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Fibrinogen
Kinds of Fibrinogen Terms modified by Fibrinogen Selected AbstractsMechanisms of fibrinogen-induced microvascular dysfunction during cardiovascular diseaseACTA PHYSIOLOGICA, Issue 1 2010D. Lominadze Abstract Fibrinogen (Fg) is a high molecular weight plasma adhesion protein and a biomarker of inflammation. Many cardiovascular and cerebrovascular disorders are accompanied by increased blood content of Fg. Increased levels of Fg result in changes in blood rheological properties such as increases in plasma viscosity, erythrocyte aggregation, platelet thrombogenesis, alterations in vascular reactivity and compromises in endothelial layer integrity. These alterations exacerbate the complications in peripheral blood circulation during cardiovascular diseases such as hypertension, diabetes and stroke. In addition to affecting blood viscosity by altering plasma viscosity and erythrocyte aggregation, growing experimental evidence suggests that Fg alters vascular reactivity and impairs endothelial cell layer integrity by binding to its endothelial cell membrane receptors and activating signalling mechanisms. The purpose of this review is to discuss experimental data, which demonstrate the effects of Fg causing vascular dysfunction and to offer possible mechanisms for these effects, which could exacerbate microcirculatory complications during cardiovascular diseases accompanied by increased Fg content. [source] Analysis of gene expression patterns in the developing chick liverDEVELOPMENTAL DYNAMICS, Issue 3 2005Masaaki Yanai Abstract The chick embryo has been used widely for studying liver development. However, in the past 30 years, the usage has decreased markedly due to lack of appropriate marker genes for differentiation in the developing chick liver. To use the chick embryo for analyzing the molecular mechanism of liver development, we surveyed marker genes in the developing chick liver by examining the expression pattern of genes that are well-characterized in the developing mammalian liver. By whole-mount in situ hybridization, Fibrinogen - gamma (FIB) expression was first detected at stage 12, specifically in the anterior intestinal portal, and its liver-specific expression persisted in the later stages. Albumin (ALB) expression was first detected at stage 30, when the liver starts maturing. Cytokeratin 19 (CK19) was first detected at stage 37 in the ductal plate of the liver, and its expression continued in the intrahepatic bile ducts derived from the ductal plate. Hex, a transcription factor, is an additional marker of bile duct differentiation. Hence, FIB, ALB, and CK19 expression can be used to trace hepatic induction, maturation, and bile duct differentiation, respectively. Developmental Dynamics 233:1116,1122, 2005. © 2005 Wiley-Liss, Inc. [source] Effects of fibrinogen concentrate administration during severe hemorrhageACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2010H. R. THORARINSDOTTIR Background: Fibrinogen concentrate has been shown to improve coagulation in dilutional coagulopathy in experimental studies, but clinical experience is still scarce. The aim of this study was to evaluate laboratory data and the clinical outcome of fibrinogen administration in patients suffering from severe hemorrhage. Materials and methods: A retrospective study over a 3-year observation period of consecutive patients who received a single dose of fibrinogen concentrate but not recombinant factor VIIa as part of their treatment of severe hemorrhage, defined as >6 U of packed red blood cells (PRBCs). Results: Thirty-seven patients were included, most of them suffering from severe hemorrhage following open heart surgery (68%). After a median fibrinogen dose of 2 g (range 1,6 g), an absolute increase in the plasma fibrinogen concentration of 0.6 g/l was observed (P<0.001). The activated partial thromboplastin time (APTT) decreased significantly (P<0.001), from 52 to 43 s and the prothrombin time (PT) decreased from 20 to 17 s, respectively. The transfusion requirement for PRBCs decreased from 6 to 3 U (P<0.01) in the 24 h after fibrinogen administration, but fresh-frozen plasma and platelet concentrate transfusions did not change significantly. Eight patients (22%) died in intensive care unit and the pre-operative fibrinogen concentration was not significantly different in these patients. Conclusion: Administration of fibrinogen for severe hemorrhage was associated with an increased fibrinogen concentration and a significant decrease in APTT, PT and the requirement for PRBCs. [source] Does off-pump coronary artery bypass surgery reduce secretion of plasminogen activator inhibitor-1?INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 5 2007C. Ozkara Summary Prior studies showed that postoperative increase in plasminogen activator inhibitor-1 (PAI-1) levels is associated with an increased risk of graft occlusion after coronary artery bypass surgery (CABG). This prospective study aimed to compare the changes of PAI-1 antigen levels after off-pump and on-pump CABG. Forty-four patients admitted for elective CABG were randomised to on-pump (n = 22) or off-pump (n = 22) surgery. Serum samples were collected for estimation of PAI-1 and tissue plasminogen activator (t-PA) antigen levels preoperatively and 2 h after the operation. The groups were similar in terms of age, weight, gender ratio and extent of coronary disease, left ventricular function and number of grafts per patient. Fibrinogen and t-PA levels increased postoperatively in both the groups when compared with baseline values. After operation, statistical analysis revealed that increase of PAI-1 values was higher in off-pump group (44.1 ± 9.1 vs. 25.3 ± 6.9) than on-pump group (37.2 ± 5.5 vs. 27.3 ± 7.8, p = 0.002). This study shows that increase in PAI-1 antigen values in patients who undergo off-pump (beating heart) CABG is significantly higher than in those who undergo conventional CABG with cardiopulmonary bypass. [source] Phylogenetic relationships, diversification and biogeography in Neotropical Brotogeris parakeetsJOURNAL OF BIOGEOGRAPHY, Issue 9 2009Camila C. Ribas Abstract Aim, We present a molecular phylogenetic analysis of Brotogeris (Psittacidae) using several distinct and complementary approaches: we test the monophyly of the genus, delineate the basal taxa within it, uncover their phylogenetic relationships, and finally, based on these results, we perform temporal and spatial comparative analyses to help