Histopathologic analysis of gingival lesions : a 20-year retrospective study at one academic dental center

Background: The gingiva is part of the periodontium supporting structures surrounding the teeth and commonly involved in gingival and periodontal conditions. Assessing the distribution of gingival lesions is important for evaluating the prevalence of periodontal disease in the population to optimize the oral health care services. The purpose of this study is to report the frequency and distribution of gingival lesions biopsied from 1996?2016. Material and Methods: This cross-sectional retrospective study retrieved data from all gingival lesions biopsied from 1996?2016 and sent to the King Abdulaziz University Dental Hospital oral pathology laboratory. Histologic sections were reviewed in a blinded manner by a certified oral pathologist to confirm the initial histologic diagnosis. Results: Of the 1,248 oral-maxillofacial lesions, 119 (9.5%) gingival lesions were diagnosed. The mean age was 41.58 years. Gingival lesions were more prevalent in female patients than male patients (53.8%). The most common diagnoses were reactive lesions (41.2%). Pyogenic granuloma was the predominant lesion in the category (n=26, 21.8%), and followed by inflammatory conditions (24.4%), benign neoplasm (9.2%), malignant neoplasm (7.6%), epithelial lesions (7.6%), miscellaneous (5%), and immune-mediated diseases (5%). Squamous cell carci noma was the only malignant neoplasm reported (7.6%; mean age, 57.44 years) and more common in male than female patients (2:1). Most biopsies were sent from oral and maxillofacial surgeons (55.6%) followed by general dentists (22.2%) and periodontists (12.8%). Conclusions: Pyogenic granuloma was the most common gingival lesion. Squamous cell carcinoma was the only malignant lesion in which histologic examination was the definitive diagnostic measure. This study provides information about the frequencies and distributions of gingival lesions over 20 years

Diabetes Causes the Accelerated Loss of Cartilage During Fracture Repair Which Is Reversed by Insulin Treatment

Fracture healing in diabetic individuals and in animal models of diabetes is impaired. To investigate mechanisms by which diabetes may affect fracture healing we focused on the transition from cartilage to bone, a midpoint in the fracture healing process. Femoral fractures were induced in mice rendered diabetic by multiple low dose streptozotocin treatment and compared to matching normoglycemic mice. One group of diabetic animals was treated with slow release insulin to maintain normal serum glucose levels. The results indicate that there was relatively little difference in the initial formation of the fracture callus on day 10. However, on day 16 the diabetic group had significantly smaller callus, greater loss of cartilage and enhanced osteoclastogenesis that was normalized by treatment with insulin when assessed by histomorphometric analysis. Chondrocyte apoptosis was significantly higher in diabetic mice and this increase was blocked by insulin. These changes were accompanied by diabetes-increased mRNA levels of RANKL, TNF-α, and ADAMTS-4 and -5 measured by real-time PCR, which was reversed by insulin treatment. On days 16 and 22 bone formation within the callus of diabetic mice was significantly less than the normoglycemic and brought to normal levels by insulin treatment. These results suggest that a significant effect of diabetes on fracture healing is increased chondrocyte apoptosis and osteoclastogenesis that accelerates the loss of cartilage and reduces the anlage for endochondral bone formation during fracture repair. That insulin reverses these effects demonstrates that they are directly related to the diabetic condition

