RESUMO
Abstract Background: Tocilizumab (TCZ), a humanized monoclonal antibody against the interleukin-6 receptor, has been proven to be a safe and effective treatment for rheumatoid arthritis (RA). Because RA is a heterogenous disease and patient response to treatments can vary, identifying characteristics that predict which patients are more likely to respond to TCZ is important for optimal patient care. Serum levels of C-X-C motif chemokine ligand 13 (CXCL13) and soluble intercellular adhesion molecule-1 (sICAM-1) have been associated with response to TCZ in patients with RA. Objectives: To evaluate the association of CXCL13 and sICAM-1 with disease activity and response to TCZ in patients with early RA and those with inadequate response to disease-modifying antirheumatic drugs (DMARD-IR). Methods: Baseline and week 24 serum CXCL13 and sICAM-1 levels were measured using available patient samples from the FUNCTION (early RA) and LITHE (DMARD-IR) trials. Correlations between CXCL13 and sICAM-1 levels and Disease Activity Score in 28 joints calculated with erythrocyte sedimentation rate (DAS28-ESR) at baseline and between change in CXCL13 and sICAM-1 and change in DAS28-ESR at week 24 were estimated. CXCL13 and sICAM-1 changes from baseline to week 24 were compared between treatment arms. The effects of TCZ treatment and baseline DAS28-ESR, CXCL13 and sICAM-1 levels on DAS28-ESR remission and 50% improvement per the American College of Rheumatology (ACR50) response at week 24 were determined. Results: Overall, 458 patients from FUNCTION and 287 patients from LITHE were included. Correlation of baseline serum CXCL13 and sICAM-1 levels with DAS28-ESR was weak to moderate. CXCL13 and sICAM-1 levels decreased significantly at week 24 in TCZ-treated patients in both the early-RA and DMARD-IR populations. CXCL13 and sICAM-1 changes correlated moderately to weakly with DAS28-ESR changes at week 24 in both populations. The treatment regimen, but not baseline CXCL13 and sICAM-1 levels, had a significant effect on the likelihood of DAS28-ESR remission and ACR50 response. Conclusions: Although CXCL13 and sICAM-1 are modestly associated with RA disease activity, they do not predict response to TCZ in all RA populations.
Assuntos
Humanos , Artrite Reumatoide/tratamento farmacológico , Molécula 1 de Adesão Intercelular/sangue , Quimiocina CXCL13/sangue , Anticorpos Monoclonais/uso terapêutico , BiomarcadoresRESUMO
Acute coronary syndromes are associated with a high prevalence of complications including heart failure (HF). The aim of this study was to investigate the association of novel biomarkers with the occurrence of post-acute myocardial infarction (AMI) HF. A prospective study was conducted with patients admitted to the emergency department with ST-segment elevation myocardial infarction (STEMI). Blood and urine samples were collected for analysis of traditional and novel biomarkers, including interleukin-6, vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1). We compared the levels of these biomarkers between patients with and without post-STEMI HF. A total of 48 patients were assessed, with a prevalence of males. Fifteen patients (31.2%) had post-STEMI HF. Patients with HF had higher mean values of IL-6, VCAM-1, and ICAM-1 compared to those who did not develop HF (57.06 vs 14.03 pg/mL, P=0.001; 1719.58 vs 1304.34 ng/mL, P=0.001; and 1594.20 vs 1158.74 ng/mL, P<0.001, respectively). The three biomarkers were shown to be good predictors of post-STEMI HF (IL-6: AUC 0.786, P=0.002; VCAM-1: AUC 0.797, P=0.001; and ICAM-1: AUC 0.825, P<0.0001), with the respective cutoff points being calculated based on the best sensitivity and specificity indexes (IL-6: 8.67 pg/mL; VCAM-1: 1501.42 ng/mL; and ICAM-1: 1262.38 ng/mL). Of the three biomarkers, only VCAM-1 and ICAM-1 had a direct linear association between them (r=0.470, P<0.0001). IL-6, VCAM-1, and ICAM-1 were associated with the development of new post-AMI HF symptoms, but only VCAM-1 and ICAM-1 correlated with each other, possibly because they have the same pathophysiological mechanism of action.
Assuntos
Humanos , Masculino , Feminino , Idoso , Interleucina-6/sangue , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Insuficiência Cardíaca/sangue , Infarto do Miocárdio/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
OBJECTIVES: We aimed to explore the effects of diet on the inflammatory response in middle-aged and elderly people with hypertension. METHODS: Thirty overweight or obese patients with stage one hypertension (age range, 45-75 years) were allocated to either the intervention or control group (n=15 per group; age- and sex-matched). Patients in the intervention group consumed a food powder supplement (100 g) instead of a regular meal. The control group maintained their normal dietary habits. This study lasted for six weeks. Blood pressure, inflammatory marker levels, and energy intake were measured before and after the study. RESULTS: After 6 weeks, the diet composition of the intervention group changed significantly (p<0.05). The intake of proteins, dietary fibre, monounsaturated fat, and polyunsaturated fat increased significantly (p<0.05), while the total energy intake trended towards an increase (p>0.05). In the control group, the total energy intake decreased significantly (p<0.05). The levels of nuclear factor-κB (NF-κB), soluble intercellular adhesion molecule-1 (sICAM-1) and high sensitivity C-reactive protein (hs-CRP) decreased, and adiponectin increased significantly in the intervention group (p<0.05); however, no significant changes were observed in the inflammatory marker levels of the control group. In the intervention group, systolic blood pressure decreased significantly (p<0.05), and diastolic blood pressure also exhibited a decreasing trend. No significant change in blood pressure was observed in the control group. CONCLUSION: The consumption of a food powder supplement can improve diet composition, decrease blood pressure and reduce inflammation in middle-aged and elderly overweight or obese hypertensive patients. The food powder supplement may also have an anti-atherosclerotic effect in hypertensive patients.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Pressão Sanguínea/efeitos dos fármacos , Suplementos Nutricionais/análise , Sobrepeso/sangue , Hipertensão/sangue , Inflamação/sangue , Pós/uso terapêutico , População Rural , Ingestão de Energia , Proteína C-Reativa/análise , Biomarcadores/sangue , China , Inquéritos Nutricionais/estatística & dados numéricos , NF-kappa B/sangue , Molécula 1 de Adesão Intercelular/sangue , Adiponectina/sangueRESUMO
