996 resultados para Cytochrome P-450 CYP3A


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Introduction: The low back pain are a problema of health. Objective: to evaluate the effects of the Maitland´s manipulation in pain, fl exibility, functional capacity and quality of life of the patients with chronic low back pain. Method: Sxteen subjects, of both genders, with the age from 23-68 years old (48.69,± 11.61 years old) were evaluated by test sit and reach (TSA), Visual Analogue Scale (VAS) and answered the questionnaires of the quality of life Medical Outcomes Study 36- Item Short-Form Health Survey (SF-36) and the Roland-Morris Disability functional incapacity (RMDQ). The treatment was carried out twice a week, totaling 10 sessions. Each session lasted 30 minutes and consisted by Maitland´s techniques, applied as the symptoms evaluated at the beginning of each session. After 10 session, the subjects were re-evaluated. The data obtained in the assessments concerning the TSA and VAS were analyzed by Student t test, the data relating to the questionnaire were analyzed using the Wilcoxon non-parametric statistics test. For the interpretation was used signifi cance level of 5% (p≤0,05). Results: A signifi cant improvement was in the intensity of pain, disability, fl exibility and quality of life. Conclusion: The Maitland´s therapy showed effective, which suggests be an appropriate strategy for intervention for patients with chronic low back pain.

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AgSIE was used for the direct analysis of folic acid (FA), with a detection limit and lower level of quantitation of 6.8 x10-10 mol L-1 and 2.3 x 10 8 mol L-1. The analysis in fresh and processed fruits was done without any sample pretreatment. In strawberry and acerola juices, FA concentration level values were below the method detection limit. FA was detectable in peach (77.7 0.4 mg L-1 and 64.4 0.5 mgL-1), Persian lime (45.4 0.7 mg L-1), pineapple Hawaii (66.2 0.4 mgL-1), pear pineapple (35.3 0.6 mgL-1), cashew (54.4 0.5 mgL-1) , passion fruit (73.2 0.3 mgL-1), and apple (84.4 0.5 mg L-1 ).

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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

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Objective: To investigate the correlation between the Alberta Program Early CT Score (ASPECTS) and the Scandinavian Stroke Scale (SSS) for the evaluation of neurological impairment in patients with acute stroke. Method: 59 patients with a first acute ischemic stroke were evaluated. The ASPECTS were evaluated by 2 neurologists at admission and by another neurologist after 48 hours. The NIHSS and SSS was applied to determinate stroke severity. Correlations and agreements were analysed statistically by Spearman and Kappa tests. Results: ASPECTS was correlated with National Institute of Health Stroke Scale (NIHSS) at admission (r = -0.52; p < 0.001) and SSS (r = 0.50; p < 0.001). The ASPECTS and SSS items were most correlated with arm (r = 0.52; p < 0.001) and hand (r = 0.49; p < 0.001) motor power, and speech (r = 0.51; p < 0.001). The SSS of 25.5 shows sensitivity (68%) and specificity (72%) when associated with ASPECTS <= 7. Conclusion: The SSS can predict worst neurological impairment when associated with lower values of ASPECTS.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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

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The aim of this study was to determine whether image artifacts caused by orthodontic metal accessories interfere with the accuracy of 3D CBCT model superimposition. A human dry skull was subjected three times to a CBCT scan: at first without orthodontic brackets (T1), then with stainless steel brackets bonded without (T2) and with orthodontic arch wires (T3) inserted into the brackets' slots. The registration of image surfaces and the superimposition of 3D models were performed. Within-subject surface distances between T1-T2, T1-T3 and T2-T3 were computed and calculated for comparison among the three data sets. The minimum and maximum Hausdorff Distance units (HDu) computed between the corresponding data points of the T1 and T2 CBCT 3D surface images were 0.000000 and 0.049280 HDu, respectively, and the mean distance was 0.002497 HDu. The minimum and maximum Hausdorff Distances between T1 and T3 were 0.000000 and 0.047440 HDu, respectively, with a mean distance of 0.002585 HDu. In the comparison between T2 and T3, the minimum, maximum and mean Hausdorff Distances were 0.000000, 0.025616 and 0.000347 HDu, respectively. In the current study, the image artifacts caused by metal orthodontic accessories did not compromise the accuracy of the 3D model superimposition. Color-coded maps of overlaid structures complemented the computed Hausdorff Distances and demonstrated a precise fusion between the data sets.

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Exergetic analysis can provide useful information as it enables the identification of irreversible phenomena bringing about entropy generation and, therefore, exergy losses (also referred to as irreversibilities). As far as human thermal comfort is concerned, irreversibilities can be evaluated based on parameters related to both the occupant and his surroundings. As an attempt to suggest more insights for the exergetic analysis of thermal comfort, this paper calculates irreversibility rates for a sitting person wearing fairly light clothes and subjected to combinations of ambient air and mean radiant temperatures. The thermodynamic model framework relies on the so-called conceptual energy balance equation together with empirical correlations for invoked thermoregulatory heat transfer rates adapted for a clothed body. Results suggested that a minimum irreversibility rate may exist for particular combinations of the aforesaid surrounding temperatures. By separately considering the contribution of each thermoregulatory mechanism, the total irreversibility rate rendered itself more responsive to either convective or radiative clothing-influenced heat transfers, with exergy losses becoming lower if the body is able to transfer more heat (to the ambient) via convection.

