3-Hydroxykynurenine targets kainate receptors to promote defense against infection.

Bacterial infection involves a complex interaction between the pathogen and host where the outcome of infection is not solely determined by pathogen eradication. To identify small molecules that promote host survival by altering the host-pathogen dynamic, we conducted an in vivo chemical screen using zebrafish embryos and found that treatment with 3-hydroxykynurenine (3-HK) protects from lethal bacterial infection. 3-HK, a metabolite produced through host tryptophan metabolism, has no direct antibacterial activity but enhances host survival by restricting bacterial expansion in macrophages through a systemic mechanism that targets kainate-sensitive glutamate receptors.

Elevated heart rate and decreased muscle endothelial nitric oxide synthase in early development of insulin resistance.

Insulin resistance (IR) is a risk factor for the development of several major metabolic diseases. Muscle fiber composition is established early in life and is associated with insulin sensitivity. Hence, muscle fiber composition was used to identify early defects in the development of IR in healthy young individuals in the absence of clinical manifestations.

Pro-Brain-Derived Neurotrophic Factor (BDNF), but Not Mature BDNF, Is Expressed in Human Skeletal Muscle: Implications for Exercise-Induced Neuroplasticity.

Exercise promotes brain plasticity partly by stimulating increases in mature brain-derived neurotrophic factor (mBDNF), but the role of the pro-BDNF isoform in the regulation of BDNF metabolism in humans is unknown. We quantified the expression of pro-BDNF and mBDNF in human skeletal muscle and plasma at rest, after acute exercise (+/- lactate infusion), and after fasting. Pro-BDNF and mBDNF were analyzed with immunoblotting, enzyme-linked immunosorbent assay, immunohistochemistry, and quantitative polymerase chain reaction.

A tryptophan metabolite modulates the host response to bacterial infection via kainate receptors.

Bacterial infection involves a complex interaction between the pathogen and host where the outcome of infection is not solely determined by pathogen eradication. To identify small molecules that promote host survival by altering the host-pathogen dynamic, we conducted an chemical screen using zebrafish embryos and found that treatment with 3-hydroxy-kynurenine protects from lethal gram-negative bacterial infection. 3-hydroxy-kynurenine, a metabolite produced through host tryptophan metabolism, has no direct antibacterial activity but enhances host survival by restricting bacterial expansion in macrophages by targeting kainate-sensitive glutamate receptors.

Reduced glucose tolerance and insulin sensitivity after prolonged exercise in endurance athletes.

Aim: The purpose of this study was to 1. investigate if glucose tolerance is affected after one acute bout of different types of exercise; 2. assess if potential differences between two exercise paradigms are related to changes in mitochondrial function; and 3.

Insulin resistance after a 3-day fast is associated with an increased capacity of skeletal muscle to oxidize lipids.

There is a debate on whether lipid-mediated insulin resistance derives from an increased or decreased capacity of muscle to oxidize fats. Here, we examine the involvement of muscle fiber composition in the metabolic responses to a 3-day fast (starvation, which results in increases in plasma lipids and insulin resistance) in two groups of healthy young subjects: ), area occupied by type I fibers = 61.0 ± 11.

The lactate receptor GPR81 is predominantly expressed in type II human skeletal muscle fibers: potential for lactate autocrine signaling.

G-coupled protein receptor 81 (GPR81) was first identified in adipocytes as a receptor for l-lactate, which upon binding inhibits cyclicAMP (cAMP)-protein kinase (PKA)-cAMP-response element binding (CREB) signaling. Moreover, incubation of myotubes with lactate augments expression of GPR81 and genes and proteins involved in lactate- and energy metabolism. However, characterization of GPR81 expression and investigation of related signaling in human skeletal muscle under conditions of elevated circulating lactate levels are lacking.

Extreme Variations in Muscle Fiber Composition Enable Detection of Insulin Resistance and Excessive Insulin Secretion.

Context: Muscle fiber composition is associated with peripheral insulin action.

Objective: We investigated whether extreme differences in muscle fiber composition are associated with alterations in peripheral insulin action and secretion in young, healthy subjects who exhibit normal fasting glycemia and insulinemia.

