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1.
Int J Mol Sci ; 25(2)2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38255941

ABSTRACT

Many studies have been exploring the use of bone graft materials (BGMs) and mesenchymal stem cells in bone defect reconstruction. However, the regeneration potential of Algipore (highly purified hydroxyapatite) and Biphasic (hydroxyapatite/beta-tricalcium phosphate) BGMs combined with bone marrow-derived mesenchymal stem cells (BMSCs) remains unclear. Therefore, we evaluated their osseointegration capacities in reconstructing peri-implant bone defects. The cellular characteristics of BMSCs and the material properties of Algipore and Biphasic were assessed in vitro. Four experimental groups-Algipore, Biphasic, Algipore+BMSCs, and Biphasic+BMSCs-were designed in a rabbit tibia peri-implant defect model. Implant stability parameters were measured. After 4 and 8 weeks of healing, all samples were evaluated using micro-CT, histological, and histomorphometric analysis. In the energy-dispersive X-ray spectroscopy experiment, the Ca/P ratio was higher for Algipore (1.67) than for Biphasic (1.44). The ISQ values continuously increased, and the PTV values gradually decreased for all groups during the healing period. Both Algipore and Biphasic BGM promoted new bone regeneration. Higher implant stability and bone volume density were observed when Algipore and Biphasic BGMs were combined with BMSCs. Biphasic BGM exhibited a faster degradation rate than Algipore BGM. Notably, after eight weeks of healing, Algipore with BSMCs showed more bone-implant contact than Biphasic alone (p < 0.05). Both Algipore and Biphasic are efficient in reconstructing peri-implant bone defects. In addition, Algipore BGM incorporation with BSMCs displayed the best performance in enhancing implant stability and osseointegration potential.


Subject(s)
Mesenchymal Stem Cells , Plastic Surgery Procedures , Animals , Rabbits , Osseointegration , Bone Regeneration , Durapatite
2.
Polymers (Basel) ; 15(6)2023 Mar 14.
Article in English | MEDLINE | ID: mdl-36987233

ABSTRACT

This study reports a carboxymethyl cellulose (CMC)/polyvinyl alcohol (PVA) composite film that incorporates Calendula officinalis (CO) extract for biomedical applications. The morphological, physical, mechanical, hydrophilic, biological, and antibacterial properties of CMC/PVA composite films with various CO concentrations (0.1%, 1%, 2.5%, 4%, and 5%) are fully investigated using different experiments. The surface morphology and structure of the composite films are significantly affected by higher CO concentrations. X-ray diffraction (XRD) and Fourier transform infrared spectrometry (FTIR) analyses confirm the structural interactions among CMC, PVA, and CO. After CO is incorporated, the tensile strength and elongation upon the breaking of the films decrease significantly. The addition of CO significantly reduces the ultimate tensile strength of the composite films from 42.8 to 13.2 MPa. Furthermore, by increasing the concentration of CO to 0.75%, the contact angle is decreased from 15.8° to 10.9°. The MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay reveals that the CMC/PVA/CO-2.5% and CMC/PVA/CO-4% composite films are non-cytotoxic to human skin fibroblast cells, which is favorable for cell proliferation. Remarkably, 2.5% and 4% CO incorporation significantly improve the inhibition ability of the CMC/PVA composite films against Staphylococcus aureus and Escherichia coli. In summary, CMC/PVA composite films containing 2.5% CO exhibit the functional properties for wound healing and biomedical engineering applications.

