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To investigate the effect of the therapeutic treatment of the immunopeptide, peptide inhibitor of trans-endothelial migration (PEPITEM) on the severity of disease in a mouse model of experimental autoimmune encephalomyelitis (EAE) as a model for human multiple sclerosis (MS), a series of experiments were conducted. Using C57BL/6 female mice, we dosed the PEPITEM in the EAE model via IP after observing the first sign of inflammation. The disease was induced using MOG35-55 and complete Freund's adjuvants augmented with pertussis toxin. The EAE score was recorded daily until the end of the experiment (21 days). The histological and immunohistochemistry analysis was conducted on the spinal cord sections. A Western blot analysis was performed to measure the protein concentration of MBP, MAP-2, and N-Cadherin, and ELISA kits were used to measure IL-17 and FOXP3 in the serum and spinal cord lysate. The therapeutic treatment with PEPITEM reduced the CNS infiltration of T cells, and decreased levels of the protein concertations of MBP, MAP-2, and N-Cadherin were observed, in addition to reduced concertations of IL-17 and FOXP3. Using PEPITEM alleviated the severity of the symptoms in the EAE model. Our study revealed the potential of PEPITEM to control inflammation in MS patients and to reduce the harmful effects of synthetic drugs.
Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Humanos , Feminino , Camundongos , Animais , Interleucina-17/efeitos adversos , Citocinas/metabolismo , Camundongos Endogâmicos C57BL , Inflamação/tratamento farmacológico , Inflamação/patologia , Medula Espinal/metabolismo , Esclerose Múltipla/patologia , Peptídeos , Linfócitos T/metabolismo , Caderinas , Fatores de Transcrição ForkheadRESUMO
BACKGROUND: Germ cell tumors (GCT) are the most common central nervous system (CNS) tumors in individuals with Down syndrome. Patients with Down syndrome treated with CNS irradiation are at increased risk of developing cerebrovascular complications such as moyamoya disease. Embryonal carcinoma components are recognized to be more resistant to conventional chemotherapy and radiotherapy and confer a very poor prognosis. CD30 is a member of the tumor necrosis factor-receptor superfamily. CD30+ has a limited expression in normal cells but is the defining marker for embryonal carcinoma. Brentuximab-vedotin is a novel antibody-drug conjugate consisting of the chimeric anti-CD30 antibody conjugated to an anti-tubulin synthetic analog monomethyl auristatin E. METHODS: A retrospective review of the patient's records was conducted in September 2017. RESULTS: We report upon our management of a teenage girl with Down syndrome and a suprasellar pure embryonal carcinoma utilizing an intensive chemotherapy regimen followed by brentuximab-vedotin without irradiation. The patient received two cycles of carboplatin and etoposide interspersed with one cycle of cyclophosphamide and etoposide for induction followed by three cycles of marrow-ablative thiotepa and carboplatin rescued by autologous hematopoietic stem cell. Finally, She received six cycles of intravenous brentuximab-vedotin. The patient continues without evidence of recurrent tumor by MRI and tumor marker surveillance 24 months since diagnosis, with no adverse sequelae of her treatment. CONCLUSIONS: Brentuximab-vedotin may provide a selective and safe alternative (or adjunct) to radiotherapy in the management of patients with CD30-positive CNS embryonal carcinoma, especially for those patients at high risk of developing irradiation-related complications.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Embrionário/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Síndrome de Down/tratamento farmacológico , Imunoconjugados , Adolescente , Brentuximab Vedotin , Carcinoma Embrionário/complicações , Síndrome de Down/complicações , Feminino , Humanos , Antígeno Ki-1/metabolismo , Antígeno Ki-67/metabolismo , Imageamento por Ressonância Magnética , Fator 3 de Transcrição de Octâmero/metabolismo , Estudos RetrospectivosRESUMO
Neuroepithelial tumors, formerly known as primitive neuroectodermal tumors of the central nervous system, are reclassified under embryonal tumors in the 2016 WHO Classification of Tumors of the Central Nervous System. The tumor has two known genetic alterations: HGNET-MN1 and HGNET-BCOR. Previously, radiological features of the tumor have been reported as large, intra-axial lesions in the cerebral or cerebellar hemisphere, which presents mild adjacent edema. Here, we report the first case of high-grade neuroepithelial tumor not elsewhere classified (HGNET-NEC) arising from the cerebellar vermis, demonstrating good outcomes in clinical follow-up when compared with previously known types.
