Heparinase selectively sheds heparan sulphate from the endothelial glycocalyx

A healthy vascular endothelium is coated by the endothelial glycocalyx. Its main constituents are transmembrane syndecans and bound heparan sulphates. This structure maintains the physiological endothelial permeability barrier and prevents leukocyte and platelet adhesion, thereby mitigating inflammation and tissue oedema. Heparinase, a bacteria] analogue to heparanase, is known to attack the glycocalyx. However, the exact extent and specificity of degradation is unresolved. We show by electron microscopy, immunohistological staining and quantitative measurements of the constituent parts, that heparinase selectively sheds heparan sulphate from the glycocalyx, but not the synclecans

Influence of hydroxyethyl starch (6% HES 130/0.4) administration on hematology and clinical chemistry parameters

Background: The chemical inertness of hydroxyethyl starch (HES) might cause interferences of the colloid with a variety of laboratory tests. We aimed to evaluate potential influences of HES 130/0.4, the newest HES type, on several common hematology and clinical chemistry parameters. Methods and results: A convenient sample of 25 patients scheduled for rheological therapy with 500 mL 6% HES 130/0.4 was evaluated. Blood samples were drawn before and after colloid application. Comparing pre- and post-infusion values of a battery of laboratory tests (i.e., hematology and hemostasis parameters, electrolytes, enzymes, kidney and metabolic parameters, lipids, etc.) in time course, a median difference greater than the reference change value for a specific parameter was considered clinically relevant. Among all parameters tested, only serum amylase activity displayed a clinically relevant difference between pre- and post-infusion values (median increase of 85% due to HES administration). By applying in vitro experiments, we demonstrated that serum amylase values obtained in the samples diluted in a 1:1 ratio with HES 130/0.4 and in samples diluted in a 1:1 ratio with 0.9% NaCl displayed a negligible median difference of 3%. Conclusions: The in vivo effect of HES 130/0.4 administration on serum amylase activity observed in our study was pharmacological (real) in nature. With the exception of the influence of HES 130/0.4 on amylase activity, the effects of HES 130/0.4 on other parameters tested in this study can be interpreted as having no clinical relevance

Perspectives in Microvascular Fluid Handling: Does the Distribution of Coagulation Factors in Human Myocardium Comply with Plasma Extravasation in Venular Coronary Segments?

Background: Heterogeneity of vascular permeability has been suggested for the coronary system. Whereas arteriolar and capillary segments are tight, plasma proteins pass readily into the interstitial space at venular sites. Fittingly, lymphatic fluid is able to coagulate. However, heart tissue contains high concentrations of tissue factor, presumably enabling bleeding to be stopped immediately in this vital organ. The distribution of pro- and anti-coagulatively active factors in human heart tissue has now been determined in relation to the types of microvessels. Methods and Results: Samples of healthy explanted hearts and dilated cardiomyopathic hearts were immunohistochemically stained. Albumin was found throughout the interstitial space. Tissue factor was packed tightly around arterioles and capillaries, whereas the tissue surrounding venules and small veins was practically free of this starter of coagulation. Thrombomodulin was present at the luminal surface of all vessel segments and especially at venular endothelial cell junctions. Its product, the anticoagulant protein C, appeared only at discrete extravascular sites, mainly next to capillaries. These distribution patterns were basically identical in the healthy and diseased hearts, suggesting a general principle. Conclusions: Venular extravasation of plasma proteins probably would not bring prothrombin into intimate contact with tissue factor, avoiding interstitial coagulation in the absence of injury. Generation of activated protein C via thrombomodulin is favored in the vicinity of venular gaps, should thrombin occur inside coronary vessels. This regionalization of distribution supports the proposed physiological heterogeneity of the vascular barrier and complies with the passage of plasma proteins into the lymphatic system of the heart. Copyright (C) 2010 S. Karger AG, Base

