Publications by authors named "Júlia Freitas"

11 Publications

  • Page 1 of 1

A water-soluble manganese(II) octanediaoate/phenanthroline complex acts as an antioxidant and attenuates alpha-synuclein toxicity.

Biochim Biophys Acta Mol Basis Dis 2022 10 28;1868(10):166475. Epub 2022 Jun 28.

Departamento de Bioquímica, Instituto de Química, Centro de Tecnologia, Cidade Universitária, Universidade Federal do Rio de Janeiro, Brazil; Rede de Micrologia RJ-FAPERJ, Brazil. Electronic address:

The overproduction of reactive oxygen species (ROS) induces oxidative stress, a well-known process associated with aging and several human pathologies, such as cancer and neurodegenerative diseases. A large number of synthetic compounds have been described as antioxidant enzyme mimics, capable of eliminating ROS and/or reducing oxidative damage. In this study, we investigated the antioxidant activity of a water-soluble 1,10-phenantroline-octanediaoate Mn-complex on cells under oxidative stress, and assessed its capacity to attenuate alpha-synuclein (aSyn) toxicity and aggregation, a process associated with increased oxidative stress. This Mn-complex exhibited a significant antioxidant potential, reducing intracelular oxidation and increasing oxidative stress resistance in S. cerevisiae cells and in vivo, in G. mellonella, increasing the activity of the intracellular antioxidant enzymes superoxide dismutase and catalase. Strikingly, the Mn-complex reduced both aSyn oligomerization and aggregation in human cell cultures and, using NMR and DFT/molecular docking we confirmed its interaction with the C-terminal region of aSyn. In conclusion, the Mn-complex appears as an excellent lead for the design of new phenanthroline derivatives as alternative compounds for preventing oxidative damages and oxidative stress - related diseases.
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http://dx.doi.org/10.1016/j.bbadis.2022.166475DOI Listing
October 2022

Influence of two caries detection strategies on the quality of life of preschool children: An analysis of secondary outcomes of a 2-Year randomized clinical trial.

Community Dent Oral Epidemiol 2022 Jun 7. Epub 2022 Jun 7.

Department of Pediatric Dentistry, School of Dentistry, University of São Paulo, São Paulo, Brazil.

Objective: This randomized clinical trial aimed to evaluate the influence of two caries diagnosis strategies, and subsequent management, on oral health-related quality of life (OHRQoL) of preschoolers. Additionally, the association of the OHRQoL outcomes with the clinician-centred primary outcome used in the main study was also explored.

Materials And Methods: This study refers to the OHRQoL secondary outcomes analyses of the so-called RCT 'CARDEC-1'. Three- to 6-year-old children were randomly allocated in two caries detection strategies in primary molars: visual inspection (VIS) or visual + radiographic (RAD) assessment. Participants were diagnosed and treated according to the allocated group and followed up for 2 years. Caregivers answered the Early Childhood Oral Health Impact Scale (ECOHIS) at baseline and after 2 years. Intention-to-treat analysis was performed. ECOHIS scores at baseline and 2 years later were compared using the Mann-Whitney test. Effect sizes, change scores and the minimally important difference (MID) were also compared between groups. Additional analysis was performed to assess if OHRQoL variables could reflect the primary clinical outcome (number of new operative interventions during the follow-up), observing if these met the Prentice criteria.

Results: Two hundred and five children had the ECOHIS answered in both period times (18.7% attrition rate). There was a decrease in total ECOHIS scores, as well as for different domains for both trial groups, with effect sizes varying from 0.43 to 0.77. Comparisons between groups, however, did not show significant differences. In the additional analysis, the OHRQoL variables met the Prentice criteria and presented the same trends observed with the clinician-centred primary endpoint.

Conclusion: Caries detection performed by visual inspection alone or associated with radiographic method does not influence the long-term impact on OHRQoL. Furthermore, OHRQoL variables reflect clinical outcomes in this type of clinical trial.

Clinicaltrials: gov NCT02078453.
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http://dx.doi.org/10.1111/cdoe.12765DOI Listing
June 2022

Efficacy of a calcium-phosphate/fluoride varnish and ionomeric sealant on cervical dentin hypersensitivity: A randomized, double-blind, placebo-controlled clinical study.

