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Very long-chain fatty acids (VLCFAs) are degraded exclusively in peroxisomes, as evidenced by the accumulation of VLCFAs in patients with certain peroxisomal disorders. Although accumulation of VLCFAs is considered to be associated with health issues, including neuronal degeneration, the mechanisms underlying VLCFAs-induced tissue degeneration remain unclear. Here, we report the toxic effect of VLCFA and protective effect of C18: 1 FA in peroxisome-deficient CHO cells. We examined the cytotoxicity of saturated and monounsaturated VLCFAs with chain-length at C20-C26, and found that longer and saturated VLCFA showed potent cytotoxicity at lower accumulation levels. Furthermore, the extent of VLCFA-induced toxicity was found to be associated with a decrease in cellular C18:1 FA levels. Notably, supplementation with C18:1 FA effectively rescued the cells from VLCFA-induced apoptosis without reducing the cellular VLCFAs levels, implying that peroxisome-deficient cells can survive in the presence of accumulated VLCFA, as long as the cells keep sufficient levels of cellular C18:1 FA. These results suggest a therapeutic potential of C18:1 FA in peroxisome disease and may provide new insights into the pharmacological effect of Lorenzo's oil, a 4:1 mixture of C18:1 and C22:1 FA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Cluster-like headache (CLH) associated with pituitary adenoma (PA) is rare. Although numerous cases have been reported, no summary of the literature has been published. Furthermore, the mechanism and efficacy of medication in CLH associated with PA remains unknown., Methods: We reviewed 14 cases of CLHs associated with PA published in the English and Japanese literature. We have also included and presented our experience with such a case., Results: The median age of patients with CLHs associated with PA was 46 years (range, 17-58 years). The ratio of men to women was 14:1. Headache duration ranged from 15-480 min, with left fronto-orbital pain being common. The most common autonomic nervous symptoms were eye-related in 13 patients (86.6 %), followed by nasal symptoms in 12 (80.0 %). Thirteen patients (86.6 %) had functional adenomas; the remaining two were nonfunctional. Twelve of the functional adenomas were lactotroph adenomas (80.0 %), and one was a somatotroph adenoma (6.6 %). CLHs significantly improved after cabergoline administration in 7/9 patients with a lactotroph adenoma (77.7 % response rate). In 5/11 patients with either a functional or nonfunctional PA who received a triptan, CLHs improved (45.4 % response rate)., Conclusion: Based on the efficacies of cabergoline and triptans, two different mechanisms may coexist in the pathogenesis of CLHs associated with PA: endocrinological and physical effects of the tumor itself. Cabergoline is the first-line treatment for headaches caused by lactotroph adenomas. Triptans can be effective as an acute drug for headaches associated with nonfunctional PAs and persistent headaches that remain after cabergoline administration., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Repetitive electrical nerve stimulation of the lower limb may improve neurogenic claudication in patients with lumbar spinal stenosis (LSS) as originally described by Tamaki et al. We tested if this neuromodulation technique affects the F-wave conduction on both sides to explore the underlying physiologic mechanisms., Methods: We studied a total of 26 LSS patients, assigning 16 to a study group receiving repetitive tibial nerve stimulation at the ankle (RTNS) on one leg, and 10 to a group without RTNS. RTNS conditioning consisted of a 0.3-ms duration square-wave pulse with an intensity 20% above the motor threshold, delivered at a rate of 5 Hz for 5 min. All patients underwent the walking test and the F-wave and M-wave studies for the tibial nerve on both sides twice; once as the baseline, and once after either the 5-min RTNS or 5-min rest., Results: Compared to the baselines, a 5-min RTNS increased claudication distance (176 ± 96 m vs 329 ± 133 m; p = 0.0004) and slightly but significantly shortened F-wave minimal onset latency (i.e., increased F-wave conduction velocity) not only on the side receiving RTNS (50.7 ± 4.0 ms vs 49.2 ± 4.2 ms; p = 0.00081) but also on the contralateral side (50.1 ± 4.6 ms vs 47.9 ± 4.2 ms; p = 0.011). A 5-min rest in the group not receiving RTNS neither had a significant change on claudication distance nor on any F-wave measurements. The M response remained unchanged in both groups., Conclusions: The present study verified a beneficial effect of unilaterally applied RTNS of a mild intensity on neurogenic claudication and bilateral F-wave conduction. Our F-wave data suggest that this type of neuromodulation could be best explained by an RTNS-induced widespread sympathetic tone reduction with vasodilation, which partially counters a walking-induced further decline in nerve blood flow in LSS patients who already have ischemic cauda equina., (Copyright © 2017 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)