Total homocysteine (tHcy) level was identified as a strong and independent predictor of cardiovascular events. We investigated the association between tHcy and mechanical properties of large arteries in a random, general population-based sample of 251 subjects (mean age 48 years). Large artery properties, such as aortic and peripheral (lower-limb) pulse wave velocity (PWV), and augmentation index of radial artery were measured using semi-automatic Sphygmocor s device. Aortic PWV (APWV) positively correlated with tHcy (r ¼ 0.28, Po0.0001), and a significant increasing trend of APWV was found by tHcy quartiles (P ¼ 0.0003 by ANOVA). This association remained significant after adjustment for conventional cardiovascular risk factors (age, gender, smoking, overweight, hypertension, dyslipidaemia and impaired glucose metabolism) and for usual homocysteine confounders (folate, B 12 , renal function). Subjects with mild hyperhomocysteinaemia (i.e. with tHcy X15 lmol/l) had 2.74 times higher risk of having their APWV over 8.42 m/s (i.e. in the top quartile). No such association was found either for PWV measured at lower extremity or for radial augmentation index. In conclusion, in our series of subjects from general population, we found a strong and independent relationship between homocysteine concentration and APWV, a parameter of stiffness of central arteries.
Decellularized scaffolds can serve as an excellent three-dimensional environment for cell repopulation. They maintain tissue-specific microarchitecture of extracellular matrix proteins with important spatial cues for cell adhesion, migration, growth, and differentiation. However, criteria for quality assessment of the three-dimensional structure of decellularized scaffolds are rather fragmented, usually study-specific, and mostly semi-quantitative. Thus, we aimed to develop a robust structural assessment system for decellularized porcine liver scaffolds. Five scaffolds of different quality were used to establish the new evaluation system. We combined conventional semi-quantitative scoring criteria with a quantitative scaffold evaluation based on automated image analysis. For the quantitation, we developed a specific open source software tool (ScaffAn) applying algorithms designed for texture analysis, segmentation, and skeletonization. ScaffAn calculates selected parameters characterizing structural features of porcine liver scaffolds such as the sinusoidal network. After evaluating individual scaffolds, the total scores predicted scaffold interaction with cells in terms of cell adhesion. Higher scores corresponded to higher numbers of cells attached to the scaffolds. Moreover, our analysis revealed that the conventional system could not identify fine differences between good quality scaffolds while the additional use of ScaffAn allowed discrimination. This led us to the conclusion that only using the combined score resulted in the best discrimination between different quality scaffolds. Overall, our newly defined evaluation system has the potential to select the liver scaffolds most suitable for recellularization, and can represent a step toward better success in liver tissue engineering.
Thein vitroresponse of human fibroblast cell line HFL1 and human osteoblast cell line hFOB 1.19 on nanostructured titanium with different grain sizes has been compared in the present study. Used samples of titanium produced by equal channel angular (ECA) pressing have grain sizes of 160 nm, 280 nm, and 2400 nm with cross- and longitudinal sections. Similar cellular behaviour was observed on all studied biomaterials. There were significant differences related to the initial phase of attachment, but not in proliferation. Furthermore, the results indicate that osteoblasts grow best on material with grain size of 160 nm with a longitudinal section in comparison with other examined materials. Therefore, this material could be recommended for further evaluation with respect to osseointegrationin vivo.
Selective incircuit blood cooling could be an effective anticoagulation strategy during hemodialysis. However, it is currently unknown what blood temperature would ensure sufficient anticoagulation. Similarly, no information exists about potential interindividual variability in response to graded hypothermia. Therefore, the aim of this study was to analyze effects of profound hypothermia on human coagulation. Furthermore, a mathematical relationship between blood temperatures and coagulation was sought to predict individual responses to blood cooling. It was designed as a laboratory study. Thromboelastography (TEG) measurements were taken at a temperature range of 38-12°C. To enable measurements below 20°C, the TEG device was placed into an air conditioned chamber allowing for setting of the temperatures over a wide range. The data were analyzed by regression analysis for pooled and individual measurements. Decreasing temperatures always led to a progressive reduction in blood coagulation by delaying the initiation of thrombus formation, as well as by decreasing the speed of its creation and growth. However, the response to cooling was not uniform and the interindividual variability exists. The relationship between blood temperature and coagulation is not linear but exponential (parameters R and K) and sigmoid (parameter α-angle). The lower the blood temperature, the more significant effect on blood coagulation decline. To predict an individual response of the coagulation system over a wide range of temperatures, a mathematical modeling can be used.
Objective: To test the hypothesis that cooling of blood in the extracorporeal circuit of continuous veno-venous hemofiltration (CVVH) enables to realize the procedure without the need of anticoagulation. Design: Experimental animal study. Methods: We developed the device for selective cooling of extracorporeal circuit (20°C) allowing blood rewarming (38°C) just before returning into the body. Twelve anesthetized and ventilated pigs were randomized to receive either 6 h of CVVH with application of this device (COOL; n = 6) or without it (CONTR; n = 6). Measurements: Before the procedure and in 15, 60, 180, 360 min after starting hemofiltration variables related to: (1) circuit patency [time to clotting (TC), number of alarm-triggered pump stopping (AS), venous and transmembranous circuit pressures (VP, TMP)], (2) coagulation status in the extracorporeal circuit [thrombin-antithrombin complexes (TAT circ ), thromboelastography (TEG)] and (3) animal status (hemodynamics, hemolysis and biochemistry) were assessed. Results:The patency of all circuits treated with selective cooling was well maintained within the observation period. By contrast, five of six sessions were prematurely clotted in the untreated group. As a result, the number of AS was significantly higher in the CONTR group. In-circuit thrombus generation in CONTR group was associated with a markedly increasing TAT circ . TEG performed at 180 min of the procedure revealed a tendency to a prolonged initial clotting time and a significant decrease in clotting rate of in-circuit blood in the COOL group. No signs of repeated cooling/rewarming-induced hemolysis were observed in animals treated with ''hypothermic circuit'' CVVH. Conclusion: In this porcine model, regional extracorporeal blood cooling proved effective in preventing in-circuit clotting without the need to use any other anticoagulant.
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