Fed, but not Fasted, Adrenalectomized Rats Survive the Stress of Hemorrhage and Hypovolemia

We have recently shown that conscious adrenalectomized rats exhibit nearly normal recovery of arterial blood pressure during the 5 h after hemorrhage. In those experiments, it appeared that a previous reduction in food intake might have compromised the recovery of blood pressure and increased mortality. These experiments were designed to test in conscious sham-adrenalectomized (control) and adrenalectomized rats prepared with indwelling arterial and venous cannulae: 1. The effects of a 20- to 24-h fast (compared to rats fed ab libitum) on the mobilization of plasma substrates and recovery of arterial blood pressure after a 15 ml/kg - 5 min hemorrhage, and 2. Vascular responsivity to pressor agents in fed or fasted groups before or 2 h after hemorrhage. In all rats hemorrhage resulted in decreased arterial pressure and heart rate. Arterial pressure recovered to near normal in both fed and fasted control groups and in the led adrenalectomized rats, and all of these rats survived for 24 h after stress. By contrast, in the fasted adrenalectomized rats, arterial pressure recovered only during the first 1.5 - 2 h and then failed, resulting in 100% mortality by 3-5 h. Compared to the other three groups, in which substrate levels either increased or remained fairly stable, plasma glucose and beta-hydoxybutyrate concentrations fell steadily, from 1.5-2 h after hemorrhage until death occurred in the fasted adrenalectomized rats. Basal ACTH concentrations were elevated cormpared to control values in both adrenalectomized groups (fed and fasted). Hemorrhage caused increases in plasma ACTH in all groups; the magnitude of the responses did not differ among the groups. The dilution of Evans' blue dve after hemorrhage (used as an index of fluid movement into the vascular space) was not different in contol and adrenalectomized rats (either fed or fasted). There were no differences in pressor responses to phenylephrine, vasopressin, or angiotensin-II between the fed and fasted condition in the control rats either before or after hemorrhage. There was a fasting-associated decrease in vascular responsivity, to vasopressin, but normal responsivity to phenylephrine and angiotensin-II, in the adrenal-ectomized rats both before and after hemorrhage. We conclude that: (1) since fed adrenalectomized rats all survived the stress, adrenal hormones are not required for survival unless fasting is a prior condition; (2) vascular responsiveness to phenylephrine and angiotensin-II is not altered by fasting and is, therefore, probably not the proximate cause of cardiovascular svstem failure; and (3) from these data we cannot distinguish between a failure in substrate supply and a failure in some component of the cardiovascular svstem, other than vascular responsivity, that results in death after hemorrhage in fasted adrenalectomized rats

Microparticles from vascular endothelial growth factor pathway inhibitor-treated cancer patients mediate endothelial cell injury

Vascular endothelial growth factor pathway inhibitors (VEGFi), used as anti-angiogenic drugs to treat cancer are associated with cardiovascular toxicities through unknown molecular mechanisms. Endothelial cell-derived microparticles (ECMPs) are biomarkers of endothelial injury and are also functionally active since they influence downstream target cell signalling and function. We questioned whether microparticle (MP) status is altered in cancer patients treated with VEGFi and whether they influence endothelial cell function associated with vascular dysfunction. Plasma MPs were isolated from cancer patients before and after treatment with VEGFi (pazopanib, sunitinib, or sorafenib). Human aortic endothelial cells (HAECs) were stimulated with isolated MPs (106 MPs/mL). Microparticle characterization was assessed by flow cytometry. Patients treated with VEGFi had significantly increased levels of plasma ECMP. Endothelial cells exposed to post-VEGFi treatment ECMPs induced an increase in pre-pro-ET-1 mRNA expression, corroborating the increase in endothelin-1 (ET-1) production in HAEC stimulated with vatalanib (VEGFi). Post-VEGFi treatment MPs increased generation of reactive oxygen species in HAEC, effects attenuated by ETA (BQ123) and ETB (BQ788) receptor blockers. VEGFi post-treatment MPs also increased phosphorylation of the inhibitory site of endothelial nitric oxide synthase (eNOS), decreased nitric oxide (NO), and increased ONOO− levels in HAEC, responses inhibited by ETB receptor blockade. Additionally, gene expression of proinflammatory mediators was increased in HAEC exposed to post-treatment MPs, effects inhibited by BQ123 and BQ788. Our findings define novel molecular mechanism involving interplay between microparticles, the ET-1 system and endothelial cell pro-inflammatory and redox signalling, which may be important in cardiovascular toxicity and hypertension associated with VEGFi anti-cancer treatment. New and noteworthy: our novel data identify MPs as biomarkers of VEGFi-induced endothelial injury and important mediators of ET-1-sensitive redox-regulated pro-inflammatory signalling in effector endothelial cells, processes that may contribute to cardiovascular toxicity in VEGFi-treated cancer patients