elucidate the historical biogeography of the Neotropical region. Location, Neotropical lowlands, including dry and humid forests. Methods, Phylogenetic relationships within Brotogeris were investigated using the complete sequences of the mitochondrial genes cyt b and ND2, and partial sequences of the nuclear intron 7 of the gene for Beta Fibrinogen for all eight species and 12 of the 17 taxa recognized within the genus (total of 63 individuals). In order to delinetae the basal taxa within the genus we used both molecular and plumage variation, the latter being based on the examination of 597 skin specimens. Dates of divergence and confidence intervals were estimated using penalized likelihood. Spatial and temporal comparative analyses were performed including several closely related parrot genera. Results,Brotogeris was found to be a monophyletic genus, sister to Myiopsitta. The phylogenetic analyses recovered eight well-supported clades representing the recognized biological species. Although some described subspecies are diagnosably distinct based on morphology, there was generally little intraspecific mtDNA variation. The Amazonian species had different phylogenetic affinities and did not group in a monophyletic clade. Brotogeris diversification took place during the last 6 Myr, the same time-frame as previously found for Pionus and Pyrilia. Main conclusions, The biogeographical history of Brotogeris implies a dynamic history for South American biomes since the Pliocene. It corroborates the idea that the geological evolution of Amazonia has been important in shaping its biodiversity, argues against the idea that the region has been environmentally stable during the Quaternary, and suggests dynamic interactions between wet and dry forest habitats in South America, with representatives of the Amazonian biota having several independent close relationships with taxa endemic to other biomes. [source] The effect of total plasma exchange on fulminant hepatic failureJOURNAL OF CLINICAL APHERESIS, Issue 2 2006M. Akdogan Total plasma exchange (TPE) corrects coagulopathy in patients with liver disease and removes hepatotoxins/cytokines. This improvement is transient but can be used as a bridge until an organ is identified for liver transplantation (LTx) or the liver itself regenerates. Our aim was to retrospectively assess the efficacy of TPE in fulminant hepatic failure (FHF) and its impact on liver function tests. Between 1995,2001, 39 patients with FHF who had undergone TPE were reviewed. FHF was defined according to the O'Grady criteria based on the duration of encephalopathy as well as jaundice. TPE was performed using the Cobe Spectra TPE (Gambro®) in Liver Intensive Care Unit, continued on a daily basis, until either adequate clinical response was achieved, the patient expired, or transplantation occurred. INR, PTT, Fibrinogen, ALT, AST, GGT, BUN, Ammonia, and Total Bilirubin were analyzed before and after TPE. Student's t -test and chi-square test and ANOVA were used for statistical analysis. Thirty-nine patients with FHF (31 females, 8 males with mean age of 32.3, range: 7,64) underwent TPE. Coagulopathy, hyperbilirubinemia, hyperammonemia were significantly improved (P < 0.05). Twenty-one patients survived (54%), 12 required LTx, and 18 patients (including one after LTx) expired. TPE was found to be significantly effective for correction of coagulopathy and improvement of liver tests. This intervention can be considered for temporary liver support until recovery or liver transplantation. J Clin Apheresis 2005. © 2005 Wiley-Liss, Inc. [source] Recombinant factor VIIa and fibrinogen display additive effect during in vitro haemodilution with crystalloidsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 3 2009C. FENGER-ERIKSEN Background: Major blood loss requires fluid resuscitation for maintaining hemodynamic stability. Excessive volume infusions predispose to dilutional coagulopathy through loss, consumption and dilution of cells and proteins involved in haemostasis. Further treatment with fibrinogen concentrate and/or recombinant activated factor VII (rFVIIa) may be initiated, although the haemostatic effects in a situation with haemodilution are not fully detailed. The present study evaluates haemostatic effect of fibrinogen and rFVIIa and their combination in an in vitro model of haemodiluted whole blood with two commonly used crystalloids. Methods: Eight healthy, male volunteers were enrolled. Outcome variables were clot initiation, propagation and strength assessed by thrombelastographic parameters: clotting time, clot formation time, maximum velocity, time until maximum velocity, maximum clot firmness evaluated at dilution levels of 0% (control), 10%, 30% and 50% with isotonic saline and Ringer's lactate in a model of tissue factor-activated whole blood. Fibrinogen and rFVIIa were additional final reaction concentrations, reflecting commonly used clinically therapeutic dosages. Results: Dose-dependent coagulopathy developed following haemodilution with isotonic saline and Ringer's lactate, characterised by a prolonged clot initiation, reduced clot propagation and reduced clot strength. Fibrinogen improved clot strength and propagation phase while rFVIIa shortened clot initiation, both with a positive dose dependency. Conclusions: The combination of fibrinogen and rFVIIa displays an additive effect and improves overall in vitro whole blood clot formation in a model of in vitro crystalloid-induced haemodilution. [source] Elevated plasma fibrinogen ,, concentration is associated with myocardial infarction: effects of variation in fibrinogen genes and environmental factorsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2007M. N. MANNILA Summary., Background:, Fibrinogen ,,, a fibrinogen ,-chain variant generated via alternative mRNA processing, has been associated with susceptibility to thrombotic disease. Objective:, The present case,control study searched for potential determinants of the plasma fibrinogen ,, concentration and examined the relationship between this variant and risk of myocardial infarction (MI). Patients and methods:, The Stockholm Coronary Artery Risk Factor study, comprising 387 postinfarction patients and 387 healthy individuals, was employed. The fibrinogen gamma (FGG) 9340T > C [rs1049636], fibrinogen alpha (FGA) 2224G > A [rs2070011] and fibrinogen beta (FGB) 1038G > A [rs1800791] polymorphisms were determined. The plasma fibrinogen ,, concentration was measured by enzyme-linked immunosorbent