• Peroxisome Proliferator Activated Receptor-α Agonist Slows the Progression of Hypertension, Attenuates Plasma

      Wilson, Justin L.; Duan, Rong; El-Marakby, Ahmed; Alhashim, Abdulmohsin; Lee, Dexter L.; Department of Oral Biology; Department of Pharmacology and Toxicology (2012-07-16)
      The anti-inflammatory properties of PPAR-α plays an important role in attenuating hypertension. The current study determines the anti-hypertensive and anti-inflammatory role of PPAR-α agonist during a slow-pressor dose of Ang II (400 ng/kg/min). Ten to twelve week old male PPAR-α KO mice and their WT controls were implanted with telemetry devices and infused with Ang II for 12 days. On day 12 of Ang II infusion, MAP was elevated in PPAR-α KO mice compared to WT (161 ± 4mmHg versus 145 ± 4 mmHg) and fenofibrate (145 mg/kg/day) reduced MAP in WT + Ang II mice (134 ± 7 mmHg). Plasma IL-6 levels were higher in PPAR-α KO mice on day 12 of Ang II infusion (30 ± 4 versus 8 ± 2 pg/mL) and fenofibrate reduced plasma IL-6 in Ang II-treatedWT mice (10±3 pg/mL). Fenofibrate increased renal expression of CYP4A, restored renal CYP2J expression, reduced the elevation in renal ICAM-1,MCP-1 and COX-2 inWT + Ang II mice. Our results demonstrate that activation of PPAR-α attenuates Ang II-induced hypertension through up-regulation of CYP4A and CYP2J and an attenuation of inflammatory markers such as plasma IL-6, renal MCP-1, renal expression of ICAM-1 and COX-2.
    • Peroxisome Proliferator-Activated Receptor-α Activation Decreases Mean Arterial Pressure, Plasma Interleukin-6, and COX-2 While Increasing Renal CYP4A Expression in an Acute Model of DOCA-Salt Hypertension

      Lee, Dexter L.; Wilson, Justin L.; Duan, Rong; Hudson, Tamaro; El-Marakby, Ahmed; Department of Oral Biology; Department of Pharmacology and Toxicology (2011-12-07)
      Peroxisome proliferator-activated receptor-alpha (PPAR-α) activation by fenofibrate reduces blood pressure and sodium retention during DOCA-salt hypertension. PPAR-α activation reduces the expression of inflammatory cytokines, such as interleukin- 6 (IL-6). Fenofibrate also induces cytochrome P450 4A (CYP4A) and increases 20-hydroxyeicosatetraenoic acid (20-HETE) production. This study tested whether the administration of fenofibrate would reduce blood pressure by attenuating plasma IL-6 and renal expression of cyclooxygenase-2 (COX-2), while increasing expression of renal CYP4A during 7 days of DOCAsalt hypertension. We performed uni-nephrectomy on 12–14 week old male Swiss Webster mice and implanted biotelemetry devices in control, DOCA-salt (1.5mg/g) treated mice with or without fenofibrate (500 mg/kg/day in corn oil, intragastrically). Fenofibrate significantly decreased mean arterial pressure and plasma IL-6. In kidney homogenates, fenofibrate increased CYP4A and decreased COX-2 expression. There were no differences in renal cytochrome P450, family 2, subfamily c, polypeptide 23 (CYP2C23) and soluble expoxide hydrolase (sEH) expression between the groups. Our results suggest that the blood pressure lowering effect of PPAR-α activation by fenofibrate involves the reduction of plasma IL-6 and COX-2, while increasing CYP4A expression during DOCA-salt hypertension. Our results may also suggest that PPAR-α activation protects the kidney against renal injury via decreased COX-2 expression.
    • Phosphorylation of EPS8 Mediates Its Downstream Signaling and Biological Functions

      Shahoumi, Linah; Yeudall, W. Andrew; Department of Oral Biology & Diagnostic Sciences, Georgia Cancer Center (Augusta University, 2019)
      The purpose of this study was to investigate the role of EPS8 phosphorylation in modulating biochemical signaling, cell proliferation and motility in HNSCC.