J Oral Rehabil 2022 Jan 2;49(1):62-70. Epub 2021 Nov 2.

Department of Restorative Dentistry, School of Dentistry, University of São Paulo, São Paulo, Brazil.

Background: Dentin hypersensitivity (DH) is a common problem in the population that can have a significant impact on the quality of life of those who suffer from the condition.

Objectives: Compare the efficacy of two treatments for DH: Ca/PO /F varnish (Clinpro White Varnish) and ionomeric sealant (IS) (Clinpro XT Varnish) with a placebo.

Methods: Participants (121) with at least one tooth with visual analogue scale (VAS) score of 4 and above were randomly and blindly allocated to the groups. Treatments were performed by a trained researcher. DH was evaluated by another blind researcher after the treatment and after 1 week, 4 weeks, 3 months and 6 months. After 4 weeks, placebo received the DH treatment with IS; thus, the participants were not assessed after 3 and 6 months. Primary outcome was DH reduction after 4 weeks. Differences in VAS scores in the other time intervals and entire values of VAS were considered secondary outcomes. Comparisons were made among the groups (α = 0.05).

Results: IS showed the highest VAS value difference between baseline and 4 weeks (mean ± SD: 3.7 ± 2.2), differing significantly from placebo (2.3 ± 1.7) and Ca/PO4/F varnish (2.6 ± 2.0). Ca/PO4 /F varnish did not differ from placebo. In all time intervals, VAS values of all groups were significantly lower than the baseline value, without differences among groups. For the long-term differences in VAS values (3 and 6 months), the IS exhibited significantly higher values than Ca/PO4 /F varnish.

Conclusions: The IS was the most efficacious product for reducing DH, whereas Ca/PO4 /F varnish did not differ from placebo. Registered in ClinicalTrials.gov (NCT04591444).
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http://dx.doi.org/10.1111/joor.13270DOI Listing
January 2022

Negligible therapeutic impact, false-positives, overdiagnosis and lead-time are the reasons why radiographs bring more harm than benefits in the caries diagnosis of preschool children.

BMC Oral Health 2021 03 31;21(1):168. Epub 2021 Mar 31.

Department of Pediatric Dentistry, School of Dentistry, Faculty of Dentistry, University of São Paulo, Av. Lineu Prestes, 2227, São Paulo, SP, 05508-000, Brazil.

Background: To evaluate the clinical course and interventions required during two years of follow-up of dental surfaces of deciduous molars diagnosed, and consequently treated, by two different strategies: diagnosis made by clinical examination alone or associated with radiographs.

Methods: This is a secondary analysis of a two-arm randomized clinical trial with parallel groups related to the diagnostic strategy for caries detection in preschool children. 216 children (3-6 years old) were followed-up for two years. All dental surfaces were diagnosed by visual inspection and later, through radiographic assessment. Baseline treatment was made in accordance with the results obtained by visual inspection performed alone or combined with radiographic method, considering the allocated group. Dental surfaces with no restoration needs, or those restored at the beginning of the study were followed-up for two years. The treatment decision was made according to the allocated group. The outcome was the occurrence of failure (a new caries lesion or a restoration replacement) during the follow-up.

Results: 4383 proximal and occlusal surfaces of deciduous molars in 216 preschool children were diagnosed and treated according to the abovementioned diagnostic strategies and followed-up for 24 months. The assessment of radiographs made change the initial decision reached by visual inspection in about 30% of the surfaces when all types of interventions were considered. However, most disagreements occurred for initial lesions, where radiographs tended to underestimate them. Discordances between methods occurred in less than 5% of all surfaces when considered lesions requiring operative treatment. For discrepancy cases, the placed interventions guided by following the radiographic results did not present less failures against those made following only visual inspection. As a matter of fact, the use of radiographs in the diagnostic strategy for caries detection in children brought more harms than benefits due to the occurrence of false-positives, overdiagnosis and lead-time bias.

Conclusions: Simultaneous association of visual inspection and radiographic assessment for caries detection in preschool children causes more harms than benefits, and therefore, visual inspection should be conducted alone in the regular clinical practice. Trial registration Clinicaltrials.gov platform: NCT02078453, registered on 5th March 2014.
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http://dx.doi.org/10.1186/s12903-021-01528-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011211PMC
March 2021

TGF-β Inhibitors in Metastatic Pancreatic Ductal Adenocarcinoma.