Chemokine Expression Is Upregulated in Chondrocytes in Diabetic Fracture Healing

Chemokines are thought to play an important role in several aspects of bone metabolism including the recruitment of leukocytes and the formation of osteoclasts. We investigated the impact of diabetes on chemokine expression in normal and diabetic fracture healing. Fracture of the femur was performed in streptozotocin-induced diabetic and matched normoglycemic control mice. Microarray analysis was carried out and chemokine mRNA levels in vivo were assessed. CCL4 were examined in fracture calluses by immunohistochemistry and the role of TNF in diabetes-enhanced expression was investigated by treatment of animals with the TNF-specific inhibitor, pegsunercept. In vitro studies were conducted with ATDC5 chondrocytes. Diabetes significantly upregulated mRNA levels of several chemokines in vivo including CCL4, CCL8, CCL6, CCL11, CCL20, CCL24, CXCL2, CXCL5 and chemokine receptors CCR5 and CXCR4. Chondrocytes were identified as a significant source of CCL4 and its expression in diabetic fractures was dependent on TNF (P \u3c 0.05). TNF-α significantly increased mRNA levels of several chemokines in vitro which were knocked down with FOXO1 siRNA (P \u3c 0.05). CCL4 expression at the mRNA and proteins levels was induced by FOXO1 over-expression and reduced by FOXO1 knockdown. The current studies point to the importance of TNF-α as a mechanism for diabetes enhanced chemokine expression by chondrocytes, which may contribute to the accelerated loss of cartilage observed in diabetic fracture healing. Moreover, in vitro results point to FOXO1 as a potentially important transcription factor in mediating this effect

Diabetes Reduces Mesenchymal Stem Cells in Fracture Healing Through a TNFα-Mediated Mechanism

Aims/hypothesis Diabetes interferes with bone formation and impairs fracture healing, an important complication in humans and animal models. The aim of this study was to examine the impact of diabetes on mesenchymal stem cells (MSCs) during fracture repair. Methods Fracture of the long bones was induced in a streptozotocin-induced type 1 diabetic mouse model with or without insulin or a specific TNFα inhibitor, pegsunercept. MSCs were detected with cluster designation-271 (also known as p75 neurotrophin receptor) or stem cell antigen-1 (Sca-1) antibodies in areas of new endochondral bone formation in the calluses. MSC apoptosis was measured by TUNEL assay and proliferation was measured by Ki67 antibody. In vitro apoptosis and proliferation were examined in C3H10T1/2 and human-bone-marrow-derived MSCs following transfection with FOXO1 small interfering (si)RNA. Results Diabetes significantly increased TNFα levels and reduced MSC numbers in new bone area. MSC numbers were restored to normal levels with insulin or pegsunercept treatment. Inhibition of TNFα significantly reduced MSC loss by increasing MSC proliferation and decreasing MSC apoptosis in diabetic animals, but had no effect on MSCs in normoglycaemic animals. In vitro experiments established that TNFα alone was sufficient to induce apoptosis and inhibit proliferation of MSCs. Furthermore, silencing forkhead box protein O1 (FOXO1) prevented TNFα-induced MSC apoptosis and reduced proliferation by regulating apoptotic and cell cycle genes. Conclusions/interpretation Diabetes-enhanced TNFα significantly reduced MSC numbers in new bone areas during fracture healing. Mechanistically, diabetes-enhanced TNFα reduced MSC proliferation and increased MSC apoptosis. Reducing the activity of TNFα in vivo may help to preserve endogenous MSCs and maximise regenerative potential in diabetic patients

TNFα Contributes to Diabetes Impaired Angiogenesis in Fracture Healing

Diabetes increases the likelihood of fracture, interferes with fracture healing and impairs angiogenesis. The latter may be significant due to the critical nature of angiogenesis in fracture healing. Although it is known that diabetes interferes with angiogenesis the mechanisms remain poorly defined. We examined fracture healing in normoglycemic and streptozotocin-induced diabetic mice and quantified the degree of angiogenesis with antibodies to three different vascular markers, CD34, CD31 and Factor VIII. The role of diabetes-enhanced inflammation was investigated by treatment of the TNFα-specific inhibitor, pegsunercept starting 10 days after induction of fractures. Diabetes decreased both angiogenesis and VEGFA expression by chondrocytes. The reduced angiogenesis and VEGFA expression in diabetic fractures was rescued by specific inhibition of TNF in vivo. In addition, the TNF inhibitor rescued the negative effect of diabetes on endothelial cell proliferation and endothelial cell apoptosis. The effect of TNFα in vitro was enhanced by high glucose and an advanced glycation endproduct to impair microvascular endothelial cell proliferation and tube formation and to stimulate apoptosis. The effect of TNF, high glucose and an AGE was mediated by the transcription factor FOXO1, which increased expression of p21 and caspase-3. These studies indicate that inflammation plays a major role in diabetes-impaired angiogenesis in endochondral bone formation through its effect on microvascular endothelial cells and FOXO1

