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[PMID]:29438379
[Au] Autor:Säll A; Corbee D; Vikström S; Ottosson F; Persson H; Waldemarson S
[Ad] Endereço:Department of Immunotechnology, Lund University, Lund, Sweden.
[Ti] Título:Advancing the immunoaffinity platform AFFIRM to targeted measurements of proteins in serum in the pg/ml range.
[So] Source:PLoS One;13(2):e0189116, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:There is a great need for targeted protein assays with the capacity of sensitive measurements in complex samples such as plasma or serum, not the least for clinical purposes. Proteomics keeps generating hundreds of biomarker candidates that need to be transferred towards true clinical application through targeted verification studies and towards clinically applicable analysis formats. The immunoaffinity assay AFFIRM (AFFInity sRM) combines the sensitivity of recombinant single chain antibodies (scFv) for targeted protein enrichment with a specific mass spectrometry readout through selected reaction monitoring (SRM) in an automated workflow. Here we demonstrate a 100 times improved detection capacity of the assay down to pg/ml range through the use of oriented antibody immobilization to magnetic beads. This was achieved using biotin-tagged scFv coupled to streptavidin coated magnetic beads, or utilizing the FLAG tag for coupling to anti-FLAG antibody coated magnetic beads. An improved multiplexing capacity with an 11-plex setup was also demonstrated compared to a previous 3-plex setup, which is of great importance for the analysis of panels of biomarker targets.
[Mh] Termos MeSH primário: Proteínas Sanguíneas/análise
Cromatografia de Afinidade/métodos
[Mh] Termos MeSH secundário: Seres Humanos
Limite de Detecção
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Blood Proteins)
[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:180214
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189116


  2 / 55447 MEDLINE  
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[PMID]:29389946
[Au] Autor:Okhovat MA; Ziari K; Ranjbaran R; Nikouyan N
[Ad] Endereço:Diagnostic Laboratory Sciences and Technology Research Center, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran.
[Ti] Título:The effect of histone deacetylase inhibitors on AHSP expression.
[So] Source:PLoS One;13(2):e0189267, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Alpha-hemoglobin stabilizing protein (AHSP) is a molecular chaperone that can reduce the damage caused by excess free α-globin to erythroid cells in patients with impaired ß-globin chain synthesis. We assessed the effect of sodium phenylbutyrate and sodium valproate, two histone deacetylase inhibitors (HDIs) that are being studied for the treatment of hemoglobinopathies, on the expression of AHSP, BCL11A (all isoforms), γ-globin genes (HBG1/2), and some related transcription factors including GATA1, NFE2, EKLF, KLF4, and STAT3. For this purpose, the K562 cell line was cultured for 2, 4, and 6 days in the presence and absence of sodium phenylbutyrate and sodium valproate. Relative real-time qRT-PCR analysis of mRNA levels was performed to determine the effects of the two compounds on gene expression. Expression of all target mRNAs increased significantly (p < 0.05), except for the expression of BCL11A, which was down-regulated (p < 0.05) in the cells treated with both compounds relative to the levels measured for untreated cells. The findings indicated that sodium valproate had a more considerable effect than sodium phenylbutyrate (p < 0.0005) on BCL11A repression and the up-regulation of other studied genes. γ-Globin and AHSP gene expression continuously increased during the culture period in the treated cells, with the highest gene expression observed for 1 mM sodium valproate after 6 days. Both compounds repressed the expression of BCL11A (-XL, -L, -S) and up-regulated GATA1, NFE2, EKLF, KLF4, STAT3, AHSP, and γ-globin genes expression. Moreover, sodium valproate showed a stronger effect on repressing BCL11A and escalating the expression of other target genes. The findings of this in vitro experiment could be considered in selecting drugs for clinical use in patients with ß-hemoglobinopathies.
