Publications by authors named "Sanívia Aparecida de Lima Pereira"

26 Publications

  • Page 1 of 1

Overexpression of HIF-1α and Morphological Alterations in the Tongue of Rats Exposed To Secondhand Smoke.

Braz Dent J 2020 Jun 13;31(3):281-289. Epub 2020 Jul 13.

Cefores, Universidade Federal do Triângulo Mineiro, Uberaba, MG, Brazil.

Smoking is a risk factor for serious health problems and is associated with several changes in the tissues of the oral cavity. The aim of this study was to evaluate the collagen percentage, mast cells density, intensity of immunolabeled cells by anti-HIF-1α in the musculature lingual of rats exposed to secondhand smoke. Twenty-seven female Wistar albino rats were divided into three groups: rats not exposed to tobacco smoke inhalation (Control group) (n=7); rats exposed to smoke inhalation for 30 days (TAB 30) (n=10); and rats exposed to smoke inhalation for 45 days (TAB 45) (n=10). Subsequently, the animals were submitted to euthanasia and removal of the tongue for histological and immunohistochemistry processing and analysis. In the groups TAB 30 and TAB 45 there were a lower percentage of collagen, a higher density of mast cells and a greater intensity of anti-HIF-1α immunolabeled cells compared to Control group. There was also a positive and significant correlation between the percentage of collagen and mast cell density. There was not significative difference between TAB 30 e TAB 45 in any of the parameters evaluated. Therefore, the exposure of rats to secondhand smoke for 45 days causes decrease in perimysial collagen fibers, increase in the number of mast cells and increase in the immunolabeling for HIF-1α in lingual muscle cells. The present study was the first to evaluate the percentage of collagen, mast cell density and immunostaining for HIF-1α in rat tongues exposed to tobacco smoke.
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http://dx.doi.org/10.1590/0103-6440202002898DOI Listing
June 2020

Although with intact mucosa at colonoscopy, chagasic megacolons have an overexpression of Gal-3.

Einstein (Sao Paulo) 2020 6;18:eAO5105. Epub 2020 Mar 6.

Universidade de Uberaba , Uberaba , MG , Brazil .

Objective: To evaluate the density of anti-galectin-3-immunostained cells, collagen percentage, mast cell density and presence of pathological processes in intestinal muscle biopsies of patients.

Methods: Thirty-five patients who underwent intestinal biopsy were selected from 1997 to 2015. Patients were divided into three groups: chagasic patients with mucosal lesion (n=13), chagasic patients with intact mucosa (n=12) and non-chagasic patients with no mucosal lesion (n=10). Histological processing of the biopsied fragments and immunohistochemistry for galectin-3 were performed. Additional sections were stained with hematoxylin and eosin to evaluate the general pathological processes, picrosirius for evaluation of collagen and toluidine blue to evaluate the mast cell density.

Results: Patients of mucosal lesion group had a significantly higher frequency of ganglionitis and myositis when compared to the chagasic patients with intact mucosa and non-chagasic group. The density of anti-galectin-3-immunostained cells was significantly higher in the chagasic patients with intact mucosa group when compared to the non-chagasic group. The group of chagasic patients with intact mucosa presented a higher percentage of collagen in relation to the patients with mucosal lesion and to the non-chagasic group, with a significant difference. There was no significant difference in mast cell density among the three groups.

Conclusion: The higher density of anti-galectin-3-immunostained cells in patients in the chagasic patients with intact mucosa group suggested the need for greater attention in clinical evaluation of these patients, since this protein is associated with neoplastic transformation and progression.
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http://dx.doi.org/10.31744/einstein_journal/2020AO5105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7046340PMC
April 2020

Lingual salivary gland hypertrophy and decreased acinar density in chagasic patients without megaesophagus.

Rev Inst Med Trop Sao Paulo 2019 20;61:e67. Epub 2019 Dec 20.

Universidade Federal do Triângulo Mineiro, Programa de Pós-Graduação em Ciências da Saúde, Uberaba, Minas Gerais, Brazil.

Although the salivary glands present several functions, there are few studies evaluating these glands in Chagas disease (CD). This study aimed to compare the percentage of collagen, the presence of inflammation, the density of chimase and tryptase mast cells, the area and density of lingual salivary gland acini in autopsied individuals with and without (CD). We analyzed 400 autopsy reports performed in a tertiary public hospital from 1999 to 2015 and selected all the cases in which tongue fragments were collected (27 cases), 12 with chronic CD without megaesophagus (CH) and 15 without CD (non-chagasic - NC). The histological sections of the tongue were stained by Picrosirius red for collagen evaluation and Hematoxylin-eosin for morphometric evaluation of salivary gland acini and inflammation. Anti-chimase and anti-tryptase antibodies were used for the immunohistochemical evaluation of mast cells. The chagasic patients presented higher volume and lower density of salivary glands acini. There was no difference in the collagen percentage, inflammation and density of mast cell chymase and tryptase between the groups. Although we did not observe a significant difference between the groups regarding the collagen percentage, inflammatory process and mast cell density, our results suggest that even without megaesophagus, chagasic patients present hypertrophy of the lingual salivary glands and lower acinar density probably due to mechanisms independent of the esophagus-glandular stimulus.
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http://dx.doi.org/10.1590/S1678-9946201961067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6907416PMC
February 2020

Arginase-1 and Treg Profile Appear to Modulate Inflammatory Process in Patients with Chronic Gastritis: May Be the Alarm Cytokine in -Positive Patients.

Mediators Inflamm 2019 20;2019:2536781. Epub 2019 Jun 20.

