Mesenchymal stem cells derived from human dental follicle modulate the aberrant immune response in atopic dermatitis.

Background: Atopic dermatitis (AD) is an inflammatory cutaneous disorder. The advancements in the understanding of AD immunological pathogenesis have caused the development of therapies that suppress the dysregulated immune response. We aimed to evaluate the immunomodulatory effect of dental stem cells (dental follicle-mesenchymal stem cells [DF-MSCs]) on AD patients. Materials & methods: We investigated the immunoregulatory potential of DF-MSCs on T cell response in AD and compared them with psoriasis and healthy individuals and the underlying mechanisms. Results: DF-MSCs significantly reduced Fas, FasL and TNFR II frequency in T cells, increased naive T cell population while reducing memory T cell, decreased inflammatory cytokine levels and promoted Tregs frequency in the AD population. Conclusion: These results imply that DF-MSCs are modulating inflammation through decreasing T cell apoptosis, inducing Treg expansion and stabilizing cytokine levels.

Lay abstract Background: Atopic dermatitis (AD) is an inflammatory cutaneous disorder characterized by immune-mediated inflammation and epidermal barrier dysfunction. There is no definite solution for the treatment of AD. We aimed to evaluate the immunomodulatory and immunosuppressive effect of dental stem cells (dental follicle-mesenchymal stem cell [DF-MSCs]) on AD. Materials & methods: We investigated the immunoregulatory potential of DF-MSCs on inflammatory response in AD and compared them with psoriasis and healthy individuals and the mechanism underlying it. Results: DF-MSCs significantly reduced apoptosis-related markers in immune cells, decreased inflammatory cytokine levels and promoted Treg frequency in the AD. Conclusion: Our findings provide basic evidence for the potential role of DF-MSCs as a cellular therapy option in the treatment of AD and shed light on future clinical studies.

Human dental follicle mesenchymal stem cells alleviate T cell response in inflamed tissue of Crohn's patients.

BACKGROUND/AIMS: Crohn's Disease (CD) is a chronic inflammatory condition characterized by various abnormalities that lead to overly aggressive T-cell responses. Our in vitro experiments aimed to investigate the potential use of Dental Follicle Mesenchymal Stem Cells (DF-MSCs) to suppress the exaggerated immune response in inflamed and non-inflamed tissue of Crohn's Disease (CD). MATERIAL AND METHODS: Dental follicle tissues were obtained from extracted third molar teeth of 3 healthy volunteers who have no abscess or inflammatory diseases. Eleven patients included the experiment who had been diagnosed with CD and not received steroid maintenance therapy for more than 1 month. Mononuclear Cells (MNCs) were isolated from inflamed and non-inflamed tissue of CD. Isolated cells were stimulated with anti-CD3/anti-CD28 monoclonal antibodies in the presence and absence of DF-MSCs and analyzed for lymphocytes proliferation capacity and viability, T lymphocyte subsets, CD4+IL22BP and CD4+CD25+Foxp3+ regulatory T cell (Tregs) frequencies and cytokine levels. RESULTS: A significant downregulation of lymphocyte proliferation and CD4+IL22BP T cell ratio were found in inflamed cultures with DF-MSCs (p<0,005). Also, the frequency of Tregs increased with DF-MSCs (p<0,05). Pro-inflammatory cytokine levels (TNF-α and IL-6) were decreased (p<0,05) and IL-10 levels were increased (p<0,05) in the supernatant of inflamed cultures. CONCLUSION: DF-MSCs reduced the inflammatory immune response, induced Tregs and downregulated CD4+IL22BP T cell ratio in inflamed samples of CD patients, which may be exploited for significant therapeutic use.

Effect of Ankaferd Blood Stopper on Skin Superoxide Dismutase and Catalase Activities in Warfarin-Treated Rats.