3.
J Am Dent Assoc ; 153(6): 542-551, 2022 06.
Article in English | MEDLINE | ID: mdl-35241270

ABSTRACT

BACKGROUND: The objective of this study was to analyze the association between tooth loss and uncontrolled diabetes among US adults. METHODS: The authors used National Health and Nutrition Examination Survey data from 2011 through 2018. The sample included 16,635 participants 20 years and older who represent 187,596,215 people in the United States in a probability weighted sample. The authors used bivariate analysis and multiple regressions to analyze factors associated with edentulism and number of missing teeth. RESULTS: The multiple logistic regression model significantly predicted edentulism using diabetes status (adjusted odds ratio controlled diabetes, 1.44 [95% CI, 1.12 to 1.86]; adjusted odds ratio uncontrolled diabetes, 2.26 [95% CI, 1.33 to 3.85]), missing annual dental visits, seeing a dentist only for treatment, family income below 200% of the federal poverty guideline, being female, being 65 years or older, tobacco smoking, and no college education. After controlling for the same covariates, multiple Poisson regression analysis showed that dentate adults with controlled and uncontrolled diabetes had higher relative risk of tooth loss than those without diabetes (adjusted risk ratio controlled diabetes, 1.52 [95% CI, 1.35 to 1.71]; adjusted risk ratio uncontrolled diabetes, 1.57 [95% CI, 1.35 to 1.83]). CONCLUSIONS: US adults with uncontrolled (glycated hemoglobin ≥ 9%) and controlled diabetes (glycated hemoglobin < 9%) were more likely to be edentulous and experience tooth loss than adults without diabetes. PRACTICAL IMPLICATIONS: US health policy officials should adopt benefits policies to provide regular dental examinations to people who have diabetes, have low income (< 200% of the federal poverty guideline), or are 65 years or older to reduce tooth loss and improve their quality of life. Dentists should work with physicians to help patients control glycemic levels.


Subject(s)
Diabetes Mellitus , Tooth Loss , Adult , Diabetes Mellitus/epidemiology , Female , Glycated Hemoglobin , Humans , Male , Nutrition Surveys , Quality of Life , Tooth Loss/complications , Tooth Loss/epidemiology , United States/epidemiology
4.
Stem Cell Res Ther ; 13(1): 73, 2022 02 19.
Article in English | MEDLINE | ID: mdl-35183254

ABSTRACT

BACKGROUND: Mesenchymal stem cell (MSC)-based tissue engineering plays a major role in regenerative medicine. However, the efficiency of MSC transplantation and survival of engrafted stem cells remain challenging. Melatonin can regulate MSC biology. However, its function in the osteogenic differentiation of dental pulp-derived MSCs (DPSCs) remains unclear. We investigated the effects and mechanisms of melatonin on the osteogenic differentiation and bone regeneration capacities of DPSCs. METHODS: The biological effects and signaling mechanisms of melatonin with different concentrations on DPSCs were evaluated using a proliferation assay, the quantitative alkaline phosphatase (ALP) activity, Alizarin red staining, a real-time polymerase chain reaction, and a western blot in vitro cell culture model. The in vivo bone regeneration capacities were assessed among empty control, MBCP, MBCP + DPSCs, and MBCP + DPSCs + melatonin preconditioning in four-created calvarial bone defects by using micro-computed tomographic, histological, histomorphometric, and immunohistochemical analyses after 4 and 8 weeks of healing. RESULTS: In vitro experiments revealed that melatonin (1, 10, and 100 µM) significantly and concentration-dependently promoted proliferation, surface marker expression (CD 146), ALP activity and extracellular calcium deposition, and osteogenic gene expression of DPSCs (p < 0.05). Melatonin activated the protein expression of ALP, OCN, and RUNX-2 and inhibited COX-2/NF-κB expression. Furthermore, the phosphorylation of mitogen-activated protein kinase (MAPK) p38/ERK signaling was significantly increased in DPSCs treated with 100 µM melatonin, and their inhibitors significantly decreased osteogenic differentiation. In vivo experiments demonstrated that bone defects implanted with MBCP bone-grafting materials and melatonin-preconditioned DPSCs exhibited significantly greater bone volume fraction, trabecular bone structural modeling, new bone formation, and osteogenesis-related protein expression than the other three groups at 4 and 8 weeks postoperatively (p < 0.05). CONCLUSIONS: These results suggest that melatonin promotes the proliferation and osteogenic differentiation of DPSCs by regulating COX-2/NF-κB and p38/ERK MAPK signaling pathways. Preconditioning DPSCs with melatonin before transplantation can efficiently enhance MSCs function and regenerative capacities.


