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Pesquisa : E01.370.225.500.607.512.240 [Categoria DeCS]
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[PMID]:29377929
[Au] Autor:Allard D; Charlebois R; Gilbert L; Stagg J; Chrobak P
[Ad] Endereço:Centre de Recherche du Centre Hospitalier l'Université de Montréal (CRCHUM), Faculté de Pharmacie de l'Université de Montréal et Institut du Cancer de Montréal, Montréal, Quebec, Canada.
[Ti] Título:CD73-A2a adenosine receptor axis promotes innate B cell antibody responses to pneumococcal polysaccharide vaccination.
[So] Source:PLoS One;13(1):e0191973, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Many individuals at risk of streptococcal infection respond poorly to the pneumococcal polysaccharide vaccine Pneumovax 23. Identification of actionable pathways able to enhance Pneumovax responsiveness is highly relevant. We investigated the contribution of the extracellular adenosine pathway regulated by the ecto-nucleotidase CD73 in Pneumovax-induced antibody responses. Using gene-targeted mice, we demonstrated that CD73-or A2a adenosine receptor deficiency significantly delayed isotype switching. Nevertheless, CD73- or A2aR- deficient adult mice ultimately produced antigen-specific IgG3 and controlled Streptococcus pneumoniae infection as efficiently as wild type (WT) mice. Compared to adults, young WT mice failed to control S. pneumoniae infection after vaccination and this was associated with lower levels of CD73 on innate B cells. We hypothesized that pharmacological activation of A2a receptor may improve Pneumovax 23 immunization in young WT mice. Remarkably, administration of the A2a adenosine receptor agonist CGS 21680 significantly increased IgG3 responses and significantly enhanced survival after S. pneumoniae challenge. Our study thus suggests that pharmacological activation of the A2a adenosine receptor could improve the efficacy of Pneumovax 23 vaccination in individuals at risk of streptococcal infection.
[Mh] Termos MeSH primário: 5´-Nucleotidase/metabolismo
Linfócitos B/imunologia
Imunidade Inata
Vacinas Pneumocócicas/imunologia
Receptor A2A de Adenosina/metabolismo
[Mh] Termos MeSH secundário: 5'-Nucleotidase/genética
Animais
Ensaio de Imunoadsorção Enzimática
Imunofluorescência
Imunoglobulina G/imunologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Receptor A2A de Adenosina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Immunoglobulin G); 0 (Pneumococcal Vaccines); 0 (Receptor, Adenosine A2A); EC 3.1.3.5 (5'-Nucleotidase)
[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:180130
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191973


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[PMID]:29320817
[Au] Autor:Linh NTP; Park H; Lee J; Liu DX; Seo GE; Sohn HJ; Han JH; Han ET; Shin HJ; Yeo SJ
[Ad] Endereço:Zoonosis Research Center, Department of Infection Biology, School of Medicine, Wonkwang University, Iksan 54538, Korea.
[Ti] Título:Development of Monoclonal Antibodies for Diagnosis of Plasmodium vivax.
[So] Source:Korean J Parasitol;55(6):623-630, 2017 Dec.
[Is] ISSN:1738-0006
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:Plasmodium lactate dehydrogenase (pLDH) is a strong target antigen for the determination of infection with Plasmodium species specifically. However, a more effective antibody is needed because of the low sensitivity of the current antibody in many immunological diagnostic assays. In this study, recombinant Plasmodium vivax LDH (PvLDH) was experimentally constructed and expressed as a native antigen to develop an effective P. vivax-specific monoclonal antibody (mAb). Two mAbs (2CF5 and 1G10) were tested using ELISA and immunofluorescence assays (IFA), as both demonstrated reactivity against pLDH antigen. Of the 2 antibodies, 2CF5 was not able to detect P. falciparum, suggesting that it might possess P. vivax-specificity. The detection limit for a pair of 2 mAbs-linked sandwich ELISA was 31.3 ng/ml of the recombinant antigen. The P. vivax-specific performance of mAbs-linked ELISA was confirmed by in vitro-cultured P. falciparum and P. vivax-infected patient blood samples. In conclusion, the 2 new antibodies possessed the potential to detect P. vivax and will be useful in immunoassay.