assay. The multifactor dimensionality reduction method was used for interaction analyses on risk of MI. Results:, The FGG 9340T > C and FGA 2224G > A polymorphisms, total plasma concentrations of fibrinogen, insulin and high-density lipoprotein, and gender appeared to be independent determinants of plasma fibrinogen ,, concentration in patients, and the corresponding determinants in controls included FGG 9340T > C and FGA 2224G > A polymorphisms and plasma fibrinogen concentration. An elevated plasma fibrinogen ,, concentration proved to be an independent predictor of MI [adjusted odds ratio (OR) (95% CI): 1.24 (1.01, 1.52)]. The plasma fibrinogen ,, concentration was involved in a high-order interaction with total plasma fibrinogen and the FGG 9340T > C and FGA 2224G > A polymorphisms, associated with a further increased risk of MI [OR (95% CI): 3.22 (2.35, 4.39)]. Conclusions:, Plasma fibrinogen ,, concentration influences the risk of MI, and this relationship seems to be strengthened by the presence of an elevated total plasma fibrinogen concentration and the FGG 9340T and FGA 2224G alleles. [source] Two novel fibrinogen variants found in patients with pulmonary embolism and their familiesJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 6 2003M. M. L. Hanss Summary.,Background:,The occurrence of dysfibrinogen is quite rare in comparison with other hemostatic defects, specially in cases of venous thrombosis. Objectives:,Fibrinogen is known to have multiple functions, which are not evaluated by simple coagulation testing. We have used gel electrophoresis to search for new mutations. Patients and methods:,Specimens of purified fibrinogen from 217 consecutive patients with familial or recurrent or early thrombosis and from 490 control subjects were evaluated by electrophoresis. Plasma fibrinogen levels and coagulation-dependent tests (electromechanical and optical coagulometric determinations, immunological measurement, thrombin and Reptilase® times) were normal. Results:,Two novel familial variants were detected. For a 42-year-old patient, an in-frame 117 base pair insertion in the A,-chain gene caused a 5-kDa mobility shift of the A, chain. This corresponds to a 39 amino acid duplication in the connector domain (fibrinogen Champagne au Mont d'Or). This pattern was also found in the patient's mother and child. A second 31-year-old patient presented an extra band under non-reducing conditions, 30 kDa larger than HMW fibrinogen and reacting with antifibrinogen antibodies (fibrinogen Lozanne). A heterozygous 5909A,G mutation was found on the B,-chain gene leading to heterozygous B, Tyr236, stop codon. The predicted truncated B, chain could participate in chain assembly. Two family members were also affected, one of whom had suffered early venous thrombosis. Conclusions:,Electrophoretic testing of apparently normal fibrinogens can reveal new variants which may be clinically relevant. [source] Fibrinogen, homocyst(e)ine, and C-reactive protein concentrations relative to sex and socioeconomic status in British young peopleAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 6 2005Non-Eleri Thomas This study assesses the prevalence of recently identified coronary heart disease (CHD) risk factors in young people of differing socioeconomic status (SES). From November 2001 through March 2002, 100 boys and 108 girls, of age 12.9 ± 0.3 years, selected from differing SES were assessed for CHD risk factors. Measurements included fibrinogen (Fg), homocyst(e)ine (Hcy), and C-reactive protein (CRP). Fibrinogen was significantly greater among boys from a higher SES compared with those from a low SES (P , 0.05). Differences according to sex (P , 0.05) were identified for Fg and CRP. The data indicate the prevalence of recently identified CHD risk factors in this cohort of British schoolchildren. For the purpose of this article, the phrase "young people" embraces both children and adolescents. Am. J. Hum. Biol. 17:809,813, 2005.© 2005 Wiley-Liss, Inc. [source] Interaction of Plasma Deposited HMDSO-Based Coatings with Fibrinogen and Human Blood Plasma: The Correlation between Bulk Plasma, Surface Characteristics and Biomolecule InteractionPLASMA PROCESSES AND POLYMERS, Issue 5 2010Ram P. Gandhiraman Abstract The success of a biomaterial depends on the nature of interaction and the progressive reaction between the biological components and the surface of the biomaterial. In order to control the interaction between the biomaterial and biological component, it is necessary to understand the factors that influence the protein adsorption and cell proliferation. Surface chemistry plays a crucial role in the success of any blood contacting biomaterial. Plasma enhanced chemical vapour deposition (PECVD) is an interesting commonly used technique for tailoring surface characteristics while retaining bulk material properties. Two different films, namely polymer-like and silica-like coatings, with varying surface characteristics have been deposited from hexamethyldisiloxane, by PECVD, on 316L stainless steel. A correlation between the bulk plasma, interfacial adhesion of the coating to 316L steel, surface characteristics and biomolecule interaction is presented in this work. The interfacial adhesion strength analysis demonstrated that silica-like coatings have higher adhesion strength to 316L stainless steel than polymer-like coatings, caused due to the formation of a strong FeOSi and CrOSi bonds. It was observed that the effect of nanoscale surface roughness (close to 6,nm) was less significant, and that the surface chemistry played a significant role in governing the fibrinogen adsorption. Highest fibrinogen adsorption on plain steel was due to the electrostatic interaction of the metal oxide layer with the protein. Hydrophobicity of the polymer-like film resulted in a higher fibrinogen binding than the silica-like films. [source] Interaction between Fibrinogen and IL-6 Genetic Variants and Associations with Cardiovascular Disease Risk in the Cardiovascular Health StudyANNALS OF HUMAN GENETICS, Issue 1 2010Cara L. Carty SUMMARY The inflammatory cytokine interleukin-6 (IL-6) is a main regulator of fibrinogen synthesis, though its interaction with fibrinogen genes (FGA, FGB, FGG) and subsequent impact on cardiovascular disease (CVD) risk is not well-studied. We investigated joint associations of fibrinogen and IL6 tagSNPs with fibrinogen concentrations, carotid intima-media thickness, and myocardial infarction or ischemic stroke in 3900 European-American