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Biomedical subjects

Howard C Tenenbaum

Publications and source records attributed to Howard C Tenenbaum.

11 recordsLinked to original sources

Characterization of patients presenting for treatment to a university refractory periodontal diseases unit: three case reports.

BACKGROUND: Of the many forms of periodontal disease, refractory periodontal diseases are the least characterized. They are defined as the continued degeneration of the periodontium despite adequate management. This has led to the suggestion that there may be a systemic component that is a contributing factor to the development of this condition. The objectives of this report were to follow the progression of clinical changes associated with periodontal disease over a number of years in this unique population and review various hematologic and microbiologic factors that may be contributing to the disease progression. METHODS: Three subjects were profiled. They were referred to the Refractory Periodontal Disease Unit at the University of Toronto by periodontists or general practitioners in the Southern Ontario region. Complete medical and dental histories were obtained along with baseline clinical measurements. Periodontal examinations were facilitated with the use of a computer-assisted periodontal probe. A microbiologic analysis using immunofluorescence techniques was able to detect Prevotella intermedia, Porphyromonas gingivalis, Tannerella forsythia, and Actinobacillus actinomycetemcomitans and spirochetes. A hematologic analysis, including a complete blood count (CBC), immune profile, and glycosylated hemoglobin assay, was also performed. RESULTS: The clinical presentation revealed that patients receiving adequate maintenance therapy and with good to excellent oral hygiene demonstrated sites with continual loss of attachment. Few periodontal pathogens were detected. However, the most significant finding appeared to be the report elevated levels of CD8+ cells within this group of patients compared to normal laboratory ranges. CONCLUSIONS: This report is an attempt at characterizing a unique population within the periodontal realm. The long-term monitoring of these patients allowed for an assessment of factors that may be involved in the continued decline of the periodontal health of these patients. Based on the immune profile, it is possible that a hyperresponsive state may be the primary feature of this population. Future assessments, including full-mouth interleukin (IL)-1 and matrix metalloproteinase (MMP)-8 levels, may assist in characterizing this population further, with the goal of producing markers that will assist clinicians in predicting treatment outcome.

Adult↗

Future treatment and diagnostic strategies for periodontal diseases.

Many new technologies have been developed or are being developed that could enhance the ability to diagnose, predict, and treat periodontitis. Newer treatment strategies may allow clinicians to achieve limited or more robust regeneration of the periodontium. New or refreshed approaches to disease control are being pursued that will benefit those suffering from chronic periodontal disease. In addition to novel therapeutics, there has been increasing focus on the development of more sensitive and specific diagnostic tests for periodontal diseases. Such tests will allow the clinician to determine whether a patient has active disease and what sort of attachment loss might be expected if the patient is not treated. By developing newer diagnostic tests, it also may be possible to detect and monitor active disease during therapy.

Anti-Bacterial Agents↗

Replantation of permanent incisors in children using Emdogain.

The aim of this study was to determine whether application of an enamel matrix protein derivative, Emdogain (Biora AB Malmo, Sweden) to the root surface of avulsed permanent incisors would improve postreplantation outcomes in a pediatric population. Between June 1999 and May 2002, 25 avulsed permanent maxillary incisors (22 centrals and three laterals) were treated with Emdogain and followed for up to 32 months, mean duration 20.6 months (range: 6.9-32.5 months). Mean patient age at the time of treatment was 12.0 years (range: 7.7-17.6 years) and mean extra-alveolar duration was 185 min (range: 100-300 min). At the end of their follow-up each of the replanted incisors demonstrated radiographic evidence of replacement root resorption and clinical evidence of ankylosis. None of the replanted teeth were affected by inflammatory root resorption and there was no evidence of infection. When compared with the control samples from Barrett and Kenny (Endod Dent Traumatol 1997;15:269-72.) and Andersson et al. (Endod Dent Traumatol 1989;5:38-47.) this sample treated with the Emdogain protocol demonstrated significantly less root resorption than either of the control samples (anova, P < 0.0001). Although the Emdogain protocol did not produce periodontal regeneration, it did eliminate inflammatory resorption and infection and led to significantly less root resorption compared with the two historical controls.

Adolescent↗

Bisphosphonate modulates cementoblast behavior in vitro.

