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[PMID]:29412476
[Au] Autor:Bakela K; Dimakopoulou M; Batsou P; Manidakis N; Athanassakis I
[Ad] Endereço:Laboratory of Immunology, Department of Biology, University of Crete, Heraklion, Crete, Greece.
[Ti] Título:Soluble MHC class II-driven therapy for a systemic lupus erythematosus murine experimental in vitro and in vivo model.
[So] Source:Scand J Immunol;87(3), 2018 Mar.
[Is] ISSN:1365-3083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Taking into consideration the multiparametric nature of systemic lupus erythematosus (SLE), the severity and variability of symptoms and the lack of effective therapeutic approaches, this study took advantage of the recently described role of soluble major histocompatibility complex class II (sMHCII) molecules in maintaining tolerance to the organism and attempted to apply sMHCII proteins as a treatment to murine SLE experimental models in vitro as well as in vivo. After breaking tolerance to DNA in vitro, which was accompanied by development of specific anti-dsDNA antibodies, syngeneic or allogeneic sMHCII molecules, purified from healthy mouse serum, could significantly reduce the specific antibody levels and drive the system towards immunosuppression, as assessed by specific marker analysis on T cells and cytokine production by flow cytometry and ELISA, respectively. The in vivo experimental model consisted of pristane-induced SLE symptoms to BALB/c mice, which developed maximal levels of anti-dsDNA 2 months after pristane inoculation. Syngeneic or allogeneic sMHCII administration could alleviate pristane-induced symptoms, significantly decrease specific anti-dsDNA antibody production and develop immunosuppression to the host, as manifested by increase of CD4 + CTLA-4 +  and CD4 + CD25 +  cell populations in the spleen. Thus, the results presented in this study introduced the ability of sMHCII proteins to suppress specific autoantigen response, opening new areas of research and offering novel therapeutic approaches to SLE with expanding features to other autoimmune diseases.
[Mh] Termos MeSH primário: Anticorpos Antinucleares/imunologia
Autoantígenos/imunologia
Antígenos de Histocompatibilidade Classe II/imunologia
Tolerância Imunológica/imunologia
Imunoterapia/métodos
Lúpus Eritematoso Sistêmico/imunologia
Lúpus Eritematoso Sistêmico/terapia
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Animais
Antígenos CD4/metabolismo
Antígeno CTLA-4/metabolismo
Células Cultivadas
DNA/imunologia
Modelos Animais de Doenças
Imunossupressão
Subunidade alfa de Receptor de Interleucina-2/metabolismo
Lúpus Eritematoso Sistêmico/induzido quimicamente
Camundongos
Camundongos Endogâmicos BALB C
Baço/citologia
Baço/imunologia
Terpenos/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Antinuclear); 0 (Autoantigens); 0 (CD4 Antigens); 0 (CTLA-4 Antigen); 0 (Histocompatibility Antigens Class II); 0 (Il2ra protein, mouse); 0 (Interleukin-2 Receptor alpha Subunit); 0 (Terpenes); 26HZV48DT1 (pristane); 9007-49-2 (DNA)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180208
[St] Status:MEDLINE
[do] DOI:10.1111/sji.12644


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[PMID]:29332223
[Au] Autor:Togasaki E; Shimizu N; Nagao Y; Kawajiri-Manako C; Shimizu R; Oshima-Hasegawa N; Muto T; Tsukamoto S; Mitsukawa S; Takeda Y; Mimura N; Ohwada C; Takeuchi M; Sakaida E; Iseki T; Yoshitomi H; Ohtsuka M; Miyazaki M; Nakaseko C
[Ad] Endereço:Department of Hematology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan.
[Ti] Título:Long-term efficacy of partial splenic embolization for the treatment of steroid-resistant chronic immune thrombocytopenia.
