Stability of poly(D,L-lactide-co-glycolide) and leuprolide acetate in in-situ forming drug delivery systems.

In-situ forming drug delivery systems are prepared by dissolving a drug and a biodegradable polymer (poly(D,L-lactide-co-glycolide), PLGA) in a biocompatible organic solvent (In-situ implant, ISI) or further emulsified into an external phase (oil or aqueous solution), resulting in oil-in-oil or oil-in-water emulsions (In-situ forming microparticles, ISM). The chemical stability of PLGA and the drug is a major concern. In this study, the stability of PLGA and leuprolide acetate in the in-situ forming systems and lyophilized sponges was investigated. The degradation of PLGA increased with increasing storage temperature and water content in the biocompatible solvents. A faster degradation occurred in polar protic solvents (2-pyrrolidone, PEG 400, triethyl citrate) than in polar aprotic solvents (N-methyl-2-pyrrolidone, DMSO, triacetin, ethyl acetate). The presence of leuprolide acetate significantly accelerated PLGA degradation, especially in solution state. PLGA was stable in oily suspensions at 4 degrees C and degraded only slightly faster than solid powder at 25 degrees C. No interaction between the oils and the PLGA was observed as indicated by an unchanged T(g) of approx. 47 degrees C. PLGA underwent a slight degradation at 4 degrees C after 150 days in water and saturated sodium chloride solution. The degradation was slower in saturated sodium chloride solution than in water at 25 degrees C. Residual acetic acid in lyophilized sponges facilitated the PLGA degradation in contrast to dioxane. Leuprolide acetate did not affect the PLGA stability negatively. However, lidocaine significantly enhanced the polymer degradation in the sponges. Finally, leuprolide acetate was chemically stable in the sponges, the oils and the polymer solutions in suspension state, but unstable (aggregation) when dissolved in the polymer solutions and stored at 25 degrees C and 40 degrees C.     

Erste-Hilfe-Ausbildung in der Grundschule

To shorten the interval between the occurrence of an emergency situation when the patient remains without treatment until the time when therapeutic measures can be initiated, in Germany improved training particularly for laypersons is necessary. Although a large proportion of the population has already participated in a first aid course, there is much uncertainty over how to proceed. Repeated teaching units, begun early and adapted to the various age groups, serve as countermeasures. Thus, a project was developed in the Saarland involving the on-site educators who teach the first basic principles of first aid. The project is aimed specifically at shortening the time interval when the injured receive no treatment and deals with the topics of emergency call, monitoring and maintaining vital functions, and organization of emergency medical services. The present article describes initial experiences gathered during implementation of the project.     

Highly resolved in vivo 1H NMR spectroscopy of the mouse brain at 9.4 T.

An efficient shim system and an optimized localization sequence were used to measure in vivo 1H NMR spectra from cerebral cortex, hippocampus, striatum, and cerebellum of C57BL/6 mice at 9.4 T. The combination of automatic first- and second-order shimming (FASTMAP) with strong custom-designed second-order shim coils (shim strength up to 0.04 mT/cm2) was crucial to achieve high spectral resolution (water line width of 11-14 Hz). Requirements for second-order shim strengths to compensate field inhomogeneities in the mouse brain at 9.4 T were assessed. The achieved spectral quality (resolution, S/N, water suppression, localization performance) allowed reliable quantification of 16 brain metabolites (LCModel analysis) from 5-10-microL brain volumes. Significant regional differences (up to 2-fold, P < 0.05) were found for all quantified metabolites but Asp, Glc, and Gln. In contrast, 1H NMR spectra measured from the striatum of C57BL/6, CBA, and CBA/BL6 mice revealed only small (<13%, P < 0.05) interstrain differences in Gln, Glu, Ins, Lac, NAAG, and PE. It is concluded that 1H NMR spectroscopy at 9.4 T can provide precise biochemical information from distinct regions of the mouse brain noninvasively that can be used for monitoring of disease progression and treatment as well as phenotyping in transgenic mice models.     

Die laparoskopische Chirurgie des Kolonkarzinoms. Kommentar aufgrund der aktuellen Studienlage

Zusammenfassung Die genauere Bestimmung von Leitfunktionen soll das früher zum strukturdynamischen Ansatz Gesagte ergänzen, korrigieren und zum Abschluss bringen. Auf vormenschlichen Entwicklungsstufen geht es um die autopraktischen Antriebe der Lebensbewegung und ihre instinktive Hemmung und Aktivierung. Auf der menschlichen Ebene hat sich die Richtung der Antriebe differenziert. Ihre Autopraxis als das bewegende Prinzip ist geblieben. Hemmung und Aktivierung sind in die Entwicklung einer Innenwelt und ihres strukturellen Hintergrundes einbezogen worden und haben sich aus der instinktiven Abhängigkeit gelöst. An der Funktion der Aktivierung hat sich wenig geändert. Hemmung hat sich in die komplexe Funktion der Desaktualisierung ausgeweitet; sie greift als steuerndes Prinzip in das autopraktische Geschehen ein. Abschließend werden mit einem Exkurs in die Willensthematik die Funktionen von Autopraxis, Desaktualisierung und Aktivierung in ihrem Zusammenwirken erläutert.

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