Publications by authors named "Cleber Machado-Souza"

21 Publications

  • Page 1 of 1

Association Between COVID-19 Pregnant Women Symptoms Severity and Placental Morphologic Features.

Front Immunol 2021 26;12:685919. Epub 2021 May 26.

Postgraduate Program of Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná-PUCPR, Curitiba, Brazil.

Since the beginning of the pandemic, few papers describe the placenta's morphological and morphometrical features in SARS-CoV-2-positive pregnant women. Alterations, such as low placental weight, accelerated villous maturation, decidual vasculopathy, infarcts, thrombosis of fetal placental vessels, and chronic histiocytic intervillositis (CHI), have been described.

Objective: To analyze clinical data and the placental morphological and morphometric changes of pregnant women infected with SARS-CoV-2 (COVID-19 group) in comparison with the placentas of non-infected pregnant women, matched for maternal age and comorbidities, besides gestational age of delivery (Control group).

Method: The patients in the COVID-19 and the Control group were matched for maternal age, gestational age, and comorbidities. The morphological analysis of placentas was performed using Amsterdam Placental Workshop Group Consensus Statement. The quantitative morphometric evaluation included perimeter diameter and number of tertiary villi, number of sprouts and knots, evaluation of deposition of villous fibrin, and deposition of intra-villous collagen I and III by Sirius Red. Additionally, Hofbauer cells (HC) were counted within villi by immunohistochemistry with CD68 marker.

Results: Compared to controls, symptomatic women in the COVID-19 group were more likely to have at least one comorbidity, to evolve to preterm labor and infant death, and to have positive SARS-CoV-2 RNA testing in their concepts. Compared to controls, placentas in the COVID-19 group were more likely to show features of maternal and fetal vascular malperfusion. In the COVID-19 group, placentas of symptomatic women were more likely to show CHI. No significant results were found after morphometric analysis.

Conclusion: Pregnant women with symptomatic SARS-CoV-2 infection, particularly with the severe course, are more likely to exhibit an adverse fetal outcome, with slightly more frequent histopathologic findings of maternal and fetal vascular malperfusion, and CHI. The morphometric changes found in the placentas of the COVID-19 group do not seem to be different from those observed in the Control group, as far as maternal age, gestational age, and comorbidities are paired. Only the deposition of villous fibrin could be more accentuated in the COVID-19 group (p = 0.08 borderline). The number of HC/villous evaluated with CD68 immunohistochemistry did not show a difference between both groups.
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http://dx.doi.org/10.3389/fimmu.2021.685919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187864PMC
July 2021

Lung Neutrophilic Recruitment and IL-8/IL-17A Tissue Expression in COVID-19.

Front Immunol 2021 30;12:656350. Epub 2021 Mar 30.

Laboratory of Experimental Pathology, Postgraduate Program of Health Sciences, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.

The new SARS-CoV-2 virus differs from the pandemic Influenza A virus H1N1 subtype (H1N1pmd09) how it induces a pro-inflammatory response in infected patients. This study aims to evaluate the involvement of SNPs and tissue expression of IL-17A and the neutrophils recruitment in lung samples from patients who died of severe forms of COVID-19 comparing to those who died by H1N1pdm09. Twenty lung samples from patients SARS-CoV-2 infected (COVID-19 group) and 10 lung samples from adults who died from a severe respiratory H1N1pdm09 infection (H1N1 group) were tested. The tissue expression of IL-8/IL-17A was identified by immunohistochemistry, and hematoxylin and eosin (H&E) stain slides were used for neutrophil scoring. DNA was extracted from paraffin blocks, and genotyping was done in real time-PCR for two target polymorphisms. Tissue expression increasing of IL-8/IL-17A and a higher number of neutrophils were identified in samples from the H1N1 group compared to the COVID-19 group. The distribution of genotype frequencies in the gene was not statistically significant between groups. However, the G allele (GG and GA) of rs3819025 was correlated with higher tissue expression of IL-17A in the COVID-19 group. SARS-CoV-2 virus evokes an exacerbated response of the host's immune system but differs from that observed in the H1N1pdm09 infection since the IL-8/IL-17A tissue expression, and lung neutrophilic recruitment may be decreased. In SNP rs3819025 (G/A), the G allele may be considered a risk allele in the patients who died for COVID-19.
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http://dx.doi.org/10.3389/fimmu.2021.656350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044579PMC
May 2021

Deregulated miRNA expression is associated with endothelial dysfunction in post-mortem lung biopsies of COVID-19 patients.

Am J Physiol Lung Cell Mol Physiol 2020 Dec 2. Epub 2020 Dec 2.