[Mh] Termos MeSH primário: Anticorpos Monoclonais
L-Lactato Desidrogenase/imunologia
Malária Vivax/diagnóstico
Plasmodium vivax/enzimologia
Plasmodium vivax/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais/sangue
Biomarcadores/sangue
Ensaio de Imunoadsorção Enzimática
Feminino
Imunofluorescência
Camundongos Endogâmicos BALB C
Proteínas Recombinantes/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Biomarkers); 0 (Recombinant Proteins); EC 1.1.1.27 (L-Lactate Dehydrogenase)
[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:180112
[St] Status:MEDLINE
[do] DOI:10.3347/kjp.2017.55.6.623


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[PMID]:28467316
[Au] Autor:Chen R; Cai X; Ma K; Zhou Y; Wang Y; Jiang T
[Ad] Endereço:The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
[Ti] Título:The fabrication of double-layered chitosan/gelatin/genipin nanosphere coating for sequential and controlled release of therapeutic proteins.
[So] Source:Biofabrication;9(2):025028, 2017 Jun 01.
[Is] ISSN:1758-5090
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Bone regeneration is a complicated process and includes a number of distinct and sequential stages of coordinated cellular actions under the regulation of multiple growth factors. Therefore, bone grafting materials in which growth factors can be incorporated and released in a programmed order in line with the bone tissue healing process may lead to desirable clinical outcomes. In the present study, a double-layered chitosan/gelatin/genipin (d-CSG/G) nanosphere coating is developed by using layer-by-layer electrophoretic deposition and genipin crosslinking. The surface morphology, physicochemical and mechanical properties of the coatings are explored. Cytochrome C is used as a therapeutic model protein and is successfully loaded on the inner and outer layers of the coating. The protein release can be controlled by the loading position, genipin concentration and thickness of the outer layer. Furthermore, the cell response to the coatings was evaluated. Real-time polymerase chain reactions, immunofluorescence staining and extracellular matrix mineralization assay confirmed that the functions of the loaded growth factor are fully preserved after fabrication. Overall, the d-CSG/G nanosphere coating could be a promising growth factor delivery system to promote bone tissue regeneration.
[Mh] Termos MeSH primário: Biomimética/métodos
Quitosana/química
Materiais Revestidos Biocompatíveis/química
Citocromos c/uso terapêutico
Gelatina/química
Iridoides/química
Nanosferas/química
[Mh] Termos MeSH secundário: Animais
Proteína Morfogenética Óssea 2/química
Calcificação Fisiológica
Bovinos
Reagentes para Ligações Cruzadas/química
Preparações de Ação Retardada
Matriz Extracelular/metabolismo
Imunofluorescência
Células Mesenquimais Estromais/citologia
Nanosferas/ultraestrutura
Osteocalcina/metabolismo
Ratos
Reação em Cadeia da Polimerase em Tempo Real
Proteínas Recombinantes/química
Soluções
Espectroscopia de Infravermelho com Transformada de Fourier
Propriedades de Superfície
Fator de Crescimento Transformador beta/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bone Morphogenetic Protein 2); 0 (Coated Materials, Biocompatible); 0 (Cross-Linking Reagents); 0 (Delayed-Action Preparations); 0 (Iridoids); 0 (Recombinant Proteins); 0 (Solutions); 0 (Transforming Growth Factor beta); 0 (recombinant human bone morphogenetic protein-2); 104982-03-8 (Osteocalcin); 9000-70-8 (Gelatin); 9007-43-6 (Cytochromes c); 9012-76-4 (Chitosan); A3V2NE52YG (genipin)
[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:170504
[St] Status:MEDLINE
[do] DOI:10.1088/1758-5090/aa70c3


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[PMID]:29185091
[Au] Autor:Kolben T; Jeschke U; Reimer T; Karsten N; Schmoeckel E; Semmlinger A; Mahner S; Harbeck N; Kolben TM
[Ad] Endereço:Department of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377, Munich, Germany. Thomas.Kolben@med.uni-muenchen.de.
