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BACKGROUND: Vascular endothelial growth factor (VEGF) is a master regulator and is required for the effective coupling of angiogenesis and osteogenesis supporting both skeletal development and postnatal bone repair. A direct role for VEGF in intramembranous-derived osteoblast growth and differentiation is not clear. We investigated the expression of primary alveolar osteoblast VEGF receptors and the subsequent effects on mineralization and nodule formation in vitro following VEGFR inhibition. METHODS: Primary human alveolar osteoblasts (HAOBs) were cultured in the presence of VEGF receptor inhibitors, exogenous VEGF or the bisphosphonate, zoledronic acid. VEGF, VEGFR1 and VEGFR2 mRNA expression and nodule formation following 21 days of culture. VEGFR1 protein expression was examined using immunofluorescence after 48 h. RESULTS: The HAOBs expressed high levels of VEGF and VEGFR1 protein but VEGFR2 was not detected. The VEGFR1/2 inhibitors, ZM306416 and KRN633, lead to a dose-dependent decrease in mineralization. Treatment with zoledronic acid showed no difference in HAOB VEGF receptor expression. CONCLUSION: VEGF/VEGFR1 pathway appears to be important for intramembranous-derived osteoblast differentiation and maturation in vitro.
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Osteoblastos , Factor A de Crecimiento Endotelial Vascular , Diferenciación Celular , Humanos , Osteogénesis , Receptores de Factores de Crecimiento Endotelial VascularRESUMEN
BACKGROUND AND OBJECTIVE: The salivary transcriptome may present as a readily available and non-invasive source of potential biomarkers. The development of chronic periodontitis is determined by individual patient susceptibility; hence, the aim of this study was to determine the potential of the salivary transcriptome as a biomarker of disease susceptibility using chronic periodontitis as an example. MATERIAL AND METHODS: Using an Oragene® RNA kit, the total RNA was purified from the saliva of 10 patients with chronic periodontitis and 10 patients without chronic periodontitis. The quantity and quality of the total RNA was determined, and a measure of gene expression via cDNA was undertaken using the Affymetrix microarray system. The microarray profiling result was further validated by real-time quantitative polymerase chain reaction. RESULTS: Spectrophotometric analysis showed the total RNA purified from each participant ranged from 0.92 µg/500 µL to 62.85 µg/500 µL. There was great variability in the quantity of total RNA obtained from the 2 groups in the study with a mean of 10.21 ± 12.71 µg/500 µL for the periodontitis group and 15.97 ± 23.47 µg/500 µL for the control group. Further the RNA purity (based on the A260 /A280 ratio) for the majority of participants (9 periodontitis and 6 controls) were within the acceptable limits for downstream analysis (2.0 ± 0.1). The study samples, showed 2 distinct bands at 23S (3800 bp) and 16S (1500 bp) characteristic of bacterial rRNA. Preliminary microarray analysis was performed for 4 samples (P2, P6, H5 and H9). The percentage of genes present in each of the 4 samples was not consistent with about 1.8%-18.7% of genes being detected. Quantitative real-time polymerase chain reaction confirmed that the total RNA purified from each sample was mainly bacterial RNA (Uni 16S) with minimal human mRNA. CONCLUSION: This study showed that minimal amounts of human RNA were able to be isolated from the saliva of patients with periodontitis as well as controls. Further work is required to enhance the extraction process of human mRNA from saliva if the salivary transcriptome is to be used in determining individual patient susceptibility.
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Biomarcadores , Periodontitis Crónica/diagnóstico , Susceptibilidad a Enfermedades/diagnóstico , Perfilación de la Expresión Génica/métodos , Patología Molecular/métodos , Saliva/metabolismo , Transcriptoma , Bacterias/genética , Bacterias/metabolismo , Periodontitis Crónica/genética , Periodontitis Crónica/metabolismo , Femenino , Expresión Génica , Humanos , Masculino , Análisis por Micromatrices , Persona de Mediana Edad , ARN/análisis , ARN Mensajero/análisis , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
AIMS: This study investigated the association between the prevalence of oral health problems (caries, gingivitis, mucosal pigmentation and enamel defects in one to 5 year-old children exposed and not exposed to environmental tobacco smoke before and/or after birth. Exposure to environmental tobacco smoke (ETS) in childhood may have significant health effects. METHODS: A structured questionnaire was used to collect data on a child's current and previous illnesses, oral health behaviours, dietary habits, parental smoking behaviours and parents' dental history. The intraoral examination recorded dental caries (dmfs), enamel defects, gingival health, melanin pigmentation and soft tissue health. Stimulated saliva was collected. Total sIgA levels were quantified using indirect competitive ELISA with a SalimetricsTM kit. RESULTS: The 44 children (aged 15-69 months) recruited were divided into two groups: ETS and non-ETS (control). There were 22 children in each: 16 who were exposed to ETS during and after gestation were identified as the ETSB subgroup. Participants exposed to ETS were more likely to have had upper respiratory tract and middle ear infections during the neonatal period and had higher mean dmft, mean dmfs, mean percent of surfaces with demarcated opacities and mean GI than the non-ETS participants. The children exposed to ETS before and after birth had the highest occurrence of enamel opacities showed a higher risk for dental caries even though more children in this group used the recommended fluoride toothpaste (1000 ppm fluoride). Mothers who smoked either never breastfed their children or breastfed their children for less than the recommended period of 6 months. Children exposed to ETS were shown to have higher mean total sIgA (µg/ml) than the children in the control group. CONCLUSIONS: Associations between ETS exposure before and after gestation and oral health, including salivary changes in young children were shown in the present study. Dental health professionals should include a question about household smoking in children's dental histories, which would allow opportunities to discuss the impact of smoking on child oral health. Longitudinal oral health studies should include a history of maternal smoking during pregnancy and afterwards.
