RESUMO
The syndrome of benign familial infantile convulsions (BFIC) is an autosomal dominant epileptic disorder that is characterized by convulsions, with onset at age 3-12 mo and a favorable outcome. BFIC had been linked to chromosome 19q, whereas the infantile convulsions and choreoathetosis (ICCA) syndrome, in which BFIC is associated with paroxysmal dyskinesias, had been linked to chromosome 16p12-q12. BFIC appears to be frequently associated with paroxysmal dyskinesias, because many additional families from diverse ethnic backgrounds have similar syndromes that have been linked to the chromosome 16 ICCA region. Moreover, one large pedigree with paroxysmal kinesigenic dyskinesias only, has also been linked to the same genomic area. This raised the possibility that families with pure BFIC may be linked to chromosome 16 as well. We identified and studied seven families with BFIC inherited as an autosomal dominant trait. Genotyping was performed with markers at chromosome 19q and 16p12-q12. Although chromosome 19q could be excluded, evidence for linkage in the ICCA region was found, with a maximum two-point LOD score of 3.32 for markers D16S3131 and SPN. This result proves that human chromosome 16p12-q12 is a major genetic locus underlying both BFIC and paroxysmal dyskinesias. The unusual phenotype displayed by one homozygous patient suggests that variability of the ICCA syndrome could be sustained by genetic modifiers.
Assuntos
Cromossomos Humanos Par 16 , Epilepsia Neonatal Benigna/genética , Epilepsia/genética , Ligação Genética , Idade de Início , Argentina , Mapeamento Cromossômico , Etnicidade/genética , Feminino , França , Genes Dominantes , Marcadores Genéticos , Humanos , Lactente , Escore Lod , Masculino , Linhagem , SíndromeRESUMO
Bleomycin may produce diffuse pulmonary damage. Our objective was to evaluate the effect of imidazole, a thromboxane-synthetase inhibitor, on pulmonary damage induced by endotracheal instillation of bleomycin in rats. Bleomycin 1 U/100 g body weight produced diffuse pulmonary damage and increased number of inflammatory cells after 3 days, hemorrhage and focal fibrosis after 7 days, and diffuse fibrosis and pneumocyte hyperplasia after 14 to 30 days. Imidazole 5 mg/100 g body weight, given intraperitoneally 30 min before bleomycin, decreased the 3rd day lesions without altering the histopathology in subsequent periods. Imidazole reduced (p < 0.05) the increases in cell number (3rd and 14th days) as well as in proteins in bronchoalveolar lavage (3rd day), without modifying the increase in phospholipids observed in rats treated with bleomycin. We conclude that imidazole decreases initial bleomycin-induced pulmonary damage, but it does not interfere with fibrosis and late development of epithelial hyperplasia.
Assuntos
Bleomicina , Inibidores Enzimáticos/uso terapêutico , Imidazóis/uso terapêutico , Pneumopatias/tratamento farmacológico , Fibrose Pulmonar/tratamento farmacológico , Animais , Bleomicina/administração & dosagem , Lavagem Broncoalveolar , Pneumopatias/induzido quimicamente , Masculino , Fibrose Pulmonar/induzido quimicamente , Ratos , Ratos Sprague-DawleyRESUMO
Bleomycin may produce diffuse pulmonary damage. Our objective was to evaluate the effect of imidazole, a thromboxane-synthetase inhibitor, on pulmonary damage induced by endotracheal instillation of bleomycin in rats. Bleomycin 1 U/100 g body weight produced diffuse pulmonary damage and increased number of inflammatory cells after 3 days, hemorrhage and focal fibrosis after 7 days, and diffuse fibrosis and pneumocyte hyperplasia after 14 to 30 days. Imidazole 5 mg/100 g body weight, given intraperitoneally 30 min before bleomycin, decreased the 3rd day lesions without altering the histopathology in subsequent periods. Imidazole reduced (p < 0.05) the increases in cell number (3rd and 14th days) as well as in proteins in bronchoalveolar lavage (3rd day), without modifying the increase in phospholipids observed in rats treated with bleomycin. We conclude that imidazole decreases initial bleomycin-induced pulmonary damage, but it does not interfere with fibrosis and late development of epithelial hyperplasia
Assuntos
Animais , Masculino , Ratos , Bleomicina , Inibidores Enzimáticos/uso terapêutico , Imidazóis/uso terapêutico , Pneumopatias/tratamento farmacológico , Fibrose Pulmonar/tratamento farmacológico , Bleomicina/administração & dosagem , Lavagem Broncoalveolar , Pneumopatias/induzido quimicamente , Fibrose Pulmonar/induzido quimicamente , Ratos Sprague-DawleyRESUMO
Aspiration of gastric contents to the lung is a cause of Adult Respiration Distress syndrome. We studied the effects of endotracheal instillation of hydrochloric acid (2 ml/kg, 0.1 N solution) in anesthetized rats who were sacrificed 4 or 48 hr later. A control group received 0.9% saline solution instead. Total protein, phospholipids, disaturated phosphatidylcholine (DSPC) and number of cells were determined in the bronchoalveolar lavage fluid. Histologic studies were performed in one rat in each group. HCl caused edema and inflammatory reaction characterized by a rise in protein and cells in the bronchoalveolar fluid 48 hr after endotracheal instillation. This was associated with an increase in total phospholipid and in DSPC. Therefore, the inflammatory response to HCl is associated to an increase in alveolar surfactant 48 hr after instillation.