[Ti] Título:Induction of apoptosis in breast cancer cells in vitro by Fas ligand reverse signaling.
[So] Source:J Cancer Res Clin Oncol;144(2):249-256, 2018 Feb.
[Is] ISSN:1432-1335
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: The Fas-antigen is a cell surface receptor that transduces apoptotic signals into cells. The purpose of this study was to evaluate FasL expression in breast cancer and to elucidate the role of its signaling in different breast cancer cell lines. METHODS: T47D and MCF7 cells were used and cultured in Dulbecco's modified Eagle's medium. FasL translocation to the membrane was achieved by culturing the cells in the presence of human interferon-γ (IFNγ). Translocation was detected by immunofluorescence. The ability of a Fas:Fc fusion protein to trigger apoptosis in these cells was investigated by cell death detection ELISA. After incubation with IFNγ for 4 h and 18 h, apoptosis was assessed in response to treatment with Fas:Fc. RESULTS: Immunofluorescence revealed that the used cell lines were positive for FasL which was increased and changed to more membrane-bound FasL expression after IFNγ stimulation. After stimulation with 50 IU/ml IFNγ, Fas:Fc significantly increased MCF7 apoptosis (1.39 ± 0.06-fold, p = 0.0004) after 18 h. After stimulation with 100 IU/ml, Fas:Fc significantly increased apoptosis both after 4 h (1.49 ± 0.15-fold, p = 0.018) and 18 h (1.30 ± 0.06-fold, p = 0.013). In T47D cells this effect was seen after 4 h of stimulation with 50 IU/ml and addition of Fas:Fc (1.6 ± 0.08-fold, p = 0.03). CONCLUSION: Membrane-bound FasL expression could be induced by IFNγ in a breast cancer cell model. More importantly, in the presence of IFNγ the Fas:Fc fusion protein was able to transmit pro-apoptotic signals to T47D and MCF7 cells, significantly inducing apoptosis. The current findings support further in vivo studies regarding FasL activation as a potential target for therapeutic intervention in breast cancer.
[Mh] Termos MeSH primário: Neoplasias da Mama/metabolismo
Neoplasias da Mama/patologia
Proteína Ligante Fas/metabolismo
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Apoptose/fisiologia
Neoplasias da Mama/tratamento farmacológico
Ensaio de Imunoadsorção Enzimática
Proteína Ligante Fas/genética
Feminino
Imunofluorescência
Seres Humanos
Fragmentos Fc das Imunoglobulinas/genética
Interferon gama/farmacologia
Células MCF-7
Proteínas Recombinantes de Fusão/genética
Proteínas Recombinantes de Fusão/farmacologia
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (FASLG protein, human); 0 (Fas Ligand Protein); 0 (IFNG protein, human); 0 (Immunoglobulin Fc Fragments); 0 (Recombinant Fusion Proteins); 82115-62-6 (Interferon-gamma)
[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:171130
[St] Status:MEDLINE
[do] DOI:10.1007/s00432-017-2551-y


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[PMID]:28453188
[Au] Autor:Moritz ED; Tonnetti L; Hewins ME; Berardi VP; Dodd RY; Stramer SL
[Ad] Endereço:Scientific Affairs Department, American Red Cross, Gaithersburg, Maryland.
[Ti] Título:Description of 15 DNA-positive and antibody-negative "window-period" blood donations identified during prospective screening for Babesia microti.
[So] Source:Transfusion;57(7):1781-1786, 2017 07.
