RESUMEN
Matrix metalloproteinases (MMPs) are enzymes involved in periodontal tissue destruction. Hemagglutinin B (HagB) from the periodontal pathogen Porphyromonas gingivalis induces an elevated MMP response in dendritic cells, but responses from cultures of single-cell types do not reflect the local tissue environment. The objective of this study was to measure HagB-induced MMP responses in a transwell co-culture system containing dendritic cells, gingival epithelial (GE) keratinocytes, and CD4+ T-cells. Transwell co-cultures were assembled and treated with or without HagB. Immunoassays were used to determine production of MMP1, MMP7, MMP9, and MMP12 in response to HagB up to 64 h. Control responses were subtracted from HagB-induced responses. A two-way fixed effect ANOVA was fit to log-transformed concentrations and pairwise group comparisons were conducted (p < 0.05). At 64 h, dendritic cells produced elevated MMP1 and MMP9 responses, which were attenuated in the 3-cell co-culture (p < 0.05). There were also significant differences in MMP7 and MMP12 production between single-cell cultures and co-cultures. These results support the need to use multiple cell types in culture models to evaluate a more representative response to proinflammatory agonists. This three-cell transwell co-culture model may help us better understand the inflammatory process in periodontal disease and test novel therapeutic approaches.
Asunto(s)
Células Dendríticas/metabolismo , Hemaglutininas/farmacología , Queratinocitos/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Porphyromonas gingivalis/química , Linfocitos T/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Técnicas de Cultivo de Célula , Técnicas de Cocultivo , Células Dendríticas/citología , Células Dendríticas/efectos de los fármacos , Encía/citología , Humanos , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Metaloproteinasa 1 de la Matriz/metabolismo , Linfocitos T/citología , Linfocitos T/efectos de los fármacosRESUMEN
PURPOSE: Several complications may arise in patients wearing complete prosthetic appliances, including denture-associated infections and mucosal stomatitis due to Candida species. This study evaluated the activity of anti-Candida agents in denture adhesive and the cytotoxicities of these preparations for primary human gingival epithelial (GE) keratinocytes. MATERIALS AND METHODS: The anti-Candida activities of antimicrobial peptides, antimicrobial lipids, and antifungal agents against C. albicans ATCC 64124 or HMV4C were assessed in microdilution assays containing water or 1% denture adhesive. The minimal inhibitory concentrations (MIC) and the minimal bactericidal concentrations (MBC) were determined. The cytotoxicities of denture adhesive compounded with these agents were assessed in 1.0 × 105 primary GE keratinocytes in LGM-3 media with resazurin. RESULTS: Lactoferricin B, SMAP28, sphingosine, dihydrosphingosine, and phytosphingosine in 1% denture adhesive lost antimicrobial activity for C. albicans (p < 0.05). Amphotericin B, chlorhexidine dihydrochloride, chlorhexidine gluconate, fluconazole, and nystatin in 1% denture adhesive or compounded directly into denture adhesive and then diluted to 1% adhesive, did not lose antimicrobial activity. Compounded formulations were not cytotoxic (LD50 > 100.0 µg/ml) against primary human GE keratinocytes. CONCLUSIONS: Antimicrobial peptides and antimicrobial lipids had diminished activities in 1% adhesive, suggesting that components in adhesives may inactivate local innate immune factors in the oral cavity, possibly predisposing denture wearers to Candida species infections. More importantly, antifungal agents retained their anti-C. albicans activities in denture adhesive, strongly suggesting that antifungal agents could be candidates for inclusion in adhesive formulations and used as prescribed topical treatments for individuals with denture stomatitis.