Research Institute Pelé Pequeno Príncipe.

MicroRNAs (miRNAs) are critical modulators of endothelial homeostasis, which highlights their involvement in vascular diseases, including the ones caused by virus infections. Our main objective was to identify miRNAs involved in the endothelial function and determine their expression in post-mortem lung biopsies of COVID-19 patients with severe respiratory injuries and thrombotic events. Based on functional enrichment analysis, miR-26a-5p, miR-29b-3p, and miR-34a-5p were identified as regulators of mRNA targets involved in endothelial, and inflammatory signaling pathways as well as in viral diseases. A miRNA/mRNA network, constructed based on protein-protein interactions of the miRNA targets and the inflammatory biomarkers characterized in the patients, revealed a close interconnection of these miRNAs with relevance to the endothelial activation/dysfunction. Reduced expression levels of selected miRNAs were observed in the lung biopsies of COVID-19 patients (n=9) compared to the Controls (n=10)(P<0.01-0.0001). MiR-26a-5p and miR-29b-3p presented the best power to discriminate these groups (AUC=0.8286, and AUC=0.8125, respectively). The correlation analysis of the miRNAs with inflammatory biomarkers in the COVID-19 patients was significant for miR-26a-5p [IL-6 (r=0.5414), and ICAM-1(r=0.5624)], and miR-29b-3p [IL-4 (r=0.8332), and IL-8 (r=0.2654)]. Altogether, these findings demonstrate the relevance and the non-random involvement of miR-26a-5p, miR-29b-3p, and miR-34a-5p in endothelial dysfunction and inflammatory response in patients with SARS-CoV-2 infection and the occurrence of severe lung injury and immunothrombosis.
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http://dx.doi.org/10.1152/ajplung.00457.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938642PMC
December 2020

The role of polymorphism of the IL6 gene in tooth replantation.

Aust Endod J 2021 Aug 7;47(2):314-319. Epub 2021 Jan 7.

School of Life Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.

The absence or presence of root resorption on the root surface of a replanted tooth indicates an immune-inflammatory reaction. Since interleukin-6 (IL-6) is considered an inflammatory marker in bone resorption, this study aimed to investigate the association between clinical variables and polymorphisms in IL6, with the outcome of replanted teeth at 1-year follow-up. Altogether, 127 avulsed teeth that were replanted and had their root canals treated were selected for this study. Periapical radiographs were taken after replantation and after 1 year. Real-time PCR was used to genotype IL6 polymorphisms. Chi-square and 'Z' tests were performed to verify the association between genetic variables and the prognosis of replanted teeth (P < 0.05). An association was observed between the rs2069843 polymorphism of IL6 and the outcome of replanted teeth (P < 0.05). The rs2069843 polymorphism of IL6 may influence the outcome of avulsed and replanted teeth in the first year post-trauma.
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http://dx.doi.org/10.1111/aej.12483DOI Listing
August 2021

Gene-environment interaction in molar-incisor hypomineralization.

PLoS One 2021 6;16(1):e0241898. Epub 2021 Jan 6.

Department of Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.

Molar incisor hypomineralization (MIH) is an enamel condition characterized by lesions ranging in color from white to brown which present rapid caries progression, and mainly affects permanent first molars and incisors. These enamel defects usually occur when there are disturbances during the mineralization or maturation stage of amelogenesis. Both genetic and environmental factors have been suggested to play roles in MIH's development, but no conclusive risk factors have shown the source of the disease. During head and neck development, the interferon regulatory factor 6 (IRF6) gene is involved in the structure formation of the oral and maxillofacial regions, and the transforming growth factor alpha (TGFA) is an essential cell regulator, acting during proliferation, differentiation, migration and apoptosis. In this present study, it was hypothesized that these genes interact and contribute to predisposition of MIH. Environmental factors affecting children that were 3 years of age or older were also hypothesized to play a role in the disease etiology. Those factors included respiratory issues, malnutrition, food intolerance, infection of any sort and medication intake. A total of 1,065 salivary samples from four different cohorts were obtained, and DNA was extracted from each sample and genotyped for nine different single nucleotide polymorphisms. Association tests and logistic regression implemented in PLINK were used for analyses. A potential interaction between TGFA rs930655 with all markers tested in the cohort from Turkey was identified. These interactions were not identified in the remaining cohorts. Associations (p<0.05) between the use of medication after three years of age and MIH were also found, suggesting that conditions acquired at the age children start to socialize might contribute to the development of MIH.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241898PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787379PMC
April 2021

The role of the lectin pathway of the complement system in SARS-CoV-2 lung injury.

Transl Res 2021 05 20;231:55-63. Epub 2020 Nov 20.

