Evidence of a Redox-Dependent Regulation of Immune Responses to Exercise-Induced Inflammation

We used thiol-based antioxidant supplementation (n-acetylcysteine, NAC) to determine whether immune mobilisation following skeletal muscle microtrauma induced by exercise is redox-sensitive in healthy humans. According to a two-trial, double-blind, crossover, repeated measures design, 10 young men received either placebo or NAC (20 mg/kg/day) immediately after a muscle-damaging exercise protocol (300 eccentric contractions) and for eight consecutive days. Blood sampling and performance assessments were performed before exercise, after exercise, and daily throughout recovery. NAC reduced the decline of reduced glutathione in erythrocytes and the increase of plasma protein carbonyls, serum TAC and erythrocyte oxidized glutathione, and TBARS and catalase activity during recovery thereby altering postexercise redox status. The rise of muscle damage and inflammatory markers (muscle strength, creatine kinase activity, CRP, proinflammatory cytokines, and adhesion molecules) was less pronounced in NAC during the first phase of recovery. The rise of leukocyte and neutrophil count was decreased by NAC after exercise. Results on immune cell subpopulations obtained by flow cytometry indicated that NAC ingestion reduced the exercise-induced rise of total macrophages, HLA+ macrophages, and 11B+ macrophages and abolished the exercise-induced upregulation of B lymphocytes. Natural killer cells declined only in PLA immediately after exercise. These results indicate that thiol-based antioxidant supplementation blunts immune cell mobilisation in response to exercise-induced inflammation suggesting that leukocyte mobilization may be under redox-dependent regulation

Is There a Role of Inferior Frontal Cortex in Motor Timing? A Study of Paced Finger Tapping in Patients with Non-Fluent Aphasia

The aim of the present study was to investigate the deficits in timing reproduction in individuals with non-fluent aphasia after a left hemisphere lesion including the inferior frontal gyrus, in which Broca’s region is traditionally localised. Eighteen stroke patients with non-fluent aphasia and twenty-two healthy controls were recruited. We used a finger-tapping Test, which consisted of the synchronisation and the continuation phase with three fixed intervals (450 ms, 650 ms and 850 ms). Participants firstly had to tap simultaneously with the device’s auditory stimuli (clips) (synchronisation phase) and then continue their tapping in the same pace when the stimuli were absent (continuation phase). Patients with aphasia demonstrated less accuracy and greater variability during reproduction in both phases, compared to healthy participants. More specifically, in the continuation phase, individuals with aphasia reproduced longer intervals than the targets, whereas healthy participants displayed accelerated responses. Moreover, patients’ timing variability was greater in the absence of the auditory stimuli. This could possibly be attributed to deficient mental representation of intervals and not experiencing motor difficulties (due to left hemisphere stroke), as the two groups did not differ in tapping reproduction with either hand. Given that previous findings suggest a potential link between the IFG, timing and working memory, we argue that patients’ extra-linguistic cognitive impairments should be accounted for, as possible contributing factors to timing disturbances

Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise

Background: The major thiol-disulfide couple of reduced glutathione (GSH) and oxidized glutathione is a key regulator of major transcriptional pathways regulating aseptic inflammation and recovery of skeletal muscle after aseptic injury. Antioxidant supplementation may hamper exercise-induced cellular adaptations. Objective: The objective was to examine how thiol-based antioxidant supplementation affects skeletal muscle's performance and redox-sensitive signaling during the inflammatory and repair phases associated with exercise-induced microtrauma. Design: In a double-blind, crossover design, 10 men received placebo or N-acetylcysteine (NAC; 20 mg . kg(-1) . d(-1)) after muscle-damaging exercise (300 eccentric contractions). In each trial, muscle performance was measured at baseline, after exercise, 2 h after exercise, and daily for 8 consecutive days. Muscle biopsy samples from vastus lateralis and blood samples were collected before exercise and 2 h, 2 d, and 8 d after exercise. Results: NAC attenuated the elevation of inflammatory markers of muscle damage (creatine kinase activity, C-reactive protein, proinflammatory cytokines), nuclear factor kappa B phosphorylation, and the decrease in strength during the first 2 d of recovery. NAC also blunted the increase in phosphorylation of protein kinase B, mammalian target of rapamycin, p70 ribosomal S6 kinase, ribosomal protein S6, and mitogen activated protein kinase p38 at 2 and 8 d after exercise. NAC also abolished the increase in myogenic determination factor and reduced tumor necrosis factor-alpha 8 d after exercise. Performance was completely recovered only in the placebo group. Conclusion: Although thiol-based antioxidant supplementation enhances GSH availability in skeletal muscle, it disrupts the skeletal muscle inflammatory response and repair capability, potentially because of a blunted activation of redox-sensitive signaling pathways

No difference in osteoarthritis after surgical and non-surgical treatment of ACL-injured knees after 10 years

Purpose: Aim of this study was to record and compare the functional and activity level as well as the manifestations of osteoarthritis after isolated ACL ruptures between patients with conservative treatment and ACL reconstruction with hamstrings tendon graft.Methods: Thirty-two patients diagnosed with ACL rupture were recorded. Clinical examination included the Tegner and Lysholm activity scale, the International Knee Documentation Committee Subjective Form and KT-1000 arthrometer. Narrowing of the medial and lateral joint spaces was assessed using the IKDC knee examination score. Results: Median follow-up was 10.3 years (range 10–11). Fifteen patients were conservatively treated (median age 33 years, range 25–39). Seventeen patients were operated (median age 31 years, range 20–36). There was significant difference between the mean values of IKDC scores in favour of the ACL-reconstruction group of patients, 86.8 (SD 6.5) versus 77.5 (SD 13.8), respectively (p = 0.04). The mean value of anteroposterior tibial translation was 1.5 mm (SD 0.2) for ACL-reconstruction group of patients, while the corresponding mean value for ACL-conservative group was 4.5 mm (SD 0.5), p = 0.03. Four patients in ACL-reconstruction group had radiological findings of grade C or D according to IKDC form. In ACL-conservative group, five patients presented similar signs (n.s.). Conclusions: ACL reconstruction using hamstrings autograft resulted in better functional outcome and laxity measurements than ACL-conservative management. However, the incidence of radiological osteoarthritis was similar between the two groups and independent on the pre-operative grade of laxity and functional status of the patients. Equally, bone bruises were not found as a risk factor for the development of osteoarthritis after ACL rupture. Level of evidence: Prospective randomized study, Level II. © 2015 European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA