Assessing Leg Blood Flow and Cardiac Output During Running Using Thermodilution.

Cardiac output (Q̇C) and leg blood flow (Q̇LEG) can be measured simultaneously with high accuracy using transpulmonary and femoral vein thermodilution with a single-bolus injection. The invasive measure has offered important insight into leg hemodynamics and blood flow distribution during exercise. Despite being the natural modality of exercise in humans, there has been no direct measure of Q̇LEG while running in humans. We sought to determine the feasibility of the thermodilution technique for measuring Q̇LEG and conductance during high-intensity running, in an exploratory case study. A trained runner (30 years male) completed two maximal incremental tests on a cycle ergometer and motorized treadmill. Q̇LEG and Q̇C were determined using the single-bolus thermodilution technique. Arterial and venous blood were sampled throughout exercise, with continuous monitoring of metabolism, intra-arterial and venous pressure, and temperature. The participant reached a greater peak oxygen uptake (V̇O2peak) during running relative to cycling (74 vs. 68 mL/kg/min) with comparable Q̇LEG (19.0 vs. 19.5 L/min) and Q̇C (27.4 vs. 26.2 L/min). Leg vascular conductance was greater during high-intensity running relative to cycling (82 vs. 70 mL/min/mmHg @ ~80% V̇O2peak). The "beat phenomenon" was apparent in femoral flow while running, producing large gradients in conductance (62-90 mL/min/mmHg @ 70% V̇O2peak). In summary, we present the first direct measure of Q̇LEG and conductance in a running human. Our findings corroborate several assumptions about Q̇LEG during running compared with cycling. Importantly, we demonstrate that using thermodilution in running exercise can be completed effectively and safely.

Cross-education effects of unilateral accentuated eccentric isoinertial resistance training on lean mass and function.

PURPOSE: We investigated the effects of three different unilateral isoinertial resistance training protocols with eccentric overload on changes in lean mass and muscle function of trained (TL) and contralateral non-trained (NTL) legs. METHODS: Physically active university students were randomly assigned to one of three training groups or a control group (n = 10/group). Participants in the training groups performed dominant leg isoinertial squat training twice a week for 6 weeks (4 sets of 7 repetitions) using either an electric-motor device with an eccentric phase velocity of 100% (EM100) or 150% (EM150) of concentric phase velocity or a conventional flywheel device (FW) with the same relative inertial load. Changes in thigh lean mass, unilateral leg-press one-repetition maximum (1-RM), muscle power at 40-80% 1-RM, and unilateral vertical jump height before and after training were compared between the groups and between TL and NTL. RESULTS: No changes in any variable were found for the control group. In TL, all training groups showed similar increases (p < 0.05) in 1-RM strength (22.4-30.2%), lean tissue mass (2.5-5.8%), muscle power (8.8-21.7%), and vertical jump height (9.1-32.9%). In NTL, 1-RM strength increased 22.0-27.8% without significant differences between groups; however, increases in lean mass (p < 0.001) were observed for EM150 (3.5%) and FW (3.8%) only. Unilateral vertical jump height (6.0-32.9%) and muscle power (6.8-17.5%) also increased in NTL without significant differences between training groups. CONCLUSION: The three eccentric-overload resistance training modalities produced similar neuromuscular changes in both the trained and non-trained legs, suggesting that strong cross-education effects were induced by the eccentric-overload training.

Coevolutionary Couplings Unravel PAM-Proximal Constraints of CRISPR-SpCas9.

The clustered regularly interspaced short palindromic repeats (CRISPR) system, an immune system analog found in prokaryotes, allows a single-guide RNA to direct a CRISPR-associated protein (Cas) with combined helicase and nuclease activity to DNA. The presence of a specific protospacer adjacent motif (PAM) next to the DNA target site plays a crucial role in determining both efficacy and specificity of gene editing. Herein, we introduce a coevolutionary framework to computationally unveil nonobvious molecular interactions in CRISPR systems and experimentally probe their functional role. Specifically, we use direct coupling analysis, a statistical inference framework used to infer direct coevolutionary couplings, in the context of protein/nucleic acid interactions. Applied to Streptococcus pyogenes Cas9, a Hamiltonian metric obtained from coevolutionary relationships reveals, to our knowledge, novel PAM-proximal nucleotide preferences at the seventh position of S. pyogenes Cas9 PAM (5'-NGRNNNT-3'), which was experimentally confirmed by in vitro and functional assays in human cells. We show that coevolved and conserved interactions point to specific clues toward rationally engineering new generations of Cas9 systems and may eventually help decipher the diversity of this family of proteins.