Cardiovascular Health Study participants. To identify combinations of genetic main effects and interactions associated with outcomes, we used logic regression. We also evaluated whether the relationship between fibrinogen SNPs and fibrinogen level varied by IL-6 level using linear regression models with multiplicative interaction terms. Combinations of fibrinogen and IL6 SNPs were significantly associated with fibrinogen level (p < 0.005), but not with other outcomes. Fibrinogen levels were higher in individuals having FGB1437 (rs1800790) and lacking FGA6534 (rs6050) minor alleles; these SNPs interacted with IL6 rs1800796 to influence fibrinogen level. Marginally significant (p= 0.03) interactions between IL-6 level and FGA and FGG promoter SNPs associated with fibrinogen levels were detected. We identified potential gene-gene interactions influencing fibrinogen levels. Although IL-6 responsive binding sites are present in fibrinogen gene promoter regions, we did not find strong evidence of interaction between fibrinogen SNPs and IL6 SNPs or levels influencing CVD. [source] Fibrinogen and detached retina with or without proliferationACTA OPHTHALMOLOGICA, Issue 6 2000I. P. Theoharis ABSTRACT. Purpose: Fibrinogen is a multifunctional molecule, participating in processes such as wound healing, inflammation and cell proliferation. Therefore a comparative study of plasma fibrinogen levels was performed on patients with rhegmatogenous retinal detachment (RRD) and proliferative vitreoretinopathy after RRD (PVR). Method: Plasma fibrinogen levels were measured preoperatively in three groups of patients; twenty-two (n=22) patients from the ORL department of our hospital, serving as a control group; twenty-eight (n=28) patients with RRD; and twenty (n=20) patients with PVR after RRD. Patients' ages were matched for all three groups; diabetics and patients with cardiovascular disease were excluded. T-Student's test was performed for the comparison of the plasma fibrinogen mean values of the aforementioned groups. Results: Statistically significant (p value: 0.013) elevation of fibrinogen plasma levels was observed in patients with RRD compared to those of the control group. In addition, patients with PVR had significantly higher plasma fibrinogen levels (p value: 0.03) than RRD patients. Conclusion: The results suggest a correlation between fibrinogen plasma levels and the development of RRD and PVR. [source] Activation of the coagulation system occurs within rather than outside cutaneous haemangiomasACTA PAEDIATRICA, Issue 10 2001J Antovic Haemangiomas are the commonest tumours of infancy. They can become even more serious if followed by consumption coagulopathy and even life-threatening in cases of Kasabach,Merritt syndrome, with thrombocytopenia and haemorrhage. Data exist concerning systemic coagulation abnormalities in children with haemangiomas but to our knowledge there are no data on local consumption coagulopathy in haemangioma per se. We examined blood coagulation and fibrinolysis parameters in blood withdrawn from haemangioma blood vessels and blood withdrawn from the systemic vein in 14 children with cutaneous haemangiomas (3M, 11F; age range 3 mo to 10 y). Compared with controls, significant decreases in fibrinogen levels, FVII activity, antithrombin and plasmin inhibitor levels and increases in international normalized ratio (INR) and D-dimer levels were observed in the blood samples withdrawn directly from haemangioma blood vessels. Fibrinogen and antithrombin levels in samples withdrawn from systemic veins were reduced in relation to control values whilst INR values increased, but within normal ranges. D-dimer levels were increased in peripheral blood. The fibrinogen level was significantly lower and the INR and D-dimer levels were significantly higher in blood samples from haemangiomas compared to systemic blood. Clinical signs of systemic disseminated intravascular coagulation were not observed. Conclusions: Our results suggest a strong local activation and local consumption coagulopathy in haemangioma, along with less conspicuous but observable systemic changes in coagulation and fibrinolysis parameters, although without signs of consumptive coagulopathy. These systemic changes could be a reflection of intra-lesion coagulation activation although there is no evidence to suggest truly systemic disseminated intravascular coagulation. [source] Proteolytically Degradable Photo-Polymerized Hydrogels Made From PEG,Fibrinogen Adducts,ADVANCED ENGINEERING MATERIALS, Issue 6 2010Daniel Dikovsky Abstract We develop a biomaterial based on protein,polymer conjugates where poly(ethylene glycol) (PEG) polymer chains are covalently linked to multiple thiols on denatured fibrinogen. We hypothesize that conjugation of large diacrylate-functionalized linear PEG chains to fibrinogen could govern the molecular architecture of the polymer network via a unique protein,polymer interaction. The hypothesis is explored using carefully designed shear rheometry and swelling experiments of the hydrogels and their precursor PEG/fibrinogen conjugate solutions. The physical properties of non-cross-linked and UV cross-linked PEGylated fibrinogen having PEG molecular weights ranging from 10 to 20,kDa are specifically investigated. Attaching multiple hydrophilic, functionalized PEG chains to the denatured fibrinogen solubilizes the denatured protein and enables a rapid free-radical polymerization cross-linking reaction in the hydrogel precursor solution. As expected, the conjugated protein-polymer macromolecular complexes act to mediate the interactions between radicals and unsaturated bonds during the free-radical polymerization reaction, when compared to control PEG hydrogels. Accordingly, the cross-linking kinetics and stiffness of the cross-linked hydrogel are highly influenced by the protein,polymer conjugate architecture and molecular entanglements arising from hydrophobic/hydrophilic interactions and steric hindrances. The proteolytic degradation products of the protein,polymer conjugates proves to be were different from those of the non-conjugated denatured protein degradation products, indicating that steric hindrances may alter the proteolytic susceptibility of the PEG,protein adduct. A more complete understanding of the molecular complexities associated with this type of protein-polymer conjugation can help to identify the full potential of a biomaterial that combines the advantages of synthetic polymers and bioactive proteins. [source] The