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Dissertations |
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MARIA EDUARDA TENORIO OLIVEIRA
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MULTI-OMIC ANALYSIS OF THE GUT MICROBIOME IN RATS WITH LITHIUM-PILOCARPINE INDUCED TEMPORAL LOBE EPILEPSY
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Advisor : DANIEL LEITE GOES GITAI
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COMMITTEE MEMBERS :
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DANIEL LEITE GOES GITAI
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JEAN PHELLIPE MARQUES DO NASCIMENTO
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TIAGO GOMES DE ANDRADE
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Data: Jan 25, 2022
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Show Abstract
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Evidence supports that the gut microbiota and bacteria-dependent metabolites influence the maintenance of epileptic brain activity. However, the alterations in the gut microbiota between epileptic versus healthy individuals are poorly understood. We used a multi-omic approach to evaluate the changes in the composition of gut bacteriome as well in the fecal metabolomic profile in rats before and after being submitted to Status Epilepticus (SE)-induced Temporal Lobe Epilepsy (TLE). The 16S ribosomal RNA (rRNA) sequencing of fecal samples coupled to bioinformatic analysis revealed taxonomic, compositional, and functional shifts in epileptic rats. The species richness (Chao1 index) was significantly lower in the post-TLE group, and the ß-diversity analysis revealed clustering separated from the pre-TLE group. The taxonomic abundance analysis showed a significant increase of Desulfobacterota phylum and a decrease of Patescibacteria. The DESEq2 and LEfSe analysis resulted in 18 genera significantly enriched between pos-TLE and pre-TLE groups at the genus level. We observed that epileptic rats present a peculiar metabolic phenotype, including a lower concentration of D-glucose and L-lactic and a higher concentration of L-glutamic acid and glycine. The microbiota-host metabolic correlation analysis showed that the genera differentially abundant in pos-TLE rats are associated with the altered metabolites, especially the proinflammatory Desulfovibrio and Marvybiatria, which were enriched in epileptic animals and positively correlated with these excitatory neurotransmitters and carbohydrate metabolites. Therefore, our data support the notion that post-SE dysbacteriosis contributes to the development of epilepsy by enhancing chronic inflammation, an excitatory-inhibitory imbalance, and/or a metabolic disturbance.
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2
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RAYANE MARTINS BOTELHO
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Seric cytokines and anaphylotoxins analyses in COVID-19 patients
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Advisor : ALEXANDRE URBAN BORBELY
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COMMITTEE MEMBERS :
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ALEXANDRE URBAN BORBELY
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KAREN STEPONAVICIUS CRUZ BORBELY
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ROBINSON SABINO DA SILVA
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Data: Feb 15, 2022
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Show Abstract
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Introduction: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection fastly spread, resulting in the pandemic coronavirus disease 2019 (COVID-19). The pathogenesis of COVID-19 is associated with an inadequate or exaggerated immune response that can result in significantly elevated levels of cytokines, increased thrombosis, lung injury, acute myocarditis and multiple organs failure. Although several data have been published, knowledge gaps still exist and prognostic markers are needed. As such, our aim was to evaluate the cytokines and anaphylotoxins profile in patients with COVID-19 in Alagoas, Brazil to find prognostic markers. Methodology: A cross-sectional observational study, with 76 participants, of which 56 had COVID-19 with diagnosis confirmed by qRT-PCR, while 20 were donors without COVID-19. The study was approved by the human ethical committee (30732120.1.0000.5013). Control participants were age, sex and comorbidities-matched to the COVID-19 group. Blood samples were obtained as soon as patients arrived in the HUPAA/UFAL and their plasma were quantified for cytokines (IL-1β, IL-6, IL-8, IL-10, IL-12p70, IFN-α2, IFN-β, IFN-λ1, IFN-λ2/3, IFN-γ, TNF-α, IP-10, GM-CSF, IL-2, IL-4, IL-6 and IL-17A) and anaphylotoxins (C3a, C4a and C5a) by flow cytometry bead-based assays. Results: COVID-19 patients had reduced levels of GM-CSF, and increased levels of C3a and C4a, which were also found as markers of severity. We also found increased levels of IL-10 and IL-12p70 in COVID-19 diceased patients in comparison to those hospital discharged. Elderly with COVID-19 had increased IFN-λ1, C3a and C4a in comparison to elderly controls. Sex comparison of COVID-19 patients showed that women had increased levels of IFN-α2, IFN-λ2/3, IFN-γ and GM-CSF. In comparison to control of the same sex, COVID-19 women had increased IFN-γ, C3a and C4a, while men had reduced IL-1β, IL-12p70 and GM-CSF, and increased C3a and C4a. Lastly, the ROC curve of C3a+C4a measures had high specificity (100%) and sensitivity (85%). Conclusion: Age, sex and comorbidities change specific cytokines that could be markers for them, while IL-10 and IL-12p70 increase could indicate a bad prognosis. C3a and C4a were remarkably increased in COVID-19 patients and could be markers of COVID-19 severity, indicating with high accuracy patients that would require ICU admission.
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3
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JAQUELINE CORREIA SANTOS
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Placental infection by the Zika Virus: investigation of the action of natural products with antiviral activity
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Advisor : ALEXANDRE URBAN BORBELY
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COMMITTEE MEMBERS :
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ANDREA MOLLICA DO AMARANTE PAFFARO
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ALEXANDRE URBAN BORBELY
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JADRIANE DE ALMEIDA XAVIER
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Data: Mar 30, 2022
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Show Abstract
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Introduction: The Zika virus (ZIKV) is an emerging arbovirus, which has spread rapidly in recent years and has caused large outbreaks. It is originally from Africa and has spread to Asia, Oceania and the Americas, and its main transmitter is the genus Aedes mosquito. In 2015, in the face of an outbreak in Brazil, it drew the attention of health authorities, where the association of the virus infection with fetal neurological complications began, supported by studies carried out during the ZIKV outbreaks in Brazil and French Polynesia. Although ZIKV activity has declined significantly in recent years, the potential for ZIKV introduction and transmission in new areas is high and unpredictable. Thus, the development of vaccines and drugs against ZIKV remains a research priority, with natural products being important sources in the discovery of compounds with antiviral activity. Objective: To characterize the antiviral effect of ethanol extracts obtained from the species Passiflora edulis, Schinus terebinthifolius Raddi, Moringa oleífera and Cocos lucífera, on the response of placental cells exposed to ZIKV. Methods: HTR-8/SVneo cells derived from the first trimester of pregnancy and term placental explants were exposed to the extracts and cell viability was evaluated. The extracts that proved to be viable were exposed to infection by the ZIKV strains in the trophoblast cells and the antiviral potential was analyzed by qRT-PCR and flow cytometry. In view of the infection and the treatments of the extracts, the cell cycle and production of cytokines were analyzed. Results: None of the extracts tested decreased the viability of placental explants, on the other hand, only extracts of Passiflora edulis seed, Schinus terebinthifolius Raddi fruit and Schinus terebinthifolius Raddi bark did not decrease the viability of HTR-8SV/neo cells. All the extracts tested were effective in reducing the viral load both in HTR-8SV/neo cells and in placental explants, with more impressive results with the Passiflora edulis seed extract. In the production of cytokines, none of the extracts intervened in the modulation of interferons. Infection-induced IL-8 was reduced by the bark extract of Schinus terebinthifolius Raddi, while IL-10 was increased with the fruit extract of Schinus terebinthifolius Raddi. TNF-a was decreased in the presence of treatments with Schinus terebinthifolius Raddi and Passiflora edulis. Conclusion: All these results show that the tested extracts are promising sources of compounds with antiviral action against ZIKV, mainly from Schinus terebinthifolius Raddi and Passiflora edulis.