Laboratory of Biopathology and Molecular Biology, University of Uberaba (UNIUBE), Uberaba, MG, Brazil.

() is a highly prevalent bacterium in our environment, directly involved in various upper digestive tract diseases, such as gastritis, peptic ulcer, and gastric cancer. Several molecules activating the immune system have been reported to be involved in containing infection. This study is aimed at analyzing the mRNA expression of the cytokines , , , , , , , and ; transcription factors , , and ; enzymes , , and ; and neuropeptides and and their respective receptors and in the stomach lining of patients with severe digestive disorders. One hundred and twenty six patients have been evaluated, presenting with symptoms in the upper digestive tract, with the clinical indication for an Upper Digestive Endoscopy exam. Two fragments of the mucosa of the gastric body and antrum have been collected for anatomopathological examination and to analyze the expression of enzymes, cytokines, and transcription factors using qPCR. Expression of the gene was seen as significantly higher in the group of patients with chronic inactive gastritis than in the control group. Expression of the gene and its transcription factor was significantly higher in the group of chronic inactive gastritis patients than in the control. Expression of , , , and and the transcription factors, and , in the presence or absence of showed no significant difference. However, the expression of was significantly lower in -positive patients than that in -negative patients. ARG1 and Treg profile appeared to be modulating the inflammatory process, protecting patients from the tissue lesions with chronic inactive gastritis. Furthermore, we suggest that may be a crucial mediator of the immune response against an infection, after gastric mucosal damage.
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http://dx.doi.org/10.1155/2019/2536781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6610761PMC
February 2020

Levels of Pro and Anti-inflammatory Citokynes and C-Reactive Protein in Patients with Chronic Periodontitis Submitted to Nonsurgical Periodontal Treatment

Asian Pac J Cancer Prev 2018 Jul 27;19(7):1927-1933. Epub 2018 Jul 27.

University of Uberaba, Uberaba, MG, Brazil.Email:

Aim: to compare the levels of IFN-γ, TGF-β and C-reactive protein (CRP) in healthy patients (HP) and chronic periodontitis patients (CP) before and seven days after the last session of Non-Surgical Periodontal Treatment (NSPT). Materials and Methods: 40 subjects were divided into two groups: healthy (n= 20), and with chronic periodontitis (n = 20). Serum and gingival crevicular fluid (GCF) were collected from each patient and quantified for IFN-γ, TGF-β and CRP using the enzyme-linked immunosorbent assay (ELISA). Results: IFN-γ was found to be higher in the GCF of the CP group before NSPT in relation to the HP group (p<0.05), and it had significant higher levels after seven days of NSPT (p<0.05). The levels of TGF-β in the GCF of CP patients before NSPT were significantly higher when compared to HP (p<0.05), but they decreased after seven days of NSPT (p>0.05). Serum CRP levels did not show statistical difference between CP and HP before or after NSPT. Conclusion: Therefore, our results demonstrated for the first time that NSPT causes early exacerbation of the immune response at the local level represented by increased levels of IFN-γ and decreased levels of TGF-β in the gingival crevicular fluid after seven days of treatment.
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http://dx.doi.org/10.22034/APJCP.2018.19.7.1927DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165634PMC
July 2018

Modulation of Galectin-3 and Galectin 9 in gastric mucosa of patients with chronic gastritis and positive Helicobacter pylori infection.

Pathol Res Pract 2017 Oct 25;213(10):1276-1281. Epub 2017 Aug 25.

Laboratory of Biopathology and Molecular Biology, University of Uberaba (UNIUBE), Uberaba, MG, Brazil; Federal University of Triângulo Mineiro (UFTM), Uberaba, MG, CEFORES, Brazil. Electronic address:

Objectives: Galectins are mediators that play an important role in the inflammatory response and in this study we analyzed the expression of Galectins (Gal) -1, -3 and -9 in biopsies of the gastric antrum of patients with upper gastrointestinal symptoms.

Methodology: 44 patients with upper digestive tract symptoms were evaluated, and underwent Upper Digestive Endoscopy examination. Sections of the gastric antrum were fixed in buffered formaldehyde at 4% in order to perform the anatomopathological examination and immunohistochemical analysis for Galectins-1, -3 and -9 expression. Fresh sections of gastric antrum were used for DNA extraction and evaluation of Helicobacter pylori (H. pylori). P values<0.05 were considered statistically significant.

Results: Gal-1 was significantly more expressed on stroma than epithelium (p<0.0001), whereas Gal-3 and Gal-9 were more expressed on epithelium (p<0.0001). Gal-3 was found to be significantly higher in the stroma of patients with H. pylori infection, mainly on Cag-A positive H. pylori (p<0.0001). Gal-9 was down modulated in stroma of patients with chronic gastritis.

Conclusion: Up modulation of Gal-3 expression was associated with H. pylori infection and down modulation of Gal-9 with the inflammatory process of chronic gastritis.
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http://dx.doi.org/10.1016/j.prp.2017.08.005DOI Listing
October 2017

Chitosan-based mucoadhesive gel for oral mucosal toluidine blue O delivery: The influence of a non-ionic surfactant.

Photodiagnosis Photodyn Ther 2017 Dec 31;20:48-54. Epub 2017 Aug 31.

Department of Mechanical Engineering, Federal University of Triangulo Mineiro (UFTM), Av. Frei Paulino, 30, CEP: 38025-180, Uberaba, MG, Brazil.