[Is] ISSN:1537-2995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Blood donation screening detecting only antibodies fails to identify donors in the earliest stage of infection, before a detectable immunologic response, that is, the "window period" (WP). We present data on WP donations identified during prospective screening for Babesia microti, a transfusion-transmissible parasite of increasing concern in the United States. STUDY DESIGN AND METHODS: Blood donations collected in Connecticut, Massachusetts, Minnesota, and Wisconsin were screened using polymerase chain reaction (PCR) and arrayed fluorescence immunoassay (AFIA) to detect B. microti DNA and antibodies, respectively. Parasite loads were estimated using quantitative PCR. Red blood cell (RBC) samples were inoculated into hamsters to assess infectivity. Donors screening reactive were indefinitely deferred, tested by supplemental methods, and followed to assess DNA and antibody clearance. Demographic data from WP donors (i.e., those screening PCR positive and AFIA negative) were compared to data from other positive donors. RESULTS: Of 220,479 donations screened from June 2012 to August 2016, a total of 700 were positive, of which 15 (2% of positive donations or 1 per 14,699 screened donations) were confirmed WP donations. The median estimated parasite load in WP donations was 350 parasites/mL, no different than AFIA-positive and PCR-positive donors. Parasite loads in RBC samples from WP units ranged from 14 to 11,022 parasites/mL; RBC samples from three of 10 (30%) WP donations infected hamsters. The mean age of WP donors was 48 years (range, 17-75 years); three (20%) were female. WP donor demographics did not differ significantly from demographics of other donors. CONCLUSIONS: We report one per 15,000 B. microti WP infections in blood donors in endemic areas, demonstrating the importance of nucleic acid testing to mitigate the risk of transfusion-transmitted babesiosis.
[Mh] Termos MeSH primário: Anticorpos Antiprotozoários/sangue
Babesia microti/isolamento & purificação
Doadores de Sangue
DNA de Protozoário/sangue
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Babesia microti/genética
Babesia microti/imunologia
Feminino
Imunofluorescência
Seres Humanos
Masculino
Meia-Idade
Reação em Cadeia da Polimerase
Estudos Prospectivos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Protozoan); 0 (DNA, Protozoan)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1111/trf.14103


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[PMID]:28469105
[Au] Autor:Li SY; Wang YL; Liu WW; Lyu DJ; Wang F; Mao CJ; Yang YP; Hu LF; Liu CF
[Ad] Endereço:Department of Neurology and Suzhou Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China.
[Ti] Título:Long-term Levodopa Treatment Accelerates the Circadian Rhythm Dysfunction in a 6-hydroxydopamine Rat Model of Parkinson's Disease.
[So] Source:Chin Med J (Engl);130(9):1085-1092, 2017 May 05.
[Is] ISSN:0366-6999
[Cp] País de publicação:China
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Parkinson's disease (PD) patients with long-term levodopa (L-DOPA) treatment are suffering from severe circadian dysfunction. However, it is hard to distinguish that the circadian disturbance in patients is due to the disease progression itself, or is affected by L-DOPA replacement therapy. This study was to investigate the role of L-DOPA on the circadian dysfunction in a rat model of PD. METHODS: The rat model of PD was constructed by a bilateral striatal injection with 6-hydroxydopamine (6-OHDA), followed by administration of saline or 25 mg/kg L-DOPA for 21 consecutive days. Rotarod test, footprint test, and open-field test were carried out to evaluate the motor function. Striatum, suprachiasmatic nucleus (SCN), liver, and plasma were collected at 6:00, 12:00, 18:00, and 24:00. Quantitative real-time polymerase chain reaction was used to examine the expression of clock genes. Enzyme-linked immunosorbent assay was used to determine the secretion level of cortisol and melatonin. High-performance liquid chromatography was used to measure the neurotransmitters. Analysis of variance was used for data analysis. RESULTS: L-DOPA alleviated the motor deficits induced by 6-OHDA lesions in the footprint and open-field test ( P < 0.01, P < 0.001, respectively). After L-DOPA treatment, Bmal1 decreased in the SCN compared with 6-OHDA group at 12:00 ( P < 0.01) and 24:00 ( P < 0.001). In the striatum, the expression of Bmal1, Rorα was lower than that in the 6-OHDA group at 18:00 (P < 0.05) and L-DOPA seemed to delay the peak of Per2 to 24:00. In liver, L-DOPA did not affect the rhythmicity and expression of these clock genes (P > 0.05). In addition, the cortisol secretion was increased (P > 0.05), but melatonin was further inhibited after L-DOPA treatment at 6:00 (P < 0.01). CONCLUSIONS: In the circadian system of advanced PD rat models, circadian dysfunction is not only contributed by the degeneration of the disease itself but also long-term L-DOPA therapy may further aggravate it.
