Browsing by Author "Biomedical Sciences and Comprehensive Care, School of Dentistry"
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Item Adipose-derived stem cell conditioned medium impacts asymptomatic peripheral neuromuscular denervation in the mutant superoxide dismutase (G93A) transgenic mouse model of amyotrophic lateral sclerosis(IOS, 2018-09) Walker, Chandler L.; Meadows, Rena M.; Merfeld-Clauss, Stephanie; Du, Yansheng; March, Keith L.; Jones, Kathryn J.; Biomedical Sciences and Comprehensive Care, School of DentistryBackground:Amyotrophic lateral sclerosis (ALS) is devastating, leading to paralysis and death. Disease onset begins pre-symptomatically through spinal motor neuron (MN) axon die-back from musculature at ∼47 days of age in the mutant superoxide dismutase 1 (mSOD1G93A) transgenic ALS mouse model. This period may be optimal to assess potential therapies. We previously demonstrated that post-symptomatic adipose-derived stem cell conditioned medium (ASC-CM) treatment is neuroprotective in mSOD1G93A mice. We hypothesized that early disease onset treatment could ameliorate neuromuscular junction (NMJ) disruption. Objective:To determine whether pre-symptom administration of ASC-CM prevents early NMJ disconnection. Methods:We confirmed the NMJ denervation time course in mSOD1G93A mice using co-labeling of neurofilament and post-synaptic acetylcholine receptors (AchR) by α-bungarotoxin. We determined whether ASC-CM ameliorates early NMJ loss in mSOD1G93A mice by systemically administering 200μl ASC-CM or vehicle medium daily from post-natal days 35 to 47 and quantifying intact NMJs through co-labeling of neurofilament and synaptophysin with α-bungarotoxin in gastrocnemius muscle. Results:Intact NMJs were significantly decreased in 47 day old mSOD1G93A mice (p < 0.05), and daily systemic ASC-CM prevented disease-induced NMJ denervation compared to vehicle treated mice (p < 0.05). Conclusions:Our results lay the foundation for testing the long-term neurological benefits of systemic ASC-CM therapy in the mSOD1G93A mouse model of ALS.Item Advanced Scaffolds for Dental Pulp and Periodontal Regeneration(Elsevier, 2017-10) Bottino, Marco C.; Pankajakshan, Divya; Nör, Jacques E.; Biomedical Sciences and Comprehensive Care, School of DentistryNo current therapy promotes root canal disinfection and regeneration of the pulp-dentin complex in cases of pulp necrosis. Antibiotic pastes used to eradicate canal infection negatively affect stem cell survival. Three-dimensional easy-to-fit antibiotic-eluting nanofibers, combined with injectable scaffolds, enriched or not with stem cells and/or growth factors, may increase the likelihood of achieving predictable dental pulp regeneration. Periodontitis is an aggressive disease that impairs the integrity of tooth-supporting structures and may lead to tooth loss. The latest advances in membrane biomodification to endow needed functionalities and technologies to engineer patient-specific membranes/constructs to amplify periodontal regeneration are presented.Item Alveolar bone protection by targeting the SH3BP2-SYK axis in osteoclasts(Wiley, 2020-02) Kittaka, Mizuho; Yoshimoto, Tetsuya; Schlosser, Collin; Rottapel, Robert; Kajiya, Mikihito; Kurihara, Hidemi; Reichenberger, Ernst J.; Ueki, Yasuyoshi; Biomedical Sciences and Comprehensive Care, School of DentistryPeriodontitis is a bacterially induced chronic inflammatory condition of the oral cavity where tooth-supporting tissues including alveolar bone are destructed. Previously, we have shown that the adaptor protein SH3-domain binding protein 2 (SH3BP2) plays a critical role in inflammatory response and osteoclastogenesis of myeloid lineage cells through spleen tyrosine kinase (SYK). In this study, we show that SH3BP2 is a novel regulator for alveolar bone resorption in periodontitis. Micro-CT analysis of SH3BP2-deficient (Sh3bp2 -/- ) mice challenged with ligature-induced periodontitis revealed that Sh3bp2 -/- mice develop decreased alveolar bone loss (male 14.9% ± 10.2%; female 19.0% ± 6.0%) compared with wild-type control mice (male 25.3% ± 5.8%; female 30.8% ± 5.8%). Lack of SH3BP2 did not change the inflammatory cytokine expression and osteoclast induction. Conditional knockout of SH3BP2 and SYK in myeloid lineage cells with LysM-Cre mice recapitulated the reduced bone loss without affecting both inflammatory cytokine expression and osteoclast induction, suggesting that the SH3BP2-SYK axis plays a key role in regulating alveolar bone loss by mechanisms that regulate the bone-resorbing function of osteoclasts rather than differentiation. Administration of a new SYK inhibitor GS-9973 before or after periodontitis induction reduced bone resorption without affecting inflammatory reaction in gingival tissues. In vitro, GS-9973 treatment of bone marrow-derived M-CSF-dependent macrophages suppressed tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation with decreased mineral resorption capacity even