulas Seminais/efeitos dos fármacos , Glândulas Seminais/patologia , Epitélio Seminífero/efeitos dos fármacos , Epitélio Seminífero/patologia , Espermatogênese/efeitos dos fármacos , Testículo/patologia , Testículo/fisiopatologia , Teobromina/administração & dosagem , Fatores de Tempo , Testes de ToxicidadeRESUMO
We examined the level of sialic acid in cerebrospinal fluid (CSF) in 20 patients with brain tumor, and 5 patients with non-neoplastic disease of central nervous system. CSF concentration of sialic acid in the patients with malignant and semi-malignant or benign brain tumor was 5.26 +/- 2.39 mg/dl, and 1.82 +/- 1.61 mg/dl, respectively. In patients with non-neoplastic disease, it was 1.64 +/- 1.53 mg/dl. The difference between groups was statistically significant (p less than 0.005). In two patients with malignant brain tumor, the level of sialic acid was decreased by radiation therapy or intrathecal chemotherapy. In conclusion, CSF concentration of sialic acid was significant of diagnosis of brain tumor character of malignancy, and effect of therapy for CSF dissemination.
Assuntos
Aracnoide-Máter , Biomarcadores Tumorais/líquido cefalorraquidiano , Neoplasias Encefálicas/diagnóstico , Neoplasias Meníngeas/secundário , Pia-Máter , Ácidos Siálicos/líquido cefalorraquidiano , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Humanos , Neoplasias Meníngeas/terapia , Valor Preditivo dos TestesRESUMO
Six children are reported in whom subarachnoid hemorrhage was an initial symptom of brain tumor. In our neurosurgical clinics, this represented 3.6% of pediatric brain tumors and showed a frequency equal to aneurysmal rupture among nontraumatic subarachnoid hemorrhage of children. In pediatric patients, hemorrhages from brain tumors occur predominantly in the posterior fossa. The medulloblastoma, which had been believed to bleed rarely, is now realized to be a common source of tumor hemorrhages in such cases. The introduction of CT scan facilitates early recognition of hemorrhagic stroke from brain tumors and prompt management for acute intracranial hypertension and brainstem dysfunction. Although the patients achieve favorable recovery from their initial catastrophic condition, the ultimate prognosis, in the majority of cases, is still rather poor because such hemorrhages usually develop from a malignant tumor. The present and other recent reports indicate that the incidence of hemorrhagic stroke from brain tumors in pediatric patients is much higher than has been thought and is an important cause of subarachnoid hemorrhage in this age group.
Assuntos
Neoplasias Encefálicas/complicações , Hemorragia Subaracnóidea/etiologia , Adolescente , Neoplasias Encefálicas/diagnóstico por imagem , Cerebelo/diagnóstico por imagem , Ventriculografia Cerebral , Criança , Pré-Escolar , Ependimoma/complicações , Ependimoma/diagnóstico por imagem , Feminino , Glioblastoma/complicações , Glioblastoma/diagnóstico por imagem , Humanos , Hipotálamo/diagnóstico por imagem , Recém-Nascido , Masculino , Meduloblastoma/complicações , Meduloblastoma/diagnóstico por imagem , Estudos Retrospectivos , Hemorragia Subaracnóidea/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
To determine whether cimetidine increases serum gastrin levels by elevation of intragastric pH or by other mechanisms, the effects of two different H2-receptor antagonists, cimetidine and YM-11170, on serum gastrin levels were compared in rats with controlled intragastric pH. When the intragastric pH was maintained between 4.5 and 5.5, 2-10 mumol/kg of cimetidine increased serum gastrin levels significantly, whereas no significant increase was observed after 0.02-0.1 mumol/kg of YM-11170. This occurred despite the same extent of inhibition of histamine-stimulated acid secretion as with cimetidine. When the intragastric pH was fixed at 5.5, the serum gastrin responses to cimetidine were significantly greater than to saline or YM-11170. Therefore, the increase in serum gastrin levels by cimetidine is due neither to the elevation of intragastric pH nor the result of H2-receptor blockade, but is probably due to a direct action to release gastrin.
