Hormonal change and cytokine mRNA expression in peripheral blood mononuclear cells during the development of canine autoimmune thyroiditis

To elucidate the hormonal change and alteration in cytokine expression in peripheral blood mononuclear cells (PBMC) during the early stage of autoimmune thyroiditis, we have developed a canine model of this disease, in which normal dogs were immunized with bovine thyroglobulin (Tg) and/or canine thyroid extract. Serum samples were collected weekly, anti-canine Tg antibody was measured by enzyme-linked immunosorbent assay (ELISA) and thyroid stimulating hormone (TSH) and total T4 levels by radioimmunoassay. We also assayed T lymphocyte proliferation in response to Tg, as well as measuring cytokine mRNA by semiquantitative reverse transcription–polymerase chain reaction (RT–PCR). All six dogs immunized with bovine Tg had both canine Tg autoantibody and anti-T4 antibody. When the sample from the highest TgAA titre time-point was compared with baseline the expression of mRNA encoding the Th1-type cytokine such as interferon (IFN)-γ, interleukin (IL)-18 and IL-15 was increased during the development of autoimmune thyroiditis. Expression of the Th2-type cytokine, IL-6 showed minimal change and IL-4 expression was not detected in any of the samples. Expression of the T suppressive cytokine, IL-10 and transforming growth factor (TGF)-β was increased in the presence of antigen stimulation. These findings suggest that, although autoimmune thyroiditis is an organ-specific autoimmune disease, systemic cytokine mRNA expression is also changed

Alterações neurológicas nas cardiopatias congênitas um estudo neuropatológico

Estudo neuropatológico foi realizado em 190 autópsias consecutivas de pacientes com cardiopatias congênitas: 116 casos foram operados (grupo cirúrgico, GCg) e os 74 restantes formam o grupo clínico (GCI). Alterações neuropatológicas foram observadas em 71 casos (41 no GCg e 30 no GCI). Entretanto, a maior parte dos 129 casos com exame normal morreu nas primeiras 72 horas após a cirurgia ou os eventos clínicos responsáveis pela morte. Quase todas as alterações foram hipóxico-isquêmicas. Infartos, únicos ou múltiplos, foram encontrados em 41 casos (23 no GCg e 18 no GCI). Mecanismo embólico foi detectado em 12 casos. Alterações hipóxicas difusas estavam presentes em 17 casos (10 no GCg e 7 no GCI). Hemorragias foram encontradas em 11 (6 no GCg e 5 no GCI). Em 17 casos (5 no GCI e 12 no GCg), o quadro foi o de uma leucomalacia periventricular. Todos os casos eram concernentes a crianças abaixo de 6 meses de idade. Em 7 casos, alterações inflamatórias foram detectadas (micro-abscessos difusos em 6 e abscesso de lobo frontal em 1). Quase todos os casos em ambos os grupos apresentaram complicações clínicas, isoladas ou associadas, potencialmente danosas para o cérebro, como parada cardíaca, baixo débito cardíaco, hipoxemia e insuficiência respiratória. Foi impossível determinar, em cada caso, a magnitude do fator ou fatores responsáveis pelo padrão neuropatológico correspondente. Não houve diferenças do padrão neuropatológico entre as cardiopatias com hiper ou hipofluxo pulmonar

Extracerebellar MRI-lesions in ataxia telangiectasia go along with deficiency of the GH/IGF-1 axis, markedly reduced body weight, high ataxia scores and advanced age

Ataxia telangiectasia (AT) is a rare autosomal recessive disorder characterized by progressive ataxia, neurodegeneration, immunodeficiency, and cancer predisposition. Pathoanatomical studies reported a degeneration of cerebellar Purkinje cells as the striking feature of the disease. Although recent studies suggested the involvement of extracerebellar structures such as the brainstem and basal ganglia, this has rarely been studied in human AT. Thus, we performed a detailed cliniconeuroradiological investigation of 11 AT patients, aged 8 to 26 years by collecting clinical neurological data, ataxia scores, growth status, body mass index (BMI), growth hormone (GH), and insulin-like-growth factor 1 (IGF-1) and correlated them to extracerebellar neuroimaging findings in human AT. Neuroimaging was done by cranial and spine magnetic resonance imaging (MRI) with T1- and T2-weighted spin-echo and fluid attenuated inversion recovery sequences. We compared clinical and neuroradiological findings of six patients with IGF-1 levels and BMI below the third percentile to five patients with normal IGF-1 serum levels and BMI above the third percentile. Three of the six first mentioned patients older than 20 years and two patients older than 12 years showed noticeable high Klockgether ataxia scores above 25 points. Three of these patients presented with marked hyperintense lesions in the cerebral white matter of T2-weighted MR images. Interestingly, all six patients suffered from marked spinal atrophy. Two of the patients presented with severe extra-pyramidal symptoms, but only one patient showed associated MRI abnormalities of the basal ganglia. MRI in patients with normal IGF-1 levels showed the expected cerebellar lesions in four patients, whereas spinal atrophy was found only in two patients. There was no affection of the cerebral white matter or basal ganglia in this group. We conclude that central cerebral white matter affection, spinal atrophy, and extrapyramidal symptoms are more often present in patients with pronounced deficiency of the GH/IGF-1 axis accompanied by markedly reduced body weight and high ataxia scores. This may point to a major role of IGF-1 and nutritional status in neuroprotective signaling

Agenesia do cerebelo associada a microcefalia e agiria: relato de um caso autopsiado em recém-nascido e revisão da literatura

É apresentado um caso autopsiado de agenesia do cerebelo associada a microcefalia, agiria e deformidades das extremidades e pavilhões auriculares, associação esta até então não relatada na literatura. Este é o sétimo caso de agenesia cerebelar registrado na literatura. Compara-se este caso com os outros previamente publicados e comentam-se os possíveis fatores etiológicos envolvidos bem como a época do aparecimento das malformações encefálicas presentes