Photodynamic therapy (PDT) has been successfully employed in the treatment of oral cancer. Toluidine blue O (TBO) is a photosensitizer (PS) that has exhibited remarkable photocytotoxicity in a variety of tumour cells; however, its physicochemical properties, as well as the physicochemical properties of oral mucosa, prevent the drug from reaching the target site at a therapeutic concentration. The aim of this study was to evaluate the influence of Tween 80 (TW), which has shown potential as a penetration enhancer, on the mucosal retention of TBO for the PDT of oral cancer. 4% Chitosan-based mucoadhesive gels (CH gels) containing or not 5%TW were prepared (both containing 1%TBO), and their physicochemical properties (pH, rheology and mucoadhesion), TBO in vitro release profiles and TBO in vitro mucosal retention were evaluated. In vivo mucosal penetration studies of TBO followed by laser exposition were also carried out. The results showed that 4%CH gels containing 5%TW and 1%TBO have adequate mucoadhesive and rheological properties for oral mucosa use, although they present a slightly acid pH. TBO release studies showed that TW reduces TBO release, but it prolongs TBO release and increases TBO retention in the mucosa. In vivo studies showed that 4%CH gels containing 5%TW and 1%TBO cause an increase in the number of apoptotic cell, after laser exposition. In summary, 4%CH gels containing 5%TW may be a promising vehicle to optimize the penetration of TBO in oral mucosa and to improve the PDT response for the treatment of oral cancer.
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http://dx.doi.org/10.1016/j.pdpdt.2017.08.009DOI Listing
December 2017

Analysis of CD15, CD57 and HIF-1α in biopsies of patients with peri-implantitis.

Pathol Res Pract 2017 Sep 23;213(9):1097-1101. Epub 2017 Jul 23.

Laboratory of Biopathology and Molecular Biology, University of Uberaba (UNIUBE), Uberaba, MG, Brazil; Cefores, Federal University of Triangulo Mineiro (UFTM), Uberaba, MG, Brazil. Electronic address:

Peri-implantitis is an infectious disease characterized by inflammation of the tissues surrounding the implant, bleeding on probing with or without suppuration, and bone loss. Peri-implant lesions contain a leukocyte infiltrate of plasma cells, lymphocytes, macrophages and neutrophils. A survey of the literature did not show any studies reporting an association between hypoxia and peri-implantitis. The aim of the present cross-sectional study was to evaluate histological changes and immunostaining for CD15, CD57 and HIF-1α in the peri-implant mucosa of patients with and without peri-implantitis. Mucosal biopsies were obtained from 18 patients with peri-implantitis and 10 control subjects without peri-implantitis at a private health care center between 2010 and 2012. The sections were fixed in 10% buffered formalin, processed and embedded in paraffin for histopathological and immunohistochemical study. Acanthosis, spongiosis and exocytosis were observed in both groups, with no significant difference between them. The peri-implantitis group showed increased immunostaining for CD15, a neutrophil marker, and HIF-1α, a tissue hypoxia marker, but no significant difference in immunostaining for CD57, a Natural Killer cell marker. The increase in neutrophil (CD15) and hypoxia (HIF-1α) markers in patients with peri-implantitis suggests an active participation of neutrophils and hypoxia in the pathogenesis of this disease. Since the present study was the first to evaluate the expression of CD15, CD57 and HIF-1α in peri-implant tissues, further studies should be performed to better understand the role of these molecules in peri-implantitis.
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http://dx.doi.org/10.1016/j.prp.2017.07.020DOI Listing
September 2017

Evaluation of the immunohistochemical expression of Gal-1, Gal-3 and Gal-9 in the colon of chronic chagasic patients.

Pathol Res Pract 2017 Sep 20;213(9):1207-1214. Epub 2017 Apr 20.

Laboratory of Biopathology and Molecular Biology, University of Uberaba (UNIUBE), Uberaba, MG, Brazil; Cefores, Federal University of Triangulo Mineiro (UFTM), Uberaba, MG, Brazil. Electronic address:

Objective And Design: The aim of the present study was to evaluate the immunohistochemical expression of Gal-1, Gal-3 and Gal-9 in the colon of chronic chagasic patients compared to biopsied non-chagasic patients.

Material Or Subjects: Thirty-two colon fragments were selected from chagasic patients with megacolon (n=25) and nonchagasic patients without megacolon (n=7).

Methods: Immunohistochemistry for Gal-1, Gal-3 and Gal-9 was performed using a common light microscope and the results were scored 0-3 according to labeling intensity. Data were analyzed statistically by the chi-square test.

Results: Higher Gal-1, Gal-3 and Gal-9 expression was observed in the myenteric plexus ganglia of chagasic patients compared to non-chagasic patients, p=0.0487, p=0.0019 and p=0.0325, respectively, whereas no significant differences were observed between groups regarding the expression of Gal-1, Gal-3 and Gal-9 in the muscle layer.

Conclusion: Since Gal-1, Gal-3 and Gal-9 galectin expression was higher in the myenteric plexus ganglia of chagasic patients, we believe that these lectins may be associated with ganglionitis in the chagasic megacolon. However, since the present study was the first to report the participation of Gal-9 in Chagas disease, further investigations are needed to elucidate the role of galectin 9 in this disease.
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http://dx.doi.org/10.1016/j.prp.2017.04.014DOI Listing
September 2017

Modulation of Matrix Metalloproteinase 14, Tissue Inhibitor of Metalloproteinase 3, Tissue Inhibitor of Metalloproteinase 4, and Inducible Nitric Oxide Synthase in the Development of Periapical Lesions.

J Endod 2017 Jul 17;43(7):1122-1129. Epub 2017 May 17.

