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Role of the CYP2D6, EPHX1, MPO, and NQO1 Genes in the Susceptibility to Acute Lymphoblastic Leukemia in Brazilian Children

SILVEIRA, Vanessa da Silva; CANALLE, Renata; SCRIDELI, Carlos Alberto; QUEIROZ, Rosane Gomes de Paula; TONE, Luiz Gonzaga
Fonte: WILEY-LISS Publicador: WILEY-LISS
Tipo: Artigo de Revista Científica
Português
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Polymorphic variations of several genes associated with dietary effects and exposure to environmental carcinogens may influence susceptibility to leukemia development. The objective of the present study was to evaluate the effect of the polymorphisms of debrisoquine hydroxylase (CYP2D6), epoxide hydrolase (EPHX1), myeloperoxidase (MPO), and quinone-oxoreductase (NQO1), which have been implicated in xenobiotic metabolism, on the risk of childhood acute lymphoblastic leukemia (ALL). We evaluated the frequency of polymorphisms in the CYP2D6 (*3 and *4), EPHX1 (*2 and *3), MPO (*2), and NQO1 (*2) genes in 206 patients with childhood ALL and in 364 healthy individuals matched for age and gender from a Brazilian population separated by ethnicity (European ancestry and African ancestry), using the PCR-RFLP method. The CYP2D6 polymorphism variants were associated with an increased risk of ALL. The EPHX1, NQO1, and MPO variant genotypes were significantly associated with a reduced risk of childhood ALL. A significantly stronger protective effect is observed when the EPHX1, NQO1, and MPO variant genotypes are combined suggesting that, CYP2D6 polymorphisms may play a role in the susceptibility to pediatric ALL, whereas the EPHX1, NQO1, and MPO polymorphisms might have a protective function against leukemogenesis. Environ. Mal. Mulagen. 51:48-56...

Gingival crevicular fluid levels of MMP-8, MMP-9, TIMP-2, and MPO decrease after periodontal therapy

MARCACCINI, Andrea M.; MESCHIARI, Cesar A.; ZUARDI, Leonardo R.; SOUSA, Tiago Sampaio de; TABA JR., Mario; TEOFILO, Juliana M.; JACOB-FERREIRA, Anna L. B.; TANUS-SANTOS, Jose E.; NOVAES JR., Arthur B.; GERLACH, Raquel F.
Fonte: WILEY-BLACKWELL PUBLISHING, INC Publicador: WILEY-BLACKWELL PUBLISHING, INC
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
37.25026%
P>Background This study aimed at comparing the levels of matrix metalloproteinase (MMP)-8, tissue Inhibitor of MMPs (TIMP)-1 and TIMP-2, Myeloperoxidase (MPO), and MMP-9 in the gingival crevicular fluid (GCF) of chronic periodontitis (CP) patients and controls at baseline and 3 months after non-surgical therapy. Materials and Methods GCF was collected from one site of 15 control subjects and 27 CP patients. MMP-8, MMP-9, TIMP-1, and TIMP-2 were determined by Enzyme-linked immunoabsorbent assay; different forms of MMP-9, by gelatin zymography; and MPO, colorimetrically. Results At baseline, higher levels of MMP-8, TIMP-2, MPO, and the 87 kDa-MMP-9 were found in patients compared with controls (p < 0.001), and these molecules decreased after therapy (p < 0.03). There were no differences between the groups with respect to the higher molecular forms of MMP-9 (180, 130, 92 kDa) or total MMP-9 at baseline. No differences were observed in TIMP-1 levels. In controls, decreased levels of TIMP-2 and the higher molecular forms of MMP-9 (180, 130, 92 kDa) were found 3 months after therapy compared with baseline (p < 0.01). Conclusions Higher levels of MMP-8, TIMP-2, MPO, and 87 kDa MMP-9 were found in the GCF of patients compared with controls...

