Induction of CYP1A in the beagle dog by an inhibitor of kinase insert domain-containing receptor: differential effects in vitro and in vivo on mRNA and functional activity.

Compound I [3-[5-(4-methanesulfonyl-piperazin-1-ylmethyl)-1H-indol-2-yl]-1H-quinolin-2-one] is a potent inhibitor of human kinase insert domain-containing receptor (KDR kinase), which is under investigation for the treatment of cancer. Bile duct-cannulated male beagle dogs were administered 6 mg/kg compound I q.d. for 14 days. There was an approximately 2.5-fold decrease in the mean plasma area under the curve of I on days 7 and 14 (approximately 11.3 microM . h), relative to day 1 (28.2 microM . h). In the dog, compound I was eliminated by metabolism, with a major pathway being aromatic hydroxylation and subsequent sulfation to form the metabolite M3. Metabolic profiling suggested that the pathway leading to the formation of the sulfated conjugate M3 was induced upon multiple dosing of I. Studies conducted in vitro suggested that CYP1A1/2 was responsible for the formation of the hydroxylated metabolite, which is sulfated to yield M3. Additional studies confirmed induction of CYP1A protein and activity in the livers of dogs treated with I. However, studies in a dog hepatocyte model of induction showed a surprising decrease both in CYP1A mRNA and enzymatic activity in the presence of I, emphasizing the need to consider the results from a variety of in vitro and in vivo studies in deriving an understanding of the metabolic fate of a drug candidate. It is concluded that the autoinduction observed after multiple treatments with compound I occurs since compound I is both an inducer and a substrate for dog CYP1A.     

Über den Vitamin A-Nachweis im Blute,in Exsudaten,im Duodenalsaft und in Faeces

Ohne Zusammenfassung     

Health and human rights--development of a questionnaire for measuring perceived human rights status

Zusammenfassung Gesundheit und Menschenrechte stellen in ihrer Verbindung ein wichtiges und innovatives Konzept für die zukünftige Public-Health-Forschung dar. Das Ziel der vorliegenden Studie war die Entwicklung eines Instrumentes zur Erfassung des empfundenen Menschenrechtsstatus und die Evaluation seiner psychometrischen Werte. Die Reliabilität und Validität dieses innovativen Fragebogens für Menschenrechte (MR) wurde an einer Gruppe von Public-Health-Studenten der Universität München (n=42) und an Teilnehmern der KORA-Frakturstudie (n=458) geprüft. Die Studien zeigten zufriedenstellende Ergebnisse für die zeitliche Stabilität (Pearson's r: 0,73; ICC: 0,69) und die interne Konsistenz (Cronbach's Alpha: 0,66–0,79). Die Prüfung der Validität mittels einer Faktoren-analyse und einer Zuordnungsstudie gab Hinweise darauf, dass der Menschenrechtsstatus ein nicht teilbares Konstrukt darstellt. Inhatlich zeigten sich in beiden Gruppen Defizite bei Items aus den Dimensionen Gerechtigkeit und Partizipation.

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Summary Health and human rights as interlinked concepts are a promising new avenue in public health. The aim of this study was the development of a reliable and valid instrument for the measurement of the human right status. The reliability and validity of this new questionnaire for human rights (HRS=human right scale) was measured within a group of Public Health students (n=42) and the participants of the KORA-fracture-study. Test-retest-reliability was 0.73 (ICC: 0.69) and Cronbach's alpha was 0.66–0.79. The evaluation of the validity with the help of a factor analysis and a reconstruction study pointed out, that the perceived human rights status has to be treated as an interlinked and not divisible concept. Both study groups showed deficits for items in the dimension justice and participation.

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Résumé La santé et les droits de l'homme représentent dans leur union un nouveau et important concept dans la recherche de la santé public. Le but de notre étude était le développment d'un questionnaire valide et reliable pour mesurer le status du droit de l'homme. La reliabilité et la validité furent mesuré parmis un groupe d' étudiants de santé public et les participants de l'étude KORA sur les fractures. L'analyse de l' étude montre des résultats satisfaisants pour la réliabilité (stabilité: 0.73; ICC 0.69 et alpha de Cronbach: 0.66–0.79). L'évaluation de la validité a indiqué, que le status du droit de l'homme représente une construction non divisible. Les deux groupes de l'étude montrent un déficit pour des critères dans les dimensions de la justice et de la participation.

     

Spontaneous rupture of the liver

A patient with systemic lupus erythematosus developed an acute surgical abdomen secondary to spontaneous rupture of the liver and died. Postmortem examination revealed an arteritis of the liver, pancreas, adrenal gland, skeletal muscle, and spleen. It appeared that an arteritis of the liver produced areas of infarction that ruptured and caused the clinical findings.     

Neurogene Wirbelsäulendeformitäten

Neurogenic spinal deformities develop primarily due to insufficient dynamic stabilization against gravity. Unilateral muscle overactivity is another but rare cause. The aim of treatment is to provide stability as well as to prevent deformity. In mild cases, the treatment of choice is a spinal brace because stabilization can be combined with residual mobility and adequate correction of shape. Seating shells are more readily accepted but less appropriate for this purpose. In severe cases, surgery is a good option despite the considerable effort involved and high rate of complications.