[Mh] Termos MeSH primário: Proteínas Sanguíneas/metabolismo
Inibidores de Histona Desacetilases/farmacologia
Chaperonas Moleculares/metabolismo
[Mh] Termos MeSH secundário: Regulação da Expressão Gênica/efeitos dos fármacos
Hemoglobinopatias/tratamento farmacológico
Hemoglobinopatias/genética
Inibidores de Histona Desacetilases/uso terapêutico
Seres Humanos
Células K562
Fenilbutiratos/farmacologia
Reação em Cadeia da Polimerase em Tempo Real
Ácido Valproico/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (AHSP protein, human); 0 (Blood Proteins); 0 (Histone Deacetylase Inhibitors); 0 (Molecular Chaperones); 0 (Phenylbutyrates); 614OI1Z5WI (Valproic Acid); 7WY7YBI87E (4-phenylbutyric acid)
[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:180202
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189267


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[PMID]:29385206
[Au] Autor:Petersson F; Kilsgård O; Shannon O; Lood R
[Ad] Endereço:Division of Infection Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
[Ti] Título:Platelet activation and aggregation by the opportunistic pathogen Cutibacterium (Propionibacterium) acnes.
[So] Source:PLoS One;13(1):e0192051, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cutibacterium (Propionibacterium) acnes, considered a part of the skin microbiota, is one of the most commonly isolated anaerobic bacteria from medical implants in contact with plasma. However, the precise interaction of C. acnes with blood cells and plasma proteins has not been fully elucidated. Herein, we have investigated the molecular interaction of C. acnes with platelets and plasma proteins. We report that the ability of C. acnes to aggregate platelets is dependent on phylotype, with a significantly lower ability amongst type IB isolates, and the interaction of specific donor-dependent plasma proteins (or concentrations thereof) with C. acnes. Pretreatment of C. acnes with plasma reduces the lag time before aggregation demonstrating that pre-deposition of plasma proteins on C. acnes is an important step in platelet aggregation. Using mass spectrometry we identified several plasma proteins deposited on C. acnes, including IgG, fibrinogen and complement factors. Inhibition of IgG, fibrinogen or complement decreased C. acnes-mediated platelet aggregation, demonstrating the importance of these plasma proteins for aggregation. The interaction of C. acnes and platelets was visualized using fluorescence microscopy, verifying the presence of IgG and fibrinogen as components of the aggregates, and co-localization of C. acnes and platelets in the aggregates. Here, we have demonstrated the ability of C. acnes to activate and aggregate platelets in a bacterium and donor-specific fashion, as well as added mechanistic insights into this interaction.
[Mh] Termos MeSH primário: Ativação Plaquetária
Agregação Plaquetária
Propionibacterium acnes/fisiologia
[Mh] Termos MeSH secundário: Proteínas Sanguíneas/metabolismo
Seres Humanos
Espectrometria de Massas
Microscopia de Fluorescência
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Blood Proteins)
[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:180201
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0192051


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[PMID]:29366405
[Au] Autor:Walaszczyk A; Pietrowska M; Wojakowska A; Abramowicz A; Chmura A; Maslyk B; Rodziewicz P; Polanska J; Behrendt K; Nowicka E; Tarnawski R; Widlak P
[Ti] Título:Therapy-Related Changes in the Serum Proteome Patterns of Early Stage Breast Cancer Patients with Different Outcomes.
[So] Source:Protein Pept Lett;24(1):37-45, 2017.
[Is] ISSN:1875-5305
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Adjuvant chemo- and/or radiotherapy is applied in a majority of patients treated for early stage breast cancer, although only a small percentage of these individuals are at high risk of metastasis or recurrence. Hence, knowledge of the biomarkers associated with the risk of disease progression might facilitate the planning of an optimal therapy and protect many patients from the toxicity of unnecessary treatment. In this study, we characterized the serum proteome of patients diagnosed with early-stage breast cancer, exhibiting either no evidence of disease five years after the end of therapy or suffering from metastasis, relapse or a second cancer during the corresponding follow-up. Samples collected before treatment and one year after the end of therapy, when no clinical symptoms of a treatment failure was evidenced, were analyzed using two classical proteomics approaches: LC-MS/MS and 2D-PAGE. A total of 42 proteins with relative quantities that were significantly different between pre- and post-treatment samples were identified in either group of patients; however, the observed changes were more frequent in the treatment-failure group. Among the posttreatment samples, 30 proteins were upregulated, and 10 proteins were downregulated, while 11 proteins were upregulated, and eight proteins were downregulated in the control group. Moreover, several proteins exhibited different patterns of changes in both groups of patients. For example, haptoglobin expression increased in the treatment-failure group but decreased in the control group (this pattern of changes was confirmed using an immunoassay). Notably, proteins affected in posttreatment samples in either group of patients could be associated with different molecular and cellular functions, including angiogenesis, blood coagulation and wound healing in the treatment-failure group and cell adhesion and cell death in the control group.