J Gastrointest Cancer 2019 Jun;50(2):207-213

Department of Surgery, University of Tennessee Health Science Center, 910 Madison Ave., Suite 300, Memphis, TN, 38163, USA.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancerrelated mortality in the USA, and the overall incidence of the disease is increasing such that it is expected to be the third leading cause of cancer-related deaths in the next decade. Minimal improvements in therapy have not changed the overall mortality rate over the past decade for patients with PDAC. The purpose of this review is to identify new data regardign the role of Transforming growth factor beta (TGF-β) based therapeuics in patients with PDAC.

Methods: The literature was searched for peer reviewed manuscripts regarding the use of TGF-β inhibitors in PDAC therapy and the mechanism in which TGF-β intracellular signaling effects patient survival.

Results: TGF-β plays a vital, context-dependent role as both a tumor suppressor and promoter of PDAC. The downstream effects of this duality play a significant role in the immunologic response of the tumor microenvironment (TME), epithelial-mesenchymal transformation (EMT), and the development of metastatic disease. Immunologic pathways have been shown to be successful targets in the treatment of other diseases, though they have not been shown efficacious in PDAC. TGF-β-mediated EMT does play a critical role in PDAC progression in the development of metastases. The use of anti-TGF-β-based therapies in phase I and II clinical trials for metastatic PDAC demonstrate the importance of understanding the role of TGF-β in PDAC progression.

Conclusion: This review clarifies the recent literature investigating the role of anti-TGF-β-based therapy in PDAC and areas ripe for targeted investigations and therapies.
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http://dx.doi.org/10.1007/s12029-018-00195-5DOI Listing
June 2019

Responsiveness of the Early Childhood Oral Health Impact Scale (ECOHIS) is related to dental treatment complexity.

Health Qual Life Outcomes 2017 Sep 20;15(1):182. Epub 2017 Sep 20.

Department of Pediatric Dentistry, School of Dentistry, University of São Paulo, Av. Lineu Prestes, 2227, São Paulo, 05508-000, SP, Brazil.

Background: The responsiveness of the Early Childhood Oral Health Impact Scale (ECOHIS) has varied greatly across studies; hence, we hypothesized that this discrepancy could be related to the complexity of dental treatment received. Thus, we aimed to evaluate the responsiveness of the ECOHIS to changes in oral health-related quality of life (OHRQoL) following dental treatments of varying complexity in preschool children.

Methods: Preschool children aged 3 to 6 years were selected; their parents responded to the ECOHIS at baseline. The parents responded to the ECOHIS again and a global transition question 30 days after the children were treated. The type of treatment received by the children was categorized according to complexity, as follows: 1) non-operative treatment only, 2) restorative treatment, and 3) endodontic treatment and/or tooth extraction. Change scores and effect sizes (ES) were calculated for total scores, as well as considering the different treatment types and global transition question responses.

Results: Of the 152 children who completed the study, the ECOHIS yielded large ES for total scores (0.89). The children showed increasing ES values associated with better perception of improvement, assessed by the global transition question. The magnitude of ES after treatment was related to treatment complexity (0.53, 0.92 and 1.43, for children who received non-operative treatment only, restorative treatment, and endodontic treatment and/or tooth extraction, respectively).

Conclusions: Parents whose children required more complex dental treatment are more likely to perceive treatment-related changes to OHRQoL assessed with the ECOHIS.
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http://dx.doi.org/10.1186/s12955-017-0756-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5608161PMC
September 2017

Effect of an intensive nutrition intervention of a high protein and low glycemic-index diet on weight of kidney transplant recipients: study protocol for a randomized clinical trial.

Trials 2017 09 6;18(1):413. Epub 2017 Sep 6.

Post Graduate Program in Health Sciences, Endocrinology, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2400, 90035-003, Porto Alegre, RS, Brazil.

Background: Excessive weight gain is commonly observed within the first year after kidney transplantation and is associated with negative outcomes, such as graft loss and cardiovascular events. The purpose of this study is to evaluate the effect of a high protein and low glycemic-index diet on preventing weight gain after kidney transplantation.

