New immunological aspects of peri-implantitis.

BACKGROUND: The authors compared the levels of HIF1-α, VEGF, TNF-α, and IL-10 in peri-implant crevicular fluid between patients with or without peri-implantitis. HIF-1α levels were significantly high in the peri-implantitis possibly due to hypoxia triggered by persistent inflammation. OBJECTIVE: This study aimed to compare the levels of HIF1-α, VEGF, TNF-α, and IL-10 in the peri-implant crevicular fluid of patients with and without peri-implantitis. METHODS: Forty patients, comprising 16 with and 24 without peri-implantitis were selected. RESULTS: Patients with peri-implantitis exhibited significantly higher HIF-1α levels than those without peri-implantitis (p=0.0005). TNF-α revealed significant positive correlations with IL-10 (p=0.0008) and VEGF (p=0.0246), whereas HIF-1α and IL-10 levels (p=0.0041) demonstrated a negative and significative correlation in the peri-implantitis group. CONCLUSION: This study, for the first time demonstrates the balance of HIF-1α, TNFα, IL-10, and VEGF in peri-implantitis. It shows an elevated HIF-1α levels in patients with peri-implantitis, which could have stemmed from persistent inflammation- triggered hypoxia. Furthermore, the positive correlation between TNF-α and VEGF suggests intensified proinflammatory activity in peri-implantitis. Nevertheless, further studies are essential to understand these immune dynamics in peri-implantitis. BACKGROUND: Higher levels of HIF-1α in patients with peri-implantitis occurred possibly due to persistent hypoxia triggered by inflammation. BACKGROUND: Tissue hypoxia in peri-implantitis induced increase in HIF-1α consequently increased VEGF and angiogenesis, contributing to the persistence of inflammation.

New immunological aspects of peri-implantitis

ABSTRACT Objective: This study aimed to compare the levels of HIF1-α, VEGF, TNF-α, and IL-10 in the peri-implant crevicular fluid of patients with and without peri-implantitis. Methods: Forty patients, comprising 16 with and 24 without peri-implantitis were selected. Results: Patients with peri-implantitis exhibited significantly higher HIF-1α levels than those without peri-implantitis (p=0.0005). TNF-α revealed significant positive correlations with IL-10 (p=0.0008) and VEGF (p=0.0246), whereas HIF-1α and IL-10 levels (p=0.0041) demonstrated a negative and significative correlation in the peri-implantitis group. Conclusion: This study, for the first time demonstrates the balance of HIF-1α, TNFα, IL-10, and VEGF in peri-implantitis. It shows an elevated HIF-1α levels in patients with peri-implantitis, which could have stemmed from persistent inflammation- triggered hypoxia. Furthermore, the positive correlation between TNF-α and VEGF suggests intensified proinflammatory activity in peri-implantitis. Nevertheless, further studies are essential to understand these immune dynamics in peri-implantitis.

Inalação da fumaça do tabaco provoca alterações histopatológicas no nervo olfatório de ratas / Inhalation of tobacco smoke causes histopathological changes in the olfactory nerve of rats

Introdução: o tabagismo é uma das principais causas evitáveis de mortes no mundo representando um problema de saúde pública. Objetivo: investigar a relação da exposição passiva à fumaça principal do cigarro e as possíveis alterações histomorfométricas das células gliais, arteríolas e da matriz extracelular do nervo olfatório de ratas. Metodologia: trata-se de um estudo experimental, analítico e quantitativo. Vinte ratas randomizadas divididas em dois grupos, controle e tabaco, foram expostas à inalação da fumaça principal do cigarro por 60 dias utilizando dispositivo validado na literatura. Resultados: a exposição à inalação da fumaça principal do cigarro resultou em alterações significativas no grupo tabaco, tais como, elevação nos níveis de cotinina no plasma sanguíneo, aumento na espessura da parede dos vasos sanguíneos, aumento na porcentagem do colágeno total do tecido, diminuição no número total de astrócitos e aumento no número total de micróglias. Conclusão: a exposição à fumaça principal do cigarro resulta em alterações histomorfométricas que poderiam causar alterações funcionais no nervo olfatório como perda sensorial olfativa. Os achados constatados são fortes o suficiente para servir como alerta a toda a população e às autoridades de saúde, no que se refere às leis antifumo, principalmente em ambientes fechados.