Assuntos
Cimetidina/farmacologia , Gastrinas/sangue , Tiazóis/farmacologia , Animais , Famotidina , Ácido Gástrico/metabolismo , Determinação da Acidez Gástrica , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Histamina/administração & dosagem , Infusões Parenterais , Masculino , Perfusão , Ratos , Ratos EndogâmicosRESUMO
To evaluate the transgenic mouse carrying a human prototype c-Ha-ras gene (rasH2 mouse) as a model for 26-week carcinogenicity tests, Di(2-ethylhexyl)phthalate (DEHP), a peroxisome proliferator, was administered to 15 rasH2 mice/sex/group at concentrations of 1,500, 3,000 or 6,000 ppm, and to 15 wild-type (non-Tg) mice/sex/group at a concentration of 6,000 ppm in their diets for 26 weeks. Survival rates and food consumption in the groups treated with DEHP and in the control group were similar. Body weight gain in rasH2 and non-Tg mice at 6,000 ppm in the terminal week decreased about 10% as compared to the control group. Common findings related to treatment with DEHP in rasH2 and non-Tg mice included hypertrophy with coarse granules and deposit of pigment in the liver, hydronephrosis and tubular regeneration in the kidney, focal atrophy in the testis, and increased eosinophilic body in the nasal cavity. Hepatocellular adenoma was induced by treatment with DEHP, and was confined to male rasH2; mice the incidence being 7%(1/15), 13%(2/15), and 27%(4/15) in the 1,500-, 3,000-, and 6,000-ppm group, respectively. Point mutation was not detected in codon 12 and 61 of human c-Ha-ras transgene upon DNA analyses on frozen samples taken from these hepatocellular adenomas. From the results obtained in this 26-week carcinogenicity study, it is concluded that DEHP is a hepato-carcinogen for transgenic mouse carrying a human prototype c-Ha-ras gene.
Assuntos
Adenoma de Células Hepáticas/genética , Dietilexilftalato/toxicidade , Genes ras , Neoplasias Hepáticas Experimentais/genética , Proliferadores de Peroxissomos/toxicidade , Adenoma de Células Hepáticas/induzido quimicamente , Adenoma de Células Hepáticas/patologia , Administração Oral , Animais , Testes de Carcinogenicidade/métodos , Dietilexilftalato/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Rim/efeitos dos fármacos , Rim/patologia , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/patologia , Masculino , Camundongos , Camundongos Transgênicos , Cavidade Nasal/efeitos dos fármacos , Cavidade Nasal/patologia , Proliferadores de Peroxissomos/administração & dosagem , Polimorfismo Conformacional de Fita Simples , Fatores Sexuais , Taxa de Sobrevida , Testículo/efeitos dos fármacos , Testículo/patologia , Fatores de TempoRESUMO
Highly potent 1,3-beta-D-glucan synthase inhibitors 10, 11 and 13 have been identified by the chemical modification of the fungicidal macrocyclic lipopeptidolactone, RO-09-3655 (1), isolated from the cultured broth of Deuteromycotinia spp. D-Ornithine derivative (10) showed improved antifungal activity in the systemic candidiasis model in mice and reduced hepatotoxicity in vitro, as compared with 1.
Assuntos
Antifúngicos/síntese química , Antifúngicos/farmacologia , Glucosiltransferases/antagonistas & inibidores , Proteínas de Membrana , Proteínas de Schizosaccharomyces pombe , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Candidíase/complicações , Candidíase/tratamento farmacológico , Técnicas de Química Combinatória , Modelos Animais de Doenças , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Corpos de Inclusão/efeitos dos fármacos , Corpos de Inclusão/microbiologia , Concentração Inibidora 50 , Lactonas/síntese química , Lactonas/química , Lactonas/farmacologia , Fígado/efeitos dos fármacos , Fígado/microbiologia , Fígado/patologia , Camundongos , Testes de Sensibilidade Microbiana , Peptídeos , Relação Estrutura-Atividade , Taxa de Sobrevida , Equivalência TerapêuticaRESUMO
Highly potent 1,3-beta-D-glucan synthase inhibitors, 7b, 10a, 10b and 12, have been identified by the chemical modification of the ornithine residue of a fungicidal macrocyclic lipopeptidolactone, RO-09-3655 (1), isolated from the cultured broth of Deuteromycotinia spp. These compounds showed stronger antifungal activity against systemic candidiasis as well as pulmonary aspergillosis in mice, and less hepatotoxicity as compared with 1.
Assuntos
Antifúngicos/síntese química , Glucosiltransferases/antagonistas & inibidores , Proteínas de Membrana , Peptídeos Cíclicos/síntese química , Proteínas de Schizosaccharomyces pombe , Animais , Antifúngicos/farmacologia , Antifúngicos/toxicidade , Aspergilose Broncopulmonar Alérgica/complicações , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Aspergillus fumigatus/efeitos dos fármacos , Candida/efeitos dos fármacos , Candidíase/complicações , Candidíase/tratamento farmacológico , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/toxicidade , Hospedeiro Imunocomprometido/efeitos dos fármacos , Corpos de Inclusão/efeitos dos fármacos , Injeções Intravenosas , Camundongos , Testes de Sensibilidade Microbiana , Fungos Mitospóricos/química , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/toxicidade , Fatores de TempoRESUMO
A novel Candida albicans chitin synthase 1 (CaChs1) inhibitor, RO-41-0986 (1) was discovered by random screening. Systematic modification led to the identification of a highly potent CaChs1 inhibitor, RO-09-3024 (2), having strong antifungal activity against Candida spp. in vitro.