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1.
Arch Dermatol Res ; 315(3): 409-417, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35768620

RESUMO

To obtain current epidemiological information on primary focal hyperhidrosis in Japan, a large epidemiological survey was conducted using a web-based questionnaire. The prevalence of primary focal hyperhidrosis was 10.0% and the site-specific prevalence was highest for primary axillary hyperhidrosis (5.9%). The proportion of respondents with primary focal hyperhidrosis who had consulted a physician was 4.6%, which was similar to the low prevalence reported previously in 2013 in Japan. A questionnaire survey for physicians and individuals with primary axillary hyperhidrosis on the current medical management of primary axillary hyperhidrosis showed that physicians recognized the existence of patients who were very worried about hyperhidrosis, but failed to provide active treatment. Regarding the information provided by patients to physicians at presentation, it was found that patients failed to provide sufficient information to the physicians about their worries in daily life. Among individuals who had sought medical care with primary axillary hyperhidrosis, 62.3% reported that they were not currently receiving treatment, highlighting a challenge to be addressed regarding continued treatment. Frequently chosen options leading to willingness to receive treatment were less expensive treatment and highly effective treatment as well as feeling free to consult a physician, suggesting a desire for an improved medical environment.


Assuntos
Hiperidrose , Humanos , Japão/epidemiologia , Hiperidrose/diagnóstico , Hiperidrose/epidemiologia , Hiperidrose/terapia , Resultado do Tratamento , Axila , Inquéritos e Questionários
2.
Neurosci Lett ; 736: 135268, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32712353

RESUMO

Parkinson disease (PD) is a neurodegenerative disorder characterized by a selective loss of dopaminergic neurons in the substantia nigra, and oxidative stress is thought to contribute to this pathogenesis. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, which induces the production of antioxidant enzymes, is thereby a potential target for therapeutics to reduce neurodegeneration in PD. Previously, we identified TPNA10168 from a chemical library as an activator of the Nrf2-ARE pathway, and the present study examined the effects of TPNA10168 on an in vivo PD model. Subcutaneous administration of TPNA10168 was associated with inhibited dopaminergic neuronal loss and behavioral impairment in 6-hydroxydopamine-induced PD model mice. Heme oxygenase-1 (HO-1) is an antioxidant enzyme expressed downstream of the Nrf2-ARE signaling pathway, and we observed that HO-1 protein levels were upregulated by TPNA10168 in the mouse brain. These results suggest that TPNA10168 inhibits dopaminergic neuronal death in PD model mice, and that upregulation of HO-1 might participate in this effect.


Assuntos
Elementos de Resposta Antioxidante/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Fator 2 Relacionado a NF-E2/agonistas , Doença de Parkinson Secundária/tratamento farmacológico , Animais , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Corpo Estriado/patologia , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Camundongos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Oxidopamina , Doença de Parkinson Secundária/induzido quimicamente , Doença de Parkinson Secundária/metabolismo , Doença de Parkinson Secundária/patologia , Transdução de Sinais/efeitos dos fármacos , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , Substância Negra/patologia , Regulação para Cima/efeitos dos fármacos
3.
J Infect Chemother ; 24(8): 669-673, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29429850

RESUMO

Streptococcus suis, a gram-positive facultative anaerobe commonly found in pigs, is an emerging zoonotic pathogen. Herein, we describe a case of a 45-year-old male Japanese meat wholesaler with S. suis meningitis and pyogenic ventriculitis. S. suis was isolated from his blood and cerebrospinal fluid culture, and sequence type (ST) and serotype were confirmed to be ST1 and serotype 2, respectively, by multilocus sequence typing and the Quellung reaction. Magnetic resonance imaging (MRI) revealed right labyrinthitis and pyogenic ventriculitis. The patient was treated with ceftriaxone and ampicillin for 24 days; the treatment was deemed successful based on negative blood cultures on day 4. However, the patient experienced hearing loss and a vestibular nerve disorder. S. suis is a rare pathogen in Japan but can cause severe infection and sequelae. To the best of our knowledge, this is the first report of a human case of pyogenic ventriculitis caused by S. suis. Our findings suggest that S. suis infection should be considered when hearing impairment is present in a patient with bacterial infection and that MRI can help detect ventriculitis, which can necessitate a prolonged treatment duration.