MPO Inhibitors Selected by Virtual Screening

MALVEZZI, Alberto; QUEIROZ, Raphael F.; REZENDE, Leandro de; AUGUSTO, Ohara; AMARAL, Antonia T-do
Fonte: WILEY-BLACKWELL Publicador: WILEY-BLACKWELL
Tipo: Artigo de Revista Científica
Português
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The hemeprotein myeloperoxidase (MPO) participates in innate immune defense through its ability to generate potent microbicidal oxidants. However, these oxidants are also key mediators of the tissue damage associated with many inflammatory diseases. Thus, there is considerable interest in developing therapeutically useful MPO inhibitors. Here, we used structure-based drug design (SBDD) and ligand-based drug design (LBDD) to select for potentially new and selective MPO inhibitors. A pharmacophore model was developed based on the crystal structure of human MPO in complex with salicylhydroxamic acid (SHA), a known inhibitor of the enzyme. The pharmacophore model was used to screen the ZINC database for potential ligands, which were further filtered on the basis of their physical-chemical properties and docking score. The filtered compounds were visually inspected, and nine were purchased for experimental studies. Surprisingly, almost all of the selected compounds belonged to the aromatic hydrazide class, which had been previously described as MPO inhibitors. The compounds selected by virtual screening were shown to inhibit the chlorinating activity of MPO; the top four compounds displayed IC(50) values ranging from 1.0 to 2.8 mM. MPO inactivation by the most effective compound was shown to be irreversible. Overall...

Evaluation of plasmatic MMP-8, MMP-9, TIMP-1 and MPO levels in obese and lean women

Andrade, Vanessa L.; Petruceli, Eveline; Belo, Vanessa A.; Andrade-Fernandes, Claudia M.; Caetano Russi, Cristiane V.; Bosco, Adriana Ap.; Tanus-Santos, Jose Eduardo; Sandrim, Valeria Cristina
Fonte: PERGAMON-ELSEVIER SCIENCE LTD; OXFORD Publicador: PERGAMON-ELSEVIER SCIENCE LTD; OXFORD
Tipo: Artigo de Revista Científica
Português
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Objectives: To compare the plasma concentrations of matrix metalloproteinase (MMP)-9, tissue inhibitor of MMP (TIMP)-1, MMP-8, and myeloperoxidase (MPO) for obese and lean women. Design and methods: We recruited 30 lean and 36 obese women without comorbidities. The MMP-9, TIMP-1, and MMP-8 levels were measured using enzyme-linked immunosorbent assay (ELISA). MPO activity was assessed by a colorimetric assay. Results: Obese women had higher MMP-9 levels and MMP-9:TIMP-1 ratios than lean women. Conversely, the MMP-8 levels and MMP-8:TIMP-1 ratios in the obese women were significantly lower than those in the lean women despite neutrophil activation, which was assessed by MPO activity., Conclusion: We observed that MMP-9 and MMP-8 had distinct profiles, which suggested that these 2 enzymes play different roles in obesity. (C) 2012 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.; Fundacdo de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG-Brazil); Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior (CAPES-Brazil); Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq-Brazil); IEPSCBH Instituto de Ensino e Pesquisa da Santa Casa de Belo Horizonte

Concentrações de MMP-8, MMP-9, MPO, TIMP-1 e TIMP-2 na saliva e correlações com plasma; Concentrations of MMP-8, MMP-9, MPO, TIMP-1 and TIMP-2 in saliva and their correlations with plasma

Meschiari, César Arruda
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 06/07/2011 Português
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Metaloproteinases da matriz extracelular (MMPs) são uma família de endopeptidases zinco-dependentes conhecidas por degradar componentes do tecido conjuntivo em processos fisiológicos e patológicos. A regulação da atividade das MMPs pode ser feita pelos inibidores teciduais de metaloproteinases (TIMPs). A doença periodontal (DP) é a inflamação crônica em que atividade excessiva das MMPs e mieloperoxidase (MPO) são apontadas como responsáveis pela destruição dos tecidos suporte dos dentes. Os componentes da saliva são derivados da vascularização local sendo possível encontrar neste fluido o reflexo de muitas moléculas presentes no plasma. Desta forma, os objetivos deste trabalho foram: 1) Comparar os níveis de MMPs, TIMPs e MPO na saliva total estimulada (STE) e plasma de pacientes com DP antes (DA) e após (DT) o tratamento periodontal não cirúrgico, e em voluntários saudáveis no início do estudo (CA) e após 3 meses (CT); 2) Avaliar se existe correlação entre os resultados. Foram realizadas as dosagens de MMP-8, MMP-9, TIMP-1 e TIMP-2 pelo método de ELISA; a atividade gelatinolítica das formas da MMP-9 por zimografia; e a atividade da MPO por ensaio colorimétrico. Houve uma menor atividade gelatinolítica...

