Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis

The innate immune system protects against infection and tissue injury through the specialized organs of the reticuloendothelial system, including the lungs, liver, and spleen. The central nervous system regulates innate immune responses via the vagus nerve, a mechanism termed the cholinergic antiinflammatory pathway. Vagus nerve stimulation inhibits proinflammatory cytokine production by signaling through the α7 nicotinic acetylcholine receptor subunit. Previously, the functional relationship between the cholinergic antiinflammatory pathway and the reticuloendothelial system was unknown. Here we show that vagus nerve stimulation fails to inhibit tumor necrosis factor (TNF) production in splenectomized animals during lethal endotoxemia. Selective lesioning of the common celiac nerve abolishes TNF suppression by vagus nerve stimulation, suggesting that the cholinergic pathway is functionally hard wired to the spleen via this branch of the vagus nerve. Administration of nicotine, an α7 agonist that mimics vagus nerve stimulation, increases proinflammatory cytokine production and lethality from polymicrobial sepsis in splenectomized mice, indicating that the spleen is critical to the protective response of the cholinergic pathway. These results reveal a specific, physiological connection between the nervous and innate immune systems that may be exploited through either electrical vagus nerve stimulation or administration of α7 agonists to inhibit proinflammatory cytokine production during infection and tissue injury

Small average differences in attenuation corrected images between men and women in myocardial perfusion scintigraphy: a novel normal stress database

<p>Abstract</p> <p>Background</p> <p>The American Society of Nuclear Cardiology and the Society of Nuclear Medicine state that incorporation of attenuation-corrected (AC) images in myocardial perfusion scintigraphy (MPS) will improve image quality, interpretive certainty, and diagnostic accuracy. However, commonly used software packages for MPS usually include normal stress databases for non-attenuation corrected (NC) images but not for attenuation-corrected (AC) images. The aim of the study was to develop and compare different normal stress databases for MPS in relation to NC vs. AC images, male vs. female gender, and presence vs. absence of obesity. The principal hypothesis was that differences in mean count values between men and women would be smaller with AC than NC images, thereby allowing for construction and use of gender-independent AC stress database.</p> <p>Methods</p> <p>Normal stress perfusion databases were developed with data from 126 male and 205 female patients with normal MPS. The following comparisons were performed for all patients and separately for normal weight vs. obese patients: men vs. women for AC; men vs. women for NC; AC vs. NC for men; and AC vs. NC for women.</p> <p>Results</p> <p>When comparing AC for men vs. women, only minor differences in mean count values were observed, and there were no differences for normal weight vs. obese patients. For all other analyses major differences were found, particularly for the inferior wall.</p> <p>Conclusions</p> <p>The results support the hypothesis that it is possible to use not only gender independent but also weight independent AC stress databases.</p

Electroacupuncture pretreatment attenuates cerebral ischemic injury through α7 nicotinic acetylcholine receptor-mediated inhibition of high-mobility group box 1 release in rats

<p>Abstract</p> <p>Background</p> <p>We have previously reported that electroacupuncture (EA) pretreatment induced tolerance against cerebral ischemic injury, but the mechanisms underlying this effect of EA are unknown. In this study, we assessed the effect of EA pretreatment on the expression of α7 nicotinic acetylcholine receptors (α7nAChR), using the ischemia-reperfusion model of focal cerebral ischemia in rats. Further, we investigated the role of high mobility group box 1 (HMGB1) in neuroprotection mediated by the α7nAChR and EA.</p> <p>Methods</p> <p>Rats were treated with EA at the acupoint "Baihui (GV 20)" 24 h before focal cerebral ischemia which was induced for 120 min by middle cerebral artery occlusion. Neurobehavioral scores, infarction volumes, neuronal apoptosis, and HMGB1 levels were evaluated after reperfusion. The α7nAChR agonist PHA-543613 and the antagonist α-bungarotoxin (α-BGT) were used to investigate the role of the α7nAChR in mediating neuroprotective effects. The roles of the α7nAChR and HMGB1 release in neuroprotection were further tested in neuronal cultures exposed to oxygen and glucose deprivation (OGD).</p> <p>Results</p> <p>Our results showed that the expression of α7nAChR was significantly decreased after reperfusion. EA pretreatment prevented the reduction in neuronal expression of α7nAChR after reperfusion in the ischemic penumbra. Pretreatment with PHA-543613 afforded neuroprotective effects against ischemic damage. Moreover, EA pretreatment reduced infarct volume, improved neurological outcome, inhibited neuronal apoptosis and HMGB1 release following reperfusion, and the beneficial effects were attenuated by α-BGT. The HMGB1 levels in plasma and the penumbral brain tissue were correlated with the number of apoptotic neurons in the ischemic penumbra. Furthermore, OGD in cultured neurons triggered HMGB1 release into the culture medium, and this effect was efficiently suppressed by PHA-543,613. Pretreatment with α-BGT reversed the inhibitory effect of PHA-543,613 on HMGB1 release.</p> <p>Conclusion</p> <p>These data demonstrate that EA pretreatment strongly protects the brain against transient cerebral ischemic injury, and inhibits HMGB1 release through α7nAChR activation in rats. These findings suggest the novel potential for stroke interventions harnessing the anti-inflammatory effects of α7nAChR activation, through acupuncture or pharmacological strategies.</p