Laboratory of Experimental Pathology, School of Medicine, Pontifícia Universidade Católica do Paraná - PUCPR, Curitiba, PR, Brazil.

Although some evidence showed the activation of complement systems in COVID-19 patients, proinflammatory status and lectin pathway remain unclear. Thus, the present study aimed to demonstrate the role of MBL and ficolin-3 in the complement system activation and compared to pandemic Influenza A virus H1N1 subtype infection (H1N1pdm09) and control patients. A total of 27 lungs formalin-fixed paraffin-embedded samples (10 from H1N1 group, 6 from the COVID-19 group, and 11 from the control group) were analyzed by immunohistochemistry using anti-IL-6, TNF-alfa, CD163, MBL e FCN3 antibodies. Genotyping of target polymorphisms in the MBL2 gene was performed by real-time PCR. Proinflammatory cytokines such as IL-6 and TNF-alpha presented higher tissue expression in the COVID-19 group compared to H1N1 and control groups. The same results were observed for ICAM-1 tissue expression. Increased expression of the FCN3 was observed in the COVID-19 group and H1N1 group compared to the control group. The MBL tissue expression was higher in the COVID-19 group compared to H1N1 and control groups. The genotypes AA for rs180040 (G/A), GG for rs1800451 (G/A) and CC for rs5030737 (T/C) showed a higher prevalence in the COVID-19 group. The intense activation of the lectin pathway, with particular emphasis on the MBL pathway, together with endothelial dysfunction and a massive proinflammatory cytokines production, possibly lead to a worse outcome in patients infected with SARS-Cov-2. Moreover, 3 SNPs of our study presented genotypes that might be correlated with high MBL tissue expression in the COVID-19 pulmonary samples.
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http://dx.doi.org/10.1016/j.trsl.2020.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677075PMC
May 2021

From adrenarche to aging of adrenal zona reticularis: precocious female adrenopause onset.

Endocr Connect 2020 Dec;9(12):1212-1220

Pelé Pequeno Príncipe Research Institute, Água Verde, Curitiba, Parana, Brazil.

Objective: Adaptive changes in DHEA and sulfated-DHEA (DHEAS) production from adrenal zona reticularis (ZR) have been observed in normal and pathological conditions. Here we used three different cohorts to assess timing differences in DHEAS blood level changes and characterize the relationship between early blood DHEAS reduction and cell number changes in women ZR.

Materials And Methods: DHEAS plasma samples (n = 463) were analyzed in 166 healthy prepubertal girls before pubarche (<9 years) and 324 serum samples from 268 adult females (31.9-83.8 years) without conditions affecting steroidogenesis. Guided by DHEAS blood levels reduction rate, we selected the age range for ZR cell counting using DHEA/DHEAS and phosphatase and tensin homolog (PTEN), tumor suppressor and cell stress marker, immunostaining, and hematoxylin stained nuclei of 14 post-mortem adrenal glands.

Results: We confirmed that overweight girls exhibited higher and earlier DHEAS levels and no difference was found compared with the average European and South American girls with a similar body mass index (BMI). Adrenopause onset threshold (AOT) defined as DHEAS blood levels <2040 nmol/L was identified in >35% of the females >40 years old and associated with significantly reduced ZR cell number (based on PTEN and hematoxylin signals). ZR cell loss may in part account for lower DHEA/DHEAS expression, but most cells remain alive with lower DHEA/DHEAS biosynthesis.

Conclusion: The timely relation between significant reduction of blood DHEAS levels and decreased ZR cell number at the beginning of the 40s suggests that adrenopause is an additional burden for a significant number of middle-aged women, and may become an emergent problem associated with further sex steroids reduction during the menopausal transition.
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http://dx.doi.org/10.1530/EC-20-0416DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774755PMC
December 2020

Endothelial Dysfunction and Thrombosis in Patients With COVID-19-Brief Report.

Arterioscler Thromb Vasc Biol 2020 10 7;40(10):2404-2407. Epub 2020 Aug 7.

Laboratory of Experimental Pathology (L.d.N.), School of Medicine, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Brazil.

