Co-expression of NPY and VIP in human dental pulp

Introduction: The regulation of pulpal haemodynamics in health and disease involves sympathetic and parasympathetic mechanisms in which both neuropeptide Y (NPY; a sympathetic vasoconstrictor) and vasoactive intestinal polypeptide (VIP; a parasympathetic vasodilator) may play potential pathophysiological roles. We have previously investigated the levels of NPY or VIP present in human dental pulp tissue and shown that their expression is up-regulated in caries induced pulpal inflammation. Objectives: The aim of this study was to investigate the potential correlation between NPY and VIP levels measured in the same dental pulp samples using radioimmunoassay (RIA). Methods: Pulp tissue was obtained from extracted teeth, classified as follows; healthy (n=22), moderately carious (n=20) and grossly carious (n=26). Samples were processed for RIA by boiling in acetic acid as previously described. The levels of NPY and VIP, measured by RIA, were expressed as ng/gram of pulp tissue. The nature of the relationship between NPY and VIP levels in human pulp tissue was tested by calculating Pearson's product moment correlation coefficient using the linear regression test. Results: Calculation of Pearson product moment correlation coefficient showed a significant negative correlation between NPY and VIP levels in pulp tissue samples from non-carious teeth (p = 0.02, r = -.48). This negative correlation in non-carious teeth changed to a significant positive correlation in carious teeth when the levels of NPY and VIP were compared (p = 0.03, r= 0.311). Conclusions: In non-carious teeth, the negative correlation between NPY and VIP levels is in keeping with the previously described modulatory influence of cholinergic nerves on sympathetic function which may be perturbed as caries develops.

Neuropeptide Receptors in the Dental Pulp

Objectives: The inflammatory response to pulpal injury or infection has major clinical significance. The aim of the study is to investigate the presence and regulation of expression of neuropeptide receptors on human pulp fibroblasts and whole pulp tissue. This study will investigate the expression of Substance P (NK-1) and Neuropeptide Y (NPY-Y1) receptors on pulp fibroblasts, determine the effects of Transforming Growth Factor Beta-1 (TGF-b1) and Interleukin 1-Beta (IL-1b) on the expression of NK-1 and NPY-Y1 receptors on pulp fibroblasts and examine the levels of receptor expression in whole pulp samples. Methods: Primary pulp fibroblast cell lines were obtained from patients undergoing extractions for orthodontic reasons. The cells were grown to confluence and stimulated for 5 days with IL-1b or TGF-b1. Pulp tissue fragments were obtained from freshly extracted sound and carious teeth, snap frozen in liquid nitrogen and cracked open using a vice. The monolayer was removed with cell scrapers and pelleted. The cell membranes of the cultured cells and the whole tissue were isolated using a Mem-PER® Eukaryotic Membrane Protein Extraction Reagent Kit (Pierce, UK). The membrane proteins were separated by SDS-PAGE and Western blotting was used to detect the presence of NK-1 and NPY-Y1. Results: Initial results demonstrated the presence of NK-1 and NPY-Y1 in cultured pulp fibroblasts. Following the 5 day incubation with TGF-b1, the cells appeared not to express NK-1. IL-1b had a slight stimulatory effect on NK-1 expression. The NPY-Y1 expression was not affected by either TGF-b1 or IL-1b. In whole pulp samples, levels of NK-1 were increased in carious teeth compared to caries-free teeth. The NPY-Y1 levels were similar in carious and non-carious teeth. Conclusion: These findings give an insight into how pulp cells react to inflammatory stimuli with regards to neuropeptide receptor expression and their roles in health and disease

