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[PMID]:29406049
[Au] Autor:Salim SA; Yousuf T; Patel A; Fülöp T; Agarwal M
[Ad] Endereço:Department of Internal Medicine, University of Mississippi Medical Center, Jackson, Mississippi.
[Ti] Título:Hypocomplementemic Urticarial Vasculitis Syndrome With Crescentic Glomerulonephritis.
[So] Source:Am J Med Sci;355(2):195-200, 2018 Feb.
[Is] ISSN:1538-2990
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare autoimmune disease characterized by multiple organ system involvement, including renal disease, with low complement levels. We report the case of a 31-year-old woman who presented with nonspecific symptoms including fatigue, diarrhea, macular rash and abdominal pain with acute renal failure leading to end-stage kidney disease. Laboratory results showed hematuria, nephrotic range proteinuria, worsening creatinine and low C1q levels. Left kidney biopsy showed proliferative glomerulonephritis with crescent formation. She was treated with 6 months of intravenous cyclophosphamide, followed by 2 doses of intravenous rituximab (1g each), thereafter maintained on mycophenolate mofetil and glucocorticoid-based therapy. She experienced a full recovery of renal function after 12 months of dialysis dependence. Hypocomplementemic urticarial vasculitis syndrome with crescentic glomerulonephritis is a rare disease with only 5 other reported cases in literature. In our case, we document a delayed but excellent renal recovery during a 2-year follow-up.
[Mh] Termos MeSH primário: Ciclofosfamida/administração & dosagem
Glomerulonefrite Membranoproliferativa
Ácido Micofenólico/administração & dosagem
Rituximab/administração & dosagem
Urticária
Vasculite
[Mh] Termos MeSH secundário: Adulto
Complemento C1q/metabolismo
Feminino
Glomerulonefrite Membranoproliferativa/complicações
Glomerulonefrite Membranoproliferativa/tratamento farmacológico
Glomerulonefrite Membranoproliferativa/metabolismo
Glomerulonefrite Membranoproliferativa/patologia
Hematúria/complicações
Hematúria/tratamento farmacológico
Hematúria/metabolismo
Hematúria/patologia
Seres Humanos
Falência Renal Crônica/complicações
Falência Renal Crônica/tratamento farmacológico
Falência Renal Crônica/metabolismo
Falência Renal Crônica/patologia
Proteinúria/complicações
Proteinúria/tratamento farmacológico
Proteinúria/metabolismo
Proteinúria/patologia
Síndrome
Urticária/complicações
Urticária/tratamento farmacológico
Urticária/metabolismo
Urticária/patologia
Vasculite/complicações
Vasculite/tratamento farmacológico
Vasculite/metabolismo
Vasculite/patologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
4F4X42SYQ6 (Rituximab); 80295-33-6 (Complement C1q); 8N3DW7272P (Cyclophosphamide); HU9DX48N0T (Mycophenolic Acid)
[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:180207
[St] Status:MEDLINE


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[PMID]:27779572
[Au] Autor:Lee D; Keymeulen B; Hilbrands R; Ling Z; Van de Velde U; Jacobs-Tulleneers-Thevissen D; Maleux G; Lapauw B; Crenier L; De Block C; Mathieu C; Pipeleers D; Gillard P
[Ad] Endereço:1 Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven and University Hospitals Leuven, Leuven, Belgium. 2 University Hospital and Diabetes Research Center, Vrije Universiteit Brussel (VUB), Brussels, Belgium. 3 Department of Interventional Radiology, University Hospitals Leuven, KUL, Leuven, Belgium. 4 Department of Endocrinology, Gent University Hospital, Gent, Belgium. 5 Department of Endocrinology, Université Libre de Bruxelles-Hôpital Erasme, Bruxelles, Belgium. 6 Department of Diabetology, University Hospital Antwerp-UA, Antwerp, Belgium.
[Ti] Título:Age and Early Graft Function Relate With Risk-Benefit Ratio of Allogenic Islet Transplantation Under Antithymocyte Globulin-Mycophenolate Mofetil-Tacrolimus Immune Suppression.
[So] Source:Transplantation;101(9):2218-2227, 2017 09.
