Calcium signaling and the novel anti-proliferative effect of the UTP-sensitive P2Y11 receptor in rat cardiac myofibroblasts

During myocardial ischemia and reperfusion both purines and pyrimidines are released into the extracellular milieu, thus creating a signaling wave that propagates to neighboring cells via membrane-bound P2 purinoceptors activation. Cardiac fibroblasts (CF) are important players in heart remodeling, electrophysiological changes and hemodynamic alterations following myocardial infarction. Here, we investigated the role UTP on calcium signaling and proliferation of CF cultured from ventricles of adult rats. Co-expression of discoidin domain receptor 2 and -smooth muscle actin indicate that cultured CF are activated myofibroblasts. Intracellular calcium ([Ca2+]i) signals were monitored in cells loaded with Fluo-4 NW. CF proliferation was evaluated by the MTT assay. UTP and the selective P2Y4 agonist, MRS4062, caused a fast desensitizing [Ca2+]i rise originated from thapsigargin-sensitive internal stores, which partially declined to a plateau providing the existence of Ca2+ in the extracellular fluid. The biphasic [Ca2+]i response to UTP was attenuated respectively by P2Y4 blockers, like reactive blue-2 and suramin, and by the P2Y11 antagonist, NF340. UTP and the P2Y2 receptor agonist MRS2768 increased, whereas the selective P2Y11 agonist NF546 decreased, CF growth; MRS4062 was ineffective. Blockage of the P2Y11receptor or its coupling to adenylate cyclase boosted UTP-induced CF proliferation. Confocal microscopy and Western blot analysis confirmed the presence of P2Y2, P2Y4 and P2Y11 receptors. Data indicate that besides P2Y4 and P2Y2 receptors which are responsible for UTP-induced [Ca2+]i transients and growth of CF, respectively, synchronous activation of the previously unrecognized P2Y11 receptor may represent an important target for anti-fibrotic intervention in cardiac remodeling.

Challenges for e-learning and adult students in higher education

This article examines Lifelong Learning, from the perspective of the adult learner in higher education, by presenting some of the results of a project, funded by the European Commission's Socrates Programme, LIHE, Learning in Higher Education. It is structured as follows: first, the background of the project is described, then the experiences of the adult student, concerning their induction and tuition, are presented. Some future trends concerning adults in higher education and lifelong learning are outlined and conclusions drawn.

Educational characteristics of adult students in portuguese technological schools

Despite a massive expansion of education in Portugal, since the 1970’s, educational attainment of the adult population in the country remains low. The numbers of working-age people in some form of continuing education are among the lowest, according to the OECD and EU-27 statistics. Technological Schools(TS), initially created in the 1990’s, under the umbrella of the Ministry of Economy in partnership with industry and industrial associations, aimed to prepare qualified staff for industries and services in the country, particularly in the engineering sector, through the provision of post secondary non-university programmes of studies, the CET (Technological Specialization Courses). Successful CET students are awarded a DET(Diploma of Technological Specialization), which corresponds to Vocational Qualification level IV of the EU, according to the latest alteration (2005) of the Education Systems Act (introduced in 1986). In this, CET’s are also clearly defined as one of the routes for access to Higher Education (HE), in Portugal. The PRILHE (Promoting Reflective and Independent Learning in Higher Education) multinational project, funded by the European Socrates Grundtvig Programme, aimed to identify the learning processes which enable adult students in higher education to become autonomous reflective learners and search best practices to support these learning processes. During this research, both quantitative and qualitative methods were used to determine how students organise their studies and develop their learning skills. The Portuguese partner in the project’ consortium used a two case studies approach, one with students of Higher Education Institutions and other with students of TS. This paper only applies to students of TS, as these have a predominant bias towards engineering. Results show that student motivation and professional teaching support contribute equally to the development of an autonomous and reflective approach to learning in adult students; this is essential for success in a knowledge economy, where lifelong learning is the key to continuous employment.

Adult learners in higher education

Copyright © 2005, Idea Group Inc., distributing in print or electronic forms without written permission of IGI is prohibited.

Building a knowledge and learning society in Portugal: adult students in technological schools and higher education institutions

Lifelong learning (LLL) has received increasing attention in recent years. It implies that learning should take place at all stages of the “life cycle and it should be life-wide, that is embedded in all life contexts from the school to the work place, the home and the community” (Green, 2002, p.613). The ‘learning society’, is the vision of a society where there are recognized opportunities for learning for every person, wherever they are and however old they happen to be. Globalization and the rise of new information technologies are some of the driving forces that cause depreciation of specialised competences. This happens very quickly in terms of economic value; consequently, workers of all skills levels, during their working life, must have the opportunity to update “their technical skills and enhance general skills to keep pace with continuous technological change and new job requirements” (Fahr, 2005, p. 75). It is in this context that LLL tops the policy agenda of international bodies, national governments and non-governmental organizations, in the field of education and training, to justify the need for LLL opportunities for the population as they face contemporary employability challenges. It is in this context that the requirement and interest to analyse the behaviour patterns of adult learners has developed over the last few years

Lifelong learning: case study of adult students in portuguese technological schools and higher education institutions

Paper to be presented in ESREA 2007 ADC Network Seminar - Changing Relationships between the State, Civil Society and the Citizen: Implications for adult education and adult learning, 14 -16 June 2007 - University of Minho - Campus de Gualtar, Braga (Portugal).

