CD34 and CD105 Microvessels in Resected Bone Specimen May Implicate Wound Healing in MRONJ

Clinical treatment outcome of MRONJ (medication-related osteonecrosis of the jaw) surgery despite radical osseous removal and primary closure healing still shows differences in terms of outcome and disease recurrence. The study aims to assess the rate of angiogenesis of MRONJ lesions in order to understand the impact of angiogenesis and neoangiogenesis status on MRONJ surgical treatment outcome. This is the first study correlating microvessel density with prognosis in MRONJ surgically-treated patients. The immunohistochemical expression of CD34 and CD105 in MRONJ specimens obtained from surgically-treated patients was evaluated. The most vascularized areas detected by CD34 and CD105 were selected and the microvessel density value of the samples was registered. Samples were retrospectively divided according to the clinical outcome of MRONJ surgical treatment, dividing patients into two groups, “healed” and “not healed”. Statistical analysis was performed to assess if neovessels could influence treatment outcome in patients undergoing radical surgery. In the examined cohort, this value was highly predictive of better treatment outcome after radical surgery of MRONJ. Understanding of angiogenesis-dependent factors deserves further attention as a future target for MRONJ prevention and therapies

WY-14643, a Potent Peroxisome Proliferator Activator Receptor-α PPAR-α Agonist Ameliorates the Inflammatory Process Associated to Experimental Periodontitis

We have investigated the effects of WY14643, a potent peroxisome proliferator activator receptor-α (PPAR-α) agonist, in a rat model of ligature-induced periodontitis. Male Sprague-Dawley rats were lightly anaesthetized with pentobarbitone (35 mg/kg). Sterile, 2-0 black braided silk thread was placed around the cervix of the lower left first molar and knotted medially. Animals received WY14643 (1 mg/kg i.p, daily for eight days). Eighths days after placement of the ligature, we evaluated several markers of inflammation such us (1) myeloperoxidase activity, (2) a cytokines and adhesion molecules expression, (3) NF-κB expression, (4) iNOS expression, (5) the nitration of tyrosine residues, (6) activation of the nuclear enzyme poly(ADP-ribose) polymerase, (7) apoptosis, and (8) the degree of gingivomucosal tissues injury. Administration of WY14643 significantly decreased all of the parameters of inflammation as described above. These results demonstrate that WY14643 exerts an anti-inflammatory role during experimental periodontitis and is able to ameliorate the tissue damage

Emerging Role of PPAR-β/δ in Inflammatory Process Associated to Experimental Periodontitis

The aim of the present study was to evaluate the contribution of peroxisome proliferator-activated receptor (PPAR-β/δ) in animal model of periodontitis. Male Sprague-Dawley rats were lightly anaesthetized with pentobarbitone (35 mg/kg). Sterile, 2-0 black braided silk thread was placed around the cervix of the lower left first molar and knotted medially. Animals received GW0742 (0.3 mg/kg, 10% DMSO, i.p. after the ligature placement and daily for eight days). At day 8, the gingivomucosal tissue encircling the mandibular first molar was removed. One the eighth day after placement of the ligature, we evaluated (1) NF-κB expression, (2) cytokines expression, (3) iNOS expression, (5) the nitration of tyrosine, (6) apoptosis, and (8) the degree of gingivomucosal tissues injury. Administration of GW0742 significantly decreased all of the parameters of inflammation as described above. Taken together, these results demonstrate that GW0742 exerts an anti-inflammatory role during experimental periodontitis and is able to ameliorate the tissue damage

Histological findings of osteonecrosis spotted prior to tooth extractions. Should we consider tooth extraction still the main trigger event?

Osteonecrosis of the jaw (ONJ) is an adverse drug reaction described as the progressive destruction and death of bone that affects the mandible and maxilla of patients exposed to the treatment with medications known to increase the risk of disease, in the absence of a previous radiation treatment. Tooth extraction often precedes the manifestation of ONJ; indeed, it is sometimes called trigger event and it have also been considered as risk factors for the onset of ONJ. As a consequence, some of the guidelines recommend avoiding tooth extractions in patients at risk of ONJ; however, a growing body of evidence indicates that dental/periodontal infection prior to extraction, rather than dental extraction may represent the main local risk factor for ONJ. Ten patients at risk of ONJ have undergone tooth extractions. They were identified and included in our retrospective monocentric clinical investigation. Patients underwent tooth extractions with standardized procedures (PROMaF protocol), and bone biopsies were taken. Extractions were performed due to symptomatic, non-restorable teeth in patient at risk of ONJ; histological findings of ONJ were observed in all samples. This outcome may highlight that the proof of non‐exposed ONJ might be the histopathologic confirmation of necrotic bone, as stated by European task force on MRONJ. Additionally, alveolar biopsy should possibly be taken in every case of suspected ONJ, which needs an proper and prompt management for successful healin

MRONJ in breast cancer patients under bone modifying agents for cancer treatment-induced bone loss (CTIBL): a multi-hospital-based case series

