Research Spotlight

Gao, X., Wu, L., Tsai, R.Y.L., Ma, J., Liu, X., Chow, D.S., Liang, D. and Xie, H. (2021). “Pharmacokinetic Model Analysis of Supralingual, Oral and Intravenous Deliveries of Mycophenolic Acid.” Pharmaceutics 13(4).

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Mycophenolic acid (MPA) is commonly used for organ rejection prophylaxis via oral administration in the clinic. Recent studies have shown that MPA also has anticancer activities. To explore new therapeutic options for oral precancerous/cancerous lesions, MPA was designed to release topically on the dorsal tongue surface via a mucoadhesive patch. The objective of this study was to establish the pharmacokinetic (PK) and tongue tissue distribution of mucoadhesive MPA patch formulation after supralingual administration in rats and also compare the PK differences between oral, intravenous, and supralingual administration of MPA. Blood samples were collected from Sprague Dawley rats before and after a single intravenous bolus injection, a single oral dose, or a mucoadhesive patch administration on the dorsal tongue surface for 4 h, all with a dose of 0.5 mg/kg of MPA. Plots of MPA plasma concentration versus time were obtained. As multiple peaks were found in all three curves, the enterohepatic recycling (EHR) model in the Phoenix software was adapted to describe their PK parameters with an individual PK analysis method. The mean half-lives of intravenous and oral administrations were 10.5 h and 7.4 h, respectively. The estimated bioavailability after oral and supralingual administration was 72.4% and 7.6%, respectively. There was a 0.5 h lag-time presented after supralingual administration. The results suggest that the systemic plasma MPA concentrations were much lower in rats receiving supralingual administration compared to those receiving doses from the other two routes, and the amount of MPA accumulated in the tongue after patch application showed a sustained drug release pattern. Studies on the dynamic of drug retention in the tongue after supralingual administration showed that ~3.8% of the dose was accumulated inside of tongue right after the patch removal, ~0.11% of the dose remained after 20 h, and ~20.6% of MPA was not released from the patches 4 h after application. The data demonstrate that supralingual application of an MPA patch can deliver a high amount of drug at the site of administration with little systemic circulation exposure, hence lowering the potential gastrointestinal side effects associated with oral administration. Thus, supralingual administration is a potential alternative route for treating oral lesions.

Endo, H., Rees, T.D., Niwa, H., Kuyama, K., Oshima, M., Serizawa, T., Tanaka, S., Iijima, M. and Komiya, M. (2021). “High frequency of upper aerodigestive tract manifestations in mucous membrane pemphigoid.” Oral Dis.

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OBJECTIVE: The objective of this study was to evaluate the frequency of upper aerodigestive tract involvement in patients with mucous membrane pemphigoid associated with desquamative gingivitis. SUBJECTS AND METHODS: Data from 25 patients were collected by retrospective chart review. Their upper aerodigestive had been evaluated using a conventional flexible fiberscope. Oral disease activity was quantified on the basis of the Mucous Membrane Pemphigoid Disease Area Index activity score. RESULTS: Lesions of the upper aerodigestive tract were confirmed in nine symptomatic patients (9/25, 36%), of which five (5/25, 20%) had laryngeal involvement. No lesions were seen in the asymptomatic patients on fiberscope examination. There was a statistically significant difference in the symptoms, high oral disease activity score, and linear IgA deposition on direct immunofluorescence between patients with and without upper aerodigestive tract lesions (p = .001, .001, .002, respectively). CONCLUSION: The high frequency of considerable complications highlights the importance of confirming the presence of upper aerodigestive tract involvement in patients with mucous membrane pemphigoid having desquamative gingivitis. Signs including the presence of symptoms, high oral disease activity score, or linear IgA deposition on direct immunofluorescence might indicate a higher risk of upper aerodigestive tract involvement.

Couto, S.R., Luan, X., Rossmann, J.A., Stenberg, W.V., Yen, K., Atwi, S. and Svoboda, K.K. (2021). “An in vivo comparison of wound healing characteristics of two commercial acellular dermal matrices.” Clin Exp Dent Res.

