Severe loss of mechanical efficiency in COVID‐19 patients

Background: There is limited information about the impact of coronavirus disease (COVID-19) on the muscular dysfunction, despite the generalized weakness and fatigue that patients report after overcoming the acute phase of the infection. This study aimed to detect impaired muscle efficiency by evaluating delta efficiency (DE) in patients with COVID-19 compared with subjects with chronic obstructive pulmonary disease (COPD), ischaemic heart disease (IHD), and control group (CG). Methods: A total of 60 participants were assigned to four experimental groups: COVID-19, COPD, IHD, and CG (n = 15 each group). Incremental exercise tests in a cycle ergometer were performed to obtain peak oxygen uptake (VO2 peak). DE was obtained from the end of the first workload to the power output where the respiratory exchange ratio was 1. Results: A lower DE was detected in patients with COVID-19 and COPD compared with those in CG (P ≤ 0.033). However, no significant differences were observed among the experimental groups with diseases (P > 0.05). Lower VO2 peak, peak ventilation, peak power output, and total exercise time were observed in the groups with diseases than in the CG (P < 0.05). A higher VO2 , ventilation, and power output were detected in the CG compared with those in the groups with diseases at the first and second ventilatory threshold (P < 0.05). A higher power output was detected in the IHD group compared with those in the COVID-19 and COPD groups (P < 0.05) at the first and second ventilatory thresholds and when the respiratory exchange ratio was 1. A significant correlation (P < 0.001) was found between the VO2 peak and DE and between the peak power output and DE (P < 0.001). Conclusions: Patients with COVID-19 showed marked mechanical inefficiency similar to that observed in COPD and IHD patients. Patients with COVID-19 and COPD showed a significant decrease in power output compared to IHD during pedalling despite having similar response in VO2 at each intensity. Resistance training should be considered during the early phase of rehabilitation

Variability of protein level and phosphorylation status caused by biopsy protocol design in human skeletal muscle analyses

<p>Abstract</p> <p>Background</p> <p>Bergström needle biopsy is widely used to sample skeletal muscle in order to study cell signaling directly in human tissue. Consequences of the biopsy protocol design on muscle protein quantity and quality remain unclear. The aim of the present study was to assess the impact of different events surrounding biopsy protocol on the stability of the Western blot signal of eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), Akt, glycogen synthase kinase-3β (GSK-3β), muscle RING finger protein 1 (MuRF1) and p70 S6 kinase (p70 S6K). Six healthy subjects underwent four biopsies of the <it>vastus lateralis</it>, distributed into two distinct visits spaced by 48 hrs. At visit 1, a basal biopsy in the right leg was performed in the morning (R1) followed by a second in the left leg in the afternoon (AF). At visit 2, a second basal biopsy (R2) was collected from the right leg. Low intensity mobilization (3 × 20 right leg extensions) was performed and a final biopsy (Mob) was collected using the same incision site as R2.</p> <p>Results</p> <p>Akt and p70 S6K phosphorylation levels were increased by 83% when AF biopsy was compared to R1. Mob condition induced important phosphorylation of p70 S6K when compared to R2. Comparison of R1 and R2 biopsies revealed a relative stability of the signal for both total and phosphorylated proteins.</p> <p>Conclusions</p> <p>This study highlights the importance to standardize muscle biopsy protocols in order to minimize the method-induced variation when analyzing Western blot signals.</p

WRAP53 Is Essential for Cajal Body Formation and for Targeting the Survival of Motor Neuron Complex to Cajal Bodies

The WRAP53 protein regulates the formation and maintenance of Cajal bodies (nuclear sub-organelles), as well as directs the recruitment of nuclear factors to Cajal bodies

A comparison of skating economy on-ice and on the skating treadmill

On compare la dépense énergétique du patinage sur la glace et sur tapis roulant conçu pour patiner, chez des joueurs de hockey sur glace masculins, athlètes universitaires. L'épreuve de patinage dure 4 minutes pour chacune des vitesses sous-maximales (18, 20,22 km/h), séparées par 5 minutes de récupération passive. La consommation d'oxygène sur la glace est similaire sur la glace et sur ergomètre spécifique (54,7 ml kg/min). Par contre les données cinématiques du patinage et la fréquence cardiaque sont différentes

Oxidative enzyme activities of the vastus lateralis muscle and the functional status in patients with COPD

BACKGROUND—Enzymatic and histochemical abnormalities of the peripheral muscle may play a role in exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to measure the mitochondrial enzyme activity of the vastus lateralis muscle in patients with COPD and to evaluate the relationship between enzyme activities and functional status.
METHODS—Fifty seven patients with COPD of mean (SD) age 66 (7) years with forced expiratory volume in one second (FEV(1)) 39 (15)% predicted and peak oxygen uptake (V̇O(2)) of 14 (4) ml/min/kg and 15 normal subjects of similar age were included in the study. Each subject performed a stepwise exercise test up to maximal capacity during which five-breath averages of V̇O(2) were measured. Muscle specimens were obtained by percutaneous needle biopsy of the vastus lateralis muscle and the activity of two mitochondrial enzymes (citrate synthase (CS) and 3-hydroxyacyl CoA dehydrogenase (HADH)) was measured. The functional status of the patients was classified according to peak V̇O(2).
RESULTS—CS and HADH activities were markedly reduced in patients with COPD compared with normal subjects (22.3 (2.7) versus 29.5 (7.3) µmol/min/g muscle (p<0.0001) and 5.1 (2.0) versus 6.7 (1.9) µmol/min/g muscle (p<0.005), respectively). The activity of CS decreased progressively with the deterioration in the functional status while that of HADH was not related to functional status. Using a stepwise regression analysis, percentage predicted functional residual capacity (FRC), the activity of CS, oxygen desaturation during exercise, age, and inspiratory capacity (% pred) were found to be significant determinants of peak V̇O(2). The regression model explained 59% of the variance in peak V̇O(2) (p<0.0001).
CONCLUSIONS—The oxidative capacity of the vastus lateralis muscle is reduced in patients with moderate to severe COPD compared with normal subjects of similar age. In these individuals the activity of CS correlated significantly with peak exercise capacity and independently of lung function impairment.