Abstract INTRODUCTION: Dengue is an important mosquito-borne disease in tropical and subtropical regions. Adhesion molecules have not been systematically characterized in the renal tissue of patients with severe dengue (SD). The objective of this study was to detect viral antigens in samples from patients that evolved with SD, correlating with the expression of ICAM-1, VCAM-1, VE-cadherin, and E-selectin to contribute to a better understanding of the pathophysiology of SD. METHODS: Kidney specimens from patients with SD were selected according to clinical and laboratorial data and submitted to histological and immunohistochemistry analysis. A semiquantitative evaluation was performed considering positive immunostaining in 20 glomeruli. RESULTS: Viral antigens were mainly detected in distal tubules. The intense immunostaining of VCAM-1 and ICAM-1 was observed. The expression of E-selectin was discrete, and VE-cadherin expression varied from mild to moderate. VCAM-1 was slightly intense in the glomerular capsule; the expression of ICAM-1 was diffuse. E-selectin was diffuse, and VE-cadherin varied from mild to moderate. The most frequent histological findings were glomerular congestion, mild glomerulitis, acute renal injury, and glomerular atrophy. CONCLUSIONS: The results appear to demonstrate an imbalance between vascular endothelial permeability regulating events in renal lesions in SD. The increase in the expression of ICAM-1 and VCAM-1 is an in-situ indicator of higher permeability with a consequent influx of cells favoring the inflammation of the endothelium. These molecules are important in the pathophysiology of the disease and provide the possibility of developing new markers for the evaluation, clinical follow-up, and therapeutic response of patients with SD.
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Criança , Adolescente , Adulto , Adulto Jovem , Molécula 1 de Adesão Intercelular/fisiologia , Molécula 1 de Adesão de Célula Vascular/fisiologia , Selectina E/fisiologia , Dengue Grave/fisiopatologia , Dengue Grave/sangue , Endotélio/fisiopatologia , Imuno-Histoquímica , Biomarcadores/sangue , Antígenos CD/fisiologia , Antígenos CD/sangue , Caderinas/fisiologia , Caderinas/sangue , Regulação para Cima , Molécula 1 de Adesão Intercelular/sangue , Progressão da Doença , Molécula 1 de Adesão de Célula Vascular/sangue , Selectina E/sangue , Pessoa de Meia-Idade , Antígenos Virais/sangueRESUMO
OBJECTIVES: Inflammatory molecules play a role in the development of atherosclerosis, which is the primary origin of cardiovascular disorders. However, to the best of our knowledge, no study has attempted to investigate the relationship between these circulating molecules and the prediction of cardiovascular risk. The present study aimed to investigate the relationships of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 serum concentrations with the extent of coronary lesions. METHODS: Seventy-four individuals who were undergoing coronary angiography for the first time for diagnostic purposes were enrolled in this study. The extent of the coronary lesion was assessed using the Friesinger Index, and subjects were classified into four groups: no lesions, minor lesions, intermediate lesions and major lesions. Serum biochemical parameters and serum concentrations of vascular cell adhesion molecule-1, intercellular adhesion molecule-1, E-selectin and matrix metalloproteinase 9 were analyzed. RESULTS: The vascular cell adhesion molecule-1 concentration was higher than 876 ng/mL in individuals with intermediate and major lesions (p<0.001 and p=0.020, respectively). Moreover, logistic regression analysis showed that these patients had an increased risk of having an intermediate lesion (p=0.007). Interestingly, all individuals with major lesions had vascular cell adhesion molecule-1 concentrations higher than 876 ng/mL. No association was found between the concentrations of the other proteins and the Friesinger Index. CONCLUSIONS: Serum vascular cell adhesion molecule-1 may be associated with the extent of coronary lesions. Moreover, it may represent an alternative to improve the cardiovascular risk classification in patients without acute coronary syndrome.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Doença da Artéria Coronariana/sangue , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Selectina E/sangue , Metaloproteinase 9 da Matriz/sangue , Prognóstico , Índice de Gravidade de Doença , Doença da Artéria Coronariana/patologia , Biomarcadores/sangue , Placa Aterosclerótica/diagnósticoRESUMO
ABSTRACT BACKGROUND: Endothelial dysfunction is one of the early stages of vascular diseases. OBJECTIVE: The aim of this study was to investigate the endothelial dysfunction markers in patients with chronic gastritis associated with Helicobacter pylori (H. pylori) infection. METHODS: By a cross sectional study, basic and clinical information of 120 participants (40 patients with positive H. pylori infection, 40 patients with negative H. pylori infection and 40 healthy people) were analyzed. Carotid intima media thickness and flow-mediated dilation levels were measured in all patients and controls. Soluble vascular cell adhesion molecule-1 (sVCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were measured with Elisa for all subjects. IgG level was assessed in chronic gastritis patients. RESULTS: The flow-mediated dilation level in patients with positive H. pylori infection (0.17%±0.09) was significantly lower than those with negative H. pylori infection (0.21% ±0.10, P<0.05) and compared to the control group (0.27% ±0.11, P<0.05). Carotid intima media thickness level in patients with positive H. pylori infection (0.58±0.13 mm) was significantly higher than those with negative H. pylori infection (0.48±0.32 mm, P<0.05) and compared to the control group (0.36±0.44mm, P<0.05). The mean level of sICAM-1 in positive H. pylori infection group (352.16±7.54 pg/mL) was higher than negative H. pylori infection group (332.64±8.75 pg/mL =0.75) and compared to the control group (236.32±12.43 pg/mL, P<0.05). A direct relationship was revealed between flow-mediated dilation and carotid intima media thickness changes and between sICAM-1 and sVCAM-1 associated with the level of H. pylori IgG in chronic gastritis. CONCLUSION: The levels of flow-mediated dilation, carotid intima media thickness and sICAM-1 were higher among patients with positive H. pylori infection. Patients with chronic gastritis associated with H. pylori infection are at risk of endothelial dysfunction due to flow-mediated dilation and carotid intima media thickness abnormalities and increased level of sICAM-1 and sVCAM-1.