[Is] ISSN:1534-6080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Induction therapy with a T cell-depleting agent followed by mycophenolate mofetil and tacrolimus is presently the most frequently used immune suppression (IS) regimen in islet transplantation. This study assesses its safety and tolerability in nonuremic type 1 diabetic recipients. METHODS: Fifty-one patients (age, between 29 and 63 years) with high glycemic variability and problematic hypoglycemia received intraportal islet grafts under anti-thymocyte globulin-mycophenolate mofetil-tacrolimus protocol. They were followed up for over 48 months for function of the implant and adverse events. RESULTS: Severe hypoglycemia and diabetic ketoacidosis were absent in patients with functioning graft. Immune suppressive therapy was maintained for 48 months in 29 recipients with sustained function (group A), whereas 16 patients stopped earlier due to graft failure (group B) and in 6 for other reasons. Group A was significantly older at the time of implantation and achieved higher graft function at posttransplantation month 6 under similar dose of IS. Prevalence of IS-related side effects was similar in groups A and B, occurring predominantly during the first year posttransplantation. IS-related serious adverse events (SAE) were reported in 47% of patients, with 4 presenting with cytomegalovirus infection and 4 (age, 42-59 years) diagnosed with cancer. Except in 1 patient with cancer, all SAEs resolved after appropriate treatment. CONCLUSIONS: These risk/benefit data serve as a basis for clinical decision-making before entering an intraportal islet transplantation protocol. A longer benefit is observed in recipients of higher age (≥40 years), but it is not associated with more side effects and SAE.
[Mh] Termos MeSH primário: Soro Antilinfocitário/uso terapêutico
Diabetes Mellitus Tipo 1/cirurgia
Imunossupressores/uso terapêutico
Transplante das Ilhotas Pancreáticas
Ácido Micofenólico/uso terapêutico
Tacrolimo/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Soro Antilinfocitário/efeitos adversos
Biomarcadores/sangue
Glicemia/metabolismo
Peptídeo C/sangue
Diabetes Mellitus Tipo 1/sangue
Quimioterapia Combinada
Feminino
Seres Humanos
Imunossupressores/efeitos adversos
Transplante das Ilhotas Pancreáticas/efeitos adversos
Masculino
Meia-Idade
Ácido Micofenólico/efeitos adversos
Complicações Pós-Operatórias/etiologia
Medição de Risco
Fatores de Risco
Tacrolimo/efeitos adversos
Fatores de Tempo
Transplante Homólogo
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antilymphocyte Serum); 0 (Biomarkers); 0 (Blood Glucose); 0 (C-Peptide); 0 (Immunosuppressive Agents); D7RD81HE4W (thymoglobulin); HU9DX48N0T (Mycophenolic Acid); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180216
[Lr] Data última revisão:
180216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[Cl] Clinical Trial:ClinicalTrial
[St] Status:MEDLINE
[do] DOI:10.1097/TP.0000000000001543


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[PMID]:28461070
[Au] Autor:Albulescu IC; Kovacikova K; Tas A; Snijder EJ; van Hemert MJ
[Ad] Endereço:Molecular Virology Laboratory, Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
[Ti] Título:Suramin inhibits Zika virus replication by interfering with virus attachment and release of infectious particles.
[So] Source:Antiviral Res;143:230-236, 2017 07.
[Is] ISSN:1872-9096
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Zika virus (ZIKV) is a mosquito-borne flavivirus that mostly causes asymptomatic infections or mild disease characterized by low-grade fever, rash, conjunctivitis, and malaise. However, the recent massive ZIKV epidemics in the Americas have also linked ZIKV infection to fetal malformations like microcephaly and Guillain-Barré syndrome in adults, and have uncovered previously unrecognized routes of vertical and sexual transmission. Here we describe inhibition of ZIKV replication by suramin, originally an anti-parasitic drug, which was more recently shown to inhibit multiple viruses. In cell culture-based assays, using reduction of cytopathic effect as read-out, suramin had an EC of ∼40 µM and a selectivity index of 48. In single replication cycle experiments, suramin treatment also caused a strong dose-dependent decrease in intracellular ZIKV RNA levels and a >3-log reduction in infectious progeny titers. Time-of-addition experiments revealed that suramin inhibits a very early step of the replication cycle as well as the release of infectious progeny. Only during the first 2 h of infection suramin treatment strongly reduced the fraction of cells that became infected with ZIKV, suggesting the drug affects virus binding/entry. Binding experiments at 4 °C using S-labeled ZIKV demonstrated that suramin interferes with attachment to host cells. When suramin treatment was initiated post-entry, viral RNA synthesis was unaffected, while both the release of genomes and the infectivity of ZIKV were reduced. This suggests the compound also affects virion biogenesis, possibly by interfering with glycosylation and the maturation of ZIKV during its traffic through the secretory pathway. The inhibitory effect of suramin on ZIKV attachment and virion biogenesis and its broad-spectrum activity warrant further evaluation of this compound as a potential therapeutic.
