Inflammatory cytokine response to exercise in alpha-1-antitrypsin deficient COPD patients ‘on’ or ‘off’ augmentation therapy

Background: There is still limited information on systemic inflammation in alpha-1-antitrypsin-deficient (AATD) COPD patients and what effect alpha-1-antitrypsin augmentation therapy and/or exercise might have on circulating inflammatory cytokines. We hypothesized that AATD COPD patients on augmentation therapy (AATD + AUG) would have lower circulating and skeletal muscle inflammatory cytokines compared to AATD COPD patients not receiving augmentation therapy (AATD-AUG) and/or the typical non-AATD (COPD) patient. We also hypothesized that cytokine response to exercise would be lower in AATD + AUG compared to AATD-AUG or COPD subjects. Methods: Arterial and femoral venous concentration and skeletal muscle expression of TNFα, IL-6, IL-1β and CRP were measured at rest, during and up to 4-hours after 50% maximal 1-hour knee extensor exercise in all COPD patient groups, including 2 additional groups (i.e. AATD with normal lung function, and healthy age-/activity-matched controls). Results: Circulating CRP was higher in AATD + AUG (4.7 ± 1.6 mg/dL) and AATD-AUG (3.3 ± 1.2 mg/dL) compared to healthy controls (1.5 ± 0.3 mg/dL, p < 0.05), but lower in AATD compared to non-AATD-COPD patients (6.1 ± 2.6 mg/dL, p < 0.05). TNFα, IL-6 and IL-1β were significantly increased by 1.7-, 1.7-, and 4.7-fold, respectively, in non-AATD COPD compared to AATD COPD (p < 0.05), and 1.3-, 1.7-, and 2.2-fold, respectively, compared to healthy subjects (p < 0.05). Skeletal muscle TNFα was on average 3–4 fold greater in AATD-AUG compared to the other groups (p < 0.05). Exercise showed no effect on these cytokines in any of our patient groups. Conclusion: These data show that AATD COPD patients do not experience the same chronic systemic inflammation and exhibit reduced inflammation compared to non-AATD COPD patients. Augmentation therapy may help to improve muscle efflux of TNFα and reduce muscle TNFα concentration, but showed no effect on IL-6, IL-1β or CRP

Gender Comparisons of Mechanomyographic Amplitude and Mean Power Frequency Versus Isometric Torque Relationships

This is the publisher's version, also found at http://ehis.ebscohost.com/ehost/detail?sid=e7a03093-e666-4634-b895-d6b4313857c2%40sessionmgr13&vid=1&hid=17&bdata=JnNpdGU9ZWhvc3QtbGl2ZQ%3d%3d#db=s3h&AN=15943883This study compared the patterns of mechanomyographic (MMG) amplitude and mean power frequency vs. torque relationships in men and women during isometric muscle actions of the biceps brachii. Seven men (mean age 23.9 ± 3.5 yrs) and 8 women (mean 21.0 ± 1.3 yrs) performed submaximal to maximal isometric muscle actions of the dominant forearm flexors. Following determination of the isometric maximum voluntary contraction (MVC), they randomly performed submaximal step muscle actions in 10% increments from 10% to 90% MVC. Polynomial regression analyses indicated that the MMG amplitude vs. isometric torque relationship for the men was best fit with a cubic model (R2 = 0.983), where MMG amplitude increased slightly from 10% to 20% MVC, increased rapidly from 20% to 80% MVC, and plateaued from 80% to 100% MVC. For the women, MMG amplitude increased linearly (r2 = 0.949) from 10% to 100% MVC. Linear models also provided the best fit for the MMG mean power frequency vs. isometric torque relationship in both the men (r2 = 0.813) and women (r2 = 0.578). The results demonstrated gender differences in the MMG amplitude vs. isometric torque relationship, but similar torque-related patterns for MMG mean power frequency. These findings suggested that the plateau in MMG amplitude at high levels of isometric torque production for the biceps brachii in the men, but not the women, may have been due to greater isometric torque, muscle stiffness, and/or intramuscular fluid pressure in the men, rather than to differences in moto

Tissue‐specific regulation of cytochrome c by post‐translational modifications: respiration, the mitochondrial membrane potential, ROS, and apoptosis

Cytochrome c (Cytc) plays a vital role in the mitochondrial electron transport chain (ETC). In addition, it is a key regulator of apoptosis. Cytc has multiple other functions including ROS production and scavenging, cardiolipin peroxidation, and mitochondrial protein import. Cytc is tightly regulated by allosteric mechanisms, tissue‐specific isoforms, and post‐translational modifications (PTMs). Distinct residues of Cytc are modified by PTMs, primarily phosphorylations, in a highly tissue‐specific manner. These modifications downregulate mitochondrial ETC flux and adjust the mitochondrial membrane potential (ΔΨm), to minimize reactive oxygen species (ROS) production under normal conditions. In pathologic and acute stress conditions, such as ischemia–reperfusion, phosphorylations are lost, leading to maximum ETC flux, ΔΨm hyperpolarization, excessive ROS generation, and the release of Cytc. It is also the dephosphorylated form of the protein that leads to maximum caspase activation. We discuss the complex regulation of Cytc and propose that it is a central regulatory step of the mammalian ETC that can be rate limiting in normal conditions. This regulation is important because it maintains optimal intermediate ΔΨm, limiting ROS generation. We examine the role of Cytc PTMs, including phosphorylation, acetylation, methylation, nitration, nitrosylation, and sulfoxidation and consider their potential biological significance by evaluating their stoichiometry.—Kalpage, H. A., Bazylianska, V., Recanati, M. A., Fite, A., Liu, J., Wan, J., Mantena, N., Malek, M. H., Podgorski, I., Heath, E. I., Vaishnav, A., Edwards, B. F., Grossman, L. I., Sanderson, T. H., Lee, I., Hüttemann, M. Tissue‐specific regulation of cytochrome c by post‐translational modifications: respiration, the mitochondrial membrane potential, ROS, and apoptosis. FASEB J. 33, 1540–1553 (2019). www.fasebj.orgPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154496/1/fsb2fj201801417r.pd