[Mh] Termos MeSH primário: Ritmo Circadiano/efeitos dos fármacos
Levodopa/uso terapêutico
Oxidopamina/toxicidade
[Mh] Termos MeSH secundário: Animais
Western Blotting
Peso Corporal/efeitos dos fármacos
Ensaio de Imunoadsorção Enzimática
Imunofluorescência
Masculino
Ratos
Ratos Sprague-Dawley
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
46627O600J (Levodopa); 8HW4YBZ748 (Oxidopamine)
[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:170505
[St] Status:MEDLINE
[do] DOI:10.4103/0366-6999.204920


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[PMID]:28452458
[Au] Autor:Patel M; Moon HJ; Hong JH; Jeong B
[Ad] Endereço:Department of Chemistry and Nanoscience, Ewha Womans University , 52 Ewhayeodae-gil, Seodaemun-gu, Seoul 03760 Korea.
[Ti] Título:Chiro-Optical Modulation for NURR1 Production from Stem Cells.
[So] Source:ACS Chem Neurosci;8(7):1455-1458, 2017 07 19.
[Is] ISSN:1948-7193
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nuclear receptor related 1 (NURR1) is an essential protein for maintenance of dopaminergic neurons in adult midbrain of which deficiency leads to Parkinson's disease. To enhance the NURR1 production of neural cells, various approaches are under investigation. Here we report that NURR1 is highly expressed in stem cells by exposure to an L-polarized blue light emitting diode (LED). Compared to stem cells cultured in the absence of a LED, under polarized green and red LEDs, the stem cells exposed to a polarized blue LED significantly enhanced neuronal biomarkers such as neurofilament M (NFM) and neuron specific enolase (NSE) at both mRNA and protein levels. In particular, NURR1 was selectively enhanced by the stem cells exposed to the L-polarized blue LED. Stem cells exposed to the L-polarized blue LED increased mitochondrial ATP and intracellular calcium ions, which support neuronal differentiation of the stem cells. This study suggests that chiro-optical treatments by using polarized light with a specific wavelength can be used for engineering of stem cells with enhanced specific biochemicals, which may open a new method for a specific disease.
[Mh] Termos MeSH primário: Luz
Células Mesenquimais Estromais/metabolismo
Neurogênese
Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/biossíntese
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/metabolismo
Cálcio/metabolismo
Técnicas de Cultura de Células/instrumentação
Sobrevivência Celular
Criança
Feminino
Imunofluorescência
Expressão Gênica/efeitos da radiação
Seres Humanos
Células Mesenquimais Estromais/citologia
Células Mesenquimais Estromais/efeitos da radiação
Mitocôndrias/metabolismo
Mitocôndrias/efeitos da radiação
Proteínas de Neurofilamentos/biossíntese
Proteínas de Neurofilamentos/genética
Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares/genética
Tonsila Palatina
Fosfopiruvato Hidratase/biossíntese
Fosfopiruvato Hidratase/genética
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (NR4A2 protein, human); 0 (Neurofilament Proteins); 0 (Nuclear Receptor Subfamily 4, Group A, Member 2); 0 (RNA, Messenger); 111365-29-8 (neurofilament protein M); 8L70Q75FXE (Adenosine Triphosphate); EC 4.2.1.11 (Phosphopyruvate Hydratase); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180223
[Lr] Data última revisão:
180223
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1021/acschemneuro.7b00136


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[PMID]:29346407
[Au] Autor:Martin B; Gabris-Weber BA; Reddy R; Romero G; Chattopadhyay A; Salama G
[Ad] Endereço:Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, United States of America.
