Aerobic Training Affects Fatty Acid Composition of Erythrocyte Membranes

The effect of exercise training on the fatty acid composition of erythrocyte membranes was evaluated in an experimental animal model where rats were subjected to a ten-wk aerobic training. Five groups of rats were compared: sedentary rats at 19 or 23 wks of age, rats trained at moderate or high intensity sacrificed at 19 wks of age, and rats trained at high intensity, and sacrificed following 4 weeks of sedentary life. We had already demonstrated that cardioprotection correlates with training intensity and partially persists in detrained rats. Main findings are that rats trained at higher intensity display consistent signs of lipid peroxidation but a lower ω6/ω3 ratio and a lower content of trans fatty acids when compared to rats trained at lower intensity and to older sedentary rats. Trans fatty acids negatively affect cell membrane fluidity and permeability. Detrained rats showed intermediate values. Gene expression evaluation of selected enzymes involved in lipid biosynthesis revealed some of the adaptive mechanisms leading to the maintenance of membrane fatty acid homeostasis following exercise. The decrease in the amount of trans fatty and in the inflammatory pathways (i.e. ω6/ω3 ratio) in high-intensity trained rats underscores the protective effect of high intensity aerobic training

Na+, K+-ATPase activity in children with autism spectrum disorder: Searching for the reason(s) of its decrease in blood cells

Na+, K+-ATPase (NKA) activity, which establishes the sodium and potassium gradient across the cell membrane and is instrumental in the propagation of the nerve impulses, is altered in a number of neurological and neuropsychiatric disorders, including autism spectrum disorders (ASD). In the present work, we examined a wide range of biochemical and cellular parameters in the attempt to understand the reason(s) for the severe decrease in NKA activity in erythrocytes of ASD children that we reported previously. NKA activity in leukocytes was found to be decreased independently from alteration in plasma membrane fluidity. The different subunits were evaluated for gene expression in leukocytes and for protein expression in erythrocytes: small differences in gene expression between ASD and typically developing children were not apparently paralleled by differences in protein expression. Moreover, no gross difference in erythrocyte plasma membrane oxidative modifications was detectable, although oxidative stress in blood samples from ASD children was confirmed by increased expression of NRF2 mRNA. Interestingly, gene expression of some NKA subunits correlated with clinical features. Excess inhibitory metals or ouabain-like activities, which might account for NKA activity decrease, were ruled out. Plasma membrane cholesterol, but not phosphatidylcholine and phosphatidlserine, was slighty decreased in erythrocytes from ASD children. Although no compelling results were obtained, our data suggest that alteration in the erytrocyte lipid moiety or subtle oxidative modifications in NKA structure are likely candidates for the observed decrease in NKA activity. These findings are discussed in the light of the relevance of NKA in ASD. Autism Research 2018. \ua9 2018 The Authors. Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. Lay Summary: The activity of the cell membrane enzyme NKA, which is instrumental in the propagation of the nerve impulses, is severely decreased in erythrocytes from ASD children and in other brain disorders, yet no explanation has been provided for this observation. We strived to find a biological/biochemical cause of such alteration, but most queries went unsolved because of the complexity of NKA regulation. As NKA activity is altered in many brain disorders, we stress the relevance of studies aimed at understanding its regulation in ASD

Oxidative stress and erythrocyte membrane alterations in children with autism: correlation with clinical features

