RESUMO
Mutations in mitochondrial DNA (mtDNA) have been found to be associated with sensorineural hearing loss. We report the clinical, genetic, and molecular characterization of one Argentinean family with aminoglycoside-induced impairment in two of their members. Clinical evaluation revealed the variable phenotype of hearing impairment including audiometric configuration in these subjects. Mutational analysis of the mtDNA in these pedigrees showed the presence of homoplasmic 12S rRNA A827G mutation, which has been associated with hearing impairment. The A827G mutation is located at the A-site of the mitochondrial 12S rRNA gene which is highly conserved in mammals. It is possible that the alteration of the tertiary or quaternary structure of this rRNA by the A827G mutation may lead to mitochondrial dysfunction, thereby playing a role in the pathogenesis of hearing loss and aminoglycoside hypersensitivity. However, incomplete penetrance of hearing impairment indicates that the A827G mutation itself is not sufficient to produce clinical phenotype.
Assuntos
Aminoglicosídeos/efeitos adversos , Perda Auditiva Neurossensorial/induzido quimicamente , Perda Auditiva Neurossensorial/genética , Mitocôndrias/genética , RNA Ribossômico/genética , Antibacterianos/efeitos adversos , Argentina , Genes Mitocondriais/genética , Predisposição Genética para Doença/genética , Humanos , Mitocôndrias/efeitos dos fármacos , Mutação , LinhagemRESUMO
INTRODUCTION: The launching of mycophenolate mofetil (MMF) has reduced the incidence of acute rejection episodes. We sought to evaluate the efficacy of decreasing the steroid dose. MATERIALS AND METHODS: This was a quasiexperimental, randomized, prospective trial. We enrolled 150 patients who received de novo renal transplantations from living or cadaveric donors, fulfilling the screening criteria. Patients were randomized to one of the following two arms: (A) MMF at a 2 g/d dose, cyclosporine (CsA) at a dose necessary to achieve target levels, and corticosteroids at the usual doses; (B) MMF at a 2 g/d dose, CsA at a dose necessary to achieve target levels, and corticosteroids at doses 50% lower than those of group A. RESULTS: Group A included 72 (48%) and group B, 78 patients (52%). There were no differences among the variables: leukopenia occurred in 11 patients in group A, and five patients in group B. Complications occurred in 67.4% (56) of group A, but only 32.6% (27) were related to infections. One case of urinary infection occurred in group B, while six occurred in group A. There was one case of acute rejection in group A, and none in group B. One graft loss occurred in group A. There were no differences in the remaining variables under study. DISCUSSION: The results showed an increased complication rate related to receiving usual steroid doses. There was no increase in acute rejection episodes among patients receiving 50% of the usual steroid dose.
Assuntos
Corticosteroides/uso terapêutico , Ciclosporina/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Transplante de Rim/imunologia , Ácido Micofenólico/análogos & derivados , Corticosteroides/efeitos adversos , Ciclosporina/efeitos adversos , Quimioterapia Combinada , Humanos , Imunossupressores/uso terapêutico , Infecções/epidemiologia , Leucopenia/epidemiologia , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Complicações Pós-Operatórias/epidemiologia , Transplante Homólogo/imunologia , Resultado do TratamentoRESUMO
In order to know the spectrum of beta-thalassemia alleles and other mutations affecting the beta-globin gene, we analyzed the hemoglobin abnormalities in 24 patients from the Province of Cordoba in Argentina. Molecular screening of samples was performed by the polymerase chain reaction (PCR), using six sets of oligonucleotides to amplify fragments encompassing the whole beta-globin coding region and splice junctions, as well as the promoter and 3' untranslated regions. The altered fragments were determined by denaturing gradient gel electrophoresis (DGGE), and the corresponding mutations were identified by restriction enzyme analysis or by direct sequencing of PCR products. Using this approach, three different beta-thalassemia mutations were detected, codon 39 (C-->T), IVS-1-110 (G-->A), and IVS-1-1 (G-->A), and also the hemoglobin S trait. This is the first report of beta-thalassemia mutations described in Argentina. Our results show that these mutations are similar to those found in Spain and Italy, possibly due to the important Mediterranean migratory stream received in our country, and could be important for prenatal diagnosis of these diseases in Cordoba, Argentina.
