Wound healing after therapy of oral potentially malignant disorders with a 445-nm semiconductor laser: a randomized clinical trial.

OBJECTIVES: Oral potentially malignant disorders (OPMDs) are the most clinically relevant precursor lesions of the oral squamous cell carcinoma (OSCC). OSCC is one of the 15 most common cancers worldwide. OSCC is with its high rate of mortality an important cause of death worldwide. The diagnosis and therapy of clinically relevant precursor lesions of the OSCC is one of the main parts of prevention of this malignant disease. Targeted therapy is one of the main challenges concerning an oncologically safe tissue removal without overwhelming functional and aesthetic impairment. MATERIALS AND METHODS: In this randomized controlled trial, a newly introduced intraoral 445-nm semiconductor laser (2W; cw-mode; SIROLaser Blue, Dentsply Sirona, Bensheim, Germany) was used in the therapy of OPMDs. Duration and course of wound healing, pain, and scar tissue formation were compared to classical cold blade removal with primary suture by measuring remaining wound area, tissue colorimetry, and visual analogue scale. The study includes 40 patients randomized using a random spreadsheet sequence in two groups (n1 = 20; n2 = 20). RESULTS: This comparative analysis revealed a significantly reduced remaining wound area after 1, 2, and 4 weeks in the laser group compared to the cold blade group (p < 0.05). In the laser group, a significantly reduced postoperative pain after 1 week was measured (p < 0.05). CONCLUSION: Laser coagulation of OPMDs with the investigated 445-nm semiconductor laser is a safe, gentle, and predictable surgical procedure with beneficial wound healing and reduced postoperative discomfort. CLINICAL RELEVANCE: Compared to the more invasive and bloody cold blade removal with scalpel, the 445-nm semiconductor laser could be a new functional less traumatic tool in the therapy of OPMDs. The method should be further investigated with regard to the identification of further possible indications. TRAIL REGISTRATION: German Clinical Trials Register No: DRKS00032626.

A large animal model of periodontal defects in bisphosphonate-related osteonecrosis of the jaw: a comparison of clinical and radiological findings.

PURPOSE: The objective of this study was to demonstrate the suitability of cone-beam computed tomography (CBCT) for in vivo research in periodontology, with implications for oral implantology, facial traumatology, and all disciplines involved in treating patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ). METHODS: Halves of the jaws of 9 Swiss mountain sheep, assigned to a control group (n=3), an osteoporosis group (n=3) and a zoledronate-exposed group (n=3), were examined. Clinical and radiological evaluations were conducted using CBCT imaging to assess whether periodontitis and bone defects were observed to a significant extent after surgical tooth extraction. RESULTS: In contrast to the control and osteoporosis groups, the zoledronate group exhibited significant residual bone defects following tooth extraction (P<0.05). CBCT more objectively revealed these effects and enabled a numerical evaluation (in mm3). CONCLUSIONS: Evaluating residual defects in bone blocks from sheep using CBCT analysis was found to be as effective as a clinical examination conducted by specialists in oral and maxillofacial surgery. The strong correlation between radiological findings and clinical conditions suggests that CBCT may become increasingly important in the future, particularly in periodontological research related to BRONJ.

Geranylgeraniol Application in Human Osteoblasts and Osteoclasts for Reversal of the Effect of Bisphosphonates.

Nitrogen-containing bisphosphonates lead to the depletion of geranylgeranyl pyrophosphate involved in the mevalonate pathway. The effect of geranylgeraniol (GGOH) on human osteoblast and osteoclast activities suppressed by zoledronate was investigated in this study. The effect of GGOH on human osteoblasts and osteoclasts subjected to treatment with zoledronate was analyzed by assessing cell viability, osteoclast differentiation, resorption ability, gene expression, and protein synthesis. Cell viability suppressed by bisphosphonates in osteoblasts and osteoprogenitor cells was restored with GGOH. Osteoclast differentiation was analyzed by vitronectin receptor immunofluorescence staining, and the addition of GGOH to zoledronate significantly increased osteoclast differentiation compared with zoledronate alone. A trend of reversal of osteoclast resorption by GGOH was observed; however, it was not significant in all groups. The expression of ALP, type 1 collagen, and RUNX2 in osteoblasts was recovered by the addition of GGOH. Only CALCR expression in osteoclasts was significantly recovered by GGOH addition in the zoledronate group. Although the activities of osteoblasts and osteoclasts were not entirely restored, the possibility that the topical application of GGOH in MRONJ patients or patients with dental problems and bisphosphonates might lessen the risk of development and recurrence of MRONJ is shown.