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Salud Bucal , Contaminación por Humo de Tabaco/efectos adversos , Lactancia Materna/estadística & datos numéricos , Estudios de Casos y Controles , Niño , Preescolar , Caries Dental/epidemiología , Femenino , Humanos , Inmunoglobulina A/análisis , Lactante , Masculino , Nueva Zelanda/epidemiología , Otitis Media/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Saliva/química , Encuestas y Cuestionarios , Contaminación por Humo de Tabaco/estadística & datos numéricosRESUMEN
BACKGROUND AND OBJECTIVE: Triclosan/copolymer toothpaste is effective in controlling plaque and gingivitis and in slowing the progression of periodontitis. This study describes its influence on microbiological and clinical outcomes, over a 5-year period, in patients with established cardiovascular disease (CVD). MATERIAL AND METHODS: Four-hundred and thirty-eight patients were recruited from the Cardiovascular Unit at The Prince Charles Hospital, Brisbane, Australia, and randomized to triclosan or placebo groups. Six sites per tooth were examined annually for probing pocket depth and loss of attachment. These outcomes were analysed, using generalized linear modelling, in 381 patients who had measurements from consecutive examinations. Concurrent load of the periodontal pathogens Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Tannerella forsythia and Porphyromonas gingivalis was determined, using quantitative real-time PCR, in 437 patients with baseline plaque samples. Group comparisons were expressed as geometric means. The chi-square test was used to test for differences between the two groups of patients with regard to the proportion of patients with different numbers of bacterial species. RESULTS: There was no difference in general health or periodontal status between the groups at baseline. There was a significant reduction in the number of interproximal sites showing loss of attachment between examinations, by 21% on average (p < 0.01), in the triclosan group compared with the placebo group. The prevalence of patients with F. nucleatum and A. actinomycetemcomitans was high and remained relatively constant throughout the 5 years of the study. In contrast, the prevalence of T. forsythia and P. gingivalis showed more variability; however, there was no significant difference between the groups, at any time point, in the prevalence of any organism. A significant difference in the geometric means for P. gingivalis (p = 0.01) was seen at years 1 and 4, and for F. nucleatum (p = 0.01) and in the total bacterial load (p = 0.03) at year 2; however, these differences were not statistically significant following a Bonferroni correction for multiple comparisons. There was no difference between the groups in the geometric means for each organism at year 5. CONCLUSION: Within the limitations of the study, these data suggest that the use of triclosan/copolymer toothpaste significantly slowed the progression of periodontitis in patients with CVD but that it had little influence on key subgingival periodontopathic bacteria in these patients over the 5 years of the study.
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Antiinfecciosos Locales/uso terapéutico , Enfermedades Cardiovasculares/complicaciones , Periodontitis/prevención & control , Pastas de Dientes/uso terapéutico , Triclosán/uso terapéutico , Aggregatibacter actinomycetemcomitans/efectos de los fármacos , Progresión de la Enfermedad , Femenino , Fusobacterium nucleatum/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Pérdida de la Inserción Periodontal/complicaciones , Pérdida de la Inserción Periodontal/tratamiento farmacológico , Pérdida de la Inserción Periodontal/prevención & control , Bolsa Periodontal/complicaciones , Bolsa Periodontal/tratamiento farmacológico , Bolsa Periodontal/prevención & control , Periodontitis/complicaciones , Periodontitis/tratamiento farmacológico , Periodontitis/microbiología , Porphyromonas gingivalis/efectos de los fármacos , Reacción en Cadena en Tiempo Real de la Polimerasa , Tannerella forsythia/efectos de los fármacosRESUMEN
Several systematic reviews with meta-analyses on the effectiveness of periodontal treatment to improve glycaemic control have been published. So far no overview of these systematic reviews has been performed. The main objective of this report was to assess critically these systematic reviews to provide the reader with a high-level synthesis of research evidence. MEDLINE (via PubMed) and EMBASE databases were searched independently and in duplicate to identify systematic reviews with meta-analyses of clinical studies that assessed the relationship between diabetes mellitus and periodontitis. The last database search was performed on 10 March 2015. The reference lists of included systematic reviews were also scrutinized for further publications. The methodological quality of the included systematic reviews was assessed independently with two validated checklists (AMSTAR and OQAQ) by two authors. Disagreements in the assessment were resolved by consensus. A total of 226 potential publications were initially retrieved. Eleven systematic reviews with meta-analyses were finally included. Glycosylated haemoglobin A1c (HbA1c) was the most commonly used clinical endpoint. Meta-analytic estimates from systematic reviews generated an average reduction of 0.46% (median 0.40%) of HbA1c in patients with diabetes mellitus who received periodontal treatment. These meta-analyses had, nevertheless, methodological limitations such as inclusion of trials with different types of risk of bias that hinder more robust conclusions. A recent meta-analysis that included recently published large randomized controlled trials did not show significant change in the level of HbA1c at the 6 mo follow-up. The AMSTAR checklist generated results that were more conservative than OQAQ. Findings from this overview do not support the information that periodontal treatment may improve glycaemic control. Methodological issues described in this overview may guide further research on this topic.