Asunto(s)
Adhesivos/uso terapéutico , Antifúngicos/uso terapéutico , Candidiasis Bucal/prevención & control , Retención de Dentadura/métodos , Adhesivos/administración & dosificación , Antifúngicos/administración & dosificación , Antifúngicos/efectos adversos , Candida albicans/efectos de los fármacos , Encía/efectos de los fármacos , Humanos , Pruebas de Sensibilidad MicrobianaRESUMEN
PURPOSE: Interaction of the programmed death-1 (PD-1) co-receptor on T cells with the programmed death-ligand 1 (PD-L1) on tumor cells can lead to immunosuppression, a key event in the pathogenesis of many tumors. Thus, determining the amount of PD-L1 in tumors by immunohistochemistry (IHC) is important as both a diagnostic aid and a clinical predictor of immunotherapy treatment success. Because IHC reactivity can vary, we developed computational simulation models to accurately predict PD-L1 expression as a complementary assay to affirm IHC reactivity. METHODS: Multiple myeloma (MM) and oral squamous cell carcinoma (SCC) cell lines were modeled as examples of our approach. Non-transformed cell models were first simulated to establish non-tumorigenic control baselines. Cell line genomic aberration profiles, from next-generation sequencing (NGS) information for MM.1S, U266B1, SCC4, SCC15, and SCC25 cell lines, were introduced into the workflow to create cancer cell line-specific simulation models. Percentage changes of PD-L1 expression with respect to control baselines were determined and verified against observed PD-L1 expression by ELISA, IHC, and flow cytometry on the same cells grown in culture. RESULT: The observed PD-L1 expression matched the predicted PD-L1 expression for MM.1S, U266B1, SCC4, SCC15, and SCC25 cell lines and clearly demonstrated that cell genomics play an integral role by influencing cell signaling and downstream effects on PD-L1 expression. CONCLUSION: This concept can easily be extended to cancer patient cells where an accurate method to predict PD-L1 expression would affirm IHC results and improve its potential as a biomarker and a clinical predictor of treatment success.
Asunto(s)
Antígeno B7-H1/metabolismo , Carcinoma de Células Escamosas/genética , Neoplasias de la Boca/genética , Mieloma Múltiple/genética , Adulto , Carcinoma de Células Escamosas/patología , Simulación por Computador , Humanos , Persona de Mediana Edad , Modelos Biológicos , Simulación de Dinámica Molecular , Neoplasias de la Boca/patología , Mieloma Múltiple/patologíaRESUMEN
UNLABELLED: Leadership is vital to future growth and change in the dental hygiene profession. BACKGROUND AND PURPOSE: As health care reform emerges, state practice acts expand and new models of dental hygiene practice are created and implemented, dental hygienists will assume leadership positions that may be quite different from the more traditional leadership roles they assume today. These dental hygienist leaders will envision, creatively design and implement oral health care programs to improve the oral health of the public. Mentoring, a vital component of leadership development, is critical for dental hygienists to acquire knowledge, guidance, and growth. METHODS: This paper provides a literature-supported overview of leadership and mentoring principles applicable to dental hygienists in their personal and professional lives. Opportunities for dental hygienists to assume leadership roles are also described. CONCLUSIONS: Dental hygienists are poised to become leaders and vital members of the professional team promoting and integrating oral health care as a part of general health. Consequently, the dental hygienist's leadership roles are likely to expand and can be strengthened through mentoring relationships and mentoring teams. Ultimately, this can increase professional growth and career satisfaction for the dental hygienist as well as improve oral health care for the public.
Asunto(s)
Higienistas Dentales , Liderazgo , Mentores , Poder Psicológico , Higienistas Dentales/organización & administración , Promoción de la Salud , Humanos , Salud Bucal , Patient Protection and Affordable Care Act , Estados UnidosRESUMEN
In recent decades, the application of coaching for career development and supporting faculty in leadership roles has greatly expanded in higher education. Coaching can offer transformational and life-changing experiences, inspire critical reflection in early career decisions, and (re)ignite passion and commitment at all career stages. While coaching focuses on transforming individuals, it also has the potential to impact organizations and professional environments. The power of coaching deserves appropriate recognition within dental education and scholarship. In this article, the authors discuss the potential for career coaching as a tool for developing future leaders in dental education. After differentiating between coaching and mentoring, coaching for professional development is reviewed as an evidence-based approach that can enhance traditional leadership and professional development programs. Although this article was inspired by programming supporting the development of female leaders, coaching applies to all leaders and may be particularly helpful in supporting the development of diverse leaders including but not limited to individuals from different backgrounds, national origins, gender, racial, socioeconomic, and cultural distinctions. After a review of existing coaching initiatives in dental education, a variety of coaching strategies for faculty, staff, and trainees will be described that can be implemented by oral health educational institutions. Examples of coaching strategies range from developing internal coaching programs to contractual agreements with external coaching groups. Step-by-step guidelines are included.
