Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 44
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Front Immunol ; 12: 648754, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790913

RESUMO

Background and Aims: Emerging evidence has revealed that innate lymphoid cells (ILCs) play a key role in regulating metabolic disorders. Here, we investigated the role of group 3 ILCs (ILC3s) in the modulation of Non-alcoholic fatty liver disease (NAFLD). Methods: RORγ gfp/gfp (RORgt KI/KI) and Rag2-/- mice with the administration of A213, RORgt antagonist, fed with a high-fat-diet (HFD) for 12 weeks, were used. We performed flow cytometry, real time PCR, and lipidomics analysis of serum and liver, and used RAW264.7 cells and murine primary hepatocytes in vitro. Results: HFD increased ILC3s and M1 macrophages in the liver, and RORgt KI/KI mice deficient in ILC3 showed significant fatty liver, liver fibrosis and significantly increased palmitic acid levels in serum and liver. In addition, administration of A213 to Rag2-/- mice caused significant fatty liver, liver fibrosis, and a significant increase in serum and liver palmitate concentrations, as in RORgt KI/KI mice. Addition of palmitc acid stimulated IL-23 production in cell experiments using RAW264.7. IL-22 produced by ILC3s inhibited the palmitate-induced apoptosis of primary hepatocytes. Conclusions: HFD stimulates IL-23 production by M1 macrophages, thus promoting ILC3 proliferation, whereas IL-22 secreted by ILC3s contributes to the upregulation of hepatic lipid metabolism and has anti-apoptosis activity.


Assuntos
Fígado Gorduroso/imunologia , Imunidade Inata/imunologia , Fígado/imunologia , Linfócitos/imunologia , Macrófagos/imunologia , Animais , Apoptose/imunologia , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Hepatócitos/citologia , Hepatócitos/imunologia , Fígado/metabolismo , Fígado/patologia , Linfócitos/metabolismo , Macrófagos/classificação , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Ácido Palmítico/sangue , Ácido Palmítico/imunologia , Ácido Palmítico/metabolismo , Substâncias Protetoras/metabolismo , Células RAW 264.7
2.
Oral Dis ; 25(5): 1352-1362, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30912198

RESUMO

OBJECTIVE: The usefulness of the amniotic membrane as a cell culture substrate has led to its use in the development of dental pulp-derived cell sheets. We induced osteoblastic differentiation of dental pulp-derived cell sheets and conducted histological and immunological examinations in addition to imaging assessments for regeneration of bone defects. METHODS: Dental pulp cells were obtained by primary culture of the dental pulp tissue harvested from extracted wisdom teeth. These cells were maintained for three to four passages. Subsequently, the dental pulp cells were seeded onto an amniotic membrane to produce dental pulp-derived cell sheets. Following the induction of osteoblastic differentiation, the sheets were grafted into the subcutaneous tissue of the lower back and maxillary bone defect of a nude mouse. Histological and immunological examinations of both grafts were performed. RESULTS: Dental pulp-derived cell sheets cultured on an osteoblast differentiation-inducing medium demonstrated resemblance to dental pulp tissue and produced calcified tissue. Mineralization was maintained following grafting of the sheets. Regeneration of the maxillary bone defect was observed. CONCLUSION: Induction of osteoblastic differentiation of the dental pulp-derived cell sheets may be indicated for the regeneration of periodontal tissue.


Assuntos
Polpa Dentária , Transplante de Células-Tronco , Âmnio , Animais , Diferenciação Celular , Células Cultivadas , Humanos , Camundongos
3.
Arch Oral Biol ; 94: 62-68, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29979974

RESUMO

OBJECTIVES: Wound healing of the oral mucosal epithelium through the application of far infrared radiation emitted by isotropic high-density carbon was investigated in order to clarify the preventive and therapeutic effects of isotropic high-density carbon on oral mucosal injury. MATERIALS AND METHODS: A carbon massager with an isotropic high-density carbon tip was used. Far infrared radiation was applied to the human buccal mucosal squamous cell carcinoma cell line, HO-1-N-1 using a carbon massager, and cell growth factors and heat shock protein levels were measured using real-time RT-PCR and ELISA. Far infrared radiation was applied to oral mucosal injury in SD rats over time using the carbon massager, and its effects were examined by HE staining and immunostaining. The immunostaining positive rate was measured and analyzed using image analysis software. RESULTS: Far infrared radiation induced stronger mRNA expression and higher HSP27 and HSP70 protein levels on real-time RT-PCR and ELISA than in the control group. The far infrared radiation of oral mucosal injury in rats induced strong positive reactions, and positive rates for Ki67, HSP27, and HSP70 were higher than those in the control group. CONCLUSIONS: The treatment of oral mucosal injury with far infrared radiation emitted by isotropic high-density carbon appears to have promoted heat shock protein production and induced regenerative reactions more strongly than in the control group.