Laboratory of Immunology, Department of Biological Sciences and Cefores, Triângulo Mineiro Federal University, Uberaba, Minas Gerais, Brazil; Uberaba University, Uberaba, Minas Gerais, Brazil. Electronic address:

Introduction: Periapical cysts and granulomas are chronic lesions caused by an inflammatory immune response against microbial challenge in the root canal. Different cell types, cytokines, and molecules have been associated with periapical lesion formation and expansion. Therefore, because of the chronic inflammatory state of these lesions, the aim of this study was to evaluate the in situ expression of matrix metalloproteinase (MMP)-14 and -19, tissue inhibitor of metalloproteinase (TIMP)-3 and -4, CD68, and inducible nitric oxide synthase (iNOS) in periapical cysts and granulomas.

Methods: Sixteen cases of periapical cysts and 15 cases of periapical granulomas were analyzed. Ten normal dental pulps were used as the negative control. Immunohistochemistry was performed with anti-MMP-19, anti-MMP-14, anti-TIMP-3, anti-TIMP-4, anti-iNOS, and anti-CD68 antibodies.

Results: The expression of TIMP-3, TIMP-4, iNOS, and CD68 was significantly higher in both the cyst and granuloma groups than in the control group. TIMP-4 was also significantly higher in cases of chronic apical abscess. There was also a significant difference in the expression of MMP-14 between the cyst and control groups. However, there were no differences in the expression of MMP-19 between the 3 groups.

Conclusions: Our data suggest that the expression of MMP-14, TIMP-3, and TIMP-4 is associated with the development of periapical lesions.
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http://dx.doi.org/10.1016/j.joen.2017.02.020DOI Listing
July 2017

Expression of IL-6, IL-10, IL-17 and IL-33 in the peri-implant crevicular fluid of patients with peri-implant mucositis and peri-implantitis.

Arch Oral Biol 2016 Dec 24;72:194-199. Epub 2016 Aug 24.

Federal University of Triangulo Mineiro (UFTM), Brazil; University of Uberaba, Brazil; Cefores, Federal University of Triangulo Mineiro (UFTM), Brazil. Electronic address:

Objectives: The aim of this study was to compare the levels of IL-6, IL-10, IL-17 and IL-33 in the peri-implantar crevicular fluid (PICF) and in parotid gland saliva (PGS) of healthy patients, and peri-implantitis and peri-implant mucositis patients.

Materials And Methods: The PICF was collected from 40 implants as follows: 10 peri-implant mucositis patients, 20 peri-implantitis patients and 10 healthy patients. The PICF and PGS samples collected from each patient were quantified for IL-6, IL-10, IL-17 and IL-33 by enzymatic immunosorbent assay (ELISA).

Results: IL-6, IL-17 and IL-33 levels on PIFC were significantly higher in peri-implantitis group when compared to healthy group. IL-17 and IL-33 levels in PIFC were significantly higher in peri-implant mucositis group than in healthy group. There was no significant difference when comparing IL-6, IL-10, IL-17 and IL-33 levels in PGS among healthy, peri-implant mucositis and peri-implantitis groups.

Conclusions: Therefore, as in patients with peri-implantitis there were significantly higher levels of IL-6, IL-17 and IL-33 in PICF, we believe that these cytokines were intensifying local inflammatory process, and contributing to clinical aspects such as increased marginal bleeding and probing depth found in patients with peri-implantitis. Furthermore, as IL-17 and IL-33 were increased in patients with peri-implant mucositis, hypothesized that these cytokines were also contributing to the inflammatory process observed in this disease.
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http://dx.doi.org/10.1016/j.archoralbio.2016.08.021DOI Listing
December 2016

Galectin-9 as an important marker in the differential diagnosis between oral squamous cell carcinoma, oral leukoplakia and oral lichen planus.

Immunobiology 2015 Aug 27;220(8):1006-11. Epub 2015 Apr 27.

Laboratory of Biopathology and Molecular Biology, University of Uberaba (UNIUBE), Uberaba, MG, Brazil; CEFORES/Federal University of Triângulo Mineiro (UFTM), Uberaba, MG, Brazil. Electronic address:

Objectives: To evaluate the expression of Galectins (Gal) 1, 3 and 9, Metalloproteinase 3 (MMP-3) and mast cell density in oral lesions of patients with potentially malignant disorders (PMD) and oral squamous cell carcinomas (OSCC) by comparison with the controls.

Study Design: We selected 40 cases of PMD, 40 OSCC and 13 with normal histopathological profile. Immunohistochemistry was performed for Gal-1, Gal-3, Gal-9 and MMP-3.

Results: Gal-9 was significantly higher in patients with OSCC than in others groups (p < 0.001). Gal-1 expression was significantly lower in patients with leukoplakia than those with OSCC and controls (p = 0.0001). Gal-3 was significantly lower in patients with OSCC than those with leukoplakia (p = 0.03). MMP-3 was lower in patients with leukoplakia in comparison with the lichen planus group (p = 0.013).

Conclusion: The increased expression of Gal-9 may be helpful to differentiate of OSCC from other oral cavity lesions.
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http://dx.doi.org/10.1016/j.imbio.2015.04.004DOI Listing
August 2015

Chagas disease reactivation in HIV-coinfected patients: histopathological aspects.

Immunobiology 2015 May 28;220(5):656-62. Epub 2014 Nov 28.

Laboratory of Biopathology and Molecular Biology, University of Uberaba, Uberaba, Brazil; Cefores, Federal University of Triangulo Mineiro, Uberaba, Brazil. Electronic address:

Introduction: Chagas disease reactivation has been described in severely immunocompromised patients by various etiologies, including in HIV-coinfected patients.

Objective: This study aimed to perform histopathological and immunohistochemical evaluation of the brain, myocardium, esophagus and large bowel of autopsied patients with CHD and/or acquired immunodeficiency syndrome in comparison with control patients.