      Bowerman, Brielle; Rueggeberg, FA; Brenes, C; Department of Restorative Sciences, Department of General Dentistry (Augusta University Libraries, 2019)
      A variety of manufacturing techniques have been used throughout the history of dentistry, in order to fabricate indirect restorations. Formative processes (pouring or pressing items into molds) are used when making conventional dentures, or when pressing ceramics. Recently, subtractive fabrication methods have enabled clinicians to mill a wide variety of ceramic and resin-based blanks directly into final forms, fitting the oral structures with high degrees of precision. Examples of older additive techniques include wax buildups to establish missing tooth structure for fabrication of subsequent cast restorations and the manual layering of powdered porcelains for development of ceramic facings on metallic substrates, or for ceramic veneers themselves. Tremendous advancements have been made in the field of 3D digital printing for many industrially based applications. Advances in research and development have resulted in tabletop 3D printers that produce rapid prototype specimens having very high accuracy and surface feature details. Recently, these advances have resulted in the manufacture and availability of a wide variety of 3D digital printers that dental offices now use to directly fabricate a wide range of restorative appliances (denture bases and teeth, temporary restorations, splints) as well as ancillary devices (impression trays, surgical implant guides, casts, try-in set-ups, and stents). Contemporary dental 3D printing typically involves use of near or true ultraviolet radiation (405 nm & 385 nm, respectively) in order to fabricate the basic desired form from a vat of photo-polymerizable monomers. Subsequent to initial form fabrication, the specimen is alcohol-washed of excess surface monomer, and is then subjected to an additional exposure of strong near/UV light, in order to maximize the polymerization process and provide optimal physical properties, as well as to minimize cytotoxicity resulting from leaching of unreacted, residual monomer within the bulk of the as-printed item.
    • Plasma Membrane Disruption in Orthodontic Tooth Movement

      Orellana, Maria F.; Department of Oral Biology (2002-04)
      (Introduction) One hundred years ago, in 1900, Dr. Edward H. Angle and a dozen colleagues came together to establish dentistry's first specialty, which is known today as orthodontics and dentofacial orthopedics. Orthodontics is a science and an art. It is the art o f creating healthy, beautiful smiles by moving teeth with precise, gradual force expertly applied, and the science concerned with the study o f the growth o f the craniofacial complex, the development o f occlusion and the treatment o f dentofacial abnormalities. Mechanical forces exerted on tooth roots and transmitted to the periodontal tissues initiate the remodeling activity that facilitates the movement o f teeth through bone. The specific changes in the bone surrounding the root o f an orthodontically moved tooth are characterized as resorption and deposition. Resorption o f bone is seen on the compression side o f the tooth. In contrast, bone is deposited in the tension side of the tooth that is being moved in the opposite direction. The biologic response to sustained force against the teeth is a function o f force magnitude; forces great enough to occlude blood vessels lead to pain, sterile necrosis and a process described as undermining resorption that inevitably leads to a delay in tooth movement. Lighter forces allow activation o f osteoclasts, and thus the removal of bone from the compression side by the painless process o ffrontal resorption. Clinicians face the challenge o f maintaining tissue vitality by avoiding undermining resorption, while applying forces heavy enough to produce frontal resorption. An understanding of the cellular and molecular mechanisms that enable bone to adapt to changes in its mechanical environment is important for solving the different challenges o f clinical orthodontics. Almost a century of research has been devoted to examining this phenomenon by morphologic methods. The histologic changes have consequently been well documented, but there are many unanswered questions that must be addressed in order to explain how mechanical deformation is transduced into a desirable biologic response. The aim o f the present investigation was to characterize a novel cellular mechanism for uptake and release of molecules important in bone remodeling by periodontal ligament cells. Specifically, the plasma membrane disruption theory was examined in light o f its role in mechanotransduction in orthodontic tooth movement. These are the first studies linking the placement o f mechanical loading, as occurs in orthodontic tooth movement, with plasma membrane disruption and resealing of periodontal ligament cells. The release o f bFGF and II-ip from the cells of the periodontal ligament was also examined following application o f in vivo strain.
    • Polymeric-calcium phosphate cement composites-material properties: in vitro and in vivo investigations.

