943 resultados para Dose-response relationship (Biochemistry)


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Aim. To establish a protocol for the early introduction of inhaled nitric oxide (iNO) therapy in children with acute respiratory distress syndrome (ARDS) and to assess its acute and sustained effects on oxygenation and ventilator settings.Patients and Methods. Ten children with ARDS, aged 1 to 132 months (median, 11 months), with arterial saturation of oxygen <88% while receiving a fraction of inspired oxygen (FiO(2)) 0.6 and a positive end-expiratory pressure of greater than or equal to 10 cm H2O were included in the study. The acute response to iNO was assessed in a 4-hour dose-response test, and positive response was defined as an increase in the PaO2/FiO(2) ratio of 10 mmHg above baseline values. Conventional therapy was not changed during the test. In the following days, patients who had shown positive response continued to receive the lowest iNO dose. Hemodynamics, PaO2/FiO(2), oxygenation index, gas exchange, and methemoglobin levels were obtained when needed. Inhaled nitric oxide withdrawal followed predetermined rules.Results. At the end of the 4-hour test, all the children showed significant improvement in the PaO2/FiO(2) ratio (63.6%) and the oxygenation index (44.9%) compared with the baseline values. Prolonged treatment was associated with improvement in oxygenation, so that FiO(2) and peak inspiratory pressure could be quickly and significantly reduced., No toxicity from methemoglobin or nitrogen dioxide was observed.Conclusion. Administration of iNO to children is safe. iNO causes rapid and sustained improvement in oxygenation without adverse effects. Ventilator settings can safely be reduced during iNO treatment.

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

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Despite a plethora of in situ studies and clinical trials evaluating the efficacy of fluoridated dentifrices on caries control, in vitro pH cycling models are still broadly used because they mimic the dynamics of mineral loss and gain involved in caries formation. This paper critically reviews the current literature on existing pH-cycling models for the in vitro evaluation of the efficacy of fluoridated dentifrices for caries control, focusing on their strengths and limitations. A search was undertaken in the MEDLINE electronic journal database using the keywords "pH-cycling", "demineralization", "remineralization", "in vitro", "fluoride", "dentifrice". The primary outcome was the decrease of demineralization or the increase of remineralization as measured by different methods (e. g.: transverse microradiography) or tooth fluoride uptake. Inclusion of studies, data extraction and quality assessment were undertaken independently and in duplicate by two members of the review team. Disagreements were solved by discussion and consensus or by a third party. One hundred and sixteen studies were included, of which 42 addressed specifically the comparison of dentifrices using different pH-cycling models. The other studies included meta-analysis or reviews, data about the effect of different fluoride sources on de-remineralization, different methods for analysis de-remineralization and chemical variables and characteristics of dental hard tissues that might have influence on de-remineralization processes. Generally, the studies presented ability to detect known results established by clinical trials, to demonstrate dose-related responses in the fluoride content of the dentifrices, and to provide repeatability and reproducibility between tests. In order to accomplish these features satisfactorily, it is mandatory to take into account the type of substrate and baseline artificial lesion, as well as the adequate response variables and statistical approaches to be used. This critical review of literature showed that the currently available pH-cycling models are appropriate to detect dose-response and pH-response of fluoride dentifrices, and to evaluate the impact of new active principles on the effect of fluoridated dentifrices, as well as their association with other anti-caries treatments.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Calcium channels mediate the actions of many drugs. The present work investigated whether diltiazem, an L-type calcium channel blocker, alters the inhibition of sodium appetite induced by noradrenaline and the alpha(2)-adrenoceptor agonist clonidine. Adult male Holtzman rats (N=4-8) with cannula implanted into the third cerebral ventricle were submitted to sodium depletion {furosemide sc+24-h removal of ambiente sodium). Sodium depleted control animals that received 0.9% NaCl as vehicle injected intracerebroventricularly (i.c.v) ingested 13.0+/-1.5 ml/120 min of 1.8% NaCl. Intracerebroventricular injection of either noradrenaline (80 nmol) or clonidine (20 nmol) inhibited 1.8% NaCl intake from 70 to 90%. Prior i.c.v. injection of diltiazem (6-48 nmol) inhibited from 50 to 100% the effect of noradrenaline and clonidine in a dose-response manner. Diltiazem alone at 100 nmol inhibited, but at 50 nmol had no effect on, sodium appetite. The results suggest: (1) common ionic mechanisms involving calcium channels for the inhibition that noradrenaline and clonidine exert on sodium appetite and (2) a dual role for the benzothiazepine site of L-type calcium channels in the control of sodium appetite. (C) 2002 Elsevier B.V. B V. All rights reserved.

