Corneal Confocal Microscopy Detects Small-Fiber Neuropathy in Burning Mouth Syndrome: A Cross-Sectional Study.

AIMS: To assess the utility of corneal confocal microscopy in identifying small fiber damage in patients with burning mouth syndrome (BMS). METHODS: A prospective cross-sectional cohort study was conducted at two United Kingdom dental hospitals between 2014 and 2017. A total of 17 consecutive patients with idiopathic BMS aged between 18 and 85 years and 14 healthy age-matched control subjects were enrolled in this study. Corneal subbasal nerve plexus measures were quantified in images acquired using a laser-scanning in vivo corneal confocal microscope. The main outcome measures were corneal nerve fiber density, nerve branch density, nerve fiber length, and Langerhans cell density. RESULTS: Of the 17 patients with BMS, 15 (88%) were women, and the mean (standard deviation) age of the sample was 61.7 (6.5) years. Of the healthy controls, 7 (50%) were women, and the mean (standard deviation) age was 59.3 (8.68) years. Corneal nerve fiber density (no./mm2) (BMS: 29.27 ± 6.22 vs controls: 36.19 ± 5.9; median difference = 6.71; 95% CI: 1.56 to 11.56; P = .007) and corneal nerve fiber length (mm/mm2) (BMS: 21.06 ± 4.77 vs controls: 25.39 ± 3.91; median difference = 4.5; 95% CI: 1.22 to 6.81; P = .007) were significantly lower in BMS patients compared to controls, and Langerhans cell density (no./mm2) (BMS: 74.04 ± 83.37 vs controls: 29.17 ± 45.14; median difference = -21.27; 95% CI: -65.35 to -2.91; P = .02) was significantly higher. CONCLUSION: Using a rapid noninvasive ophthalmic imaging technique, this study provides further evidence for small fiber damage in BMS and has potential utility for monitoring disease progression and/or response. Furthermore, this technique shows a hitherto undocumented increased density of immune cells in this group of patients.

Protection by beta-Hydroxybutyric acid against insulin glycation, lipid peroxidation and microglial cell apoptosis.

BACKGROUND: Diabetes mellitus is characterized jointly by hyperglycemia and hyperinsulinemia that make insulin more prone to be glycated and evolve insulin advanced glycation end products (Insulin- AGE). Here, we report the effect of beta-hydroxy butyrate (BHB) (the predominant ketone body) on the formation of insulin-AGE, insulin glycation derived liposomal lipid peroxidation and insulin-AGE toxicity in microglial cells. METHODS: The inhibitory effect of BHB was monitored as a result of insulin incubation in the presence of glucose or fructose using AGE-dependent fluorescence, Tyr fluorescence as well as anilinonaphthalenesulfonate (ANS) andthioflavin T (ThT) binding, and circular dichroism (CD) investigations. To study lipid peroxidation induced by insulin glycation, thiobarbituric acid (TBA) assay and thiobarbituric acid reactive substance (TBARS) monitoring were used. The effect of insulin-AGE on microglial viability was investigated by 3-(4, 5 dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT) cell assay and Annexin V/propidium iodide (PI) staining. RESULTS: Here we are reporting the inhibitory effect of BHB on insulin glycation and generation of insulin-AGE as a possible explanation for insulin resistance. Moreover, the protective effect of BHB on consequential glycation derived liposomal lipid peroxidation as a causative event in microglial apoptosis is reported. CONCLUSION: The reduced insulin fibril formation, structural inertia to glycation involved conformational changes, anti-lipid peroxidation effect, and increasing microglia viability indicated the protective effect of BHB that disclose insight on the possible preventive effect of BHB on Alzheimer's disease.