[So] Source:Ann Hematol;97(4):655-662, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Thrombopoietin-receptor agonists have been recently introduced for a second-line treatment of immune thrombocytopenia (ITP). Splenectomy has tended to be avoided because of its complications, but the response rate of splenectomy is 60-80% and it has still been considered for steroid-refractory ITP. We performed partial splenic embolization (PSE) as an alternative to splenectomy. Between 1988 and 2013, 91 patients with steroid-resistant ITP underwent PSE at our hospital, and we retrospectively analyzed the efficacy and long-term outcomes of PSE. The complete response rate (CR, platelets > 100 × 10 /L) was 51% (n = 46), and the overall response rate (CR plus response (R), > 30 × 10 /L) was 84% (n = 76). One year after PSE, 70% of patients remained CR and R. The group with peak platelet count after PSE ≥ 300 × 10 /L (n = 29) exhibited a significantly higher platelet count than the group with platelet count < 300 × 10 /L (n = 40) at any time point after PSE. The failure-free survival (FFS) rates at 1, 5, and 10 years were 78, 56, and 52%, respectively. Second PSE was performed in 20 patients who relapsed (n = 14) or had no response to the initial PSE (n = 6), and the overall response was achieved in 63% patients. There were no PSE-related deaths. These results indicate that PSE is a safe and effective alternative therapy to splenectomy for patients with steroid-resistant ITP as it generates long-term, durable responses.
[Mh] Termos MeSH primário: Embolização Terapêutica
Púrpura Trombocitopênica Idiopática/terapia
Baço/irrigação sanguínea
[Mh] Termos MeSH secundário: Adolescente
Corticosteroides/uso terapêutico
Adulto
Idoso
Idoso de 80 Anos ou mais
Intervalo Livre de Doença
Resistência a Medicamentos
Resistência a Múltiplos Medicamentos
Embolização Terapêutica/efeitos adversos
Feminino
Seguimentos
Hospitais Universitários
Seres Humanos
Japão
Masculino
Meia-Idade
Tamanho do Órgão
Púrpura Trombocitopênica Idiopática/diagnóstico por imagem
Púrpura Trombocitopênica Idiopática/tratamento farmacológico
Púrpura Trombocitopênica Idiopática/patologia
Estudos Retrospectivos
Baço/diagnóstico por imagem
Baço/efeitos dos fármacos
Baço/patologia
Esteroides/uso terapêutico
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Adrenal Cortex Hormones); 0 (Steroids)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180115
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-018-3232-x


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[PMID]:29200850
[Au] Autor:Aliu H; Rask C; Brimnes J; Andresen TL
[Ad] Endereço:Immunology Department, In vivo Biology Team, ALK Abelló A/S, Hørsholm.
[Ti] Título:Enhanced efficacy of sublingual immunotherapy by liposome-mediated delivery of allergen.
[So] Source:Int J Nanomedicine;12:8377-8388, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:Immunotherapy by sublingual administration of allergens provides high patient compliance and has emerged as an alternative to subcutaneous immunotherapy for the treatment of IgE-associated allergic diseases. However, sublingual immunotherapy (SLIT) can cause adverse events. Development of allergen delivery systems enabling more efficient delivery and hence lower allergen load might reduce the adverse events. In the present study, we have investigated neutral and cationic liposomes as delivery systems of ovalbumin (OVA), as a model allergen, in an OVA-induced allergic airway inflammation model. We investigated the liposome carriers' ability to improve tolerance induction of antigens compared to the corresponding dose of free OVA. Mice were treated sublingually over 2 weeks with free or liposome encapsulated OVA followed by intraperitoneal injections and intranasal challenge. Mice sublingually treated with OVA-liposomes showed a significant reduction of airway eosinophilia and splenocyte proliferation in comparison to free OVA. A similar nonsignificant pattern was seen for OVA-specific IgE antibodies. In addition, reduced levels of interferon-γ and interleukin-5 were observed in spleen cell culture supernatants from OVA-liposome-treated mice compared to the sham-treated group. In conclusion, in vivo efficacy data showed that prophylactic SLIT with OVA-liposomes is significantly more effective in preventing allergic inflammation than the corresponding dose of free OVA.