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The effect of scarification with sodium hypochloride on light sensitivity in seeds of Lactuca sativa L. cv. Grand Rapids is presented in the paper. Light-requiring lettuce seeds germinated in both dark and continuous light after scarification and 36 degrees C pre-incubation restored light sensitivity at 25 degrees C. Curves of dose-response indicated that chemical scarification induced a change in the control of seed germination from Low Fluence Response to the Very Low Fluence Response. Pre-incubation at 36 degrees C return the control to the Low Fluence Response of phytochrome action.

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Hypochlorous acid (HOCl) released by activated leukocytes has been implicated in the tissue damage that characterizes chronic inflammatory diseases. In this investigation, 14 indole derivatives, including metabolites such as melatonin, tryptophan and indole-3-acetic acid, were screened for their ability to inhibit the generation of this endogenous oxidant by stimulated leukocytes. The release of HOCl was measured by the production of taurine-chloramine when the leukocytes (2 x 10(6) cells/mL) were incubated at 37ºC in 10 mM phosphate-buffered saline, pH 7.4, for 30 min with 5 mM taurine and stimulated with 100 nM phorbol-12-myristate acetate. Irrespective of the group substituted in the indole ring, all the compounds tested including indole, 2-methylindole, 3-methylindole, 2,3-dimethylindole, 2,5-dimethylindole, 2-phenylindole, 5-methoxyindole, 6-methoxyindole, 5-methoxy-2-methylindole, melatonin, tryptophan, indole-3-acetic acid, 5-methoxy-2-methyl-3-indole-acetic acid, and indomethacin (10 µM) inhibited the chlorinating activity of myeloperoxidase (MPO) in the 23-72% range. The compounds 3-methylindole and indole-3-acetic acid were chosen as representative of indole derivatives in a dose-response study using purified MPO. The IC50 obtained were 0.10 ± 0.03 and 5.0 ± 1.0 µM (N = 13), respectively. These compounds did not affect the peroxidation activity of MPO or the production of superoxide anion by stimulated leukocytes. By following the spectral change of MPO during the enzyme turnover, the inhibition of HOCl production can be explained on the basis of the accumulation of the redox form compound-II (MPO-II), which is an inactive chlorinating species. These results show that indole derivatives are effective and selective inhibitors of MPO-chlorinating activity.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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BACKGROUND: A dichloromethane-methanol extract of the seeds of Piper tuberculatum Jacq. (Piperaceae) and two isobutyl amides, 4,5-dihydropiperlonguminine (1) and pellitorine (2), which were isolated by chromatographic methods, were assayed for their lethality against the sugarcane borer Diatraea saccharalis F. (Lepidoptera: Pyralidae).RESULTS: Bioassays were carried out with fourth-instar caterpillars through topical application of test solutions to the dorsal surface of the prothorax, and dose-response correlations were determined. Significant insect mortalities were observed 24, 48 and 72 h after treatment at concentrations of >= 100 mu g insect(-1). The LD(50) and LD(90) values for compound 1 were 92.83 and 176.50 mu g insect(-1), and for compound 2 they were 91.19 and 184.56 mu g insect(-1).CONCLUSION: According to the LD(50) and LD(90) for compounds 1 and 2, it can be inferred that the values reflect an acute lethal response to both compounds, based on interaction(s) of the toxicants with a primary target or series of targets. Thus, the amides were demonstrated to have potential value in the control of the sugarcane borer. (C) 2008 Society of Chemical Industry