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Dental implants have a high success and survival rate. However, complications such as peri-implantitis (PI) are highly challenging to treat. PI is characterized by inflammation in the tissues around dental implants with progressive loss of supporting bone. To optimize dental implants' longevity in terms of health and functionality, it is crucial to understand the peri-implantitis pathophysiology. In this regard, using mouse models in research has proven clear benefits in recreating clinical circumstances. This study aimed to describe an experimental model of ligature-induced peri-implantitis in mice and determine whether there is effectiveness in inducing this disease, given the observed bone and tissue changes. The experimental peri-implantitis induction comprehends the following steps: teeth extraction, implant placement, and ligature-inducted PI. A sample of eighteen 3-week-old C57BL/6J male mice was divided into two groups, ligature (N=9) and control non-ligature (N=9). The evaluation of clinical, radiographical, and histological factors was performed. The ligature group showed significantly higher bone loss, increased soft tissue edema, and apical epithelial migration than the non-ligature group. It was concluded that this pre-clinical model can successfully induce peri-implantitis in mice.
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Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Periimplantitis , Animales , Ratones , Periimplantitis/etiología , Periimplantitis/patología , Masculino , Ligadura/métodos , Implantes Dentales/efectos adversosRESUMEN
OBJECTIVE: To assess which decontamination method(s) used for the debridement of titanium surfaces (disks and dental implants) contaminated with bacterial, most efficiently eliminate bacterial biofilms. MATERIAL AND METHODS: A systematic search was conducted in four electronic databases between January 1, 2010 and October 31, 2022. The search strategy followed the PICOS format and included only in vitro studies completed on either dental implant or titanium disk samples. The assessed outcome variable consisted of the most effective method(s)-chemical or mechanical- removing bacterial biofilm from titanium surfaces. A meta-analysis was conducted, and data was summarized through single- and multi-level random effects model (p < .05). RESULTS: The initial search resulted in 5260 articles after the removal of duplicates. After assessment by title, abstract, and full-text review, a total of 13 articles met the inclusion criteria for this review. Different decontamination methods were assessed, including both mechanical and chemical, with the most common method across studies being chlorhexidine (CHX). Significant heterogeneity was noted across the included studies. The meta-analyses only identified a significant difference in biofilm reduction when CHX treatment was compared against PBS. The remaining comparisons did not identify significant differences between the various decontamination methods. CONCLUSIONS: The present results do not demonstrate that one method of decontamination is superior in eliminating bacterial biofilm from titanium disk and implant surfaces.
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Biopelículas , Descontaminación , Implantes Dentales , Periimplantitis , Titanio , Humanos , Implantes Dentales/microbiología , Descontaminación/métodos , Periimplantitis/microbiología , Biopelículas/efectos de los fármacos , Titanio/química , Propiedades de Superficie , Clorhexidina/farmacología , Clorhexidina/uso terapéuticoRESUMEN
Cerebral small vessel disease (CSVD) is a term used to describe abnormalities in the intracranial microvasculature affecting small arteries, arterioles, capillaries, and venules. The etiology of these conditions is not fully understood but inflammation appears to play a significant role. Periodontal diseases have been associated with conditions such as stroke and dementia, which are clinical consequences of CSVD. Periodontitis is a highly prevalent chronic multifactorial inflammatory disease regulated by the host immune response against pathogenic bacterial colonization around the teeth. The inflammatory response and the microbial dysbiosis produce pro-inflammatory cytokines that can reach the brain and promote local changes. This review will explore the potential association between periodontitis and CSVD by assessing the impact of periodontitis-induced inflammation and periodontopathogenic bacteria on the underlying mechanisms leading to CSVD. Given the association of periodontitis with stroke and dementia, which are clinical features of CSVD, it may be possible to suggest a link with CSVD. Current evidence linking periodontitis with neuroimaging findings of CSVD enforces the possible link between these conditions.
