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1.
PLoS One ; 14(4): e0215209, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30973928

RESUMO

OBJECTIVE: The primary aim of this study was to examine whether markers of cell damage and of the psycho-neuroendocrino-inflammatory/immune (PNI) system could be associated in patients with stable coronary artery disease (CAD) on the next day following percutaneous coronary intervention (PCI). MATERIALS AND METHODS: Blood samples of 23 patients (18 men and five women, mean age 62.9 ± 10.6 years), were collected immediately before (pre-PCI), immediately after (post-PCI), and on the day following PCI (1d-PCI). Lactoferrin, LL-37 and interleukin-6 (IL-6) were assayed in plasma, in addition to cortisol and chromogranin A (CgA), as well as CK, ASAT and ALAT. Total and differential leukocyte counts were also analysed. RESULTS: At all the three time points, the monocyte fractions, the monocyte-to-lymphocyte and the neutrophil-to-lymphocyte ratios and CgA levels were elevated. We detected significant peri-procedural changes in the plasma levels of our PNI markers: IL-6 (p<0.05), lactoferrin, LL-37 (both: p <0.0001), CgA, (p<0.05), and cortisol (p<0.01). On the first day after PCI, highly significant associations were found of ASAT with IL-6 and neutrophil count (both: r>0.75, p<0.0001), and of CgA with neutrophil count and monocyte count (both: r>0.79, p<0.0001); furthermore, cortisol was also associated with neutrophil count (r>0.7, p<0.0001). CONCLUSIONS: The findings suggest that myocardial damage could correlate not only with an inflammatory reaction but, via neutrophil count, also with increased level of stress in stable CAD after PCI. Furthermore, 1d-PCI neutrophil count may serve as an easy-to-obtain integrative PNI measure in stable CAD.


Assuntos
Angina Estável/sangue , Neutrófilos , Adulto , Idoso , Alanina Transaminase/sangue , Angina Estável/fisiopatologia , Angina Estável/terapia , Peptídeos Catiônicos Antimicrobianos/sangue , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Cromogranina A/sangue , Creatina Quinase/sangue , Feminino , Humanos , Hidrocortisona/sangue , Interleucina-6/sangue , Lactoferrina/sangue , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Sistemas Neurossecretores/fisiopatologia , Intervenção Coronária Percutânea , Stents , Estresse Fisiológico , Catelicidinas
2.
Neuroimmunomodulation ; 23(2): 67-74, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26926300

RESUMO

BACKGROUND: Psychosocial stress and depression have been recognized as major risk factors of coronary artery disease (CAD). Although monocytes are known to be key players in atherosclerosis, monocyte-based associations with psychoneuroendocrino-immuno-inflammatory (PNI) markers have not been widely investigated in stable CAD. OBJECTIVE: We examined associations between the monocyte-to-lymphocyte ratio (MLR) and key PNI markers in stable CAD. METHODS: We studied 23 patients with stable CAD who completed the Beck Depression Inventory (BDI) and Rahe's Brief Stress and Coping Inventory. A white blood cell differential was performed, and levels of cortisol, chromogranin A (CgA), LL-37, interleukin-6 (IL-6) and C-reactive protein (CRP) were assayed in plasma. RESULTS: Monocyte fraction, MLR and plasma CgA levels exceeded reference values, the social support score was low, and 7 patients had elevated BDI scores. In the multivariate-adjusted analysis, a higher MLR was associated with greater depressive symptom severity (r = 0.624, p < 0.01) as well as with higher concentrations of CgA (r = 0.660, p < 0.01), LL-37 (r = 0.643, p < 0.01), IL-6 (r = 0.532, p < 0.05) and CRP (r = 0.470, p < 0.05). BDI scores associated with CgA concentration (r = 0.618, p < 0.01) and CgA level correlated negatively with the social support score (r = -0.511, p < 0.05). CONCLUSIONS: Our findings suggest that, in patients with stable CAD, elevated MLR may be associated with depressive symptoms, with increased neuroendocrine-sympathetic activity (marked by CgA) and inflammatory markers that are pertinent to atherosclerosis initiation and progression. The increased neuroendocrine-sympathetic activity correlated with low social support and depressive symptom severity. The MLR might serve as an easy-to-obtain and inexpensive proxy measure of an activated PNI network in stable CAD.