Significance of bisphosphonates on angiogenesis in vivo and their effect under geranyl-geraniol addition - could it alter the treatment of bisphosphonate-associated necrosis of the jaw?

PURPOSE: The aim of this study was to contribute to the understanding of the inhibitory effects of bisphosphonates on tissues, with a special focus on angiogenesis. Referring to bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ), it should be shown that the local addition of the isoprenoid geranyl-geraniol (GGOH) prevents vascularization processes. METHODS: A mouse model with n = 24 animals which received an injection of a collagen matrix was used. In 4 subgroups (n = 6), we examined the effect of zoledronate on the sprouting of capillary-like structures into the matrix, with and without the presence of geranyl-geraniol, as well as testing against control groups with PBS injections or collagen matrix containing PBS instead of GGOH. This was followed by a histological evaluation of the capillary-like structures. RESULTS: Zoledronate inhibits the sprouting of blood vessels into a collagen matrix in vivo; in the presence of GGOH this effect is significantly weakened by a factor of 3.9 (p = 0.00068). CONCLUSION: This work commits to the investigation of the pathophysiology of BP-ONJ and shows a possible causal therapeutic path via the topical application of GGOH.

One year of COVID-19 pandemic: Health care workers' infection rates and economical burden in medical facilities for oral and maxillofacial surgery.

The aim of this study was to create an overview on the COVID-associated burdens faced by the oral and maxillofacial surgery (OMS) workforce during 1 year of the pandemic. OMS hospitals and private practices nationwide were surveyed regarding health care worker (HCW) screening, infection status, pre-interventional testing, personal protective equipment (PPE), and economic impact. Participants were recruited via the German Society for Oral and Maxillofacial Surgery. A total of 11 hospitals (416 employees) and 55 private practices (744 employees) participated. The HCW infection rate was significantly higher in private practices than in clinics (4.7% vs. 1.4%, p<0.01), although most infections in HCW occurred in private environment (hospitals 88.2%, private practice 66.7%). Pre-interventional testing was performed significantly less for outpatients in private practices than in hospitals (90.7% vs. 36.4%, p<0.01). Polymerase chain reaction (PCR) was used significantly more for inpatients in hospitals than in private practices (100.0% vs. 27.3%, p<0.01). FFP2/3 use rose significantly in hospitals (0% in second quarter vs. 46% in fourth quarter, p<0.05) and private practices (15% in second quarter vs. 38% in fourth quarter, p<0.01). The decrease in procedures (≤50%) was significantly higher in hospitals than in private practices (90.9% vs. 40.0%, p<0.01). Despite higher infection rates in private practices, declining procedures and revenue affected hospitals more. Future COVID-related measures must adjust the infrastructure especially for hospitals to prevent further straining of staff and finances.

Geranyl-geraniol addition affects potency of bisphosphonates-a comparison in vitro promising a therapeutic approach for bisphosphonate-associated osteonecrosis of the jaw and oral wound healing.