      Khashaba, Rania M.; Moussa, Mervet M; Mettenburg, Donald J; Rueggeberg, Frederick A.; Chutkan, Norman B.; Borke, James L.; Department Oral Biology; Department Orthopedic Surgery; Department of Oral Rehabilitation (2010-09-02)
      New polymeric calcium phosphate cement composites (CPCs) were developed. Cement powder consisting of 60 wt% tetracalcium phosphate, 30 wt% dicalcium phosphate dihydrate, and 10 wt% tricalcium phosphate was combined with either 35% w/w poly methyl vinyl ether maleic acid or polyacrylic acid to obtain CPC-1 and CPC-2. The setting time and compressive and diametral tensile strength of the CPCs were evaluated and compared with that of a commercial hydroxyapatite cement. In vitro cytotoxicity and in vivo biocompatibility of the two CPCs and hydroxyapatite cement were assessed. The setting time of the cements was 5-15 min. CPC-1 and CPC-2 showed significantly higher compressive and diametral strength values compared to hydroxyapatite cement. CPC-1 and CPC-2 were equivalent to Teflon controls after 1 week. CPC-1, CPC-2, and hydroxyapatite cement elicited a moderate to intense inflammatory reaction at 7 days which decreased over time. CPC-1 and CPC-2 show promise for orthopedic applications.
    • Porphyromonas gingivalis Escape-from Autophagy in Human Myeloid Dendritic Cells via Minor Mfa-1 Fimbra-DC-Sign Interactions

      El-Awady, Ahmed; Department of Oral Biology (2014-03)
      In professional phagocytes, early receptor recognition is crucial to determine the fate of engulfed microorganisms. Among the many pattern recognition receptors (PRRs) expressed by dendritic cells (DCs), the C-type lectin DC-SIGN is of particular interest as it has been associated with immunosuppression by infecting pathogens. While autophagy has emerged as a major immune mechanism against microbes, very little is presently understood about its role in elimination o f intracellular pathogens; especially in the context o f the PRR diversity expressed by DCs. Hence, the study aimed to investigate the role of DC-SIGN targeting by the anaerobic pathogen Porphyromonas gingivalis in its intracellular survival within myeloid DCs and how intracellular routing through early and late endosomes, autophagosomes and lysosomes relate to this survival. Employed in this investigation were human monocyte derived DCs and a panel of isogenic fimbriae deficient mutant strains of P. gingivalis that express the DC-SIGN ligand (Mfa-1 fimbriae) and/or the TLR2 ligand (FimA fimbriae). The results show that uptake of P. gingivalis by the nonDC-SIGN dependent route resulted in intracellular killing and elimination of intracellular content of P. gingivalis. This route was associated with early endosomal routing through Rab5, increased LC3-II and LAMP-1, as well as the formation of double membrane intracellular phagophores. In contrast, DC-SIGN dependent uptake did not induce significant levels of Rab5, LC3- II, and LAMP1. Moreover, P. gingivalis was mostly contained within single membrane vesicles where it survived intracellularly. Survival was ameliorated by forced autophagy. These results suggest that myeloid DCs are fully capable of eliminating intracellular pathogens by autophagy but that selective engagement of DC-SIGN is a microbial tactic for evasion of antibacterial autophagy leading to intracellular survival.

      Faigen, A; James, J; Stevens, M; Department of Oral and Maxillofacial Surgery (Augusta University, 2019)
      Lifetime implant success, in both esthetic and functional categories is a multifactorial process. Connective tissues, hard and soft, play a major role in the health of an implant platform and its associated restoration. While bone loss around the crestal portion of the implant up to 2.0mm within the first year of use is expected. We desire to determine factors which predict bone loss and overall implant success.. Many of the factors which can be used to account for such bone loss are inappropriate stresses and force distribution, trauma during surgery, micromechanical movement, infection, and multiple other patient factors. Bone loss has not been linked to a single implant type, placement procedure, or specialty, but remains a significant challenge in the long-term success of implants.
    • The potential role of indoleamine 2,3 dioxygenase (IDO) as a predictive and therapeutic target for diabetes treatment: a mythical truth