Efeito do L-Name na expressão de iNOS, MPO e na perda óssea alveolar em ratos diabéticos com periodontite experimental

Gomes, Débora Aline Silva
Fonte: Universidade Estadual Paulista (UNESP) Publicador: Universidade Estadual Paulista (UNESP)
Tipo: Tese de Doutorado Formato: 104 f. : il. + Anexo
Português
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Pós-graduação em Odontologia - FOAR; Mediadores inflamatórios como mieloperoxidase (MPO) e óxido nítrico (NO) participam do processo inflamatório da doença periodontal e na associação ao diabetes. Inibidores da Óxido Nítrico Sintase (NOS), como o L-NAME têm sido administrados na tentativa de minimizar danos teciduais decorrentes da inflamação. O objetivo deste estudo foi avaliar o efeito do L-NAME sobre os níveis da isoforma induzível de óxido nítrico (iNOS), sobre a perda óssea alveolar e sobre os níveis de mieloperoxidase (MPO) em ratos diabéticos com periodontite induzida. Foram utilizados 192 ratos divididos em grupos de 24 animais cada: grupo C: Controle com ingestão de água; grupo C-L: Controle com ingestão de LNAME; grupo D: Ratos diabéticos com ingestão de água; grupo D-L: Ratos diabéticos com ingestão de L-NAME; grupo P: Ratos com periodontite experimental e ingestão de água; grupo P-L: Ratos com periodontite experimental e ingestão de L-NAME; grupo DP: Ratos diabéticos com periodontite experimental e ingestão de água; e grupo DP-L: Ratos diabéticos com periodontite experimental e ingestão de L-NAME. O sacrifício dos animais foram realizados aos 3,7,15,e 30 dias após a indução da periodontite experimental. Foram realizadas análises da taxa glicêmica...

N-acetylglucosaminidase, myeloperoxidase and vascular endothelial growth factor serum levels in breast cancer patients

Coelho, Bertha Andrade; Belo, Andrezza Vilaca; Andrade, Silvia Passos; Amorim, Washington Cancado; Uemura, Gilberto; Silva Filho, Agnaldo Lopes da
Fonte: Elsevier B.V. Publicador: Elsevier B.V.
Tipo: Artigo de Revista Científica Formato: 185-189
Português
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Inflammatory cells surround breast carcinomas and may act promoting tumor development or stimulating anti-tumor immunity. N-acetylglucosaminidase (NAG) has been employed to detect macrophage accumulation/activation. Myeloperoxidase (MPO) is considered a marker for neutrophils activity/accumulation. Vascular Endothelial Growth Factor (VEGF) is as strong pro-angiogenic cytokine. The aim of this study was to measure the systemic inflammatory response by measuring serum levels of NAG, MPO and VEGF in women diagnosed with breast cancer and associate this response to the peritumoral inflammatory infiltrate and to prognostic factors. Serum samples obtained from women with no evidence of disease (n = 31) and with breast cancer (n = 68) were analyzed for the activities of NAG, MPO and VEGF by enzymatic assay. Serum levels of NAG and VEGF were higher in healthy volunteers (P < 0.0001) and serum levels of MPO were higher in patients with breast cancer (P = 0.002). Serum levels of NAG were positively correlated to serum levels of MPO and VEGF (P < 0.0001 and P = 0.0012, respectively) and MPO and VEGF serum levels had also a positive correlation (P = 0.0018). The inflammatory infiltrate was not associated to serum levels of the inflammatory markers...

