Kimura disease (KD) is a chronic inflammatory disorder with angiolymphatic proliferation, usually affecting young men of Asian race but is rare in other races. The etiology of KD is still unknown. It is often accompanied by nephrotic syndrome. Herein, we present an atypical manifestation of Kimura disease occurring in a Caucasian man with steroid-responsive early membranous glomerulonephritis. Kimura disease can present atypically in a middle-aged Caucasian man with secondary steroid-responsive nephrotic syndrome. Steroid, endoxan, and MMF can be used safely and successfully in such situation. The diagnosis of KD can be difficult and misleading, and patients with this disease are often evaluated using avoidable procedures by just not being aware of KD.

Cannabidiol (CBD) is the primary nonpsychotropic phytocannabinoid found in Cannabis sativa, which has been proposed to be therapeutic against many conditions, including muscle spasms. Among its putative targets are voltage-gated sodium channels (Navs), which have been implicated in many conditions. We investigated the effects of CBD on Nav1.4, the skeletal muscle Nav subtype. We explored direct effects, involving physical block of the Nav pore, as well as indirect effects, involving modulation of membrane elasticity that contributes to Nav inhibition. MD simulations revealed CBD’s localization inside the membrane and effects on bilayer properties. Nuclear magnetic resonance (NMR) confirmed these results, showing CBD localizing below membrane headgroups. To determine the functional implications of these findings, we used a gramicidin-based fluorescence assay to show that CBD alters membrane elasticity or thickness, which could alter Nav function through bilayer-mediated regulation. Site-directed mutagenesis in the vicinity of the Nav1.4 pore revealed that removing the local anesthetic binding site with F1586A reduces the block of INa by CBD. Altering the fenestrations in the bilayer-spanning domain with Nav1.4-WWWW blocked CBD access from the membrane into the Nav1.4 pore (as judged by MD). The stabilization of inactivation, however, persisted in WWWW, which we ascribe to CBD-induced changes in membrane elasticity. To investigate the potential therapeutic value of CBD against Nav1.4 channelopathies, we used a pathogenic Nav1.4 variant, P1158S, which causes myotonia and periodic paralysis. CBD reduces excitability in both wild-type and the P1158S variant. Our in vitro and in silico results suggest that CBD may have therapeutic value against Nav1.4 hyperexcitability.

Background and Purpose: Cardiovascular complications are the major cause of mortality in diabetic patients. However, the molecular mechanisms underlying diabetesassociated arrhythmias are unclear. We hypothesized that high glucose could adversely affect Na v 1.5, the major cardiac sodium channel isoform of the heart, at least partially via oxidative stress. We further hypothesized that cannabidiol (CBD), one of the main constituents of Cannabis sativa, through its effects on Na v 1.5, could protect against high glucose-elicited oxidative stress and cytotoxicity.Experimental Approach: To test these ideas, we used CHO cells transiently cotransfected with cDNA encoding human Na v 1.5 α-subunit under control and high glucose conditions (50 or 100 mM for 24 hr). Several experimental and computational techniques were used, including voltage clamp of heterologous expression systems, cell viability assays, fluorescence assays and action potential modelling.Key Results: High glucose evoked cell death associated with elevation in reactive oxygen species (ROS) right shifted the voltage dependence of conductance and steady-state fast inactivation, and increased persistent current leading to computational prolongation of action potential (hyperexcitability) which could result in long QT3 arrhythmia. CBD mitigated all the deleterious effects provoked by high glucose.Perfusion with lidocaine (a well-known sodium channel inhibitor with antioxidant effects) or co-incubation of Tempol (a well-known antioxidant) elicited protection, comparable to CBD, against the deleterious effects of high glucose.Conclusion and Implications: These findings suggest that, through its favourable antioxidant and sodium channel inhibitory effects, CBD may protect against high glucose-induced arrhythmia and cytotoxicity.