[Reproducibility study of the "400 Points assessment", a measurement of the hand's functional ability]. / Étude de reproductibilité de la cotation du « Bilan 400 points ¼, une mesure de capacité fonctionnelle de la main.

OBJECTIVES: Evaluate the inter-rater and test-retest reproducibility of the "400 Points assessment", a measurement of the functional ability of the hand. The scale included four tests: function of the hand, prehension strengths, handling and displacement of things, and function with both hands. METHODS: Thirty patients with hand injuries were participated. The inter-rate agreements were examinated between three occupational therapists. The First rater was an experienced user of this instrument (observer 1), the second one was a novice user (observer 2), the last rater is a student who had never used it before (observer 3). Subjects were tested twice by the same raters independently, with 30 minutes intervals between tests. Statistical analysis was done by calculating average differences and intraclass correlation coefficient. RESULTS: (i) The difference between the three raters agreements was small for the two measurements, except for function with both hands in the second period. Every intraclass correlation coefficient was higher than 0.95. (ii) Difference between the two measurements was small for every observer. These differences are not significant except for function with both hands. Intraclass correlation coefficients are all higher than 0.82 even than 0.90 for the total score. The difference between the two periods for the overall test is small, from 5% to 10% for seven patients and from 10 to 15% for two patients. Differences at two times had the same agreement for the three observers. CONCLUSION: "400 Points assessment" is reproducible (inter-rater and test-retest reproductibility). The test "function with both hands" requires more experience of the assessment.

Discovery of orally bioavailable NK1 receptor antagonists.

Benzyloxyphenethylpiperazines are a new class of high affinity NK1 receptor antagonists. Oral bioavailability and selectivity can be fine tuned by the nature of the substituents on the basic nitrogen atom. Addition of substituents with a carboxylic acid group led to very selective and orally active NK1 antagonists free of interaction with L-type calcium channels.

A reversible monoamine oxidase A inhibitor, befloxatone: structural approach of its mechanism of action.

Experimental and theoretical physico-chemical methods were used to investigate the interaction between several reversible monoamine oxidase A inhibitors in the oxazolidinone series and the active site of the enzyme. Phenyloxazolidinones include toloxatone and analogues, among which befloxatone was selected as drug candidate for the treatment of depression. Identification of the forces responsible for the crystal cohesion of befloxatone reveals functional groups that could interact with monoamine oxidase. Calculation of electronic properties of those compounds using ab initio molecular orbital methods lead to a description of the mode of interaction between befloxatone and the cofactor of the enzyme. Electronic absorption spectroscopy measurements confirm the hypothesis of a privileged interaction of phenyloxazolidinone-type inhibitors with the flavin cofactor of MAO. Additional sites of interaction with the protein core of MAO A are also examined with regard to the primary structure of the enzyme. As a result of this work, a model is proposed for the reversible inhibition of MAO A by befloxatone via long distance, reversible interactions with the flavin adenine dinucleotide (FAD) cofactor of the enzyme and with specific amino acids of the active site. This model is partially corroborated by experimental evidence and should be helpful in designing new potent inhibitors of monoamine oxidase.

Experimental and theoretical study of reversible monoamine oxidase inhibitors: structural approach of the active site of the enzyme.

Experimental and theoretical physico-chemical methods were used to investigate the interaction between aryl-oxazolidinones and monoamine oxidase (MAO). Several arguments suggest that these compounds interact with the flavin adenine dinucleotide (FAD) cofactor of MAO. The calculation using ab initio molecular orbital methods of the electronic properties of flavin and befloxatone, a reversible inhibitor of MAO A, led to a description of the interaction between aryl-oxazolidinones and the cofactor of the enzyme. Structure activity relationship results revealed additional sites of interaction with the protein core of MAO A. As a result of this work, a model is proposed for the reversible inhibition of MAO by oxazolidinones via long distance, reversible interactions with the FAD cofactor of the enzyme.