Moderate Exercise Modulates Inflammatory Responses and Improves Survival in a Murine Model of Acute Pneumonia.

OBJECTIVES: An association between physical inactivity and worse outcome during infectious disease has been reported. The effect of moderate exercise preconditioning on the immune response during an acute pneumonia in a murine model was evaluated. SETTING: Laboratory experiments. SUBJECTS: C57BL6/j male mice. INTERVENTIONS: Six-week-old C57BL/6J mice were divided in two groups: an exercise group and a control group. In the exercise group, a moderate, progressive, and standardized physical exercise was applied for 8 weeks. It consisted in a daily treadmill training lasting 60 minutes and with an intensity of 65% of the maximal theoretical oxygen uptake. Usual housing recommendation were applied in the control group during the same period. After 8 weeks, pneumonia was induced in both groups by intratracheal instillation of a fixed concentration of a Klebsiella pneumoniae (5 × 103 colony-forming unit) solution. MEASUREMENTS AND MAIN RESULTS: Mice preconditioned by physical exercise had a less sever onset of pneumonia as shown by a significant decrease of the Mouse Clinical Assessment Severity Score and had a significantly lower mortality compared with the control group (27% vs. 83%; p = 0.019). In the exercise group, we observed a significantly earlier but transient recruitment of inflammatory immune cells with a significant increase of neutrophils, CD4+ cells and interstitial macrophages counts compared with control group. Lung tumor necrosis factor-α, interleukin (IL)-1ß, IL-6, and IL-10 were significantly decreased at 48 hours after pneumonia induction in the exercise group compared with the control group. CONCLUSIONS: In our model, preconditioning by moderate physical exercise improves outcome by reducing the severity of acute pneumonia with an increased but transient activation of the innate immune response.

Long-term atorvastatin treatment decreases heart maximal oxygen consumption and its vulnerability to in vitro oxidative stress in Watanabe heritable hyperlipidemic rabbit.

Statins are currently used in prevention of cardiovascular diseases in high-risk populations, and could be considered in primary prevention. However, few studies are available on the long-term effects of low doses of statins, especially on mitochondrial function and reactive oxygen species (ROS) metabolism at cardiac level. This study aimed to determine potential effects of a long-term atorvastatin treatment, at low-dose concentration, on the myocardium mitochondrial respiration. Thirty-four Watanabe rabbits were treated or not with atorvastatin (2.5 mg·kg-1·day-1) from the age of 3 to 12 months. Every 3 months, proton leak, basal (V0), and maximal (Vmax) mitochondrial respiration on cardiac permeabilized fibers were measured. Additionally, the vulnerability to ROS, cardiac enzymatic antioxidant defenses, and oxidative damage (lipoperoxidation) were analyzed. Proton leak increased over the duration of the experiment (up to 60% from Vmax at 12 months). Moreover, the statin treatment induced a decrease of Vmax and a decrease of ROS susceptibility of cardiac mitochondria. However, the lipoperoxidation and the antioxidant defenses were not dependent on the presence of statin treatment, or on its duration. This is the first study showing a protective effect of long-term statins treatment against the ROS susceptibility in the cardiac muscle.

The hamstrings are more impacted than the quadriceps after severe ankle sprain.

Ankle sprains (AS) are common in the military population, with a prevalence 5 to 8 times higher than that for civilians. The aim of this study was to evaluate in patients with severe AS the impact of disuse on thigh muscle induced by unloading and immobilization due to care. This study focused on muscle trophicity and dynamometric strength. In this observational prospective study, assessments were repeated at 3 visits: close to injury, 15 and 30 days following the sprain. The injured limb was compared to the contralateral limb. A dynamometer assessment was used to monitor changes in strength and fatigue of the thigh muscles of both limbs. Isometric and isokinetic concentric evaluation of peak torque (PTiso and PTdyn), total work (Wt), and peak torque time integral (IPT) of thigh muscles. Full follow-up was obtained in 30 subjects. The injured limbs showed significant deficits in the mean (SD). The quadriceps PTiso and IPT deficits were -12.6% ± 1.9% (P < .0001) and -13.27% ± 1.8% (P < .0001), respectively. The quadriceps PTdyn showed a significant deficit since V2 (-12.2.5% ± 2.0). The quadriceps Wt presented a significant deficit of -4.2% ± 2.4 (P < .0007) at 1 month. The hamstring PTdyn deficit presented a mean loss of -16.5% ± 2.4% (P < .0001). The hamstring Wt deficit was -13.7% ± 2.3% (P < .001). The analysis of variance showed that the grade of the sprain had a significant effect on the quadriceps PTq deficit (P < .016) but not the type of discharge. Our study showed that disuse leads to a significant deficit in the strength of knee muscles within 1 month. It is noteworthy that the hamstrings are more affected than the quadriceps. The rehabilitation protocol to prevent the risk of iterative ankle injuries and secondary knee injuries should incorporate early training of both quadriceps and hamstrings.

Linear diattenuation imaging of biological tissues with near infrared Mueller scanning microscopy.

Among the multitude of optical polarization contrasts that can be observed in complex biological specimens, linear diattenuation (LD) imaging has received little attention. It is indeed challenging to image LD with basic polarizing microscopes because it is often relatively small in comparison with linear retardance (LR). In addition, interpretation of LD images is not straightforward when experiments are conducted in the visible range because LD can be produced by both dichroism and anisotropic scattering. Mueller polarimetry is a powerful implementation of polarization sensing able to differentiate and measure the anisotropies of specimens. In this article, near infrared transmission Mueller scanning microscopy is used to image LD in thin biological specimen sections made of various proteins with unprecedented resolution and sensitivity. The near infrared spectral range makes it possible to lower the contribution of dichroism to the total linear diattenuation in order to highlight anisotropic scattering. Pixel-by-pixel comparison of LD images with LR and multiphoton images demonstrates that LD is produced by under-resolved structures that are not revealed by other means, notably within the sarcomere of skeletal muscles. LD microscopy appears as a powerful tool to provide new insights into the macro-molecular organization of biological specimens at the sub-microscopic scale without labelling.

