Dissertations/Thesis

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2024
Dissertations
1
  • HELOISA DE ALMEIDA FREITAS
  • GENETIC POLYMORPHISMS IN IMMUNE RESPONSE MOLECULES IN LEPROSY IN A POPULATION IN NORTHEAST BRAZIL

  • Advisor : CAROLINNE DE SALES MARQUES
  • COMMITTEE MEMBERS :
  • CARLOS ALBERTO DE CARVALHO FRAGA
  • ELAINE VIRGINIA MARTINS DE SOUZA FIGUEIREDO
  • EMILIANO DE OLIVEIRA BARRETO
  • Data: Feb 22, 2024


  • Show Abstract
  • Leprosy is a disease caused by the obligate intracellular bacillus
    Mycobacterium leprae, and Mycobacterium lepromatosis, which mainly
    affects the skin and peripheral nerves. The state of Alagoas, in 2022,
    presented an incidence rate of new cases of 9.67/100 thousand inhabitants
    (average endemicity), with several municipalities showing hyperendemicity.
    The interactions between the characterization of the pathogen, the genetics
    of the host and the environment are factors to be considered for the
    development of leprosy. Among the host's genetics, there are immune
    response genes, and in them, there are single or simple nucleotide
    polymorphisms (SNPs) that are present equal to or greater than 1% of a
    given population and are risk or protective factors against leprosy. Among the
    immune response genes, there is the IL23R gene, which plays an important
    role in immune regulation, CCDC122-LACC1, which is one of the regulators
    of the metabolic function of macrophages, and RAB32, responsible for
    regulating the clearance of aggregated proteins by autophagy. To understand
    the genetic basis of leprosy, the SNPs rs4942254/CCDC122-LACC1,
    rs3762318/IL23R
    and
    rs2144658/IL23R
    were
    investigated,
    and
    rs2275606/RAB32, which have already been investigated in Brazilian and
    Chinese populations, but their influence on the population has not yet been
    verified. from Alagoas. The objective was to investigate the association of
    SNPs belonging to the IL23R, CCDC122-LACC1 and RAB32 genes with
    leprosy in a population sample from Alagoas. A case-control study was
    carried out, using samples of individuals with leprosy (cases) and without
    leprosy (controls), recruited in Alagoas. After collecting biological samples
    and extracting DNA (salting out), genotyping of the SNPs rs2144658/IL23R
    and rs3762318/IL23R, rs4942254/CCDC122-LACC1, and rs2275606/RAB32
    was performed using real-time PCR (Taqman assay, StepOne PlusTM).
    Statistical analyzes used OR (Odds Ratio), CI (Confidence Interval) and p-
    values, as a measure of association, and were carried out in the R
    environment (version 4.3.0) using the “genetics” and “SNPassoc” packages.
    As a result, 313 cases and 264 controls were included in the genetic study.
    To date, the results have demonstrated that the rs3762318 and rs2144658
    polymorphisms, both in the IL23R gene, are not associated with leprosy in the
    population investigated, even after adjusting for the covariate sex (ORAG:
    1.04, p-value: 0.84; ORAG: 0.87, p-value: 0.58, respectively). As for the
    frequencies of the CC homozygote of the rs4942254/CCDC122-LACC1
    polymorphism, they were 15% for cases and 22% for controls. The results
    demonstrated that the SNP investigated in the CCDC122-LACC1 gene was
    associated with protection against leprosy in the Alagoas population (ORCC:
    0.51, p: 0.016). As for the SNP rs2275606, an association with the risk of
    leprosy was identified in the population of Alagoas (ORAA: 3.12, p: 0.0028,
    adjusted). Therefore, it was possible to identify that the SNP
    rs4942254/CCDC122-LACC1 was associated with a lower risk of leprosy,
    while rs2275606/RAB32 was associated with a higher risk of leprosy. These

    findings integrated the panel of markers and their genetic influence on leprosy
    in the Alagoas population.

2
  • JAMES HENRIQUE ALMEIDA
  • VALIDATION OF A LOW-COST PORTABLE LIGHT ON HUMAN KERATINOCYTES AND PROTECTIVE EFFECT OF PERSONAL PROTECTIVE EQUIPMENT (PPE)
  • Advisor : JAMYLLE NUNES DE SOUZA FERRO
  • COMMITTEE MEMBERS :
  • EMILIANO DE OLIVEIRA BARRETO
  • JAMYLLE NUNES DE SOUZA FERRO
  • JULIANE CABRAL SILVA
  • Data: Feb 27, 2024


  • Show Abstract
  • Admissions and preventable deaths occur annually in healthcare facilities due to infections acquired in these environments. Surface contamination by pathogenic microorganisms exacerbates this scenario, necessitating disinfection measures. Ultraviolet (UV) radiation is a well-established method in the literature, inactivating microorganisms by damaging their nucleic acids. Exposure to radiation can affect not only the intracellular material of the microorganism but also a set of cells in exposed individuals. In response to COVID-19 in 2020, researchers from the Federal Institute of Alagoas developed a low-cost UV-C radiation luminaire for comprehensive disinfection, especially in healthcare units. The efficacy of this device requires validation of its proposed effects to validate its subsequent use. Therefore, the present study aimed to contribute to the validation of the efficacy of a low-cost UV-C radiation luminaire, investigating potential cellular damage caused by exposure in a lineage of non-tumoral human keratinocytes (HaCaT) at different exposure times. For this purpose, keratinocytes were exposed for different periods (10, 60, or 300s) to UVC radiation (±16 mW/cm², 254 nm) and evaluated at 1, 6, 24, or 72 hours after exposure, with or without the presence of personal protective equipment (PPE). The parameters evaluated included cell viability, morphological analysis by optical microscopy on violet-stained cells, fluorescent dye staining to assess cell death by apoptosis or necrosis (acridine orange and propidium iodide - AO/PI staining), and clonogenic assay. Exposure to radiation for 10 seconds resulted in a significant reduction in cell viability, with a noticeable percentage decrease in viable cells over the assessed time intervals. Cell density and morphological characteristics were altered after exposure, revealing atypical features compared to unexposed cells. The fluorescence assay with AO/PI revealed an increase in dead cell quantification, reflecting a lower density of cells adhered to the plate. The clonogenic assay demonstrated complete elimination of cells after 10 seconds of exposure during the 14-day trial period.Tests conducted using Personal Protective Equipment (PPE) revealed a level of protection to cells that varied depending on the material used. Notably, latex and nitrile gloves yielded the best results, maintaining cell viability, morphology, and the quantity of dead cells similar to the unexposed group, indicating positive outcomes.The results of this study demonstrate, as expected, that the luminaire induces toxic effects on cells by promoting DNA damage. The presence of specific PPEs provides considerable protection in cases of accidental exposure by luminaire users. These findings contribute to the validation process for the use of the fabricated device.

3
  • KARLA REGINA CELESTINO NOGUEIRA
  • STUDY OF ASSOCIATION BETWEEN THE MBL2 GENE AND LEPROSY IN THE POPULATION OF ALAGOAS, BRAZIL

  • Advisor : CAROLINNE DE SALES MARQUES
  • COMMITTEE MEMBERS :
  • CAMILA BRAGA DORNELAS
  • DALMO ALMEIDA DE AZEVEDO
  • JAMYLLE NUNES DE SOUZA FERRO
  • Data: Mar 1, 2024


  • Show Abstract
  • Leprosy, a chronic infectious disease, is identified as a serious public health
    problem, as it is still considered the infectious disease that causes the largest
    number of physical deformities in the world. The etiological agent of the
    disease is the bacillus Mycobacterium leprae, and the recently associated
    Mycobacterium lepromatosis. These microorganisms are able to overcome a
    succession of physical barriers until reaching the Schwann cell. Some studies
    have shown, in different populations, the importance of SNPs in genes
    associated with leprosy. In this sense, studies that evaluated mutations in the
    MBL2 gene have received attention. Genetic studies of SNPs in the MBL2
    gene have already been associated in Brazilian populations, however, there
    is no investigation into the role of this gene in Alagoas. The objective of the
    present study was to investigate the association of the SNPs rs1800450 and
    rs1800451 in the MBL2 gene with leprosy in the population of Alagoas, Brazil.
    A case-control study was conducted, where the cases included patients
    diagnosed with leprosy at reference centers in the cities of Maceió, Arapiraca,
    Santana do Ipanema and Penedo, and the controls included healthy
    individuals, blood donors at HEMOAL-Arapiraca. The DNA of individuals who
    agreed to participate in the study was extracted using the salting out method
    and genotyped using real-time PCR using allelic discrimination using TaqMan
    probes. The allele, genotypic and allele carrier frequencies were obtained,
    which were later compared between the groups using logistic regression. All
    statistical analyzes were carried out using the R environment (version
    1.4.1717). As a result of population recruitment in Alagoas, we obtained 592
    individuals, of which 328 were cases and 264 were controls. For the
    rs1800450 polymorphism in the MBL2 gene, a frequency of 89% was
    observed in the total population for the C allele, with a frequency of 91% in
    the group of cases and 86% in controls, being identified as the present
    polymorphic allele study. In relation to the genotype, CC presented a higher
    frequency in both cases (84%) and controls (72%), suggesting the distribution
    of genotypes of this SNP in the Alagoas population. In the genotypic
    association analysis, we can observe that there was an association between
    the CT genotype of the SNP rs1800450 of the MBL2 gene and the leprosy
    protection factor both before (p: 0.0007, OR: 0.49, CI: 0.32-0.74 ) as well as
    after adjusting for sex in the logistic regression (p: 0.001, OR: 0.51, CI: 0.33-
    0.77). The frequencies of T allele carriers were also obtained, and a positive
    result of association of the SNP rs1800450 of the MBL2 gene for protection
    against leprosy was observed, both before (p: 0.001, OR: 0.50, CI: 0.34-
    0 .76) and how much after adjustment for the covariate sex (p: 0.002, OR:
    0.52, CI: 0.35-0.79). The findings of the present study add information

    regarding the genetic influence on leprosy in a population from Alagoas,
    which may be useful in understanding the development of the disease in the
    region

4
  • ALDILANE LAYS XAVIER MARQUES
  • TEMPORAL ANALYSIS OF HUMAN PLACENTAL BIOACCUMULATION OF MICROPLASTICS

  • Advisor : ALEXANDRE URBAN BORBELY
  • COMMITTEE MEMBERS :
  • ALEXANDRE URBAN BORBELY
  • MULLER RIBEIRO ANDRADE
  • SAMUEL TEIXEIRA DE SOUZA
  • Data: Mar 6, 2024


  • Show Abstract
  • Microplastics are created for commercial use, are shed from textiles, or result from the breakdown of larger plastic items. Recent reports have shown that microplastics accumulate in human tissues and may have adverse health consequences. Currently, there are no standardized environmental monitoring systems to track microplastic accumulation within human tissues. Using Raman spectroscopy, we investigated the temporal exposures to plastic pollution in Hawaiʻi and noted a significant increase in the accumulation of microplastics in discarded placentas over the past 15 years, with changes in the size and chemical composition of the polymers. These findings provide a rare insight into the vulnerability and sensitivity of Pacific Island residents to plastic pollution and illustrate how discarded human tissues can be used as an innovative environmental plastic pollution monitoring system.

5
  • BEATRIZ SANTANA MENDONCA
  • Morphological and molecular characterization of human thymic epithelial cells after stimulation with TGF-β1 in vitro

  • Advisor : EMILIANO DE OLIVEIRA BARRETO
  • COMMITTEE MEMBERS :
  • CAMILA BRAGA DORNELAS
  • JULIANE CABRAL SILVA
  • MARIA DANIELMA DOS SANTOS REIS
  • Data: Mar 21, 2024


  • Show Abstract
  • The thymus is a lymphoid organ responsible for fundamental events for the development of the organism’s cellular immunity, such as maturation, differentiation and selection of T lymphocytes. In this context, thymic epithelial cells (TECs), which make up the majority of the thymic microenvironment, they actively participate in the differentiation stages of functionally competent T lymphocytes. TGF-β1 is a protein related to epithelial-mesenchymal transistion (EMT) and oxidative stress, important events for the process of thymus involution with age. Therefore, the objective of this work was to evaluate the morphological and molecular changes induced by TGF-β1 in thymic epithelial cells in vitro. For this, TECs from the human THPN lineage were used and the parameters of morphology, laminin production, activation of the canonical TGF-β pathway and expression of genes related to TEM and oxidative stress were evaluated. Furthermore, expression of the leucemia inhibitory factor (LIF) and its receptor, LIF-R, genes was seen. TGF-β1 was able to induce changes in the morphology of TECs, which presented a larger and more elongated morphology compared to cells without stimulation. Furthermore, an increase in fluorescence intesity for phosphorylated SMAD3 was seen when cells were stimulated with TGF-β1 and an increase in laminin production. Through qPCR, it was possible to observe that TGF-β1 increased the relative expression of the gene for N-cadherin, a marker of EMT, and decreased the expression of the LIFR gene. Finally, a reduction in the relative expression of the gene for the Catalase enzyme (CAT) was seen when TECs were stimulated with TGF-β1. Thus, it can be concluded that TECs, when stimulated with TGF-β1, present cellular and molecular modifications similar to those found in TECs during thymic involution, such as an increase in extracellular matrix, modification to a mesenchymal profile and loss of antioxidant homeostasis, making it a possible instrument for studying changes in TECs during aging.

Thesis
1
  • CARMEM LÚCIA DE ARROXELAS SILVA
  • EFFECT OF THE SOLUTOL® HS 15 IN AN ANIMAL MODEL OF MESIAL TEMPORAL LOBE EPILEPSY

  • Advisor : DANIEL LEITE GOES GITAI
  • COMMITTEE MEMBERS :
  • AXEL HELMUT RULF COFRE
  • DANIEL LEITE GOES GITAI
  • IGOR SANTANA DE MELO
  • MARCELO DUZZIONI
  • TIAGO GOMES DE ANDRADE
  • Data: Mar 20, 2024


  • Show Abstract
  • Introduction: Epilepsy is a neurological disorder characterized by a chronic predisposition of the brain to generate recurrent and spontaneous epileptic seizures (SEs). Mesial Temporal Lobe Epilepsy (MTLE) is the most common form in adults and often resistant to available treatments. Therefore, finding new therapeutic options is urgent. Previous studies from our research group have shown that Solutol® HS 15 (SOL), a pharmaceutical excipient used to carry drugs, may have anticonvulsant and antiepileptogenic effects. In this study, we investigated this possibility using an animal model of Pilocarpine-induced Status Epilepticus. Objective: To evaluate whether SOL affects Status Epilepticus (SE) and the chronic phase of epileptogenesis. Methodology: To analyze the acute phase of epileptogenesis, male Wistar rats were pretreated with SOL (experimental groups) or saline solution (SAL) (control groups) via intrahippocampal (I.H.) or intraperitoneal (I.P.) administration, and then subjected to 90 minutes of SE. They were euthanized 24 hours after SE reversal for histological and molecular analyses. In the chronic phase, epileptic animals received treatment with SOL or SAL via intraperitoneal route for 15 days. All animals were video-monitored during SE, latency, and chronic phase, and their seizures were evaluated using the Racine scale. Total hippocampal neurodegeneration and in its subregions (Ammon's Horn: CA1 and CA3; and Hilus) were assessed with Fluoro-Jade. The expression of transcripts associated with epileptogenesis was measured by RT-qPCR. Statistical analysis was performed using GraphPad, Prism 9.0. Results: Pretreatment with SOL reduced the total number of seizures during SE by 29.94% (via I.H.) and 33.93% (via I.P.). It also reduced hippocampal neurodegeneration by 25.02% to 43.43% in all tested models. Additionally, animals pretreated with SOL showed increased expression of BDNF (via I.H.) and decreased expression of GFAP (via I.P.), indicating a neuroprotective effect. In the chronic phase, treatment with SOL had an anticonvulsant effect in 70% of the animals. Conclusion: The study demonstrates that SOL has anticonvulsant effects during SE and in the chronic phase of epileptogenesis, as well as reducing hippocampal neurodegeneration and altering the expression of BDNF and GFAP. These findings are promising for the potential role of SOL in epilepsy treatment, but further studies are needed to better understand these mechanisms

2023
Dissertations
1
  • MIRELLA PRISCILLA DOS SANTOS VIEIRA
  • Increased risk of symptoms associated with anxiety and depressive disorders in parents during the emergency remote teaching in COVID-19 pandemic.  