when GS-9973 was added after RANKL stimulation. Thus, the data suggest that SH3BP2-SYK is a novel signaling axis for regulating alveolar bone loss in periodontitis and that SYK can be a potential therapeutic target to suppress alveolar bone resorption in periodontal diseases.Item Analyzing Medication Documentation in Electronic Health Records: Dental Students’ Self-Reported Behaviors and Charting Practices(ADEA, 2019-06) Burcham, Wesley K.; Romito, Laura M.; Moser, Elizabeth A.; Gitter, Bruce D.; Biomedical Sciences and Comprehensive Care, School of DentistryThe aim of this two-part study was to assess third- and fourth-year dental students’ perceptions, self-reported behaviors, and actual charting practices regarding medication documentation in axiUm, the electronic health record (EHR) system. In part one of the study, in fall 2015, all 125 third- and 85 fourth-year dental students at one U.S. dental school were invited to complete a ten-item anonymous survey on medication history-taking. In part two of the study, the EHRs of 519 recent dental school patients were randomly chosen via axiUm query based on age >21 years and the presence of at least one documented medication. Documentation completeness was assessed per EHR and each medication based on proper medication name, classification, dose/frequency, indication, potential oral effects, and correct medication spelling. Consistency was evaluated by identifying the presence/absence of a medical reason for each medication. The survey response rate was 90.6% (N=187). In total, 64.5% of responding students reported that taking a complete medication history is important and useful in enhancing pharmacology knowledge; 90.4% perceived it helped improve their understanding of patients’ medical conditions. The fourth-year students were more likely than the third-year students to value the latter (p=0.0236). Overall, 48.6% reported reviewing patient medications with clinic faculty 76-100% of the time. The respondents’ most frequently cited perceived barriers to medication documentation were patients’ not knowing their medications (68.5%) and, to a much lesser degree, axiUm limitations (14%). Proper medication name was most often recorded (93.6%), and potential oral effects were recorded the least (3.0%). Medication/medical condition consistency was 70.6%. In this study, most of the students perceived patient medication documentation as important; however, many did not appreciate the importance of all elements of a complete medication history, and complete medication documentation was low.Item Antibacterial Activities of Methanol and Aqueous Extracts of Salvadora persica against Streptococcus mutans Biofilms: An In Vitro Study(MDPI, 2021-12-01) Balhaddad, Abdulrahman A.; Mokeem, Lamia; Melo, Mary Anne S.; Gregory, Richard L.; Biomedical Sciences and Comprehensive Care, School of DentistryThe use of herbal products in oral hygiene care has a long history, and their use is popular today. A tree stick, named Salvadora persica (S. persica), is commonly used to remove dental plaque and clean teeth in many countries. In addition, extracts of S. persica can be used as a mouthwash, as they demonstrate antimicrobial properties. This study aimed to investigate the antibacterial effect of S. persica methanol and aqueous extracts against Streptococcus mutans (S. mutans) biofilm. A S. mutans biofilm formation assay was conducted using different concentrations of S. persica methanol or water extracts in tryptic soy broth (TSB) supplemented with 1% sucrose. The biofilm was stained with crystal violet dye, and the absorbance was assessed to examine biofilm formation. One-way analysis of variance (ANOVA) and Tukey tests were used to analyze the results. The S. persica methanol extract displayed a significant inhibition (p ≤ 0.001) against the S. mutans biofilm. The 10 mg/mL concentration of the S. persica methanol extract was determined as the minimum biofilm inhibitory concentration (MBIC). The used methanol concentration, mixed with TSB supplemented with 1% sucrose and without the S. persica extract, did not inhibit the S. mutans biofilm. The S. persica aqueous extract did not demonstrate any biofilm inhibition at any concentration (p ≥ 0.05). The findings of this study suggest the potential of using S. persica methanol extract as a mouthwash or adjunctive to oral hygiene tools.Item The anticariogenic effect of xylitol on seven Streptococcus mutans strains(Discovery Scientific Society, 2021-07) Nassar, Hani M.; Alhazzazi, Turki Y.; Hazzazi, Loai W.; Gregory, Richard L.; Biomedical Sciences and Comprehensive Care, School of DentistryIntroduction: Xylitol can affect caries-inducing bacteria; however, different Streptococcus mutans strains might respond differently. Aim: To investigate the effect of xylitol on biofilm formation and metabolic activity of seven S. mutans strains. Methods: Seven S. mutans strains (UA159, A32-2, NG8, 10449, UA130, LM7, and OMZ175) were