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.     

Untersuchungen über den osmotischen Wert polyploider Pflanzen

Zusammenfassung In der Mehrzahl der untersuchten Fälle (insgesamt über 1000 Einzelmessungen) wurden die osmotischen Werte der Tetraploiden niedriger gefunden als die der Diploiden, doch sind die Unterschiede im allgemeinen gering. Junge Pflanzen hatten immer niedrigere 4n-Werte; bei alten Pflanzen und bei Pflanzen unter extremen Kulturbedingungen waren aber vielfach die Werte der 4n höher. Es wird die Hypothese aufgestellt, daß niedrigere osmotische Werte der Tetraploiden den Normalzustand darstellen, daß aber die Polyploiden wie in anderen Eigenschaften, so auch in ihrer Osmotik variabler sind und unter dem Einfluß von Außen-bedingungen ihre osmotischen Werte stärker modifizieren.Unter physiologischen Zwangsbedingungen (Trockenkultur, Pfropfungen) wurde an den Tetraploiden eine unter den gegebenen Verhältnissen zweckmäßige Erhöhung ihrer osmotischen Werte über das Niveau der 2n beobachtet. Gegen Trockenklima erwiesen sich die untersuchten Tetraploiden im Vergleich mit den Diploiden resistenter.Irgendwelche artspezifischen Eigentümlichkeiten konnten im Rahmen der untersuchten Pflanzen nicht festgestellt werden.Mit 6 Textabbildungen.     

Detection of hydrogen peroxide by lactoperoxidase-mediated dityrosine formation

The aim of this work was to study the dityrosine-forming activity of lactoperoxidase (LPO) and its potential application for measuring hydrogen peroxide (H₂O₂). It was observed that LPO was able to form dityrosine at low H₂O₂ concentrations. Since dityrosine concentration could be measured in a simple fluorimetric reaction, this activity of the enzyme was utilized for the measurement of H₂O₂ production in different systems. These experiments successfully measured the activity of NADPH oxidase 4 (Nox4) by this method. It was concluded that LPO-mediated dityrosine formation offers a simple way for H₂O₂ measurement.     

Etiological study on isolated esophageal atresia

Summary A study group of 160 index patients with isolated esophageal atresia, a control group of 160 matched healthy controls, and the first-degree relatives of patients and controls were examined; epidemiological, family planning, teratological, and genetic data were obtained by personal interview in the study and control groups. One half of the index patients were male. Intrauterine growth retardation, a higher proportion of mothers under 19 or over 30 years of age, and less skilled professions of the parents were found in the study group. There were more extramarital conceptions, more pregnancies in spite of the use of contraceptive pills, and more delayed conceptions in index patients' mothers. The teratogens studied did not have an obvious pathological effect here. The sib occurrence of isolated esophageal atresia was 0.43%, which did not correspond too well to the expected figure of 1.34% based on the polygenic model.