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Die Aussagenlogik beschaftigt sich mit Aussagen, das sind Satze, die die Eigenschaft haben, wahr oder falsch zu sein. Man spricht deswegen auch von einer zweiwertigen Logik, weil neben den beiden Wahrheitswerten wahr und falsch keine weitere Moglichkeit existiert (Prinzip vom ausgeschlossenen Dritten). Daneben gibt es auch mehrwertige Logiken, auf die wir hier aber nicht eingehen. Die zweiwertige Logik hat zahlreiche Anwendungen in der Informatik. Den beiden Wahrheitswerten kann man auch Zahlen zuordnen, zum Beispiel die 1 fur wahr (oder Strom an) und die 0 fur falsch (oder Strom aus).

Zahlreiche okonomische Sachverhalte sind dadurch gekennzeichnet, dass der Wert einer bestimmten veranderlichen Grose, einer Variablen, vom Wert einer anderen Variablen abhangt. Zum Beispiel hangt der Betrag, den Sie an Einkommensteuer zahlen mussen, von Ihrem Einkommen ab. Man kann daher sagen, der Steuerbetrag ist eine Funktion des Einkommens.

Human and murine studies showed that GM-CSF exerts beneficial effects in intestinal inflammation. To explore whether GM-CSF mediates its effects via monocytes, we analyzed effects of GM-CSF on monocytes in vitro and assessed the immunomodulatory potential of GM-CSF–activated monocytes (GMaMs) in vivo. We used microarray technology and functional assays to characterize GMaMs in vitro and used a mouse model of colitis to study GMaM functions in vivo. GM-CSF activates monocytes to increase adherence, migration, chemotaxis, and oxidative burst in vitro, and primes monocyte response to secondary microbial stimuli. In addition, GMaMs accelerate epithelial healing in vitro. Most important, in a mouse model of experimental T cell–induced colitis, GMaMs show therapeutic activity and protect mice from colitis. This is accompanied by increased production of IL-4, IL-10, and IL-13, and decreased production of IFN-γ in lamina propria mononuclear cells in vivo. Confirming this finding, GMaMs attract T cells and shape their differentiation toward Th2 by upregulating IL-4, IL-10, and IL-13 in T cells in vitro. Beneficial effects of GM-CSF in Crohn’s disease may possibly be mediated through reprogramming of monocytes to simultaneously improved bacterial clearance and induction of wound healing, as well as regulation of adaptive immunity to limit excessive inflammation.

Ulcerative colitis increases the risk of developing dysplasia and colitis-associated cancer (CAC). The purpose of this study was to determine the risk factors as well as protective measures for disease burden, need for colectomy and the development of CAC in ulcerative colitis (UC) patients. A cohort of n = 434 UC patients was evaluated. Data analysis was performed by univariate and multivariate logistic regression. Odds ratios (OR) and 95 % confidence intervals (CI) were calculated, and significance was assessed by the likelihood ratio test. Mean patient age at UC diagnosis was 45.7 ± 15.1 years which manifested mainly as pancolitis (47 %) or left-sided colitis (45.2 %). CAC was detected in ten patients (2.3 %). UC disease duration was strongly associated with the risk of CAC (P

cope In previous studies, we could show that the B vitamin nicotinamide (NAM) enhanced antimicrobial activity of neutrophils. Here, we assessed the effects of NAM in two models of experimental colitis. Methods and Results Colitis was induced in C57BL/6 mice either by oral infection with Citrobacter rodentium or by DSS (dextran sodium sulphate) administration, and animals were systemically treated with NAM. Ex vivo bacterial clearance was assessed in murine and human whole blood, as well as isolated human neutrophils. In C. rodentium-induced colitis, NAM treatment resulted in markedly decreased systemic bacterial invasion, histological damage and increased fecal clearance of C. rodentium by up to 600-fold. In contrast, NAM had no effect when administered to neutrophil-depleted mice. Ex vivo stimulation of isolated human neutrophils, as well as murine and human whole blood with NAM led to increased clearance of C. rodentium and enhanced expression of antimicrobial peptides in neutrophils. Moreover, NAM treatment significantly ameliorated the course of DSS colitis, as assessed by body weight, histological damage and myeloperoxidase activity. Conclusion Pharmacological application of NAM mediates beneficial effects in bacterial and chemically induced colitis. Future studies are needed to explore the clinical potential of NAM in the context of intestinal bacterial infections and human inflammatory bowel disease (IBD).