Methods: We designed a prospective, single-center, open-label, randomized controlled study to compare the efficacy of a high protein (1.3-1.4 g/kg/day) and low-glycemic index diet versus a conventional diet (0.8-1.0 g/kg/day of protein) on preventing weight gain after kidney transplantation. A total of 120 eligible patients 2 months after transplantation will be recruited. Patients with an estimated glomerular filtration rate through the modification of diet of renal disease (MDRD) formula < 30 mL/min/1.73 m or urinary albumin excretion > 300 mg/24 h will be excluded. Patients' diets will be allocated through simple sequential randomization. Patients will be followed-up for 12 months with nine clinic appointments with a dietitian and the evaluations will include nutritional assessment (anthropometrics, body composition, and resting metabolic rate) and laboratory tests. The primary outcome is weight maintenance or body weight gain under 5% after 12 months. Secondary outcomes include body composition, resting metabolic rate, satiety sensation, kidney function, and other metabolic parameters.

Discussion: Diets with higher protein content and lower glycemic index may lead to weight loss because of higher satiety sensation. However, there is a concern about the association of high protein intake and kidney damage. Nevertheless, there is little evidence on the impact of high protein intake on long-term kidney function outcome. Therefore, we designed a study to test if a high protein diet with low-glycemic index will be an effective and safe nutritional intervention to prevent weight gain in kidney transplant patients.

Trial Registration: ClinicalTrials.gov identifier, NCT02883777 . Registered on 3 August 2016.
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http://dx.doi.org/10.1186/s13063-017-2158-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585938PMC
September 2017

Antiproliferative and ultrastructural effects of phenethylamine derivatives on promastigotes and amastigotes of Leishmania (Leishmania) infantum chagasi.

Parasitol Int 2017 Apr 22;66(2):47-55. Epub 2016 Nov 22.

Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro/RJ, CCS, Bloco I, CEP 219491-902, Brazil. Electronic address:

Leishmania (Leishmania) infantum chagasi is one of the agents that cause visceral leishmaniasis. This disease occurs more frequently in third world countries, such as Brazil. The treatment is arduous, and is dependent on just a few drugs like the antimonial derivatives and amphotericin B. Moreover, these drugs are not only expensive, but they can also cause severe side effects and require long-term treatment. Therefore, it is very important to find new compounds that are effective against leishmaniasis. In the present work we evaluated a new group of synthetic amides against the promastigote and amastigote forms of L. infantum chagasi. The results showed that one of these amides in particular, presented very effective activity against the promastigotes and amastigotes of L. infantum chagasi at low concentrations and it also presented low toxicity for mammal cells, which makes this synthetic amide a promising drug for combating leishmaniasis.
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http://dx.doi.org/10.1016/j.parint.2016.11.010DOI Listing
April 2017

Characterization of metformin by-products under photolysis, photocatalysis, ozonation and chlorination by high-performance liquid chromatography coupled to high-resolution mass spectrometry.

Rapid Commun Mass Spectrom 2016 Nov;30(21):2360-2368

Programa de Pós-Graduação em Engenharia Ambiental (ProAmb), Universidade Federal de Ouro Preto, Ouro Preto, MG, 35400-000, Brazil.

Rationale: Metformin (MTF) is the most widely prescribed drug for the treatment of patients with type 2 diabetes. Studies involving the removal of MTF from aqueous solutions and detailed information regarding the overall degradation process are scarce.

Methods: The degradation of MTF in aqueous solution induced by direct photolysis, photocatalysis, ozonation and chlorination was evaluated. The process was continuously monitored focusing on the identification and monitoring of the by-products formed by applying high-performance liquid chromatography coupled to high-resolution mass spectrometry in positive ion mode. The cytotoxicity of metformin by-products was evaluated with an MTT assay.

Results: The results from the chlorination and ozonation tests indicate metformin removal efficiencies of 60% after 30 min of exposure. On the other hand, direct photolysis (UV-C) and heterogeneous photocatalysis (TiO /UV-C) led to a lower degree of metformin degradation, with removal efficiencies of 9.2% and 31%, respectively, after 30 min of exposure. The mineralization rates varied from 20% for ozonation to 0.72% for photolysis, thereby indicating there was accumulation of degradation by-products in all experiments. Mass spectrometric analysis indicated the presence of five metformin by-products. It was not possible to identify any by-product generated in the photolysis, and, in all oxidative assays, the treated samples were nontoxic to HepG2 cells.

