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- 11 - Collagen-like materials for tissue regeneration and repairPublication . Teixeira, Cátia; Ferraz, Ricardo; Prudêncio, Cristina; Gomes, PaulaPeptides can be designed to recreate the higher-order assembly (triple helix) and biological function of natural collagens. Collagen triple-helical domain contains Gly-Xaa-Yaa triplets where Xaa and Yaa are frequently proline and hydroxyproline, respectively. Glycine must be in every third position forming a hydrogen bond to an adjacent proline to stabilize collagen structure. Hydroxyproline residues are important in the thermal stability of the collagen triple-helix conformation. Although it is difficult to produce a stable triple helix, collagen-like peptides can be used to produce scaffolds that mimic natural tissue networks for biomedical engineering, without the liabilities of nonhuman natural collagens such us immunogenicity and pathogen transmission. This chapter describes the major approaches towards synthesis of collagen-like peptides, essentially aimed at production of artificial biocompatible and biofunctional frameworks for regenerative medicine.
- 188Re-PEI-MP as potential agent for metabolic radiotherapyPublication . Ferreira, Sara; Abrantes, Ana Margarida; Metello, Luís F.; Zeevart, Jan; Louw, Werner; Dormehl, Irene D.; Botelho, Maria FilomenaIntroduction: 188Re is a promising radionuclide for metabolic therapy because of the emission of high energy beta-particles. The development of watersoluble bone-seeking polymers such as PEI-MP (polyethyleneimine, functionalised with methylphosphonate-groups) that might be labeled with 188Re are recent approaches, with a strong potential for bone cancer treatment. The aim of this study was to evaluate the efficacy of 188Re-PEI-MP, as therapeutic agent for osteosarcoma, through in vitro and in vivo models.
- 2D:4D digit ratio is associated with cognitive decline but not frailty in community-dwelling older adultsPublication . Gonçalves, Celina; Coelho, Tiago; Machado, Sérgio; Rocha, NunoObjectives To understand the relation between 2D:4D ratio, frailty, and cognitive decline in community-dwelling elderly people. Methods A total of 175 community-dwelling elderly people were included. To determine frailty, participants completed the Tilburg Frailty Indicator (TFI) and the Survey of Health, Ageing and Retirement in Europe (SHARE-FI). Cognitive functioning was determined using the Mini-Mental State Examination (MMSE). 2D and 4D finger lengths of each hand were measured using a scanner. Barthel Index, Lawton, and Brody scale were also completed for each participant to determine the level of daily living functioning. Results We did not find any correlations between 2D:4D ratio and frailty measures. We found a significant correlation between 2D:4D ratio and MMSE scores in the women sampled. Conclusions We cannot ascertain any contribution of prenatal exposure to androgens to the frailty status of community-dwelling elderly people. We found that reduced prenatal exposure to testosterone in women may contribute to the prevention of cognitive decline in elderly women
- 3-Bromopyruvate boosts the effect of chemotherapy in acute myeloid leukemia by a pro-oxidant mechanismPublication . Vieira, Joana Pereira; Preto, Ana; Granja, Sara; Queirós, Odília; Celeiro, Sónia Pires; Ko, Young Hee; Casal, Margarida; Matos, Catarina Barbosa; Baltazar, Fátima; Granja, SaraAcute myeloid leukemia (AML) comprises a diverse group of blood cancers with varying genetic, phenotypic, and clinical traits, making development of targeted therapy challenging. Metabolic reprogramming in AML has been described as relevant for chemotherapy effectiveness. 3-Bromopyruvate (3-BP) is an anticancer agent that undermines energy metabolism of cancer cells. However, the effect of 3-BP in hematologic malignancies, such as AML, needs further investigation. Thus, we aimed to explore 3-BP as a chemo-sensitizing agent in AML. Different approaches of combining 3-BP with classical chemotherapy (daunorubicin and cytarabin) were tested in diverse AML cell lines. Cell sensitivity to the different drug combinations was analyzed by Trypan blue staining. The effect of pre-treatment with a non-toxic concentration of 3-BP was assessed on the AML cell metabolic profile (Western blot and immunofluorescence), mitochondrial activity (cytometry flow), and antioxidant capacity (colorimetric detection kit). KG-1 and MOLM13 cells showed increased sensitivity to chemotherapy (decreased EC 50 values) after exposure to a non-toxic concentration (5 μ M) of 3-BP. In both cell lines, 5 glucose consumption without changing extracellular lactate levels. 5 μ μ M 3-BP decreased M 3-BP treatment increased reactive oxygen species levels and decreased cell antioxidant capacity by depleting reduced glutathione levels in both KG-1 and MOLM13 cells. Our results demonstrate that non-toxic concentrations of 3-BP enhance the effect of classical chemotherapy in AML cells through a pro-oxidant mechanism. These data unveiled a new approach for AML treatment, using 3-BP or other pro-oxidant agents as co-adjuvants of chemotherapy, subsiding chemotherapy- induced side effects.
- 3-Nitrotyrosine quantification methods: Current concepts and future challengesPublication . Teixeira, Dulce; Fernandes, Rúben; Prudêncio, Cristina; Vieira, MónicaMeasurement of 3-nitrotyrosine (3-NT) in biological samples can be used as a biomarker of nitrosative stress, since it is very stable and suitable for analysis. Increased 3-NT levels in biological samples have been associated with several physiological and pathological conditions. Different methods have been described for the detection and quantification of this molecule, such as (i) immunological methods; (ii) liquid chromatography, namely high-pressure liquid chromatography (HPLC)-based methods that use ultraviolet-visible (UV/VIS) absorption, electrochemical (ECD) and diode array (DAD) detection, liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS); (iii) gas chromatography, such as gas chromatography-mass spectrometry (GC-MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS). Methods A literature review on nitrosative stress, protein nitration, as well as 3-NT quantification methods was carried out. Results This review covers the different methods for analysis of 3-NT that have been developed during the last years as well as the latest advances in this field. Overall, all methods present positive and negative aspects, although it is clear that chromatography-based methods present good sensitivity and specificity. Regarding this, GC-based methods exhibit the highest sensibility in the quantification of 3-NT, although it requires a prior time consuming derivatization step. Conversely, HPLC does not require such derivatization step, despite being not as accurate as GC. Conclusion It becomes clear that all the methods described during this literature review, although accurate for 3-NT quantification, need to be improved regarding both sensitivity and specificity. Moreover, optimization of the protocols that have been described is clearly needed.