BACKGROUND: Cementum formation is deemed to be instrumental for the successful regeneration of periodontal tissues, and thus events and modifiers of cementum formation and mineralization need to be determined. This study aimed to determine whether the bisphosphonate 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) altered the behavior of immortalized cementoblasts (osteocalcin-cementoblasts [OCCM]). METHODS: OCCM from transgenic mice were exposed to HEBP at concentrations ranging from 0.01 to 10.0 microM. The assays performed included the count of cell number for proliferation, Northern blot analysis for gene expression (up to 10 days for core binding factor alpha-1 [Cbfa1], bone sialoprotein [BSP], osteocalcin [OCN], and osteopontin [OPN], markers for cementoblast/osteoblast maturation/mineralization), von Kossa stain and alizarin red S stain for mineralization, and enzyme assay (p-nitrophenol phosphate cleavage) for alkaline phosphatase (ALP) activity. RESULTS: Mineral nodule formation was inhibited at the higher doses of HEBP (1.0 and 10.0 microM) only. At early stages (1, 3, and 6 days), gene expression assays revealed only subtle changes in treated cells versus untreated cells, but by day 10, groups treated with lower doses (0.01 and 0.1 microM) were markedly different at the gene expression level. OCN was significantly downregulated (70%) at the lowest dose, with less pronounced effects at higher doses. In concurrence, the master switch gene for osteoblasts, Cbfa1, was also downregulated at the lower doses. Inversely, OPN mRNA was enhanced at the lower doses. ALP activity was not altered by HEBP. CONCLUSION: Bisphosphonate alters cementoblast function in vitro through the regulation of gene expression and mineral formation.

Alkaline Phosphatase↗

How predictable are periodontal regenerative procedures?

Periodontal regeneration has become one of the primary objectives of periodontal therapy. The resulting scientific endeavours have elucidated modes of periodontal wound healing, the growth of periodontal cells and their association with the surrounding matrix, and growth-promoting factors. The periodontal regeneration industry is producing better and more expensive devices, but the criteria for evaluating their success have not progressed to the same extent. Although clinical measurements of attachment level and probing depths, along with radiography, are good methods of evaluating tooth survival and prognosis, they do not indicate true biological regeneration. In addition, the regeneration industry may encourage the overuse of allografts and alloplasts which may serve as an impediment to simple wound healing. This review is a critical assessment of the clinical use of various regenerative tools, specifically bone replacements and membranes. The future of the regeneration industry may depend on the merging of various technologies and biological concepts, including the possible use of biological barriers, various bone and periodontal growth inducers, and artificial matrices that will attract or carry the cells necessary for regeneration.

Adult↗

Emdogain regulation of cellular differentiation in wounded rat periodontium.

Emdogain is an enamel matrix derivative that may promote periodontal regeneration by recapitulating critical events in tooth morphogenesis. We hypothesized that Emdogain enhances periodontal regeneration by promoting the differentiation of cells required for the synthesis of periodontal ligament, bone and cementum. Cell differentiation was examined in rat periodontal window wounds in which there is no microbial biofilm or epithelial downgrowth, thereby simplifying the model system. Defects were filled with vehicle control or Emdogain (3 mg/ml or 30 mg/ml). Rats were sacrificed at 7, 14 and 21 d after wounding. Specimens of periodontium were immunostained for osteopontin, bone sialoprotein, osteocalcin as markers of osteogenic differentiation and for alpha-smooth muscle actin, a myofibroblastic marker. Morphometry and 3H-proline radioautography were used for assessment of tissue homeostasis and matrix production. Rats treated with Emdogain (only at 30 mg/ml) showed widening of the periodontal ligament at 7 d; by 14 and 21 d, periodontal ligament width was restored to normal values for all groups. Emdogain exerted no effect on cementum thickness, bone volume, osteoid deposition rates, or extracellular staining for osteopontin, bone sialoprotein or osteocalcin. Further, the percentage of cells with intracellular staining for osteopontin, osteocalcin or bone sialoprotein was unaffected by Emdogain. Staining for alpha-smooth muscle actin was abundant in the repopulating wound but was also unaffected by Emdogain. In conclusion, Emdogain does not apparently affect the expression of differentiation markers or bone matrix protein synthesis in the repopulation response of wounded rat molar periodontium. Therefore the effect of Emdogain on wound healing in the periodontium may be independent of differentiation in the cell populations examined in this model.

Actins↗

Lethal photosensitization of periodontal pathogens by a red-filtered Xenon lamp in vitro.