Material And Methods: Autopsy reports were reviewed from 1998 to 2012 and eight adult subjects were selected and divided into four groups: RE, CH, AI and CO. Sections of brain, myocardium, esophagus and large bowel were collected from each subject and processed for histological and immunohistochemical analysis. The histological sections stained with HE, Giemsa and picrosirius were used to quantify the density of inflammatory cells, the density of mast cells, and the percentage of collagen, respectively. Immunohistochemical analysis of IL17 and CD31 was performed.

Results: The density of mast cells in the myocardium was significantly higher in the CH group than in the other groups. The density of mast cells in the esophagus and in the large bowel was significantly higher when compared to the other groups. The percentage of collagen in the esophagus, myocardium and large bowel was significantly lower in the RE group than in the CO group. The CH group had a higher percentage of collagen in the myocardium and in the large bowel in relation to the other groups. The density of cells immunostained with anti-IL17 was significantly higher in the large bowel and in the myocardium in the CH group than in the CO group. There was higher density of vessels immunostained with anti-CD31 in the myocardium and esophagus of the AI group than in the other groups. There were no significant correlations between the density of mast cells and percentage of collagen in the RE, CO, CH and AI groups.

Conclusion: Brain lesions observed in patients with CDR, as well as the higher density of cells immunostained with anti-IL17 at these sites, suggest that this cytokine was increasing local inflammation with subsequent tissue damage due to inflammation. Furthermore, the higher density of mast cells in the esophagus and large bowel of these subjects suggests that these cells might play a major role in esophageal and intestinal inflammation.
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http://dx.doi.org/10.1016/j.imbio.2014.11.013DOI Listing
May 2015

Using chitosan gels as a toluidine blue O delivery system for photodynamic therapy of buccal cancer: In vitro and in vivo studies.

Photodiagnosis Photodyn Ther 2015 Mar 25;12(1):98-107. Epub 2014 Nov 25.

School of Pharmacy, University of Uberaba (UNIUBE), Av. Nenê Sabino, 1801, Bairro Universitário, CEP: 38055-500, Uberaba, MG, Brazil; School of Pharmacy and Biochemistry, Federal University of São Paulo (UNIFESP), Campus Diadema, Rua São Nicolau, 210, CEP: 09913-030, Diadema, SP, Brazil. Electronic address:

Background: Photodynamic therapy (PDT) is an emerging treatment that has demonstrated potential for the clinical treatment of buccal cancer. It is based on the photoactivation of a photosensitizer (PS) when irradiated by light at a specific wavelength. The light-excited PS generates reactive oxygen species that cause the destruction of tumor cells by apoptosis or necrosis. Toluidine Blue O (TBO) is a PS that has shown potential for PDT in cancer treatment. However, saliva and mechanical activities quickly remove the PS from the surface of the buccal mucosa. Therefore, the bioavailability of PS at the surface of target tissues is reduced. The aim of this study was to evaluate the potential of chitosan (CH) gels in TBO delivery to buccal tissue.

Methods: CH gels were obtained at different concentrations and their physico-chemical properties (pH and rheology), mucoadhesion, in vitro release profile, in vivo retention and in vivo efficacy by the ability to induce cell apoptosis were evaluated.

Results: CH-based mucoadhesive gels optimized the release and adherence of preparations at the target site. Specifically, 4% (w/w) CH gel showed adequate properties for buccal use, such as pH value, mucoadhesion, pseudoplastic behavior, extended release, minimal permeation and higher TBO retention by the mucosa. In vivo studies showed the potential of the gel to enhance TBO retention and induce cell apoptosis after laser irradiation.

Conclusion: 4% (w/w) CH based mucoadhesive gel can be explored as a TBO delivery system in the PDT of oral cancer.
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http://dx.doi.org/10.1016/j.pdpdt.2014.11.003DOI Listing
March 2015

Evaluation of in situ expression of effector and regulatory cytokines, TLR, galectins and matrix metalloproteinases in oral manifestations of paracoccidioidomycosis.

Immunobiology 2015 Jan 14;220(1):154-63. Epub 2014 Aug 14.

Laboratory of Biopathology and Molecular Biology, University of Uberaba (UNIUBE), Uberaba, MG, Brazil; Federal University of Triângulo Mineiro (UFTM), Uberaba, MG, Brazil. Electronic address:

Background: Although the pathophysiology of paracoccidioidomycosis (PCM) is not completely understood, the study of immune response against fungus has provided insight into understanding the natural course of the disease and its clinical manifestations, hence contributing to the development of preventive measures and treatment proposals. The aim of this study was to evaluate the histopathological and immunological aspects involved in the role of different effector and regulatory responses, as well as the correlation between the TLRs, Galectins, Matrix Metalloproteinases and cytoplasmic proteases of mast cells in this infection.

Methods: Sixteen biopsy specimens with oral lesions of chronic PCM, as well as 13 sections of normal oral mucosa were analyzed. Histopathological and immunological aspects involved in the role of different effector and regulatory responses were evaluated. Indirect immunohistochemistry was performed for IL-17, IL-10, IL-4, TGF-β, FoxP3, Gal-1, Gal-3, Gal-9, TLR-2, TLR-4, MMP-3 and MMP-9, as well as for chymase and tryptase for mast cells identification. Fibrosis was quantified using Picrosirius.

