Eosinophile Ösophagitis: Die Sicht des Gastroenterologen

Zusammenfassung: Die eosinophile Ösophagitis ist charakterisiert durch Symptome ösophagealer Dysfunktion (meist Dysphagie) und eosinophile Entzündungsinfiltrate im Ösophagus. Diese kommen in anderen Abschnitten des Gastrointestinaltrakts nicht vor. Differenzialdiagnosen, die mit ösophagealer Eosinophilie einhergehen, müssen vor der Diagnose einer eosinophilen Ösophagitis ausgeschlossen werden. Der typische Patient mit eosinophiler Ösophagitis ist männlich und hat atopische Begleiterkrankungen. Zu den Behandlungsoptionen gehören medikamentöse Therapie, Eliminationsdiät sowie ösophageale Dilatatio

Therapie der CED bei Steroidversagen: Immunsuppressiva oder Biologika?

Zusammenfassung: Trotz oftmals erfolgreichem Einsatz von systemischen Steroiden in der Behandlung von Patienten mit aktiver chronisch-entzündlicher Darmerkrankung (CED) sind Limitationen vorhanden aufgrund von primärem Nichtansprechen, Steroidabhängigkeit sowie Steroidresistenz. Eine Langzeittherapie mit Steroiden ist im Hinblick auf die bekannten Nebenwirkungen zu vermeiden. Dieser Artikel erläutert Indikationen für den Einsatz von Immunmodulatoren (Azathioprin, 6-Mercaptopurin, Methotrexat), Medikamenten gegen Tumornekrosefaktor (Anti-TNF-Therapie) sowie Calcineurininhibitoren (Ciclosporin, Tacrolimus) bei Steroidresisten

Deletion of the alpha-synuclein locus in a subpopulation of C57BL/6J inbred mice

BACKGROUND: The presynaptic protein α-synuclein is involved in a range of neurodegenerative diseases. Here we analyze potential compensatory mechanisms in α-synuclein null mutant mice. Furthermore, the findings reveal problems that may be associated with inbred mouse strains. RESULTS: Expression profiling by cDNA array technology in a transgenic mouse model revealed striking differences only in the expression level of α-synuclein. This was caused by a chromosomal deletion of the α-synuclein locus in the C57BL/6J inbred strain used for backcrossing. However, the deletion is only present in a subpopulation of C57BL/6J mice, namely animals from Harlan. No other genes are known to be affected by the deletion, which is estimated to be smaller than 2 cM. We propose to name this strain C57BL/6S. C57BL/6S animals appear phenotypically normal. They show no upregulation of β-synuclein or γ-synuclein, excluding a compensatory mechanism. Also, the expression of synphilin-1 was unaffected. CONCLUSIONS: The C57BL/6S strain should help in the understanding of the physiological function of α-synuclein and its involvement in synucleinopathies. Also, the findings exemplify unexpected complications that may arise during the study of transgenic models or inbred strains, in particular when combined with genome wide screening techniques

Intermittent euxinia in the high-latitude James Ross Basin during the latest Cretaceous and earliest Paleocene

Seymour Island, in the James Ross Basin, Antarctica, contains a continuous succession of latest Cretaceous sediments deposited in a shallow marine environment at high latitude, making it an ideal place to study environmental changes prior to the K–Pg mass extinction. We measured major and trace elements and conducted petrographic analysis of two sections from the Maastrichtian–Danian López de Bertodano Formation of Seymour Island. Several lines of evidence point to intermittently anoxic to euxinic conditions during deposition, including the presence of pyrite framboids with a size distribution suggesting syngenetic formation in the water column, and enrichments in several trace elements, including molybdenum, arsenic, copper, zinc, and chromium. Molybdenum enrichments are clearly associated with enrichments in manganese and authigenic iron, suggesting “shuttling” of redox sensitive trace elements across a chemocline that fluctuated across the sediment-water interface. Comparisons with modern systems suggest relatively high frequency redox variability, possibly over approximately annual timescales, which may be related to the annual cycle of polar sunlight and associated seasonal changes in primary productivity. Glauconitic horizons are associated with more reducing conditions, including at the K–Pg boundary, though this does not appear to be a uniquely euxinic interval; similar degrees of trace element enrichment are seen in other highly glauconitic intervals. While euxinia may have contributed to low diversity in the lowermost ‘Rotularia Units’, redox conditions do not seem to have been the primary control on the transition to a mollusc dominated fauna in the latest Maastrichtian. Redox conditions show little to no response to the eruption of the Deccan Traps or Maastrichtian climatic changes. Instead, intermittent euxinia appears to have been a characteristic feature of this high-latitude environment during the Cretaceous–Paleogene transition

Eosinophile Ösophagitis : Die Sicht des Gastroenterologen [Eosinophilic esophagitis : The gastroenterologist's perspective].

Eosinophilic esophagitis is characterized by symptoms of esophageal dysfunction and eosinophil-predominant esophageal inflammation. Eosinophilic inflammation in other parts of the gastrointestinal tract is absent and several differential diagnoses for esophageal eosinophilia have to be excluded before diagnosing eosinophilic esophagitis. Most patients are male and have concomitant atopic disorders. Therapeutic options are based on drugs, diet and dilation

Investigating temperature signalling pathways in Arabidopsis thaliana using small molecules

Upon exposure to heat or cold, Arabidopsis thaliana seedlings undergo rapid transcriptional reprogramming of several hundreds of genes that promote stress tolerance. Despite extensive characterisation of the transcriptional responses to these stimuli, however, relatively little is known about the mechanisms by which temperature signals are perceived and transduced in plant cells. High or low seasonal temperatures have large impacts on crop productivity and are expected to intensify given current global climatic projections. It is therefore of agricultural importance to better understand temperature signalling pathways in plants in order to find solutions to this problem. In this thesis, a chemical genomics screen for molecules activating or repressing heat-inducible genes in A. thaliana was performed in collaboration with Syngenta and the biological targets of these chemicals were predicted based on structural similarities to compounds with known modes of action. Many molecules that affect the function of chloroplasts or mitochondria either activate or repress heat-responsive genes, thus implicating these organelles in the regulation of plant temperature responses. In addition, the translation inhibitor cycloheximide was identified as a repressor of heat-inducible genes and an activator of early cold-inducible genes. Diverse translation inhibitors trigger a cytosolic influx of calcium ions and several inhibitors of translation elongation were found to strongly activate cold-inducible gene expression in a calcium-dependent manner. Furthermore, it was demonstrated that cold shock causes rapid translation repression in A. thaliana seedlings and that the elongation factor LOS1 is involved in cold- or cycloheximide-induced gene expression, thus implicating translational machinery in the regulation of temperature signalling in plants. Finally, one of the chemicals identified in the screen, S01A463859Y, was found to improve heat resilience in A. thaliana and may therefore be of potential use in enhancing crop productivity during thermal stress.This was a BBSRC CASE PhD with Syngenta (Stein, Switzerland), involving chemicals belonging to Syngenta. Funding was provided by the BBSRC and by Syngenta