      Baban, Babak; Penberthy, W. Todd; Mozaffari, Mahmood S.; Department of Oral Biology (2010-03-19)
      Keywords: Individual tolerance
    • Prediction of diabetic retinopathy: role of oxidative stress and relevance of apoptotic biomarkers

      Al-Shabrawey, Mohamed; Smith, Sylvia B; Department of Oral Biology; Department of Ophthalmology; Vision Discovery Institute; Department of Cellular Biology and Anatomy (2010-03-23)
      Keywords: Diabetic retinopathy
    • Preparation, Physical-Chemical Characterization, and Cytocompatibility of Polymeric Calcium Phosphate Cements

      Khashaba, Rania M.; Moussa, Mervet M; Koch, Christopher; Jurgensen, Arthur R.; Missimer, David M.; Rutherford, Ronny L.; Chutkan, Norman B.; Borke, James L.; Department of Oral Biology; Department of Surgery (2011-09-20)
    • Primary versus secondary reconstruction of mandibular critical size defects using recombinant human bone morphogenetic protein 2: an experimental study in dogs

      Hussein, Khaled A.; Department of Oral Biology (2012-12)
      Very often, delayed reconstruction becomes the setting of choice in the reconstruction of large segmental defects in the mandible. Our hypothesis is that rhBMP2 delivery would elicit endogenous expression of BMP2 and VEGF in the soft tissue bed of the defect. Such response is expected to be more pronounced in the immediate than the delayed reconstruction, which will correlate with the quantity and quality of bone formation in the two settings. We also hypothesized that vascular endothelial cells (ECs) of the surrounding soft tissue contribute to the endogenous production of BMP2. In this study we used a mandibular canine segmental defect model (35 mm), periosteum was excised and also the delayed reconstruction group was included in this study in addition to the control group. We investigated the effect of different reconstruction settings on the quantity and quality of bony regenerates; on the production of endogenous BMP2 from the soft tissue bed of the defects and finally we tried to explore the source of this rhBMP2- induced endogenous BMP2 production both in vivo and in vitro. This study demonstrated that rhBMP2 delivery is more effective in immediate reconstruction of large mandibular segmental defects. Immediate delivery of rhBMP2 yielded more adequate reconstruction of the defect after 12 weeks, evident by the quantity and quality of the bone regenerate. Only in the immediate reconstruction group, the advantageous bone parameters were associated with significant up-regulation of BMP2 mRNA and protein in the soft tissue bed of the defect. This suggests that endogenous-BMP2 is important in maintaining the short-acting effect of the delivered rhBMP2. Regarding the source of the endogenous-BMP2, protein co-localization with ECs marker suggested that these cells could be the source for the endogenous BMP2 secretion in response to rhBMP2 treatment. This was confirmed by the in-vitro results on both the mRNA and protein levels. The gradual increase in expression of BMP2 mRNA and the significant upregulation of secreted BMP2 protein upon stimulation of human umbilical vein endothelial cells with 100-ng/ml rhBMP2 recognized a new mechanism of positive feed back response of ECs in response to BMP2 treatment.
    • Proliferative Verrucous Leukoplakia (PVL) Expresses High Levels of Toll-Like Receptor 2 (TLR2)

      Koh, Joon; Kurago, Zoya; Georgia Cancer Center (Augusta University, 2019)
      In the current study, we analyzed samples of human oral mucosal PVL and other epithelial disorders to test the possibility that, if TLR2 is involved in early stages of carcinogenesis, then keratinocytes in early-intermediate stages of PVL may express more TLR2 than keratinocytes in non-dysplastic epithelium.
    • The Role of Oral Microbiota in Bisphosphonate-Induced Osteonecrosis of the Jaw: Rat Tibial Defect Model

