Browsing by Author "Fernandes, R."
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- Estrogen Metabolism-Associated CYP2D6 and IL6-174G/C Polymorphisms in Schistosoma haematobium InfectionPublication . Cardoso, R.; Lacerda, P.; Costa, P.; Machado, A.; Carvalho, A.; Bordalo, A.; Fernandes, R.; Soares, R.; Richter, J.; Alves, H.; Botelho, M.Schistosoma haematobium is a human blood fluke causing a chronic infection called urogenital schistosomiasis. Squamous cell carcinoma of the urinary bladder (SCC) constitutes chronic sequelae of this infection, and S. haematobium infection is accounted as a risk factor for this type of cancer. This infection is considered a neglected tropical disease and is endemic in numerous countries in Africa and the Middle East. Schistosome eggs produce catechol-estrogens. These estrogenic molecules are metabolized to active quinones that induce modifications in DNA. The cytochrome P450 (CYP) enzymes are a superfamily of mono-oxygenases involved in estrogen biosynthesis and metabolism, the generation of DNA damaging procarcinogens, and the response to anti-estrogen therapies. IL6 Interleukin-6 (IL-6) is a pleiotropic cytokine expressed in various tissues. This cytokine is largely expressed in the female urogenital tract as well as reproductive organs. Very high or very low levels of IL-6 are associated with estrogen metabolism imbalance. In the present study, we investigated the polymorphic variants in the CYP2D6 gene and the C-174G promoter polymorphism of the IL-6 gene on S. haematobium-infected children patients from Guine Bissau. CYP2D6 inactivated alleles (28.5%) and IL6G-174C (13.3%) variants were frequent in S. haematobium-infected patients when compared to previously studied healthy populations (4.5% and 0.05%, respectively). Here we discuss our recent findings on these polymorphisms and whether they can be predictive markers of schistosome infection and/or represent potential biomarkers for urogenital schistosomiasis associated bladder cancer and infertility.
- Non-Transferrin-Bound Iron (NTBI) Uptake by T Lymphocytes: Evidence for the Selective Acquisition of Oligomeric Ferric Citrate SpeciesPublication . Arezes, J.; Costa, M.; Vieira, I.; Dias, V.; Kong, X.; Fernandes, R.; Vos, M.; Carlsson, A.; Rikers, Y.; Porto, G.; Rangel, M.; Hider, R.; Pinto, J.Iron is an essential nutrient in several biological processes such as oxygen transport, DNA replication and erythropoiesis. Plasma iron normally circulates bound to transferrin. In iron overload disorders, however, iron concentrations exceed transferrin binding capacity and iron appears complexed with low molecular weight molecules, known as non-transferrin-bound iron (NTBI). NTBI is responsible for the toxicity associated with iron-overload pathologies but the mechanisms leading to NTBI uptake are not fully understood. Here we show for the first time that T lymphocytes are able to take up and accumulate NTBI in a manner that resembles that of hepatocytes. Moreover, we show that both hepatocytes and T lymphocytes take up the oligomeric Fe3Cit3 preferentially to other iron-citrate species, suggesting the existence of a selective NTBI carrier. These results provide a tool for the identification of the still elusive ferric-citrate cellular carrier and may also open a new pathway towards the design of more efficient iron chelators for the treatment of iron overload disorders.
