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Ohne Zusammenfassung     

Fine Mapping the Spatial Distribution and Concentration of Unlabeled Drugs within Tissue Micro-Compartments Using Imaging Mass Spectrometry

Readouts that define the physiological distributions of drugs in tissues are an unmet challenge and at best imprecise, but are needed in order to understand both the pharmacokinetic and pharmacodynamic properties associated with efficacy. Here we demonstrate that it is feasible to follow the in vivo transport of unlabeled drugs within specific organ and tissue compartments on a platform that applies MALDI imaging mass spectrometry to tissue sections characterized with high definition histology. We have tracked and quantified the distribution of an inhaled reference compound, tiotropium, within the lungs of dosed rats, using systematic point by point MS and MS/MS sampling at 200 µm intervals. By comparing drug ion distribution patterns in adjacent tissue sections, we observed that within 15 min following exposure, tiotropium parent MS ions (mass-to-charge; m/z 392.1) and fragmented daughter MS/MS ions (m/z 170.1 and 152.1) were dispersed in a concentration gradient (80 fmol-5 pmol) away from the central airways into the lung parenchyma and pleura. These drug levels agreed well with amounts detected in lung compartments by chemical extraction. Moreover, the simultaneous global definition of molecular ion signatures localized within 2-D tissue space provides accurate assignment of ion identities within histological landmarks, providing context to dynamic biological processes occurring at sites of drug presence. Our results highlight an important emerging technology allowing specific high resolution identification of unlabeled drugs at sites of in vivo uptake and retention.     

Large Alterations in Ganglioside and Neutral Glycosphingolipid Patterns in Brains from Cases with Infantile Neuronal Ceroid Lipofuscinosis/Polyunsaturated Fatty Acid Lipidosis

Lipid composition was studied on cerebral tissue from nine children who had died of a progressive encephalopathy called the infantile form of neuronal ceroid lipofuscinosis (INCL) or polyunsaturated fatty acid lipidosis (PFAL). In the terminal stage of the disease, the concentrations of all lipid classes were found to be significantly reduced in the cerebral and cerebellar cortex and white matter. The concentration of gangliosides of the cerebral cortex was 15% and that of cerebrosides (galactosylceramide) in white matter 0.2-5% of the normal values for the children's ages. The reduction of gangliosides mainly affected those of the gangliotetraose series, particularly GD1a. The fatty acids of the linolenic acid series were strongly reduced in ethanolamine and serine phosphoglycerides. A very large increase up to 100-fold of oligoglycosphingolipids of the globo series and two fucose-containing lipids of the neolacto series was found in the forebrain of the three advanced cases examined. The brain tissue also contained very high concentrations of mono-, di-, and trisialogangliosides of the lacto and neolacto series, gangliosides with type 1 chain dominating. The structures of the gangliosides were tentatively identified by gas chromatography-mass spectrometry and monoclonal antibodies with carefully determined epitope specificity. The gangliosides and neutral glycosphingolipids had very similar fatty acid composition, consisting of about 40% stearic acid and 40% C24-acids.     

Fixation effects on membranous and endochondral onlay bone-graft resorption

Difficulties arise in the prediction of maintenance of graft volume over time when bone grafts are used for facial contour reconstruction. We hypothesize that graft fixation will decrease movement and lead to decreased resorption. Fixed and nonfixed endochondral (rib) and membranous (skull) onlay bone grafts measuring 30 X 10 X 4 mm were grafted to the mandible bilaterally in 10 adult sheep. Fixation was achieved using the lag-screw technique. Volume measurements using caliper technique were made 20 weeks postoperatively. The volume of graft present at 20 weeks was significantly greater for the fixed bone grafts (p less than 0.001): fixed membranous, 85.9 percent; fixed endochondral, 76.2 percent; nonfixed membranous, 55 percent; and nonfixed endochondral, 16.6 percent. The results are explained using biomechanical theories related to the effects of strain. At present, it is suggested by this study that when onlay bone grafts are stabilized, improved results with respect to graft resorption can be expected.     

Length, breadth, and elongation of avian eggs from the tables of Sch?nwetter

Summary UsingSchönwetter's data base regression equations are derived expressing egg length and egg breadth as a function of egg mass for Passerines (n=3929) and non-Passerines (n=3217). For both groups these show a variation around the mean which is twice as large for length as for breadth. The average elongation (length/breadth) ist presented for 27 orders ranging from 1.61 in Apterygiformes and Gaviiformes to 1.21 in Strigiformes as well as examples of a few families where elongation increases or decreases as egg mass becomes larger. Egg mass can be estimated from the relationship where egg mass=k(LB²). Mean values, SD, and range of k for both groups are given, but for any particular species are best derived from the dimensions of L, B, and egg mass inSchönwetter's tables.

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Länge, Breite und Form der Vogeleier auf der Grundlage der Tabellen vonSchönwetter

Zusammenfassung Regressionsgleichungen für Eilänge und Eibreite als Funktion der Eimasse ergeben für Passeres (3929 Arten) und Non-Passeres (3217 Arten) eine Streuung um den Mittelwert, die für Länge doppelt so hoch wie für die Breite ist. Das Verhältnis Länge: Breite reicht bei 27 Ordnungen von 1.61 bei Apterygiformes und Gaviiformes bis 1.21 bei den Strigiformes. In Beispielen für einzelne Familien steigt oder fällt der Wert mit zunehmender Eimasse. Letztere kann bestimmt werden gemäß k · (L · B²), wobei k eine Konstante darstellt. Mittelwerte, Standardabweichung und Konstante werden für Passeriformes und Non-Passeriformes angegeben, doch für einzelne Arten hält man sich am besten an die Werte beiSchönwetter.

     

Nitrogen in shoot litter,root litter and root exudates from nitrogen-fixingAlnus incana

Summary A pot experiment withAlnus incana (L.) Moench growing in sand was set up to compare the amounts of nitrogen released from plants shoot litter with that released below ground as root litter and/or root exudation. No nitrogen fixation by free-living microorganisms was found in the sand and the increased nitrogen content of the plant + soil system was therefore due to nitrogen fixation byFrankia in the alder root-nodules. Most of the nitrogen released from the plants was in the nitrogen-rich leaf and other shoot litter. Only small amounts of nitrogen were found in the drainage water from the pots and were recorded as increased nitrogen content of the sand.