Impact of functional determinants on 5.5-year mortality in Amazon riparian elderly.

Objective To ascertain whether modifiable physical performance-based measurements predicted 5.5-year mortality in a riparian elderly cohort in the Amazon rainforest region. Methods A longitudinal study evaluating the impact of functional determinants on 5.5-year mortality in a riparian elderly cohort from Maués City in the state of Amazonas, Brazil, was performed. The study was a follow-up of a previous observational investigation that evaluated various fitness tests in 630 Amazonian riparian elderly (291 males and 339 females) aged 72.3 ± 8.0 (60-99) years old. The cohort was selected for its adverse environmental conditions, which increased the risk of falls yet required maintenance of good physical condition for carrying out relatively rigorous daily activities, and restricted access to specialized health services. Official death records were obtained from the Maués Municipal Health Department. Results A total of 80 study participants (12.7%) died over the 5.5-year study period. Kaplan-Meier regression analysis showed significant association between Timed Up and Go (TUG) test scores ≥ 14 seconds and mortality risk, independent of sex, age, and other health variables. Conclusions The study results suggest that the TUG test can be used as an indicator for initiating therapeutic and preventive actions, including conducting exercises or physical activities adapted to the health and functional conditions of the elderly, by identifying elderly people with a higher relative risk of mortality.

Muscle damage responses and adaptations to eccentric-overload resistance exercise in men and women.

PURPOSE: This study assessed markers of muscle damage and training adaptations to eccentric-overload flywheel resistance exercise (RE) in men and women. METHODS: Dynamic strength (1 RM), jump performance, maximal power at different percentages of 1 RM, and muscle mass in three different portions of the thigh were assessed in 16 men and 16 women before and after 6 weeks (15 sessions) of flywheel supine squat RE training. Plasma creatine kinase (CK) and lactate dehydrogenase (LDH) concentrations were measured before, 24, 48 and 72 h after the first and the last training session. RESULTS: After training, increases in 1 RM were somewhat greater (interaction P < 0.001) in men (25 %) than in women (20 %). Squat and drop jump height and power performance at 50, 60, 70 and 80 % of 1 RM increased after training in both sexes (P < 0.05). Power improvement at 80 % of 1 RM was greater (interaction P < 0.02) in men than women. Muscle mass increased ~5 % in both groups (P < 0.05). CK increased in men after the first training session (P < 0.001), whereas the response in women was unaltered. In both sexes, LDH concentration was greater after the first training session compared with basal values (P < 0.05). After the last session, CK and LDH remained at baseline in both groups. CONCLUSIONS: These results suggest that although improvements in maximal strength and power at high loads may be slightly greater for men, eccentric-overload RE training induces comparable and favorable gains in strength, power, and muscle mass in both men and women. Equally important, it appears muscle damage does not interfere with the adaptations triggered by this training paradigm.

TLR4-mediated blunting of inflammatory responses to eccentric exercise in young women.

This study assessed the inflammatory response mediated by the toll-like receptor 4 (TLR4) signaling pathway after acute eccentric exercise before and after an eccentric training program in women. Twenty women performed two acute eccentric bouts using a squat machine over a ~9 week interval. The training group (TG) carried out an eccentric training program during 6 weeks, while the control group (CG) did not follow any training. Protein content of markers involved in the TLR4-mediated activation of several nuclear transcription factors, such as nuclear factor κB (NF-κB), and interferon regulatory transcription factor 3 (IRF3), was analyzed. The inflammatory response after the first acute bout was similar between TG and CG, showing an upregulation of all the markers analyzed, with the exception of IRF3. After the second bout, the upregulation of TLR4 signaling pathway was blunted in TG, but not in CG, through both the myeloid differentiation factor 88- and toll/interleukin-1 receptor domain containing adapter inducing interferon-ß-dependent pathways. These results highlight the role of the TLR4 in controlling the exercise-induced inflammatory response in young women. More importantly, these data suggest eccentric training may help to prevent TLR4 activation principally through NF-κB, and perhaps IRF3, downstream signaling in this population.

The Fluorescent Cell Line SW620-GFP Is a Valuable Model to Monitor Magnetic Hyperthermia.