A comprehensive overview of radioguided surgery using gamma detection probe technology

The concept of radioguided surgery, which was first developed some 60 years ago, involves the use of a radiation detection probe system for the intraoperative detection of radionuclides. The use of gamma detection probe technology in radioguided surgery has tremendously expanded and has evolved into what is now considered an established discipline within the practice of surgery, revolutionizing the surgical management of many malignancies, including breast cancer, melanoma, and colorectal cancer, as well as the surgical management of parathyroid disease. The impact of radioguided surgery on the surgical management of cancer patients includes providing vital and real-time information to the surgeon regarding the location and extent of disease, as well as regarding the assessment of surgical resection margins. Additionally, it has allowed the surgeon to minimize the surgical invasiveness of many diagnostic and therapeutic procedures, while still maintaining maximum benefit to the cancer patient. In the current review, we have attempted to comprehensively evaluate the history, technical aspects, and clinical applications of radioguided surgery using gamma detection probe technology

Investigation of dynamic behaviour of a reversible pump turbine operating with air as working fluid

Abweichender Titel nach Übersetzung der Verfasserin/des VerfassersDie steigende Nutzung von regenerativen Energien senkt einerseits die Schadstoffemissionen, erhöht aber andererseits die Anforderungen an die Stabilisierung und Regelung des Verbundnetzes. Deshalb werden unter anderem Pumpspeicherkraftwerke immer häufiger im Phasenschieberbetrieb betrieben. Bei dieser Betriebsart wird die Maschine ausgeblasen, d. h. der Wasserpegel wird so weit abgesenkt, dass das Laufrad der Pumpturbine in Luft, oberhalb einer freien Wasseroberfläche, rotiert. Unter bestimmten Bedingungen wird eine Oszillation der Wasseroberfläche angeregt, die unter Umständen sogar ins Laufrad ragt. In dieser Arbeit wurde untersucht, ob das Überschreiten der Pumpgrenze (= Stabilitätsgrenze) der Pumpturbine, während des Phasenschieberbetriebes, ein möglicher Anregungsmechanismus für diese Oszillation ist. Dafür wurde das Modell mit konzentrierten Parametern von Greitzer auf den Francis-Pumpturbinen-Prüfstand der TU Wien angewandt. Dieses Modell wurde ursprünglich für Axialkompressoren entwickelt und später von Hansen auch erfolgreich auf Radialmaschinen angewandt. Mit diesem Modell lässt sich das Instabilitätsverhalten eines stationär betriebenen Kompressors bestimmen. Dafür wird das Kompressorsystem in drei Bereicheaufgeteilt: Kompressorkanal, Plenum und Drosselkanal. Die Anwendung des Modells mit konzentrierten Parametern erfordert neben gewissen Systemparametern auch die stationäre Kompressorcharakteristik. Die Charakteristik wurde durch gesammelte Messdaten des 4-Quadranten-Kennfelds bestimmt. Die Lösung des Differentialgleichungssystem wurde mit dem Berechnungsprogramm MATLAB durchgeführt. Dabei wurden Simulationen mit verschiedenen Aufteilungen der drei Bereiche, sowie Variationen diverser Parameter durchgeführt. Die Ergebnisse werden in dieser Arbeit gezeigt und mit Messdaten der Oszillation der freien Wasseroberfläche verglichen.The increasing use of regenerative energies reduces pollutant emissions, but also leads to higher efforts for the stabilization and regulation of the power grid. For this reason, pumped storage power plants, among other things, are increasingly being operated in synchronous condenser mode. In this operating mode is the water level lowered and the runner of the pump turbine rotates in air, above a free water surface. Under certain conditions an oscillation of the water surface is stimulated. In this thesis it was investigated whether exceeding the surge margin (= stability limit) of the pump turbine is a possible excitation mechanism for this oscillation. Therefore the so-called Lumped Parameter Model of Greitzer was applied to the Francis pump turbine test rig of the Vienna University of Technology. This model was originally developed for axial compressors and later successfully applied by Hansen to radial machines. With this model the instability behaviour of a compressor during stationary operation can be determined. For this purpose the compressor system is divided into three areas: Compressor duct, plenum and throttle duct. The application of the Lumped Parameter Model requires certain system parameters as well as the stationary compressor characteristics. The characteristic was determined by collected measurement data of the 4-quadrant characteristic map. The solution of the differential equation system was performed with the program MATLAB. Simulations with different divisions of the three areas and variation of various parameters were performed. The results are shown in this thesis and compared with measured data of the oscillation of the free water surface.6