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1.
Postgrad Med J ; 95(1121): 162-168, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31109934

RESUMO

Elevated levels of proinflammatory markers are evident in patients with diabetic retinopathy (DR) and are associated with disease progression and prognosis. Intercellular adhesion molecule-1 (ICAM-1) is involved in inflammation and acts as a local intensifying signal in the pathological processes associated with chronic eye inflammation. The aim of this systematic review and meta-analysis was to investigate the relationship between ICAM-1 level and DR. Online electronic databases were searched to retrieve all relevant articles published before December 2017. The standard mean difference (SMD) and their 95% CI were included and then pooled with a random effects model. Subgroup analysis and metaregression analysis were applied to explore the sources of heterogeneity, and publication bias was calculated to assess the quality of pooled studies. A total of 11 articles, containing 428 patients with DR and 789 healthy controls, were included in this meta-analysis. The results indicated a significant increase in ICAM-1 level in the DR group compared with the control group (SMD: 1.20, 95%CI 0.83 to 1.57, p<0.001). Subgroup analyses and metaregression analysis indicated that publication year, region, study method, diabetes mellitus type, Newcastle-Ottawa Scale and sample size were not the potential sources of heterogeneity. The results of this current meta-analysis indicated that the increased level of ICAM-1 generally exists in the patients with DR and it may associated with the severity of DR. However, large-scale and high-quality studies are required to confirm this finding in the future.


Assuntos
Retinopatia Diabética/sangue , Molécula 1 de Adesão Intercelular/sangue , Biomarcadores/sangue , Progressão da Doença , Humanos , Prognóstico
2.
Mol Cell Biochem ; 458(1-2): 133-142, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31093850

RESUMO

Changes in the ecto-5'-nucleotidase activity-an extracellular nucleotide catabolic enzyme may lead to the inflammation and endothelial dysfunction. We investigated the effect of CD73 deletion on the endothelial function and L-arginine metabolism in various age groups of mice. 1-,3-,6-, and 12-month-old, male C57BL/6 J wild type (WT) and C57BL/6 J CD73-/- (CD73-/-) mice were used. Blood samples were used for the analysis of adenine nucleotide concentrations. Serum samples were analyzed for the concentration of amino acids, Interleukin 6 (IL-6), Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), and endothelial nitric oxide synthase (eNOS) level. Serum and aortic nitrate/nitrite, as well as aortic arginase and NOS activity in endothelial cells (EC) were evaluated. CD73 deletion led to age-dependent increase in IL-6, ICAM-1, and VCAM-1 concentration compared to WT. All CD73-/- mice age groups were characterized by reduced L-Arginine concentration and eNOS level. Significantly lower NOS activity was noticed in EC isolated from CD73-/- mice lungs in comparison to EC isolated from WT lungs. The L-Arginine/ADMA ratio in the CD73-/- decreased in age-dependent manner in comparison to WT. The nitrate/nitrite ratio was reduced in serum and in aortas of 6-month-old CD73-/- mice as compared to WT. The ornithine/arginine and ornithine/citrulline ratios were increased in CD73-/- compared to controls. Blood (erythrocyte) Adenosine-5'-triphosphate and Adenosine-5'-diphosphate levels were reduced in favor to higher blood Adenosine-5'-monophosphate concentration in CD73-/- mice in comparison to WT. The CD73 deletion leads to the development of age-dependent endothelial dysfunction in mice, associated with impaired L-arginine metabolism. CD73 activity seems to protect endothelium.


Assuntos
5'-Nucleotidase/deficiência , Arginina/sangue , Endotélio Vascular/metabolismo , Difosfato de Adenosina/sangue , Difosfato de Adenosina/genética , Trifosfato de Adenosina/sangue , Trifosfato de Adenosina/genética , Animais , Arginina/genética , Endotélio Vascular/patologia , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão Intercelular/genética , Interleucina-6/sangue , Interleucina-6/genética , Camundongos , Camundongos Knockout , Óxido Nítrico Sintase Tipo III/sangue , Óxido Nítrico Sintase Tipo III/genética , Molécula 1 de Adesão de Célula Vascular/sangue , Molécula 1 de Adesão de Célula Vascular/genética
3.
Lipids Health Dis ; 18(1): 92, 2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-30961613

RESUMO

BACKGROUND: This study investigated the pathways and genes involved in coronary artery disease (CAD) and the associated mechanisms. METHODS: Two array data sets of GSE19339 and GSE56885 were downloaded. The limma package was used to analyze the differentially expressed genes (DEGs) in normal and CAD specimens. Examination of DEGs through Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and Gene Ontology annotation was achieved by Database for Annotation, Visualization and Integrated Discovery (DAVID). The Cytoscape software facilitated the establishment of the protein-protein interaction (PPI) network and Molecular Complex Detection (MCODE) was performed for the significant modules. RESULTS: We identified 413 DEGs (291 up-regulated and 122 down-regulated). Approximately 256 biological processes, only 1 cellular component, and 21 molecular functions were identified by GO analysis and 10 pathways were enriched by KEGG. Moreover, 264 protein pairs and 64 nodes were visualized by the PPI network. After the MCODE analysis, the top 4 high degree genes, including interleukin 1 beta (IL1B, degree = 29), intercellular adhesion molecule 1 (ICAM1, degree = 25), Jun proto-oncogene (JUN, degree = 23) and C-C motif chemokine ligand 2 (CCL2, degree = 20) had been identified to validate in RT-PCR and Cox proportional hazards regression between CAD and normals. CONCLUSIONS: The relative expression of IL1B, ICAM1 and CCL2 was higher in CAD than in normal controls (P < 0.05-0.001), but only IL1B and CCL2 genes were confirmed after testing the gene expression in blood and/or analyzing in Cox proportional hazards regression (P < 0.05-0.001), and the proper mechanism may involve in the AGE-RAGE signaling pathway, fluid shear stress, the tumor necrosis factor (TNF) and cytokine-cytokine receptor interaction.