In this work, the cell line SW620-GFP has been used in a complete magnetic hyperthermia assay, from the preparation of the ferrofluid with folate-coated iron oxide nanoparticles to in vivo experiments. The physical and chemical characterization of the nanoparticles evidenced their superparamagnetic behaviour, an average diameter of 12 ± 4 nm, a 2 nm coat thickness, and a high-power loss density. The main innovation of the work is the exclusive capability of viable SW620-GFP cells to emit fluorescence, enabling fast analysis of both, cell viability in vitro with an epifluorescence microscope and tumour size and shape in vivo in a non-invasive manner using the iBox technology. Moreover, with this imaging technique, it was possible to demonstrate the successful tumour size reduction in mice applying magnetic hyperthermia three times a week over 3 weeks.

Effects of submaximal and supramaximal accentuated eccentric loading on mass and function.

Introduction: Eccentric-overload (EO) resistance training emerges as an alternative to more optimally prescribe intensity relative to the force generation capabilities of the eccentric muscle contraction. Given the difficulties to individually prescribe absolute eccentric loads relative to each person's eccentric ability, setting the load relative to the concentric one-repetition maximum (1-RM) is the most used EO training approach. Therefore, we investigated the effects of submaximal and supramaximal (i.e., eccentric loads above 100% of 1-RM) accentuated eccentric training on changes in lean mass, anabolic hormonal responses and muscle function. Methods: Physically active university students (n = 27) were randomly assigned to two training groups. Participants in the training groups performed dominant leg isotonic training twice a week for 10 weeks (four sets of eight repetitions). Isotonic resistance was generated by an electric-motor device at two different percentages of 1-RM for the eccentric phase; 90% submaximal load, SUB group) and 120% (supramaximal load, SUPRA group). Concentric load was the same for both groups (30% of 1-RM). Changes in total thigh lean mass (TTLM), anabolic hormonal responses (growth hormone, IGF-1, IL-6, and total testosterone), unilateral leg-press 1-RM, maximal voluntary isometric contractions (MVIC), local muscle endurance (XRM), muscle power at 40 (PP40), 60 (PP60) and 80% (PP80) of the 1-RM, and unilateral vertical jump height before and after training were compared between groups. Results: After training, both SUB and SUPRA groups showed similar increases (p < 0.05) in MVIC (19.2% and 19.6%), XRM (53.8% and 23.8%), PP40 (16.2% and 15.7%), TTLM (2.5% and 4.2%), IGF-1 (10.0% and 14.1%) and IL-6 (58.6% and 28.6%). However, increases in 1-RM strength (16.3%) and unilateral vertical jump height (10.0%-13.4%) were observed for SUPRA only. Indeed, SUPRA was shown to be more favorable than SUB training for increasing 1-RM [ES = 0.77 (1.49-0.05)]. Unilateral muscle power at medium and high intensity (10.2% and 10.5%) also increased in SUB but without significant differences between groups. Discussion: Similar functional and structural effects were demonstrated after 10 weeks EO training with submaximal and supramaximal eccentric loads. Although supramaximal loading might be superior for increasing 1-RM, the use of this approach does not appear to be necessary in healthy, active individuals.

Effects of an exercise programme on self-esteem, self-concept and quality of life in women with fibromyalgia: a randomized controlled trial.

This study was aimed to investigate the effects of an exercise trial on self-esteem, self-concept and quality of life in patients with fibromyalgia and to evaluate whether improvements in psychological distress were related to changes in physical functioning. Twenty-eight women with a primary diagnosis of fibromyalgia were randomized to a usual care control group or to a 12-week supervised training programme consisting of 3 weekly sessions of aerobic, strengthening and flexibility exercises. Outcomes were physical functioning (Fibromyalgia Impact Questionnaire (FIQ), lower-body strength and flexibility) and psychological functioning (SF-36, Rosenberg self-esteem scale and Erdmann self-concept scale). Outcomes were measured at study entry and at the end of the intervention. Compared to the control group, statistically significant improvements in self-esteem, self-concept, FIQ, physical functioning, role physical, bodily pain, vitality, role emotional, social functioning, mental health, isometric strength, muscular endurance and flexibility were evident in the exercise group at the end of treatment. Self-esteem and self-concept scores were correlated positively with role emotional, mental health and the mental component summary of SF-36 and were negatively correlated to FIQ scores. No significant correlation existed between self-esteem or self-concept and isometric strength, muscular endurance or flexibility. Our results highlight the need for a broader array of physical and mental outcomes and the importance of examining patient's perceptions in future research therapies.

Resistance Training Modulates Reticulum Endoplasmic Stress, Independent of Oxidative and Inflammatory Responses, in Elderly People.