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4
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DIOGO BRANDÃO
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LEISHMANICIDE POTENTIAL OF BACTERIA EXTRACTS ISOLATED FROM ANTARCTICA LIQUENS
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Advisor : MAGNA SUZANA ALEXANDRE MOREIRA
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COMMITTEE MEMBERS :
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MAGNA SUZANA ALEXANDRE MOREIRA
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ALINE CAVALCANTI DE QUEIROZ
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MARIANA DA SILVA SANTOS
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Data: May 26, 2022
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Show Abstract
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Leishmaniasis is an infectious parasitic disease, neglected and widely distributed geographically, affecting millions of individuals on all continents of the planet. The pharmacological list available for the treatment of infections caused by leishmania is limited and has high toxicity. Therefore, there is a relentless search for new, safer and more effective therapeutic options for the treatment of leishmaniasis. This study aimed to investigate the activity of candidates for prototype leishmanicidal drugs based on bacterial extracts isolated from Antarctic lichens that constitute safer therapeutic options for the treatment of leishmaniasis. The pigment-producing bacteria were reactivated in Nutrient Agar medium at 15ºC for 7 days and the inocula were standardized and seeded in 50ml of nutrient broth. The metabolites were extracted by centrifugation and pellet separation, which was subjected to cell lysis with methanol followed by vortexing and centrifugation to obtain intracellular pigments. The MTT colorimetric assay was used to assess the cytotoxicity effect on J774.A1 lineage macrophages. The extracts 8LB19, 5LB35, 23LB3, 7LB4, 10 AUVB14, 6AUVB13 did not show cytotoxicity to macrophages, except for 5AUVB13 which presented cytotoxicity to the host cell with maximum observed effect of 38.2 ± 3.7%. Promastigote cultures of L. chagasi and L. amazonensis were counted directly under an optical microscope to verify the leishmanicidal activity. Statistical calculations were obtained using the GraphPad Prism program. Of the methanol extracts tested to date on L. chagasi, 5 AUVB 13 and 6 AUVB 13 exhibited potent activity with a maximum effect of 97.93 ± 1.88%, 96.10 ± 0.01% and IC50 of 18. 31 µg/ml (11.22 - 30.47) 22.05 µg/ml (13.51 - 30.59), 7 LB 4 and 23 LB 3 demonstrated activity below 50%, with a maximum effect of 32.47 ± 5.19, 16.30 ± 1.88 respectively. 8 LB 19, 5 LB 35 and 10 AUVB 14 were not active. Against L. amazonensis, 8 LB 19, 5 LB 35 and 10 AUVB 14 were not active; 23 LB 3 and 7 LB 4, however, exhibited moderate activity with a maximum effect of 37.50 ± 1.80 and 39.58 ± 4.54, respectively. 5 AUVB 13 and 6 AUVB 13 exhibited activity greater than 50% with the respective maximum effects of 65.63 ± 1.80 and 60.42 ± 1.04 and IC50 of 52.72 (37.14 - 68.29) and 44.63 (33.61-55.65), with emphasis on 5 AUVB 13 and 6 AUVB 13 that were active in both species. Pharmacological tests to determine the leishmanicidal activity are still to be completed, as well as the dosage of nitric oxide.
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5
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ANA LUCIA MENDES DA SILVA
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Uvaol effects on trophoblast cells in the chorioamnionitis induced by group B streptococcus
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Advisor : ALEXANDRE URBAN BORBELY
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COMMITTEE MEMBERS :
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ALEXANDRE URBAN BORBELY
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ELIANA MARA OLIVEIRA LIPPE
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SILVIA DAHER
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Data: Jul 28, 2022
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Show Abstract
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serious complications during pregnancy, such as maternal sepsis, chorioamnionitis,
prematurity, neonatal sepsis and neurodevelopmental disorders. GBS-induced
chorioamnionitis leads to changes in trophoblastic cells, with the production of
inflammatory mediators that can modify the way they interact within the placental
microenvironment, especially with endothelial cells, causing the modification of the
placental vascular structure in pregnant women due to production abnormal
angiogenic mediators. There is no prophylaxis for the deleterious effects caused by
GBS infection. Knowing that maternal nutrition directly influences pregnancy, we
evaluated whether uvaol, a triterpene present in olive oil, could be used preventively,
using different in vitro models. Objective: To investigate whether uvaol prevents
cellular changes caused by GBS incubation in vitro. Methodology: The HTR-8SV/neo
cell line and chorionic villi explants were pre-treated with uvaol and exposed to a non
lethal concentration of inactivated GBS (106 CFU), confirmed by MTT and labeling by
annexin V and propidium iodide. HTR-8SV/neo cells were evaluated for their
biochemical composition by Raman spectroscopy; morphology using phalloidin
fluorescein labeling; production of mitochondrial reactive oxygen species; cytokine
production by flow cytometry; phagocytosis by Giemsa staining; migration by in vitro
wound assay; endothelial invasion by 3D coculture with Ea.hy926 cells; and production
of angiogenic factors by flow cytometry. Placental explants were evaluated by MTT
and their production of angiogenic factors by flow cytometry. Results: Despite not
altering the viability of HTR-8SV/neo cells, GBS modified the cytoskeleton and
biochemical composition. GBS increased the production of IL-1β (p<0.05) and IFN-γ
(p<0.001) and oxidative stress, in addition to promoting phagocytosis. Cell migration
and invasion were reduced after incubation with GBS. Exposure to GBS led to
increased production of CXCL-8 (p<0.01) and IL-6 (p<0.05) in the 3D endothelial
invasion model, while uvaol prevented this increase (both p<0.05). With respect to
placental explants, the same effect was observed. Treatment with Uvaol proved to be
effective in preventing most of the changes caused by incubation with GBS, with an
important prophylactic potential. Conclusions: Even at a non-lethal concentration, the
presence of inactivated GBS caused inflammation, reduced trophoblast motility and
increased production of CXCL-8 and IL-6, factors that participate in vascular
dysregulation observed in several diseases and that can be triggered by placental GBS
infection. Due to its protective effect, it is possible that Uvaol is an alternative to prevent
the harmful effects caused by GBS in the maternal-fetal interface.
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THAYANE KELLY DOS SANTOS CÂNDIDO
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FREQUENCY OF METABOLIC SYNDROME AND ITS IMPACT ON QUALITY OF LIFE IN SUBJECTS CARE AT A RHEUMATOLOGY SERVICE IN ALAGOAS
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Advisor : LUIZA ANTAS RABELO
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COMMITTEE MEMBERS :
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LUIZA ANTAS RABELO
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ALANE CABRAL MENEZES DE OLIVEIRA
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SANDRA MARY LIMA VASCONCELOS
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Data: Aug 22, 2022
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Show Abstract
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Introduction: Patients with rheumatoid arthritis (RA) have accelerated atherosclerosis and an elevated risk of premature morbidity and mortality from cardiovascular disease (CVD). Metabolic syndrome (MetS), a cluster of factors associated with increased risk of CVD, has a higher frequency in these patients, due to the inflammatory process of RA. Objective: To estimate the frequency of MetS and its impact on quality of life in a sample of patients with and without RA treated at a rheumatology facility from Alagoas. Methods: Outpatients with and without RA were cross-sectionally evaluated with respect to demographic, clinical, laboratory, anthropometric and quality of life data. The criterion used to define RA was the one adopted by the American College of Rheumatology in collaboration with the European League Against Rheumatism in 2010, and the criterion used to identify MetS was the Harmonized version of 2009. Results: 70 patients were enrolled, being 45 cases and 26 controls, which after screening were subdivided into 20 cases, 24 cases with MetS, 16 controls and 10 controls with MetS. The frequency of MetS in RA was 54% and 38.4% in patients without RA. Patients with RA had higher levels of HDL-c and worse quality of life. Conclusion: Based on current knowledge, it is possible to state that the frequency of MetS was higher in patients with RA compared to those without RA, and this process was associated with the inflammatory activity of RA. Furthermore, a greater impairment on quality of life in individuals with RA and MetS was observed when compared with CT individuals with and without MetS.
