Adv Exp Med Biol
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We describe the extension of a computational model of blood flow and metabolism in the piglet brain to investigate changes in neonatal intracellular brain pH during hypoxia-ischemia (HI). The model is able to simulate near-infrared spectroscopy (NIRS) and magnetic resonance spectroscopy (MRS) measurements obtained from HI experiments conducted in piglets. We adopt a method of using (31)P-MRS data to estimate of intracellular pH and compare measured pH and oxygenation with their modelled counterparts. We show that both NIRS and MRS measurements are predicted well in the new version of the model.
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Phosphodiesterases (PDEs) are enzymes responsible for degradation of cAMP and cGMP in cells. Thus, PDE inhibitors may have significant clinical benefit in respiratory diseases associated with inflammation. The aim of the present study was to evaluate the effects of selective PDE4 (rolipram, ROL) and PDE7 inhibitors (BRL50481, BRL) on citric acid-induced cough, in vivo and in vitro airway smooth muscle reactivity in both healthy and ovalbumin sensitized guinea pigs. ⋯ In healthy guinea pigs, the only significant relaxation was observed after ROL in ACH-induced contractions in vitro and the effect on cough was negligible. In ovalbumin-sensitized animals, more pronounced in vitro relaxing effects of BRL in HIS-induced contractions and of combination (ROL+BRL) in ACH-induced contractions were observed, with similar results in vivo, and no significant change in the number of cough efforts was observed in any of the groups tested. The results suggest that PDE4 and PDE7 inhibitors have stronger anti-inflammatory effects compared with direct effects on smooth muscle and cough, with a potential benefit of their concomitant administration.
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Portable near-infrared spectroscopy (NIRS) has been shown to be a useful and reliable tool for monitoring muscle oxygenation and blood volume changes during dynamic exercise in elite athletes. The wearable nature of such technology permits the measurement of specific muscles/muscle groups during realistic sport-specific exercise tasks in an outdoor environment. The aim of this case study was to observe the effect on arm and leg muscle oxygenation of roller skiing over a typical outdoor racing course. ⋯ During the steep uphill section of the course, arm and leg TSI decreased equally in one subject (ΔTSI = -10 %), whereas there was a difference between the two muscle groups in the other subject (ΔTSIquadriceps = -2 %; ΔTSItriceps = -7 %). A difference was also seen between subjects during the downhill section of the course. This study presents the first example of the use of portable NIRS to assess oxygenation and blood volume changes in multiple muscle groups during roller skiing in a realistic, outdoor setting.
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Paroxysmal nocturnal hemoglobinuria (PNH) is a hematological disorder characterized by complement-mediated hemolytic anemia, thrombophilia, and bone marrow failure. PNH is due to a somatic, acquired mutation in the X-linked phosphatidylinositol glycan class A (PIG-A) gene, which impairs the membrane expression on affected blood cells of a number of proteins, including the complement regulators CD55 and CD59. The most evident clinical manifestations of PNH arise from dysregulated complement activation on blood cells; in fact, the hallmark of PNH is chronic, complement-mediated, intravascular hemolysis, which results in anemia, hemoglobinuria, fatigue, and other hemolysis-related disabling symptoms. ⋯ These findings have renewed the interest for the development of novel complement inhibitors which aim to modulate early phases of complement activation, more specifically at the level of C3 activation. As proof of principle of this concept, an anti-C3 monoclonal antibody has been proven effective in vitro to prevent hemolysis of PNH erythrocytes. More intriguingly, a human fusion protein consisting of the iC3b/ C3d-binding region of complement receptor 2 and of the inhibitory domain of the CAP regulator factor H has been recently shown effective in inhibiting, in vitro, both intravascular hemolysis of and surface C3-deposition on PNH erythrocytes, and is now under investigation in phase 1 clinical trials.
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Randomized Controlled Trial
Indacaterol add-on therapy improves lung function, exercise capacity and life quality of COPD patients.
Chronic obstructive pulmonary disease (COPD) is a progressive, inflammatory condition, involving airways and lung parenchyma. The disease leads to airflow limitation, and pulmonary hyperinflation, resulting in dyspnea, decreased exercise tolerance, and impaired quality of life. COPD pharmacotherapy guidelines are based on a combination of long-acting beta2-agonists (LABA), long-acting antimuscarinic agents (LAMA) and methyloxantins. ⋯ We also found that the degree of desaturation before and after 6MWD, and fatigue levels significantly improved in the indacaterol group. The patients' quality of life also changed favorably in the indacaterol treatment arm. We conclude that the add-on therapy with indacaterol exerts positive effects in COPD patients.