Objective: Alveolar-capillary endothelial cells can be activated by severe acute respiratory syndrome coronavirus 2 infection leading to cytokine release. This could trigger endothelial dysfunction, pyroptosis, and thrombosis, which are the vascular changes, commonly referred to as coronavirus disease 2019 (COVID-19) endotheliopathy. Thus, this study aimed to identify tissue biomarkers associated with endothelial activation/dysfunction and the pyroptosis pathway in the lung samples of patients with COVID-19 and to compare them to pandemic influenza A virus H1N1 subtype 2009 and control cases. Approach and Results: Postmortem lung samples (COVID-19 group =6 cases; H1N1 group =10 cases, and control group =11 cases) were analyzed using immunohistochemistry and the following monoclonal primary antibodies: anti-IL (interleukin)-6, anti-TNF (tumor necrosis factor)-α, anti-ICAM-1 (intercellular adhesion molecule 1), and anticaspase-1. From the result, IL-6, TNF-α, ICAM-1, and caspase-1 showed higher tissue expression in the COVID-19 group than in the H1N1 and control groups.

Conclusions: Our results demonstrated endothelial dysfunction and suggested the participation of the pyroptosis pathway in the pulmonary samples. These conditions might lead to systemic thrombotic events that could impair the clinical staff's efforts to avoid fatal outcomes. One of the health professionals' goals should be to identify the high risk of thrombosis patients early to block endotheliopathy and its consequences.
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http://dx.doi.org/10.1161/ATVBAHA.120.314860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7505138PMC
October 2020

The role of IL-17A/IL-17RA and lung injuries in children with lethal non-pandemic acute viral pneumonia.

Immunobiology 2020 07 6;225(4):151981. Epub 2020 Jul 6.

Laboratory of Experimental Pathology, School of Medicine, Pontifical Catholic University of Parana - PUCPR, R. Imaculada Conceição, 1155 - Prado Velho, Curitiba, PR, Brazil; Department of Medical Pathology, Federal University of Parana - UFPR, R. Padre Camargo, 280 - Alto da Glória, Curitiba, PR, Brazil. Electronic address:

This study aimed to evaluate IL-17A (interleukin 17A) and IL-17RA (IL-17A receptor) in a pediatric population that died with non-pandemic acute viral pneumonia compared to the non-viral pneumonia group. Necropsy lung samples (n = 193) from children that died after severe acute infection pneumonia were selected and processed for viral antigen detection by immunohistochemistry. After this, they were separated into two groups: virus-positive (n = 68) and virus-negative lung samples (n = 125). Immunohistochemistry was performed to assess the presence of IL-17A and IL-17RA in the lung tissue. The virus-positive group showed stronger immunolabeling for IL-17A and IL-17RA (p = 0.020 and p < 0.001, respectively). The result of this study may suggest that IL-17A and IL-17RA plays an essential role in the maintenance of viral infection and lung injuries. These aspects may increase the severity of the inflammatory response leading to lethal lung injuries in these patients. Children with community-acquired non-pandemic pneumonia that requiring hospitalization could benefit from using IL-17RA/IL-17A monoclonal antibodies to block their injurious effects.
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http://dx.doi.org/10.1016/j.imbio.2020.151981DOI Listing
July 2020

Analysis of interleukins 6, 8, 10 and 17 in the lungs of premature neonates with bronchopulmonary dysplasia.

Cytokine 2020 07 11;131:155118. Epub 2020 May 11.

Laboratory of Experimental Pathology, School of Medicine, Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil. Electronic address:

Bronchopulmonary dysplasia (BPD) is an abnormality that occurs in premature neonate lung development. The pathophysiology is uncertain, but the inflammatory response to lung injury may be the responsible pathway. The objective of this study is to evaluate the role of interleukins 6, 8, 10, and 17 through the anatomopathological and immunohistochemical study of the lungs of premature neonates with BPD. Thirty-two cases of neonatal autopsies from the Pathology Department of the Clinics Hospital of the Universidade Federal do Paraná, who presented between 1991 and 2005 were selected. The sample included neonates less than 34 weeks of gestational age who underwent oxygen therapy and had pulmonary formalin-fixed paraffin-embedded (FFPE) samples. Pulmonary specimens were later classified into three groups according to histopathological and morphometric changes (classic BPD, new BPD, and without BPD) and subjected to immunohistochemical analysis. The antibodies selected for the study were anti-IL-6, anti-IL-8, anti-IL-10, and anti-IL-17A monoclonal antibodies. IL-6, IL-8, and IL-10 showed no significant differences in tissue expression among the groups. IL-17A had higher tissue immunoreactivity in the group without BPD compared with the classic BPD group (1686 vs. 866 μm, p = 0.029). This study showed that the involvement of interleukins 6, 8, and 10 might not be significantly different between the two types of BPD. We speculated that IL-17A could be a protective factor in this disease.
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http://dx.doi.org/10.1016/j.cyto.2020.155118DOI Listing
July 2020

Penetrance of the R337H Mutation and Pediatric Adrenocortical Carcinoma Incidence Associated with Environmental Influences in a 12-Year Observational Cohort in Southern Brazil.