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Periodontal diseases is a highly prevalent chronic condition regulated by the host immune response to pathogenic bacterial colonization on the teeth surfaces. Nutrition is a critical component in the modulation of the immune system, hence the importance of a balanced diet. With the understanding of how dietary intake composition affects various health outcomes, nutrient diversity has been reported as a modifiable risk factor for periodontal disease. Eating disorders and different dietary patterns can be associated with periodontal diseases. In this sense, balanced and healthy nutrition plays a major role in maintaining the symbiosis between oral microbiota and periodontal health. Therefore, this review seeks to report the associations found in the literature between high- or low-fat/sodium/sugar, eating disorders and periodontal diseases. It was found that some dietary patterns such as high carbohydrate/sugar, high fat, and low fiber intake may be associated with periodontal disease. In addition, the presence of eating disorders can negatively impact patients' oral health and it is related to the development of several complications, including periodontal diseases. In both situations, nutritional and vitamin deficiencies can aggravate the periodontal condition. However, the relationship between periodontal disease, dietary patterns, and eating disorders still needs more scientific support to be well established, mainly in the sense of pointing out a protective relationship between both.
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AIM: To identify Pseudomonas aeruginosa and Staphylococcus aureus in oral biofilms of intubated and non-intubated patients admitted to an Intensive Care Unit (ICU). METHODS: This was a cross-sectional study, with 30 biofilm sites sampled. S. aureus and P. aeruginosa were identified by conventional biochemical assays. Antimicrobial susceptibility was tested by disk-diffusion. RESULTS: Of 30 sites, 50% contained P. aeruginosa and 3.33% S. aureus. P. aeruginosa was detected in similar amounts in all 3 sample sites, with 5 colonized sites (50%). S. aureus colonized a single supragingival site (3.33%). There was resistance to multiple antimicrobial agents of P. aeruginosa in 7 sites (100%) and S. aureus in 1 (100%). CONCLUSIONS: This study revealed an important relationship between P. aeruginosa and S. aureus colonization at supragingival, subgingival and lingual sites and intubation, thus revealing antimicrobial resistant bacteria colonization of medical interest, which may contribute to the therapy choice directed to these microorganisms.
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Antiinfecciosos , Staphylococcus aureus , Humanos , Proyectos Piloto , Estudios Transversales , Unidades de Cuidados Intensivos , Biopelículas , Antibacterianos/farmacología , Antibacterianos/uso terapéuticoRESUMEN
OBJECTIVES: This experimental study was carried out to investigate the effects of locally delivered nanoparticles (AMG-487 NP) containing a CXCR3 antagonist in inhibiting the progression of LPS-induced inflammation, osteoclastic activity, and bone resorption on a murine model. MATERIALS AND METHODS: Thirty, 7-week-old C57BL/6 J male mice were used. Inflammatory bone loss was induced by Porphyromonas gingivalis-lipopolysaccharide (P.g.-LPS) injections between the first and second maxillary molars, bilaterally, twice a week for 6 weeks (n = 20). AMG-487 NP were incorporated into a liposome carrier and locally delivered on sites where P.g.-LPS was injected. Control mice (n = 10) were injected with vehicle only. Experimental groups included (1) control, (2) LPS, and (3) LPS + NP. At the end of 1 and 6 weeks, mice were euthanized, maxillae harvested, fixed, and stored for further analysis. RESULTS: Volumetric bone loss analysis revealed, at 1 week, an increase in bone loss in the LPS group (47.9%) compared to control (27.4%) and LPS + NP (27.8%) groups. H&E staining demonstrated reduced inflammatory infiltrate in the LPS + NP group compared to LPS group. At 6 weeks, volumetric bone loss increased in all groups; however, treatment with the CXCR3 antagonist (LPS + NP) significantly reduced bone loss compared to the LPS group. CXCR3 antagonist treatment significantly reduced osteoclast numbers when compared to LPS group at 1 and 6 weeks. CONCLUSIONS: This study showed that local delivery of a CXCR antagonist, via nanoparticles, in a bone resorption model, induced by LPS injection, was effective in reducing inflammation, osteoclast numbers, and bone loss. CLINICAL RELEVANCE: CXCR3 blockade can be regarded as a novel target for therapeutic intervention of bone loss. It can be a safe and convenient method for periodontitis treatment or prevention applicable in clinical practice.
