12 research outputs found
The effects of physical exercise on plasma levels of relaxin, NTproANP, and NTproBNP in patients with ischemic heart disease
The insulin-like and vasodilatatory polypeptide relaxin (RLX), formerly known as a pregnancy hormone, has gained interest as a potential humoral mediator in human heart failure. Controversy exists about the relation between plasma levels of RLX and the severity of heart failure. The present study was designed to determine the course of RLX, atrial, and brain natriuretic peptide (NT-proANP and NT-proBNP) during physical exercise in patients with ischemic heart disease (IHD) and to relate hormone levels to peak cardiac power output (CPO) as a measure of cardiopulmonary function with prognostic relevance. 40 patients with IHD were studied during right-heart-catheterization at rest and during supine bicycle ergometry. RLX, NTproBNP, and NTproANP were determined before, during exercise, and after recovery. NT-proANP and NT-proBNP levels increased during maximal charge, and recovery while RLX levels decreased. Cardiac power output at maximal charge correlated inversely with NTproANP and NTproBNP but positively with RLX. Patients with high degree heart failure (CPO < 1.96 W) had higher NTproANP and NTproB-NP and lower RLX levels than patients with low degree heart failure. While confirming the role of NTproANP and NTproBNP as markers for the severity of heart failure, the present data do not support the concept that plasma levels of RLX are related to the severity of myocardial dysfunction and that systemic RLX acts as a compensatory vasodilatatory response hormone in ischemic heart disease
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Building commissioning costs and savings across three decades and 1500 North American buildings
Building commissioning (Cx) is a process for assuring efficient building operations that can be applied to new construction and existing buildings, resulting in energy and non-energy benefits. Quantifying the benefits of commissioning is challenging, but a 2009 study of 643 commercial buildings provided a solid initial data set to which we added 839 additional buildings for a significantly expanded and updated meta-analysis representing 34.7 million square meters (373 million square feet) of floor area. Since 2009 the commissioning industry has continued to grow, driven by building codes, utility programs, and rising awareness of commissioning benefits. In parallel, building controls have become more sophisticated, and analytics software has emerged to assist with commissioning. We find that delivery mechanism and market segment are key determinants of outcomes, although significant and cost-effective savings are found across the spectrum. Median primary energy savings for Cx projects in existing buildings ranged from 5 percent for those conducted under utility programs, 9 percent for monitoring-based commissioning utility programs (i.e., augmented with submetering and diagnostics), and 14 percent for Cx projects outside of utility programs. Across all project types, median savings ranged from 3 percent for the lodging market segment to 16 percent for public order and safety facilities. Outcomes did not vary significantly by building size or by market segment. Energy savings are rarely estimated for new construction commissioning. We found that the median costs of Cx were lower for the 2018 sample than for the 2009 sample—0.26 per square foot) for existing buildings (a 33 percent reduction) and 0.82 per square foot) for new construction (a reduction of almost 50 percent). The median simple payback time for existing buildings was 1.7 years, with a 25th–75th percentile range of 0.8–3.5 years. This article summarizes these and other key findings, and discusses how the 2018 data reflects shifts in commissioning practice and outcomes
BRAF activates PAX3 to control muscle precursor cell migration during forelimb muscle development
Migration of skeletal muscle precursor cells is a key step during limb muscle development and depends on the activity of PAX3 and MET. Here, we demonstrate that BRAF serves a crucial function in formation of limb skeletal muscles during mouse embryogenesis downstream of MET and acts as a potent inducer of myoblast cell migration. We found that a fraction of BRAF accumulates in the nucleus after activation and endosomal transport to a perinuclear position. Mass spectrometry based screening for potential interaction partners revealed that BRAF interacts and phosphorylates PAX3. Mutation of BRAF dependent phosphorylation sites in PAX3 impaired the ability of PAX3 to promote migration of C2C12 myoblasts indicating that BRAF directly activates PAX3. Since PAX3 stimulates transcription of the Met gene we propose that MET signaling via BRAF fuels a positive feedback loop, which maintains high levels of PAX3 and MET activity required for limb muscle precursor cell migration
Mesenchymal stem cells attenuate inflammatory processes in the heart and lung via inhibition of TNF signaling
Mesenchymal stem cells ( MSC) have been used to treat different clinical conditions although the mechanisms by which pathogenetic processes are affected are still poorly understood. We have previously analyzed the homing of bone marrow-derived MSC to diseased tissues characterized by a high degree of mononuclear cell infiltration and postulated that MSC might modulate inflammatory responses. Here, we demonstrate that MSC mitigate adverse tissue remodeling, improve organ function, and extend lifespan in a mouse model of inflammatory dilative cardiomyopathy ( DCM). Furthermore, MSC attenuate Lipopolysaccharide-induced acute lung injury indicating a general role in the suppression of inflammatory processes. We found that MSC released sTNF-RI, which suppressed activation of the NFjBp65 pathway in cardiomyocytes during DCM in vivo. Substitution of MSC by recombinant soluble TNF-R partially recapitulated the beneficial effects of MSC while knockdown of TNF-R prevented MSC-mediated suppression of the NFjBp65 pathway and improvement of tissue pathology. We conclude that sTNF-RI is a major part of the paracrine machinery by which MSC effect local inflammatory reactions
Concomitant Activation of OSM and LIF Receptor by a Dual-Specific hlOSM Variant Confers Cardioprotection after Myocardial Infarction in Mice
Oncostatin M (OSM) and leukemia inhibitory factor (LIF) signaling protects the heart after myocardial infarction (MI). In mice, oncostatin M receptor (OSMR) and leukemia inhibitory factor receptor (LIFR) are selectively activated by the respective cognate ligands while OSM activates both the OSMR and LIFR in humans, which prevents efficient translation of mouse data into potential clinical applications. We used an engineered human-like OSM (hlOSM) protein, capable to signal via both OSMR and LIFR, to evaluate beneficial effects on cardiomyocytes and hearts after MI in comparison to selective stimulation of either LIFR or OSMR. Cell viability assays, transcriptome and immunoblot analysis revealed increased survival of hypoxic cardiomyocytes by mLIF, mOSM and hlOSM stimulation, associated with increased activation of STAT3. Kinetic expression profiling of infarcted hearts further specified a transient increase of OSM and LIF during the early inflammatory phase of cardiac remodeling. A post-infarction delivery of hlOSM but not mOSM or mLIF within this time period combined with cardiac magnetic resonance imaging-based strain analysis uncovered a global cardioprotective effect on infarcted hearts. Our data conclusively suggest that a simultaneous and rapid activation of OSMR and LIFR after MI offers a therapeutic opportunity to preserve functional and structural integrity of the infarcted heart