RESUMO CONTEXTO: A disfunção endotelial é um dos estágios iniciais de doenças vasculares. OBJETIVO: O objetivo deste estudo foi investigar os marcadores de disfunção endotelial em pacientes com gastrite crônica associada com infecção por Helicobacter pylori (H. pylori). MÉTODOS: Através de estudo cruzado seccional, foram analisadas informações básicas e clínicas de 120 participantes (40 pacientes com infecção pelo H. pylori, 40 pacientes sem infecção pelo H. pylori e 40 pessoas saudáveis). A espessura da camada íntima-média da carótida e níveis de dilatação mediada por fluxo foram medidos em todos os pacientes e controles. A adesão da molécula-1 solúvel (sVCAM-1) à célula vascular e da molécula de adesão intercelular-1 (ICAM-1) foram medidas pelo método Elisa para todas os indivíduos. O nível de H. pylori IgG foi avaliado em pacientes de gastrite crônica. RESULTADOS: O nível de dilatação mediada por fluxo em pacientes com infecção positiva pelo H. pylori foi significativamente menor do que em aqueles com infecção negativa (0,17% ±0, 09) X (0,21% ±0,10) P<0,05 e em relação ao grupo controle (0,27% ±0,11) P<0,05). O nível da espessura da íntima-média da carótida em pacientes com infecção positiva pelo H. pylori foi significativamente maior (0,58±0,13 mm) do que aqueles com negativa (0,48±0,32 mm) P<0,05) e em relação ao grupo controle (0,36±0,44 mm) P<0,05). O nível médio de sICAM-1 grupo de infecção H. pylori positiva (352,16±7,54 pg/mL) foi maior do que o grupo de infecção negativa (332,64±8,75 pg/mL = 0,75) e em relação ao grupo controle (236,32±12,43 pg/mL) P<0,05). Revelou-se uma relação direta entre a dilatação mediada por fluxo e alterações da espessura da íntima-média da carótida e sICAM-1 e sVCAM-1, associada com o nível de H. pylori IgG em gastrite crônica. CONCLUSÃO: Os níveis de dilatação mediada por fluxo, da espessura da íntima-média da carótida e sICAM-1 foram maiores entre os pacientes com infecção positiva pelo H. pylori. Pacientes com gastrite crônica associada a infecção por H. pylori correm o risco de disfunção endotelial, devido à dilatação mediada por fluxo e anormalidades da espessura da íntima-média da carótida e aumento do nível de sICAM-1 e sVCAM-1.
Assuntos
Humanos , Masculino , Feminino , Artérias Carótidas/fisiopatologia , Helicobacter pylori , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Gastrite/fisiopatologia , Gastrite/microbiologia , Biomarcadores/sangue , Doença Crônica , Estudos Transversais , Infecções por Helicobacter/fisiopatologia , Infecções por Helicobacter/sangue , Espessura Intima-Media Carotídea , Gastrite/sangue , Pessoa de Meia-IdadeRESUMO
ABSTRACT Objective Endothelial dysfunction (ED) plays an important role in the pathogenesis of diabetic nephropathy. The purpose of the study was to determine flow mediated endothelial dependent vasodilatation (FMD) measurements and serum soluble (s) endothelin-1 (ET-1), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule (VCAM-1) levels in patients with type 1 diabetes mellitus (T1DM) with or without increased urinary albumin excretion (UAE) and compare them with the healthy controls. Subjects and methods Seventy three patients with T1DM were enrolled. Patients were divided into two subgroups according to microalbumin measurements in 24-hr urine collections. The diabetic patients without microalbuminuria (41 patients) were defined as Group I and those with microalbuminuria (32 patients) were defined as group II. A hundred age and sex matched healthy subjects participated as the control group (Group III). Serum sET-1, sICAM-1, sVCAM-1 levels and FMD measurements were determined in all participants. Results Median FMD measurement was significantly lower in the diabetic groups compared with the control group (6.6, 6.4 and 7.8% in Group I, II and III, respectively) (p < 0.05). FMD was negatively correlated with age (p = 0.042). Median serum sICAM-1 level was higher in the patient groups compared to the control group (p < 0.05). Median serum sVCAM-1 level was higher in the group of patients with increased albuminuria compared to the normoalbuinuric and the control group (p < 0.05). Serum sVCAM-1 level was found to be positively correlated with degree of urinary albumin excretion (p < 0.001). Conclusion We assume that sVCAM-1 may be used as a predictive marker for risk stratification for nephropathy development and progression.
