DGH - Livros científicos
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- Talc and AcrylonitrilePublication . IARC Working Group on the Identification of Carcinogenic Hazards to HumansThis volume of the IARC Monographs provides evaluations of the carcinogenicity of talc and acrylonitrile. Talc was defined as mineral (natural) or synthetic product, a hydrated magnesium silicate, that exists in both lamellar and fibrous (including asbestiform) types. Asbestiform talc is not asbestos; however, asbestos is present in some talc deposits and has been shown to contaminate some talc products. A mineral with a high production volume, talc is used in plastics, ceramics, paint, paper, roofing materials, rubber products, animal feed, food, fertilizers, cosmetics, and pharmaceuticals. It is also used in clinical settings for pleurodesis. Occupational exposure to talc dust occurs predominantly during mining and milling, mainly via inhalation, but can also occur among workers in downstream industries. The general population may be exposed via talc-based consumer products, and pathways of exposure include ingestion, inhalation, and dermal contact, including via the perineum. Acrylonitrile is a chemical with a high production volume that is mostly used as a monomer to prepare polymers for the manufacture of fibres for textiles (acrylic fibres) used in clothing and carpets and other textiles, resins, synthetic rubber, and plastics. Occupational exposure occurs mainly in production industries via inhalation and dermal routes. The general population can be exposed to acrylonitrile via cigarette smoking, air pollution, and contact with contaminated consumer products. An IARC Monographs Working Group reviewed evidence from epidemiological studies, cancer bioassays in experimental animals, and mechanistic studies to assess the carcinogenic hazard to humans of exposure to these agents and concluded that: - Talc is probably carcinogenic to humans (Group 2A); - Acrylonitrile is carcinogenic to humans (Group 1).
- Nanotoxicology in Safety Assessment of NanomaterialsPublication . Louro, Henriqueta; Silva, Maria JoãoSince its advent, nanotechnologies are considered key enabling technologies that take advantage of a wide array of nanomaterials (NMs) for biomedical and industrial applications generating significant societal and economic benefits. However, such innovation increases human exposure to these substances through inhalation, ingestion or dermal contact raising public health concerns. Furthermore, the NMs’ specific physicochemical properties, that confer them unique beneficial characteristics, can also elicit nano-bio interactions leading to toxicity and concerns for public health. In addition, such properties can be affected by the surrounding matrix, particularly when incorporated in complex matrices such as food products, leading to secondary features potentially more relevant than primary characteristics for determining their toxicological outcome. These nano specific issues raise the question of whether the NMs may produce adverse outcomes that are not accounted for when using conventional toxicological approaches to assess their safety. Such uncertainties about the safety of NMs for human health and the environment may hamper a faster and more widespread exploration of their potentials. In response, the NMs definition has evolved, and nanotoxicology has developed towards new and more integrative approach methods to support regulatory and policy actions. This book provides a perspective on recent developments in the synthesis, application, and characterization of NMs and the related nanotechnologies, focusing on nanotoxicology for their accurate safety assessment early in the product development stage. The use of complex in vitro models, including multicellular systems and organoids, and “omics-based” approaches, such as transcriptomics or epigenomics, have greatly contributed to an in-depth understanding of the cellular and molecular mechanisms behind some NMs toxicity. Such mechanistic knowledge is equally addressed in this book and has set the basis for a predictive nanotoxicology approach building on adverse outcome pathways. In addition, considering the knowledge provided by the above-mentioned approaches, insights into risk assessment, standardization, and regulation of NMs are also included. Incorporating adequate nanosafety assessment early in the life-cycle of NMs will allow the implementation of the safe and sustainable-by-design paradigm enabling safety to keep pace with innovation.