AIM: Ankaferd Blood Stopper (ABS) is a new promising local hemostatic agent, and its mechanism on hemostasis has been shown by many studies. However, the effects of ABS on skin superoxide dismutase (SOD) and catalase (CAT) activities have not been investigated before. The aim of this study was to evaluate the effects of this new generation local hemostatic agent on warfarin-treated rats focusing on its the antioxidant potential in short-term soft tissue healing. METHODS: Twelve systemically warfarin treated (warfarin group) and 12 none treated Wistar Albino rats (control group) were selected for the trial. Rats in the warfarin group were treated intraperitonally with 0.1 mg/kg warfarin, and rats in the control group were given 1 mL/kg saline 3 days earlier to surgical procedure and continued until killing. All rats had incisions on dorsal dermal tissue, which was applied ABS or no hemostatic agent before suturing. Six of each group were killed on day 4, and the other 6 were killed on day 8. Blood and skin samples were taken. Prothrombin time (PT) in blood samples, CAT, and SOD activities in skin samples were determined. RESULTS: Warfarin treatment dose was found to be convenient and warfarin treatment increased the PT levels as expected. Warfarin treatment decreased CAT activity significantly compared to the control group. The ABS treatment significantly increased SOD activities in the warfarin group at the end of the eighth day. CONCLUSION: Ankaferd Blood Stopper acted positively in short-term tissue healing by increasing SOD activity in warfarin-treated rats. Therefore, ABS may be suggeted as a promoting factor in tissue healing.

The Comparison of the Immunologic Properties of Stem Cells Isolated from Human Exfoliated Deciduous Teeth, Dental Pulp, and Dental Follicles.

Aim. To compare the effects of various mesenchymal stem cells, those isolated from human exfoliated deciduous teeth (SHEDs), dental pulp stem cells (DPSCs), and dental follicle stem cells (DFSCs), on human peripheral blood mononuclear cells (PBMCs). Method. Mesenchymal stem cells were isolated from three sources in the orofacial region. Characterization and PCR analyses were performed. Lymphocytes were isolated from healthy peripheral venous blood. Lymphocytes were cocultured with stem cells in the presence and absence of IFN-γ and stimulated with anti-CD2, anti-CD3, and anti-CD28 for 3 days. Then, lymphocyte proliferation, the number of CD4(+)FoxP3(+) T regulatory cells, and the levels of Fas/Fas ligand, IL-4, IL-10, and IFN-γ in the culture supernatant were measured. Results. The DFSCs exhibited an enhanced differentiation capacity and an increased number of CD4(+)FoxP3(+) T lymphocytes and suppressed the proliferation and apoptosis of PBMCs compared with SHEDs and DPSCs. The addition of IFN-γ augmented the proliferation of DFSCs. Furthermore, the DFSCs suppressed IL-4 and IFN-γ cytokine levels and enhanced IL-10 levels compared with the other cell sources. Conclusion. These results suggest that IFN-γ stimulates DFSCs by inducing an immunomodulatory effect on the PBMCs of healthy donors while suppressing apoptosis and proliferation and increasing the number of CD4(+)FoxP3(+) cells.

Dental follicle mesenchymal stem cell administration ameliorates muscle weakness in MuSK-immunized mice.

BACKGROUND: Myasthenia gravis (MG) is an antibody-mediated autoimmune disease of the neuromuscular junction (NMJ), mostly associated with acetylcholine receptor (AChR) antibodies. Around 5-10 % of MG patients show antibodies to muscle-specific tyrosine kinase (MuSK). Mesenchymal stem cell (MSC) administration has been shown to ameliorate muscle weakness in the experimental autoimmune myasthenia gravis (EAMG) model induced by AChR immunization. METHODS: To investigate the efficacy of stem cell treatment in MuSK-related EAMG, clinical and immunological features of MuSK-immunized mice with or without dental follicle MSC (DFMSC) treatment were compared. RESULTS: MuSK-immunized mice intravenously treated with DFMSC after second and third immunizations showed significantly lower EAMG incidence and severity and reduced serum anti-MuSK antibody, NMJ IgG, and C3 deposit levels and CD11b+ lymph node cell ratios. Moreover, lymph node cells of DFMSC-administered mice showed reduced proliferation and IL-6 and IL-12 production responses to MuSK stimulation. By contrast, proportions of B and T cell populations and production of a wide variety of cytokines were not affected from DFMSC treatment. CONCLUSIONS: Our results suggest that DFMSC treatment shows its beneficial effects mostly through suppression of innate immune system, whereas other immune functions appear to be preserved. Stem cell treatment might thus constitute a specific and effective treatment method in MuSK-associated MG.