Perception of tobacco hazards on general and periodontal health and tobacco cessation counseling among dental students

Introduction Tobacco use is one of the leading worldwide health risk factors and a primary cause of premature death and disability. Tobacco cessation programs might work well if provided by all healthcare providers. This study aimed to evaluate dental students' knowledge, attitudes, beliefs, and practices towards tobacco hazards on general and periodontal health and tobacco cessation councling. Methods A descriptive cross-sectional study was conducted among dental students who were in their clinical years (the fourth, fifth and sixth year of study), in Saudia Arabia in 2022. A self-administered questionnaire derived from the TCC questionnaire survey was carried out among 315 dental students. Knowledge was considered poor if correct answers were below the median value. Attitude was on a five-point Likert scale. Adjusted logistic regression analyses were performed. Results The study revealed that about 52% have poor knowledge, 64% have negative attitudes, 69% have negative beliefs, and 44% poor practice. All these ratings were below median values. It also showed that younger dental students were 2 times more likely to have poor knowledge (AOR=1.97; 95% CI: 1.1–3.53) and smokers were less likely to have poor knowledge (AOR=0.34; 95% CI: 0.12–0.95). One third of students perceived patient resistance as a barrier to TCC while 50% reported lack of knowledge, 32% lack of time, and 24% lack of materials. Conclusions The study findings urge the inclusion of programs to encourage dental students to help patients quit tobacco use and to make educational material available to them

Impact of TNF dysregulation on diabetic fracture repair

PLEASE NOTE: This work is protected by copyright. Downloading is restricted to the BU community: please click Download and log in with a valid BU account to access. If you are the author of this work and would like to make it publicly available, please contact [email protected] (DSc) --Boston University, Henry M. Goldman School of Dental Medicine, 2009 (Department of Periodontology and Oral Biology)Includes bibliography: leaves 126-143.Introduction: Fracture healing in diabetic individuals and in animal models of diabetes is impaired. Several mechanisms by which diabetes may affect fracture healing were reported. We investigated the effect of diabetes on the catabolic aspect of fracture healing focusing on the transition from cartilage to bone, a midpoint in the fracture healing process. Methods: CD-1 mice animals were used in this study. Using multiple low-dose streptozotocin diabetes was induced in these animals. Simple closed transverse fractures were then induced in the left femur. Groups of diabetic and normoglycemic mice were treated with TNF inhibitor, Pegsunercept starting from day 10 after fracture. Fracture calluses were collected 10, 16 and 22 days after fracture for histomorphometric analysis. RNA samples were collected from 10, and 16 days groups for gene expression of factors related to cartilage and bone remodeling by real time PCR. Apoptotic, TNF-[alpha], RANKL and CCL4 posistive chondrocytes were investigated by immunhistochemistry. FOXO1 ; a transcriptional factor which was activated by TNF-[alpha] in previous reported studies was also investigated by real time PCR and in chondrocytes by confocal laser scanning microscopy. RNA samples from 16-day group were used for microarray analysis focusing on inflammatory cytokines. An in vitro study was conducted using TNF-[alpha] treated ATDC5 chondrogenic cells to investigate FOXO1 association with TNF-[alpha] and RANKL promoters by chromatin imunoprecipitation assay. Results: Diabetes was associated with elevated osteoclast numbers and accelerated removal of cartilage as well as pronounced chondrocytes apoptosis (P[less than]0.05). These changes were reflected by smaller callus size on day 16, a stage when cartilage is resorbed and replaced by new bone. No significant changes were noticed between groups on day. When diabetic mice were treated with the TNF-specific inhibitor, pegsunercept, the number of osteoclasts, cartilage loss and apoptotic chondrocytes were significantly reduced (P[less than]0.05). Diabetes also was associated with increased levels of mRNA of TNF-[alpha], RANKL, ADAMTS4 and ADAMTS5 (P[less than]0.05). Immunohistochemical analysis showed that diabetes was associated with increase in TNF-[alpha], RANKL and MIP- 1[beta]/CCL4 positive chondrocytes (P[less than]0.05) each of which was significantly reduced with TNF inhibition in diabetic mice (P[less than]0.05). Diabetes also increased FOXO1 mRNA levels in fracture callus and nuclear accumulation in chondrocytes (P[less than]0.05). Moreover, an association between FOXO1 and the TNF-[alpha] and RANKL promoter was demonstrated by ChIP assay. Microarray analysis revealed an up-regulation of genes related to inflammation including TNF in the diabetic group when cartilage is being replaced by bone on day 16. Conclusion: These results suggest that diabetes enhanced inflammatory cytokines including TNF-[alpha] and increases osteoclastogenesis, chondrocytes apoptosis and cartilage loss during fracture repair particularly at stage when cartilage is replaced by bone. TNF inhibition reverses these effects demonstrates that they are significantly related to the TNF dysregulation