Subject(s)
Melatonin , Mesenchymal Stem Cells , Bone Regeneration , Cell Differentiation , Cell Proliferation , Cells, Cultured , Dental Pulp , Melatonin/pharmacology , Mitogen-Activated Protein Kinases/pharmacology , Osteogenesis
5.
Article in English | MEDLINE | ID: mdl-35060966

ABSTRACT

This article presents a retrospective case series of implant site development using titanium mesh (Ti-mesh) in the maxilla. A total of 58 mesh procedures in combination with several different bone grafts (allograft, cellular allograft, and bovine xenograft) and biologics (including recombinant human platelet-derived growth factor, autogenous platelet-rich growth factor, and recombinant human bone morphogenetic protein-2) were performed in 48 patients. Ti-mesh guided bone regeneration procedures were performed 2 to 3 months after extraction of nonrestorable/hopeless teeth, and the implants were placed 6 to 8 months postaugmentation. The mean initial ridge width was 2.0 ± 1.0 mm, and the mean horizontal gain after Ti-mesh procedures was 4.7 ± 1.6 mm. The ridge width was first measured on the cross-sectional presurgical CBCT image and then confirmed clinically during surgical procedures. No statistical difference in the horizontal gain was found among different combinations of bone grafts and biomaterials. Ti-mesh exposure occurred 22% of the time. The middle-aged adults (odds ratio [OR] = 8.59; P = .046) and older adults (OR = 16.66; P = .02) had significantly higher chances of mesh exposure compared to young adults. While all implants were successfully placed, about 56% of the implants had < 2 mm of bone to the facial aspect of the osteotomy and received additional contour augmentation when placed in a prosthetically appropriate position for a screw-retained restoration. This study demonstrates that although Ti-mesh procedures result in significant bone regeneration in narrow alveolar ridges to predictably allow implant placement, the age-related mesh exposure rate and frequency of need for additional contour grafting should be discussed with patients.


Subject(s)
Alveolar Ridge Augmentation , Dental Implants , Aged , Animals , Bone Regeneration , Bone Transplantation , Cattle , Cross-Sectional Studies , Dental Implantation, Endosseous , Humans , Maxilla/diagnostic imaging , Maxilla/surgery , Middle Aged , Retrospective Studies , Surgical Mesh , Titanium , Young Adult
6.
Int J Mol Sci ; 22(15)2021 Jul 28.
Article in English | MEDLINE | ID: mdl-34360864

