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.

Does Decreased Diffusing Capacity of the Lungs for Carbon Monoxide Constitute a Risk of Decompression Sickness in Occupational Divers?

Long-term alterations of pulmonary function (mainly decreased airway conductance and capacity of the lungs to diffuse carbon monoxide (DLCO)) have been described after hyperbaric exposures. However, whether these alterations convey a higher risk for divers' safety has never been investigated before. The purpose of the present pilot study was to assess whether decreased DLCO is associated with modifications of the physiological response to diving. In this case-control observational study, 15 "fit-to-dive" occupational divers were split into two groups according to their DLCO measurements compared to references values, either normal (control) or reduced (DLCO group). After a standardized 20 m/40 min dive in a sea water pool, the peak-flow, vascular gas emboli (VGE) grade, micro-circulatory reactivity, inflammatory biomarkers, thrombotic factors, and plasmatic aldosterone concentration were assessed at different times post-dive. Although VGE were recorded in all divers, no cases of decompression sickness (DCS) occurred. Compared to the control, the latency to VGE peak was increased in the DLCO group (60 vs. 30 min) along with a higher maximal VGE grade (p < 0.0001). P-selectin was higher in the DLCO group, both pre- and post-dive. The plasmatic aldosterone concentration was significantly decreased in the control group (-30.4 ± 24.6%) but not in the DLCO group. Apart from a state of hypocoagulability in all divers, other measured parameters remained unchanged. Our results suggest that divers with decreased DLCO might have a higher risk of DCS. Further studies are required to confirm these preliminary results.

Skin temperature influence on transcutaneous carbon dioxide (CO2) conductivity and skin blood flow in healthy human subjects at the arm and wrist.

Objective: present transcutaneous carbon dioxide (CO2)-tcpCO2-monitors suffer from limitations which hamper their widespread use, and call for a new tcpCO2 measurement technique. However, the progress in this area is hindered by the lack of knowledge in transcutaneous CO2 diffusion. To address this knowledge gap, this study focuses on investigating the influence of skin temperature on two key skin properties: CO2 permeability and skin blood flow. Methods: a monocentric prospective exploratory study including 40 healthy adults was undertaken. Each subject experienced a 90 min visit split into five 18 min sessions at different skin temperatures-Non-Heated (NH), 35, 38, 41, and 44°C. At each temperature, custom sensors measured transcutaneous CO2 conductivity and exhalation rate at the arm and wrist, while Laser Doppler Flowmetry (LDF) assessed skin blood flow at the arm. Results: the three studied metrics sharply increased with rising skin temperature. Mean values increased from the NH situation up to 44°C from 4.03 up to 8.88 and from 2.94 up to 8.11 m·s-1 for skin conductivity, and from 80.4 up to 177.5 and from 58.7 up to 162.3 cm3·m-2·h-1 for exhalation rate at the arm and wrist, respectively. Likewise, skin blood flow increased elevenfold for the same temperature increase. Of note, all metrics already augmented significantly in the 35-38°C skin temperature range, which may be reached without active heating-i.e. only using a warm clothing. Conclusion: these results are extremely encouraging for the development of next-generation tcpCO2 sensors. Indeed, the moderate increase (× 2) in skin conductivity from NH to 44°C tends to indicate that heating the skin is not critical from a response time point of view, i.e. little to no skin heating would only result in a doubled sensor response time in the worst case, compared to a maximal heating at 44°C. Crucially, a skin temperature within the 35-38°C range already sharply increases the skin blood flow, suggesting that tcpCO2 correlates well with the arterial paCO2 even at such low skin temperatures. These two conclusions further strengthen the viability of non-heated tcpCO2 sensors, thereby paving the way for the development of wearable transcutaneous capnometers.

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.

A training program for fibromyalgia management: A 5-year pilot study.