  • Advisor : MARCELO DUZZIONI
  • COMMITTEE MEMBERS :
  • MARCELO DUZZIONI
  • CLAUDIO TORRES DE MIRANDA
  • DANILO ALVES PINTO NAGEM
  • Data: Feb 28, 2023


  • Show Abstract
  • The social deprivation caused by the COVID-19 pandemic brought changes to people’s daily routines and to the family dynamic. Consequently, the school closings and the implementation of emergency remote teaching (ERT) may have intensified the stress caused by the pandemic and increased anxiety and depressive disorders, particularly for those responsible for students in ERT. In this sense, this study assessed whether parental obligations to ERT in the COVID-19 pandemic represented risk factors for the onset of symptoms of anxiety and depression disorders. For this, an online cross-sectional survey was conducted using a convenience sample of parents/guardians of students in ERT residing in Maceió, Alagoas, Brazil. The participants answered a three-section questionnaire, with the first section including demographic information, knowledge, and time spent focusing on COVID-19. In the second and third sections, self-report questionnaires were applied to measure symptoms of anxiety [General Anxiety Disorder-7 (GAD-7)] and depression [Patient Health Questionnaire-9 (PHQ-9)], respectively. Multivariate logistic regression models were performed to explore the predictors of mental health problems. For the analysis, 348 valid questionnaires were used. The majority of our sample’s participants had a higher education degree (college/university education) and a better financial background (family income > US$ 600.00/month; minimum wage ≅ US$ 200,00/month). However, despite having a sample that presents protective factors against the development of anxiety and depressive disorders, the responsibility and support in ERT as a result of the COVID-19 pandemic were considered risk factors for the development of anxiety and depressive disorders symptoms in parents/guardians. Meanwhile, receiving emergency financial support, which amounts to approximately US$ 115.00/month for those with per capita incomes of at least half the Brazilian minimum wage (US$ 100.00/month), was identified as a protective against the onset of depressive disorder symptoms. Thus, our results showed that the parents’ mental health was affected by changes in the home context brought on by COVID-19. Alternatively, our study highlights the importance of offering psychological assistance to this group of individuals.

2
  • GABRIELA FERREIRA DE SOUZA
  • EVALUATION OF THE HALLUCINOGEN AND ANTIDEPRESSANT EFFECTS OF SUBSTITUTED PHENETYLAMINE 25I-NBOME AND 25I-NBOH IN SWISS MICE

  • Advisor : MARCELO DUZZIONI
  • COMMITTEE MEMBERS :
  • AXEL HELMUT RULF COFRE
  • DANIEL LEITE GOES GITAI
  • MARCELO DUZZIONI
  • Data: Feb 28, 2023


  • Show Abstract
  • New psychoactive substances (NPS) appear on the illegal market as alternatives to controlled or illicit drugs. Such is the diversity and complexity of NPS that many users may not be aware of the substances’ nature. The substituted phenethylamines 25INBOMe and 25I-NBOH are hallucinogenic NPS due to their agonistic effects on serotonin receptors. Several studies have shown the potential therapeutic use of hallucinogenic substances in mental conditions, including depression. However, there are no studies involving 25I-NBOMe and 25I-NBOH as possible antidepressants. In this sense, we evaluated their hallucinogenic and antidepressant effects in female Swiss mice on head twitch response (HTR) and immobility time, when evaluated in open field (OF) and forced swimming (FS) tests, respectively. For this, mice were treated with either 25INBOMe (0.3, 1 or 3 mg/Kg, i.p.), 25I-NBOH (0.3, 1 or 3 mg/Kg, i.p.), or vehicle (NaCl 0.9%+DMSO 0.3%), and immediately evaluated for 60 min in the OF. Alternatively, identically treated mice were subjected to FS after 40 min of treatment, when no changes in motor activity were observed. Our results show that both, 25I-NBOMe and 25I-NBOH, do not alter exploratory and anxiety-like behaviors in OF. However, they promote an increase in HTR in OF, indicating a hallucinogenic-like effect. In FS, only the lowest dose of 25I-NBOMe reduced immobility, indicating, for the first time, the antidepressantlike effect of the compound. These data increases evidence on the therapeutical potential of the use of hallucinogenic substances as antidepressants. Future studies are needed to further characterize 25I-NBOMe antidepressant-like effect, including alternative animal models and temporal evaluation.

3
  • PEDRO AUGUSTO TIBURCIO PAULINO
  • EFFECT OF MIR 196B INHIBITION ON THE ACUTE PHASE OF EPILEPTOGENESIS IN AN EXPERIMENTAL MODEL OF
    TEMPORAL LOBE EPILEPSY

  • Advisor : DANIEL LEITE GOES GITAI
  • COMMITTEE MEMBERS :
  • AXEL HELMUT RULF COFRE
  • DANIEL LEITE GOES GITAI
  • GUSTAVO GOMES DE ARAUJO
  • Data: Mar 23, 2023


  • Show Abstract
  • Epilepsy is a neurological disorder characterized by spontaneous and recurrent seizures. Temporal lobe epilepsy (TLE) is associated with a high rate (30-40%) of refractoriness to treatment with antiepileptic drugs (AEDs). The search for new therapeutic approaches is an urgent need. Manipulation of gene expression has been explored in the development of therapeutic interventions in many neuropathogenetic processes. In this sense, non-coding RNAs, such as microRNAs (miRs), are preferred targets due to the regulatory role they play in the reorganization of gene expression. Recently, we identified that miR 196b-5p has increased expression in the acute phase of epileptogenesis. In this work, we depleted miR-196b-5p levels to gain insights into the functional significance and therapeutic potential of this dysregulation. For this purpose, Wistar rats received, via the intracerebroventricular (ICV) route, the miR-196b-5p inhibitor (0.4 nmol/2mL) 24 hours before being submitted to Status Epilepticus induced by Lithium-Pilocarpine. We observed a significant depletion of miR-196-5p hippocampal levels. The effect of this depletion was evaluated in terms of molecular (expression of epileptogenesis markers and the SLC9A6 target), histochemical (marking of Fluoro-Jade positive neurons) and behavioral parameters (assessment of self-sustained seizures through latency, severity and frequency). As a control group, wistar rats were used that received, via ICV, 2mL of phosphate saline buffer (PBS). The animals that received the miR-196b-5p inhibitor (0.4 nmol/2mL) did not show a significant change in the latency time for the onset of SE, as well as in the severity and frequency of seizures during 90 minutes of SE. Regarding the analysis of neurodegeneration, we did not observe a significant difference in Fluoro-Jade positive cells between the groups. Regarding epileptogenesis, we did not observe a significant difference in the expression of GFAP (astrogliosis), BDNF (neuroplasticity) and TNF-a (neuroinflammation) markers. The joint analysis of these data indicates that miR-196 depletion does not have anticonvulsant and antiepileptogenic potential. On the other hand, we observed that animals administered the miR-196b-5p inhibitor (0.4 nmol/2mL) showed an even greater increase in the levels of neuropeptide Y (NPY) transcripts, indicating a possible regulatory role of miR-196b about NPY. A decrease in the levels of miR 146a transcripts was also observed in animals administered the miR-196b-5p inhibitor (0.4 nmol/2mL), indicating a possible decrease in neuroinflammation. In conclusion, our data suggest that the LNA-type inhibitor is a useful tool for functional assays of miRs inhibition, however, the inhibition of miR-196b-5p, at the doses and times used here, did not alter the epileptogenic processes investigated.

4
  • JOYELANNE KALINE CHAGAS SOUZA
  • Investigation of the PVP/bentonite/NPAg nanocomposite in the production of films for application in the health area

  • Advisor : CAMILA BRAGA DORNELAS
  • COMMITTEE MEMBERS :
  • CAMILA BRAGA DORNELAS
  • ANA CATARINA REZENDE LEITE
  • LUISE LOPES CHAVES
  • LIGIA MARIA MANZINE COSTA
  • Data: Mar 29, 2023


  • Show Abstract
  • In view of the increasing resistance of microorganisms to antimicrobials, silver nanoparticles (NPAg) emerge as an effective alternative for the treatment of various health-related problems, given their high antimicrobial activity. Its placement through polymeric membranes with curative purposes has been highlighted by the possibility of using biocompatible polymers, among these, polyvinylpyrrolidone (PVP) stands out for acting in the NPAg synthesis process and preventing the formation of agglomerates. In this context, the addition of a polymer to a layered nanostructured clay, such as bentonite (Bt), forming a so-called lamellar silicate polymer (PSL) nanocomposite, constitutes an interesting material for study, given the ability to release sustained actives already described. in literature. Thus, the objective of this work is to synthesize and characterize the PVP/Bt/NPAg nanocomposite, evaluate its release and antimicrobial activity. The synthesis of the nanoparticles was performed using PVP as a silver reducing agent and as a stabilizer. The colloidal suspension was characterized by UV-Vis spectrophotometry, dynamic light scattering and zeta potential. After that, there was addition of bentonite in different proportions and interference in membrane formation was verified. Once the material was obtained, it went on to physicochemical characterization using X-ray diffraction (XRD), infrared spectroscopy (FTIV), scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy. (EDS). The colloidal suspension was obtained and showed stability and a slow silver reduction aspect by PVP. The membranes produced showed, through XRD, that there was formation of the PSL nanocomposite and the amorphous characteristic of the polymer, crystalline of silver and bentonite, which was in its exfoliated mode. The FTIV indicated the participation of groups containing oxygen and nitrogen, from PVP, in the reduction of silver. The surface morphology of the samples was altered with the addition of bentonite, presented in flakes, and nanosilver, which exhibited a shiny appearance. The composition was confirmed by EDS without showing contamination peaks in the material. Thus, it is legitimate to continue the study with evaluation of the release of NPAg from the nanocomposite and the antimicrobial activity. Thus, it is expected that there will be formation of a modified release membrane for application as a dressing.

5
  • MARIANE SOARES VIEGAS MOURA REZENDE
  • Impact of hypovitaminosis D on the pathophysiology of pityriasis alba in adults
  • Advisor : EURICA ADELIA NOGUEIRA RIBEIRO
  • COMMITTEE MEMBERS :
  • EURICA ADELIA NOGUEIRA RIBEIRO
  • MARIA ALINE BARROS FIDELIS DE MOURA
  • OLAGIDE WAGNER DE CASTRO
  • Data: Jul 27, 2023


  • Show Abstract
  • Introduction: Pityriasis Alba (PA) is a condition mottled by asymptomatic, hypopigmented, slightly
    scaly patches with indistinct margins. The etiology of PA is not well established. Vitamin D exerts
    its effect through a nuclear receptor present mainly in cells involved in bone metabolism; These
    receptors are also present on other cell types in the skin such as melanocytes, keratinocytes, immune
    system cells and fibroblasts. Calcium controls the activity of thioredoxin reductase which is
    cytosolic and associated with the plasma membrane. If the level of intracellular calcium decreases,
    this leads to reduced high levels of thioredoxin, which, in turn, inhibit tyrosinase activity,
    progressively initiated in melanin synthesis. Objective: There are few studies correlating the effect
    of hypovitaminosis D with the pathogenesis of AP, therefore, the objective of our study was to
    correlate vitamin D with the pathophysiology of AP. Patients and methods: This was a case-
    control, open and non-randomized study, where 9 patients over 18 years of age with AP clinically
    diagnosed at the Clinical Dermatology outpatient clinics of CER III of PAM Salgadinho in Maceió
    were selected, over an estimated period of 6 months. The control group consisted of 9 patients not
    affected by AP or any other hypopigmented disorders. Blood samples were collected from both
    groups (cases and controls) and circulating serum 25(OH)D levels were measured. Primary variables
    analyzed were serum levels of vitamin D, number and size of lesions, degree of depigmentation
    and/or presence of erythema, affected region and present symptoms. The secondary variables were
    the demographic profile of the patients and the tertiary variables were the habits related to bathing.
    Calculations were performed using the BIOESTAT v.5.3 software and the two-sample “T” test. Data
    were statistically analyzed using the Mann-Whitney U test, the chi-square test and the Fischer test
    for primary, secondary and tertiary variables, respectively. An alpha value equal to or less than 0.05
    was used to reject the null hypothesis. Results: The results of the vitamin D assessment among the
    cases showed that none of them had a sufficient level of vitamin D and the level varied between
    11.1-27.5 ng/ml (mean: 19.666 ± 5.099 ng/ml). Five patients (55.5%) had impairment and four
    patients (44.4%) had impairment. In the control group, the level ranged from 11.3 to 44.7 ng/ml
    (mean: 31.777 ± 10.195 ng/ml). Only 01 patient in the control group (11.1%) had vitamin D
    deficiency, 03 (33.3%) were insufficient and 5 (55.5%) had sufficiency. Comparing the vitamin D
    levels of both groups, there was a statistically significant difference (p = 0.0071). In the case group,
    3 out of 4 patients with severe hypochromia had deficient levels of vitamin D, 1 of which was
    insufficient. Furthermore, of the 6 patients with more than 5 PA lesions, half had vitamin D deficient
    and the other half insufficiency levels. The only patient with more than 10 lesions had a deficient
    serum level of vitamin D. Conclusions: The association between hypovitaminosis D and the
    occurrence and severity of AP in adults is a relevant finding, as it suggests that vitamin D
    supplementation may be a therapeutic option for this condition.

6
  • KELLYSSON BRUNO OLIVEIRA
  • SARS-CoV-2 and Hypertension: Evidence Supporting Invasion into the Brain Via Baroreflex Circuitry and the Role of Imbalanced Renin-Angiotensin-Aldosterone Syste

  • Advisor : OLAGIDE WAGNER DE CASTRO
  • COMMITTEE MEMBERS :
  • EMILIANO DE OLIVEIRA BARRETO
  • OLAGIDE WAGNER DE CASTRO
  • VICTOR RODRIGUES DOS SANTOS
  • Data: Dec 18, 2023


  • Show Abstract
  • Hypertension is considered one of the most critical risk factors for COVID-19. Evidence suggests that SARS-CoV-2 infection produces intense effects on the cardiovascular system by weakening the wall of large vessels via vasa-vasorum. In this commentary, we propose that SARS-CoV-2 invades carotid and aortic baroreceptors, leading to infection of the nucleus tractus solitari (NTS) and paraventricular hypothalamic nucleus (PVN), and such dysregulation of NTS and PVN following infection causes blood pressure alteration at the central level. We
    additionally explored the hypothesis that SARS-CoV-2 favors the internalization of membrane ACE2 receptors generating an imbalance of the renin-angiotensin-aldosterone system (RAAS), increasing the activity of angiotensin II (ANG-II), disintegrin, and metalloproteinase 17 domain (ADAM17/TACE), eventually modulating the integration of afferents reaching the NTS from baroreceptors and promoting increased blood pressure. These mechanisms are related to the increased sympathetic activity, which leads to transient or permanent hypertension associated with
    SARS-CoV-2 invasion, contributing to the high number of deaths by cardiovascular implications.