Assuntos
Quimiocina CCL2/genética , Doença da Artéria Coronariana/genética , Molécula 1 de Adesão Intercelular/genética , Interleucina-1beta/genética , Proteínas Proto-Oncogênicas c-jun/genética , Transcriptoma , Idoso , Atlas como Assunto , Biomarcadores/sangue , Estudos de Casos e Controles , Quimiocina CCL2/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/patologia , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Humanos , Molécula 1 de Adesão Intercelular/sangue , Interleucina-1beta/sangue , Masculino , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Modelos de Riscos Proporcionais , Mapeamento de Interação de Proteínas , Proteínas Proto-Oncogênicas c-jun/sangue , Software
4.
Clinics (Sao Paulo) ; 74: e890, 2019 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-30994713

RESUMO

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
Pressão Sanguínea/efeitos dos fármacos , Suplementos Nutricionais/análise , Hipertensão/sangue , Inflamação/sangue , Sobrepeso/sangue , Adiponectina/sangue , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , China , Ingestão de Energia , Feminino , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Pessoa de Meia-Idade , NF-kappa B/sangue , Inquéritos Nutricionais/estatística & dados numéricos , Pós/uso terapêutico , População Rural
5.
Iran J Kidney Dis ; 13(1): 48-55, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30851719

RESUMO

INTRODUCTION: Protein-energy wasting (PEW) is prevalent in dialysis patients, and cardiovascular disease (CVD) is the leading cause of mortality in these patients. This study aimed to determine the prevalence of PEW and its relationship with CVD risk factors in peritoneal dialysis (PD) patients in Tehran, Iran. MATERIALS AND METHODS: All eligible PD patients in Tehran peritoneal dialysis centers were included in this cross-sectional study. The diagnosis of PEW was done based on the criteria of the International Society of Renal Nutrition and Metabolism. Serum high-sensitivity C-reactive protein, soluble intercellular adhesion molecule type 1, malondialdehyde, and lipid profile were measured. RESULTS: The prevalence of PEW was 29% in the PD patients. Significant associations were found between the prevalence of PEW in PD patients and sex (P = .01), age (P = .03), type of PD dialysis solution (P = .04), and microinflammation (P = .03). Serum C-reactive protein (P = .02), soluble intercellular adhesion molecule type 1 (P = .001), and triglyceride (P = .03) were significantly higher in the PD patients without PEW as compared to those with PEW, whereas high-density lipoprotein cholesterol level was significantly lower in the PD patients without PEW as compared to those with PEW (P = .003). CONCLUSIONS: Our study shows that PEW is prevalent in Iranian PD patients. In addition, serum concentrations of CVD risk factors are dependent on the amount of glucose absorbed from PD solutions and are more impaired in PD patients without PEW as compared to those with PEW.


Assuntos
Doenças Cardiovasculares/complicações , Falência Renal Crônica/complicações , Diálise Peritoneal/efeitos adversos , Desnutrição Proteico-Calórica/epidemiologia , Proteína C-Reativa/metabolismo , Estudos Transversais , Feminino , Humanos , Molécula 1 de Adesão Intercelular/sangue , Irã (Geográfico)/epidemiologia , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Prevalência , Desnutrição Proteico-Calórica/sangue , Fatores de Risco , Triglicerídeos/sangue
6.
Eur J Gastroenterol Hepatol ; 31(5): 618-625, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30920976

