-
Frontiers in Neurology 2023Betahistine is widely used for the treatment of various vestibular disorders. However, the approved oral administration route and maximum daily dose are evidently not...
INTRODUCTION
Betahistine is widely used for the treatment of various vestibular disorders. However, the approved oral administration route and maximum daily dose are evidently not effective in clinical trials, possibly due to a major first-pass metabolism by monoamine oxidases (MAOs). The current study aimed to test different application routes (i.v./s.c./p.o.), doses, and concurrent medication (with the MAO-B inhibitor selegiline) for their effects on behavioral recovery and cerebral target engagement following unilateral labyrinthectomy (UL) in rats.
METHODS
Sixty rats were subjected to UL by transtympanic injection of bupivacaine/arsanilic acid and assigned to five treatment groups: i.v. low-dose betahistine (1 mg/kg bid), i.v. high-dose betahistine (10 mg/kg bid), p.o. betahistine (1 mg/kg bid)/selegiline (1 mg/kg once daily), s.c. betahistine (continuous release of 4.8 mg/day), and i.v. normal saline bid (sham treatment; days 1-3 post-UL), respectively. Behavioral testing of postural asymmetry, nystagmus, and mobility in an open field was performed seven times until day 30 post-UL and paralleled by sequential cerebral [F]-FDG-μPET measurements.
RESULTS
The therapeutic effects of betahistine after UL differed in extent and time course and were dependent on the dose, application route, and selegiline co-medication: Postural asymmetry was significantly reduced on 2-3 days post-UL by i.v. high-dose and s.c. betahistine only. No changes were observed in the intensity of nystagmus across groups. When compared to sham treatment, movement distance in the open field increased up to 5-fold from 2 to 30 days post-UL in the s.c., i.v. high-dose, and p.o. betahistine/selegiline groups. [F]-FDG-μPET showed a dose-dependent rCGM increase in the ipsilesional vestibular nucleus until day 3 post-UL for i.v. high- vs. low-dose betahistine and sham treatment, as well as for p.o. betahistine/selegiline and s.c. betahistine vs. sham treatment. From 1 to 30 days post-UL, rCGM increased in the thalamus bilaterally for i.v. high-dose betahistine, s.c. betahistine, and p.o. betahistine/selegiline vs. saline treatment.
DISCUSSION
Betahistine has the potential to augment the recovery of dynamic deficits after UL if the administration protocol is optimized toward higher effective plasma levels. This may be achieved by higher doses, inhibition of MAO-based metabolism, or a parenteral route. imaging suggests a drug-target engagement in central vestibular networks.
PubMed: 37538257
DOI: 10.3389/fneur.2023.1175481 -
Materials (Basel, Switzerland) Dec 2023As a kind of emerging contaminant, organoarsenic compounds have drawn wide concern because of their considerable solubilities in water, and the highly toxic inorganic...
As a kind of emerging contaminant, organoarsenic compounds have drawn wide concern because of their considerable solubilities in water, and the highly toxic inorganic arsenic species formed during their biotic and abiotic degradation in the natural environment. Thus, the effective removal and studying of the adsorption mechanism of organoarsenic compounds are of significant urgency. In this work, MnFeO and MnFeO/graphene were prepared through a facile solvothermal method. From the results of the Transmission Electron Microscope (TEM) characterization, it can be found that MnFeO nanoparticles were uniformly distributed on the surface of the graphene. And the specific surface area of the MnFeO/graphene was about 146.39 m g, much higher than that of the MnFeO (86.15 m g). The interactions between organoarsenic compounds and adsorbents were conducted to study their adsorption behavior and mechanism. The maximum adsorption capacities of MnFeO/graphene towards p-arsanilic acid (p-ASA) and roxarsone (ROX) were calculated to be 22.75 and 30.59 mg g. Additionally, the ionic strength, negative ions, and humus were introduced to investigate the adsorption performance of organoarsenic compounds. Electrostatic adsorption and surface complexation are the primary adsorption mechanisms on account of X-ray photoelectron spectroscopy (XPS) and the Fourier-transform infrared spectroscopy (FT-IR) analysis. This research extends the knowledge into studying the interaction between organoarsenic species and hybrid nanomaterials in the natural environment.
PubMed: 38138778
DOI: 10.3390/ma16247636