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MONALY DE OLIVEIRA LIMA
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Treatment of temporomandibular joint osteoarthritis: systematic review of the literature and evaluation of the effects of simvastatin on human osteoblasts in vitro
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Advisor : EMILIANO DE OLIVEIRA BARRETO
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COMMITTEE MEMBERS :
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EMILIANO DE OLIVEIRA BARRETO
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JAMYLLE NUNES DE SOUZA FERRO
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JANAINA ANDRADE LIMA SALMOS DE BRITO
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Data: Aug 25, 2022
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Show Abstract
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Osteoarthritis of the temporomandibular joint (TMJ-OA) is a chronic, non-infectious, focal degenerative disease associated with the subchondral bone remodeling with functional dysregulation of osteoblasts. Studies suggest that statins are promising candidates for new drugs for osteoarthritis (OA) because of their effects on modulating the inflammatory response. Therefore, the present study aimed to carry out a systematic review of the scientific literature to answer which drugs would be available for the treatment of OA. Furthermore, we also sought to use an experimental approach to evaluate the in vitro effects of simvastatin on human osteoblasts. For the systematic review, search strategies were used in the MEDLINE, Cochrane Central, Web of Science, BBO, and EMBASE databases, including articles until July 2022. After analyzing the abstracts, and applying the inclusion and exclusion criteria, 6 studies met the established eligibility criteria. The methodological assessment was performed using the Jadad Scale, the analysis for risk of bias was determined by the table for risk of bias, and the analysis of evidence was determined by the GRADE tool. The analysis of the studies revealed that pharmacological treatment caused a decrease in pain intensity in all evaluated studies, with emphasis on the high level of evidence according to the GRADE tool for intra-articular treatment with sodium hyaluronate associated with therapy with oral glucosamine. In the experimental approach of the present study, the human osteoblast lineage MG-63 was used to evaluate in vitro the effects of simvastatin. Our results demonstrated that concentrations of 1-10 μM of simvastatin did not affect the cell viability of osteoblasts. However, when the morphology of osteoblasts was evaluated, it was observed that simvastatin altered the morphology of the cells as the polarized shape was replaced by an increase in the number of cells with a rounded profile. This change in morphology was also observed when cells were stimulated with LPS. However, when evaluating the phagocytic capacity of these cells, treatment with simvastatin was not able to induce/alter the phagocytosis of zymosan particles. In another experimental set, LPS-stimulated production of nitric oxide by osteoblasts was inhibited by treatment with simvastatin. Taken together, the results of this study demonstrate that the scientific literature gathered in the systematic review presents therapeutic alternatives that support the improvement of pain and noise in TMJ-OA. However, studies with detailed standardized variables and methods are necessary to reduce the risk of bias found, which may compromise the conclusion of a certain therapeutic option for clinical practice. In addition, the importance of correlation of clinical studies with biomarkers evaluated in vitro is emphasized that can contribute to the analysis of drugs aimed at preventing and/or stagnating the progression of TMJ-OA. Therefore, we demonstrated in vitro that simvastatin proved to be a promising candidate for a drug that modulates some osteoblast functions, indicating the potential for clinical use in TMJ-OA.
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8
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SUSANA PAIVA OLIVEIRA
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ASSOCIATION STUDY OF IL10 AND IL6 GENES WITH LEPROSY IN A POPULATION FROM AGRESTE OF ALAGOAS STATE
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Advisor : CAROLINNE DE SALES MARQUES
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COMMITTEE MEMBERS :
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ANA CAROLINE MELO DOS SANTOS
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CAROLINNE DE SALES MARQUES
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JAMYLLE NUNES DE SOUZA FERRO
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Data: Aug 29, 2022
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Show Abstract
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Leprosy is a chronic infectious disease caused by the bacteria Mycobcterium leprae and mainly affects the skin and peripheral nerves. Brazil is the second country in the world in number of cases of leprosy. From 2014 to 2019, around 164,000 new cases of leprosy were reported in the country. In 2015, the Northeast region had an incidence rate of the disease (per 100,000 inhabitants) of 21.53, while Alagoas had an incidence of 10.57, considered to be very high and high endemicity rates, respectively. Despite this, there are still no published studies investigating the possible risk factors related to the occurrence of the disease in the region of Alagoas. One of the factors related to the development of leprosy is the genetic component of the host, especially SNPs in genes related to cytokines of the immune response in the pathophysiology of the disease. Previous studies have shown an association of polymorphisms in the genes of the cytokines IL-10 and IL-6. The aim of the present study was to investigate associations of cytokine genes with leprosy and to verify the correlation between associated polymorphisms and the immuno-inflammatory profile of individuals. A case-control study was carried out including leprosy patients and healthy individuals recruited in Arapiraca-AL. After that, DNA extraction from peripheral blood was performed by the salting-out method (or DNA precipitation method). From the extracted DNA, the genotyping of SNPs in these genes was performed, using allelic discrimination assays by real-time PCR. The analyzes were performed using the logistic regression model, which also allows for the inclusion of possible covariates that may introduce some kind of bias in the analyses, generating measures of genetic association with leprosy. To assess the immuno-inflammatory profile, the cytokines IL-10 and IL-6 were measured in the serum of individuals by ELISA and compared between individuals with different genetic profiles (one-way ANOVA test between medians), seeking a genetic-functional correlation . All analyzes will be performed in an R environment. As a result of population recruitment in Alagoas, we obtained 422 individuals, 158 cases and 264 controls. In polymorphisms in the population of Alagoas for the CT genotype of the SNP rs1800871 of the IL10 gene, it was observed that the CT genotype was more frequent in patients (56%) than in the control group (48%), not showing to be a significant difference, and therefore, the polymorphism was not associated with leprosy in this particular model (OR= 1.50; p-value= 0.2; CI= 0.95-2.36; OR: 1.50). The AG genotype for the rs2069845 SNP of the IL6 gene was frequent in 45% of cases and 47% of controls. According to the codominant model that evaluated the individual categories of genotypes and comparing the frequency in cases and controls, it was observed that there is no statistically significant difference between these frequencies (OR= 0.73; CI= 0.45-1.17; p-value= 0.11 ), with no association with leprosy. The cytokine dosage step is in progress with the perspective of characterizing the inflammatory profile of leprosy patients according to the SNPs genotypes in the IL10 and IL6 genes. The results will significantly contribute to the understanding of the genetic influence on leprosy, making it possible to enrich a panel of predictive markers for the development of the disease in the population of Alagoas and Brazil.
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9
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THIAGO PINA GOES DE ARAUJO
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PI3Ks signaling pathway as a molecular target for glioblastoma therapy: a review
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Advisor : MAGNA SUZANA ALEXANDRE MOREIRA
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COMMITTEE MEMBERS :
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ALINE CAVALCANTI DE QUEIROZ
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ANDRESSA LETICIA LOPES DA SILVA
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MAGNA SUZANA ALEXANDRE MOREIRA
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Data: Aug 31, 2022
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Show Abstract
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Glioblastoma (GBM) is the most common type of cancer of the central nervous system (CNS). It currently accounts for about 2% of diagnosed malignant tumors, with 296,000 new cases reported each year. The gold standard treatment consists of surgical resection, radiotherapy and adjuvant chemotherapy which increases patient survival by 15 months and few survive more than 5 years after diagnosis. New clinical and pre-clinical research aims to improve this prognosis by proposing the search for new drugs that act effectively in the elimination of cancer cells bypassing problems such as resistance to treatment. One of the promising therapeutic strategies in the treatment of GBM is the inhibition of the phosphatidylinositol 3-kinase (PI3Ks) pathway, which is closely related to the process of tumor carcinogenesis. This review sought to address the main scientific studies of synthetic or natural drug prototypes that target specific therapy co-directed to the PI3Ks pathway, against human glioblastoma.