Effect of Septal Deviation, Concha Bullosa and Haller's Cell on Maxillary Sinus's Inferior Pneumatization; a Retrospective Study.

PURPOSE: Maxillary sinus's inferior pneumatization is a physiological process, which increase with time and accelerates following extraction. The aim of this study was to determine the prevalence of nasal septal deviation (NSD), concha bullosa (CB), and Haller's cells (HC) and to examine the correlation of maxillary sinus inferior pneumatization (MSIP) with these anatomical variations. Material and Methods : 300 (150 m, 150 f) CBCT scans taken at the Marmara University School of Dentistry from 2011 to 2014 were retrospectively reviewed for the presence of CB, NSD, HC and MSIP. The correlation between pneumatization to the anatomic variants was then compared. Data were analyzed with a Chi-square test. Results : Of the 300 CBCT scans, 44.3% have CB, 37.3% NSD, 19.3% HC and 27.7% MSIP. There was no statistical significancewhen comparing the relationship of patients with CB, NSD, HC and pneumatization. Conclusion : NSD, CB and HC do not have a definite role on sinus's inferior pneumatization. Further studies should be conducted including potential factors related pneumatization with more sample size for further correlation with NSD, CB,HC.

Effect of submucosal application of tramadol on postoperative pain after third molar surgery.

The aim of this study was to evaluate the effectiveness of submucosal application of tramadol, for acute postoperative facial pain, following the extraction of impacted third molar teeth. This prospective, double-blind, randomised placebo-controlled study included 60 ASA I-II patients undergoing impacted third molar surgery under local anaesthesia. Following the surgical procedure, patients were randomly divided into two groups; group T (1 mg/kg tramadol) and group S (2-mL saline). Treatments were applied submucosally after surgery. Pain after extraction was evaluated using a visual analogue scale (VAS) 0.5, 1, 2, 4, 6, 12, 24, and 48 h postoperatively. The time at which the first analgesic drug was taken, the total analgesic dose used, and adverse tissue reactions were also evaluated. In group T, postoperative VAS scores were significantly lower compared to that in group S (p < 0.05). This study demonstrated that post-operative submucosal application of tramadol is an effective method for reducing acute post-operative facial pain after impacted third molar surgery.

The antioxidant and anti-inflammatory efficiency of hyaluronic acid after third molar extraction.

PURPOSE: Hyaluronic acid (HA) has a number of clinical applications in current practice. Therefore, correlation of HA with free radicals and inflammatory cells is clinically important. The purpose of this study is to measure the efficacy of high molecular weight HA on the oxidative stress of oral wounds (glutathione (GSH) and lipid peroxidation (LPO) levels), the inflammatory reaction (leucocytes, collagen and angiogenesis content), pain (visual analogue scale (VAS) records) and trismus (maximum interincisal opening (MIO) records) after third molar (M3) extraction. PATIENTS AND METHODS: 40 patients were included in this study. 0.2 ml 0.8% HA was applied immediately after surgery within the HA group (n = 20). Nothing was applied to the control group (n = 20). The primary outcome variables were the changes in the inflammatory reaction (leucocyte, angiogenesis and collagen content), oxidative stress (GSH, LPO) and clinical parameters (VAS, MIO). Results were compared immediately after extraction (T0) and 1 week after surgery (T1). Bivariate analyses were used to assess the differences between the HA and control groups for each study variable. RESULTS: There was a statistically significant difference of leucocyte infiltration and angiogenesis between the groups at T1. The HA group showed less leucocyte infiltration and more angiogenesis than the control group. There was no statistically significant difference in oxidative stress, VAS or MIO levels between the groups. CONCLUSION: Our results confirm the hypothesis that HA has an anti-inflammatory effect following M3 extraction. However, the oxidative stress levels and clinical outcomes were similar after one week. Further studies examining these parameters at different times are necessary.

Comparison of the Effects of Topical Ketamine and Tramadol on Postoperative Pain After Mandibular Molar Extraction.