- p53 in Cancer and beyond - 40 Years after Its DiscoveryPublication . Candeias, Marco M.; Ohki, RiekoThe “p53 team” dictates cell fate and sacrifices cell life as demanded, for the greater good of the organism. The p53 team consists of its close family (p53, p63, and p73 genes), a varied number of isoforms, and a plethora of downstream target genes. Together they control cell stemness, division, chromosome integrity, epigenetics, differentiation, senescence and death; response to stress, infection and disease; reproduction, immunity, metabolism, and regeneration. As a consequence, p53 team function is central to our lives, from birth and development to aging and life span in both health and disease. Forty years after its discovery, we aim to cover important and new aspects of p53 and its team, not only in cancer, but in all the diversity of p53-dependent activities. Authors are invited to review recent work or submit original research in all areas of recent and current p53 research, with an emphasis on work providing molecular insight, including but not limited to novel physiological and pathological functions, or regulatory mechanisms.
- The mRNA Metabolism in Human DiseasePublication . Romão, LuísaIntroduction: The eukaryotic gene expression pathway involves a number of interlinked steps, with messenger RNA (mRNA) being the key intermediate. The precursor mRNA is transcribed from DNA, processed by removal of introns and addition of the cap structure and the poly(A) tail. The mature mRNA is then exported to the cytoplasm where it is translated into protein and finally degraded. In this process, mRNA is associated with RNA-binding proteins forming ribonucleoprotein complexes, whose protein content evolves throughout the lifetime of the mRNA. While the complexity of eukaryotic gene expression allows the production of proteins to be controlled at many levels, it also makes the process vulnerable to errors. Although eukaryotic cells have evolved elaborate mRNA quality control mechanisms that ensure the fidelity of gene expression, some defects are not detected, thus affecting mRNA metabolism. This condition plays a fundamental role in the pathogenesis of several disease processes, such as neurodegeneration and oncogenesis. Besides, exciting recent data have shown that cellular RNAs can be modified post-transcriptionally via dynamic and reversible chemical modifications, the so-called epitranscriptome. These modifications can alter mRNA structure, being able to modulate different steps of the mRNA metabolism that can be associated with various human diseases, such as systemic lupus erythematosus and cancer. This book provides a collection of novel studies and hypotheses aimed to define the pathophysiological consequences of altered mRNA metabolism events in human cells, and is written for a wide spectrum of readers in the field of gene expression regulation. The last chapter highlights how the discovery of disease-causing defects (or modifications) in mRNA can provide a variety of therapeutic targets that can be used for the development of new RNA-based therapeutics. Hopefully, it may also contribute to inspire the drug-developing scientific community.
- Targeted Therapy of Colorectal Cancer SubtypesPublication . Jordan, PeterIn this book, a group of researchers shares their expertise on the identification and characterization of genetic colorectal cancer subtypes. They describe solid pathobiological knowledge on the distinct sporadic tumour subtypes, including the mutations found in oncogenes and tumour suppressor genes, the types of genomic instability encountered, and the cellular signalling pathways activated. The book content indicates opportunities for the development of further pathway-specific therapeutic drugs or drug combinations, allowing to cope with the appearance of resistant tumours. The nine chapters of this book cover the main aspects underlying colorectal cancer development but also of its therapeutic options, which have been undergoing substantial changes by moving from the use of general cytotoxic agents that affect rapidly growing cells to more tumour-specific drugs. In the first case, all dividing cells in the patient’s body are affected and this causes severe and debilitating side effects. In the second case, the increasing knowledge about the molecular genetics of tumours has led to a new generation of drugs, which specifically interfere with the cell survival pathways that are activated in a given tumour. This allowed to identify groups of patients for targeted therapy that is much better tolerated.
- Food contaminants and human health: challenges in chemical mixturesPublication . Alvito, Paula; Assunção, Ricardo; Louro, Henriqueta; Silva, Maria João; Vasco, ElsaThis book compiles the extended abstracts from some of the world-renowned researchers invited to give a lecture at the ICFC2015, in addition to the abstracts from oral and poster sessions.