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10
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RAYANE FERREIRA DA SILVA
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Descriptive epidemiology and the IRF6 gene implications in a series of cases of typical oral clefts
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Advisor : ISABELLA LOPES MONLLEO
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COMMITTEE MEMBERS :
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CAROLINNE DE SALES MARQUES
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ISABELLA LOPES MONLLEO
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THALITA CRISTINA FIGUEIREDO CUNHA
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Data: Oct 24, 2022
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Show Abstract
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Background: Typical orofacial clefts (TOC) are among the most frequent human malformations, with a prevalence rate of 1:700 to 1000 live births. IRF6 gene (Interferon Regulatory Factor 6) has been worldwide implicated in cases of familial non-syndromic TOC and in the Van der Woude syndrome (VWS). Aim: To describe the epidemiology and the implications of IRF6 gene in a series of non-syndromic TOC and VWS from the Ambulatório de Genética Craniofacial do Serviço de Genética Clínica do Hospital Universitário Professor Alberto Antunes da Universidade Federal de Alagoas (SGC-HUPAA-UFAL). Patients and methods: From 2009 to 2021, 375 patients entered the Alagoas database, 255 (71.6%) of whom, presenting non-syndromic TOC, were selected for sociodemographic, clinical, and familial profiling. Information was extracted from the Brazilian Database on Craniofacial Anomalies and tabulated using Excel. Fisher test and Qui-square were used for statistics with a p-value of 0,05 through Epi infoTM. The IRF6 gene was selected for molecular analysis of 21 multiplex families and the single case of VWS of the sample. Six families presenting parent-child transmission were studied through whole exome sequencing in collaboration with the State University of Campinas. The remaining families as well as the patient diagnosed with VWS were studied through Sanger sequencing at our laboratory at SGC-HUPAA-UFAL. The in-house experiments comprised: Phenolic DNA extraction, the polymerase chain reaction of all exons and splice sites, purification, quantification, and sequencing reaction. Software Chromas was used for electropherogram analysis and the CLC Sequencing Viewer for sequences alignment. Identified variants were checked against free access databases. In silico predictive analyses using software PROVEAN, SIFT, PolyPhen-2, Mutation Taster, Align GVGD e MutPred-2 were used for the classification purpose of the new variants. The amino acid conservation among mammalians analysis was through Clustal Omega, and the protein modeling through Swiss-model and PyMol software. Results: Among 255 patients with non-syndromic TOC, the male biologic sex (55,8%), and the unilateral (74,2%), left-sided (51,0%) cleft lip and palate (51,0%) were predominant. These results corroborate the literature. There were 97 (38,6%) familial cases, almost twice the expected frequency. Cleft lip with/without cleft palate (p=0,14), parental consanguinity (p=0,02) and twining (p=0,008) were significantly high in familial cases compared to sporadic. The IRF6 complete sequencing did reveal no pathogenic variants among the six parent-child transmission families. Sanger sequencing of the remaining families is not finished, and, up to now, no pathogenic variants have been recognized. The clinical diagnosis of VWS was based on the typical association between cleft lip and palate, and paramedian lower-lip small mounds. The novel p.Phe266Ser heterozygous (TTT/TCT) variant was identified through Sanger sequencing. It has achieved pathogenic scores in all prediction software used. According to Clustal Omega, the amino acid phenylalanine is highly conserved, and the parental sequencing showed this is a de novo variant. According to the model obtained, the phenylalanine-serine exchange disrupts the IRF6 protein. Conclusions: Apart from the high rate of familial cases and consanguinity, the sociodemographic and clinical profile of non-syndromic TOC corroborates the literature. Up to now, no IRF6 pathogenic variant was found among 27 families presenting non-syndromic TOC, including the six families with parent-child transmission for which the IRF6 sequencing is finished. The novel p.Phe266Ser variant, present in the single case of VWS in this series, was classified as pathogenic and de novo.
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CARMELITA BASTOS MENDES
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Thyroid hormones as possible co-regulators of aquaporins 1 and 4 in human gliomas: a pilot study using a bioinformatics approach.
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Advisor : ADRIANA XIMENES DA SILVA
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COMMITTEE MEMBERS :
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ADRIANA XIMENES DA SILVA
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EMILIANO DE OLIVEIRA BARRETO
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MYKAELLA ANDRADE DE ARAUJO
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Data: Nov 18, 2022
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Show Abstract
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In 2016 the World Health Organization (WHO) included molecular markers (genotypic expression) as important predictive factors for diagnostic of brain tumors. In the brain, the expression and localization of water channel transporters, aquaporins (AQPs), are substantially modified in gliomas during tumorigenesis, cell migration, edema formation and resolution. Therefore, we hypothesized that molecular changes associated with AQP1 and AQP4 in the brain may be potential anticancer therapeutic targets. Our research group, for instance, has already shown a modulating action of triiodothyronine (T3), the biologically active form of thyroid hormone, on the AQP4 expression in the developing nervous system and on GBM cells. To test it, a bioinformatic analysis from publicly available data from international consortia was carried out. Here, we used RNA-seq as an experimental strategy and identified the differential expression of AQP1 and AQP4 transcripts numbers in gliomas tissue if compared to normal brain tissues. Indeed, the AQPs genes were overexpressed in glioma patients. Among gliomas subtypes, AQP1 and AQP4 were overexpressed in astrocytoma (low grade-glioma) and classical (high grade-glioma). The overall survival analysis demonstrated both AQP genes can be used as a prognostic factor for patients with low grade-glioma, confirming the results of previous studies and reinforcing their clinical value. We also observed a correlation between the expression of genes involved in tyrosine and thyroid hormone pathways and AQPs. Namely: PNMT, ALDH1A3, AOC2, HGDATP1B1, ADCY5, PLCB4, ITPR1, ATP1A3, LRP2, HDAC1, MED24, MTOR and ACTB1 (Spearman’s coefficient = ≥ 0.20 and p-value = ≤ 0.05). These molecular pathways and AQP1 and AQP4 genes may be used to study new anti-tumor drugs and the molecular diagnosis of gliomas because showing potential as diagnostic and therapeutic biomarkers for malignant gliomas.
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DENISE MACEDO DA SILVA
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ASSOCIATION OF POLYMORPHISM OF THE TLR4 896 A>G (rs4986790) AND iNOS -1173 C>T (rs9282799) GENES WITH CERVICAL CANCER IN HPV-INFECTED WOMEN IN A SAMPLE OF THE POPULATION OF ALAGOAS, BRAZIL: A CASE-CONTROL AND META-ANALYSIS STUDY
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Advisor : ELAINE VIRGINIA MARTINS DE SOUZA FIGUEIREDO
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COMMITTEE MEMBERS :
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ANA CAROLINE MELO DOS SANTOS
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ELAINE VIRGINIA MARTINS DE SOUZA FIGUEIREDO
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MARCIO BEZERRA SANTOS
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Data: Dec 1, 2022
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Show Abstract
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Cervical canceris one of the leading causes of death among women in the world, representing the fourth most frequent and fourth leading cause ofcancer death in the female population worldwide.This malignant neoplasm mainly affects socioeconomically vulnerable women
and approximately 90% of cases are associated with high-risk HPV infection.In addition, immunological and genetic factors such as Single NucleotidePolymorphisms (SNPs) present in host genes may play animportant role in virus clearanceor cervical cancer susceptibility, such as SNPs in Toll-Like Receptor 4 genes (TLR4) and Inducible Nitric Oxide Synthase (iNOS).Thus, the present study aimed to evaluatethe association of TRL4 896 A>G (rs4986790) and iNOS -1173 C>T (rs9282799) gene polymorphisms with cervical cancer in women infected with HPV in a sample of the populationof Alagoas, Brazil.Thisis a case-control study, where 99 samples were genotyped for the TRL4 896 A>G gene (72 healthycontrols, 27 cases of HPV+ cervical cancer) and 120 samples for iNOS -1173 C>T (82 healthy controls, 38 cases of HPV+ cervical cancer) using the real-time Polymerase Chain Reaction (PCR) technique.Additionally, a systematic review and meta-analysis of the TLR4 896 A>G (rs4986790) polymorphism was performed.In the case-controlstudy, the results referring to SNP 896A>G in the TLR4 gene showed a statistically significant difference when comparing allele and genotypic frequencies, wherethe 896G allele (p=0.01; OR with 95% CI=5.87 [1.41-24.40]) and 896A/G genotype were associated with increased risk of cervical cancer (p=0.01; OR with 95% CI=6.57 [1.51-28.56]).This demonstrates tha twhen comparingthe 896A/A homozygotewiththe 896A/G heterozygote the presence of a G allele was sufficient to increase the risk.The sampling power was 100% and the population was in agreement with the Hardy-Weinberg equilibrium (p=0.63).The resultsof the meta-analysisof the TLR4 896 A>G (rs4986790) polymorphism did not demonstrate significant associations, differing from the results found in thepopulation of Alagoas.This fact can be explained by the scarcity of association studies between the SNP TLR4 896 A>G (rs4986790) and cervical cancer, as well as thelow sample sizeofthestudiesincluded in the meta-analysis.In the overall analysis of the association between the polymorphic variant -1173C>T of iNOS and cervical cancer, no association was found.The rare genotype -1173T/T was notidentified in any groupand the heterozygote -1173T/C had a low frequency in this population.The distribution of genotypic frequencies in the populationwas in accordance with the Hardy-Weinberg equilibrium (p=0.88).It is concluded that the G allele in the SNP TLR4 896 A>G (rs4986790) represents a risk factor for cervical cancer in the population of Alagoas.In the meta-analysis with other populations, no associations were found.The iNOS -1173 C>T SNP wasnotassociatedwith cervical cancer in thispopulation.However, the results regarding the polymorphismof the iNOS -1173 C>T gene are inconclusive due to the limited sample size, which presented a low sampling power.Studies with a larger sample number can elucidate the influenceof this polymorphism on the cervical carcinogenesis process, since the number of current studies is limited.