Aging is related to changes in the redox status, low-grade inflammation, and decreased endoplasmic reticulum unfolded protein response (UPR). Exercise has been shown to regulate the inflammatory response, balance redox homeostasis, and ameliorate the UPR. This work aimed to investigate the effects of resistance training on changes in the UPR, oxidative status, and inflammatory responses in peripheral blood mononuclear cells of elderly subjects. Thirty elderly subjects volunteered to participate in an 8-week resistance training program, and 11 youth subjects were included for basal assessments. Klotho, heat shock protein 60 (HSP60), oxidative marker expression (catalase, glutathione, lipid peroxidation, nuclear factor erythroid 2-related factor 2, protein carbonyls, reactive oxygen species, and superoxide dismutase 1 and 2), the IRE1 arm of UPR, and TLR4/TRAF6/pIRAK1 pathway activation were evaluated before and following training. No changes in the HSP60 and Klotho protein content, oxidative status markers, and TLR4/TRAF6/pIRAK1 pathway activation were found with exercise. However, an attenuation of the reduced pIRE1/IRE1 ratio was observed following training. Systems biology analysis showed that a low number of proteins (RPS27A, SYVN1, HSPA5, and XBP1) are associated with IRE1, where XBP1 and RPS27A are essential nodes according to the centrality analysis. Additionally, a gene ontology analysis confirms that endoplasmic reticulum stress is a key mechanism modulated by IRE1. These findings might partially support the modulatory effect of resistance training on the endoplasmic reticulum in the elderly.

A Ferrofluid with High Specific Absorption Rate Prepared in a Single Step Using a Biopolymer.

An exhaustive characterization of the physicochemical properties of gum arabic (GA)-coated Fe3O4 magnetic nanoparticles was conducted in this work. These nanoparticles were obtained via the in-situ coprecipitation method (a fast single-step method) in two GA:Fe ratios, 10:1 and 20:1, respectively. Several experimental techniques were applied in the characterization process, all of them described below. Using Transmission Electron Microcopy images, they were shown to have spherical-like morphology with 11 nm diameter. The Fourier Transform Infrared spectra confirmed the attachment of the GA on the surface of the magnetic nanoparticles (MNPs), providing good colloidal stability from pH 7 to 8. The thickness of the coatings (1.7 nm and 1.1 nm) was determined using thermogravimetric measurements. A high specific absorption rate and superparamagnetic properties were determined using alternant and static magnetic fields, respectively. The GA-coated MNPs were non-cytotoxic, according to tests on HT-29 human intestine cells. Additionally, HT-29 cells were exposed to magnetic fluid hyperthermia at 530 kHz, and the induction of cell death by the magnetic field, due to the heating of GA-coated MNP, was observed.

Resistance Training Diminishes the Expression of Exosome CD63 Protein without Modification of Plasma miR-146a-5p and cfDNA in the Elderly.

Aging-associated inflammation is characterized by senescent cell-mediated secretion of high levels of inflammatory mediators, such as microRNA (miR)-146a. Moreover, a rise of circulating cell-free DNA (cfDNA) is also related to systemic inflammation and frailty in the elderly. Exosome-mediated cell-to-cell communication is fundamental in cellular senescence and aging. The plasma changes in exercise-promoted miR-146a-5p, cfDNA, and exosome release could be the key to facilitate intercellular communication and systemic adaptations to exercise in aging. Thirty-eight elderly subjects (28 trained and 10 controls) volunteered in an 8-week resistance training protocol. The levels of plasma miR-146a-5p, cfDNA, and exosome markers (CD9, CD14, CD63, CD81, Flotillin [Flot]-1, and VDAC1) were measured prior to and following training. Results showed no changes in plasma miR-146a-5p and cfDNA levels with training. The levels of exosome markers (Flot-1, CD9, and CD81) as well as exosome-carried proteins (CD14 and VDAC1) remained unchanged, whereas an attenuated CD63 response was found in the trained group compared to the controls. These findings might partially support the anti-inflammatory effect of resistance training in the elderly as evidenced by the diminishment of exosome CD63 protein expression, without modification of plasma miR-146a-5p and cfDNA.

The comparative measurement of body segment parameters using dual energy X-ray absorptiometry between sexes.

