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Clinical hemorheology and microcirculation [journal]
- Organotypical vascular model for characterization of radioprotective compounds: Studies on antioxidant 2,3-diaryl-substituted indole-based cyclooxygenase-2 inhibitors. [Journal Article]
- Clin Hemorheol Microcirc 2014 Jan 1; 58(1):281-95.
Radiotherapy of various cancers is closely associated with increased cardiovascular morbidity and mortality. Arachidonic acid metabolites are supposed to play a key role in radiation-induced vascular dysfunction. This study was designed to evaluate the effects of novel, antioxidative 2,3-diaryl-substituted indole-based selective cyclooxygenase-2 (COX-2) inhibitors (2,3-diaryl-indole coxibs) on radiation-induced formation of arachidonic acid metabolites via COX-2 and oxidant stress pathways in an organotypical vascular model of rat aortic rings. Acute and subacute effects of X-ray radiation (4 and 10 Gy; 1 and 3 days post irradiation) with or without the presence of 1 μM of the 2,3-diaryl-indole coxib 2-[4-(aminosulfonyl)phenyl]-3-(4-methoxyphenyl)-1H-indole (C1) or celecoxib as reference compared to sham-irradiated controls were assessed. The following parameters were measured: metabolic activity of the aortic rings; induction and regulation of COX-2 expression; release of prostaglandin E2 and F2α-isoprostane. Irradiation without presence of coxibs resulted in a dose-dependent augmentation of all parameters studied. When aortic rings were exposed to the 2,3-diaryl-indole coxib 1 h before irradiation, metabolic activity was restored and the release of both prostaglandin and isoprostane was inhibited. The latter indicates a direct interaction with oxidant stress pathways. By contrast, celecoxib exhibited only slight effects on the formation of isoprostane. The reduction of radiation-induced vascular dysfunction by antioxidative coxibs may widen the therapeutic window of COX-2 targeted treatment.
- Monitoring parotid gland tumors with a new perfusion software for contrast-enhanced ultrasound. [Journal Article]
- Clin Hemorheol Microcirc 2014 Jan 1; 58(1):261-9.
Contrast enhanced ultrasound (CE-US) is a promising imaging modality for non-invasive analysis of functional vascularisation. Lesions of the parotid gland are associated with a vascularisation that differs from normal gland tissue. The aim of this clinical study was to further analyse the perfusion in parotid gland lesions with CE-US. The new quantification software VueBox (Bracco, Italy) was used to assess the perfusion, based on DICOM datasets of CE-US examination.CE-US measurements were performed by intravenous application of a contrast agent (SonoVue, Bracco, Italy) before surgical tumor resection. From the analysis of a time sequence of 2D DICOM contrast images, area under time intensity curve (AUC), peak enhancement (PE), wash-in-rate (WiR) and wash-in-perfusion-index (WiPI) were calculated using VueBox. These were correlated with the histological analyses of the tumor tissue.Significant difference of area below intensity time curve (AUC), peak enhancement (PE), wash-in-rate (WiR) and wash-in perfusion index (WiPI) were observed in the malign lesions compared to benign tumors (p < 0,05) and in pleomorphic adenoma compared to cystadenolymphoma (p < 0,05).CE-US seems to be a quantitative and independent method for discriminating between malign and benign parotid gland tumors.
- Value of high-resolution contrast-enhanced ultrasound in detection and characterisation of endoleaks after EVAR. [Journal Article]
- Clin Hemorheol Microcirc 2014 Jan 1; 58(1):247-60.
To compare the value of high-resolution contrast-enhanced ultrasound in the detection and characterisation of endoleaks after EVAR.In this retrospective study, a cohort of 80 patients underwent both standard examination using a curved array 5 MHz transducer and a second examination using a curved array 9 MHz transducer. The examination included B-mode, color Doppler and contrast-enhanced ultrasound using the Philips EPIQ 7 scanner.80 patients were included in the study. CEUS was used as the preferred examination in determining the presence of an endoleak. The sensitivity and specificity for the detection of endoleak using the 5 MHz transducer was: CEUS (96.8%, 100%), Color Doppler (47.6%, 94.1%), B-mode (15.8%, 94.1%), while for the 9 MHz transducer: CEUS (100%, 100%), Color Doppler (39.7%, 94.1%), B-mode (23.8%, 24.1%).High resolution ultrasound (9 MHz) in detection and characterization of endoleaks after EVAR has some minor advantages in comparison to lower resolution ultrasound (5 MHz).