PURPOSE: Analysis of the influence of geranyl-geraniol (GG) addition on four bisphosphonate derivatives regarding their influence on cell viability and migration ability of bone metabolism and endothelial cells in vitro. METHODS: Clodronate, pamidronate, ibandronate, and zoledronate were observed with and without GG addition, for their effect on human osteoblasts (HOB), normal human dermal fibroblasts (NHDF), human endothelial progenitor cells (EPC), and endothelial cells of the human umbilical cord (HUVEC) using migration-, MTT-, and colony-forming cell assays. RESULTS: Data pointed to a depressing effect of all bisphosphonates on the migration ability of NHDF, EPC, and HOB. MTT assay demonstrated a decreased cell viability of HUVEC of all bisphosphonates in a 50 µM concentration and of NHDF when treated with 50 µM of clodronate, ibandronate, or zoledronate. Tested drugs showed a depressing effect on colony-forming potential of EPC even in a 5 µM concentration. GG addition demonstrated an attenuate impact on bisphosphonate effect on all primary cell cultures, respectively. CONCLUSION: In vitro comparison showed that the addition of GG weakens the effect of all bisphosphonates examined. It supports investigations that suggest GG to be able to prevent bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) in vivo. Future clinical trials may discover the local therapeutic use of GG for the prevention of BP-ONJ.

Clinical Evaluation of Pathognomonic Salivary Protease Fingerprinting for Oral Disease Diagnosis.

Dental decay (Caries) and periodontal disease are globally prevalent diseases with significant clinical need for improved diagnosis. As mediators of dental disease-specific extracellular matrix degradation, proteases are promising analytes. We hypothesized that dysregulation of active proteases can be functionally linked to oral disease status and may be used for diagnosis. To address this, we examined a total of 52 patients with varying oral disease states, including healthy controls. Whole mouth saliva samples and caries biopsies were collected and subjected to analysis. Overall proteolytic and substrate specific activities were assessed using five multiplexed, fluorogenic peptides. Peptide cleavage was further described by inhibitors targeting matrix metalloproteases (MMPs) and cysteine, serine, calpain proteases (CSC). Proteolytic fingerprints, supported by supervised machine-learning analysis, were delineated by total proteolytic activity (PepE) and substrate preference combined with inhibition profiles. Caries and peridontitis showed increased enzymatic activities of MMPs with common (PepA) and divergent substrate cleavage patterns (PepE), suggesting different MMP contribution in particular disease states. Overall, sensitivity and specificity values of 84.6% and 90.0%, respectively, were attained. Thus, a combined analysis of protease derived individual and arrayed substrate cleavage rates in conjunction with inhibitor profiles may represent a sensitive and specific tool for oral disease detection.

Local Anesthetic Usage Among Dentists: German and International Data.

The aim of this study was to analyze the use of dental local anesthetics in Germany compared with international data. The type and distribution of dental local anesthetics and added vasoconstrictors based on a representative sample of German dentists itemized over a period of 7 years (2011 to 2017) were evaluated and statistically analyzed. The results were compared with international dental local anesthetic consumption data published since 2005. With a consistent market share of nearly 98%, articaine was the first-line local dental anesthetic agent in Germany. During the investigation period, German dental local anesthetics with epinephrine 1:200,000 had ∼50% market shares, whereas formulations with epinephrine 1:100,000 had 40% to 45% market shares. Articaine, with market shares between 38% and 81%, was also the preferred anesthetic agent in various other countries, with the notable exceptions of the United Kingdom and the United States, where lidocaine was the preferred local anesthetic agent. Epinephrine was the preferred vasoconstrictor internationally, similar to Germany. The larger market share of higher concentrated epinephrine 1:100,000 was remarkable, considering the increasing number of medically compromised patients. Increased consideration for using agents with reduced dosages of epinephrine (1:200,000) is generally recommended.

Targeted sensitization of tumor cells for radiation through monocarboxylate transporters 1 and 4 inhibition in vitro.