Asunto(s)
Educación en Odontología , Liderazgo , Tutoría , Tutoría/métodos , Humanos , Educación en Odontología/métodos , Docentes de Odontología , Desarrollo de Personal , Mentores , FemeninoRESUMEN
INTRODUCTION: As part of curriculum innovation, the University of North Carolina (UNC) Adams School of Dentistry identified core entrustable professional activities (EPAs) that graduates must demonstrate for practice readiness. This paper describes the development of the UNC EPAs and the perceptions of the general dentistry faculty. METHODS: Upon establishing a blueprint of knowledge, skills, and attitudes of UNC graduates, using a distributed leadership approach, faculty teams developed EPAs focused on the patient care process. The American Dental Education Association Compendium of Clinical Competency Assessments and Commission on Dental Accreditation Standards informed the team's work. Perceptions of the assessment framework were examined using a questionnaire completed by 13 general dentistry faculty considering the importance, accuracy, and agreement of each EPA, associated domains of competence, and encounter management on a 6-point rating scale. RESULTS: Distributed leadership was a useful strategy in EPA development to disperse decision-making and build ownership. Through multiple iterations, four EPAs (assessment, plan of care, collaborative care, and provision of care) with associated sub-EPAs emerged. EPAs included a description, required knowledge and skills, and rubrics for assessment. The general dentistry faculty reported a high level of importance, accuracy, and agreement with EPAs, domains of competence, and encounter management. DISCUSSION: EPAs provide a standardized manner to describe the comprehensive work dentists perform, shifting away from individual competencies. The UNC EPAs provide the foundation for longitudinal measures of competence preparing graduates for independent practice. With limited EPAs frameworks available in dentistry, we aim to inform the development and implementation of EPAs across dental education.
Asunto(s)
Educación Basada en Competencias , Internado y Residencia , Humanos , Evaluación Educacional , Curriculum , Competencia Clínica , OdontologíaRESUMEN
AIM: The aim of this study was to compare the expression of 22 chemokines and cytokines in gingival crevicular fluid (GCF) from smokers and non-smokers with periodontitis and periodontally healthy control subjects. MATERIALS AND METHODS: Forty subjects with generalized severe chronic periodontitis (20 smokers and 20 non-smokers) and 12 periodontally healthy control subjects participated in this study. Four diseased and two healthy sites were selected from each of the periodontitis subjects. GCF samples were collected and cytokines analysed utilizing a multiplexed immunoassay (Luminex(®) ). Statistical analyses employed non-parametric tests including the Mann-Whitney and Wilcoxon matched-pairs signed-rank tests. RESULTS: Compared with healthy control subjects, GCF in subjects with chronic periodontitis contained significantly higher amounts of interleukin (IL)-1α, IL-1ß, IL-6, IL-12(p40) (pro-inflammatory cytokines); IL-8, macrophage chemotactic protein (MCP)-1, macrophage inflammatory protein (MIP)-1α, regulated on activation normal T-cell expressed and secreted (RANTES) (chemokines); IL-2, IFN-γ, IL-3, IL-4 (Th1/Th2 cytokines); IL-15 [regulator of T-cells and natural killer (NK) cells]. Smokers displayed decreased amounts of pro-inflammatory cytokines [IL-1α, IL-6, IL-12(p40)], chemokines (IL-8, MCP-1, MIP-1, RANTES), and regulators of T-cells and NK cells (IL-7, IL-15). CONCLUSIONS: Periodontitis subjects had significantly elevated cytokine and chemokine profiles. Smokers exhibited a decrease in several pro-inflammatory cytokines and chemokines and certain regulators of T-cells and NK-cells. This reflects the immunosuppressant effects of smoking which may contribute to an enhanced susceptibility to periodontitis.
Asunto(s)
Periodontitis Crónica/inmunología , Citocinas/análisis , Líquido del Surco Gingival/inmunología , Fumar/inmunología , Quimiocina CCL2/análisis , Quimiocina CCL3/análisis , Quimiocina CCL5/análisis , Quimiocinas/análisis , Quimiocinas CC/análisis , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/análisis , Humanos , Inmunoensayo , Interferón gamma/análisis , Subunidad p40 de la Interleucina-12/análisis , Interleucina-13/análisis , Interleucina-15/análisis , Interleucina-1alfa/análisis , Interleucina-1beta/análisis , Interleucina-2/análisis , Interleucina-4/análisis , Interleucina-6/análisis , Interleucina-8/análisis , Células Asesinas Naturales/inmunología , Masculino , Persona de Mediana Edad , Linfocitos T/inmunologíaRESUMEN
Antimicrobial peptides coupled to a ligand, receptor or antibody for a specific pathogenic bacteria could be used to develop narrow-spectrum pharmaceuticals with 'targeted' antimicrobial activity void of adverse reactions often associated with the use of broad-spectrum antibiotics. To assess the feasibility of this approach, in this study sheep myeloid antimicrobial peptide (SMAP) 28 was linked to affinity- and protein G-purified rabbit immunoglobulin G (IgG) antibodies specific to the outer surface of Porphyromonas gingivalis strain 381. The selective activity of the P. gingivalis IgG-SMAP28 conjugate was then assessed by adding it to an artificially generated microbial community containing P. gingivalis, Aggregatibacter actinomycetemcomitans and Peptostreptococcus micros. The specificity of the P. gingivalis IgG-SMAP28 conjugate in this mixed culture was concentration-dependent. The conjugate at 50 microg protein/mL lacked specificity and killed P. gingivalis, A. actinomycetemcomitans and P. micros. The conjugate at 20 microg protein/mL was more specific and killed P. gingivalis. This is an initial step to develop a selective antimicrobial agent that can eliminate a specific periodontal pathogen, such as P. gingivalis, from patients with periodontal disease without harming the normal commensal flora.
Asunto(s)
Anticuerpos Antibacterianos/farmacología , Especificidad de Anticuerpos , Péptidos Catiónicos Antimicrobianos/farmacología , Inmunoglobulina G/inmunología , Inmunoglobulina G/farmacología , Porphyromonas gingivalis/efectos de los fármacos , Animales , Anticuerpos Antibacterianos/química , Anticuerpos Antibacterianos/inmunología , Péptidos Catiónicos Antimicrobianos/síntesis química , Péptidos Catiónicos Antimicrobianos/química , Reactivos de Enlaces Cruzados/química , Medios de Cultivo , Ecosistema , Humanos , Inmunoglobulina G/química , Maleimidas/química , Pruebas de Sensibilidad Microbiana/métodos , Pasteurellaceae/crecimiento & desarrollo , Peptostreptococcus/crecimiento & desarrollo , Porphyromonas gingivalis/crecimiento & desarrollo , Porphyromonas gingivalis/inmunología , OvinosRESUMEN
Research has proliferated in recent years regarding the relationship of oral disease to systemic conditions. Specifically, periodontal disease has been studied as a potential risk factor for multiple conditions such as cardiovascular disease (CVD) and adverse pregnancy outcomes, while other research focuses on exposures or behaviors associated with oral disease. However, few articles have been published reporting how this information is integrated into schools of dentistry, both in the classroom and clinical curriculum. For our study, a thirty-three-item survey and cover letter were electronically mailed to academic deans at sixty-five accredited dental schools in the United States and Canada in the fall of 2007. The response rate was 77 percent. According to the responses to this survey, the primary topics covered in the didactic curriculum regarding periodontal oral-systemic disease are aging, CVD, diabetes, and tobacco use. Eighty-eight percent of the respondents reported that their students are knowledgeable about the role of inflammation and its impact on oral-systemic conditions. Forty-eight percent of the respondents said they provide formal training for their students in how to discuss or communicate aspects of periodontal oral-systemic disease with patients. Only seven schools reported teaching didactic content to dental students intermixed with other health professions students, and only two schools reported conducting joint projects. Only 9 percent of the respondents said they think nurses and physicians are knowledgeable about oral-systemic disease. The findings indicate that dental schools are confident about the knowledge of their students regarding oral-systemic content. However, much work is needed to educate dental students to work in a collaborative fashion with other health care providers to co-manage patients at risk for oral-systemic conditions.
