Browsing by Author "Lopes, S."
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- 4-hydroxyquinolin-2(1H)-one isolated in cryogenic argon and xenon matrices: tautomers and photochemistryPublication . Secrieru, Alina; Lopes, S.; Nikitin, T.; Cristiano, Maria de Lurdes; Fausto, R.4-Hydroxyquinolin-2(1H)-one (4HQ2O) was synthesized, isolated in cryogenic matrices (argon and xenon), and studied by infrared spectroscopy. Quantum chemical calculations carried out at the DFT(B3LYP)/6-311++G (3df,3pd) level of theory were used to determine the conformational and tautomeric properties of the molecule. Two tautomeric forms were identified in the as-deposited matrices with the help of the theoretical data. To investigate the photochemistry of the compound, in situ broadband ultraviolet (lambda > 283 nm) irradiation of the asdeposited argon matrix was performed. This irradiation led to the generation of an additional tautomer, together with the products of fragmentation of the heterocyclic ring of the molecule, specifically isocyanic acid and carbon monoxide. Photoproducts such as 1,3-dihydro-2H-indol-2-one and cyclohepta-1,2,4,6-tetraene were also observed in the photolyzed argon matrix. A comprehensive assignment of the infrared spectra of all the species observed experimentally is presented.
- Characterization of polymorphic microsatellite markers for the Neotropical leaf-frog Phyllomedusa burmeisteri and cross-species amplificationPublication . Brunes, T. O.; van de Vliet, M. S.; Lopes, S.; Alexandrino, J.; Haddad, C. F. B.; Sequeira, F.Twelve polymorphic tetranucleotide microsatellite loci were isolated and characterized for the leaf-frog Phyllomedusa burmeisteri, an endemic species of the Brazilian Atlantic forest. These loci were screened in 25 individuals from two populations of the Minas Gerais State (Carangola and Juiz de Fora). The number of alleles per locus ranged from 3 to 16 (mean = 8). Observed and expected heterozygosities ranged from 0.25 to 0.92 and 0.56 to 0.92, respectively. Evidence for both the presence of null alleles and Hardy-Weinberg equilibrium deviations were found in loci Phybu4, Phybu17, and Phybu21. Genotypic disequilibrium for each pair of loci across populations was not significant. Cross-species amplification was successful for 11 of the 12 developed loci for the sister-species, P. bahiana. These microsatellites will be important for future fine-scale population structure analyses.
- Low Golimumab trough levels at week 6 are associated with poor clinical, endoscopic and histological outcomes in ulcerative colitis patients: pharmacokinetic and pharmacodynamic sub-analysis of the evolution studyPublication . Magro, F.; Lopes, S.; Silva, M.; Coelho, R.; Portela, F.; Branquinho, D.; Correia, L.; Fernandes, S.; Cravo, M.; Caldeira, Paulo; Sousa, Helena Tavares; Patita, M.; Lago, P.; Ramos, J.; Afonso, J.; Redondo, I.; Machado, P.; Cornillie, F.; Lopes, J.; Carneiro, F.Background and Aims: Golimumab has an established exposure-response relationship in patients with ulcerative colitis [UC]. However, the association of serum golimumab trough levels [TL] with objective markers of disease activity, such as endoscopic and histological activity scores and concentrations of biomarkers, remains less understood. This report describes the relationship of serum golimumab TL at the end of the induction period [Week 6] with clinical, endoscopic, histological, and biomarker parameters. Methods: This was an open-label, uncontrolled, prospective and interventional study. Moderate to severely active UC patients naive to biologic therapy were treated with golimumab. Serum golimumab TL and faecal calprotectin levels were measured at baseline [Week 0 of induction] and Week 6. Results: A total of 34 patients completed the induction phase [Week 6] and were included in this analysis. Overall, 47.1% and 14.7% of patients achieved clinical response and remission with significantly higher serum golimumab TL in patients with early response or remission [3.7 mu g/mL vs 1.3 mu g/mL, p = 0.0013; and 3.1 mu g/mL vs 1.7 mu g/mL, p = 0.0164, respectively]. In addition, golimumab TL were significantly higher in patients achieving histological remission [4.2 mu g/mL vs 1.7 mu g/mL, p = 0.0049]. Week 6 golimumab TL were inversely correlated with the total Mayo score [rs = -0.546; p = 0.0008], the Mayo endoscopic subscore [rs = -0.381; p = 0.0262], the Geboes histological activity score [rs = -0.464; p = 0.0057], and faecal calprotectin levels [rs = -0.497; p = 0.0044]. Conclusions: A higher early exposure to golimumab is associated with a better objective response in active UC patients and appears to drive the outcome at Week 6.