Introduction: smoking is one of the main preventable causes of death in the world and represents a worldwide public health problem. Objective: to investigate the relationship of second hand tobacco smoke and possible histomorphometric changes of glial cells, arterioles and extracellular matrix of the olfactory nerve in rats. Methodology: experimental, analytical and quantitative study, twenty wistar animals randomized into two control and tobacco groups, were exposed to inhalation of main cigarette smoke for 60 days using a device validated in the literature. Results: exposure to inhalation of main cigarette smoke resulted in changes in the tobacco group, such as increased levels of cotinine in the blood plasma, increased thickness of the blood vessel wall, increased percentage of total tissue collagen, decreased in the total number of astrocytes and increase in the total number of microglia. Conclusion: exposure to main cigarette smoke results in histomorphometric changes that can cause changes in the olfactory nerve such as sensory olfactory loss. Our findings are strong enough to serve as a warning to the entire population and to health authorities in relation to smokefree laws especially in closed environments.

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

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.

Overexpression of hif-1α and morphological alterations in the tongue of rats exposed to secondhand smoke

Abstract 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.

Resumo O tabagismo é um fator de risco para sérios problemas de saúde e está associado a diversas alterações nos tecidos da cavidade oral. O objetivo deste estudo foi avaliar a porcentagem de colágeno, densidade de mastócitos e intensidade de células imunomarcadas por anti-HIF-1α na musculatura lingual de ratos expostos passivamente à fumaça principal do cigarro. Vinte e sete ratos Wistar albinos fêmeas foram divididos em três grupos: ratos não expostos à inalação da fumaça do tabaco (grupo controle) (n=7); ratos expostos à inalação da fumaça por 30 dias (TAB 30) (n=10); e ratos expostos à inalação da fumaça por 45 dias (TAB 45) (n=10). Posteriormente, os animais foram submetidos à eutanásia e remoção da língua para processamento e análise histológica e imuno-histoquímica. Nos grupos TAB 30 e TAB 45, houve diminuição do percentual de colágeno, maior densidade de mastócitos e maior intensidade de células imunomarcadas por anti-HIF-1α em comparação ao grupo controle. Houve também correlação positiva e significativa entre a porcentagem de colágeno e a densidade de mastócitos. Não houve diferença significativa entre TAB 30 e TAB 45 em nenhum dos parâmetros avaliados. Portanto, a exposição passiva de ratos à fumaça principal do cigarro por 45 dias provoca diminuição das fibras de colágeno perimisial, aumento do número de mastócitos e aumento da imunomarcação para o HIF-1α em células musculares linguais. O presente estudo foi o primeiro a avaliar a porcentagem de colágeno, densidade de mastócitos e imunomarcação para o HIF-1α em línguas de ratos expostos à fumaça do tabaco.

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

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.

Computerized morphometry of the area of the hard palate and of palatal rugae: a cross-sectional study / Morfometría computarizada del área del paladar duro y de las arrugas palatinas: un estudio transversal

Abstract Background: The evaluation of palatal rugae in human identification is important because these structures can remain intact for up to seven days after death. Aim: To compare the area and density of the palatal rugae between ages groups and genders. Settings and Design: A cross-sectional study. Methods and Material: Dental plaster models obtained from patients at the Orthodontic Clinic of University of Uberaba were selected. Two hundred patients were divided into four groups: Group 1:10-15 years; Group 2:16-30 years; Group 3:31-50 years; and Group 4:51-70 years. The palatal rugae and hard palate of each plaster model were outlined and photographed. The evaluation of the area of the hard palate and palatal rugae was performed using the ImageJ software. Statistical analysis used: Kolmogorov-Smirnov, Kruskal-Wallis, Chi-square and Spearman correlation tests using GraphPad Prism 5 statistical software. Results and conclusión: The areas of the palatal rugae and of the hard palate were significantly smaller in the group 4. There was a significant negative correlation between age and palatal rugae area, and between age and hard palatal area. The present study was the first to demonstrate that patients between 51 and 70 years have a smaller palatal rugae area and a smaller hard palate area when compared to other groups. Thus, the evaluation of the hard palate area and of palatal rugae could be used as an adjunct with other methods to determine the age group of an individual; however studies using larger sample size are needed to validate this observation.

Although with intact mucosa at colonoscopy, chagasic megacolons have an overexpression of Gal-3 / Embora com mucosa íntegra à colonoscopia, megacólons chagásicos apresentam superexpressão de Gal-3

ABSTRACT 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.