Assuntos
Carbono/análise , Raios Infravermelhos/efeitos adversos , Mucosa Bucal/patologia , Mucosa Bucal/efeitos da radiação , Cicatrização/efeitos da radiação , Animais , Carcinoma de Células Escamosas/radioterapia , Linhagem Celular Tumoral/efeitos da radiação , Epitélio/lesões , Epitélio/patologia , Epitélio/efeitos da radiação , Fibrose/patologia , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico/análise , Proteínas de Choque Térmico/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/análise , Peptídeos e Proteínas de Sinalização Intercelular/genética , Antígeno Ki-67/metabolismo , Masculino , Mucosa Bucal/lesões , Neoplasias Bucais/radioterapia , RNA Mensageiro/metabolismo , Ratos
4.
Odontology ; 104(1): 27-34, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25957627

RESUMO

Although many reports have been published on the functional roles of periodontal ligament (PDL) cells, the mechanisms involved in the maintenance and homeostasis of PDL have not been determined. We investigated the effects of biomechanical force on growth factor production, phosphorylation of MAPKs, and intracellular transduction pathways for growth factor production in human periodontal ligament (hPDL) cells using MAPK inhibitors. hPDL cells were exposed to mechanical force (6 MPa) using a hydrostatic pressure apparatus. The levels of growth factor mRNA and protein were examined by real-time RT-PCR and ELISA. The phosphorylation of MAPKs was measured using BD™ CBA Flex Set. In addition, MAPKs inhibitors were used to identify specific signal transduction pathways. Application of biomechanical force (equivalent to occlusal force) increased the synthesis of VEGF-A, FGF-2, and NGF. The application of biomechanical force increased the expression levels of phosphorylated ERK and p38, but not of JNK. Furthermore, the levels of VEGF-A and NGF expression were suppressed by ERK or p38 inhibitor. The growth factors induced by biomechanical force may play a role in the mechanisms of homeostasis of PDL.


Assuntos
Fator 2 de Crescimento de Fibroblastos/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Fator de Crescimento Neural/metabolismo , Ligamento Periodontal/citologia , Estresse Mecânico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fenômenos Biomecânicos , Sobrevivência Celular , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Humanos , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Fosforilação , Pressão , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais
5.
Biomed Mater Eng ; 25(2): 203-12, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25813958

RESUMO

OBJECTIVE: Mesenchymal stem cells (MSC) are transplanted for periodontal tissue regeneration, and the periodontal ligament (PDL) is regenerated using a cultured cell sheet. This cultured cell sheet is prepared using PDL-derived cells, growth factors, and amniotic membrane (AM). Dental pulp (DP)-derived cells can be easily obtained from extracted wisdom teeth, proliferate rapidly, and are less susceptible to bacterial infection than PDL-derived cells. Thus, to prepare a novel cell sheet, DP-derived cells were cultured on AM as a culture substrate for immunohistochemical examination. METHODS: Wisdom teeth extracted from three adults were cut along the cement-enamel border. DP tissue was collected, minced, and primarily cultured. After three or four passage cultures, DP-derived cells were cultured on AM, followed by hematoxylin-eosin (H-E) and immunofluorescence staining. RESULTS: DP-derived cells cultured on AM formed a layered structure. Cells positive for vimentin, Ki-67, ZO-1, desmoplakin, CD29, 44, 105 or 146, STRO-1, collagen IV or VII or laminin 5 or α5 chain were localized. CONCLUSIONS: DP-derived cells proliferated on AM, while retaining the properties of DP, which allowed the cultured cell sheet to be prepared. In addition, the cultured cell sheet contained MSC, which suggests its potential application in periodontal tissue regeneration.


Assuntos
Âmnio/química , Polpa Dentária/citologia , Células-Tronco Mesenquimais/citologia , Adulto , Proliferação de Células , Células Cultivadas , Desmoplaquinas/genética , Desmoplaquinas/metabolismo , Células Epiteliais/metabolismo , Feminino , Marcadores Genéticos , Humanos , Imuno-Histoquímica , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Células-Tronco Mesenquimais/metabolismo , Ligamento Periodontal/citologia , Engenharia Tecidual , Vimentina/genética , Vimentina/metabolismo , Cicatrização , Adulto Jovem , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo
6.
J Clin Biochem Nutr ; 54(2): 67-74, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24688213

