A Longitudinal Study of Disability,Cognition and Gray Matter Atrophy in Early Multiple Sclerosis Patients According to Evidence of Disease Activity

New treatment options may make “no evidence of disease activity” (NEDA: no relapses or disability progression and no new/enlarging MRI lesions, as opposed to “evidence of disease activity” (EDA) with at least one of the former), an achievable goal in relapsing-remitting multiple sclerosis (RRMS). The objective of the present study was to determine whether early RRMS patients with EDA at one-year follow-up had different disability, cognition, treatment and gray matter (GM) atrophy rates from NEDA patients and healthy controls (HC). RRMS patients (mean age 34 years, mean disease duration 2.2 years) were examined at baseline and one-year follow-up with neurological (n = 72), neuropsychological (n = 56) and structural MRI (n = 57) examinations. Matched HC (n = 61) were retested after three years. EDA was found in 46% of RRMS patients at follow-up. EDA patients used more first line and less second line disease modifying treatment than NEDA (p = 0.004). While the patients groups had similar disability levels at baseline, they differed in disability at follow-up (p = 0.010); EDA patients progressed (EDSS: 1.8–2.2, p = 0.010), while NEDA patients improved (EDSS: 2.0–1.7, p<0.001). Cognitive function was stable in both patient groups. Subcortical GM atrophy rates were higher in EDA patients than HC (p<0.001). These results support the relevance of NEDA as outcome in RRMS and indicate that pathological neurodegeneration in RRMS mainly occur in patients with evidence of disease activity.     

A Role for the Protein Tyrosine Phosphatase CD45 in Macrophage Adhesion through the Regulation of Paxillin Degradation

CD45 is a protein tyrosine phosphatase expressed on all cells of hematopoietic origin that is known to regulate Src family kinases. In macrophages, the absence of CD45 has been linked to defects in adhesion, however the molecular mechanisms involved remain poorly defined. In this study, we show that bone marrow derived macrophages from CD45-deficient mice exhibit abnormal cell morphology and defective motility. These defects are accompanied by substantially decreased levels of the cytoskeletal-associated protein paxillin, without affecting the levels of other proteins. Degradation of paxillin in CD45-deficient macrophages is calpain-mediated, as treatment with a calpain inhibitor restores paxillin levels in these cells and enhances cell spreading. Inhibition of the tyrosine kinases proline-rich tyrosine kinase (Pyk2) and focal adhesion kinase (FAK), kinases that are capable of mediating tyrosine phosphorylation of paxillin, also restored paxillin levels, indicating a role for these kinases in the CD45-dependent regulation of paxillin. These data demonstrate that CD45 functions to regulate Pyk2/FAK activity, likely through the activity of Src family kinases, which in turn regulates the levels of paxillin to modulate macrophage adhesion and migration.     

Stepwise incorporation of white clover (Trifolium repens L.) as fertiliser increases nitrogen fixation and improves nitrogen retention when intercropped with leek (Allium porrum L.)

Plant and Soil - We investigated whether the incorporation of intercropped white clover as a split-dose fertiliser improves N retention of the plant-soil system in leek production. White clover and...     

Senescence in oat leaf segments under hypobaric conditions

The physiological effects of storing plants under hypobaric conditions were studied using oat ( Avena sativa L. cv. Victory) leaf segments as a test system. The segments from seven day old plants were floated on water and stored in darkness at 12°C, 1.6 kPa or at 25°C, 6 kPa. Low temperature or hypobaric conditions delayed senescence, whereas the combination arrested the syndrome at an early stage. One of the effects of low pressure was to force the stomata open. The hormones abscisic acid and kinetin, which affect the stomatal aperture and also senescence, did not show any effect in hypobarically stored plant material. The stomata were forced open in darkness when the pressure was lower than 77 kPa and opening time was 8 h. The senescence syndrome in hypobarically stored segments developed similar to those treated with kinetin at 101 kPa.     

Studies on curcumin and curcuminoids. XXIX. Photoinduced cytotoxicity of curcumin in selected aqueous preparations.

