The diversity of the Brazilian population, evident in the distribution of VKORC1 polymorphisms, must be taken into account in the design of pharmacogenetic clinical trials and dealt with as a continuous variable. Warfarin dosing algorithms that include 'race' terms defined for other populations are clearly not applicable to the heterogeneous and extensively admixed Brazilian population.

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A liquid chromatographic atmospheric pressure chemical ionization tandem mass spectrometric method is described for the determination of 21‐hydroxydeflazacort in human plasma using dexamethasone 21‐acetate as an internal standard. The procedure requires a single diethyl ether extraction. After evaporation of the solvent under a nitrogen flow, the analytes are reconstituted in the mobile phase, chromatographed on a C18 reversed‐phase column and analyzed by mass spectrometry via a heated nebulizer interface where they are detected by multiple reaction monitoring. The method has a chromatographic run time of less than 5 min and a linear calibration curve with a range of 1–400 ng ml−1 (r > 0.999). The between‐run precision, based on the relative standard deviation for replicate quality controls, was ≤5.5% (10 ng ml−1), 1.0% (50 ng ml−1) and 2.7% (200 ng ml−1). The between‐run accuracy was ±7.1, 3.8 and 4.8% for the above concentrations, respectively. This method was employed in a bioequivalence study of two DFZ tablet formulations (Denacen from Marjan Industria e Comercio, Brazil, as a test formulation, and Calcort from Merrell Lepetit, Brazil, as a reference formulation) in 24 healthy volunteers of both sexes who received a single 30 mg dose of each formulation. The study was conducted using an open, randomized, two‐period crossover design with a 7‐day washout interval. The 90% confidence interval (CI) of the individual geometric mean ratio for Denacen/Calcort was 89.8–109.5% for area under the curve AUC(0–24 h) and 80.7–98.5% for Cmax. Since both the 90% CI for AUC(0–24 h) and Cmax were included in the 80–125% interval proposed by the US Food and Drug Administration, Denacen was considered bioequivalent to Calcort according to both the rate and extent of absorption. Copyright © 2000 John Wiley & Sons, Ltd.

ABSTRACT.Biflorin is an o-naphthoquinone isolated from the roots of the plant Capraria biflora L. (Scrophulariaceae). In this study, the cytotoxic effects of biflorin were verified, and late apoptosis was detected in various cancer cell lines by in situ analysis. The cytotoxicity was further evaluated exclusively for 48 h of treatment in different tumor and non-tumor cell lines (Hep-2, HeLa, HT-29, A-375, and A-549, and HEK-293, respectively). The results indicated that biflorin induced selective cytotoxicity in tumor cells. HeLa cells were more susceptible to biflorin, followed by HT-29, A-549, A-375, and Hep-2 at all concentrations (range 5-50 µg/mL), and the highest half-maximal inhibitory concentration IC 50 (56.01 ± 1.17 µg/mL) was observed in HEK-293 cells. Late apoptotic/necrotic events, observed by in situ immunostaining with Annexin V, varied with each cell line; an increase in late apoptotic events was observed corresponding to the increase in biflorin dosage. Hep-2 cells showed a greater percentage of late apoptotic events among the tumor cell lines when treated with higher concentrations of biflorin (69.63 ± 2.28%). The non-tumor HEK-293 line showed greater resistance to late apoptotic events, as well as a lower level of cytotoxicity (77.69 ± 6.68%) than the tested tumor lines. The data presented indicate that biflorin showed an important, possibly selective, cytotoxicity against tumor cell lines, thereby revealing a promising novel substance with potential anticancer activity for tumor therapy.

Leishmaniasis is a group of diseases with a large spectrum, cosmopolitan, but with broad and significant impact in the tropical zone. Leishmaniasis presents itself in two forms, one visceral involving hemolinfopoietic system structures, other with skin and/or mucosa involvement, often without visceralizing. The latter, known as American Cutaneous Leishmaniasis (ACL) is the aim of this study. One of the major problems in the ACL is treatment procedure using injectable formulations, with risk for complications from the injection and the risk of damage to the liver and kidney function and cardiac complications. Several tests have demonstrated satisfactory results using Fluconazole ®. In order to consolidate the results described in the literature, this study sought to demonstrate the therapeutic efficacy of Fluconazole ® with high-dose treatment of ACL in patients from an endemic area in the Southern State of Ceará, Brazil, City of Barbalha. It's conducted a prospective randomized study with two groups of patients. Sixty of the Group I: they were treated with 300mg or 450mg of Fluconazole ® for six weeks. Sixty Group II: they were treated with Glucantime 20mg/kg/ day for 20 consecutive days. The diagnosis of ACL was performed with Imprint, culture, biopsy and histopathological stain with Giemsa and immunohistochemistry. Montenegro's Intradermoreaction was also performed. All patients were evaluated clinically and followed up for ninety days. Continuous variables were evaluated by Student's t test, and for the correlation of variables the Pearson correlation coefficient (r) was used. The time healing of each group had its evaluation by Kaplan-Meier method. In all tests the hypothesis α was considered significant when less than 5% (p <0.05). The therapeutic efficacy (TE) was calculated based on the reduction of relative risk. The study population was predominantly made up of individuals between 30 and 40 years, brown skin color, peasants, rural people, with a slight pre