Assuntos
Humanos , Masculino , Feminino , Adulto , Vasodilatação/fisiologia , Endotélio Vascular/fisiopatologia , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 1/sangue , Albuminúria/fisiopatologia , Valores de Referência , Velocidade do Fluxo Sanguíneo/fisiologia , Biomarcadores/sangue , Estudos de Casos e Controles , Valor Preditivo dos Testes , Fatores de Risco , Análise de Variância , Estatísticas não Paramétricas , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Endotelina-1/sangue , Nefropatias Diabéticas/fisiopatologia , Nefropatias Diabéticas/sangueRESUMO
The levels of serum inflammatory cytokines and the activation of nuclear factor kappa B (NF-κB) and hypoxia inducible factor-1α (HIF-1α) in heart tissues in response to different frequencies of intermittent hypoxia (IH) and the antioxidant tempol were evaluated. Wistar rats (64 males, 200-220 g) were randomly divided into 6 experimental groups and 2 control groups. Four groups were exposed to IH 10, 20, 30, or 40 times/h. The other 2 experimental groups were challenged with IH (30 times/h) plus tempol, either beginning on day 0 (IH30T0) or on day 29 (IH30T29). After 6 weeks of challenge, serum levels of tumor necrosis factor (TNF)-α, intracellular adhesion molecule (ICAM)-1, and interleukin-10 were measured, and western blot analysis was used to detect NF-κB p65 and HIF-1α in myocardial tissues. Serum levels of TNF-α and ICAM-1 and myocardial expression of NF-κB p65 and HIF-1α were all significantly higher in IH rats than in controls (P<0.001). Increased IH frequency resulted in more significant changes. Administration of tempol in IH rats significantly reduced levels of TNF-α, ICAM-1, NF-κB and HIF-1α compared with the non-tempol-treated group (F=16.936, P<0.001). IH induced an inflammatory response in a frequency-dependent manner. Additionally, HIF-1α and NF-κB were increased following IH administration. Importantly, tempol treatment attenuated this effect.
Assuntos
Animais , Masculino , Hipóxia/complicações , Antioxidantes/administração & dosagem , Óxidos N-Cíclicos/administração & dosagem , Inflamação/prevenção & controle , Hipóxia/sangue , Gasometria , Western Blotting , Ensaio de Imunoadsorção Enzimática , Subunidade alfa do Fator 1 Induzível por Hipóxia/análise , Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/sangue , /sangue , Miocárdio/metabolismo , Miocárdio/patologia , NF-kappa B/análise , Ratos Wistar , Marcadores de Spin , Fator de Necrose Tumoral alfa/sangueRESUMO
Coal workers' pneumoconiosis (CWP) is characterized as a chronic inflammation of the lung associated with activation of macrophages and endothelial cells in the lung. The aim of the present study was to compare the levels of serum interleukin-8 (IL-8), macrophage inflammatory protein-1alpha (MIP-alpha), and intercellular adhesion molecule-1 (ICAM-1) as biomarkers for progressive massive fibrosis (PMF) in 106 subjects (27 non-CWP and 79 CWP patients). The levels of serum IL-8 (P<0.001) and ICAM-1 (P=0.001) of subjects with PMF were higher than those of non-CWP subjects. The IL-8 levels of PMF subjects were also higher than those of simple CWP subjects (P=0.003). Among the subjects without PMF, IL-8 levels in the subjects with International Labour Organization (ILO) category II or III were higher than those in the subjects with ILO category 0 (P=0.006) and with category I (P=0.026). These results suggest that high serum levels of IL-8 and ICAM-1, which are important as neutrophil attractants and adhesion molecules, are associated with PMF.
Assuntos
Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Antracose/sangue , Biomarcadores/sangue , Quimiocina CCL3/sangue , Minas de Carvão , Molécula 1 de Adesão Intercelular/sangue , Interleucina-8/sangue , Pulmão/patologia , Doenças Profissionais/sangue , Fibrose Pulmonar/sangueRESUMO
Coal workers' pneumoconiosis (CWP) is characterized as a chronic inflammation of the lung associated with activation of macrophages and endothelial cells in the lung. The aim of the present study was to compare the levels of serum interleukin-8 (IL-8), macrophage inflammatory protein-1alpha (MIP-alpha), and intercellular adhesion molecule-1 (ICAM-1) as biomarkers for progressive massive fibrosis (PMF) in 106 subjects (27 non-CWP and 79 CWP patients). The levels of serum IL-8 (P<0.001) and ICAM-1 (P=0.001) of subjects with PMF were higher than those of non-CWP subjects. The IL-8 levels of PMF subjects were also higher than those of simple CWP subjects (P=0.003). Among the subjects without PMF, IL-8 levels in the subjects with International Labour Organization (ILO) category II or III were higher than those in the subjects with ILO category 0 (P=0.006) and with category I (P=0.026). These results suggest that high serum levels of IL-8 and ICAM-1, which are important as neutrophil attractants and adhesion molecules, are associated with PMF.
Assuntos
Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Antracose/sangue , Biomarcadores/sangue , Quimiocina CCL3/sangue , Minas de Carvão , Molécula 1 de Adesão Intercelular/sangue , Interleucina-8/sangue , Pulmão/patologia , Doenças Profissionais/sangue , Fibrose Pulmonar/sangueRESUMO