RESUMO

INTRODUCTION: Microcirculation is essential for adequate tissue perfusion and organ function. Microcirculatory changes may occur in cirrhosis, inducing loss of multiorgan function. The aim was to evaluate preliver transplantation and postliver transplantation aspects of multiorgan function, microcirculation, inflammatory, and endothelial biomarkers and survival in a controlled study including cirrhotic outpatients. PATIENTS AND METHODS: We accessed functional capillary density (FCD) and red blood cell acceleration (RBCA) by nailfold videocapillaroscopy. Inflammatory and endothelial biomarkers [interleukin-6 (IL-6), soluble intercellular adhesion molecule-1, endothelin-1, and tumor necrosis factor-α] were analyzed. Cerebral and renal functions were assessed to represent organ dysfunction and regression analyses were carried out. Receiver operating characteristic curves were constructed and survival Kaplan-Meier analysis was carried out. RESULTS: Fifty-four patients and 18 controls were included. Inflammatory and endothelial markers increased in advanced disease. FCD was reduced and RBCA was progressively lower according to disease severity. RBCA correlated inversely with inflammatory and endothelial biomarkers, and directly with renal function. The presence of hepatic encephalopathy correlated inversely with RBCA and directly with IL-6 and endothelin-1. In multivariate analysis, RBCA was an independent factor for organ dysfunction. The area under the receiver operating chartacteristic curve for IL-6 for survival was 0.74 (0.59-0.89), P=0.05. Transplant-free survival was 97.5% for values under 5.78 ng/ml (IL-6 best cutoff) and 83.9% above 5.78 ng/ml, log-rank=0.018. Eleven patients underwent transplantation, with an overall improvement in microcirculatory function. CONCLUSION: Our results suggest a mechanism of organ damage in cirrhosis, where microcirculatory dysfunction could be correlated to inflammatory and endothelial biomarkers, and loss of multiorgan function. IL-6 seems to be an important survival marker of inflammation. Liver transplantation improved microcirculatory dysfunction, corroborating this hypothesis.


Assuntos
Capilares/fisiopatologia , Cirrose Hepática/complicações , Microcirculação , Insuficiência de Múltiplos Órgãos/etiologia , Unhas/irrigação sanguínea , Idoso , Biomarcadores/sangue , Capilares/diagnóstico por imagem , Estudos de Casos e Controles , Eritrócitos , Feminino , Encefalopatia Hepática/sangue , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/fisiopatologia , Humanos , Mediadores da Inflamação/sangue , Molécula 1 de Adesão Intercelular/sangue , Interleucina-6/sangue , Nefropatias/sangue , Nefropatias/etiologia , Nefropatias/fisiopatologia , Cirrose Hepática/sangue , Cirrose Hepática/fisiopatologia , Cirrose Hepática/cirurgia , Transplante de Fígado , Estudos Longitudinais , Masculino , Angioscopia Microscópica , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/sangue , Insuficiência de Múltiplos Órgãos/fisiopatologia , Fluxo Sanguíneo Regional , Fatores de Risco , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue
7.
Ann Endocrinol (Paris) ; 80(2): 72-76, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30825997

RESUMO

OBJECTIVE: To investigate the relations of circulating adhesion molecule vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) with carotid artery elasticity in patients with impaired glucose regulation (IGR). METHODS: A total of 208 subjects were enrolled from January 2013 to March 2014. One hundred forty-eight were IGR patients, and 60 had normal glucose tolerance (NGT). Carotid intima-media thickness (IMT), carotid artery pressure-strain elasticity coefficient (Eρ), stiffness (ß), arterial compliance (AC), and pulse wave velocity (PWVß), as well as blood pressure, body mass index, blood glucose, blood lipids, insulin resistance index, VCAM-1, and ICAM-1 were measured and compared between IGR and NGT patients. RESULTS: Eρ, ß and PWVß were significantly higher in the IGR group than in the NGT group (P<0.05), but the IMT showed no significant difference (P>0.05). VCAM-1 and ICAM-1 were significantly higher in the IGR group than in the NGT group (P<0.05). VCAM-1 and ICAM-1 were positively correlated with Eρ, ß, and PWVß and negatively correlated with AC in IGR patients. CONCLUSIONS: Changes in carotid artery elasticity and endothelial dysfunction are found in patients with IGR. Early comprehensive intervention should be performed in such IGR populations.


Assuntos
Artérias Carótidas/fisiopatologia , Intolerância à Glucose/sangue , Intolerância à Glucose/fisiopatologia , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão de Célula Vascular/sangue , Rigidez Vascular/fisiologia , Adulto , Idoso , Glicemia/metabolismo , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Elasticidade/fisiologia , Feminino , Intolerância à Glucose/diagnóstico , Humanos , Resistência à Insulina/fisiologia , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estado Pré-Diabético/fisiopatologia , Análise de Onda de Pulso , Ultrassonografia , Adulto Jovem
8.
Nutrients ; 11(3)2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30841605

RESUMO

Glomerular fibrosis is caused by an accumulation of intercellular spaces containing mesangial matrix proteins through either diffused or nodular changes. Dianthus superbus has been used in traditional medicine as a diuretic, a contraceptive, and an anti-inflammatory agent. The aim of this study was to investigate the effects of Dianthus superbus-EtOAc soluble fraction (DS-EA) on glomerular fibrosis and renal dysfunction, which has been implicated in diabetic nephropathy in human renal mesangial cells and db/db mice. DS-EA was administered to db/db mice at 10 or 50 mg/kg/day for 8 weeks. DS-EA treatment significantly ameliorated blood glucose, insulin, the homeostasis model assessment of insulin resistance (HOMA-IR) index, and HbA1c in diabetic mice. DS-EA decreased albumin excretion, creatinine clearance (Ccr), and plasma creatinine levels. DS-EA also ameliorated the levels of kidney injury molecules-1 (KIM-1) and C-reactive protein. DS-EA reduced the periodic acid-Schiff (PAS) staining intensity and basement membrane thickening in glomeruli of the diabetic nephropathy model. In addition, DS-EA suppressed transforming growth factor-ß (TGF-ß)/Smad signaling. Collagen type IV, a glomerular fibrosis biomarker, was significantly decreased upon DS-EA administration. DS-EA pretreatment attenuated levels of inflammation factors such as intracellular cell adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1). DS-EA inhibited the translocation of nuclear factor kappa B (NF-κB) in Angiotensin II (Ang II)-stimulated mesangial cells. These findings suggest that DS-EA has a protective effect against renal inflammation and fibrosis. Therefore, DS-EA may serve as a potential therapeutic agent targeting glomerulonephritis and glomerulosclerosis, which lead to diabetic nephropathy.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Dianthus , Fitoterapia , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Animais , Glicemia/efeitos dos fármacos , Quimiocina CCL2/sangue , Colágeno Tipo IV/sangue , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/etiologia , Modelos Animais de Doenças , Fibrose , Humanos , Inflamação , Insulina/sangue , Resistência à Insulina/fisiologia , Molécula 1 de Adesão Intercelular/sangue , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Células Mesangiais , Camundongos , Transdução de Sinais , Fator de Crescimento Transformador beta/sangue
9.
Diabetes Res Clin Pract ; 150: 57-63, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30825562