Gingival crevicular fluid levels of MMP-8, MMP-9, TIMP-2, and MPO decrease after periodontal therapy

MARCACCINI, Andrea M.; MESCHIARI, Cesar A.; ZUARDI, Leonardo R.; SOUSA, Tiago Sampaio de; TABA JR., Mario; TEOFILO, Juliana M.; JACOB-FERREIRA, Anna L. B.; TANUS-SANTOS, Jose E.; NOVAES JR., Arthur B.; GERLACH, Raquel F.
Fonte: WILEY-BLACKWELL PUBLISHING, INC Publicador: WILEY-BLACKWELL PUBLISHING, INC
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
37.25026%
P>Background This study aimed at comparing the levels of matrix metalloproteinase (MMP)-8, tissue Inhibitor of MMPs (TIMP)-1 and TIMP-2, Myeloperoxidase (MPO), and MMP-9 in the gingival crevicular fluid (GCF) of chronic periodontitis (CP) patients and controls at baseline and 3 months after non-surgical therapy. Materials and Methods GCF was collected from one site of 15 control subjects and 27 CP patients. MMP-8, MMP-9, TIMP-1, and TIMP-2 were determined by Enzyme-linked immunoabsorbent assay; different forms of MMP-9, by gelatin zymography; and MPO, colorimetrically. Results At baseline, higher levels of MMP-8, TIMP-2, MPO, and the 87 kDa-MMP-9 were found in patients compared with controls (p < 0.001), and these molecules decreased after therapy (p < 0.03). There were no differences between the groups with respect to the higher molecular forms of MMP-9 (180, 130, 92 kDa) or total MMP-9 at baseline. No differences were observed in TIMP-1 levels. In controls, decreased levels of TIMP-2 and the higher molecular forms of MMP-9 (180, 130, 92 kDa) were found 3 months after therapy compared with baseline (p < 0.01). Conclusions Higher levels of MMP-8, TIMP-2, MPO, and 87 kDa MMP-9 were found in the GCF of patients compared with controls...

Binding and inhibition of myeloperoxidase (MPO): a major function of ceruloplasmin?

SEGELMARK, M; PERSSON, B; HELLMARK, T; WIESLANDER, J
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /04/1997 Português
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Interactions between plasma proteins and MPO were studied. The protein fraction of normal plasma and serum was shown to exhibit an inhibitory effect on the peroxidase activity of MPO. Most of the inhibitory effect could be retained on an MPO-coupled affinity chromatography column. In particular, a protein with apparent mol. wt of 130 kD showed affinity for MPO. The protein was identified as ceruloplasmin by N-terminal amino acid sequencing and immunochemistry. During separation procedures the peroxidase inhibitory effect was limited to ceruloplasmin-containing fractions of plasma. Purified ceruloplasmin inhibited the peroxidase activity of MPO in a concentration-dependent manner, and exhibited selective binding to MPO-coated microtitre plates. This binding could be inhibited by MPO dissolved in buffer. Correspondingly the binding of MPO to ceruloplasmin-coated plates could be blocked by ceruloplasmin in solution, showing a physical interaction to occur between the two proteins under physiological conditions. We also found affinity to exist between MPO and C3 (and its C3d-containing fragments). However, C3 and C3 fragments did not inhibit the peroxidase reaction in vitro. We propose that ceruloplasmin takes part in the clearance and inactivation of MPO...

T cell responses to myeloperoxidase (MPO) and proteinase 3 (PR3) in patients with systemic vasculitis