We studied the effects of a specific cardio training program lasting 5 years on pain and quality of life in fibromyalgia patients. METHOD: An observational longitudinal pilot study was conducted in 138 fibromyalgia women. Fibromyalgia women recruited were asked to carry out three sessions per week, each lasting 45 min, of moderate-intensity continuous training (64%-75% Maximal Heart rate [HRmax]). During the first year, the patients progressively increased their training intensity. During the last 2 years, the patients were asked to associate moderate-intensity continuous training and high-intensity interval training (85%-90% HRmax). Pain on a visual analog scale, anxiety and depression state on the Hospital Anxiety and Depression Scale, impact of fibromyalgia on daily life using the Fibromyalgia Impact Questionnaire, heart rate and sleep quality (visual analog scale) were assessed at baseline and each year for 5 years. RESULTS: Forty-nine patients dropped out in the first year. Depending on their training status, the remaining 89 patients were retrospectively assigned to one of the three groups: Active (moderate-intensity continuous training), Semi-Active (one or two sessions, low-intensity continuous training <60% HRmax) and Passive (non-completion of training), based on their ability to comply with the program. Alleviation of all symptoms (p < 0.0001) was observed in the Active group. Increasing exercise intensity enhanced the effects obtained with moderate-intensity continuous training. Significant change in the Fibromyalgia Impact Questionnaire (p < 0.0001) and depression (Hospital Anxiety and Depression Scale; p < 0.0001), and no significant decrease in pain were noted in the Semi-Active group. No effect of the training was observed in the Passive group. CONCLUSION: The study intervention associated with multidisciplinary care alleviated pain, anxiety and depression, and improved both quality of life and quality of sleep, in fibromyalgia patients.

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.

Relationship between baseline and post-bronchodilator interrupter resistance and specific airway resistance in preschool children.

BACKGROUND: The assessment of airway function in preschool children can be done using simple measurement techniques such as interrupter resistance (Rint) or specific airway resistance (sRaw). OBJECTIVE: The aim of the study was to assess the relationship and the agreement between Rint and sRaw baseline measurements expressed in z-score and bronchodilator response (BDR) in accordance with the latest reference equations and recommended procedures. METHODS: One hundred thirty children aged 3 to 6 years old, referred to our pediatric pulmonary function test unit for assessment of airway function were consecutively included. Children performed baseline and post-bronchodilator measurements of Rint and sRaw. RESULTS: One hundred twenty baseline measurements were obtained (98.7%) with both techniques. At baseline there was a strong correlation between Rint and sRaw z-score (r = 0.5, P < .01) despite the poor agreement (Cohen Kappa coefficient 0.09 [-0.08; 0.26]). The agreement for BDR was fair, with Cohen Kappa coefficient (95% IC) = 0.33 (0.13; 0.54). Children with poorly or partially controlled asthma had both higher baseline Rint and sRaw (P < .01), and higher post-bronchodilator mean change (P < .01), than children with well-controlled asthma. CONCLUSION: The poor agreement between the Rint and sRaw reference measurements demonstrates the lack of reliability of sole Rint or sRaw technique for airway obstruction diagnosis and the need to perform each technique concomitantly with BDR test. Other longitudinal and larger sample studies are needed to confirm the threshold value for a positive BDR, especially for sRaw.

Impact of a specific training programme on the neuromodulation of pain in female patient with fibromyalgia (DouFiSport): a 24-month, controlled, randomised, double-blind protocol.