inoculated into 96-well microtiter plates and were tested with various xylitol concentrations (0.0, 0.0016, 0.0031, 0.0063, 0.0125, 0.025, 0.05, 0.1, 0.2, 0.4 and 0.8 g/mL) for inhibition of biofilm formation and bacterial metabolic activity by recording absorbance values. Lactate dehydrogenase and extracellular polysaccharide assays were conducted at 0.0, 0.1, 0.2, 0.4, and 0.8 g xylitol/mL. Data were analyzed by one-way analysis of variance, Tukey’s, paired t, and LSD tests at 0.05 significance level. Results: Xylitol produced a significant decrease in bacterial biofilm formation compared to controls at 0.4 g/mL, with almost complete lack of biofilm formation at 0.8 g/mL. This was consistent with metabolic activity which demonstrated a significant activity reduction occurring for all strains at 0.4 g/mL, and a complete lack of activity at 0.8 g/mL for all seven strains. There was a trend for lower LDH and EPS production with the increase in xylitol concentration especially with UA159, UA130, and NG8. Conclusion: Xylitol has a clear anticariogenic effect on S. mutans which was slightly different depending on the tested strain confirming that the benefit of xylitol might vary from one patient to another. The effect is more apparent at concentrations of 0.4 g/mL and higher.Item Antimicrobial Efficacy of Triple Antibiotic-Eluting Polymer Nanofibers against Multispecies Biofilm(Elsevier, 2017-09) Albuquerque, Maria T.P.; Nagata, Juliana; Bottino, Marco C.; Biomedical Sciences and Comprehensive Care, School of DentistryThe elimination of microbial flora in cases of immature permanent teeth with necrotic pulp is both key and a challenging goal for the long-term success of regenerative therapy. Recent research has focused on the development of cell-friendly intracanal drug delivery systems. This in vitro study aimed to investigate the antimicrobial action of 3-dimensional (3D) tubular-shaped triple antibiotic-eluting nanofibrous constructs against a multispecies biofilm on human dentin. Polydioxanone polymer solutions, antibiotic-free or incorporated with metronidazole, ciprofloxacin, and minocycline, were electrospun into 3D tubular-shaped constructs. A multispecies biofilm consisting of Actinomyces naeslundii, Streptococcus sanguinis, and Enterococcus faecalis was forced inside the dentinal tubules via centrifugation in a dentin slice in vitro model. The infected specimens were exposed to 2 experimental groups (ie, 3D tubular-shaped triple antibiotic-eluting constructs and triple antibiotic paste [TAP]) and 2 control groups (7-day biofilm untreated and antibiotic-free 3D tubular-shaped constructs). Biofilm elimination was quantitatively analyzed with confocal laser scanning microscopy. Confocal laser scanning microscopic (CLSM) analysis showed a dense population of viable (green) bacteria adhered to dentin and penetrated into the dentinal tubules. Upon 3D tubular-shaped triple antibiotic-eluting nanofibrous construct exposure, nearly complete elimination of viable bacteria on the dentin surface and inside the dentinal tubules was shown in the CLSM images, which was similar (P < .05) to the bacterial death promoted by the TAP group but significantly greater when compared with both the antibiotic-free 3D tubular-shaped constructs and the control (saline). The proposed 3D tubular-shaped antibiotic-eluting construct showed pronounced antimicrobial effects against the multispecies biofilm tested and therefore holds significant clinical potential as a disinfection strategy before regenerative endodontics.Item Bioactive Materials Subjected to Erosion/Abrasion and Their Influence on Dental Tissues(Allen Press, 2020) Viana, Í. E. L.; Alania, Y.; Feitosa, S.; Feitosa, A. B.; Braga, R. R.; Scaramucci, T.; Biomedical Sciences and Comprehensive Care, School of DentistryObjective: The objective of this study was to evaluate the effect of erosion or erosion-abrasion on bioactive materials and adjacent enamel/dentin areas. Methods and Materials: Enamel and dentin blocks (4×4×2 mm) were embedded side by side in acrylic resin, and a standardized cavity (1.2×4×1.5 mm) was prepared between them. Preparations were restored with the following materials: composite resin (Filtek Z350, control); experimental composite containing di-calcium phosphate dihydrate particles (DCPD); Giomer (Beautifil II), high viscosity glass ionomer cement (GIC, Fuji IX); and a resin-modified GIC (Fuji II LC). The specimens were submitted to two cycling models (n=10): erosion or erosion-abrasion. The challenges consisted of five-minute immersion in 0.3% citric acid solution, followed by 60-minute exposure to artificial saliva. Toothbrushing was carried out twice daily, 30 minutes after the first and last exposures to acid. Dental and material surface loss (SL, in μm) were determined by optical profilometry. Data were analyzed with Kruskal-Wallis and Dunn tests (α=0.05). Results: Under erosion, for enamel, only the GIC groups presented lower SL values