GRIFFITH, M E; COULTHART, A; PUSEY, C D
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /02/1996 Português
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T cell-mediated immune responses are likely to be important in the pathogenesis of systemic vasculitis. However, identifying the T cells involved has proved difficult, and there are conflicting reports regarding T cell proliferation in response to different autoantigens. Perinuclear (P) and cytoplasmic (C) anti-neutrophil cytoplasmic antibodies (ANCA) are closely associated with systemic vasculitis, and are generally specific for MPO or PR3, respectively. We studied the proliferative responses to MPO and PR3 of peripheral blood mononuclear cells from patients with P-ANCA or C-ANCA specific for these antigens by ELISA. These responses were compared with those of normal controls, and of disease controls with P- or C-ANCA not specific for MPO or PR3. The patient group as a whole showed significant T cell proliferation in response to the autoantigens compared with controls (P =0·005). Cells from nine of 13 P-ANCA-positive, anti-MPO-positive patients proliferated in response to MPO, compared with five of 16 controls (P =0·04). Cells from five of eight C-ANCA-positive, anti-PR3-positive patients proliferated in response to PR3, compared with two of 11 controls (P =0·05). These experiments demonstrate that patients with P-ANCA or C-ANCA possess T cells which respond to MPO or PR3...

A prospective study of genetic polymorphism in MPO, antioxidant status, and breast cancer risk

He, Chunyan; Tamimi, Rulla M.; Hankinson, Susan E.; Hunter, David J.; Han, Jiali
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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Oxidative stress may be involved in breast carcinogenesis. Myeloperoxidase (MPO) is an endogenous oxidant enzyme that generates reactive oxygen species (ROS). A single nucleotide polymorphism (SNP) G-463A in the promoter region has been associated with a decrease in risk of breast cancer. We assessed the association between this polymorphism and breast cancer risk in a nested case-control study within the Nurses’ Health Study (1269 incident breast cancer cases and 1761 matched controls). We further investigated potential gene-gene and gene-environment interactions. There were no significant associations between MPO or COMT genotypes and risk of breast cancer. However, the combination of a priori hypothesized low-risk genotypes in MPO and COMT genes was associated with a marginally significant decrease in breast cancer risk (OR, 0.28; 95% CI, 0.08–1.00). Dietary intake and plasma antioxidant levels may modify the association between the MPO polymorphism and breast cancer risk. Although the test for departure from multiplicative interaction was not significant, inverse associations with MPO genotype were more pronounced among women who consumed higher amounts of total fruits and vegetables (OR, 0.58; 95% CI, 0.30–1.12); this association was not found among the low-consumption group (OR...

Using modified whole-mount in situ hybridization to study mpo expression in zebrafish

SHEN, LI-JING; CAO, LAN-FANG; CHEN, FANG-YUAN; ZHANG, YONG; ZHONG, JI-HUA; ZHONG, HUA
Fonte: D.A. Spandidos Publicador: D.A. Spandidos
Tipo: Artigo de Revista Científica
Português
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In this study, we cloned the myeloperoxidase (mpo) gene of zebrafish and prepared a digoxigenin-labeled mpo RNA probe to investigate mpo gene expression in zebrafish during embryonic development by whole-mount in situ hybridization (WISH). The earliest mpo expression was detected in cells of the intermediate cell mass (ICM) at 18 h post-fertilization (hpf). It was detected 1 to 2 h later in cells in the rostral blood island (RBI) and strong signals were observed in the anterior ICM. Then, it spread over the yolk sac. By 72 hpf these mpo-expressing cells were in the circulation and distributed throughout the embryo. We identified that the level of mpo expression detected by WISH at an early stage was consistent with the data of cytological analyses of adult fish. The use of this method enabled us to track the gene changes that took place before morphological phenotypes were detected, as well to as investigate the hematopoietic cell fate in mutational or transgenic models in vivo. In this study, we modified several steps of WISH. The improved hybridization results demonstrated high specificity, distinct coloration and low background figures.

The role of myeloperoxidase and myeloperoxidase–antineutrophil cytoplasmic antibodies (MPO-ANCAs) in the pathogenesis of human MPO-ANCA-associated glomerulonephritis

Arimura, Yoshihiro; Kawashima, Soko; Yoshihara, Ken; Komagata, Yoshinori; Kaname, Shinya; Yamada, Akira
Fonte: Springer Japan Publicador: Springer Japan
Tipo: Artigo de Revista Científica
Português
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It is well known that antineutrophil cytoplasmic antibodies (ANCAs) are pathogenic and have a diagnostic value for ANCA-associated vasculitis. We demonstrated that a rise in myeloperoxidase (MPO)-ANCA titers during remission is often predictive of a future relapse in MPO-ANCA-associated vasculitis. Pathological examination of renal biopsies indicated that not only MPO-ANCAs, but also extracellular MPO, an in situ immune complex composed of MPO and MPO antibodies, may play important roles in the pathogenesis of glomerular capillary injury in MPO-ANCA-associated vasculitis.

