Tissue Localization and Extracellular Matrix Degradation by PI, PII and PIII Snake Venom Metalloproteinases: Clues on the Mechanisms of Venom-Induced Hemorrhage

20 páginas, 4 figuras, 3 tablas y 7 tablas en material suplementario.Snake venom hemorrhagic metalloproteinases (SVMPs) of the PI, PII and PIII classes were compared in terms of tissue localization and their ability to hydrolyze basement membrane components in vivo, as well as by a proteomics analysis of exudates collected in tissue injected with these enzymes. Immunohistochemical analyses of co-localization of these SVMPs with type IV collagen revealed that PII and PIII enzymes co-localized with type IV collagen in capillaries, arterioles and post-capillary venules to a higher extent than PI SVMP, which showed a more widespread distribution in the tissue. The patterns of hydrolysis by these three SVMPs of laminin, type VI collagen and nidogen in vivo greatly differ, whereas the three enzymes showed a similar pattern of degradation of type IV collagen, supporting the concept that hydrolysis of this component is critical for the destabilization of microvessel structure leading to hemorrhage. Proteomic analysis of wound exudate revealed similarities and differences between the action of the three SVMPs. Higher extent of proteolysis was observed for the PI enzyme regarding several extracellular matrix components and fibrinogen, whereas exudates from mice injected with PII and PIII SVMPs had higher amounts of some intracellular proteins. Our results provide novel clues for understanding the mechanisms by which SVMPs induce damage to the microvasculature and generate hemorrhage.This work was performed in partial fulfillment of the requirements for the PhD degree for Cristina Herrera at Universidad de Costa Rica.Peer reviewe

Técnica de clareamiento interno en la Clínica de Operatoria V A

Introducción: Los dientes son parte integral de la estética facial y están involucrados en una compleja interacción social, cultural y psicológica. Para las personas con graves decoloraciones, el aclaramiento puede ser un tratamiento importan. Paciente femenino que concurre a la cátedra por una demanda estética. Presentaba pieza dentaria 21 con una endodoncia de 15 años de antigüedad y recordaba que en el momento en que se la realizó, la pieza había tenido un sangrado abundante. Se evaluó la obturación de la misma y se determinó la reintervención endodóntica para obtener mayor hermetismo.Introduction: Teeth are an integral part of facial aesthetics and are involved in a complex social, cultural and psychological interaction. For people with severe discoloration, clearance can be a treatment that matters. Female patient who attends the chair for an aesthetic demand. He presented tooth 21 with a 15-year-old endodontics and remembered that at the time it was made, the piece had had a lot of bleeding. The obturation of the same was evaluated and the endodontic re-intervention was determined to obtain greater hermetism.Facultad de Odontologí

Desenvolvendo para significar : um estudo de caso sobre os pontos de contato entre o processo de desenvolvimento de uma empresa de utilidades domésticas e a abordagem da inovação orientada pelo design

Existem dois fatores fundamentais que definem a sociedade ocidental contemporânea e suas relações mercadológicas: o primeiro é sua busca pela construção de identidade própria perante a massa e a complementação emocional através da aquisição e fruição de produtos significativos, muito evidenciados nos artefatos concebidos pelo design; o outro diz respeito à crescente demanda de consumo por novidades radicais e a velocidade com a qual entram em defasagem, muito em função da escalada tecnológica, colocando os produtores em permanente estado de vigília na garantia de sobrevivência dos negócios. Em resposta a esse cenário, surge a abordagem da inovação orientada pelo design, ou design-driven innovation, com a premissa de que o monitoramento, identificação e captação de transformações em diferentes âmbitos da sociedade permitem às organizações produtoras a antecipação de demandas por novos produtos, o que pode lhes conferir valorosas vantagens competitivas. A fim de estudar a aplicabilidade dessa abordagem de design ao contexto da indústria regional,foi desenvolvido um estudo de caso único e holístico com uma empresa fabricante de utilidades domésticas de expressividade nacional, cujos dados foram obtidos através de entrevistas em profundidade e documentos secundários, posteriormente analisados via análise de conteúdo. Os resultados obtidos apontam baixa proximidade do caso aos pressupostos da inovação orientada pelo design, demonstrando a oportunidade de um esforço entre as diversas camadas funcionais da organização na tarefa de estabelecer uma cultura de inovação pelo design

Gastric Syphilis Mimicking Adenocarcinoma: A Case Report

Syphilis is an unexpected diagnosis in the stomach, and the reduced incidence of syphilis has made its clinical presentation less widely appreciated. We report a 43-yr-old man suffering from epigastric tenderness with an initial diagnosis of gastric carcinoma; gastric syphilis was confirmed by demonstrating spirochetes in a gastric biopsy specimen by silver impregnation. Excessive lymphoplasmacytic infiltration with diffuse thickening of gastric rugae should raise suspicion of gastric syphilis, which should be considered in the differential diagnosis of diffuse erosive gastritis and infiltrative lesions of the stomach

Effects of PI and PIII Snake Venom Haemorrhagic Metalloproteinases on the Microvasculature: A Confocal Microscopy Study on the Mouse Cremaster Muscle