Methods: Relaxation time following a tetanic contraction was used to identify subjects with a high or low expression of type I muscle fibers: group 1 (n = 11), area occupied by type I muscle fibers = 61.

Acute normobaric hypoxia blunts contraction-mediated mTORC1- and JNK-signaling in human skeletal muscle.

Aim: Hypoxia has been shown to reduce resistance exercise-induced stimulation of protein synthesis and long-term gains in muscle mass. However, the mechanism whereby hypoxia exerts its effect is not clear. Here, we examine the effect of acute hypoxia on the activity of several signalling pathways involved in the regulation of muscle growth following a bout of resistance exercise.

Contemporary Outcomes After Partial Resection of Infected Aortic Grafts.

Introduction: Aortic graft infection remains a considerable clinical challenge, and it is unclear which variables are associated with adverse outcomes among patients undergoing partial resection.

Methods: A retrospective, multi-institutional study of patients who underwent partial resection of infected aortic grafts from 2002 to 2014 was performed using a standard database. Baseline demographics, comorbidities, operative, and postoperative variables were recorded.

Role of nitration in control of phosphorylase and glycogenolysis in mouse skeletal muscle.

Phosphorylase is one of the most carefully studied proteins in history, but knowledge of its regulation during intense muscle contraction is incomplete. Tyrosine nitration of purified preparations of skeletal muscle phosphorylase results in inactivation of the enzyme and this is prevented by antioxidants. Whether an altered redox state affects phosphorylase activity and glycogenolysis in contracting muscle is not known.

Increasing disparity between Society for Vascular Surgery guidelines for infrarenal abdominal aortic aneurysm repair and real-world practice.

Objective: The current Society for Vascular Surgery (SVS) guidelines, based on randomized controlled trials published more than a decade ago, recommend a minimum threshold diameter of 5.5 cm for infrarenal abdominal aortic aneurysm (iAAA) repair. It is unknown whether practice patterns with respect to size of repair have changed since the publication of these guidelines.

In situ bypass and extra-anatomic bypass procedures result in similar survival in patients with secondary aortoenteric fistulas.

Objective: The optimal revascularization modality in secondary aortoenteric fistula (SAEF) remains unclear in the literature. The purpose of this investigation was to determine the revascularization approach associated with the lowest morbidity and mortality using real-world data in patients with SAEF.

Methods: A retrospective, multi-institutional study of SAEF from 2002 to 2014 was performed using a standardized database.

Transcranial contrast-enhanced ultrasound in the rat brain reveals substantial hyperperfusion acutely post-stroke.

Direct and real-time assessment of cerebral hemodynamics is key to improving our understanding of cerebral blood flow regulation in health and disease states such as stroke. While a number of sophisticated imaging platforms enable assessment of cerebral perfusion, most are limited either spatially or temporally. Here, we applied transcranial contrast-enhanced ultrasound (CEU) to measure cerebral perfusion in real-time through the intact rat skull before, during and after ischemic stroke, induced by intraluminal filament middle cerebral artery occlusion (MCAO).

Emergency intraoperative vascular surgery consultations at a tertiary academic center.

Objective: Vascular surgeons are frequently called on to provide emergency assistance to surgical colleagues. Whereas previous studies have included elective preoperative vascular consultations, we sought to characterize the breadth of assistance provided during unplanned intraoperative consultations at a single tertiary academic center.

Methods: We queried our institutional billing department during a 15-year period and reviewed the records (January 1, 2002-December 31, 2016) and identified unanticipated unplanned vascular surgery intraoperative consultations from all surgical services.

Isoproterenol enhances force production in mouse glycolytic and oxidative muscle via separate mechanisms.

Fight or flight is a biologic phenomenon that involves activation of β-adrenoceptors in skeletal muscle. However, how force generation is enhanced through adrenergic activation in different muscle types is not fully understood. We studied the effects of isoproterenol (ISO, β-receptor agonist) on force generation and energy metabolism in isolated mouse soleus (SOL, oxidative) and extensor digitorum longus (EDL, glycolytic) muscles.