- Heart valve stenosis in laser spotlights: Insights into a complex disease. [Journal Article]
- Clin Hemorheol Microcirc 2014 Jan 1; 58(1):65-75.
Degenerative heart valve disease is a life-threatening disease affecting about 3% of the population over 65 years. Up to date, cardiac surgery with heart valve replacement is the only available therapy. The disease is characterized by degenerative disorganization of the heart valve structure and alterations in the residing cell populations. Causes and mechanisms of disease genesis are still not fully understood and until now pharmacological therapies are not available. Thus there is enormous interest in new technologies that enable a better characterization of structure and composition of diseased valves. Currently most research techniques demand for extensive processing of extracted valve material. We present a novel approach combining coherent anti-Stokes Raman scattering, endogenous two-photon excited fluorescence and second harmonic generation. Cusp constituents can be examined simultaneously, three-dimensionally and without extensive manipulation of the sample enabling impressive insights into a complex disease.
- Subclinical hypothyroidism and cardiovascular risk. [Journal Article]
- Clin Hemorheol Microcirc 2014 Jan 1; 58(1):1-7.
Subclinical hypothyroidism (SCH) has been suggested to be associated with increased cardiovascular risk by different mechanisms. Several cardiovascular risk factors have been analysed, but yielded controversial results.We aimed to analyse whether there are differences in several cardiovascular risk markers, such as lipids, inflammatory parameters: plasma viscosity (PV), fibrinogen and C reactive protein (CRP); homocysteine (Hcy) and red blood cell distribution width (RDW), when comparing SCH and controls. We also analysed which of these parameters predict SCH risk and constitute independent markers.We determined PV in a Fresenius capillary plasma viscosimeter, Hcy by a chemiluminiscent enzyme immunoassay, and biochemical and haematological parameters by conventional laboratory methods in 58 SCH outpatients and 58 controls matched for age and gender.SCH patients did not show statistical differences for glucose, lipids or leucocytes (p > 0.05). However, patients showed a higher prevalence for use of hypolipidaemic drugs, body mass index (BMI), thyroid stimulating hormone (TSH), PV, CRP, fibrinogen, Hcy and RDW (p < 0.05). RDW correlated with inflammation parameters: PV (r = 0.331, p < 0.05), fibrinogen (r = 0.424, p < 0.05), CRP (r = 0.433, p < 0.01) and leucocytes (r = 0.613, p < 0.01). None of the cardiovascular markers correlated with the TSH levels (p > 0.05) In the unadjusted logistic regression analyses, BMI ≥28 kg/m2, RDW ≥14%, Hcy ≥12 μm/L, fibrinogen ≥400 mg/dL and MCV ≤88 fL increased SCH risk, but only RDW ≥14% and fibrinogen ≥400 mg/dL independently increased this risk in the adjusted logistic regression analyses (OR = 4.68, 95% CI 1.20-18.30 P = 0.026; OR = 3.48, 95% CI 1.08-11.23 P = 0.037).SCH patients show a higher cardiovascular risk, characterised by increased PV, fibrinogen, Hcy and RDW. However, only fibrinogen ≥400 mg/dL and RDW ≥14% are independent predictors of SCH.
- Influence of erythrocyte aggregation at pathological levels on cell-free marginal layer in a narrow circular tube. [JOURNAL ARTICLE]
- Clin Hemorheol Microcirc 2014 Oct 20.
Human red blood cells (RBCs) were perfused in a circular micro-tube (inner diameter of 25 μm) to examine the dynamic changes of cell-free marginal region at both physiological (normal) and pathophysiological (hyper) levels of RBC aggregation. The cell-free area (CFA) was measured to provide additional information on the cell-free layer (CFL) width changes in space and time domains. A prominent enhancement in the mean CFL width was found in hyper-aggregating conditions as compared to that in non-aggregating conditions (P < 0.001). The frequent contacts between RBC and the tube wall were observed and the contact frequency was greatly decreased when the aggregation level was increased from none to normal (P < 0.05) and to hyper (P < 0.001) levels. In addition, the enhanced aggregation from none to hyper levels significantly enlarged the CFA (P < 0.01). We concluded that the RBC aggregation at pathophysiological levels could promote not only the CFL width (one-dimensional parameter) but also the spatiotemporal variation of CFA (two-dimensional parameter).
