Einfluß der parenteralen Gabe von langkettigen Fettsäuren auf den Prostanoidstoffwechsel bei septischen Patienten

In der vorliegenden Studie wurde im Rahmen einer totalen parenteralen Ernährung der Einfluß von Liposyn 20%, einer Fettemulsion die aus ungesättigten langkettigen Fettsäuren, insbesondere Linolsäure besteht, auf den Eikosanoidstoffwechsel von septischen Patienten untersucht. Auf der septischen Intensivstation des Zentralklinikums Augsburg wurden eine Kurzzeit-studie und eine Langzeitstudie an septischen Patienten durchgeführt. An der Kurzzeitstudie, die über 4 Tage ging nahmen 12 Patienten teil, an der Langzeit-studie mit einer Dauer von 10 Tagen nahmen 6 Patienten teil. In jeder der beiden Studien wurde die eine Hälfte der Patienten ausschließlich mit einem Kohlenhydratgemisch ernährt, während in der anderen Gruppe 50% der Nichteiweißkalorien durch Liposyn 20% bereitgestellt wurden. Insgesamt bekamen die Patienten 30 kcal/kg Körpergewicht pro Tag an Nichteiweißkalorien parenteral verabreicht. Zusätzlich wurde in allen Gruppen den Patienten 100g Aminosäuren pro Tag gegeben. Zur Vergleichbarkeit der Patienten in Hinblick auf ihre Erkrankungsschwere untereinander wurde nachträglich bei jedem Patienten der APACHE III-Score für jeden Studientag ermittelt. In dem Eikosanoidlabor der Kinderklinik der Universität Marburg wurden mittels Gaschromatographie/Massenspektrometrie folgende Indexmetabolite der Eikosanoide gemessen: - 11-dehydro-TxB2 im Plasma (Maß für die phasische TxA2-Produktion), - TxB2 im 24h Urin (Maß für die renale TxA2-Produktion), - 2,3-dinor-TxB2 im 24h Urin (Maß für die systemische TxA2-Produktion), - 2,3-dinor-6-keto-PGF1 im 24h Urin (Maß für die systemische PGI2- Produktion), - PGE-M im 24h-Urin (Maß für die systemische PGE2-Produktion). Zusätzlich wurden die Triglyceride und Cholesterinester im Plasma, sowie der Linolsäuregehalt in den Cholesterinestern bestimmt. Unter Berücksichtigung des APACHE-Score bestanden keine wesentlichen Unterschiede in Hinblick auf die Erkrankungsschwere bei den untersuchten Patienten. Die Letalität war in der Kurzzeitstudie in der Kontrollgruppe etwas höher als in der Fettgruppe. In der Langzeitstudie war die Letalität in beiden Gruppen gleich groß. Die Triglycerid- und Cholesterinwerte lagen im Normbereich was für eine gute Elimination und Verstoffwechslung der infundierten Fettemulsion spricht. Bei allen Patienten zeigten sich stark erhöhte Eikosanoidwerte. Weder in der Kurzzeit- noch in der Langzeitstudie ließen sich deutliche Unterschiede in der Eikosanoidproduktion unter Gabe von Liposyn 20% nachweisen. Ursache hierfür scheint zu sein, dass es durch die bei der Sepsis verstärkte Lipolyse zu einer vermehrten Freisetzung von Arachidonsäure aus den Phospholipiden der Zellmembranen kommt. Dieser Anstieg an verfügbarer Arachidonsäure führte zu einer Erhöhung der Eikosanoidproduktion in beiden Gruppen. Die zusätzliche Gabe von Linolsäure führte offensichtlich jedoch nicht zu einer vermehrten Bereitstellung von Arachidonsäure in der Fettgruppe, was durch die geschwindigkeitsbestimmenden Desaturasen erklärt werden kann. Sicherlich besteht bei Zufuhr von Linolsäure über einen längeren Zeitraum auch die Möglichkeit einer vermehrten Bereitstellung von Arachidonsäure. Die in der Studie gewählten Zeiträume waren aber offensichtlich zu kurz, um dies zu bewirken. Die Ergebnisse dieser Studie zeigen somit, dass in Bezug auf die gemessenen Eikosanoide keine Gründe gegen die Verwendung von langkettigen ungesättigten Fettsäuren als Bestandteil der totalen parenteralen Ernährung für die Dauer des untersuchten Beobachtungszeitraumes sprechen