The precise mechanisms by which Snake Venom Metalloproteinases (SVMPs) disrupt the microvasculature and cause haemorrhage have not been completely elucidated, and novel in vivo models are needed. In the present study, we compared the effects induced by BaP1, a PI SVMP isolated from Bothrops asper venom, and CsH1, a PIII SVMP from Crotalus simus venom, on cremaster muscle microvasculature by topical application of the toxins on isolated tissue (i.e., ex vivo model), and by intra-scrotal administration of the toxins (i.e., in vivo model). The whole tissue was fixed and immunostained to visualize the three components of blood vessels by confocal microscopy. In the ex vivo model, BaP1 was able to degrade type IV collagen and laminin from the BM of microvessels. Moreover, both SVMPs degraded type IV collagen from the BM in capillaries to a higher extent than in PCV and arterioles. CsH1 had a stronger effect on type IV collagen than BaP1. In the in vivo model, the effect of BaP1 on type IV collagen was widespread to the BM of arterioles and PCV. On the other hand, BaP1 was able to disrupt the endothelial barrier in PCV and to increase vascular permeability. Moreover, this toxin increased the size of gaps between pericytes in PCV and created new gaps between smooth muscle cells in arterioles in ex vivo conditions. These effects were not observed in the case of CsH1. In conclusion, our findings demonstrate that both SVMPs degrade type IV collagen from the BM in capillaries in vivo. Moreover, while the action of CsH1 is more directed to the BM of microvessels, the effects of BaP1 are widespread to other microvascular components. This study provides new insights in the mechanism of haemorrhage and other pathological effects induced by these toxins

Indirect three-dimensional printing: A method for fabricating polyurethane-urea based cardiac scaffolds.

Biomaterial scaffolds are a key part of cardiac tissue engineering therapies. Our group has recently synthesised a novel polycaprolactone based polyurethane-urea copolymer that shows improved mechanical properties compared to its previously published counterparts. The aim of this study was to explore whether indirect 3D printing could provide a means to fabricate this novel, biodegradable polymer into a scaffold suitable for cardiac tissue engineering. Indirect 3D printing was carried out through printing water dissolvable poly(vinyl alcohol) porogens in three different sizes based on a wood-stack model, into which a polyurethane-urea solution was pressure injected. The porogens were removed, leading to soft polyurethane-urea scaffolds with regular tubular pores. The scaffolds were characterised for their compressive and tensile mechanical behaviour; and their degradation was monitored for 12 months under simulated physiological conditions. Their compatibility with cardiac myocytes and performance in novel cardiac engineering-related techniques, such as aggregate seeding and bi-directional perfusion, was also assessed. The scaffolds were found to have mechanical properties similar to cardiac tissue, and good biocompatibility with cardiac myocytes. Furthermore, the incorporated cells preserved their phenotype with no signs of de-differentiation. The constructs worked well in perfusion experiments, showing enhanced seeding efficiency. This article is protected by copyright. All rights reserved

A New Malaria Agent in African Hominids

Plasmodium falciparum is the major human malaria agent responsible for 200 to 300 million infections and one to three million deaths annually, mainly among African infants. The origin and evolution of this pathogen within the human lineage is still unresolved. A single species, P. reichenowi, which infects chimpanzees, is known to be a close sister lineage of P. falciparum. Here we report the discovery of a new Plasmodium species infecting Hominids. This new species has been isolated in two chimpanzees (Pan troglodytes) kept as pets by villagers in Gabon (Africa). Analysis of its complete mitochondrial genome (5529 nucleotides including Cyt b, Cox I and Cox III genes) reveals an older divergence of this lineage from the clade that includes P. falciparum and P. reichenowi (∼21±9 Myrs ago using Bayesian methods and considering that the divergence between P. falciparum and P. reichenowi occurred 4 to 7 million years ago as generally considered in the literature). This time frame would be congruent with the radiation of hominoids, suggesting that this Plasmodium lineage might have been present in early hominoids and that they may both have experienced a simultaneous diversification. Investigation of the nuclear genome of this new species will further the understanding of the genetic adaptations of P. falciparum to humans. The risk of transfer and emergence of this new species in humans must be now seriously considered given that it was found in two chimpanzees living in contact with humans and its close relatedness to the most virulent agent of malaria

ANALYSIS OF MORPHOLOGICAL AND HYDROLOGICAL CHANGES IN THE CORRENTES RIVER

Meandering rivers have a number of features that differentiate them from rectilinear and anastomosing channels, such as the rapid change of course, which is the result of continuous adjustments of hydro-sedimentary factors. Studying these changes helps to inform on the potential future changes, and generates valuable data for landuse planning. This study aims to identify the morphological changes in the lower Correntes River between 1984 and 2016, and generate information that is currently scarce about the watershed. A temporal analysis of migrating meanders using remote sensing, literature search, and field work was conducted. This river is highly mobile with lateral and downstream migration, exhibiting a rectilinear channel tendency as shown by the decreased sinuosity between 1984 and 2016. This trend reflects channel adjustment in relation to hydro-sedimentary factors. Because the upstream hydroelectric dam retained sediment and enhanced flow velocity, erosion and meander migration increased. In addition to the channel modification, the dam caused observable changes to the river stage and discharg