Red blood cell ATP release correlates with red blood cell hemolysis.

The precise matching of blood flow to skeletal muscle during exercise remains an important area of investigation. Release of adenosine triphosphate (ATP) from red blood cells (RBCs) is postulated as a mediator of peripheral vascular tone in response to shear stress, hypoxia, and mechanical deformation. We tested the following hypotheses: ) RBCs of different densities contain different quantities of ATP; ) hypoxia is a stimulus for ATP release from RBCs; and ) hypoxic ATP release from RBCs is related to RBC lysis.

Real-Time Monitoring of a Protein Biomarker.

The ability to monitor protein biomarkers continuously and in real-time would significantly advance the precision of medicine. Current protein-detection techniques, however, including ELISA and lateral flow assays, provide only time-delayed, single-time-point measurements, limiting their ability to guide prompt responses to rapidly evolving, life-threatening conditions. In response, here we present an electrochemical aptamer-based sensor (EAB) that supports high-frequency, real-time biomarker measurements.

Effect of acute nitrite infusion on contractile economy and metabolism in isolated skeletal muscle in situ during hypoxia.

Key Points: Increased plasma nitrite concentrations may have beneficial effects on skeletal muscle function. The physiological basis explaining these observations has not been clearly defined and it may involve positive effects on muscle contraction force, microvascular O delivery and skeletal muscle oxidative metabolism. In the isolated canine gastrocnemius model, we evaluated the effects of acute nitrite infusion on muscle force and skeletal muscle oxidative metabolism.

Correction to: Ten weeks of branched-chain amino acid supplementation improves select performance and immunological variables in trained cyclists.

For the author R. Mac Thompson, the first name should be R. Mac and the last name should be Thompson.

Arteriolar vasodilation involves actin depolymerization.

It is generally assumed that relaxation of arteriolar vascular smooth muscle occurs through hyperpolarization of the cell membrane, reduction in intracellular Ca concentration, and activation of myosin light chain phosphatase/inactivation of myosin light chain kinase. We hypothesized that vasodilation is related to depolymerization of F-actin. Cremaster muscles were dissected in rats under pentobarbital sodium anesthesia (50 mg/kg).

Chronic interval exercise training prevents BK channel-mediated coronary vascular dysfunction in aortic-banded miniswine.

Conventional treatments have failed to improve the prognosis of heart failure with preserved ejection fraction (HFpEF) patients. Thus, the purpose of this study was to determine the therapeutic efficacy of chronic interval exercise training (IT) on large-conductance Ca-activated K (BK) channel-mediated coronary vascular function in heart failure. We hypothesized that chronic interval exercise training would attenuate pressure overload-induced impairments to coronary BK channel-mediated function.

Chronic low-intensity exercise attenuates cardiomyocyte contractile dysfunction and impaired adrenergic responsiveness in aortic-banded mini-swine.

Exercise improves clinical outcomes in patients diagnosed with heart failure with reduced ejection fraction (HFrEF), in part via beneficial effects on cardiomyocyte Ca cycling during excitation-contraction coupling (ECC). However, limited data exist regarding the effects of exercise training on cardiomyocyte function in patients diagnosed with heart failure with preserved ejection fraction (HFpEF). The purpose of this study was to investigate cardiomyocyte Ca handling and contractile function following chronic low-intensity exercise training in aortic-banded miniature swine and test the hypothesis that low-intensity exercise improves cardiomyocyte function in a large animal model of pressure overload.

Lactate metabolism: historical context, prior misinterpretations, and current understanding.

Lactate (La) has long been at the center of controversy in research, clinical, and athletic settings. Since its discovery in 1780, La has often been erroneously viewed as simply a hypoxic waste product with multiple deleterious effects. Not until the 1980s, with the introduction of the cell-to-cell lactate shuttle did a paradigm shift in our understanding of the role of La in metabolism begin.

Is the Rational Addiction model inherently impossible to estimate?

The Rational Addiction (RA) model is increasingly often estimated using individual level panel data with mixed results; in particular, with regard to the implied rate of time discount. This paper suggests that the odd values of the rate of discount frequently found in the literature may in fact be a consequence of the saddle-point dynamics associated with individual level inter-temporal optimization problems. We report the results of Monte Carlo experiments estimating RA-type difference equations that seem to suggest the possibility that the presence of both a stable and an unstable root in the dynamic process may create serious problems for the estimation of RA equations.