ABSTRACT

This study evaluated the new bone formation potential of micro-macro biphasic calcium phosphate (MBCP) and Bio-Oss grafting materials with and without dental pulp-derived mesenchymal stem cells (DPSCs) and bone marrow-derived mesenchymal stem cells (BMSCs) in a rabbit calvarial bone defect model. The surface structure of the grafting materials was evaluated using a scanning electron microscope (SEM). The multipotent differentiation characteristics of the DPSCs and BMSCs were assessed. Four circular bone defects were created in the calvarium of 24 rabbits and randomly allocated to eight experimental groups: empty control, MBCP, MBCP+DPSCs, MBCP+BMSCs, Bio-Oss+DPSCs, Bio-Oss+BMSCs, and autogenous bone. A three-dimensional analysis of the new bone formation was performed using micro-computed tomography (micro-CT) and a histological study after 2, 4, and 8 weeks of healing. Homogenously porous structures were observed in both grafting materials. The BMSCs revealed higher osteogenic differentiation capacities, whereas the DPSCs exhibited higher colony-forming units. The micro-CT and histological analysis findings for the new bone formation were consistent. In general, the empty control showed the lowest bone regeneration capacity throughout the experimental period. By contrast, the percentage of new bone formation was the highest in the autogenous bone group after 2 (39.4% ± 4.7%) and 4 weeks (49.7% ± 1.5%) of healing (p < 0.05). MBCP and Bio-Oss could provide osteoconductive support and prevent the collapse of the defect space for new bone formation. In addition, more osteoblastic cells lining the surface of the newly formed bone and bone grafting materials were observed after incorporating the DPSCs and BMSCs. After 8 weeks of healing, the autogenous bone group (54.9% ± 6.1%) showed a higher percentage of new bone formation than the empty control (35.3% ± 0.5%), MBCP (38.3% ± 6.0%), MBCP+DPSC (39.8% ± 5.7%), Bio-Oss (41.3% ± 3.5%), and Bio-Oss+DPSC (42.1% ± 2.7%) groups. Nevertheless, the percentage of new bone formation did not significantly differ between the MBCP+BMSC (47.2% ± 8.3%) and Bio-Oss+BMSC (51.2% ± 9.9%) groups and the autogenous bone group. Our study results demonstrated that autogenous bone is the gold standard. Both the DPSCs and BMSCs enhanced the osteoconductive capacities of MBCP and Bio-Oss. In addition, the efficiency of the BMSCs combined with MBCP and Bio-Oss was comparable to that of the autogenous bone after 8 weeks of healing. These findings provide effective strategies for the improvement of biomaterials and MSC-based bone tissue regeneration.


Subject(s)
Bone Regeneration , Bone Substitutes/therapeutic use , Craniofacial Abnormalities/surgery , Minerals/therapeutic use , Tissue Engineering/methods , Tissue Scaffolds , Animals , Bone Transplantation , Male , Osteogenesis , Rabbits , Wound Healing
7.
Stem Cell Rev Rep ; 17(5): 1810-1826, 2021 10.
Article in English | MEDLINE | ID: mdl-33893620

ABSTRACT

BACKGROUND: Three-dimensional (3D) culture of mesenchymal stem cells has become an important research and development topic. However, comprehensive analysis of human dental pulp-derived mesenchymal stem cells (DPSCs) in 3D-spheroid culture remains unexplored. Thus, we evaluated the cellular characteristics, multipotent differentiation, gene expression, and related-signal transduction pathways of DPSCs in 3D-spheroid culture via magnetic levitation (3DM), compared with 2D-monolayer (2D) and 3D-aggregate (3D) cultures. METHODS: The gross morphology and cellular ultrastructure were observed in the 2D, 3D, and 3DM experimental groups using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Surface markers and trilineage differentiation were evaluated using flow cytometry and staining analysis. Quantitative reverse transcription-polymerase chain reaction and immunofluorescence staining (IF) were performed to investigate the expression of differentiation and stemness markers. Signaling transduction pathways were evaluated using western blot analysis. RESULTS: The morphology of cell aggregates and spheroids was largely influenced by the types of cell culture plates and initial cell seeding density. SEM and TEM experiments confirmed that the solid and firm structure of spheroids was quickly formed in the 3DM-medium without damaging cells. In addition, these three groups all expressed multilineage differentiation capabilities and surface marker expression. The trilineage differentiation capacities of the 3DM-group were significantly superior to the 2D and 3D-groups. The osteogenesis, angiogenesis, adipogenesis, and stemness-related genes were significantly enhanced in the 3D and 3DM-groups. The IF analysis showed that the extracellular matrix expression, osteogenesis, and angiogenesis proteins of the 3DM-group were significantly higher than those in the 2D and 3D-groups. Finally, 3DM-culture significantly activated the MAPK and NF-kB signaling transduction pathways and ameliorated the apoptosis effects of 3D-culture. CONCLUSIONS: This study confirmed that 3DM-spheroids efficiently enhanced the therapeutic efficiency of DPSCs.