Dedicated severe asthma services improve health-care use and quality of life

Background: Systematic assessment of severe asthma can be used to confirm the diagnosis, identify comorbidities, and address adherence to therapy. However, the prospective usefulness of this approach is yet to be established. The objective of this study was to determine whether the systematic assessment of severe asthma is associated with improved quality of life (QoL) and health-care use and, using prospective data collection, to compare relevant outcomes in patients referred with severe asthma to specialist centers across the United Kingdom. Methods: Data from the National Registry for dedicated UK Difficult Asthma Services were used to compare patient demographics, disease characteristics, and health-care use between initial assessment and a median follow-up of 286 days. Results: The study population consisted of 346 patients with severe asthma. At follow-up, there were significant reductions in health-care use in terms of primary care or ED visits (66.4% vs 87.8%, P < .0001) and hospital admissions (38% vs 48%, P = .0004). Although no difference was noted in terms of those requiring maintenance oral corticosteroids, there was a reduction in steroid dose (10 mg [8-20 mg] vs 15 mg [10-20 mg], P = .003), and fewer subjects required short-burst steroids (77.4% vs 90.8%, P = .01). Significant improvements were seen in QoL and control using the Asthma Quality of Life Questionnaire and the Asthma Control Questionnaire. Conclusions: To our knowledge, this is the first time that a prospective study has shown that a systematic assessment at a dedicated severe asthma center is associated with improved QoL and asthma control and a reduction in health-care use and oral steroid burden.

Endothelial Function in Hypertension: Victim or Culprit?

Far from simply lining the inner surface of blood vessels, the cellular monolayer that comprises the endothelium is a highly active organ that regulates vascular tone. In health, the endothelium maintains the balance between opposing dilator and constrictor influences, while in disease, it is the common ground on which cardiovascular risk factors act to initiate the atherosclerotic process. As such, it is the site at which cardiovascular disease begins and consequently acts as a barometer of an individual's likely future cardiovascular health. The vascular endothelium is a very active organ responsible for the regulation of vascular tone through the effects of locally synthesized mediators, predominantly nitric oxide (NO), endothelial NO synthase (eNOS), and superoxide. NO is abundantly evident in normally functioning vasculature where it acts as a vasodilator, inhibits inflammation, and has an antiaggregant effect on platelets. Its depletion is both a sign and cause of endothelial dysfunction resulting from reduced activity of eNOS and amplified production of nicotinamide adenine dinucleotide oxidase, which, in turn, results in raised levels of reactive oxygen species. This cascade is the basis for reduced vascular compliance through an imbalanced regulation of tone with a predominance of vasoconstrictive elements. Further, structural changes in the microvasculature are a critical early step in the loss of normal function. This microvascular dysfunction is known to be highly predictive of future macrovascular events and is consequently a very attractive target for intervention in the hypertensive population in order to prevent cardiovascular events.

A vivência emocional dos enfermeiros nos cenários da prestação de cuidados ao doente oncológico: o caso dos enfermeiros de um serviço de oncologia médica do Instituto Português de Oncologia de Lisboa Francisco Gentil, E.P.E.