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Diabetes Mellitus/terapia , Hemoglobina Glucada/análisis , Enfermedades Periodontales/terapia , Diabetes Mellitus/etiología , Humanos , Enfermedades Periodontales/complicaciones , Periodontitis/complicaciones , Periodontitis/terapia , Resultado del TratamientoRESUMEN
INTRODUCTION: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious complication of bisphosphonate therapy. The mechanism underlying BRONJ pathogenesis is poorly understood. OBJECTIVES: To determine the effects of zoledronic acid (ZA) and geranylgeraniol (GGOH) on the mevalonate pathway (MVP) in osteoblasts generated from the human mandibular alveolar bone in terms of cell viability/proliferation, migration, apoptosis and gene expression. MATERIALS AND METHODS: Primary human osteoblasts (HOBs) isolated from the mandibular alveolar bone were phenotyped. HOBs were cultured with or without ZA and GGOH for up to 72 h. Cellular behaviour was examined using a CellTiter-Blue® viability assay, an Ibidi culture-insert migration assay, an Apo-ONE® Homogeneous Caspase-3/7 apoptosis assay and transmission electron microscopy (TEM). Quantitative real-time reverse transcriptase polymerase chain reaction (qRT2-PCR) was used to determine the simultaneous expression of 168 osteogenic and angiogenic genes modulated in the presence of ZA and GGOH. RESULTS: ZA decreased cell viability and migration and induced apoptosis in HOBs. TEM revealed signs of apoptosis in ZA-treated HOBs. However, the co-addition of GGOH ameliorated the effect of ZA and partially restored the cells to the control state. Twenty-eight genes in the osteogenic array and 27 genes in the angiogenic array were significantly regulated in the presence of ZA compared with those in the controls at one or more time points. CONCLUSION: The cytotoxic effect of ZA on HOBs and its reversal by the addition of GGOH suggests that the effect of ZA on HOBs is mediated via the MVP. CLINICAL RELEVANCE: The results suggest that GGOH could be used as a possible therapeutic/preventive strategy for BRONJ.
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Proceso Alveolar/citología , Conservadores de la Densidad Ósea/farmacología , Difosfonatos/farmacología , Diterpenos/farmacología , Imidazoles/farmacología , Osteoblastos/efectos de los fármacos , Adolescente , Adulto , Apoptosis , Biomarcadores/análisis , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Femenino , Expresión Génica , Humanos , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Ácido ZoledrónicoRESUMEN
BACKGROUND: Inflammatory periodontal diseases are initiated by microbial biofilms. The reduction of the biofilm is important in the management of the disease. This study compares periodontopathogen levels following the treatment of chronic periodontitis using Er:YAG laser (ERL) debridement and mechanical scaling and root planing (SRP). METHODS: Using a split-mouth design, two quadrants were randomly allocated for treatment. Two hundred and fifty-two subgingival plaque samples were collected from 21 patients, before treatment (baseline) and at 6 and 12 weeks post-therapy. Multiplex qPCR was used to determine relative levels of Porphyromonas gingivalis (Pg), Treponema denticola (Td), Tannerella forsythensis (Tf), and Aggregatibacter actinomycetemcomitans (Aa). RESULTS: Tf and Pg were significantly reduced post-treatment for both ERL and SRP. ERL treatment resulted in a reduction of Td at 12 weeks. Following SRP treatment Aa was significantly reduced at 12 weeks. No statistically significant difference was seen when treatments were compared at 6 and 12 weeks. CONCLUSIONS: A comparable reduction in the level of the four periodontal pathogens assayed was achieved with Er:YAG laser debridement and mechanical scaling and root planing.