[Mh] Termos MeSH primário: Suramina/antagonistas & inibidores
Vírion/efeitos dos fármacos
Ligação Viral/efeitos dos fármacos
Liberação de Vírus/efeitos dos fármacos
Replicação Viral/efeitos dos fármacos
Zika virus/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Cercopithecus aethiops
Efeito Citopatogênico Viral/efeitos dos fármacos
Replicação do DNA/efeitos dos fármacos
Flavivirus/efeitos dos fármacos
Glicosilação/efeitos dos fármacos
Ácido Micofenólico/administração & dosagem
Ácido Micofenólico/antagonistas & inibidores
RNA Viral/análise
RNA Viral/biossíntese
RNA Viral/efeitos dos fármacos
Suramina/administração & dosagem
Fatores de Tempo
Células Vero
Internalização do Vírus/efeitos dos fármacos
Zika virus/crescimento & desenvolvimento
Zika virus/fisiologia
Infecção pelo Zika virus/tratamento farmacológico
Infecção pelo Zika virus/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (RNA, Viral); 6032D45BEM (Suramin); HU9DX48N0T (Mycophenolic Acid)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:28461110
[Au] Autor:Zhu J; Zeng Y; Dolff S; Bienholz A; Lindemann M; Brinkhoff A; Schedlowski M; Xu S; Sun M; Guberina H; Kirchhof J; Kribben A; Witzke O; Wilde B
[Ad] Endereço:Department of Nephrology, University Hospital Essen, University Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.
[Ti] Título:Granzyme B producing B-cells in renal transplant patients.
[So] Source:Clin Immunol;184:48-53, 2017 11.
[Is] ISSN:1521-7035
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: A separate subset of Granzyme B (GrB) producing B-cells regulating T-cell mediated immunity has been identified. In the present study, we investigated the role of GrB B-cells in renal transplant patients (RTX). METHODS: 12 healthy controls (HC) and 26 RTX patients were enrolled. In addition, 19 healthy volunteers treated with cyclosporine A (CsA) were enrolled. GrB B-cells were determined via flow cytometry. RESULTS: RTX Patients showed a diminished fraction of GrB B-cells as compared to HC. CsA treatment of healthy volunteers had no impact on the development of GrB B-cells. RTX patients with a history of allograft rejection showed an increased frequency of GrB B-cells. RTX patients with at least one episode of CMV viremia tended to have lower GrB B-cells as compared to patients without viremic episodes. CONCLUSION: We demonstrate that treatment with CsA does not impair the development of GrB B-cells. GrB B-cells may have a dual role in renal transplantation as regulatory cells to maintain allospecific tolerance and as effector cells enhancing viral control.
[Mh] Termos MeSH primário: Linfócitos B/metabolismo
Granzimas/metabolismo
Transplante de Rim
[Mh] Termos MeSH secundário: Corticosteroides/uso terapêutico
Idoso
Linfócitos B/efeitos dos fármacos
Estudos de Casos e Controles
Ciclosporina/farmacologia
Ciclosporina/uso terapêutico
Feminino
Rejeição de Enxerto/prevenção & controle
Granzimas/efeitos dos fármacos
Seres Humanos
Imunossupressores/farmacologia
Imunossupressores/uso terapêutico
Interleucinas/farmacologia
Masculino
Meia-Idade
Ácido Micofenólico/uso terapêutico
Tacrolimo/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adrenal Cortex Hormones); 0 (Immunosuppressive Agents); 0 (Interleukins); 0 (interleukin-21); 83HN0GTJ6D (Cyclosporine); EC 3.4.21.- (GZMB protein, human); EC 3.4.21.- (Granzymes); HU9DX48N0T (Mycophenolic Acid); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:28461109
[Au] Autor:Amrouche K; Jamin C
[Ad] Endereço:UMR 1227, Lymphocytes B et Autoimmunité, Université de Brest, INSERM, Brest, France; LabEx IGO "Immunotherapy, Graft, Oncology", Brest, France.