Assuntos
Ventriculite Cerebral/microbiologia , Meningites Bacterianas/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus suis/patogenicidade , Antibacterianos/uso terapêutico , Encéfalo/diagnóstico por imagem , Ventriculite Cerebral/diagnóstico por imagem , Ventriculite Cerebral/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Japão , Imageamento por Ressonância Magnética , Masculino , Meningites Bacterianas/diagnóstico por imagem , Meningites Bacterianas/tratamento farmacológico , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Tipagem de Sequências Multilocus , Sorogrupo , Infecções Estreptocócicas/diagnóstico por imagem , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus suis/efeitos dos fármacos , Streptococcus suis/genética , Streptococcus suis/isolamento & purificação
4.
Eur J Pharmacol ; 818: 470-479, 2018 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-29154837

RESUMO

The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, which induces the production of antioxidant enzymes, is a possible therapeutic target for treating diseases related to oxidative stress. Nrf2 activators often exhibit cytotoxicity due to nonspecific electrophilic reactions with thiol groups. We screened a chemical library to explore Nrf2 activators with a wide safety margin. In at least in vitro experiments, TPNA10168, identified from the library, showed a higher efficacy in Nrf2 activation and a lower cytotoxicity than sulforaphane, a well-known Nrf2 activator. The present study demonstrated the protective effect of TPNA10168 against 6-hydroxydopamine-induced cytotoxicity. In PC12 cells, NAD(P)H:quinone oxidoreductase 1 was upregulated by TPNA10168 and participated in the protective effect. In primary mesencephalic cultures, heme oxygenase-1, upregulated by TPNA10168 in astrocytes, provided protection of dopaminergic neurons via a guanylate cyclase/protein kinase G signaling pathway via carbon monoxide. These results suggest that the compound identified from the chemical library may be suitable as a neuroprotective agent with the ability to induce antioxidant enzymes.


Assuntos
Antioxidantes/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fármacos Neuroprotetores/farmacologia , Elementos de Resposta/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia , Animais , Morte Celular/efeitos dos fármacos , Neurônios Dopaminérgicos/citologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Heme Oxigenase-1/genética , Oxidopamina/toxicidade , Células PC12 , Ratos , Regulação para Cima/efeitos dos fármacos
5.
Neuropathology ; 35(3): 209-23, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25443158

RESUMO

In acute stage of ischemic stroke, the surrounding zone of fresh infarcts is termed penumbra, where microglia are activated in response to damaged cell-derived proinflammatory mediators. Rescuing penumbra by regulating inflammatory activity would minimize infarct volume, which positively correlates with functional outcome. To elucidate mechanisms by which inflammation occurs in penumbra, we performed immunohistochemical investigations using autopsied human brains affected by acute, subacute and chronic stages of cerebral infarction as well as cell culture experiments using a murine microglia-derived cell line (BV-2). In penumbra of fresh infarcts, immunoreactivity for secretory phospholipase A2 group X (sPLA2 -X), which is responsible for the production and release of the proinflammatory mediator lysophosphatidylcholine (LPC), was intensely detected in neurons and astrocytes. Furthermore, immunoreactivities for the LPC receptors G protein-coupled receptor 132 (G2A) and P2X purinoreceptor 7 (P2X7R), as well as the CC chemokine monocyte chemoattractant protein-1 (MCP-1) and its receptor CCR2, were detectable in activated microglia. Prior to cell culture experiments, it was confirmed that BV-2 cells were immunoreactive for ionized Ca(2+) -binding adaptor molecule 1 (Iba1), G2A, P2X7R, MCP-1 and CCR2. Reverse transcription-quantitative polymerase chain reaction analysis revealed that MCP-1 and CCR2 mRNA expression levels were significantly increased by LPC stimulation. The LPC-driven increase in MCP-1 transcripts was lowered by blockade of G2A or P2X7R or by inhibition of Rho-associated protein kinase (ROCK) or inhibitor of κBα kinase. The LPC-driven increase in CCR2 transcripts was lowered by blockade of G2A or P2X7R or by inhibition of ROCK, phosphatidylinositide 3-kinanse, extracellular signal-regulated kinase kinase, or p38 mitogen-activated protein kinase. The present results provide in vivo and in vitro evidence that in acute stage of ischemic stroke, the sPLA2 -X enzyme product LPC is released from neurons and astrocytes and stimulates penumbra microglia via G2A and P2X7R, thereby exerting the MCP-1/CCR2-mediated neurotoxicity through distinct cell-signaling pathways.


