Life and Health science Research Institute 3Bs

Braga, Portugal

Life and Health science Research Institute 3Bs

Braga, Portugal
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Soares Da Costa D.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | Soares Da Costa D.,Life and Health science Research Institute 3Bs | Reis R.L.,European Institute of Excellence on Tissue Engineering and Regenerative Medicine | Reis R.L.,Life and Health science Research Institute 3Bs | And 2 more authors.
Annual Review of Biomedical Engineering | Year: 2017

Sulfation is a dynamic and complex posttranslational modification process. It can occur at various positions within the glycosaminoglycan (GAG) backbone and modulates extracellular signals such as cell-cell and cell-matrix interactions; different sulfation patterns have been identified for the same organs and cells during their development. Because of their high specificity in relation to function, GAG sulfation patterns are referred to as the sulfation code. This review explores the role of GAG sulfation in different biological processes at the cell, tissue, and organism levels. We address the connection between the sulfation patterns of GAGs and several physiological processes and discuss the misregulation of GAG sulfation and its involvement in several genetic and metabolic disorders. Finally, we present the therapeutic potential of GAGs and their synthetic mimics in the biomedical field. © 2017 by Annual Reviews. All rights reserved.


Pinto P.R.,University of Minho | Pinto P.R.,Life and Health science Research Institute 3Bs | Pinto P.R.,Newcastle University | McIntyre T.,University of Houston | And 4 more authors.
Journal of Pain Research | Year: 2013

This study compares the incidence, nature, and impact of persistent post-surgical pain after total knee arthroplasty (TKA) and total hip arthroplasty (THA) and investigates differences between these procedures, with the focus on potential presurgical and post-surgical issues that could be related to the distinct persistent post-surgical pain outcomes between these two groups. A consecutive sample of 92 patients was assessed prospectively 24 hours before, 48 hours, and 4-6 months after surgery. The data show that TKA patients had a higher likelihood of developing persistent post-surgical pain, of reporting higher pain levels, and of using more neuropathic descriptors when classifying their pain. In addition, TKA patients more often reported interference from pain on functional domains, including general activity, walking ability, and normal work. Demographic factors, like gender and age, along with presurgical clinical factors like disease onset, existence of medical comorbidities, and other pain problems, may have contributed to these differences, whereas baseline psychologic factors and functionality levels did not seem to exert an influence. Heightened acute post-surgical pain experience among TKA patients could also be related to distinct outcomes for persistent post-surgical pain. Future prospective studies should therefore collect TKA and THA samples wherein patients are homogeneous for demographic and presurgical clinical issues. Overall, these findings contribute to a small but growing body of literature documenting persistent post-surgical pain after major arthroplasty, conducted in different countries and across different health care settings. © 2013 Pinto et al.


Rosa B.,Centro Hospitalar do Alto Ave | Cotter J.,Centro Hospitalar do Alto Ave | Cotter J.,University of Minho | Cotter J.,Life And Health Science Research Institute 3Bs
Acta Medica Portuguesa | Year: 2015

Introduction: Small bowel capsule endoscopy is currently the first line diagnostic examination for many diseases affecting the small bowel. This article aims to review and critically address the current indications of small bowel capsule endoscopy in clinical practice. Material and Methods: Bibliographic review of relevant and recent papers indexed in PubMed. Results and Discussion: Small bowel capsule endoscopy enables a non-invasive full-assessment of the small bowel mucosa, with high diagnostic yield even for subtle lesions. In patients with obscure gastrointestinal bleeding, diagnostic yield is higher when performed early after the onset of bleeding. Endoscopic treatment of angioectasias using balloon-assisted enteroscopy may contribute to reduce rebleeding, while the risk of rebleeding in patients with “negative“ small bowel capsule endoscopy is debatable. Cross-sectional imaging may be more accurate than small bowel capsule endoscopy for the diagnosis of large small bowel tumors. The Smooth Protruding Index on Capsule Endoscopy (SPICE score) may help to differentiate submucosal tumors from innocent bulges. Small bowel capsule endoscopy is also a key diagnostic instrument in patients with suspected Crohn’s disease and non-diagnostic ileocolonoscopy; it may also influence prognosis and therapeutic management, by determining disease extent and activity in patients with known Crohn’s disease. The role of small bowel capsule endoscopy to investigate possible complications in patients with non-responsive coeliac disease is evolving. Conclusions: Small bowel capsule endoscopy is a valuable diagnostic instrument for patients with obscure gastrointestinal bleeding and/or suspected small bowel tumors; it may also be a key examination in patients with suspected Crohn’s disease, or patients with known Crohn’s disease to fully assess disease extension and activity; finally, it may contribute for the diagnosis of complications of non-responsive coeliac disease. © Ordem dos Médicos 2015.