Assuntos
Hemoglobinas/classificação , Hemoglobinas/genética , Mutação , Talassemia beta/sangue , Talassemia beta/genética , Alelos , Argentina , Frequência do Gene , Globinas/genética , HumanosRESUMO
The present study evaluated the effect of sodium saccharin on mouse tracheal epithelium, in relation to its possible structural alterations. Mice of the C3H strain were fed with standard pellets supplemented with sodium saccharin for 180 days. At that time the mice were sacrificed and their trachea were processed for transmission electronic microscopy. We demonstrated that sodium saccharin produces alterations in cellular surface cilia, with cytoplasmic excrescences and ciliary malformations. These results suggest that sodium saccharin is not an innocuous sweetener and that it may cause structural alterations in epithelial tissues.
Assuntos
Sacarina/farmacologia , Traqueia/efeitos dos fármacos , Animais , Epitélio/efeitos dos fármacos , Masculino , CamundongosRESUMO
Sodium saccharin has found to be a tumoral promoter in the rat's bladder epithelium, property not demonstrated in humans. Nevertheless, at present there's no references on the possible alterations produced by sodium saccharin in the epithelium of the mice colon. In this work we describe the alterations produced by low doses of sodium saccharin in the epithelium of the mice colon. The changer produced by sodium saccharin consist in pleomorphic microvill with variations of form, length diameter and curvature and demonstrate by transmission electron microscopy.
Assuntos
Colo/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Sacarina/efeitos adversos , Edulcorantes/efeitos adversos , Animais , Colo/patologia , Feminino , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Mucosa Intestinal/ultraestrutura , Neoplasias Intestinais/induzido quimicamente , Masculino , Camundongos , Microscopia Eletrônica , Microvilosidades , SódioRESUMO
A comprehensive biochemical, immunological and histological study was undertaken during different stages of experimental allergic encephalomyelitis (EAE). Wistar rats with EAE induced by sensitization with bovine myelin showed a maximum decrease of body weight 14-16 days post-inoculation (dpi), coincident with the appearance of the paralysis symptom (acute period). Quantitation of some brain components indicated a temporal dissociation among the alterations observed. The higher diminution of myelin basic protein (MBP) occurred at 6 dpi and then increased to reach 21 dpi, a normal value. Also, the activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase was reduced by 40% with respect to control animals only at 6 dpi. The total lipid content was normal; however, among the individual lipids, sulfatides were principally degraded during the acute stage but the amount of cerebrosides was decreased during the recovery period (29-40 dpi). Free cholesterol was similar in both groups of animals, whereas cholesterol esters were detected in EAE animals from 14 to 40 dpi. Central nervous system meningeal and parenchymal infiltration with mononuclear cells was recognized principally at 14 dpi, but some of cells were still present at 40 dpi. Deposits of immunoglobulins in the infiltrated regions as well as in spinal cord motor neurons were observed among 14-29 dpi. Total circulating antibodies to MBP began to increase at 14 dpi, reaching a plateau at 21 dpi and then maintaining this value until 40 dpi. However, the population of anti-MBP antibodies that also recognizes the neuronal protein synapsin was only present at 14 dpi. The present results suggest that the neurological symptoms can be related to some early changes in the myelin membrane followed by alterations involving neuronal structures. The existence of immunological factors against some epitopes in MBP that also recognize a synaptosomal protein might account, at least in part, for the axonal damage and disruption of the normal interneuronal activity in EAE and lead together with the alterations in some specific myelin constituents and the concomitant CNS inflammatory process to the observed hindlimb paralysis.