Thesis
1
  • JUCILENE FREITAS DOS SANTOS
  • BEHAVIORAL AND DEVELOPMENTAL CHANGES ASSOCIATED WITH PSYCHOACTIVE DRUGS IN HUMANS AND IN A DROSOPHILA MELANOGASTER MODEL

  • Advisor : OLAGIDE WAGNER DE CASTRO
  • COMMITTEE MEMBERS :
  • OLAGIDE WAGNER DE CASTRO
  • MARCELO DUZZIONI
  • ABELARDO SILVA JUNIOR
  • KAROL FIREMAN DE FARIAS
  • VICTOR RODRIGUES DOS SANTOS
  • Data: Feb 14, 2023


  • Show Abstract
  • Psychoactive substances interact with the brain and cause changes in mood, consciousness, thoughts, feelings, or behavior. Among the most used are marijuana, nicotine, cocaine, crack cocaine and the like. Crack cocaine consumption leads to public health challenges with an increasing number of children intoxicated by crack cocaine during pregnancy. Substance abuse and dependence is an important areas of research for which animal experiments play a critical role. Drosophila melanogaster is a well-studied and highly treatable genetic model organism for understanding the molecular mechanisms of human disease and drug-of-abuse studies. In this context, the main objective of this work was to describe the maternal, fetal and neonatal consequences of crack use during pregnancy and to describe the changes in the development and behavior of D. Melanogaster. Two systematic reviews with meta-analysis were performed. The first, based on observational studies, had the use of the random effects model, odds ratio (OR) for categorical variables, and mean difference for continuous variables. Statistical heterogeneity was assessed using the I-square statistic and the risk of bias was assessed using the Newcastle–Ottawa Quality Rating Scale. Ten studies met the eligibility criteria and were used for data extraction. The second was carried out from pre-clinical studies, including experimental studies with Drosophila melanogaster exposed to psychoactive drugs. Two reviewers independently extracted data. DerSimonian and Laird's random effects model was used, using the inverse variance method to assign the weight of the studies. Statistical heterogeneity was verified by Cochran's Q test and inconsistency by the I² statistic. Sensitivity analysis was performed in case of significant heterogeneity, removal of one study at a time, and subgroup analysis. For all analyses, an alpha value of 5% was adopted, using the metan package of the Stata v13.0 software (StataCorp, College Station, TX, USA). The quality of reports was assessed using the adapted CAMARADES. In the results, it was observed that the use of crack during pregnancy was associated with significantly higher chances of premature birth [(OR), 2.22; 95% confidence interval (CI), 1.59–3.10], placental displacement (OR, 2.03; 95% CI 1.66–2.48), smaller head circumference (−1.65 cm; 95% CI −3.12 to −0.19), small for gestational age (SGA) (OR, 4.00; 95% CI 1.74–9.18) and low birth weight (LBW) (OR , 2.80; 95% CI 2.39–3.27). Forty-nine studies met the eligibility criteria and were used to extract data from the second review, but only fifteen were eligible for meta-analysis. We observed that cocaine exposure causes increased locomotor activity in D. melanogaster (SMD, -1.11; 95% CI -1.81, -0.42). For the other variables, no significant difference was observed due to the great heterogeneity of the studies. This analysis provides clear evidence that crack contributes to adverse perinatal outcomes. Maternal or prenatal crack exposure is linked to low birth weight, preterm birth, placental displacement, and smaller head circumference. Drugs of abuse such as cocaine, nicotine and marijuana cause molecular, morphological, behavioral and survival changes in D. melanogaster at different stages of development.

2
  • DELMA HOLANDA DE ALMEIDA
  • DIFFERENTIAL GENE EXPRESSION IN PATIENTS WITH TEMPORAL LOBE EPILEPSY: SYSTEMATIC REVIEW COUPLED TO BIOINFORMATICS ANALYSIS

  • Advisor : DANIEL LEITE GOES GITAI
  • COMMITTEE MEMBERS :
  • AXEL HELMUT RULF COFRE
  • DANIEL LEITE GOES GITAI
  • GUSTAVO GOMES DE ARAUJO
  • MARCELO DUZZIONI
  • RENATO SANTOS RODARTE
  • Data: Mar 2, 2023


  • Show Abstract
  • Temporal Lobe Epilepsy associated with Hippocampal Sclerosis I (TLE-
    EH) is the most common type of partial epilepsy in adults. Characterized by a complex
    pathological process, which involves neuronal losses, reorganization of synapses,
    inflammation and molecularly by the global reorganization of gene expression, in
    addition to a refractoriness of (30-40%) of patients to existing antiepileptic drugs
    (AEDs). Many gene expression studies, both in animal models and in humans, seek to
    investigate the molecular alterations underlying the epileptogenic process, but due to the
    heterogeneity of the studies, it was necessary to carry out a careful systematic review
    with the objective of identifying the consistent genes that participate of the
    epileptogenic process in humans with ELT-EH. Methodology: This is a systematic
    review registered in PROSPERO under the ID number: CRD42020180745, according to
    the protocol described by prism 2020. We carried out the search on January 30, 2021,
    using the PubMed and LILACS databases. , EMBASE and SIGLE, open gray, with the
    keywords: “Gene Expression” AND “Epilepsy”; “Gene Expression” AND “Seizure”;
    “Protein Expression” AND “Seizure” AND “Human”; “Protein Expression” AND
    “Epilepsy” AND “Human”. The results extracted and analyzed had a focus on gene
    expression data, as well as tissue, molecules, and techniques evaluated. In addition, for
    genes that are differentially expressed and consistent in more than one study, we
    proceed with bioinformatics analyses, such asassessingg the functional categories of the
    Gene Ontology (GO) and searching for regulators of gene expression, such as validated
    microRNAs (miRs) experimentally and analysis of transcriptional factors. To reduce
    biases, three researchers independently performed all steps and inclusion and exclusion
    criteria were applied for study eligibility. Results: 202 studies met the eligibility
    criteria, with 448 genes studied in ELT-EH. 95 genes at least twice, of which 47 showed
    consistent data. Thirty-four genes were up- regulated in the brain, seven down regulated
    and six genes showed no statistically significant difference. The 41 genes were
    submitted to functional analysis in GO to obtain pathways in molecular function,
    cellular component,s and biological processes. To analyzes activating ways; we got
    seven genes with the potential for transcriptional regulation. As for the analysis of
    miRs, for the 34 genes up-regulated in epileptic tissue, we found 105 validated miRs in
    total for the seven genes with reduced expression. Furthermore, we found more than

    three validated miRs from the overexpressed genes: BCL2, DNMT1, TLR4, BDNF,
    NFKB1, VEGFA, CASP3, TNF, COX2 and from the negatively regulated genes
    GSK3B AND HCN2. Conclusion: In this sense, our work provides a compilation of
    vital information on gene expression associated with drug-resistant ELT and its
    regulators. In addition, it subsidizes precious data for future studies of discovering and
    validating new therapeutic targets based on manipulating gene expression in mTLE.

3
  • YNGRID MICKAELLI OLIVEIRA DOS SANTOS
  • Ontogenic, immunological and behavioral changes from exposure to crack during the gestational period

  • Advisor : OLAGIDE WAGNER DE CASTRO
  • COMMITTEE MEMBERS :
  • ABELARDO SILVA JUNIOR
  • CAROLINNE DE SALES MARQUES
  • EUCLIDES MAURÍCIO TRINDADE FILHO
  • KAROL FIREMAN DE FARIAS
  • OLAGIDE WAGNER DE CASTRO
  • Data: Mar 31, 2023


  • Show Abstract
  • Crack cocaine has potentiated actions in nervous system (CNS), due to the substances generated by its pyrolysis, increasing the bioavailability, the speed of metabolism and drug addiction. The increased consumption of psychoactive drugs by women of childbearing age has generated many challenges in the public health. Crack cocaine use by pregnant women has been correlated with a higher incidence of premature fetuses, CNS malformations and cell damage, as well as changes in the immune system. Here we evaluated the effects of gestational exposure to crack cocaine in pregnant rats on placental cells, immune organs, maternal and anxiety-like behavior, and sensorimotor reflex development. Pregnant rats were exposed to air or crack cocaine (200 mg, for 10 min) from the 5th to the 9th day or until the end of pregnancy. Gestational exposure to crack cocaine increased trophoblastic cell death and reduced viable cells, associated with reduced growth of ectoplacental cones. In addition, exposure to crack cocaine during pregnancy reduced the relative weight of the spleen, as well as the number of total splenocytes and CD8+ T lymphocytes subpopulations. Finally, exposure to crack led to anxiogenic-like behavior and negligence in maternal care. Taken together, our findings provide insight into gestational changes promoted following exposure to crack cocaine and support future clinical interventions and treatments.

4
  • MAISA DE ARAÚJO COSTA
  • N-formyl-methion yl-leucyl-phenylalanine plays a neuroprotective and anticonvulsant role in the Status Epilepticus model

  • Advisor : OLAGIDE WAGNER DE CASTRO
  • COMMITTEE MEMBERS :
  • CLAUDIO TORRES DE MIRANDA
  • EUCLIDES MAURÍCIO TRINDADE FILHO
  • EURICA ADELIA NOGUEIRA RIBEIRO
  • MARCELO DUZZIONI
  • OLAGIDE WAGNER DE CASTRO
  • Data: Apr 28, 2023


  • Show Abstract
  • Status epilepticus (SE) is described as continuous and self-sustaining seizures, which trigger hippocampal neurodegeneration, inflammation, and gliosis. N- formyl peptide receptor (FPR) has been associated with inflammatory processes. N-formyl-methionyl-leucyl-phenylalanine (fMLP) peptide plays an anti-inflammatory role, mediated by activation of G-protein-coupled FPR. Here, we evaluated the influence of fMLP peptides on the behavior of limbic seizures, memory consolidation, and hippocampal neurodegeneration process. Male Wistar rats (Rattus norvegicus) received microinjections of pilocarpine in the hippocampus (H-PILO, 1.2mg/μL, 1μL) followed by fMLP (1mg/mL, 1μL) or vehicle (VEH, saline 0.9%, 1μL). During the 90 minutes of SE, epileptic seizures
    were analyzed according to Racine’s Scale. After 24 hours of SE, memory impairment was assessed by the inhibitory avoidance test and the neurodegeneration process was evaluated in hippocampal areas. There was no
    change in latency and number of wet dog shakes (WDS) after administration of fMLP. Our results showed that the intrahippocampal infusion of fMLP was able to reduce the severity of seizures, as well as the number of limbic seizures. In addition, fMLP infusion protected memory dysfunction followed by SE. Finally, the intrahippocampal administration of fMLP attenuated the process of neurodegeneration in both hippocampi. Taken together our data suggest a new insight into the functional role of fMLP peptides, with important implications for their potential use as a therapeutic agent for the treatment of brain disorders, such as epilepsy.

5
  • ELOIZA LOPES DE LIRA TANABE
  • ANALYSIS OF POTENTIAL BIOMARKERS LINKED TO THE CYTOTOXIC IMMUNE RESPONSE IN SARS-COV-2 INFECTED PATIENTS

  • Advisor : ALEXANDRE URBAN BORBELY
  • COMMITTEE MEMBERS :
  • ALEXANDRE URBAN BORBELY
  • ABELARDO SILVA JUNIOR
  • GUSTAVO GOMES DE ARAUJO
  • NASSIB BEZERRA BUENO
  • SABRINA JOANY FELIZARDO NEVES
  • Data: May 23, 2023


  • Show Abstract
  • The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection leads
    to several clinical outcomes, including death. One possible hypothesis for such clinical
    variations could be due to the cytotoxic immune responses of the patients. Previous
    studies showed that in patients with severe lungs inflammation the number of cytotoxic
    T cells is reduced, presenting exhausted phenotypes and impaired functionality.
    Therefore, our aim was to investigate the prognostic value of plasmatic and cellular
    changes correlated with the cytotoxic response. The study was observational
    transversal with 75 human subjects, and approval of the human research ethical
    committee (30732120.1.0000.5013). From the total amount, 56 samples were from
    patients admitted in the Hospital Universitário Professor Alberto Antunes da
    Universidade Federal de Alagoas (HUPAA/UFAL) (COVID-19 group), and 19 donators
    (Control group) with paired ages, sex, and commorbities. We conducted hematological
    and biochemical blood analysis, plasmatic analysis by Raman spectroscopy and by
    flow cytometry bead assay for sFas, sFasL, perforin, granulysin, and granzimes (Gzm)
    A and B, and immunephenotyping for lymphocytes and lymphoid cells subpopulations.
    The results indicated that COVID-19 group presented several altered hematological
    and biochemical parameters which were predictive for severity and mortality. In Raman
    spectroscopy we observed a reduction in spectra attributed for aminoacids
    (phenylalanine [p ≤ 0.001], proline [p ≤ 0.05], tryptophan [p ≤ 0.01] and tyrosine [p ≤
    0.01]) and carotenoids (p ≤ 0.05), whereas an increase in a single spectra attributed to
    lipids was observed as well (p ≤ 0.001). The COVID-19 group had increased levels of
    GzmA (p =0,04) and GzmB (p =0.01), although the GzmB was the molecule that most
    contributed to groups discrimination (21.43 covariance; 0.81 correlation). The GzmB
    also was elevated in women (p = 0.01) and elderly (p = 0.01), positively correlating to
    patient’s reduced survival (p = 0.03). It was also detected increased amounts of innate
    lymphoid cells (ILC)1 and ILC3 (p ≤ 0.05), and reduction of naive and memmory
    effector T CD4+ cells, and effector and memmory effector T CD8+ cells (p ≤ 0.01). Our
    results indicate that the granzymes are acting in their extracellular functions
    corroborating with the pathogeny of the disease, and that they can be employed as
    worse prognosis markers for COVID-19.