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13
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BRUNA BRANDAO DOS SANTOS
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SOCIODEMOGRAPHIC, MENTAL HEALTH AND GENETIC PROFILE OF TNF-A (-308 G>A), IL-10(-819 C>T) AND 5-HTT (rs2020933 A>T) SNPs IN ALCOHOL USERS.
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Advisor : ELAINE VIRGINIA MARTINS DE SOUZA FIGUEIREDO
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COMMITTEE MEMBERS :
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ELAINE VIRGINIA MARTINS DE SOUZA FIGUEIREDO
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ANA CAROLINE MELO DOS SANTOS
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RENISE BASTOS FARIAS DIAS
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Data: Dec 5, 2022
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Show Abstract
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The use of psychoactive substances is considered a health problem worldwide, among these substances is alcohol. In addition, studies point to a relationship between alcohol use and mental health disorders. From the gender point of view, the use of alcohol by women is linked to social factors and stigmatization. Several neurotransmitters and their respective pathways are involved in the effects caused by alcohol in the body, such as: serotonergic, GABAergic and glutamatergic. In this sense, it is noteworthy that polymorphisms may be involved in susceptibility or protection to alcohol use. Therefore, the objective of this study is to analyze the sociodemographic, mental health and genetic characteristics of polymorphisms in the IL-10 -819 C>T (rs1800871), TNFA -308 G>A (rs1800629) and 5-HTT (rs2020933) genes. in individuals using alcohol. This was a cross-sectional study with alcohol users. The identification of the genotypes of the genes: IL-10 -819 C>T (rs1800871), TNFA -308 G>A (rs1800629) and 5-HTT (rs2020933 A>T) was determined by means of a timed polymerase chain reaction. real (qPCR). For statistical analysis, the IBM SPSS software version 22.0 was used. P values less than 0.05 were considered statistically significant. The study consisted of a total of 91 individuals, 31 belonging to the case group, alcohol users, and 60 to the control group (non-alcohol users). As for sociodemographic characteristics, the mean age was 29.8 years for women and 32.9 years for men. Most living in urban areas, own house or apartment, single and brown. High levels of impulsivity and aggression were identified. the most prevalent mental disorders in the population studied were: Current major depressive episode 84.2% (n=16), suicide risk 63.1% (n=11), Antisocial personality disorder 73.6% (n=14) and generalized anxiety 52.6% (n=10). No statistically significant values were found for the TNFA -308 G>A (rs1800629) and 5-HTT (rs2020933) polymorphisms, while for the IL-10 (-819 C>T) polymorphism the T allele (18.2%) was associated with reduced risk for alcohol consumption in women (OR=0.203; CI=0.638; p=0.011).
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Thesis |
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1
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LIDIA BEZERRA BARBOSA
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FOOD CONSUMPTION AND ASSOCIATION WITH THE METABOLIC SYNDROME AND ITS COMPONENTS: A POPULATION-BASED STUDY WITH QUILOMBOLA WOMEN IN THE STATE OF ALAGOAS, BRAZIL
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Advisor : HAROLDO DA SILVA FERREIRA
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COMMITTEE MEMBERS :
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Poliana Coelho Cabral
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ALANE CABRAL MENEZES DE OLIVEIRA
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HAROLDO DA SILVA FERREIRA
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JAMILE FERRO DE AMORIM
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SANDRA MARY LIMA VASCONCELOS
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Data: Feb 23, 2022
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Show Abstract
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Objective: To investigate the dietary patterns and processing levels of food consumed by quilombola women and verify their association with metabolic syndrome (MS) and its components. Methods: Cross-sectional population-based household survey study conducted in remnant communities of quilombos in the state of Alagoas, Brazil. A probabilistic sample of 876 women aged between 19 and 59 years (38.8 ± 11.0) was used. Socioeconomic, demographic, lifestyle, anthropometric, health status and food intake characteristics were evaluated. Food consumption was estimated using a 24-hour recall survey (24hR). Metabolic syndrome was the dependent variable and food consumption the independent variable. Dietary patterns were derived by factor analysis using the principal components method followed by varimax orthogonal rotation. Foods consumed were categorized according to the NOVA classification. Associations were estimated by the crude and adjusted prevalence ratios and respective 95%CI, calculated by Poisson regression with robust variance. Results: The prevalence of MS was 48.1%. Six main dietary patterns were identified: meat, beans and seasoning pattern; standard cereals/roots, oils and infusions; standard sugars and fast food; standard fruits and vegetables; standard alcohol and vegetables; standard dairy products and protein broths. SM was not associated with any dietary pattern. The sugar and fast food pattern was associated with abdominal obesity. A lower prevalence of hyperglycemia and low HDL was associated with the pattern of dairy products and protein broths. According to the NOVA classification, consumption of processed culinary ingredients increased the probability of metabolic syndrome by 1.24 times. Conclusion: A higher consumption of dairy products and protein broths was associated with an increase in HDL rates and a reduction in the prevalence of hyperglycemia. MS was associated with the consumption of processed culinary ingredients. The results presented can be used as a guide for the development of interventions in the clinical and public policy spheres.
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2
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LARISSA TENORIO ANDRADE CORREIA
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Mother and infant associations between chronotype, sleep quality, maternal mental health and child development
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Advisor : TIAGO GOMES DE ANDRADE
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COMMITTEE MEMBERS :
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TIAGO GOMES DE ANDRADE
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CLAUDIO TORRES DE MIRANDA
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AUXILIADORA DAMIANNE PEREIRA VIEIRA DA COSTA E SILVA
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LIVIA LEITE GOES GITAI
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JULIANA FREITAS MARQUES
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Data: Mar 4, 2022
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Show Abstract
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The study of circadian rhythms throughout development and their physiological and behavioral impact at early stages is still scarce.We investigated herein the potential association between infant´s chronotype and development and their correlation with maternal mental health state, sleep disruptions and socioeconomic status(n = 111 dyads). The infants' sleep phase was partially explained by the mother's chronotype and sleep quality. The mother's sleep quality was also associated with total infant sleep time. Moreover, infants with atypical development presented a higher sleep latency. These findings highlight the relevance of healthcare interventions for better sleep hygiene during pregnancy and at early stages to support infants and their mothers.