Service and Protocol Architecture for the MAFTIA Middleware

This document describes the specification of the MAFTIA middleware architecture. This specification focusses on the models, building blocks and services. It describes the tradeoffs made in terms of models, the choices of building blocks and their topology, and the portfolio of services to be offered by the MAFTIA middleware to applications and high-level services. In particular, regarding the system model, it presents a detailed discussion on the fault, synchrony, topological, and group models, which were used to guide the overall architecture. The architecture was divided into two main levels, the site part which connects to the network and handles all inter-host operations, and a participant part which takes care of all distributed activities and relies on the services provided by the site-part component

Complete Specification of APIs and Protocols for the MAFTIA Middleware

This document describes the complete specification of the APIs and Protocols for the MAFTIA Middleware. The architecture of the middleware subsystem has been described in a previous document, where the several modules and services were introduced: Activity Services; Communication Services; Network Abstraction; Trusted and Untrusted Components. The purpose of the present document is to make concrete the functionality of the middleware components, by defining their application programming interfaces, and describing the protocols implementing the above-mentioned functionalit

First Specification of APIs and Protocols for the MAFTIA Middleware

This document describes the first specification of the APIs and Protocols for the MAFTIA Middleware. The architecture of the middleware subsystem has been described in a previous document, where the several modules and services were introduced: Activity Services; Communication Services; Network Abstraction; Trusted and Untrusted Components. The purpose of the present document is to make concrete the functionality of the middleware components, by defining their application programming interfaces, and describing the protocols implementing the above-mentioned functionalit

Increased risk of venous thrombosis by AB alleles of the ABO blood group and Factor V Leiden in a Brazilian population

Most cases of a predisposition to venous thrombosis are caused by resistance to activated protein C, associated in 95% of cases with the Factor V Leiden allele (FVL or R506Q). Several recent studies report a further increased risk of thrombosis by an association between the AB alleles of the ABO blood group and Factor V Leiden. The present study investigated this association with deep vein thrombosis (DVT) in individuals treated at the Hemocentro de Pernambuco in northeastern Brazil. A case-control comparison showed a significant risk of thrombosis in the presence of Factor V Leiden (OR = 10.1), which was approximately doubled when the AB alleles of the ABO blood group were present as well (OR = 22.3). These results confirm that the increased risk of deep vein thrombosis in the combined presence of AB alleles and Factor V Leiden is also applicable to the Brazilian population suggesting that ABO blood group typing should be routinely added to FVL in studies involving thrombosis

The Prosensory Function of Sox2 in the Chicken Inner Ear Relies on the Direct Regulation of Atoh1

The proneural gene Atoh1 is crucial for the development of inner ear hair cells and it requires the function of the transcription factor Sox2 through yet unknown mechanisms. In the present work, we used the chicken embryo and HEK293T cells to explore the regulation of Atoh1 by Sox2. The results show that hair cells derive from Sox2-positive otic progenitors and that Sox2 directly activates Atoh1 through a transcriptional activator function that requires the integrity of Sox2 DNA binding domain. Atoh1 activation depends on Sox transcription factor binding sites (SoxTFBS) present in the Atoh1 3′ enhancer where Sox2 directly binds, as shown by site directed mutagenesis and chromatin immunoprecipitation (ChIP). In the inner ear, Atoh1 enhancer activity is detected in the neurosensory domain and it depends on Sox2. Dominant negative competition (Sox2HMG-Engrailed) and mutation of the SoxTFBS abolish the reporter activity in vivo. Moreover, ChIP assay in isolated otic vesicles shows that Sox2 is bound to the Atoh1 enhancer in vivo. However, besides activating Atoh1, Sox2 also promotes the expression of Atoh1 negative regulators and the temporal profile of Atoh1 activation by Sox2 is transient suggesting that Sox2 triggers an incoherent feed-forward loop. These results provide a mechanism for the prosensory function of Sox2 in the inner ear. We suggest that sensory competence is established early in otic development through the activation of Atoh1 by Sox2, however, hair cell differentiation is prevented until later stages by the parallel activation of negative regulators of Atoh1 function