RESUMO

Scavenging rate constants of eight hydrophilic antioxidants, including caffeic acid, chlorogenic acid, genistein, glutathione, N-acetylcysteine, rutin, trolox, and uric acid against multiple ROS, namely superoxide anion, hydroxyl radical, singlet oxygen, and alkoxyl radical were determined with the electron spin resonance method. Direct flash photolysis measurement of the second-order rate constant in the reaction of alkoxyl radical plus the spin trap 5,5-dimethyl-pyrroline N-oxide made it possible to evaluate scavenging rate constants in antioxidants. The magnitudes of scavenging rate constants were notably dependent on the character of each ROS and the overall rate constants were highest in hydroxyl radical scavenging and the lowest in superoxide anion. The highest scavenging rate constant against superoxide anion was obtained by chlorogenic acid (2.9 × 10(5) M(-1) s(-1)) and the lowest was by N-acetylcysteine (5.0 × 10(2) M(-1) s(-1)). For singlet oxygen, the highest was by glutathione (9.4 × 10(8) M(-1) s(-1)) and the lowest was by uric acid (2.3 × 10(6) M(-1) s(-1)). All other numbers are listed and illustrated. Redox potential measurements of the antioxidants indicated that the antioxidants are likely to react with superoxide anion and singlet oxygen through electron transfer processes.

7.
Int J Neuropsychopharmacol ; 17(5): 739-51, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24345557

RESUMO

Serotonin 2C receptors (5-HT(2C)R) are G-protein-coupled receptors with various actions, including involvement in drug addiction. 5-HT2CR undergoes mRNA editing, converting genomically encoded adenosine residues to inosines via adenosine deaminases acting on RNA (ADARs). Here we show that enhanced alcohol drinking behaviour in mice is associated with the degree of 5-HT(2C)R mRNA editing in the nucleus accumbens and dorsal raphe nuceus, brain regions important for reward and addiction. Following chronic alcohol vapour exposure, voluntary alcohol intake increased in C57BL/6J mice, but remained unchanged in C3H/HeJ and DBA/2J mice. 5-HT(2C)R mRNA editing frequency in both regions increased significantly in C57BL/6J mice, as did expressions of 5-HT(2C)R, ADAR1 and ADAR2, but not in other strains. Moreover, mice that exclusively express the unedited isoform (INI) of 5-HT(2C)R mRNA on a C57BL/6J background did not exhibit increased alcohol intake compared with wild-type mice. Our results indicate that alterations in 5-HT(2C)R mRNA editing underlie alcohol preference in mice.


Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Núcleo Accumbens/metabolismo , Edição de RNA , Núcleos da Rafe/metabolismo , Receptor 5-HT2C de Serotonina/metabolismo , Adenosina Desaminase/metabolismo , Consumo de Bebidas Alcoólicas/genética , Animais , Immunoblotting , Isomerismo , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , RNA Mensageiro/metabolismo , Receptor 5-HT2C de Serotonina/genética , Especificidade da Espécie
8.
Arch Virol ; 159(2): 267-75, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23979178

RESUMO

To enhance the effect of anti-influenza-virus agent treatment, the effect of combined administration of oseltamivir phosphate and hochu-ekki-to (Japanese traditional herbal medicine, HET) on early viral clearance was examined. Senescence-accelerated mice were given HET in drinking water for 2 weeks, followed by intranasal infection with influenza A virus strain PR8. After 4 hours of infection, oseltamivir was administered orally for 5 days. The viral loads in the lungs of the group receiving combined treatment were dramatically lower when compared with the viral loads in the lungs of the group receiving oseltamivir alone. HET significantly increased the induction of IL-1ß and TNF-α in the lungs of PR8-infected mice and stimulated alveolar macrophage phagocytosis. From these results, we conclude that these functions may be responsible the increased effect on viral load reduction. Here, we show that the combined administration of oseltamivir and HET is very useful for influenza treatment in senescence-accelerated mice.


Assuntos
Antivirais/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Fatores Imunológicos/administração & dosagem , Pulmão/virologia , Infecções por Orthomyxoviridae/tratamento farmacológico , Oseltamivir/administração & dosagem , Carga Viral , Administração Oral , Envelhecimento , Animais , Modelos Animais de Doenças , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Vírus da Influenza A/isolamento & purificação , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Infecções por Orthomyxoviridae/virologia , Resultado do Tratamento
9.
Neurol Res ; 36(1): 47-52, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24083683

