Selenium-Binding Protein 1 Indicates Myocardial Stress and Risk for Adverse Outcome in Cardiac Surgery

Selenium-binding protein 1 (SELENBP1) is an intracellular protein that has been detected in the circulation in response to myocardial infarction. Hypoxia and cardiac surgery affect selenoprotein expression and selenium (Se) status. For this reason, we decided to analyze circulating SELENBP1 concentrations in patients (n = 75) necessitating cardioplegia and a cardiopulmonary bypass (CPB) during the course of the cardiac surgery. Serum samples were collected at seven time-points spanning the full surgical process. SELENBP1 was quantified by a highly sensitive newly developed immunological assay. Serum concentrations of SELENBP1 increased markedly during the intervention and showed a positive association with the duration of ischemia (ρ = 0.6, p < 0.0001). Elevated serum SELENBP1 concentrations at 1 h after arrival at the intensive care unit (post-surgery) were predictive to identify patients at risk of adverse outcome (death, bradycardia or cerebral ischemia, "endpoint 1"; OR 29.9, CI 3.3-268.8, p = 0.00027). Circulating SELENBP1 during intervention (2 min after reperfusion or 15 min after weaning from the CPB) correlated positively with an established marker of myocardial infarction (CK-MB) measured after the intervention (each with ρ = 0.5, p < 0.0001). We concluded that serum concentrations of SELENBP1 were strongly associated with cardiac arrest and the duration of myocardial ischemia already early during surgery, thereby constituting a novel and promising quantitative marker for myocardial hypoxia, with a high potential to improve diagnostics and prediction in combination with the established clinical parameters

Antagonistic Autoantibodies to Insulin-Like Growth Factor-1 Receptor Associate with Poor Physical Strength

Natural autoantibodies to the IGF1 receptor (IGF1R-aAb) have been described in relation to Graves' ophthalmopathy. Other physiological roles of natural IGF1R-aAb are not known. We hypothesized that IGF1R-aAb may be related to muscle development. Serum samples (n = 408) from young overweight subjects (n = 143) were collected during a lifestyle intervention study. Anthropometric parameters, along with leptin, IGF1 and IGF1R-aAb concentrations, were analyzed, and the subjects were categorized into positive or negative for IGF1R-aAb. Eleven out of 143 subjects (7.7%) were positive for IGF1R-aAb. Identified IGF1R-aAb were molecularly characterized and showed antagonistic activity in vitro impairing IGF1-mediated IGF1R activation. Mean body weight, height or age were similar between IGF1R-aAb-positive and -negative subjects, but IGF1 concentrations differed. Jumping ability, as well as right and left handgrip strengths, were lower in the IGF1R-aAb-positive as compared to the IGF1R-aAb-negative subjects. We conclude that natural IGF1R-aAb are detectable in apparently healthy subjects and are capable of antagonizing IGF1-dependent IGF1R activation. Moreover, the presence of IGF1R-aAb is associated with poor physical strength. Although the causality of this association is unclear, the data imply a potential influence of IGF1R autoimmunity on muscle development

On-line and real time cell counting and viability determination for animal cell process monitoring by in situ microscopy

International audienc

Adenosine induces growth-cone turning of sensory neurons

The formation of appropriate connections between neurons and their specific targets is an essential step during development and repair of the nervous system. Growth cones are located at the leading edges of the growing neurites and respond to environmental cues in order to be guided to their final targets. Directional information can be coded by concentration gradients of substrate-bound or diffusible-guidance molecules. Here we show that concentration gradients of adenosine stimulate growth cones of sensory neurons (dorsal root ganglia) from chicken embryos to turn towards the adenosine source. This response is mediated by adenosine receptors. The subsequent signal transduction process involves cAMP. It may be speculated that the in vivo function of this response is concerned with the formation or the repair and regeneration of the peripheral nervous system

Detection, prevalence and physiological significance of autoantibodies to the insulin like growth factor-1 receptor in humans