Learning in higher education: strategies to overcome challenges faced by adult students - lessons drawn from two studies in portugal

Int’l J. of Information and Communication Technology Education, 3(2), 1-14, April-June 2007

Descending pain modulation in a Kaolin-induced hydrocephalus rat model

Pain transmission at the spinal cord is modulated by descending actions that arise from supraspinal areas which collectively form the endogenous pain control system. Two key areas involved of the endogenous pain control system have a circunventricular location, namely the periaqueductal grey (PAG) and the locus coeruleus (LC). The PAG plays a crucial role in descending pain modulation as it conveys the input from higher brain centers to the spinal cord. As to the LC, it is involved in descending pain inhibition by direct noradrenergic projections to the spinal cord. In the context of neurological defects, several diseases may affect the structure and function of the brain. Hydrocephalus is a congenital or acquired disease characterized by an enlargement of the ventricles which leads to a distortion of the adjacent tissues, including the PAG and LC. Usually, patients suffering from hydrocephalus present dysfunctions in learning and memory and also motor deficits. It remains to be evaluated if lesions of the periventricular brain areas involved in pain control during hydrocephalus may affect descending pain control and, herein, affect pain responses. The studies included in the present thesis used an experimental model of hydrocephalus (the rat injected in the cisterna magna with kaolin) to study descending modulation of pain, focusing on the two circumventricular regions referred above (the PAG and the LC). In order to evaluate the effects of kaolin injection into the cisterna magna, we measured the degree of ventricular dilatation in sections encompassing the PAG by standard cytoarquitectonic stanings (thionin staining). For the LC, immunodetection of the noradrenaline-synthetizing enzyme tyrosine hydroxylase (TH) was performed, due to the noradrenergic nature of the LC neurons. In general, rats with kaolin-induced hydrocephalus presented a higher dilatation of the 4th ventricle, along with a tendency to a higher area of the PAG. Due to the validated role of detection the c-fos protooncogene as a marker of neuronal activation, we also studied neuronal activation in the several subnuclei which compose the PAG, namely the dorsomedial, dorsolateral, lateral and ventrolateral (VLPAG) parts. A decrease in the numbers of neurons immunoreactive for Fos protein (the product of activation of the c-fos protooncogene) was detected in rats injected with kaolin, whereas the remaining PAG subnuclei did not present changes in Fos-immunoreactive nuclei. Increases in the levels of TH in the LC, namely at the rostral parts of the nucleus, were detected in hydrocephalic animals. The following pain-related parameters were measured, namely 1) pain behavioural responses in a validated pain inflammatory test (the formalin test) and 2) the nociceptive activation of spinal cord neurons. A decrease in behavioral responses was detected in rats with kaolin-induced hydrocephalus was detected, namely in the second phase of the test (inflammatory phase). This is the phase of the formalin test in which the motor behaviour is less important, which is important since a semi-quantitative analysis of the motor performance of rats injected with kaolin indicates that these animals may present some motor impairments. Collectively, the results of the behavioral studies indicate that rats with kaolin-induced hydrocephalus exhibit hypoalgesia. A decrease in Fos expression was detected at the superficial dorsal layers of the spinal cord in rats with kaolin-induced hydrocephalus, further indicating that hydrocephalus decreases nociceptive responses. It remains to be ascertained if this is due to alterations in the PAG and LC in the rats with kaolin-induced hydrocephalus, which may affect descending pain modulation. It remains to be evaluated what are the mechanisms underlying the increased pain inhibition at the spinal dorsal horn in the hydrocephalus rats. Regarding the VLPAG, the decrease in neuronal activity may impair descending modulation. Since the LC has higher levels of TH in rats with kaolininduced hydrocephalus, which also appears to increase the noradrenergic innervation in the spinal dorsal horn, it is possible that an increase in the release of noradrenaline at the spinal cord accounts for pain inhibition. Our studies also determine the need to study in detail patients with hydrocephalus namely in what concerns their thresholds to pain and to perform imaging studies focused on the structure and function of pain control areas in the brain.

QuEChERS: a sample preparation for extraction of carbaryl from rat feces

Carbamate compounds are an important group of cholinesterase inhibitors. There is a need for creating awareness regarding the risks of the inadequate carbamate use in the residential areas due to potential adverse human effects. Carbaryl is a commonly used pesticide worldwide. A simple, fast, and high throughput method was developed employing liquid chromatography with fluorescence detector to determine carbaryl residues in rat feces. The extraction was performed by using a rapid, easy, cheap, effective, reliable, and safe (QuEChERS) method, using acetonitrile as the extracting solvent. The parameters for the performance of the extraction method were optimized, such as ratio of mass of sample per volume of extraction solvent, QuEChERS content, and cleanup columns. Linear response was obtained for all calibration curves (solven and matrix-matched) over the established concentration range (5 500 mg/L) with a correlation coefficients higher than 0.999. The achieved recovery was 97.9% with relative standard deviation values of 1.1% (n D 4) at 167 mg/kg fortified concentration level and the limits of detection and quantification were 27.7 and 92.3 mg/kg respectively.

Detrimental role of prolonged sleep deprivation on adult neurogenesis

Adult mammalian brains continuously generate new neurons, a phenomenon called adult neurogenesis. Both environmental stimuli and endogenous factors are important regulators of adult neurogenesis. Sleep has an important role in normal brain physiology and its disturbance causes very stressful conditions, which disrupt normal brain physiology. Recently, an influence of sleep in adult neurogenesis has been established, mainly based on sleep deprivation studies. This review provides an overview on how rhythms and sleep cycles regulate hippocampal and subventricular zone neurogenesis, discussing some potential underlying mechanisms. In addition, our review highlights some interacting points between sleep and adult neurogenesis in brain function, such as learning, memory, and mood states, and provides some insights on the effects of antidepressants and hypnotic drugs on adult neurogenesis.