Effects of combined candesartan and ACE inhibitors on BNP, markers of inflammation and oxidative stress, and glucose regulation in patients with symptomatic heart failure

Background&lt;p&gt;&lt;/p&gt; We assessed the effects of candesartan in addition to angiotensin-converting enzyme (ACE) inhibitors on N-terminal pro-type natriuretic peptide (Nt-proBNP), systemic markers of inflammation and oxidative stress as well as on glucose regulation in patients with heart failure (HF).&lt;p&gt;&lt;/p&gt; Methods and Results&lt;p&gt;&lt;/p&gt; Eighty patients with HF ages 62.5 ± 8.4 years presenting mostly with New York Heart Association class II symptoms (class II = 57.5%, III = 41.3%), and mean left ventricular ejection fraction 27.1 ± 7.3% were recruited. The patients were randomized to receive candesartan titrated to 32 mg 1 per day versus placebo in double-blind fashion for 6 months. Nt-proBNP, markers of inflammation and oxidative stress, glucose, insulin, and fasting insulin resistance index were analyzed. Candesartan decreased Nt-proBNP (median value = 12.4% versus −20.4%; [candesartan] P = .05), and high-sensitivity C-reactive protein (hsCRP) (+5.32% versus −20.3% [candesartan]; P = 0.046), without significantly influencing serum interleukin-6, interleukin-18, adhesion molecules, or markers of oxidative stress. Blood glucose decreased in patients treated with candesartan with a significantly greater effect in patients with higher blood glucose levels (P &#60; .01 for interaction).&lt;p&gt;&lt;/p&gt; Conclusions&lt;p&gt;&lt;/p&gt; The addition of candesartan to ACE inhibitor and β-blocker decreases Nt-proBNP and hsCRP, but does not change the other markers of inflammation or oxidative stress in patients with heart failure. Dual angiotensin-II suppression also decreased blood glucose with a greater impact in patients with higher blood glucose level

Effects of AGTR1 A1166C gene polymorphism in patients with heart failure treated with candesartan

&lt;b&gt;BACKGROUND:&lt;/b&gt; The benefits of angiotensin II receptor blockers (ARBs) in patients with heart failure who are treated with standard pharmacotherapy, including an angiotensin-converting enzyme (ACE) inhibitor, were demonstrated in 2 large randomized trials. It is currently impossible to determine which patient will benefit from the addition of an ARB.&lt;p&gt;&lt;/p&gt; &lt;b&gt;OBJECTIVE:&lt;/b&gt; To explore the impact of selected candidate genes on the hemodynamic, neurohormonal, and antiinflammatory effects of candesartan in patients with heart failure who are already being treated with an ACE inhibitor.&lt;p&gt;&lt;/p&gt; &lt;b&gt;METHODS:&lt;/b&gt; We investigated the impact of 10 candidate genetic polymorphisms on the effects of candesartan in patients with heart failure who are treated with an ACE inhibitor. We evaluated their impact on acute (2 wk) and long-term (24 wk) changes in blood pressure and N-terminal proB-type natriuretic peptide (NT-proBNP) and high sensitivity C-reactive protein (hsCRP) during treatment with candesartan.&lt;p&gt;&lt;/p&gt; &lt;b&gt;RESULTS:&lt;/b&gt; Thirty-one patients were included. Homozygotes of the AGTR1 A1166 allele (n = 13) had a greater decrease in systolic (–9.1 ± 4.7 vs 1.1 ± 3.3 mm Hg; p = 0.04 by analysis of variance [ANOVA], adjusting for dose) and diastolic blood pressure (–5.1± 1.5 vs 1.9 ± 1.9 mm Hg; p = 0.005 by ANOVA, adjusting for dose) compared with C1166 allele carriers (n = 18) following 2 weeks of treatment. After 6 months of treatment, C1166 carriers experienced a greater decrease in NT-proBNP (–151.4 [–207; –19.8] ng/L vs 147.3 [–61.3; 882.9] ng/L; p = 0.03) and hsCRP (–0.8 [–2.2;– 0.03] mg/L) vs 0.2 [–1.8; 5.3] mg/L; p = 0.09) compared with patients carrying the AA1166 genotype. No other significant association was found.&lt;p&gt;&lt;/p&gt; &lt;b&gt;CONCLUSIONS:&lt;/b&gt; The results of this proof-of concept study provide the first evidence that the AGTR1 A1166C polymorphism could influence the response to candesartan in patients with heart failure who are receiving ACE inhibitors. Validation of these exploratory findings in larger populations is required before use of the AGTR1 A1166C genotype can be incorporated into clinical practice