Com a presente investigação pretendemos conhecer a vivência das emoções dos enfermeiros nos cenários da prestação de cuidados ao doente oncológico e simultaneamente contribuir para uma melhoria das práticas de intervenção e de gestão emocional em enfermagem nos contextos de trabalho em Oncologia, procurando dar resposta à pergunta inicial de investigação: Qual a vivência emocional dos enfermeiros nos cenários da prestação de cuidados ao doente oncológico? Nas opções metodológicas optámos pelo paradigma qualitativo, onde a entrevista narrativa foi a técnica privilegiada de recolha de informação, tendo permitido compreender com profundidade a forma como os enfermeiros vivem a prestação de cuidados ao doente oncológico. As experiências emocionais consideradas mais marcantes foram na generalidade aquelas que mais penosas se constituíram para os entrevistados, relacionadas com uma relação mais próxima e profunda com o doente e com situações de morte e sofrimento. Consequentemente os sentimentos e emoções referidos foram na sua maioria negativa. Na prática de cuidar do doente oncológico verificou-se a influência marcada dos mitos sociais e pessoais associados à doença cancro, tendo sido reconhecida de forma global a complexidade e especificidade inerentes a esta prestação de cuidados, tão gratificante, quanto desgastante. O uso de mecanismos de gestão das experiências emocionais refletiu-se no recurso a estratégias pessoais e externas, usadas na sua maioria com o objetivo de o desgaste emocional. Foram sugeridas várias medidas de intervenção organizacional no reconhecer uníssono da necessidade de acompanhamento e suporte por parte da organização de saúde. Os resultados desta investigação acrescentam assim todo um conjunto de novos dados que ajudam na compreensão da problemática da vivência emocional dos enfermeiros, na certeza de que esta melhorará a prestação de cuidados ao doente oncológico, com consequente otimização organizacional. /ABSTRACT - With this present investigation we intend to study the emocional life of nurses while providing health care to oncological patients and simultaneously contribute to an improvement of the intervention and emotional management practices in nursing in the contexts of working in Oncology, trying to answer the initial question of the inquiry: What is the emotional life of nurses in health care scenerjy to oncological patients? As far as the methodology is concerned we chose the qualitative paradigm, in which the narrative interview was the privileged technique to gather information. That allowed us to deeply understand the way nurses live the providing of health care to the oncological patient, their emotional experiences, what they feel and express, what moves and consumes them, as well as the forms of emotional management. The most striking emotional experiences have, in general, been those considered most painful by the interviewed nurses, usually related to a closer and deeper relation with the patient and situations of death and suffering. The consequent feelings and emotions have been mostly negative. Health care provided to oncologic patients is strongly influenced by social and personal myths related to cancer and both the complexity and specificity inherent to this kind of health care has been acknowledged as rewarding, as consuming. The use of means of emotional management is visible in the resource to personal and external strategies, used to diminish the emotional consumption. They have also suggested some measures of organizational intervention in the unison recognition of the need of accompaniment and support from the health care institution. The results of this investigation, thus add whole a set of new data that helps in the understanding of the problematic of the emotional life of nurses, in the certainty that this will improve the providing of care to the oncolologically sick person, with consequent organizational optimization.

Cuidar na "Entrada na reforma": uma intervenção conducente à promoção da saúde de indivíduos e de famílias

ENQUADRAMENTO: Ao longo do ciclo vital, os indivíduos e as suas famílias estão em constante desenvolvimento. Os acontecimentos de vida transicionais, pelos fenómenos de mudança e adaptação que envolvem, são em grande parte responsáveis por esse processo e dada a vulnerabilidade em saúde a que os poderá expor; constituem momentos cruciais de intervenção para a Enfermagem (Meleis, 2010). A “entrada na reforma” constitui um desses acontecimentos que, quando não devidamente preparado, poderá pôr em causa o processo de envelhecimento activo (Fonseca, 2004a; Veríssimo, 2008). Estudar os efeitos que esta transição exerce nas vivências dos indivíduos e das suas famílias, ajudará a compreender a forma como esta poderá comprometer o envelhecimento e, simultaneamente, poderá trazer um conhecimento mais profícuo para aquele que deverá ser o cuidar de indivíduos e famílias num período da “entrada na reforma”. OBJECTIVO: Conhecer as vivências percepcionadas pelos indivíduos e suas famílias durante o processo de transição originado pela “entrada na reforma”, de forma a apresentar estratégias e linhas orientadoras de intervenção de Enfermagem, conducentes à promoção do seu estado de saúde. MÉTODO: O estudo foi desenvolvido em duas fases. Uma primeira, de carácter quantitativo, na qual foi aplicado um questionário a 432 indivíduos, que se encontravam aposentados há menos de cinco anos. A selecção da amostra foi conseguida pelo método “bola de neve” e os dados obtidos foram analisados com recurso ao programa SPSS17 e à técnica de análise de conteúdo de Bardin. Uma segunda fase, de carácter qualitativo, na qual foram entrevistadas 14 famílias de indivíduos que tinham percepcionado alterações e/ou dificuldades, na primeira fase deste estudo. A análise da informação sustentou-se num referencial teórico de interaccionismo simbólico e numa metodologia de investigação narrativa, contando com o auxílio do Nvivo8. RESULTADOS E DISCUSSÃO: As características sócio-demográficas, os motivos da aposentação e as expectativas que detinham relativamente à “entrada na reforma”, interferiram na forma como os indivíduos viveram a transição. Para os protagonistas, as principais alterações e/ou dificuldades percepcionadas na referida vivência foram a adaptação à alteração das rotinas diárias (26,5%), a dificuldade em ocupar o tempo (14,7%) e a diminuição do poder económico (14,0%) e as famílias constituíram a principal fonte de apoio (71,5%), para fazer face às mesmas. As famílias percepcionaram uma idêntica mudança e traduziram-na por uma dualidade de significados que se identificou com percepções de ganho e de perda, para as suas vidas. Os significados reaprender a “estar”, a “sentir” e a “ser”, traduziram o processo de adaptação a que estiveram sujeitos. IMPLICAÇÕES PARA A PRÁTICA DA ENFERMAGEM: Cuidar no período da “entrada na reforma” deverá obedecer a um modelo de intervenção muito próprio que se harmonize, não apenas com a singularidade dos indivíduos e famílias que protagonizam este acontecimento de vida, mas, também, e de forma muito particular, com a especificidade das mudanças que essa vivência transicional lhes possa vir a suscitar.