Therapy with Plasma Purified Alpha1-Antitrypsin (Prolastin®) Induces Time-Dependent Changes in Plasma Levels of MMP-9 and MPO

Koepke, Janine; Dresel, Marc; Schmid, Severin; Greulich, Timm; Beutel, Björn; Schmeck, Bernd; Vogelmeier, Claus Franz; Janciauskiene, Sabina; Koczulla, Andreas Rembert
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 30/01/2015 Português
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The common Z mutation (Glu342Lys) of α1-antitrypsin (A1AT) results in the polymerization and intracellular retention of A1AT protein. The concomitant deficiency of functional A1AT predisposes PiZZ subjects to early onset emphysema. Clinical studies have implied that, among the biomarkers associated with emphysema, matrix metalloproteinase 9 (MMP-9) is of particular importance. Increased plasma MMP-9 levels are proposed to predict the decline of lung function as well as greater COPD exacerbations in A1AT deficiency-associated emphysema. The aim of the present study was to investigate the effect of A1AT therapy (Prolastin) on plasma MMP-9 and myeloperoxidase (MPO) levels. In total 34 PiZZ emphysema patients were recruited: 12 patients without and 22 with weekly intravenous (60 mg/kg body weight) A1AT therapy. The quantitative analysis of A1AT, MMP-9 and MPO was performed in serum and in supernatants of blood neutrophils isolated from patients before and after therapy. Patients with Prolastin therapy showed significantly lower serum MMP-9 and MPO levels than those without therapy. However, parallel analysis revealed that a rapid infusion of Prolastin is accompanied by a transient elevation of plasma MMP-9 and MPO levels. Experiments with freshly isolated blood neutrophils confirmed that therapy with Prolastin causes transient MMP-9 and MPO release. Prolastin induced the rapid release of MMP-9 and MPO when added directly to neutrophil cultures and this reaction was associated with the presence of IgA in A1AT preparation. Our data support the conclusion that changes in plasma levels of MMP-9 and MPO mirror the effect of Prolastin on blood neutrophils.

MPO-ANCA crescentic glomerulonephritis complicated by membranous nephropathy: MPO demonstrated in epimembranous deposits

Matsumoto, Kei; Honda, Hirokazu; Shibata, Takanori; Sanada, Daisuke; Wada, Yukihiro; Ashikaga, Eijin; Kuroki, Aki; Kitazawa, Kozo; Akizawa, Tadao
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
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An elderly woman presented with haematuria and proteinuria accompanied by elevated serum myeloperoxidase (MPO)-specific anti-neutrophil cytoplasmic antibodies (MPO-ANCA). A renal biopsy revealed mild mesangial proliferation with fibrocellular crescent formation and a membranous glomerular lesion. Immunofluorescence microscopy using FITC-labelled rabbit anti-human MPO antibodies revealed granular MPO deposition along the glomerular capillary walls (GCW) with a staining profile similar to that of glomerular IgG deposition. The one-year follow-up renal biopsy revealed minimal IgG and undetectable MPO deposition. Both MPO and MPO-ANCA might have been responsible for the IgG immune depositions along the GCW in this patient.