Cancers (Basel) 2019 Nov 16;11(11). Epub 2019 Nov 16.

Oncologia Pediátrica, Hospital Erasto Gaertner, R. Dr. Ovande do Amaral, 201, Jardim das Américas, 81520-060 Curitiba, PR, Brazil.

The R337H mutation is associated with increased incidence of pediatric adrenocortical tumor (ACT). The different environmental conditions where R337H carriers live have not been systematically analyzed. Here, the R337H frequencies, ACT incidences, and R337H penetrance for ACT were calculated using the 2006 cohort with 4165 R337H carriers living in Paraná state (PR) subregions. The effectiveness of a second surveillance for R337H probands selected from 42,438 tested newborns in PR (2016 cohort) was tested to detect early stage I tumor among educated families without periodical exams. Estimation of R337H frequencies and ACT incidence in Santa Catarina state (SC) used data from 50,115 tested newborns without surveillance, ACT cases from a SC hospital, and a public cancer registry. R337H carrier frequencies in the population were 0.245% (SC) and 0.306% (PR), and 87% and 95% in ACTs, respectively. The ACT incidence was calculated as ~6.4/million children younger than 10 years per year in PR (95% CI: 5.28; 7.65) and 4.15/million in SC (CI 95%: 2.95; 5.67). The ACT penetrance in PR for probands followed from birth to 12 years was 3.9%. R337H carriers living in an agricultural subregion (C1) had a lower risk of developing pediatric ACT than those living in industrial and large urban subregion (relative risk = 2.4). One small ACT (21g) without recurrence (1/112) was detected by the parents in the 2016 cohort. ACT incidence follows R337H frequency in each population, but remarkably environmental factors modify these rates.
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http://dx.doi.org/10.3390/cancers11111804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6896071PMC
November 2019

Anxiety and genetic polymorphisms in catechol-O-methyltransferase (COMT) and serotonin transportation gene (5HTT) are associated with benign migratory glossitis.

Oral Surg Oral Med Oral Pathol Oral Radiol 2019 Mar 10;127(3):218-224. Epub 2018 Nov 10.

Professor at School of Life Sciences, Pontifical Catholic University of Paraná, Curitiba, Brazil.

Objective: The aim of this case-control study was to investigate whether benign migratory glossitis (BMG) is associated with catechol-O-methyltransferase (COMT) and serotonin transportation gene (5HTT) polymorphisms and anxiety.

Study Design: The study comprised 43 patients with BMG and 114 patients without a history of BMG. We used the Hamilton Anxiety (HAM-A) rating scale to assess each individual's anxiety. We collected DNA from buccal cells and analyzed polymorphisms of COMT and 5HTT. We conducted statistical evaluations by using SPSS software (SPSS Inc., Chicago, IL) and STATA (StataCorp, College Station, TX). Alpha value was set at 0.05.

Results: Overall anxiety level was significantly higher in the case group than in the control group (P < .001). In adjusted multiple logistic regression, the COMT markers were not associated with BMG. Individuals with the CC genotype, in rs3813034 of 5HTT, presented an odds ratio (OR) of 2.85 (95% confidence interval [CI] 1.03-7.82; P = .042). Individuals with the TT genotype, in the rs1042173 of 5HTT, presented an OR of 3.77 (95% CI 1.32-10.74; P = .013). For each incremental increase in the anxiety score, there was an 8% increase in the probability of BMG (OR=1.08; 95% CI 1.03-1.14; P = .007).

Conclusions: Anxiety increases the risk of BMG. Moreover, the occurrence of BMG was associated with polymorphisms in the 5HTT gene.
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http://dx.doi.org/10.1016/j.oooo.2018.10.011DOI Listing
March 2019

Clinical aspects and polymorphisms in the LTA, TNFA, LTB genes and association with dental implant loss.

Clin Implant Dent Relat Res 2018 Dec 18;20(6):954-961. Epub 2018 Oct 18.

Postgraduate Program in Dentistry and Health Sciences, Pontifícia Universidade Católica do Paraná (PUCPR), Curitiba, Paraná, Brazil.

Background: This study shows the relationship between host factors and environmental factors in the influence of susceptibility to loss of dental implants.

Purpose: The aim of this study was to investigate the association of clinical aspects and tag SNPs of the genes LTA, TNFA, and LTB with dental implant loss.

Materials And Methods: The subjects consisted of 244 patients, divided into two groups: control group (C)-163 individuals who did not lose any implants, being in function for at least 6 months; and study group (S)-81 individuals who had lost at least one implant. DNA was collected from saliva, and the genotypes were determined by real time PCR. Univariate and multivariate analysis were employed p < .05.

