Association of circulating angiotensin converting enzyme activity with respiratory muscle function in infants

<p>Abstract</p> <p>Background</p> <p>Angiotensin converting enzyme (ACE) gene contains a polymorphism, consisting of either the presence (I) or absence (D) of a 287 base pair fragment. Deletion (D) is associated with increased circulating ACE (cACE) activity. It has been suggested that the D-allele of ACE genotype is associated with power-oriented performance and that cACE activity is correlated with muscle strength. Respiratory muscle function may be similarly influenced. Respiratory muscle strength in infants can be assessed specifically by measurement of the maximum inspiratory pressure during crying (Pi_max). Pressure-time index of the respiratory muscles (PTImus) is a non-invasive method, which assesses the load to capacity ratio of the respiratory muscles.</p> <p>The objective of this study was to determine whether increased cACE activity in infants could be related to greater respiratory muscle strength and to investigate the potential association of cACE with PTImus measurements as well as the association of ACE genotypes with cACE activity and respiratory muscle strength in this population.</p> <p>Methods</p> <p>Serum ACE activity was assayed by using a UV-kinetic method. ACE genotyping was performed by polymerase chain reaction amplification, using DNA from peripheral blood. PTImus was calculated as (Pi_mean/Pi_max) × (Ti/Ttot), where Pi_meanwas the mean inspiratory pressure estimated from airway pressure, generated 100 milliseconds after an occlusion (P_0.1), Pi_maxwas the maximum inspiratory pressure and Ti/Ttot was the ratio of the inspiratory time to the total respiratory cycle time. Pi_maxwas the largest pressure generated during brief airway occlusions performed at the end of a spontaneous crying effort.</p> <p>Results</p> <p>A hundred and ten infants were studied. Infants with D/D genotype had significantly higher serum ACE activity than infants with I/I or I/D genotypes. cACE activity was significantly related to Pi_maxand inversely related to PTImus. No association between ACE genotypes and Pdi_maxmeasurements was found.</p> <p>Conclusions</p> <p>These results suggest that a relation in cACE activity and respiratory muscle function may exist in infants. In addition, an association between ACE genotypes and cACE activity, but not respiratory muscle strength, was demonstrated.</p

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Influence of anthropometric characteristics on changes in maximal exercise ventilation and breathing pattern during growth in boys.

International audienceThe aim of this study was to investigate the effect of growth on ventilation and breathing pattern during maximal exercise oxygen consumption (VO2max) and their relationships with anthropometric characteristics. Seventy six untrained schoolboys, aged 10.5-15.5 years, participated in this study. Anthropometric measurements made included body mass, height, armspan, lean body mass, and body surface area. During an incremental exercise test, maximal ventilation (VEmax), tidal volume (VTmax), breathing frequency (fmax), inspiratory and expiratory times (tImax and tEmax), total duration of respiratory cycle (tTOTmax), mean inspiratory flow (VT/tImax), and inspiration fraction (tI/tTOTmax) were measured at VO2max. A power function was calculated between anthropometric characteristics and ventilatory variables to determine the allometric constants. The results showed firstly, that VEmax, VTmax, tImax, tEmax, tTOTmax, and VT/tImax increased with age and anthropometric characteristics (P less than 0.001), fmax decreased (P less than 0.001), and tI/tTOTmax remained constant during growth; secondly that lean body mass explained the greatest percentage of variance of VEmax (62.1%), VTmax (76.8%), and VT/tImax (70.6%), while anthropometric characteristics explained a slight percentage of variance of fmax and timing; and thirdly that VEmax, VTmax, and VT/tImax normalized by lean body mass did not change significantly with age. We concluded that at VO2max there were marked changes in ventilation and breathing pattern with growth. The changes in VEmax, VTmax, and VT/tImax were strongly related to the changes in lean body mass

Chronic AMPK activation improved mitochondrial function and endurance capacity of aged myostatin deficient mice

Chronic AMPK activation improved mitochondrial function and endurance capacity of aged myostatin deficient mice. 8. Congrès de Physiologie, de Pharmacologie et de Thérapeutiqu

Effect of inspiratory threshold loading on ventilatory kinetics during constant-load exercise.

Humoral factors play an important role in the control of exercise hyperpnea. The role of neuromechanical ventilatory factors, however, is still being investigated. We tested the hypothesis that the afferents of the thoracopulmonary system, and consequently of the neuromechanical ventilatory loop, have an influence on the kinetics of oxygen consumption (VO2), carbon dioxide output (VCO2), and ventilation (VE) during moderate intensity exercise. We did this by comparing the ventilatory time constants (tau) of exercise with and without an inspiratory load. Fourteen healthy, trained men (age 22.6 +/- 3.2 yr) performed a continuous incremental cycle exercise test to determine maximal oxygen uptake (VO2max = 55.2 +/- 5.8 ml x min(-1) x kg(-1)). On another day, after unloaded warm-up they performed randomized constant-load tests at 40% of their VO2max for 8 min, one with and the other without an inspiratory threshold load of 15 cmH2O. Ventilatory variables were obtained breath by breath. Phase 2 ventilatory kinetics (VO2, VCO2, and VE) could be described in all cases by a monoexponential function. The bootstrap method revealed small coefficients of variation for the model parameters, indicating an accurate determination for all parameters. Paired Student's t-tests showed that the addition of the inspiratory resistance significantly increased the tau during phase 2 of VO2 (43.1 +/- 8.6 vs. 60.9 +/- 14.1 s; P &lt; 0.001), VCO2 (60.3 +/- 17.6 vs. 84.5 +/- 18.1 s; P &lt; 0.001) and VE (59.4 +/- 16.1 vs. 85.9 +/- 17.1 s; P &lt; 0.001). The average rise in tau was 41.3% for VO2, 40.1% for VCO2, and 44.6% for VE. The tau changes indicated that neuromechanical ventilatory factors play a role in the ventilatory response to moderate exercise