From breathing to respiration.

The purpose of breathing remained an enigma for a long time. The Hippocratic school described breathing patterns but did not associate breathing with the lungs. Empedocles and Plato postulated that breathing was linked to the passage of air through pores of the skin. This was refuted by Aristotle who believed that the role of breathing was to cool the heart. In Alexandria, breakthroughs were accomplished in the anatomy and physiology of the respiratory system. Later, Galen proposed an accurate description of the respiratory muscles and the mechanics of breathing. However, his heart-lung model was hampered by the traditional view of two non-communicating vascular systems - veins and arteries. After a period of stagnation in the Middle Ages, knowledge progressed with the discovery of pulmonary circulation. The comprehension of the purpose of breathing progressed by steps thanks to Boyle and Mayow among others, and culminated with the contribution of Priestley and the discovery of oxygen by Lavoisier. Only then was breathing recognized as fulfilling the purpose of respiration, or gas exchange. A century later, a controversy emerged concerning the active or passive transfer of oxygen from alveoli to the blood. August and Marie Krogh settled the dispute, showing that passive diffusion was sufficient to meet the oxygen needs. © 2014 S. Karger AG, Basel.

Comparison of the power spectral changes of the voluntary surface electromyogram and M wave during intermittent maximal voluntary contractions.

INTRODUCTION: To compare the power spectral changes of the voluntary surface electromyogram (sEMG) and of the compound action potential (M wave) in the vastus medialis and vastus lateralis muscles during fatiguing contractions. METHODS: Interference sEMG and force were recorded during 48 intermittent 3-s isometric maximal voluntary contractions (MVC) from 13 young, healthy subjects. M waves and twitches were evoked using supramaximal femoral nerve stimulation between the successive MVCs. Mean frequency (F mean), and median frequency were calculated from the sEMG and M waves. Muscle fiber conduction velocity (MFCV) was computed by cross-correlation. RESULTS: The power spectral shift to lower frequencies was significantly greater for the voluntary sEMG than for the M waves (P < 0.05). Over the fatiguing protocol, the overall average decrease in MFCV (~25 %) was comparable to that of sEMG F mean (~22 %), but significantly greater than that of M-wave F mean (~9 %) (P < 0.001). The mean decline in MFCV was highly correlated with the mean decreases in both sEMG and M-wave F mean. CONCLUSIONS: The present findings indicated that, as fatigue progressed, central mechanisms could enhance the relative weight of the low-frequency components of the voluntary sEMG power spectrum, and/or the end-of-fiber (non-propagating) components could reduce the sensitivity of the M-wave spectrum to changes in conduction velocity.

Réponses cardiorespiratoires lors d'une évaluation musculaire isocinétique du tronc

Objectif Évaluer les sollicitations cardiorespiratoires d'une évaluation isocinétique des muscles extenseurs/fléchisseurs du tronc. Méthode Huit sujets masculins (24,9±1,4ans) ont réalisé des exercices d'extension-flexion du rachis en mode isocinétique. Ce test comportait trois répétitions à 30°/s, trois répétitions à 60°/s et 15 répétitions à 120°/s en mode concentrique. Deux minutes de récupération étaient respectées entre chaque série. Des mesures de fréquence cardiaque, pression artérielle, consommation d'oxygène, et lactates sanguins étaient réalisées au repos et en fin d'exercice. Résultats Une augmentation significative de 84 % de la FC max, correspondant à 80 % de la FC maximale théorique a été mesurée. L'élévation de la TA systolique à l'effort correspondait à une augmentation de 20 % par rapport au repos. Une augmentation de 47 % de la VO2max a été mesurée. Le pic de lactates observé lors de la série de 15 répétitions montrait une augmentation significative de 230 % par rapport à la valeur de repos. La recherche de facteurs de risque cardiovasculaires doit être faite avant tout test isocinétique. Une épreuve d'effort conventionnelle peut être proposée aux patients à risque si une série correspondant à un test de résistance à la fatigue est envisagée.