Asunto(s)
Enfermedad , Educación en Odontología , Enfermedades Periodontales/complicaciones , Envejecimiento/fisiología , Canadá , Enfermedades Cardiovasculares/complicaciones , Comunicación , Curriculum , Relaciones Dentista-Paciente , Complicaciones de la Diabetes , Educación Médica , Educación en Enfermería , Femenino , Humanos , Inflamación , Grupo de Atención al Paciente , Educación del Paciente como Asunto , Embarazo , Resultado del Embarazo , Factores de Riesgo , Facultades de Odontología , Fumar/efectos adversos , Materiales de Enseñanza , Estados UnidosRESUMEN
Chemokines and cytokines produced in gingival tissues exposed to microorganisms and microbial products in dental plaque lead to local inflammation and tissue damage seen in periodontal disease. Bates et al. 2018 [1] reported that Porphyromonas gingivalis hemagglutinin B (HagB)-induced matrix metalloproteinase (MMP) responses of single cell cultures containing dendritic cells, gingival epithelial (GE) keratinocytes, or T cells were significantly different from the MMP responses of these same cells grown in multi-cell cultures. Here we report the concentrations (pg/ml) of HagB-induced IL1α, IL6, IL8, IL12(p40), GM-CSF, MIP1α, MIP1ß, RANTES, TNFα, and VEGF produced by dendritic cells, GE keratinocytes, or T cells in single cell cultures, two-cell cultures, or three-cell cultures.
RESUMEN
Individual computational models of single myeloid, lymphoid, epithelial, and cancer cells were created and combined into multi-cell computational models and used to predict the collective chemokine, cytokine, and cellular biomarker profiles often seen in inflamed or cancerous tissues. Predicted chemokine and cytokine output profiles from multi-cell computational models of gingival epithelial keratinocytes (GE KER), dendritic cells (DC), and helper T lymphocytes (HTL) exposed to lipopolysaccharide (LPS) or synthetic triacylated lipopeptide (Pam3CSK4) as well as multi-cell computational models of multiple myeloma (MM) and DC were validated using the observed chemokine and cytokine responses from the same cell type combinations grown in laboratory multi-cell cultures with accuracy. Predicted and observed chemokine and cytokine responses of GE KER + DC + HTL exposed to LPS and Pam3CSK4 matched 75% (15/20, p = 0.02069) and 80% (16/20, P = 0.005909), respectively. Multi-cell computational models became 'personalized' when cell line-specific genomic data were included into simulations, again validated with the same cell lines grown in laboratory multi-cell cultures. Here, predicted and observed chemokine and cytokine responses of MM cells lines MM.1S and U266B1 matched 75% (3/4) and MM.1S and U266B1 inhibition of DC marker expression in co-culture matched 100% (6/6). Multi-cell computational models have the potential to identify approaches altering the predicted disease-associated output profiles, particularly as high throughput screening tools for anti-inflammatory or immuno-oncology treatments of inflamed multi-cellular tissues and the tumor microenvironment.
