Browsing by Author "Moreira, L."
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- Aqueous humor erythropoietin levels in open-angle glaucoma patients with and without TTR V30M familial amyloid polyneuropathyPublication . Beirão, J.; Moreira, L.; Oliveira, J.; Menéres, M.; Pessoa, B.; Matos, M.; Pinho-Costa, P.; Torres, P.; Beirão, I.Purpose: Glaucoma is the leading cause of irreversible blindness in familial amyloidotic polyneuropathy (FAP) patients. Erythropoietin (EPO) is a cytokine that has been shown to play a role in neuroprotection and is endogenously produced in the eye. EPO levels in the aqueous humor are increased in eyes with glaucoma. In this study, we evaluated the EPO concentration in the aqueous humor of FAP and non-FAP patients, with and without glaucoma. Methods: Undiluted aqueous humor samples were obtained from 42 eyes that underwent glaucoma surgery, phacoemulsification, or vitrectomy. EPO concentration in the aqueous humor and blood were measured using the Immulite 2000 Xpi using an automatic analyzer (Siemens Healthcare Diagnostics). Results: The mean EPO concentration in the aqueous humor of non-FAP glaucoma eyes group 2(75.73±13.25 mU/ml)was significantly higher than non-FAP cataract eyes (17.22±5.33 mU/ml; p<0.001), FAP glaucoma eyes (18.82±10.16 mU/ml; p<0.001), and FAP nonglaucoma eyes (20.62±6.22 mU/ml; p<0.001). There was no statistically significant difference between FAP nonglaucoma eyes versus non-FAP cataract eyes (p = 0.23) and FAP glaucoma eyes versus FAP nonglaucoma eyes (p = 0.29). In the glaucoma groups, there was no correlation between the aqueous humor EPO concentration and the ocular pressure (p = 0.95) and mean deviation (p = 0.41). There was no correlation between the EPO serum concentration and EPO aqueous humor concentration in our patients (p = 0.77). Conclusions: Unlike other glaucomatous patients, FAP patients with glaucoma do not show increased and potentially neuroprotective endocular EPO production in the aqueous humor and may need more aggressive glaucoma management
- Comparative assessment of the acute toxicity of commonly used metal nanoparticles in two in vitro models of human barriersPublication . Pires, J.; Moreira, L.; Teixeira, João; Fraga, SóniaMetal nanoparticles (M-NP) have application in several areas such as industry, environment, agriculture, and biomedicine. Consequently, human exposure to these nanosized materials is increasing, which raises serious concerns regarding their safety to the human health and the environment. Biological barriers are important lines of defence to xenobiotics, thus expected targets for M-NP. The present study investigated the in vitro toxicity of different types of M-NP in two cell models of biological barriers: human intestinal (Caco-2) and trophoblastic (BeWo clone b30) epithelial cells. Cells were exposed for 24 h to varied concentrations (0.8-48 µg/cm2) of M NP of different chemical composition (Au, Ag, TiO2), primary size (10, 30 and 60 nm), capping (citrate, PEG) and crystal structure (rutile, anatase) and toxicity assessed by determining changes in cell morphology, metabolic activity, plasma membrane integrity, generation of intracellular reactive oxygen species (ROS) and intracellular ATP levels. Our data show that the potential toxicity of the tested M-NPs is similar for both cell lines with AgNPs > AuNPs > TiO2NPs, being the effects more visible at higher concentrations. The influence of the size in the cytotoxic-induced effects was more evident for AgNP than for AuNP, with the smaller NP causing more toxicity, being the BeWo cells more sensitive to these M-NP. In addition, PEG-capping effectively attenuated AuNP-induced toxicity both in Caco-2 and BeWo cells. Only cells exposed to AgNP exhibited significant increased levels of ROS. Thus, our data support that the physicochemical properties of the nanomaterials, in this particular case of M-NP, is an important determinant of their cytotoxicity and that intestinal and trophoblastic cells exhibit different sensitivity to the tested M-NP. Future studies would be useful to further explore the effects of M-NP in the human barriers
- In vitro acute toxicity of metal-based nanoparticles in human trophoblast BeWo b30 cellsPublication . Pires, J.; Moreira, L.; Teixeira, J.P.; Fraga, S.Metal nanoparticles (M-NP) are among the most widely used nanomaterials in consumer products available in the market. Thus, human exposure to these nanosized materials is increasing, which raises serious concerns regarding their environmental and human safety. Biological barriers are important lines of defence to xenobiotics, thus expected targets for M-NP. In this regard, special consideration must be given to the placenta that acts as barrier between maternal and the developing fetus. The present study aimed at evaluating in vitro toxicity of different M-NP in a human cell model of placental barrier: trophoblastic (BeWo clone b30) epithelial cells. BeWo b30 cells were exposed for 24 h to varied concentrations (0.8–48 µg/cm2) of M-NP of different chemical composition (Au, Ag and TiO2), primary size (10, 30 and 60 nm), capping (citrate and PEG) and crystal structure (rutile and anatase).