RESUMO

OBJECTIVE: Meteorin-like (Metrnl) is a novel secreted protein that has a beneficial effect on glucose homeostasis with anti-inflammatory properties. Our goal is to determine whether low serum Metrnl levels are associated with worsening of glucose tolerance, impaired endothelial function, and atherosclerosis. METHODS: This study included 260 adults, 89 of whom had normal oral glucose tolerance (nOGT), 77 with glucose tolerance impairment (GTI) and 94 with type 2 diabetes (T2DM). Insulin resistance was assessed by evaluating the homeostasis model assessment of insulin resistance (HOMA-IR). Serum Metrnl level, proinflammatory, biochemical, endothelial and atherosclerosis parameters were measured. RESULTS: Serum Metrnl levels decreased significantly in patients with T2DM versus subjects with nOGT (P < 0.001). Metrnl levels were negatively correlated with fasting blood glucose, 2-h postload glucose (2 h-PLG), fasting insulin, HOMA-IR, HbA1c, high-sensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), Carotid intima media thickness (CIMT), brachial-ankle pulse wave velocity (baPWV), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. High serum Metrnl level was significantly correlated with reduced risk of T2DM as revealed by multivariate logistic regression analysis after control of potential risk factors for diabetes. Furthermore, the association remains significant after further adjustment for IL-6, TNF-α, hs-CRP, CIMT, baPWV, ICAM-1, VCAM-1 and E-selectin. CONCLUSIONS: Low Serum Metrnl may be associated with worsening of glucose tolerance, impaired endothelial function and atherosclerosis. It may also be considered a possible surrogate marker of endothelial dysfunction, and atherosclerosis and an independent risk factor of T2DM.


Assuntos
Adipocinas/sangue , Aterosclerose/sangue , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/sangue , Endotélio Vascular/metabolismo , Intolerância à Glucose/sangue , Resistência à Insulina , Adulto , Idoso , Índice Tornozelo-Braço , Aterosclerose/epidemiologia , Glicemia/análise , Proteína C-Reativa/metabolismo , Espessura Intima-Media Carotídea , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Selectina E/sangue , Egito/epidemiologia , Endotélio Vascular/patologia , Feminino , Intolerância à Glucose/epidemiologia , Humanos , Molécula 1 de Adesão Intercelular/sangue , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Fatores de Risco , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/sangue , Adulto Jovem
10.
PLoS One ; 14(1): e0210732, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30653588

RESUMO

STUDY OBJECTIVES: Untreated obstructive sleep apnea (OSA) patients have an increased risk of cardiovascular disease (CVD). Adhesion molecules, including soluble E-selectin (sE-selectin), intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1), are associated with incident CVD. We hypothesized that specific genetic variants will be associated with plasma levels of adhesion molecules in suspected OSA patients. We also hypothesized that there may be an interaction between these variants and OSA. METHODS: We measured levels of sE-selectin, sICAM-1 and sVCAM-1 in 491 patients with suspected OSA and genotyped them for 20 polymorphisms. RESULTS: The most significant association was between the ABO rs579459 polymorphism and sE-selectin levels (P = 7×10-21), with the major allele T associated with higher levels. The direction of effect and proportion of the variance in sE-selectin levels accounted for by rs579459 (16%) was consistent with estimates from non-OSA cohorts. In a multivariate regression analysis, addition of rs579459 improved the model performance in predicting sE-selectin levels. Three polymorphisms were nominally associated with sICAM-1 levels but none with sVCAM-1 levels. The combination of severe OSA and two rs579459 T alleles identified a group of patients with high sE-selectin levels; however, the increase in sE-selectin levels associated with severe OSA was greater in patients without two T alleles (P = 0.05 test for interaction). CONCLUSIONS: These genetic polymorphisms may help to identify patients at greatest risk of incident CVD and may help in developing a more precision-based approach to OSA care.