- Biobancos e Investigação Genética: Orientações ÉticasPublication . Ventura, CéliaNas últimas décadas, muitas instituições de saúde ou académicas foram estabelecendo colecções organizadas de amostras biológicas associadas a dados pessoais. Estes biobancos têm suscitado o interesse da comunidade científica pela sua pertinência relativamente à investigação sobre doenças comuns com impacto em saúde pública. Este interesse levou, inclusivamente, ao aparecimento de vários biobancos privados com fins comerciais. A tendência actual é a construção de biobancos com milhares de amostras para estudar a associação entre variantes genéticos e doenças complexas, a sua interacção com factores ambientais e também com os fármacos, no último caso para garantir uma medicação mais dirigida e eficaz. O sucesso da implementação de um biobanco depende da participação colectiva da sociedade, sendo esta fortemente influenciada por factores socioculturais, tais como a confiança nas instituições e nos seus profissionais. Estes têm a responsabilidade moral de salvaguardar a autonomia e integridade dos participantes em investigação. Uma das formas de respeitar esta autonomia é através do consentimento informado. Contudo, o consentimento informado do participante relaciona-se frequentemente com a utilização primária da amostra, enquanto o seu uso a longo prazo não é mencionado. Assim, é necessário definir princípios para a utilização de amostras antigas em novos estudos, quando um novo consentimento do participante se torna difícil ou impossível de obter. Por outro lado, a obtenção de amostras para biobancos, com o intuito de as utilizar em múltiplos estudos indefinidos à data da colheita, levou a formas alternativas de consentimento informado, consideradas por alguns autores como distorções do conceito original. Neste trabalho é proposto um modelo base de consentimento informado genérico para ser aplicado em associação com medidas adicionais de controlo dos biobancos, como a anonimização reversível ou codificação das amostras, associada a um sistema honest broker, bem como à vigilância por comissões de ética. É também proposto um modelo para a administração de biobancos, assim como critérios para a divulgação e integração responsável dos resultados de investigação na área clínica. A comercialização dos produtos biológicos é outro tema de discussão, pois o seu direito de propriedade e a partilha de benefícios estão ainda por definir na maioria dos países. Muitas organizações nacionais e internacionais elaboraram códigos de conduta, mas as discrepâncias são imensas. O debate social, com a intervenção de eticistas, legisladores e cientistas é necessário para atingir o equilíbrio entre os interesses individuais e colectivos. In the last decades many health services or academic institutions have established organized collections of biological samples associated with personal data. These biobanks have captured the interest of the scientific community for their relevance to the study of common disorders with public health impact. This interest as also led to the emergence of private for-profit biobanks. The trend is to build biobanks with thousands of samples in order to investigate an association of genetic variants with complex diseases and their interaction with environmental factors, as well as with drugs, in the last case to achieve a more direct and efficient medication. The success of biobanks depends on the society’s participation, which is influenced by sociocultural factors like trust in the institutions and in their professionals. These have the moral responsibility of safeguarding the autonomy and integrity of the study participants. One way of respecting this autonomy is through informed consent. However, most often the participant informed consent in genetic research refers to the primary use of the sample whereas its long term use is not addressed. Therefore, it is necessary to define principles for using previously collected samples when a new consent is difficult or even impossible to obtain. Moreover, collection of samples for biobanks with the purpose of using those in several unforeseen studies has also led to alternative forms of informed consent, which are considered by some as distortions of the original concept. A model of a general informed consent is here presented, which is associated with additional forms of biobank control including sample reversible anonymization or codification associated with an honest broker system, as well as surveillance by research ethics committees. A model for biobank administration is also proposed as well as criteria for the responsible disclosing and integration of research results in the clinical setting. Commercialization of biological products is another issue of discussion because in most countries sample property rights and benefit sharing are poorly defined. Guidelines have been proposed by many governmental or non-governmental organizations, although the lack of harmonization is enormous. A societal debate, including ethicists, legislators and scientists is needed to achieve a balance between individual and collective interests.