OBJECTIVES: Monocarboxylate transporters (MCT) 1, 2 and 4 play an important role in tumor metabolism. The amount of lactate transported by MCT's highly correlates with overall survival. Furthermore, glycolysis and hypoxia are possible causes for radiation resistance. MATERIALS AND METHODS: An oral squamous cell carcinoma cell line (CAL27, ATCC) was analyzed in an in vitro cell assay. After incubation with two different inhibitors for MCT1 (AR-C122982/SR-13800 and AR-C155858/SR-13801, Tocris) or for MCT4 (simvastatin, Sigma-Aldrich and 2-cyano-3-(4-hydroxyphenyl)-2-propenoic acid (CHC), Tocris), cells were irradiated with six gray with a Gammacell 2000 (Nuklear Data). For analysis, cell counting assay, wound healing assay, MTT assay and clonogenic assay were applied. RESULTS: Cell counting assay showed significant lower results for simvastatin, CHC and for the highest concentrations of AR-C122982 and AR-C155858 (p < 0.03). Additionally, cell counts decreased significantly with irradiation after 72 hours (p < 0.05) only for AR-C122982, CHC and simvastatin. The clonogenic assay confirmed these results with substantially reduced growth when incubated with CHC, simvastatin and AR-C155858 (p < 0.002). Furthermore, MCT1 and 4 inhibition led to highly reduced migration (p < 0.05). There again, comparing the wound healing assay of irradiated to non-irradiated tests showed contrary results (controls: p < 0.001; AR-C155858: p > 0.05; AR-C122982: p > 0.32; CHC: p > 0.1; simvastatin p > 0.1). The MTT assay presented significant effects with MCT1 and 4 inhibition (simvastatin/AR-C122982/CHC: p < 0.007). Irradiated cells showed significantly lower expression after only 48 h compared to non-irradiated cells (simvastatin/AR-C122982/CHC: p < 0.02). CONCLUSIONS: Inhibition of MCT, especially MCT4 may represent a possible tool to overcome radiation resistance in tumor cell lines. CLINICAL RELEVANCE: MCT Inhibitors may be used as a possible therapeutic approach to sensitize OSCC to radiation.

One Year of the COVID-19 Pandemic in Dental Medical Facilities in Germany: A Questionnaire-Based Analysis.

(1) Background: The COVID-19 pandemic forced healthcare workers to adapt to challenges in both patient care and self-protection. Dental practitioners were confronted with a potentially high possibility of infection transmission due to aerosol-generating procedures. This study aims to present data on healthcare worker (HCW) screening, infection status of HCWs, pre-interventional testing, the use of personal protective equipment (PPE) and the economic impact of the pandemic in dental facilities. (2) Methods: Dental facilities were surveyed nationwide using an online questionnaire. The acquisition of participants took place in cooperation with the German Society for Dentistry, Oral and Maxillofacial Medicine. (3) Results: A total of 1094 private practices participated. Of these, 39.1% treated fewer than 600 patients per quarter and 59.9% treated over 600 patients per quarter. Pre-interventional testing was rarely performed in either small (6.6%) or large practices (6.0%). Large practices had a significantly higher incidence of at least one SARS-CoV-2-positive HCW than small practices (26.2% vs.14.4%, p < 0.01). The main source of infection in small practices was the private environment, and this was even more significant in large practices (81.8% vs. 89.7%, p < 0.01). The procedure count either remained stable (34.0% of small practices vs. 46.2% of large practices) or decreased by up to 50% (52.6% of small practices vs. 44.4% of large practices). Revenue remained stable (24.8% of small practices vs. 34.2% of large practices) or decreased by up to 50% (64.5% of small practices vs. 55.3% of large practices, p = 0.03). Overall, employee numbers remained stable (75.5% of small practices vs. 76.8% of large practices). A vaccination readiness of 60-100% was shown in 60.5% (n = 405) of large practices and 59.9% (n = 251) of small practices. (4) Conclusion: Pre-interventional testing in dental practices should be increased further. Economic challenges affected small practices as well as large practices. Overall, a steady employee count could be maintained. Vaccination readiness is high in dental practices, although with some room for improvement.

The risk of tooth root injuries using cortical screws for intermaxillary fixation and osteosynthesis plates - A retrospective analysis.