Sepsis is one of the leading causes of acute kidney injury [AKI] and increases risk of death. Bused on the hemodynamic effects and anti-inflammatory properties of the hydrogen sulfide [H[2]S], this study aimed to examine its effects on renal damage using a rat model of lipopolysaccharide [LPS]-induced AKI where LPS promotes inflammation-mediated kidney damage. A total of forty adult male Wistar albino rats were included in the study. The rats were randomly divided into 4 groups: [I] control group was treated with saline. [2] H[2]S group received a single intravenous [i.v.] bolus of sodium hydrosulfide [NaHS] as H[2]S donor in ci dose of 0.2 mg/kg. [3] LPS group in which endoloxemic shock was induced through the intraperitoneal [i.p.] injection of 20 mg/kg LPS. [4] LPS H[2]S group received LPS with the same dose as the previous group, then 5 minutes later NaHS, in a single dose [0.2 mg/kg] was injected. Administration of NaHS as H[2]S donor in LPS + H[2]S group significantly abrogated kidney inflammation as evident by significant decrease of renal intercellular adhesion molecule- 1 [ICAM- 1], myeloperoxidase [MPO] and attenuated kidney cellular damage as observed by the increase of the Na -K- ATPase activity as compared with LPS group. These renoprotective effects were accompanied by improvement of hemodynamic with increase of the mean arterial blood pressure [MAP] via reduction of nitric oxide [NO] level. Kidney functions were also effectively enhanced where glomerular filtration rate [GFR], renal blood flow [RBF], filtration fraction [FF.], renal vascular resistance [RVR], urine flow rate and urinary sodium excretion [U[Na]V] were significantly increased while proteinuria, serum urea and serum creatnine were significantly decreased. Urinary kidney injury molecule-1 [KIM-1] which is a specific tubular biomarker was greatly attenuated. Consistent with these observations, H[2]S treatment significantly alleviated renal hitopatholgical changes of LPS-induced AKI. Taken together, our results indicated the enhanced renal inflamination during LPS-induced AKI and the improvement of renal hemodynamic and functions as well as suppression of both renal cellular damage and inflammation by H[2]S which may signify its renoprotective effects in septic AKI
Assuntos
Masculino , Animais de Laboratório , Injúria Renal Aguda/induzido quimicamente , Lipopolissacarídeos , Molécula 1 de Adesão Intercelular/sangue , Peroxidase/sangue , RatosRESUMO
Cardiovascular disease is an increasingly recognized contributor to excess morbidity and mortality in psoriatic arthritis [PsA]. Traditional cardiovascular risk factors do not adequately account for the extent of cardiovascular disease in PsA. To examine the prevalence of subclinical atherosclerosis in patients with PsA to emphasize the potential role of serum uric acid on endothelial dysfunction, as an early predictor for atherosclerosis in PsA patients. This study included 60 PsA patients as well as 60 age and sex matched healthy controls. Assay of serum uric acid, interleukin-6 [IL-6] and soluble intercellular adhesion molecule-1 [sICAM-1] was done for all patients and controls. Patients were subjected to psoriasis area severity index [PASI] and assessment of disease activity. Patients and controls underwent brachial flow-mediated dilatation [FMD] assessment by color duplex sonography to determine endothelial dysfunction as well as extracranial carotid arteries assessment by high-resolution B-mode ultrasound to measure the common carotid intima-media thickness [CIMT] and the detection of atheromatous plaques. PsA patients have a high significant difference in CIMT, FMD of the brachial artery and mean levels of serum uric acid compared to healthy controls [p < 0.001]. PsA patients with hyperuricemia have a high significant difference in CIMT and FMD of the brachial artery than those with normal serum uric acid. Serum uric acid levels showed a high significant positive correlation with each of CIMT, disease duration, markers of inflammation [ESR, CRP, IL-6, sICAM-1], disease activity score in 28 joints [DAS 28] and PASI [r = 0.71, 0.893, 0.956, 0.858, 0.853, 0.877, 0.907, 0.847, respectively, as p < 0.001]. A high significant negative correlation was found between serum uric acid levels and FMD of the brachial artery as r = -0.634, p < 0.001. Patients with PsA have a high prevalence of subclinical atherosclerosis dependent on serum uric acid, suggesting that chronic systemic inflammation and endothelial dysfunction appear to be the link between asymptomatic hyperuricemia and atherosclerosis. Therefore, proper control of serum uric acid may play a preventive role in the development of atherosclerosis in PsA patients
Assuntos
Humanos , Masculino , Feminino , Hiperuricemia/sangue , Molécula 1 de Adesão Intercelular/sangue , Progressão da DoençaRESUMO
PURPOSE: Emerging insights underline a link among chronic inflammation and endothelial activation with benign prostatic hyperplasia (BPH) and prostate cancer (PCa). We aim to investigate whether specific plasma markers of inflammation and endothelial activation allow to discriminate BPH and PCa. MATERIALS AND METHODS: Fifteen patients affected by BPH, 15 by PCa and 15 controls, were enrolled. Interleukin-6 (IL-6), CD40 ligand (CD40L), endothelial-selectin (E-selectin), platelet-selectin (P-selectin), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) were measured. RESULTS: In systemic blood samples, IL-6 has been found increased in patients affected by BPH (4.25 ± 0. pg/mL) and PCa (5.08 ± 0.24) respect to controls (2.62 ± 0.34; p < 0.05). CD40L was higher in BPH (4.25 ± 0.65 ng/mL; p < 0.05) than in control (2.31 ± 0.20) and PCa group (2.60 ± 0.56). E-selectin, P-selectin and VCAM-1 did not show any significant difference. Higher levels of ICAM-1 were detected in patients with PCa (573.04 ± 52.23) and BPH (564.40 ± 74.67) than in the controls (215.30 ± 11.53 ng/mL; p < 0.05). In local blood samples, IL-6 has been found significantly increased in PCa in comparison with patients with BPH; there was no difference in CD40L, E-selectin, P-selectin, VCAM-1 ed ICAM-1. CONCLUSIONS: Changes in inflammation and endothelial activation markers may be not considered to be of value in discriminating BPH and PCa.