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BACKGROUND: Osteonecrosis of the jaws is recognised as a serious complication for patients receiving bisphosphonates. The anti-angiogenic effects of bisphosphonates have been implicated in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). The purpose of this study was to determine the effects of zoledronic acid on cultured human gingival fibroblasts in relation to the modulation of genes associated with angiogenic regulation. METHODS: Primary cultures of fibroblasts were developed from gingival tissues excised during crown-lengthening surgery from three patients. Cells were cultured with and without 30µM zoledronic acid for 6, 12 and 24h and cellular proliferation and migration investigated using CellTiter-Blue and scratch wound assays, respectively. Gene expression was determined using semi-quantitative PCR array technology that allowed the analysis of 84 pathway-focused genes known to be important in the regulation of angiogenesis. RESULTS: Zoledronic acid increased the proliferation of the gingival fibroblasts in a dose dependent manner with 12 and 24h of exposure. Scratch wounding of the human gingival fibroblasts and treatment with increasing doses and time exposure to zoledronic acid (ZA) inhibited their migration. Statistically significant increases in gene expression were found for RHOB, VEGFA, CD55 and BMP2 (p≤0.05) in response to 30µM zoledronic acid. CCL2 and IL6 genes were significantly downregulated (p≤0.05). CONCLUSIONS: The regulation of the prenylated protein RHOB in this study was consistent with the known effects of zoledronic acid on the mevalonate pathway. The down regulation of CCL2 and IL6 and the upregulation of CD55 may be associated with suppression of inflammation. An increase in VEGFA and BMP2 gene expression suggests that fibroblasts respond to zoledronic acid by producing a proangiogenic environment.
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Conservadores de la Densidad Ósea/farmacología , Difosfonatos/farmacología , Fibroblastos/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Encía/citología , Imidazoles/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Proteína Morfogenética Ósea 2/metabolismo , Antígenos CD55/metabolismo , Movimiento Celular , Proliferación Celular , Células Cultivadas , Quimiocina CCL2/metabolismo , Humanos , Interleucina-6/metabolismo , Reacción en Cadena de la Polimerasa , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/metabolismo , Ácido Zoledrónico , Proteína de Unión al GTP rhoB/metabolismoRESUMEN
The aims of this study were to determine the presence and distribution of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor-2 (VEGFR2) in dentigerous cysts compared with normal dental follicles as a control tissue and to evaluate endothelial cells and proliferating cells as indicators of angiogenic activity in these tissues.Twenty specimens histologically diagnosed as dentigerous cysts and 20 dental follicle specimens were included. Immunohistochemistry (IHC) using anti-VEGF and anti-VEGFR2 antibodies stained for the growth factor and its receptor, while anti-CD34 and anti-CD146 antibodies were used to identify endothelial cells. Anti-proliferating cell nuclear antigen (PCNA) antibody detected proliferating cells within the specimens. Slides were examined microscopically and results evaluated using kappa statistics, negative binomial regression and ordinal logistic regression.The mean age for patients with dentigerous cysts was 23 years and they were more common in males. Proteins for VEGF, VEGFR2, PCNA, CD34, and CD146 were expressed in all dentigerous cysts and dental follicles. VEGF and VEGFR2 were expressed on several cell types within the tissues, however there was a significantly greater percentage of positive staining in dentigerous cysts compared with dental follicles (odds ratioâ=â31.24, pâ<â0.001). CD34(+), CD146(+), and PCNA(+) cells were observed in both dentigerous cysts and dental follicles but for all markers there were significantly more positive cells in dentigerous cysts (pâ<â0.001); this was especially evident in cases associated with inflammation. PCNA was seen in most endothelial cells lining small thin walled blood vessels suggesting endothelial proliferation. There was a high level of intra- and inter-examiner agreement (kappa 0.77 and 0.75, respectively).VEGF and VEGFR2 and angiogenic activity are present in dental follicles and dentigerous cysts and may contribute to local bone resorption for tooth eruption or the development and progression of dentigerous cysts.
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Quiste Dentígero/metabolismo , Células Endoteliales/metabolismo , Tercer Molar/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adolescente , Adulto , Proliferación Celular/fisiología , Quiste Dentígero/patología , Femenino , Humanos , Inmunohistoquímica/métodos , Inflamación/patología , Masculino , Neovascularización Patológica/patología , Adulto JovenRESUMEN
OBJECTIVES: This study aimed to investigate treatment protocols and opinions towards direct pulp capping (DPC) amongst New Zealand (NZ) general dental practitioners (GDP) through a Practice Based Research Network (PBRN) study. DESIGN: Mixed-methods approach using qualitative thematic and quantitative analysis. METHODS: An on-line survey containing Likert scale items and open-ended questions was distributed to GDPs on the Dental Council of New Zealand (DCNZ) register (2012) to collect information on practitioner demographics, treatment protocols, continuing professional development (CPD) and philosophies towards DPC. RESULTs: Two hundred and ten GDPs from North and South Islands providing care in main centres and rural areas engaged with the PBRN and participated in the study. Almost all performed DPC treatment although it was not a common procedure. DPC was perceived as 'successful' or 'very successful' by 95% of respondents, mostly for cases of reversible pulpitis. Most provided DPC for patients of all ages but younger patients were perceived to have the best clinical outcomes. Calcium hydroxide and MTA were the most commonly used materials for DPC. MTA was believed to have the best outcome but cost and handling properties were barriers to its use. The majority of respondents had participated in CPD related to vital pulp therapy and regarded this treatment as conservative and providing time and financial benefits compared with more invasive treatment. Clinicians' timeframes for assessing healing were variable, and combined clinical and radiographic findings were considered most useful. CONCLUSION: New Zealand dentists perceive DPC as a successful and conservative treatment in selected cases. The findings have provided insights into engagement of NZ dentists in using research to inform everyday clinical practice through a PBRN study.