[Mh] Termos MeSH primário: Proteínas Sanguíneas/análise
Neoplasias da Mama/sangue
Neoplasias da Mama/terapia
[Mh] Termos MeSH secundário: Idoso
Biomarcadores Tumorais/análise
Biomarcadores Tumorais/sangue
Eletroforese em Gel Bidimensional
Feminino
Haptoglobinas/análise
Seres Humanos
Meia-Idade
Proteoma/análise
Proteômica
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Blood Proteins); 0 (Haptoglobins); 0 (Proteome)
[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:180126
[St] Status:MEDLINE
[do] DOI:10.2174/0929866523666161128154412


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[PMID]:29406024
[Au] Autor:Ke CY; Lu GM; Sun WJ; Zhang XL
[Ad] Endereço:College of Chemistry and Chemical Engineering, Xi'an Shiyou University, Xi'an 710065, P.R. China. Electronic address: kcy@xsyu.edu.cn.
[Ti] Título:High efficiency and fast separation of active proteins by HIC chromatographic pie with sub-2 µm polymer packings.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1076:110-116, 2018 Feb 15.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:This paper reports the development of hydrophobic interaction chromatography (HIC) by synthesizing sub-2 µm polymer packings which was packed into a chromatographic pie for fast separation of native proteins at low pressures demonstrating high efficiency. Using styrene as monomer and ethylene dimethacrylate (EDMA)as swelling agent, the polystyrene seeds with an average particle size of 0.8 µm and monodisperse polymeric microspheres with a particle size of 1.5-5.0 µm were synthesized through dispersion polymerization and one-step swelling method, respectively. In order to separate active proteins, the microspheres were modified to hydrophobic chromatographic packings through covalent bonding with benzene methanol. Compared with the traditional column chromatography, the sub-2 µm polymer packings in chromatographic pie exhibited higher column efficiency for protein separation at lower column pressures, even at higher flow rates. The van Deemter curve showed that the flow rate had insignificant effect on column efficiency of chromatographic pie. Seven example proteins were clearly separated within 3 min at a flow rate of 10 mL/min. The applicability of this method was further demonstrated by the separation of human serum samples. The results indicated that this chromatographic mode can be potentially applied for the fast separation of complex active proteins, such as protein drugs from natural products.
[Mh] Termos MeSH primário: Proteínas Sanguíneas/isolamento & purificação
Cromatografia Líquida de Alta Pressão/métodos
[Mh] Termos MeSH secundário: Seres Humanos
Interações Hidrofóbicas e Hidrofílicas
Tamanho da Partícula
Poliestirenos/química
Fatores de Tempo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Proteins); 0 (Polystyrenes)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180207
[St] Status:MEDLINE


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[PMID]:28470789
[Au] Autor:Kulkarni SS; Vasantha K; Gogri H; Parchure D; Madkaikar M; Férec C; Fichou Y
[Ad] Endereço:National Institute of Immunohaematology, Indian Council of Medical Research (NIIH-ICMR), Mumbai, India.
[Ti] Título:First report of Rh individuals in the Indian population and characterization of the underlying molecular mechanisms.
[So] Source:Transfusion;57(8):1944-1948, 2017 08.
