Fenotipagem de enzimas metabolizadoras polimórficas e monitoramento terapêutico como uma ferramenta na farmacologia clínica dos antidepressivos tricíclicos, uma revisão / Phenotyping of polymorpghic metabolizing enzymes and therapeutic drug monitoring as a tool in the clinical pharmacology of tryicyclic antidepressants, a review

Polymorphism in drug metabolizing enzymes is related with interindividual variability in drug therapy effectiveness. The polymorphisms of oxidative enzymes of the P450 cytochrome system have been characterized, and their impacts in enzyme activity are already known. Considering their substrate specificity, CY2D6 and CYP2c19 are the most important enzymes in the tricyclic antidepressant metabolism. Several methods are avaiable in order to classify an individual regarding metabolic activity of these enzymes. Although genotyping is a fast growing approach, phenotyping seems to be more feasible as a "moment picture" of CYPs activity. Phenotyping of CYp2D6 and CYP2c19 is usually done by the use of probe drugs, with some degree of specificity for the tested enzymes. The simultaneous administration of probe drugs specific for samples of blood or urine are taken at standarized time intervals. After parent drug and metabolite quantitative analysis, usually by high-performance liquid chromatography, a pharmacokinetic parameter is used to classify the individuals as poor, extensive or ultra-fast metbolizers. One of the most promising possibilities of the individual metabolic characterization is costomizing drug therapy, wich has not been fully exploited until now...

Microtubule cytoskeleton distribution using fluorescent taxoid in tetratrichomonas didelphidis

Tetratrichomonas didelphidis is a flagellated protozoan found in the intestine of opossums. The specimens were stained by the Giemsa method and by FLUTAX-2, an active fluorescent derivative of Taxol which binds to the ab-tubulin polimerized of microtubules of cells. Giemsa stain revealed the morphological features of trichomonads such as four anterior flagella, undulating membrane, axostyle and posterior flagellum. An intense fluorescence was observed in living trophozoites of T. didelphidis and Trichomonas vaginalis (used as control), incubated with FLUTAX-2. An analysis of the composition of the cytoskeleton of T. didelphidis will contribute to understanding the cellular morphology of the parasites. Key words: Tetratrichomonas didelphidis, microtubule cytoskeleton, fluorescent taxoid.

Perspective of a new diagnostic for human trichomonosis

Several diagnostic techniques have been employed for the detection of Trichomonas vaginalis. Microtubules constitute the cytoskeleton in eukaryotic cells and are sensitive to antimitotic drugs, such as Taxol (paclitaxel). We used FLUTAX a fluorescent taxoid - to analyze the microtubule distribution in living trophozoites of T. vaginalis in urine and in vaginal discharge. A high intensity of fluorescence was observed in living T. vaginalis, epithelial cells and leukocytes present in urine and vaginal discharge. Our preliminary results show the perspective of a new diagnostic technique for trichomonosis and will contribute to the understanding of the cytoskeleton of T. vaginalis