- Maintaining remission after an episode of steroid-responsive acute severe ulcerative colitis: what is the best strategy?Publication . Bravo, C.; Gomes, C. Frias; Blesl, A.; Damasceno, J.; Drygiannakis, I.; Argyriou, K.; Festa, S.; Aratari, A.; Todeschini, A.; Jelakovic, M.; Kani, H. Tarik; Idrees, Z.; Feijó, D.; Chaves, C.; Bacsur, P.; Michalopoulos, G.; Turcan, S.; Nardone, O. M.; Spyridon, V.; Bernardi, A. De; Nagmeldin, I.; Denjagic, M. Basic; Ribaldone, D. Giuseppe; Ploutarchos, P.; Karakan, T.; Oliveira, R.; Balestrieri, P.; Lopes, S.; Vasilakis, T.; Taelman, T.; Neri, B.; Clarke, M.; Mocci, G.; Kiudelis, G.; Vieujean, S.; Sciberras, N.; Milenkovic, Z.; Bonazzi, E.; Karmiris, K.; Torres, J.The best maintenance therapy after a steroid-responsive acute severe ulcerative colitis (ASUC) episode remains poorly studied and is not addressed in current guidelines. We aimed to compare the impact of different treatment strategies following hospitalization for steroid-responsive ASUC.
- Proactive therapeutic drug monitoring of infliximab: a comparative study of a new point-of-care quantitative test with two established ELISA assaysPublication . Afonso, J.; Lopes, S.; Gonçalves, R.; Caldeira, Paulo; Lago, P.; Sousa, Helena Tavares; Ramos, J.; Gonçalves, A. R.; Ministro, P.; Rosa, I.; Vieira, A. I.; Dias, C. C.; Magro, F.BackgroundTherapeutic drug monitoring is a powerful strategy known to improve the clinical outcomes and to optimise the healthcare resources in the treatment of autoimmune diseases. Currently, most of the methods commercially available for the quantification of infliximab (IFX) are ELISA-based, with a turnaround time of approximately 8h, and delaying the target dosage adjustment to the following infusion.AimTo validate the first point-of-care IFX quantification device available in the market - the Quantum Blue Infliximab assay (Buhlmann, Schonenbuch, Switzerland) - by comparing it with two well-established methods.MethodsThe three methods were used to assay the IFX concentration of spiked samples and of the serum of 299 inflammatory bowel diseases (IBD) patients undergoing IFX therapy.ResultsThe point-of-care assay had an average IFX recovery of 92%, being the most precise among the tested methods. The Intraclass Correlation Coefficients of the point-of-care IFX assay vs. the two ELISA-based established methods were 0.889 and 0.939. Moreover, the accuracy of the point-of-care IFX compared with each of the two reference methods was 77% and 83%, and the kappa statistics revealed a substantial agreement (0.648 and 0.738).ConclusionsThe Quantum Blue IFX assay can successfully replace the commonly used ELISA-based IFX quantification kits. This point-of-care IFX assay is able to deliver the results within 15min makes it ideal for an immediate target concentration adjusted dosing. Moreover, it is a user-friendly desktop device that does not require specific laboratory facilities or highly specialised personnel.
- The performance of Remicade (R)-optimized quantification assays in the assessment of Flixabi (R) levelsPublication . Magro, F.; Rocha, C.; Vieira, A. I.; Sousa, H. T.; Rosa, I; Lopes, S.; Carvalho, J.; Dias, C. C.; Afonso, J.Background: The advent of Remicade (R) biosimilars, Remsima (R), Inflectra (R) and, more recently, Flixabi (R), has brought along the potential to decrease the costs associated with this therapy, therefore increasing its access to a larger group of patients. However, and in order to assure a soft transition, one must make sure the assays and algorithms previously developed and optimized for Remicade perform equally well with its biosimilars. This study aimed to: (a) validate the utilization of Remicade-optimized therapeutic drug monitoring assays for the quantification of Flixabi; and (b) determine the existence of Remicade, Remsima and Flixabi cross-immunogenicity. Methods: Healthy donors' sera spiked with Remicade, Remsima and Flixabi were quantified using three different Remicade-quantification assays, and the reactivity of anti-Remicade and anti-Remsima sera to Remicade and to its biosimilars was assessed. Results: The results show that all tested Remicade-infliximab-optimized assays measure Flixabi as accurately as they measure Remicade and Remsima: the intraclass correlation coefficients between theoretical and measured concentrations varied from 0.920 to 0.990. Moreover, the interassay agreement values for the same compounds were high (intraclass correlation coefficients varied from 0.936 to 0.995). Finally, the anti-Remicade and anti-Remsima sera reacted to the different drugs in a similar fashion. Conclusions: The tested assays can be used to monitor Flixabi levels. Moreover, Remicade, Remsima and Flixabi were shown to have a high cross-immunogenicity, which supports their high similarity but prevents their switching in nonresponders with antidrug antibodies.