RESUMO

OBJECTIVES: Elevated expression of transforming growth factor (TGF)-beta1 has been reported in hereditary cerebral small-vessel (HCSV) disease. The aim of this study was to clarify whether TGF-beta1 is a risk factor for intracranial deep white matter lesions (DWLs) and their progression in a general elderly population. METHODS: The subjects included 81 participants (Groups DWL, DWLP, and C) who had voluntarily undergone a health examination and brain magnetic resonance imaging (MRI) in 2003 and 2008 and 43 age-matched patients with previous symptomatic brain infarctions. Deep white matter lesions were graded from Grade 0 to 3 according to the Fazekas classification. Group DWL (23 subjects) was defined as DWLs with no progression in the grade level, and Group DWLP (progression of DWL) (12 subjects) was defined as DWLs with an increase in one or more grade number and an apparent worsening of Grade 3. Forty-six age-matched control subjects with consistent normal brain MRI were included in Group C. The associations between DWLs and various vascular risk factors, including peripheral blood TGF-beta1 levels, were examined. RESULTS: In addition to the classical risk factors, the highest TGF-beta1 levels were found in Group DWLP. The TGF-beta1 levels were significantly higher in Group DWLP than in Group DWL, and DWLP was significantly correlated with elevated TGF-beta1 levels (odds ratio [OR]  =  1·72). CONCLUSIONS: The present data suggest that TGF-beta1 may be important in the pathogenesis and progression of DWLs, and it is expected to be useful as a clinical indicator reflecting the presence of intracranial white matter lesions.


Assuntos
Encefalopatias/sangue , Encefalopatias/patologia , Encéfalo/patologia , Fibras Nervosas Mielinizadas/patologia , Fator de Crescimento Transformador beta1/sangue , Idoso , Progressão da Doença , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Razão de Chances , Projetos Piloto , Fatores de Risco , Índice de Gravidade de Doença
10.
Arch Oral Biol ; 58(7): 880-6, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23452546

RESUMO

OBJECTIVE: ß-cryptoxanthin (ß-cry) is a type of carotenoid found in certain fruits and vegetables. Although it has been shown that ß-cry inhibits alveolar bone resorption, the molecular mechanisms for this have not yet been clarified. In the present study, we investigated the effects of ß-cry on bone resorption related-cytokine production in human periodontal ligament (hPDL) cells. DESIGN: hPDL cells were stimulated with ß-cry (1×10(-7)mol/l), mechanical stress (1 or 6MPa), and P. gingivalis. The production of interleukin (IL)-1ß, IL-6, IL-8, tumour necrosis factor (TNF)-α, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) were analyzed by RT-PCR and ELISA. RESULTS: The production of IL-1ß, IL-6, IL-8, and TNF-α was not induced in hPDL cells after stimulation with ß-cry, although these cytokines were produced after stimulation with P. gingivalis. On the other hand, IL-6 and IL-8 were produced after exposure to 6MPa of mechanical stress. The production of IL-6 and IL-8 was significantly decreased by the addition of ß-cry. Furthermore, ß-cry up-regulated the production of OPG, but not RANKL. CONCLUSION: ß-cry inhibited the production of IL-6 and IL-8 induced by mechanical stress and periodontopathogenic bacteria in hPDL cells. Moreover, ß-cry up-regulated OPG production. These results suggest that ß-cry may prevent bone resorption in periodontitis.


Assuntos
Reabsorção Óssea/prevenção & controle , Citocinas/biossíntese , Ligamento Periodontal/efeitos dos fármacos , Periodontite/fisiopatologia , Xantofilas/farmacologia , Infecções por Bacteroidaceae , Células Cultivadas , Criptoxantinas , Citocinas/genética , Ensaio de Imunoadsorção Enzimática , Expressão Gênica , Humanos , Osteoprotegerina/biossíntese , Ligamento Periodontal/citologia , Porphyromonas gingivalis/patogenicidade , RNA Mensageiro/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estresse Mecânico , Regulação para Cima
11.
Arch Oral Biol ; 56(11): 1290-8, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21683342

