Postoperative Immune Suppression in Visceral Surgery: Characterisation of an Intestinal Mouse Model

Background: Postoperatively acquired immune dysfunction is associated with a higher mortality rate in case of septic complications. As details of this severe clinical problem are still unknown, animal models are essential to characterise the mechanisms involved. Methods: Mice were laparotomised and the small intestine was pressed smoothly in antegrade direction. For extension of trauma, the intestine was manipulated three times consecutively. Following this, the ex vivo cytokine release of splenocytes was determined. The degree of surgical trauma was analysed by detection of HMGB1 and IL-6 in serum and by neutrophil staining in the muscularis mucosae. Results: We adapted the previously described animal model of intestinal manipulation to provide a model of surgically induced immune dysfunction. Following intestinal manipulation, the mice showed elevated serum levels of HMGB1 and IL-6 and increased infiltration of granulocytes into the muscularis mucosae. Ex vivo cytokine release by splenocytes was suppressed in the postoperative period. The degree of suppression correlated with the extent of surgical trauma. Conclusions: In this study, we describe a surgically induced immune dysfunction animal model, in which a significant surgical trauma is followed by an immune dysfunction. This model may be ideal for the characterisation of the postoperative immune dysfunction syndrome

Surgical Trauma and Postoperative Immune Dysfunction

Background: In postoperative sepsis, mortality is increased due to the surgically induced immune dysfunction. Further causes of this traumatic effect on the immune system include burn injuries and polytrauma, as well as endogenous traumata like stroke. Several animal models have been defined to analyse the characteristics of trauma-induced immune suppression. This article will correlate our results from animal studies and clinical observations with the recent literature on postoperative immune suppression. Methods: The previously described model of surgically induced immune dysfunction (SID) was performed in mice by laparotomy and manipulation of the small intestine in the antegrade direction. Blood samples were collected 6 and 72 h following SID to analyse the white blood cell count and corticosterone levels. To assess the postoperative immune status in humans, we analysed expression of HLA-DR on monocytes of 118 patients by flow cytometry prior to and 24, 48 and 72 h after surgery. Results: The postoperative immune suppression in our SID model is characterised by lymphocytopenia and significantly increased corticosterone levels in mice dependent on the degree of surgical trauma. This is comparable to the postoperative situation in humans: major and especially long-lasting surgery results in a significantly reduced expression of HLA-DR on circulating monocytes. Previous studies describe a similar situation following burn injury and endogenous trauma, i.e. stroke. Conclusions: We suggest the completion of our previously published sepsis classification due to the immune status at the onset of sepsis: type A as the spontaneously acquired sepsis and type B as sepsis in trauma-induced pre-existing immune suppression

A Syngeneic Orthotopic Murine Model of Pancreatic Adenocarcinoma in the C57/BL6 Mouse Using the Panc02 and 6606PDA Cell Lines

Background/Aims: To develop a clinically relevant immunocompetent murine model to study pancreatic cancer using two different syngeneic pancreatic cancer cell lines and to assess MRI for its applicability in this model. Methods: Two cell lines, 6606PDA and Panc02, were employed for the experiments. Cell proliferation and migration were monitored in vitro. Matrigel™ was tested for its role in tumor induction. Tumor cell growth was assessed after orthotopic injection of tumor cells into the pancreatic head of C57/BL6 mice by MRI and histology. Results: Proliferation and migration of Panc02 were significantly faster than those of 6606PDA. Matrigel did not affect tumor growth/migration but prevented tumor cell spread after injection thus avoiding undesired peritoneal tumor growth. MRI could reliably monitor longitudinal tumor growth in both cell lines: Panc02 had a more irregular finger-like growth, and 6606PDA grew more spherically. Both tumors showed local invasiveness. Histologically, Panc02 showed a sarcoma-like undifferentiated growth pattern, whereas 6606PDA displayed a moderately differentiated glandular tumor growth. Panc02 mice had a significantly shorter (28 days) survival than 6606PDA mice (50 days). Conclusion: This model closely mimics human pancreatic cancer. MRI was invaluable for longitudinal monitoring of tumor growth thus reducing the number of mice required. Employing two different cell lines, this model can be used for various treatment and imaging studies