Assuntos
Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão Intercelular/genética , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/genética , Molécula 1 de Adesão de Célula Vascular/sangue , Molécula 1 de Adesão de Célula Vascular/genética , Adulto , Proteínas Sanguíneas/análise , Selectina E/sangue , Feminino , Técnicas de Genotipagem , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Polissonografia , Análise de Regressão
11.
PLoS One ; 14(1): e0210544, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30629692

RESUMO

INTRODUCTION: VWD-affected females often experience menorrhagia. Periodical fluctuations of the sex steroids during the menstrual cycle cause changes both in the coagulation and immune system. The aim of the current study was to assess the changes in selected inflammatory and endothelial markers in women with VWD during two phases of the menstrual cycle (follicular and luteal) and to compare it with corresponding data from healthy controls. MATERIALS AND METHODS: The study group included 12 VWD-affected females with regular menstrual cycle, with none of them being prescribed hormone treatment. They were not pregnant or breastfeeding. The control group consisted of 102 healthy females, matched for age and BMI. RESULTS: Within the VWD group, endostatin was higher during the follicular phase, compared to the luteal phase, although the difference was not significant (p = 0.062). sICAM-1 and IL-6 were higher in VWD-affected females, compared to the controls, sVCAM-1, cathepsin S and sP-selectin were lower (p<0.003 for all cases). The pattern was constant throughout the menstrual cycle. CONCLUSIONS: Higher levels of endostatin during early follicular phase could potentially predispose women with VWD to the development of heavy menstrual bleeding, due to antiangiogenic properties and ability to suppress several coagulation factors. Lower p-selectin levels in VWD group, compared to controls, may also contribute to the bleeding tendency. Changes in other proteins, involved in angiogenesis are hypothetically related to the formation of angiodysplasia-common complication of VWF deficiency. The latter statement requires confirmation in larger studies.


Assuntos
Inflamação/sangue , Doenças de von Willebrand/sangue , Adulto , Biomarcadores/sangue , Catepsinas/sangue , Feminino , Humanos , Molécula 1 de Adesão Intercelular/sangue , Interleucina-6/sangue , Ciclo Menstrual , Selectina-P/sangue
12.
J Toxicol Sci ; 44(1): 35-45, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30626778

RESUMO

Due to its excellent properties such as ultraviolet obscuration, chemical stability and small particle size, nano-titanium dioxide (nano-TiO2) is widely used, particularly in sunblock products. The skin is therefore a chief route for exposure. Studies have found that oral or respiratory exposure to nano-TiO2 has an adverse impact on the cardiovascular system. The relationship between dermal exposure to nano-TiO2 and cardiovascular system toxicity, particularly the causative mechanisms, remain unclear. In this study, we used Balb/c mice to evaluate cardiovascular toxicity from nano-TiO2 dermal exposure, and the underlying mechanisms associated with the human umbilical vein endothelial cells (HUVECs) were explored. Our results showed that nano-TiO2 treatment resulted in an obvious increase in reactive oxygen species and 8-hydroxy-2'-deoxyguanosine, indicating the appearance of oxidative stress. Moreover, the levels of inflammatory biomarkers, such as immunoglobulin E, soluble intercellular adhesion molecule-1, interleukin-8, and hypersensitive C-reactive protein, also increased. Exposing HUVECs to nano-TiO2 led to a decline in cell vitality, and an increase in caspase-3 levels, suggesting that nano-TiO2 exposure caused cytotoxicity and even cell apoptosis. Interestingly, neutralizing oxidative stress by administering Vitamin E was shown to reduce the inflammatory response and cytotoxicity. Our findings suggest that nano-TiO2 can injure the cardiovascular system via dermal exposure, and does this via oxidative stress-induced inflammation and cytotoxicity. Vitamin E treatment may be a strategy to mitigate the damage.


Assuntos
Nanopartículas/toxicidade , Titânio/toxicidade , Administração Cutânea , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Feminino , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Imunoglobulina E/metabolismo , Inflamação/metabolismo , Molécula 1 de Adesão Intercelular/sangue , Interleucina-8/sangue , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio/sangue , Vitamina E/farmacologia
13.
Chest ; 154(6): 1359-1370, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30526970

RESUMO

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with 3 to 5 years' survival. Although FVC is used to assess disease progression and treatment response, identifying predictive circulating blood biomarkers could help identify specific biologic pathways for treatment. An international, prospective, noninterventional, case-controlled, 52-week study was therefore conducted to identify a clinical and biomarker baseline profile predictive of longitudinal disease behavior. METHODS: Patients with IPF and control subjects had lung function tests and blood sampling for biomarker quantification (control subjects at baseline only). The primary end point was disease progression rate (composite end point: decrease ≥ 10% from baseline in FVC % predicted, decrease ≥ 15% from baseline in diffusing capacity of the lung for carbon monoxide % predicted, lung transplantation, death) at week 52 and its relationship to selected biomarkers at baseline. RESULTS: Altogether, 211 subjects (154 patients with IPF and 57 control subjects) were enrolled; one-third of patients (n = 47) with IPF had progressed by week 52. Biomarkers CC-chemokine ligand 18 (CCL18), intercellular adhesion molecule 1, Krebs von den Lungen-6, surfactant protein (SP)-A, SP-D, matrix metallopeptidase 7, urokinase-type plasminogen activator receptor, and two novel biomarkers, human epididymis protein-4 (HE4) and prostasin, discriminated patients with IPF vs control subjects. There was no difference in baseline CCL18 concentration between progressors and nonprogressors at week 52 (area under the receiver operating characteristic curve, 0.62; corrected P = .161). No biomarkers were predictive for disease progression. CONCLUSIONS: Several biomarkers, including CCL18, were associated with IPF, but none predicted disease progression. Two novel biomarkers, HE4 and prostasin, were identified and warrant further investigation.


