RESUMEN
Autism is a neurodevelopmental disorder of unknown origin that manifests in early childhood. Autism spectrum disorders (ASDs) refer to a broader group of neurobiological conditions, pervasive developmental disorders. Despite several arguments for a strong genetic contribution, the molecular basis in most cases remains unexplained. Several studies have reported an association between ASDs and mutations in the mitochondrial DNA (mtDNA) molecule. In order to confirm these causative relationship, we screened 21 individuals with idiopathic ASDs for a number of the most common mtDNA mutations. We identified two patients with candidate mutations: m.6852G>A that produces an amino acid change of glycine to serine in the MT-CO1 gene and m.8033A>G (IleâVal) in the MT-CO2 gene. Overall, these findings support the notion that mitochondrial mutations are associated with ASDs. Additional studies are needed to further define the role of mitochondrial defects in the pathogenesis of autism.
RESUMEN
The occurrence of multiple sclerosis (MS) in subjects clustering to a particular mitochondrial DNA (mtDNA) haplogroup/haplotype or carrying mtDNA mutations associated with Leber's hereditary optic neuropathy (LHON) has suggested that mitochondrial genome may contribute to susceptibility to MS. In the present study, 58 unrelated Bulgarian patients with relapsing remitting form of MS and 104 randomly selected healthy individuals were analysed for the presence of 14 mtDNA polymorphisms determining major European haplogroups as well as three (4216, 14 798, 13 708) secondary LHON mutations. Restriction enzyme analysis used to screen patients and controls for the common haplogroup-associated polymorphisms showed that each of these changes was present in MS patients at a similar frequency to control subjects. However, 21 of the 58 patients (36.2%) were positive for T4 216C mutation, while only 11.3% of the controls carried this secondary LHON base change (P < 0.01; OR = 4.38). Our finding indicated that 4216C base substitution could be considered as a predisposing marker for MS and supported the hypothesis that particular mtDNA variants could contribute to genetic susceptibility of MS, and merits further investigation.
Asunto(s)
ADN Mitocondrial/genética , Variación Genética , Esclerosis Múltiple/genética , Adulto , Bulgaria , Estudios de Cohortes , Femenino , Frecuencia de los Genes/genética , Haplotipos/genética , Humanos , Masculino , Persona de Mediana EdadRESUMEN
We investigated the in vivo and in vitro cytokine inducing effects of Deodan, an oral preparation from Lactobacillus bulgaricus "LB-51", using the rabbit pyrogen test. In the first experimental approach we administered Deodan, or its chromatographically purified fraction, via the i.m. or i.v. routes. Low doses of Deodan i.m. caused the formation of a single temperature peak, whereas large doses produced a biphasic temperature curve. Intravenous injection of Deodan produced a monophasic fever in all tested doses. Chromatographically purified Deodan injected i.v. to rabbits caused a febrile response with a dose-dependent pattern, strikingly similar to that of lipopolysaccharide. LAL-testing of Deodan, however, showed that the preparation does not contain endotoxin. In in vivo neutralization studies we demonstrated that IL-1, TNF alpha, and IL-6 mediate the rabbit febrile response to Deodan. Interestingly, the effects of Deodan on the production of TNF alpha and IL-6 were more pronounced than its IL-1 inducing activity. In the second approach, we injected supernatants from mononuclear cells incubated with nonpyrogenic doses of Deodan, intravenously to rabbits ("monocyte type" of pyrogen test). Rapid-onset monophasic fevers were observed, typical for the rabbit pyrogen reaction to i.v. administration of exogenous IL-1 and TNF. Finally, we demonstrated the presence of pyrogenic cytokines in the supernatants from macrophages of Deodan-treated mice. Together, these results indicate that Deodan induces the production of cytokines with endogenous pyrogenic activity.
Asunto(s)
Adyuvantes Inmunológicos/farmacología , Citocinas/metabolismo , Glicopéptidos/farmacología , Lactobacillus/química , Animales , Proteínas Bacterianas/farmacología , Pared Celular/química , Fiebre/inducido químicamente , Lipopolisacáridos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos ICR , ConejosRESUMEN
The effects of BCG vaccine on antibody-dependent cell mediated cytotoxic (ADCC) activity of spleen lymphocytes were examined after BCG treatment. A modified plaque assay method, using sheep red blood cells (SRBC) as targets and IgG antibodies from rabbit anti-SRBC serum, was applied. The changes of ADCC activity were different in spleen lymphocytes according to the route and the timing of the administration of the vaccine. Following i.p. administration we observed an immunosuppressive effect in mouse and rat spleen effector cells within the first seven days. The ADCC activity level returned to normal by the 14th day. The cytolytic activity was maximal at the 21st day after treatment, and decreased slowly thereafter. The ADCC activity of mouse spleen lymphocytes did not change within the first seven days after i.v. BCG administration while the maximal cytolytic activity was induced on the 14th day but it was lower than the peak value found after i.p. treatment.