Assuntos
Isquemia Encefálica/metabolismo , Encefalite/metabolismo , Microglia/metabolismo , Acidente Vascular Cerebral/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Astrócitos/metabolismo , Isquemia Encefálica/patologia , Linhagem Celular , Quimiocina CCL2/metabolismo , Feminino , Fosfolipases A2 do Grupo X/metabolismo , Humanos , Lisofosfatidilcolinas/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Neurônios/metabolismo , Receptores CCR2/metabolismo , Transdução de Sinais , Acidente Vascular Cerebral/patologia , Regulação para Cima
6.
Acta Neuropathol Commun ; 1: 21, 2013 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-24252211

RESUMO

BACKGROUND: Emerging evidence suggests that innate immunity and increased oxidative stress contribute to pathomechanisms in amyotrophic lateral sclerosis (ALS). The aim of the present study was to verify the involvement of monocyte chemoattractant protein-1 (MCP-1) and its specific CC chemokine receptor 2 (CCR2) in the disease progression of ALS. We here demonstrate the expression state of MCP-1 and CCR2 in lumbar spinal cords of mice overexpressing a transgene for G93A mutant human superoxide dismutase 1 (SOD1) (ALS mice) as a mouse model of ALS as well as the involvement of MCP-1/CCR2-mediated signaling in behavior of cultured astrocytes derived from those mice. RESULTS: Quantitative polymerase chain reaction analysis revealed that MCP-1 and CCR2 mRNA levels were significantly higher in ALS mice than those in nontransgenic littermates (control mice) at the presymptomatic stage. Immunoblot analysis disclosed a significantly higher CCR2/ß-actin optical density ratio in the postsymptomatic ALS mouse group than those in the age-matched control mouse group. Immunohistochemically, MCP-1 determinants were mainly localized in motor neurons, while CCR2 determinants were exclusively localized in reactive astrocytes. Primary cultures of astrocytes derived from ALS mice showed a significant increase in proliferation activity under recombinant murine MCP-1 stimuli as compared to those from control mice. CONCLUSIONS: Our results provide in vivo and in vitro evidence that MCP-1 stimulates astrocytes via CCR2 to induce astrocytosis in ALS with SOD1 gene mutation. Thus, it is likely that MCP-1/CCR2-mediated sigaling is involved in the disease progression of ALS.


Assuntos
Esclerose Lateral Amiotrófica/fisiopatologia , Astrócitos/fisiologia , Quimiocina CCL2/metabolismo , Gliose/fisiopatologia , Receptores CCR2/metabolismo , Medula Espinal/fisiopatologia , Actinas/metabolismo , Animais , Células Cultivadas , Modelos Animais de Doenças , Vértebras Lombares , Camundongos Transgênicos , Neurônios Motores/metabolismo , RNA Mensageiro/metabolismo , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1
7.
Intern Med ; 51(1): 87-91, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22214630

RESUMO

Adenoid cystic carcinoma (ACC) is a malignant neoplasm that commonly arises in the major or minor salivary gland and usually forms mass lesions. Here, we report a case of ACC involving a 56-year-old man, who displayed right multiple cranial nerve palsies with ipsilateral severe facial pain but not any mass formation. Right submaxillary gland biopsy after repeated challenges at last revealed the primary focus of ACC with perineural invasion and without lymph node metastasis. The neurological manifestations were considered to be attributed to the perineural spread of ACC. It is extremely rare for ACC to show Garcin's syndrome without mass formation.


Assuntos
Carcinoma Adenoide Cístico/diagnóstico , Doenças dos Nervos Cranianos/diagnóstico , Neoplasias das Glândulas Salivares/diagnóstico , Carcinoma Adenoide Cístico/complicações , Doenças dos Nervos Cranianos/etiologia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias das Glândulas Salivares/complicações , Glândula Submandibular , Síndrome
8.
Neuropathology ; 31(2): 122-8, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20667012