[Ti] Título:Influence of drug molecules on regulatory B cells.
[So] Source:Clin Immunol;184:1-10, 2017 11.
[Is] ISSN:1521-7035
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:By their suppressive functions, regulatory B (Breg) cells are considered as key elements in the control and development of various disease states. Many signals can induce Bregs in vivo and in vitro and often from heterogeneous populations. Several specific signals delivered in a timely immunological context contribute to the establishment of Bregs. These are endogenous and physiological signals or stimuli, widely discussed in the literature participating in the establishment of an effective immune response. However, exogenous signals, much less clearly identified can also be considered as Bregs inducers. These extrinsic signals are capable of directly or indirectly influencing the suppressive capacity of Bregs, but also their expansion and functional restoration in its absence. Faced with the excitement generated by the development of processes favoring the expansion of Bregs in mice for therapeutic purposes, the challenge today is to extrapolate such approaches in humans. This perspective may already be in effect.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Linfócitos B Reguladores/efeitos dos fármacos
Imunossupressores/farmacologia
Vitaminas/farmacologia
[Mh] Termos MeSH secundário: Corticosteroides/farmacologia
Animais
Anticorpos Monoclonais Humanizados/farmacologia
Fator Ativador de Células B/imunologia
Linfócitos B Reguladores/imunologia
Antígenos CD40/imunologia
Citocinas/imunologia
Seres Humanos
Metotrexato/farmacologia
Ácido Micofenólico/farmacologia
Pirróis/farmacologia
Quinazolinas/farmacologia
Receptores de Antígenos de Linfócitos B/imunologia
Semaforinas/farmacologia
Sirolimo/farmacologia
Receptores Toll-Like/imunologia
Tretinoína/farmacologia
Vitamina D/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adrenal Cortex Hormones); 0 (Antibodies, Monoclonal, Humanized); 0 (Antineoplastic Agents); 0 (B-Cell Activating Factor); 0 (CD40 Antigens); 0 (Cytokines); 0 (Immunosuppressive Agents); 0 (Pyrroles); 0 (Quinazolines); 0 (Receptors, Antigen, B-Cell); 0 (Semaphorins); 0 (Toll-Like Receptors); 0 (Vitamins); 1406-16-2 (Vitamin D); 5688UTC01R (Tretinoin); 7I279E1NZ8 (sotrastaurin); HU9DX48N0T (Mycophenolic Acid); I031V2H011 (tocilizumab); W36ZG6FT64 (Sirolimus); YL5FZ2Y5U1 (Methotrexate)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180206
[Lr] Data última revisão:
180206
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:29216563
[Au] Autor:Siebert A; Wysocka M; Krawczyk B; Cholewinski G; Rachon J
[Ad] Endereço:Department of Organic Chemistry, Gdansk University of Technology, ul. G. Narutowicza 11/12, 80-233 Gdansk, Poland.
[Ti] Título:Synthesis and antimicrobial activity of amino acid and peptide derivatives of mycophenolic acid.
[So] Source:Eur J Med Chem;143:646-655, 2018 Jan 01.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:The series of 16 novel amino acid and peptide mycophenolic acid (MPA) derivatives was obtained as potential antibacterial agents. Coupling of MPA with respective amines was optimized with condensing reagents such as EDCI/DMAP and T3P/TEA. Amino acid analogs were received both as methyl esters and also with the free carboxylic group. The biological activity of the products was tested on five references bacterial strains: Klebsiella pneumoniae ATCC 700603 (ESBL), Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus MRSA ATCC 43300, Staphylococcus aureus MSSA ATCC 25923. Peptide derivatives proved to be the most versatile ones, their MIC values relative to most strains was lower than MPA alone. It has been noted that the activity of amino acid derivatives depends on the configuration at the chiral center in the amino acid unit and methyl esters indicated better antimicrobial activity than analogs with free carboxylic group.