role of the inflammatory markers ferritin, transferrin and fibrinogen in the relationship between major depression and cardiovascular disorders , The German Health Interview and Examination SurveyACTA PSYCHIATRICA SCANDINAVICA, Issue 2 2010B. T. Baune Baune BT, Neuhauser H, Ellert U, Berger K. The role of the inflammatory markers ferritin, transferrin and fibrinogen in the relationship between major depression and cardiovascular disorders , The German Health Interview and Examination Survey. Objective:, To determine levels of inflammation (ferritin, transferrin and fibrinogen) in major depression (MDD) and comorbid cardiovascular disease (CVD) in an adult population. Method:, In 4181 participants of the German Health Interview and Examination Survey MDD was assessed through the Composite International Diagnostic Interview (CIDI). Coronary heart disease, stroke, and hypertension were diagnosed by a computer-assisted physician interview. Analyses were performed using anova models stratified for gender. Results:, Ferritin, transferrin and fibrinogen levels showed opposing patterns in individuals with either CVD or MDD alone. In comorbidity analyses, male participants with MDD plus comorbid CHD or hypertension had lower levels of ferritin and lower fibrinogen levels in hypertension compared to men without MDD, while in women, results were inconsistent. Conclusion:, Opposing patterns of inflammatory markers in CVD or MDD alone were reversed when both conditions were present. MDD reduced levels of ferritin, transferrin and fibrinogen in CVD in a gender-specific way. [source] Association of components of the metabolic syndrome with the appearance of aggregated red blood cells in the peripheral blood.DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2005An unfavorable hemorheological finding Abstract Background Components of the metabolic syndrome are associated with low-grade inflammation. This can be accompanied by the synthesis of sticky proteins and erythrocyte aggregation. Methods The degree of erythrocyte aggregation was evaluated by a simple slide test and image analysis along with other markers of the acute-phase response, including the white blood cell count (WBCC), erythrocyte sedimentation rate (ESR), fibrinogen and high sensitivity C-reactive protein (hs-CRP) concentrations. Patients were categorized in four groups according to the absence or presence of 1, 2 and 3 or more components of the metabolic syndrome. Results We examined a total of 1447 individuals (576 women and 871 men) who gave their informed consent for participation. A significant cardiovascular risk factors, age and hemoglobin adjusted correlation was noted between the degree of erythrocyte aggregation and the number of components of the metabolic syndrome (r = 0.17, p < 0.0005). This correlation was better than that observed for clottable fibrinogen (r = 0.13 p < 0.0005), for ESR (r = 0.11 p < 0.0005) or WBCC (r = 0.13 p < 0.0005). A somewhat better correlation was noted for hs-CRP (r = 0.26 p < 0.0005). Conclusions The multiplicity of components of the metabolic syndrome is associated with enhanced erythrocyte aggregation, probably related to the presence of multiple adhesive macromolecules in the peripheral blood. The enhanced aggregation might contribute to capillary slow flow, tissue deoxygenation as well as vasomotor tone changes in the presence of multiple components of this syndrome. Copyright © 2004 John Wiley & Sons, Ltd. [source] Effect of long-term treatment with rosiglitazone on arterial elasticity and metabolic parameters in patients with Type 2 diabetes mellitus: a 2-year follow-up studyDIABETIC MEDICINE, Issue 11 2007M. Shargorodsky Abstract Aims, Thiazolidinediones may influence the atherogenic process by improving cardiovascular risk factors. The present study was designed to determine the long-term effect of rosiglitazone on arterial compliance and metabolic parameters in patients with Type 2 diabetes. Methods, In an open-label, prospective study, 65 diabetic patients received rosiglitazone orally (4,8 mg/day) for 6 months. After 6 months, the patients continued an open follow-up study and were divided into two groups: group 1 included patients continuing rosiglitazone for 2 years, group 2 included patients discontinuing rosiglitazone and receiving other oral glucose-lowering agents. Lipid profile, glycated haemoglobin (HbA1c), insulin, C-peptide, fibrinogen, high-sensitivity-CRP and homeostasis model assessment,insulin resistance were measured. Arterial elasticity was assessed using pulse wave contour analysis. Results, In patients treated with rosiglitazone for 2 years: the large artery elasticity index (LAEI) increased from 10.0 ± 4.6 to 13.9 ± 4.7 ml/mmHg × 100 after 2 years (P = 0.003). The small artery elasticity (SAEI) index increased significantly from 3.2 ± 1.2 to 5.1 ± 1.9 (P < 0.0001). In patients who discontinued rosiglitazone: LAEI did not change after 6 months, but decreased from 12.1 ± 5.4 to 8.9 ± 3.9 ml/mmHg × 10 (P < 0.0001) at the end of 2 years. SAEI increased during the first 6 months of treatment, from 3.9 ± 1.8 to 5.1 ± 1.5 ml/mmHg × 100 (P < 0.0001) and decreased after discontinuation of rosiglitazone (P = 0.042). Conclusions, Prolonged treatment with rosiglitazone improved arterial elasticity. However, significant deterioration in LAEI and SAEI was observed in patients who discontinued rosiglitazone. The beneficial vascular effect of rosiglitazone on arterial elasticity was independent of glycaemic control. [source] Decreased red blood cell aggregation subsequent to improved glycaemic control in Type 2 diabetes mellitusDIABETIC MEDICINE, Issue 4 2003B. Chong-Martinez Abstract Aims Reports of rheological changes following intensification of metabolic control are limited and not concordant. The present study was designed to test the hypothesis that intensification of management of Type 2 diabetes (T2DM) with diet, exercise and insulin improves haemorheological behaviour by reducing red blood cell (RBC) aggregation. Methods Blood was sampled from 55 subjects before and following 14 ± 3 weeks of intensified management. RBC aggregation was measured in vitro for cells in plasma or in an aggregating 70 kD dextran solution. Plasma viscosity and whole blood viscosity were also measured. Results During treatment, fasting glucose fell 27%, HbA1c fell 21%, and serum triglycerides and total cholesterol fell 28% and 12%, respectively (P < 0.0001 for each). The extent and strength of RBC aggregation in plasma fell by 10,13% (P < 0.002). Similar decreases of RBC aggregation were seen for cells suspended in dextran (P < 0.002). Plasma viscosity decreased by 3% (P < 0.02) and high shear blood viscosity by 6,7% (P < 0.0001). Changes of RBC aggregation in plasma and in dextran were significantly correlated, supporting a cellular rather than a plasmatic origin for these changes. However, there were no significant correlations between RBC aggregation changes and changes of fasting glucose, HbA1c, serum triglycerides, serum cholesterol, or plasma fibrinogen. Conclusions Intensified metabolic control results in a reduction of RBC aggregation that appears to be intrinsic to RBC. Since increased RBC aggregation can impair microcirculatory flow, it is possible that haemorheological factors may contribute to the reduction of microvascular complications resulting from improved metabolic control in T2DM. [source] Rheological determinants of red blood cell aggregation in diabetic patients in relation to their metabolic controlDIABETIC MEDICINE, Issue 2 2002K. Elishkevitz Abstract Aims To determine whether increased red blood cell adhesiveness/aggregation in diabetic patients is related to the extent of their metabolic control. Methods We measured erythrocyte adhesiveness/aggregation in a group of 85 adult patients with diabetes mellitus by using citrated venous whole blood and a simple slide test. The erythrocyte adhesiveness/aggregation was determined by measuring the size of the spaces that are formed between the aggregated erythrocytes. We divided the patients into those with either low or high erythrocyte adhesiveness/aggregation values. Results The erythrocyte adhesiveness/aggregation values of the two groups differed significantly in terms of their fibrinogen concentration, erythrocyte sedimentation rate, high sensitive C-reactive protein (CRP), total cholesterol and triglyceride concentrations. There was no difference between the two groups regarding the concentrations of HbA1c. Logistic regression was applied to construct a model to predict the belonging of a patient in the low or high erythrocyte adhesiveness/aggregation group. A linear regression was applied to construct a model to predict the erythrocyte adhesiveness/aggregation values. Both models turned out to include gender, age, fibrinogen, triglyceride, retinopathy, coronary artery disease and age and gender interaction. Neither HbA1c nor CRP entered the models. Conclusions The degree of erythrocyte adhesiveness/aggregation and several variables of the acute-phase response in patients with diabetes mellitus are not directly related to the degree of metabolic control as evaluated by means of HbA1c concentration. Diabetic patients might benefit from rheological or anti-inflammatory interventions regardless of their metabolic control. [source] Prevalence and serum protein values of strangles (Streptococcus equi) affected mules at Remount Depot, Sargodha (Pakistan)EQUINE VETERINARY EDUCATION, Issue 4 2010M. Ijaz Summary The prevalence of Streptococcus equi serovar equi (S.equi) in nasal discharge and pus samples from sub-mandibular lymph nodes in mules at the Remount Depot, Sargodha was examined and total serum proteins, serum albumin, serum globulin and fibrinogen measured. A total of 250 nasal swabs and pus samples were collected from mules and examined microbiologically: 99 (39.6%) were positive for S. equi. A higher occurrence of S. equi was recorded in foals as compared to adults. The concentrations of total serum protein, serum globulin and fibrinogen were significantly increased (P<0.05), while the concentration of serum albumin significantly decreased (P<0.05) in strangles-affected mules. It was concluded that increased total serum proteins, serum globulin and fibrinogen along with decreased serum albumin were important indicators of infection by S. equi in mules. [source] The PPAR, agonist GW501516 suppresses interleukin-6-mediated hepatocyte acute phase reaction via STAT3 inhibitionEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2007T. Kino Abstract Background, Interleukin-6 and downstream liver effectors acute phase reactants are implicated in the systemic inflammatory reaction. Peroxisome proliferator-activated receptor , (PPAR,), which binds to and is activated by a variety of fatty acids, was recently shown to have anti-inflammatory actions. Materials and methods, We examined the ability of the synthetic PPAR, agonist GW501516 to suppress interleukin-6-induced expression of acute phase proteins in human hepatoma HepG2 cells and rat primary hepatocytes. Results, GW501516 dose-dependently suppressed interleukin-6-induced mRNA expression of the acute phase protein ,1-antichymotrypsin in HepG2 cells. The compound also suppressed interleukin-6-induced mRNA expression of ,2-acid glycoprotein, ,-fibrinogen and ,2-macroglobulin in and the secretion of C-reactive protein by rat primary hepatocytes. Depletion of the PPAR, receptor, but not of PPAR, or ,, attenuated the suppressive effect of GW501516 on interleukin-6-induced ,1-antichymotrypsin mRNA expression, indicating that PPAR, specifically mediated this effect. Since interleukin-6 stimulates the transcriptional activity of the ,1-antichymotrypsin promoter by activating the signal transducer and activator of transcription (STAT) 3, we examined functional interaction of this transcription factor and PPAR, on this promoter. Overexpression of PPAR, enhanced the suppressive effect of GW501516 on STAT3-activated transcriptional activity of the ,1-antichymotrypsin promoter, while GW501516 suppressed interleukin-6-induced binding of this transcription factor to this promoter. Conclusions, These findings indicate that agonist-activated PPAR, interferes with interleukin-6-induced acute phase reaction in the liver by inhibiting the transcriptional activity of STAT3. PPAR, agonists might be useful for the suppression of systemic inflammatory reactions in which IL-6 plays a central role. [source] Endothelial dysfunction in Buerger's disease and its relation to markers of inflammationEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2006M. Joras Abstract Background, Buerger's disease (BD) is a segmental occlusive vascular disease. The aim of this study was to detect functional changes in brachial artery and asymptomatic morphological changes in extra-cranial carotid arteries not affected by the disease process and to assess markers of inflammation and endothelial damage. Materials and methods, Fourteen patients in the remission phase of BD and the