Cotter J.,Centro Hospitalar Do Alto Ave | Cotter J.,University of Minho | Cotter J.,Life and Health science Research Institute 3Bs | Dias De Castro F.,Centro Hospitalar Do Alto Ave | And 3 more authors.
Endoscopy | Year: 2015

Background and study aims: The Lewis score was developed to measure mucosal inflammatory activity as detected by small-bowel capsule endoscopy (SBCE). The aim of the current study was to validate the Lewis score by assessing interobserver correlation and level of agreement in a clinical setting. Patients and methods: This was a retrospective, single-center, double-blind study including patients with isolated small-bowel Crohn's disease who underwent SBCE. The Lewis score was calculated using a software application, based on the characteristics of villous edema, ulcers, and stenoses. The Lewis score was independently calculated by one of three investigators and by a central reader (gold standard). Interobserver agreement was assessed using intraclass correlation (ICC) coefficient and Bland-Altman plots. Results: A total of 70 patients were consecutively included (mean age 33.9±11.7 years). The mean Lewis score was 1265 and 1320 for investigators and the central reader, respectively. There was a high correlation, both for scores obtained for each tertile (first tertile r=0.659-0.950, second tertile r=0.756-0.906, third tertile r=0.750-0.939), and for the global score (r=0.745-0.928) (P<0.0001). Interobserver agreement was almost perfect between the investigators and the central reader (first tertile ICC=0.788-0.971, second tertile ICC=0.824-0.943, third tertile ICC=0.857-0.968, global score ICC=0.852-0.960; P<0.0001). The inflammatory activity was classified as normal (score<135) in 2.9% vs. 2.9%, mild (score≥135-<790) in 51.4% vs. 55.7%, and moderate to severe (score≥790) in 45.8% vs. 41.4% of patients, respectively (P<0.001). Conclusion: A strong interobserver agreement was demonstrated for the determination of the Lewis score in a practical clinical setting, validating this score for the reporting of small-bowel inflammatory activity. The Lewis score might be used for diagnosing, staging, follow-up, and therapeutic assessment of patients with isolated small-bowel Crohn's disease.


Pinto L.,University of Minho | Pinto L.,Life and Health science Research Institute 3Bs | Mateus-Pinheiro A.,University of Minho | Mateus-Pinheiro A.,Life and Health science Research Institute 3Bs | And 6 more authors.
PLoS ONE | Year: 2012

Characterization of neuronal dendritic structure in combination with the determination of specific neuronal phenotype or temporal generation is a challenging task. Here we present a novel method that combines bromodioxyuridine (BrdU) immunohistochemistry with Golgi-impregnation technique; with this simple non-invasive method, we are able to determine the tridimensional structure of dendritic arborization and spine shape of neurons born at a specific time in the hippocampus of adult animals. This analysis is relevant in physiological and pathological conditions in which altered neurogenesis is implicated, such as aging or emotional disorders. © 2012 Pinto et al.


Andrade E.B.,Abel Salazar Biomedical Sciences Institute | Andrade E.B.,University of Porto | Alves J.,Abel Salazar Biomedical Sciences Institute | Alves J.,University of Porto | And 12 more authors.
Journal of Immunology | Year: 2013

Sepsis is the third most common cause of neonatal death, with Group B Streptococcus (GBS) being the leading bacterial agent. The pathogenesis of neonatal septicemia is still unsolved. We described previously that host susceptibility to GBS infection is due to early IL-10 production. In this study, we investigated whether triggering TLR2 to produce IL-10 is a risk factor for neonatal bacterial sepsis. We observed that, in contrast to wild-type (WT) pups, neonatal TLR2-deficient mice were resistant to GBSinduced sepsis. Moreover, if IL-10 signaling were blocked in WT mice, they also were resistant to sepsis. This increased survival rate was due to an efficient recruitment of neutrophils to infected tissues that leads to bacterial clearance, thus preventing the development of sepsis. To confirm that IL-10 produced through TLR2 activation prevents neutrophil recruitment, WT pups were treated with the TLR2 agonist Pam3CSK4 prior to nebulization with the neutrophil chemotactic agent LTB 4. Neutrophil recruitment into the neonatal lungs was inhibited in pups treated with Pam3CSK4. However, the migration was restored in Pam3CSK 4 treated pups when IL-10 signaling was blocked (either by anti-IL-10R mAb treatment or by using IL-10-deficient mice). Our findings highlight that TLR2-induced IL-10 production is a key event in neonatal susceptibility to bacterial sepsis. Copyright © 2013 by The American Association of Immunologists, Inc.