PURPOSE: This study compared the analgesic efficacy of postoperative tramadol versus ketamine for preventing pain after mandibular molar extraction. PATIENTS AND METHODS: Ninety patients who had undergone molar extraction were randomly divided into 3 groups: group T (tramadol 1 mg/kg), group K (ketamine 0.5 mg/kg), and group P (saline 2 mL). The treatment was applied to the extraction sockets using resorbable gelatin sponges. Pain after extraction was evaluated using a visual analog scale (VAS) 0.5, 1, 2, 4, 6, 12, 24, and 48 hours postoperatively. RESULTS: The VAS scores after extraction were statistically higher in group P than in either treatment group. Group K had the lowest pain intensity. CONCLUSION: This study shows that topical tramadol and ketamine are effective alternatives for decreasing pain after molar extractions.

Effects of Ankaferd Blood Stopper and Celox on the tissue factor activities of warfarin-treated rats.

The aim of this study is to evaluate the effect of these new generation hemostatic agents on early-stage soft tissue healing of warfarin-treated rats by measuring the tissue factor (TF) activities. Rats in the warfarin group were treated intraperitonally with 0.1 mg/kg warfarin, and rats in the control group were treated with 1 mL/kg saline. All rats had 3 incisions on dorsal dermal tissue applied Celox, Ankaferd Blood Stopper (ABS), or no hemostatic agent. Six rats from each group were killed on day 4, and the other 6 were killed on day 8. Prothrombin time (PT) and TF activities were evaluated, respectively. Both the hemostatic agents positively affected the hemostasis. Warfarin treatment increased the PT levels as expected. Celox-treated dermal tissues had higher TF activity when compared to ABS-treated ones. The ABS affected the early-stage healing positively in clinical aspect, whereas Celox was more effective on hemostasis by means of increasing TF activities.

Comparison of the effects of sedation and general anesthesia in surgically assisted rapid palatal expansion.

OBJECTIVE: To compare the effects of sedation and general anesthesia for surgically assisted rapid palatal expansion (SARPE). METHODS: This randomized prospective study included 30 patients who were scheduled for SARPE, and was performed between January 2008 to February 2010 in the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Marmara University, Istanbul, Turkey. Patients were allocated into Group S - midazolam + fentanyl sedation (n=15), and Group G - general anesthesia (n=15). Hemodynamic parameters, duration of anesthesia, surgery, recovery time, time to discharge, visual analogue scale (VAS) pain scores at 30 minutes (min), one hour (hr), 4 hours, 12 hours, and 24 hours, first consumption of analgesic time, total amount of consumption of analgesics, patient and surgeon satisfaction, nausea, and vomiting were recorded. RESULTS: Analgesic time was significantly longer in Group S (p=0.008), and total analgesic consumption was significantly lower in Group S than in Group G (p=0.031). Patient satisfaction was statistically higher in Group S (p=0.035). At 30 min, one hr, and 12 hrs, VAS satisfaction scores in Group S were statistically lower than those in Group G, and at 4 hrs and 24 hrs there was no statistical difference in VAS scores for both groups. CONCLUSION: The use of sedation for outpatient SARPE resulted in lower pain scores at discharge, lower analgesic consumption, and greater patient satisfaction.

A comparison of the effects of midazolam/fentanyl and midazolam/tramadol for conscious intravenous sedation during third molar extraction.

PURPOSE: This study evaluated the effects of fentanyl and tramadol, used in combination, as sedation for third molar surgical extraction. PATIENTS AND METHODS: This prospective, randomized, double-blind, placebo-controlled study included 60 patients undergoing extraction of a horizontal third molar with an Amsterdam Preoperative Anxiety and Information Scale score above 10 points. All of the patients were first given a 0.03-mg/kg bolus of midazolam, and then they were randomized into 3 groups: group A, midazolam only; group B, midazolam and 1-µg/kg fentanyl; and group C, midazolam and 1-mg/kg tramadol. The vital signs were recorded. Patients were assessed for postoperative pain and adverse effects, and patient and surgeon satisfaction was assessed. RESULTS: No differences were found in the heart rate among groups (P > .05). The mean blood pressure was also similar until the 40th minute, after which the mean blood pressure in the patients in group A was lower than that in the other 2 groups (P < .01). In the postoperative pain assessment, the visual analog scale scores of the patients in group C were lower than those in the other 2 groups in the first postoperative hour (P < .05). The time at which the first rescue analgesic was taken in groups A, B, and C was 3, 3.5, and 5 hours postoperatively, respectively, and was significantly later in group C (P < .01). No difference was found in patient/surgeon satisfaction among the groups. CONCLUSIONS: Tramadol has a better analgesic effect in third molar surgery than fentanyl and placebo.