[Is] ISSN:1537-2995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Rh phenotype is an extremely rare condition characterized by no expression of Rh antigens at the surface of red blood cells. Although rare, genetic bases of this phenotype are well known and include mutations within either the RH (RHD and RHCE) genes or the RHAG gene. So far Rh has been reported in individuals of Caucasian, African, and Asian origin. Here, we report individuals from two families of Indian origin representing such a rare phenotype. STUDY DESIGN AND METHODS: Serologic analysis was carried out by testing with anti-D, -C, -c, -E, and -e in Rh individuals and their family members. RH genes were analyzed by standard molecular approaches, including Sanger sequencing and quantitative multiplex polymerase chain reaction (PCR) of short fluorescent fragments. RHAG gene was investigated by exon-specific PCR amplification and Sanger sequencing. RESULTS: In one family, RHAG gene was found to be deleted at the homozygous state in the propositus, suggesting Rh of the regulator type. In the other family, a novel splice site variant in RHCE in cis with whole RHD gene deletion was identified at the homozygous state. Further functional analysis by minigene splicing assay showed that this variation, that is, c.801 + 1G>A, completely impairs normal splicing, then inactivating the expression of RhCE protein. Contrary to the former case, these data suggest Rh of the amorph type. CONCLUSION: Overall, we report for the first time the molecular mechanisms responsible for Rh phenotype in individuals of Indian origin. This study contributes to extend the molecular spectrum of variations in Rh individuals.
[Mh] Termos MeSH primário: Grupo com Ancestrais do Continente Asiático/genética
Linhagem
Sistema do Grupo Sanguíneo Rh-Hr/genética
[Mh] Termos MeSH secundário: Proteínas Sanguíneas/genética
Família
Feminino
Deleção de Genes
Seres Humanos
Índia/epidemiologia
Masculino
Glicoproteínas de Membrana/genética
Processamento de RNA/genética
Testes Sorológicos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Blood Proteins); 0 (Membrane Glycoproteins); 0 (RHAG protein, human); 0 (RHCE protein, human); 0 (Rh-Hr Blood-Group System)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1111/trf.14150


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[PMID]:28470742
[Au] Autor:Lee DD; Muskaj I; Savage W
[Ad] Endereço:Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.
[Ti] Título:Platelet proteins cause basophil histamine release through an immunoglobulin-dependent mechanism.
[So] Source:Transfusion;57(7):1709-1716, 2017 07.
[Is] ISSN:1537-2995
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: A general understanding of allergic transfusion reaction mechanisms remains elusive. Multiple mechanisms have been proposed, but none have been compared experimentally. STUDY DESIGN AND METHODS: We used histamine release (HR) from healthy human donor basophils to model allergic transfusion reactions. Platelet component supernatant (plasma), platelet lysate, and manipulated platelet lysates (dialyzed, delipidated, trypsinized, mild heat-inactivated, and ultracentrifuged) were used to characterize allergic stimuli. Immunoglobulin-dependent mechanisms were investigated through cell surface immunoglobulin depletion and ibrutinib signaling inhibition. HR induced by platelet mitochondria was compared with HR by platelet lysate with or without DNase treatment. RESULTS: Robust, dose-responsive HR to platelet lysate was observed in two of eight nulliparous, never-transfused, healthy donors. No HR was observed with plasma. Among manipulated platelet lysates, only trypsin treatment significantly reduced HR (39% reduction; p = 0.008). HR in response to platelet lysate significantly decreased with either cell surface immunoglobulin depletion or ibrutinib pretreatment. Platelet mitochondria induced minimal basophil HR, and DNase treatment did not inhibit platelet lysate-induced HR. CONCLUSION: Type I immediate hypersensitivity to platelet proteins may be an allergic transfusion reaction mechanism. Prior sensitization to human proteins is not required for basophil responses to platelet proteins. Further study into the relative contributions of hypersensitivity to platelet versus plasma proteins in transfusion is warranted.
[Mh] Termos MeSH primário: Basófilos/fisiologia
Plaquetas/imunologia
Proteínas Sanguíneas/imunologia
Liberação de Histamina
Hipersensibilidade Imediata/etiologia
Imunoglobulina E/imunologia
Reação Transfusional/etiologia
[Mh] Termos MeSH secundário: Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Blood Proteins); 37341-29-0 (Immunoglobulin E)
[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:170505
[St] Status:MEDLINE
[do] DOI:10.1111/trf.14126


  8 / 55447 MEDLINE  
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[PMID]:27771981
[Au] Autor:Sabherwal S; English JA; Föcking M; Cagney G; Cotter DR
[Ad] Endereço:a Department of Psychiatry, Royal College of Surgeons in Ireland , ERC Beaumont Hospital , Dublin , Ireland.