Results: There was a significant increase in the area of fibrosis and in the number of cells expressing IL-10, IL-4, IL-17, FoxP3, Gal-3, TLR-2, MMP3 and MMP9 in patients with PCM in comparison with patients in the group control. There was no difference in the expression of TGF-β, TLR-4, Gal-1 or Gal-9. Mast cells number was found to be significantly lower in oral chronic PCM when compared to control samples after quantification of mast cells and expression of chymase and tryptase. PCM granulomas were classified to the morphological aspects in organized ou non-organized. Expression of IL-4 in non-organized granulomas was significantly higher.

Conclusion: The proteins studied herein appear to play an important role in the development and maintenance of oral lesions of PCM, as well as in the processes of development and progression of lesions caused by the fungus and by the immune response associated with the infection.
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http://dx.doi.org/10.1016/j.imbio.2014.08.006DOI Listing
January 2015

Evaluation of peri-implant mucosa: clinical, histopathological and immunological aspects.

Arch Oral Biol 2014 May 15;59(5):470-8. Epub 2014 Feb 15.

Laboratory of Biopathology and Molecular Biology, University of Uberaba (UNIUBE), Brazil; Cefores, Federal University of Triangulo Mineiro (UFTM), Brazil. Electronic address:

Objective: The aim was to compare the inflammatory response in peri-implant mucosa between patients with peri-implantitis (PP-group) and patients with healthy peri-implant tissues (HP-group).

Materials And Methods: Two fragments of peri-implant mucosa of 18 patients were collected and serial sections were performed for histological and immunohistochemical analysis.

Results: When compared with HP-group, PP-group showed higher immunostained cell density for TGF-β, IL-17 and CD31, beyond greater density of red cells, leukocytes, mast cells chymase (MCC) and mast cell tryptase (MCT). HP-group patients showed higher IL-13 expression and increased amount of collagen fibres when compared with PP-group. In PP-group there was significant positive correlation between MCT density and density of blood vessels immunostained, and between MCC density and density of blood vessels immunostained. There was significant negative correlation between the IL-17 density and collagen percentage.

Conclusions: This study demonstrated that in patients with peri-implantitis there was higher of TGF-β and IL-17, indicating that these cytokines are directly involved in the inflammatory process. Thus, understanding the influence of cytokines in the peri-implantitis installation, new therapies could be developed in order to inhibit the synthesis of IL-17 and induce synthesis of IL-13 in peri-implant tissue, contributing to increase the longevity of the implant.
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http://dx.doi.org/10.1016/j.archoralbio.2014.01.011DOI Listing
May 2014

Higher expression of galectin-3 and galectin-9 in periapical granulomas than in radicular cysts and an increased toll-like receptor-2 and toll-like receptor-4 expression are associated with reactivation of periapical inflammation.

J Endod 2014 Feb 12;40(2):199-203. Epub 2013 Dec 12.

Laboratory of Biopathology and Molecular Biology, University of Uberaba (UNIUBE), Uberaba, Minas Gerais, Brazil; Federal University of Triângulo Mineiro (UFTM/CEFORES), Uberaba, Minas Gerais, Brazil. Electronic address:

Introduction: Cysts and periapical granulomas are inflammatory reactions that develop in response to periapical infection by microbial species in dental root canal. It is known that toll-like receptors (TLRs) are pathogen recognition molecules and that galectins are lectins that can be associated with the inflammatory process, stimulating or inhibiting the immune system. The objective of this study was to evaluate the in situ expression of TLRs and galectins in radicular cysts and periapical granulomas.

Methods: We analyzed 62 cases (30 radicular cysts, 27 periapical granulomas, and 5 control cases). Indirect immunohistochemistry was used to evaluate the expression of TLRs (TRL-2 and TLR-4) and galectins (Gal-3 and Gal-9).

Results: The expression of Gal-3 and Gal-9 was significantly higher in periapical granulomas and radicular cysts than in the control group. Similarly, both Gal-3 and Gal-9 were expressed significantly more in periapical granulomas than in radicular cysts. The expression of TLR-2 was significantly higher in periapical granulomas and radicular cysts than in the control group, and it was also significantly higher in radicular cysts with sinus tract than in the cases without sinus tract. Furthermore, the expression of TLR-4 was significantly higher in the cases of periapical granulomas with sinus tract than in the cases without sinus tract.

Conclusions: Gal-3/Gal-9 and TLR-2/TLR-4 expression in the periapical granulomas and radicular cysts is associated with reactive periapical inflammation. Pathobiology of periapical disease is a very complex interplay of many bioactive molecules involved in immunoinflammatory responses. Up-regulation of these bioactive molecules might be an important modulator of inflammatory periapical lesions.
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http://dx.doi.org/10.1016/j.joen.2013.10.031DOI Listing
February 2014

Correlation of lifetime progress of atherosclerosis and morphologic markers of severity in humans: new tools for a more sensitive evaluation.

Clinics (Sao Paulo) 2012 Sep;67(9):1071-5

Triângulo Mineiro Federal University, Uberaba, MG, Brazil.

Objectives: To describe the morphological features of atherosclerosis in the aortas of autopsied patients (ranging from young adults to the elderly), thus providing new tools for a more sensitive morphological evaluation.

Method: We collected 141 aorta samples. We assessed the macroscopic degree of atherosclerosis, thickness of the intima and media, lipid and collagen depositions in the intima, and the infiltration of mast cells into the layers of the aorta. We correlated the findings with gender, age, race and cause of death.

Results: The degree of atherosclerosis was significantly higher in the elderly. The aorta was thicker in the elderly and in cases with a cardiovascular cause of death. The thickness of the intima was significantly greater in the elderly, in males and in cases with a cardiovascular cause of death. The lipid content in the intima of the aorta was significantly higher in Caucasians. Older people and men had a significantly higher number of mast cells.

