ObjectivesThere is a critical need to develop effective treatments for diabetic neuropathy. This study determined if a selective mGluR2/3 receptor agonist prevented or treated experimental diabetic peripheral neuropathy (DPN) through glutamate recycling and improved mitochondrial function.MethodsAdult male streptozotocin treated Sprague‐Dawley rats with features of type 1 diabetes mellitus (T1DM) or Low Capacity Running (LCR) rats with insulin resistance or glucose intolerance were treated with 3 or 10 mg/kg/day LY379268. Neuropathy end points included mechanical allodynia, nerve conduction velocities (NCV), and intraepidermal nerve fiber density (IENFD). Markers of oxidative stress, antioxidant response, glutamate recycling pathways, and mitochondrial oxidative phosphorylation (OXPHOS) associated proteins were measured in dorsal root ganglia (DRG).ResultsIn diabetic rats, NCV and IENFD were decreased. Diabetic rats treated with an mGluR2/3 agonist did not develop neuropathy despite remaining diabetic. Diabetic DRG showed increased levels of oxidized proteins, decreased levels of glutathione, decreased levels of mitochondrial DNA (mtDNA) and OXPHOS proteins. In addition, there was a 20‐fold increase in levels of glial fibrillary acidic protein (GFAP) and the levels of glutamine synthetase and glutamate transporter proteins were decreased. When treated with a specific mGluR2/3 agonist, levels of glutathione, GFAP and oxidized proteins were normalized and levels of superoxide dismutase 2 (SOD2), SIRT1, PGC‐1α, TFAM, glutamate transporter proteins, and glutamine synthetase were increased in DRG neurons.InterpretationActivation of glutamate recycling pathways protects diabetic DRG and this is associated with activation of the SIRT1‐PGC‐1α–TFAM axis and preservation of mitochondrial OXPHOS function.

Axon degeneration in diabetic peripheral neuropathy (DPN) is associated with impaired NAD+ metabolism. We tested whether the administration of NAD+ precursors, nicotinamide mononucleotide (NMN) or nicotinamide riboside (NR), prevents DPN in models of Type 1 and Type 2 diabetes. NMN was administered to streptozotocin (STZ)-induced diabetic rats and STZ-induced diabetic mice by intraperitoneal injection at 50 or 100 mg/kg on alternate days for 2 months. mice The were fed with a high fat diet (HFD) for 2 months with or without added NR at 150 or 300 mg/kg for 2 months. The administration of NMN to STZ-induced diabetic rats or mice or dietary addition of NR to HFD-fed mice improved sensory function, normalized sciatic and tail nerve conduction velocities, and prevented loss of intraepidermal nerve fibers in skin samples from the hind-paw. In adult dorsal root ganglion (DRG) neurons isolated from HFD-fed mice, there was a decrease in NAD+ levels and mitochondrial maximum reserve capacity. These impairments were normalized in isolated DRG neurons from NR-treated mice. The results indicate that the correction of NAD+ depletion in DRG may be sufficient to prevent DPN but does not significantly affect glucose tolerance, insulin levels, or insulin resistance.

No abstract

Snorers represent a heterogeneous group that requires adequate assessment before recommending surgical treatment. Most studies of the pathophysiology of snoring and obstructive sleep apnea have emphasized anatomical abnormalities in the oropharyngeal and hypopharyngeal airways. It is still unclear if nasal airway restriction plays an important role in sleep-disordered breathing and there is no general consensus if treatment of nasal pathology should be included in the management of patients with snoring or sleep apnea. The aim of this study was to compare nasal dimensions and airflow resistance of habitual snorers with non-snoring individuals by means of acoustic rhinometry and rhinomanometry. Sixty individuals were enrolled in this analytical cross-sectional study. They were divided in two groups: group A (case) consisted of 30 patients with a main complaint of chronic snoring referred to ear, nose, and throat (ENT) clinic of Hazrat-e-Rasoul University Hospital, Tehran, Iran. Group B (control) consisted of 30 individuals without any complaint of snoring. The subjects were assessed objectively with acoustic rhinometry and rhinomanometry. Nasal dimensions and airflow resistance were recorded for all individuals. The most common site of minimum cross-sectional area (MCA) was at the left concha-notch in both snoring and non-snoring individuals. Significant reduction of cross-sectional area of both isthmus and concha notches was seen in habitual snorers (P < 0.05). The mean total airflow resistances in both pressures of 75 and 150 Pa was higher in habitual snorers. Whereas, these differences were not statistically significant (P > 0.05). The results of our study illustrate that acoustic rhinometry, rhinomanometry may be helpful methods for quantitative assessments of nasal airway respiratory function, and configuration in snorers; especially to evaluate site of MCA, decreased nasal cross-sectional area and increased nasal airflow resistance in habitual snorers which may lead to OSA.

No abstract

No abstract

Introduction Racial disparities in the prevalence and severity of Obstructive Sleep Apnea (OSA) in Black Americans may play an important contributory role in the increased burden of cardiometabolic disease experienced by this population. Effective screening for OSA could permit early recognition and treatment, thereby preventing future the adverse cardiovascular outcomes which contribute to a decreased life expectancy. The STOP-BANG questionnaire is a validated screening tool for OSA as demonstrated in many populations and settings. Unfortunately, Blacks have typically been underrepresented in studies evaluating the sensitivity and specificity of the tool. Potentially unique biologic and psychosocial factors may affect the phenotypic expression of OSA and influence the performance of the STOP-BANG. Data are needed regarding the reliability of the tool for this population and potentially modifications to optimize its usefulness. Methods Data were from 204 patients evaluated at the Howard University Hospital Sleep Disorder Center between April 2018 and June 2019. Records were reviewed for demographic information, body mass index (BMI), neck circumference, and medical history, including the presence of snoring, tiredness/sleepiness, observed apneas, and hypertension and results of sleep study testing. Data were analyzed using SPSS software. Subcomponents of the STOP-BANG scoring criteria were adjusted to improve performance. Results Mean age was 48.5. 62% of subjects were female and mean BMI was 40.2 The mean ESS was 9.9. The mean AHI was 27.7 with a prevalence of mild or greater OSA (AHI &gt;5) of 80%. Scoring of the STOP-BANG using a criterion of 3 or greater as indicating increased risk demonstrated a sensitivity of 90%, specificity of 8%, PPV of 80%, and NPV of 17%. Performance was worse for women then men. Multiple adjustments to scoring were evaluated to improve accuracy. Conclusion Similar to its performance in other populations, the STOP-BANG demonstrated high sensitivity but very poor specificity and overall poor accuracy in a Black population referred for Sleep Medicine Consultation to an urban university hospital. Performance was worse for women than men. Modifications are presented to try to improve performance and the clinical utility for this population. Support Howard University RCMI