Phytocannabinoids and gingival inflammation: Preclinical findings and a placebo-controlled double-blind randomized clinical trial with cannabidiol.

OBJECTIVE: The aim of this study was to: (1) evaluate the anti-inflammatory effects of cannabidiol (CBD) on primary cultures of human gingival fibroblasts (HGFs) and (2) to clinically monitor the effect of CBD in subjects with periodontitis. BACKGROUND: The use of phytocannabinoids is a new approach in the treatment of widely prevalent periodontal disease. MATERIALS AND METHODS: Cannabinoid receptors were analyzed by western blot and interleukin production detected using enzyme immunoassay. Activation of the Nrf2 pathway was studied via monitoring the mRNA level of heme oxygenase-1. Antimicrobial effects were determined by standard microdilution and 16S rRNA screening. In the clinical part, a placebo-control double-blind randomized study was conducted (56 days) in three groups (n = 90) using dental gel without CBD (group A) and with 1% (w/w) CBD (group B) and corresponding toothpaste (group A - no CBD, group B - with CBD) for home use to maintain oral health. Group C used dental gel containing 1% chlorhexidine digluconate (active comparator) and toothpaste without CBD. RESULTS: Human gingival fibroblasts were confirmed to express the cannabinoid receptor CB2. Lipopolysaccharide-induced cells exhibited increased production of pro-inflammatory IL-6 and IL-8, with deceasing levels upon exposure to CBD. CBD also exhibited antimicrobial activities against Porphyromonas gingivalis, with an MIC of 1.5 µg/mL. Activation of the Nrf2 pathway was also demonstrated. In the clinical part, statistically significant improvement was found for the gingival, gingival bleeding, and modified gingival indices between placebo group A and CBD group B after 56 days. CONCLUSIONS: Cannabidiol reduced inflammation and the growth of selected periodontal pathogenic bacteria. The clinical trial demonstrated a statistically significant improvement after CBD application. No adverse effects of CBD were reported by patients or observed upon clinical examination during the study. The results are a promising basis for a more comprehensive investigation of the application of non-psychotropic cannabinoids in dentistry.

Combination of plant phenolics and isoquinolinium alkaloids protects gingival fibroblast and improves post-extraction healing after lower third molar extraction.

AIMS: The effect of polyphenolic fraction of Lonicera caerulea (PFLC) and alkaloid fraction of Macleaya cordata (AFMC) mix on the production of inflammatory mediators in human gingival fibroblasts pretreated with lipopolysaccharide (LPS) was investigated. In addition, protective effects of mucoadhesive paste containing combination of PFLC and AFMC (0.05% and 0.01%, respectively; n=15, Group A) and placebo (n=15, Group B) were evaluated in patients after surgical extraction of lower third molars. METHODS: Gingival fibroblasts were pre-treated with LPS (10 µg/mL; 24 h) and PFLC/AFMC (25/0.25; 50/0.25; 100/0.25; 25/0.5; 50/0.5; 100/0.5 µg/mL) in serum-free medium was applied for 4 h. Then the interleukin-6 (IL-6), reactive oxygen species (ROS) generation, level of intracellular glutathione (GSH) and expression of cyclooxygenase-2 (COX-2) were evaluated. The study was a 6-day, single-center, randomized, double-blind and placebo-controlled trial consisting of two parallel treatment arms. A modified Oral health impact profile questionnaire including both general oral condition and extraction related questions, was used to evaluate the oral condition and other changes before (day 0) and on the days 1, 3 and 6 after surgical extraction. RESULTS AND CONCLUSION: The combination of PFLC with AFMC caused a reduction of ROS generation, reduced IL-6 production and suppressed the expression of COX-2. In group A the paste treatment contributed to improvement of oral health-related quality of life. Topical application of PFLC and AFMC into the extraction wound improved post-extraction site wound healing probably by antioxidant and anti-inflammatory mechanisms.

Traumatic dislocation of the eye into the maxillary sinus: Case report and literature review.

Traumatic dislocation of the eye is usually encountered in high-energy injuries. These include traffic accidents, accidents at work, sporting accidents, falling from a height, impact of the hooves or horns of animals, gunshot injuries, and physical assault. Such incidents are accompanied by facial soft tissue damage and injuries to the facial skeleton, especially the orbit, and can be associated with varying degrees of dislocation of the eye. We describe a rare case of non-fatal traumatic eye dislocation into the maxillary sinus, coupled with an orbital fracture resulting from a physical assault on a 63-year-old woman. The cause of death was asphyxiation due to manual strangulation and mechanical asphyxia. Even though dislocations of the eye are relatively rare, forensic pathologists should be aware of such injuries to correct assessment of injury mechanism. The available literature regarding eye dislocation is summarized, and the forensic issues applicable to the assessment of such cases are reviewed.

Immunotherapy in mucosal melanoma: a case report and review of the literature.

BACKGROUND: Mucosal melanoma is a rare form of melanoma presenting variably as sores or unexplained bleeding located mainly in the head and neck region, anorectal region or female genital tract. Mucosal melanoma is usually diagnosed at an advanced stage and is characterized by an aggressive behavior. Surgery represents the mainstay of treatment for early stage melanomas, but for advanced disease there have been until recently very limited treatment options. Ipilimumab, a human monoclonal antibody directed against the cytotoxic T lymphocyte antigen 4, was the first treatment modality to demonstrate survival benefit in advanced malignant melanoma. METHOD: Description of a new case and review of the literature. RESULTS: We present here a patient with mucosal melanoma with aggressive biological behavior and documented late response to ipilimumab. CONCLUSIONS: Ipilimumab represents an effective treatment option in selected patients with mucosal melanoma.