It has been suggested that oxidative stress may play a role in the pathogenesis of Autism Spectrum Disorders (ASD), but the literature reports somewhat contradictory results. To further investigate the issue, we evaluated a high number of peripheral oxidative stress parameters, and some related issues such as erythrocyte membrane functional features and lipid composition. Twenty-one autistic children (Au) aged 5 to 12 years, were gender and age-matched with 20 typically developing children (TD). Erythrocyte thiobarbituric acid reactive substances, urinary isoprostane and hexanoyl-lysine adduct levels were elevated in Au, thus confirming the occurrence of an imbalance of the redox status of Au, whilst other oxidative stress markers or associated parameters (urinary 8-oxo-dG, plasma radical absorbance capacity and carbonyl groups, erythrocyte superoxide dismutase and catalase activities) were unchanged. A very significant reduction of Na+/K+-ATPase activity (-66%, p<0.0001), a reduction of erythrocyte membrane fluidity and alteration in erythrocyte fatty acid membrane profile (increase in monounsaturated fatty acids, decrease in EPA and DHA-\u3c93 with a consequent increase in \u3c96/\u3c93 ratio) were found in Au compared to TD, without change in membrane sialic acid content. Some Au clinical features appear to be correlated with these findings; in particular, hyperactivity score appears to be related with some parameters of the lipidomic profile and membrane fluidity. Oxidative stress and erythrocyte membrane alterations may play a role in the pathogenesis of ASD and prompt the development of palliative therapeutic protocols. Moreover, the marked decrease in NKA could be potentially utilized as a peripheral biomarker of ASD

Reporting of rehabilitation intervention for low back pain in randomized controlled trials : Is the treatment fully replicable?

Study Design. Methodological review of randomized controlled trials (RCTs). Objective. To assess the quality of reporting of rehabilitation interventions for mechanical low back pain (LBP) in published RCTs. Summary of Background Data. Reporting of interventions in RCTs often focused on the outcome value and failed to describe interventions adequately. Methods. We systematically searched for all RCTs in Cochrane systematic reviews on LBP published in the Cochrane Database of Systematic Reviews until December 2013. The description of rehabilitation interventions of each RCT was evaluated independently by 2 of the investigators, using an ad hoc checklist of 7 items. The primary outcome was the number of items reported in sufficient details to be replicable in a new RCT or in everyday practice. Results. We found 11 systematic reviews, including 220 eligible RCTs, on LBP. Of those, 185 RCTs were included. The median publication year was 1998 (I-III quartiles, 1990 to 2004). The most reported items were the characteristics of participants (91.3%; 95% confidence interval [CI], 87.3-95.4), the intervention providers (81.1%; 95% CI, 75.4-86.7), and the intervention schedule (69.7%; 95% CI, 63-76). Based on the description of the intervention, less than one fifth would be replicable clinically. The proportion of trials providing all essential information about the participants and interventions increased from 14% (n=7) in 1971 to 1980 to 20% (n=75) in 2001 to 2010. Conclusion. Despite the remarkable amount of energy spent producing RCTs in LBP rehabilitation, the majority of RCTs failed to report sufficient information that would allow the intervention to be replicated in clinical practice. Improving the quality of intervention description is urgently needed to better transfer research into rehabilitation practices

More than a cell biosensor: Aryl hydrocarbon receptor at the intersection of physiology and inflammation

Aryl hydrocarbon receptor (AhR), a highly conserved intracellular transcription factor, is activated by a plethora of ligands of both exogenous and endogenous nature. Besides activating xenobiotic-metabolizing enzymes, it is involved in the differentiation and development of hematopoietic, hepatic, nervous and immune systems. More and more data describe its role in the regulation of immune responses and in the onset and progression of inflammation. Particularly, established results view AhR as a downstream target of inflammatory molecules, since its transcription is regulated by the inflammatory cascade. Interleukin 6 (IL-6) has been described to sustain early stages of inflammation and to influence the expression of AhR either directly, following signal transducer and activator of transcription 3 (STAT3) activation, or in combination with other inflammatory mediators, e.g., transforming growth factor- f (TGF- f). In selected inflammatory milieus, once activated, AhR interacts with its targets including the IL-6 promoter, thus originating an autoinflammatory loop. This perspective review brings together evidence that, in some IL-6-driven pathways, AhR is a downstream target that amplifies the duration and extent of inflammation. Considering that many inflammatory mediators can also trigger the activities of AhR as biosensor and activator of xenobiotics metabolism, this issue is of pivotal importance. The individual susceptibly to some environmental ligands of AhR can be probably explained by considering the individual inflammatory state, which could additionally fuel the proinflammatory activity of AhR. Thus, AhR could be considered a transductor of a dynamic, bidirectional connection between internal and external environmental stimuli and the inflammatory response