[Mh] Termos MeSH primário: Alérgenos/administração & dosagem
Sistemas de Liberação de Medicamentos
Imunoterapia Sublingual
[Mh] Termos MeSH secundário: Alérgenos/imunologia
Animais
Citocinas/metabolismo
Ensaio de Imunoadsorção Enzimática
Feminino
Lipídeos/química
Lipossomos
Camundongos Endogâmicos BALB C
Ovalbumina/imunologia
Pneumonia/imunologia
Pneumonia/patologia
Pneumonia/prevenção & controle
Baço/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Allergens); 0 (Cytokines); 0 (Lipids); 0 (Liposomes); 9006-59-1 (Ovalbumin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171205
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S137033


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[PMID]:28468914
[Au] Autor:Engel C; Brügmann G; Lambing S; Mühlenbeck LH; Marx S; Hagen C; Horváth D; Goldeck M; Ludwig J; Herzner AM; Drijfhout JW; Wenzel D; Coch C; Tüting T; Schlee M; Hornung V; Hartmann G; Van den Boorn JG
[Ad] Endereço:Institute for Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn, Bonn, Germany.
[Ti] Título:RIG-I Resists Hypoxia-Induced Immunosuppression and Dedifferentiation.
[So] Source:Cancer Immunol Res;5(6):455-467, 2017 Jun.
[Is] ISSN:2326-6074
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A hypoxic tumor microenvironment is linked to poor prognosis. It promotes tumor cell dedifferentiation and metastasis and desensitizes tumor cells to type-I IFN, chemotherapy, and irradiation. The cytoplasmic immunoreceptor retinoic acid-inducible gene-I (RIG-I) is ubiquitously expressed in tumor cells and upon activation by 5'-triphosphate RNA (3pRNA) drives the induction of type I IFN and immunogenic cell death. Here, we analyzed the impact of hypoxia on the expression of RIG-I in various human and murine tumor and nonmalignant cell types and further investigated its function in hypoxic murine melanoma. 3pRNA-inducible RIG-I-expression was reduced in hypoxic melanoma cells compared with normoxic controls, a phenomenon that depended on the hypoxia-associated transcription factor HIF1α. Still, RIG-I functionality was conserved in hypoxic melanoma cells, whereas responsiveness to recombinant type-I IFN was abolished, due to hypoxia-induced loss of type I IFN receptor expression. Likewise, RIG-I activation in hypoxic melanoma cells, but not exposure to recombinant IFNα, provoked melanocyte antigen-specific CD8 T-cell and NK-cell attack. Scavenging of hypoxia-induced reactive oxygen species by vitamin C restored the inducible expression of RIG-I under hypoxia , boosted anti-melanoma NK- and CD8 T-cell attack, and augmented 3pRNA antitumor efficacy These results demonstrate that RIG-I remains operational under hypoxia and that RIG-I function is largely insensitive to lower cell surface expression of the IFNα receptor. RIG-I function could be fortified under hypoxia by the combined use of 3pRNA with antioxidants. .
[Mh] Termos MeSH primário: Hipóxia/metabolismo
Tolerância Imunológica
Melanoma/metabolismo
Receptores do Ácido Retinoico/metabolismo
[Mh] Termos MeSH secundário: Animais
Antioxidantes/farmacologia
Ácido Ascórbico/farmacologia
Linhagem Celular
Linhagem Celular Tumoral
Feminino
Técnicas de Inativação de Genes
Seres Humanos
Camundongos Endogâmicos C57BL
RNA/farmacologia
Espécies Reativas de Oxigênio/metabolismo
Receptores do Ácido Retinoico/genética
Baço/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antioxidants); 0 (RARRES3 protein, human); 0 (Reactive Oxygen Species); 0 (Receptors, Retinoic Acid); 63231-63-0 (RNA); PQ6CK8PD0R (Ascorbic Acid)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1158/2326-6066.CIR-16-0129-T


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[PMID]:29289273
[Au] Autor:Bhatia K; Maiti A; Chatterjee S
[Ad] Endereço:Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, Texas.
