Evidence that the degree of band 3 phosphorylation modulates human erythrocytes nitric oxide efflux – in vitro model of hyperfibrinogenemia

© 2011 – IOS Press and the authors. All rights reservedRecent evidence has shown that plasma fibrinogen, a major cardiovascular risk factor, interacts with the erythrocyte membrane and acts to influence blood flow via erythrocyte nitric oxide (NO) modulation. In the present pioneer in-vitro study, whole blood samples were harvested from healthy subjects and aliquots were incubated in the absence (control aliquots) and presence of fibrinogen at different degrees of band 3 phosphorylation, and the levels of NO, nitrite, nitrate and S-nitroglutathione (GSNO) were determined. Hyperfibrinogenemia interferes with erythrocyte NO mobilization without changing its efflux in a way that seems to be dependent of the degree of band 3 phosphorylation. In presence of higher fibrinogen concentrations the NO efflux is reinforced when band 3 is phosphorylated (p < 0.001). Higher levels of nitrite, nitrate and GSNO were documented (p < 0.05). However, the mechanisms by which fibrinogen signalling modulates erythrocyte function remain to be clarified and are currently under study. These conditions may be considered an approach to be followed in blood storage for transfusions.This study was supported by grants from the FCT - Fundação para a Ciência e a Tecnologia (project reference PTDC/SAU-OSM/73449/2006

Validation of plasma fibrinogen as a marker of carotid atherosclerosis in subjects free of clinical cardiovascular disease

BACKGROUND AND OBJECTIVES: Fibrinogen has been found to be an independent risk factor for cardiovascular disease. The aim of this study was to validate the measurement of plasma fibrinogen as a marker of subclinical atherosclerosis in a series of asymptomatic subjects (n=519, median age 55.5 years, 80% men). DESIGN AND METHODS: All individuals had a complete clinical examination, lipid profile (cholesterol and its high and low density lipoprotein fractions and triglycerides), global vascular risk assessment (PROCAM), and B-mode ultrasonography of the carotid arteries to determine the intima-media thickness (IMT) and the presence of atheroma plaques. C-reactive protein (CRP), and von Willebrand factor (vWF) were also measured in all subjects as markers of inflammation/endothelial damage. RESULTS: In the univariate model, a positive relationship was found between plasma fibrinogen concentration and carotid IMT (p<0.001). Fibrinogen concentration also correlated positively with age (p<0.001), systolic blood pressure (p<0.001), smoking (p<0.05), diabetes (p<0.05), PROCAM (p<0.001), CRP and vWF (p<0.001). In the multivariate analysis, the association of fibrinogen with carotid IMT remained significant (p=0.008) after adjustment for all parameters analyzed. INTERPRETATION AND CONCLUSIONS: In a population sample of adults without clinically overt atherosclerotic disease, elevated fibrinogen levels was related to carotid IMT independently of a wide range of important confounding variables. Plasma fibrinogen may represent a systemic marker of carotid atherosclerosis

Pneumonia Caused by Klebsiella spp. in 46 Horses.

BackgroundKlebsiella spp. are implicated as a common cause of bacterial pneumonia in horses, but few reports describe clinical presentation and disease progression.Hypothesis/objectivesTo describe the signalment, clinicopathologic data, radiographic and ultrasonographic findings, antimicrobial susceptibility, outcome, and pathologic lesions associated with Klebsiella spp. pneumonia in horses.AnimalsForty-six horses from which Klebsiella spp. was isolated from the lower respiratory tract.MethodsRetrospective study. Medical records from 1993 to 2013 at the William R. Pritchard Veterinary Medical Teaching Hospital, University of California, Davis were reviewed. Exact logistic regression was performed to determine if any variables were associated with survival to hospital discharge.ResultsSurvival in horses &lt;1 year old was 73%. Overall survival in adults was 63%. For adults in which Klebsiella pneumoniae was the primary isolate, survival was 52%. Mechanical ventilation preceded development of pneumonia in 11 horses. Complications occurred in 25/46 horses, with thrombophlebitis and laminitis occurring most frequently. Multi-drug resistance was found in 47% of bacterial isolates. Variables that significantly impacted survival included hemorrhagic nasal discharge, laminitis, and thoracic radiographs with a sharp demarcation between marked caudal pulmonary alveolar infiltration and more normal-appearing caudodorsal lung.Conclusions and clinical importanceKlebsiella spp. should be considered as a differential diagnosis for horses presenting with hemorrhagic pneumonia and for horses developing pneumonia after mechanical ventilation. Multi-drug resistance is common. Prognosis for survival generally is fair, but is guarded for adult horses in which K. pneumoniae is isolated as the primary organism

