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1.
Sci Rep ; 11(1): 14237, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244578

RESUMO

Brain endothelial cells (BECs) are involved in the pathogenesis of ischemic stroke. Recently, several microRNAs (miRNAs) in BECs were reported to regulate the endothelial function in ischemic brain. Therefore, modulation of miRNAs in BECs by a therapeutic oligonucleotide to inhibit miRNA (antimiR) could be a useful strategy for treating ischemic stroke. However, few attempts have been made to achieve this strategy via systemic route due to lack of efficient delivery-method toward BECs. Here, we have developed a new technology for delivering an antimiR into BECs and silencing miRNAs in BECs, using a mouse ischemic stroke model. We designed a heteroduplex oligonucleotide, comprising an antimiR against miRNA-126 (miR-126) known as the endothelial-specific miRNA and its complementary RNA, conjugated to α-tocopherol as a delivery ligand (Toc-HDO targeting miR-126). Intravenous administration of Toc-HDO targeting miR-126 remarkably suppressed miR-126 expression in ischemic brain of the model mice. In addition, we showed that Toc-HDO targeting miR-126 was delivered into BECs more efficiently than the parent antimiR in ischemic brain, and that it was delivered more effectively in ischemic brain than non-ischemic brain of this model mice. Our study highlights the potential of this technology as a new clinical therapeutic option for ischemic stroke.


Assuntos
MicroRNAs/genética , Oligonucleotídeos/química , Oligonucleotídeos/uso terapêutico , alfa-Tocoferol/química , Animais , Encéfalo/metabolismo , Linhagem Celular , Imuno-Histoquímica , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/genética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Reação em Cadeia da Polimerase Via Transcriptase Reversa
2.
BMC Neurol ; 20(1): 11, 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31918670

RESUMO

BACKGROUND: Hypertrophic pachymeningitis (HP) is a rare disorder that involves localized or diffuse thickening of the dura mater. HP is associated with various inflammatory, infectious, and malignant diseases, such as rheumatic arthritis, sarcoidosis, anti-neutrophil cytoplasmic antibody-associated vasculitis, IgG4-related disorders, syphilis, tuberculosis, bacterial and fungal infections, cancer, and idiopathic diseases, when evaluation fails to reveal a cause. Among them, chronic infection with Propionibacterium acnes is a rare etiology of HP, and its pathology remains unclear. CASE PRESENTATION: An 80-year-old man having refractory otitis media with effusion of the right ear presented with progressive right-sided headache and nausea. Post-contrast brain magnetic resonance imaging revealed right mastoiditis and remarkable thickening of the dura mater and enhancement of pia mater extending from the right middle cranial fossa to the temporal lobe. HP secondary to middle ear infection was suspected, and a biopsy of the right mastoid was performed. An anaerobic culture of the biopsied right mastoid showed the growth of P. acnes, and histopathological examination using P. acnes-specific monoclonal antibody (PAB antibody) revealed the infiltration of inflammatory cells with P. acnes. Moreover, using PAB antibody, P. acnes was detected in the biopsy specimen of the thickening dura mater. No granulomas were identified in either specimen. HP was resolved with long-term administration of antibiotics and steroids. CONCLUSION: This is the first documentation of pathologically demonstrated chronic HP associated with P. acnes infection followed by refractory otitis media. This report showed that chronic latent P. acnes infection induces chronic inflammation.


Assuntos
Infecções por Bactérias Gram-Positivas/complicações , Meningite/microbiologia , Otite Média/complicações , Otite Média/microbiologia , Propionibacterium acnes , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Humanos , Hipertrofia , Masculino , Meningite/tratamento farmacológico , Otite Média/tratamento farmacológico , Recidiva
5.
Ann Thorac Cardiovasc Surg ; 25(4): 215-218, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-29515082

RESUMO

A 34-year-old man was diagnosed with thymoma, which was evaluated preoperatively as stage II or III, with myasthenia gravis (MG). The size of the tumor was 70 × 44 × 80 mm. No invasion to neighboring organs was observed. Prednisolone was prescribed for stabilization of MG. However, a myasthenic crisis (MC) occurred, and intensive care, including emergent endobronchial intubation followed by artificial ventilation, pulse steroid therapy, high-dose intravenous immunoglobulin, and tacrolimus hydrate, was initiated. A chest computed tomography on day 6 revealed tumor reduction to 50 × 30 × 60 mm. An extended total thymectomy by median sternotomy was performed, and artificial ventilation was continued after that. Scheduled artificial ventilation and steroid therapy together can, therefore, enable complete resection of thymoma in patients undergoing treatment for MC. While ventilation helps avert a respiratory failure, the steroid therapy temporarily reduces the tumor size, making resection easier.