Subject(s)
Mesenchymal Stem Cells , Cell Differentiation/genetics , Dental Pulp , Humans , NF-kappa B/genetics , Signal Transduction
8.
Article in English | MEDLINE | ID: mdl-33528451

ABSTRACT

The purpose of this prospective study was to evaluate the success rates and prosthetic complications of implants with a modified sandblasted and acid-etched (SLA) surface inserted for posterior single-implant crown restorations. Final crowns were placed 3 to 4 weeks after surgery, and patient follow-up spanned 10 years in a private practice setting. A total of 22 patients (8 women, 14 men) with 25 posterior implants placed (16 mandible, 9 maxilla) were selected, including only implants for posterior single-implant crowns with insertion torque values of ≥ 35 Ncm at placement. Twenty-one implants passed the reverse torque test at 3 to 4 weeks after implant placement, and final restorations were placed. Three patients (4 implants) had "spinners," and there was one patient dropout after completion of the final restoration. All patients were recalled for clinical exams, digital periapical radiographs, and clinical photos at short-term (≤ 5 years) and long-term (> 5 years) follow-up appointments. The Community Periodontal Index of Treatment Needs was also determined at the initial and follow-up visits. Crestal bone level was measured at crown placement (T1), short-term follow-up (T2; mean: 29.4 months), and long-term follow-up appointments (T3; mean: 114.4 months). Twenty patients (23 implants) returned for examination at T2, and 15 (18 implants) were available at T3. For the 17 implants available at all evaluations, statistically significant bone loss was found from T1 to T2 (0.23 ± 0.30 mm), and the mean crestal bone level appeared stable from T2 to T3. Based on clinical and radiographic findings, the success rate for the implants and restorations at T2 and T3 was graded as 100%. Therefore, it can be stated that an early loading protocol of 3 to 4 weeks using a modified SLA surface at premolar/molar single-tooth locations can result in favorable clinical and radiographic long-term results.


Subject(s)
Alveolar Bone Loss , Dental Implants , Alveolar Bone Loss/diagnostic imaging , Crowns , Dental Implantation, Endosseous , Dental Prosthesis Design , Dental Prosthesis, Implant-Supported , Female , Follow-Up Studies , Humans , Male , Osseointegration , Prospective Studies , Titanium
9.
Clin Exp Dent Res ; 2(1): 35-43, 2016 Jun.
Article in English | MEDLINE | ID: mdl-29744147

ABSTRACT

Invasive infections by Porphyromonas gingivalis are associated with persistent periodontal attachment loss and can be difficult to eliminate by scaling and root planing. Azithromycin (AZM) inhibits P. gingivalis and is actively accumulated by most human cells. We used an in vitro infection model to compare the effectiveness of AZM in killing intracellular P. gingivalis to the combined regimen of amoxicillin (AMX) and metronidazole (MET). Transport of [3H]-AZM by human gingival fibroblasts was characterized. Monolayers of Smulow-Glickman gingival epithelial cells or gingival fibroblasts were infected with P. gingivalis (strain 33277 or W83). After extracellular bacteria were eliminated with teicoplanin, infected cells were treated with therapeutic concentrations of AZM, AMX, or AMX + MET. Viable intracellular bacteria were released by cell lysis and plated on blood agar for enumeration. Antimicrobial activity against planktonic P. gingivalis was also evaluated. While survival of intraepithelial P. gingivalis 33277 was not significantly different after treatment with the three regimens, survival in infected fibroblasts was significantly lower after AZM treatment (65.9 ± 5.5%) compared with AMX (92.2 ± 3.5%) or AMX + MET (79.8 ± 5.2%, P < 0.01). Carnitine, a competitive inhibitor of AZM transport, reduced killing by AZM by ~55% (P < 0.05). Survival of intrafibroblast P. gingivalis W83 was also significantly lower after AZM treatment compared with the other regimens (P < 0.05). At therapeutic concentrations, AZM was significantly more active against intracellular P. gingivalis than against planktonic P. gingivalis (P < 0.0083). Gingival epithelial cells and fibroblasts possess a transport system that accumulates AZM and enhances elimination of intracellular P. gingivalis. Compared with the combination of AMX and MET, AZM was equally effective against intraepithelial P. gingivalis 33277 and significantly more effective against both strains of P. gingivalis from infected gingival fibroblasts. The results suggest that AZM could be a reasonable alternative to the regimen of AMX and MET for periodontal patients who should not take these agents due to known side effects or compliance issues.

