The objective was to examine duloxetine 60–120mg/day treatment for relapse prevention in adults with generalized anxiety disorder (GAD). Adult patients (N=887; mean age=43.3 years; 61.0% female) with DSM-IV-TR-defined GAD diagnosis were treated with duloxetine for 26 weeks. Patients who completed open-label phase and were treatment responders (≥50% reduction in Hamilton Anxiety Rating Scale total score to ≤11 and “much”/“very much improved” ratings for the last 2 visits of open-label phase) were randomly assigned to receive duloxetine or placebo for a 26-week double-blind continuation phase. Relapse was defined as ≥2-point increase in illness severity ratings or by discontinuation due to lack of efficacy. During the double-blind phase, placebo-treated patients (N=201) relapsed more frequently (41.8%) than duloxetine-treated patients (13.7%, N=204, P≤0.001) and worsened on each outcome measure (P≤0.001, all comparisons). Duloxetine 60–120 mg/day treatment was efficacious and reduced risk of relapse in patients with GAD.

This study investigated the impact of customary fluoride based mouthrinses on the ultrastructure and the functional properties of the in situ pellicle, considering the prevention of erosion (8 volunteers) and initial biofilm formation (12 volunteers). Bovine enamel slabs were carried intraorally. After 1 min of pellicle formation, the subjects rinsed with elmex Kariesschutz (A), Dontodent Med Care (B), meridol (C) or elmex Zahnschmelzschutz Professional (D) for 1 min. In situ pellicle formation was continued up to 30 min/8 h before processing the slabs in vitro. Erosion was simulated by incubating the specimens in HCl (pH 3.0, 2.3, 2.0) for 120 s, measuring the kinetics of calcium/phosphate release photometrically; representative samples were evaluated by TEM and EDX. Bacterial adhesion was visualized fluorescence microscopically (DAPI/BacLight). Native enamel slabs or physiological pellicle samples served as controls. All investigated mouthrinses enhanced the erosion preventive pellicle effect in dependence of the pH-value. A significant decrease of Ca/P release at all pH values was achieved after rinsing with D; TEM/EDX confirmed ultrastructural pellicle modifications. All mouthrinses tendentially reduced bacterial adherence, however not significantly. The mouthrinse containing NaF/AmF/SnCl2 (D) offers an effective oral hygiene supplement to prevent caries and erosion.

This study investigated the impact of customary fluoride based mouthrinses on the ultrastructure and the functional properties of the in situ pellicle, considering the prevention of erosion (8 volunteers) and initial biofilm formation (12 volunteers). Bovine enamel slabs were carried intraorally. After 1 min of pellicle formation, the subjects rinsed with elmex Kariesschutz (A), Dontodent Med Care (B), meridol (C) or elmex Zahnschmelzschutz Professional (D) for 1 min. In situ pellicle formation was continued up to 30 min/8 h before processing the slabs in vitro. Erosion was simulated by incubating the specimens in HCl (pH 3.0, 2.3, 2.0) for 120 s, measuring the kinetics of calcium/phosphate release photometrically; representative samples were evaluated by TEM and EDX. Bacterial adhesion was visualized fluorescence microscopically (DAPI/BacLight). Native enamel slabs or physiological pellicle samples served as controls. All investigated mouthrinses enhanced the erosion preventive pellicle effect in dependence of the pH-value. A significant decrease of Ca/P release at all pH values was achieved after rinsing with D; TEM/EDX confirmed ultrastructural pellicle modifications. All mouthrinses tendentially reduced bacterial adherence, however not significantly. The mouthrinse containing NaF/AmF/SnCl2 (D) offers an effective oral hygiene supplement to prevent caries and erosion.

Die invasiven und metastatischen Eigenschaften vieler Tumore werden mit einer Veränderung im physiologischen Gleichgewicht der Matrix Metalloproteinasen (MMP) und ihrer spezifischen und unspezifischen Inhibitoren in Zusammenhang gebracht. Das Ziel dieser Dissertation war es, die Wirkung von Batimastat, einem synthetischen Inhibitor der MMP, auf hormonabhängige und hormonunabhängige Prostatakarzinomzellinien sowie auf das Tumorwachstum im orthotopen Tumormodell des Dunning Tumor (R3327) zu untersuchen. Methoden: Im Zellkulturversuch wurde die Wirkung verschiedener Konzentrationen von Batimastat untersucht und die Proliferation mit dem MTT Test gemessen. Die Induktion des orthotopen Tumors erfolgte durch Inokulation von MATLyLu Zellen in die Rattenprostata (Dunning Tumor der Copenhagen Ratte). 10 Tiere wurden nach Tumorinduktion täglich mit 30 mg/kg Batimastat durch intraperitoneale Gabe behandelt, 10 weitere Ratten erhielten nur das Vehikel. Zehn Kontrolltiere blieben unbehandelt. Der Effekt auf des lokale Tumorwachstum wurden durch Bestimmung des Tumorgewichtes nach 20 Tagen definiert. Results:Batimastat zeigte eine dosisabhänige Hemmung des Wachstums der Prostatakarzinomzellinien in vitro. Bei 4000 ng/ml kam es zu einer eindeutigen Hemmung des Zellwachstums. Im Tierversuch fand sich nach 20 Tagen in der Kontrollgruppe ein mittleres Tumorgewicht von 18.9 ± 5,4 g, in der Vehikelgruppe von 22.3 ± 4,3 g und in der mit Batimastat behandelten Gruppe von 11.1 ± 2,6 g. Im Vergleich zur Kontroll- und Vehikelgruppe, zeigte sich in der Batimastatgruppe ein signifikant geringeres Tumorgewicht. Zusammenfassung: Batimastat kann das Tumorwachstum in einem Standardtiermodell des Prostatakarzinoms vermindern. Der Dunning Tumor der Copenhagen Ratte ist ein zuverlässiges Tiermodell zur weiteren Untersuchung von synthetischen Inhibitoren der MMP. / Background: Increased concentrations of metalloproteinases are associated with the invasive and metastatic behavior of several human malignant tumors. Normally, enzymatic activity is tightly regulated by nonspecific mechanisms and specific inhibitors. The aim of this dissertation was to determine the potential of a synthetic metallproteinase inhibitor, batimastat, to show its in vitro effect on hormonedependent and hormoneindependent prostate cancer cell lines and its in vivo effect on tumor growth in orthotopic cancer (R3327 Dunning tumor) in rats. Methods: In vitro, a dose response curve of batimastat was generated over 5 days using the MTT assay. Prostate cancer was injected in vivo in male Copenhagen rats by inoculating R3327 Dunning tumor cells (MATLyLu) into the ventral prostatic lobe of 30 rats. Each of 10 rats received batimastat (30 mg / kg / body weight) or vehicle once a day by i.p. application beginning the day of cell inoculation. Ten rats remained untreated. The effect on local tumor growth was evaluated by measuring tumor weights 20 days after tumor cell inoculation. Results: Significant inhibiton of tumor cell proliferation in vitro occurred at 4000 ng / ml batimastat. After orthotopic cell inoculation, tumors grew to mean weights of 18.9 ± 5,4 g in the control group without treatment, to 22.3 ± 4,3 g in the vehicle group, an to 11.1 ± 2,6 g in the treated group. In comparison to the control group and to the vehicle group, tumor weights increased significantly less under treatment with batimastat. Conclusions: Batimastat is able to reduce tumor growth in the standard prostate cancer model. Using this model, activity against cancer progression of future inhibitory agents can be reliably assessed.