Exhaustive exercise modifies different gene expression profiles and pathways in LPS-stimulated and un-stimulated whole blood cultures.

Exhaustive exercise can interfere with immunity, causing transient immunosuppression and infections/inflammation in athletes. We used microarray technology to analyze the gene expression profiles of whole blood in short time (1h) LPS-stimulated and un-stimulated cultures drawn before, 30min after, 3h after and 24h after a half-marathon run. Four male and 4 female athletes participated. Exercise induced differential expression of genes known to be involved in innate immunity/inflammatory response, metabolic response, DNA methylation, apoptosis and regulation of brain function. Several genes with prominent anti-inflammatory function were up-regulated in un-stimulated cultures, including ARG-1, SOCS3, DUSP-1, ORMs, IRAK3, and GJB6. Some of these genes were also strongly up-regulated in LPS-stimulated cultures (ARG-1, ORM2, and GJB6). Some genes were strongly up-regulated through exercise in LPS-stimulated cultures, but not in un-stimulated cultures (TNIP3, PLAU, and HIVEP1). There was also a row of genes, which were strongly down-regulated by exercise in LPS-stimulated cultures, notably IFN-ß1 and CXCL10. Exercise also significantly changed the expression of genes (OLIG2, TMEM106B) which are known to be related to brain function and expression of which has never been documented in peripheral blood. In summary, exhaustive exercise, in addition to modifying gene expression in un-stimulated cells, could also interfere with the early gene expression response to endotoxin. There was an anti-inflammatory bias of gene regulation by exercise, including genes involved in the negative regulation of TLRs signalling. The results of the present study demonstrate that some potentially important effects of exercise can only be detected in relation to pathogen stimulation.

Changes in spontaneous and LPS-induced ex vivo cytokine production and mRNA expression in male and female athletes following prolonged exhaustive exercise.

PURPOSE: The capacity of whole blood cultures to produce cytokines in response to endotoxin (LPS) was studied in athletes before, 30 min after, 3 h after and 24 h after a half-marathon run. METHODS: Eight well trained men and 8 well trained women (6 of them in the late luteal phase of their cycle) participated. EDTA blood was incubated with or without LPS for 1 h, and cytokine concentration and gene expression were determined. To quantify LPS-dependent release on a per monocyte basis (LDR), the mean values of the difference (delta) between cytokine concentration in stimulated and unstimulated cultures, normalized to monocyte numbers, were calculated. RESULTS: LDR of TNF-alpha was significantly reduced by exercise with identical kinetic in men and women. TNF-alpha mRNA expression was slightly down-regulated following exercise (P < 0.05), but significantly so only in women. LDR of IL-6 was also reduced, but with a faster kinetic in women than in men. Similarly, 30 min post-exercise; LDR and spontaneous release of IL-1ra were significantly less in women than men. Concomitantly, IL-Ira mRNA was significantly elevated in unstimulated and in stimulated cultures in men only. IL-10 and IL-10 mRNA were significantly induced 30 min following exercise in absence of any detectable LDR. Women showed significantly lower levels than men. LDR and spontaneous release of IL-8 was enhanced in men and TGF-beta1 in women. A significant up-regulation was seen in unstimulated IL-8 mRNA for women and LPS-stimulated IL-8 mRNA expression for men following exercise. CONCLUSION: Altogether, LPS-dependent ex vivo cytokine release was strongly influenced by exercise and these changes could only in part be attributed to changes in messenger RNA. Results for IL-1ra, IL-6 and IL-10 pointed to a less pronounced anti-inflammatory response in women as compared with men. Our results also indicate an early production of IL-10 by peripheral blood cells in response to exercise.

A simple new device to examine human stance: the totter-slab.