10.
Dent Clin North Am ; 59(4): 919-33, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26427574

ABSTRACT

Although scaling and root planing is a cost-effective approach for initial treatment of chronic periodontitis, it fails to eliminate subgingival pathogens and halt progressive attachment loss in some patients. Adjunctive use of systemic antibiotics immediately after completion of scaling and root planing can enhance the degree of clinical attachment gain and probing depth reduction provided by nonsurgical periodontal treatment. This article discusses the rationale for prescribing adjunctive antibiotics, reviews the evidence for their effectiveness, and outlines practical issues that should be considered before prescribing antibiotics to treat chronic periodontitis.


Subject(s)
Anti-Bacterial Agents , Chronic Periodontitis/drug therapy , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Biofilms , Chronic Periodontitis/surgery , Humans , Root Planing
11.
J Periodontol ; 86(1): 155-61, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25186779

ABSTRACT

BACKGROUND: Aggregatibacter actinomycetemcomitans resists killing by neutrophils and is inhibited by azithromycin (AZM) and amoxicillin (AMX). AZM actively concentrates inside host cells, whereas AMX enters by diffusion. The present study is conducted to determine whether AZM is more effective than AMX at enhancing phagocytic killing of A. actinomycetemcomitans by neutrophils. METHODS: Killing assays were conducted in the presence of either 2 µg/mL AZM or 16 µg/mL AMX (equipotent against A. actinomycetemcomitans). Neutrophils were loaded by incubation with the appropriate antibiotic. Opsonized A. actinomycetemcomitans strain Y4 was incubated with the indicated antibiotic alone, with loaded neutrophils and antibiotic, or with control neutrophils (without antibiotic) at multiplicities of infection (MOIs) of 30 and 90 bacteria per neutrophil. RESULTS: Neutrophil incubation with 2 µg/mL AZM yielded an intracellular concentration of 10 µg/mL. At an MOI of 30, neutrophils loaded with AZM failed to kill significantly more bacteria than control neutrophils during the 60- and 90-minute assay periods. At an MOI of 90, neutrophils loaded with AZM killed significantly more bacteria than either AZM alone or control neutrophils during 60- and 90-minute incubations (P < 0.05), and killed significantly more bacteria after 90 minutes than the sum of the killing produced by AZM alone or neutrophils alone. Neutrophils incubated with AMX under identical conditions also killed significantly more bacteria than either AMX alone or control neutrophils, but there was no evidence of synergism between AMX and neutrophils. CONCLUSIONS: Neutrophils possess a concentrative transport system for AZM that may enhance killing of A. actinomycetemcomitans. Its effects are most pronounced when neutrophils are greatly outnumbered by bacteria.


Subject(s)
Aggregatibacter actinomycetemcomitans/drug effects , Anti-Bacterial Agents/pharmacology , Azithromycin/pharmacology , Neutrophils/physiology , Phagocytosis/physiology , Adult , Amoxicillin/pharmacokinetics , Amoxicillin/pharmacology , Anti-Bacterial Agents/pharmacokinetics , Azithromycin/pharmacokinetics , Biological Transport, Active/physiology , Cell Culture Techniques , Humans , Male , Middle Aged , Neutrophils/metabolism , Phagocytosis/drug effects , Time Factors , Young Adult
12.
Case Rep Dent ; 2014: 391503, 2014.
Article in English | MEDLINE | ID: mdl-24876977