Assuntos
Doença da Artéria Coronariana/sangue , Depressão/sangue , Mediadores da Inflamação/sangue , Linfócitos/metabolismo , Monócitos/metabolismo , Adulto , Idoso , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/psicologia , Estudos Transversais , Depressão/epidemiologia , Depressão/psicologia , Feminino , Humanos , Inflamação/sangue , Inflamação/epidemiologia , Inflamação/psicologia , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica
3.
PLoS One ; 8(8): e71902, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23967262

RESUMO

BACKGROUND: Psychosocial stress and activation of neutrophil granulocytes are increasingly recognized as major risk factors of coronary artery disease (CAD), but the possible relationship of these two factors in CAD patients is largely unexplored. Activation of neutrophils was reported to be associated with stenting; however, the issue of neutrophil state in connection with percutaneous coronary intervention (PCI) is incompletely understood from the aspect of stress and its hypothalamic-pituitary-adrenal axis (HPA) background. Thus, we aimed to study cortisol- and ACTH-associated changes in granulocyte activation in patients undergoing PCI. METHODOLOGY/PRINCIPAL FINDINGS: Blood samples of 21 stable angina pectoris (SAP) and 20 acute coronary syndrome (ACS) patients were collected directly before (pre-PCI), after (post-PCI) and on the following day of PCI (1d-PCI). Granulocyte surface L-selectin, CD15 and (neutrophil-specific) lactoferrin were analysed by flow cytometry. Plasma cortisol, ACTH, and lactoferrin, IL-6 were also assayed. In both groups, pre- and post-PCI ratios of lactoferrin-bearing neutrophils were relatively high, these percentages decreased substantially next day; similarly, 1d-PCI plasma lactoferrin was about half of the post-PCI value (all p≤0.0001). Post-PCI ACTH was reduced markedly next day, especially in ACS group (SAP: p<0.01, ACS: p≤0.0001). In ACS, elevated pre-PCI cortisol decreased considerably a day after stenting (p<0.01); in pre-PCI samples, cortisol correlated with plasma lactoferrin (r∼0.5, p<0.05). In 1d-PCI samples of both groups, ACTH showed negative associations with the ratio of lactoferrin-bearing neutrophils (SAP: r = -0.601, p<0.005; ACS: r = -0.541, p<0.05) and with plasma lactoferrin (SAP: r = -0.435, p<0.05; ACS: r = -0.609, p<0.005). CONCLUSIONS/SIGNIFICANCE: Pre- and post-PCI states were associated with increased percentage of activated/degranulated neutrophils indicated by elevated lactoferrin parameters, the 1d-PCI declines of which were associated with plasma ACTH in both groups. The correlation of plasma cortisol with plasma lactoferrin in the extremely stressed ACS before stenting, however, suggests an association of cortisol with neutrophil activation.


Assuntos
Hormônio Adrenocorticotrópico/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/cirurgia , Hidrocortisona/sangue , Neutrófilos/citologia , Stents , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Angina Estável/sangue , Angina Estável/cirurgia , Biomarcadores/sangue , Feminino , Humanos , Interleucina-6/sangue , Selectina L/sangue , Lactoferrina/sangue , Antígenos CD15/sangue , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea
4.
Life Sci ; 88(3-4): 156-62, 2011 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-21062630