Beaver Research in the Uvs Nuur Region

In 1985, 1988, and 2002 Castor fiber birulai was introduced to the Tes Gol of the Uvs Nuur basin in North-western Mongolia. The beavers migrated through the Republic of Tyva and settled in the middle part of Tes Gol near the Tyvinian-Mongolian border. About 10 colonies were recorded in this region in 2002. Strict protection of Castor fiber birulai has to be ensured in Mongolia and the Republic of Tyva in future

A retrospective of the GREGOR solar telescope in scientific literature

In this review, we look back upon the literature, which had the GREGOR solar telescope project as its subject including science cases, telescope subsystems, and post-focus instruments. The articles date back to the year 2000, when the initial concepts for a new solar telescope on Tenerife were first presented at scientific meetings. This comprehensive bibliography contains literature until the year 2012, i.e., the final stages of commissioning and science verification. Taking stock of the various publications in peer-reviewed journals and conference proceedings also provides the "historical" context for the reference articles in this special issue of Astronomische Nachrichten/Astronomical Notes.Comment: 6 pages, 2 color figures, this is the pre-peer reviewed version of Denker et al. 2012, Astron. Nachr. 333, 81

A large-scale experiment to evaluate control of invasive muskrats

The muskrat (Ondatra zibethicus) is an invasive species in Europe. The extensive waterways of the Netherlands provide ideal habitat for muskrats, and a large population established itself after arrival in 1941. A control program was put into effect immediately because muskrat burrowing can compromise the integrity of dikes and, hence, poses a significant public safety risk. The current (2015) annual catch of approximately 89,000 individuals is equivalent to approximately 0.30 muskrats/km of waterway, well above the national objective in spite of decades of effort. The control program is expensive (€35 M annually) and contested by animal rights groups. These factors created the need for a careful evaluation of the full range of control possibilities, from ‘no control’ to ‘extermination.’ As part of this, we experimentally evaluated the validity of a previously published correlation (based on historical data) between catch and effort. We raised or lowered removal effort (2013–2016) in a stratified random sample of 117 5-km × 5-km ‘atlas squares’ from the national grid. We found that catch-per-unit effort (CPUE) decreased after effort was increased, and rose after effort was decreased, by amounts slightly greater than expected based on the correlational data, though confidence intervals enclose zero. As anticipated, CPUE varied consistently and strongly between seasons. The biggest (and unanticipated) effects were those of the catch in the preceding 3 years (‘history’), and surrounding area (‘neighborhood’). Our experiment confirms estimates of intensity of control required to lower muskrat populations. These results will help with more effective allocation of control effort, and better-informed evaluation of the economic costs of various control options

Decision-support tools to build climate resilience against emerging infectious diseases in Europe and beyond

Climate change is one of several drivers of recurrent outbreaks and geographical range expansion of infectious diseases in Europe. We propose a framework for the co-production of policy-relevant indicators and decision-support tools that track past, present, and future climate-induced disease risks across hazard, exposure, and vulnerability domains at the animal, human, and environmental interface. This entails the co-development of early warning and response systems and tools to assess the costs and benefits of climate change adaptation and mitigation measures across sectors, to increase health system resilience at regional and local levels and reveal novel policy entry points and opportunities. Our approach involves multi-level engagement, innovative methodologies, and novel data streams. We take advantage of intelligence generated locally and empirically to quantify effects in areas experiencing rapid urban transformation and heterogeneous climate-induced disease threats. Our goal is to reduce the knowledge-to-action gap by developing an integrated One Health—Climate Risk framework

Hantaviren und Nagetiere in Deutschland: Das Netzwerk „Nagetier-übertragene Pathogene”