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Docetaxel (Taxotere(®) ) is currently used intravenously as an anticancer agent and is primarily metabolized by Cytochrome P450 3A (CYP3A). The HIV protease inhibitor ritonavir, a strong CYP3A4 inhibitor, decreased first-pass metabolism of orally administered docetaxel. Anticancer effects of ritonavir itself have also been described. We here aimed to test whether ritonavir co-administration could decrease intratumoral metabolism of intravenously administered docetaxel and thus increase the antitumor activity of docetaxel in an orthotopic, immunocompetent mouse model for breast cancer. Spontaneously arising K14cre;Brca1(F/F) ;p53(F/F) mouse mammary tumors were orthotopically implanted in syngeneic mice lacking Cyp3a (Cyp3a(-/-) ) to limit ritonavir effects on systemic docetaxel clearance. Over 3 weeks, docetaxel (20 mg/kg) was administered intravenously once weekly, with or without ritonavir (12.5 mg/kg) administered orally for 5 days per week. Untreated mice were used as control for tumor growth. Ritonavir treatment alone did not significantly affect the median time of survival (14 vs. 10 days). Median time of survival in docetaxel-treated mice was 54 days. Ritonavir co-treatment significantly increased this to 66 days, and substantially reduced relative average tumor size, without altering tumor histology. Concentrations of the major docetaxel metabolite M2 in tumor tissue were reduced by ritonavir co-administration, whereas tumor RNA expression of Cyp3a was unaltered. In this breast cancer model, we observed no direct antitumor effect of ritonavir alone, but we found enhanced efficacy of docetaxel treatment when combined with ritonavir. Our data, therefore, suggest that decreased docetaxel metabolism inside the tumor as a result of Cyp3a inhibition contributes to increased antitumor activity.

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Benzene was studied in its target organ of effect, the bone marrow, with the micronucleus test and metaphase chromosomal analysis. Groups of 5 or 10, male and female CD-1 mice were treated with one or two p.o. or i.p. doses of benzene (440 mg/kg) or toluene (430, 860 or 1720 mg/kg) or both, and sacrificed 30 or 54h after the first dose. Benzene-treated animals were pretreated with phenobarbital (PB), 3-methylcholanthrene (3MC), (beta)-naphthoflavone ((beta)NF), SKF-525A, or Aroclor 1254. Toluene showed no clastogenic activity and reduced the clastogenic effect of co-administered benzene. None of the pretreatments protected against benzene clastogenicity. 3MC and (beta)NF greatly promoted benzene myeloclastogenicity. Dose response curves for benzene myeloclastogenicity were much steeper with 3MC induction than without. Micronuclei (MN) were 4-6 times higher by p.o. than i.p. benzene administration. This was not due to bacterial flora since no difference was found between germ-free and conventional males gavaged with benzene. A sensitive high-pressure liquid chromatographic method was developed and used to explore the relation between metabolic profiles of benzene in urine and MN after various pretreatments. Phenol (PH), trans-trans-muconic acid (MA) and hydroquinone (HQ) in the 48h male mouse urine accounted, respectively, for 12.8-22.8, 1.8-4.7 and 1.5-3.7% of the single oral dose of benzene (880, 440 and 220 mg/kg). Catechol (CT) was seen in trace amounts. MA was identified by ultraviolet and infrared spectroscopy and elemental analysis. Urinary metabolites--especially MA, HQ, and phenol glucuronide--correlated well with MN and were dependent on both the dose and the metabolism of benzene. Benzene metabolism was most inducible by cytochrome P-448 enzyme inducers, by p.o. > i.p., in males > females, and inhibited by toluene. Ph, CT or HQ administered p.o., 250, 150 and 250 mg/kg, respectively, or at 150 mg/kg x 2 after 3MC pretreatment, failed to reproduce the potent myeloclastogenicity of benzene. In fact, only HQ was mildly clastogenic. ^

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The pregnane X receptor (PXR) is the molecular target for catatoxic steroids such as pregnenolone 16α-carbonitrile (PCN), which induce cytochrome P450 3A (CYP3A) expression and protect the body from harmful chemicals. In this study, we demonstrate that PXR is activated by the toxic bile acid lithocholic acid (LCA) and its 3-keto metabolite. Furthermore, we show that PXR regulates the expression of genes involved in the biosynthesis, transport, and metabolism of bile acids including cholesterol 7α-hydroxylase (Cyp7a1) and the Na+-independent organic anion transporter 2 (Oatp2). Finally, we demonstrate that activation of PXR protects against severe liver damage induced by LCA. Based on these data, we propose that PXR serves as a physiological sensor of LCA, and coordinately regulates gene expression to reduce the concentrations of this toxic bile acid. These findings suggest that PXR agonists may prove useful in the treatment of human cholestatic liver disease.

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Bibliography: p. [450]-460.