Conclusion: A macroscopic evaluation is a good indicator of the severity of atherosclerosis, but a more detailed analysis, namely evaluating the thickness of the layers of the aorta and the number of mast cells, may further elucidate the changes in the constituents of this vessel.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438249PMC
http://dx.doi.org/10.6061/clinics/2012(09)15DOI Listing
September 2012

Distinct expression of interleukin 17, tumor necrosis factor α, transforming growth factor β, and forkhead box P3 in acute rejection after kidney transplantation.

Ann Diagn Pathol 2013 Feb 8;17(1):75-9. Epub 2012 Sep 8.

Laboratory of Immunology, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brasil.

The kidney transplant is the main therapeutic alternative for end-stage kidney disease, and rejection is a major complication. The expression of proinflammatory cytokines is related to graft loss, whereas anti-inflammatory cytokines are associated with graft protection. The objective of this study is to evaluate the "in situ" expression of cytokines T helper 1 (tumor necrosis factor α [TNF-α]), T helper 17 (interleukin 17 [IL-17]), and regulatory T cell (transforming growth factor β [TGF-β]) and the expression of forkhead box P3 (FoxP3) in allograft kidney. We evaluated in situ expression of cytokines in allograft kidney under rejection process by indirect immunohistochemistry. Eighteen renal graft biopsies were from patients with episodes of rejection. The in situ expression of IL-17, TNF-α, and TGF-β was significantly higher in patients with acute rejection when compared with the control group. In contrast, analysis of FoxP3 expression showed few positive cells in patients with acute rejection compared with the control group. The results suggest that the expression of proinflammatory cytokines (IL-17 and TNF-α) contributes to the mechanisms of kidney transplant rejection. The increase in TGF-β expression might be an attempt to establish a process of immunoregulation or even to induce higher production of IL-17. The last hypothesis is supported by the observation of a reduced expression of FoxP3 and elevated levels of IL-17.
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http://dx.doi.org/10.1016/j.anndiagpath.2012.08.002DOI Listing
February 2013

In situ expression of regulatory cytokines by heart inflammatory cells in Chagas' disease patients with heart failure.

Clin Dev Immunol 2012 3;2012:361730. Epub 2012 Jul 3.

Laboratory of Immunology, Institute of Biological Sciences, Federal University of Triângulo Mineiro, 38125-180 Uberaba, MG, Brazil.

Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi. The immune system plays an important role in the reduction of parasite load, but may also contribute to the development of lesions observed during the chronic phase of the disease. We analyzed cytokines produced by inflammatory heart cells in 21 autopsy samples obtained from patients with Chagas' disease divided according to the presence or absence of heart failure (HF). Left ventricular sections were analyzed by immunohistochemistry using antibodies against human IL-4, IFN-γ, TGF-β, TNF-α, and NOS2. In situ mRNA expression was quantified by a Low Density Array. The number of IFN-γ-positive cells was significantly higher than IL-4 positive cells. TNF-α, TGF-β and NOS2 were detected in 65%, 62% and 94% of samples respectively. There was an association between TNF-α-producing cells and the presence of HF. Subjects with HF presented higher levels of STAT4 mRNA, whereas FoxP3 and STAT6 levels were similar in the two groups. A Th1 cytokine pattern predominated in the cardiac inflammatory cell infiltrate of Chagas' disease patients associated with HF. High degree of fibrosis was associated with low NOS2 expression. These results support the idea that Th1 immune responses are involved in heart lesions of Chagas' disease patients.
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http://dx.doi.org/10.1155/2012/361730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397162PMC
October 2012

Role of mast cell chymase and tryptase in the progression of atherosclerosis: study in 44 autopsied cases.

Ann Diagn Pathol 2013 Feb 1;17(1):28-31. Epub 2012 Jun 1.

General Pathology Division, Triângulo Mineiro Federal University, Uberaba-MG, Brazil.

The aim of this study was to describe the role of mast cell chymase and tryptase in the progression of atherosclerosis. Forty-four sections of aortas were obtained from autopsies. We assessed the macroscopic degree of atherosclerosis, microscopic intensity of lipid deposition in the tunica intima, percentage of collagen in the tunica intima, and density of immunostained mast cells. There was no significant difference between the density of mast cell tryptase and chymase concerning ethnicity, sex, cause of death, or degree of atherosclerosis. The density of mast cell chymase was significantly higher in the nonelderly group. The percentage of collagen was significantly higher in elderly patients. There was a positive and significant correlation between the degree of macroscopic atherosclerosis and lipidosis, the density of mast cell chymase and the percentage of collagen, the density of mast cell tryptase and the percentage of collagen, and lipidosis and the density of mast cell tryptase. The degree of macroscopic lesion of atherosclerosis increased proportionally with the increase in the density of mast cell chymase and tryptase and in the intensity of lipid deposition and with the percentage of collagen in the atherosclerotic plaques. Thus, mast cells may play a crucial role in aggravating atherosclerotic lesions.
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http://dx.doi.org/10.1016/j.anndiagpath.2012.04.007DOI Listing
February 2013

[Role of nitric oxide in the development of cardiac lesions during the acute phase of experimental infection by Trypanosoma cruzi].

Rev Soc Bras Med Trop 2009 Mar-Apr;42(2):170-4

Laboratório de Imunologia, Universidade Federal do Triângulo Mineiro, Uberaba, MG.