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Recubrimiento de la Pulpa Dental/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Anciano , Compuestos de Aluminio/economía , Compuestos de Aluminio/uso terapéutico , Actitud del Personal de Salud , Compuestos de Calcio/economía , Compuestos de Calcio/uso terapéutico , Hidróxido de Calcio/uso terapéutico , Investigación Participativa Basada en la Comunidad , Toma de Decisiones , Recubrimiento de la Pulpa Dental/economía , Exposición de la Pulpa Dental/terapia , Combinación de Medicamentos , Costos de los Medicamentos , Educación Continua en Odontología , Femenino , Odontología General , Humanos , Masculino , Persona de Mediana Edad , Nueva Zelanda , Óxidos/economía , Óxidos/uso terapéutico , Pautas de la Práctica en Odontología , Materiales de Recubrimiento Pulpar y Pulpectomía/uso terapéutico , Pulpitis/terapia , Investigación Cualitativa , Silicatos/economía , Silicatos/uso terapéutico , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVE: Modeling of periodontal bone regeneration in a large animal enables better examination of the spatial and temporal regulation of osteogenesis and the remodeling of the healing defect. RANK, RANKL and osteoprotegerin (OPG) are known to be important regulators of bone healing. The aim of this study was to create periodontal defects surgically in a large animal model and to examine bone regeneration and the expression of RANK, RANKL and OPG proteins in the defect site during bone regeneration. MATERIAL AND METHODS: Periodontal defects were made in the furcation of the second mandibular premolar of sheep. Wound healing was examined 6 h, and 1, 4 and 6 wk after surgery and in control tissue. The teeth and defect region were decalcified and paraffin embedded. Immunohistochemistry for RANK, RANKL and OPG was conducted. Osteoclasts were identified using TRAP staining. RESULTS: The defects were examined at different time points after surgery and by 6 wk the defect region had fully regenerated with new bone, albeit less dense than that in the unwounded controls. RANK-positive osteoclasts were present at the edge of the wound from week 1 and were found within the defect at week 6, corresponding to osteoclast activation and bone remodeling. RANKL staining increased from week 1 compared with unwounded tissue, and peaked at 4 and 6 wk, as the osteoblast numbers increased. At the same time, OPG immunostaining was high in controls and at week 6, suggesting that it may act to block RANKL and control the bone remodeling within the defect. CONCLUSION: Distinctive temporal and spatial expression patterns for RANK, RANKL and OPG proteins were observed during healing of surgically created periodontal wounds in a sheep model. The research identifies possible therapeutic approaches to periodontal bone repair via modulation of these members of the tumor necrosis factor family.
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Defectos de Furcación/metabolismo , Osteoprotegerina/análisis , Ligando RANK/análisis , Receptor Activador del Factor Nuclear kappa-B/análisis , Animales , Diente Premolar/patología , Densidad Ósea/fisiología , Regeneración Ósea/fisiología , Remodelación Ósea/fisiología , Tejido Conectivo/patología , Modelos Animales de Enfermedad , Femenino , Defectos de Furcación/patología , Enfermedades Mandibulares/metabolismo , Osteoblastos/patología , Osteoclastos/patología , Osteogénesis/fisiología , Ovinos , Fosfatasa Ácida Tartratorresistente/análisis , Factores de Tiempo , Cicatrización de Heridas/fisiologíaRESUMEN
BACKGROUND: Systemic antimicrobials have been used as an adjunctive therapy for the treatment of periodontitis. Nevertheless, it is unclear whether the use of antimicrobials may improve tooth survival in patients with periodontitis. The main objective of this overview of systematic reviews (SRs) with meta-analyses was to assess the evidence supporting systemic antimicrobials for improving tooth survival in patients suffering from periodontitis. Information on adverse events was also extracted from SRs. METHODS: PubMed and EMBASE databases were searched independently (up to 1st August 2013) to identify SRs with meta-analyses on the use of systemic antimicrobials as an adjunctive treatment to scaling and root planing (SRP) in the treatment of periodontitis. Tooth survival and adverse events were assessed. Clinical effect was also assessed based on endpoints including clinical attachment level and probing depth. The methodological quality of the SRs was assessed by two authors using two checklists (AMSTAR and OQAQ). RESULTS: No data on tooth survival after treatment with SRP and antimicrobials were found. Nine SRs were included in this overview. Three SRs showed statistically significant outcome improvement with the use of antimicrobials, although the clinical relevance may be questionable. One SR showed better results based on surrogate endpoints; however, short-term adverse events were more pronounced with the use of antimicrobials. The reporting of long-term data on clinical effects, adverse events and bacterial resistance is scarce. The SRs were of heterogeneous quality. CONCLUSIONS: Evidence of the efficacy of systemic antimicrobials on improving tooth survival is lacking. Further research focused on tooth survival and adverse events should be performed to provide more robust evidence of the benefits of using systemic antimicrobials for treating periodontitis.