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Pérdida de Hueso Alveolar , Resorción Ósea , Pérdida de Hueso Alveolar/tratamiento farmacológico , Pérdida de Hueso Alveolar/prevención & control , Animales , Resorción Ósea/tratamiento farmacológico , Resorción Ósea/prevención & control , Modelos Animales de Enfermedad , Inflamación , Lipopolisacáridos/farmacología , Masculino , Ratones , Ratones Endogámicos C57BL , Osteoclastos , Porphyromonas gingivalisRESUMEN
Objectives: To perform a comprehensive and integrative review of the available literature on the potential changes in the microbiome of healthy and individuals with diabetes under periodontal health and disease. Materials and Methods: The review was conducted by two independent reviewers. Indexed electronic databases (PubMed/Medline, Cochrane Library, Web of Science and Scopus) were searched, including articles published in English and dated from 5 years ago until December 2021. A manual search also was performed to identify co-related articles. Following the removal of duplicates and eligibility criteria, the articles were included in tables for analysis and described in the manuscript. Results: According to this review, diabetes mellitus was associated with significant changes in the subgingival and salivary microbiome, either in its association with periodontitis or in cases of periodontal health. In addition to affecting microbial diversity in terms of taxonomy, metagenomic studies have shown that this endocrine disorder may also be directly related to increased pathogenicity in the oral microbiome. Conclusion: Although the reviewed studies demonstrate important differences in the subgingival and salivary microbiome composition because of diabetes mellitus, further studies are needed to clarify the real effects of hyperglycemia on oral microbial profiles and support new diagnostic approaches and innovative treatments.
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Six previously undescribed tropane alkaloids, designated as erythrobezerrines A-F, were isolated from the EtOH extract from the stem bark of Erythroxylum bezerrae Plowman. Their structures were elucidated based on the interpretation of the NMR and MS data and in some instances, confirmed by X-ray diffraction analysis. The cytotoxicity of the isolated compounds was evaluated against the cancer cell lines L929, PC-3, HCT-116, SNB-19 and NCI-H460, but only erythrobezerrine C showed moderate activity with IC50 values of 3.38 and 5.43⯵M for HCT-116 and NCI-H460, respectively.
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Erythroxylaceae , Espectroscopía de Resonancia Magnética , Estructura Molecular , Corteza de la Planta , TropanosRESUMEN
AIM: To systematically review buccal bone thickness (BBT) in the anterior maxilla in different teeth, age groups and genders. MATERIALS AND METHODS: PubMed, EMBASE and Cochrane databases were searched up to April 2020. Clinical and radiographic studies reporting on BBT of maxillary anterior teeth, with at least 10 patients, were included. A meta-analysis was performed using random effect models to report differences of BBT. RESULTS: 50 studies were included. Using bone crest (BC) as a reference point, no significant differences were found in BBT between different tooth types, except for 0.16 mm (95%-CI: 0.02-0.30) increased mid-root thickness of premolars compared to canines. Using the CEJ as a reference point, canines presented with a significantly increased thickness of 0.32 mm (95%-CI: 0.11-0.54) coronally compared to laterals. When BC was used as reference, males demonstrated a significantly increased thickness of 0.21 mm (95%-CI: 0.15-0.27) apically, while middle-aged adults showed a 0.06 mm (95%-CI: -0.12, -0.01) statistically significant increase in the coronal level compared to older adults. CONCLUSIONS: Few maxillary anterior teeth have BBT greater than 1 mm. Buccal bone tends to get thicker from a coronal to apical position along the root surface and from an anterior to posterior position in the arch.
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Proceso Alveolar , Incisivo , Anciano , Tomografía Computarizada de Haz Cónico , Femenino , Humanos , Masculino , Maxilar/diagnóstico por imagen , Persona de Mediana Edad , CigomaRESUMEN
The cis-[Ru(bpy)2(Met)](PF6)2 complex, where Met = L-methionine and bpy = 2,2'-bipyridine, was prepared and fully characterized. This complex was subjected to blue and green light photolysis (453 and 505 nm, respectively) in aqueous solution, leading to the release of methionine and formation of the cis-[Ru(bpy)2(H2O)2]2+ ion. This latter photoproduct was shown to subsequently interact with DNA, while DNA photocleavage was noticed. In agreement with these reactivities, this compound exhibited an exciting antibacterial action, particularly against Gram-positive bacteria Staphylococcus aureus and Staphylococcus epidermidis, which was enhanced upon blue light irradiation. Altogether, these results showed that our strategy was successful in producing light-triggered DNA-binding agents with pharmacological potential and a likely blocking reagent for efficient peptide chemistry formation.