- Patient-physician discordance in assessment of adherence to inhaled controller medication: a cross-sectional analysis of two cohortsPublication . Jácome, C.; Pereira, A.; Almeida, R.; Ferreira-Magalhães, Manuel; Couto, M.; Araujo, L.; Pereira, M.; Correia, M.; Loureiro, C.; Catarata, M.; Maia Santos, L.; Pereira, J.; Ramos, B.; Lopes, C.; Mendes, A.; Cidrais Rodrigues, J.; Oliveira, G.; Aguiar, A.; Afonso, I.; Carvalho, J.; Arrobas, A.; Coutinho Costa, J.; Dias, J.; Todo Bom, A.; Azevedo, J.; Ribeiro, C.; Alves, M.; Leiria Pinto, P.; Neuparth, N.; Palhinha, A.; Gaspar Marques, J.; Pinto, N.; Martins, P.; Todo Bom, F.; Alvarenga Santos, M.; Gomes Costa, A.; Silva Neto, A.; Santalha, M.; Lozoya, C.; Santos, N.; Silva, D.; Vasconcelos, M.; Taborda-Barata, L.; Carvalhal, C.; Teixeira, M.; Alves, R.; Moreira, A.; Sofia Pinto, C.; Morais Silva, P.; Alves, C.; Câmara, R.; Coelho, D.; Bordalo, D.; Fernandes, R.; Ferreira, R.; Menezes, F.; Gomes, R.; Calix, M.; Marques, A.; Cardoso, J.; Emiliano, M.; Gerardo, R.; Nunes, C.; Câmara, R.; Ferreira, J.; Carvalho, A.; Freitas, P.; Correia, R.; Fonseca, J.Objective: We aimed to compare patient's and physician's ratings of inhaled medication adherence and to identify predictors of patient-physician discordance. Design: Baseline data from two prospective multicentre observational studies. Setting: 29 allergy, pulmonology and paediatric secondary care outpatient clinics in Portugal. Participants: 395 patients (≥13 years old) with persistent asthma. Measures: Data on demographics, patient-physician relationship, upper airway control, asthma control, asthma treatment, forced expiratory volume in one second (FEV1) and healthcare use were collected. Patients and physicians independently assessed adherence to inhaled controller medication during the previous week using a 100 mm Visual Analogue Scale (VAS). Discordance was defined as classification in distinct VAS categories (low 0-50; medium 51-80; high 81-100) or as an absolute difference in VAS scores ≥10 mm. Correlation between patients' and physicians' VAS scores/categories was explored. A multinomial logistic regression identified the predictors of physician overestimation and underestimation. Results: High inhaler adherence was reported both by patients (median (percentile 25 to percentile 75) 85 (65-95) mm; 53% VAS>80) and by physicians (84 (68-95) mm; 53% VAS>80). Correlation between patient and physician VAS scores was moderate (rs=0.580; p<0.001). Discordance occurred in 56% of cases: in 28% physicians overestimated adherence and in 27% underestimated. Low adherence as assessed by the physician (OR=27.35 (9.85 to 75.95)), FEV1 ≥80% (OR=2.59 (1.08 to 6.20)) and a first appointment (OR=5.63 (1.24 to 25.56)) were predictors of underestimation. An uncontrolled asthma (OR=2.33 (1.25 to 4.34)), uncontrolled upper airway disease (OR=2.86 (1.35 to 6.04)) and prescription of short-acting beta-agonists alone (OR=3.05 (1.15 to 8.08)) were associated with overestimation. Medium adherence as assessed by the physician was significantly associated with higher risk of discordance, both for overestimation and underestimation of adherence (OR=14.50 (6.04 to 34.81); OR=2.21 (1.07 to 4.58)), while having a written action plan decreased the likelihood of discordance (OR=0.25 (0.12 to 0.52); OR=0.41 (0.22 to 0.78)) (R2=44%). Conclusion: Although both patients and physicians report high inhaler adherence, discordance occurred in half of cases. Implementation of objective adherence measures and effective communication are needed to improve patient-physician agreement.
- Thrombus aspiration in patients with ST-elevation myocardial infarction: results of a national registry of interventional cardiologyPublication . Pereira, H.; Caldeira, D.; Teles, R.; Costa, M.; Silva, P.; Ribeiro, V.; Brandão, V.; Martins, D.; Matias, F.; Pereira-Machado, F.; Baptista, J.; Abreu, P.; Santos, R.; Drummond, A.; Carvalho, H.; Calisto, J.; Silva, J.; Pipa, J.; Marques, J.; Sousa, P.; Fernandes, R.; Ferreira, R.; Ramos, S.; Oliveira, E.; Almeida, M.BACKGROUND: We aimed to evaluate the impact of thrombus aspiration (TA) during primary percutaneous coronary intervention (P-PCI) in 'real-world' settings. METHODS: We performed a retrospective study, using data from the National Registry of Interventional Cardiology (RNCI 2006-2012, Portugal) with ST-elevation myocardial infarction (STEMI) patients treated with P-PCI. The primary outcome, in-hospital mortality, was analysed through adjusted odds ratio (aOR) and 95% confidence intervals (95%CI). RESULTS: We assessed data for 9458 STEMI patients that undergone P-PCI (35% treated with TA). The risk of in-hospital mortality with TA (aOR 0.93, 95%CI:0.54-1.60) was not significantly decreased. After matching patients through the propensity score, TA reduced significantly the risk of in-hospital mortality (OR 0.58, 95%CI:0.35-0.98; 3500 patients). CONCLUSIONS: The whole cohort data does not support the routine use of TA in P-PCI, but the results of the propensity-score matched cohort suggests that the use of selective TA may improve the short-term risks of STEMI.