Natural curcumin was evaluated as a potential photosensitizer for oral applications. The photocytotoxicity of curcumin on salivary gland acinar cells (SM 10-12) was investigated in five aqueous preparations consisting of 5% DMSO, non-ionic micelles, cyclodextrin, liposomes, or a hydrophilic polymer. The difference in phototoxic effects between natural curcumin and synthetic curcumin was examined. Cytotoxicity in SM 10-12 cells exposed to curcumin in the concentration range 0.4-13.5 microM was investigated by MTT test, a fluorescence-staining microscopic test, and by Western immunoblotting techniques. The potential formation of a photoreaction product, hydrogen peroxide, was evaluated by a fluorescence assay. The light source was a halogen lamp used in the dental clinic, emitting mainly in the blue part of the spectrum. The phototoxic effect on SM 10-12 cells was dependent on curcumin concentration, the light dose and the type of preparation. Natural and synthetic curcumin induced phototoxicity to the same extent. Significant effects on the cells were obtained at low curcumin concentrations (< or =0.5 microM) and at a low light dose (< or =6 J cm(-2)), after 3 h incubation. Neither the activation of caspases-3, -7, -8 or -9, nor the formation of hydrogen peroxide could be detected in cells exposed to curcumin and light. The liposome preparation was the most efficient vehicle for curcumin to induce cell death. The phototoxic effect induced by curcumin is highly dependent on the type of preparation. Curcumin might be a potential photosensitizer in the treatment of oral lesions and cancers provided careful selection of the vehicle.     

Über den Einfluß der Kultivierungsbedingungen auf die Farbstoffbildung durch Penicillium-Arten

Zusammenfassung Es wird gezeigt, daß sich die Farbstoffbildung der Penicillium-arten in recht erheblichem Ausmaß durch die Züchtungsbedingungen beeinflussen läßt. Bereits bei der vergleichenden Kultivierung der Pilze in der Oberflächen- und Submerskultur können auffallende Unterschiede beobachtet werden. Ferner konnte durch den Zusatz von Asparagin, Glutaminsäure und Zinksulfat besonders in der Submerskultur die Farbstoffbildung recht erheblich geändert werden. Dabei verhielten sich allerdings die einzelnen Pilze individuell außerordentlich verschieden, so daß keine allgemein gültigen Gesetzmäßigkeiten über die Beeinflußbarkeit des Prozesses abgeleitet werden können. Wohl aber können bestimmte Typen von Fällen aufgestellt werden, denen jeweils eine Reihe von Penicillien zuzuordnen ist.Aus dem vormaligen Institut für Biochemie u. Nahrungsmittelchemie der Deutschen Technischen Hochschule in Prag. — Vgl. auch Diplom-Arbeit H. Kundtner, Prag, März 1945.     

Block-Surface Staining

A method is described by which the tissue exposed on sectioning a specimen embedded in paraffin can be visualized in situ. The fixed specimen is impregnated with lead acetate, dehydrated in dioxane, infiltrated with paraffin and embedded. Tissues exposed on sectioning are developed by applying to the cut surface of the block a solution of potassium sulphide in water. Concentrations of the reagents used and the time intervals for the procedure are dependent upon the size of the specimen and upon the degree of contrast required. The method is described as it was applied to the study of a small human fetus in cross section. Representative photographs are included to show the results obtained.     

Die Wirkung von Thymuswirkstoffen auf Wachstum und Metamorphose sowie deren Einfluß auf Endokrine Drüsen beiXenopus laevis Daudin

Ohne Zusammenfassung     

Prevalence of skull pathologies in European harbor seals (<Emphasis Type="Italic">Phoca vitulina</Emphasis>) during 1981–2014

Harbor seals (Phoca vitulina) inhabit the seas surrounding Denmark and are an important top predator in the marine food chain. This trophic position exposes them to environmental contaminants with disease epidemics and hunting being additional threats to this population. It is therefore important to study how environmental pollution at the current order of magnitude affects the health of the population. Earlier studies have shown that occurrence of periodontitis could be linked to the amount of pollution the seals were subjected to. In order to investigate this further, 380 skulls and 141 mandibles of harbor seals (Phoca vitulina) from the Wadden Sea, the Limfjord, and Kattegat collected during the period 1970–2014 were examined. The skulls were examined for pathological lesions. The Hounsfield Units (HU) which are correlated to the bone mineral density (BMD) were measured in a subsample (n = 34) using CT scans. The macroscopic examination revealed (with the exception of the Swedish part of Kattegat) a significant increase of pathological lesions over the study period of 1981–2014. The examination of HU showed that median HU measured at multiple sites was highest in the healthy skulls compared to the skulls with one or more of the lesions. A discriminant analysis allowed high discriminatory capacity to separate healthy skulls from the skulls with pathologies, simply by the utilization of the HU data. Former studies of BMD in marine mammals have shown that exposure to environmental chemicals alter BMD and cause periodontitis. The present study, based on temporal and spatial trends in BMD, confirms the results of previous studies.