Browsing by Author "Alves, Paula"
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- Anti-inflammatory effect of erythropoietin in the TNBS-induced colitisPublication . Mateus, Vanessa; Rocha, João; Alves, Paula; Mota-Filipe, Helder; Sepodes, Bruno; Pinto, Rui Manuel AmaroErythropoietin is a potent stimulator of erythroid progenitor cells, which is able to inhibit NF-kB activation, due to its pleiotropic properties, thus promoting an anti-inflammatory effect. As inflammatory bowel disease is a chronic disease with reduced quality of life, and the current pharmacotherapy only induces or maintains the patient in remission, there is a crucial need of new pharmacological approaches. The main objective of this study was to evaluate the effect of erythropoietin in the TNBS-induced colitis model in mice with a normal intestinal flora. Mice with TNBS-induced colitis were treated with a daily dose of erythropoietin at 500 IU/kg bw/day and 1000 IU/Kg bw/day IP during 4 days. As to clinical symptoms/signs, erythropoietin attenuated the decreased body-weight and reduced diarrhoea and oedema of the anus registered in the non-treated mice group in a dose-dependent manner. The anti-inflammatory properties of erythropoietin in the TNBS-induced colitis were confirmed by suppression of pro-inflammatory mediators, such as TNF-α, IL-1β and MPO, as well as a significant increase in the anti-inflammatory cytokine, IL-10, was promoted. These treated mice also presented a reduction in haemoglobin faecal and ALP, suggesting a beneficial effect of erythropoietin in the haemorrhagic focus and destruction of the enterocyte associated with the colon injury induced by TNBS, respectively. The histopathological score was reduced after treatment with erythropoietin, decreasing the severity and extension of the colitis. Furthermore, renal and hepatic biomarkers, as well as haematocrit concentration, remained stabilized after treatment. In conclusion, erythropoietin reduces the inflammatory response associated with TNBS-induced colitis in mice.
- A malnutrição associada à doença e as suas repercussões em PortugalPublication . Marinho, Anibal; Lopes, Ana; Sousa, Gabriela; Antunes, Henedina; Fonseca, Jorge; Mendes, Lino; Carvalho, Mamede de; Veríssimo, Manuel Teixeira; Carvalho, Nuno; Alves, Paula; Alves, PauloA malnutrição associada à doença é frequente do ponto de vista clínico, apresentando elevada morbilidade, mortalidade e impacto na qualidade de vida, em especialidades como a medicina interna, a oncologia, a neurologia, a gastroenterologia e a pediatria, entre outras. Estudos realizados em Portugal estimam existirem cerca de 40% de doentes em risco nutricional à data da admissão hospitalar, dependendo do estadio da doença e do grau/severidade. O custo da hospitalização destes doentes, é cerca de 20% superior ao dos doentes com o mesmo grupo de diagnóstico homogéneo, mas sem risco nutricional associado. No nosso país, o acesso dos doentes malnutridos a avaliação, aconselhamento e tratamento nutricional adequados ainda é limitado, mesmo em ambiente hospitalar. Um conhecimento detalhado da malnutrição associada à doença nas referidas especialidades, permitiria uma melhor caracterização da situação em Portugal, e permitiria estabelecer uma estratégia de intervenção clínica e terapêutica, para melhorar este panorama e as suas consequências no nosso país.
- Real-world challenges in first-line treatment of metastatic EGFR-mutated non-small cell lung cancerPublication . Barreto, Inês; Figueiredo, Sara; Tonin, Fernanda; Vilariça, Ana Sofia; Hasmucrai, Direndra; Alves, PaulaOsimertinib, a third-generation tyrosine kinase inhibitor (TKI), was recently introduced in several countries, including Portugal (reimbursement in 2021), as first-line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with activating proto-oncogene epidermal growth factor receptor mutations (EGFRm), after showing significant efficacy and safety when used in patients with EGFR-T790M resistance mutations. However, despite advances in personalized target treatments in this field, challenges regarding patients’ journey (e.g., therapy selection criteria, EGFR-TKI optimal sequencing, treatment beyond second-line) still exist.
- Thiadiazolidinone-8 ameliorates inflammation associated with experimental colitis in micePublication . Mateus, Vanessa; Rocha, João; Alves, Paula; Mota-Filipe, Hélder; Sepodes, Bruno; Pinto, RuiThiadiazolidinone-8 (TDZD-8) is an effective thiadiazolidinone derivate that is able to suppress the expression of inflammatory cytokines; it also presents tissue protective actions by glycogen synthase kinase (GSK)-3β inhibition, promoting thus an anti-inflammatory effect. Since inflammatory bowel disease is a chronic disease with reduced quality of life, where currently available therapies are only able to induce or maintain the patient in remission, it is crucial to investigate new pharmacological approaches. The main objective of this study was to evaluate the effect of TDZD-8 in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Male CD-1 mice with TNBS-induced colitis were treated with a daily dose of TDZD-8 5 mg/kg/day IP for 4 days. The anti-inflammatory properties of TDZD-8 in the TNBS-induced colitis were confirmed by suppression of pro-inflammatory mediators, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β and myeloperoxidase, as well as by the significant increase of the anti-inflammatory cytokine, IL-10. These treated mice also presented a reduction in fecal hemoglobin and alkaline phosphatase, suggesting a beneficial effect of TDZD-8. Furthermore, renal and hepatic biomarkers remained stabilized after treatment. In conclusion, TDZD-8 reduces the inflammatory response associated with TNBS-induced colitis in mice, and modulation of GSK-3β seems to be an interesting pharmacological target in colitis.