Role of Cannabidiol and Tetrahydrocannabivarin on Paclitaxel-induced neuropathic pain in rodents.

The purpose of this study was to evaluate if phytocannabinoids, synthetic cannabidiol (CBD), and tetrahydrocannabivarin (THCV), and their combination, could protect mice from Paclitaxel-induced peripheral neuropathy (PIPN). Six groups of C57BL/6J mice (n = 6) were used in this study. The mice were given paclitaxel (PTX) (8 mg/kg/day, i.p.) on days 1, 3, 5, and 7 to induce neuropathy. Mice were evaluated for behavioral parameters, and dorsal root ganglions (DRG) were collected from the animals and subjected to RNA sequencing and westernblot analysis at the end of the study. On cultured DRGs derived from adult male rats, immunocytochemistry and mitochondrial functional assays were also performed. When compared to individual treatments, the combination of CBD and THCV improved thermal and mechanical neurobehavioral symptoms in mice by twofold. Targets for CBD and THCV therapy were identified by KEGG (RNA sequencing). PTX reduced the expression of p-AMPK, SIRT1, NRF2, HO1, SOD2, and catalase while increasing the expression of PI3K, p-AKT, p-P38 MAP kinase, BAX, TGF-ß, NLRP3 inflammasome, and caspase 3 in DRG homogenates of mice. Combination therapy outperformed monotherapy in reversing these protein expressions. The addition of CBD and THCV to DRG primary cultures reduced mitochondrial superoxides while increasing mitochondrial membrane potentials. WAY100135 and rimonabant altered the neuroprotective effects of CBD and THCV respectively by blocking 5-HT1A and CB1 receptors in mice and DRG primary cultures. The entourage effect of CBD and THCV against PIPN appears to protect neurons in mice via 5HT1A and CB1 receptors respectively.

Chairside quantitative immunochromatographic evaluation of salivary cotinine and its correlation with chronic periodontitis.

BACKGROUND: Cigarette smoking is an established and modifiable risk factor for periodontitis. Periodontitis appears to be dose-dependent on smoking. The purpose of this study was to assess a reliable marker of tobacco smoke exposure (salivary cotinine) chairside and to confirm the quantitative association between smoking and chronic periodontitis. MATERIALS AND METHODS: Saliva samples from 80 males, aged 30-60 years, with chronic periodontitis, were evaluated chairside using NicAlert™ cotinine test strips (NCTS). Patients were divided into two groups: A (cotinine negative) and B (cotinine positive). Plaque index (PI), Gingival index (GI), gingival bleeding index (GBI), probing pocket depth (PPD), clinical attachment level (CAL), and gingival recession (GR) were compared between the two groups and among the subjects of group B. RESULTS: Comparison showed that the severity of PPD (P<0.001), CAL (P<0.001), and GR (P<0.001) was more in group B than in group A. Severity of all periodontal parameters increased with increased salivary cotinine among the subjects in group B. CONCLUSION: Quantitative direct association can be established between salivary cotinine and the severity of periodontitis. Immunochromatography-based cotinine test strips are a relatively easy method for quantification of salivary cotinine chairside. Immediate and personalized feedback from a chairside test can improve compliance, quit rates, and ease reinforcing smoking cessation.