- Insights into corrosion behaviour of uncoated Mg alloys for biomedical applications in different aqueous mediaPublication . Neves, C.S.; Sousa, I.; Freitas, M.A.; Moreira, L.; Costa, C.; Teixeira, J.P.; Fraga, S.; Pinto, E.; Almeida, A.; Scharnagl, N.; Zheludkevich, M.L.; Ferreira, M.G.S.; Tedim, J.MgCa and MgGd series of alloys are often reported as promising candidates for biomedical applications. In the present study, cytotoxicity and corrosion behavior of Mg1Ca and Mg10Gd alloys in different electrolytes (NaCl, PBS, MEM) have been investigated in order to make a direct comparison and understand the mechanisms behind their performance. Potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) were employed to analyze corrosion processes depending on media composition, whereas X-Ray diffraction (XRD) and scanning electron microscopy (SEM) were used to evaluate crystalline structure, phase composition and surface morphology of the corroded substrates after immersion in the different electrolytes. Moreover, cytotoxicity of the Mg alloys was assessed using the WST-1 reduction and lactate dehydrogenase (LDH) release assays in L929 mouse fibroblasts. The electrochemical results showed that Mg1Ca has a lower degradation rate when compared to Mg10Gd, due to the lower microgalvanic effects and the presence of Ca as an alloying element. Furthermore, the corrosion activity is reduced in MEM, for both alloys, when compared to NaCl and PBS. The cytotoxicity assays revealed that Mg10Gd was cytotoxic in all the conditions tested, while the toxicity of Mg1Ca was low. Overall, these findings show that Mg1Ca alloy presents a higher corrosion resistance and biocompatibility and is a promising material to be used in biomedical implants.
- Renal amyloidosis: classification of 102 consecutive casesPublication . Tavares, I.; Vaz, R.; Moreira, L.; Pereira, P.; Sampaio, S.; Vizcaíno, J.; Oliveira, J.; Pinho-Costa, P.; Lobato, L.[PT] As amiloidoses são um grupo heterogéneo de doenças classificadas de acordo com a composição das suas proteínas amiloidogénicas. Frequentemente, os tecidos preservados em parafina são usados para identificação imunohistoquímica. A análise de ADN deve ser sempre considerada se houver suspeita de amiloidose hereditária. Dado que os rins são um dos órgãos mais frequentemente envolvidos nas amiloidoses sistémicas, procedemos à classificação imunohistoquímica de 102 casos consecutivos de doença amiloide confirmada por biópsia renal. A análise de ADN foi realizada para confirmar o diagnóstico de amiloidose hereditária. As características demográficas, doença subjacente e dados clínicos à data da biópsia foram obtidos pela revisão retrospetiva dos registos médicos. O tipo de amiloidose obtido por identificação imunohistoquímica foi AA em 60 (58,8%) doentes, AL em 21 (20,6%), AFib em quatro (3,9%), ATTR em dois (2,0%), AApoAI em um (2,0%), ALys em um (2,0%), e em um (2,0%) coexistiam os tipos AL e AA. Em 12 (11,7%) não foi identificado o tipo de amiloide: oito (7,8%) por imunohistoquímica negativa e quatro (3,9%) devido a amostra insuficiente. A análise de ADN confirmou os casos AFib e ATTR pela identificação das mutações pontuais FGA p.Glu545Val e TTR p.Met51Val, respetivamente. A média de idade à data do diagnóstico foi 53,3 anos (49,4 para AA, 63,0 para AL e 53,9 para AFib). As infeções crónicas foram a principal causa de amiloidose AA, sobretudo a tuberculose, e foi apenas identificada uma AA familiar associada a síndrome de Muckle-Wells. A síndrome nefrótica foi a manifestação clínica mais frequente, independentemente do tipo de amiloide. Na nossa série, a amiloidose AA continua a ser a amiloidose sistémica mais frequente. Seis doentes tiveram amiloidose hereditária inequívoca. A imunohistoquímica não identificou a proteína precursora em quase 8% dos doentes; contudo, a utilização de um painel de anticorpos mais alargado poderá melhorar o diagnóstico.
- The disease modelling value of a folklore FAIRYtale: SHEDing light over a special group of genetic disordersPublication . Carvalho, S.; Santos, J.I.; Moreira, L.; Gaspar, P.; Gonçalves, M.; Encarnação, M.; Ribeiro, D.; Duarte, A.; Prata, M.J.; Coutinho, M.F.; Alves, SandraThe problem we are addressing: Despite extensive research, the links between accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of Mucopolysaccharidoses (MPSs) have yet to be further elucidated. These Lysosomal Storage Diseases (LSDs) present symptoms, which may (or may not) include critical musculoskeletal and cardiovascular alterations, respiratory problems, and serious neurological dysfunctions. The skeletal and brain systems are the hardest ones to access and, consequently, those in greatest need of additional knowledge and novel therapeutic solutions.
- TTRV30M oligomeric aggregates inhibit proliferation of renal progenitor cells but maintain their capacity to differentiate into podocytes in vitroPublication . Moreira, L.; Ballerini, L.; Peired, A.; Sagrinati, C.; Parente, E.; Angelotti, M.L.; Ronconi, E.; Lazzeri, E.; Mazzinghi, B.; Lacerda, P.; Beirão, I.; Lasagni, L.; Costa, P.P.; Romagnani, P.In Familial Amyloidotic Polyneuropathy, the amyloid deposition of mutant transthyretin TTR V30M can lead to renal complications. An unexplored mechanism is the toxicity of oligomeric TTR aggregates. A subset of renal progenitor cells (RPC) in the adult human kidney can induce regeneration of podocytes and tubular structures of the nephron, which can be critical for preventing irreversible renal failure. We assessed whether RPC are vulnerable, in vitro, to TTRV30M oligomers. RPC proliferation was reduced by 16.3±9.7% and 32.6±6.3% after 48 and 72 hours, respectively, in the presence of the oligomers. However, oligomers did not induce apoptosis or alterations in cell cycle to any significant extent, and did not influence RPC differentiation into podocytes. From this first attempt, we can say that TTRV30M oligomers inhibit RPC proliferation but do not influence their capacity to differentiate into mature podocytes, and thus should not compromise tissue regeneration.