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Antiinfecciosos/uso terapéutico , Periodontitis/tratamiento farmacológico , Antiinfecciosos/administración & dosificación , Antiinfecciosos/efectos adversos , HumanosRESUMEN
The mevalonate pathway (MVP) and the anti-angiogenic effect of bisphosphonates have been shown to play a role in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). This study determined the effect of the bisphosphonate, zoledronic acid and the replenishment of the MVP by geranylgeraniol on human gingival fibroblasts. Cell viability, apoptosis, morphological analysis using transmission electron microscopy, and gene expression for vascular endothelial growth factor A, bone morphogenic protein 2, ras homologue gene family member B, epiregulin and interferon-alpha were conducted. Results showed cellular viability was decreased in the presence of zoledronic acid and the co-addition of zoledronic acid with geranylgeraniol restored cell viability to control levels. Caspase 3/7 was detected in zoledronic-acid-treated cells indicating apoptosis. Transmission electron microscopy revealed dilation of the rough endoplasmic reticulum with zoledronic acid and the appearance of multiple lipid-like vesicles following the addition of geranylgeraniol. Zoledronic acid significantly (P < 0.05, FR > ± 2) up-regulated vascular endothelial growth factor A, bone morphogenic protein 2, ras homologue gene family member B and epiregulin at one or more time points but not interferon-alpha. Addition of geranylgeraniol resulted in a reduction in the expression of all five genes compared with zoledronic-acid-treated human gingival fibroblasts. The study concluded geranylgeraniol partially reversed the effects of zoledronic acid in human gingival fibroblasts both at the cellular and genetic levels, suggesting the regulation of these genes is mediated via the mevalonate pathway.
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Conservadores de la Densidad Ósea/farmacología , Difosfonatos/farmacología , Diterpenos/farmacología , Fibroblastos/efectos de los fármacos , Encía/efectos de los fármacos , Imidazoles/farmacología , Neovascularización Fisiológica/efectos de los fármacos , Adulto , Apoptosis/efectos de los fármacos , Proteína Morfogenética Ósea 2/efectos de los fármacos , Técnicas de Cultivo de Célula , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Epirregulina/análisis , Farnesol/farmacología , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Encía/citología , Humanos , Interferón-alfa/efectos de los fármacos , Ácido Mevalónico/metabolismo , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Neovascularización Fisiológica/genética , Fosfatos de Poliisoprenilo/metabolismo , Sesquiterpenos/metabolismo , Transducción de Señal/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/genética , Ácido Zoledrónico , Proteína de Unión al GTP rhoB/efectos de los fármacosRESUMEN
BACKGROUND AND OBJECTIVE: There is a paucity of data in relation to the possible emergence of triclosan (TCS)-resistant bacteria following long-term exposure to TCS toothpaste. Therefore, this study investigated whether long-term continuous exposure to TCS in toothpaste selects for TCS-resistant bacteria within the oral biofilm. MATERIAL AND METHODS: Dental plaque samples were collected from 40 individuals during year 5 of a randomised controlled trial. Participants had been randomly assigned to use TCS (3000 µg/mL TCS) (n = 18) or placebo toothpaste (n = 22). Diluted plaque samples were plated on to Wilkins-Chalgren agar plates containing 5% (v/v) laked sheep red blood cells and TCS (concentrations ranging from 25 to 150 µg/mL) and incubated at 37 °C under microaerophilic and anaerobic conditions for 2-10 d. Selected bacterial isolates were identified by partial 16S rDNA sequencing and TCS minimum inhibitory concentration (MIC) determined for each isolate. RESULTS: At 3000 µg/mL TCS no growth was observed under microaerophilic or anaerobic conditions in either group. The MICs of TCS for all isolates ranged from 125 to 1000 µg/mL in both groups. Species common to both groups had similar MICs. Veillonella parvula and Campylobacter gracilis were the most frequent isolates from both groups, with similar MICs in both groups. CONCLUSION: The use of TCS-containing toothpaste did not appear to lead to an increase in MIC of TCS of oral bacterial isolates.