Effects of midazolam/low-dose ketamine conscious intravenous sedation on pain, swelling, and trismus after surgical extraction of third molars.

PURPOSE: To assess the clinical efficacy of midazolam plus low-dose ketamine conscious intravenous sedation on relief from or prevention of postoperative pain, swelling, and trismus after the surgical extraction of third molars. PATIENTS AND METHODS: Patients admitted for surgical extraction of mandibular third molars (n = 50) were included. All patients received an initial dose of 0.03 mg/kg intravenous midazolam; then patients in the midazolam-placebo (MP) group received 2 mL of a placebo IV, while patients in the midazolam-ketamine (MK) group received 2 mL of a ketamine + saline combination (0.3 mg/kg ketamine + saline) IV. RESULTS: Facial swelling on postoperative days was significantly lower in the MK group than in the MP group (P = .001). Mouth opening on postoperative days was significantly greater in the MK group than in the MP group (P = .001). Pain scores measured on a visual analog scale at 4, 12, and 24 hours after surgery were significantly higher in the MP group than in the MK group (P = .001). CONCLUSIONS: Conscious intravenous sedation with midazolam/low-dose ketamine during surgical extraction of third molars can provide the patient with a comfortable procedure and good postoperative analgesia, with less swelling and significantly less trismus. Intravenous low-dose ketamine may be safe and effective in reducing postoperative pain.

Assessment of combined local anesthesia and ketamine for pain, swelling, and trismus after surgical extraction of third molars.

PURPOSE: The aim of this study was to assess the clinical efficacy of combined treatment with local anesthetic and subanesthetic ketamine for the relief or prevention of postoperative pain, swelling, and trismus after the surgical extraction of third molars. PATIENTS AND METHODS: Fifty patients undergoing the extraction of impacted mandibular third molars were included in the study. The patients were randomly divided into 2 groups: local anesthetic alone (LAA) and local anesthetic plus ketamine (LAK). The patients in the LAA group received 5 mL of a local anesthetic and saline combination comprising 2 mL of local anesthetic and 3 mL of saline. The patients in the LAK group received 5 mL of a local anesthetic, ketamine, and saline combination comprising 2 mL of local anesthetic and 0.3 mg/kg ketamine and saline. RESULTS: Facial swelling on postoperative days was significantly lower in the LAK group than in the LAA group (P = .0001). The mouth opening on the postoperative days was significantly greater in the LAK group than in the LAA group (P = .0001). The pain scores on the VAS at 30 minutes and 1, 4, 12, and 24 hours after surgery were significantly higher in the LAA group than in the LAK group (P = .0001, P = .005). CONCLUSION: The combination of a local anesthetic and subanesthetic doses of ketamine during surgical extraction of third molars can produce good local anesthesia while affording a comfortable procedure for the surgeon and patient and providing good postoperative analgesia with less swelling and significantly less trismus.

Inhibitory effect of alendronate on bone resorption of autogenous free bone grafts in rats.

PURPOSE: This study was designed to investigate the effect of alendronate on the resorption of autogenous free bone grafts by biochemical and histopathologic methods. Alendronate is a potent inhibitor of osteoclast-mediated bone resorption with no adverse effect on the mineralization of bone. MATERIALS AND METHODS: In this experimental study, 56 male Wistar rats were used. Autogenous free bone grafts were prepared with standard trephine bur in the right femur of each rat. The animals were then divided into 2 groups. In the first group, rats were treated with a daily subcutaneous injection of alendronate (0.25 mg/kg/day) for 2, 4, and 12 weeks, respectively. In the second group, rats were treated with saline solution injection for the same time periods. At the end of these periods, serum and overnight fasting urine samples were collected from all animals. In serum, the level of calcium, phosphate, parathyroid hormone, and 25 dihydroxyvitamin D were measured. In urine, pyridinoline, deoxypyridinoline, calcium, and creatinine were analyzed. The rats were sacrificed at 2, 4, and 12 weeks postsurgery. The number of osteoclasts and the number and size of resorptive lacunae were evaluated histopathologically. RESULTS: Alendronate caused significant reduction in urinary pyridinoline, deoxypyridinoline levels biochemically, and the number of osteoclasts and resorptive lacunae histopathologically. CONCLUSION: Suppression of the graft resorption occurred in the alendronate-treated group.