Hemorheological Failure in the Pathology of Cardio-vascular Complications in Patients with Diabetic Foot Syndrome

The literature that includes the study of cardiovascular complications in patients with diabetic foot syndrome was analyzed. The topicality of this problem is caused by the steady growth of diabetes mellitus morbidity among people. For today there are more than 170 mln people throughout the world with diabetes mellitus, among them 65–80 % have cardiovascular complications (myocardium infarction, acute disorder of brain blood circulation and so on).It is established for today, that pathogenesis of diabetic foot syndrome is multi-factor one and the development of purulent-necrotic stages of DFS is connected with the combination of different factors, especially microcirculation disorder. In this article we\u27ll consider the mechanisms of diabetic angiopathy development, the state of platelet-vascular hemostasis link in this category of patients

Indagini sulla incidenza della microcitosi e/o ipocromia nel cane

La microcitosi è una caratteristica alterazione ematologica comune a diversi stati patologici; molte di queste cause riconducono la loro patogenesi, seppur con meccanismi diversi, all’alterazione del metabolismo marziale, per altre i meccanismi sono ancora da accertare. L’obbiettivo della presente tesi è stato quello di valutare l’incidenza della microcitosi nel cane, associata o meno all’ipocromia, in un campione di 2300 emogrammi. Per gli emogrammi risultati microcitici, sono state esaminate le relative cartelle cliniche; queste sono state valutate singolarmente ricavandone informazioni riguardo l’anamnesi, lo stato patologico, la razza, il sesso ed altre variabili. Sono stati valutati anche il leucogramma, la morfologia cellulare ed altri parametri ematologici che potevano avere una possibile relazione con l’argomento trattato. Dalla casistica esaminata è scaturita una incidenza del 8,5% della microcitosi nell’emogramma del cane con maggior incidenza delle razze Rottweiler e Labrador. Le diagnosi più frequenti associate a microcitosi sono state di sindrome gastroenterica cronica, leishmaniosi, shunt portosistemico e artriti-artrosi . Le alterazioni ematologiche più rilevanti sono risultate: anemia non rigenerativa, anisocitosi eritrocitaria, macrotrombocitosi, ipocromia, iposideremia, iperfibrinogenemia

Relationship between plasma sialic acid and fibinogen concentration and incident micro-and macrovascular complications in type 1 diabetes

AIMS/HYPOTHESIS: Type 1 diabetes is associated with an increased risk of vascular complications. This increased risk could be explained by sialic acid and/or fibrinogen. It is also not clear what explains the abolition of sex-related differences affecting risk of CHD in the presence of type 1 diabetes. Therefore, we examined whether fibrinogen and sialic acid are related to incident micro- and macrovascular complications in patients with type 1 diabetes. METHODS: A subset (n=2329) of the EURODIAB Prospective Complications Study was analysed. Sialic acid and fibrinogen concentrations were measured at baseline. The main outcomes after 7 years were development of albuminuria, retinopathy, neuropathy and CHD. RESULTS: Univariable and multivariable models using Cox proportional survival analyses showed that an SD unit increase in sialic acid and fibrinogen levels was significantly associated with CHD in men only. Adjusted standardised hazard ratios (sHRs) were 1.50 (95% CI 1.05-2.15) and 1.40 (95% CI 1.06-1.86) for sialic acid and fibrinogen, respectively. Initial associations between (1) sialic acid and incident retinopathy [standardised odds ratio (sOR) men 1.68, 95% CI 1.10-2.57], (2) fibrinogen and retinopathy (sOR women 1.37, 95% CI 1.06-1.78) and (3) sialic acid and neuropathy (sOR men 1.37, 95% CI 1.06-1.77) were shown, but became non-significant in multivariable models. CONCLUSIONS/INTERPRETATION: Sialic acid and fibrinogen are strong predictors of CHD in men with type 1 diabetes, beyond the effect of established risk factors. The associations found with microvascular complications were not independent of other risk factors