Ziel der vorliegenden Studie war der Vergleich der Kapselendoskopie des Kolons („colon capsule endoscopy“, CCE) mit der Standardkoloskopie („standard colonoscopy“, SC) zur Ermittlung der mukosalen Krankheitsaktivitat und Lokalisation entzundlich veranderter Kolonmukosa bei Patienten mit bekannter Colitis ulcerosa („ulcerative colitis“, UC). Es wurden 13 Patienten mit Symptomen (8 Manner, 5 Frauen, Durchschnittsalter: 38,5±12,0 Jahre) und der Diagnose einer UC (mittlere Dauer der Kolitis: 9,7±8,1 Jahre) sowie der Indikation fur eine Endoskopie wegen des Verdachts auf derzeitige Krankheitsaktivitat in die Studie aufgenommen. Bei allen Patienten erfolgte eine CCE (Kapsel der 1. Generation, Fa. Given Imaging, Yokneam, Israel) an Tag 1 und anschliesend eine SC an Tag 2 im Rahmen einer nichtrandomisierten, nicht placebokontrollierten diagnostischen Einzelzentrumstudie (NCT00837304). Die SC und die CCE wurden per Video aufgenommen und unabhangig von 6 erfahrenen Endoskopikern ausgewertet. Dabei wurde der modifizierte Rachmilewitz-Score berechnet und der Wilcoxon-Vorzeichen-Rang-Test zur Analyse verwendet. Der Unterschied bei der Erkennung der Krankheitsaktivitat durch die Endoskopiker wurde durch Anwendung des Kruskal-Wallis-Tests ermittelt. Die Bestimmung der Krankheitsaktivitat ergab einen signifikant hoheren Rachmilewitz-Score von 7,3±2,9 in der SC-Gruppe im Vergleich zu 4,8±3,4 in der CCE-Gruppe. Mit der SC waren Gefasvulnerabilitat, granulierte Mukosa und Mukosalasionen in signifikant hoherem Ausmas zu erkennen als mit der CCE. Die Krankheitsausdehnung wurde mit der CCE im Vergleich zur SC unterschatzt. Zwischen den Untersuchern unterschied sich die Bestimmung der Krankheitsaktivitat mit der SC bzw. der CCE statistisch nicht (p=0,26 bzw. p=0,1). Nach Durchfuhrung der CCE betrug die Kapselausscheidungsrate 77%. Die Gesamtakzeptanz beider Verfahren war ahnlich. Angesichts der signifikant unterschiedlichen Bestimmung der Krankheitsaktivitat und erheblich genauerer Ermittlung der horizontalen Entzundungsausbreitung durch SC vs. CCE empfehlen die Autoren den bevorzugten Einsatz der SC zur Bestimmung des Ausmases der Entzundung bei UC-Patienten.

Although endoscopic ultrasound (EUS) has improved the diagnostic of potential malignancies, gastric lesions with suspicion of gastrointestinal stromal tumors (GIST) or benign lesions like lipoma or leiomyoma can often not be accurately differentiated by EUS, therefore, requiring tissue sampling with the risk of bleeding complications especially in GIST. As with the newest generation of EUS machines, contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) has become a new option to determine perfusion characteristics. The aim of this analysis was to evaluate whether CEH-EUS may help to discriminate various submucosal lesions.Data sets of 17 patients with suspicious gastric or esophageal lesions, who were investigated with CEH-EUS were analyzed. Perfusion characteristics were classified by the investigator immediately and statistically analyzed after investigation. Samples from EUS-fine needle aspirates, biopsy samples after needle cut or surgical specimen served as gold standard.CEH-EUS showed nine lesions with reduced contrast enhancement (maximum intensity 6.2 ± 1.9 db) and eight lesions with hyperenhancement (47.3 ± 11.6 db). The latter eight lesions were all histologically identified as GIST, while the nine hypoenhanced lesions emerged to be four lipoma and five leiomyoma. Statistical analysis corresponded with initial perfusion classification in all cases.This is the first study showing that CEH-EUS can discriminate GIST from benign lesions with good accuracy. In the future, CEH-EUS-guided discrimination may lead to individualized diagnostic and therapeutic strategies in handling submucosal lesions.

The role of cytomegalovirus (CMV) infection in the pathogenesis and exacerbation of Inflammatory Bowel Disease (IBD) has been unresolved. Typically, the CMV genome remains dormant in infected cells, but a breakdown of immune surveillance can lead to re-activation of viral replication in the gut mucosa, which is not necessarily associated with viremia or changes in antibody titers. We hypothesized that the detection of CMV-specific CD8 effector T cells should permit the distinction between dormant and active CMV infection. As CD8 effector T cells, unlike memory CD8 T cells, have perforin (PFN) and granzyme B (GzB) preformed in their cytoplasmic granules, we employed single cell resolution ELISPOT assays to measure the CMV antigen-triggered release of these molecules by CD8 T cells isolated from subjects with IBD, and age-matched healthy controls. The frequencies of CMV-specific (GzB) and PFN-producing CD8 T cells were increased in IBD patients compared to healthy controls. Furthermore, the increased CMV reactivity was associated with active IBD disease and with longer disease duration. Notably, PCR on serum frequently failed to detect CMV DNA during flares. The data show that during active IBD there is a flare of CD8 T cell activity against CMV in a substantial proportion of IBD patients, suggesting CMV reactivation that serum PCR does not detect. While it remains open whether CMV reactivation is a cause or consequence of IBD, our data suggest that monitoring CMV antigen-specific effector CD8 T cells with GzB and PFN ELISPOT analysis can provide novel insights into the role of CMV infection in IBD. Additionally, our data have implications for the fields of transplantation, HIV, cancer, and autoimmune diseases, in all of which patient care critically depends on sensitive and reliable detection of a reactivation of CMV infection.