6
  • VÍVIAN MARCELLA DOS SANTOS SILVA
  • Chronotype and sleep in patients with depression: a case-control study


  • Advisor : TIAGO GOMES DE ANDRADE
  • COMMITTEE MEMBERS :
  • TIAGO GOMES DE ANDRADE
  • GUSTAVO GOMES DE ARAUJO
  • MAGNA SUZANA ALEXANDRE MOREIRA
  • JORGE ARTUR PECANHA DE MIRANDA COELHO
  • MARIA CICERA DOS SANTOS DE ALBUQUERQUE
  • Data: Jun 28, 2023


  • Show Abstract
  • The circadian rhythm is closely linked to the sleep regulation process (sleep/wake), which has demonstrated a bidirectional relationship with several diseases, including depression. Evening chronotype, a behavioral manifestation of the circadian timing system, has been shown to be a risk factor for the development of psychiatric disorders. Furthermore, sleep problems are observed in the clinical histories of depressive patients. However, in psychiatric clinical practice, little emphasis is given to diagnostic and therapeutic approaches related to chronobiological aspects. Furthermore, it is important that these relationships be investigated in different clinical settings and populations. Thus, the objective of this cross-sectional study was to investigate the chronotype and sleep in patients diagnosed with depression (MD) (n= 16, 11 women) compared with healthy subjects (CTR) (n= 29, 17 women), treated at HUPAA/UFAL and in the CAPS of Maceió, AL. The patients were residents of the city of Maceió, Alagoas, and were assisted in the research settings: Psychiatry Ambulatory of the University Hospital Dr. Alberto Antunes (HUPAA/UFAL), at CAPS Dr Rostan Silvestre, and CAPS Noraci Pedrosa. To assess the diagnosis of depression, the “Mini International Neuropsychiatric Interview” (M.I.N.I - brief structured diagnostic interview for the main psychiatric disorders) was used. To assess the intensity of depressive symptoms, the “Beck Depression Inventory (BDI) was used. To determine the chronotype, the Horne-Ostberg Test (HO) and the Munich Chronotype Questionnaire (MCTQ) were used, which was also used to determine sleep parameters. To assess sleep quality, the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESP) were used. The results showed that patients have worse body mass index (BMI) (p=0.01) when compared with CTR. The HO/MEQ (p= 0.01) and MSFsc scores in hours (p= 0.01) were significantly lower in the MD group, indicating eveningness in this group. There was a significant association between MD and worse sleep quality (p=0.001) compared to CTR. Depressed patients Patients with depression may experience greater weekday sleep inertia (SIW) (p=0.04), having greater difficulty waking up and feeling alert compared to healthy individuals in the control group and and taking longer to leave out of bed during the week (p= 0.02) and on days off (p = 0.01). There was a positive correlation between the Pittsburgh (sleep quality) and BDI (severity of depression) scores, indicating that as sleep quality worsens, depression symptoms tend to intensify (p=0.05). Circadian dysregulations and poor sleep quality have already been considered precursors to mood disorders in previous studies, as well as depression has been considered a risk factor for poor sleep. Likewise, nutritional problems and afternoon chronotype are factors with a greater risk of being present in samples with depression. In the clinic, it is essential to research the chronotype and sleep quality of patients with depression so that professional care guidelines can be implemented, as well as care and preventive conduct in the general population.

7
  • EDILSON LEITE DE MOURA
  • INFLUENCE OF POLYMORPHISMS IN CYTOKINE AND TLRS GENES IN SUSCEPTIBILITY TO SQUAMOUS INTRAEPITHELIAL LESION AND CERVICAL CANCER: META-ANALYSES AND A CASE-CONTROL STUDY IN A SAMPLE FROM ALAGOAS, BRAZIL

  • Advisor : ELAINE VIRGINIA MARTINS DE SOUZA FIGUEIREDO
  • COMMITTEE MEMBERS :
  • ELAINE VIRGINIA MARTINS DE SOUZA FIGUEIREDO
  • ALEXANDRE URBAN BORBELY
  • TIAGO GOMES DE ANDRADE
  • VERONICA DE MEDEIROS ALVES
  • GUILHERME BENJAMIN BRANDAO PITTA
  • Data: Jul 31, 2023


  • Show Abstract
  • The high-risk Human Papillomavirus (HPV) is considered the main etiological agent of cervical cancer, however, most of these infections are spontaneously eliminated by the host's immune system. Therefore, HPV is a necessary but not sufficient factor for the development of cervical cancer. Host immune dysfunctions, which are attributed to dysregulations in cytokine molecules and Toll-Like Receptors (TLRs), have been associated with persistent HPV infection and cervical cancer. These dysregulations can be driven by polymorphisms in their respective genes and can affect protein expression, structure and/or function. Therefore, the main objective of this thesis was to evaluate the role of polymorphisms in cytokine and TLRs genes in the development of SIL and cervical cancer, through two systematic reviews with meta-analysis and a case-control study in the population of Alagoas, Brazil. The study was divided into 3 main parts: (1) systematic review with meta-analysis of polymorphisms in cytokines genes and SIL/cervical cancer, (2) systematic review with meta-analysis of polymorphisms in TLRs genes and cervical cancer, (3) study of case-control in the population of Alagoas. The case-control study involved 57 cases (11 High-grade Intraepithelial Lesion - HSIL and 46 cervical cancer) and 67 clinically healthy controls. The detection of HPV was performed using the technique of nested Polymerase Chain Reaction (nPCR) with primers MY09/MY11 and GP5+/GP6+ from the L1 region of HPV. Genotyping of polymorphisms was obtained through real-time PCR, using TaqMan probes, through the allelic discrimination method. The results of the systematic review with meta-analysis of polymorphisms in cytokine genes and SIL/cervical cancer, showed that polymorphisms in the TNFA (rs361525, rs1800629), IL-1B (rs16944), IL-6 (rs1800795), IL-10 (rs1800896) , IL-12A (rs568408), IL-12B (rs3212227), IL-17A (rs2275913, rs3748067), IL-17F (rs763780) were associated with increased risk for cervical cancer. In the systematic review with meta-analysis of polymorphisms in TLR genes and cervical cancer, polymorphisms in the TLR4 (rs4986791, rs10759931, rs1927911) and TLR9 (rs187084, rs352140, rs5743836) genes were identified as risk factors for cervical cancer. In the case-control study, the heterozygous genotype +4221T/A in the codominant and overdominant models; the +4221T/A+A/A genotypes in the dominant model and the +4221A allele of the Single nucleotide polymorphism (SNP) IL-6 +4221T>A (rs13306435) were associated with increased risk for HSIL/cervical cancer. The +6703T/C heterozygous genotype of the TLR1 SNP +6703T>C (rs4833095), in the overdominant model, has been shown to increase the risk for HSIL/cervical cancer. There was no significant association of TLR4 +8552A>G (rs4986790) and TLR9 -1486A>G (rs187084) SNPs with HSIL/cervical cancer. In conclusion, the present study identified that polymorphisms in cytokine and TLR genes can affect the phenotype of their respective genes and contribute to the development of HSIL or cervical cancer.

     

8
  • JULIANDERSON DE OLIVEIRA DOS SANTOS CARMO
  • Effects of friedelin on thymocytes and lymphocytes and its influence on regulatory T cells in ovalbumin-induced inflammatory response in experimental allergic asthma

  • Advisor : EMILIANO DE OLIVEIRA BARRETO
  • COMMITTEE MEMBERS :
  • AXEL HELMUT RULF COFRE
  • CAMILA BRAGA DORNELAS
  • EMILIANO DE OLIVEIRA BARRETO
  • ENIO JOSE BASSI
  • MARCELO DUZZIONI
  • RENATO SANTOS RODARTE
  • Data: Aug 24, 2023


  • Show Abstract
  • Allergic asthma is a chronic inflammatory disease characterized by bronchial hyperresponsiveness and abnormal airway remodeling. In this disease, the pathogenesis is driven by an intense type 2 immune response and a diminished population of regulatory T cells (Tregs). Currently, inhaled glucocorticoids are the first-line therapy for asthma. However, the prolonged use of these drugs at high doses can cause side effects and increase the risk of other pathologies. Thus, the search for alternatives for asthma treatment is very important. Friedelin, a natural pentacyclic triterpene, has garnered considerable attention due to its wide range of pharmacological actions, including antitumor, anti-inflammatory, analgesic, antipyretic, and antioxidant effects. Despite all these effects, the actions of friedelin on thymocytes and T lymphocytes, as well as its possible anti-inflammatory mechanism of action in experimental allergic asthma have not been explored yet. In this study, we aim to evaluate the effects of friedelin on thymocytes and lymphocytes in vitro and in vivo, as well as to investigate the possible anti-inflammatory mechanism of this triterpene in an experimental model of ovalbumin-induced allergic asthma. Firstly, we confirmed that friedelin did not alter the cell viability of thymocytes at all tested concentrations (0.1 - 100 µM). Then, we observed in vitro that friedelin increased the CXCL12-induced migration in immature thymocytes (CD4-CD8- and CD4+CD8+), while inhibiting the migration of CD4+ thymocytes. Additionally, friedelin also reduced the production of the cytokine IL-2 in thymocytes stimulated with concanavalin-A (Con-A). In the population of lymphocytes obtained from axillary lymph nodes, friedelin did not interfere with the migratory response induced by CXCL12 but suppressed the ConA-stimulated IL-2 production. The intraperitoneal injection of friedelin in C57BL6 mice for 4 consecutive days did not induce any noticeable changes in the macroscopic aspects of the thymus, nor did it affect its relative weight. Furthermore, the different thymocyte subsets remained unchanged after treatment with friedelin. On the other hand, treatment with dexamethasone, a reference drug, caused thymic atrophy with marked reduction in the number of thymocytes and thymus weight. Based on the direct effects of friedelin on immune cells, as well as the absence of detrimental effects on the thymus, we decided to evaluate the effects of topical treatment with friedelin in asthma. Our results revealed that friedelin significantly reduced the accumulation of total leukocytes in the airways of OVA-stimulated asthmatic animals. Moreover, friedelin treatment increased the percentage of regulatory T cells in the airways of asthmatic animals, which may justify the anti-inflammatory effects of friedelin. Taken together, these findings indicates that friedelin may be a promising candidate for the treatment of allergic asthma.

9
  • HIGOR VINICIUS RODRIGUES SPINELI SILVA
  • EFFECTS OF ACUTE CAFFEINE INGESTION AT DIFFERENT TIMES, ASSOCIATED WITH THE 163 C>A POLYMORPHISM OF CYP1A2 (rs762551), ON PHYSICAL AND SPORTS PERFORMANCE IN VOLLEYBALL ATHLETES: A METABOLOMIC ANALYSIS

  • Advisor : GUSTAVO GOMES DE ARAUJO
  • COMMITTEE MEMBERS :
  • ADRIANO EDUARDO LIMA DA SILVA
  • DANIEL LEITE GOES GITAI
  • FILIPE ANTONIO DE BARROS SOUSA
  • GUSTAVO GOMES DE ARAUJO
  • THAYS DE ATAIDE E SILVA
  • Data: Dec 13, 2023


  • Show Abstract
  • The present study constructed a narrative review to analyze the current state of the art on caffeine supplementation (CAF) and the CYP1A2 163 C>A polymorphism on aerobic and anaerobic physical performance. The findings indicate that CAF improves performance in aerobic tests, but the results of the interaction with the genotype are still very controversial and require more studies with better methodological qualities and with higher sample sizes to have a more reliable population inference. Regarding anaerobic performance, the analysis shows that CAF appears to have an influence in relation to the dosage, duration of exercise and its fatigue-inducing profile. In short-duration exercises with a low fatigue-inducing profile, the results of CAF are less effective and more controversial, while for exercises with a slightly longer duration and with a greater fatigue-inducing profile, CAF has a more precise benefit. Regarding polymorphism in anaerobic performance, the results are still very controversial, but the few articles that found a significant interaction between CAF supplementation and the CYP1A2 genotypes studied, showed that AA homozygotes seem to have more influence on performance. However, although polymorphism studies associate the different genotypes of CYP1A2 as possible causes of divergent responses to CAF supplementation, especially in anaerobic exercise, no work has proven whether or not there are different responses in human metabolism with these polymorphisms. The present study analyzed the urine of volleyball athletes to identify the metabolomic profile in sports and performance situations with different moments of CAF supplementation and placebo. It was identified that, regardless of CAF, the human body has a different metabolic profile for the AA and AC genotype of CYP1A2 and this can help to elucidate many of the gaps present in the literature on CAF supplementation and genetic polymorphisms. Despite large variations in the metabolic profile, this factor is not statistically reflected in sports practice, and does not cause large variations in physical performance. Technical actions in volleyball, however, seem to be more effective, economical and more precise (with a lower rate of errors) when supplemented with CAF, whether at 30 CAF, 60 or 90 CAF of tests, compared to placebo, which significantly increased the number of technical actions, whether right or wrong. We conclude that the metabolic profile of subjects with different genotypes of 163 C>A of CYP1A2 is different when compared, however, this difference does not seem to be sufficient to change physical and sports performance.

2022
Dissertations
1
  • MARIA EDUARDA TENORIO OLIVEIRA
  • MULTI-OMIC ANALYSIS OF THE GUT MICROBIOME IN RATS WITH LITHIUM-PILOCARPINE INDUCED TEMPORAL LOBE EPILEPSY

  • Advisor : DANIEL LEITE GOES GITAI
  • COMMITTEE MEMBERS :
  • DANIEL LEITE GOES GITAI
  • JEAN PHELLIPE MARQUES DO NASCIMENTO
  • TIAGO GOMES DE ANDRADE
  • Data: Jan 25, 2022


  • Show Abstract
  • 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.  

2
  • RAYANE MARTINS BOTELHO
  • Seric cytokines and anaphylotoxins analyses in COVID-19 patients


  • Advisor : ALEXANDRE URBAN BORBELY
  • COMMITTEE MEMBERS :
  • ALEXANDRE URBAN BORBELY
  • KAREN STEPONAVICIUS CRUZ BORBELY
  • ROBINSON SABINO DA SILVA
  • Data: Feb 15, 2022


  • Show Abstract
  • 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.

3
  • JAQUELINE CORREIA SANTOS
  • Placental infection by the Zika Virus: investigation of the action of natural products
    with antiviral activity

     

  • Advisor : ALEXANDRE URBAN BORBELY
  • COMMITTEE MEMBERS :
  • ANDREA MOLLICA DO AMARANTE PAFFARO
  • ALEXANDRE URBAN BORBELY
  • JADRIANE DE ALMEIDA XAVIER
  • Data: Mar 30, 2022


  • Show Abstract
  • 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.

4
  • DIOGO BRANDÃO
  • LEISHMANICIDE POTENTIAL OF BACTERIA EXTRACTS ISOLATED FROM ANTARCTICA LIQUENS

  • Advisor : MAGNA SUZANA ALEXANDRE MOREIRA
  • COMMITTEE MEMBERS :
  • MAGNA SUZANA ALEXANDRE MOREIRA
  • ALINE CAVALCANTI DE QUEIROZ
  • MARIANA DA SILVA SANTOS
  • Data: May 26, 2022


  • Show Abstract
  • 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.

5
  • ANA LUCIA MENDES DA SILVA
  • Uvaol effects on trophoblast cells in the chorioamnionitis induced by group B streptococcus
  • Advisor : ALEXANDRE URBAN BORBELY
  • COMMITTEE MEMBERS :
  • ALEXANDRE URBAN BORBELY
  • ELIANA MARA OLIVEIRA LIPPE
  • SILVIA DAHER
  • Data: Jul 28, 2022


  • Show Abstract
  • 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. 
6
  • THAYANE KELLY DOS SANTOS CÂNDIDO
  • FREQUENCY OF METABOLIC SYNDROME AND ITS IMPACT ON QUALITY OF LIFE IN SUBJECTS CARE AT A RHEUMATOLOGY SERVICE IN ALAGOAS

  • Advisor : LUIZA ANTAS RABELO
  • COMMITTEE MEMBERS :
  • LUIZA ANTAS RABELO
  • ALANE CABRAL MENEZES DE OLIVEIRA
  • SANDRA MARY LIMA VASCONCELOS
  • Data: Aug 22, 2022


  • Show Abstract
  • 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.