RESUMO Objetivo Avaliar a densidade de células imunomarcadas por anti-galectina-3, a percentagem de colágeno, a densidade de mastócitos e a presença de processos patológicos na musculatura intestinal de pacientes biopsiados. Métodos Foram selecionados 35 pacientes submetidos à biópsia de intestino entre 1997 a 2015. Os pacientes foram divididos em três grupos: chagásicos com lesão de mucosa (n=13), chagásicos com mucosa íntegra (n=12) e não chagásicos sem lesão de mucosa (n=10). Foram realizados processamento histológico dos fragmentos biopsiados e imunohistoquímica para galectina-3. Cortes adicionais foram corados por hematoxilina e eosina, para avaliar os processos patológicos gerais, pelo picrosírius, para avaliação do colágeno, e pelo azul de toluidina, para avaliar a densidade de mastócitos. Resultados Os pacientes do grupo chagásicos com lesão de mucosa apresentaram frequência significativamente maior de ganglionite e miosite quando comparados aos dos grupos chagásico com mucosa íntegra e não chagásicos. A densidade das células imunomarcadas por anti-galectina-3 foi significativamente maior no grupo chagásicos com mucosa íntegra quando comparada ao grupo não chagásico. O grupo de chagásicos com mucosa íntegra apresentou maior percentagem de colágeno em relação aos grupos chagásicos com mucosa lesada e ao grupo de não chagásicos, com diferença significativa. Não houve diferença significativa com relação à densidade de mastócitos entre os três grupos. Conclusão A maior densidade de células imunomarcadas por anti-galectina-3 nos pacientes do grupo chagásico com mucosa íntegra sugere a necessidade de maior atenção na avaliação clínica desses pacientes, uma vez que essa proteína está associada com transformação e progressão neoplásica.

Hemophagocytic Lymphohistiocytosis in Autopsied Adults: Clinical, Laboratory and Immunohistochemical Evaluation for CD68 and CD57. Case Report and Literature Review / Linfohistiocitose Hemofagocítica em Adultos Autopsiados: Avaliação Clínica, Laboratorial e Imunohistoquímica para CD68 e CD57. Relato de Caso e Revisão de Literatura

Hemophagocytic lymphohistiocytosis (HLH) is a rare, usually fatal and underdiagnosed autoimmune-activated disease. The present study aimed to perform a macroscopic, histopathological and immunohistochemical evaluation for CD68 and CD57 in organs of autopsied adults with HLH. A total of 604 autopsy reports were analyzed, and all the patients that filled the diagnostic criteria for HLH (n = 2) were selected. These patients were 18 and 37 years old. Were evaluated both clinical and autopsy reports and performed histopathological and immunohistochemical analysis of the liver and spleen. Both patients filled the diagnostic criteria for HLH, as well as presented common signs and symptoms of this disease, such as chills, abdominal pain, diaphoresis, and jaundice. Hemophagocytosis was observed in the spleen, bone marrow, and lymph nodes of the two patients at autopsy. Immunostaining in the liver and spleen of both patients was mainly severe for CD68, and predominantly mild for CD57, indicating a decrease in NKC numbers and an increase in the number of macrophages, respectively. This was the first study to evaluate CD57 and CD68 in autopsies of adults with HLH. Thus, more studies are required, not only to better elucidate the pathogenetic mechanisms involved in the secondary HLH, but also to disseminate the results in the clinical environment, contributing to the early diagnosis and treatment with consequent reduction of mortality rate. (AU)

A Linfohistiocitose Hemofagocítica (HLH) é uma doença autoimune rara, geralmente fatal e subdiagnosticada. Este estudo tem como objetivo realizar avaliação macroscópica, histopatológica e imunohistoquímica para CD68 e CD57 em órgãos de pacientes adultos com HLH submetidos a autópsia. Um total de 604 laudos de autópsias foram analisados e todos os pacientes que preencheram os critérios diagnósticos para HLH (n = 2) foram selecionados. Esses pacientes tinham 18 e 37 anos de idade. Foram analisados tanto os prontuários quanto os laudos de autópsia, bem como foram realizadas análises histopatológicas e imunohistoquímicas do fígado e baço dos pacientes. Ambos preencheram os critérios diagnósticos para HLH e apresentarem sinais e sintomas comuns da doença, como calafrios, dor abdominal, sudorese e icterícia. A hemofagocitose foi observada no baço, medula óssea e linfonodos dos dois pacientes na autópsia. A imunohistoquímica do fígado e do baço de ambos os pacientes demonstrou imunomarcação acentuada para CD68 e predominantemente discreta para CD57, que indicam diminuição do número de NKC e aumento do número de macrófagos, respectivamente. Este foi o primeiro estudo a avaliar o CD57 e CD68 em autópsias de adultos com HLH. Assim, mais estudos são necessários, não apenas para melhor elucidar os mecanismos patogenéticos envolvidos na HLH secundária, mas também para disseminar os resultados no ambiente clínico, contribuindo para o diagnóstico e tratamento precoces com consequente redução da taxa de mortalidade. (AU)