Effect of Subantimicrobial Dose Doxycycline Treatment on Gingival Crevicular Fluid Levels of MMP-9 and MMP-13 in Periodontitis Stage 2, Grade B in Subjects with Type 2 Diabetes Mellitus

The aim of this study was to investigate the effect of using subantimicrobial dose doxycycline as an adjunct in periodontitis stage 2, grade B in subjects with type 2 diabetes mellitus. A total of thirty patients were divided into the following two groups with reference to periodontitis, type 2 diabetes mellitus, and administration of the doxycycline drug: Group I: patients with periodontitis stage 2, grade B and type 2 diabetes mellitus who received SRP only. Group II: patients with periodontitis stage 2, grade B and type 2 diabetes mellitus who received SRP and doxycycline 20 mg. The following clinical measurements were recorded at baseline (prior to scaling and root planning) and after one and three months postoperatively: GI, PI, and PD with a periodontal calibrated probe. The levels of both MMP-9 and MMP-13, from 60 GCF samples, were analyzed by ELISA. Patients treated with SRP and doxycycline 20 mg showed a significant reduction of PD, PI, GI, MMP-9, and MMP-13 than patients who received SRP only. Improvements in parameters clinically and biochemically were observed following the adjunctive use of doxycycline subantimicrobial dose therapy for the management of stage 2, grade B periodontitis patients with type 2 diabetes mellitus

Development and Optimization of a Novel Lozenge Containing a Metronidazole-Peppermint Oil-Tranexamic Acid Self-Nanoemulsified Delivery System to Be Used after Dental Extraction: In Vitro Evaluation and In Vivo Appraisal

In-depth studies on essential oil–based nanoemulsions (NEs) have centered on a variety of oral health issues. NEs improve the delivery of nonpolar active agents to sites and thereby boost the dissolution and distribution of the agents. Metronidazole-peppermint oil-tranexamic acid self-nanoemulsifying drug delivery systems (MZ-PO-TX-SNEDDS) were created and loaded into novel lozenges to act as antifungal, hemostatic, antimicrobial, and analgesic dosage forms after dental extractions. The design-of-experiments approach was used in creating them. To generate the NEs, different concentrations of MZ-PO (240, 180, and 120 mg), 2% TX (600, 450, and 300 mg), and Smix1:1 (600, 400, and 200 mg) were used. The ideal formulation had serum levels of 1530 U/mL of interleukin-6, a minimal inhibitory concentration against bacteria of 1.5 µg/mL, a droplet size of 96 nm, and a blood coagulation time of 16.5 min. Moreover, the produced NE offered better MZ release. The adopted design was used to produce the ideal formulation; it contained 240 mg of MZ-PO, 600 mg of 2% TX, and 600 mg of Smix1:1. It was incorporated into lozenges with acceptable characteristics and an improved capability for drug release. These lozenges had reasonable coagulation times, IL-6 serum levels, and MIC values. All of these characteristics are desirable for managing symptoms following tooth extractions. Therefore, these lozenges loaded with MZ-PO-TX-SNEDDs might be considered a beneficial paradigm for relieving complications encountered after tooth extractions