INTRODUCTION: The main symptom of fibromyalgia (FM) is diffuse pain. There is currently no aetiological treatment for FM. However, all pain associations and best practice guidelines strongly advocate the practice of aerobic physical activity to improve the symptoms of FM subjects. The mechanisms of dysfunctional pain are mostly central and related to stress axis dysfunction (autonomic nervous system and corticotropic axis). Our main objective is to assess the efficacy of a specific training programme on endogenous pain control mechanisms in female patients with FM. Further aims include rebalancing the autonomic neurovegetative system, improving quality of life and sleep quality, and reintegrating patients into society and work. METHODS AND ANALYSIS: 110 female patients with FM diagnosed on American College of Rheumatology 2010 criteria, aged 18-65 years and meeting inclusion conditions will be recruited and randomised into two groups (active and semiactive). The training programme will consist of three 45 min sessions per week of supervised, individualised physical activity over 2 years. Only the intensity of the exercises will differ between the two groups (moderate intensity vs low intensity).All outcome measures will be conducted at baseline (T0), after 6-9 months of training (T6-9) and after 24 months of training (T24). The primary endpoint will be an improvement of pain modulation (activation of diffuse noxious inhibitory control) evaluated by the stimulation test. The secondary endpoint will be relief of pain, anxiety, depression, stress, sleep disorders, pain impact on life quality, and improved heart rate, blood pressure and salivary cortisol. ETHICS AND DISSEMINATION: This study is approved by the Committee for the Protection of Persons West VI. The results will be published in specialised scientific journals and will be presented at scientific meetings on pain and/or physical activity. TRIAL REGISTRATION NUMBER: NCT02486965; Pre-results.

Cytoprotective and antioxidant effects of the red alga Alsidium corallinum against hydrogen peroxide-induced toxicity in rat cardiomyocytes.

CONTEXT: Sepsis is the manifestation of the immune and inflammatory responses to infection that may ultimately result in multiorgan failure. Many substances are involved in myocardial dysfunction in sepsis, including hydrogen peroxide. OBJECTIVE: This study evaluates the protective activity of the red alga Alsidium corallinum against hydrogen peroxide (H2O2)-induced toxicity in H9c2 cardiomyocytes. MATERIAL AND METHODS: The biological properties of A. corallinum were firstly investigated. Secondly, the H9c2 cells were pre-treated with alga extract, and then exposed to H2O2. RESULTS: Our results showed richness of the alga in antioxidant compounds, and its biological activities. H2O2 induced a morphological changes and decrease in H9c2 cell viability correlating with an increase in enzymatic and non-enzymatic antioxidants. Pre-treatment with A. corallinum, reduces toxicity and decreased the antioxidants status induced by H2O2. CONCLUSION: These findings indicated for the first time the protective effect of A. corallinum against H2O2-induced toxicity in H9c2 cells.

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.

Early follow-up of lung disease in infants with cystic fibrosis using the raised volume rapid thoracic compression technique and computed tomography during quiet breathing.

BACKGROUND: Among the different techniques used to monitor lung disease progression in infants with CF diagnosed by Newborn screening (NBS), raised volume-rapid thoracic compression (RVRTC) remains a promising tool. However, the need of sedation and positive pressure ventilation considerably limits its clinical use. We recently described a semi-quantitative method to evaluate air trapping by chest tomography during quite breathing without sedation (CTqb score). This parameter is the radiological sign of airway obstruction and could be also used for lung disease follow-up in infants with CF. However, its discriminative power compared with RVRTC and correlation with lung function parameters are not known. OBJECTIVES: To compare the discriminative powers of the CTqb score and RVRTC parameters and to determine their correlation during the first year of life of infants with CF. METHODS: In this multicenter longitudinal study, infants with CF diagnosed by NBS underwent RVRTC and CT during quite breathing at 10 ± 4 weeks (n = 30) and then at 13 ± 1 months of age (n = 28). RESULTS: All RVRTC parameters and the CTqb score remained stable between evaluations. The CTqb score showed a higher discriminative power than forced expiratory volume in 0.5 s (FEV0.5 ; the main RVRTC parameter) at both visits (66% and 50% of abnormal values vs 30% and 28%, respectively). No correlation was found between CTqb score and, the different RVRTC parameters or the plethysmographic functional residual capacity, indicating that they evaluate different aspect of CF lung disease.

Limoniastrum guyonianum prevents H2O2-induced oxidative damage in IEC-6 cells by enhancing enzyamtic defense, reducing glutathione depletion and JNK phosphorylation.