[Ti] Título:Relaxin reverses inflammatory and immune signals in aged hearts.
[So] Source:PLoS One;13(1):e0190935, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: 'Healthy' aging drives structural and functional changes in the heart including maladaptive electrical remodeling, fibrosis and inflammation, which lower the threshold for cardiovascular diseases such as heart failure (HF) and atrial fibrillation (AF). Despite mixed results in recent clinical trials, Relaxin-therapy for 2-days could reduce mortality by 37% at 180-days post-treatment, in patients with acute decompensated HF. Relaxin's short life-span (hours) but long-lasting protective actions led us to test the hypothesis that relaxin acts at a genomic level to reverse maladaptive remodeling in aging and HF. METHODS AND RESULTS: Young (9-month) and aged (24-month), male and female F-344/Brown Norway rats were treated with relaxin (0.4 mg/kg/day) for 2-weeks delivered by subcutaneous osmotic mini-pumps or with sodium acetate (controls). The genomic effects of aging and relaxin were evaluated by extracting RNA from the left ventricles and analyzing genomic changes by RNA-sequencing, Ingenuity Pathway Analysis, MetaCore and tissue immunohistochemistry. We found that aging promotes a native inflammatory response with distinct sex-differences and relaxin suppresses transcription of multiple genes and signaling pathways associated with inflammation and HF in both genders. In addition, aging significantly increased: macrophage infiltration and atrial natriuretic peptide levels in female ventricles, and activation of the complement cascade, whereas relaxin reversed these age-related effects. CONCLUSION: These data support the hypothesis that relaxin alters gene transcription and suppresses inflammatory pathways and genes associated with HF and aging. Relaxin's suppression of inflammation and fibrosis supports its potential as a therapy for cardiovascular and inflammation-related diseases, such as HF, AF and diabetes.
[Mh] Termos MeSH primário: Envelhecimento/imunologia
Modelos Animais de Doenças
Coração/efeitos dos fármacos
Inflamação/tratamento farmacológico
Relaxina/uso terapêutico
[Mh] Termos MeSH secundário: Fatores Etários
Animais
Fibrilação Atrial/metabolismo
Biomarcadores/metabolismo
Estudos de Coortes
Feminino
Imunofluorescência
Insuficiência Cardíaca/metabolismo
Seres Humanos
Macrófagos/imunologia
Masculino
Ratos
Ratos Endogâmicos F344
Relaxina/farmacologia
Análise de Sequência de RNA
Fatores Sexuais
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers); 9002-69-1 (Relaxin)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180119
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190935


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[PMID]:29381916
[Au] Autor:Fournier PE; Gouriet F; Casalta JP; Lepidi H; Chaudet H; Thuny F; Collart F; Habib G; Raoult D
[Ad] Endereço:Aix-Marseille Université, UM63, CNRS7278, IRD198, Inserm1095, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes, IHU Méditerranée-Infection.
[Ti] Título:Blood culture-negative endocarditis: Improving the diagnostic yield using new diagnostic tools.