[Ti] Título:Blood biomarker discovery in drug-free schizophrenia: the contributionof proteomics and multiplex immunoassays.
[So] Source:Expert Rev Proteomics;13(12):1141-1155, 2016 12.
[Is] ISSN:1744-8387
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Recent evidence supports an association between systemic abnormalities and the pathology of psychotic disorders which has led to the search for peripheral blood-based biomarkers. Areas covered: Here, we summarize blood biomarker findings in schizophrenia from the literature identified by two methods currently driving biomarker discovery in the human proteome; mass spectrometry and multiplex immunoassay. From a total of 14 studies in the serum or plasma of drug-free schizophrenia patients; 47 proteins were found to be significantly altered twice or more, in the same direction. Pathway analysis was performed on these proteins, and the resulting pathways discussed in relation to schizophrenia pathology. Future directions are also discussed, with particular emphasis on the potential for high-throughput validation techniques such as data-independent analysis for confirmation of biomarker candidates. Expert commentary: We present promising findings that point to a convergence of pathophysiological mechanisms in schizophrenia that involve the acute-phase response, glucocorticoid receptor signalling, coagulation, and lipid and glucose metabolism.
[Mh] Termos MeSH primário: Biomarcadores/sangue
Proteínas Sanguíneas/análise
Proteômica/métodos
Esquizofrenia/sangue
[Mh] Termos MeSH secundário: Feminino
Seres Humanos
Imunoensaio/métodos
Masculino
Espectrometria de Massas/métodos
Esquizofrenia/diagnóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biomarkers); 0 (Blood Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


  9 / 55447 MEDLINE  
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[PMID]:29223049
[Au] Autor:Li M; Chen X; Hu S; Wang R; Peng X; Bai X
[Ad] Endereço:School of Pharmacy, Shanxi Medical University, Taiyuan 030001, China.
[Ti] Título:Determination of blood concentrations of main active compounds in Zi-Cao-Cheng-Qi decoction and their total plasma protein binding rates based on hollow fiber liquid phase microextraction coupled with high performance liquid chromatography.
[So] Source:J Chromatogr B Analyt Technol Biomed Life Sci;1072:355-361, 2018 Jan 01.
[Is] ISSN:1873-376X
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Oil-in-salt hollow fiber liquid phase microextraction coupled with high performance liquid chromatography ultraviolet detection (HPLC-UV) was developed for determination of the blood concentrations of the main active compounds, hesperidin, honokiol, shikonin, magnolol, emodin and ß,ß'-dimethylacrylshikonin, after oral administration of Zi-Cao-Cheng-Qi decoction (ZCCQD) and their total plasma protein binding rates. In the procedure, a hollow fiber segment was immersed in organic solvent to fill the solvent in the fiber lumen and wall pore, and then the fiber was immersed into sodium chloride solution to cover a thin salt membrane on the fiber wall pore filling organic solvent. Various factors affecting the procedure, such as extraction solvent, sample phase pH, stirring rate, extraction time, NaCl concentration and fiber immersion time in the NaCl solution, were optimized. Under the optimum conditions, good linearities (r ≥0.9905), low limits of detection (0.7-2.5ng/mL) or quantitation (1.2-12ng/mL), satisfactory precision (2.6%-12.8%) and accuracy (81.0%-114.2%) of this method, were observed. The results showed that, after oral administration of a 25g/kg dose, (1) the blood concentrations (at 0.5h) of hesperidin, honokiol, shikonin, magnolol, emodin and ß,ß'-dimethylacrylshikonin were 0.45, 0.40, 0.48, 0.74, 0.11 and 1.11µg/mL, respectively; (2) the total plasma protein binding rates of the six active compounds were 42.0% (hesperidin), 71.8% (honokiol), 64.6% (shikonin), 77.7% (magnolol), 75.3% (emodin) and 75.7% (ß,ß'-dimethylacrylshikonin), respectively. The proposed procedure coupled with HPLC shows obvious advantages, such as low solvent consumption, simple operation, high sensitivity and strong purifying and can be used for the determination of both the blood concentrations and total plasma protein binding rates of active compounds in traditional Chinese medicine.