RESUMO

OBJECTIVES: Although an association between periodontitis and cardiovascular diseases has been suggested, the role of Porphyromonas gingivalis in cardiovascular diseases is not clear. In this study, we examined whether experimental bacteremia of P. gingivalis causes cardiovascular diseases and investigated the mechanism of pathogenesis of cardiovascular diseases induced by P. gingivalis. DESIGN: C57BL/6 mice were intravenously inoculated with 2.0 × 10(8)CFU of P. gingivalis A7436 strain. Mice were sacrificed at specified days and their hearts were collected. The collected organs were divided into two halves and used for histological evaluation and cytokine analysis. IL-17A(-/-), IFN-γ(-/-) and TNF-α(-/-) mice were also intravenously inoculated and the histological changes of hearts in mice were examined. RESULTS: Myocarditis and/or myocardial infarction were observed in mice injected with P. gingivalis. The levels of IL1-ß, IL-6, IL-17A, IL-18, TNF-α and IFN-γ mRNA increased significantly after P. gingivalis injection. In particular, high levels of IL-17A and IFN-γ mRNA expression were observed in hearts of mice after P. gingivalis injection in comparison with these levels before injection. Furthermore, the production of IL-17A was detected in hearts of wild-type mice after P. gingivalis injection. In wild-type, TNF-α(-/-) and IFN-γ(-/-) mice, moderate infiltration of neutrophils and monocytes was observed in hearts at 5 days after injection. In contrast, no inflammatory findings were observed in hearts of IL-17A(-/-) mice. CONCLUSION: We have demonstrated that an experimental bacteremia of P. gingivalis could induce myocarditis and/or myocardial infarction in mice, and IL-17A plays an important role in the pathogenesis of these diseases.


Assuntos
Interleucina-17/fisiologia , Infarto do Miocárdio/microbiologia , Miocardite/microbiologia , Porphyromonas gingivalis/patogenicidade , Animais , Bacteriemia/microbiologia , Interferon gama/biossíntese , Interferon gama/genética , Interleucina-17/biossíntese , Interleucina-17/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Organismos Livres de Patógenos Específicos , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genética
12.
J Gastroenterol Hepatol ; 26(2): 398-404, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21261732

RESUMO

BACKGROUND AND AIMS: The pathogenesis of enteropathy induced by non-steroidal anti-inflammatory drugs (NSAIDs) is still unclear, and there are no established treatments. Interleukin-17A (IL-17A) is a pro-inflammatory cytokine that has been associated with the development of chronic inflammatory diseases, including autoimmune diseases. To define the role of IL-17A in small intestinal injury and inflammation, we studied the effects of indomethacin administration in mice with targeted deletions of the IL-17A gene. METHODS: Male C57BL/6 (wild-type) and homozygous IL-17A(-/-) C57BL/6 mice were subjected to this study. Indomethacin (10 mg/kg) was subcutaneously administered to induce small-intestinal damage. Indomethacin-induced lesions in the small intestine were evaluated by measuring the injured area and by histopathology. Also assessed were myeloperoxidase (MPO) activity, as an index of neutrophil accumulation, and intestinal mRNA expression for inflammatory cytokines. RESULTS: The area of macroscopic ulcerative lesions, the MPO activity and the mRNA expression of inflammatory-associated chemokines, such as keratinocyte chemoattractant (KC), monocyte chemotactic protein-1 (MCP-1), and granulocyte-colony stimulating factor (G-CSF), were significantly increased in indomethacin-treated groups compared with the sham groups. The development of intestinal lesions by indomethacin was inhibited in IL-17A(-/-) mice compared with wild-type mice, together with significant suppression of the increased levels of MPO activities and KC, MCP-1, and G-CSF levels. CONCLUSION: These findings demonstrate that IL-17A contributes to the development of indomethacin-induced small intestinal injury through upregulation of G-CSF, KC, and MCP-1. IL-17A might be a promising new therapeutic target to treat NSAID-induced enteritis.


Assuntos
Anti-Inflamatórios não Esteroides , Íleo/imunologia , Indometacina , Interleucina-17/deficiência , Jejuno/imunologia , Úlcera Péptica/prevenção & controle , Animais , Quimiocina CCL2/genética , Quimiocina CXCL1/genética , Modelos Animais de Doenças , Fator Estimulador de Colônias de Granulócitos/genética , Íleo/patologia , Mediadores da Inflamação/metabolismo , Interleucina-17/genética , Jejuno/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infiltração de Neutrófilos , Neutrófilos/enzimologia , Neutrófilos/imunologia , Úlcera Péptica/induzido quimicamente , Úlcera Péptica/genética , Úlcera Péptica/imunologia , Úlcera Péptica/patologia , Peroxidase/metabolismo , RNA Mensageiro/metabolismo , Fatores de Tempo
13.
Int J Mol Med ; 27(3): 353-9, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21249312