Mitochondrial dysfunction in fatty acid β-oxidation disorders

Mitochondria are central organelles for cell survival with particular relevance in energy production and signalling, being mitochondrial fatty acid β–oxidation (FAO) one of the metabolic pathways harboured in this organelle. FAO disorders (FAOD) are among the most well studied inborn errors of metabolism, mainly due to their impact in health. Nevertheless, some questions remain unsolved, as their prevalence in certain European regions and how pathophysiological determinants combine towards the phenotype. Analysis of data from newborn screening programs from Portugal and Spain allowed the estimation of the birth prevalence of FAOD revealing that this group of disorders presents in Iberia (and particularly in Portugal) one of the highest European birth prevalence, mainly due to the high birth prevalence of medium chain acyl-CoA dehydrogenase deficiency. These results highlight the impact of this group of genetic disorders in this European region. The characterization of mitochondrial proteome, from patients fibroblasts with FAOD, namely multiple acyl-CoA dehydrogenase deficiency (MADD) and long chain acyl-CoA dehydrogenase deficiency (LCHADD), provided a global perspective of the mitochondrial proteome plasticity in these disorders and highlights the main molecular pathways involved in their pathogenesis. Severe MADD forms show an overexpression of chaperones, antioxidant enzymes (MnSOD), and apoptotic proteins. An overexpression of glycolytic enzymes, which reflects cellular adaptation to energy deficiency due to FAO blockage, was also observed. When LCHADD fibroblasts were analysed a metabolic switching to glycolysis was also observed with overexpression of apoptotic proteins and modulation of the antioxidant defence system. Severe LCHADD present increased ROS alongside with up regulation of MnSOD while moderate forms have lower ROS and down-regulation of MnSOD. This probably reflects the role of MnSOD in buffering cellular ROS, maintain them at levels that allow cells to avoid damage and start a cellular response towards survival. When ROS levels are very high cells have to overexpress MnSOD for detoxifying proposes. When severe forms of MADD were compared to moderate forms no major differences were noticed, most probably because ROS levels in moderate MADD are high enough to trigger a response similar to that observed in severe forms. Our data highlights, for the first time, the differences in the modulation of antioxidant defence among FAOD spectrum. Overall, the data reveals the main pathways modulated in FAOD and the importance of ROS levels and antioxidant defence system modulation for disease severity. These results highlight the complex interaction between phenotypic determinants in FAOD that include genetic, epigenetic and environmental factors. The development of future better treatment approaches is dependent on the knowledge on how all these determinants interact towards phenotype.!

Modelling health state preference data using fixed and random effects models

The use of preference-based measures of health in the measurement of Health Related Quality of Life has become widely used in health economics. Hence, the development of preference-based measures of health has been a major concern for researchers throughout the world. This study aims to model health state preference data using a new preference-based measure of health (the SF- 6D) and to suggest alternative models for predicting health state utilities using fixed and random effects models. It also seeks to investigate the problems found in the SF-6D and to suggest eventual changes to it.