The role of metabolomics approach in Chronic Obstructive Pulmonary Disease

Trabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de MedicinaChronic Obstructive Pulmonary Disease is one of the most prevalent lung diseases worldwide and according to the World Health Organization is predicted to be the third leading cause of death throughout the world by 2030. It is a complex, multifactorial and heterogeneous disease associated to a high morbidity and high mortality rate in which its prevention, early diagnosis and therapeutic approach is a major challenge in current medicine.Metabolomics and their studies allow an unbiased, qualitative and quantitative systematic analysis of the metabolites in a given biological system, using analytical techniques such as Proton Nuclear Magnetic Resonance spectrometry or Mass Spectrometry. These studies have contributed with important data on the pathogenesis and etiology of COPD, as well as in establishing biomarkers of disease, progression and exacerbation. They also have been shown to be a potential tool in the differential diagnosis between COPD and other respiratory diseases, by distinguishing metabolic profiles, as well as the monitoring therapy response and the identification of new therapeutic targets in COPD.This review intends to systematize current knowledge provided by the most recent metabolomic studies performed in the area of COPD, including the understanding of its role and potential future in the different areas of this pathology. .A Doença Pulmonar Obstrutiva Crónica é uma das doenças respiratórias mais prevalentes em todo o mundo e de acordo com a Organização Mundial de Saúde prevê-se que seja a terceira causa de morte a nível mundial em 2030. É uma doença complexa, multifactorial e heterogénea associada a uma elevada taxa de mortalidade e morbilidade, em que a sua prevenção, diagnóstico precoce e abordagem terapêutica são grandes desafios na medicina atual. A área científica da metabolómica e os seus estudos permitem a análise sistemática imparcial, qualitativa e quantitativa dos metabolitos num determinado sistema biológico, recorrendo a técnicas analíticas como espectrometria por Ressonância Nuclear Magnética de Hidrogénio ou espectrometria de massa. Estes estudos têm contribuído com dados sobre a patogénese e etiologia da DPOC e com propostas de biomarcadores de doença, de progressão e exacerbação. Tem igualmente demonstrado ser um potencial instrumento no diagnóstico diferencial entre a DPOC e outras doenças respiratórias através da distinção dos perfis metabolómicos, assim como na monitorização da terapêutica e identificação de possíveis novos alvos terapêuticos na DPOC.Esta revisão pretende sistematizar o conhecimento atual fornecido pelos mais recentes estudos metabolómicos realizados na área da DPOC, compreendendo o seu papel e o potencial futuro nas diferentes áreas desta patologia.

Portuguese recommendations for the use of methotrexate in the treatment of rheumatoid arthritis

Objectives:To develop Portuguese evidence-based recommendations for the use of methotrexate (MTX) in daily clinical practice in rheumatic disorders. Methods:The Portuguese project was integrated in the multinational 3E Initiative (Evidence, Expertise, Exchange) 2007-2008 where a total of 751 rheumatologists from 17 countries have participated. Ten clinical questions concerning the use of MTX in rheumatic diseases were formulated and the Portuguese group added three more questions. A systematic literature search in Medline, Embase, Cochrane Library and 2005-2007 ACR/EULAR meeting abstracts was conducted. Selected articles were systematically reviewed and the evidence was appraised according to the Oxford Levels of Evidence. In Portugal, a national meeting was held in Obidos on February 15 th and 16 th, 2008, involving 50 rheumatologists who discussed and voted by Dephi method the recommendations. Finally, the agreement among the rheumatologists and the potential impact on their clinical practice was assessed. Results: Thirteen national key recommendations on the use of MTX were formulated: work-up before starting MTX, optimal dosage and route of administration, use of folic acid, monitoring, management of hepatotoxicity, long-term safety, mono versus combination therapy, management in the perioperative period, during infections, before/during pregnancy and after clinical remission, screening and treatment of tuberculosis and the role of MTX as a steroid-sparing agent in rheumatic diseases. Discussion: The Portuguese recommendations for the use of MTX in daily clinical practice were developed, which are evidence-based and supported by a panel of 50 rheumatologists, enhancing their validity and practical use. This project was integrated in a multinational initiative that led to the recent publication of ten multinational recommendations which differ from ours in some specific aspects.publishersversionpublishe

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved