The effects of chest wall loading on perceptions of fatigue, exercise performance, pulmonary function, and muscle perfusion.

BACKGROUND: Load carriage (LC), which directly affects the chest wall and locomotor muscles, has been suggested to alter the ventilatory and circulatory responses to exercise, leading to increased respiratory muscle work and fatigue. However, studies exploring the impact of LC on locomotion increased internal work, complicating their interpretation. To overcome this issue, we sought to determine the effect of chest wall loading with restriction (CWL + R) on cycling performance, cardiopulmonary responses, microvascular responsiveness, and perceptions of fatigue. METHODS: In a randomized crossover design, 23 young healthy males (22 \ub1 4 years) completed a 5 km cycling time trial (TT) in loaded (CWL + R; tightened vest with 10% body weight) and unloaded conditions. After baseline pulmonary function testing (PFT; forced expiratory volume in 1 s, FEV1; forced vital capacity, FVC), cardiopulmonary indices (HR, heart rate; O2 uptake, VO2; ventilation, VE; tidal volume, VT; and breathing frequency, Bf), rating of perceived exertion (RPE), lactate (BLa), and microvascular responses (oxy-, deoxy-, total hemoglobin; and tissue saturation; StO2) of the vastus lateralis using near infrared spectroscopy were collected during the TT; and PFT was repeated post-exercise. RESULTS: Pre-exercise, CWL + R reduced (p < 0.05) FVC (5.6 \ub1 0.8 versus 5.5 \ub1 0.7 L), FEV1 (4.8 \ub1 0.7 versus 4.7 \ub1 0.6 L), and FEV1/FVC (0.9 \ub1 0.1 versus 0.8 \ub1 0.1). CWL + R modified power output (PO) over time (interaction, p = 0.02), although the 5 km time (461 \ub1 24 versus 470 \ub1 27 seconds), VT (3.0 \ub1 0.3 versus 2.8 \ub1 0.8 L), Bf, VE, HR, VO2, microvascular and perceptual (visual analog scale, or VAS, and RPE) responses were unchanged (p > 0.05). CWL + R increased (p < 0.05) the average BLa (7.6 \ub1 2.6 versus 8.6 \ub1 3 mmol/L). CONCLUSIONS: Modest CWL + R negatively affects pre-exercise pulmonary function, modifies cycling power output over time, and increases lactate production during a 5 km cycling trial, although the cardiorespiratory, microvascular, and perceptual responses were unaffected

Effects of Capsaicin on the Hemodynamic Responses to Handgrip Exercise: Potential Influence of Race

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Exercise training improves vascular function in patients with Alzheimer’s disease

Purpose: Vascular dysfunction has been demonstrated in patients with Alzheimer’s disease (AD). Exercise is known to positively affect vascular function. Thus, the aim of our study was to investigate exercise-induced effects on vascular function in AD. Methods: Thirty-nine patients with AD (79 ± 8 years) were recruited and randomly assigned to exercise training (EX, n = 20) or control group (CTRL, n = 19). All subjects performed 72 treatment sessions (90 min, 3 t/w). EX included moderate–high-intensity aerobic and strength training. CTRL included cognitive stimuli (visual, verbal, auditive). Before and after the 6-month treatment, the vascular function was measured by passive-leg movement test (PLM, calculating the variation in blood flow: ∆peak; and area under the curve: AUC) tests, and flow-mediated dilation (FMD, %). A blood sample was analyzed for vascular endothelial growth factor (VEGF). Arterial blood flow (BF) and shear rate (SR) were measured during EX and CTRL during a typical treatment session. Results: EX group has increased FMD% (+ 3.725%, p ' 0.001), PLM ∆peak (+ 99.056 ml/min, p = 0.004), AUC (+ 37.359AU, p = 0.037) and VEGF (+ 8.825 pg/ml, p = 0.004). In the CTRL group, no difference between pre- and post-treatment was found for any variable. Increase in BF and SR was demonstrated during EX (BF + 123%, p ' 0.05; SR + 134%, p ' 0.05), but not during CTRL treatment. Conclusion: Exercise training improves peripheral vascular function in AD. These ameliorations may be due to the repetitive increase in SR during exercise which triggers NO and VEGF upregulation. This approach might be included in standard AD clinical practice as an effective strategy to treat vascular dysfunction in this population

Inhibition of Rac controls NPM–ALK-dependent lymphoma development and dissemination

Nucleophosmin-anaplastic lymphoma kinase (NPM–ALK) is a tyrosine kinase oncogene responsible for the pathogenesis of the majority of human ALK-positive lymphomas. We recently reported that it activated the Rac1 GTPase in anaplastic large-cell lymphoma (ALCL), leading to Rac-dependent formation of active invadopodia required for invasiveness. Herein, we went further into the study of this pathway and used the inhibitor of Rac, NSC23766, to validate its potential as a molecular target in ALCL in vitro and in vivo in a xenograft model and in a conditional model of NPM–ALK transgenic mice. Our data demonstrate that Rac regulates important effectors of NPM–ALK-induced transformation such as Erk1/2, p38 and Akt. Moreover, inhibition of Rac signaling abrogates NPM–ALK-elicited disease progression and metastasis in mice, highlighting the potential of small GTPases and their regulators as additional therapic targets in lymphomas

Loss of p19Arf Facilitates the Angiogenic Switch and Tumor Initiation in a Multi-Stage Cancer Model via p53-Dependent and Independent Mechanisms

The Arf tumor suppressor acts as a sensor of oncogenic signals, countering aberrant proliferation in large part via activation of the p53 transcriptional program, though a number of p53-independent functions have been described. Mounting evidence suggests that, in addition to promoting tumorigenesis via disruptions in the homeostatic balance between cell proliferation and apoptosis of overt cancer cells, genetic alterations leading to tumor suppressor loss of function or oncogene gain of function can also incite tumor development via effects on the tumor microenvironment. In a transgenic mouse model of multi-stage pancreatic neuroendocrine carcinogenesis (PNET) driven by inhibition of the canonical p53 and Rb tumor suppressors with SV40 large T-antigen (Tag), stochastic progression to tumors is limited in part by a requirement for initiation of an angiogenic switch. Despite inhibition of p53 by Tag in this mouse PNET model, concomitant disruption of Arf via genetic knockout resulted in a significantly accelerated pathway to tumor formation that was surprisingly not driven by alterations in tumor cell proliferation or apoptosis, but rather via earlier activation of the angiogenic switch. In the setting of a constitutional p53 gene knockout, loss of Arf also accelerated tumor development, albeit to a lesser degree. These findings demonstrate that Arf loss of function can promote tumorigenesis via facilitating angiogenesis, at least in part, through p53-independent mechanisms