ZusammenfassungHantavirus-Infektionen sind in Deutschland seit etwa 25 Jahren bekannt. Die durchschnittliche Antikörperprävalenz in der Bevölkerung liegt bei ca. 1 bis 2%. Nach Einführung der Meldepflicht im Jahr 2001 sind jährlich durchschnittlich etwa 70 bis 240 Fälle gemeldet worden. Im Jahr 2005 und insbesondere im Jahr 2007 ist jedoch ein deutlicher Anstieg der Zahl der gemeldeten Fälle registriert worden. Die am meisten betroffenen Regionen lagen in den Bundesländern Baden-Württemberg, Bayern, Nordrhein-Westfalen und Niedersachsen. Im Gegensatz zur gut dokumentierten Situation beim Menschen ist die Kenntnis der geografischen Verbreitung und Häufigkeit von Hantavirus-Infektionen in den Nagetier-Reservoiren und deren Schwankungen sehr begrenzt. Aus diesem Grund wurde in Deutschland das Netzwerk „Nagetier-übertragene Pathogene“ etabliert, das interdisziplinäre Untersuchungen zur Nagetier-Populationsdynamik, Prävalenz und Evolution von Hantaviren und anderen Nagetier-assoziierten Zoonoseerregern und den zugrunde liegenden Mechanismen sowie deren Auswirkungen auf die Häufigkeit humaner Infektionen erlaubt. Ein Monitoring von Hantaviren in Nagetieren wurde in Endemiegebieten (Baden-Württemberg, Bayern, Nordrhein-Westfalen, Niedersachsen) und Regionen mit einer geringen Zahl humaner Fälle (Mecklenburg-Vorpommern, Brandenburg, Sachsen, Sachsen-Anhalt, Thüringen, Schleswig-Holstein, Hessen, Rheinland-Pfalz) initiiert. Insgesamt wurde eine breite geographische Verbreitung des Puumalavirus (PUUV) in Rötelmäusen und des Tulavirus in Microtus-Mäusen dokumentiert. Dobrava-Belgrad-Virus-positive Apodemus-Mäuse wurden bisher ausschließlich in Brandenburg, Mecklenburg-Vorpommern und Niedersachsen gefunden. In den Hantavirus-Ausbruchsgebieten in Baden-Württemberg, Bayern, Nordrhein-Westfalen und Niedersachsen wurde bei Rötelmäusen eine hohe PUUV-Prävalenz beobachtet. Initiale Longitudinalstudien in Nordrhein-Westfalen (Stadt Köln), Bayern (Niederbayern) und Niedersachsen (ländliche Region bei Osnabrück) zeigten ein stabiles Vorkommen des PUUV in den Rötelmaus-Populationen. Neben den Untersuchungen zu Hantaviren ist auch mit Studien zum Vorkommen von anderen Nagetier-assoziierten Zoonoseerregern begonnen worden. Die begonnenen Longitudinalstudien werden Schlussfolgerungen zur Evolution von Hantaviren und anderen Nagetierassoziierten Erregern und zu Veränderungen in deren Häufigkeit und Verbreitung ermöglichen. Diese Untersuchungen werden zukünftig eine verbesserte Risikoabschätzung für die Gefährdung der Bevölkerung ermöglichen, die auch die möglichen zukünftigen Klimawandel-bedingten Veränderungen in der Epidemiologie Nagetier-assoziierter Zoonoseerreger berücksichtigt

Identification of pediatric septic shock subclasses based on genome-wide expression profiling

<p>Abstract</p> <p>Background</p> <p>Septic shock is a heterogeneous syndrome within which probably exist several biological subclasses. Discovery and identification of septic shock subclasses could provide the foundation for the design of more specifically targeted therapies. Herein we tested the hypothesis that pediatric septic shock subclasses can be discovered through genome-wide expression profiling.</p> <p>Methods</p> <p>Genome-wide expression profiling was conducted using whole blood-derived RNA from 98 children with septic shock, followed by a series of bioinformatic approaches targeted at subclass discovery and characterization.</p> <p>Results</p> <p>Three putative subclasses (subclasses A, B, and C) were initially identified based on an empiric, discovery-oriented expression filter and unsupervised hierarchical clustering. Statistical comparison of the three putative subclasses (analysis of variance, Bonferonni correction, <it>P </it>< 0.05) identified 6,934 differentially regulated genes. K-means clustering of these 6,934 genes generated 10 coordinately regulated gene clusters corresponding to multiple signaling and metabolic pathways, all of which were differentially regulated across the three subclasses. Leave one out cross-validation procedures indentified 100 genes having the strongest predictive values for subclass identification. Forty-four of these 100 genes corresponded to signaling pathways relevant to the adaptive immune system and glucocorticoid receptor signaling, the majority of which were repressed in subclass A patients. Subclass A patients were also characterized by repression of genes corresponding to zinc-related biology. Phenotypic analyses revealed that subclass A patients were younger, had a higher illness severity, and a higher mortality rate than patients in subclasses B and C.</p> <p>Conclusion</p> <p>Genome-wide expression profiling can identify pediatric septic shock subclasses having clinically relevant phenotypes.</p