Assuntos
Quimiocina CCL18/sangue , Fibrose Pulmonar Idiopática , Molécula 1 de Adesão Intercelular/sangue , Proteínas/análise , Receptores de Ativador de Plasminogênio Tipo Uroquinase/sangue , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Correlação de Dados , Progressão da Doença , Feminino , Humanos , Fibrose Pulmonar Idiopática/sangue , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/fisiopatologia , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Testes de Função Respiratória/métodos , Serina Endopeptidases/sangue
14.
Transplant Proc ; 50(10): 3650-3655, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30586839

RESUMO

BACKGROUND: Cardiovascular disease is a major contributing factor to long-term mortality after liver transplantation (LT). METHODS: This study evaluated the evolution of atherogenic risk in liver transplant recipients (LTRs). Thirty-six subjects were prospectively enrolled at 12 months and followed for 48 months after liver transplantation. Serum biomarkers of endothelial dysfunction (sICAM-1 and sVCAM-1), chronic inflammation (serum amyloid A), and oxidative stress (myeloperoxidase) were measured at 12 and 48 months after LT. Additionally, at 12 months all patients underwent a cardiac computed tomography (CT) scan and a coronary artery calcium score (CACS). RESULTS: The prevalence of risk factors of metabolic syndrome (MS) increased over the course of the study. The patients' sVCAM-1 and sICAM-1 increased from 1.82 ± 0.44 ng/mL to 9.10 ± 5.82 ng/mL (P < .001) and 0.23 ± 0.09 ng/mL to 2.7 ± 3.3 ng/mL, respectively from month 12 to 48. Serum myeloperoxidase increased from 0.09 ± 0.07 ng/mL to 3.46 ± 3.92 ng/mL (P < .001) over the course of the study. Serum amyloid A also increased from 21.4 ± 40.7 ng/mL at entry to 91.5 ± 143.6 ng/mL at end of study (P < .001). CONCLUSION: No association between these biomarkers and MS was noted. The cardiac CT revealed mild and moderate disease in 19% and 25% of the cohort, respectively. No association between serum biomarkers and CACS was noted. Serum biomarkers of atherogenic risk increase rapidly in LTRs and precede coronary plaques.


Assuntos
Aterosclerose/etiologia , Doenças Cardiovasculares/etiologia , Transplante de Fígado/efeitos adversos , Síndrome Metabólica/etiologia , Complicações Pós-Operatórias/etiologia , Adulto , Aterosclerose/epidemiologia , Biomarcadores/sangue , Cálcio/análise , Doenças Cardiovasculares/epidemiologia , Feminino , Seguimentos , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Peroxidase/sangue , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Prevalência , Estudos Prospectivos , Fatores de Risco , Proteína Amiloide A Sérica/metabolismo , Molécula 1 de Adesão de Célula Vascular/sangue
15.
Mar Drugs ; 16(12)2018 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-30544795

RESUMO

(1) Background: Spirulina (Arthrospira) maxima has shown beneficial effects such as being anti-dyslipidemic, antiviral, antioxidant and antihypertensive. However, there are few and limited clinical studies. (2) Methods: a prospective, randomized, parallel pilot study of 4.5 g administration of Spirulina maxima or placebo for 12 weeks in 16 patients with systemic arterial hypertension (SAH) undergoing treatment with angiotensin-converting enzyme (ACE) inhibitors was performed to assess the effects on endothelial damage and oxidative stress indicators. The blood levels of sICAM-1, sVCAM-1, endothelin-1, and sE-selectin were quantified; the activities of catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase and concentrations of reduced glutathione, oxidized glutathione, and thiobarbituric acid reactive substances, were also quantified before and after the treatment period. (3) Results: There were statistically significant (p < 0.05) decreases in systolic blood pressure, sVCAM-1, sE-selectin and endothelin-1 levels, and increases in glutathione peroxidase activity and oxidized glutathione levels. (4) Conclusion: The effects found in the present study agree with antihypertensive and antioxidant effects previously reported for Spirulina maxima. However, this is the first report about the effects on indicators of endothelial damage. More research in this field is necessary to gain an insight into the effects of Spirulina on these indicators.