7
  • MONALY DE OLIVEIRA LIMA
  • Treatment of temporomandibular joint osteoarthritis: systematic review of the literature and evaluation of the effects of simvastatin on human osteoblasts in vitro

  • Advisor : EMILIANO DE OLIVEIRA BARRETO
  • COMMITTEE MEMBERS :
  • EMILIANO DE OLIVEIRA BARRETO
  • JAMYLLE NUNES DE SOUZA FERRO
  • JANAINA ANDRADE LIMA SALMOS DE BRITO
  • Data: Aug 25, 2022


  • Show Abstract
  • 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.

8
  • SUSANA PAIVA OLIVEIRA
  • ASSOCIATION STUDY OF IL10 AND IL6 GENES WITH LEPROSY IN A POPULATION FROM AGRESTE OF ALAGOAS STATE

  • Advisor : CAROLINNE DE SALES MARQUES
  • COMMITTEE MEMBERS :
  • ANA CAROLINE MELO DOS SANTOS
  • CAROLINNE DE SALES MARQUES
  • JAMYLLE NUNES DE SOUZA FERRO
  • Data: Aug 29, 2022


  • Show Abstract
  • 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.

9
  • THIAGO PINA GOES DE ARAUJO
  • PI3Ks signaling pathway as a molecular target for glioblastoma therapy: a review

  • Advisor : MAGNA SUZANA ALEXANDRE MOREIRA
  • COMMITTEE MEMBERS :
  • ALINE CAVALCANTI DE QUEIROZ
  • ANDRESSA LETICIA LOPES DA SILVA
  • MAGNA SUZANA ALEXANDRE MOREIRA
  • Data: Aug 31, 2022


  • Show Abstract
  •  

    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.

10
  • RAYANE FERREIRA DA SILVA
  • Descriptive epidemiology and the IRF6 gene implications in a series of cases of typical oral clefts

  • Advisor : ISABELLA LOPES MONLLEO
  • COMMITTEE MEMBERS :
  • CAROLINNE DE SALES MARQUES
  • ISABELLA LOPES MONLLEO
  • THALITA CRISTINA FIGUEIREDO CUNHA
  • Data: Oct 24, 2022


  • Show Abstract
  • 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 PROVEANSIFTPolyPhen-2Mutation TasterAlign 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.

11
  • CARMELITA BASTOS MENDES
  • Thyroid hormones as possible co-regulators of aquaporins 1 and 4 in human gliomas: a pilot study using a bioinformatics approach.

  • Advisor : ADRIANA XIMENES DA SILVA
  • COMMITTEE MEMBERS :
  • ADRIANA XIMENES DA SILVA
  • EMILIANO DE OLIVEIRA BARRETO
  • MYKAELLA ANDRADE DE ARAUJO
  • Data: Nov 18, 2022


  • Show Abstract
  • 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, AOC2HGDATP1B1, ADCY5, PLCB4, ITPR1, ATP1A3LRP2HDAC1, 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.

12
  • DENISE MACEDO DA SILVA
  • 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 

  • Advisor : ELAINE VIRGINIA MARTINS DE SOUZA FIGUEIREDO
  • COMMITTEE MEMBERS :
  • ANA CAROLINE MELO DOS SANTOS
  • ELAINE VIRGINIA MARTINS DE SOUZA FIGUEIREDO
  • MARCIO BEZERRA SANTOS
  • Data: Dec 1, 2022


  • Show Abstract
  • 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.  

13
  • BRUNA BRANDAO DOS SANTOS
  • 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.

  • Advisor : ELAINE VIRGINIA MARTINS DE SOUZA FIGUEIREDO
  • COMMITTEE MEMBERS :
  • ELAINE VIRGINIA MARTINS DE SOUZA FIGUEIREDO
  • ANA CAROLINE MELO DOS SANTOS
  • RENISE BASTOS FARIAS DIAS
  • Data: Dec 5, 2022


  • Show Abstract
  • 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).


Thesis
1
  • LIDIA BEZERRA BARBOSA
  • FOOD CONSUMPTION AND ASSOCIATION WITH THE METABOLIC SYNDROME AND ITS COMPONENTS: A POPULATION-BASED STUDY WITH QUILOMBOLA WOMEN IN THE STATE OF ALAGOAS, BRAZIL

  • Advisor : HAROLDO DA SILVA FERREIRA
  • COMMITTEE MEMBERS :
  • Poliana Coelho Cabral
  • ALANE CABRAL MENEZES DE OLIVEIRA
  • HAROLDO DA SILVA FERREIRA
  • JAMILE FERRO DE AMORIM
  • SANDRA MARY LIMA VASCONCELOS
  • Data: Feb 23, 2022


  • Show Abstract
  • 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.

2
  • LARISSA TENORIO ANDRADE CORREIA
  • Mother and infant associations between chronotype, sleep quality, maternal mental health and child development


  • Advisor : TIAGO GOMES DE ANDRADE
  • COMMITTEE MEMBERS :
  • TIAGO GOMES DE ANDRADE
  • CLAUDIO TORRES DE MIRANDA
  • AUXILIADORA DAMIANNE PEREIRA VIEIRA DA COSTA E SILVA
  • LIVIA LEITE GOES GITAI
  • JULIANA FREITAS MARQUES
  • Data: Mar 4, 2022


  • Show Abstract
  • 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.


3
  • JOAO FLAVIO MONTEIRO SILVA
  • Leishmanicidal activity semi-synthetic compounds: a proposal for new strategies in the treatment of leishmaniasis
  • Advisor : MAGNA SUZANA ALEXANDRE MOREIRA
  • COMMITTEE MEMBERS :
  • MAGNA SUZANA ALEXANDRE MOREIRA
  • ALINE CAVALCANTI DE QUEIROZ
  • ALYSSON WAGNER FERNANDES DUARTE
  • JOAO XAVIER DE ARAUJO JUNIOR
  • CAMILA DE BARROS PRADO MOURA SALES
  • Data: Mar 30, 2022


  • Show Abstract
  • 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.

4
  • FERNANDA MARIA ARAUJO DE SOUZA
  • VALIDATION OF A NEW ANIMAL MODEL IN THE STUDY OF ANXIETY AND DEPRESSION IN MICE INDUCED BY A LOW 
    DOSE OF PILOCARPINE
  • Advisor : MARCELO DUZZIONI
  • COMMITTEE MEMBERS :
  • DANIEL LEITE GOES GITAI
  • Elaine Cristina Gavioli
  • FILIPE SILVEIRA DUARTE
  • MARCELO DUZZIONI
  • OLAGIDE WAGNER DE CASTRO
  • Data: Apr 1, 2022


  • Show Abstract
  • 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.

5
  • LANNI SARMENTO DA ROCHA
  • Effect of Triheptanoate-rich Ketogenic Diet on Memory and Cerebral Glucose Transport in Young and Aged Mice

  • Advisor : ADRIANA XIMENES DA SILVA
  • COMMITTEE MEMBERS :
  • ADRIANA XIMENES DA SILVA
  • ANA CATARINA REZENDE LEITE
  • FABIANA ANDREA MOURA
  • NASSIB BEZERRA BUENO
  • VIVIAN SARMENTO DE VASCONCELOS
  • Data: May 9, 2022


  • Show Abstract
  • 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.       

6
  • OLAVO BARBOSA DE OLIVEIRA NETO
  • PREVALENCE OF CANALIS SINUOSUS AND ACCESSORY CANALS OF CANALIS SINUOSUS IN CONE-BEAM COMPUTERIZED TOMOGRAPHIES: A SYSTEMATIC REVIEW AND META-ANALYSIS

  • Advisor : CELIO FERNANDO DE SOUSA RODRIGUES
  • COMMITTEE MEMBERS :
  • CELIO FERNANDO DE SOUSA RODRIGUES
  • GEORGE AZEVEDO LEMOS
  • LUIZ ALEXANDRE MOURA PENTEADO
  • OLAGIDE WAGNER DE CASTRO
  • RODRIGO FREITAS MONTE BISPO
  • Data: May 27, 2022


  • Show Abstract
  • 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.

7
  • JESSYKA CAROLINA GALVÃO DA SILVA
  • CARDIOVASCULAR EFFECTS OF AAL 195, AN INHIBITOR OF PHOSPHODIESTERASE 4 IN SPONTANEOUSLY HYPERTENSIVE RATS

  • Advisor : EURICA ADELIA NOGUEIRA RIBEIRO
  • COMMITTEE MEMBERS :
  • EURICA ADELIA NOGUEIRA RIBEIRO
  • OLAGIDE WAGNER DE CASTRO
  • HUGO JUAREZ VIEIRA PEREIRA
  • LUCIANO APARECIDO MEIRELES GRILLO
  • MARIA ALINE BARROS FIDELIS DE MOURA
  • Data: Aug 29, 2022


  • Show Abstract
  • 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.

8
  • CLARISSIANE SERAFIM CARDOSO
  • Investigation of a Glass Ionomer Cement modified from the incorporation of Fluorinated Lamellar Double Hydroxide (HDL-F): an in vitro and in silico study

  • Advisor : CAMILA BRAGA DORNELAS
  • COMMITTEE MEMBERS :
  • CAMILA BRAGA DORNELAS
  • ISABEL CRISTINA CELERINO DE MORAES PORTO
  • LUCAS MEILI
  • NATANAEL BARBOSA DOS SANTOS
  • RODRIGO BARROS ESTEVES LINS
  • Data: Nov 29, 2022


  • Show Abstract
  • 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.

9
  • LUCAS JOSE SA DA FONSECA
  • Coexisting Metabolic Syndrome in Rheumatoid Arthritis: impact on redox status and insulin resistance

  • Advisor : LUIZA ANTAS RABELO
  • COMMITTEE MEMBERS :
  • ALANE CABRAL MENEZES DE OLIVEIRA
  • LUIZA ANTAS RABELO
  • ODAIR ALVES DA SILVA
  • SANDRA MARY LIMA VASCONCELOS
  • VALERIA NUNES DE SOUZA
  • Data: Dec 22, 2022


  • Show Abstract
  • 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.

     

10
  • TAMARA RODRIGUES DOS SANTOS
  • 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

  • Advisor : HAROLDO DA SILVA FERREIRA
  • COMMITTEE MEMBERS :
  • HAROLDO DA SILVA FERREIRA
  • MARLY AUGUSTO CARDOSO
  • MYRTIS KATILLE DE ASSUNCAO BEZERRA
  • REGINA COELI DA SILVA VIEIRA
  • THATIANA REGINA FAVARO
  • Data: Dec 22, 2022


  • Show Abstract
  • 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.

2021
Dissertations
1
  • BEATRIZ DE ARAÚJO CORDEIRO
  • Angiotensin-(1-7) actions on diet models of studying metabolic syndrome in rats: systematic review and meta-analysis

  • Advisor : PRISCILA DA SILVA GUIMARAES
  • COMMITTEE MEMBERS :
  • PRISCILA DA SILVA GUIMARAES
  • OLAGIDE WAGNER DE CASTRO
  • MARIANA FLÁVIA DE OLIVEIRA
  • Data: Mar 12, 2021


  • Show Abstract
  • Metabolic syndrome (MS) has been considered a health problem and convincing evidence has suggested that Angiotensin (Ang) - (1-7) may be a potential pharmacological approach to treat it. This systematic review aims to collect all available data from Ang- (1-7) in animal models to study MS. Methods: The following electronic bibliographic databases were searched: PubMed, EMBASE, Web of Science and SCOPUS. The search strategy was based on the “animal models”, “metabolic syndrome” and “angiotensin- (1-7)” search components. No publication date or language restrictions were applied. Results: The protocol for this study is available online at PROSPERO. The research retrieved a total of 2056 citations (EMBASE, n = 816; PubMed, n = 285; SCOPUS, n = 290; Web of Science, n = 665). All citations were saved to a file in the reference software. After removing duplicates (n = 891), a total of 1419 citations were screened based on the title and abstract, resulting in 150 citations selected as potentially relevant articles. Of these, 61 citations were summaries at conferences, leading to 89 citations to be assessed for eligibility, considering the content of the full text, this stage is in progress. All surveys were conducted in July 2019. Conclusion: This systematic review aims to summarize all available data from Ang- (1-7) in animal models for studying MS, based on original full-text articles, and categorize them by type of interventions, animal models, SM induction method and outcome measures.

2
  • CHARLLES PETTERSON ANDRADE DE OMENA
  • Analysis of the knowledge of primary health care professionals in the city of Maceió on the assessment of the degree of physical disability in patients with leprosy.

  • Advisor : EMILIANO DE OLIVEIRA BARRETO
  • COMMITTEE MEMBERS :
  • AUGUSTO CESAR ALVES DE OLIVEIRA
  • CAROLINNE DE SALES MARQUES
  • EMILIANO DE OLIVEIRA BARRETO
  • Data: Jul 29, 2021


  • Show Abstract
  • The main problems arising from leprosy are physical disabilities. Such disabilities can be permanent, as Hansen's bacillus affects peripheral nerves, affecting motor, sensitive and autonomic fibers, making patients more susceptible to accidents, burns, wounds and even amputations, resulting in social and psychological damage that interfere in the quality of life of these individuals. The city of Maceió is the absolute record holder in number of new cases in the State of Alagoas. The Ministry of Health has developed recommendations for the assessment of the Degree of Physical Disability (GIF) in leprosy patients, which should be performed on all patients at various times: at diagnosis, every three months during treatment and at discharge for cure, using the simplified neurological assessment, composed of tests that assess the neurological function (sensory and motor) of eyes, hands and feet. However, the data made available by the State Health Department show that, in the last 10 years, 15% of patients in the capital of Alagoas did not have their GIF evaluated when diagnosed. This research aims to analyze the knowledge of these professionals regarding the assessment of the degree of physical disability in leprosy. This is quantitative, observational, analytical, cross-sectional research. A specific form was applied involving 38 doctors, 40 nurses and 08 physiotherapists working in Basic Health Units in the city of Maceió-AL. The results obtained in this study demonstrate that most doctors and physiotherapists know the simplified neurological assessment, however, they do not know how to perform it, unlike nursing professionals, who, in their majority, reported knowing how to perform the ANS. Regarding the GIF assessment, our results showed that most doctors and nurses interviewed knew about the GIF assessment, but did not know how to perform it, while most physiotherapists did not even know the GIF assessment. It is also worth noting that despite the professionals knowing how to perform the ANS and the GIF evaluation, it was reported that in the Health Units there are not enough materials to carry out a more precise work. With the completion of this study, the need for investments in the continuing education of professionals became evident in the face of a topic of great relevance to public health. In addition, the health system itself needs to be better structured to offer all professionals the tools to carry out the simplified neurological assessment and the classification of the degree of physical disability with greater precision.