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Antiinfecciosos Locales/uso terapéutico , Bacterias/efectos de los fármacos , Biopelículas/efectos de los fármacos , Farmacorresistencia Bacteriana , Pastas de Dientes/uso terapéutico , Triclosán/uso terapéutico , Aggregatibacter actinomycetemcomitans/efectos de los fármacos , Aggregatibacter actinomycetemcomitans/aislamiento & purificación , Bacterias/clasificación , Técnicas Bacteriológicas , Campylobacter/efectos de los fármacos , Campylobacter/aislamiento & purificación , Periodontitis Crónica/prevención & control , Placa Dental/microbiología , Placa Dental/prevención & control , Estudios de Seguimiento , Fusobacterium nucleatum/efectos de los fármacos , Fusobacterium nucleatum/aislamiento & purificación , Humanos , Pruebas de Sensibilidad Microbiana , Placebos , Porphyromonas gingivalis/efectos de los fármacos , Porphyromonas gingivalis/aislamiento & purificación , Prevotella/efectos de los fármacos , Prevotella/aislamiento & purificación , Streptococcus anginosus/efectos de los fármacos , Streptococcus anginosus/aislamiento & purificación , Streptococcus mutans/efectos de los fármacos , Streptococcus mutans/aislamiento & purificación , Veillonella/efectos de los fármacos , Veillonella/aislamiento & purificaciónRESUMEN
Modern population based oral health management requires a complete understanding of the impact of disease in order to provide efficient and effective oral health care and guidance. Periodontitis is an important cause of tooth loss and has been shown to be associated with a number of systemic conditions. The impact of oral conditions and disorders on quality of life has been extensively studied. However, the impact of periodontitis on quality of life has received less attention. This review summarizes the literature on the impact of periodontitis on oral health-related quality of life (OHRQoL). Relevant publications were identified after searching the MEDLINE and EMBASE electronic databases. Screening of titles and abstracts and data extraction was conducted. Only observational studies were included in this review. Most of the reviewed studies reported a negative impact of periodontitis on OHRQoL. However, the reporting standards varied across studies. Moreover, most of the studies were conducted in developed countries.
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Salud Bucal , Periodontitis/complicaciones , Calidad de Vida , Humanos , Estudios Observacionales como AsuntoRESUMEN
BACKGROUND: Previous studies have demonstrated variable effects on systemic inflammatory and immune responses following improved periodontal health. This study examined changes in serum levels of the inflammatory mediators IL-1ß, IL-6, TNF-α and sICAM-1, and antibodies to Porphyromonas gingivalis, human heat shock protein (hHSP) 60 and P. gingivalis GroEL following improvement in periodontal health in high cardiovascular (CV) risk and low CV-risk patients. METHODS: Patients retrospectively selected from a longitudinal study, had undergone yearly periodontal examinations and peripheral blood collections. They had demonstrated a quantifiable improvement in periodontal health (>60% reduction in number of sites with probing depth ≥ 4 mm from the baseline visit) and could be classified as either high CV-risk (≥ 6 classical risk factors, n = 13) or low CV-risk (≤ 1 classical risk factor, n = 14). Serum levels of the cytokines and antibodies were measured using ELISA. RESULTS: For sICAM-1 and anti-P. gingivalis GroEL and anti-hHSP60 antibodies, most patients recorded decreased levels. Reductions in serum sICAM-1 levels were more notable in low CV-risk patients (p = 0.006); and reductions in levels of anti-P. gingivalis GroEL and anti-hHSP60 antibodies (p = 0.001 and 0.009 respectively) were more notable in high CV-risk patients. CONCLUSIONS: This study found that subsequent to improved periodontal health, the anti-HSP (HSP60 and GroEL) antibody response was reduced, particularly for high CV-risk patients. sICAM-1 levels were also lowered, more so for low CV-risk patients.
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Enfermedades Cardiovasculares/etiología , Periodontitis Crónica/terapia , Adulto , Anticuerpos Antibacterianos/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/inmunología , Chaperonina 60/inmunología , Periodontitis Crónica/sangre , Periodontitis Crónica/complicaciones , Periodontitis Crónica/inmunología , Citocinas/sangre , Femenino , Humanos , Mediadores de Inflamación/sangre , Molécula 1 de Adhesión Intercelular/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Estadísticas no ParamétricasRESUMEN
Ethical standards and current law demand that acute care psychiatric patients be treated with respect, using the least restrictive interventions. Unfortunately, as restraint use has decreased, assault and injury of mental health care workers has increased. Violence against those working in acute care psychiatry is a serious global issue that needs further examination. This study provides current, in depth information about the nature, frequency and severity of assaults and injuries of psychiatric nurses. This study also examined assault and injury in relation to the nurse's decision to restrain. The findings of this study were compared with findings of an earlier study carried out by one of the authors (Moylan) prior to the institution of policies, which are more restrictive in the use of restraint. In a sample of 110 nurses from five institutions, 80% of the nurses were assaulted, 65% had been injured and 26% had been seriously injured. Injuries included fractures, eye injuries and permanent disability. The number and severity of injuries have increased significantly since the 1996 study. Nurses who had been injured decided to restrain later in the progression of aggression than those who had not been injured.