Results: After multivariate analysis, dental implant loss remained associated with the presence of teeth (p = .011), a larger amount of placed implants (p = .001), and allelle C of rs2009658 of the LTA gene (p = .006). For the other tag SNPs of these studied genes, there was no association between the groups C and S with dental implants loss.

Conclusion: Presence of teeth, number of placed implants and allele C of rs2009658 of LTA gene were associated with implant loss.
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http://dx.doi.org/10.1111/cid.12677DOI Listing
December 2018

Vitamin D Receptor Gene Polymorphisms and Environment Influencing the Impact on Survival in Hemodialysis Patients.

Iran J Kidney Dis 2018 07;12(4):223-231

School of Life Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.

Introduction: The vitamin D-receptor axis is involved in multiple physiological functions and altered states such as hypertension, mineral metabolism disorders, and inflammation. These disturbances are major risk factors for progression to end-stage kidney disease and cardiovascular disease. In addition, changes in internal systemic environment could be influencing the impact of survival in patients with kidney disease. This study aimed to evaluate the impact of vitamin D receptor (VDR) polymorphisms on hemodialysis patients' survival.

Material And Methods: A total of 122 hemodialysis patients and 120 healthy controls were compared for VDR gene polymorphism. Markers for full coverage in the VDR gene were selected and genotyped. The hemodialysis patients were followed until death event, which was considered the primary endpoint for the survival analysis.

Results: Two tag SNPs (rs10875695 and rs11168293) showed significant differences between the hemodialysis and healthy patients. In survival analysis, the CC genotype for rs2248098, compared to the TT genotype, was associated with a worse mortality rate. After adjustments for age, sex, diabetes mellitus, and cardiovascular disease, the genotype CC (rs2248098) was associated with a higher risk of mortality in a multivariable analysis.

Conclusions: Polymorphisms specific to patients with kidney disease could be influencing different conditions associated with mortality. Thus, these genetic markers, rs2248098 for example, would act in a specific time in the history of kidney disease and would bring different results of patient survival outcomes.
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July 2018

Types of External Root Resorption of Replanted Teeth: Analysis of the Clinical Aspects and of Interleukin-4 Gene Polymorphisms Involvement.

J Endod 2017 Nov 14;43(11):1792-1796. Epub 2017 Aug 14.

School of Life Sciences, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil.

Introduction: The absence or presence of root resorption on the surface of a replanted tooth indicates an immune-inflammatory reaction. Recent research even suggests the participation of host predominant immunologic profile on types of resorptions detected on the root surface. Because interleukin 4 (IL-4) is an important anti-inflammatory cytokine, this study aimed to investigate the association of clinical variables and polymorphisms in IL4 with types of resorption of replanted teeth after 1 year of follow-up.

Methods: One hundred twenty-seven avulsed teeth that were replanted were selected. Periapical radiographs were taken after replantation and for 1 year to detect the types of root resorption. Real-time polymerase chain reaction was used to genotype IL4 polymorphisms. The χ and Z tests were performed to verify the association of clinical and genetic variables with the outcomes of replanted teeth (P < .05).

Results: An association was observed of extra-alveolar time, storage medium, and development of the root (P < .05), but not of IL4 polymorphisms, with the outcomes of replanted teeth (P > .05).

Conclusions: Extraoral time, storage medium, and development of the root, but not IL4 polymorphisms, may influence the types of resorption of avulsed and replanted teeth in the first year after trauma.
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http://dx.doi.org/10.1016/j.joen.2017.06.027DOI Listing
November 2017

Host and clinical aspects in patients with benign migratory glossitis.

Arch Oral Biol 2017 Jan 26;73:259-268. Epub 2016 Oct 26.

Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brazil.

Objective: Investigate the association of clinical, cytological and genetic characteristics with benign migratory glossitis (BMG).

Study Design: Sample consisted of 175 patients, 44 with BMG and 131 control patients. Clinical examination and DMFT index were assessed. Cytological evaluation determined cell morphology and morphometry. Genetic evaluation was performed by analysing IL6 polymorphisms by real-time PCR. Univariate and multivariate analyses were performed (p<0.05).

Results: There was a higher level of anxiety, DMFT score and a prevalence of fissured tongue in BMG group. A high mean nuclear/cytoplasmic area ratio was observed in patients with BMG. There was predominance of Papanicolaou class II I BMG group. IL6 allele G rs2069843 polymorphism was associated with BMG in the dominant model. In multivariate analysis, DMFT and anxiety scale remained associated with BMG.
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http://dx.doi.org/10.1016/j.archoralbio.2016.10.027DOI Listing
January 2017

Comparative Analysis of Psychological, Hormonal, and Genetic Factors Between Burning Mouth Syndrome and Secondary Oral Burning.