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3
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JOAO FLAVIO MONTEIRO SILVA
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Leishmanicidal activity semi-synthetic compounds: a proposal for new strategies in the treatment of leishmaniasis
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Advisor : MAGNA SUZANA ALEXANDRE MOREIRA
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COMMITTEE MEMBERS :
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MAGNA SUZANA ALEXANDRE MOREIRA
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ALINE CAVALCANTI DE QUEIROZ
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ALYSSON WAGNER FERNANDES DUARTE
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JOAO XAVIER DE ARAUJO JUNIOR
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CAMILA DE BARROS PRADO MOURA SALES
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Data: Mar 30, 2022
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Show Abstract
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Leishmaniasis is a set of diseases caused by protozoa of the genus Leishmania. They manifest through varied symptoms classified into two major branches: tegumentary and visceral disorders, which in the American continent are mainly associated with L. amazonensis and L. chagasi, respectively, despite being caused by different species around the world. They are considered neglected endemic diseases, as they occur mainly in populations under socioeconomic vulnerability. The association of the disease with morbidities or other infectious diseases such as AIDS has a great impact on the duration, intensity and outcome of the disease, and current treatments are associated with a high risk of therapeutic failure and toxicity. With the search for improvement in the pharmacotherapy of leishmaniasis, new technologies such as the synthesis of drugs from bioactive substances are used by the public initiative of Federal Universities for the development of new drugs. The objective of this work was to evaluate the pharmacological potential of semi-synthetic derivatives through their activity against L. amazonensis and L. chagasi and the possible cytotoxicity in J774.A1 macrophages. Derivatives with different known bioactive groups were tested, such as triazol-amino-quinones and hydrazones. The results indicated leishmanicidal activity among the derivatives. For the most part, the toxicity profile was concentration-dependent. It is suggested the structural modification of some derivatives and the selection of those that can be explored even in higher concentrations in subsequent experiments. The development of new drugs continues to be a strategic branch of the fight against leishmaniasis, although joint actions in other spheres within the scope of public health also need to act in parallel to eradicate the diseases.
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4
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FERNANDA MARIA ARAUJO DE SOUZA
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VALIDATION OF A NEW ANIMAL MODEL IN THE STUDY OF ANXIETY AND DEPRESSION IN MICE INDUCED BY A LOW
DOSE OF PILOCARPINE
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Advisor : MARCELO DUZZIONI
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COMMITTEE MEMBERS :
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DANIEL LEITE GOES GITAI
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Elaine Cristina Gavioli
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FILIPE SILVEIRA DUARTE
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MARCELO DUZZIONI
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OLAGIDE WAGNER DE CASTRO
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Data: Apr 1, 2022
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Show Abstract
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Animal models for the study of anxiety and depression disorders are important tools for understanding the pathophysiology and developing new pharmacological therapies. Recently, studies have shown that subconvulsant doses of pilocarpine (PILO; nonselective muscarinic receptor agonist) produce short- and long-term anxiogenic-like behavior in Wistar rats. Our research group extended these data by demonstrating that Swiss mice (of both sexes) showed anxiogenic and depressive-like behavior after treatment with a low dose of PILO, with females being more susceptible to long-term effects. This research aimed to evaluate the pharmacological validity of this new animal model for anxiety and depression induced after administration of a low dose of PILO in mice. Futhermore, we also aimed to investigate serum levels of corticosterone and hippocampal neurogeneration. For pharmacological validity, Swiss mice received a PILO-injection (75 mg/Kg, i.p.) and 24 hours or for 30 consecutive days after were treated with diazepam (1.5 mg / Kg, i.p.) or fluoxetine (10 mg/Kg, i.p.). The short- (24h) and long-term (30d) effects of the treatments on behaviors related to fear, anxiety and depression were observed in the elevated plus-maze (EPM) and forced swim (FS) tests, respectively. The spontaneous locomotor activity of the animals was evaluated in the open field (OF). After the tests, blood and brains were collected from the animals to analyze the serum levels of corticosterone and hippocampal neurodegeneration (by Fluoro-Jade C; FJ-C). As a result, we observed that treatment with diazepam blocked both short- and long-term anxiogenic-like behavior (e.g., increased time and number of open arms entries in the EPM) induced by PILO, but not depressive-like behavior in the NF. Treatment with fluoxetine was able to block the anxiogenic-(e.g. increased time and number of open arms entries in the EPM) and depressive-like (e.g. decreased immobility time in the NF) behavior induced by PILO only in the long-term. Animals treated with PILO and later with diazepam or fluoxetine did not show changes in spontaneous locomotion in the OF. Treatment with PILO increased serum corticosterone levels in the short-, but not in the long-term. After 24h or 30d, animals treated with PILO did not show hippocampal neurodegeneration (FJ-C-). These results showed that the anxiogenic- and depressive-like behaviors induced by PILO can be blocked with acute or chronic treatment with standard anxiolytic and antidepressant, in a similar way to that found in the clinic, demonstrating the pharmacological validity of this new animal model.
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5
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LANNI SARMENTO DA ROCHA
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Effect of Triheptanoate-rich Ketogenic Diet on Memory and Cerebral Glucose Transport in Young and Aged Mice
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Advisor : ADRIANA XIMENES DA SILVA
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COMMITTEE MEMBERS :
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ADRIANA XIMENES DA SILVA
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ANA CATARINA REZENDE LEITE
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FABIANA ANDREA MOURA
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NASSIB BEZERRA BUENO
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VIVIAN SARMENTO DE VASCONCELOS
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Data: May 9, 2022
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Show Abstract
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The brain aging process triggers cognitive function impairment, like memory loss, compromising life quality. The cognitive impairment has a basis in bioenergetic status, with reduced glucose uptake and metabolization in aged brains. To access whether the improvement of oxidative capacity ameliorates cognitive function in aging, adult (12 weeks) and aged (22-month-old) C57/6BJ mice received (1) ketogenic, (2) ketogenic supplement with triheptanoin, or (3) show diets for 12 weeks. Spontaneous alternation and time spent in previously closed arm in the Y maze test and, time interacting with an unknown object in the novel object recognition test (NORT) evaluated memory. Acetylcholinesterase (AChE) activity in the prefrontal lobe, brain, and cerebellum was evaluated. GLUT3 expression in the prefrontal lobe was analyzed by the western blot method. Ketogenic diet (KD) decreased spontaneous alternation in aged mice, led to lower AChE activity in young and aged mice, and to lower GLUT3 expression in the prefrontal lobe of young mice. The supplementation of triheptanoin to KD prevented the impairment in memory and show similar values of AChE activity and GLUT3 expression compared to controls. Our data suggest that triheptanoin has a potential role in the bioenergetic capacity of the brain, though in improving cognitive function, which could impact life quality within the aging process.
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6
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OLAVO BARBOSA DE OLIVEIRA NETO
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PREVALENCE OF CANALIS SINUOSUS AND ACCESSORY CANALS OF CANALIS SINUOSUS IN CONE-BEAM COMPUTERIZED TOMOGRAPHIES: A SYSTEMATIC REVIEW AND META-ANALYSIS
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Advisor : CELIO FERNANDO DE SOUSA RODRIGUES
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COMMITTEE MEMBERS :
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CELIO FERNANDO DE SOUSA RODRIGUES
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GEORGE AZEVEDO LEMOS
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LUIZ ALEXANDRE MOURA PENTEADO
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OLAGIDE WAGNER DE CASTRO
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RODRIGO FREITAS MONTE BISPO
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Data: May 27, 2022
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Show Abstract
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Aim: To determine the prevalence of Canalis Sinuosus and accessory canals of Canalis Sinuosus using cone-beam computed tomography. Methodology: Two systematic reviews were carried out, one of them with meta-analysis, with electronic searches performed in MEDLINE via PubMed, Scopus, LILACS, Cochrane CENTRAL, Web of Science and SIGLE via OpenGrey. The primary variable was the prevalence of Canalis Sinuosus and accessory canals of Canalis Sinuosus. The secondary variables related to Canalis Sinuosus and its accessory canals were: ending in the vestibulo-palatal and mesio-distal direction; diameter; and distance to anatomic landmarks. Complementary variables were: number of participants and age of participants, distributed according to sex (male/female). Kappa statistics were calculated to determine the level of agreement between raters. The risk of bias of the primary studies was assessed using the AQUA tool. In one of the articles produced, a prevalence meta-analysis was performed with a 95% confidence interval. Heterogeneity, publication bias and sensitivity analyzes were also performed. Results: Seventeen primary studies were included, evaluated predominantly as of moderate risk of bias. The meta-analysis with 1994 participants showed a prevalence of Canalis Sinuosus of 0.80 (95% CI= 0.51.0.99; p=0.001; I2=99%) and of Canalis Sinuosus accessory channels, considering 4505 participants, showed a prevalence of 0.52 (95% CI). = 0.36,0.69; p=0.001; I2=99%). Sensitivity analyzes of Canalis Sinuosus accessory canals considering studies with more and less than 1000 participants did not change their condition of normal anatomical structure presented in the overall meta-analysis. Conclusion: With the results obtained from the meta-analyses carried out, both the Canalis Sinuosus and the accessory canals of the Canalis Sinuosus should be considered as normal anatomical structures, that is, present in most people, thus discrediting their conditions of anatomical variations.