Intermaxillary fixation (IMF) and osteosynthesis plates (OP) are widely used for the non-surgical and surgical treatment of mandible and condyle fractures. The aim of this retrospective study was to analyze the frequency of tooth root injuries by IMF and OP screws. Electronic patient reports (2004-2013) were screened for patients treated with either IMF screws and/or OP in the Department of Oral- and Maxillofacial Surgery, University Medical Center Mainz, Germany. The frequency and the position of endangered and injured teeth were analyzed by orthopantomogram (OPTG) and cone beam computer tomography (CBCT). Next, possible predictive factors for tooth root injuries, namely interdental- and crestal distance, screw length and distance between tooth root and screw were evaluated. Further, the accuracy of OPTG vs. CBCT concerning the diagnosis of tooth root injuries was analyzed. Three-hundred sixty-six patients were included and 3388 teeth were defined as endangered by IMF- and OP screws. Overall, 16 injured teeth (0.5%) in 13 patients (3.55%) were detected. Nine injuries (56.3%) were caused by IMF- and seven injuries (43.8%) by OP screws. Three teeth were non-vital, one tooth had to be extracted. No correlation between the predictive factors crestal distance, screw length and tooth root injuries was found. If tooth injury occurred, a significant correlation between the interdental distance and the distance between tooth root and screw was found (κ = 0.48; p < 0,0001). Comparison between OPTG vs. CBCT demonstrated that many of the injuries that were seen in the OPTG (n = 230) could not be verified in the CBCT scans (n = 16) (κ = 0.12). To conclude, screws for IMF and OP can be considered as a safe procedure concerning the risk of tooth root injuries.

The expression of melanoma-associated antigen A (MAGE-A) in oral squamous cell carcinoma: an evaluation of the significance for tumor prognosis.

OBJECTIVES: Melanoma-associated antigens A had been detected repeatedly in oral squamous cell carcinoma, but not in healthy mucosa. Additionally, patients with MAGE-A expressing cancers are regarded to have a worse survival prognosis, so that MAGE-A are supposed to be part of carcinogenesis. Which role these antigens fulfill within OSCC is still, up today, largely unknown. This study examines the hypothesis that MAGE-A is being produced in OSCC but not in mucosa tissue and if MAGE-A has any correlation to clinical patient's parameters like tumor size, lymph node metastasis, distant metastasis, overall survival, and recurrence. MATERIALS AND METHODS: For this purpose, 50 tumor samples and 39 mucosa samples were analyzed by means of PCR and immunohistochemical staining with the antibody 6C1. RESULTS: Forty of 41 stained tumor samples showed a positive antibody reaction with a maximum staining rate of 53%. Sixteen mucosa samples showed a mild positive reaction. The PCR revealed a linear expression pattern of MAGE-A in which the genes are proportionally expressed in OSCC. We did not find any relationship between MAGE-A and tumor size, overall survival, or recurrence. There was also no connection between MAGE-A and tumor parameters Hif-1 and LDH. Their expression was detected tendentially in tumors with higher staging, advanced lymph node metastasis, and rising age of the patients. The genes MAGE-A3+6 and MAGE-A4 had a statistically significant correlation with lymph node metastasis (p = 0.007 and p = 0.004). Patients got distant metastasis and influence of MAGE-A on metastatic behavior could not be verified. The genes MAGE-A3 and -A4 are consequently qualified as tumor markers in the field of diagnosis and follow-up of OSCC. CONCLUSIONS AND CLINICAL RELEVANCE: Two genes have great potential as target proteins in immunotherapy. The genes MAGE-A3+6 and MAGE-A4 had a statistically significant correlation with lymph node metastasis.

Influence of buffy coat-derived putative endothelial progenitor cells on tumor growth and neovascularization in oral squamous cell carcinoma xenografts.