Effect of postexercise temperature elevation on postexercise glycogen metabolism of isolated mouse soleus muscle.

The effects of temperature elevation after intense repeated contractions on glycogen and energy metabolism as well as contractile function of isolated mouse soleus muscle (slow twitch, oxidative) were investigated. Muscles were stimulated electrically to perform repeated tetanic contractions for 10 min at 25°C, which reduced tetanic force by ~85% and glycogen by 50%. After 120-min recovery at 25°C glycogen was fully restored (~125% of basal), whereas after recovery at 35°C glycogen decreased further (~25% of basal).

Pulsatile interaction between the macro-vasculature and micro-vasculature: proof-of-concept among patients with type 2 diabetes.

Purpose: It is widely thought that excess pulsatile pressure from increased stiffness of large central arteries (macro-vasculature) is transmitted to capillary networks (micro-vasculature) and causes target organ damage. However, this hypothesis has never been tested. We sought to examine the association between macro- and micro-vasculature waveform features in patients with type 2 diabetes (i.

Heating after intense repeated contractions inhibits glycogen accumulation in mouse EDL muscle: role of phosphorylase in postexercise glycogen metabolism.

The effects of heating on glycogen synthesis (incorporation of [C]glucose into glycogen) and accumulation after intense repeated contractions were investigated. Isolated mouse extensor digitorum longus muscle (type II) was stimulated electrically to perform intense tetanic contractions at 25°C. After 120 min recovery at 25°C, glycogen accumulated to almost 80% of basal, whereas after recovery at 35°C, glycogen remained low (~25% of basal).

Strategies and outcomes for aortic endograft explantation.

Background: Failure of endovascular aneurysm repairs (EVARs) requiring open conversion remains a major challenge. We analyzed indications for repair, operative strategies, and outcomes with a focus on iliac artery degeneration after endograft removal.

Methods: A prospective, institutional database was reviewed to identify patients who underwent explantation of a failed EVAR device.

Hallux Valgus/Medial Column Instability and Their Relationship with Posterior Tibial Tendon Dysfunction.

Historically, bunions have focused on the coronal plane; however, there is tension and compression failure in the sagittal plane of the midfoot during arch collapse. Correction of all 3 planes of deformity, coronal, sagittal, and rotational, can be achieved in several ways. Taking a big picture of global foot mechanics by recognizing the common types of conditions associated with arch collapse, including hallux valgus deformities, can serve as a useful roadmap for navigating more complicated deformities where hallux valgus exists.

Skeletal Muscle Microvascular-Linked Improvements in Glycemic Control From Resistance Training in Individuals With Type 2 Diabetes.

Objective: Insulin increases glucose disposal in part by enhancing microvascular blood flow (MBF) and substrate delivery to myocytes. Insulin's microvascular action is impaired with insulin resistance and type 2 diabetes. Resistance training (RT) improves glycemic control and insulin sensitivity, but whether this improvement is linked to augmented skeletal muscle microvascular responses in type 2 diabetes is unknown.

Determination of Skeletal Muscle Microvascular Flowmotion with Contrast-Enhanced Ultrasound.

Most methods of assessing flowmotion (rhythmic oscillation of blood flow through tissue) are limited to small sections of tissue and are invasive in tissues other than skin. To overcome these limitations, we adapted the contrast-enhanced ultrasound (CEUS) technique to assess microvascular flowmotion throughout a large region of tissue, in a non-invasive manner and in real time. Skeletal muscle flowmotion was assessed in anaesthetised Sprague Dawley rats, using CEUS and laser Doppler flowmetry (LDF) for comparison.

Regulation of microvascular flow and metabolism: An overview.

Skeletal muscle is an important site for insulin to regulate blood glucose levels. It is estimated that skeletal muscle is responsible for ~80% of insulin-mediated glucose disposal in the post-prandial period. The classical action of insulin to increase muscle glucose uptake involves insulin binding to insulin receptors on myocytes to stimulate glucose transporter 4 (GLUT 4) translocation to the cell surface membrane, enhancing glucose uptake.