TGF-ß Pathway Inhibition Protects the Diaphragm From Sepsis-Induced Wasting and Weakness in Rat.

Sepsis is a frequent complication in patients in intensive care units (ICU). Diaphragm weakness, one of the most common symptoms observed, can lead to weaning problems during mechanical ventilation. Over the last couple of years, members of the transforming growth factor (TGF) ß family, such as myostatin, activin A, and TGF-ß1, have been reported to strongly trigger the activation of protein breakdown involved in muscle wasting. The aim of this study was to investigate the effect of TGF-ß inhibitor LY364947 on the diaphragm during chronic sepsis.Rats were separated into four groups exposed to different experimental conditions: Control group, Septic group, Septic group with inhibitor from day 0 (LY D0), and Septic group with inhibitor from day 1 (LY D1). Sepsis was induced in rats by cecal ligation and puncture, and carried out for 7 days.Chronic sepsis was responsible for a decrease in body weight, food intake and diaphragm's mass. The inhibitor was able to abolish diaphragm wasting only in the LY D1 group. Similarly, LY364947 had a beneficial effect on the diaphragm contraction only for the LY D1 group. SMAD3 was over-expressed and phosphorylated within rats in the Septic group; however, this effect was reversed by LY364947. Calpain-1 and -2 as well as MAFbx were over-expressed within individuals in the Septic group. Yet, calpain-1 and MAFbx expressions were decreased by LY364947.With this work, we demonstrate for the first time that the inhibition of TGF-ß pathway during chronic sepsis protects the diaphragm from wasting and weakness as early as one day post infection. This could lead to more efficient treatment and care for septic patients in ICU.

Polarization-resolved second harmonic microscopy of skeletal muscle in sepsis.

Polarization-resolved second harmonic generation (P-SHG) microscopy is able to probe the sub-micrometer structural organization of myosin filaments within skeletal muscle. In this study, P-SHG microscopy was used to analyze the structural consequences of sepsis, which is the main cause of the critical illness polyneuromyopathy (CIPNM). Experiments conducted on two populations of rats demonstrated a significant difference of the anisotropy parameter between healthy and septic groups, indicating that P-SHG microscopy is promising for the diagnosis of CIPNM. The difference, which can be attributed to a change of myosin conformation at the sub-sarcomere scale, cannot be evidenced by classical SHG imaging.

A non-hypocholesterolemic atorvastatin treatment improves vessel elasticity by acting on elastin composition in WHHL rabbits.

BACKGROUND AND AIMS: Statins are prescribed for their preventative effects within atherosclerosis development. To our knowledge, no study focusing on very low-dose (non-hypolipidemic effect) and long-term atorvastatin treatment in vivo was available. Our aim was to assess the effect of such atorvastatin treatment on the mechanical and functional characteristics of arteries in the context of primary prevention. METHODS: An atorvastatin treatment (2.5 mg/kg/day) was tested against controls on 34 male 3 to 12 month-old WHHL rabbits. No effect on total cholesterol, triglycerides, HDL or LDL was observed. The arterial stiffness was evaluated on vigil animals by pulse wave velocity (PWV) measurement. Then, in vitro measurements were made to evaluate (1) the endothelial and vascular smooth muscle function, (2) the elasticity of the arterial wall and (3) the composition in collagen and elastin in the aorta. RESULTS: The PWV increasing observed with age in control group was canceled by treatment, creating a significance difference between groups at 12 months (5.17 ± 0.50 vs 2.14 ± 0.34 m s(-1) in control and treated groups respectively). Vasoreactivity modifications can't explain this result but maintain of elasticity with treatment in large arteries was confirm by a static tensile test. A first possible explanation is the change of wall composition with treatment, validated by the percentage of elastin at 12 months, 4.4% lower in the control group compared to the treated group (p < 0.05). CONCLUSIONS: This study shows that a non-hypocholesterolemic statin treatment could improve vessel elasticity in the atherosclerotic WHHL model. The great novelty of this work is the vessel wall composition changing associated. This first approach in animal opens the reflection on the use of these low doses in humans. This could be interesting in the context of arterial stiffening with aging, non-hyperlipidemic atherosclerosis or with cholesterol reduce by another therapy or lifestyle modification.

Effect of dispersed crude oil on cardiac function in seabass Dicentrarchus labrax.

In this study, the impact of dispersed oil was assessed in Dicentrarchus labrax, a fish frequently used as an oil contamination indicator species. Fish were exposed for 48h to (mechanically and chemically) dispersed oil and dispersant alone. The impact of these exposure conditions was assessed on cardiac function by measuring (i) the contraction strength, the contraction and the relaxation speeds (ii) the cardiac energy metabolism using respirometry on permeabilized cardiac fibers. Compared to control, the increase of polycyclic aromatic metabolites observed in the bile indicated oil contamination in our fish. Following 48h of oil exposure at realistic oil concentrations, alterations of cardiac performances were observed. A decrease in contraction strength, contraction and relaxation speeds was observed in the presence of oil without effect of dispersant on these three parameters. Looking at cardiac energy metabolism, dispersant alone decreases all the activity of the respiratory chain and increases the proton leak. From these results, it appears that the observed decrease in cardiac performance in fish exposed to oil was not linked to a decrease in energy availability.