- Fractal analysis of circulating platelets in type 2 diabetic patients. [JOURNAL ARTICLE]
- Clin Hemorheol Microcirc 2014 Oct 20.
This paper investigates the use of computerized fractal analysis for objective characterization by means of transmission electron microscopy of the complexity of circulating platelets collected from healthy individuals and from type 2 diabetic patients, a pathologic condition in which platelet hyperreactivity has been described. Platelet boundaries were extracted by means of automatically image analysis. Local fractal dimension by box counting (measure of geometric complexity) was automatically calculated. The results showed that the platelet boundary observed by electron microscopy is fractal and that the shape of the circulating platelets is significantly more complex in the diabetic patients in comparison to healthy subjects (p < 0.01), with 100% correct classification. In vitro activated platelets from healthy subjects show an analogous increase of geometric complexity. Computerized fractal analysis of platelet shape by transmission electron microscopy can provide accurate, quantitative, data to study platelet activation in diabetes mellitus.
- Effect of diabetes on the cutaneous microcirculation of the feet in patients with intermittent claudication. [JOURNAL ARTICLE]
- Clin Hemorheol Microcirc 2014 Oct 20.
Aims: To evaluate endothelial-dependent and -independent cutaneous vasodilator responses in the feet of patients with peripheral arterial disease (PAD) with or without Type 2 diabetes. Methods: Cutaneous microvascular responses in the dorsum of both lower limbs were measured in the supine position using Laser Doppler Fluximetry combined with iontophoretic administration of endothelial-dependent (acetylcholine, Ach) and -independent (sodium nitroprusside, SNP) vasodilators in diabetic (n = 19) and non diabetic (n = 17) patients with PAD (presenting as unilateral calf intermittent claudication (IC). Results: In patients with diabetes and IC, endothelial-dependent vasodilation was significantly impaired in the symptomatic limb [74 (57,105) vs 68 (24,81) PU, Z = -2.79, p = 0.005] compared to the asymptomatic limb. Patients without diabetes showed no impairment of vasodilation. Resting ankle-brachial pressure index did not identify the presence of abnormalities in microvascular function. Conclusions: The combination of diabetes and PAD is associated with a reduction in endothelial-dependent cutaneous vasodilation in the feet without an associated reduction in endothelial independent vasodilation.
- Rheology of red blood cells in patients with HbC disease. [JOURNAL ARTICLE]
- Clin Hemorheol Microcirc 2014 Oct 20.
Patients with hemoglobin C disease (CC) usually do not develop severe complications in comparison with individuals with sickle cell anemia (SS) or with sickle cell hemoglobin C disease (SC). The present study compared the hematological, biochemical, hemorheological and clinical characteristics of CC patients to those of SS, SC and healthy individuals (AA). Blood viscosity was measured at 225 s-1 with a cone plate viscometer. The hematocrit-to-blood viscosity ratio (HVR), i.e. an index of red blood cell (RBC) oxygen transport effectiveness, was calculated. RBC deformability was determined at 30 Pa by ektacytometry, and RBC aggregation properties by syllectometry. CC and SC had higher blood viscosity and lower HVR than AA. Nevertheless, HVR was higher in CC compared to SS and tended to be higher than in SC. The CC group exhibited very rigid hyperchromic RBC compared to the three other groups. RBC aggregation abnormalities were observed in CC: low RBC aggregation index and high RBC aggregates strength. Despite these hemorheological abnormalities, CC never had hospitalized painful vaso-occlusive crisis or acute chest syndrome. In contrast, all of them had splenomegaly. Of note, 2 out of 7 CC developed retinopathy or otologic disorders. Whether the blood hyperviscosity and decreased RBC deformability are responsible for these complications is unknown. The higher oxygen transport effectiveness (i.e., HVR) of CC compared to SS is probably at the origin of the very low risk of medical complication in this population.