[Mh] Termos MeSH primário: Aminoácidos/farmacologia
Antibacterianos/farmacologia
Ácido Micofenólico/farmacologia
Peptídeos/farmacologia
[Mh] Termos MeSH secundário: Aminoácidos/química
Antibacterianos/síntese química
Antibacterianos/química
Relação Dose-Resposta a Droga
Escherichia coli/efeitos dos fármacos
Klebsiella pneumoniae/efeitos dos fármacos
Testes de Sensibilidade Microbiana
Estrutura Molecular
Ácido Micofenólico/síntese química
Ácido Micofenólico/química
Peptídeos/química
Pseudomonas aeruginosa/efeitos dos fármacos
Staphylococcus aureus/efeitos dos fármacos
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amino Acids); 0 (Anti-Bacterial Agents); 0 (Peptides); HU9DX48N0T (Mycophenolic Acid)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180110
[Lr] Data última revisão:
180110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171208
[St] Status:MEDLINE


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[PMID]:29182639
[Au] Autor:Neumann AM; Abele J; Kirschstein T; Engelmann R; Sellmann T; Köhling R; Müller-Hilke B
[Ad] Endereço:Institute of Immunology, University of Rostock, Rostock, Germany.
[Ti] Título:Mycophenolate mofetil prevents the delayed T cell response after pilocarpine-induced status epilepticus in mice.
[So] Source:PLoS One;12(11):e0187330, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Growing clinical and laboratory evidence corroborates a role for the immune system in the pathophysiology of epilepsy. In order to delineate the immune response following pilocarpine-induced status epilepticus (SE) in the mouse, we monitored the kinetics of leukocyte presence in the hippocampus over the period of four weeks. SE was induced following a ramping protocol of pilocarpine injection into 4-5 weeks old C57BL/6 mice. Brains were removed at days 1-4, 14 or 28 after SE, and the hippocampi were analyzed via flow cytometry, via quantitative reverse transcriptase PCR (qRT-PCR) and via immunohistochemistry. Epileptogenesis was confirmed by Timm staining of mossy fiber sprouting in the inner molecular layer of the dentate gyrus. The flow cytometry data revealed a biphasic immune response following pilocarpine-induced SE with a transient increase in activated CD11b+ and F4/80+ macrophages within the first four days replaced by an increase in CD3+ T-lymphocytes around day 28. This delayed T cell response was confirmed via qRT-PCR and via immunohistochemistry. In addition, qRT-PCR data could show that the delayed T cell response was associated with an increased CD8/CD4 ratio indicating a cytotoxic T cell response after SE. Intriguingly, early intervention with mycophenolate mofetil administration on days 0-3 after SE prevented this delayed T cell response. These results show an orchestrated immunological sequela and provide evidence that the delayed T cell response is sensitive to early immunomodulatory intervention.
[Mh] Termos MeSH primário: Ácido Micofenólico/farmacologia
Pilocarpina/farmacologia
Estado Epiléptico/induzido quimicamente
Linfócitos T/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Imunofenotipagem
Camundongos
Camundongos Endogâmicos C57BL
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Estado Epiléptico/imunologia
Linfócitos T/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
01MI4Q9DI3 (Pilocarpine); HU9DX48N0T (Mycophenolic Acid)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171226
[Lr] Data última revisão:
171226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0187330


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[PMID]:29017920
[Au] Autor:Cho J; Yi H; Jang EY; Lee MS; Lee JY; Kang C; Lee CH; Kim K
[Ad] Endereço:Division of Viral Disease Research, Center for Infectious Diseases Research, Korea National Institute of Health, Cheongju, Republic of Korea; Department of Microbiology, Chungbuk National University, Cheongju, Republic of Korea.
[Ti] Título:Mycophenolic mofetil, an alternative antiviral and immunomodulator for the highly pathogenic avian influenza H5N1 virus infection.