Magnetohydrodynamics dynamical relaxation of coronal magnetic fields. II. 2D magnetic X-points

We provide a valid magnetohydrostatic equilibrium from the collapse of a 2D X-point in the presence of a finite plasma pressure, in which the current density is not simply concentrated in an infinitesimally thin, one-dimensional current sheet, as found in force-free solutions. In particular, we wish to determine if a finite pressure current sheet will still involve a singular current, and if so, what is the nature of the singularity. We use a full MHD code, with the resistivity set to zero, so that reconnection is not allowed, to run a series of experiments in which an X-point is perturbed and then is allowed to relax towards an equilibrium, via real, viscous damping forces. Changes to the magnitude of the perturbation and the initial plasma pressure are investigated systematically. The final state found in our experiments is a "quasi-static" equilibrium where the viscous relaxation has completely ended, but the peak current density at the null increases very slowly following an asymptotic regime towards an infinite time singularity. Using a high grid resolution allows us to resolve the current structures in this state both in width and length. In comparison with the well known pressureless studies, the system does not evolve towards a thin current sheet, but concentrates the current at the null and the separatrices. The growth rate of the singularity is found to be tD, with 0 < D < 1. This rate depends directly on the initial plasma pressure, and decreases as the pressure is increased. At the end of our study, we present an analytical description of the system in a quasi-static non-singular equilibrium at a given time, in which a finite thick current layer has formed at the null

Locating current sheets in the solar corona

Current sheets are essential for energy dissipation in the solar corona, in particular by enabling magnetic reconnection. Unfortunately, sufficiently thin current sheets cannot be resolved observationally and the theory of their formation is an unresolved issue as well. We consider two predictors of coronal current concentrations, both based on geometrical or even topological properties of a force free coronal magnetic field. First, there are separatrices related to magnetic nulls. Through separatrices the magnetic connectivity changes discontinuously. Coronal magnetic nulls are, however, very rare. At second, inspired by the concept of generalized magnetic reconnection without nulls, quasi-separatrix layers (QSL) were suggested. Through QSL the magnetic connectivity changes continuously, though strongly. The strength of the connectivity change can be quantified by measuring the squashing of the flux tubes which connect the magnetically conjugated photospheres. We verify the QSL and separatrix concepts by comparing the sites of magnetic nulls and enhanced squashing with the location of current concentrations in the corona. Due to the known difficulties of their direct observation we simulated the coronal current sheets by numerically calculating the response of the corona to energy input from the photosphere heating a simultaneously observed EUV Bright Point. We did not find coronal current sheets not at the separatrices but at several QSL locations. The reason is that although the geometrical properties of force free extrapolated magnetic fields can indeed, hint at possible current concentrations, a necessary condition for current sheet formation is the local energy input into the corona

Plasma equilibrium reconstruction of jet discharges using the imas modelling infrastructure

International audienceThe reconstruction of Tokamak plasma equilibrium is a fundamental step in the understanding of fusion plasma physics since it sets the starting point for all subsequent plasma modelling applications and experimental data interpretation. The verification and validation of the numerical codes used to reconstruct plasma equilibrium, using as many available input experimental data e.g. magnetic field or flux measurements, density and temperature diagnostics and polarimetry diagnostics, is essential both for physics model interpretation and when qualifying and extrapolating for ITER. In the framework of the EUROfusion Work Package on Code Development for Integrated Modelling, a scientific Kepler workflow for the reconstruction of Tokamak plasma equilibrium was prototyped, using the ITER Integrated Modelling and Analysis Suite (IMAS). The workflow can seamlessly use any sort of data from Tokamak experiments and call equilibrium reconstruction codes such as EQUAL, EQUINOX, NICE, EFIT++ and SDSS, all using the same physics and engineering data ontology and methods for accessing the data. In the paper, plasma equilibrium reconstructions on dedicated JET plasma dischargesare shownusing at first magnetic data only and subsequently considering also other constrains suchas Motional Stark Effect(MSE). Results with magneticsonly give a good qualitative and quantitative agreement between the codes while including MSE, as anticipated, a substantial improvementofthe core plasma profilesis achieved