RESUMO

Several studies have suggested the involvement of neuroinflammation in the pathomechanism of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). We recently demonstrated increased levels of protein-bound 4-hydroxy-2-nonenal (HNE) as a highly reactive lipid peroxidation product and cytosolic phospholipase A(2) (cPLA(2)) as a proinflammatory enzyme in glial cells as well as motor neurons in the spinal cord of sporadic ALS patients. However, a link between HNE and cPLA(2) in ALS remains to be determined. To address this issue, we investigated effects of HNE stimulation on the state of cPLA(2) expression in cultured microglial cell line (Ra2). Exposure of Ra2 cells to HNE significantly increased expression levels of cPLA(2) and its activated form phosphorylated at amino acid residue S(505) (p-cPLA(2)) on immunoblots. Pretreatment of Ra2 cells with the antioxidant N-acetylcysteine, the extracellular signal-regulated kinase (ERK) inhibitor PD98059 or the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 prevented the HNE-induced increased expression of cPLA(2) and p-cPLA(2). Immunocytochemical analysis revealed that staining for p-cPLA(2) in Ra2 cells was localized in the cytoplasm and more intense in the HNE-stimulated group than in the vehicle group. The present results provide in vitro evidence that HNE upregulates and phosphorylates cPLA(2) in microglia via the ERK and p38 MAPK pathways.


Assuntos
Aldeídos/metabolismo , Fosfolipases A2 do Grupo IV/metabolismo , Microglia/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Transdução de Sinais/fisiologia , Aldeídos/farmacologia , Animais , Western Blotting , Linhagem Celular , Citosol/metabolismo , Ativação Enzimática/fisiologia , Imuno-Histoquímica , Peroxidação de Lipídeos , Camundongos , Estresse Oxidativo/fisiologia , Fosforilação , Regulação para Cima
9.
Acta Histochem Cytochem ; 43(2): 69-75, 2010 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-20514294

RESUMO

Recent studies have suggested implications for α-synuclein cytotoxicity in the pathomechanism of multiple system atrophy (MSA). Given in vitro evidence that α-synuclein generates oxidative stress, it is proposed that lipid peroxidation may be accelerated in MSA. To address this issue, we performed an immunohistochemical analysis of protein-bound 4-hydroxy-2-nonenal (P-HNE) in sections of archival, formalin-fixed, paraffin-embedded pontine materials of eight sporadic MSA patients and eight age-matched control subjects. In the MSA cases, P-HNE immunoreactivity was localized in all of the neuronal cytoplasmic inclusions and glial cytoplasmic inclusions, both of them identified with α-synuclein and ubiquitin. It was also detectable in reactive astrocytes and phagocytic microglia but undetectable in activated microglia. By contrast, P-HNE immunoreactivity in the control cases was only very weak or not at all in the parenchyma including neurons and glia. The present results provide in vivo evidence that HNE participates in α-synuclein-induced cytotoxicity and neuroinflammation in MSA.

10.
Rinsho Shinkeigaku ; 50(4): 241-5, 2010 Apr.
Artigo em Japonês | MEDLINE | ID: mdl-20411806

RESUMO

We report a 51-year-old man with human T lymphotropic virus type-1 (HTLV-1) associated myelopathy (HAM) manifested 10 months after renal transplantation. He had progressive spastic paralysis and neurogenic bladder for 10 years. HTLV-1 antibody are positive both serum and cerebral spinal fluid (CSF). Althoght HTLV-1 was not examined in the donor, it was suspected that the patient was infected by renal transplantation. After treatment of interferon-alpha (IFN-alpha), his motor function had improved and neopterin in CSF was decreased from 158 pmol/ml to 89 pmol/ml. This is a rare case of HAM after living renal transplantation. Cyclosporin and methylpredonisolone are used as immunosuppressants for preventing graft rejection. Time for developing HAM after renal transplantation was shorter than patients after cadaveric renal transplantation. More investigations are needed to clarify the mechanisms in the development of HAM associated with renal transplantation.


Assuntos
Transplante de Rim/efeitos adversos , Doadores Vivos , Paraparesia Espástica Tropical/etiologia , Paraparesia Espástica Tropical/transmissão , Biomarcadores/líquido cefalorraquidiano , Ciclosporina/efeitos adversos , Rejeição de Enxerto/prevenção & controle , Humanos , Interferon-alfa/uso terapêutico , Masculino , Metilprednisolona/efeitos adversos , Pessoa de Meia-Idade , Neopterina/líquido cefalorraquidiano , Paraparesia Espástica Tropical/diagnóstico , Paraparesia Espástica Tropical/tratamento farmacológico
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