[Ti] Título:Vascular and Splenic Abnormalities in Heterotaxy Syndrome.
[So] Source:Am J Med Sci;355(1):e1, 2018 Jan.
[Is] ISSN:1538-2990
[Cp] País de publicação:United States
[La] Idioma:eng
[Mh] Termos MeSH primário: Síndrome de Heterotaxia/diagnóstico por imagem
Baço
Veia Cava Inferior
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Baço/anormalidades
Baço/diagnóstico por imagem
Veia Cava Inferior/anormalidades
Veia Cava Inferior/diagnóstico por imagem
[Pt] Tipo de publicação:CASE REPORTS; LETTER
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180101
[St] Status:MEDLINE


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[PMID]:27775474
[Au] Autor:Ulndreaj A; Tzekou A; Mothe AJ; Siddiqui AM; Dragas R; Tator CH; Torlakovic EE; Fehlings MG
[Ad] Endereço:1 Division of Genetics and Development, Toronto Western Research Institute and University of Toronto Spinal Program, Krembil Neuroscience Center, University Health Network , Toronto, Ontario, Canada .
[Ti] Título:Characterization of the Antibody Response after Cervical Spinal Cord Injury.
[So] Source:J Neurotrauma;34(6):1209-1226, 2017 Mar 15.
[Is] ISSN:1557-9042
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The immune system plays a critical and complex role in the pathobiology of spinal cord injury (SCI), exerting both beneficial and detrimental effects. Increasing evidence suggests that there are injury level-dependent differences in the immune response to SCI. Patients with traumatic SCI have elevated levels of circulating autoantibodies against components of the central nervous system, but the role of these antibodies in SCI outcomes remains unknown. In rodent models of mid-thoracic SCI, antibody-mediated autoimmunity appears to be detrimental to recovery. However, whether autoantibodies against the spinal cord are generated following cervical SCI (cSCI), the most common level of injury in humans, remains undetermined. To address this knowledge gap, we investigated the antibody responses following cSCI in a rat model of injury. We found increased immunoglobulin G (IgG) and IgM antibodies in the spinal cord in the subacute phase of injury (2 weeks), but not in more chronic phases (10 and 20 weeks). At 2 weeks post-cSCI, antibodies were detected at the injury epicenter and co-localized with the astroglial scar and neurons of the ventral horn. These increased levels of antibodies corresponded with enhanced activation of immune responses in the spleen. Higher counts of antibody-secreting cells were observed in the spleen of injured rats. Further, increased levels of secreted IgG antibodies and enhanced proliferation of T-cells in splenocyte cultures from injured rats were found. These findings suggest the potential development of autoantibody responses following cSCI in the rat. The impact of the post-traumatic antibody responses on functional outcomes of cSCI is a critical topic that requires further investigation.
[Mh] Termos MeSH primário: Autoanticorpos/imunologia
Medula Cervical/lesões
Traumatismos da Medula Espinal/imunologia
[Mh] Termos MeSH secundário: Animais
Células Produtoras de Anticorpos/imunologia
Astrócitos/imunologia
Modelos Animais de Doenças
Feminino
Ratos
Ratos Wistar
Baço/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Autoantibodies)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1089/neu.2016.4498


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[PMID]:29339102
[Au] Autor:Khafaga AF; El-Sayed YS
[Ad] Endereço:Department of Pathology, Faculty of Veterinary Medicine, Alexandria University, Edfina 22758, Egypt. Electronic address: asmaa.khafaga@alexu.edu.eg.
[Ti] Título:Spirulina ameliorates methotrexate hepatotoxicity via antioxidant, immune stimulation, and proinflammatory cytokines and apoptotic proteins modulation.
[So] Source:Life Sci;196:9-17, 2018 Mar 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Methotrexate (MTX) is an efficient cytotoxic drug used against various carcinogenic, inflammatory and autoimmune diseases; however, the hepatotoxicity of MTX limits its use. Therefore, the present study aimed to evaluate the potential hepatoprotective and immune-stimulant effect of Spirulina platensis (SP) against MTX acute toxicity. MAIN METHODS: Thirty-two male Wistar rats were randomly allocated into the following four groups (n = 8): control, SP (500 mg/kg bwt, oral gavage daily for 21 days), MTX (20 mg/kg bwt, single ip injection), and MTX+SP. Hepatic and splenic histoarchitecture, leukocyte counts and serum immunoglobulins were evaluated. Hepatic oxidant/antioxidant status, proinflammatory cytokines (tumor necrosis factor-α, and interleukin 6), and pro-apoptotic proteins (caspase 3 and Bax) immunoexpression were assessed. KEY FINDINGS: MTX induced extensive hepatic necrosis and vacuolation, and sever lymphoid depletion in splenic white pulp with increased levels of serum transaminases, lactate dehydrogenase, and hepatic malondialdehyde, tumor necrosis factor-α and interleukin 6; and number of caspase 3- and Bax-positive hepatocytes. A significant decrease in leukocyte counts, serum immunoglobulins (IgA, IgM and IgG) level, and hepatic antioxidant enzymes (GSH, GPx, SOD, and CAT) was also detected. Pretreatment with SP resulted in significant improvements in hepatic and splenic histologic architecture, as well as restoring liver enzymes and reduction of lipid peroxidation product, proinflammatory cytokines, and caspase 3 and Bax immunoexpression. Additionally, a significant increase in antioxidant enzymes, serum immunoglobulins, and total leukocyte counts was demonstrated. SIGNIFICANCE: SP possesses promising antioxidant, anti-inflammatory, anti-apoptotic and immune stimulatory properties against MTX-induced hepatotoxicity and immunosuppression.
[Mh] Termos MeSH primário: Adjuvantes Imunológicos/farmacologia
Antimetabólitos/toxicidade
Antioxidantes/farmacologia
Proteínas Reguladoras de Apoptose/antagonistas & inibidores
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle
Citocinas/antagonistas & inibidores
Metotrexato/antagonistas & inibidores
Metotrexato/toxicidade
Extratos Vegetais/farmacologia
Spirulina/química
[Mh] Termos MeSH secundário: Animais
Contagem de Leucócitos
Peroxidação de Lipídeos/efeitos dos fármacos
Masculino
Necrose
Ratos
Ratos Wistar
Baço/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adjuvants, Immunologic); 0 (Antimetabolites); 0 (Antioxidants); 0 (Apoptosis Regulatory Proteins); 0 (Cytokines); 0 (Plant Extracts); YL5FZ2Y5U1 (Methotrexate)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE


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[PMID]:29443746
[Au] Autor:Wang Z; Liu X; Xu H; Qu L; Zhang D; Gao P
[Ad] Endereço:Department of Hepatology.
[Ti] Título:Platelet count to spleen thickness ratio is related to histologic severity of primary biliary cholangitis.