Alterations of Blood Brain Barrier Function in Hyperammonemia: An Overview

Ammonia is a neurotoxin involved in the pathogenesis of neurological conditions associated with hyperammonemia, including hepatic encephalopathy, a condition associated with acute—(ALF) or chronic liver failure. This article reviews evidence that apart from directly affecting the metabolism and function of the central nervous system cells, ammonia influences the passage of different molecules across the blood brain barrier (BBB). A brief description is provided of the tight junctions, which couple adjacent cerebral capillary endothelial cells to each other to form the barrier. Ammonia modulates the transcellular passage of low-to medium-size molecules, by affecting their carriers located at the BBB. Ammonia induces interrelated aberrations of the transport of the large neutral amino acids and aromatic amino acids (AAA), whose influx is augmented by exchange with glutamine produced in the course of ammonia detoxification, and maybe also modulated by the extracellularly acting gamma-glutamyl moiety transferring enzyme, gamma-glutamyl-transpeptidase. Impaired AAA transport affects neurotransmission by altering intracerebral synthesis of catecholamines (serotonin and dopamine), and producing “false neurotransmitters” (octopamine and phenylethylamine). Ammonia also modulates BBB transport of the cationic amino acids: the nitric oxide precursor, arginine, and ornithine, which is an ammonia trap, and affects the transport of energy metabolites glucose and creatine. Moreover, ammonia acting either directly or in synergy with liver injury-derived inflammatory cytokines also evokes subtle increases of the transcellular passage of molecules of different size (BBB “leakage”), which appears to be responsible for the vasogenic component of cerebral edema associated with ALF

Impaired Small-World Network Efficiency and Dynamic Functional Distribution in Patients with Cirrhosis

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome and a major complication of liver cirrhosis. Dysmetabolism of the brain, related to elevated ammonia levels, interferes with intercortical connectivity and cognitive function. For evaluation of network efficiency, a ‘small-world’ network model can quantify the effectiveness of information transfer within brain networks. This study aimed to use small-world topology to investigate abnormalities of neuronal connectivity among widely distributed brain regions in patients with liver cirrhosis using resting-state functional magnetic resonance imaging (rs-fMRI). Seventeen cirrhotic patients without HE, 9 with minimal HE, 9 with overt HE, and 35 healthy controls were compared. The interregional correlation matrix was obtained by averaging the rs-fMRI time series over all voxels in each of the 90 regions using the automated anatomical labeling model. Cost and correlation threshold values were then applied to construct the functional brain network. The absolute and relative network efficiencies were calculated; quantifying distinct aspects of the local and global topological network organization. Correlations between network topology parameters, ammonia levels, and the severity of HE were determined using linear regression and ANOVA. The local and global topological efficiencies of the functional connectivity network were significantly disrupted in HE patients; showing abnormal small-world properties. Alterations in regional characteristics, including nodal efficiency and nodal strength, occurred predominantly in the association, primary, and limbic/paralimbic regions. The degree of network organization disruption depended on the severity of HE. Ammonia levels were also significantly associated with the alterations in local network properties. Results indicated that alterations in the rs-fMRI network topology of the brain were associated with HE grade; and that focal or diffuse lesions disturbed the functional network to further alter the global topology and efficiency of the whole brain network. These findings provide insights into the functional changes in the human brain in HE