RESUMO

AIMS: Transient ischemia of osteoporotic bones during elective orthopedic surgery or fracture repair carries risks for serious complications, and estrogen loss or replacement has a potential to influence ischemia-reperfusion-induced inflammatory activation. To clarify this, we investigated the periosteal inflammatory changes in a clinically relevant time frame in ovariectomized rats, an experimental model of postmenopausal bone loss. Furthermore, the effects of chronic estrogen supplementation on the postischemic local and systemic inflammatory reactions were assessed. MAIN METHODS: Bilateral ovariectomy or sham operation was performed in 3-month-old female Sprague-Dawley rats. Five months later, estrogen replacement therapy with 17ß-estradiol (20 µg(-1) kg(-1) day(-1)) or vehicle treatment was initiated. The microcirculatory inflammatory consequences of 60-min total hindlimb ischemia followed by 180-min reperfusion were examined 11 months after ovariectomy and were compared with those in 3-month-old animals. KEY FINDINGS: The osteoporosis that developed 5 months after ovariectomy was significantly ameliorated by estrogen replacement therapy. Both in ovariectomized and in non-ovariectomized animals, ischemia-reperfusion elevated the neutrophil adherence ~3-fold in the postcapillary venules of the periosteum (intravital microscopy), with an ~50-60% increase in intravascular neutrophil activation (CD11b; FACS analysis), an enhanced TNF-α release (ELISA) and periosteal expression of ICAM-1 (the endothelial ligand of CD11b; immunohistochemistry). Exogenous 17ß-estradiol considerably reduced TNF-α release and the number of neutrophil-endothelial interactions in the periosteum, without affecting the CD11b and ICAM-1 expression changes. SIGNIFICANCE: Osteoporosis itself does not increase the magnitude of the limb ischemia-reperfusion-associated periosteal inflammatory reaction. Chronic estrogen supplementation, however, reverses osteoporosis and significantly ameliorates the microcirculatory consequences of transient ischemia.


Assuntos
Estradiol/farmacologia , Isquemia/fisiopatologia , Microcirculação/efeitos dos fármacos , Neutrófilos/imunologia , Osteoporose/fisiopatologia , Periósteo/irrigação sanguínea , Análise de Variância , Animais , Antígeno CD11b/metabolismo , Densitometria , Terapia de Reposição de Estrogênios , Feminino , Citometria de Fluxo , Membro Posterior/cirurgia , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Isquemia/imunologia , Microcirculação/fisiologia , Microscopia de Vídeo , Osteoporose/imunologia , Ovariectomia , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
5.
J Orthop Res ; 27(7): 897-902, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19105227

RESUMO

We examined local and systemic antiinflammatory consequences of ischemic preconditioning (IPC) in a rat model of limb ischemia-reperfusion (I-R) by characterizing the leukocyte-endothelial interactions in the periosteum and the expression of adhesion molecules playing a role in leukocyte-mediated inflammatory processes. IPC induction (2 cycles of 10 min of complete limb ischemia and 10 min of reperfusion) was followed by 60 min of ischemia/180 min of reperfusion or sham-operation. Data were compared with those on animals subjected to I-R and sham-operation. Neutrophil leukocyte-endothelial cell interactions (intravital videomicroscopy), intravascular neutrophil activation (CD11b expression changes by flow cytometry), and soluble and tissue intercellular adhesion molecule-1 (ICAM-1; ELISA and immunohistochemistry, respectively) expressions were assessed. I-R induced enhanced leukocyte rolling and adherence in the periosteal postcapillary venules after 120 and 180 min of reperfusion. This was associated with a significantly enhanced CD11b expression (by approximately 80% and 72%, respectively) and moderately increased soluble and periosteal ICAM-1 expressions. IPC prevented the I-R-induced increases in leukocyte adherence and CD11b expression without influencing the soluble and tissue ICAM-1 levels. The results show that limb IPC exerts not only local, but distant antiinflammatory effects through significant modulation of neutrophil recruitment.


Assuntos
Membro Posterior/irrigação sanguínea , Membro Posterior/imunologia , Precondicionamento Isquêmico , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Antígeno CD11b/metabolismo , Regulação para Baixo/imunologia , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular/metabolismo , Migração e Rolagem de Leucócitos/imunologia , Masculino , Microcirculação/imunologia , Microscopia de Vídeo , Neutrófilos/imunologia , Periósteo/irrigação sanguínea , Periósteo/imunologia , Ratos , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional/imunologia , Tíbia/irrigação sanguínea , Tíbia/imunologia , Vênulas/imunologia
6.
Crit Care Med ; 36(10): 2828-37, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18766091