[So] Source:Biochem Biophys Res Commun;494(1-2):298-304, 2017 Dec 09.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Infection with the highly pathogenic avian influenza H5N1 virus results in a high incidence of mortality in humans. Severe complications from infection are often associated with hypercytokinemia. However, current neuraminidase inhibitors (NAIs) have several limitations including the appearance of oseltamivir-resistant H5N1 virus and the inability to completely ameliorate hyper-immune responses. To overcome these limitations, we evaluated the anti-viral activity of mycophenolic mofetil (MMF) against A/Vietnam/1194/2004 (H5N1) virus infection using MDCK cells and mice. The IC of MMF (0.94 µM) was comparable to that of zanamivir (0.87 µM) in H5N1 virus-infected MDCK cells based on ELISA. Time-course assays demonstrated that MMF completely inhibited H5N1 viral mRNA replication and protein expression for approximately 8 h after the initiation of treatment. In addition, MMF treatment protected 100% of mice, and lung viral titers were substantially reduced. The anti-viral mechanism of MMF against H5N1 virus infection was further confirmed to depend on the inhibition of cellular inosine monophosphate dehydrogenase (IMPDH) by exogenous guanosine, which inhibits viral mRNA and protein expression. Moreover, IL-1ß, IFN-ß, IL-6, and IP-10 mRNA expression levels were significantly downregulated in MDCK cells with MMF treatment. These results indicated that MMF could represent a novel inhibitor of viral replication and a potent immunomodulator for the treatment of H5N1 virus infection.
[Mh] Termos MeSH primário: Antivirais/farmacologia
Fatores Imunológicos/farmacologia
Vírus da Influenza A Subtipo H5N1/efeitos dos fármacos
Ácido Micofenólico/farmacologia
Infecções por Orthomyxoviridae/tratamento farmacológico
Oseltamivir/farmacologia
[Mh] Termos MeSH secundário: Animais
Quimiocina CXCL10/antagonistas & inibidores
Quimiocina CXCL10/genética
Quimiocina CXCL10/imunologia
Embrião de Galinha
Cães
Feminino
Regulação da Expressão Gênica
Interações Hospedeiro-Patógeno/efeitos dos fármacos
IMP Desidrogenase/antagonistas & inibidores
IMP Desidrogenase/genética
IMP Desidrogenase/imunologia
Vírus da Influenza A Subtipo H5N1/crescimento & desenvolvimento
Vírus da Influenza A Subtipo H5N1/patogenicidade
Interferon beta/antagonistas & inibidores
Interferon beta/genética
Interferon beta/imunologia
Interleucina-1beta/antagonistas & inibidores
Interleucina-1beta/genética
Interleucina-1beta/imunologia
Interleucina-6/antagonistas & inibidores
Interleucina-6/genética
Interleucina-6/imunologia
Pulmão/efeitos dos fármacos
Pulmão/imunologia
Pulmão/virologia
Células Madin Darby de Rim Canino
Camundongos
Camundongos Endogâmicos BALB C
Infecções por Orthomyxoviridae/imunologia
Infecções por Orthomyxoviridae/mortalidade
Infecções por Orthomyxoviridae/patologia
RNA Viral/antagonistas & inibidores
RNA Viral/biossíntese
Análise de Sobrevida
Replicação Viral/efeitos dos fármacos
Zanamivir/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Chemokine CXCL10); 0 (Cxcl10 protein, mouse); 0 (IL1B protein, mouse); 0 (Immunologic Factors); 0 (Interleukin-1beta); 0 (Interleukin-6); 0 (RNA, Viral); 0 (interleukin-6, mouse); 20O93L6F9H (Oseltamivir); 77238-31-4 (Interferon-beta); EC 1.1.1.205 (IMP Dehydrogenase); HU9DX48N0T (Mycophenolic Acid); L6O3XI777I (Zanamivir)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171012
[St] Status:MEDLINE


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[PMID]:28763468
[Au] Autor:Le Gouellec N; Duhamel A; Perez T; Hachulla AL; Sobanski V; Faivre JB; Morell-Dubois S; Lambert M; Hatron PY; Hachulla E; Béhal H; Matran R; Launay D; Remy-Jardin M
[Ad] Endereço:Univ. Lille, U995, Lille Inflammation Research International Center (LIRIC), Lille, France.
[Ti] Título:Predictors of lung function test severity and outcome in systemic sclerosis-associated interstitial lung disease.