same number of age- and sex-matched healthy controls were included in the study. The capability of endothelium-dependent (flow-mediated) and endothelium-independent dilation of the brachial artery and intima-media thickness of the carotid arteries were measured using high-resolution ultrasound. Laboratory parameters of endogenous fibrinolytic activity, inflammation and endothelial dysfunction were also measured. Results, Patients with BD had a diminished capability of endothelium-dependent vasodilation and higher levels of some circulating markers of inflammation, such as leukocytes, C-reactive protein, intercellular adhesion molecule-1 and E-selectin. Intercellular adhesion molecule-1 levels were related to some of the inflammatory markers (sedimentation rate, C-reactive protein, ,2-globulins and fibrinogen), while E-selectin was correlated with decreased endogenous blood fibrinolytic activity. Endothelium-dependent vasodilation was in negative correlation with the relative share of neutrophil granulocytes. There were no significant differences in intima-media thickness between patients with BD and controls. Conclusions, Our study has expressed generalized functional arterial disorder in patients with BD not accompanied by any measurable morphological changes of the carotid arterial wall. Functional deterioration of brachial artery could be related to increased levels of various inflammatory markers , the process which is most probably the basic pathogenetic mechanism of the disease. [source] Prognostic value of interleukin-6, plasma viscosity, fibrinogen, von Willebrand factor, tissue factor and vascular endothelial growth factor levels in congestive heart failureEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 11 2003B. S. P. Chin Abstract Background, Congestive heart failure (CHF) carries a poor prognosis with a high mortality rate, frequent hospitalizations and increased risk of thrombotic complications such as stroke. Cytokines may contribute to the progression and prothrombotic state of CHF, including the pro-inflammatory interleukin-6 (IL-6) and the pro-angiogenic vascular endothelial growth factor (VEGF), both of which are raised in CHF. The procoagulant properties of both cytokines may be mediated via tissue factor (TF), a potent clotting activator. We hypothesized that plasma levels of these markers, as well as levels of plasma viscosity, fibrinogen, soluble P-selectin and von Willebrand factor (markers of abnormal rheology, clotting, platelet activation, and endothelial damage, respectively) will be useful in predicting morbidity and mortality in chronic stable CHF. Methods and results, One hundred and twenty consecutive out-patients with chronic stable CHF (92 males; mean [SD] age 64 [11] years, mean [SD] left ventricular ejection fraction of 29 [6]%) were recruited and followed for 2 years during which 42 patients reached a clinical end-point of all-cause mortality and cardiovascular hospitalizations, including stroke and myocardial infarction. Plasma IL-6 (P = 0·003) and TF (P = 0·013) levels, but not other research indices, were higher in those who suffered events compared with those without events. Predictors of end-points were high (, median) TF (P = 0·011), and IL-6 (P = 0·023) levels, as well as the lowest quartile of a left ventricular ejection fraction (P = 0·007). A strong correlation was present between TF and IL-6 levels (r = 0·59; P < 0·0001) and with VEGF levels (r = 0·43; P < 0·0001). Conclusion, IL-6 and TF are predictors of poor prognosis in chronic CHF, raising the hypothesis that IL-6 may contribute to the progression and thrombotic complications of CHF via its actions on TF expression. Although VEGF did not independently predict outcome in chronic CHF, the possibility arises that it may act with IL-6 to induce TF expression. [source] Disseminated intravascular coagulation in acute leukemia: clinical and laboratory features at presentationEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 4 2006Masamitsu Yanada Abstract:,Background:,Although there are two major scoring systems for the clinical diagnosis of disseminated intravascular coagulation (DIC), the validity of these systems for leukemia-associated DIC remains to be confirmed. Methods:,By analyzing 125 newly diagnosed acute leukemia patients, we investigated clinical and laboratory features of leukemia-associated DIC, and determined the validity of the two established criteria. Results:,A total of 36 patients (29%) were diagnosed with DIC according to expert opinion, a method regarded as the de facto gold standard. Leukemia-associated DIC is characterized by rare manifestation of organ failure because of thrombosis and no relevance of the platelet count for the diagnosis. The results of receiver operating characteristics analysis favored fibrin degradation product (FDP) rather than D-dimer as the fibrin-related marker test. Although prothrombin time, plasma fibrinogen, and serum FDP levels were significantly different for patients with and without DIC, multivariate analysis identified FDP levels to be the only factor associated with DIC diagnosis. The cut-off level of 15 ,g/mL for FDP was found to be the most effective to differentiate DIC from non-DIC, resulting in diagnostic sensitivity and specificity of 92% and 96%, respectively. The diagnostic results for our patients produced with this FDP-based system were at least comparable with or superior to those obtained with the two currently available scoring systems. Conclusions:,Our findings suggest that an FDP-based criterion may be applicable for the diagnosis of leukemia-associated DIC. Although it appears to be simple and practicable enough for clinical use, prospective validation of this criterion is needed. [source] Role of the complement-lectin pathway in anaphylactoid reaction induced with lipopolysaccharide in miceEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 10 2003wierzko Abstract We show that Proteus vulgaris,O25 (PO25) lipopolysaccharide (LPS) induced an anaphylactoid reaction not only in wild-type and in lipid,A non-responding mice but also in recombinase-activating gene-2-deficient (RAG-2,/,) and in mast cell-deficient (W/Wv) animals. Western blot analysis indicated that PO25 LPS bound to Ra-reactive factor (RaRF), the complex of mannan-binding lectins (MBL) and MBL-associated serine proteases. Binding of RaRF to PO25 LPS led to the activation of C4 component without participation of either C1 or Ig, via the lectin pathway. Relative concentration of RaRF and