Intermediate monocytes in ANCA vasculitis: increased surface expression of ANCA autoantigens and IL-1β secretion in response to anti-MPO antibodies

O’Brien, Eóin C.; Abdulahad, Wayel H.; Rutgers, Abraham; Huitema, Minke G.; O’Reilly, Vincent P.; Coughlan, Alice M.; Harrington, Mark; Heeringa, Peter; Little, Mark A.; Hickey, Fionnuala B.
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em 07/07/2015 Português
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ANCA vasculitis encompasses several autoimmune conditions characterised by destruction of small vessels, inflammation of the respiratory tract and glomerulonephritis. Most patients harbour autoantibodies to myeloperoxidase (MPO) or proteinase 3 (PR3). Clinical and experimental data suggest that pathogenesis is driven by ANCA-mediated activation of neutrophils and monocytes. We investigated a potential role for distinct monocyte subsets. We found that the relative proportion of intermediate monocytes is increased in patients versus control individuals, and both MPO and PR3 are preferentially expressed on these cells. We demonstrate that MPO and PR3 are expressed independently of each other on monocytes and that PR3 is not associated with CD177. MPO expression correlates with that of Fc receptor CD16 on intermediate monocytes. Monocyte subsets respond differently to antibodies directed against MPO and PR3, with anti-MPO but not anti-PR3 leading to increased IL-1β, IL-6 and IL-8 production. In concordance with the observed higher surface expression of MPO on intermediate monocytes, this subset produces the highest quantity of IL-1β in response to anti-MPO stimulation. These data suggest that monocytes, specifically, the intermediate subset...

Levosimendan displays anti-inflammatory effects and decreases MPO bioavailability in patients with severe heart failure

Adam, Matti; Meyer, Sven; Knors, Henning; Klinke, Anna; Radunski, Ulf K.; Rudolph, Tanja K.; Rudolph, Volker; Spin, Joshua M.; Tsao, Philip S.; Costard-Jäckle, Angelika; Baldus, Stephan
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
Publicado em 13/04/2015 Português
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Treatment of decompensated heart failure often includes administration of levosimendan. Myeloperoxidase (MPO) is released during polymorphonuclear neutrophil (PMN) degranulation, and mediates dysregulation of vascular tone in heart failure. We evaluated the effects of levosimendan-treatment on MPO in patients with acute decompensation of chronic heart failure over a one week course. Plasma MPO levels were significantly decreased after levosimendan treatment (from 252.1 ± 31.1 pmol/l at baseline to 215.02 ± 27.96 pmol/l at 6 h, p < 0.05). Ex vivo incubation of whole blood with levosimendan decreased MPO release after PMN-stimulation (8.2 ± 1.4-fold increase at baseline vs. 6.0 ± 1.1-fold increase with levosimendan). MPO levels also significantly correlated with diastolic blood pressure over the time course. In a multivariate linear model, the main contributor to systolic, diastolic and mean blood pressure was level of PMN elastase. MPO contributed only in heparin-treated patients, suggesting a more significant role for endothelial-bound MPO than for circulating MPO or elastase with respect to blood pressure regulation. We here provide the first evidence that levosimendan treatment inhibits MPO release by PMNs in decompensated heart failure patients. This mechanism may regulate endothelial function and vascular tone in heart failure patients.

Niveles de mieloperoxidasa (MPO) en exudado periapical de dientes con periodontitis apical asintomática (PAA) medidos pre y post medicación endodóntica con hidróxido de calcio

Castro Salas, Josefa Belén
Fonte: Universidad de Chile Publicador: Universidad de Chile
Tipo: Tesis
Português
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Trabajo de Investigación Requisito para optar al Título de Cirujano Dentista; Introducción: La periodontitis apical asintomática (PAA) corresponde a una patología infecciosa generada por la invasión microbiana del sistema de canales radiculares que resulta en la destrucción del periodonto apical. Clínicamente no presenta sintomatología, por lo que usualmente su hallazgo es radiográfico, observándose un área radiolúcida periapical. La mieloperoxidasa (MPO) es una enzima que cataliza la formación de ácido hipocloroso (HClO) y su presencia ha sido descrita en PAA. El HClO es un potente oxidante con rol defensivo contra los agentes infecciosos y que paralelamente provoca daño a los tejidos adyacentes. Las pastas de hidróxido de calcio (Ca(OH) ) son utilizadas como medicación intracanal entre sesiones en el tratamiento endodóntico de dientes con PAA para desinfectar y evitar la reinfección de los canales ya tratados. A la fecha no se ha estudiado el efecto del Ca(OH) 2 2 sobre los niveles de MPO en patologías periapicales. Objetivo: Comparar los niveles de MPO en exudado periapical de dientes con diagnóstico de PAA antes y después de la medicación intracanal con Ca(OH) Materiales y métodos: Se seleccionaron 15 pacientes con diagnóstico de PAA e indicación de endodoncia...

