Application of multielectrode array (MEA) chips for studying the neurotoxicity of mixtures

In vitro neuronal networks are a simplified and accessible model of the central nervous system. Moreover, they exhibit morphological and physiological properties and activity-dependent path-specific synaptic modification similar to the in vivo tissue. Cortical neurons grown on multi electrode array (MEA) chips have been shown to be a valuable tool to study fundamental properties of neuronal network activity, synaptic plasticity, learning in vitro, and functional pharmacological screening. The variation of spontaneous activity of in vitro neuronal networks coupled to MEAs has been studied using several binary mixtures (inhibitors with different mode of action: Verapamil and Muscimol, Fluoxetine and Muscimol; inhibitors with the same mode of action: Deltamethrin and Permethrin; and an excitatory and an inhibitory compound with different mode of action: Kainic acid and Muscimol) with the aim of characterize and assess their combined effects. Individual dose-response and binary mixtures curves have been generated. Concentration Addition (CA) and Independent Action (IA) frameworks have been used to compare calculated and experimental results. In addition, Nuclear Magnetic Resonance (NMR) spectroscopy has been employed to assess that no chemical reaction or complexation took place between mixtures components, as well as to monitor the presence of potential impurities and, in this case, to evaluate their relative amount in the tested samples. The results suggest that additivity: CA and IA are able to predict in most of the cases the total toxicity of the mixture. The variability of the results makes difficult to assess which of both approaches is the most accurate. The presence of both excitatory and inhibitory effects as in the case of Kainic acid may further complicate the analysis of the experimental datasets and biphasic concentration-dose response curves may be need to analyze the joint effect.JRC.I.6-Systems toxicolog

Effects of previous carbohydrate supplementation on muscular fatigue: double-blind, randomized, placebo-controlled crossover study

Abstract AIMS The aim of this study was to examine the effects of previous carbohydrate supplementation on high-volume resistance exercise performance METHODS Twenty males physically independent adults aged ≥18 years participated in a double-blind randomized placebo-controlled crossover study. Sixty minutes before the experimental protocol, each participant ingested 0,6 g.kg of body mass-1 of carbohydrate supplementation or placebo. Maximum voluntary isometric contraction tests were performed before and after the dynamic fatigue induction protocol consisting of 10 sets of 8 repetitions of right leg knee extensors at 120º s-1. RESULTS Lower decrement of the isometric peak torque (p<0,001) and of the rate of torque development (p<0,001) was observed in carbohydrate supplementation after the dynamic protocol. Both concentric and eccentric peak torque differed significantly (p<0,001) between carbohydrate supplementation and placebo treatments from the second set, although the slope of the force-repetitions curve was not different between them. Additionally, the carbohydrate supplementation resulted in a lower session rating of perceived exertion (p<0,05). CONCLUSIONS Previous carbohydrate supplementation attenuates muscle fatigue and internal load exercise in a high-volume isokinetic leg protocol

Application of multielectrode array (MEA) chips for the evaluation of mixtures neurotoxicity

Cortical neurons grown on multi electrode array (MEA) chips have been shown to be a valuable alternative method to study electrophysiological properties of the central nervous system and to perform functional toxicological screening. Here we studied the effects of binary mixtures on neuronal networks cultured on MEAs. We have considered compounds with similar and different mode-of-action (MoA) to characterize and assess their combined effects. Individual and binary mixture dose-response curves based on spontaneous neuronal activity have been generated and the IC50 has been considered as the end-point for neurotoxicity assessment. The two classical approaches of mixtures toxicity studies: Concentration Addition (CA) and Independent Action (IA) have been applied to compare calculated and experimental results. Nuclear Magnetic Resonance (NMR) spectroscopy has been employed to confirm no chemical reaction or complexation between mixtures components. The results suggest that both CA and IA are able to predict the toxicity of the mixture and that the combination of in vitro test methods with in silico approaches has a strong potential as an alternative tool for the prediction of mixtures neurotoxicity.JRC.I.5-Systems Toxicolog

Alterations in peak torque do not occur with hematological changes after muscle fatigue

ABSTRACT Introduction: Muscular fatigue during voluntary muscle contractions is a complex and multifactorial phenomenon associated with central changes and adaptations of the neuromuscular system. Objective: The aim of this study was to analyze the changes in both peak torque and hematological parameters in active and inactive healthy subjects following a muscular fatigue protocol. Methods: Twenty-one healthy adult males performed a muscle fatigue protocol (10 sets, 10 repetitions of knee extension at 75% of the maximal isometric torque (MIT), 120º s-1 and 40 seconds of rest). Hematocrit (Ht), red blood cells (RBC) and leukocytes (L) analysis were evaluated before (B) and after (A) a fatigue test. Results: The inactive group presented impairment only in concentric muscular action of -41±4% in relation to the active (-23±3%) group. No differences were found in hematological parameters in inactive group (Ht, B: 45.00±0.01 vs. A: 47.00±0.01; RBC, B: 442±40 vs. A: 487±41; L, B: 7,565±2,878 vs. A: 8,015±4,224) and the active group (Ht, B: 45.00±0.63 vs. A: 47.00±0.01; RBC, B: 477±30 vs. A: 559±37; L, B: 6,418±3,557 vs. A: 6,632±4,460). Conclusion: Differences were found only in concentric actions between groups. Additionally, there were no relationships found in hematological parameters between groups.</jats:p

Understanding Factors Associated With Psychomotor Subtypes of Delirium in Older Inpatients With Dementia

Objectives: Few studies have analyzed factors associated with delirium subtypes. In this study, we investigate factors associated with subtypes of delirium only in patients with dementia to provide insights on the possible prevention and treatments. Design: This is a cross-sectional study nested in the “Delirium Day” study, a nationwide Italian point-prevalence study. Setting and Participants: Older patients admitted to 205 acute and 92 rehabilitation hospital wards. Measures: Delirium was evaluated with the 4-AT and the motor subtypes with the Delirium Motor Subtype Scale. Dementia was defined by the presence of a documented diagnosis in the medical records and/or prescription of acetylcholinesterase inhibitors or memantine prior to admission. Results: Of the 1057 patients with dementia, 35% had delirium, with 25.6% hyperactive, 33.1% hypoactive, 34.5% mixed, and 6.7% nonmotor subtype. There were higher odds of having venous catheters in the hypoactive (OR 1.82, 95% CI 1.18-2.81) and mixed type of delirium (OR 2.23, CI 1.43-3.46), whereas higher odds of urinary catheters in the hypoactive (OR 2.91, CI 1.92-4.39), hyperactive (OR 1.99, CI 1.23-3.21), and mixed types of delirium (OR 2.05, CI 1.36-3.07). We found higher odds of antipsychotics both in the hyperactive (OR 2.87, CI 1.81-4.54) and mixed subtype (OR 1.84, CI 1.24-2.75), whereas higher odds of antibiotics was present only in the mixed subtype (OR 1.91, CI 1.26-2.87). Conclusions and Implications: In patients with dementia, the mixed delirium subtype is the most prevalent followed by the hypoactive, hyperactive, and nonmotor subtype. Motor subtypes of delirium may be triggered by clinical factors, including the use of venous and urinary catheters, and the use of antipsychotics. Future studies are necessary to provide further insights on the possible pathophysiology of delirium in patients with dementia and to address the optimization of the management of potential risk factors