Tongue function, salivary flow rate and IgA, IgM and IgG total salivary levels in chronic chagasic patients

Although microscopic alterations have been detected in tongues and salivary glands of chagasic patients and the identification of biomarkers in saliva has proved advantageous, there are no studies evaluating tongue function and total salivary IgA, IgG and IgM levels in chronic chagasic patients. The aim of this study was to evaluate tongue function, salivary flow rate, and total salivary IgA, IgG and IgM levels comparing chronic and non-infected individuals. 37 patients were selected: chronic cardiac chagasic patients (n=6), chronic chagasic patients with the associated form of the disease (cardiopathy and megaesophagus) (n=11), and non-chagasic individuals (n=20). The tongue function underwent a phonoaudiological evaluation. The salivary flow rate was measured by sialometry. The total salivary IgA, IgG and IgM levels were evaluated by sandwich ELISA assay. Chagasic patients with the associated form of the disease presented higher salivary flow rate and lower salivary protein levels. No significant differences were noted in the lingual function or in the total salivary immunoglobulin levels among the groups. Although patients with chagasic megaesophagus presented higher levels of salivary flow and lower salivary protein, the fact that there were no significant differences in lingual function and total salivary immunoglobulin levels among the groups led to the conclusion that chronic chagas disease does not modify the lingual function or the total IgA, IgG and IgM salivary levels. The present study was the first to evaluate the function of the tongue and salivary total immunoglobulin levels in Chagas disease.

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

Aim: to compare the levels of IFN-γ, TGF-ß 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-ß 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-ß 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-ß in the gingival crevicular fluid after seven days of treatment.

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

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.

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

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.

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

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.

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

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.

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.

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.

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

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.

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

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-ß, 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-ß 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.

Dieta hiperlipídico-proteica utilizada para emagrecimento induz obesidade em ratos / Low-carbohydrate diet used for weight loss induces obesity in rats

OBJETIVO: Neste trabalho, analisa-se o efeito de dieta hiperlipídico-proteica com baixo teor de carboidrato sobre o peso corporal, peso de órgãos, consumo de ração, parâmetros bioquímicos e alterações histopatológicas no fígado de ratos. MÉTODOS: Foram utilizados 24 animais - 12 no grupo-controle e 12 no grupo-experimental - com peso médio de 160 gramas no início do experimento. Semanalmente, foram verificados o peso corporal e o consumo de ração, e ao final de oito semanas foram feitas as dosagens bioquímicas sanguíneas, pesagem de órgãos e análise histopatológica dos fígados. RESULTADOS: Os animais do grupo-experimental tiveram maior ganho de peso corporal e acumularam mais tecido adiposo que os animais do grupo-controle. Fígado, rins e baço não sofreram alterações quanto ao peso. Os animais que receberam dieta hiperlipídico-proteica tiveram um aumento na ingestão energética acumulada nas oito semanas do estudo. O grupo-experimental desenvolveu hiperglicemia e hipertrigliceridemia, aumento da fração lipoproteína de alta densidade do colesterol e da creatinina sérica quando comparado ao grupo-controle. Foi detectada esteatose hepática no grupo-experimental. CONCLUSÃO: Os resultados demonstraram que dietas pobres em carboidratos e ricas em gordura e proteínas podem acarretar alterações metabólicas prejudiciais ao organismo.

OBJECTIVE: This study analyzed the effect of a high fat, high protein and low carbohydrate diet on the body weight, organ weight, food intake and biochemical parameters of rats and the histopathological changes in their livers. METHODS: A total of 24 animals were used, 12 in the control group and 12 in the experimental group, with a mean weight of 160 grams at baseline. Body weight and food intake were collected weekly. At the end of 8 weeks, the animals were killed for the biochemical tests and weighing of organs and the livers were submitted to histopathological analysis. RESULTS: The animals in the experimental group gained more weight and accumulated more body fat than the animals in the control group. The weight of the liver, kidneys and spleen did not change. The animals fed the low carbohydrate diet consumed more calories during the 8 weeks of the study period. They also developed hyperglycemia and hypertriglyceridemia and presented high high-density lipoprotein cholesterol and serum creatinine. The experimental group also presented hepatic steatosis. CONCLUSION: The results show that low carbohydrate diets that are rich in fats and proteins may result in harmful metabolic changes in rats.