3
  • KAROLINE CRISTINA JATOBA DA SILVA
  • IN VITRO LEISHMANICIDE ACTIVITY OF SYNTHETIC DERIVATIVES OF PURPUROGALIN
  • Advisor : MAGNA SUZANA ALEXANDRE MOREIRA
  • COMMITTEE MEMBERS :
  • MAGNA SUZANA ALEXANDRE MOREIRA
  • ALINE CAVALCANTI DE QUEIROZ
  • MARIANA DA SILVA SANTOS
  • Data: Aug 3, 2021


  • Show Abstract
  • Leishmaniasis is an infectious, non-contagious disease that has protozoa of the genus Leishmania as its etiological agent . A disease with a broad clinical spectrum, considered a public health problem in many countries, with poor treatments mainly due to toxicity, variable efficacy and the ability to induce parasitic resistance. Knowing that the existing pharmacotherapy is unsatisfactory, it is essential to plan and develop new drugs, one of the main strategies for this is the discovery of new drug prototypes through chemical synthesis. Thus, the aim of the present study was to investigate the in vitro cytotoxic and leishmanicidal activity of purpurogaline derivatives aiming at the discovery of new prototype candidates for leishmanicidal drugs . Through the colorimetric assay of MTT and the leishmanicidal activity in cultures of L. chagasi and L. amazonensis promastigotes through direct counting under an optical microscope. Statistical analyzes were performed using the GraphPad Prism software . The derivatives tested showed cytotoxicity below 60% to the host cell up to the maximum tested concentration of 100 µM, with the exception of derivatives IAS 2 and IAS 5. In the evaluation of direct activity on L. chagasi promastigotes, derivatives IAS 6 to IAS 8 showed maximum effect (ME) greater than 98% and IC50less than 20 µM, with an MS of 99.27 ± 1.46 %, 98.10 ± 3.30 % and IC50 of 10.08 µM (5.11 - 18.46), 9.46 µM (6 .08 – 14.23), respectively. Against L. amazonenses, derivatives IAS 3, IAS 4, IAS 5 and IAS 7 presented IC50 below 30 µM and MS above 60%, with emphasis on IAS 3 with IC50 of 17.97 (7.76 – 41.99 ) and MS of 100%. The derivatives have shown promise molecules for their activity leishmanicide, however , aspects related to the toxicity of some derivatives also p fear be improved.

4
  • ANA RUBIA BATISTA RIBEIRO
  • Raman spectroscopy applied to the study of functional cell differentiation: an evaluation on the macrophages phenotypes M1 and M2

  • Advisor : EMILIANO DE OLIVEIRA BARRETO
  • COMMITTEE MEMBERS :
  • EMILIANO DE OLIVEIRA BARRETO
  • ANA CATARINA REZENDE LEITE
  • MARVIN PAULO LINS
  • Data: Aug 4, 2021


  • Show Abstract
  • Macrophages are important cells of the immune system, distributed by different tissues and considered the first cells of defense against aggressive agents, playing a fundamental role in the development of the inflammatory process. Macrophages have great functional plasticity and are classified within a phenotypic spectrum that basically includes two activation profiles called phenotype M1 (classical activation) and phenotype M2 (alternative activation). It is known that each of these phenotypes is involved with different pathophysiological processes, and that their identification basically depends on the quantification of secreted mediators and/or the presence of typical surface markers of each phenotype. Therefore, in order to develop a methodology that allows the rapid identification of the macrophage phenotype without the need to use staining or labeling techniques, we aim in this study to apply the Raman spectroscopy technique as an alternative tool to distinguish M1 and M2 of macrophages. For this, the cell line J774.1 was used, submitted to stimulation with LPS/IFNγ for differentiation in the M1 profile, and with IL-4 for differentiation in the M2 profile. To certify the differentiation in each phenotype, the cytokines typical of each M1 (IL-6) or M2 (IL-10) profile were quantified by ELISA. In addition, we also determined morphological changes in each phenotypic profile using scanning electron microscopy. Then, the Raman analyzes were performed on each profile already defined, with the results of the variables being evaluated from the principal component analysis (PCA). The increased production of cytokines IL-6 and IL-10 confirmed the success of the polarization protocol for profiles M1 and M2, respectively. The morphological analysis of the groups observed a significant change only with regard to the M2 profile. The Raman spectra submitted to the analysis by the PCA technique allowed to distinguish the M1 and M2 profiles. In conclusion, the present study demonstrated that the polarization of macrophages in the M1 and M2 profile can be identified by Raman spectroscopy, opening the possibility of applying this technique to distinguish other cell types that show phenotypic differentiation.

5
  • BARBARA RAYSSA CORREIA DOS SANTOS
  • Association of IL6 T15A (rs13306435) and INOS -1173 C>T (rs9282799) polymorphisms with susceptibility to infection and progression of dengue.

  • Advisor : ELAINE VIRGINIA MARTINS DE SOUZA FIGUEIREDO
  • COMMITTEE MEMBERS :
  • ELAINE VIRGINIA MARTINS DE SOUZA FIGUEIREDO
  • CAROLINNE DE SALES MARQUES
  • ALINE CRISTINE PEREIRA E SILVA
  • Data: Aug 24, 2021


  • Show Abstract
  • Background: Dengue is a public health problem. Millions of cases are reported
    worldwide. The infection with dengue virus has a variety of signs and symptoms
    including asymptomatic and symptomatic cases. The immune system it is involved in
    the host&#39;s response to infections as well as in the pathogenesis of diseases, including
    dengue. Cytokines and nitric oxide are components of the immune system.
    Interleukin 6 is a cytokine that plays an important role in linking the innate immune
    response to the acquired immune response. iNOS is an enzyme responsible for
    inhibiting viral replication through the production of nitric oxide. Objective: To
    investigate the relationship of polymorphisms in the inducible nitric oxide (-1173 C /
    T) and interleukin 6 (T15A) genes with dengue infection and disease progression.
    Methodology: It was a case-control study with patients infected with dengue virus
    and healthy controls of the population. The genotypes of the iNOS (-1173 C / T) and
    cytokine IL-6 (T15A) genes were determined by the real-time polymerase chain
    reaction (qPCR), using the allelic discrimination method. The analyzes of the correlations between genotypic and allele frequencies concerning susceptibility to infection were obtained using the SNPstats and BioEstat 5.3 software. Results: The study was composed of a total of 179 individuals, 27 composing the dengue fever group, 33 to the dengue hemorrhagic fever group, and 119 composing the control group. For the T15A polymorphism of the IL-6 gene, no difference was found in the llelic and genotypic distribution between the groups. For the -1173 polymorphism of the iNOS gene, no difference was found in the allelic and genotypic distribution between the groups. Conclusion: No association was found between the polymorphism of IL-6 T15A (rs13306435) and iNOS -1173C / T (rs9282799) with dengue infection.

6
  • LUANA KAREN CORREIA DOS SANTOS
  • Immune Response Receptors Genes and Leprosy in an Alagoana Population

  • Advisor : CAROLINNE DE SALES MARQUES
  • COMMITTEE MEMBERS :
  • ALINE CRISTINE PEREIRA E SILVA
  • CAROLINNE DE SALES MARQUES
  • LUCIA ELENA ALVARADO ARNEZ
  • Data: Aug 25, 2021


  • Show Abstract
  • Leprosy is an infectious disease caused by Mycobacterium leprae that affects the skin and peripheral nerves, leading to physical deformities. It is considered a complex disease that suffers the influence of many factors, furthermore, the low diversity in your genome makes leprosy a great model to study the host genetic influence of the disease. Evidence shows that genes in the innate immune response, mainly TLR1 and NOD2, are important in the outcome and differentiation of clinical forms and, have been associated in Brazilian populations, however, there is no investigation of the role of these genes in Alagoas. The study aimed to evaluate the association of polymorphisms in the genes TLR1 and NOD2 in leprosy and its clinical forms in an alagoana population. We conducted a case-control study, where the cases were constituted by patients at CRIA (Integrated Reference Center of Arapiraca) and, the controls were healthy individuals, blood donors at Hemoal-Arapiraca. We evaluated the rs4833095 and rs8057341 in the genes TLR1 and NOD2, respectively. The individuals’ DNA who accepted to participate in the study was extracted through the salting-out method and genotyped through Real-Time qPCR via allelic discrimination (Applied Biosystems) using TaqMan probes. We obtained the genotypes and allele carriers frequencies, that afterward were compared between the groups through logistic regression. We conducted a systematic review to group the results obtained in a meta-analysis about polymorphisms in the TLR1 gene following Moose guidelines. All statistical analyses were performed in R studio version 1.4.1103 using the packages “genetics” and “SNPassoc” for the genetic association analysis and “meta” and “metafor” to meta-analysis”. As result, we achieved 399 recruited individuals, 134 cases, and 265 controls. The frequency of polymorphisms in the alagoana population (controls) was 18% to TT genotype of rs4833095-TLR1 SNP and 12% to TT genotype of rs8057341-NOD2 SNP. In the case-control and genetic association with leprosy the estimates of association were the following: rs4833095-TLR1 TC genotype with OR=0,87 (p=0,71) and CC with OR=1,0 (p=0,98); rs8057341-NOD2 CT genotype with OR= 0,92 (p=0,78) and TT with OR=1,03 (p=0,93). The results show that the studied SNPs do not have an association with leprosy in the investigated population, even after correction to sex co-variate. In the meta-analysis, only carriers of the C allele of the SNP rs5743618-TLR1 showed association with leprosy OR= 0,57 (p=0,048) exhibited a protector effect. When performed the sensitivity analysis and omitting a study, this protector effect was observed in all genetics models to the same SNP, showing OR=0,48 (p=0,010) to the C allele, OR=0,47 (p=0,028) to C carriers and, OR=0,26 (p=0,003) to CC genotype. The results obtained in the meta-analysis indicate a protector association of SNP rs5743618 of the TLR1 gene and leprosy. The findings of this study aggregate information regarding the genetic influence in leprosy in Alagoas, which may be useful to understand the disease development in the region.

7
  • KEYLA SILVA NOBRE PIRES
  • ZIKA VIRUS PLACENTAL INFECTION: SIGNALING PATHWAY INVESTIGATION AND AFFECTED CELL FUNCTIONS

  • Advisor : ALEXANDRE URBAN BORBELY
  • COMMITTEE MEMBERS :
  • OTÁVIO CABRAL MARQUES
  • ALEXANDRE URBAN BORBELY
  • ESTELA MARIS ANDRADE FORELL BEVILACQUA
  • Data: Aug 31, 2021


  • Show Abstract
  • Introduction: The Zika Virus (ZIKV) is considered a major public health problem, due to its ability to cross the placental barrier and infect the fetus, causing the Congenital Zika Virus Syndrome. Although, despite the ZIKV epidemics have ceased, the infection still deserves great attention, as it generates a disease that involves public spending in the short, medium and long term and that despite the scientific efforts made in recent years, it still does not have biomarkers, or known prophylaxis, research on viral pathogenesis during pregnancy is of great relevance, which can provide important information and targets that can be targeted therapeutically, preventing the passage of ZIKV through the placenta. Objective: To investigate the immunological and molecular aspects associated with the pathophysiology of gestational infection by ZIKV in different experimental models. Methods: HTR-8/SVneo cells derived from the first trimester of gestation, primary culture of extravillous cytotrophoblast (EVT) cells  and placental explants from term pregnancies were infected with an African strain (MR766) and an Asian strain (PE243) of the ZIKV and the immune response was analyzed, through the analysis of the production of genes and cytokines, as well as activation of specific molecular pathways. Results: Placental explants were infected only with the PE243 strain and showed increased IFN-α gene expression (p < 0.05), as well as IL-6 (p < 0.05) and IL-8 (p < 0.05), although no change in IFN secretion has been found. HTR-8/SVneo cells were infected by both strains (72.2% for MR766 and 80.2% for PE243), but showed no changes in gene expression or IFN secretion. While EVT cells were also infected with both strains (63.8% for MR766 and 66.5% for PE243), but showed increased secretion of IFN-α2 (p < 0.0005), IFN-λ1 (p < 0.01) and IL-6 (p < 0.01) after infection by PE243, and only an increase in IFN-λ1 (p < 0.05) after infection by MR766. Signaling by the analyzed molecules differed only in infection by PE243, which increased the expression of p-IRF3 (p < 0.05) and IRF9 (p < 0.05), while p-STAT-2 remained unchanged after infection with both strains. Conclusions: The response to ZIKV is different at different gestational ages and depending on the viral strain. At the end of pregnancy, EVT cells differ from other models, producing some IFN and maintaining active antiviral response pathways, which can make it difficult for the virus to surpass the placenta and infect the fetus.

8
  • ADLA RENATA DOS SANTOS SILVA
  • BIOSYNTHESIS OF SILVER NANOPARTICLES FOR RESEARCH ON ENTEROCOCCUS FAECALIS
  • Advisor : CAMILA BRAGA DORNELAS
  • COMMITTEE MEMBERS :
  • CAMILA BRAGA DORNELAS
  • FERNANDA CRISTINA DE ALBUQUERQUE MARANHAO
  • FÁBIO CORREIA SAMPAIO
  • Data: Sep 6, 2021


  • Show Abstract
  • Enterococcus faecalis plays an important role in persistent endodontic infections, contributing to its high resistance to calcium hydroxide-Ca (OH) 2, the main intracanal medication in dentistry. In this context, the development of new antimicrobial formulations is of fundamental importance. Silver-containing nanomaterials have stood out, especially for their antimicrobial properties, and biogenic synthesis presents itself as an alternative to reducing the toxicity of nanoparticles (NPs). Thus, the objective of this research is to synthesize and evaluate the antibacterial potential of silver NPs with red propolis from Alagoas (NPsAg-PV) against E. faecalis. NPsAg-PV were synthesized by reducing silver salts by hydroalcoholic extract of red propolis from Alagoas (EHPV), characterized in the form of colloidal suspension by the technique of ultraviolet and visible spectrophotometry (UV-Vis), dynamic light scattering (EDL) and Zeta potential, followed by its incorporation into the Ca (OH) 2 paste. The spectral analysis showed absorbance at 425 and 421 nm, after 24 h and 72 h, respectively, values characteristic of the formation of silver Nps, the EDL showed a hydrodynamic diameter of 131.5 nm ± 1.19 and a polydispersion index (PDI) 0.266, suggesting the absence of agglomerated particles, the Zeta potential was -61 mV ± 1.59, indicating the stability of the silver colloid. Regarding the antimicrobial activity, the NPsAg-PV isolated and associated with the Ca (OH) 2 paste showed greater efficiency when compared to the Ca (OH) 2 paste. In pulp infection, bacteria organize themselves into biofilm, thus, it is expected that on E. faecalis biofilm, NPsAg-PV will also be effective. Nanotechnology has stood out for presenting new preventive and therapeutic possibilities, and this study can develop an innovative material for endodontic treatment.
9
  • REINALDO LUNA DE OMENA FILHO
  • Genital ambiguity in a series of cases from the disorders/differences of sex development ambulatory of the Prof. Alberto Antunes University Hospital of UFAL - 2008 – 2018.