BACKGROUND: The ability of Helium-Neon (He-Ne) laser irradiation of a photosensitizer to induce localized phototoxic effects that kill periodontal pathogens is well documented and is termed photodynamic therapy (PDT). OBJECTIVES: We investigated the potential of a conventional light source (red-filtered Xenon lamp) to activate toluidine blue O (TBO) in vitro and determined in vitro model parameters that may be used in future in vivo trials. MATERIALS AND METHODS: Porphyromonas gingivalis 381 was used as the primary test bacterium. RESULTS: Treatment with a 2.2 J/cm2 light dose and 50 micro g/ml TBO concentration resulted in a bacterial kill of 2.43 +/- 0.39 logs with the He-Ne laser control and 3.34 +/- 0.24 logs with the lamp, a near 10-fold increase (p = 0.028). Increases in light intensity produced significantly higher killing (p = 0.012) that plateaued at 25 mW/cm2. There was a linear relationship between light dose and bacterial killing (r2 = 0.916); as light dose was increased bacterial survival decreased. No such relationship was found for the drug concentrations tested. Addition of serum or blood at 50% v/v to the P. gingivalis suspension prior to irradiation diminished killing from approximately 5 logs to 3 logs at 10 J/cm2. When serum was washed off, killing returned to 5 logs for all species tested except Bacteroides forsythus (3.92 +/- 0.68 logs kill). CONCLUSIONS: The data indicate that PDT utilizing a conventional light source is at least as effective as laser-induced treatment in vitro. Furthermore, PDT achieves significant bactericidal activity in the presence of serum and blood when used with the set parameters of 10 J/cm2, 100 mW/cm2 and 12.5 micro g/ml TBO.

Aggregatibacter actinomycetemcomitans↗

Interdisciplinary, web-based, self-study, interactive programs in the dental undergraduate program: a pilot.

The goal of this project was to encourage interdisciplinary, integrative health teaching and research in dental education through the development of web-accessible programs, collectively called the "StudyWeb." The specific objective of the project was the construction and integration of a series of prototypes of self-study modules. Four pilot modules were developed using existing teaching materials in histology, pharmacology, prosthodontics, and oral radiology and utilizing a variety of widely available software programs, including FrontPage and Photoshop. Low-end technological choices were made in order to facilitate compatibility with a wide range of hardware, software, and types of Internet access. Modules were tested for functionality, usability, and ease of navigation. The scope of the initial project was limited to development and functionality testing of the original modules. The next phase of this project will involve testing of the effectiveness of these web-based self-instruction tools.

Computer Systems↗

alpha 2-HS glycoprotein/fetuin, a transforming growth factor-beta/bone morphogenetic protein antagonist, regulates postnatal bone growth and remodeling.

Soluble transforming growth factor-beta (TGF-beta)/bone morphogenetic protein (BMP)-binding proteins are widely distributed in mammalian tissues and control cytokine access to membrane signaling receptors. The serum and bone-resident glycoprotein alpha2-HS-glycoprotein/fetuin (ASHG) binds to TGF-beta/BMP cytokines and blocks TGF-beta1 binding to cell surface receptors. Therefore, we examined bone growth and remodeling phenotypes in ASHG-deficient mice. The skeletal structure of Ahsg(-/-) mice appeared normal at birth, but abnormalities were observed in adult Ahsg(-/-) mice. Maturation of growth plate chondrocytes was impaired, and femurs lengthened more slowly between 3 and 18 months of age in Ahsg(-/-) mice. However, bone formation was increased in Ahsg(-/-) mice as indicated by greater cortical thickness, accelerated trabecular bone remodeling, and increased osteoblast numbers on bone surfaces. The normal age-related increase in cortical thickness and bone mineral density was accelerated in Ahsg(-/-) mice and was associated with increased energy required to fracture. Bone formation in response to implanted BMP cytokine extended further from the implant in Ahsg(-/-) compared with Ahsg(+/+) mice, confirming the interaction between ASHG and TGF-beta/BMP cytokines in vivo. Our results demonstrate that ASHG blocks TGF-beta-dependent signaling in osteoblastic cells, and mice lacking ASHG display growth plate defects, increased bone formation with age, and enhanced cytokine-dependent osteogenesis.

Adipocytes↗

Bisphosphonates and periodontics: potential applications for regulation of bone mass in the periodontium and other therapeutic/diagnostic uses.

Bisphosphonates are widely utilized in the management of systemic metabolic bone disease due to their ability to inhibit bone resorption. Recently, new uses of this unique class of pharmacological agents have been suggested. Given their known affinity to bone and their ability to increase osteoblastic differentiation and inhibit osteoclast recruitment and activity, there exists a possible use for bisphosphonates in the diagnosis and management of periodontal diseases. These bone-specific properties could also provide an interesting management strategy to stimulate osteogenesis in conjunction with regenerative materials around osseous defects and may also result in the promotion of bone formation around endosseous implants. The objective of this article is to review the scientific evidence regarding the potential applications of bisphosphonate drugs in the therapeutic management of periodontal diseases. Moreover, the mechanism of action and the pharmacology of these drugs will be reviewed. Finally, the potential role of bisphosphonates regarding their potential to accelerate bone formation, in addition to their usual uses for inhibition of bone resorption, is discussed.

Alendronate↗