The ingestion of caustic agents is mostly accidental, especially in children. In adults, intentional, mainly suicidal cases of corrosive ingestion are frequently reported, which are more often fatal. Most corrosive ingestion is of cleaning substances, which mainly contain alkali substances. Since declaration rules for harmful substances have been restricted, the incidental ingestion of caustic substances has become rarer in the last years. However, the American Association of Poison Control Centres reported 216 228 poisonous human exposures to cleaning substances in 2007, which were mainly accidental.

Background: Despite some progress in recent years, the options for treating inflammatory bowel disease (IBD) are still dissatisfying, and surgery rates are still high. The anti-inflammatory effects of melanocortin peptides such as alpha-melanocyte-stimulating hormone (α-MSH) have been described recently in, for example, dextran sodium sulfate (DSS) colitis in mice. The aim of this study was to investigate the therapeutic potential of the melanocortin-derived tripeptide α-MSH(11–13) (KPV) and its mode of action in 2 models of intestinal inflammation. Methods: The anti-inflammatory activity of KPV was analyzed in 2 well-described models of IBD: DSS colitis, and CD45RBhi transfer colitis. Furthermore, animals expressing a nonfunctional melanocortin-1 receptor (MC1Re/e) received DSS for induction of colitis and were treated with KPV. The course of inflammation was monitored by weight loss and histological changes in the colon as well as by myeloperoxidase (MPO) activity. Results: In the DSS-colitis model, treatment with KPV led to earlier recovery and significantly stronger regain of body weight. Histologically, inflammatory infiltrates were significantly reduced in KPV-treated mice, which was confirmed by the significant reduction of MPO activity in colonic tissue after KPV treatment. Supporting these findings, KPV treatment of transfer colitis led to recovery, regain of body weight, and reduced inflammatory changes histologically. In MC1Re/e mice, KPV treatment rescued all animals in the treatment group from death during DSS colitis. Conclusions: The melanocortin-derived tripeptide KPV showed significant anti-inflammatory effects in 2 murine models of colitis. These effects seem to be at least partially independent of MC1R signaling. In conclusion, our data suggest KPV as an interesting therapeutic option for the treatment of IBD. (Inflamm Bowel Dis 2007)

Glucocorticoids (GCs) are used as first-line therapies for generalized suppression of inflammation (e.g., allergies or autoimmune diseases), but their long-term use is limited by severe side effects. Our previous work revealed that GCs induced a stable anti-inflammatory phenotype in monocytes, the GC-stimulated monocytes (GCsMs) that we exploited for targeted GC-mediated therapeutic effects. We demonstrate that GCsMs interact with T cells in suppressing proliferation, as well as cytokine release of CD8+ and, especially, CD4+ T cells in vitro, and that they support generation of Foxp3+ cells. Therefore, we tested their immunosuppressive potential in CD4+ T cell–induced colitis in vivo. We found that injection of GCsMs into mice with severe colitis abolished the inflammation and resulted in significant clinical improvement within a few days. T cells recovered from GCsM-treated mice exhibited reduced secretion of proinflammatory cytokines IFN-γ and IL-17. Furthermore, clusters of Foxp3+ CD4+ T cells were detectable at local sites of inflammation in the colon. Thus, GCsMs are able to modify T cell responses in vitro and in vivo, as well as to downregulate and clinically cure severe T cell–mediated colitis.

Okonomische Sachverhalte sind in aller Regel nicht durch eine einzige Einflussgrose zu erklaren. In der Sprache von mathematischen Funktionen ausgedruckt hangt die Variable y also haufig nicht nur von einer Variablen x ab, sondern von einer Vielzahl von Variablen. Gerade in den Wirtschaftswissenschaften ist es daher wichtig, sich auch mit Funktionen mehrerer Variablen zu befassen.