Assuntos
Miastenia Gravis/complicações , Respiração Artificial , Timectomia , Timoma/cirurgia , Neoplasias do Timo/cirurgia , Adulto , Humanos , Masculino , Miastenia Gravis/diagnóstico , Miastenia Gravis/terapia , Estadiamento de Neoplasias , Pulsoterapia , Esteroides/administração & dosagem , Timoma/complicações , Timoma/diagnóstico por imagem , Timoma/patologia , Neoplasias do Timo/complicações , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/patologia , Resultado do Tratamento , Carga Tumoral
7.
BMC Infect Dis ; 18(1): 313, 2018 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-29980175

RESUMO

BACKGROUND: Although paradoxical reactions (PRs) to anti-tuberculosis (anti-TB) therapy during treatment are well-established occurrences, PRs presenting as a new lesion after the completion of treatment are extremely rare, and little is known about the management of such cases, particularly of central nervous system (CNS) tuberculosis. CASE PRESENTATION: A 27-year-old female, with a past medical history of tuberculous meningitis 10 years ago and who completed the anti-TB treatment with asymptomatic remnant tuberculomas in the basal cistern, was admitted to our hospital because of a headache and the worsening of pre-existing visual disturbance. Contrast-enhanced T1-weighted brain magnetic resonance imaging (MRI) revealed new tuberculomas in the left sylvian fissure with a diffuse low signal around it. Because repeated polymerase chain reaction and Mycobacterium tuberculosis culture presented negative results and the patient had no laboratory data suggestive of a relapse of tuberculous meningitis, she was diagnosed with late-onset post-treatment PRs and treated with oral corticosteroids, tapered off over 1 year. Eventually, the symptoms were relieved, and the tuberculomas disappeared. CONCLUSIONS: Clinicians should consider the possibility of PRs long after the completion of tuberculous meningitis treatment. Hence, a precise MRI-based examination is imperative for the follow-up of CNS tuberculosis, and the unnecessary administration of anti-TB drugs should be avoided. The use of corticosteroids as a treatment option for post-treatment PRs is seemingly safe when the isolated M. tuberculosis is sensitive to the first-line anti-TB therapy.


Assuntos
Antituberculosos/efeitos adversos , Tuberculoma/diagnóstico por imagem , Tuberculose Meníngea/tratamento farmacológico , Administração Oral , Corticosteroides/uso terapêutico , Adulto , Antituberculosos/uso terapêutico , Encéfalo/diagnóstico por imagem , Feminino , Soronegatividade para HIV , Cefaleia/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificação , Reação em Cadeia da Polimerase , Prednisolona/administração & dosagem , Tuberculoma/tratamento farmacológico , Tuberculose Meníngea/complicações
8.
J Stroke Cerebrovasc Dis ; 27(1): e11-e14, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28967591

RESUMO

Lumbar spinal fluid drainage is a common procedure for treating hydrocephalus and alleviating vasospasm by egesting blood in the subarachnoid cavity after subarachnoid hemorrhage. Despite being an effective and safe procedure, cerebrospinal fluid overdrainage might result in serious complications. Here we report the case of a 49-year-old man who suffered from tonsillar herniation with subsequent cervicothoracic syringomyelia in the acute phase of subarachnoid hemorrhage due to vertebral artery dissection. About 2 weeks after lumbar drainage was switched from external ventricular drainage initiated on the day of subarachnoid hemorrhage, the recovery from the disturbance of consciousness revealed tetraplegia, and magnetic resonance imaging demonstrated tonsillar herniation and syringomyelia. Removal of the spinal drain and resumption of external ventricular drainage resulted in the restoration of the herniated tonsils to the normal position and the complete disappearance of syringomyelia 11 days later. We should consider that spinal syringomyelia could develop as a complication of lumbar spinal fluid drainage in the acute phase of thick subarachnoid hemorrhage, particularly in the posterior cranial fossa.


Assuntos
Drenagem/efeitos adversos , Punção Espinal/efeitos adversos , Hemorragia Subaracnóidea/terapia , Siringomielia/etiologia , Angiografia Cerebral/métodos , Angiografia por Tomografia Computadorizada , Imagem de Difusão por Ressonância Magnética , Drenagem/instrumentação , Drenagem/métodos , Encefalocele/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Punção Espinal/instrumentação , Hemorragia Subaracnóidea/líquido cefalorraquidiano , Hemorragia Subaracnóidea/diagnóstico por imagem , Siringomielia/diagnóstico por imagem
9.
J Clin Neurosci ; 47: 120-123, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29066240

RESUMO

Midbrain infarction causing oculomotor nerve palsy with contralateral ataxia is named Claude's syndrome. Herein we report the case of a variant of Claude's syndrome, which shows pupil-sparing oculomotor nerve palsy without the accompanying neurological deficits other than subtle truncal ataxia. MRI and Diffusion Tensor Imaging revealed that midbrain infarction was located rostrally above the decussation of the superior cerebellar peduncle (SCP) and might have partially destructed the tectospinal tract, which resulted in the absence of limb ataxia and presence of subtle truncal ataxia. In this variant of Claude's syndrome, we should carefully assess truncal ataxia to avoid misdiagnosing it as isolated pupil-sparing oculomotor nerve palsy because the patient showed apparently normal gait and truncal ataxia was only revealed by unstable tandem gait.


Assuntos
Ataxia/diagnóstico , Infartos do Tronco Encefálico/diagnóstico , Doenças do Nervo Oculomotor/diagnóstico , Idoso , Imagem de Tensor de Difusão , Humanos , Imageamento por Ressonância Magnética/efeitos adversos , Masculino
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