Chagas disease is caused by Trypanosoma cruzi and the heart is the organ most affected. Nitric oxide has notable anti-Trypanosoma action, but with little evidence regarding its role in the mechanism for tissue injury. The objective of this study was to analyze the contribution of nitric oxide towards the development of inflammation and cardiac fibrosis during the acute phase of experimental infection by Y and Colombian strains of Trypanosoma cruzi. The inflammation was significantly more intense in animals infected with the Colombian strain, compared with those infected with the Y strain, both in C57BL/6 animals (3.98 vs 1.87%; p = 0.004) and in C57BL/6 animals deficient in inducible nitric oxide synthase (3.99 vs 2.4%; p = 0.013). The cardiac parasite load in inducible nitric oxide synthase-deficient C57BL/6 animals infected with the Colombian strain was significantly greater than in those infected with the Y strain (2.78 vs. 0.17 nests/mm(2); p = 0.004), and also significantly greater than in the C57BL/6 infected with both the Colombian strain (2.78 vs 1.33 nests/mm(2); p = 0.006) and Y strains (2.78 vs 0.53 nests/mm(2); p = 0.005). The data confirm that nitric oxide has a role in parasite load control and suggest that it has a role in tissue protection, through controlling inflammation and potentially reducing cardiac lesions during the acute phase of Chagas disease.
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http://dx.doi.org/10.1590/s0037-86822009000200015DOI Listing
July 2009

External multiple invasive cervical resorption with subsequent arrest of the resorption.

Dent Traumatol 2008 Oct;24(5):556-9

University of Uberaba, Uberaba, Minas Gerais, Brazil.

A rare, the uncommon, case of multiple invasive cervical resorption (MICR) with subsequent arrest of the resorption involving eight teeth of the mandible (tooth 46 to tooth 32) is presented. This case is noteworthy because of the characteristics of its clinical evolution. There have only been a few cases in the literature were found presenting involvement of such a large number of teeth. Furthermore, no reports on cases of MICR with arrest of the resorption, as described in this report, were found.
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http://dx.doi.org/10.1111/j.1600-9657.2007.00553.xDOI Listing
October 2008

Inflammation and glandular duct dilatation of the tongue from patients with chronic Chagas disease.

Parasitol Res 2006 Jan 25;98(2):153-6. Epub 2005 Nov 25.

General Pathology Division, University of Uberaba, Uberaba, MG, Brazil.

The purpose of this study was to evaluate morphologically the tongue of individuals with chronic Chagas disease (CD) in comparison to the non-chagasic ones. Twenty-four protocol cases of autopsies were selected. They were subdivided into CD patients (10 cases) and non-chagasic ones (14 cases). The morphometric analysis was accomplished for the tongue muscle and salivary glands duct lumen area. In three CD patients, perineuritis was found, and two of them showed megaesophagus and megacolon. The intensity of the inflammation in the von Ebner's glands, the tongue muscles, and the salivary glands duct lumen area was significantly higher in the CD patients. We concluded that the CD patients show salivary glands duct dilatation, which probably would have a relation with alterations in the autonomic nervous system. The inflammation found in CD patients is in accordance with that described in comparative studies on the digestive tract and heart. These morphological findings suggest that the histopathological analysis of the tongue associated with other organs, or even in an isolated manner, can add in the diagnosis and pathogenesis of the CD chronic phase.
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http://dx.doi.org/10.1007/s00436-005-0023-9DOI Listing
January 2006

[Identification of infectious agents in the lungs in autopsies of patients with acquired immunodeficiency syndrome].

Rev Soc Bras Med Trop 2002 Nov-Dec;35(6):635-9. Epub 2003 Feb 26.

Disciplina de Patologia Geral, Universidade de Uberaba, Uberaba, MG, Brasil.

Lung diseases are frequently observed in individuals infected with HIV. The aim of this study was to identify infectious agents in the lungs in the autopsied individuals with AIDS performed between march 1990 and july 2000 at the school of medicine (Uberaba- Brazil), using histochemical and immunohistochemical techniques. Analysis was made on lungs obtained from 40 individuals with AIDS. Infectious agents were observed in 34 (85%) cases of the 40 analyzed. Regarding fungis, Pneumocystis carinii was found in 8 (19.1%)cases; Cryptococcus sp in 4 (9.5%)cases, Histoplasma sp in 2 (4.8%)cases and Candida sp in 1 (2.4%)case. Association of Pneumocystis carinii, Citomegalovirus and Cryptococcus sp, was observed in one case, and in another, the association of CMV, and Toxoplasma gondii. There were 5 cases with Candida sp, CMV and Pneumocystis carinii associated with bacteria. In conclusion, this study shows that following bacterial agents fungi were the second most common infectious agents in post mortem examination of the lungs from patients with AIDS, being Pneumocystis carinii the most prevalent.
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http://dx.doi.org/10.1590/s0037-86822002000600015DOI Listing
May 2003

Morphometric study of the spleen in chronic Chagas' disease.

Am J Trop Med Hyg 2002 Apr;66(4):401-3

Disciplina de Patologia Geral da Universidade de Uberaba, Minas Gerais, Brasil.

There is frequently an increase in spleen size in infectious systemic and chronic venous congestion. The aim of this report was to perform a comparative study of the spleen tissue of chagasic or nonchagasic autopsied patients with or without congestive heart failure. Evaluations were made of 111 cases. Connective tissue intensity, follicular density and area, and follicular arterioles wall area were determined through the morphometric study. The connective tissue was similar in all groups. The density of the lymphoid follicles was significantly less among the chagasic cases (P = 0.032). The follicular area was larger among the chagasic cases and in the chagasic group with congestive heart failure. The chagasic group without congestive heart failure presented a greater area of follicular arteriole walls. Therefore, the spleen modifications in chronic Chagas' disease could be a consequence not only of the heart failure but also of the Chagas infection itself.
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http://dx.doi.org/10.4269/ajtmh.2002.66.401DOI Listing
April 2002