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Antibacterianos/farmacología , Complejos de Coordinación/farmacología , Metionina/farmacología , Rutenio/farmacología , Staphylococcus aureus/efectos de los fármacos , Staphylococcus epidermidis/efectos de los fármacos , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , ADN/efectos de los fármacos , División del ADN , Luz , Masculino , Metionina/química , Pruebas de Sensibilidad Microbiana , Procesos Fotoquímicos , Rutenio/química , Salmón , Espermatozoides/químicaRESUMEN
Supramolecular interactions between ß-lapachone (ß-lap) and cyclodextrins (CDs) were investigated by isothermal titration calorimetry. The most favorable host: guest interaction was characterized using X-ray powder diffraction (XRD), differential scanning calorimetry and thermogravimetry (DSC/TG), spectroscopy (FT-IR), spectroscopy (2D ROESY) nuclear magnetic resonance (NMR), and molecular modeling. Phase solubility diagrams showed ß-, HP-ß-, SBE-ß-, γ-, and HP-γ-CDs at 1.5% (w/w) allowed an increase in apparent solubility of ß-lap with enhancement factors of 12.0, 10.1, 11.8, 2.4, and 2.2, respectively. ß-lap has a weak interaction with γ- and HP-γ-CDs and tends to interact more favorably with ß-CD and its derivatives, especially SBE-ß-CD (K = 4160 M-1 ; ΔG = -20.66 kJ·mol-1 ). Thermodynamic analysis suggests a hydrophobic interaction associated with the displacement of water from the cavity of the CD by the ß-lap. In addition, van der Waals forces and hydrogen bonds were responsible for the formation of complexes. Taken together, the results showed intermolecular interactions between ß-lap and SBE-ß-CD, thereby confirming the formation of the inclusion complex. Molecular docking results showed 2 main orientations in which the interaction of benzene moiety at the wider rim of the SBE-ß-CD is the most stable (average docking energy of -7.0 kcal/mol). In conclusion, ß-lap:SBE-ß-CD is proposed as an approach for use in drug delivery systems in cancer research.
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Calorimetría/métodos , Ciclodextrinas/química , Modelos Moleculares , Naftoquinonas/química , Rastreo Diferencial de Calorimetría , Entropía , Cinética , Simulación del Acoplamiento Molecular , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Termogravimetría , Difracción de Rayos XRESUMEN
In this pioneer study, 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) was used to improve the solubility of the diffractaic acid (DA) via inclusion complex (DA:HP-ß-CD). Subsequently, DA:HP-ß-CD was incorporated into poly-ε-caprolactone (PCL) microspheres (DA:HP-ß-CD-MS). Microspheres containing DA (DA-MS) or DA:HP-ß-CD (DA:HP-ß-CD-MS) were prepared using the multiple W/O/W emulsion-solvent evaporation technique. The phase-solubility diagram of DA in HP-ß-CD (10-50mM) showed an AL type curve with a stability constant K1:1=821M-1. 1H NMR, FTIR, X-ray diffraction and thermal analysis showed changes in the molecular environment of DA in DA:HP-ß-CD. The molecular modeling approach suggests a guest-host complex formation between the carboxylic moiety of both DA and the host (HP-ß-CD). The mean particle size of the microspheres were ∅DA-MS=5.23±1.65µm and ∅DA:HP-ß-CD-MS=4.11±1.39µm, respectively. The zeta potential values of the microspheres were ζDA-MS=-7.85±0.32mV and ζDA:HP-ß-CD-MS=-6.93±0.46mV. Moreover, the encapsulation of DA:HP-ß-CD into microspheres resulted in a more slower release (k2=0.042±0.001; r2=0.996) when compared with DA-MS (k2=0.183±0.005; r2=0.996). The encapsulation of DA or DA:HP-ß-CD into microspheres reduced the cytotoxicity of DA (IC50=43.29µM) against Vero cells (IC50 of DA-MS=108.48µM and IC50 of DA:HP-ß-CD-MS=142.63µM).