  • Advisor : ISABELLA LOPES MONLLEO
  • COMMITTEE MEMBERS :
  • ISABELLA LOPES MONLLEO
  • SAMIR BUAINAIN KASSAR
  • TIAGO GOMES DE ANDRADE
  • Data: Sep 10, 2021


  • Show Abstract
  • Genital ambiguity (GA) is a phenotype in which the anatomic sex attribution is not clear and belongs to the wide group of disorders/differences of sex development (DSD). The prevalence is of 1:4,500 live births and its aetiology is predominantly genetic. The GA occurs either in individuals with XX, XY normal sexual chromosomes or among those with numerical or structural sexual chromosomes abnormalities. In 2008, at the University Hospital of the Federal University of Alagoas, the DSD ambulatory was initiated. Nowadays this is a regular service delivered by a multidisciplinary team. The aim of this study was to describe the demographic, genetic, and clinical profile of individuals with GA assisted from 2008 to 2018. Data was gathered using a unique protocol and database. The karyotype was a universal test. The ARSRD5A2HSD17B3NR5A1, and CYP21A2 genes analyses were performed according to clinical indication, after the karyotyping. During this period, 146 individuals with DSD were seen, 73 (50%) of which with GA, belonging to 71 families, 21.9% living in Maceió. Parental consanguinity and phenotype recurrence were observed in 16.9% and 14.1%, respectively. Age at the first specialized assessment was over 90 days of life (inadequate) for 56.2% of the sample, and 78.1% presented moderate to severe AG. Disorders of androgen synthesis or action (DSD XY) were the largest group (50.7%), followed by androgen excess (32.9%) and the disorders of gonadal differentiation (DGD) (16.4%). Congenital adrenal hyperplasia was the most prevalent nosology (32.9%). New variants in HSD17B3NR5A1, and CYP21A2 genes were identified. Among DGD, two rare cases of Klinefelter Syndrome plus ovotesticular DSD, and gonadal mixed dysgenesis plus Down Syndrome were identified. This is the first description of the demographic, genetic, and clinical profile of GA in Alagoas. Overall data corroborate the literature. The study has also identified rare and new aetiologies which may contribute to rise the knowledge on DSD. These results inform the debate on health policies for patients with GA in Alagoas.

10
  • ERIVALDO DAVI DOS SANTOS JUNIOR
  • Layered double hydroxide-based nanosystem for inhibition of microRNAs:
    characterization of toxicity and inhibition efficiency.

  • Advisor : DANIEL LEITE GOES GITAI
  • COMMITTEE MEMBERS :
  • AXEL HELMUT RULF COFRE
  • DANIEL LEITE GOES GITAI
  • OLAGIDE WAGNER DE CASTRO
  • Data: Nov 15, 2021


  • Show Abstract
  • Temporal Lobe Epilepsy (TLE) is the most common epilepsy and 30% of patients do not present complete remission of seizures, even with the use of antiepileptic drugs (AEDs). Thus, there is a need to seek new therapeutic approaches, such as functional modulation of microRNAs (miRs) by pharmacological approach (MIMIC / miRs inhibitors). Layered Double Hydroxide (LDH) based nanoparticles have been used as siRNA carriers, however, the application of LDH for the delivery of miRs inhibitors still requires investigation. In this work, we produced and tested a nanocarrier based on Mg-Al-LDH complexed with miRs inhibitor against miR-196b-5p. LDHs were synthesized by coprecipitation method and subjected to physicochemical characterization regarding hydrodynamic size, surface charge, crystallinity and the chemical groups present. Regarding the biological effects, thymus endothelial cells (tEnd.1) were transfected with LDH/inhibitor and were evaluated for: i. cell viability by MTT, trypan blue and propidium iodide assays; ii. transfection efficiency by flow cytometry and iii. depletion of miR-196b-5p by RT-qPCR. In addition, Drosophila melanogaster larvae were fed LDH and were evaluated for: i. impairment of larval motility; ii. pupation rate; iii. delay to pupation; iv. lethality, and V. number of adult hatches. Finally, LNA inhibitors were used for miR-196b-5p inhibition assay in an experimental TLE model, where the relative expression of miR-196b-5p and its predicted target SLC9A6 was evaluated by RT-qPCR. We observed that LDH-type nanoparticles are stable in aqueous solutions and exhibit a regular hexagonal shape. The LDH/inhibitor complex showed a transfection efficiency of 93% and led to significant depletion of miR-196b-5p 48h after transfection. We observed no cytotoxic effects in tEnd.1 cells at concentrations up to 50 μg/ml, as well as in Drosophilas exposed up to 500 μg of LDH. In vivo functional assay in rats induced Status Epilepticus revealed a significant depletion of hippocampal levels of miR196b-5p as well as a significant increase in the relative expression of the target gene SLC9A6. In conclusion, our data suggest that LDH presents itself as a biocompatible and efficient carrier for miRNA inhibitors and can be used as a viable and effective tool in functional miRNA inhibition assays.

11
  • ELLYDA FERNANDA LOPES COSTA
  • Modulatory effect of Lithium on mania-like behavior induced by photoperiodic variations

  • Advisor : TIAGO GOMES DE ANDRADE
  • COMMITTEE MEMBERS :
  • GEISON SOUZA IZÍDIO
  • OLAGIDE WAGNER DE CASTRO
  • TIAGO GOMES DE ANDRADE
  • Data: Nov 30, 2021


  • Show Abstract
  • Bipolar disorder (BD) is a chronic mood disorder, affecting approximately 2-3% of the global population. Mania is a cardinal feature of BD and is characterized by symptoms as exposure to risk and impaired decision-making. Epidemiological studies show higher occurrence of hospitalizations for manic episodes in periods of accentuated increments in day length, or photoperiod. Consistently, preliminary studies performed by our group indicate that a gradual increase of the photoperiod is associated with a mania-like behavior in C57BL/6 mice. The hypothesis is that gradual variations in photoperiod modulate the circadian rhythms in brain regions associated with mood disorders. Lithium (Li) is a mood stabilizer used in the treatment of bipolar disorders in humans with antimanic and antidepressant properties. Furthermore, Li treatment modulates mood-related behavior in rodents. The aim of this work is to validate the photoperiodic induced mania-like animal model by pharmacologically testing lithium as a mood stabilizer. The animals that were used in the present study are male C57BL/6J mice, distributed into the three groups: (1) Equatorial (Eq), (2) DTM (Daylength Transition Model) and (3) DTM-Li. The animals of Eq group were exposed to CE12:12. The DTM group consists of mice exposed to a regime of gradual photoperiodic variations (30min at the beginning and 30 min at the end of light phase/day) from 08h:16h CE to a 16h:8h CE, with food and water ad libitum. The DTM-Li group animals were submitted to the same photoperiodic protocol but Lithium Chloride was administered in drinking water for eight days, from the first day to the last day of the DTM regime. Elevated Pluz Maze, Open Field Test, Forced Swimming Test and Hole Board were performed to evaluate hyperactivity, anxiety, risk-taking, depression and mania. The date were analyzed using the ANOVA (post-hoc Tukey), using prism 8 software, with a significance cut-off value of P < 0.05 and 95% confidence interval.. The animals in the DTM-Li group showed a decrease in risk exposure evaluated by the elevated plus maze test; exploratory and hyperlocomotion behaviors, assessed through behavioral tests, when compared to the TMD and similar to the control group. The findings demonstrate that administration of lithium stabilizes mood and prevents the mania-like behavior observed in the experimental condition. This study contributes to the establishment of a new model for bipolar disorder based on the manipulation of ambient light.

Thesis
1
  • RENISE BASTOS FARIAS DIAS
  • Biological, epidemiological and sociocultural factors that contribute to the care of
    newborns exposed to drugs in the prenatal period: a multiphase mixed methods study

  • Advisor : ELAINE VIRGINIA MARTINS DE SOUZA FIGUEIREDO
  • COMMITTEE MEMBERS :
  • AMUZZA AYLLA PEREIRA DOS SANTOS
  • ANA CAROLINA SANTANA VIEIRA
  • CARLOS DORNELS FREIRE DE SOUZA
  • ELAINE VIRGINIA MARTINS DE SOUZA FIGUEIREDO
  • ELISIANE LORENZINI
  • Data: Nov 16, 2021


  • Show Abstract
  • The use of drugs during pregnancy can have consequences for the mother, fetus or
    newborn. In this context, the present study aimed to analyze the integration knowledge
    about epidemiological and sociocultural aspects with knowledge about the biological and
    behavioral subsystems of newborns exposed to drugs in the prenatal period for mediated
    neonatal care. This is a multiphase study of a concurrent triangulation mixed methods
    approach. The mixing occurs at an interactive level, with equal emphasis, in addition, also
    was conducted priority quantitative studies followed by supplementary qualitative studies.
    The development of this study occurring in five phases that followed specific
    methodological criteria, developed between February/2019 and May/2021, in two
    maternity hospitals in Alagoas, whose participants were 105 dyads (mothers who were
    drug users in the prenatal period and newborns). In the first phase, a qualitative,
    exploratory, descriptive study was conducted, with a realistic ethnographic perspective on
    the care provided to the dyad (mother and newborn). In the second phase, an
    ethnoepidemiological, cross-sectional, descriptive study with a quantitative-qualitative
    approach was developed. In the third phase, an observational study, prevalence, with a
    quantitative-qualitative approach. The understanding of data from phases 1 and 2 was
    supported by Leininger's Theory and phase 3 by Jhonson's Theory. In the fourth phase, a
    case-control study of genetic association by polymorphisms was conducted. The fifth
    phase resulted from the mixed of quantitative and qualitative elements obtained in the
    previous phases. The phase 1 study made it possible to elucidate the key points for
    subsequent studies: the identification and interpretation of the maternal context and
    neonatal signs to guide the mediate care of newborns exposed to drugs in the prenatal
    period. Subsequent studies provided knowledge of the characteristics of the population,
    above all, based on the observation of health indicators. Among the main results obtained,
    the combination of signs: excessive strident crying, myoclonic spasms and excessive
    sucking was considered an important clinical marker of prenatal drug exposure. From the
    results of phase four, it was possible to conclude that the SNP -819C/T (IL-10) and -308G/A
    (TNFA) were not related to the susceptibility and protection for neurobehavioral
    dysfunctions in neonates exposed to drugs in the pre- natal. In addition that three
    different neurobehavioral responses are not associated with -819C/T (IL-10) SNP alleles.
    And to indicating paths for further studies to confirm or refute the hypothesis that
    prenatal exposure to tobacco has a higher odds ratio for developing neurobehavioral
    alterations in neonates. In phase 5, the integration of sociocultural, epidemiological and
    behavioral system knowledge allowed for the elucidation of the elements that contribute
    to the care of newborns exposed to drugs in the prenatal period, in addition to building
    integrated resolution propositions that converged as a decisive tool for qualification of
    care. Finally, five meta-inferences were presented. The results brought in this study
    encourage new reflections, new studies for more effective diagnoses and the qualification
    of best practices in the process of caring for newborns exposed to drugs in the prenatal
    period, considering the clinical context and sociocultural.

2020
Dissertations
1
  • ALESSANDRO CESAR BERNARDINO
  • INVESTIGATION OF THE ACTION MECHANISM INVOLVED IN THE CARDIOPROTECTIVE EFFECT OF THE HYDROALCOHOLIC EXTRACT OF Alpinia zerumbet LEAVES IN INFARTED RATS

  • Advisor : EURICA ADELIA NOGUEIRA RIBEIRO
  • COMMITTEE MEMBERS :
  • EURICA ADELIA NOGUEIRA RIBEIRO
  • ALFREDO DIAS DE OLIVEIRA FILHO
  • ELIANE APARECIDA CAMPESATTO
  • Data: Feb 12, 2020


  • Show Abstract
  • Introduction: Alpinia zerumbet, popularly known as cologne, has been used in folk
    medicine due to its antihypertensive and diuretic properties. Several cardiovascular
    actions have been related, such as hypotensive, vasorelaxant, antihypertensive,
    antioxidant, cardiodepressant and antiplatelet effects. A recent study from our group
    showed that the hydroalcoholic extract of A. zerumbet (AZE) leaves induced
    cardioprotective activity in infarcted rats. This study aimed to investigate the mechanisms
    involved in the cardioprotective effect induced by AZE in rats. Methods: Evaluation of
    cytotoxicity of AZE was evaluated using macrophages in the MTT test. In this study, we
    used isoproterenol (ISO, 85 mg / kg, s.c.) to induce acute myocardial infarction in rats.
    Rats were anesthetized and polyethylene catheters were inserted into the lower abdominal
    aorta and lower vena cava for blood pressure measurements and drug administration. The
    hemodynamic parameters applied were mean arterial pressure (MAP), myocardial
    oxygen demand (BMD) and heart rate (HR). Calcium level in aortas, ventricles and serum
    was quantified with a colorimetric assay. The antioxidant effect of AZE was evaluated in
    chemical tests by reducing activity of oxidizing species (DPPH, ABTS, reactive NO
    species, Fe3 + reduction, Fe2 chelator). Results were expressed as ± S.E.M medium and
    statistically analyzed by ANOVA, following Newman-Keuls. The study was approved
    by the Ethics Committee of the Federal University of Alagoas (nº 010852 / 2009-01).
    Results: Exposure of macrophages to AZE produces a maximum inhibitory response (I
    max = 39.88 ± 2.78%) without promoting a cytotoxic effect. In control rats (not infarcted),
    or AZE (0.1 to 60 mg / kg, i.v., randomly) produced hypotension and bradycardia, result
    was seen as infarcted animals. The bradycardic response to AZE was attenuated after
    nifedipine (1 mg / kg, i.v., calcium channel blocker) in infarcted rats. Infarcted rats
    showed a significant increase in HR (317 ± 3 bpm), BMD (38 ± 3 mmHg / min) and a
    decrease in MAP (81 ± 5 mmHg). Pretreatment with AZE (300 mg / kg / day) for 26 days
    offers important protection against CF-induced changes in ISO (253 ± 8 bpm) and BMD
    (18 ± 2 mmHg / min) compared to infarcted animals. In addition, AZE reduces the levels
    of calcium in the ventricles and aortas without alteration in serum. AZE (0.5 to 15 mg /
    mL) showed antioxidant effect when compared with natural antioxidant products [ABTS
    + AZE, IC50% = 196.5 vs. Quercertin, IC 50% = 462.1; Coffee acid, IC50% = 418.2 and
    gallic acid, IC50% = 546.4). By Griess reaction, or AZE (250 mg / mL), time-dependent
    antioxidant effects (Imax = 60% vs. Quercertin: Imax = 63%; Caffeic acid: Imax = 75%
    and Gallic acid: Imax = 50% in 150 minutes). However, the same effect was not observed
    in DPPH and fluorescence recovery after photodegradation methods. Conclusions: These
    suggested results on the cardioprotective effect of AZE may cause a blockage of tension-
    operated calcium channels (VOCC's). However, antioxidant effects may be involved in
    the cardioprotective response of AZE.

