S 50131 and S 51434, two novel small molecule glucokinase activators, lack chronic efficacy despite potent acute antihyperglycaemic activity in diabetic mice.

Background And Purpose: Small molecule glucokinase activators (GKAs) have been associated with potent antidiabetic efficacy and hepatic steatosis in rodents. This study reports the discovery of S 50131 and S 51434, two novel GKAs with an original scaffold and an atypical pharmacological profile.

Experimental Approach: Activity of the compounds was assessed in vitro by measuring activation of recombinant glucokinase, stimulation of glycogen synthesis in rat hepatocytes and increased insulin secretion from rat pancreatic islets of Langerhans.

Small molecule glucokinase activators disturb lipid homeostasis and induce fatty liver in rodents: a warning for therapeutic applications in humans.

Background And Purpose: Small-molecule glucokinase activators (GKAs) are currently being investigated as therapeutic options for the treatment of type 2 diabetes (T2D). Because liver overexpression of glucokinase is thought to be associated with altered lipid profiles, this study aimed at assessing the potential lipogenic risks linked to oral GKA administration.

Experimental Approach: Nine GKA candidates were qualified for their ability to activate recombinant glucokinase and to stimulate glycogen synthesis in rat hepatocytes and insulin secretion in rat INS-1E cells.

Evaluation of an OSCE assessment tool for abdominal ultrasound courses.

Purpose: The purpose of this study was the conception and evaluation of a standardized and reliable assessment tool in the OSCE format to measure the performance and practical skills of abdominal ultrasound users in PGME.

Materials And Methods: The design, logistics, pacing and the choice of tested competencies of a rotating OSCE parcours, as well as the options for quality control using detailed checklists versus global rating scales and different approaches to the training of the involved raters are described. Over the last 15 years the parcours has undergone incremental improvement and has been used in final examinations of abdominal ultrasound courses with approximately 5000 medical students and 2000 residents and fellows.

[Performance-related middle management in medical teaching. Attractiveness of incentive tools from the perspective of the teachers].

Background And Objective: German medical schools are increasingly challenged by the competition for public funds and talented students. Therefore. many curriculum planners, deans and school administrators plan to implement a systematic and comprehensive awarding system for good teaching.

[The use of nitric oxide in the treatment of acute respiratory failure].

Background: Nitric oxide was used as an important selective vasodilator in the treatment of acute respiratory failure accompanied with high pulmonary resistance in children and adults since late 80's.

Methods And Results: Paper includes remarks about nitric oxide physiology in organism. Group of 33 patients is presented (group I 26 newborns, group II 7 children) in which selective pulmonary vasodilation with nitric oxide was used.

[Sodium nitrite poisoning in a neonate].

Natrium nitrosum intoxication is usually associated with a subsequent methemoglobinemia. Beside it, nitrates can cause also some other pathological states. Treatment with the toluidine blue may have various adverse side effects.

Reduced food intake in response to CGP 71683A may be due to mechanisms other than NPY Y5 receptor blockade.

Introduction: The purpose of this study was to test the continuing validity of the hypothesis that neuropeptide Y (NPY) produced in the brain controls food intake through an interaction with the NPY Y(5) receptor subtype.

Methods: The hypothesis was tested using CGP 71683A a potent and highly selective non-peptide antagonist of the NPY Y(5) receptor which was administered into the right lateral ventricle of obese Zucker fa/fa rats.

Results: Intraventricular injection of 3.