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Anisoles/farmacología , Hidroxibenzoatos/farmacología , Microesferas , Modelos Moleculares , beta-Ciclodextrinas/química , 2-Hidroxipropil-beta-Ciclodextrina , Animales , Anisoles/química , Rastreo Diferencial de Calorimetría , Muerte Celular/efectos de los fármacos , Chlorocebus aethiops , Concentración de Iones de Hidrógeno , Hidroxibenzoatos/química , Cinética , Microscopía Electrónica de Rastreo , Conformación Molecular , Tamaño de la Partícula , Poliésteres/química , Polvos , Espectroscopía de Protones por Resonancia Magnética , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Electricidad Estática , Termogravimetría , Células Vero , Difracción de Rayos XRESUMEN
INTRODUÇÃO: A presente investigação traça o percurso teórico alicerçado na Psicologia Social do Trabalho, a qual dialoga com a Ergonomia, sabido que a prática em relacionar a Ergonomia com a Psicologia não é nova e se remete a sua constituição quanto uma disciplina científica do trabalho, já que em sua proposição estavam psicólogos e essa prática se perdura até os dias de hoje, esses em sua maioria buscam analisar em seus estudos as condições de trabalho. A nomenclatura condições de trabalho ganhou seu espaço em averiguações na área da psicologia e sociologia, contudo, pode ser vista também em outras áreas como nas engenharias e na administração. Sendo assim, a empregabilidade conceitual ganha amplitude em discussões e investigações. Sobre as condições de trabalho, é pertinente elucidar que a Ergonomia aponta as atividades repetitivas, os trabalhos detentores de força, problemas ligados à organização do trabalho, quanto ao local propriamente físico, como um fio potencializador no surgimento de transtornos psíquicos ligados ao trabalhador, e como consequência é acarretado prejuízos à organização como faltas, rotatividade e de ligamento. OBJETIVO: Diante do que foi discorrido, o estudo em questão toma como objetivo avaliar o contexto de trabalho dos profissionais do Serviço de Atendimento Móvel de Urgência (SAMU) de Fortaleza, com ênfase especial sobre a organização do trabalho, condições de trabalho e relações socioprofissionais. MATERIAL E MÉTODOS: Utilizou-se a metodologia da pesquisa descritivo-exploratória, de cunho quantitativo numa amostra composta por 247 profissionais do SAMU, tais como: enfermeiros, médicos, condutores-socorristas, pessoal do administrativo, estagiários e o pessoal do apoio. O SAMU de Fortaleza conta com 470 profissionais ativos. Aplicou-se como instrumento a Escala de Avaliação do Contexto de Trabalho (EACT) do tipo Likert de 5 pontos, que se referem à frequência de ocorrência de determinados acontecimentos, em que o valor 1 indica nunca, 2: raramente, 3: às vezes, 4: frequentemente e 5: sempre. Tal instrumento é composto por três fatores: organização do trabalho (Retrata a divisão e conteúdo das tarefas, normas, controles e ritmos de trabalho), condições de trabalho (Retrata a qualidade do ambiente físico, posto de trabalho, equipamentos e material disponibilizados para a execução do trabalho) e relações socioprofissionais (Retrata os modos de gestão do trabalho, comunicação e interação profissional). RESULTADOS: Os níveis de avaliação da EACT são como: Nível acima de 3,7: Avaliação mais negativa, grave; entre 2,3 e 3,69: Avaliação mais moderada, crítico; e abaixo de 2,29: Avaliação mais positiva, satisfatório. Posteriormente, os dados coletados foram depositados no Programa SPSS e realizadas as análises descritivas, tais como médias, desvios padrão, mínimo e máximo. Salienta-se que o projeto de pesquisa foi submetido ao Comitê de Ética da UNIFOR e recebeu parecer favorável para sua realização. Como resultado, foi verificado que o contexto de trabalho apresentou-se de modo moderado-crítico, sendo que dos fatores, separadamente, as Condições de Trabalho obtiveram escores mais altos, seguidos pelos fatores Organização do Trabalho e Relações Sócioprofissionais. CONCLUSÃO: Concluiu-se, portanto, que o contexto de trabalho em que os profissionais do SAMU realizam suas atividades carece de intervenção, principalmente, nas condições de trabalho, fazendo-se necessária a atuação dos gestores e sindicalistas responsáveis pelo SAMU, a fim de sanar a situação desfavorável observada.