[So] Source:Medicine (Baltimore);96(47):e8392, 2017 Nov.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Blood culture-negative endocarditis (BCNE) may represent up to 70% of all endocarditis cases, depending on series. From 2001 to 2009, we implemented in our laboratory a multimodal diagnostic strategy for BCNE that included systematized testing of blood, and when available, valvular biopsy specimens using serological, broad range molecular, and histopathological assays. A causative microorganism was identified in 62.7% of patients.In this study from January 2010 to December 2015, in an effort to increase the number of identified causative microorganisms, we prospectively added to our diagnostic protocol specific real-time (RT) polymerase chain reaction (PCR) assays targeting various endocarditis agents, and applied them to all patients with BCNE admitted to the 4 public hospitals in Marseille, France.A total of 283 patients with BCNE were included in the study. Of these, 177 were classified as having definite endocarditis. Using our new multimodal diagnostic strategy, we identified an etiology in 138 patients (78.0% of cases). Of these, 3 were not infective (2.2%) and 1 was diagnosed as having Mycobacterium bovis BCG endocarditis. By adding specific PCR assays from blood and valvular biopsies, which exhibited a significantly greater sensitivity (P < 10) than other methods, causative agents, mostly enterococci, streptococci, and zoonotic microorganisms, were identified in an additional 27 patients (14 from valves only, 11 from blood only, and 2 from both). Finally, in another 107 patients, a pathogen was detected using serology in 37, valve culture in 8, broad spectrum PCR from valvular biopsies and blood in 19 and 2, respectively, immunohistochemistry from valves in 3, and a combination of several assays in 38.By adding specific RT-PCR assays to our systematic PCR testing of patients with BCNE, we increased the diagnostic efficiency by 24.3%, mostly by detecting enterococci and streptococci that had not been detected by other diagnostic methods, but also agents requiring specific management such as Mycoplasma hominis and Tropheryma whipplei.
[Mh] Termos MeSH primário: Endocardite/diagnóstico
Endocardite/microbiologia
Reação em Cadeia da Polimerase em Tempo Real/métodos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Biópsia
Hemocultura
Criança
Pré-Escolar
Feminino
Imunofluorescência
França
Seres Humanos
Lactente
Masculino
Meia-Idade
Estudos Prospectivos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000008392


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[PMID]:29300773
[Au] Autor:Truong K; Bradley S; Baginski B; Wilson JR; Medlin D; Zheng L; Wilson RK; Rusin M; Takacs E; Dean D
[Ad] Endereço:Department of Bioengineering, Clemson University, Clemson, South Carolina, United States of America.
[Ti] Título:The effect of well-characterized, very low-dose x-ray radiation on fibroblasts.
[So] Source:PLoS One;13(1):e0190330, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The purpose of this study is to determine the effects of low-dose radiation on fibroblast cells irradiated by spectrally and dosimetrically well-characterized soft x-rays. To achieve this, a new cell culture x-ray irradiation system was designed. This system generates characteristic fluorescent x-rays to irradiate the cell culture with x-rays of well-defined energies and doses. 3T3 fibroblast cells were cultured in cups with Mylar® surfaces and were irradiated for one hour with characteristic iron (Fe) K x-ray radiation at a dose rate of approximately 550 µGy/hr. Cell proliferation, total protein analysis, flow cytometry, and cell staining were performed on fibroblast cells to determine the various effects caused by the radiation. Irradiated cells demonstrated increased proliferation and protein production compared to control samples. Flow cytometry revealed that a higher percentage of irradiated cells were in the G0/G1 phase of the cell cycle compared to control counterparts, which is consistent with other low-dose studies. Cell staining results suggest that irradiated cells maintained normal cell functions after radiation exposure, as there were no qualitative differences between the images of the control and irradiated samples. The result of this study suggest that low-dose soft x-ray radiation might cause an initial pause, followed by a significant increase, in proliferation. An initial "pause" in cell proliferation could be a protective mechanism of the cells to minimize DNA damage caused by radiation exposure. The new cell irradiation system developed here allows for unprecedented control over the properties of the x-rays given to the cell cultures. This will allow for further studies on various cell types with known spectral distribution and carefully measured doses of radiation, which may help to elucidate the mechanisms behind varied cell responses to low-dose x-rays reported in the literature.
[Mh] Termos MeSH primário: Fibroblastos/efeitos da radiação
[Mh] Termos MeSH secundário: Animais
Relação Dose-Resposta a Droga
Fibroblastos/citologia
Citometria de Fluxo
Imunofluorescência
Fase G1
Camundongos
Células NIH 3T3
Proteínas/metabolismo
Fase de Repouso do Ciclo Celular
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Proteins)
[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:180105
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190330



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