BackgroundCancer treatment-induced bone loss (CTIBL) is the most common adverse event experienced by patients affected by breast cancer (BC) patients, without bone metastases. Bone modifying agents (BMAs) therapy is prescribed for the prevention of CTIBL, but it exposes patients to the risk of MRONJ.MethodsThis multicentre hospital-based retrospective study included consecutive non-metastatic BC patients affected by MRONJ related to exposure to low-dose BMAs for CTIBL prevention. Patients' data were retrospectively collected from the clinical charts of seven recruiting Italian centres.ResultsMRONJ lesions were found in fifteen females (mean age 67.5 years), mainly in the mandible (73.3%). The mean duration of BMAs therapy at MRONJ presentation was 34.9 months. The more frequent BMAs was denosumab (53.3%). Ten patients (66.7%) showed the following local risk factors associated to MRONJ development: periodontal disease (PD) in three cases (20%) and the remaining six (40%) have undergone PD-related tooth extractions. One patient presented an implant presence-triggered MRONJ (6.7%). In five patients (33.3%) no local risk factors were observed.ConclusionsThis is the first case series that investigated BC patients under BMAs for CTIBL prevention suffering from MRONJ. These patients seem to have similar probabilities of developing MRONJ as osteo-metabolic ones. Breast cancer patients under BMAs for CTIBL prevention need a regular prevention program for MRONJ, since they may develop bone metastases and be treated with higher doses of BMAs, potentially leading to a high-risk of MRONJ

Treatment With a Flavonoid-Rich Fraction of Bergamot Juice Improved Lipopolysaccharide-Induced Periodontitis in Rats

Objective: In this study, we investigated the effects of a flavonoid-rich fraction of Bergamot juice (BJe) in rats subjected to experimental periodontitis induced by a single intragingival injection of lipopolysaccharides (LPS).Main Methods: Periodontitis was induced by a single intragingival injection of 1 μl LPS (10 μg/μl) derived from Salmonella typhimurium in sterile saline solution. The injection was made in the mesolateral side at the interdental papilla between the first and the second molar. Fourteen days after LPS injection, we performed radiographic analyses and then we surgically removed the gingivomucosal tissue surrounding the mandibular first molar for histological, immunohistochemical and molecular analysis.Results: LPS significantly induced oedema, tissue damage and increased neutrophil infiltration. At molecular level, we found increased NF-κB translocation as well as raised both TNF-α and IL-1β expression, other than modulation of apoptosis-associated proteins. Moreover, the increased myeloperoxidase activity was associated with up-regulation of adhesion molecules. Immunohistochemical analysis for nitrotyrosine and poly ADP-ribose displayed an intense staining in the gingivomucosal tissue. Oral administration of BJe for 14 consecutive days reduced tissue injury and several markers of gingival inflammation including nuclear NF-κB translocation, cytokines expression, myeloperoxidase activity and the expression of some adhesion molecules such as ICAM and P-selectin. BJe also decreased both nitrosative stress and PARP positive staining. Moreover, it caused down-regulation of Bax and up-regulation of Bcl-2 expression.Conclusion: Our findings demonstrate that BJe improves LPS-induced periodontitis in rats by reducing the typical markers of inflammation, thus suggesting its potential in the treatment of periodontal diseases

Clinical validation of 13-Gene DNA methylation analysis from oral brushing: a non invasive sampling procedure for early detection of oral squamous cell carcinoma. A multicentric study

1. Introduction In a recent study our research group described a non-invasive sampling procedure based on DNA methylation analysis of a set of 13 genes with a high level of accuracy (sensitivity 96.6%, specificity 100%) in the detection of squamous cell carcinoma of the oral cavity (OSCC) [1]. The purpose of the present study was to test the diagnostic performance of this non invasive sampling procedure in an italian multicentric study. 2. Materials and Methods Oral brushing specimens were collected in ten different italian units of oral medicine. Each oral medicine unit collected blindly 10 brushing specimens from patients affected by OSCC and an equal number of age and sex-matched healthy controls. 13-gene DNA methylation analysis was performed and each sample was considered positive or negative in relation to a predefined cut-off value. 3. Results 181 out of 200 planned specimens were analyzed. DNA could not be amplified in 4 cases (2.2%). 86/93 (92.5%) specimens derived from OSCC patients were detected as positive and 70/84 (83.3%) specimens derived from healthy donors showed a negative score. 4. Conclusions Data from multicentric study confirmed a high level of sensitivity of our procedure whereas level of specificity is slightly lower if compared to our previous study. These data suggest that our procedure may be proposed as a first level diagnostic test with the aim to avoid a diagnostic delay in Oral Squamous Cell Carcinoma. Conflicts of Interest: As a possible conflict of interest, L. Morandi and D.B.G. submitted a patent (the applicant is the University of Bologna) in November 2016 to the National Institute of 398 Industrial Property; however, we believe that this is a natural step of translational research (bench-to-bedside) 399 and guarantee that the scientific results are true. The remaining authors declare that they have no competing 400 interest

Effects of Hypericum Perforatum, in a rodent model of periodontitis

<p>Abstract</p> <p>Background</p> <p><it>Hypericum perforatum </it>is a medicinal plant species containing many polyphenolic compounds, namely flavonoids and phenolic acids. In this study we evaluate the effect of <it>Hypericum perforatum </it>in animal model of periodontitis.</p> <p>Methods</p> <p>Periodontitis was induced in adult male Sprague-Dawley rats by placing a nylon thread ligature around the lower 1st molars. Hypericum perforatum was administered at the dose of 2 mg/kg os, daily for eight days. At day 8, the gingivomucosal tissue encircling the mandibular first molar was removed.</p> <p>Results</p> <p>Periodontitis in rats resulted in an inflammatory process characterized by edema, neutrophil infiltration and cytokine production that was followed by the recruitment of other inflammatory cells, production of a range of inflammatory mediators such as NF-κB and iNOS expression, the nitration of tyrosine residues and activation of the nuclear enzyme poly (ADP-ribose) polymerase; apoptosis and the degree of gingivomucosal tissues injury. We report here that Hypericum perforatum exerts potent anti-inflammatory effects significantly reducing all of the parameters of inflammation as described above.</p> <p>Conclusions</p> <p>Taken together, our results clearly demonstrate that treatment with Hypericum reduces the development of inflammation and tissue injury, events associated with periodontitis.</p