      Jernigan, Joshua; Awad, Mohamed E.; Elsayed, Ranya; Elsalanty, Mohammed (Augusta University, 2019)
      This study aims to develop a rat model for post-traumatic osteonecrosis at an extra-oral bone site that simulates the oral micro-environment, specifically the proximal tibia.
    • The role of Toll-like receptor (TLR) 2 in the systemic immune response profile of mice induced to develop squamous cell carcinoma of the upper aerodigestive tract

      El-Shafey, Sally; El-Shafey, Sally; Department of Oral Biology (4/1/2017)
      Background Head and necksquamous cell carcinomais associated with immunosuppression, a state in which the progression of cancer is associated with disturbances in the immune system functions. Emerging studies suggest a fundamental role for the innate immune system, particularly Toll-like receptor 2 (TLR2), in this process.QuestionsIn this study, we investigated the potential roles of TLR2 on systemic immune profile in a mouse model of headand necksquamous cell carcinoma.MethodsTwo different protocols of a mouse model of 4-nitroquinoline 1-oxide and ethanol-induced carcinogenesis to induce head and neck squamous cell carcinoma were used. To evaluate the systemic immune profiles, total RNA wasisolated from the spleens of four groups of animals, including carcinogen-treated and control untreated wild-type and toll-like receptor 2-deficient animals. Quantitative real-time PCR was performed forgenesrepresentative of house-keeping genes, type 1 and type 2 immune responses, regulatory T and B cells, and adenosine receptors.Results and ConclusionIn the standard protocol of 4-nitroquinoline 1-oxide and ethanol-induced carcinogenesis, there was asignificant upregulation of adenosine receptor A2a in the spleens of wild type iiimice treatedwith4-nitroquinoline 1-oxide and ethanolrelative to wild type untreatedanimals. In the standard protocol of carcinogenesis, there was a significant upregulation of CD39 in the spleens of TLR2-koanimalstreated with 4-nitroquinoline 1-oxide and ethanol relative to untreated TLR2-ko mice. These results suggest that carcinogenesis in the upper aerodigestive tract is associated with alterations in the systemic immune profile reflected in the spleen. However, the specific impact on the immune profiles appears to be affected by the presence or absence of TLR2.

      Baxter, John; Brenes, C; Rueggeberg, FA; Departments of General Dentistry; Department of Restorative Sciences (Augusta University, 2019)
      Direct, tissue-borne, full denture restoration of edentulous arches has become a well accepted restoration modality for millions of people. In this methodology, the tissue-bearing surface of a polymeric material replacing the form and structure of lost alveolar bond and overlying mucosa rests directly on the residual ridge tissue. Retention of the denture is attained through capillary adhesion forces acting to wet (cover) both the oral mucosa and the polymeric denture bases that rests upon it. Good wetting by saliva is thus one of the many critical features affecting adhesion of the denture base to the oral mucosa. Measurement of the ability of a fluid to wet a surface is performed using the shape of a fluid droplet on that surface. If the fluid wets that surface, then the droplet will spread out. If the fluid does not wet that surface, it will bead up. Quantitative measurement of fluid flow on a surface is performed using measurement of the “contact angle.” In this method, a controlled volume is dispensed onto a surface, and while viewing the interaction of that fluid in silhouette, the angle formed at the tangent of that drop and the flat surface is determined. The lower the contact angle, the more a fluid wets a surface, and the higher its value, the less wetting is that fluid on a specific surface.

      Sun, Christina; Awad, Mohamed E; Jernigan, Joshua; College of Science and Mathematics; Department of Oral Biology; Dental College of Georgia; Elsalanty, Mohammed; Augusta University (2019-02-13)
      The aim of this systematic review was to evaluate the validity of using preoperative serum C-terminal crosslinking telopeptide (CTX) levels as predictive factor of increased risk of developing medication-related osteonecrosis of the jaw (MRONJ) in patients on bisphosphonate (BP) therapy who undergo invasive dental procedures. A search was conducted through PubMed, MEDLINE, and Web of Science, following PRISMA guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. Meta-analysis was conducted on the risk ratio. The methodological index for nonrandomized studies (MINORS) and Quality Appraisal of Reliability Studies (QAREL) checklist were used to assess quality. Eighteen clinical trials, involving 2301 patients were included. Most patients received Alendronate or Risedronate for an average of 62.14 months. The average serum CTX level in BP-treated patients before surgery was 217.67 pg/ml. Meta-analysis demonstrated that the cutoff in CTX level (150 pg/ml) was not predictive of BRONJ risk. The sensitivity of CTX value <150 pg/ml was 34.26% and the specificity was 77.08%. The use of CTX to diagnose BRONJ risk following dental procedures in bisphosphonate-treated patients is not justified. Further studies are needed to develop other reliable biomarkers.
    • Soft Tissue and Bone Healing at Platform Shift Abutment in One-Stage Implants: A Radiographic, Histologic, and Histometric Study in Dogs