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Agresión/psicología , Toma de Decisiones/fisiología , Personal de Enfermería en Hospital/psicología , Enfermería Psiquiátrica/métodos , Restricción Física/efectos adversos , Restricción Física/estadística & datos numéricos , Adulto , Anciano , Actitud del Personal de Salud , Femenino , Hospitales Psiquiátricos , Humanos , Entrevista Psicológica , Masculino , Persona de Mediana Edad , Salud Laboral , Restricción Física/psicología , Factores de Tiempo , Índices de Gravedad del Trauma , Violencia/prevención & control , Violencia/psicología , Heridas y Lesiones/psicología , Adulto JovenRESUMEN
Recent evidence suggests that strain variation in the serum IgG response to Porphyromonas gingivalis occurs in periodontal disease and cardiovascular disease (CVD). This study aimed to test the hypothesis that different P. gingivalis strains would elicit different levels of IgG, depending on a patient's cardiovascular (CV) and periodontal health. For CVD patients, serum antibody levels increased significantly with increasing numbers of deep pockets for all strains of P. gingivalis, except W50 (p < 0.001). We used a two-way analysis of variance to examine differences in antibody responses across several CV and periodontal groups simultaneously. There was a significant interaction effect (p < 0.05) between periodontal status and CV status for antibody levels to ATCC33277, UQD605, and Su63. This study shows variation in strain type with respect to serum IgG response in several CV and periodontal categories, providing further support for the role of the immune response to P. gingivalis in the relationship between periodontal disease and CVD.
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Anticuerpos Antibacterianos/sangre , Enfermedades Cardiovasculares/sangre , Periodontitis Crónica/sangre , Porphyromonas gingivalis/patogenicidad , Adolescente , Adulto , Anciano , Análisis de Varianza , Enfermedades Cardiovasculares/microbiología , Estudios de Casos y Controles , Periodontitis Crónica/microbiología , Estudios Transversales , Femenino , Humanos , Técnicas para Inmunoenzimas , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Porphyromonas gingivalis/clasificación , Porphyromonas gingivalis/inmunología , Factores de Riesgo , Especificidad de la Especie , Estadísticas no Paramétricas , Adulto JovenRESUMEN
Injury to an immature permanent tooth may result in cessation of dentine deposition and root maturation leaving an open root apex and thin dentinal walls that are prone to fracture. Endodontic treatment is often complicated and protracted with an uncertain prognosis frequently resulting in premature tooth loss. Postnatal stem cells, which are capable of self-renewal, proliferation and differentiation into multiple specialized cell lineages have been isolated and identified within the dental pulp, apical papilla and periodontal ligament. The ability of these cells to produce pulp-dentine and cementum-periodontal ligament complexes in vivo suggest potential applications involving stem cells, growth factors and scaffolds for apexification or apexogenesis. Similar protein expression amongst dental stem cells possibly implicates a common origin; however, the dominant cells to repopulate an open apex will be directed by local environmental cues. A greater understanding of the structure and function of cells within their environment is necessary to regulate and facilitate cellular differentiation along a certain developmental path with subsequent tissue regeneration. This review focuses on development of the apical tissues, dental stem cells and their possible involvement clinically in closing the open root apex. MEDLINE and EMBASE computer databases were searched up to January 2009. Abstracts of all potentially relevant articles were scanned and their contents identified before retrieval of full articles. A manual search of article reference lists as well as a forward search on selected authors of these articles was undertaken. It appears that dental stem cells have the potential for continued cell division and regeneration to replace dental tissues lost through trauma or disease. Clinical applications using these cells for apexogenesis and apexification will be dependent on a greater understanding of the environment at the immature root end and what stimulates dental stem cells to begin dividing and then express a certain phenotype.
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Apexificación/métodos , Células Madre/fisiología , Ápice del Diente/crecimiento & desarrollo , Papila Dental/citología , Pulpa Dental/citología , Sustancias de Crecimiento/fisiología , Humanos , Ligamento Periodontal/citología , Regeneración , Células Madre/citologíaRESUMEN
Treatment planning in periodontics, as with any disease, must be based on an understanding of the aetiology and pathogenesis of the disease. In this context, it has slowly become recognized over the past three decades that while plaque is the cause of the disease, it is the innate susceptibility of the host that determines the ultimate outcome of the disease process. Innate susceptibility, in turn, is determined by the nature of the immune response to the specific periodontopathic complexes comprising the plaque biofilm. The aim of this review was to examine current understanding of the immunopathogenesis of chronic periodontitis with respect to its possible clinical implications in terms of treatment planning and risk assessment. Numerous studies have demonstrated that the periodontitis lesion itself involves predominantly B cells and plasma cells, while the gingivitis lesion is primarily a T cell mediated response. This led to the concept over 30 years ago that the development of periodontitis involves a switch from a T cell lesion to one involving large numbers of B cells and plasma cells. It is also well recognized that control of this shift is mediated by a balance between the so-called Th1 and Th2 subsets of T cells, with chronic periodontitis being mediated by Th2 cells. More recently, T regulatory (Treg) and Th17 cells have been demonstrated in periodontal tissues, raising the possibility that these cells are also important in the immunoregulation of periodontal disease. The clinical implications of these observations can be seen in the fact that identification of Th1/Th2 and Treg/Th17 cytokine gene expression in the peripheral blood and salivary transcriptomes is now being trialled as a possible marker of disease susceptibility. If this proves to be the case, a chairside salivary diagnostic could be developed within the next five to 10 years.