Asunto(s)
Células Dendríticas/metabolismo , Epitelio/patología , Encía/patología , Inflamación/inmunología , Queratinocitos/metabolismo , Mieloma Múltiple/metabolismo , Neoplasias/inmunología , Biomarcadores/metabolismo , Línea Celular Tumoral , Biología Computacional , Simulación por Computador , Citocinas/metabolismo , Células Dendríticas/patología , Ensayos Analíticos de Alto Rendimiento , Humanos , Inflamación/diagnóstico , Queratinocitos/patología , Mieloma Múltiple/patología , Neoplasias/diagnóstico , PronósticoRESUMEN
BACKGROUND: Bisphosphonates have received attention in the dental and medical scientific literature because of spontaneous necrosis of the jaw subsequent to their use. As the population ages, the use of these medications is increasing; the medical benefits seem to outweigh the risk for osteonecrosis of the jaw (ONJ). METHODS: A 71-year-old white male with a history of multiple myeloma, for which he was receiving intravenous (IV) zoledronic acid, presented for routine periodontal maintenance therapy. Intraoral observation revealed a 9x4-mm area of exposed bone on the lingual aspect of tooth #31. Initially, the site was treated conservatively with topical 0.12% chlorhexidine gluconate application. Over a 12-month period, the area of exposed bone increased in size to 20x9 mm and became symptomatic. RESULTS: The osseous necrosis progressed, ultimately resulting in a pathologic fracture of the right posterior mandible that was managed by reduction and stabilization. At 5 months post-surgery, bone exposure persisted in the region, and a new site of osteonecrosis developed on the contralateral side of the jaw. CONCLUSIONS: ONJ associated with IV bisphosphonate therapy is extremely difficult to manage. Dental treatment of ONJ should be conservative and provide relief to the patient. Patients with cancer who are candidates for IV bisphosphonate therapy should be informed of the potential risks and be referred for dental evaluation. Dentists should collaborate with physicians to minimize the risk for ONJ.
Asunto(s)
Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos/efectos adversos , Enfermedades Maxilomandibulares/inducido químicamente , Mieloma Múltiple/tratamiento farmacológico , Osteonecrosis/inducido químicamente , Anciano , Humanos , Imidazoles/efectos adversos , Enfermedades Maxilomandibulares/diagnóstico por imagen , Enfermedades Maxilomandibulares/tratamiento farmacológico , Masculino , Fracturas Mandibulares/inducido químicamente , Fracturas Mandibulares/diagnóstico por imagen , Fracturas Mandibulares/cirugía , Osteonecrosis/diagnóstico por imagen , Osteonecrosis/tratamiento farmacológico , Radiografía , Ácido ZoledrónicoRESUMEN
CONTEXT: Polymicrobial diseases, caused by combinations of viruses, bacteria, fungi, and parasites, are being recognised with increasing frequency. In these infections, the presence of one micro-organism generates a niche for other pathogenic micro-organisms to colonise, one micro-organism predisposes the host to colonisation by other micro-organisms, or two or more non-pathogenic micro-organisms together cause disease. STARTING POINT: Recently, Gili Regev-Yochay (JAMA 2004; 292: 716-20) and Debby Bogaert (Lancet 2004; 363: 1871-72), and their colleagues, suggested another interaction: microbial interference-the ability of Streptococcus pneumoniae carriage to protect against Staphylococcus aureus carriage, and the inverse effect of pneumococcal conjugate vaccination on the increased carriage of Staph aureus and Staph-aureus-related disease. Strep pneumoniae carriage protected against Staph aureus carriage, and the bacterial interference could be disrupted by vaccinating children with pneumococcal conjugate vaccines that reduced nasopharyngeal carriage of vaccine-type Strep pneumoniae. WHERE NEXT: The medical community is recognising the significance of polymicrobial diseases and the major types of microbial community interactions associated with human health and disease. Many traditional therapies are just starting to take into account the polymicrobial cause of diseases and the repercussions of treatment and prevention.