RESUMO

The pathogenesis of small intestinal damage caused by non-steroidal anti-inflammatory drugs (NSAIDs) such as indomethacin is still unclear. For this reason, there is currently no therapeutic strategy for ameliorating such damage. On the other hand, molecular treatment strategies targeting tumor necrosis factor (TNF)-α exert beneficial effects on intestinal lesions in patients with inflammatory bowel disease (IBD). To clarify the participation of TNF-α in NSAID-induced small intestinal damage, we investigated the effects of indomethacin administration in mice with targeted deletion of the TNF-α gene. Indomethacin (10 mg/kg) was administered subcutaneously to male C57BL/6 (wild-type: WT) mice and TNF-α-deficient (TNF-α-/-) mice to induce small intestinal damage. The ulcer score, the tissue-associated myeloperoxidase (MPO) activity as an index of neutrophil infiltration, and the expression of keratinocyte chemoattractant (KC) mRNA in the small intestinal mucosa were measured. In addition, we performed a TUNEL assay to evaluate indomethacin-induced apoptosis of intestinal epithelial cells and measured the expression of caspase-3 protein and Bcl-2 mRNA. The ulcer score, MPO activity, and expression of KC mRNA were significantly increased after indomethacin administration. These increases were significantly inhibited in TNF-α-/- mice compared with WT mice. Apoptotic cells were observed by the TUNEL assay in the area of the ulcerative lesion, and they were significantly fewer in TNF-α-/- mice compared with WT mice. The expression of cleaved caspase-3 protein was induced by indomethacin administration, and significantly inhibited in TNF-α-/- mice compared with that of WT mice. The expression level of Bcl-2 mRNA in indomethacin-treated TNF-α-/- mice was significantly higher than that in WT mice. TNF-α plays an important role in the pathogenesis of indomethacin-induced small intestinal damage. These results suggest that TNF-α could become a new therapeutic target for NSAID-induced small intestinal damage.


Assuntos
Apoptose/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Indometacina/efeitos adversos , Doenças Inflamatórias Intestinais/imunologia , Intestino Delgado/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Anti-Inflamatórios não Esteroides , Apoptose/genética , Apoptose/imunologia , Caspase 3 , Quimiocina CXCL1/biossíntese , Quimiocina CXCL1/genética , Quimiocina CXCL1/imunologia , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Deleção de Genes , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/imunologia , Indometacina/farmacologia , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/imunologia , Mucosa Intestinal/lesões , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Intestino Delgado/lesões , Intestino Delgado/patologia , Masculino , Camundongos , Camundongos Knockout , Peroxidase/genética , Peroxidase/imunologia , Peroxidase/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/imunologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , RNA Mensageiro/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/genética
14.
Food Chem ; 129(3): 866-70, 2011 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25212311

RESUMO

Nitric oxide (NO)-scavenging capacities of several hydrophilic antioxidants were determined by using the PTIO method, a competitive NO-scavenging method with 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO). Relative NO-scavenging rates of antioxidants were measured with respect to PTIO and the scavenging rate constants were calculated based on PTIO's rate constant. Results indicated that NO-scavenging rate constants of the antioxidants were: uric acid (2.5)>caffeic acid (1.2)>trolox (1.0)>genistein (0.19)>glutathione (0) ≈N-acetylcysteine (0), where the numbers are expressed in trolox equivalent unit. The oxidation potentials of these antioxidants were measured and the order in the magnitude of oxidation potential was in good accordance with NO-scavenging capacity. Based on the results, we have suggested that the primary chemical process of the antioxidant reaction with NO can be characterised with the electron transfer from NO to the antioxidant.

15.
Arch Oral Biol ; 56(3): 251-7, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20970115

RESUMO

OBJECTIVE: We have previously reported that human periodontal ligament (hPDL) cells produced many kinds of cytokines as a result of bacterial stimulation, including stimulation with Porphyromonas gingivalis (P. gingivalis). However, the effects of mechanical stress on cytokine production in hPDL cells stimulated by periodontopathogenic bacteria are not clearly understood. In this study, we investigated the effects of mechanical stress on the production of inflammatory cytokines in hPDL cells induced by stimulation with P. gingivalis. METHODS: The hPDL cells were exposed to various levels of mechanical stress (1, 6, 10 and 50MPa) and costimulated with mechanical stress and P. gingivalis for 24h. Cytokine mRNA expressions were determined by RT-PCR. Cytokines in the culture supernatant were assessed by ELISA, and morphologic changes in hPDL cells were observed. RESULTS: The expressions of interleukin (IL)-6, IL-8 and tumor necrosis factor-α mRNA were observed in hPDL cells after exposure to mechanical stress. Moreover, the production of IL-6 and IL-8 increased significantly after exposure to mechanical stress ranging from 1 to 10MPa. The amount of IL-8 in the culture supernatants of hPDL cells costimulated with P. gingivalis and mechanical stress was significantly higher than the expected additive amount. The morphology of hPDL cells did not change after exposure to 6MPa, but these cells were partly detached from the Petri dish after exposure to 50MPa. CONCLUSIONS: These results suggest that local inflammation of the periodontal ligament may be induced mainly by periodontal bacteria, and mechanical stress may promote local inflammation.