Dietary effects on muscle fatty acid composition of finished heifers

The effects of diet on Longissimus muscle fatty acid composition was determined using 24 crossbred heifers of Simmental vs. Nelore and Limousin vs. Nelore. The experimental diets were: 1) corn and yeast (CY); 2) corn, cottonseed meal + meat and bones meal (CMB); 3) cassava hull and yeast (CHY); 4) cassava hull, cottonseed meal + meat and bones meal (CHMB). Feeding CHMB diets resulted in lower lipid and higher cholesterol contents (P<0.05) for both crosses. Most of the identified fatty acids were monounsaturated, and the highest percentage was found to oleic acid (C18:1w9), with values ranging from 32.54 to 46.42%. Among the saturated fatty acids the palmitic acid (C16:0) showed the highest percentage, with its contents ranging between 19.40 and 32.44%. The highest polyunsaturated/saturated fatty acid ratio was of 0.30, and the lowest was of 0.08. Feeding CY diets resulted in lower cholesterol and higher polyunsaturated fatty acid contents of the Longissimus muscle.

Analyse critique des résultats de biopsies musculaires et de la méthodologie utilisée dans 889 cas d'affections neuromusculaires [Critical analysis of the results of muscle biopsies and of the methods used in 889 cases of neuromuscular disorders]

The contribution of muscle biopsies to the diagnosis of neuromuscular disorders and the indications of various methods of examination are investigated by analysis of 889 biopsies from patients suffering from myopathic and/or neurogenic disorders. Histo-enzymatic studies performed on frozen material as well as immunohistochemistry and electron microscopy allowed to provide specific diagnoses in all the neurogenic disorders (polyneuropathies and motor neuron diseases), whereas one third of myopathies remained uncertain. Confrontation of neuropathological data with the clinical indications for histological investigations shows that muscle biopsies reveal the diagnosis in 25% of the cases (mainly in congenital and metabolic myopathies) and confirm and/or complete the clinical diagnosis in 50%. In the remaining cases with non specific abnormalities neuropathological investigations may help the clinician by excluding well defined neuromuscular disorders. Analysis of performed studies and results of investigations show the contribution and specificity of each method for the diagnosis. Statistical evaluation of this series indicates that cryostat sectioning for histo- and immunochemical and electron microscopy increases the rate of diagnoses of neuromuscular diseases: full investigation was necessary for the diagnosis in 30% of the cases. The interpretation of the wide range of pathological reactions in muscles requires a close cooperation with the clinician.

Effects of paralysis with pancuronium bromide on joint mobility in premature infants.

To study the effects of muscle paralysis on joint mobility, we compared eight premature infants treated with pancuronium bromide with a control group. A significant reduction was observed in hip and knee flexion, and in ankle dorsal extension, which tended to resolve in time. We conclude that muscle paralysis reduces the mobility of selected joints; spontaneous activity appears to prevent long-term contractures.

Laser scanning evaluation of atrophy after autologous free muscle transfer.

Denervated muscle tissue undergoes morphologic changes that result in atrophy. The amount of muscle atrophy after denervation following free muscle transfer has not been measured so far. Therefore, the amount of muscle atrophy in human free muscle transfer for lower extremity reconstruction was measured in a series of 10 patients. Three-dimensional laser surface scanning was used to measure flap volume changes 2 weeks as well as 6 and 12 months after the operation. None of the muscles transferred was re-innervated.All muscles healed uneventfully without signs of compromised perfusion resulting in partial flap loss. The muscle volume decreased to 30 ± 4% and 19 ± 4% 6 and 12 months, respectively, after the operation, ie, the volume decreased by approximately 80% within a 12-month period.Denervated free muscle flap tissue undergoes massive atrophy of approximately 80%, mostly within the first 6 months.

Phenylbutyrate therapy for pyruvate dehydrogenase deficiency

Deficiency of pyruvate dehydrogenase complex (PDHC) is the most common disorder leading to lactic acidemia. Phosphorylation of specific serine residues of the E1-alpha subunit of the PDHC by pyruvate dehydrogenase kinase (PDK) inactivates the enzyme, whereas dephosphorylation restores PDHC activity. We recently found that phenylbutyrate prevents phosphorylation of the E1-alpha subunit of the branched-chain ketoacid dehydrogenase complex (BCKDC) and reduces plasma concentrations of neurotoxic branched chain amino acids in patients with maple syrup urine disease (MSUD), due to the deficiency of BCKDC. We hypothesized that, similarly to BCKDC, phenylbutyrate enhances PDHC enzymatic activity by increasing the portion of unphosphorylated enzyme. To test this hypothesis, we treated wild-type human fibroblasts at different concentrations of phenylbutyrate and found that it reduces the levels of phosphorylated E1-alpha as compared to untreated cells. To investigate the effect of phenylbutyrate in vivo, we administered phenylbutyrate to C57B6 wild-type mice and we detected a significant increase in Pdhc enzyme activity and a reduction of phosphorylated E1-alpha subunit in brains and muscles as compared to saline treated mice. Being a drug already approved for human use, phenylbutyrate has great potential for increasing the residual enzymatic activity of PDHC and to improve the clinical phenotype of PDHC deficiency.

Surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry: A tool to predict pork quality

Expression of water soluble proteins of fresh pork Longissimus thoracis from 4 pure breed pigs (Duroc, Large White, Landrace, and Piétrain) was studied to identify candidate protein markers for meat quality. Surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF-MS) was used to obtain the soluble protein profiles of Longissimus thoracis muscles. The pure breeds showed differences among the studied meat quality traits (pHu, drip loss, androstenone, marbling, intramuscular fat, texture, and moisture), but no significant differences were detected in sensory analysis. Associations between protein peaks obtained with SELDI-TOF-MS and meat quality traits, mainly water holding capacity, texture and skatole were observed. Of these peaks, a total of 10 peaks from CM10 array and 6 peaks from Q10 array were candidate soluble protein markers for pork loin quality. The developed models explained a limited proportion of the variability, however they point out interesting relationships between protein expression and meat quality

Analysis of raw hams using SELDI-TOF-MS to predict the final quality of dry-cured hams

The relationship between protein profiles of Gluteus medius (GM) muscles of raw hams obtained from 4 pure breed pigs (Duroc, Large White, Landrace, and Piétrain) with the final quality of the Semimembranosus and Biceps femoris muscles of dry-cured hams was investigated. As expected, Duroc hams showed higher levels of marbling and intramuscular fat content than the other breeds. Piétrain hams were the leanest and most conformed, and presented the lowest salt content in dry-cured hams. Even if differences in the quality traits (colour, water activity, texture, composition, intramuscular fat, and marbling) of dry-cured hams were observed among the studied breeds, only small differences in the sensory attributes were detected. Surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry (SELDI-TOF-MS) was used to obtain the soluble protein profiles of GM muscles. Some associations between protein peaks obtained with SELDI-TOF-MS and quality traits, mainly colour (b*) and texture (F0, Y2, Y90) were observed. Candidate protein markers for the quality of processed dry-cured hams were identified

Correlation of CXCL10, tumor necrosis factor receptor type II, and galectin 9 with disease activity in juvenile dermatomyositis.

OBJECTIVE: Juvenile dermatomyositis (DM) is a systemic autoimmune disorder of unknown immunopathogenesis in which the immune system targets the microvasculature of skeletal muscles, skin, and other organs. The current mainstay of therapy is a steroid regimen in combination with other immunosuppressive treatments. To date, no validated markers for monitoring disease activity have been identified, which hampers personalized treatment. This study was undertaken to identify a panel of proteins specifically related to active disease in juvenile DM. METHODS: We performed a multiplex immunoassay for plasma levels of 45 proteins related to inflammation in 25 patients with juvenile DM in 4 clinically well-defined groups, as determined by clinical activity and treatment. We compared them to 14 age-matched healthy children and 8 age-matched children with nonautoimmune muscle disease. RESULTS: Cluster analysis of circulating proteins showed distinct profiles for juvenile DM patients and controls based on a group of 10 proteins. In addition to CXCL10, tumor necrosis factor receptor type II (TNFRII) and galectin 9 were significantly increased in active juvenile DM. The levels of these 3 proteins were tightly linked to active disease and correlated with clinical scores (as measured by the Childhood Myositis Assessment Scale and physician's global assessment of disease activity on a visual analog scale). CONCLUSION: Our findings indicate that CXCL10, TNFRII, and galectin 9 correspond to disease status in juvenile DM and thus could be helpful in monitoring disease activity and guiding treatment. Furthermore, they might provide new knowledge about the pathogenesis of this autoimmune disease.

Reduction of choroidal neovascularization in mice by adeno-associated virus-delivered anti-vascular endothelial growth factor short hairpin RNA.