[So] Source:Medicine (Baltimore);97(7):e9843, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to evaluate the ability of noninvasive markers to identify the histological severity of primary biliary cholangitis (PBC).Fifty-eight treatment-naïve PBC patients who had undergone liver biopsy were enrolled in our study. The patients' histological stages were based on the classifications of Ludwig and Scheuer. Aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis index based on the 4 factors (FIB-4), red blood cell distribution width to platelet ratio (RPR), and platelet count to spleen thickness (PC/ST) ratio were calculated. Using the area under the receiver operating characteristic curve (AUROC) to evaluate the accuracy of different markers for predicting the histological severity.Among the 58 treatment-naïve PBC patients, the patients of Scheuer stage I/II/III/IV were 17/25/11/5, respectively. PC/ST ratio (AUROC = 0.807) was superior to RPR (AUROC = 0.717), APRI (AUROC = 0.726), FIB-4 (AUROC = 0.722), and mean platelet volume (MPV) (AUROC = 0.671) in discriminating between stage I and stage ≥II. The AUROC of PC/ST ratio, RPR, APRI, FIB-4, and MPV were 0.939, 0.872, 0.816, 0.831 and 0.572, respectively, for Scheuer stage ≥III; 0.968, 0.795, 0.744, and 0.723, respectively for stage IV. The sensitivity and specificity of PC/ST ratio were 73.4%,79.1%; 81%,100%;88.7%,100% for detection of Scheuer stage ≥ II, Scheuer stage ≥ III and Scheuer stage IV, respectively.Our study findings indicated that compared with previous noninvasive test PRP, APRI, FIB-4 and MPV, PC/ST ratio shows the most accurate for distinguish the histologic severity of PBC patients.
[Mh] Termos MeSH primário: Colangite/sangue
Cirrose Hepática Biliar/sangue
Contagem de Plaquetas
Índice de Gravidade de Doença
Baço/patologia
[Mh] Termos MeSH secundário: Área Sob a Curva
Aspartato Aminotransferases/sangue
Biomarcadores/análise
Colangite/patologia
Índices de Eritrócitos
Feminino
Seres Humanos
Cirrose Hepática Biliar/patologia
Masculino
Meia-Idade
Valor Preditivo dos Testes
Curva ROC
Estudos Retrospectivos
Sensibilidade e Especificidade
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); EC 2.6.1.1 (Aspartate Aminotransferases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009843


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[PMID]:27771353
[Au] Autor:Peng W
[Ad] Endereço:Institute of Rheumatology and Immunology, Affiliated Hospital of North Sichuan Medical College, Nanchong City, Sichuan 637000, P. R. China; Laboratory of Experimental Surgery, Hadassah-Hebrew University Medical Center, Mount Scopus, Sderot Churchill, Jerusalem, 91240, Israel. Electronic address: pengwei39@hotmail.com.
[Ti] Título:G-CSF treatment promotes apoptosis of autoreactive T cells to restrict the inflammatory cascade and accelerate recovery in experimental allergic encephalomyelitis.
[So] Source:Exp Neurol;289:73-84, 2017 03.
[Is] ISSN:1090-2430
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:G-CSF is a hematopoietic growth factor that regulates the proliferation, differentiation and survival of myeloid lineage cells, which has protective effects in autoimmune neuroinflammatory diseases such as EAE. Here we use EAE model treated by G-CSF to address the hypothesis that G-CSF inhibits the proliferative response of splenic T cells via the enhancement of apoptosis, and this priming effect of G-CSF depends on the cell cycle. Our results show that G-CSF administration reduced EAE frequency and severity of attacks. The inflammatory cells and demyelination areas were decreased in the CNS of G-CSF-treated mice. G-CSF treatment altered cytokine profiles in vivo to inhibit the productions of IFN-γ, IL-1ß, IL-2, TNF-α, IL-17 and NO, while the secretions of IL-4 and IL-10 were increased. Splenic T cells from G-CSF-treated mice showed significantly lower proliferative response to specific antigen MOG stimulation. G-CSF enhanced the percentage of a CD4 CD25 T cell subset in spleen T cells. Moreover, G-CSF promoted the G0/G1 to S phase transition of MOG autoreactive T cells inducing apoptosis and elevating Bax gene expression of apoptosis marker. These findings indicate that G-CSF treatment induces the apoptosis of MOG autoreactive T cells, which decreases the production of pro-inflammatory cytokines and NO, suppresses the proliferation of autoreactive T cells and elevates a CD4 CD25 T cell subset to inhibit inflammatory infiltration and demyelination within CNS of EAE. The conclusions of G-CSF treatment in EAE mice suggest that G-CSF is clinically applicable and may be considered for future use in therapeutic measures for multiple sclerosis treatment.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Linfócitos T CD4-Positivos/efeitos dos fármacos