Assuntos
Interleucina-6/biossíntese , Interleucina-8/biossíntese , Ligamento Periodontal/metabolismo , Periodontite/etiologia , Porphyromonas gingivalis/fisiologia , Estresse Mecânico , Células Cultivadas , Feminino , Humanos , Pressão Hidrostática , Interleucina-1beta/biossíntese , Lipopolissacarídeos , Masculino , Ligamento Periodontal/citologia , Ligamento Periodontal/microbiologia , Ligamento Periodontal/fisiopatologia , RNA Mensageiro/biossíntese , Fator de Necrose Tumoral alfa/biossíntese , Adulto Jovem
16.
J Interferon Cytokine Res ; 29(11): 729-34, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19642908

RESUMO

The mechanism of the inflammatory response in the vascular wall in atherothrombosis and during the progression of atherosclerosis has attracted attention. We focused on the potential usefulness of inflammatory markers in chronic recurrent brain infarction, and analyzed the role of inflammatory markers in atherosclerosis of the intracranial artery. The subjects were 2 groups of patients treated between 2004 and 2006: a group of outpatients with recurrent infarction (group RI), who developed atherothrombotic brain infarction twice; another group of outpatients with brain infarction without recurrence (group BI), who developed brain infarction once and remained free of recurrence for >1 year; and a group of control subjects with normal brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) (group C). Plasma samples were collected from each group of patients for the simultaneous measurement of 17 kinds of candidate inflammatory markers, using a fluorescent microbead array system, and the results were compared with head MRA findings. The levels of high-sensitivity C-reactive protein (hsCRP) and monocyte chemoattractant protein-1 (MCP-1) were significantly higher in group RI patients than in groups C and BI. Subjects with a hsCRP level > or =0.3 and a MCP-1 level > or =200 in the serum have, respectively, a 1.92 and 2.98 relative risk to have a potential recurrent infarction. Regarding the relation of inflammatory marker levels with MRA findings, group RI showed significantly higher levels of hsCRP at M1 lesions and MCP-1 at A1 and M1 lesions than group BI (P < 0.05). In conclusion, the MCP-1 level as well as hsCRP in the blood can be a potential predictive marker of recurrent thrombotic brain infarction, and may reflect inflammation that promotes intracranial large-artery atherosclerosis.


Assuntos
Biomarcadores/metabolismo , Infarto Encefálico/diagnóstico , Proteína C-Reativa/metabolismo , Quimiocina CCL2/sangue , Mediadores da Inflamação/metabolismo , Idoso , Infarto Encefálico/sangue , Infarto Encefálico/patologia , Infarto Encefálico/fisiopatologia , Progressão da Doença , Feminino , Humanos , Arteriosclerose Intracraniana , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Recidiva
17.
Microbiol Immunol ; 53(5): 287-94, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19457170

RESUMO

Periapical lesions are induced by bacterial infection of the dental pulp and result in destruction of the surrounding alveolar bone. Although various immunological studies concerning periapical bone resorption have been reported, the role of cytokines in the formation of periapical lesions remains unclear. In this study, the role of IL-17A in periapical lesions in mice was investigated. Normal C57BL/6, IFN-gamma(-/-), TNF-alpha(-/-), and IL-17A(-/-) mice were subjected to pulp exposure and infected with Prevotella intermedia (ATCC25611) and Porphyromonas gingivalis (ATCC33277) in the mandibular first molar. Periapical lesions were determined by muCT on day 21 after infection, and 3D visual construction was performed using 3D picture quantification software. The expression of IL-17A mRNA in periapical lesions was determined by the RT-PCR and real-time RT-PCR method. Periapical lesions developed in wild-type, IFN-gamma(-/-), and TNF-alpha(-/-) mice after infection with P. intermedia and P. gingivalis. However, periapical lesions were not observed in IL-17A(-/-) mice. The expression of IL-17A mRNA was significantly induced in periapical lesions of wild-type mice after infection. These results suggest that IL-17A, but not IFN-gamma or TNF-alpha, plays an important role in the formation of periapical lesions.


