Generalisation of conditioned fear and its behavioural expression in mice

Mice are favourite subjects in molecular and genetic memory research and frequently studied with classical fear conditioning paradigms that use an auditory cue (conditioned stimulus, CS(+)) to predict an aversive, unconditioned stimulus (US). Yet the conditions that control fear memory specificity and generalisation and their behavioural expression in such conditioned mice have not been analysed systematically. In the current study we addressed these issues in the most widely used mouse strain of behavioural genetics, C57Bl/6. In keeping with findings in other species we demonstrate the dependence of fear memory generalisation on training intensity (i.e. both US intensity and the number of CS(+) and US applied) after both excitatory (explicitly paired presentation of CS(+) and US) and inhibitory training (explicitly unpaired presentation of CS(+) and US). Furthermore, inhibitory overtraining was associated with changes of uncued anxiety-like behaviour in a light/dark exploration test, indicative of an emotional sensitisation reaction as consequence of a lack of US predictability. Together our results describe the qualitatively and quantitatively different increases of defensive behaviour in response to conditioned stimuli of different salience and identify training conditions that lead to fear memory generalisation and emotional sensitisation in C57Bl/6 inbred mice.     

Diffusion- and perfusion-weighted MR imaging in a patient with acute demyelinating encephalomyelitis (ADEM).

To monitor changes of brain tissue metabolism in acute demyelinating encephalitis (ADEM), we examined a patient with suspected ADEM by serial MRI including diffusion- and perfusion-weighted imaging (DWI, PWI). Within the inflammatory tissue, the apparent diffusion coefficients were reduced, normal, and increased. Perfusion varied between reduced and normal values, except for small hyperperfused regions. Combining standard MRI with DWI and PWI may elucidate different overlapping phases in cerebral inflammation.     

OncoTREAT: a software assistant for cancer therapy monitoring

ObjectCancer is one of the leading causes of death worldwide and therapy options are often associated with severe stress for the patient and high costs. Therefore, precise evaluation of therapy success is essential. Material and Methods In the framework of the VICORA research project (Virtual Institute for Computer Assistance in Clinical Radiology), a software application was developed to support the radiologist in evaluating the response to tumor therapy. The application provides follow-up support for oncological therapy monitoring by volumetric quantification of lung, liver and brain metastases as well as enlarged lymph nodes and assists the user by temporal registration of lesion positions. Results With close cooperation between computer scientists and radiologists the application was tested and optimized to achieve a high degree of usability. Several clinical studies were carried out to evaluate the robustness and reproducibility of the volumetry methods. Conclusion Automatic volumetry and segmentation allows reliable detection of tumor growth and has the potential to increase reliability and significance of monitoring tumor growth in follow-up examinations.     

Pr?diktoren für die medizinische Inanspruchnahme am Beispiel von Patienten mit der Diagnose Morbus Crohn

PURPOSE: The objective of the study was to identify predictors of health-care utilization in Crohn's disease. PATIENTS AND METHODS: Therefore, data of 499 patients was collected over a 2-year period. A sample of 87 patients was taken and analyzed. Health-care utilization was measured as work disability days and hospital bed days. Sociodemographic, mental as well as somatic variables were used as possible predictors of health-care utilization. RESULTS: In a linear regression model with work disability days, the variables gender (b = 43.01; p = 0.032) and depressiveness (b = 2.949; p = 0.014) turned out to be significant (R(2) = 0.189). In a linear regression model with hospital bed days, the variables gender (b = 19.863; p = 0.006) and age (b = 0.785; p = 0.029) proved to be significant (R(2) = 0.114). No significant result was found for somatic variables such as severity of disease. CONCLUSION: Psychosocial variables such as depressiveness, gender and age have, therefore, a low but measurable impact on health-care utilization of patients with Crohn's disease. Increased consideration of these variables in clinical practice would not only improve the quality of life of these patients but also reduce health-care utilization.     

Risk factors for metabolic syndrome after liver transplantation: A systematic review and meta-analysis

Introduction

Metabolic syndrome is associated with increased risk of cardiovascular events, which contributes to the elevated mortality rate among liver transplant recipients. The objective of this systematic review and meta-analysis was to assess the prevalence and risk factors for metabolic syndrome after liver transplantation.

Ephrin-A1 binding to CD4+ T lymphocytes stimulates migration and induces tyrosine phosphorylation of PYK2

Eph receptors, the largest subfamily of receptor tyrosine kinases, and their ephrin ligands are important mediators of cell-cell communication regulating cell attachment, shape, and mobility. Here we demonstrate that CD4+ T lymphocytes express the EphA1 and EphA4 receptors and that these cells bind the ligand ephrin-A1. Further we show ephrin-A1 expression in vivo on high endothelial venule (HEV) endothelial cells. Ephrin-A1 binding to CD4+ T cells stimulates both stromal cell-derived factor 1alpha (SDF-1alpha)- and macrophage inflammatory protein 3beta (MIP3beta)-mediated chemotaxis. In line with the increased chemotactic response, increased actin polymerization is observed in particular with the combination of ephrin-A1 and SDF-1alpha. Signaling through EphA receptors induces intracellular tyrosine phosphorylation. In particular, proline-rich tyrosine kinase 2 (PYK2) is phosphorylated on tyrosine residues 402 and 580. Ephrin-A1-induced chemotaxis and intracellular tyrosine phosphorylation, including EphA1 and Pyk2, was inhibited by Tyrphostin-A9. In conclusion, ligand engagement of EphA receptors on CD4+ T cells stimulates chemotaxis, induces intracellular tyrosine phosphorylation, and affects actin polymerization. This, together with our finding that ephrin-A1 is expressed by HEV endothelial cells, suggests a role for Eph receptors in transendothelial migration.     

Efficacy of sulfonamides and Baycox(®) against Isospora suis in experimental infections of suckling piglets

Sulfonamide treatment of piglets against neonatal coccidiosis has frequently been suggested in the literature. In order to evaluate the efficacy of sulfonamides against experimental Isospora suis infections in suckling piglets (oral infection with 1,500 sporulated oocysts of I. suis per piglet on the fourth day of life), two trials were conducted. In trial I, oral sulfadimidine (group Sulfa-Oral) was applied in doses of 100 mg/kg of body weight (BW) 1 day before infection and 75 mg/kg BW daily for the following 5 days, and sulfamethoxypyrimidine (SMP) was applied parenterally in daily doses of 75 mg/kg BW for the same time period. In trial II, SMP was applied parenterally in doses of 75 mg/kg BW (a) from the day of infection daily for 7 days (SMP-Standard), (b) for 2 days starting on the day of infection (SMP-Early), (c) for 3 days starting 2 days post-infection (d.p.i.; SMP-Middle), (d) for 2 days starting 5 d.p.i. (SMP-Late), and (e) every other day from the day of infection until 6 d.p.i. (SMP-Alternating), as well as (f) orally in doses of 75 mg/kg BW from the day of infection for 7 days (SMP-Oral). The sulfonamide-treated groups were compared to a toltrazuril-treated group (single oral treatment with Baycox? 5% suspension, 20 mg/kg BW 2 d.p.i.) and to a water-treated Control group. Each group consisted of seven to nine piglets. The parameters evaluated were oocyst excretion and fecal consistency/diarrhea from 4 to 15 d.p.i. Sulfa-Oral, SMP-Early, and SMP-Late had no significant effect in reduction of oocyst excretion and diarrhea, whereas treatment for 3–7 days with SMP reduced both parasite shedding and diarrhea significantly. Oral treatment with SMP was comparable to parenteral application. Baycox? in a single application had the most pronounced effect and completely suppressed oocyst excretion and diarrhea during the examination period. It could be shown that repeated application of sulfonamides, provided that the appropriate time period after infection is covered, can in principle be used to control piglet coccidiosis; however, the amount of work required is considerable, and the practicability is poor. Due to the short half-life of sulfonamides in pigs and the lack of predictability of the time point of infection, an efficient application of sulfonamides to control piglet coccidiosis under field conditions appears unlikely. Baycox?, on the other hand, applied once during the prepatent period of infection, had a lasting effect and can be used to most effectively control I. suis.     

The effect of estrogen and progesterone on spreading depression in rat neocortical tissues

Although gender differences in the incidence of migraine with aura appear to be related to high circulating levels of ovarian hormones, the underlying mechanisms are not yet fully understood. Several studies have suggested a major role for spreading depression (SD) in the pathogenesis and symptomatology of migraine with aura. To investigate a possible role of SD in the association of high female hormones and attacks of migraine with aura, the effects of beta-estradiol and progesterone on SD were studied in rat neocortical tissues. Application of both hormones enhanced the repetition rate as well as the amplitude of SD in neocortical slices treated with hypotonic artificial cerebrospinal fluid. beta-Estradiol and progesterone also dose dependently increased the amplitude of SD induced by KCl microinjection. Both hormones exhibited a pronounced, persisting, and significant enhancement of long-term potentiation of the field excitatory postsynaptic potential in the neocortical tissues. The changes in SD characteristics in the presence of estrogen and progesterone may responsible for increased migraine with aura attacks associated by high female hormones. These hormones may exert their effects on SD via facilitation of synaptic transmission.