The aim of our study was to compare colon capsule endoscopy (CCE) with standard colonoscopy (SC) in the assessment of mucosal disease activity and localization of inflammatory colonic mucosa in patients with known ulcerative colitis (UC).Thirteen symptomatic patients (8 males, 5 females, mean age 38.5 ± 12.0 years) with known UC (mean duration of colitis: 9.7 ± 8.1 years) and indication for endoscopy due to suspected disease activity were included. All patients underwent CCE (first generation capsule, Given Imaging Ltd., Yokneam, Israel) on day 1 followed by SC on day 2 in a single center non-randomized, non-placebo-controlled diagnostic study (NCT00837304). SC and CCE were video recorded, and analysis was independently performed by 6 experienced endoscopists. The modified Rachmilewitz score was calculated, and Wilcoxon signed-rank test was used for analysis. Difference in recognition of disease activity by the endoscopists was assessed by application of the Kruskal-Wallis test.Assessment of disease activity revealed a significantly higher Rachmilewitz score of 7.3 ± 2.9 in the SC group compared to 4.8 ± 3.4 in the CCE group. Significantly, more detection of vessel vulnerability, granulated mucosa and mucosal damage was seen by SC. Disease extension was underestimated by CCE compared to SC. Disease activity assessment by means of SC or CCE did not differ statistically between the investigators (p = 0.26 and p = 0.1, respectively). After CCE, the capsule egestion rate was 77 %. The overall acceptance of both procedures was similar.Considering the significantly different assessment of disease activity and significantly more appropriate assignment of the horizontal spread of inflammation by SC versus CCE, we recommend the preferential use of SC in the assessment of inflammation in UC patients.

Summary The chemokine receptor CCR6 is expressed by dendritic cells, B and T cells predominantly within the organized structures of the gut-associated lymphatic tissue. Its ligand CCL20 is synthesized by the follicle-associated epithelium and is crucial for the development of M cells within Peyer's patches. In addition, lineage-negative c-kit positive lymphocytes within cryptopatches (CP) express CCR6. CCR6-deficient mice exhibit an altered intestinal immune system containing increased amounts of intraepithelial lymphocytes and show smaller Peyer's patches, while progression of cryptopatches to mature isolated lymphoid follicles (ILF) is inhibited. In this report, we show that lin- c-kit+ lymphocytes express a variety of different chemokine receptors and that CCR6 identifies those cells located within CP. In contrast, cells found outside CP are positive for CXCR3 and exhibit a different surface marker profile, suggesting that at least two different populations of lin- c-kit+ cells are present. The presence of CCR6 does not influence the expression of Notch molecules on lin- c-kit+ cells, nor does it influence Notch ligand expression on bone marrow-derived dendritic cells. In the human gut, CCR6 identifies clusters of lymphocytes resembling murine CP. CCR6 seems to have an important role for lin- c-kit+ cells inside CP, is expressed in a regulated manner and identifies potential human CP.

Citrobacter rodentium induces an acute, self-limited colitis in mice which is histologically associated with crypt hyperplasia. The infection serves as a model for human infectious colitis induced by enteropathogenic Escherichia coli. We investigated if Balb/c mice, which had spontaneously cleared C. rodentium infection, were protected against re-infection and if resistance against intestinal infection can be systemically transferred using spleen cells. The course of infection was monitored by faecal excretion. Spleen cells, splenic CD3+ and CD4+ cells were transferred from resistant mice to non-infected recipients prior to infection. Cytokine secretion, serum and faecal antibody titres and histological disease severity were assessed. Balb/c mice were resistant against re-infection. The course of infection was shorter in mice receiving primed spleen cells, CD3+ and CD4+ cells. Transfer of CD4+ T cells from resistant mice induced gamma-interferon, interleukin (IL)-2 and IL-17 secretion and suppressed IL-10 secretion. Anti-Citrobacter serum IgG1 and IgG2a enzyme-linked immunosorbent assay OD levels were increased. Faecal IgA secretion was increased while serum IgA was suppressed in recipients of CD4+ cells. Large bowel histology showed protection from colitis in recipients of primed cells as indicated by normal colonic epithelium. In Balb/c mice, C. rodentium infection is followed by resistance, which can be transferred by CD4+ cells. Transfer of protection is associated with IL-17 secretion, enhanced serum IgG and faecal IgA secretion. This is the first study to demonstrate the mechanisms by which systemic resistance from previously C. rodentium-infected mice can be transferred to non-infected animals.

This paper extends an economic geography model by tariffs to analyze their impact on welfare and sustainability of agglomerations. Policies with and without cooperation are compared, with the goal of maximizing aggregated welfare in the former and regional welfare in the latter case. The main result is that under cooperation poorer regions are worse off in two respects. In the short-run they loose even more welfare and in the long-run sustainable agglomerations in richer regions get more likely. Thus, although cooperation could generate aggregated welfare gains the potential losers face even in the short-run no incentive to remove tariffs unless they are compensated appropriately, for instance by transfers. In this sense transfers from the rich to the poor are not only a policy to reach the goal of equity but also a necessary precondition to reach aggregated efficiency.