      Wenzel, Brent A.; Department of Oral Biology (2011-04)
      Matching-diameter and platform shift abutments were randomized to 40 dental implants placed into 5 dogs following mucoperiosteal flap elevation. 1x5 (width x height) mm peri-implant gap defects were surgically created in randomly assigned jaw quadrants. All implants were placed 2 mm subcrestally. Mucoperiosteal flaps were sutured around the abutments for primary intention healing. Radiographs were recorded immediately, 4-, and 8 weeks postsurgery when block biopsies were removed for histometric analysis. The histological examination showed the junctional epithelium was arrested coronal to the implant platform without significant differences among experimental conditions. Crestal bone height demonstrated no significant differences among groups at buccal or lingual sites. Bone-implant contact reached 0.4 mm below the platform at buccal sites. Higher variability was observed at lingual sites without differences among groups. Platform shift abutments offer negligible benefit compared to conventional abutments to maintain peri-implant crestal bone and soft tissue contours.
    • The stability of an increased vertical dimension of occlusion in growing and non-growing golden hamsters

      Berman, Scott C.; Department of Oral Biology (Augusta University, 1993-03)
    • Sustained Release Formulation for Vascular Endothelial Growth Factor

      Elzinga, Jennifer Lynn; Department of Oral Biology (2013-03)
      Necrosis of tissue due to trauma or a surgical procedure is a complication of wound healing. This necrosis, or tissue death, occurs when the vasculature is unable to perfuse involved tissue with the oxygen and nutrients necessary to maintain viability. To provide adequate access, reflecting a flap of tissue is often necessary in a variety of surgical procedures, including periodontal surgeries. The success of these procedures is limited by the development of tissue flap necrosis. The survival of these tissue flaps is dependent upon adequate perfusion by the blood vessel supply at the base of the flap, followed by the growth of new vascular channels from the recipient site. However, if angiogenesis does not promptly reach the distal extent of the flap, this portion becomes ischemic, leading to necrosis. Loss of the protective flap delays healing and increases the risk of scarring and infection. Necrosis of this distal region of a tissue flap begins as early as 24 hours following the surgical procedure and progresses rapidly until day 3 when the unaffected tissue begins to stabilize.1 A variety of pharmacological strategies to enhance tissue flap perfusion have been tested in an attempt to prevent necrosis. One such strategy is the administration of angiogenic growth factors such as vascular endothelial growth factor (VEGF). VEGF is known to stimulate the proliferation of endothelial cells from existing vasculature to create new blood vessels, thus enhancing 8 tissue survival.2-7 In addition, VEGF contributes to other aspects of wound healing, including inflammation, granulation tissue formation, reepithelialization, matrix formation, and remodeling.2 Administration of VEGF to wound healing models has shown promising results by increasing vascular formation, leading to enhanced tissue perfusion. However, its short duration of action and rapid dissipation from the target site reduces its effectiveness.8 Maintaining therapeutic concentrations of VEGF at the target site to maximize new vessel growth and reduce necrosis, either multiple applications or an extended-release delivery system is required. An ideal system would provide ease of use and delivery kinetics for sustained therapeutic dosing of VEGF to the wound environment for the duration of healing, thereby minimizing tissue necrosis. A variety of application methods and delivery systems are under investigation in the search to develop one that provides utility as well as improved clinical outcome.