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BACKGROUND: Intracranial tuberculomas are uncommon yet devastating forms of extrapulmonary tuberculosis with a high mortality rate and morbidity risk. A high level of suspicion is required for a prompt diagnosis and treatment. CASE DESCRIPTION: A 67-year-old male, medically free, presented at the Emergency Department with a 1-day history of nausea and vomiting, and a 15-day history of imbalance and dizziness. Radiological imaging demonstrated right well-defined ring-enhancing lesions. He underwent a sup-occipital craniotomy with lesion resection. The diagnosis of an intracranial tuberculoma was confirmed histopathologically. Anti-tuberculosis therapy was prescribed, and the patient was discharged with mild cerebellar dysfunction. DISCUSSION: Intracranial tuberculomas have a high rate of mortality and morbidity. It is critical to consider tuberculoma in the differential diagnosis of intracranial lesions with such clinico-radiological characteristics, especially in developing countries. CONCLUSION: In this article, we are reporting an interesting case with multiple intracranial tuberculomas with an extensive review of the literature.
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Inflammatory bowel diseases (IBDs) are idiopathic autoimmune diseases that are characterized by inflammation of both the small and large intestine. Although IBD is common in the general population, the pathophysiology remains ambiguous. Clear understanding of IBD pathophysiology would be a major step toward curative treatment in the future. Hyperhomocysteinemia has been associated with multiple autoimmune diseases including IBD, but homocystinuria has not been associated with IBD before. We report a 9-year-old girl with Crohn's disease and homocystinuria. Her gastrointestinal symptoms improved significantly upon classical homocystinuria treatment, and her last colonoscopy showed a pronounced remission. This case supports the inflammatory role of homocysteine in the gastrointestinal tract and the association between hyperhomocysteinemia and IBD manifestations.
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Improved survival rates in premature infants and more sensitive neuroimaging techniques have expanded the scope of recognized neurodevelopmental disabilities in this vulnerable population and have implicated a role for cerebellar pathology in their origin. Although supratentorial pathologies are well studied, cerebellar pathology has been under-recognized in premature infants. The purpose of this review is to provide a concise description of established acquired cerebellar pathologies in premature infants including cerebellar atrophy/hypoplasia, hemorrhage, and infarction. The cerebellum develops over an extended period during which time cerebellar injury tends to occur with the potential to derail the cerebellum from its expected growth trajectory and perturb the establishment of cerebellar neural circuitry. The occurrence of cerebellar injury in this vulnerable period may have life-long implications that extend beyond the immediate damage sustained by the cerebellum, all of which needs to be considered as we research the causes and effects of neurodevelopmental disabilities in these patients.
Assuntos
Doenças Cerebelares/patologia , Cerebelo/patologia , Doenças do Prematuro/patologia , Nascimento Prematuro , Atrofia/patologia , Humanos , Recém-Nascido , Recém-Nascido PrematuroRESUMO
Pathologic findings in surgical resections from patients with temporal lobe epilepsy include a wide range of diagnostic possibilities that can be categorized into different groups on the basis of etiology. This paper outlines the various pathologic entities described in temporal lobe epilepsy, including some newly recognized epilepsy-associated tumors, and briefly touch on the recent classification of focal cortical dysplasia. This classification takes into account coexistent pathologic lesions in focal cortical dysplasia.