Bologna process, higher education and a few considerations about the New University

O presente artigo analisa o que se convencionou chamar de Processo de Bolonha, isto é, a produção de uma “política pública de um meta-Estado para um meta-campo universitário”, constituindo-se em uma política educacional supranacional, comum aos estados-membros da União Européia, com vista à construção de um “espaço europeu de educação superior”. O processo político e de reformas institucionais, realizado por cada governo nacional, conduzirá ao estabelecimento efetivo do novo sistema europeu de educação superior até 2010, incluindo atualmente 45 países – todos os da UE e outros 18 países europeus não pertencentes a ela. Nesse sentido, por se tratar de um vastíssimo número de “subsistemas nacionais” e de instituições educativas, atribui-se um grande protagonismo às questões relativas à “garantia de qualidade”. Analisam-se, igualmente, as recentes transformações na educação superior no Brasil, em que o projeto da chamada “Universidade Nova” e o Programa de Apoio a Planos de Reestruturação e Expansão das Universidades Federais (REUNI) constituem-se nas manifestações mais claras do reordenamento desse nível de ensino (seguindo os parâmetros de Bolonha), que já experimentara grandes transformações nos governos de Fernando Henrique Cardoso (1995-2002) e teve prosseguimento nos governos de Luiz Inácio Lula da Silva (2003-2006; 2007), embora com distintos matizes.This article analyzes what is conventionally known as the Bologna Process, or the making of a “public policy of a meta-State for a University meta-field” that corresponds to a supranational educational policy for all the European Union membership States, with the goal of building a “European higher education space.” The political process and the institutional reforms of each national government intends to establish the new European higher education system until 2010, with 45 countries – the number reflects current developments, including the EU membership States and 18 non-EU countries. Given the high quantity and the myriads of “national subsystems” and educational institutions involved, “quality assurance” becomes a major task in this process. We analyze, in the same way, the recent higher education changes in Brazil, where the so-called “New University” project and the Program of Support for the Restructuring and Expansion of Brazilian Federal Universities (REUNI, in Portuguese) are the clearest expressions of the reshaping of the higher education system (in accordance with the Bologna standards) after the dramatic changes made by Fernando Henrique Cardoso´s government (1995-2002) and continued by Luiz Inácio Lula da Silva´s government (2003-2006; 2007), despite some differences between both administrations

Development and characterization of microsatellite markers for the tsetse species Glossina brevipalpis and preliminary population genetics analyses

Tsetse flies, the vectors of African trypanosomes are of key medical and economic importance and one of the constraints for the development of Africa. Tsetse fly control is one of the most effective and sustainable strategies used for controlling the disease. Knowledge about population structure and level of gene flow between neighbouring populations of the target vector is of high importance to develop appropriate strategies for implementing effective management programmes. Microsatellites are commonly used to identify population structure and assess dispersal of the target populations and have been developed for several tsetse species but were lacking for Glossina brevipalpis. In this study, we screened the genome of G. brevipalpis to search for suitable microsatellite markers and nine were found to be efficient enough to distinguish between different tsetse populations. The availability of these novel microsatellite loci will help to better understand the population biology of G. brevipalpis and to assess the level of gene flow between different populations. Such information will help with the development of appropriate strategies to implement the sterile insect technique (SIT) in the framework of an area-wide integrated pest management (AW-IPM) approach to manage tsetse populations and ultimately address the trypanosomoses problem in these targeted areas