Limoniastrum guyonianum is used in several regions of North Africa as a folk medicine. The objective of this study was to determine the in vitro antioxidant activities of L. guyonianum roots and their cytoprotective action on H2O2-challenged rat small intestine epithelial cells (IEC-6 cells). To assess the cytoprotective effect of L. guyonianum extract (LGE), IEC-6 cells were pre-incubated with different LGE concentrations. Then, IEC-6 cultures were exposed to 40µM H2O2 during 4h. Modulation of endogenous antioxidant system including SOD, CAT, MDA, GSH and the expression of possibly involved MAPKs was evaluated. Main results reported that L. guyonianum was rich in polyphenols and exhibited an important antioxidant activity as revealed by different tests (DPPH Assay, IC50=1.6µg/mL; ABTS+ test, IC50=27µg/mL; Fe-reducing power, EC50=44µg/mL). HPLC analysis showed that quercetin, catechin, and isorhamnetin-3-O-rutinoside were major phenolics. The exposure of IEC-6 cells to 40µM H2O2 during 4h resulted in oxidative stress manifested by (i) over 70% cell mortality, (ii) over-activity of CAT (246%), (iii) decrease in GSH level (10.4nmol/mg), (iv) excess in MDA content (18.4nmol/mg), and (v) a trigger of JNK phosphorylation. Pretreatment with LGE, especially at 0.25µg/mL, restored cell viability to 100%, and normal cell morphology in H2O2-chalenged cells. In addition, this extract maintained a high CAT activity, enhanced SOD capacity (120%) and increased GSH level (45.5nmol/mg). Furthermore, reducing cell death seems to be due to dephosphorylated JNK MAPK exerted by L. guyonianum bioactive compounds. In all, L. guyonianum components provided a cross-talk between regulatory pathways, implying their role as cytoprotector against oxidative stress.

Cytoprotective effects of essential oil of Pinus halepensis L. against aspirin-induced toxicity in IEC-6 cells.

CONTEXT: Essential oils from Pinus species have been reported to have various therapeutic properties. OBJECTIVE: This study was undertaken to identify the chemical composition and cytoprotective effects of the essential oil of Pinus halepensis L. against aspirin-induced damage in cells in vitro. MATERIAL AND METHODS: The cytoprotection of the oil against toxicity of aspirin on the small intestine epithelial cells IEC-6 was tested. RESULTS: The obtained results have shown that 35 different compounds were identified. Aspirin induced a decrease in cell viability, and exhibited significant damage to their morphology and an increase in superoxide dismutase (SOD) and catalase (CAT) activities. However, the co-treatment of aspirin with the essential oil of Pinus induced a significant increase in cell viability and a decrease in SOD and CAT activities. CONCLUSION: Overall, these finding suggest that the essential oil of Pinus halepensis L. has potent cytoprotective effect against aspirin-induced toxicity in IEC-6 cells.

Potential protective effects of alpha-pinene against cytotoxicity caused by aspirin in the IEC-6 cells.

Alpha-pinene is a key compound of the essential oils extracted from many species of coniferous trees. It is known for its biological activities. The aim of the present study was to determine the preventive effect of alpha-pinene on aspirin-induced toxicity in vitro, using IEC-6 cells, and to investigate its antioxidant activities. The antioxidant activities were determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP). The cytotoxicity and oxidative stress were detected by cell viability, antioxidant enzyme activity, malondialdehyde (MDA) and GSH production, and the activation of MAPK pathways. The results indicated that alpha-pinene revealed an important antioxidant activity. It was evaluated by DPPH test (EC50=310±10µg/mL) and FRAP test (EC50=238±18.92µg/mL). The co-exposure of alpha-pinene with aspirin on cells significantly increased the survival of cells and the level of GSH, and decreased the levels of MDA and total SOD and the activity of Mn-SOD. In addition, the activation of p38 and JNK was blocked by alpha-pinene. Therefore, these findings suggest that alpha-pinene can protect IEC-6 cells against aspirin-induced oxidative stress.