hemolytic activity in mouse serum decreased rapidly during the process of anaphylactoid reaction. A significant drop of MBL-A, but not MBL-C level was observed. Administrationwith antiserum to RaRF prevented animals from death as a consequence of the inhibition of interaction of RaRF with the carbohydrate target and complement activation. These results indicate that complement-lectin pathway activation is responsible for the anaphylactoid reaction induced with LPS in muramyldipeptide-primed mice. RaRF also activated fibrinogen in vitro suggesting the involvement of the coagulation system in the process investigated. [source] Fibrinogen-CD11b/CD18 interaction activates the NF-,B pathway and delays apoptosis in human neutrophilsEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2003Carolina Rubel Abstract The regulation of neutrophil half-life by members of the coagulation cascade is critical for the resolution of the inflammatory response. We have demonstrated that soluble fibrinogen (sFbg) delays human neutrophil (PMN) apoptosis through a mechanism that involves CD11b interactions, and phosphorylation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase,1/2 (ERK1/2). Since NF-,B is a key element in the regulation of apoptotic mechanisms in several immune cells, we investigated whether NF-,B is involved in the control of PMN survival by sFbg. We showthat sFbg triggers inhibitor protein ,B (I,B-,) degradation and NF-,B activation. Furthermore, pharmacological inhibition of NF-,B abrogates sFbg effects on apoptosis. In addition, specific inhibition of MAPK ERK1/2 significantly reduces NF-,B translocation by sFbg, suggesting a relationship between ERK1/2 and NF-,B activation. Similar results are obtained when granulocytic-differentiated HL-60 cells are treated with sFbg, making this model highly attractive for integrin-induced gene expression studies. It can be concluded that NF-,B participates in the prevention of apoptosis induced by sFbg with the participation of MAPK ERK1/2. These results shed light on the molecular mechanisms that control human granulocyte apoptosis, and suggest that NF-,B regulation may be of benefit for the resolution of the inflammatory response. [source] Proteolytically Degradable Photo-Polymerized Hydrogels Made From PEG,Fibrinogen Adducts,ADVANCED ENGINEERING MATERIALS, Issue 6 2010Daniel Dikovsky Abstract We develop a biomaterial based on protein,polymer conjugates where poly(ethylene glycol) (PEG) polymer chains are covalently linked to multiple thiols on denatured fibrinogen. We hypothesize that conjugation of large diacrylate-functionalized linear PEG chains to fibrinogen could govern the molecular architecture of the polymer network via a unique protein,polymer interaction. The hypothesis is explored using carefully designed shear rheometry and swelling experiments of the hydrogels and their precursor PEG/fibrinogen conjugate solutions. The physical properties of non-cross-linked and UV cross-linked PEGylated fibrinogen having PEG molecular weights ranging from 10 to 20,kDa are specifically investigated. Attaching multiple hydrophilic, functionalized PEG chains to the denatured fibrinogen solubilizes the denatured protein and enables a rapid free-radical polymerization cross-linking reaction in the hydrogel precursor solution. As expected, the conjugated protein-polymer macromolecular complexes act to mediate the interactions between radicals and unsaturated bonds during the free-radical polymerization reaction, when compared to control PEG hydrogels. Accordingly, the cross-linking kinetics and stiffness of the cross-linked hydrogel are highly influenced by the protein,polymer conjugate architecture and molecular entanglements arising from hydrophobic/hydrophilic interactions and steric hindrances. The proteolytic degradation products of the protein,polymer conjugates proves to be were different from those of the non-conjugated denatured protein degradation products, indicating that steric hindrances may alter the proteolytic susceptibility of the PEG,protein adduct. A more complete understanding of the molecular complexities associated with this type of protein-polymer conjugation can help to identify the full potential of a biomaterial that combines the advantages of synthetic polymers and bioactive proteins. [source] Formation and Topotactical Orientation of Fibrinogen Nanofibrils on Graphite Nanostructures,ADVANCED ENGINEERING MATERIALS, Issue 11 2009Jörg Reichert We studied the adsorption of human plasma fibrinogen and investigated the formation of amyloid-like fibrinogen nanofibrils and fibrinogen networks in the absence of thrombin and Ca·2+ with high resolution atomic force microscopy (AFM). We propose a possible mechanisms for the surface nanostructure mediated self assembly of fibrinogen molecules and the formation of fibrinogen nanofibrils and nanofibril networks in the absence of thrombin. [source] Aptamer-Conjugated Nanoparticles Efficiently Control the Activity of ThrombinADVANCED FUNCTIONAL MATERIALS, Issue 18 2010Yen-Chun Shiang Abstract Thrombin-binding aptamer-conjugated gold nanoparticles (TBA-Au NPs) for highly effective control of thrombin activity towards fibrinogen are demonstrated. While a 29-base long oligonucleotide (TBA29) has known no enzymatic inhibitory functions for thrombin-mediated coagulation, the ultrahigh anticoagulant potency of TBA29 -Au NPs can be demonstrated via the steric blocking effect, at two orders of magnitude higher than that of free TBA29. The surface aptamer density on the Au NPs is important in determining their enzymatic inhibition of thrombin and their stability in the presence of nuclease. The practicality of 100TBA29 -Au NPs (100 TBA29 molecules per Au NP) for controlling thrombin-mediated coagulation in plasma is found, and the 100TBA29 -Au NPs has an ultra binding affinity towards thrombin (Kd = 2.7 × 10,11M) due to their high ligand density. The anticoagulant activity of TBA29 -Au NPs is found to be suppressed by TBA29 complementary sequence (cTBA29) modified Au NPs (cTBA29 -Au NPs), with a suppression rate 4.6-fold higher than that of cTBA29. The easily prepared and low-cost TBA29 -Au NPs and cTBA29 -Au NPs show their potential in biomedical applications for treating various diseases related to blood clotting disorders. In principle, this study opens the possibility of regulation of molecule binding, protein recognizing, and enzyme activity by using aptamer-functionalized nanomaterials. [source] | |||||||||||||||||||||||||||||||||||||