RESUMO

OBJECTIVE: To compare the microhemodynamics and possible anti-inflammatory reactions of colloid resuscitation with 4% gelatin, 6% dextran, or 6% hydroxyethyl starch 130/0.4 solutions. DESIGN AND SETTING: A randomized control in vivo animal study in a university research laboratory. ANIMALS: Adult male Wistar rats (280 +/- 20 g). INTERVENTIONS: Sodium pentobarbital-anesthetized animals were subjected to a 60-min complete hindlimb ischemia and a 180-min reperfusion. Volume resuscitation, either with a colloid (dextran, gelatin, or hydroxyethyl starch, 25 mL kg(-1) during 3 hr intravenously) or with lactated Ringer's solution, was initiated 10 min before reperfusion. Fluorescence intravital videomicroscopy was performed before ischemia and 30, 60, 120, and 180 min postresuscitation to quantify the tibial periosteal functional capillary density, the capillary red blood cell velocity changes, and leukocyte rolling and firm adherence in postcapillary venules. In a separate series blood samples were drawn to determine the release of soluble intercellular adhesion molecule-1 (enzyme-linked immunosorbent assay technique), and the surface expression of CD11b (flow cytometry) on peripheral blood granulocytes. MEASUREMENTS AND MAIN RESULTS: Reperfusion significantly increased the leukocyte rolling and firm adhesion (by 2.6 and 7.1-fold, respectively), evoked marked decreases in periosteal functional capillary density and red blood cell velocity (56% and 39%, respectively), and increased the CD11b expression on the circulating leukocytes (by 85%). Hydroxyethyl starch, but not gelatin or dextran pretreatment, significantly inhibited the firm adherence of the leukocytes and reduced the elevated CD11b expression. Hydroxyethyl starch pretreatment also effectively attenuated the decreases in functional capillary density and red blood cell velocity, whereas gelatin and dextran did not improve the microhemodynamics. Finally, ischemia had no direct effect on the soluble intercellular adhesion molecule-1 levels, whereas gelatin treatment increased significantly this parameter. CONCLUSIONS: When compared with gelatin or dextran solutions, hydroxyethyl starch provided a therapeutic advantage in this setting by exerting an inhibitory effect on the ischemia-reperfusion-induced local and systemic leukocyte reactions and the postischemic periosteal microvascular dysfunction.


Assuntos
Coloides/farmacologia , Membro Posterior/irrigação sanguínea , Microcirculação/efeitos dos fármacos , Substitutos do Plasma/farmacologia , Traumatismo por Reperfusão/terapia , Animais , Permeabilidade Capilar/efeitos dos fármacos , Dextranos/farmacologia , Modelos Animais de Doenças , Gelatina/farmacologia , Membro Posterior/efeitos dos fármacos , Derivados de Hidroxietil Amido/farmacologia , Masculino , Microcirculação/fisiologia , Periósteo/irrigação sanguínea , Periósteo/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar , Soluções para Reidratação/farmacologia , Sensibilidade e Especificidade , Soluções
7.
Stress ; 10(3): 271-81, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17613941

RESUMO

Our aim was to study the possible relationship between psychological stress and granulocyte activation primarily in healthy students during an examination period (n = 11) and also in chronically anxious patients (n = 15). We employed cell surface markers: lactoferrin, L-selectin, alphaMbeta2-integrin and CD15s and flow cytometry to detect changes in the activation state of granulocytes, with the start of the stressed state in students at the beginning of an examination period, which was associated with elevated blood plasma cortisol level, and following relaxation hypnosis in both students, during their examination term, and patients. The ratios of all four types of marker-carrier granulocytes increased at the start of the examination period in students; an especially dramatic (ca. 5-fold) enhancement was observed in the proportion of lactoferrin-bearing cells relatively to the pre-examination term value. After hypnosis, the percentage of lactoferrin-exposing granulocytes decreased considerably both in students and in patients, by about half; a similar decrease was observed in the ratio of CD15s-carrier cells in patients. No significant alteration was observed during the study in state or trait anxiety levels, and in total or differential leukocyte counts. Thus, granulocyte activation could be associated with stress, while relaxation may facilitate reducing activation of these cells. In both groups of subjects, granulocyte surface lactoferrin appeared to be a sensitive "stress indicator". This needs further evaluation.


Assuntos
Ansiedade/sangue , Granulócitos/metabolismo , Relaxamento , Estresse Psicológico/sangue , Adulto , Ansiedade/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Citometria de Fluxo , Granulócitos/imunologia , Humanos , Hidrocortisona/sangue , Hipnose , Selectina L/sangue , Lactoferrina/sangue , Contagem de Leucócitos , Antígenos CD15/sangue , Antígeno de Macrófago 1/sangue , Masculino , Pessoa de Meia-Idade , Terapia de Relaxamento , Estresse Psicológico/imunologia
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