[So] Source:PLoS One;12(8):e0181692, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Systemic sclerosis-related interstitial lung disease (SSc-ILD) is the leading cause of death in SSc. In this study, we aimed to describe the baseline severity and evolution of forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) in patients with SSc-ILD and to assess the baseline clinical, biological and high-resolution CT scan (HRCT) predictors of this evolution. Baseline and serial FVC and DLCO were collected in 75 SSc-ILD patients followed during 6.4±4.2 years (n = 557 individual data). FVC and DLCO evolution was modelled using a linear mixed model with random effect. During follow-up, FVC was stable while DLCO significantly decreased (-1.5±0.3%/year (p<0.0001). Baseline NYHA functional class III/IV, extensive SSc-ILD on HRCT and DLCO<80% were associated with a lower baseline FVC. Absence of digital ulcers extensive SSc-ILD, and FVC<80% and were associated with a lower baseline DLCO. Presence or history of digital ulcers and presence of pulmonary hypertension at baseline or during follow-up were associated with a faster decline of DLCO overtime. Neither age, gender, subtype of SSc nor specificity of autoantibodies were associated with baseline severity or outcome of lung function tests. In this SSc-ILD population, FVC was therefore stable while DLCO significantly declined over time. ILD extension was associated with baseline FVC and DLCO but not with their evolution. Presence or history of digital ulcers and pulmonary hypertension were predictors of a faster decline of DLCO over time.
[Mh] Termos MeSH primário: Doenças Pulmonares Intersticiais/complicações
Capacidade de Difusão Pulmonar
Testes de Função Respiratória
Escleroderma Sistêmico/complicações
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Monóxido de Carbono/química
Ciclofosfamida/uso terapêutico
Difusão
Ecocardiografia
Feminino
Dedos/patologia
Seguimentos
Seres Humanos
Hipertensão Pulmonar/fisiopatologia
Modelos Lineares
Pulmão/fisiopatologia
Doenças Pulmonares Intersticiais/fisiopatologia
Masculino
Metotrexato/uso terapêutico
Meia-Idade
Ácido Micofenólico/uso terapêutico
Escleroderma Sistêmico/fisiopatologia
Úlcera/patologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
7U1EE4V452 (Carbon Monoxide); 8N3DW7272P (Cyclophosphamide); HU9DX48N0T (Mycophenolic Acid); YL5FZ2Y5U1 (Methotrexate)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170802
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181692


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Texto completo
[PMID]:28692371
[Au] Autor:Shahid S; Rait S; Sharples E; Gorard D
[Ad] Endereço:Gastroenterology Registrar, Gastroenterology Office, Wycombe Hospital, Buckinghamshire Healthcare NHS Trust, High Wycombe HP11 2TT.
[Ti] Título:Chronic hepatitis in the transplant patient.
[So] Source:Br J Hosp Med (Lond);78(7):408-409, 2017 Jul 02.
[Is] ISSN:1750-8460
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Rejeição de Enxerto/prevenção & controle
Hepatite E/diagnóstico
Hepatite Crônica/diagnóstico
Imunossupressores/efeitos adversos
Transplante de Rim
Doenças Renais Policísticas/cirurgia
[Mh] Termos MeSH secundário: Idoso
Alanina Transaminase/sangue
Antivirais/uso terapêutico
Hepatite E/sangue
Hepatite E/tratamento farmacológico
Hepatite E/etiologia
Vírus da Hepatite E/genética
Vírus da Hepatite E/imunologia
Hepatite Crônica/sangue
Hepatite Crônica/tratamento farmacológico
Hepatite Crônica/etiologia
Seres Humanos
Hospedeiro Imunocomprometido
Imunoglobulina M/sangue
Masculino
Ácido Micofenólico/efeitos adversos
Reação em Cadeia da Polimerase
RNA Viral/sangue
Ribavirina/uso terapêutico
Tacrolimo/efeitos adversos
Carga Viral
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antiviral Agents); 0 (Immunoglobulin M); 0 (Immunosuppressive Agents); 0 (RNA, Viral); 49717AWG6K (Ribavirin); EC 2.6.1.2 (Alanine Transaminase); HU9DX48N0T (Mycophenolic Acid); WM0HAQ4WNM (Tacrolimus)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170711
[St] Status:MEDLINE
[do] DOI:10.12968/hmed.2017.78.7.408



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