Conclusions: It is also observed that all systems exhibited low mineralization rates, with the chlorination process being slightly more efficient in promoting the degradation, whereas the ozonation was more efficient in promoting the mineralization of metformin. Based on these results a route for the chlorination, photodegradation and ozonation of MTF, which comprised of its successive oxidation in the aqueous medium, could be proposed. It could also be concluded that the treated samples were not cytotoxic to HepG2 cells in a MTT assay. Copyright © 2016 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/rcm.7724DOI Listing
November 2016

The Solution Structure and Dynamics of Full-length Human Cerebral Dopamine Neurotrophic Factor and Its Neuroprotective Role against α-Synuclein Oligomers.

J Biol Chem 2015 Aug 6;290(33):20527-40. Epub 2015 Jul 6.

From the Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21.941-902, Brazil,

Cerebral dopamine neurotrophic factor (CDNF) is a promising therapeutic agent for Parkinson disease. As such, there has been great interest in studying its mode of action, which remains unknown. The three-dimensional crystal structure of the N terminus (residues 9-107) of CDNF has been determined, but there have been no published structural studies on the full-length protein due to proteolysis of its C-terminal domain, which is considered intrinsically disordered. An improved purification protocol enabled us to obtain active full-length CDNF and to determine its three-dimensional structure in solution. CDNF contains two well folded domains (residues 10-100 and 111-157) that are linked by a loop of intermediate flexibility. We identified two surface patches on the N-terminal domain that were characterized by increased conformational dynamics that should allow them to embrace active sites. One of these patches is formed by residues Ser-33, Leu-34, Ala-66, Lys-68, Ile-69, Leu-70, Ser-71, and Glu-72. The other includes a flexibly disordered N-terminal tail (residues 1-9), followed by the N-terminal portion of α-helix 1 (residues Cys-11, Glu-12, Val-13, Lys-15, and Glu-16) and residue Glu-88. The surface of the C-terminal domain contains two conserved active sites, which have previously been identified in mesencephalic astrocyte-derived neurotrophic factor, a CDNF paralog, which corresponds to its intracellular mode of action. We also showed that CDNF was able to protect dopaminergic neurons against injury caused by α-synuclein oligomers. This advises its use against physiological damages caused by α-synuclein oligomers, as observed in Parkinson disease and several other neurodegenerative diseases.
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http://dx.doi.org/10.1074/jbc.M115.662254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536457PMC
August 2015

Undertreatment of depressive symptomatology in the elderly living in long stay institutions (LSIs) and in the community in Brazil.

Arch Gerontol Geriatr 2010 Mar-Apr;50(2):151-5. Epub 2009 Apr 8.

Cardiorespiratory Physical Therapy Laboratory, Department of Physical Therapy, Federal University of Pernambuco (UFPE), Av. Prof. Moraes Rego, 1235, Recife-PE, 50.670 901, Brazil.

The aim of the present study was to assess the presence of depressive symptomatology among elderly residents in long stay institution (LSI) and in the community of Recife, Brazil. In total, 81 LSI elderly patients (mean age of 75.55 + or - 9.18 years) and 132 elderly (mean age of 73.14 + or - 8.27 years) individuals from the community were evaluated. Depressive symptomatology was assessed by the geriatric depression scale (GDS-15), cognitive status by the mini mental state examination (MMSE) and capacity to perform the activities of daily living (ADL) by the Katz Index. Comorbidities and the use of medication were recorded. The LSI elderly exhibited more depressive symptoms (p < 0.001) and more dependency (p < 0.001). We observed no differences in MMSE (p = 0.058). The elderly in the community displayed more comorbidities and the LSI elderly consumed more medication (p < 0.001 and < 0.001, respectively). According to multivariate analysis (logistic regression), being male, having no spouse and having a low schooling level are risk factors for depressive symptoms. In conclusion, most elderly with depressive symptoms received no medication for depression.
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http://dx.doi.org/10.1016/j.archger.2009.03.002DOI Listing
April 2010
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