Electron transport in the dye sensitized nanocrystalline cell

Dye sensitised nanocrystalline solar cells (Gr\"{a}tzel cells) have achieved solar-to-electrical energy conversion efficiencies of 12% in diffuse daylight. The cell is based on a thin film of dye-sensitised nanocrystalline TiO$_2$ interpenetrated by a redox electrolyte. The high surface area of the TiO$_2$ and the spectral characteristics of the dye allow the device to harvest 46% of the solar energy flux. One of the puzzling features of dye-sensitised nano-crystalline solar cells is the slow electron transport in the titanium dioxide phase. The available experimental evidence as well as theoretical considerations suggest that the driving force for electron collection at the substrate contact arises primarily from the concentration gradient, ie the contribution of drift is negligible. The transport of electrons has been characterised by small amplitude pulse or intensity modulated illumination. Here, we show how the transport of electrons in the Gr\"{a}tzel cell can be described quantitatively using trap distributions obtained from a novel charge extraction method with a one-dimensional model based on solving the continuity equation for the electron density. For the first time in such a model, a back reaction with the I$_3^-$ ions in the electrolyte that is second order in the electron density has been included.Comment: 6 pages, 5 figures, invited talk at the workshop 'Nanostructures in Photovoltaics' to appear in Physica

Towards new recommendations to reduce the burden of alcohol-induced hypertension in the European Union

Background Hazardous and harmful alcohol use and high blood pressure are central risk factors related to premature non-communicable disease (NCD) mortality worldwide. A reduction in the prevalence of both risk factors has been suggested as a route to reach the global NCD targets. This study aims to highlight that screening and interventions for hypertension and hazardous and harmful alcohol use in primary healthcare can contribute substantially to achieving the NCD targets. Methods A consensus conference based on systematic reviews, meta-analyses, clinical guidelines, experimental studies, and statistical modelling which had been presented and discussed in five preparatory meetings, was undertaken. Specifically, we modelled changes in blood pressure distributions and potential lives saved for the five largest European countries if screening and appropriate intervention rates in primary healthcare settings were increased. Recommendations to handle alcohol-induced hypertension in primary healthcare settings were derived at the conference, and their degree of evidence was graded. Results Screening and appropriate interventions for hazardous alcohol use and use disorders could lower blood pressure levels, but there is a lack in implementing these measures in European primary healthcare. Recommendations included (1) an increase in screening for hypertension (evidence grade: high), (2) an increase in screening and brief advice on hazardous and harmful drinking for people with newly detected hypertension by physicians, nurses, and other healthcare professionals (evidence grade: high), (3) the conduct of clinical management of less severe alcohol use disorders for incident people with hypertension in primary healthcare (evidence grade: moderate), and (4) screening for alcohol use in hypertension that is not well controlled (evidence grade: moderate). The first three measures were estimated to result in a decreased hypertension prevalence and hundreds of saved lives annually in the examined countries. Conclusions The implementation of the outlined recommendations could contribute to reducing the burden associated with hypertension and hazardous and harmful alcohol use and thus to achievement of the NCD targets. Implementation should be conducted in controlled settings with evaluation, including, but not limited to, economic evaluation

The endothelial glycocalyx prefers albumin for evoking shear stress-induced, nitric oxide-mediated coronary dilatation

Background: Shear stress induces coronary dilatation via production of nitric oxide ( NO). This should involve the endothelial glycocalyx ( EG). A greater effect was expected of albumin versus hydroxyethyl starch ( HES) perfusion, because albumin seals coronary leaks more effectively than HES in an EG-dependent way. Methods: Isolated hearts ( guinea pigs) were perfused at constant pressure with Krebs-Henseleit buffer augmented with 1/3 volume 5% human albumin or 6% HES ( 200/0.5 or 450/0.7). Coronary flow was also determined after EG digestion ( heparinase) and with nitro-L-arginine ( NO-L-Ag). Results: Coronary flow ( 9.50 +/- 1.09, 5.10 +/- 0.49, 4.87 +/- 1.19 and 4.15 +/- 0.09 ml/ min/ g for `albumin', `HES 200', `HES 450' and `control', respectively, n = 5-6) did not correlate with perfusate viscosity ( 0.83, 1.02, 1.24 and 0.77 cP, respectively). NO-L-Ag and heparinase diminished dilatation by albumin, but not additively. Alone NO-L-Ag suppressed coronary flow during infusion of HES 450. Electron microscopy revealed a coronary EG of 300 nm, reduced to 20 nm after heparinase. Cultured endothelial cells possessed an EG of 20 nm to begin with. Conclusions: Albumin induces greater endothelial shear stress than HES, despite lower viscosity, provided the EG contains negative groups. HES 450 causes some NO-mediated dilatation via even a rudimentary EG. Cultured endothelial cells express only a rudimentary glycocalyx, limiting their usefulness as a model system. Copyright (c) 2007 S. Karger AG, Basel