Pain Med 2016 09 5;17(9):1602-11. Epub 2016 Feb 5.

*Department of Oral Pathology, Federal University of Rio Grande Do Norte (UFRN), Natal, RN, Brazil.

Objective: The objective of this study was to evaluate the association between psychological, hormonal, and genetic factors with the development of burning mouth syndrome (BMS) and secondary oral burning (SOB) in order to provide a better characterization and classification of these conditions.

Design: Cross sectional study.

Setting: Patients with complaints of mouth burning registered at the Oral Diagnostic Service of the Federal University of Rio Grande do Norte between 2000 and 2013.

Subjects: The sample consisted of 163 subjects divided into a group of patients with BMS (n = 64) and a group of subjects with SOB (n = 99).

Methods: The following variables were analyzed: passive and stimulated saliva flow, stress levels and phase, depression, anxiety, serum cortisol and dehydroepiandrosterone (DHEA) levels, and the presence of polymorphisms in the interleukin 6 (IL-6) gene.

Results: The results showed significant differences in the presence of xerostomia (p = 0.01), hyposalivation at rest (p < 0.001) and symptoms of depression (p = 0.033) between the two groups, which were more prevalent in the BMS group. DHEA levels were lower in the BMS group (p = 0.003) and were sensitive and specific for the diagnosis of this condition. Genetic analysis revealed no significant association between the polymorphisms analyzed and the development of BMS.

Conclusion: These results suggest a possible role of depression, as well as of reduced DHEA levels, as associated factors for development of BMS.
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http://dx.doi.org/10.1093/pm/pnv087DOI Listing
September 2016

Immunohistochemical expression of sulfhydryl oxidase (QSOX1) in pediatric medulloblastomas.

Diagn Pathol 2015 Apr 24;10:37. Epub 2015 Apr 24.

School of Medicine, Pontifical Catholic University of Paraná, Curitiba, Brazil.

Background: Medulloblastoma is a malignant, invasive embryonal tumor of the cerebellum and accounts for 20% of intracranial tumors in children. QSOX1, whose functions include formation of disulphide bridges, which are needed for correct protein folding and stability, formation of the extracellular matrix, regulation of the redox status and cell cycle control, appears to be involved in apoptosis in pathological states such as cancer. Thus, the aim of this study was to investigate the immunohistochemical expression of QSOX1 in medulloblastomas and nonneoplastic cerebellum.

Methods: Histology blocks of pediatric medulloblastomas were separated and two representative areas of the tumors and non-neoplastic cerebellum samples were used to construct tissue microarrays (TMAs) that were stained with an anti-QSOX1 antibody, and the slides were read using image analysis software.

Results: QSOX1 immunoexpression was observed in the non-neoplastic cerebellum samples and the medulloblastoma samples. There was no statistically significant relationship between QSOX1 immunopositivity in the medulloblastoma samples and the clinical and pathological variables.

Conclusions: Although QSOX1 did not prove useful for stratifying patients into risk groups, tumor cells and the fibrillar extracellular matrix were positive for this marker, indicating that this enzyme may be involved in the pathogenesis of medulloblastoma.

Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1822040654139436.
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http://dx.doi.org/10.1186/s13000-015-0268-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4414442PMC
April 2015

Association analysis of clinical aspects and vitamin D receptor gene polymorphism with external apical root resorption in orthodontic patients.

Am J Orthod Dentofacial Orthop 2012 Sep;142(3):339-47

School of Health and Biosciences, Pontifícia Universidade Católica do Paraná, Curitiba-PR, Brazil.

Introduction: Vitamin D is responsible for the regulation of certain genes at the transcription level, via interaction with the vitamin D receptor, and influences host immune responses and aspects of bone development, growth, and homeostasis. Our aim was to investigate the association of TaqI vitamin D receptor gene polymorphism with external apical root resorption during orthodontic treatment.

Methods: Our subjects were 377 patients with Class II Division 1 malocclusion, divided into 3 groups: (1) 160 with external apical root resorption ≤1.43 mm, (2) 179 with external apical root resorption >1.43 mm), and (3) 38 untreated subjects. External apical root resorption of the maxillary incisors was evaluated on periapical radiographs taken before and after 6 months of treatment. After DNA collection and purification, vitamin D receptor TaqI polymorphism analysis was performed by polymerase chain reaction-restriction fragment length polymorphism. Univariate and multivariate analyses were performed to verify the association of clinical and genetic variables with external apical root resorption (P <0.05).