Tamarix gallica phenolics protect IEC-6 cells against H2O2 induced stress by restricting oxidative injuries and MAPKs signaling pathways.

Polyphenolic compounds gained interest in the pharmaceutical research area due to their beneficial properties. Herein, antioxidant and cytoprotective capacities of T. gallica extract on H2O2-challenged rat small intestine epithelial cells were investigated. To set stress conditions, IEC-6 cultures were challenged with numerous H2O2 doses and durations. Then, 40µM H2O2 during 4h were selected to assess the cytoprotective effect of different T. gallica extract concentrations. Oxidative parameters, measured through CAT and SOD activities as well as MDA quantification were assessed. In addition, the expression of possibly involved MAPKs was also valued. Main results reported that T. gallica was rich in polyphenols and exhibited an important antioxidant activity (DPPH Assay, IC50=6µgmL-1; ABTS+ test, IC50=50µgmL-1; Fe-reducing power, EC50=100µgmL-1). The exposure of IEC-6 cultures to 40µM H2O2 during 4h caused oxidative stress manifested by (i) over 70% cell mortality, (ii) over-activity of CAT (246%), (iii) excess in MDA content (18.4nmolmg-1) and (iiii) a trigger of JNK phosphorylation. Pretreatment with T. gallica extract, especially when used at 0.25µgmL-1, restored cell viability to 122%, and normal cell morphology in H2O2-chalenged cells. In addition, this extract normalized CAT activity and MDA content (100% and 14.7nmolmg-1, respectively) to their basal levels as compared to control cells. Furthermore, stopping cell death seems to be due to dephosphorylated JNK MAPK exerted by T. gallica bioactive compounds. In all, T. gallica components provided a cross-talk between regulatory pathways leading to an efficient cytoprotection against harmful oxidative stimulus.

Protective effects of essential oil of Citrus limon against aspirin-induced toxicity in IEC-6 cells.

Aspirin, one of the widely used nonsteroidal anti-inflammatory drugs, is the most highly consumed pharmaceutical product in the world. However, it has several side effects in cells. This study was designed to investigate the antioxidative activity and cytoprotective effects of essential oil of Citrus limon (EOC) extracted from leaves against aspirin-induced damages in the rat small intestine epithelial cells (IEC-6). Biochemical indicators were used to assess cytotoxicity and oxidative damages caused by aspirin treatment on IEC-6. Our results showed that the chemical characterization of EOC identified 25 compounds representing 98.19% of the total oil. The major compounds from this oil were z-citral (53.21%), neryl acetate (13.06%), geranyl acetate (10.33%), and limonene (4.23%). Aspirin induced a decrease in cell viability as well as an increase in superoxide dismutase (SOD) and catalase (CAT) activities. Contrariwise, the co-exposure of cells to aspirin and EOC alleviated every above syndrome by an increase in cell survival and decrease in SOD and CAT activities. In conclusion, the essential oil of C. limon has a potent cytoprotective effect against aspirin-induced toxicity in IEC-6 cells.

Biological properties of citral and its potential protective effects against cytotoxicity caused by aspirin in the IEC-6 cells.

Citral, 3,7-dimethyl-2,6-octadienal, is a key component of several essential oils extracted from lemon-scented herbal plants. The present study was designed to investigate the antioxidant activities of citral and assess its possible protective effects against aspirin-induced toxicity in vitro. We used IEC-6 cells (rat small intestine epithelial cells). The antioxidant activities were determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH), ß-carotene/linoleic acid and Ferric reducing antioxidant power (FRAP). Cytotoxicity was evaluated by cell viability, anti-oxidant enzyme activities, malondialdehyde (MDA) production and by the expression of MAPKs (Mitogen-Activated Protein Kinases) pathways. According to results, citral showed an important antioxidant activity. It inhibited the oxidation of linoleic acid, a moderate DPPH was found and it showed a Ferric reducing antioxidant potential with an EC50 value of 125±28.86µg/mL. Then, the co-treatment of aspirin with citral significantly decreased the aspirin-induced cell death, and the MDA level. It modulated the superoxide dismutase (SOD) and glutathione (GSH) activities. Also, the activation of MAPKs was attenuated by citral. These findings suggest that citral can protect IEC-6 cells against aspirin-induced oxidative stress that may help to discover new chemicals out of natural antioxidant substances.