2
  • LUCAS CHAGAS SILVA
  • TRANSCRANIAL STIMULATION DIRECT CURRENT APPLIED AT DIFFERENT MOMENTS OF THE AEROBIC PHYSICAL EXERCISE AND ITS EFFECTS ON THE DESIRE TO SMOKE IN SMOKERS

  • Advisor : ADRIANA XIMENES DA SILVA
  • COMMITTEE MEMBERS :
  • ADRIANA XIMENES DA SILVA
  • EUCLIDES MAURÍCIO TRINDADE FILHO
  • JOSÉ CLEMENTINO NETO
  • Data: Sep 1, 2020


  • Show Abstract
  • Tobacco use with a sedentary lifestyle is among the main behavioral causes of mortality
    worldwide. Studies have reported a series of changes in behavior related to aerobic exercise
    (AE) in smokers, has a positive effect on cognitive functioning, especially in the cognitive
    domains dependent on the prefrontal cortex. Another method that has been shown to be a
    promising to reduce the desire to smoke is Transcranial Direct Current Stimulation (TDCS).
    Since the cognitive benefits of AE and TDCS activate common brain areas such as the
    prefrontal cortex, in addition, they are two techniques that can be used in combinations, for
    these reasons it is plausible that they may have additive effects. Given the above, the main
    objective of this study is to verify whether the association of AE with TDCS has an additive
    effect on the desire to smoke in smokers when compared to the use of isolated TDCS and to
    identify when (before, during or after) AE must be applied, associated with TDCS. We
    conducted a randomized clinical trial, with pre- and post-test design of four groups: G1 (TDCS);
    G2 (1st TDCS 2nd AE); G3 (1st AE 2nd TDCS) and G4 (AE and TDCS concurrently), with
    altogether 39 participants. The volunteers received anodal TDCS in the area of the prefrontal
    cortex (F4) and cathodal TDCS in the temporal region (T3) at an intensity of 2.0 mA for 20
    minutes for five consecutive days. Groups G2, G3 and G4 in addition to TDCS were submitted
    to moderate intensity AE on a treadmill for 40 minutes (5 minutes of warm-up, 30 minutes of
    moderate exercise and 5 minutes of calm back) before, after or during TDCS depending on the
    group. The level of dependence, exhaled carbon monoxide, degree of motivation, number of
    cigarettes smoked, and level of desire were evaluated. The results were analyzed statistically
    by the Student test or by the Wilcoxon test and one-way ANOVA or by the Kruskal-Wallis test,
    they were considered significant when p <0.05. Groups G2 and G4 showed a significant
    reduction of 32.95% and 50.13% respectively in the desire to smoke, when comparing the pre-
    and post-test moments. For the level of dependence, the groups showed a significant reduction
    of 23.08%, 31.38%, 43.19% and 39.54% respectively when comparing the pre- and post-test
    moments. Exhaled carbon monoxide showed significant reductions of 46.78%, 42.17% and
    44.50% for groups G2, G3 and G4 respectively when comparing the pre- and post-test
    moments. For the variable number of cigarettes smoked, there was a significant reduction over
    time in consumption for all groups. Although we found a more accentuated decrease profile in
    the groups where there is an association, there was no significant difference between these
    groups and the TDCS for any evaluated variable. The results demonstrate that five AE sessions
    performed during or after TDCS can reduce the desire to smoke, the level of dependence, the
    levels of exhaled carbon monoxide and the number of cigarettes smoked between the pre- and
    post-test moments, and the more accentuated decrease profile in groups where there is an
    association, suggests AE as a probable enhancer of the positive modulators effects of TDCS in
    smokers.

3
  • MARCÍLIO FERREIRA DE MELO NETO
  • CHANGES IN GUT MICROBIOTA IN AN EXPERIMENTAL MODEL OF MENOPAUSE AND ITS RELATIONSHIP WITH HIGH-FRUCTOSE DIET

  • Advisor : PRISCILA DA SILVA GUIMARAES
  • COMMITTEE MEMBERS :
  • PRISCILA DA SILVA GUIMARAES
  • LUCIANA COSTA MELO
  • CRISTIANE MONTEIRO DA CRUZ
  • Data: Sep 17, 2020


  • Show Abstract
  • Changes in gut microbiota (GM) were evaluated due to menopause and its association with
    high-fructose diet. Adult female Wistar rats were subjected to ovariectomy (ovx; an
    experimental model of menopause) or sham surgery (control) and divided into 4 groups:
    rats fed high-fructose diet (10% solution in drinking water; sham-F and ovx-F) and rats fed
    control diet (drinking water; sham-C and ovx-C). Faeces (1g) was collected immediately
    before surgery (T0), and at the 4 th (T4), 8 th (T8) and 12 th (T12) subsequent weeks for
    processing, culture in 5% blood agar, in duplicates, and incubation (24h; 36°C). Manual
    counting of colony forming units (CFUs) was performed and 10 random colonies of each
    culture were subcultured in brain-heart-infusion agar (BHIA) for quantitative and
    qualitative analysis. Biochemical analysis was performed in Gram-positive cocci (GPC) and
    Gram-negative bacilli (GNB). Two-way ANOVA repeated measures (RM) followed by
    Student Newman-Keuls (SNK); One-way ANOVA RM or Friedman RM ANOVA on
    Ranks followed by SNK or Dunnett´s; Two-way ANOVA followed by SNK or Kruskal-
    Wallis One-way ANOVA on Ranks followed by Dunn’s; and the Fisher’s exact test were
    used, considering the level of significance as p< 0.05. At T0, similar quantity of CFUs was
    observed between groups. Differently, from T4 to T12, fructose-fed groups presented
    increased CFUs compared to controls (p<0.05). Interestingly, sham-F had several
    uncountable plates (extremely high quantity of CFUs), in which odds ratio of occurring it
    was 16.1 times more in sham-F compared sham-C. In contrast, ovx-F had only 1
    uncountable plate at T4, displaying it again only at T12 (n=6), reflecting that ovx-F had no
    difference in odds ratio for uncountable plates until T12 compared to ovx-C. Moreover,
    ovx-F odds ratio for uncountable plates was 0.09 in relation to sham-F. Of the total of 1.320
    isolates (T0 to T12) that were obtained, 971 isolates were Gram-positive cocci (GPC), 222
    Gram-positive bacilli (GPB), 98 Gram-negative bacilli (GNB), 22 Gram-negative cocci
    (GNC) and 7 yeasts (Y), in which the latter was observed only in ovx groups. Except for
    fructose-fed groups at T4, the majority of isolates were GPC (at least 55%) in all groups at
    any time. Also, all the groups, but ovx-C, had considerable increase in GPB, GNC and/or
    GNB at T4 (p<0.05) compared to T0. Biochemical analysis of GPC revealed that
    commensal microorganisms constituted at least 80% in all groups at any time, except for
    ovx-F at T8, in which it represented 52.1%. Sixty-seven (n=67) GNB recovered isolates, 49
    isolates were fermenters, 3 isolates were non-fermenters and 15 isolates did not grow on
    MacConkey. The majority of GNB were obtained at T4 (n=51, wherein 48 were fermenters,
    of which 32 were detected in ovx group). All non-fermenters isolates (n=3) were negative
    on cetrimide agar, thus, non- identified Pseudomonas aeruginosa. Despite such percentual
    variations, no statistical differences were observed between groups in any time for
    biochemical analysis of GPC or GNB. Fructose-fed rats drank more solution and ate less
    food than their respective controls (p<0.05). In addition, as expected, ovx-F had increased
    body weight (BW) gain compared to sham groups (p<0.05). However, no difference was
    observed on BW gain due to fructose intake. In conclusion, chronic fructose intake
    increased CFUs in both sham and ovx females, but ovariectomy prevented the occurrence
    of overgrowth of CFUs. The percentual of GPB increased in fructose-fed rats from T4
    onwards; while the increase of GNB and/or GNC occurred only at T4 and in all groups.
    Changes in GM seemed to be independently of BW gain. The data herein suggest that
    ovariectomy attenuated the overgrowth of CFUs, even when it is associated with fructose
    feeding. Despite that, general changes in GM are likely to be similar to fructose-fed sham
    rats.

Thesis
1
  • ABEL BARBOSA LIRA NETO
  • PREVALENCE OF eNOS, IGFBP3 AND TCF7L2 POLYMORPHISMS AND ITS ASSOCIATION WITH SYSTEMIC ARTERIAL HYPERTENSION: A STUDY OF  POPULATION BASIS WITH BRAZILIAN WOMEN DESCENDING FROM  AFRICAN SLAVES.
  • Advisor : HAROLDO DA SILVA FERREIRA
  • COMMITTEE MEMBERS :
  • HAROLDO DA SILVA FERREIRA
  • KAROL FIREMAN DE FARIAS
  • MONICA LOPES DE ASSUNCAO
  • ALINE CRISTINE PEREIRA E SILVA
  • Data: Dec 21, 2020


  • Show Abstract
  • Individuals of African descent have higher prevalence of arterial hypertension, which
    seems to be related, among other factors, to genetic predisposition, however, this
    population is underrepresented in genetic studies. Thus, this thesis aimed to investigate
    the prevalence of NOS3 polymorphisms rs1799983, IGFBP3, rs11977526 and TCF7L2,
    rs7903146 in women of African descent from a state of Alagoas and their activities with
    arterial hypertension. A cross-sectional study was carried out with a probabilistic sample
    of 1021 women, aged 20 to 49 years, living in the quilombola community in the state of
    Alagoas. The present study evidences that the polymorphic variants NOS3 rs1799983,
    IGFBP3, rs11977526 are associated with higher blood pressure levels in Afro-descendant

    populations, consequently, with a higher prevalence of arterial hypertension. Afro-
    descendant Alagoas women with the TT genotype for the NOS3 gene and AA genotype

    for the IGFBP3 gene are more susceptible to arterial hypertension. These findings
    highlight the need to study groups of African descent to identify biological factors that
    contribute to hypertension.

2019
Dissertations
1
  • JULIANDERSON DE OLIVEIRA DOS SANTOS CARMO
  • Tratamento tópico com friedelina acelera a cicatrização de feridas cutâneas em camundongos diabéticos e induz a ativação de fibroblastos in vitro

  • Advisor : EMILIANO DE OLIVEIRA BARRETO
  • COMMITTEE MEMBERS :
  • EMILIANO DE OLIVEIRA BARRETO
  • KLAYSA MOREIRA RAMOS
  • MARIA DANIELMA DOS SANTOS REIS
  • Data: Feb 13, 2019


  • Show Abstract
  • O comprometimento do processo de cicatrização é uma complicação frequente do diabetes mellitus (DM) que contribui para a formação de feridas crônicas. Desta forma, substâncias que aceleram o processo de cicatrização despertam interesses na prática clínica. Neste contexto, o triterpeno pentacíclico natural friedelina tem sido relatado na literatura como possuidor de diversas atividades biológicas, incluindo efeitos gastroprotetores, antibacterianos e antiinflamatórios, no entanto, seus efeitos sobre a cicatrização na condição diabética ainda não foram descritos. Assim, o objetivo do presente trabalho foi avaliar a capacidade cicatrizante deste triterpeno em feridas cutâneas de camundongos diabéticos e avaliar seu efeito sobre funções de fibroblastos in vitro. Para isso, uma ferida excisional foi provocada no dorso de camundongos Swiss não diabéticos e diabéticos induzidos por aloxana. Após 21 dias do estímulo diabetogênico, os animais foram divididos nos seguintes grupos: 1) Animais não diabéticos tratados com salina (NDB); 2) Animais diabéticos tratados com salina (DB); 3) Animais diabéticos tratados com 0,1% de friedelina (DB-FD 0,1%); 4) Animais diabéticos tratados com 1% de friedelina (DB-FD 1%). No sétimo dia após a indução da ferida, amostras de pele foram coletadas para a avaliação do padrão histopatológico, da expressão de MMP e TIMP, da deposição de colágeno total e da angiogênese. Adicionalmente, fibroblastos expostos à friedelina in vitro tiveram o seu potencial de migração, capacidade de produção de matriz extracelular e produção de TGF-β1 avaliados por scratch assay e imunofluorescência, respectivamente. Nossos resultados demonstraram que a aplicação tópica de friedelina acelerou a contração da ferida por estimular a formação do tecido de granulação devido a maior presença de fibroblastos no local da ferida. Além disso, verificamos que a friedelina reduziu a expressão de MMP e aumentou a expressão de TIMP na ferida diebética. Também foi demonstrado que o tratamento tópico com friedelina aumentou a deposição de colágeno total, assim como estimulou o processo de angiogênese em camundongos diabéticos. A análise in vitro revelou que a friedelina estimulou a migração, bem como a produção de fibronectina, laminina e TGF-β1 em fibroblastos. Com base nesses resultados, sugerimos que a friedelina pode ser uma importante alternativa terapêutica para o desenvolvimento de fármacos visando o tratamento de feridas diabéticas.

2
  • JOSÉ GOMES DOS SANTOS NETO
  • INVOLVEMENT OF THE HYPOCAMPLE CHOLINERGIC SYSTEM IN THE DEPRESSIVE-TYPE EFFECT CAUSED BY CRACK WITHDRAWAL

    INVOLVEMENT OF THE HYPOCAMPLE CHOLINERGIC SYSTEM IN THE DEPRESSIVE-TYPE EFFECT CAUSED BY CRACK WITHDRAWAL


  • Advisor : MARCELO DUZZIONI
  • COMMITTEE MEMBERS :
  • MARCELO DUZZIONI
  • OLAGIDE WAGNER DE CASTRO
  • FILIPE SILVEIRA DUARTE
  • Data: Feb 26, 2019


  • Show Abstract
  • Introduction: Crack, when withdrawn abruptly after repeated administrations, is associated
    with physical and psychological disorders, such as mental disorders. The hippocampal cholinergic
    system has been implicated in several pathologies, such as in addiction to drugs of abuse and in
    anxiety and depression disorders. Objective: Evaluate the involvement of the hippocampal cholinergic
    system in the behaviors related to anxiety and depression associated with crack withdrawal in Swiss
    male mice. Material and methods: The nimals were exposed to crack smoke (burning of 200 or
    800 mg of crack) once daily for 5 minutes, for 5 consecutive days. After 24 and 48 hours
    of the last exposure the animals were submitted to tests of anxiety (elevated plus maze; EPM),
    locomotion (open field, OF) and depression (forced swim test, FST). The hippocampal activity
    of the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) was evaluated in one
    group of animals 24h after the last exposure to crack smoke (200 or 800 mg); while another group of
    animals, in the same withdrawal period and exposed to only 200 mg of crack, was treated with
    intra-hippocampal administration with PBS or Pirenzepine (0.06 nmol; selective M1 muscarinic
    receptor antagonist), and, after 5 min, submitted to FST. Finally, serological levels of
    corticosterone were evaluated 24 hours and 48 hours after the last exposure to crack smoke (200
    mg). Results: Our results showed that 24h or 48h after the last exposure to crack smoke (200 mg,
    only) there was a reduction in the number of head dipping in the EPM; in the time of 48 hours and in
    this same amount of crack we found an increase in the percentage of time in the open arms of the EPM.
    When evaluated 24 hours (200 and 800 mg) or 48 hours (200 mg, only), we found na increase
    in locomotor activity in the OF and an increase in the time of immobility in the FST. These
    results taken together indicate that the animals presented a depressive-like behavior, but not anxious.
    In relation to hippocampal enzymes AChE and BChE, exposure to crack smoke (800 mg, only)
    decreased the activity of these enzymes. However, this same amount of crack decreased significantly
    the concentration of total proteins in the hippocampus, indicating a neurotoxic effect of this amount of
    crack. In addition, administration of pirenzepine was able to reverse the effect of the depressive-
    like effect triggered 24 hours after the last exposure to crack smoke. Finally, 24h or 48h after
    the last exposure to crack smoke (200 or 800 mg) animals had increased levels of corticosterone,
    indicating high levels of stress in animals. Conclusion: Our results indicated that 24 h after the last
    exposure to crack smoke (200 mg, non-toxic dose) the animals presented a depressive-like behavior –
    from the activation of M1-muscarinic receptors in the hippocampus and from elevation in
    serologic levels of corticosterone. In addition, the established experimental protocol will allow
    better study of the involvement of the hippocampal cholinergic system in the withdrawal of drugs of
    abuse and associated comorbidities, especially crack and depression, respectively.

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