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Marine-derived polymers are environmentally friendly and sustainable biomaterials that have structural similarities with the main components of the extracellular matrix. Moreover, some marine polymers have specific bioactivity that can be transferred to the systems made of these biomolecules. Herein, we developed antibacterial adhesive films combining two marine polysaccharides, namely, fucoidan and chitosan. Fucoidan was functionalized with catechol groups (FCat) to improve its adhesive properties. This modification enhanced also the fucoidan antibacterial properties: while fucoidan is active against Gram-positive bacteria, FCat showed bactericidal activity against Gram-positive and Gram-negative bacteria. To improve the processability and mechanical properties, FCat was blended with chitosan and solvent-casted to obtain films. These films exhibited an adhesion strength similar to the one of clinically used natural adhesives and no cytotoxicity: fibroblastic cells attached and remained viable on the films. Altogether our results demonstrated that the developed antibacterial and adhesive films are a feasible alternative of cytotoxic synthetic adhesives used for soft tissue healing applications., The authors acknowledge the Portuguese Foundation for Science and Technology (FCT) and the European program FEDER/FEEI for the financial support through the PTDC/BTM-MAT/28123/2017 project. FCT is also acknowledged for the PhD scholarship SFRH/BD/143209/2019 granted to C.C. This article has also been prepared with the support of REMIX Project, funded by the European Union’s Horizon 2020 Research and Innovation programme under the Maria Sklodowska-Curie grant agreement no. 778078. Dr. Luisa Rodrigues is acknowledged for performing the XPS analysis.

Objectives: To compare the effectiveness of a 2nd TNF inhibitor (TNFi), Tocilizumab (TCZ) and Rituximab (RTX), measured by drug retention and by response rates, in RA patients after discontinuing a first-line TNFi and to clarify the reasons and predictors for discontinuation of a second-line biologic. Material and Methods: Non-interventional prospective study of RA patients exposed to a 2nd TNFi, TCZ or RTX after previous TNFi discontinuation using real-world data from Reuma.pt database. Drug retention was estimated using Kaplan-Meier analysis and Cox models. Crude and LUNDEX adjusted response rates were evaluated at 6 months, 1 and 2 years and reasons for discontinuation were compared according to biologic class. Results: In total, 643 patients were included, 88.8% females, with a mean age of 59.4±12.8 years. Of those, 390 (60.7%) initiated a 2nd TNFi, 147 (22.9%) TCZ and 106 (16.5%) RTX. Drug retention was significantly greater among patients who initiated TCZ (76.4±4.3 months) or RTX (80.8±4.8 months), compared with those who initiated a 2nd TNFi (52.7±2.6 months) (log rank test, p < 0.001). In the adjusted Cox model, hazards of discontinuation were significantly lower for TCZ (HR 0.39, 95% CI 0.23-0.64, p < 0.001) and RTX (HR 0.42, 95% CI 0.25-0.72, p=0.001). Smokers had a significantly higher risk for discontinuation (HR 2.43, 95%CI 1.50-3.95, p < 0.001) as well as patients with higher HAQ at baseline (HR 1.51, 95%CI 1.14-2.00, p=0.004). The proportion of patients in remission or low disease activity according to Clinical Disease Activity Index (CDAI) at 6 months, 1 and 2 years was, respectively, 46.5%/50.0%/61.2% for TNFi, 52.9%/53.6%/ 69.2% for TCZ and 37.7%/48.0%/50.0% for RTX. After LUNDEX adjustment, response rates were, respectively, 33.0%/31.0%/31.8% for 2nd TNFi, 42.8%/41.8%/53.3% for TCZ and 32.0%/39.4%/39.0% for RTX. The main reasons for discontinuation were inefficacy for 2nd TNFi and RTX and adverse events for TCZ (p < 0.001). Conclusions: Our findings showed a significantly higher drug retention for TCZ and RTX, compared with 2nd TNFi, and similar persistence among TCZ and RTX, in patients who discontinued a first-line TNFi. These data corroborate the notion that switching to a biologic with a different mode of action is more effective than to a second TNFi.

Made available in DSpace on 2022-04-30T07:05:12Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-01-01 Body mass is one of the most influencing factors of metabolic rate and gas exchange of animals, and also related to activity pattern and occupancy of ecological niches. This study aimed to understand the relationships between body mass (MB) and morpho-functional features of the lungs of Iguana iguana, through morphological and morphometric characterization of the structural elements of the respiratory system. Iguana iguana has lungs of the transitional type, the heterogeneously distributed parenchyma being faveolar in cranial and medial regions and trabecular in the caudal region. Within the parenchyma, 43.6 ± 25.5% corresponds to faveoli, 18.0 ± 5.9% to interfaveolar septa, and 38.7 ± 31.6% to trabeculae. Within the interfaveolar septa, 9.4 ± 4.0% corresponds to blood capillaries, 4.4 ± 1.0% to type I pneumocytes and 3.9 ± 1.1% to type II pneumocytes. Allometric analyses showed that lung (MB0.8949) and parenchymal volume (MB1.030) scale with MB in I. iguana just as in other lizards with unicameral or transitional lungs, which was unexpected for lung volume, since reptilian lung volume is generally considered to scale as MB0.75. The functional morphology of the lungs in I. iguana seems to play an important role to meet the metabolic demands through ontogenetic growth. Federal University of Bahia Institute of Biology Laboratory of Animal Physiology, Rua Barão de Geremoabo s/n, Ondina School of Philosophy Sciences and Literature of Ribeirão Preto University of São Paulo (USP), Avenida Bandeirantes, 3900. Monte Alegre São Paulo State University Rio Claro Campus Institute of Biosciences, Avenida 24-A, 1515. Bela Vista National Institute of Science and Technology in Comparative Physiology São Paulo State University Rio Claro Campus Institute of Biosciences, Avenida 24-A, 1515. Bela Vista

Background: Alzheimer's disease (AD) is the most common form of dementia and causes a progressive and irreversible neurodegeneration. The loss of cholinergic neurons leads to the progressive reduction of acetylcholine (ACh) in the brain and resulting cognitive impairment in AD. ACh is hydrolyzed by both acetylcholinesterase (AChE) and butirylcholinesterase (BuChE). It was found that in the course of the disease, levels of AChE in the central nervous system (CNS) decrease, inversely to BuChE levels, so both enzymes represent legitimate therapeutic targets for ameliorating the cholinergic deficit characteristic of AD. Objective: Screen a library of new isoquinoline, indolinone and benzoazepinone derivatives for their ability to inhibit AChE and BuChE activities, using galantamine and rivastigmine as standards. Methods: The enzyme activities and inhibition studies were carried out using spectrophotometric techniques, based on the Ellman’s method, with acetylthiocholine (ATCI) and butirylthiocholine (BTCI) as substrates, for AChE and BuChE, respectively. The data were complemented with modeling to analyze the structure-activity relationship. Results: Our results show that the tested compounds are competitive inhibitors for AChEs and BuChEs, as the benchmarks galantamine and rivastigmine. The isoquinoline and indolinone derivative compounds showed strong anti-cholinesterases activities, with IC50 values ranging from 0.4 to 400 micromolar. Conclusions: The results presented are promising and provide a pathway for the design of new AChE and BuChE inhibitors.