Melatonin oral gel(Spherium Biomed SL)

A recent case study reported a non-24 h sleep-wake disorder in a patient with myotonic dystrophy type 1 (DM1). Research on intrinsic circadian rhythm sleep-wake disorders (CRSWDs) in DM1 patients is though lacking. This study utilized actigraphy to ascertain the presence of CRSWDs in DM1 patients and establish a comparison with healthy control subjects.

Thirty-three patients with genetic diagnosis of DM1 and 33 age- and sex-matched healthy control subjects wore an actigraph and filled out a sleep diary for two consecutive weeks. Sleep, light exposure, and nonparametric measures were computed from actigraphic data.

DM1 patients exhibit poorer sleep quality and delayed sleep-wake episodes as well as reduced daylight exposure compared to healthy control subjects. Importantly, 3 DM1 patients (9.1 %) had a delayed sleep phase disorder and 3 DM1 patients had an irregular sleep-wake rhythm disorder (ISWRD) (9.1 %) whereas no control subject exhibited a CRSWD. DM1 patients with an ISWRD presented lower inter-daily stability (IS) (0.16 vs. 0.44, p < 0.05) and relative amplitude (RA) (0.36 vs. 0.79, p < 0.01) as well as higher intra-daily variability (IV) (1.22 vs. 0.79, p < 0.05) than DM1 patients with a normal sleep phenotype. DM1 patients with CRSWDs were more likely to exhibit excessive daytime sleepiness (EDS) than those with a normal sleep phenotype (83.3 % vs. 37.0 %, p < 0.05).

Core clinical implications are the need to systematically screen DM1 patients for CRSWDs and apply a multimodal chronotherapy (sleep hygiene, timed light, and melatonin). Recognizing and treating CRSWDs can help address significant sleep disturbances, like EDS.

Drug-related factors represent a primary cause of acute kidney injury. Gentamicin (GM), while being one of the most effective and commonly used clinical agents against Gram-negative bacteria, frequently induces nephrotoxicity and triggers acute kidney injury during treatment. Melatonin, a natural antioxidant produced by the pineal gland, has been shown in recent studies to mitigate drug-induced nephrotoxicity. This study aimed to delineate the dose-dependent effects and underlying mechanisms of GM-induced acute kidney injury, along with the protective role of melatonin. Results demonstrated that GM administration elicited dose-dependent nephrotoxicity in rats, significantly elevating urinary biomarkers of tubular injury (KIM-1 and NGAL) and serum markers of renal dysfunction (BUN and SCr) at doses ≥50 mg/kg. Histopathological analysis revealed progressive renal damage including brush border loss, epithelial necrosis, basement membrane disruption, and interstitial inflammation. GM further exacerbated renal oxidative stress, depleting SOD and GSH while elevating MDA levels. Mechanistically, GM dose-dependently upregulated Keap1 and downregulated NRF2 expressions, consequently suppressing downstream antioxidants (GPX1, NQO1, HO-1). However, melatonin treatment significantly ameliorated high-dose GM-induced acute kidney injury by normalizing biochemical markers of renal impairment, attenuating histopathological damage, restoring antioxidant capacity, and reactivating the KEAP1/NRF2 pathway through suppression of Keap1 while enhancing NRF2 and its target proteins (GPX1/NQO1/HO-1) to nearly double of GM-H group levels, confirming its renoprotective role against GM-induced oxidative injury.