[Mh] Termos MeSH primário: Proteínas Sanguíneas/metabolismo
Cromatografia Líquida de Alta Pressão/métodos
Medicamentos de Ervas Chinesas/análise
Medicamentos de Ervas Chinesas/metabolismo
Microextração em Fase Líquida/métodos
[Mh] Termos MeSH secundário: Animais
Proteínas Sanguíneas/química
Estabilidade de Medicamentos
Medicamentos de Ervas Chinesas/química
Concentração de Íons de Hidrogênio
Limite de Detecção
Modelos Lineares
Masculino
Ligação Proteica
Ratos
Ratos Sprague-Dawley
Reprodutibilidade dos Testes
Cloreto de Sódio
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Blood Proteins); 0 (Drugs, Chinese Herbal); 451W47IQ8X (Sodium Chloride)
[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:171210
[St] Status:MEDLINE


  10 / 55447 MEDLINE  
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[PMID]:29384862
[Au] Autor:Sperk M; Zhang W; Nowak P; Neogi U
[Ad] Endereço:Divison of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge.
[Ti] Título:Plasma soluble factor following two decades prolonged suppressive antiretroviral therapy in HIV-1-positive males: A cross-sectional study.
[So] Source:Medicine (Baltimore);97(5):e9759, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Acute human immunodeficiency virus (HIV) infection is associated with a marked induction of several pathways that are linked to inflammation and CD4 T-cell depletion. Many of these processes do not fully resolve on short-term combination antiretroviral therapy (cART) (<5 years), despite complete and durable suppression of viremia. The effects of long-term (>15 years) successful antiretroviral therapy (ART) and the linkage between levels of biomarkers remain unclear. Therefore, the present study aims to assess the host plasma proteome in a well-defined clinical material from HIV-1-positive male patients on successful long-term ART (>15 years) and compared them with age-matched healthy controls and treatment-naïve male patients with viremia in a cross-sectional manner.Plasma samples were obtained from 3 categories of age-matched HIV-1-positive male patients on long-term successfully (ART, n = 10) with a median (Interquartile range, IQR) of 19 (17-20) years, treatment-naïve patients with viremia (VP, n = 14), and HIV-1-negative persons (HC, n = 11). Plasma proteome was analyzed using the proximity extension assay targeting 92 factors. Statistical analyses were performed with GraphPad Prism v7, R-packages, and Qlucore Omics Explorer v3.2. Functional enrichment analysis was performed by Kyoto Encyclopedia of Genes and Genomes (KEGG), and interactions of specific molecules were identified using Path Designer integrated into Ingenuity Pathway Analysis (IPA).Group wise comparison identified 53 soluble factors, which differed between the groups (P < .05). Cluster analysis identified 13 discrete soluble factors (CD8A, CRTAM, CXCL13, EGF, CD5, CD40, CXCL9, Gal-1, IL12RB1, KLRD1, PD-1, CASP-8 and TNFRSF9) between the studied groups (adjusted P < .001). The long-term successfully ART-treated individuals clustered and networked with the HC while VPs clustered separately. All of the proinflammatory cytokines and chemokines were normalized back to levels of healthy controls in long-term successfully ART-treated individuals, but not the levels of KLRD1 and PGDFB.sKLRD1 that is involved in the regulation of natural killer cell (NK) mediated cytotoxicity, failed to be restored to the level of HIV-negative individuals despite successful long-term ART. Additional analysis of NK cells along with T-cell subsets can provide insights into the long-term effects of ART on the immune system.
[Mh] Termos MeSH primário: Fármacos Anti-HIV/uso terapêutico
Proteínas Sanguíneas/metabolismo
Citocinas/sangue
Infecções por HIV/sangue
Infecções por HIV/tratamento farmacológico
[Mh] Termos MeSH secundário: Terapia Antirretroviral de Alta Atividade
Biomarcadores/sangue
Estudos de Casos e Controles
Estudos Transversais
Esquema de Medicação
Seres Humanos
Masculino
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Anti-HIV Agents); 0 (Biomarkers); 0 (Blood Proteins); 0 (Cytokines)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180221
[Lr] Data última revisão:
180221
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009759



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