ROS/RNS-related adaptations of skeletal muscles to aerobic exercise

Cellular metabolic processes produce Reactive Oxygen and Nitrogen Species (ROS/RNS) in small amounts in the course of normal activities. In skeletal muscle ROS/RNS production is greatly enhanced by contractile activity (1). Aerobic exercise training is known to induce a number of relevant adaptations in skeletal muscle, including fiber-type and metabolic shift of fast-twitch/glycolytic fibers towards a more fatigue-resistant and oxidative phenotype (2,3). On the other hand, excess ROS/RNS production is potentially damaging (4). Aim of the present work was to evaluate which adaptations are induced by moderate aerobic training in two opposite types of muscle cells: Tibialis Anterior (fast-twitch/glycolytic) and Soleus (slow-twitch/oxidative), with special attention to ROS/RNS-induced or -regulated pathways. Moreover, we intended to examine whether moderate exercise training caused ROS/RNS-related damages and/or activated defensive responses. Experimentation was carried out on 12 young male Sprague-Dowley rats which were gradually trained to run on a treadmill 1hr/day, 3 times/week, 14 weeks and reached ~60% VO2max at the end of training. Unexpectedly, training-induced ROS/RNS signaling promoted cell proliferation in both types of muscle cells; the small consequent redox unbalance activated, rather than inhibited, calcium-handling molecules and channels. Moderate exercise training was not damaging, probably because anti-oxidant and cytoprotective mechanisms were induced, however some oxidative stress markers appeared. Relevant results are summarized in the diagram below. References: 1. McArdle A et al. Am. J Physiol Cell Physiol 2001; 280: C621-C627. 2. Fl\ufcck M, Hoppeler H.. Rev Physiol Biochem Pharmacol 2003; 146: 159-216. 3. Marini M, Veicsteinas A. European Journal Translational Myology - Myology Reviews 2010; 20: 113-128. 4. Sahlin K et al. J Appl Physiol 2010; 108: 780-787

Frataxin mRNA abundance and their isoforms in Friedriech&apos;s VAtaxia patients and in normal subjects; effect of tocotrienol supplementation

Most Friedriech's Ataxia patients are homozygous for large expansions of a GAA triplet repeat tract within the first intron of the human FRDA gene on chromosome 9. As a result, the synthesis of the mRNA coding for an ubiquitous protein - frataxin, is markedly reduced. Frataxin is mainly located in the mitochondria. Although its precise cellular role is not known, it is clear that several mitochondrial functions are affected in patient cells, including respiration, iron\u2013sulfur cluster assembly, iron homeostasis, and maintenance of the redox status. Mitochondrial dysfunction and oxidative damage are at the origin of the neurodegenerative tract of this disease. Three splicing isoforms are known for the frataxin gene. The major transcript (isoform 1) codes for a 210 aminoacid-protein, the other transcripts differ in their 3' terminus and are shorter (171 and 196 aminoacids, respectively). Apart from the initial discovery, the scientific literature reports very little about these splice variants. Taking advantage of the fact that frataxin is ubiquitous and may be studied in circulating mononuclear cells, we evaluated the relative amount of the three mRNA isoforms in 5 Friedriech's Ataxia patients and in 5 healthy subjects. Total amount of messenger mRNA coding for frataxin increased in both patients and controls following a two-month supplementation of tocotrienol (5 mg/kg body weight/die), however the increase was not the same for the three isoforms. The study, carried out mostly by RT-qPCR, was accompanied by the bioinformatic evaluation of the characteristics of the minor protein isoforms, in the attempt to understand their possible roles