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7
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JESSYKA CAROLINA GALVÃO DA SILVA
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CARDIOVASCULAR EFFECTS OF AAL 195, AN INHIBITOR OF PHOSPHODIESTERASE 4 IN SPONTANEOUSLY HYPERTENSIVE RATS
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Advisor : EURICA ADELIA NOGUEIRA RIBEIRO
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COMMITTEE MEMBERS :
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EURICA ADELIA NOGUEIRA RIBEIRO
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OLAGIDE WAGNER DE CASTRO
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HUGO JUAREZ VIEIRA PEREIRA
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LUCIANO APARECIDO MEIRELES GRILLO
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MARIA ALINE BARROS FIDELIS DE MOURA
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Data: Aug 29, 2022
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Show Abstract
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Hypertension is a disease with high prevalence and represents one of the main risk factors for cardiovascular disease. Despite the antihypertensive drugs available, many hypertensive patients do not reach ideal blood pressure levels, demonstrating the need to search for more effective pharmacological agents. Phosphodiestarases (PDE), enzymes that hydrolyze cAMP and cGMP, are widely distributed in the cardiovascular system. Inhibitors of these enzymes have been shown to be useful in the therapy of diseases of multifactorial origin, such as hypertension. Therefore, the objective of this work is to evaluate the actions of the PDE4 inhibitor, AAL 195, on the cardiovascular system of hypertensive rats. For this purpose, male spontaneously hypertensive rats (SHR) were used for all experiments, under CEUA-UFAL approval. Cardiovascular effects induced by AAL 195 were assessed by direct measurement of blood pressure and superior mesenteric artery preparations. Thus, in non-anesthetized SHR rats, AAL 195 (0.1; 0.5, 1 and 5 mg/kg, iv) induced hypotension (-24.6±1.7; -28.5±2.1; -28.9±4.6; -40.9±3.8%, respectively) associated with tachycardia (7.8±2.5; 13.4±3.7; 10.9±3.3; 12.1±3.8%, respectively), in a dose-independent manner. The hypotensive (-44.7±3.5 %) and tachycardic (34.5±5.7%) effects were also observed after administration of the ED50 of AAL 195 (1.48 mg/Kg, i.v.). In rats treated with atropine (2 mg/kg, i.v.), the hypotensive effect was not altered. However, there was a significant attenuation of tachycardia (5.2 ± 0.7%). This suggests that the hypotensive and tachycardic effects are independent. Treatment with L-NAME (20 mg/kg, iv) or indomethacin (3 mg/kg, iv) did not alter the hypotensive or tachycardic response. However, in rats treated with nifedipine (1 mg/kg, iv), the hypotensive (-27.0±3.5 %) and tachycardic (7.6±3.8 %) effects were significantly attenuated, suggesting the participation of L-type voltage-sensitive Ca2+ channels in these effects. In superior mesenteric artery rings of SHR rats, AAL 195 (10-9 – 3x10-5 M) promoted vasorelaxation in rings pre-contracted with phenylephrine (10 µM) (Emax = 100.0 ± 5.15%, pD2 = 6 .65 ± 0.08 M) in a concentration-dependent manner. After removal of the endothelium, the AAL 195 concentration-response curve was shifted to the right (pD2 = 6.25±0.05 M), without changing the maximum effect (Emax = 95.50±1.54%). In preparations without endothelium, incubated with 5mM of TEA, the vasorelaxation was attenuated (Emax = 81.05±4.91 %), indicating a possible participation of K+ channels in this effect. In preparations pre-incubated with GLIB (10 µM) or with 4-AP (1 mM), the vasorelaxant effect was potentiated, and the presence of apamine (0.1 µM) did not alter this effect. However, in the presence of 1 mM TEA, vasorelaxation was attenuated (Emax = 85.71±3.73 %), probably there is a participation of BKCa in this effect. AAL 195 (3x10-8 – 10-3 M) was also able to promote vasorelaxation in rings pre-contracted with 80 mM of KCl, which demonstrates a nonspecific effect of the compound. Therefore, AAL 195 was able to promote hypotensive and vasorelaxant effects in SHR. However, it also promoted a tachycardic effect, probably due to the inhibition of PDE4 in cardiomyocytes.
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8
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CLARISSIANE SERAFIM CARDOSO
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Investigation of a Glass Ionomer Cement modified from the incorporation of Fluorinated Lamellar Double Hydroxide (HDL-F): an in vitro and in silico study
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Advisor : CAMILA BRAGA DORNELAS
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COMMITTEE MEMBERS :
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CAMILA BRAGA DORNELAS
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ISABEL CRISTINA CELERINO DE MORAES PORTO
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LUCAS MEILI
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NATANAEL BARBOSA DOS SANTOS
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RODRIGO BARROS ESTEVES LINS
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Data: Nov 29, 2022
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Show Abstract
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The study aimed to develop a conventional hybrid glass ionomer cement (GIC) from the incorporation of a fluoridated layer double hydroxide (HDL-F) clay in concentrations of 1, 2, 5 and 10% by weight, aiming at improving strength. mechanical, antimicrobial and fluoride release profile (F-). Specimens (6 x 4mm) were made, crushed and sieved to obtain the powder and further characterized using X-ray diffraction (DRX), Fourier transform infrared spectroscopy (FTIR) and spectrometry. energy dispersive X-ray fluorescence (EDX). For mechanical evaluation, the axial compression test was performed according to the ISO 9917-1:2007 standard. For analysis of F- release, specimens were submerged in deionized water, which was replaced at pre-set times of 6h, 1, 2, 3, 5, 7, 14 and 21 days. The solution obtained was reserved for quantification of F- by a specific electrode of this ion. Release profiles were evaluated using kinetic models such as: zero order, first order, Higuchi and Korsmeyer-Peppas. The in silico analysis was performed in order to validate the in vitro mechanical analysis. The groups were designated as follows: CIV/HDL-F 1; CIV/HDL-F 2; CIV/HDL-F 5, CIV/HDL-F 10 and the clay-free control group: G0 = CIV, with variations in the conditioning of the specimens (temperature, time and humidity). Structurally, clay was crystalline different from CIV and from hybrid products that followed an amorphous pattern. Spectral bands were observed in the FTIR, characteristic of the studied materials. Elemental analysis of EDX revealed the predominance of magnesium and aluminum for clay and for cement calcium, silicon, aluminum, phosphorus and sodium were seen. For the products, in addition to these, magnesium was present, characterizing the presence of clay in the composites. Axial compression analysis revealed less resistant hybrid products compared to the control. The release of fluoride for the products revealed a slow and sustained release and the kinetic model that best fit was the Korsmeyer-Peppas with Fick and non-Fick formulations with slow diffusion through the outer layer of the material. It was concluded that the hybrid civ’s were easily obtained and characterized, showing a good fluoride release behavior and may become a strong ally in clinical practice with a view to reducing initial and secondary caries lesions.
