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

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

Home lands: island and archipelagic states’ policymaking for human mobility in the context of climate change

Climate change related migration and displacement are already a reality for many people around the world. A growing body of research suggests that the number of people affected will rise over the coming decades, which will create additional risks for the achievement of the Sustainable Development Goals. This trend and the related issues are an increasing topic of discussion at international policy fora. The Task Force on Displacement under the United Nations Framework Convention on Climate Change (UNFCCC) and the Platform on Disaster Displacement (PDD) are addressing these policy challenges. The Global Compact for Safe, Orderly and Regular Migration (GCM) is calling for the development of “coherent approaches to address the challenges of migration movements in the context of sudden-onset and slow-onset natural disasters”. This report reflects what is currently known about the impacts of climate change on people living in island nations and highlights the necessity to develop policies that address human mobility dynamics resulting from adaptation to these changes. By looking at island and archipelagic states as diverse as Kiribati, Saint Lucia and the Philippines, the various political frameworks within which they operate and the different response mechanisms they have adopted can be examined. First-hand interviews with experts from across the regions show the multiplicity of challenges governments are facing: from difficulties in distribution of relief goods to land scarcity, aid dependency, insufficient data and personnel capacities. Yet the key interviewees underline ways in which governments can capitalise on the strengths inherent to island and coastal communities to further build resilience using existing and innovative practices

Exogenous nitric oxide requires an endothelial glycocalyx to prevent postischemic coronary vascular leak in guinea pig hearts

Introduction Postischemic injury to the coronary vascular endothelium, in particular to the endothelial glycocalyx, may provoke fluid extravasation. Shedding of the glycocalyx is triggered by redox stress encountered during reperfusion and should be alleviated by the radical scavenger nitric oxide (NO). The objective of this study was to investigate the effect of exogenous administration of NO during reperfusion on both coronary endothelial glycocalyx and vascular integrity. Methods Isolated guinea pig hearts were subjected to 15 minutes of warm global ischemia followed by 20 minutes of reperfusion in the absence (Control group) and presence (NO group) of 4 mu M NO. In further experiments, the endothelial glycocalyx was enzymatically degraded by means of heparinase followed by reperfusion without (HEP group) and with NO (HEP+NO group). Results Ischemia and reperfusion severely damaged the endothelial glycocalyx. Shedding of heparan sulfate and damage assessed by electron microscopy were less in the presence of NO. Compared with baseline, coronary fluid extravasation increased after ischemia in the Control, HEP, and HEP+NO groups but remained almost unchanged in the NO group. Tissue edema was significantly attenuated in this group. Coronary vascular resistance rose by 25% to 30% during reperfusion, but not when NO was applied, irrespective of the state of the glycocalyx. Acute postischemic myocardial release of lactate was comparable in the four groups, whereas release of adenine nucleotide catabolites was reduced 42% by NO. The coronary venous level of uric acid, a potent antioxidant and scavenger of peroxynitrite, paradoxically decreased during postischemic infusion of NO. Conclusion The cardioprotective effect of NO in postischemic reperfusion includes prevention of coronary vascular leak and interstitial edema and a tendency to forestall both no-reflow and degradation of the endothelial glycocalyx

The German fibromyalgia consumer reports - a cross-sectional survey

Background: Consumer surveys provide information on effectiveness and side effects of medical interventions in routine clinical care. A report of fibromyalgia syndrome (FMS) consumers has not been carried out in Europe. Methods: The study was carried out from November 2010 to April 2011. Participants diagnosed with FMS rated the effectiveness and side effects of pharmacological and non-pharmacological FMS interventions on a 0 to 10 scale, with 10 being most efficacious (harmful). The questionnaire was distributed by the German League for people with Arthritis and Rheumatism and the German Fibromyalgia Association to their members and to all consecutive FMS patients of nine clinical centers of different levels of care. Results: 1661 questionnaires (95% women, mean age 54 years, mean duration since FMS diagnosis 6.8 years) were analysed. The most frequently used therapies were self-management strategies, prescription pain medication and aerobic exercise. The highest average effectiveness was attributed to whole body and local warmth therapies, thermal bathes, FMS education and resting. The highest average side effects were attributed to strong opioids, local cold therapy, gamma-amino-butyric acid analogues (pregabalin and gabapentin), tramadol and opioid transdermal systems. Conclusion: The German fibromyalgia consumer reports highlight the importance of non-pharmcological therapies in the long-term management of FMS, and challenges the strong recommendations for drug therapies given by FMS-guidelines

Validation of the Fibromyalgia Survey Questionnaire within a Cross-Sectional Survey

The Fibromyalgia Survey Questionnaire (FSQ) assesses the key symptoms of fibromyalgia syndrome. The FSQ can be administrated in survey research and settings where the use of interviews to evaluate the number of pain sites and extent of somatic symptom intensity and tender point examination would be difficult. We validated the FSQ in a cross-sectional survey with FMS patients. In a cross-sectional survey, participants with physician diagnosis of FMS were recruited by FMS-self help organisations and nine clinical institutions of different levels of care. Participants answered the FSQ (composed by the Widespread Pain Index [WPI] and the Somatic Severity Score [SSS]) assessing the Fibromyalgia Survey Diagnostic Criteria (FSDC) and the Patient Health Questionnaire PHQ 4. American College of Rheumatology 1990 classification criteria were assessed in a subgroup of participants. 1,651 persons diagnosed with FMS were included into analysis. The acceptance of the FSQ-items ranged between 78.9 to 98.1% completed items. The internal consistency of the items of the SSS ranged between 0.75–0.82. 85.5% of the study participants met the FSDC. The concordance rate of the FSDC and ACR 1990 criteria was 72.7% in a subsample of 128 patients. The Pearson correlation of the SSS with the PHQ 4 depression score was 0.52 (p<0.0001) and with the PHQ anxiety score was 0.51 (p<0.0001) (convergent validity). 64/202 (31.7%) of the participants not meeting the FSDC criteria and 152/1283 (11.8%) of the participants meeting the FSDC criteria reported an improvement (slightly too very much better) in their health status since FMS-diagnosis (Chi2 = 55, p<0.0001) (discriminant validity). The study demonstrated the feasibility of the FSQ in a cross-sectional survey with FMS-patients. The reliability, convergent and discriminant validity of the FSQ were good. Further validation studies of the FSQ in clinical and general population settings are necessary

Empfehlung zur Weiterentwicklung des Berliner Energie- und Klimaschutzprogramms 2030

EMPFEHLUNG ZUR WEITERENTWICKLUNG DES BERLINER ENERGIE- UND KLIMASCHUTZPROGRAMMS 2030 Empfehlung zur Weiterentwicklung des Berliner Energie- und Klimaschutzprogramms 2030 / Alt-Harnack, Claudia (Rights reserved) ( -

Flavonoid wing pigments increase attractiveness of female common blue (Polyommatus icarus) butterflies to mate-searching males

Common blue butterflies (Polyommatus icarus) sequester flavonoids from their larval host plants and allocate these UV-absorbing pigments to the wings. In field experiments using dummies constructed from female butterflies, mate-searching males inspected flavonoid-rich dummies more intensively than those with little or no flavonoids. Flavonoid content as signalled by UV-wing pattern may indicate ontogenetically determined female quality or enhance detectability to males

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