Die Inzidenz von Autoimmunitäten nimmt weltweit zu, und die Beteiligung von Autoantikörpern (aAK) wird zunehmend als pathologisches Prinzip bei Erkrankungen anerkannt. Natürliche Autoantikörper gegen den IGF1-Rezeptor (IGF1R-aAK) wurden im Zusammenhang mit der Endokrinen Orbitopathie (Graves‘ Ophthalmopathy, GO) beschrieben. Andere physiologische Funktionen von natürlichen IGF1R-aAK sind aktuell nicht bekannt. Bei Patienten mit Morbus Basedow und gesunden Kontrollen zeigte sich eine relativ hohe Prävalenz von IGF1R-aAK. Der IGF1-Rezeptor (IGF1R) ist für die Energiehomöostase, körperliche Entwicklung und für Wachstum von Knochen und Muskulatur von hoher Bedeutung. Für die Identifizierung von Patienten mit IGF1RaAK wurde im Rahmen dieser Arbeit ein Test aufgebaut, bei dem ein Luciferase-IGF1RFusionsprotein genutzt wird. Anhand einer klinischen Beobachtungsstudie sollte getestet werden, ob die IGF1R-aAK mit der Körperkraft im Menschen assoziiert ist. Hierzu wurden Serumproben (n = 408) von jungen übergewichtigen Probanden (n = 143) während einer Lebensstilinterventionsstudie analysiert. Die Probanden konnten in zwei Kategorien eingeteilt werden, i.e., mit oder ohne nachweisbare IGF1RaAK. Elf von 143 Probanden (7,7%) erwiesen sich anhand der Kriterien für Ausreißer- Werte als positiv für IGF1R-aAK. Von einigen der positiven und negativen Seren wurden die Antikörper isoliert. Diese zeigten in vitro eine antagonistische Aktivität am IGF1R. Beim Vergleich der Probanden zeigten sich keine Unterschiede im mittleren Körpergewicht, BMI, Körpergröße oder Alter. Allerdings unterschieden sich die IGF1- und Leptin-Konzentrationen zwischen den IGF1R-aAK-positiven und -negativen Probanden in einer Weise, die ein ungünstiges Verhältnis von Muskel- zu Fett-Anteil bei den IGF1R-aAK positiven Probanden erwarten lassen. Diese Hypothese wurde beim Vergleich von drei Parametern der Körperkraft unterstrichen. Die Sprungfähigkeit aus dem Stand sowie die Stärke der rechten und linken Hand waren bei den IGF1R-aAKpositiven Probanden im Vergleich zu den IGF1R-aAK-negativen Probanden signifikant geringer. Wir schlussfolgern, dass natürlich vorkommende IGF1R-aAK bei scheinbar gesunden Probanden nachweisbar sind und für die IGF1-abhängige IGF1R-Aktivierung als Antagonisten wirken können und mit einer reduzierten physischen Kraft verbunden sind. Obwohl die Kausalität dieser Assoziation unklar ist, implizieren die Daten einen möglichen Einfluss der IGF1R-Autoimmunität auf die Muskelentwicklung.The incidence of autoimmunity is globally on the rise, and the involvement of autoantibodies (aAb) is increasingly recognized as a pathological principle in a growing number of human diseases. Natural autoantibodies to the IGF1 receptor (IGF1R-aAb) have been described in relation to Graves' ophthalmopathy (GO). Other physiological roles of natural IGF1R-aAb are not known. We reported a relatively high prevalence of aAb against the IGF1R in Graves´ disease patients and controls. The IGF1 receptor (IGF1R) is important for energy homeostasis, physical development and growth of bone and muscle. In order to enable the identification of patients with IGF1R-aAb, new diagnostic methods were developed as part of this work. An assay based on an immunoprecipitation step was developed employing a fusion protein of the IGF1R with firefly luciferase. In this study, the hypothesis was tested that IGF1R-aAb is associated with the development of muscles and physical strength in humans. Serum samples (n = 408) from young overweight subjects (n = 143) were collected during a lifestyle intervention study. Anthropometric parameters along with leptin, IGF1 and IGF1R-aAb concentrations were analyzed, and the subjects were categorized into positive or negative for IGF1R-aAb. Eleven out of 143 subjects (7.7%) were positive for IGF1R-aAb based on the mathematical criteria for outlier values. Identified IGF1R-aAb were molecularly characterized and showed antagonistic activity in vitro impairing IGF1-mediated IGF1R activation. Mean body weight, height or age were similar between IGF1R-aAb positive and negative subjects. However, the IGF1 and leptin concentrations differed between the IGF1R-aAb positive and negative subjects in a way that an unfavorable muscle-to-fat ratio can be expected in the IGF1R-aAb positive subjects. This hypothesis was underlined when comparing three parameters of physical strength. Jumping ability as well as right and left handgrip strengths were significantly lower in the IGF1R-aAb positive as compared to the IGF1R-aAb negative subjects. We conclude that natural IGF1R-aAb are detectable in apparently healthy subjects and are capable of antagonizing IGF1-dependent IGF1R activation. Moreover, presence of IGF1R-aAb is associated with poor physical strength. Even though the causality of this association is unclear, the data imply a potential influence of IGF1R autoimmunity on muscle development

Postconditioning by xenon and hypothermia in the rat heart in vivo

Background and objective Hypothermia protects against myocardial reperfusion injury. However, inducing hypothermia takes time, which makes it unsuitable as an emergency treatment. Combining mild hypothermia with low-dose xenon, applied either simultaneously or one after the other, protects the neonatal rat brain against reperfusion injury. We investigated whether xenon, administered prior to hypothermia or simultaneously with hypothermia, also protects the rat heart from reperfusion injury. Methods Anaesthetized rats (chloralose, ketamine, diazepam) were randomly allocated to five groups and subjected to 25 min coronary artery occlusion, followed by 120 min reperfusion. At the onset of reperfusion, controls received no intervention and inhaled oxygen in air with an inspired oxygen fraction of 0.8 (Con80). Further groups received either 1 h of mild hypothermia of 34 degrees C (Hypo34) or 30 min of xenon 20% (Xe20). Additional groups received xenon 20% and hypothermia 34 degrees C simultaneously (Xe20+Hypo34) or in succession (Xe20! Hypo34). Infarct sizes were assessed by triphenyltetrazolium chloride staining. Results The combination of xenon 20% and hypothermia 34 degrees C significantly reduced infarct size [Xe20+Hypo34: 55(22)%, mean (SD)] compared with control [Con80: 76(12)%, P = 0.03]. Xenon and hypothermia in succession produced no infarct size reduction. Conclusion The combination of xenon 20% and hypothermia of 34 degrees C, applied during early reperfusion, reduces infarct size in the rat heart in vivo. Eur J Anaesthesiol 2010; 27:734-73