Mechanomyographic amplitude and frequency responses during dynamic muscle actions: a comprehensive review

The purpose of this review is to examine the literature that has investigated mechanomyographic (MMG) amplitude and frequency responses during dynamic muscle actions. To date, the majority of MMG research has focused on isometric muscle actions. Recent studies, however, have examined the MMG time and/or frequency domain responses during various types of dynamic activities, including dynamic constant external resistance (DCER) and isokinetic muscle actions, as well as cycle ergometry. Despite the potential influences of factors such as changes in muscle length and the thickness of the tissue between the muscle and the MMG sensor, there is convincing evidence that during dynamic muscle actions, the MMG signal provides valid information regarding muscle function. This argument is supported by consistencies in the MMG literature, such as the close relationship between MMG amplitude and power output and a linear increase in MMG amplitude with concentric torque production. There are still many issues, however, that have yet to be resolved, and the literature base for MMG during both dynamic and isometric muscle actions is far from complete. Thus, it is important to investigate the unique applications of MMG amplitude and frequency responses with different experimental designs/methodologies to continually reassess the uses/limitations of MMG

Strategies for cardiopulmonary exercise testing of pectus excavatum patients

The purpose of this paper is to provide strategies for cardiopulmonary exercise testing of pectus excavatum patients. Currently, there are no standardized methods for assessing cardiovascular and pulmonary responses in this population; therefore, making comparisons across studies is difficult if not impossible. These strategies are intended for physicians, pulmonary technicians, exercise physiologists, and other healthcare professionals who conduct cardiopulmonary exercise testing on pectus excavatum patients. By using the strategies outlined in this report, comparisons across studies can be made, and the effects of pectus excavatum on cardiopulmonary function can be assessed with greater detail

Examination of the relationship between the slow component of oxygen uptake kinetics and plasma ammonia concentrations during cycle ergometer exercise

The purposes of this study were to: (1) compare the patterns of responses for plasma ammonia concentration ([NH3]) during moderate- and heavy intensity cycle ergometry; and (2) examine the relationship between the V˙O2 slow component (V˙O2SC) and plasma [NH3]. Thirteen healthy, untrained college males who performed less than a total of two hours of aerobic and/or resistance exercise per week visited the laboratory on six separate occasions. The initial visit included a V˙O2max test, whereas subsequent visits involved constant power output exercise (7-minutes in duration) at two different intensities [moderate 60%GET = 60% of the gas exchange threshold; and heavy, Δ50% = 50% of the difference between GET and V˙O2max)]. Plasma was collected from an antecubital vein prior to the exercise, during the last three minutes of the six minute warm-up, and during each minute of the seven minute constant power output workbout. The time course of changes in plasma [NH3] and V˙O2 during the two constant power output exercise intensities (60%GET and Δ50%) were assessed separately using 2 (intensity: 60%GET and Δ50%) × 7 (time: each minute of 7-minute workbout) repeated-measures ANOVAs. When appropriate, Scheffé\u27s post-hoc analyses were used to determine significantly different mean values. In addition, a Pearson\u27s correlation coefficient was calculated to assess the relationship between plasma [NH3] and the amplitude of the V˙O2SC for the heavy intensity exercise. For moderate intensity exercise (60%GET), there were no significant differences in the mean normalized plasma [NH3] during the 7-minute workbout. In addition, the mean normalized V˙O2 values were not significantly different from each other during the final 5-minutes of the exercise workbout. For heavy intensity exercise (Δ50%), there was a significant increase in the mean normalized plasma [NH3] during the 7-minute workbout. Similarly, the mean normalized V˙O 2 response increased significantly during the entire 7-minute workbout. Pearson\u27s correlation coefficient indicated a significant (r = 0.76, p \u3c 0.05) relationship between [NH3]Δ7-3 (the difference in normalized [NH3] between the 7 th- and 3rd-minute ([NH3]Δ7-3 ) of the Δ50% constant power output exercise) and the V˙O2SC amplitude. The results indicated that during moderate intensity exercise, the V˙O2 response reached a steady-state with no change in plasma [NH3] from baseline values. For the heavy intensity exercise, however, there was a V˙O 2SC and plasma [NH3] increased continuously until the end of exercise. These findings suggest a potential relationship between exercise-induced increase in plasma [NH3] and the V˙O 2SC during heavy intensity exercise

Strategies for cardiopulmonary exercise testing of pectus excavatum patients

The purpose of this paper is to provide strategies for cardiopulmonary exercise testing of pectus excavatum patients. Currently, there are no standardized methods for assessing cardiovascular and pulmonary responses in this population; therefore, making comparisons across studies is difficult if not impossible. These strategies are intended for physicians, pulmonary technicians, exercise physiologists, and other healthcare professionals who conduct cardiopulmonary exercise testing on pectus excavatum patients. By using the strategies outlined in this report, comparisons across studies can be made, and the effects of pectus excavatum on cardiopulmonary function can be assessed with greater detail

On the Inappropriateness of Stepwise Regression Analysis for Model Building and Testing

My colleagues and I recently read the study by Sanada et al. (2007) on the development of prediction models for maximal oxygen uptake (\ifmmode\expandafter\else˙\expandafter\.\fiVO2max). We would like to focus our comments on two particular areas of the study: (1) the use of stepwise regression, and (2) the practical application of the prediction equations