RESUMO
We have demonstrated previously that histone deacetylase (HDAC6) expression is increased in animal models of systemic lupus erythematosus (SLE) and that inhibition of HDAC6 decreased disease. In our current studies, we tested if an orally active selective HDAC6 inhibitor would decrease disease pathogenesis in a lupus mouse model with established early disease. Additionally, we sought to delineate the cellular and molecular mechanism(s) of action of a selective HDAC6 inhibitor in SLE. We treated 20-week-old (early-disease) New Zealand Black (NZB)/White F1 female mice with two different doses of the selective HDAC6 inhibitor (ACY-738) for 5 weeks. As the mice aged, we determined autoantibody production and cytokine levels by enzyme-linked immunosorbent assay (ELISA) and renal function by measuring proteinuria. At the termination of the study, we performed a comprehensive analysis on B cells, T cells and innate immune cells using flow cytometry and examined renal tissue for immune-mediated pathogenesis using immunohistochemistry and immunofluorescence. Our results showed a reduced germinal centre B cell response, decreased T follicular helper cells and diminished interferon (IFN)-γ production from T helper cells in splenic tissue. Additionally, we found the IFN-α-producing ability of plasmacytoid dendritic cells was decreased along with immunoglobulin isotype switching and the generation of pathogenic autoantibodies. Renal tissue showed decreased immunoglobulin deposition and reduced inflammation as judged by glomerular and interstitial inflammation. Taken together, these studies show selective HDAC6 inhibition decreased several parameters of disease pathogenesis in lupus-prone mice. The decrease was due in part to inhibition of B cell development and response.
Assuntos
Imunidade Adaptativa , Desacetilase 6 de Histona/antagonistas & inibidores , Inibidores de Histona Desacetilases/farmacologia , Imunidade Inata , Nefrite Lúpica/imunologia , Nefrite Lúpica/metabolismo , Animais , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Feminino , Perfilação da Expressão Gênica , Interferon-alfa/biossíntese , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/patologia , Camundongos , Baço/imunologia , Baço/metabolismoRESUMO
OBJECTIVES: To describe the clinical features, magnetic resonance imaging (MRI) findings, and outcome of dogs and cats with central nervous system (CNS) lymphoma that involved the choroid plexus. MATERIALS AND METHODS: A bi-institutional retrospective study of MRI of dogs and cats with CNS lymphoma, in which the choroid plexus was affected on MRI. Signalment, clinical, MRI, clinicopathologic and histopathologic findings were recorded and evaluated. RESULTS: CNS lymphoma with choroid plexus involvement on the MRI was identified in five dogs and one cat. MRI revealed diffuse enlargement and multifocal nodularity in the choroid plexus in most cases, with the fourth ventricle the most common site affected. Five of the cases had signs of extraneural involvement (including the cat), while the sixth case was not staged. Four of five CSF samples analysed provided a diagnosis of lymphoma. CLINICAL SIGNIFICANCE: We report MRI findings of CNS lymphoma involving the choroid plexus. These results show the importance of recognising novel imaging patterns and the potential utility of CSF collection in diagnosing CNS lymphoma involving the choroid plexus ante mortem.
Assuntos
Doenças do Gato , Doenças do Cão , Animais , Doenças do Gato/diagnóstico por imagem , Gatos , Plexo Corióideo/diagnóstico por imagem , Doenças do Cão/diagnóstico por imagem , Cães , Imageamento por Ressonância Magnética/veterinária , Estudos RetrospectivosRESUMO
A 9-week-old male puppy was submitted for necropsy examination after a reported history of developing acute melaena and vomiting blood before death. Grossly, the animal had multiple skull fractures, mostly affecting the occipital region and cranial floor, associated with extensive regions of subcutaneous, periosteal and subdural haemorrhages, as well as petechial haemorrhages within the right middle and caudal lung lobes. Histopathology of the brain revealed multifocal acute meningeal and parenchymal haemorrhage with laceration of the cerebellar folia. In the lung, multiple small- and medium-calibre branches of pulmonary arteries were occluded by aggregates of brain tissue, which exhibited weak immunoreactivity for glial fibrillary acidic protein and strong labelling for neuron specific enolase on immunohistochemistry. These findings were consistent with brain tissue pulmonary embolism, an infrequent phenomenon following severe head trauma. To the best of the authors' knowledge, this is the first reported case of canine brain tissue pulmonary embolism.
Assuntos
Encéfalo , Doenças do Cão/patologia , Traumatismos Cranianos Fechados/veterinária , Embolia Pulmonar/veterinária , Animais , Cães , MasculinoRESUMO
A 7-year-old neutered male domestic shorthair cat was presented with chronic lameness in the right forelimb. A cystic bony lesion was identified in the distal right humerus and amputation was performed. The epiphyseal trabecular bones of the capitulum and trochlea was replaced by a tan to pink, expansile mass that was surrounded by a thin rim of cortical bone. Microscopically, the tumour was composed of a bland, osteoid producing spindle cell population within a well-vascularized fibrous stroma. Radiographical and histological features were consistent with osteoblastoma. Osteoblastoma and the related osteoid osteoma are uncommon, benign osteoblastic tumours that are reported rarely in animals. These tumours should be considered as differential diagnoses for slow growing, cystic bony lesions in cats.