OBJECTIVES: The aim of this murine in vivo study was to investigate whether buffy coat-derived putative endothelial progenitor cells (BCEPC) alter tumor growth and neovascularization in oral squamous cell carcinomas (OSCC). MATERIALS AND METHODS: A murine xenograft model using the PCI-13 oral cancer cell line was deployed of which n = 24 animals received 2 × 106 BCEPC by transfusion whereas the control group (n = 24) received NaCl (0.9%) instead. Tumor size, volume, and capillary density were determined by sonography and measurement with a caliper. Immunohistochemical analysis was carried out with antibodies specific for Cytokeratins, Flt-4, Podoplanin, and Vimentin. RESULTS: In the experimental group, systemic application of BCEPC significantly increased tumor volume to 362.49% (p = 0.0012) and weight to 352.38% (p = 0.0018) as well as vascular densities to 162.15% (p = 0.0021) compared with control tumors. In addition, BCEPC-treated xenografts exhibited higher Cytokeratin expression levels by a factor of 1.47 (p = 0.0417), Podoplanin by a factor of 3.3 (p = 0.0020) and Vimentin by a factor of 2.5 (p = 0.0001), respectively. CONCLUSIONS: Immunohistochemical investigations support the notion that BCEPC transfusion influences neovascularization and lymphatic vessel density, thereby possibly promoting tumor progression. Future studies, which will include gene expression analysis, should help to define the possible role of BCEPC during OSCC progression in more detail. CLINICAL RELEVANCE: Endothelial progenitor cells (EPCs) could serve as a target structure for the treatment of OSCC and possibly other solid tumors.

A 5-year prospective clinical trial on short implants (6 mm) for single tooth replacement in the posterior maxilla: immediate versus delayed loading.

The aim of this paper was to demonstrate the treatment outcomes following immediate functional loading concept of short implants inserted for single tooth replacement in the posterior maxilla. The study was performed on 63 patients who received short (6 mm) implants for single tooth replacement in the posterior maxilla. Forty-eight patients underwent immediate functional concept, whereas 15 of the implants were loaded 3 months after insertion. The patients were evaluated for up to 5 years after prosthesis completion. The endpoints included the evaluation of implant survival rate, crown length, bone resorption, plaque accumulation (PI), bleeding on probing (BOP), periodontal probing depth (PPD) and assessment of oral health impact profile (OHIP). At the end of the follow-up period of 5 years, three implants (6.3%) from the immediate loading group have failed during the observation period. Bone loss was significantly lower in the delayed loading group compared to the immediately loaded implants. At the end of the second year, BOP values were higher in the immediately loaded group. Throughout the observation period, PI values in the group with immediate loading were higher. PPD increased consistently and during the first 3 years in the immediate loading group. As a conclusion, short implants inserted for single tooth replacement at the posterior maxilla presented with satisfactory clinical outcomes in both immediate and delayed loading concepts. However, immediately loaded implants presented with an increased bone loss and higher BOP values. As assessed by the OHIP score, a subjective improvement was observed in both groups without significant differences.

Biofunctionalization of synthetic bone substitutes with angiogenic stem cells: Influence on regeneration of critical-size bone defects in an in vivo murine model.

PURPOSE: The aim of this study was to investigate the influence of human bone marrow-derived endothelial progenitor cells (EPC) on vascularization and bone regeneration in combination with a bone-substitute material (BSM) in a critical-size bone defect in a murine model. Critical-size bone defects were performed and the defects were filled according to the group membership. MATERIALS AND METHODS: Eighteen rats were randomized in two experimental groups: BSM (BoneCeramic) with/without EPC biofunctionalization, and a control group without BSM and EPC. Calvaria bone defects were performed and the defects were filled according to the group membership. After 8 weeks, qualitative tissue response of newly formed bone mass was analyzed by histology, cone beam CT (CBCT) and micro-CT (µCT) scans. Occurrence of tumor masses due to EPC vascularization in peripheral organs was investigated microscopically in histological slides of liver and kidney. RESULTS: The combination of EPC and BSM showed smaller bone defects in the CT scans and the histological evaluation as the single use of BSM without EPC by trend (p = 0.067). Further, a higher amount of blood vessels could be found in histological slices of BSM in combination with EPC. No inflammatory response or tumor formation could be found. CONCLUSION: These findings confirm the biocompatibility of the used BSM and provide evidence that the combination of BSM with EPC might be effective for bone vascularization and regeneration. Using EPC in augmentation sites might overall lead to faster and better bone regeneration and should be further investigated in future studies.