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9
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LUCAS JOSE SA DA FONSECA
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Coexisting Metabolic Syndrome in Rheumatoid Arthritis: impact on redox status and insulin resistance
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Advisor : LUIZA ANTAS RABELO
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COMMITTEE MEMBERS :
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ALANE CABRAL MENEZES DE OLIVEIRA
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LUIZA ANTAS RABELO
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ODAIR ALVES DA SILVA
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SANDRA MARY LIMA VASCONCELOS
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VALERIA NUNES DE SOUZA
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Data: Dec 22, 2022
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Show Abstract
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Introduction: rheumatoid arthritis (RA) is a systemic autoimmune disease with joint compromise of destructive pattern. In its local (articular) and systemic inflammatory context, it is evident the participation of oxidative stress, a condition in which the balance between oxidants and antioxidants is lost, favoring cellular and molecular damage. Individuals with RA are at increased cardiovascular risk, being more prone to present metabolic syndrome (MetS) than in the general population. Such condition cluster various cardiometabolic risk factors, with a marked systemic inflammatory component. In this multifactorial context, the intersection points among RA, oxidative stress and MetS are still yet to be determined. Aim: to assess the impact of coexisting MetS on clinical evaluation and on systemic redox status in individuals with RA, searching for complementary biomarkers in the study of the systemic inflammatory milieu. Methodology: 26 controls (CT) from the local community and 45 individuals with RA were enrolled from the local community and from the Rheumatology outpatient facility in the Professor Alberto Antunes Teaching Hospital, Federal University of Alagoas, respectively. Diagnosis of RA was established according to the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR, 2010) classification criteria, and the diagnosis of MetS, based on those defined by the its harmonized version, 2009. After clinical assessment, patients underwent peripheral venous blood samples collection for general biochemical analyses and for the markers of oxidative stress (the enzymes superoxide dismutase, SOD; catalase, CAT; arginase, and the levels of serum lipid peroxidation by using the TBARS method). Insulin resistance was evaluated by the calculation of the TyG index. Results: the majority of volunteers was represented by females on both groups, with MetS frequency of 38.5% and 53.4% for CT and RA groups, respectively. Serum lipid peroxidation evidenced elevated levels of malondialdehyde (MDA) in RA patients compared to the CT group, and during subgroup analysis, coexisting MetS implied higher concentrations of MDA in RA individuals compared to the controls, as well as in the RA group compared to CT. The antioxidant enzyme SOD showed increased activity in the RA group in comparison to that observed in the controls with MetS, without significant differences for the CAT (both in plasma and in erythrocytes) and arginase enzymatic activities. Increased levels of HDL cholesterol and alkaline phosphatase were found in RA group compared to the controls, with no significant differences for the remaining biochemical and anthropometric parameters, and blood pressure values assessed. Subgroup analyses still showed significant differences among CT and RA groups with and without MetS for the parameters fasting glucose (lower means for RA vs RA with MetS; CT vs RA with MetS), triglycerides, TyG index (lower means for CT vs CT with MetS; RA vs RA with MetS; CT vs RA with MetS) and blood pressure values (lower systolic means for CT vs CT with MetS; higher systolic means for CT with MetS vs RA; CT with MetS vs RA with MetS). Conclusion: despite the use of pharmacological therapy with antioxidant effects, the oxidative imbalance was still evident in volunteers with RA, being worsened by coexisting MetS. Lipid peroxidation and the TyG index were shown as potential adjuvant biomarkers in the clinical assessment of these patients. MetS screening after RA diagnosis is made is crucial for early intervention on cardiovascular risk factors and for better joint and cardiovascular outcomes in patients with RA.
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10
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TAMARA RODRIGUES DOS SANTOS
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Social vulnerability and nutritional and health conditions of women and children: differences between the quilombola population and the general population of the state of Alagoas
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Advisor : HAROLDO DA SILVA FERREIRA
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COMMITTEE MEMBERS :
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HAROLDO DA SILVA FERREIRA
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MARLY AUGUSTO CARDOSO
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MYRTIS KATILLE DE ASSUNCAO BEZERRA
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REGINA COELI DA SILVA VIEIRA
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THATIANA REGINA FAVARO
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Data: Dec 22, 2022
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Show Abstract
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In recent decades, significant changes in nutrition and health profiles have been observed, both in Brazil and globally. In the adult population, there was an increase in the prevalence of obesity and non-communicable chronic diseases, such as arterial hypertension. Among children, especially those living in greater social vulnerability, although the increase in overweight is a reality, other forms of malnutrition, such as chronic malnutrition and anemia, have not yet been overcome. Properly coping with these problems, whether in adults or children, requires identifying the magnitude and factors associated with these conditions in different scenarios. Therefore, special attention must be given to ethnic-racial minorities, given the intense socioeconomic inequalities they are subjected to. Among these minorities, the quilombola population stands out, which, as a result of the historical oppression suffered, lives in a particularly vulnerable situation. To contribute to this problem, the objective of this thesis was to compare the nutrition and health conditions between quilombola and non-quilombola women and children in the state of Alagoas. To meet the proposed objective, the results chapter is presented in the form of two original articles. Both were based on two independent population-based household surveys carried out in the state of Alagoas in 2015 and 2018, involving non-quilombola women and children under 5 years of age and quilombola women and children, respectively. The first article, entitled “Nutrition and health of women from the state of Alagoas (Brazil): differentials according to the condition of belonging or not to the quilombola population”, compared the prevalence and factors associated with overweight and hypertension in the two scenarios. A total of 4,627 women were evaluated, of which 1,474 were quilombolas and 3,153 were non-quilombolas. The prevalence of overweight (66.8% vs. 62.4%; p=0.005) was higher in quilombola women. There was no difference in the prevalence of hypertension between the groups (23.1% vs. 22.1%; p=447). Factors associated with excess weight in quilombola women were: age > 30 years, presence of severe food insecurity, menarche before age 12, having children, and having hypertension. Among non-quilombolas, in addition to age >30 years, menarche before age 12, having children, and presenting hypertension, schooling ≤8 years, and alcohol consumption were also conditions associated with overweight. As for hypertension, the associated factors among quilombolas were: age > 30 years, schooling ≤ 8 years, menarche before 12 years, and overweight. Among non-quilombola women, in addition to age > 30 years, schooling ≤ 8 years, and overweight, the presence of severe food insecurity and having had a health problem in the last 30 days were also associated with hypertension. The second article, entitled “Social Determinants of Health: Differences in the nutritional status of children from the state of Alagoas (Brazil), according to the condition of being or not quilombola”, aimed to compare the nutritional status and factors associated with stunting, overweight and anemia among quilombola and non-quilombola children in the state of Alagoas. For this, it involved a sample of 1,546 children under 5 years of age, 991 non-quilombolas, and 555 quilombolas. For this, it involved a sample of 1,546 children under 5 years old, 555 from quilombolas and 991 from non-quilombolas. The prevalence of stunting (6.5% vs. 3.5%, p=0.008) and anemia (38.3% vs. 27.4% p<0.001) were higher in quilombola children compared to non-quilombola children. The opposite was observed in the prevalence of overweight: 9.6% vs. 14.1% (p=0.009), respectively. Among quilombola children, the factors associated with height deficit were: wealth index below the median, low maternal height, and low birth weight. In addition to low birth weight, among non-quilombola children, factors associated with excess weight were: low maternal height, and age ≤ 24 months. The presence of moderate food insecurity, age ≤ 24 months, and high birth weight were factors associated with excess weight among quilombola children. Among non-quilombolas, being overweight was associated with an increase in quartiles of maternal BMI, and high birth weight. As for anemia, the associated factors among the quilombolas were: maternal age (<20 years), age ≤ 24 months, male gender, and health problem in the last 30 days. Among non-Quilombolas, maternal education (≤ 8 years), and age ≤ 24 months were factors associated with anemia. We concluded that, in line with the assumptions of social determination in the health and disease process, the socioeconomic disadvantages to which quilombolas women and children are historically subjected reverberate nowadays, as observed by the presence of worse nutrition and health profile. We hoped that these results will be used to guide public policies aimed at facing these conditions, which must consider that, in the state with the worst socioeconomic indicators in the country, quilombola women and children survive in an even more vulnerable scenario.
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