Results: There was a higher proportion of external apical root resorption in orthodontically treated patients compared with the untreated subjects. In patients orthodontically treated, age higher than 14 years old, initial size of the maxillary incisor root superior to 30 mm, and premolar extraction were associated with increased external apical root resorption. Genotypes containing the C allele were weakly associated with protection against external apical root resorption (CC + CT × TT [odds ratio, 0.29; 95% confidence interval, 0.07-1.23; P = 0.091]) when treated orthodontic patients were compared to untreated individuals.

Conclusions: Clinical factors and vitamin D receptor TaqI polymorphism were associated with external apical root resorption in orthodontic patients.
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http://dx.doi.org/10.1016/j.ajodo.2012.04.013DOI Listing
September 2012

Analysis of IL1 gene polymorphisms and transcript levels in periodontal and chronic kidney disease.

Cytokine 2012 Oct 13;60(1):76-82. Epub 2012 Jul 13.

Health and Biosciences School, Pontifícia Universidade Católica do Paraná (PUCPR), Imaculada Conceição Street 1155, CEP 80215-901, Curitiba, PR, Brazil.

Unlabelled: Chronic kidney disease (CKD) and periodontitis (PD) are complex inflammatory disturbances, influenced by genetic factors. Interleukin (IL)-1 genes code for inflammatory mediators involved in the physiopathogenesis of both diseases. Functional polymorphisms in IL1 genes modulate cytokine levels and have been associated with susceptibility to immune-inflammatory conditions.

Objectives: The aim of this study was investigate the association of functional IL1 gene polymorphisms and transcript levels with susceptibility to CKD and PD.

Design: The sample consisted of 246 individuals, mean age 44.8 years, divided into: group 1 (64 patients without CKD and without PD), group 2 (58 without CKD and with PD), group 3 (52 with CKD and without PD) and group 4 (72 with CKD and with PD). DNA was obtained from cells of oral mucosa and polymorphisms IL1AC-889T, IL1BC-511T, IL1BC+3954T and IL1RN (intron 2) were analyzed by PCR-RFLP. Transcript levels from gingival tissues were analyzed by real-time PCR.

Results: IL1RN(*)1 allele was associated with almost 4-fold increased risk for CKD (OR 3.92 95% CI=1.6-9.4, p=0.002). IL1RN(*)2 allele was associated with 3-fold increased risk for PD in CKD patients (OR 3.08 95% CI=1.2-7.9, p=0.019). Allele T for polymorphism IL1B+3954 was associated with CKD in PD patients (OR 2.28 95% CI=1.1-4.7, p=0.019). Significantly increased levels of transcripts of IL1A, IL1B and IL1RN genes were found in PD patients.

Conclusions: It was observed an evidence for association of IL1B and IL1RN alleles with susceptibility to CKD and PD. Higher levels of IL1 gene transcripts were found in PD patients.
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http://dx.doi.org/10.1016/j.cyto.2012.06.006DOI Listing
October 2012

Association between vitamin D receptor gene polymorphisms and susceptibility to chronic kidney disease and periodontitis.

Blood Purif 2007 3;25(5-6):411-9. Epub 2007 Oct 3.

Pontifícia Universidade Católica do Paraná, Curitiba, Paraná, Brazil.

Background/aims: Chronic kidney disease (CKD) and periodontitis (PD) are serious public-health concerns. Vitamin D is a fat-soluble steroid hormone that interacts with its nuclear receptor (VDR) to regulate a variety of biological processes, such as bone metabolism, immune response modulation and transcription of several genes involved in CKD and PD disease mechanisms. The aim of this work was to investigate the association between polymorphisms in the VDR gene and end-stage renal disease (ESRD) and PD.

Methods: 222 subjects with and without ESRD (in hemodialysis) were divided into groups with and without PD. Polymorphisms TaqI and BsmI in the VDR gene were analyzed by PCR restriction fragment length polymorphism. The significance of differences in allele, genotype and haplotype frequencies between groups was assessed by the chi2 test (p value <0.05) and odds ratio (OR).

Results: Allele G was associated with protection against ESRD: groups without versus with ESRD (GG) x (GA+AA): OR = 2.5, 95% CI = 1.4-4.6, p = 0.00; (G x A): OR = 1.5, 95% CI = 1.0-2.3, p = 0.02; (TG + CG) x (TA + CA): OR = 1.5, 95% CI = 1.0-2.3, p = 0.02. No association was observed between the study polymorphisms and susceptibility to or protection against PD.

Conclusion: Allele G of the VDR BsmI polymorphism was associated with protection against ESRD.
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http://dx.doi.org/10.1159/000109235DOI Listing
March 2008
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