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OBJECTIVES: Many acellular dermal matrices (ADMs) are available for use in periodontal surgical procedures. However, few studies exist evaluating their in vivo healing properties. The objectives of this study were to compare the wound healing and remodeling of two ADMs used for gingival augmentation procedures in the rat model. MATERIALS AND METHODS: This was a nonrandomized controlled split-mouth study. Envelope flaps were surgically created in the maxillary quadrants of 24 Sprague Dawley rats. Each received either (a) AlloDerm Regenerative Tissue Matrix, or (b) OrACELL. Gingival tissue from one mandibular quadrant served as the untreated control. Six male and six female rats were treated for 7 or 21 days. Biopsies were processed for histologic analysis (H&E, Picro-sirius red, Verhoeff’s solution) or RNA analysis (RT-PCR) to analyze the expression of type I collagen (Col1a1), fibronectin (Fn-1) and VEGF-A (Vegf-A). RESULTS: There was a greater density of fibroblasts in OrACELL compared to AlloDerm at both timepoints. There was a greater density of elastin present in AlloDerm compared to OrACELL at 7 days but no differences at 21 days. There were no differences between test groups in the percentage of birefringent collagen or in the expression of Vegf-A or Fn-1. At 7 days, there were significantly more fibroblasts for males in the OrACELL group compared to females. At 21 days, there was a significantly greater expression of Col1a1 for males in the OrACELL group compared to females. CONCLUSIONS: Early wound healing and remodeling of OrACELL appeared to occur more rapidly than AlloDerm and was accelerated in male rats. Whether these results have clinical implications for soft tissue grafting procedures in humans remains to be determined.

Nalliah, R.P., Timothé, P. and Reddy, M.S. (2021). “Diversity, equity, and inclusion interventions to support admissions have had little benefit to Black students over past 20 years.” J Dent Educ 85(4): 448-455.

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The United States has a history of systemic racism and violence toward minority communities. Unfortunately, the last year has demonstrated that systemic racism, and its consequences, persist. The dental profession has also failed to adequately resolve known issues of racial inequity and systemic racism, with persistent disparities in oral health outcomes for Black Americans compared to all other Americans, underrepresentation of minorities in the profession, and barriers to entry. However, dental education has the opportunity to address these issues. Current accreditation standards do not specifically address racial diversity among the student body, yet it is clear that representation of a population matters and the lack of representation may exacerbate race and racism as public health issues in dentistry. To explore the issue, we curated American Dental Education Association (ADEA) data on the race of students admitted and enrolled into dental programs across the United States. We used data visualization techniques to present the data and study trends. While the number of Black and African American (BAA) enrollees in dental schools has increased between 2000 and 2019, this population continues to make up a disproportionately small percentage of all enrollees, relative to the BAA percentage in the U.S. population. Much of the increase in BAA enrollment is attributable to increased places (due to the opening of new schools and increased class size in established schools) and the rate of acceptance of BAA students has had limited improvement. Very little progress has been accomplished in growing the enrollment of BAA applicants to dental school in 20 years. As a profession, we also fail to grow interest among our graduates in careers that may support historically underrepresented and marginalized racial groups-public health, rural practice, population research, academia, and health policy. This may be a contributing factor to the oral health disparities faced by Black Americans and have implications for dental education.

Zhang, H., Xu, Q., Lu, Y. and Qin, C. (2021). “Effect of high phosphate diet on the formation of dentin in Fam20c-deficient mice.” Eur J Oral Sci: e12795.

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FAM20C (family with sequence similarity 20-member C), a kinase that phosphorylates secretory proteins, plays essential roles in various biological processes. In humans, mutations in FAM20C gene cause Raine syndrome, an autosomal recessive hereditary disease manifesting a broad spectrum of developmental defects including skeletal and craniofacial deformities. Our previous studies revealed that inactivation of Fam20c in mice led to hypophosphatemic rickets and that high phosphate (hPi) diet significantly improved the development of the skeleton in Fam20c-deficient mice. In this study, we evaluated the effects of hPi diet on the formation of dentin in Fam20c-deficient mice, using plain x-ray radiography, micro-computed tomography (µCT), histology, and immunohistochemistry. Plain x-ray radiography and µCT analyses showed that the hPi diet improved the dentin volume fraction and dentin mineral density of the Fam20c-deficient mice. Histology analyses further demonstrated that the hPi diet dramatically improved the integrity of the mandibular first molars and prevented pulp infection and dental abscesses in Fam20c-deficient mice. Our results support that the hPi diet significantly increased the formation and mineralization of dentin in Fam20c-deficient mice, implying that hypophosphatemia is a significant contributor to the dentin defects in Fam20c-deficient subjects