ABSTRACT

This report, which is based on nonstandardized serial radiographs obtained over a period of 15 years, documents a case of localized chronic periodontitis associated with progressive deposition of calculus on the distal aspect of a mandibular second molar. The site was treated by scaling and root planing, followed by a course of adjunctive systemic azithromycin. Treatment yielded favorable reductions in probing depth and clinical inflammation, leaving only few isolated sites with pockets no deeper than 4 mm. Two years after completion of active treatment, there was radiographic evidence of increased bone density distal to the second molar.

13.
Antimicrob Agents Chemother ; 57(3): 1347-51, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23274657

ABSTRACT

Aggregatibacter actinomycetemcomitans invades periodontal pocket epithelium and is therefore difficult to eliminate by periodontal scaling and root planing. It is susceptible to azithromycin, which is taken up by many types of mammalian cells. This led us to hypothesize that azithromycin accumulation by gingival epithelium could enhance the killing of intraepithelial A. actinomycetemcomitans. [(3)H]azithromycin transport by Smulow-Glickman gingival epithelial cells and SCC-25 oral epithelial cells was characterized. To test our hypothesis, we infected cultured Smulow-Glickman cell monolayers with A. actinomycetemcomitans (Y4 or SUNY 465 strain) for 2 h, treated them with gentamicin to eliminate extracellular bacteria, and then incubated them with azithromycin for 1 to 4 h. Viable intracellular bacteria were released, plated, and enumerated. Azithromycin transport by both cell lines exhibited Michaelis-Menten kinetics and was competitively inhibited by l-carnitine and several other organic cations. Cell incubation in medium containing 5 µg/ml azithromycin yielded steady-state intracellular concentrations of 144 µg/ml in SCC-25 cells and 118 µg/ml in Smulow-Glickman cells. Azithromycin induced dose- and time-dependent intraepithelial killing of both A. actinomycetemcomitans strains. Treatment of infected Smulow-Glickman cells with 0.125 µg/ml azithromycin killed approximately 29% of the intraepithelial CFU of both strains within 4 h, while treatment with 8 µg/ml azithromycin killed ≥82% of the CFU of both strains (P < 0.05). Addition of carnitine inhibited the killing of intracellular bacteria by azithromycin (P < 0.05). Thus, human gingival epithelial cells actively accumulate azithromycin through a transport system that facilitates the killing of intraepithelial A. actinomycetemcomitans and is shared with organic cations.


Subject(s)
Aggregatibacter actinomycetemcomitans/drug effects , Anti-Bacterial Agents/pharmacology , Azithromycin/pharmacology , Epithelial Cells/drug effects , Gingiva/drug effects , Aggregatibacter actinomycetemcomitans/growth & development , Biological Transport/drug effects , Carnitine/pharmacology , Cell Line , Dose-Response Relationship, Drug , Epithelial Cells/cytology , Epithelial Cells/microbiology , Gingiva/cytology , Gingiva/microbiology , Humans , Kinetics , Probenecid/pharmacology , Procainamide/pharmacology , Pyrilamine/pharmacology , Quinidine/pharmacology , Time Factors
14.
J Periodontol ; 83(9): 1122-8, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22220766