This article describes a new measuring device to investigate balancing strategies of human stance: the totter-slab, i.e., a standing plate suspended with steel cables to hooks on a steel frame. First, we analysed the physical properties of the device by recording free oscillations under different conditions [varying amplitude, mass and centre of mass (COM) height]. This allowed us to determine the eigenfrequency f and the damping coefficient D<1 Ns/m for each trial. The trials showed that the measured damped eigenfrequency of f is approximately 0.63 Hz is barely dependent on the mass loaded. The ratio D/M is approximately 0.015 1/s is a constant almost independent of the different conditions. Furthermore, we determined the stiffnesses of the suspending cables and their suspension points to check for potential energy storage capacity of the totter-slab. We found that the totter-slab is a useful, well-defined, reliable and developable measuring device for different non-rigid-ground stance conditions. In a second part of the investigation, we compared the frequency spectra of six subjects balancing on the totter-slab with their spectra while standing quietly on a force plate fixed to the ground. The totter-slab spectra showed two distinct, dominant peak regions at approximately 0.3 and 1.1 Hz. This finding enforces the double inverted pendulum to be an adequate model particularly for balancing on the totter-slab. Compared with the firm ground condition, these two peak regions were more pronounced when balancing on the totter-slab. However, there is a variety of frequencies in the region 0.2...1.5 Hz specific for an individual subject in both balancing conditions.

High-frequency oscillations as a consequence of neglected serial damping in Hill-type muscle models.

High-frequency vibrations e.g., induced by legs impacting with the ground during terrestrial locomotion can provoke damage within tendons even leading to ruptures. So far, macroscopic Hill-type muscle models do not account for the observed high-frequency damping at low-amplitudes. Therefore, former studies proposed that protective damping might be explained by modelling the contractile machinery of the muscles in more detail, i.e., taking the microscopic processes of the actin-myosin coupling into account. In contrast, this study formulates an alternative hypothesis: low but significant damping of the passive material in series to the contractile machinery--e.g., tendons, aponeuroses, titin--may well suffice to damp these hazardous vibrations. Thereto, we measured the contraction dynamics of a piglet muscle-tendon complex (MTC) in three contraction modes at varying loads and muscle-tendon lengths. We simulated all three respective load situations on a computer: a Hill-type muscle model including a contractile element (CE) and each an elastic element in parallel (PEE) and in series (SEE) to the CE pulled on a loading mass. By comparing the model to the measured output of the MTC, we extracted a consistent set of muscle parameters. We varied the model by introducing either linear damping in parallel or in series to the CE leading to accordant re-formulations of the contraction dynamics of the CE. The comparison of the three cases (no additional damping, parallel damping, serial damping) revealed that serial damping at a physiological magnitude suffices to explain damping of high-frequency vibrations of low amplitudes. The simulation demonstrates that any undamped serial structure within the MTC enforces SEE-load eigenoscillations. Consequently, damping must be spread all over the MTC, i.e., rather has to be de-localised than localised within just the active muscle material. Additionally, due to suppressed eigenoscillations Hill-type muscle models taking into account serial damping are numerically more efficient when used in macroscopic biomechanical neuro-musculo-skeletal models.

Muscle growth and fiber type composition in hind limb muscles during postnatal development in pigs.

Rapid postnatal development in pigs is reflected by differentiation in skeletal muscle. This process depends on muscle function and demands, but a comprehensive overview of individual developmental characteristics of quickly growing leg muscles in pigs is still missing. This study focused on the development of 10 hind limb muscles in pigs. To determine these changes in mass, fiber type patterns and fiber diameters were analyzed 0, 2, 4, 7, 14, 28, 42, 56 and 400 days after birth. Generally, the proportion of slow fibers increased from birth to 8 weeks. Thereafter, only minor changes in muscle fiber type composition were observed. The majority of the muscles contained less then 10% slow-twitch fibers at birth, increasing to between 12 (Musculus vastus lateralis) and 38% (M. gastrocnemius medialis) in adult pigs. By contrast, postural muscles already had 20-30% slow fibers at birth, and this contribution increased up to 65% in adults (i.e. M. vastus intermedius). From birth to the 2nd week, only in slow fibers could activity of oxidative enzymes be detected. A differentiation of fast-twitch fibers into subtypes with high (comparable to type IIA) and low oxidative metabolism (equivalent to type IIB) occurred between the 2nd and 4th week of life. The ratio between type II fibers with high and low oxidative enzyme activity did not change markedly through development in any muscle, although there was a trend towards an increasing proportion of type IIA fibers in the soleus. In the majority of the muscles investigated, the fast-twitch fibers with low oxidative metabolism (IIB) obtained the largest cross-sectional area. In contrast, at birth no remarkable differences in the diameter of fast and slow fibers were found. The rapid increase in muscle mass compared to body mass reflects the high performance in meat production of the cross pig investigated.