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Humanos , Ambulancias , Servicios Médicos de Urgencia , Condiciones de Trabajo , Relaciones Interpersonales , TrabajoRESUMEN
INTRODUÇÃO: o foco deste estudo é a condição de trabalho no Serviço de Atendimento Médico Móvel. OBJETIVO: O objetivo do presente estudo foi averiguar o contexto de trabalho dos profissionais do Serviço de Atendimento Móvel de Urgência (SAMU) de Fortaleza. MATERIAL E MÉTODOS: O caminho metodológico traçou-se como um estudo descritivo-exploratório de cunho quantitativo, em que foi aplicada a Escala de Avaliação do Contexto de Trabalho entre 247 sujeitos. RESULTADOS: Posteriormente os dados coletados foram depositados no Programa SPSS e realizadas as análises descritivas, tais como médias, desvios padrão, mínimo e máximo. sobre os resultados encontrados, ficou constatado que o contexto de trabalho apresentou-se de modo moderado crítico. Sendo que dos fatores, separadamente, as Condições de Trabalho obteve escores mais altos, Em seguida estão os fatores Organização do Trabalho e Relações Sócioprofissionais. Com os dados analisados e discutidos, constatou-se que o contexto de trabalho em que os profissionais do SAMU realizam suas atividades carece de intervenção, principalmente, nas condições de trabalho. CONCLUSÃO: Faz-se necessário a atuação dos gestores e sindicalistas responsáveis pelo SAMU a procurar meios de sanar tal situação vivenciada por esses trabalhadores.
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Humanos , Salud Laboral , Servicios Médicos de Urgencia , ErgonomíaRESUMEN
Periodontal disease is the most common osteolytic disease in humans and is significantly increased by diabetes mellitus. We tested the hypothesis that bacterial infection induces bone loss in diabetic animals through a mechanism that involves enhanced apoptosis. Type II diabetic rats were inoculated with Aggregatibacter actinomycetemcomitans and treated with a caspase-3 inhibitor, ZDEVD-FMK, or vehicle alone. Apoptotic cells were measured with TUNEL; osteoblasts and bone area were measured in H&E sections. New bone formation was assessed by labeling with fluorescent dyes and by osteocalcin mRNA levels. Osteoclast number, eroded bone surface, and new bone formation were measured by tartrate-resistant acid phosphatase staining. Immunohistochemistry was performed with an antibody against tumor necrosis factor-α. Bacterial infection doubled the number of tumor necrosis factor-α-expressing cells and increased apoptotic cells adjacent to bone 10-fold (P < 0.05). Treatment with caspase inhibitor blocked apoptosis, increased the number of osteoclasts, and eroded bone surface (P < 0.05); yet, inhibition of apoptosis resulted in significantly greater net bone area because of an increase in new bone formation, osteoblast numbers, and an increase in bone coupling. Thus, bacterial infection in diabetic rats stimulates periodontitis, in part through enhanced apoptosis of osteoblastic cells that reduces osseous coupling through a caspase-3-dependent mechanism.