Assuntos
Antioxidantes/administração & dosagem , Suplementos Nutricionais , Hipertensão/dietoterapia , Spirulina/química , Adulto , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Índice de Massa Corporal , Selectina E/sangue , Endotélio Vascular/efeitos dos fármacos , Feminino , Humanos , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Molécula 1 de Adesão Intercelular/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento , Molécula 1 de Adesão de Célula Vascular/sangue
16.
Pregnancy Hypertens ; 13: 14-21, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30177042

RESUMO

BACKGROUND: Women with a history of hypertensive disorders of pregnancy and preterm delivery have an increased risk of cardiovascular disease (CVD). Chronic inflammation, endothelial dysfunction, and dyslipidemia may link pregnancy outcomes with CVD. OBJECTIVE: We evaluated whether women with a history of HDP or normotensive preterm delivery had adverse CVD biomarker profiles after pregnancy. STUDY DESIGN: We identified parous women from the Nurses' Health Study II with C-reactive protein (CRP; n = 2614), interleukin-6 (IL-6; n = 2490), glycated hemoglobin (n = 885), intracellular adhesion molecule-1 (n = 1231), high density lipoprotein cholesterol (n = 931), low density lipoprotein cholesterol (n = 931), triglycerides (n = 1428), or total cholesterol (n = 2940) assessed in stored blood samples. Multivariable-adjusted robust linear regression models evaluated percent differences and 95% confidence intervals (CIs) in each biomarker associated with a history of HDP or preterm delivery. RESULTS: Ten percent of women had a history of HDP, while 11% with normotensive pregnancies had at least one preterm delivery. Median time from first pregnancy to blood draw was 17 years (interquartile range: 12, 22). Plasma levels of CRP and IL-6 were 34.4% (95% CI: 17.2, 54.1), and 11.6% higher (95% CI: 2.1, 21.9) respectively, among women with a history of HDP compared to those with only normotensive pregnancies. Altered CVD biomarker levels were otherwise not present in women with a history of HDP or preterm delivery. CONCLUSION: CRP and IL-6, but not other CVD biomarkers, were elevated in women with a history of HDP in the years following pregnancy, suggesting inflammation may be a pathway linking HDP with future CVD risk.


Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Pré-Eclâmpsia , Nascimento Prematuro , Transtornos Puerperais/sangue , Adulto , Proteína C-Reativa/metabolismo , Colesterol/sangue , Estudos de Coortes , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/sangue , Interleucina-6/sangue , Modelos Lineares , Estudos Longitudinais , Gravidez
17.
Medicine (Baltimore) ; 97(31): e11760, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30075598

RESUMO

BACKGROUND: Previous studies have evaluated the diagnostic value of serum intercellular adhesion molecule-1 (ICAM-1) in patients with endometriosis, but the results remained inconsistent. This meta-analysis aimed to clarify the overall diagnostic accuracy of serum ICAM-1 for endometriosis. METHODS: A systematic search was performed of the Cochrane clinical trials database, PubMed, and Embase prior to December 2017. Sensitivity, specificity, and other measures were pooled and determined to evaluate the accuracy of serum ICAM-1 in the diagnosis of endometriosis. Summary receiver operating characteristic curve (SROC) analysis with calculation of the area under curve (AUC) was performed to summarize the overall test performance. RESULTS: Nine studies including 878 patients were eligible for inclusion in the analysis. The summary estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (95% confidence interval) were 0.65 (0.52-0.75), 0.78 (0.62-0.89), 3.0 (1.7-5.2), 0.45 (0.34-0.60), and 7 (3-13), respectively, and the AUC of the overall analysis was 0.76 (0.72-0.80). Subgroup analysis showed that the summary sensitivity and specificity for patients of Asian ethnicity was increased compared with those of Caucasian ethnicity. The summary specificity was increased in studies with a high ICAM-1 cut-off value compared to those with a low cut-off value. No publication bias was found across the studies. CONCLUSIONS: Our results suggest that serum ICAM-1 has moderate diagnostic accuracy for endometriosis, while the diagnostic accuracy is higher in patients of Asian ethnicity compared with those of Caucasian ethnicity.


Assuntos
Endometriose/sangue , Endometriose/diagnóstico , Molécula 1 de Adesão Intercelular/sangue , Grupo com Ancestrais do Continente Asiático , Biomarcadores , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Curva ROC , Valores de Referência , Sensibilidade e Especificidade
18.
Oxid Med Cell Longev ; 2018: 3718437, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30008985

RESUMO

The aim of the study was the analysis of adhesion molecules' profile (ICAM-1, VCAM-1, and E-selectin) in patients with allergic rhinitis and the influence of H1 antihistamines on those markers. Seventy-nine patients with persistent allergic rhinitis (PAR) and 30 healthy volunteers were included in the study. The patients with PAR were treated with desloratadine 5 mg/day or levocetirizine 5 mg/day for 4 weeks. The clinical (rhinitis symptoms and total symptoms score (TSS), type of sensitization) and biological evaluation (total IgE, eosinophils, ICAM-1, VCAM-1, and E-selectin) as well as fractionate nitric oxide in exhaled air (FeNO) measurement was performed before and after treatment. The plasmatic levels of ICAM-1, VCAM-1, total IgE, and eosinophils and FeNO were significantly increased in patients with PAR compared to healthy volunteers. H1 antihistamines significantly improved TSS, with no differences between the investigated drugs. There was a significant decrease of eosinophils, total IgE, and FeNO after treatment. H1 antihistamines significantly decreased the plasmatic levels of ICAM-1 and E-selectin but not VCAM-1 compared to basal values. There is no difference between levocetirizine and desloratadine in the reduction of CAMs. A systemic inflammation characterized by increased levels of CAMs is present in patients with PAR. H1 antihistamines improve symptoms and reduce CAMs and FeNO levels after 1 month of treatment. H1 antihistamines might reduce the systemic inflammation which could be responsible to asthma occurrence in patients with PAR.