Analgesic prescribing patterns of dental practitioners in Germany.

PURPOSE: To analyze the prescribing patterns of analgesics by dentists in Germany during an investigation period of five years in comparison to analgesic prescriptions by physicians and in relation to international prescribing data. MATERIALS AND METHODS: We analyzed nationwide data of all prescriptions of analgesics and antiphlogistics (except strong opioids) on the basis of the annual reports of the German statutory health insurances from 2012 to 2016. The types of analgesics, the number of prescriptions and the prescribed 'defined daily doses' (DDD) itemized by dentists and physicians were analyzed. The results were compared with each other and assigned to international dental prescribing data. RESULTS: During the investigation period the number of dental prescriptions of analgesics decreased by 3.4%, on the part of the physicians the increase amounted to 10.4%. Ibuprofen is the first line analgesic in Germany, its share in the dental analgesic prescription volume increased from 61.9% in 2012 to 88.1% in 2016. In the international comparison it could be demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) play the most important role in nearly all countries. CONCLUSIONS: Continual training activities and international monitoring of dental analgesic prescription patterns are necessary to develop guidelines for the rational and appropriate use of analgesics in dentistry.

Modulation of Tumor Cell Metabolism by Laser Photochemotherapy with Cisplatin or Zoledronic Acid In Vitro.

BACKGROUND/AIM: Laser photochemotherapy is a new approach in cancer treatment using low-level laser therapy (LLLT) to enhance the effect of chemotherapy. MATERIALS AND METHODS: In order to evaluate the effect of LLLT on tumor cells, HeLa cells were treated with cisplatin or zoledronic acid (ZA) followed by LLLT. Cell viability was evaluated with 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay. Oxidative phosphorylation and glycolysis were measured using extracellular flux analysis. Immunocytochemistry of heat-shock protein 70 (HSP70) and western blot analysis were performed. RESULTS: LLLT alone increased viability and was associated with lower oxidative phosphorylation but higher glycolysis rates. Cisplatin and ZA alone lowered cell viability, glycolysis and oxidative phosphorylation. This effect was significantly enhanced in conjunction with LLLT and was accompanied by reduced oxidative phosphorylation and collapse of glycolysis. CONCLUSION: Our observations indicate that LLLT may raise the cytotoxicity of cisplatin and ZA by modulating cellular metabolism, pointing to a possible application in cancer treatment.

Early cell response of osteogenic cells on differently modified implant surfaces: Sequences of cell proliferation, adherence and differentiation.

OBJECTIVES: Osseointegration of dental implants is a crucial prerequisite for long-term survival. Therefore, surface modifications are needed to interact with the extracellular environment and to trigger osteogenic cell responses such as cell proliferation, adherence, and differentiation. The purpose of this study was to investigate different surface modifications in vitro over 2 weeks. MATERIALS AND METHODS: Commercially available cells from a human osteogenic cell line (HHOB-c) were cultivated on the following surfaces: titanium with smooth surfaces (polished titanium (P), machined titanium (M), polyetheretherketone (Peek)), titanium with rough and hydrophilised surfaces (acid etched titanium (A), sandblasted acid etched titanium (SA and SA2), sandblasted acid etched hydrophilised (SAH), titanium plasma painted titanium (TPS)), titanium with calcium phosphate-containing surfaces (titanium plasma painted calcium phosphate modified titanium (TPS-CaP), sandblasted calcium phosphate modified titanium (S-CaP), sandblasted acid etched calcium phosphate modified titanium (SA-CaP)), and zirconium-oxide (yttrium amplified zirconium (Z), yttrium amplified Ca2+ delivering zirconium (Z-Ca)). Tissue culture polystyrene (TCPS) served as a control. Cell count was assessed after 24 h, 48 h, 72 h, 7 d, and 14 d; osteogenic cell adherence and differentiation were analysed by using cellular Quantitative Immuno-Cytochemistry (QIC) assay for alkaline phosphatase (AP), osteocalcin (OC), integrin alpha V (ITGAV), and talin (T). RESULTS: All tested surfaces showed a positive influence on the differentiation and adherence of osteogenic cells, especially P, M, A, TCPS, and Peek. After 48 h, the surfaces M, SA and SAH had induced a positive influence on adherence, whereas SA2, SA, and SAH triggered proliferation after 14 d. CONCLUSIONS: Rough and hydrophilised surface modifications, such as SAH, trigger osteogenic cell responses. These in vitro results highlight the potential use of SAH surface modifications of dental implants and indicate further clinical studies are warranted.