than Z350 (p<0.001 for Fuji IX and p=0.018 for Fuji II LC). For dentin, none of the materials showed significantly lower SL values than Z350 (p>0.05). For material, the GICs had significantly higher SL values than those of Z350 (p<0.001 for Fuji IX and p=0.002 for Fuji II LC). Under erosion-abrasion, the enamel SL value was significantly lower around Fuji II LC compared with the other materials (p<0.05). No significant differences were observed among groups for dentin SL (p=0.063). The GICs and Giomer showed higher SL values than Z350 (p<0.001 for the GICs and p=0.041 for Giomer). Conclusion: Both GIC-based materials were susceptible to erosive wear; however, they promoted the lowest erosive loss of adjacent enamel. Against erosion-abrasion, only Fuji II LC was able to reduce enamel loss. For dentin, none of the materials exhibited a significant protective effect.Item Bioactivity of Dental Restorative Materials: FDI Policy Statement(Elsevier, 2023) Schmalz, Gottfried; Hickel, Reinhard; Price, Richard Bengt; Platt, Jeffrey A.; Biomedical Sciences and Comprehensive Care, School of DentistryThe term bioactivity is being increasingly used in medicine and dentistry. Due to its positive connotation, it is frequently utilised for advertising dental restorative materials. However, there is confusion about what the term means, and concerns have been raised about its potential overuse. Therefore, FDI decided to publish a Policy Statement about the bioactivity of dental restorative materials to clarify the term and provide some caveats for its use in advertising. Background information for this Policy Statement was taken from the current literature, mainly from the PubMed database and the internet. Bioactive restorative materials should have beneficial/desired effects. These effects should be local, intended, and nontoxic and should not interfere with a material's principal purpose, namely dental tissue replacement. Three mechanisms for the bioactivity of such materials have been identified: purely biological, mixed biological/chemical, or strictly chemical. Therefore, when the term bioactivity is used in an advertisement or in a description of a dental restorative material, scientific evidence (in vitro or in situ, and preferably in clinical studies) should be provided describing the mechanism of action, the duration of the effect (especially for materials releasing antibacterial substances), and the lack of significant adverse biological side effects (including the development and spread of antimicrobial resistance). Finally, it should be documented that the prime purpose, for instance, to be used to rebuild the form and function of lost tooth substance or lost teeth, is not impaired, as demonstrated by data from in vitro and clinical studies. The use of the term bioactive dental restorative material in material advertisement/information should be restricted to materials that fulfil all the requirements as described in the FDI Policy Statement.Item Bisperoxovanadium promotes motor neuron survival and neuromuscular innervation in amyotrophic lateral sclerosis(BMC, 2021-10-11) Wang, Junmei; Tierney, Lydia; Mann, Ranjeet; Lonsway, Thomas; Walker, Chandler L.; Biomedical Sciences and Comprehensive Care, School of DentistryAmyotrophic lateral sclerosis (ALS) is the most common motor neuron (MN) disease, with no present cure. The progressive loss of MNs is the hallmark of ALS. We have previously shown the therapeutic effects of the phosphatase and tensin homolog (PTEN) inhibitor, potassium bisperoxo (picolinato) vanadium (bpV[pic]), in models of neurological injury and demonstrated significant neuroprotective effects on MN survival. However, accumulating evidence suggests PTEN is detrimental for MN survival in ALS. Therefore, we hypothesized that treating the mutant superoxide dismutase 1 G93A (mSOD1G93A) mouse model of ALS during motor neuron degeneration and an in vitro model of mSOD1G93A motor neuron injury with bpV(pic) would prevent motor neuron loss. To test our hypothesis, we treated mSOD1G93A mice intraperitoneally daily with 400 μg/kg bpV(pic) from 70 to 90 days of age. Immunolabeled MNs and microglial reactivity were analyzed in lumbar spinal cord tissue, and bpV(pic) treatment significantly ameliorated ventral horn motor neuron loss in mSOD1G93A mice (p = 0.003) while not significantly altering microglial reactivity (p = 0.701). Treatment with bpV(pic) also significantly increased neuromuscular innervation (p = 0.018) but did not affect muscle atrophy. We also cultured motor neuron-like NSC-34 cells transfected with a plasmid to overexpress mutant SOD1G93A and starved them in serum-free medium for 24 h with and without bpV(pic) and downstream inhibitor of Akt signaling, LY294002. In vitro, bpV(pic) improved neuronal viability, and Akt inhibition reversed this protective effect (p < 0.05). In conclusion, our study indicates systemic bpV(pic) treatment could be a valuable neuroprotective therapy for ALS.