The protective role of sex hormones in females and exercise prehabilitation in males on sternotomy-induced cranial hypoperfusion in aortic banded mini-swine.

During cardiac surgery, specifically sternotomy, cranial hypoperfusion is linked to cerebral ischemia, increased risk of perioperative watershed stroke, and other neurocognitive complications. The purpose of this study was to retrospectively examine the effect of sex hormones in females and exercise prehabilitation in males on median sternotomy-induced changes in cranial perfusion in a large animal model of heart failure. Cranial blood flow (CBF) before and 10 and 60 min poststernotomy was analyzed in eight groups of Yucatan mini-swine: female control, aortic banded, ovariectomized, and ovariectomized + aortic banded; male control, aortic banded, aortic banded + continuous exercise trained, and aortic banded + interval exercise trained.

Muscle Near-Infrared Spectroscopy Signals versus Venous Blood Hemoglobin Oxygen Saturation in Skeletal Muscle.

Purpose: The study aimed to examine the relationship between near-infrared spectroscopy (NIRS) signals and venous hemoglobin oxygen saturation (O2Hb%) and venous oxygen concentration (CvO2).

Methods: Gastrocnemius muscles (GS) in six dogs were surgically isolated and pump perfused. NIRS signals were recorded, and venous blood samples were collected at constant flow rates (control flow, high flow, and low flow) at rest as well as during electrically stimulated tetanic muscle contractions at rates of one contraction per 2 s (1/2 s) and two contractions per 3 s (2/3 s).

Carotid Artery Vascular Mechanics Serve as Biomarkers of Cognitive Dysfunction in Aortic-Banded Miniature Swine That Can Be Treated With an Exercise Intervention.

Background: Cognitive impairment in the setting of heart failure with preserved ejection fraction remains poorly understood. Using aortic-banded miniature swine displaying pathological features of human heart failure with preserved ejection fraction, we tested the hypothesis that increased carotid artery stiffness and altered carotid blood flow control are associated with impaired memory independent of decreased cardiac output. Furthermore, we hypothesized that chronic exercise prevents carotid artery vascular restructuring and preserves normal blood flow control and cognition in heart failure with preserved ejection fraction.

Saxagliptin and Tadalafil Differentially Alter Cyclic Guanosine Monophosphate (cGMP) Signaling and Left Ventricular Function in Aortic-Banded Mini-Swine.

Background: Cyclic guanosine monophosphate-protein kinase G-phosphodiesterase 5 signaling may be disturbed in heart failure (HF) with preserved ejection fraction, contributing to cardiac remodeling and dysfunction. The purpose of this study was to manipulate cyclic guanosine monophosphate signaling using the dipeptidyl-peptidase 4 inhibitor saxagliptin and phosphodiesterase 5 inhibitor tadalafil. We hypothesized that preservation of cyclic guanosine monophosphate cGMP signaling would attenuate pathological cardiac remodeling and improve left ventricular (LV) function.

Ten weeks of branched-chain amino acid supplementation improves select performance and immunological variables in trained cyclists.

We examined if supplementing trained cyclists (32 ± 2 year, 77.8 ± 2.6 kg, and 7.

Molecular Mechanisms for Exercise Training-Induced Changes in Vascular Structure and Function: Skeletal Muscle, Cardiac Muscle, and the Brain.

Compared with resting conditions, during incremental exercise, cardiac output in humans is elevated from ~5 to 25 L min(-1). In conjunction with this increase, the proportion of cardiac output directed toward skeletal muscle increases from ~20% to 85%, while blood flow to cardiac muscle increases 500% and blood flow to specific brain structures increases nearly 200%. Based on existing evidence, researchers believe that blood flow in these tissues is matched to the increases in metabolic rate during exercise.

Effects of oral phosphatidic acid feeding with or without whey protein on muscle protein synthesis and anabolic signaling in rodent skeletal muscle.

Background: Phosphatidic acid (PA) is a diacyl-glycerophospholipid that acts as a signaling molecule in numerous cellular processes. Recently, PA has been proposed to stimulate skeletal muscle protein accretion, but mechanistic studies are lacking. Furthermore, it is unknown whether co-ingesting PA with other leucine-containing ingredients can enhance intramuscular anabolic signaling mechanisms.

Effects of protein type and composition on postprandial markers of skeletal muscle anabolism, adipose tissue lipolysis, and hypothalamic gene expression.

Background: We examined the acute effects of different dietary protein sources (0.19 g, dissolved in 1 ml of water) on skeletal muscle, adipose tissue and hypothalamic satiety-related markers in fasted, male Wistar rats (~250 g).

