962 resultados para Phase I


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Pós-graduação em Zootecnia - FCAV

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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In the aquatic environment, biotransformation enzymes are established biomarkers for assessing PAH exposure in fish, but little is known about the effect of 17β-estradiol (E2) on these enzymes during exposure to benzo(a)pyrene (BaP). In this study, Nile tilapia (Oreochromis niloticus) were exposed for 3, 5, and 10 days to BaP (300 μg L(-1)) and E2 (5 μg L(-1)). These substances were applied isolated or mixed. In the mixture experiment, fish were analyzed pre- and postexposure in order to better understand whether preexposure to the hormone masks the responses activated by PAH or vice versa. Phase I enzymes ethoxyresorufin-O-deethylase (EROD), pentoxyresorufin-O-depenthylase (PROD), and benzyloxyresorufin-O-debenzylase (BROD) activities as well as the phase II enzyme glutathione S-transferase (GST) were analyzed. Isolated E2 treatment decreased EROD activity after 3 days, but this enzyme activity returned to control values after 5 and 10 days of exposure. Isolated BaP treatment significantly induced EROD activity after 3 and 5 days, and the activity returned to control levels after ten exposure days. Combined treatment (E2 + Bap) significantly increased EROD activity, both in the pre- and postexposure. This increase was even higher than in the isolated BaP treatment, suggesting a synergism between these two compounds. When E2 and BaP were used singly, they did not change BROD and PROD activities. However, combined treatment (E2 + Bap) significantly increased PROD activity. Isolated BaP treatment increased GST activity after 10 days. However, this response was not observed in the mixture treatment, suggesting that E2 suppressed the GST induction modulated by BaP. The results put together indicated that E2 altered the biotransformation pathway regarding enzymes activated by BaP in Nile tilapia.

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Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

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This study aimed at evaluating the knowledge on visceral leishmaniasis gained after the application of an educative project for the 6th and 7th grade students from three public schools of Birigui, SP, Brazil. A questionnaire before (Phase I) and after (Phase II) activities that comprehended one conference by a health agent, a comic contest and one crossword about VL was used to measure scholar’s knowledge. We interviewed 711 students in Phase I and 693 in Phase II. A criterion of VL knowledge was adopted as “Good”, “Medium” and “Bad” when, out of 10 questions analyzed by Item Response Theory, 10 to 8, 7 to 4, and 3 to 0 were right, respectively. We observed a statistically significant increase in the students’ knowledge level after the educational project, since the number of students with “Good” concept changed from 35.7% (Phase I) to 59.7% (Phase II). The educational activities carried out led to gains in knowledge among students suggesting that continuing education can bring good results to public health.

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Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP)

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Pós-graduação em Ciência e Tecnologia Animal - FEIS

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We study baryon asymmetry generation originated from the leptogenesis in the presence of hypermagnetic fields in the early Universe plasma before the electroweak phase I ransition (EWPT). For the simplest Chern-Simons (CS) wave configuration of hypermagnetic field we find the baryon asymmetry growth when the hypermagnetic field value changes due to alpha(2)-dynamo and the lepton asymmetry rises due to the Abelian anomaly. We solve the corresponding integro-differential equations for the lepton asymmetries describing such selfconsistent dynamics for lepto- and baryogenesis in the two scenarios: (i) when a primordial lepton asymmetry sits in right electrons e(R); and (ii) when, in addition to e(R), a left lepton asyninwtty for e(L) and v(eL) at due to chirality flip reactions provided by in Iiigg,s decays at the temperatures, T < T-RL similar to 10 TeV. We find that the baryon asymmetry of the Universe (BAU) rises very fast through such leptogenesis, especially, in strong hypermagnetic fields. Varying (decreasing) the CS wave number parameter k(0) < 10(-7) T-EW one can recover the observable value of BAU, eta(B) similar to 10(-9), where k(0) = 10(-7) T-EW corresponds to the ataxinittat value for CS wave number surviving ohmic dissipation of hypermagnetic field. In the scenario (ii) one predicts the essential difference of the lepton numbers of right- and left electrons at EWPT time, L-eR - L-eL similar to (mu(eR) / mu(eL))/T-EW = Delta mu/T-EW similar or equal to 10(-5) that can be used as an initial condition for chiral asymmetry after EWPT.

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Tetrahydrofuran lignans represent a well-known group of phenolic compounds capable of acting as antiparasitic agents. In the search for new medicines for the treatment of Chagas disease, one promising compound is grandisin which has shown significant activity on trypomastigote forms of Trypanosoma cruzi. In this work, the in vitro metabolism of grandisin was studied in the pig cecum model and by biomimetic phase I reactions, aiming at an ensuing a preclinical pharmacokinetic investigation. Although grandisin exhibited no metabolization by the pig microbiota, one putative metabolite was formed in a biomimetic model using Jacobsen catalyst. The putative metabolite was tested against T. cruzi revealing loss of activity in comparison to grandisin.

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This study describes the enantioselective analysis of unbound and total concentrations of tramadol and its main metabolites O-desmethyltramadol (M1) and N-desmethyltramadol (M2) in human plasma. Sample preparation was preceded by an ultrafiltration step to separate the unbound drug. Both the ultrafiltrate and plasma samples were submitted to liquid/liquid extraction with methyl t-butyl ether. Separation was performed on a Chiralpak (R) AD column and tandem mass spectrometry consisting of an electrospray ionization source, positive ion mode and multiple reaction monitoring was used as the detection system. Linearity was observed in the following ranges: 0.2-600 and 0.5-250 ng/mL for analysis of total and unbound concentrations of the tramadol enantiomers, respectively, and 0.1-300 and 0.25-125 ng/mL for total and unbound concentrations of the M1 and M2 enantiomers, respectively. The lower limits of quantitation were 0.2 and 0.5 ng/mL for analysis of total and unbound concentration of each tramadol enantiomer, respectively, and 0.1 and 0.25 ng/mL for total and unbound concentrations of M1 and M2 enantiomers, respectively. Intra- and interassay reproducibility and inaccuracy did not exceed 15%. Clinical application of the method to patients with neuropathic pain showed plasma accumulation of (+)-tramadol and (+)-M2 after a single oral dose of racemic tramadol. Fractions unbound of tramadol, M1 or M2 were not enantioselective in the patients investigated. (C) 2011 Elsevier B.V. All rights reserved.