Pereira-Terra P.,University of Minho | Pereira-Terra P.,Life and Health science Research Institute 3Bs | Moura R.S.,University of Minho | Moura R.S.,Life and Health science Research Institute 3Bs | And 6 more authors.
Journal of Physiology | Year: 2015

Congenital diaphragmatic hernia (CDH) is characterised by a spectrum of lung hypoplasia and consequent pulmonary hypertension, leading to high morbidity and mortality rates. Moreover, CDH has been associated with an increase in the levels of pulmonary neuroendocrine factors, such as bombesin and ghrelin, and a decrease in the action of retinoic acid (RA). The present study aimed to elucidate the interaction between neuroendocrine factors and RA. In vitro analyses were performed on Sprague-Dawley rat embryos. Normal lung explants were treated with bombesin, ghrelin, a bombesin antagonist, a ghrelin antagonist, dimethylsulfoxide (DMSO), RA dissolved in DMSO, bombesin plus RA and ghrelin plus RA. Hypoplastic lung explants (nitrofen model) were cultured with bombesin, ghrelin, bombesin antagonist or ghrelin antagonist. The lung explants were analysed morphometrically, and retinoic acid receptor (RAR) α, β and γ expression levels were assessed via Western blotting. Immunohistochemistry analysis of RAR was performed in normal and hypoplastic lungs 17.5 days post-conception (dpc). Compared with the controls, hypoplastic lungs exhibited significantly higher RARα/γ expression levels. Furthermore considering hypoplastic lungs, bombesin and ghrelin antagonists decreased RARα/γ expression. Normal lung explants (13.5 dpc) treated with RA, bombesin plus RA, ghrelin plus RA, bombesin or ghrelin exhibited increased lung growth. Moreover, bombesin and ghrelin increased RARα/γ expression levels, whereas the bombesin and ghrelin antagonists decreased RARα/γ expression. This study demonstrates for the first time that neuroendocrine factors function as lung growth regulators, sensitising the lung to the action of RA through up-regulation of RARα and RARγ. © 2015 The Physiological Society.


Cotter J.,Centro Hospitalar Do Alto Ave | Cotter J.,Life and Health science Research Institute 3Bs | Dias De Castro F.,Centro Hospitalar Do Alto Ave | Magalhaes J.,Centro Hospitalar Do Alto Ave | And 2 more authors.
Endoscopy | Year: 2014

Background and study aims: The Lewis score was developed to measure mucosal inflammatory activity as detected by small-bowel capsule endoscopy (SBCE). The aim of the current study was to validate the Lewis score by assessing interobserver correlation and level of agreement in a clinical setting. Patients and methods: This was a retrospective, single-center, double-blind study including patients with isolated small-bowel Crohn's disease who underwent SBCE. The Lewis score was calculated using a software application, based on the characteristics of villous edema, ulcers, and stenoses. The Lewis score was independently calculated by one of three investigators and by a central reader (gold standard). Interobserver agreement was assessed using intraclass correlation (ICC) coefficient and Bland-Altman plots. Results: A total of 70 patients were consecutively included (mean age 33.9±11.7 years). The mean Lewis score was 1265 and 1320 for investigators and the central reader, respectively. There was a high correlation, both for scores obtained for each tertile (first tertile r=0.659-0.950, second tertile r=0.756-0.906, third tertile r=0.750-0.939), and for the global score (r=0.745-0.928) (P<0.0001). Interobserver agreement was almost perfect between the investigators and the central reader (first tertile ICC=0.788-0.971, second tertile ICC=0.824-0.943, third tertile ICC=0.857-0.968, global score ICC=0.852-0.960; P<0.0001). The inflammatory activity was classified as normal (score<135) in 2.9% vs. 2.9%, mild (score≥135-<790) in 51.4% vs. 55.7%, and moderate to severe (score≥790) in 45.8% vs. 41.4% of patients, respectively (P<0.001). Conclusion: A strong interobserver agreement was demonstrated for the determination of the Lewis score in a practical clinical setting, validating this score for the reporting of small-bowel inflammatory activity. The Lewis score might be used for diagnosing, staging, follow-up, and therapeutic assessment of patients with isolated small-bowel Crohn's disease. © Georg Thieme Verlag KG Stuttgart · New York.

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