Comparative metabolic analysis in head and neck cancer and the normal gingiva.

OBJECTIVES: Chronic accumulation of lactate in malignant tumor tissue is associated with increased malignancy and radioresistance. For this study, biopsies of primary head and neck squamous cell carcinoma (HNSCC) and of the normal gingiva of the same patient were compared via metabolic profiling to the healthy gingiva from cancer-free patients. MATERIALS AND METHODS: Cryobiopsies of 140 HNSCC patients were used to determine ATP, lactate, and glucose concentrations of the tumor and normal gingiva via induced metabolic bioluminescence imaging (imBI). Additionally, these metabolites were quantified in a collective of 79 healthy (non-tumor-bearing) patients. Furthermore, tumor samples were analyzed via immunofluorescence imaging and quantitative real-time PCR for the expression of lactate and glucose transporters. RESULTS: There were significant differences in ATP concentrations detectable between the tumor, normal gingiva of tumor patients, and gingiva from healthy patients. Lactate concentrations were significantly increased in tumor tissue compared to the normal gingiva of tumor patients as well as the gingiva from healthy patients. Concerning glucose, there was a significant decrease in glucose concentrations detectable in the tumor biopsies compared to the normal gingiva of tumor patients. On the other hand, tumor samples from patients revealed significantly elevated relative expression levels of monocarboxylate transporters (MCT-1 and MCT-4), as well as glucose transporters (GLUT-1 and GLUT-3) compared to the corresponding normal gingiva of each patient. CONCLUSIONS: We could demonstrate that the lactate concentration in HNSCC correlates with primary tumor (T) stage. CLINICAL RELEVANCE: The aim of this study was to identify metabolic parameters to improve early cancer diagnosis, allow predictions on the degree of malignancy, and contribute to a personalized tumor therapy.

Trends in antibiotic prescribing by dental practitioners in Germany.

PURPOSE: To analyze the structure of antibiotic prescriptions by dentists in Germany during a time-period of four years in relation to medical antibiotic prescriptions. MATERIALS AND METHODS: We collected nationwide data from all statutory health insurances on dental prescriptions of systemic antibiotics from 2012 to 2015. The annual reports of the "Research Institute for Local Health Care Systems" (WIdO, Berlin) provided the basis for this longitudinal data base analysis. The types of antibiotics, the number of prescriptions and the prescribed 'defined daily doses' (DDD) were analyzed. The results were compared to antibiotic prescriptions of German physicians. RESULTS: An average of 8.8% per year of all antibiotic prescriptions is issued by dentists. The mostly prescribed antibiotic is amoxicillin. The share of amoxicillin on all dental prescriptions increased from 35.6% in 2012 to 45.8% in 2015 (p < 0.01). About three-quarters of all dentally prescribed DDD can be attributed to amoxicillin and clindamycin. On the part of the physicians the proportion of clindamycin is 18 fold lower than in the dental field. CONCLUSIONS: Dental and medical antibiotic prescriptions in Germany show statistically significant differences regarding the shares of the prescribed antibiotics. In an international comparison the high proportion of Clindamycin in Germany is noticeable.