Assuntos
Infecções por Bacteroidaceae/imunologia , Reabsorção Óssea , Interleucina-17/imunologia , Doenças Periapicais/imunologia , Animais , Infecções por Bacteroidaceae/diagnóstico por imagem , Infecções por Bacteroidaceae/microbiologia , Infecções por Bacteroidaceae/fisiopatologia , Feminino , Expressão Gênica , Interleucina-17/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Camundongos Knockout , Doenças Periapicais/diagnóstico por imagem , Doenças Periapicais/microbiologia , Doenças Periapicais/fisiopatologia , Porphyromonas gingivalis/imunologia , Prevotella intermedia/imunologia , Tomografia Computadorizada por Raios X
18.
Evid Based Complement Alternat Med ; 6(1): 123-8, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18955225

RESUMO

We examined how aromatherapy massage influenced psychologic and immunologic parameters in 12 breast cancer patients in an open semi-comparative trial. We compared the results 1 month before aromatherapy massage as a waiting control period with those during aromatherapy massage treatment and 1 month after the completion of aromatherapy sessions. The patients received a 30 min aromatherapy massage twice a week for 4 weeks (eight times in total). The results showed that anxiety was reduced in one 30 min aromatherapy massage in State-Trait Anxiety Inventory (STAI) test and also reduced in eight sequential aromatherapy massage sessions in the Hospital Anxiety and Depression Scale (HADS) test. Our results further suggested that aromatherapy massage ameliorated the immunologic state. Further investigations are required to confirm the anxiolytic effect of aromatherapy in breast cancer patients.

19.
Kidney Int ; 75(1): 96-103, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18843261

RESUMO

Patients on hemodialysis often have gastrointestinal complications; however, it is unclear if Helicobacter pylori infection is present in these patients. Here we determined the prevalence of H. pylori infection in 539 Japanese hemodialysis patients by measuring serum anti-H. pylori IgG antibodies. Endoscopy was performed on 299 of these patients and the results were compared to 400 patients with normal renal function who had also undergone endoscopy and sero-testing. A second cohort of 478 dialysis patients, within the original group, was checked serologically for H. pylori infection three times over a four-year observation period. The prevalence of infection in these patients was significantly lower than in those patients with normal renal function, irrespective of the clinical outcomes. The prevalence of H. pylori infection significantly decreased as the duration of dialysis increased, particularly within the first four years following initiation of dialysis. About one-third of patients on dialysis for less than four years became serologically negative for H. pylori infection within this observation period. Our study suggests that although long-term dialysis patients have low prevalence of H. pylori, they still have significant gastroduodenal diseases, such as peptic ulcers, that require endoscopic follow-up.


Assuntos
Infecções por Helicobacter/epidemiologia , Falência Renal Crônica/complicações , Diálise Renal , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Grupo com Ancestrais do Continente Asiático , Endoscopia , Helicobacter pylori/isolamento & purificação , Humanos , Falência Renal Crônica/epidemiologia , Pessoa de Meia-Idade , Prevalência
20.
J Colloid Interface Sci ; 332(1): 194-200, 2009 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-19101674

RESUMO

It has been observed that, at 25.0+/-0.1 degrees C, [Co(NH(3))(6)](ClO(4))(3), [Co(en)(3)](ClO(4))(3), [Co(bpy)(3)](ClO(4))(3), and [Co(phen)(3)](ClO(4))(3) in the regions of 1.25-5.00 mM aqueous solutions cause a significant surface tension reduction (STR) of water by the surfactants, sodium dodecylsulfate (SDS) and sodium dodecylbenzenesulfonate (SBS), suggesting the formation of the 1:1 and 1:2 association complexes, {[complex](3+)(S(-))}(2+) and {[complex](3+)(S(-))(2)}(+) where [complex](3+)=[Co(NH(3))(6)](3+), [Co(en)(3)](3+), [Co(bpy)(3)](3+), or [Co(phen)(3)](3+), S(-)=DS(-) or BS(-). The effect of [Co(en)(3)](3+) on STR in SDS-water system is the largest due to a strong hydrophilic interaction between amino protons of [Co(en)(3)](3+) and sulfate oxygen atoms of DS(-). The effects of [Co(en)(3)](3+), [Co(bpy)(3)](3+), and [Co(phen)(3)](3+) on STR in SBS-water system are significant and almost same, meaning that the hydrophilic interaction between [Co(en)(3)](3+) and the sulfonate group is comparable to the hydrophobic interaction between [Co(bpy)(3)](3+) or [Co(phen)(3)](3+) and the phenyl group of BS(-). The Co(III) complexes of 1.25-5.00 mM are precipitated as {[complex](3+)(S(-))(3)} at 0.0295-0.173 mM of S(-). The precipitates, {[Co(bpy)(3)](3+)(S(-))(3)} and {[Co(phen)(3)](3+)(S(-))(3)} can be dissolved at higher molar ratio of [S(-)]/[complex(3+)] than 3.5 for SDS and 4.0 for SBS. This observation suggests that the aggregated premicelle [Co(bpy or phen)(3)](2)(DS)(-)(7) or aggregated premicelle [Co(bpy or phen)(3)](BS)(-)(4) is formed.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...