Assuntos
Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Inflamação/imunologia , Rinite Alérgica/imunologia , Adulto , Selectina E/sangue , Eosinófilos/metabolismo , Feminino , Humanos , Imunoglobulina E/sangue , Inflamação/sangue , Inflamação/tratamento farmacológico , Molécula 1 de Adesão Intercelular/sangue , Masculino , Óxido Nítrico/sangue , Rinite Alérgica/sangue , Rinite Alérgica/tratamento farmacológico , Molécula 1 de Adesão de Célula Vascular/sangue , Adulto Jovem
19.
Rheumatology (Oxford) ; 57(10): 1795-1801, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29961816

RESUMO

Objective: Tocilizumab is effective in inducing and maintaining remission of GCA. Despite clinical and serological control of disease, magnetic resonance angiography may show persistence of inflammatory signals of unknown significance in arterial walls. Thus, there is an unmet need for tools to detect subclinical disease activity. Methods: Immune-inflammatory markers were measured in prospectively collected sera of the first randomized, double-blind, placebo-controlled trial investigating the use of tocilizumab in GCA. As a comparison, immune-inflammatory markers were also measured in sera from age- and sex-matched healthy volunteers. The biomarkers were quantified using luminex technology. Results: Of all the parameters determined, only MMP-3, pentraxin-3 and sTNFR2 were significantly elevated, while ICAM-1 and CD163 were significantly decreased during the early stages of the study, at time points of full clinical remission under treatment with tocilizumab plus glucocorticoids. In contrast, tocilizumab monotherapy towards the end of the study resulted in an almost complete normalization of immune-inflammatory molecules, as defined by the healthy controls. MMP-3 levels showed a weak association with magnetic resonance signal intensity; none of the biomarkers predicted relapse occurring within 6 months after study end. Conclusion: The data documented a subclinical disease activity in GCA that was more pronounced during the early stages of treatment and almost disappeared towards the study end. They indicated that tocilizumab treatment of at least 52 weeks is necessary in order to reset a broad range of immune-inflammatory pathways. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT01450137.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Arterite de Células Gigantes/sangue , Glucocorticoides/uso terapêutico , Quimioterapia de Indução/métodos , Monitorização Imunológica/métodos , Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Biomarcadores/sangue , Proteína C-Reativa/análise , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Feminino , Arterite de Células Gigantes/tratamento farmacológico , Arterite de Células Gigantes/patologia , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Metaloproteinase 3 da Matriz/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Receptores de Superfície Celular/sangue , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Componente Amiloide P Sérico/análise , Resultado do Tratamento
20.
Growth Horm IGF Res ; 41: 28-33, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29936324

RESUMO

INTRODUCTION: Low circulating levels of insulin-like growth factor-1 (IGF-1) are associated with endothelial dysfunction, subsequently leading to the development of cardiovascular disease. OBJECTIVE: To better understand the early phases of vascular deterioration in a young, healthy population, we investigated, cross-sectionally, whether biomarkers of endothelial function (intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand factor antigen (vWFag)) are associated with IGF-1 in a healthy study population forming part of the larger African Prospective study on the Early Detection and Identification of Cardiovascular diseases and Hypertension (African-PREDICT). METHOD: We included 825 black and white men and women (aged 20-30 years) and determined IGF-1, IGF binding protein-3 (IGFBP-3), ICAM-1, VCAM-1 and vWFag from blood samples. We also measured 24-h blood pressure and health behaviours namely waist circumference, accelerometery, cotinine and gamma glutamyl transferase. We used the IGF-1/IGFBP-3 M ratio as an estimate of bioavailable IGF-1. RESULTS: In multivariable-adjusted regression analyses performed in the total group, VCAM-1 associated positively with IGFBP-3 (ß = 0.21; p < .001) and negatively with IGF-1/IGFBP-3 (ß = -0.18; p < .001). ICAM-1 showed a borderline negative association with IGF-1 (ß = -0.09; p = .054) and IGF-1/IGFBP-3 (ß = -0.08; p = .057). vWFag was not associated with IGF-1, IGFBP-3 or bioavailable IGF-1. CONCLUSION: VCAM-1 is beneficially associated with IGF-1 in a young healthy cohort, independent of sex, ethnicity, blood pressure and health behaviours - thereby confirming the potential importance of bioavailable IGF-1 in early vascular endothelial protection.


Assuntos
Biomarcadores/sangue , Doenças Cardiovasculares/diagnóstico , Endotélio Vascular/patologia , Fator de Crescimento Insulin-Like I/metabolismo , Adulto , Doenças Cardiovasculares/sangue , Estudos Transversais , Endotélio Vascular/metabolismo , Feminino , Seguimentos , Humanos , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Molécula 1 de Adesão Intercelular/sangue , Masculino , Prognóstico , Estudos Prospectivos , Molécula 1 de Adesão de Célula Vascular/sangue , Circunferência da Cintura , Adulto Jovem
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