Methods: Oral gavage treatments included: a) whey protein concentrate (WPC, n = 15); b) 70:30 hydrolyzed whey-to-hydrolyzed egg albumin (70 W/30E, n = 15); c) 50 W/50E (n = 15); d) 30 W/70E (n = 15); and e) 1 ml of water with no protein as a fasting control (CTL, n = 14).

Lactate is always the end product of glycolysis.

Through much of the history of metabolism, lactate (La(-)) has been considered merely a dead-end waste product during periods of dysoxia. Congruently, the end product of glycolysis has been viewed dichotomously: pyruvate in the presence of adequate oxygenation, La(-) in the absence of adequate oxygenation. In contrast, given the near-equilibrium nature of the lactate dehydrogenase (LDH) reaction and that LDH has a much higher activity than the putative regulatory enzymes of the glycolytic and oxidative pathways, we contend that La(-) is always the end product of glycolysis.

L-leucine, beta-hydroxy-beta-methylbutyric acid (HMB) and creatine monohydrate prevent myostatin-induced Akirin-1/Mighty mRNA down-regulation and myotube atrophy.

Background: The purpose of this study was to examine if L-leucine (Leu), β-hydroxy-β-methylbutyrate (HMB), or creatine monohydrate (Crea) prevented potential atrophic effects of myostatin (MSTN) on differentiated C2C12 myotubes.

Methods: After four days of differentiation, myotubes were treated with MSTN (10 ng/ml) for two additional days and four treatment groups were studied: 1) 3x per day 10 mM Leu, 2) 3x per day 10 mM HMB, 3) 3x per day 10 mM Crea, 4) DM only. Myotubes treated with DM without MSTN were analyzed as the control condition (DM/CTL).

Slowed muscle oxygen uptake kinetics with raised metabolism are not dependent on blood flow or recruitment dynamics.

Oxygen uptake kinetics (τVO2) are slowed when exercise is initiated from a raised metabolic rate. Whether this reflects the recruitment of muscle fibres differing in oxidative capacity, or slowed blood flow (Q) kinetics is unclear. This study determined τVO2 in canine muscle in situ, with experimental control over muscle activation and Q during contractions initiated from rest and a raised metabolic rate.

Real-time, aptamer-based tracking of circulating therapeutic agents in living animals.

A sensor capable of continuously measuring specific molecules in the bloodstream in vivo would give clinicians a valuable window into patients' health and their response to therapeutics. Such technology would enable truly personalized medicine, wherein therapeutic agents could be tailored with optimal doses for each patient to maximize efficacy and minimize side effects. Unfortunately, continuous, real-time measurement is currently only possible for a handful of targets, such as glucose, lactose, and oxygen, and the few existing platforms for continuous measurement are not generalizable for the monitoring of other analytes, such as small-molecule therapeutics.

Microfluidic chip-based detection and intraspecies strain discrimination of Salmonella serovars derived from whole blood of septic mice.

Salmonella is a zoonotic pathogen that poses a considerable public health and economic burden in the United States and worldwide. Resultant human diseases range from enterocolitis to bacteremia to sepsis and are acutely dependent on the particular serovar of Salmonella enterica subsp. enterica, which comprises over 99% of human-pathogenic S.

Selection of phage-displayed peptides on live adherent cells in microfluidic channels.

Affinity reagents that bind to specific molecular targets are an essential tool for both diagnostics and targeted therapeutics. There is a particular need for advanced technologies for the generation of reagents that specifically target cell-surface markers, because transmembrane proteins are notoriously difficult to express in recombinant form. We have previously shown that microfluidics offers many advantages for generating affinity reagents against purified protein targets, and we have now significantly extended this approach to achieve successful in vitro selection of T7 phage-displayed peptides that recognize markers expressed on live, adherent cells within a microfluidic channel.

Integrated microfluidic electrochemical DNA sensor.

Effective systems for rapid, sequence-specific nucleic acid detection at the point of care would be valuable for a wide variety of applications, including clinical diagnostics, food safety, forensics, and environmental monitoring. Electrochemical detection offers many advantages as a basis for such platforms, including portability and ready integration with electronics. Toward this end, we report the Integrated Microfluidic Electrochemical DNA (IMED) sensor, which combines three key biochemical functionalities--symmetric PCR, enzymatic single-stranded DNA generation, and sequence-specific electrochemical detection--in a disposable, monolithic chip.