BACKGROUND: The study aimed to determine the proportion of the body segments in relation to the total body mass in healthy people, as well as analyze the composition of each segment and compare these results between sexes. METHODS: A total of 60 young adults (30 men and 30 women) were subjected to a full-body scan by dual energy X-rays absorptiometry (DXA) under standardized conditions. The regions of interest (ROI) were determined by a single trained evaluator. The body was divided into 16 segments to obtain values of total mass, lean mass (LM), fat mass, bone mineral content (BMC), lean mass percentage (%LM) and fat mass percentage (%FM) of each body segment represented by the 16 ROI. RESULTS: Men presented higher absolute mass in the upper limbs (Δ=32.87%; P<0.05). The proportion of the lower limbs (Δ=6.83%; P<0.05) and trunk (Δ=5.07%; P<0.05) of men is higher than women. In addition, males have more LM in the upper limbs (Δ=42.19%; P<0.05) and trunk (Δ=26.46%; P<0.001), and more BMC in the trunk (Δ=18.78%; P<0.05) and forearms (Δ=32.21%; P<0.05). They also present higher %LM (Δ=6.48%; P<0.001) and lower %FM (Δ=54.43%; P<0.001) than women in the forearms. CONCLUSIONS: The different body segments represent a different percentage of the total body mass in men than in women, as well as men present more LM and BMC in the trunk and upper limbs.

Adenosine kinase deficiency presenting with tortuous cervical arteries: A risk factor for recurrent stroke.

Adenosine kinase (ADK) deficiency is a very rare inborn error of methionine and adenosine metabolism. It is characterized by developmental delay, hypotonia, epilepsy, facial dysmorphism, failure to thrive, transient liver dysfunction with cholestasis, recurrent hypoglycemia, and cardiac defects. Only 26 cases (16 families) of ADK deficiency have been published since its identification in 2011. Vascular abnormalities in cervical arteries and cerebral stroke have never been reported in this condition. Here, we describe two patients with ADK deficiency and vascular tortuosity leading to stroke in one of them. ADK deficiency is a rare inborn error of methionine metabolism with a complex phenotype that might be associated with cerebrovascular abnormalities and stroke.

Comparison of technical and physiological characteristics of prepubescent soccer players of different ages.

Although soccer is one of the most widely played sports around the world, studies about young players and the success factors in soccer are still scarce. Therefore, the purpose of this study was to offer some insight into the factors contributing to success in this sport and to describe how physiological and technical performance evolves in young soccer players. Soccer technical skills during match play, maximum voluntary isometric contraction and power of lower limbs, jumping ability and endurance parameters were assessed in 30 prepubescent male soccer players with the same experience in soccer training. Subjects were divided into 2 groups of 15 children, a younger group (YG), aged 9.4 +/- 0.3 years, and an older group (OG), aged 11.8 +/- 0.2 years. Correlations between technical and physiological parameters were also described. Significant difference was set at p < 0.05. Differences between YG and OG appeared in physiological performance, mainly in VO(2)peak expressed in absolute values, VO(2) at different speeds, perceived exertion in treadmill test, jump performance, strength, and peak power of lower limbs. Among the technical skills measured, significant differences were found only in heading. The differences found between groups showed that most physical capacities that were measured here have an important increase during the first stages of puberty, pointing out that a specific training at these ages is necessary to get an appropriate basis for future performance. Besides, over 30% of the technical performance measured in this study can be explained with the physiological parameters. The data shown in this paper help to determine the most important capacities in youth soccer, which can facilitate the development of more appropriate selection models and trainings.

Exercise training modulates the gut microbiota profile and impairs inflammatory signaling pathways in obese children.

Childhood obesity has reached epidemic levels and is a serious health concern associated with metabolic syndrome, nonalcoholic fatty liver disease, and gut microbiota alterations. Physical exercise is known to counteract obesity progression and modulate the gut microbiota composition. This study aims to determine the effect of a 12-week strength and endurance combined training program on gut microbiota and inflammation in obese pediatric patients. Thirty-nine obese children were assigned randomly to the control or training group. Anthropometric and biochemical parameters, muscular strength, and inflammatory signaling pathways in mononuclear cells were evaluated. Bacterial composition and functionality were determined by massive sequencing and metabolomic analysis. Exercise reduced plasma glucose levels and increased dynamic strength in the upper and lower extremities compared with the obese control group. Metagenomic analysis revealed a bacterial composition associated with obesity, showing changes at the phylum, class, and genus levels. Exercise counteracted this profile, significantly reducing the Proteobacteria phylum and Gammaproteobacteria class. Moreover, physical activity tended to increase some genera, such as Blautia, Dialister, and Roseburia, leading to a microbiota profile similar to that of healthy children. Metabolomic analysis revealed changes in short-chain fatty acids, branched-chain amino acids, and several sugars in response to exercise, in correlation with a specific microbiota profile. Finally, the training protocol significantly inhibited the activation of the obesity-associated NLRP3 signaling pathway. Our data suggest the existence of an obesity-related deleterious microbiota profile that is positively modified by physical activity intervention. Exercise training could be considered an efficient nonpharmacological therapy, reducing inflammatory signaling pathways induced by obesity in children via microbiota modulation.