Encefalomielite Autoimune Experimental/tratamento farmacológico
Encefalomielite Autoimune Experimental/fisiopatologia
Fator Estimulador de Colônias de Granulócitos/uso terapêutico
Recuperação de Função Fisiológica/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Anexina A5/metabolismo
Ciclo Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Citocinas/metabolismo
Modelos Animais de Doenças
Encefalomielite Autoimune Experimental/induzido quimicamente
Feminino
Adjuvante de Freund/toxicidade
Expressão Gênica/efeitos dos fármacos
Camundongos
Camundongos Endogâmicos C57BL
Glicoproteína Mielina-Oligodendrócito/toxicidade
Óxido Nítrico/metabolismo
Fragmentos de Peptídeos/toxicidade
Toxina Pertussis/toxicidade
Baço/patologia
Proteína X Associada a bcl-2/genética
Proteína X Associada a bcl-2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Annexin A5); 0 (Cytokines); 0 (Myelin-Oligodendrocyte Glycoprotein); 0 (Peptide Fragments); 0 (bcl-2-Associated X Protein); 0 (myelin oligodendrocyte glycoprotein (35-55)); 143011-72-7 (Granulocyte Colony-Stimulating Factor); 31C4KY9ESH (Nitric Oxide); 9007-81-2 (Freund's Adjuvant); EC 2.4.2.31 (Pertussis Toxin)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:180218
[Lr] Data última revisão:
180218
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


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[PMID]:29293592
[Au] Autor:Lankford KL; Arroyo EJ; Nazimek K; Bryniarski K; Askenase PW; Kocsis JD
[Ad] Endereço:Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, United States of America.
[Ti] Título:Intravenously delivered mesenchymal stem cell-derived exosomes target M2-type macrophages in the injured spinal cord.
[So] Source:PLoS One;13(1):e0190358, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In a previous report we showed that intravenous infusion of bone marrow-derived mesenchymal stem cells (MSCs) improved functional recovery after contusive spinal cord injury (SCI) in the non-immunosuppressed rat, although the MSCs themselves were not detected at the spinal cord injury (SCI) site [1]. Rather, the MSCs lodged transiently in the lungs for about two days post-infusion. Preliminary studies and a recent report [2] suggest that the effects of intravenous (IV) infusion of MSCs could be mimicked by IV infusion of exosomes isolated from conditioned media of MSC cultures (MSCexos). In this study, we assessed the possible mechanism of MSCexos action on SCI by investigating the tissue distribution and cellular targeting of DiR fluorescent labeled MSCexos at 3 hours and 24 hours after IV infusion in rats with SCI. The IV delivered MSCexos were detected in contused regions of the spinal cord, but not in the noninjured region of the spinal cord, and were also detected in the spleen, which was notably reduced in weight in the SCI rat, compared to control animals. DiR "hotspots" were specifically associated with CD206-expressing M2 macrophages in the spinal cord and this was confirmed by co-localization with anti-CD63 antibodies labeling a tetraspanin characteristically expressed on exosomes. Our findings that MSCexos specifically target M2-type macrophages at the site of SCI, support the idea that extracellular vesicles, released by MSCs, may mediate at least some of the therapeutic effects of IV MSC administration.
[Mh] Termos MeSH primário: Transplante de Células
Exossomos/metabolismo
Macrófagos/patologia
Células Mesenquimais Estromais
Traumatismos da Medula Espinal/patologia
[Mh] Termos MeSH secundário: Animais
Meios de Cultivo Condicionados
Meios de Cultura Livres de Soro
Tamanho do Órgão
Ratos
Ratos Sprague-Dawley
Baço/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Culture Media, Conditioned); 0 (Culture Media, Serum-Free)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180103
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190358



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