The diaphragm is better protected from oxidative stress than hindlimb skeletal muscle during CLP-induced sepsis.

OBJECTIVES: The aim of this study was to determine whether non-lethal sepsis induced by cecal ligation and puncture (CLP) modulates oxidative damage and enzymatic antioxidant defenses in diaphragm and hindlimb skeletal muscles (soleus and Extensor Digitorus Longus (EDL)). METHODS: Female Wistar rats were divided into four experimental groups: (1) control animals, (2) animals sacrificed 2 hours or (3) 7 days after CLP, and (4) sham-operated animals. At the end of the experimental procedure, EDL, soleus, and diaphragm muscles were harvested and 4-hydroxynonenal (HNE)-protein adducts and protein carbonyl contents were examined in relation to superoxide dismutase and catalase expression and activities. RESULTS: We observed that both non-respiratory oxidative (i.e. soleus) and glycolytic skeletal muscles (i.e. EDL) are more susceptible to sepsis-induced oxidative stress than diaphragm, as attested by an increase in 4-HNE protein adducts and carbonylated proteins after 2 hours of CLP only in soleus and EDL. DISCUSSION: These differences could be explained by higher basal enzymatic antioxidant activities in diaphragm compared to hindlimb skeletal muscles. Together, these results demonstrate that diaphragm is better protected from oxidative stress than hindlimb skeletal muscles during CLP-induced sepsis.

Single Muscle Immobilization Decreases Single-Fibre Myosin Heavy Chain Polymorphism: Possible Involvement of p38 and JNK MAP Kinases.

PURPOSE: Muscle contractile phenotype is affected during immobilization. Myosin heavy chain (MHC) isoforms are the major determinant of the muscle contractile phenotype. We therefore sought to evaluate the effects of muscle immobilization on both the MHC composition at single-fibre level and the mitogen-activated protein kinases (MAPK), a family of intracellular signaling pathways involved in the stress-induced muscle plasticity. METHODS: The distal tendon of female Wistar rat Peroneus Longus (PL) was cut and fixed to the adjacent bone at neutral muscle length. Four weeks after the surgery, immobilized and contralateral PL were dissociated and the isolated fibres were sampled to determine MHC composition. Protein kinase 38 (p38), extracellular signal-regulated kinases (ERK1/2), and c-Jun- NH2-terminal kinase (JNK) phosphorylations were measured in 6- and 15-day immobilized and contralateral PL. RESULTS: MHC distribution in immobilized PL was as follows: I = 0%, IIa = 11.8 ± 2.8%, IIx = 53.0 ± 6.1%, IIb = 35.3 ± 7.3% and I = 6.1 ± 3.9%, IIa = 22.1 ± 3.4%, IIx = 46.6 ± 4.5%, IIb = 25.2 ± 6.6% in contralateral muscle. The MHC composition in immobilized muscle is consistent with a faster contractile phenotype according to the Hill's model of the force-velocity relationship. Immobilized and contralateral muscles displayed a polymorphism index of 31.1% (95% CI 26.1-36.0) and 39.3% (95% CI 37.0-41.5), respectively. Significant increases in p38 and JNK phosphorylation were observed following 6 and 15 days of immobilization. CONCLUSIONS: Single muscle immobilization at neutral length induces a shift of MHC composition toward a faster contractile phenotype and decreases the polymorphic profile of single fibres. Activation of p38 and JNK could be a potential mechanism involved in these contractile phenotype modifications during muscle immobilization.