Apocrine glands in the eyelid of primates contribute to the ocular host defense

Apocrine glands of Moll are regular components of primate eyelids. We studied the distribution and localization of these glands in three different primate species, the common marmoset, the rhesus monkey, and the hamadryas baboon. In addition, we tested the primate glands of Moll with antibodies against antimicrobial proteins, cytoskeletal proteins and the androgen receptor. The glands of Moll differ in abundance and distribution in different monkeys. In the common marmoset, a representative of the New World monkeys, Platyrrhini, the apocrine glands are frequently found at the lid margin and in the overlying epidermis of the lid. In the rhesus monkey and the hamadryas baboon, representatives of Old World monkeys, Catarrhini, apocrine glands are rarer and located predominantly at the margin of the lid. The immunohistochemical analysis indicates the presence of a variety of antimicrobial proteins, e. g. lysozyme, beta-defensin-2, adrenomedullin, lactoferrin, and IgA, in these glands. Interestingly, there are basically no androgen receptors in the nuclei of apocrine glands at the lid margin in all three monkey species. In the common marmoset, however, androgen receptors are found in apocrine glands of the overlying epidermis of the lid. We speculate that the glands of Moll are derived from apocrine glands as found in the skin of the entire body in New World monkeys which developed at the lid margins of higher primates and humans into specialized glands secreting agents of host defense in the eye. Copyright (C) 2004 S. Karger AG, Basel

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

Labial Salivary Glands in Infants: Histochemical Analysis of Cytoskeletal and Antimicrobial Proteins

Human labial glands secrete mucous and serous substances for maintaining oral health. The normal microbial flora of the oral cavity is regulated by the acquired and innate immune systems. The localization and distribution of proteins of the innate immune system were investigated in serous acinar cells and the ductal system by the method of immunohistochemistry. Numerous antimicrobial proteins could be detected in the labial glands: -defensin-1, -2, -3;lysozyme;lactoferrin;and cathelicidin. Cytoskeletal components such as actin, myosin II, cytokeratins 7 and 19, - and -tubulin were predominantly observed in apical cell regions and may be involved in secretory activities

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

«Diseño para todos» en la investigación social sobre personas con discapacidad

[EN] Social studies on disability have increased in number and importance in Spain and other countries over the last few years. Nevertheless, the majority of the available sources and studies do not adequately represent this heterogeneous group, which currently makes up about 9 per cent of the Spanish population. The implementation of social measures requires representative sources and studies containing relevant information. The aim of this paper is to identify the main diffi culties involved in designing and developing social research methods concerning persons with disabilities, and offer proposals and recommendations in order to advance towards a more inclusive social research using the concepts of accessibility and design for all.[ES] Los estudios sociales sobre la discapacidad han aumentado en número e importancia en España y otros países durante los últimos años. Sin embargo, la mayoría de fuentes de información y estudios disponibles no recogen de manera adecuada la realidad de un colectivo muy heterogéneo, que supone en la actualidad aproximadamente el 9 por ciento de la población española. La implementación de medidas sociales requiere de fuentes y estudios representativos que aporten información precisa acerca de estas personas. El objetivo de esta nota es identifi car las principales difi cultades que se plantean a la hora de diseñar y llevar a la práctica metodologías de investigación social adecuadas hacia las personas con discapacidad, así como ofrecer propuestas y recomendaciones para avanzar hacia una investigación social más inclusiva, mediante los conceptos de accesibilidad y diseño para todos.Work carried out as part of the framework of research projects: “Qualitative Tracking with Young Disabled in European States. Quali-TYDES” (European Science Foundation, 09-ECRP-032) and “Hidden Innovation: paradigm shift in innovation studies” (Spanish Ministry of Economy and Competitiveness, FFI2011-25475).Peer reviewe

Phosphatidylethanolamine critically supports internalization of cell-penetrating protein C inhibitor

Although their contribution remains unclear, lipids may facilitate noncanonical routes of protein internalization into cells such as those used by cell-penetrating proteins. We show that protein C inhibitor (PCI), a serine protease inhibitor (serpin), rapidly transverses the plasma membrane, which persists at low temperatures and enables its nuclear targeting in vitro and in vivo. Cell membrane translocation of PCI necessarily requires phosphatidylethanolamine (PE). In parallel, PCI acts as a lipid transferase for PE. The internalized serpin promotes phagocytosis of bacteria, thus suggesting a function in host defense. Membrane insertion of PCI depends on the conical shape of PE and is associated with the formation of restricted aqueous compartments within the membrane. Gain- and loss-of-function mutations indicate that the transmembrane passage of PCI requires a branched cavity between its helices H and D, which, according to docking studies, precisely accommodates PE. Our findings show that its specific shape enables cell surface PE to drive plasma membrane translocation of cell-penetrating PCI

Radiation protection value to the operator from augmented reality smart glasses in interventional fluoroscopy procedures using phantoms

Introduction: Smart glasses can be adapted to display radiographic images to allow clinician’s gaze not to be directionally fixed or predetermined by computer monitor location. This study presents an analysis of eye lens dose during interventional fluoroscopy guided procedures, comparing fixed monitor positions against the use of smart glasses. Methods: Using a head phantom (simulating the clinician), thermoluminescent dosimeters and lead shielded glasses, the dose to the eye was measured for different head ‘rotations and tilts’ for: gaze directed towards the main scattering source (patient / primary beam) to represent potential gaze direction if smart glasses are used; gaze directed to a range of potential computer monitor positions. An anthropomorphic pelvis phantom was utilised to simulate the patient. Accumulated dose rates (µGy.sˉ¹) from five 10-second exposures at 75 kV 25.2 mAs were recorded. Results: An average DAP reading of 758.84 cGy.cm2 was measured during each 10 second exposure. Whilst wearing lead shielded glasses a 6.10 – fold reduction in dose rate to the lens is possible (p<0.05). Influence of the direction of gaze by the clinician demonstrated a wide range of dose rate reduction from 3.13% (p=0.16) to 143.69% (p<0.05) when the clinician’s gaze was towards the main scattering source. Increased dose rate to the clinician’s eyes was received despite wearing lead shielded glasses, as the angle of gaze moved 45º and 90º from 0º. Conclusion: If the clinician’s gaze is directed towards the main scattering source a potential exists for reducing eye lens dose compared with fixed location computer monitors. Introduction of lead lined smart glasses into interventional radiology may lead to improvements in patient care, reducing the need for the clinician to look away from the patient to observe a radiographic image

Actin depolymerisation and crosslinking join forces with myosin II to contract actin coats on fused secretory vesicles

In many secretory cells actin and myosin are specifically recruited to the surface of secretory granules following their fusion with the plasma membrane. Actomyosin-dependent compression of fused granules is essential to promote active extrusion of cargo. However, little is known about molecular mechanisms regulating actin coat formation and contraction. Here, we provide a detailed kinetic analysis of the molecules regulating actin coat contraction on fused lamellar bodies in primary alveolar type II cells. We demonstrate that ROCK1 and myosin light chain kinase 1 (MLCK1, also known as MYLK) translocate to fused lamellar bodies and activate myosin II on actin coats. However, myosin II activity is not sufficient for efficient actin coat contraction. In addition, cofilin-1 and α-actinin translocate to actin coats. ROCK1-dependent regulated actin depolymerisation by cofilin-1 in cooperation with actin crosslinking by α-actinin is essential for complete coat contraction. In summary, our data suggest a complementary role for regulated actin depolymerisation and crosslinking, and myosin II activity, to contract actin coats and drive secretion