- 3D Vocal Tract Reconstruction Using Magnetic Resonance Imaging Data to Study Fricative Consonant ProductionPublication . Ventura, Sandra Moreira Rua; Freitas, Diamantino Rui S.; Ramos, Isabel Maria A. P.; Tavares, João Manuel R. S.The development of Magnetic Resonance Imaging (MRI) has grown rapidly in clinical practice. Currently, the use of MRI in speech research provides useful and accurate qualitative and quantitative data of speech articulation. The aim of this work was to describe an effective method to extract vocal tract and compute their volumes during speech production from MRI images. Using a 3.0 Tesla MRI system, 2D and 3D images of the vocal tract were collected and used to analyze the vocal tract during the production of fricative consonants. These images were also used to build the associated 3D models and compute their volumes. This approach showed that, in general, the volumes measured for the voiceless consonants are smaller than the counterpart voiced consonants.
- 3D vs 2D Cell Cultures in the Evaluation of Radiobiological Effects of Exposition to Low Doses - Medical Imaging Levels - of Ionizing RadiationPublication . Costa, Pedro; Caires, Hugo; Lemos, Joana; Cunha, Lídia; Bravo, Joana; Bravo, Isabel; Silva, Regina; Summavielle, Teresa; Metello, Luís F.Pretending to develop advanced biological models to study biological effects of low doses of ionizing radiation and following the actual policies on Animal Sciences, based on 3 R’s Rule (to Reduce, Refine and Replace) – that limits as much as possible the application of animal models – scientific research using cellular models is constantly increasing. Nevertheless, the intrinsic limitations of actual cellular models quite often had been recognized on a significant number of papers pointing a significant number of non-concordances between results obtained using in vitro and in vivo studies. Actually, an increasing number of authors admit that three-dimensional cell culture (and spheroid cell culture in particular) could represent an interesting solution and a step further on use of cellular models. The work here to be presented reflects the first phase on the use of this methodology on the study, evaluation and quantification of cellular effects of low doses – starting on medical imaging level - of exposition to ionizing radiation.
- 3rd International Congress of Environmental Health: Proceedings BookPublication . Vieira Da Silva, Manuela; Oliveira, Rui S.; Rodrigues, Matilde; Nunes, Mafalda; Santos, Joana; Carvalhais, C.; Rebelo, Andreia; Freitas, Marisa; Xavier, AnaThis third edition addresses to ‘Emerging risks and challenges for the environment, health and safety’ and intended as a guide to the various symposiums and workshops, to provide all present the most recent scientific and technological advances in the areas: Occupational Health and Toxicology; Exposure to Nanoparticles; Assessment and Risk Management; Occupational Safety; Exposure to Bioaerosols; Environment and Sustainability; Food Safety and Public Health.
- 4,9-Diaminoacridines and 4-Aminoacridines as Dual-Stage Antiplasmodial HitsPublication . Fonte, Mélanie; Tassi, Natália; Fontinha, Diana; Bóuzon-Arnáiz, Inês; Ferraz, Ricardo; Araújo, Maria J.; Fèrnandez-Busquets, Xavier; Prudêncio, Miguel; Gomes, Paula; Teixeira, CátiaMulti‐stage drugs have been prioritized in antimalarial drug discovery, as targeting more than one process in the Plasmodium life cycle is likely to increase efficiency, while decreasing the chances of emergence of resistance by the parasite. Herein, we disclose two novel acridine‐based families of compounds that combine the structural features of primaquine and chloroquine. Compounds prepared and studied thus far retained the in vitro activity displayed by the parent drugs against the erythrocytic stages of chloroquine‐sensitive and ‐resistant Plasmodium falciparum strains, and against the hepatic stages of Plasmodium berghei, hence acting as dual‐stage antiplasmodial hits.
- 45Ti - Titanium: from cyclotron production to potential applications evaluationPublication . Costa, Pedro; Metello, Luís F.; Cunha, Lídia; Lass, Piotr; Currie, Geoff; Johnson, Richard R.; Gelbart, W.; Obermair, J.; Artner, Christoph; Alves, Francisco; Naia, M. DuarteIntroduction: Thousands of radioisotopes are known and virtually all may be artificially produced, however clinical applications of PET imaging are mainly based on 18F, 11C, 13N and 68Ga. This trend could change in the near future, since several groups worldwide are busy developing very promising new entities aiming to contribute for spreading the use and efficacy of clinical diagnostic using Nuclear Medicine imaging techniques. Our group is developing 45Ti-Titanium, assuming it as a potential candidate, since presenting interesting properties: physical half-life of 3.09h, together with relevant chemical properties, that enable radiolabelling with bifunctional chelates, ligands or could even be useful for studies concerning the distribution of new titanium-based chemotherapy drugs or titanium oxide nanoparticles. Considering that data characterizing excitation functions is necessary for radionuclide optimal production, this work aims to disseminate results regarding the determination of excitation function of 45Sc(p,n)45Ti reaction, studied as a potential route to produce 45Ti in low energy cyclotrons.