Comparison of the musculoskeletal effects of different iso-inertial resistance training modalities: Flywheel vs. electric-motor.

This study aimed to analyse whether increasing the eccentric overload (EO) during resistance training, in terms of range of motion and/or velocity using an electric-motor device, would induce different muscle adaptations than conventional flywheel-EO resistance training. Forty physically active university students (21.7 ± 3.4 years) were randomly placed into one of the three training groups (EX1, EX2, FW) and a control group without training (n = 10 per group). Participants in the training groups completed 12 sessions (4 sets of 7 repetitions) of iso-inertial single-leg squat training over 6 weeks for the dominant leg. Resistance was generated either by an electric-motor device at two different velocities for the eccentric phase; 100% (EX1) or 150% (EX2) of concentric speed, or by a conventional flywheel device (FW). Thigh lean tissue mass, unilateral leg press one-repetition maximum (1-RM), unilateral muscle power at different percentages of the 1-RM and bilateral/unilateral vertical jump were assessed before and after the 6-week training. There were significant (p < 0.05-0.001) main effects of time in the 3 training groups, indicating increased thigh lean tissue mass (2.5-5.8%), 1-RM load (22.4-30.2%), vertical jump performance (9.1-32.9%) and muscle power (8.8-21.7%), without differences across experimental groups. Participants in the control group did not improve any of the variables measured. In addition, EX2 showed greater gains in eccentric average peak power during training than EX1 and FW (p < 0.001). Despite the different EO offered, 6 weeks of resistance training using flywheel or electric-motor devices induced similar significant gains in muscle mass, strength, muscle power and vertical jump.

Effects of a resistance-training programme on endoplasmic reticulum unfolded protein response and mitochondrial functions in PBMCs from elderly subjects.

Aging has been related with a decline in the ability to handle protein folding, which leads to endoplasmic reticulum stress and alterations in unfolded protein response (UPR). Importantly, physical activity could activate the UPR and attenuate or prevent age-induced endoplasmic reticulum (ER) dysfunction. The current study evaluated the effects of a resistance exercise on UPR and mitochondrial functions in peripheral blood mononuclear cells (PBMCs) from elderly subjects. Thirty healthy women and men (age, 72.8, sx- = 2.2 years) were randomized to a training group, which performed an 8-week resistance training programme, or a control group, which followed their daily routines. The phosphorylation of PERK and IRE1, as well as ATF4, and XBP1 protein expression, significantly increased following the training, while expression of BiP, AFT6 and CHOP remain without changes. Additionally, the intervention also induced an increase in PGC-1α and Mfn1 protein levels, while no changes were found in Drp1 expression. Finally, the resistance protocol was not able to activate PINK1/Parkin and Bnip3/Nix pathways. The results obtained seem to indicate that 8-week resistance exercise activates the UPR, stimulates mitochondrial biogenesis, maintains mitochondrial dynamics and prevents mitophagy activation by unfolded proteins in PBMCs from elderly subjects.

Eccentric training impairs NF-kappaB activation and over-expression of inflammation-related genes induced by acute eccentric exercise in the elderly.

The present study was aimed to investigate in elderly humans changes in NF-kappaB activation and in the expression of the inflammation-related genes inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and interleukin-6 (IL-6) induced in peripheral blood mononuclear cells (PBMC) by acute eccentric exercise and by submaximal eccentric training. Eleven subjects, aged 66-75 years, carried out 2 bouts of eccentric exercise separated by 8 weeks of training. Following the first bout, NF-kappaB activation, and protein level of p50/p65 subunits, phospho-IkappaBalpha and phospho-IKKalpha increased, while IkappaBalpha protein level was significantly reduced. This was accompanied by a significant increase in iNOS, COX-2 and IL-6 mRNA protein level and protein content. Changes were significantly attenuated following the second exercise bout. In conclusion, acute eccentric exercise increases NF-kappaB activation and the expression of several inflammation-related genes in PBMC from elderly individuals. Regular eccentric training might be an effective method of preventing undesirable inflammatory responses induced by eccentric exercise.