A new, transportable ergometer for the measurement of musculotendinous stiffness during wrist flexion.

We present here a new, dedicated mechanical device for monitoring quick-release movements of the wrist. The ergometer was designed to easily assess musculotendinous properties during wrist flexion. Maximal voluntary contractions (MVC) and quick-release (QR) movements during wrist flexion were performed on 14 subjects. A validation of the ergometer, using a test-retest methodology, was performed to assess its reliability and sensitivity. The device has been technically and biomechanically validated in a range of situations, including inertia measurement (mean inertia was found 0.0119+/-0.0012 N m s(2) rad(-1)) and appearance of the unloading reflex. Our results indicate that the device provides highly reliable, sensitive evaluation of wrist muscle stiffness (intraclass correlation coefficient for inertia, maximal voluntary contraction and stiffness index were 0.873, 0.994 and 0.930, respectively). Its portability facilitates measurement of the influence of repetitive, occupational activity on the musculotendinous complex of the wrist flexors.     

N alpha-arylsulfonyl-omega-amidinophenyl-alpha-aminoalkyl-carboxylic acid amides as specific thrombin inhibitors

Structure-activity relationships for the inhibition of thrombin and trypsin by N alpha-substituted amidinophenyl-alpha-aminoalkylcarboxylic acid amides are presented. Secondary cyclic amides of N alpha-substituted 4-amidinophenylalanine and 2-amino-5-(4-amidinophenyl)valeric acid were found to be potent and specific inhibitors of thrombin, whereas trypsin was inhibited strongly by primary amides of 2-amino-4-(4-amidinophenyl) butyric acid. For this type of inhibitor the carbon amide structure seems to play a decisive role in the enzyme-inhibitor interaction.     

Determination of the inorganic degradation products sulfate and sulfamate in the antiepileptic drug topiramate by capillary electrophoresis

A capillary electrophoresis (CE) method has been developed as an alternative method for the determination of the inorganic degradation products sulfate and sulfamate in topiramate drug product and drug substance, currently performed by ion chromatography. The anions are separated in a background electrolyte containing potassium chromate and boric acid, followed by indirect UV detection. By adding tetradecyltrimethylammonium bromide to the electrolyte, analysis is performed under co-electroosmotic flow conditions. Variations in injection volumes and migration times are compensated for by use of an internal standard. The validation of the method, which was performed according to ICH guidelines (International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use) [1], comprises specificity, accuracy, linearity, precision, sensitivity and robustness. In addition, the results of an actual tablet sample analysis obtained by this CE method are statistically shown to be in close agreement with those obtained by an ion chromatographic method.     

Relationships Between Animal Health Monitoring and the Risk Assessment Process

Risk assessment is part of the risk analysis process as it is used in veterinary medicine to estimate risks related to international trade and food safety. Data from monitoring and surveillance systems (MO&SS) are used throughout the risk assessment process for hazard identification, release assessment, exposure assessment and consequence assessment. As the quality of risk assessments depends to a large extent on the availability and quality of input data, there is a close relationship between MO&SS and risk assessment. In order to improve the quality of risk assessments, MO&SS should be designed according to minimum quality standards. Second, recent scientific developments on state-of-the-art design and analysis of surveys need to be translated into field applications and legislation. Finally, knowledge about the risk assessment process among MO&SS planners and managers should be promoted in order to assure high-quality data.     

Isolation and characterization of the plasma membrane from the yeast Pichia pastoris

Despite similarities of cellular membranes in all eukaryotes, every compartment displays characteristic and often unique features which are important for the functions of the specific organelles. In the present study, we biochemically characterized the plasma membrane of the methylotrophic yeast Pichia pastoris with emphasis on the lipids which form the matrix of this compartment. Prerequisite for this effort was the design of a standardized and reliable isolation protocol of the plasma membrane at high purity. Analysis of isolated plasma membrane samples from P. pastoris revealed an increase of phosphatidylserine and a decrease of phosphatidylcholine compared to bulk membranes. The amount of saturated fatty acids in the plasma membrane was higher than in total cell extracts. Ergosterol, the final product of the yeast sterol biosynthetic pathway, was found to be enriched in plasma membrane fractions, although markedly lower than in Saccharomyces cerevisiae. A further characteristic feature of the plasma membrane from P. pastoris was the enrichment of inositol phosphorylceramides over neutral sphingolipids, which accumulated in internal membranes. The detailed analysis of the P. pastoris plasma membrane is discussed in the light of cell biological features of this microorganism especially as a microbial cell factory for heterologous protein production.