Assuntos
Humanos , Masculino , Biomarcadores/sangue , Hiperplasia Prostática/diagnóstico , Neoplasias da Próstata/diagnóstico , /sangue , Moléculas de Adesão Celular/sangue , Endotélio Vascular/metabolismo , Inflamação/sangue , Molécula 1 de Adesão Intercelular/sangue , /sangue , Molécula 1 de Adesão de Célula Vascular/sangueRESUMO
Vitiligo is an acquired depigmenting disorder that is characterized by loss of melanocytes from the epidermis. A large variety of therapeutic agents are being tried for the treatment of vitiligo, but an optimal treatment is not yet available. This study was conducted to estimate the efficacy of combination of topical calcipotriol and PUVA therapy in patients with vitiligo. Twenty-one patients with vitiligo were enrolled in this study, and were classified into three groups: group 1 [control group], nonlesional [normal] skin biopsies from all included patients in the study; group 2 [pretreated group], biopsies from lesional [vitiligo] skin from all included patients in the study; and group 3 [post-treated group], all included patients in the study, randomly divided into three subgroups: group 3a, included seven patients treated with topical calcipotriol cream [0.005%] twice daily for six months; group 3b, included seven patients treated with PUVA for six months; and group 3c, seven included patients treated with combined topical calcipotriol cream and PUVA twice daily for 6 months. Skin biopsies were taken, fixed, processed, and stained to assess histological changes [H and E], melanin pigment distribution [Masson-Fontana stain], and intercellular adhesion molecule 1 [ICAM-1] expression in the dermis and epidermis [immunohistochemical techniques]. Moreover, for statistical analysis, the mean area percentage of melanin pigment distribution in the epidermis, optical density of ICAM-1 expression in the epidermis and dermis of the immunostained sections, and number of melanosomes [using electron microscope] in the basal and spinous keratinocytes were measured and counted, respectively, in each of the studied groups. Vitiligo biopsies treated with combination of topical calcipotriol and PUVA showed disappearance of mononuclear cell infiltration, highly significant increase in the amount of melanin pigment concentration, highly significant decrease in ICAM-1 expression in the epidermis and dermis, and significant increase in the number of melanosomes when compared with the vitiligo group. Moreover, reappearance of melanocytes and regeneration of keratinocytes ultrastructure were observed. Combined topical calcipotriol and PUVA therapy showed complete repigmentation in vitiligo skin associated with regeneration of keratinocytes and reappearance of melanocytes in a shorter duration when compared with topical calcipotriol or PUVA therapy alone
Assuntos
Humanos , Masculino , Feminino , Calcitriol/análogos & derivados , Terapia PUVA/estatística & dados numéricos , Administração Tópica , Biópsia , Pele/patologia , Pele/ultraestrutura , Microscopia Eletrônica , Molécula 1 de Adesão Intercelular/sangue , Imuno-Histoquímica , Resultado do TratamentoRESUMO
OBJETIVO: Avaliar se as concentrações dos mediadores inflamatórios (CCL5, soluble intercellular adhesion molecule type 1 [sICAM-1], TNF-α, IL-6 e IL-10) na secreção nasofaríngea e no soro de crianças com infecção do trato respiratório inferior (ITRI) por vírus sincicial respiratório (VSR) apresentam correlação com os marcadores clínicos de gravidade da doença. MÉTODOS: Entre julho de 2004 e dezembro de 2005, 30 crianças com idade inferior a três meses, diagnosticadas com ITRI por VSR e admitidas em uma UTI neonatal foram incluídas neste estudo. RESULTADOS: Houve uma correlação positiva significante entre a gravidade da doença na admissão hospitalar, determinada por um sistema de escore clínico modificado, e as concentrações de sICAM-1 e de IL-10 na secreção nasofaríngea e de IL-6 no soro dos pacientes. Houve também uma correlação positiva significante entre a concentração de IL-6 no soro e o tempo de oxigenoterapia e a duração da internação. CONCLUSÕES: As concentrações de sICAM-1 e IL-10 na secreção nasofaríngea e de IL-6 no soro determinadas na admissão poderiam ser usadas como marcadores de gravidade da ITRI por VSR. Os níveis de IL-6 determinados no soro na admissão também poderiam ser usados para predizer o prolongamento da oxigenoterapia e da duração da internação.
OBJECTIVE: To determine whether the concentrations of inflammatory mediators (CCL5, soluble intercellular adhesion molecule type 1 [sICAM-1], TNF-α, IL-6 and IL-10) in the nasopharyngeal secretion and in the serum of children with lower respiratory tract infection (LRTI) caused by respiratory syncytial virus (RSV) correlate with the clinical markers of disease severity. METHODS: Between July of 2004 and December of 2005, 30 children less than three months of age, diagnosed with LRTI caused by RSV and admitted to a neonatal ICU, were included in this study. RESULTS: The severity of disease at hospital admission, as determined with a modified clinical scoring system, presented a significant positive correlation with sICAM-1 and IL-10 concentrations in the nasopharyngeal secretion, as well as with IL-6 concentrations in the serum, of the patients. In addition, serum IL-6 concentrations presented a significant positive correlation with the duration of oxygen therapy and with the length of hospital stay. CONCLUSIONS: At hospital admission, the concentrations of sICAM-1 and IL-10 in the nasopharyngeal secretion, as well as the concentration of IL-6 in the serum, could be used as markers of severity in patients with LRTI caused by RSV. The serum levels of IL-6 determined at admission could also be used to predict prolonged oxygen supplementation and hospital stay.