Niveles de mieloperoxidasa (MPO) en fluido gingival crevicular (FGC) de dientes con periodontitis apical asintomática (PAa)

Aranda González, , Valentina Andrea
Fonte: Universidad de Chile Publicador: Universidad de Chile
Tipo: Tesis
Português
Relevância na Pesquisa
27.348096%
Trabajo de Investigación Requisito para optar al Título de Cirujano Dentista; “Niveles de Mieloperoxidasa (MPO) en Fluido Gingival Crevicular (FGC) de Dientes con Periodontitis Apical Asintomática (PAa)” Introducción: La mieloperoxidasa (MPO), es una peroxidasa con rol defensivo contra los agentes infecciosos y paralelamente provoca daño a los tejidos adyacentes. A la fecha, su presencia no se ha asociado a la periodontitis apical asintomática (PAa). Objetivo: Comparar los niveles de MPO presente en fluido gingival crevicular (FGC) de dientes con PAa antes del tratamiento endodóntico con dientes con PAa después del tratamiento endodóntico y dientes sin PAa. Materiales y Métodos: Se obtuvieron muestras de FGC de dientes con PAa antes del tratamiento endodóntico (n=13) y después de siete días finalizado éste (n=12) y de dientes sin PAa (n=13). Las muestras fueron eluidas y se les realizó cuantificación de proteínas totales. Para determinar los niveles de MPO se realizó test de ELISA y para el análisis estadístico el programa GraphPAD prism. 5.0. Resultados: La MPO se expresa en FGC en dientes sanos y con PAa. Si bien se observó que los niveles de MPO fueron ligeramente mayores en FGC de dientes con PAa que en dientes sanos...

Niveles de mieloperoxidasa (MPO) en exudado periapical de dientes con periodontitis apical asintomática (PAA) y abseceso apical agudo (AAA)

Cabrera González., Velentina Paz
Fonte: Universidad de Chile Publicador: Universidad de Chile
Tipo: Tesis
Português
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Trabajo de Investigación Requisito para optar al Título de Cirujano Dentista; Introducción: La periodontitis apical asintomática (PAA) es una respuesta inmunoinflamatoria local a la invasión microbiana del sistema de canales radiculares (SCR) que resulta en la destrucción de los tejidos periapicales y se caracteriza por no presentar sintomatología clínica. El absceso apical agudo (AAA) corresponde a la inflamación de los tejidos perirradiculares, asociada a la formación de exudado dentro de la lesión, con presencia de sintomatología clínica severa. La Mieloperoxidasa (MPO) es una enzima que cataliza la formación de ácido hipocloroso (HClO), potente oxidante con rol defensivo contra los agentes infecciosos y que paralelamente provoca daño a los tejidos adyacentes. A la fecha su presencia no se ha asociado a estas patologías periapicales. Objetivo: Determinar los niveles de MPO en exudado periapical de dientes con diagnóstico de AAA y PAA para poder comparar y asociar la concentración de esta enzima con la presencia de sintomatología en el tejido periapical. Materiales y Métodos: Se seleccionaron pacientes con diagnóstico de PAA (n=20) y AAA (n=13) e indicación de endodoncia, y se obtuvieron muestras de exudado periapical. Las muestras fueron eluídas y se les realizó cuantificación de proteínas totales. Para determinar los niveles de MPO se realizó test de ELISA. Los resultados se analizaron con el programa GraphPad PRISM 5.0. Resultados: La concentración de proteínas totales (CPT) en exudado periapical de dientes con AAA es significativamente mayor que en dientes con PAA. La MPO se expresa en exudado periapical tanto de dientes con PAA como con AAA. Si bien los niveles de MPO son mayores en exudado periapical de dientes con AAA que con PAA...