Asunto(s)
Infecciones/microbiología , Antibiosis , Infecciones Bacterianas/microbiología , Humanos , Infecciones/diagnóstico , Infecciones/terapia , Interferencia ViralRESUMEN
Human beta-defensins are antimicrobial peptides produced by epithelial cells. To date, 28 beta-defensins have been described and the expression of a select few has been classified as constitutive or inducible. Most studies have evaluated expression and regulation using a limited number of primary cell cultures or immortalized cell lines. The goal of this study was to quantitatively assess the in vitro expression and inducibility profiles of human beta-defensins, HBD-1, HBD-2, and HBD-3 across a number of primary gingival keratinocyte cultures. Cultured cells from 14 human subjects were stimulated with interleukin-1 beta (IL-1beta), IL-2, IL-6, IL-8, IL-12, tumor necrosis factor alpha (TNF-alpha), gamma interferon (IFN-gamma) or Escherichia coli lipopolysaccharide (LPS) and analyzed by reverse transcription (RT)-PCR. A subset of cultures were quantitatively assessed by real-time PCR. HBD-1 presented the highest and most heterogeneous expression at the basal level (non-stimulated) as compared to expression of HBD-2 and HBD-3, which was significantly lower and homogeneous. IFN-gamma was a primary inducer for HBD-1 and HBD-3, while IL-1beta and TNF-alpha were primary inducers for HBD-2. Sporadic induction was seen for IL-2, IL-6 and LPS. Synergistic expression was seen when various cytokines were combined. Interestingly, the induction potential of each beta-defensin was directly correlated to its basal expression. An inhibitor of JAK2 kinase (Janus kinase), down-regulated IFN-gamma-induced HBD-1 and HBD-3 expression, suggesting a role for the JAK/signal transducer and activator of transcription (STAT) signaling pathway in their expression. HBD-2 protein expression of supernatants and cell lysates paralleled mRNA expression. The results suggest that beta-defensin expression and induction in gingival keratinocytes is similar to that seen in other tissue. However, the novel finding of considerable variation among induction levels and the correlation of the induction with basal expression suggests that these innate response elements may play a key role in susceptibility or resistance to disease in the oral cavity.
Asunto(s)
Antiinfecciosos/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Encía/citología , Queratinocitos/efectos de los fármacos , beta-Defensinas/metabolismo , Técnicas de Cultivo de Célula , Células Cultivadas , Sinergismo Farmacológico , Humanos , Interferón gamma/farmacología , Interleucina-1/farmacología , Interleucina-8/farmacología , Queratinocitos/metabolismo , Lipopolisacáridos/inmunología , Lipopolisacáridos/farmacología , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/farmacología , beta-Defensinas/genéticaRESUMEN
The purpose of this report was to describe the management of an eight-year-old Bulgarian male with Down syndrome presenting with periodontitis as a manifestation of systemic disease in the early mixed dentition. Treatment involved full-mouth mechanical debridement and extraction of hopeless teeth under general anesthesia followed by systemic antibiotics and chemical adjunctive therapy. Microbial culture and sensitivity testing aided in diagnosis and guided treatment decisions. This case report demonstrates a multidisciplinary approach in the management of aggressive periodontal disease in an internationally adopted pediatric patient with special health care needs.
Asunto(s)
Periodontitis Crónica/terapia , Atención Dental para la Persona con Discapacidad , Síndrome de Down/complicaciones , Grupo de Atención al Paciente , Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Cariostáticos/uso terapéutico , Niño , Periodontitis Crónica/microbiología , Terapia Combinada , Dentición Mixta , Fluoruros Tópicos/uso terapéutico , Estudios de Seguimiento , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Planificación de Atención al Paciente , Desbridamiento Periodontal/métodos , Selladores de Fosas y Fisuras/uso terapéutico , Extracción Dental/métodos , Diente Primario/cirugíaRESUMEN
The postdoctoral application and matching process in dental education is a high-stakes and resource-intensive process for all involved. While programs seek the most qualified candidates, applicants strive to be competitive to increase their likelihood of being accepted to a desirable program. There are limited data regarding either subjective or objective factors underlying the complex interplay between programs and applicants. This qualitative study sought to provide insight into the stakeholders' experiences and views on the matching process. Telephone and in-person interviews were conducted with ten pediatric dentistry program directors and ten recent applicants to pediatric dentistry programs in the United States in 2013-14. Participants were selected to represent the geographic (five districts of the American Academy of Pediatric Dentistry) and institutional (hospital- or university-based) diversity of pediatric dentistry programs. Interviews were recorded and transcribed verbatim. Veracity and need for more information were the themes most often articulated by both groups. The program directors most valued teachability and self-motivation as desirable applicant characteristics. The applicants relied primarily on subjective sources to gather information about programs and prioritized location and financial factors as pivotal for their rankings. Both groups appreciated the uniformity of the current application process and highlighted several weaknesses and areas for improvement. These results shed light on the postdoctoral matching process in pediatric dentistry via a qualitative description of stakeholders' experiences and viewpoints. These insights can serve as a basis for improving and refining the matching process.