BACKGROUND: Strategies leading to the long-term suppression of inappropriate ocular angiogenesis are required to avoid the need for repetitive monthly injections for treatment of diseases of the eye, such as age-related macular degeneration (AMD). The present study aimed to develop a strategy for the sustained repression of vascular endothelial growth factor (VEGF), which is identified as the key player in exudative AMD. METHODS: We have employed short hairpin (sh)RNAs combined with adeno-associated virus (AAV) delivery to obtain the targeted expression of potent gene-regulatory molecules. Anti-VEGF shRNAs were analyzed in human retinal pigment epithelial (RPE) cells using Renilla luciferase screening. For in vivo delivery of the most potent shRNA, self-complementary AAV vectors were packaged in serotype 8 capsids (scAAV2/8-hU6-sh9). In vivo efficacy was evaluated either by injection of scAAV2/8-hU6-sh9 into murine hind limb muscles or in a laser-induced murine model of choroidal neovascularization (CNV) following scAAV2/8-hU6-sh9 subretinal delivery. RESULTS: Plasmids encoding anti-VEGF shRNAs showed efficient knockdown of human VEGF in RPEs. Intramuscular administration led to localized expression and 91% knockdown of endogenous murine (m)VEGF. Subsequently, the ability of AAV2/8-encoded shRNAs to impair vessel formation was evaluated in the murine model of CNV. In this model, the sizes of the CNV were significantly reduced (up to 48%) following scAAV2/8-hU6-sh9 subretinal delivery. CONCLUSIONS: Using anti-VEGF vectors, we have demonstrated efficient silencing of endogenous mVEGF and showed that subretinal administration of scAAV2/8-hU6-sh9 has the ability to impair vessel formation in an AMD animal model. Thus, AAV-encoded shRNA can be used for the inhibition of neovascularization, leading to the development of sustained anti-VEGF therapy. Copyright © 2012 John Wiley & Sons, Ltd.

Anterior Segment Angiography in Strabismus Surgery

Background: Anterior ciliary arteries travelling along recti muscles provide anterior segment vascularization, which can be compromised by surgery involving more than 2 muscles.Patients and Methods: We studied retrospectively the files of 10 patients in whom a fluorescein angiography of the iris had been performed as a pre-operative assessment prior to a second or third oculomotor surgery.Results: The median age of the patients was 47.5 years (range 15 to 73 years). Relative iris ischemia was present in 4 patients following multiple surgeries, none of them presenting any general cardiovascular risk. The initial surgical protocol was modified according to angiographic results in these 4 patients.Conclusion: When further surgery has to be performed on previously multi-operated patients, anterior segment angiography can be useful in the planning of surgery in order to minimize the risks of anterior segment ischemia.

Prenatal diagnosis of a fetal abdominal eventration: a rare congenital abdominal wall defect.

We report a case of abdominal eventration associated with cystic fibrosis, diagnosed by mid-trimester ultrasonography. The defect concerned the abdominal muscles and their aponevrotic sheath, but respected the skin. There was no associated malformation. The outcome was favorable after surgery, and the infant is well at the age of 6 months.

High-Resolution Mass Spectrometry applied to the identification of new metabolites and transformation products of quinolones in chicken muscle tissues

The aim of this work was the identification of new metabolites and transformation products (TPs) in chicken muscle from Enrofloxacin (ENR), Ciprofloxacin (CIP), Difloxacin (DIF) and Sarafloxacin (SAR), which are antibiotics that belong to the fluoroquinolones family. The stability of ENR, CIP, DIF and SAR standard solutions versus pH degradation process (from pH 1.5 to 8.0, simulating the pH since the drug is administered until its excretion) and freeze-thawing (F/T) cycles was tested. In addition, chicken muscle samples from medicated animals with ENR were analyzed in order to identify new metabolites and TPs. The identification of the different metabolites and TPs was accomplished by comparison of mass spectral data from samples and blanks, using liquid chromatography coupled to quadrupole time-of-flight (LC-QqToF) and Multiple Mass Defect Filter (MMDF) technique as a pre-filter to remove most of the background noise and endogenous components. Confirmation and structure elucidation was performed by liquid chromatography coupled to linear ion trap quadrupole Orbitrap (LC-LTQ-Orbitrap), due to its mass accuracy and MS/MS capacity for elemental composition determination. As a result, 21 TPs from ENR, 6 TPs from CIP, 14 TPs from DIF and 12 TPs from SAR were identified due to the pH shock and F/T cycles. On the other hand, 14 metabolites were identified from the medicated chicken muscle samples. Formation of CIP and SAR, from ENR and DIF, respectively, and the formation of desethylene-quinolone were the most remarkable identified compounds.