Assuntos
Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Mediadores da Inflamação/análise , Mucosa Nasal , Infecções por Vírus Respiratório Sincicial , Biomarcadores/análise , Biomarcadores/sangue , Mediadores da Inflamação/sangue , Molécula 1 de Adesão Intercelular/análise , Molécula 1 de Adesão Intercelular/sangue , /sangue , /análise , /sangue , Tempo de Internação , Oxigenoterapia , Admissão do Paciente , Infecções por Vírus Respiratório Sincicial/sangue , Infecções por Vírus Respiratório Sincicial/fisiopatologia , Infecções por Vírus Respiratório Sincicial/terapia , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/sangueRESUMO
The results of studies on coronary artery disease risk factors have demonstrated that some adhesion molecules could be risk factors for coronary artery disease. ICAM-1 and VACM-1 are the most important adhesion molecules. On the other hand, thrombomodulin is an anti-inflammatory factor and can reduce the risk for coronary artery disease. In this study, as well as evaluating these factors, we also studies the effect of the interaction between these factors on coronary artery disease. One hundred twenty-three patients between the ages of 45 and 70 years old who were admitted for coronary angiography in the cardiovascular center and met the inclusion criteria for the research, were selected in the first half of 2008. After recording their personal information and medical history in the questionnaires, blood samples were collected and after routine examination, the blood levels of these factors were measured. WE then entered the acquired results of the blood examination and the angiography in the patients' charts and analyzed the results using statistical methods. The angiography results in patient showed that 18 [14.7%] had normal coronary arteries, 5 [4%] had minimal coronary artery disease, 40 [32.5%] had single-vessel disease, 25 [20.3%] had two-vessel disease, and 35 [28.5%] had three-vessel disease. In laboratory tests, the mean soluble ICAM-1 level in patients with normal coronary arteries was 236 ngr/mL; however, in patients with coronary artery disease, the mean level was 274 ngr/mL. The average amount of VCAM-1 in patients with normal coronary arteries was 697 ngr/mL, whereas patients with coronary artery disase had an average of 108 ngr/mL. Thrombomodulin in the normal coronary artery group was 42 ngr/mL, but in patients with coronary artery disease the average level was 30 ngr/mL. The results in this research showed that increased levels of soluble ICAM-1 and also decreased levels of soluble thrombomodulin increased the risk and intensity of coronary artery disease, with statistical significance. The increase in soluble VCMA-1 also increased the risk of coronary artery disease; this was, however, not statistically significant. The important point is that increased levels of soluble ICAM-1 is a risk factor when the level of thrombomodulin is normal or below normal. When the levels of thrombomodulin and ICAM-1 have both increased, the increased risk and intensity of coronary disease is not statistically important
Assuntos
Humanos , Masculino , Feminino , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Trombomodulina/sangue , Fatores de Risco , Angiografia Coronária , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The role of leukocyte adhesion molecules in patients with burns and their relationship to other parameters of inflammation and lipid metabolism is only recently beginning to be explored. Therefore, we investigated the temporal changes in the levels of soluble cell adhesion molecules and other parameters of inflammation and lipoprotein metabolism in patients with thermal injury. MATERIALS AND METHODS: The serum levels of soluble adhesion molecules, intercellular cell adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and sE-selectin, C-reactive protein (CRP) and fibrinogen in seven patients with severe burns over a 30- day period were measured to determine the involvement of these factors in the pathophysiology of severe burns. Serum levels of sICAM-1, sVCAM-1 and sE-selectin were determined by ELISA. Furthermore, total cholesterol, high-density lipoprotein cholesterol (HDL chol), low-density lipoprotein cholesterol (LDL chol) and triglycerides (TG) were measured. RESULTS: Blood levels of sICAM-1, sVCAM-1, CRP and fibrinogen increased with maximum values six days after thermal injury. In contrast, serum levels of sE-selectin were elevated two days after thermal injury. The sICAM-1, sVCAM-1 and sE-selectin levels correlated significantly with both the CRP and the fibrinogen levels. Plasma total cholesterol, HDL cholesterol and LDL cholesterol decreased with minimum values four days after thermal injury. Furthermore, an increase of triglyceride levels was observed. CONCLUSION: The observed inflammatory response of soluble cell adhesion molecules could be useful in monitoring endothelial activation immediately following thermal injury. Further studies involving a larger number of patients with burns should help to clarify the extent to which measured parameters, especially the temporal changes of sCAMs, could be relevant in assessing the morbidity of patients with thermal injury.
ANTECEDENTES: El papel de las moléculas de adhesión leucocitaria en pacientes con quemaduras y su relación con otros parámetros de inflamación y metabolismo de lípidos ha comenzado a ser explorados sólo recientemente. Por lo tanto, investigamos los cambios temporales en los niveles de las moléculas de adhesión celular solubles y otros parámetros de inflamación y metabolismo de las lipoproteínas en pacientes con daños térmicos. MATERIALES Y MÉTODOS: Los niveles de suero de las moléculas de adhesión solubles, las moléculas 1 de adhesión intracelular (sICAM-1), las moléculas 1 de adhesión celular vascular (sVCAM-1) y sE-selectina, la proteína reactiva C (CRP), y el fibrinógeno en siete pacientes con quemaduras severas en un período de 30 días, fueron medidas a fin de determinar la participación de estos factores en la patofisiología de las quemaduras severas. Los niveles séricos de sICAM-1, sVCAM-1 y sE-selectina fueron determinados mediante ELISA. Además, se midieron el colesterol total, el colesterol de lipoproteína de alta densidad (HDL col), el colesterol de lipoproteína de baja densidad (LDL col), y los triglicéridos. RESULTADOS: Los niveles de sangre de sICAM-1, sVCAM-1, CRP y fibrinógeno aumentaron a valores máximos, seis días después del daño térmico. Los niveles de sICAM-1, sVCAM-1 y sE-selectina tuvieron una correlación significativa tanto con la CRP como con los niveles de fibrinógeno. El colesterol total de plasma, el colesterol HDL y el colesterol LDL disminuyeron a valores mínimos cuatro días después del daño térmico. Además, se observó un aumento en los niveles de triglicéridos. CONCLUSIÓN: La respuesta inflamatoria observada de las moléculas de adhesión celular soluble puede ser útil para monitorear la activación endotelial inmediatamente luego del daño térmico. Estudios ulteriores que comprendan un gran número de pacientes con quemaduras deben ayudar a aclarar hasta que punto los parámetros medidos, especialmente los cambios temporales de sCAMs, pudieran ser relevantes a la hora de evaluar la morbilidad de los pacientes con heridas térmicas.
Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Adulto Jovem , Queimaduras/sangue , Moléculas de Adesão Celular/sangue , Inflamação/sangue , Lipoproteínas/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Selectina E/sangue , Fibrinogênio/análise , Molécula 1 de Adesão Intercelular/sangue , Projetos Piloto , Triglicerídeos/sangue , Molécula 1 de Adesão de Célula Vascular/sangueRESUMO
Renal artery stenosis is most commonly due to either fibromuscular dysplasia or atherosclerosis. Atherosclerosis accounts for 90 percent of cases of renal-artery stenosis. Renal-artery stenosis may occur alone [isolated anatomical renal-artery stenosis] or in association with hypertension, renal insufficiency [ischemic nephropathy], or both. The aim of the present work was to study the role of renovascular disease as a novel risk marker of cognitive impairment in elderly. The study included 80 patients divided into 4 groups: Group 1: 20 cases of elderly patients above 65 years and suffering from grade 2 or 3 CKD. Group II: 20 cases aged 20-40 years and suffering from grade 2 or 3 CKD. Group III: 20 healthy controls aged above 65 years. Group IV: 20 healthy controls aged 20-40. They had been evaluated for their: Clinical condition, including physical examination and history taking, ECG, BMI estimation, MMMS examination, Routine investigation including: complete blood picture with differential counting, bleeding and coagulation time, liver functions tests, lipid profile, fasting and post-prandial plasma glucose, renal function tests, complete urine analysis, 24-hours proteins in urine, assessment of glomerular filtration rate [GFR] by MDRD and creatinine clearance and in addition specific laboratory investigations were done including: Serum CRP using turbidimetry, Microalbuminurea using turbidimetry, v-WF Ag by ELISA, s-ICAM. By ELISA and Duplex study was performed on carotid and renal arteries. The results of the present study showed that there was a significant increase in the BMI in groups land II in comparison to group III which was higher than group IV. The MMMS test was significantly lower in group I in comparison to groups II and III which were in turn significantly lower than group IV. Hemoglobin was significantly lower in groups I and II than group III and IV. Platelets count was significantly lower in groups I and II than group III which was also significantly lower than group IV. Creatinine clearance was significantly lower in groups I and II than in groups III and IV vWF levels were significantly lower in groups land II than in groups III and IV s.ICAM I was significantly higher in groups I and II compared to groups Ill and IV. CRP was significantly increased in groups I and II in comparison to groups III and IV Carotid plaque score was significantly higher in group I than group II which was higher than groups III. Resistive index was significantly lower in groups land II than in groups III and IV Acceleration index was significantly lower in groups I and II than in groups III and IV. A significant positive correlation was found between age and urinary albumin, CRP, and s.ICAM. A significant negative correlation between age and cereatinine clearance and MDRD in groups I, II and III. Reno vascular disease is common in elderly and the most important cause is atherosclerosis in this group of patients. There are many risk factors for cognitive impairment in patients suffering from renovascular disease and most of them are correctable. Renovascular disease can be considered as a novel risk factor of cognitive impairment through many interacting mechanisms
Assuntos
Humanos , Masculino , Feminino , Transtornos Cognitivos , Proteína C-Reativa/sangue , Molécula 1 de Adesão Intercelular/sangue , Artérias Carótidas/diagnóstico por imagem , Artéria Renal/diagnóstico por imagem , Ultrassonografia Doppler em Cores , Taxa de Filtração Glomerular , Idoso , Fatores de RiscoRESUMO
To evaluate circulating levels of sICAM-1, and sE-Selectin as indices of endothelial activation in a sample of obese young Egyptian females. Thirty obese and 30 non-obese premenopausal females were included in the study. They were subjected to complete clinical examination, and measurement of body mass index [BMI] and waist/hip ratio [W/H ratio]. Laboratory measurements included serum cholesterol [TC], serum LDL and HDL cholesterol, serum triglycerides [TG] and body fat%. Serum sICAM-1 and sE-Selectin concentrations were measured with ELISA technique. The treatment program included balanced low calorie food regimen and daily exercise therapy for 45-60 minutes at the intensity of 70-85% of maximum heart rate. Obese patients were reassessed after 3 months. Results: Obese females had significantly higher DM1, TC, LDL cholesterol, TG, body fat% and plasma levels of sE-Selectin and sICAM-1. HDL cholesterol was significantly lower in the obese group. Highly significant correlations were found between sE-Selectin and BMI, W/H ratio, TC, LDL cholesterol and body fat%. There was a significant correlation with TG, while sICAM-1 significantly correlated with BMI, TC and LDL cholesterol. A negative significant correlation was found between HDL cholesterol and CAMs. After treatment program, serum levels of sE-Selectin, sICAM-1 were significantly lowered with significant reductions in BMI, TC, LDL cholesterol, and TG and body fat%. Circulating levels of sE-Selectin and sICAM-1 are related to anthropometric and metabolic measures f obesity. sE-Selectin showed the strongest association with central obesity. Combined weight reduction, physical activity resulted in decrease in sE-Selectin and sICAM-1 levels
Assuntos
Humanos , Feminino , Molécula 1 de Adesão Intercelular/sangue , Selectina E/sangue , Índice de Massa Corporal , Colesterol , Triglicerídeos , Feminino , Lipoproteínas HDL , Lipoproteínas LDLRESUMO
High serum concentrations of systemic and vascular inflammation markers are two major risk factors for cardiovascular diseases in hemodialysis patients. The present study was designed to investigate the effects of dietary omega 3-fatty acid supplementation on the serum systemic and vascular inflammation markers in these patients. The study was a double-blind randomized clinical trial. Forty hemodialysis patients were randomly assigned to either an omega 3-fatty acid supplement or a placebo group. The patients in the omega 3-fatty acid supplement group received 2080 mg omega 3-fatty acids as 4 capsules, each containing 310 mg eicosapentaenoic acid and 210 mg docosahexaenoic acid, daily for 10 weeks, while the placebo group received 4 corresponding placebo capsules containing MCT oil. At baseline and the end of week 10 of the study, 7 ml blood was collected from each patient after a 12- to 14-hour fast before dialysis and serum sICAM-1, sVCAM-1, sE-selectin, sP-selectin, CRP, IL-6, TNF-alpha, malondealdehyde [MDA] and total antioxidant capacity [TAC] were measured. Serum sICAM-1 concentration decreased significantly in the omega 3-fatty acid supplement group at the end of week 10, compared to the baseline value [P<0.05]; the reduction was also significant in comparison with the decrease in placebo group [P<0.05]. No significant differences were observed between the two groups with regard to the mean changes in the serum sVCAM-1, sE-selectin, sP-selectin, CRP, IL-6, TNF-alpha, MDA, and TAC concentrations. The results of the present study indicate that dietary omega 3-fatty acid supplements can reduce serum sICAM-1 concentration in hemodialysis patients, but it has no effect on serum systemic inflammation markers and oxidative stress