Asunto(s)
Actitud del Personal de Salud , Educación de Posgrado en Odontología , Docentes de Odontología , Internado y Residencia , Odontología Pediátrica/educación , Criterios de Admisión Escolar , Acceso a la Información , Logro , Comunicación , Evaluación Educacional , Objetivos , Hospitales de Enseñanza , Humanos , Aprendizaje , Motivación , Investigación Cualitativa , Revelación de la Verdad , Estados Unidos , UniversidadesRESUMEN
Human ß-defensin 3 (HBD3) is a prominent host defense peptide. In our recent work, we observed that HBD3 modulates pro-inflammatory agonist-induced chemokine and cytokine responses in human myeloid dendritic cells (DCs), often at 20.0 µM concentrations. Since HBD3 can be cytotoxic in some circumstances, it is necessary to assess its cytotoxicity for DCs, normal human epidermal keratinocytes (NHEKs), human telomerase reverse transcriptase (hTERT) keratinocytes, and primary oral gingival epithelial (GE) keratinocytes in different cell culture conditions. Cells, in serum free media with resazurin and in complete media with 10% fetal bovine serum and resazurin, were incubated with 5, 10, 20, and 40 µM HBD3. Cytotoxicity was determined by measuring metabolic conversion of resazurin to resorufin. The lethal dose 50 (LD50, mean µM±Std Err) values were determined from the median fluorescent intensities of test concentrations compared to live and killed cell controls. The LD50 value range of HBD3 was 18.2-35.9 µM in serum-free media for DCs, NHEKs, hTERT keratinocytes, and GE keratinocytes, and >40.0 µM in complete media. Thus, HBD3 was cytotoxic at higher concentrations, which must be considered in future studies of HBD3-modulated chemokine and cytokine responses in vitro.
Asunto(s)
Células Dendríticas/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Queratinocitos/efectos de los fármacos , beta-Defensinas/toxicidad , Línea Celular , Supervivencia Celular , Células Cultivadas , Medio de Cultivo Libre de Suero , Relación Dosis-Respuesta a Droga , Encía/citología , Humanos , Dosificación Letal Mediana , Factores de TiempoRESUMEN
Long-chain bases are present in the oral cavity. Previously we determined that sphingosine, dihydrosphingosine, and phytosphingosine have potent antimicrobial activity against oral pathogens. Here, we determined the cytotoxicities of long-chain bases for oral cells, an important step in considering their potential as antimicrobial agents for oral infections. This information would clearly help in establishing prophylactic or therapeutic doses. To assess this, human oral gingival epithelial (GE) keratinocytes, oral gingival fibroblasts (GF), and dendritic cells (DC) were exposed to 10.0-640.0 µM long-chain bases and glycerol monolaurate (GML). The effects of long-chain bases on cell metabolism (conversion of resazurin to resorufin), membrane permeability (uptake of propidium iodide or SYTOX-Green), release of cellular contents (LDH), and cell morphology (confocal microscopy) were all determined. GE keratinocytes were more resistant to long-chain bases as compared to GF and DC, which were more susceptible. For DC, 0.2-10.0 µM long-chain bases and GML were not cytotoxic; 40.0-80.0 µM long-chain bases, but not GML, were cytotoxic; and 80.0 µM long-chain bases induced cellular damage and death in less than 20 min. The LD50 of long-chain bases for GE keratinocytes, GF, and DC were considerably higher than their minimal inhibitory concentrations for oral pathogens, a finding important to pursuing their future potential in treating periodontal and oral infections.