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Aggregatibacter actinomycetemcomitans , Pérdida de Hueso Alveolar , Complicaciones de la Diabetes , Diabetes Mellitus Experimental , Infecciones por Pasteurellaceae , Periodontitis , Pérdida de Hueso Alveolar/metabolismo , Pérdida de Hueso Alveolar/microbiología , Pérdida de Hueso Alveolar/patología , Animales , Apoptosis , Complicaciones de la Diabetes/metabolismo , Complicaciones de la Diabetes/microbiología , Complicaciones de la Diabetes/patología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/microbiología , Diabetes Mellitus Experimental/patología , Femenino , Humanos , Masculino , Osteoclastos/metabolismo , Osteoclastos/patología , Infecciones por Pasteurellaceae/metabolismo , Infecciones por Pasteurellaceae/microbiología , Infecciones por Pasteurellaceae/patología , Periodontitis/metabolismo , Periodontitis/microbiología , Periodontitis/patología , Ratas , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The purpose of this study was to test the hypothesis that diabetes aggravates periodontal destruction induced by Aggregatibacter actinomycetemcomitans infection. Thirty-eight diabetic and 33 normal rats were inoculated with A. actinomycetemcomitans and euthanized at baseline and at 4, 5, and 6 weeks after inoculation. Bone loss and the infiltration of polymorphonuclear leukocytes (PMNs) in gingival epithelium were measured in hematoxylin-eosin-stained sections. The induction of tumor necrosis factor alpha (TNF-α) was evaluated by immunohistochemistry and of apoptotic cells by a TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling) assay. After A. actinomycetemcomitans infection, the bone loss in diabetic rats was 1.7-fold and the PMN infiltration 1.6-fold higher than in normoglycemic rats (P < 0.05). The induction of TNF-α was 1.5-fold higher and of apoptotic cells was up to 3-fold higher in diabetic versus normoglycemic rats (P < 0.05). Treatment with a caspase-3 inhibitor significantly blocked noninflammatory cell apoptosis induced by A. actinomycetemcomitans infection in gingival epithelium and connective tissue (P < 0.05). These results provide new insight into how diabetes aggravates A. actinomycetemcomitans-induced periodontal destruction in rats by significantly increasing the inflammatory response, leading to increased bone loss and enhancing apoptosis of gingival epithelial and connective tissue cells through a caspase-3-dependent mechanism. Antibiotics had a more pronounced effect on many of these parameters in diabetic than in normoglycemic rats, suggesting a deficiency in the capacity of diabetic animals to resist infection.
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Infecciones por Actinobacillus/patología , Aggregatibacter actinomycetemcomitans , Apoptosis , Caspasa 3/metabolismo , Diabetes Mellitus/metabolismo , Periodontitis/metabolismo , Aggregatibacter actinomycetemcomitans/inmunología , Animales , Antibacterianos/farmacología , Anticuerpos Antibacterianos/sangre , Adhesión Bacteriana , Caspasa 3/genética , Inhibidores de Caspasas , Diabetes Mellitus/patología , Regulación Enzimológica de la Expresión Génica , Inmunoglobulina G/sangre , Periodontitis/patología , Ratas , Ratas WistarRESUMEN
AIM: To characterize the histologic and cellular response to A. actinomycetemcomitans (Aa) infection. MATERIAL & METHODS: Wistar rats infected with Aa were evaluated for antibody response, oral Aa colonization, loss of attachment, PMN recruitment, TNF-α in the junctional epithelium and connective tissue, osteoclasts and adaptive immune response in local lymph nodes at baseline and 4, 5 or 6 weeks after infection. Some groups were given antibacterial treatment at 4 weeks. RESULTS: An antibody response against Aa occurred within 4 weeks of infection, and 78% of inoculated rats had detectable Aa in the oral cavity (p < 0.05). Aa infection significantly increased loss of attachment that was reversed by antibacterial treatment (p < 0.05). TNF-α expression in the junctional epithelium followed the same pattern. Aa stimulated high osteoclast formation and TNF-α expression in the connective tissue (p < 0.05). PMN recruitment significantly increased after Aa infection (p < 0.05). Aa also increased the number of CD8(+) T cells (p < 0.05), but not CD4(+) T cells or regulatory T cells (Tregs) (p > 0.05). CONCLUSION: Aa infection stimulated a local response that increased numbers of PMNs and TNF-α expression in the junctional epithelium and loss of attachment. Both TNF-α expression in JE and loss of attachment was reversed by antibiotic treatment. Aa infection also increased TNF-α in the connective tissue, osteoclast numbers and CD8(+) T cells in lymph nodes. The results link Aa infection with important characteristics of periodontal destruction.