Caracterização demográfica e morfométrica das síndromes hipertensivas da gestação / Demographic and morphometric characterization of the gestational hypertensives syndromes / Caracterización demográfica y morfométrica de los síndromes hipertensivos del embarazo

As Síndromes Hipertensivas da Gestação (SHG) possuem intensidade variável de acordo com seu tipo. Com este estudo objetivou-se descrever as características demográficas materno- fetais e as alterações morfométricas placentárias nos diferentes tipos de SHG, pela análise retrospectiva dos prontuários de pacientes hipertensas, com placentas avaliadas morfologicamente, processadas para imunohistoquímica utilizando anticorpo monoclonal anti-human CD31 e analisadas morfometricamente. Os resultados demonstraram que, entre as SHG, os grupos com Hipertensão Crônica (HC) e Pré-eclâmpsia sobreposta à Hipertensão Crônica (PSHC) apresentaram idade materna superior (p=0,017). A frequência das SHG foi superior entre as multíparas. Menor idade gestacional, menores índices de Apgar e pesos placentários inferiores ao esperado para a população (p<0,05) foram observados nos casos com Pré-eclâmpsia (PE) e PSHC. Não houve diferença no número de vasos das vilosidades tronco placentárias. Nas demais, houve aumento nos casos com PE e Hipertensão Gestacional (HGE) e redução nos casos com PSHC. A importância do estudo consiste na descrição demográfica e morfológica nas SHG, visando melhorar o atendimento obstétrico e a compreensão dos diferentes tipos de SHG. A gravidade do quadro clínico das SHG tem relação com maiores intercorrências materno-fetais e com alterações no padrão vascular placentário.

The hypertensive disorders of pregnancy (SHG) have variable intensity according to their type. This study aimed to describe the demographic characteristics and maternal-fetal morphometric changes of placenta in different types of SHG by retrospective analysis of medical records of hypertensive patients with placentas evaluated morphologically, processed for immunohistochemistry using monoclonal antibody anti-human CD31 and analyzed morphometrically . The results showed that among the SHG, the groups with chronic hypertension (CH) and Pre-eclampsia superimposed on chronic hypertension (PSHC) showed higher maternal age (p = 0017). The frequency of the SHG was higher among multiparous. Lower gestational age, lower Apgar score and placental weights lower than expected for the population (p <0.05) were observed in cases with pre-eclampsia (PE) and PSHC. There was no difference in the number of vessels of placental stem villi. In the others, there was an increase in cases with PE and gestational hypertension (HGE) and reduction in cases with PSHC. The importance of the study is to describe the demographic and morphological SHG to improve the obstetric care and understanding of different types of SHG. The severity of symptoms of SHG is related to higher maternal and fetal complications and changes in placental vascular patern.

Los Síndromes Hipertensivos del Embarazo (SHG) tienen una intensidad variable de acuerdo con su tipo. El objetivo de este etudio fue describir las características demográficas materno-fetales y alteraciones morfométricas placentarias entre diferentes tipos de SHG. Los resultados mostraron que, entre los SHG, los grupos con Hipertensión Crónica (HC) e Preeclampsia relacionada a HC (PSHC) presentaron una edad materna estadísticamente superior (p=0,017). La frecuencia de los SHG fue superior entre las pacientes multíparas. Fue observada menor edad gestacional, menores índices de Apgar y pesos placentarios inferiores a los esperados para la populación general (p<0,05) en los casos con Preeclampsia (PE) y PSHC. No hubo diferencia en el número de vasos del tronco de las vellosidades placentarias. En los demás, hubo aumento en los casos con PE e Hipertensión Gestacional (HGE) y reducción en los casos con PSHC. La importancia del estudio consiste en la descripción demográfica y morfológica de los SHG, promoviendo mejorar el atendimiento obstétrico y la comprensión de los diferentes tipos de SHG. La gravedad del cuadro clínico de los SHG está relacionada con mayores complicaciones materno-fetales y con alteraciones en el padrón vascular placentario.