ABSTRACT

BACKGROUND: Macrolide antibiotics yield high concentrations in inflamed tissue, suggesting that their levels in gingival crevicular fluid (GCF) could be increased at gingivitis sites. However, the increased volume of GCF associated with gingivitis could potentially dilute macrolides. To determine whether these assumptions are correct, the bioavailability of systemically administered azithromycin was compared in GCF from healthy and gingivitis sites. METHODS: Experimental gingivitis was induced in one maxillary posterior sextant in nine healthy individuals. Contralateral healthy sextants served as controls. Participants ingested 500 mg azithromycin, followed by a 250-mg dose 24 hours later. Four hours after the second dose, plaque was removed from experimental sites. GCF was collected from eight surfaces in both the experimental and control sextants and pooled separately. GCF samples were subsequently collected on days 2, 3, 8, and 15, and azithromycin content was determined by agar diffusion bioassay. RESULTS: On days 2 and 3, the pooled GCF volume at experimental sites was significantly higher than at control sites (P <0.01), and the total azithromycin mass in 30-second GCF samples pooled from experimental sites was significantly higher than at control sites (P <0.02). However, there were no significant differences in azithromycin concentration between the experimental and control pools at any point. Concentrations exceeded 7.3 µg/mL on day 2 and 2.5 µg/mL on day 15. CONCLUSION: Azithromycin concentrations are similar in GCF from gingivitis sites and healthy sites, suggesting that the processes that regulate GCF azithromycin concentration can compensate for local inflammatory changes.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Azithromycin/pharmacokinetics , Gingival Crevicular Fluid/chemistry , Gingivitis/metabolism , Administration, Oral , Adult , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/blood , Azithromycin/administration & dosage , Azithromycin/blood , Biological Availability , Dental Plaque/metabolism , Dental Plaque Index , Female , Follow-Up Studies , Humans , Male , Periodontal Index , Prospective Studies
15.
J Periodontol ; 82(11): 1582-6, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21417585

ABSTRACT

BACKGROUND: Azithromycin is a macrolide antibiotic that is active against several periodontal pathogens. Macrolides are taken up and concentrated inside gingival fibroblasts, which could influence their pharmacokinetics. This study tests the hypothesis that steady-state levels of azithromycin are higher and more sustained in gingival crevicular fluid (GCF) than in serum. METHODS: Four healthy patients received an initial dose of 500-mg azithromycin followed by 250-mg doses on each of the next 2 days. Serum and GCF samples were obtained 2 hours after the last dose on day 2, and on days 4 and 7. GCF samples were collected from maxillary posterior sites with paper strips. The strips were pooled and eluted with high-purity water. After extraction, the azithromycin content of the serum samples and GCF eluates was determined with an agar diffusion bioassay. RESULTS: On days 2, 4, and 7, the concentrations of azithromycin in blood serum were 0.22 ± 0.02, 0.08 ± 0.02, and 0.04 ± 0.01 µg/mL, respectively. The concentrations in GCF were 8.82 ± 1.25, 7.90 ± 1.72, and 7.38 ± 1.15 µg/mL, respectively. Mean GCF levels were significantly higher than mean serum levels (P ≤0.02; paired t test). CONCLUSIONS: The findings demonstrate that the pharmacokinetic profiles of azithromycin are different in GCF and serum. At steady state, azithromycin concentrations in GCF were higher and more sustained than those in serum. Based on previous studies, the levels observed in GCF were above the minimal inhibitory concentration for Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, and Prevotella intermedia.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Azithromycin/pharmacokinetics , Gingival Crevicular Fluid/metabolism , Adult , Anti-Bacterial Agents/blood , Azithromycin/blood , Female , Humans , Male , Reference Values , Serum/metabolism
16.
Contemp Clin Dent ; 1(3): 193-5, 2010 Jul.
Article in English | MEDLINE | ID: mdl-22114416

ABSTRACT

When acrylic resin is inadvertently embedded in oral tissue, it can result in a pronounced chronic inflammatory response. This report describes a case in which temporary crown and bridge resin was forced into a surgical extraction site after the two adjacent teeth were prepared for a bridge immediately following extraction of a maxillary premolar. The patient experienced swelling at the extraction site over a ten month period despite treatment with antibiotics and anti-inflammatory drugs. After detection and removal of the foreign body, the symptoms resolved. The episode contributed to periodontal bone loss around an adjacent tooth. While morbidity of this nature is rare, this case reinforces the need to investigate persistent signs of inflammation and account for dental materials that are lost during the course of treatment.

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