A comparison of midazolam and midazolam with remifentanil for patient-controlled sedation during operations on third molars.

Our aim was to compare patients' satisfaction and cooperation, and clinical efficacy, of midazolam alone, and midazolam and remifentanil for patient-controlled sedation during removal of third molars. Forty patients, American Society of Anesthesiologists grades I and II, admitted for extraction of impacted mandibular third molars were included in this randomised, prospective study. They were given an intravenous bolus of midazolam 0.03 mg/kg and then allowed to use patient-controlled sedation. In the midazolam group, 2 ml of 0.5 mg/ml midazolam was given automatically. In the midazolam-remifentanil group, 2 ml of 0.5 mg/ml midazolam and 12.5 microg/ml remifentanil were given in the same manner. The lockout period was 5 min. Vital signs and oxygen saturation were recorded. Patients' and surgeons' satisfaction, and the patients' degree of amnesia about the local anaesthetic, drilling, removal of the tooth, and pain during extraction were also assessed. There were no significant differences between systolic and diastolic blood pressures during sedation, but heart rate after 30 min in the combined group was significantly lower than in the midazolam group (p<0.05). Surgeons described the midazolam group as excellent in 9 and good in 11. In the combined group, satisfaction was excellent in 11, good in 7, and satisfactory or unacceptable in 1 of each. Immediately postoperatively, 19 patients in each group ranked their satisfaction as excellent and 1 as good. Twenty-four hours later it was unchanged in the midazolam group, while 15 patients in the other group thought it was excellent, 3 good, and 2 poor. Patient-controlled analgesia with midazolam or midazolam and remifentanil is safe and reliable during extraction of third molars.

Endoscopic retrieval of dental implants from the maxillary sinus.

Endoscopic sinus surgery has been performed for various indications in maxillofacial surgical practices. It has been utilized for assessment of antral pathologies, removal of foreign bodies, orthognathic procedures, and treatment of facial fractures. In the cases presented, 3 dental implants which were displaced into maxillary sinuses were removed by endoscopic sinus surgery. Transantral endoscopic surgery is a reliable, minimally invasive method for retrieving displaced objects from the maxillary antrum with minimal complications.

Anxiety and extraction of third molars in Turkish patients.

Preoperative anxiety is widespread and adversely affects a patient's physical and psychological outcome. Extraction of third molars is common, and many patients complain of anxiety and emotional disturbance. We assessed the anxiety of patients in Turkey before extraction of third molars. A total of 120 patients were admitted for removal of one or more third molars under local anaesthesia. The Amsterdam Preoperative Anxiety and Information Scale (APAIS) and Spielberger's State Trait Anxiety Inventory (STAI) were used to evaluate anxiety. The results showed that women were significantly more anxious than men; women who had not had a previous operation were more anxious than other women; there was no difference in the anxiety scores of patients who had previously had a local anaesthetic and those who had not; there were no differences in anxiety as measured by trait scores; patients who wanted a lot of information were more anxious.

Management of arsenic trioxide necrosis in the maxilla.

Historically, pulp-necrotizing agents were commonly used in endodontic treatments. They act quickly and devitalize the pulp within a few days. However, they are cytotoxic to gingiva and bone. If such an agent diffuses out of the cavity, it can readily cause widespread necrosis of gingiva and bone, which can lead to osteomyelitis of the jaws. Although the use of arsenic trioxide can cause severe damage to surrounding tissues, producing complications, it is still used in certain areas in the world. This article presents and discusses two cases of tissue necrosis and their surgical management. These cases showed severe alveolar bone loss in the maxilla, which affected the patients' quality of life and limited the restorative possibilities. As dentists, we should be aware of the hazardous effects of arsenic trioxide and should abandon its use. Because of its cytotoxicity, there is no justification for the use of arsenic trioxide in the modern dental practice.