115 resultados para 3 [3 tert butylthio 1 (4 chlorobenzyl) 5 isopropyl 2 indolyl] 2


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

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Three experimental protocols were carried out with the aim of evaluating the role of protein restriction on the progression of the established adriamycin-induced nephropathy, and whether the protective effect of the diet persists after the diet is discontinued. The effect of a low protein diet (LPD) was studied for 6 weeks in protocol 1, 16 weeks in protocol 2 and for 28 weeks in protocol 3. In protocol 3, one group (LL) received LPD and another (NN) was given a normal protein diet (NPD). A third group (LN) received LPD for 16 weeks and then NPD for 12 weeks and a fourth group (NL) was fed NPD for 16 weeks and then LPD for 12 weeks. In protocol I the tubulo- interstitial index (TILl) of rats on LPD (Md = 2, P25 = 0.0; P75 = 3.5) after six weeks, was smaller than that of the animals on NPD (Md = 6.0; P25 = 3.0; P75 = 8.0; p < 0.05). In protocol 2, the group taking LPD presented an area of interstitial fibrosis (IF) (Md= 0.5%, P25 0.2%; P75 = 1.9%) smaller than that of the NPD group (Md = 6.8%; P25 = 5.2%; P75 = 7.1%; P < 0.05). No significant difference in the area of glomerulosclerosis (GSA) was observed between the animals on LPD (Md = 0.0%; P25 = 0.0%, P75 = 0.0%) and NPD (Md = 0.37%; P25 = 02% P75 = 1.25%; p > 0.05). In protocol 3, the group LL showed GSA (Md = 1.3%; P25 0.6%, P75 = 2.5%) and IF (Md = 3.60/0; P25 = 1.6%; P75 = 5.9%) smaller that those of LN (GSA Md = 10.1%; P25 = 6.6%; P75 = 14.8%; IF; Md = 17.3%; P25 = 14.1%; P75 = 24,5%), NL (GSA: Md = 9.1%; P25 = 5,8%; P75 = 11.7%; IF; Md = 25.0%; P25 = 20.4%; P75 = 30%), and NN (GSA: Md = 6. 75%; P25 = 4.9%; P75 = 11.7%; IF: Md = 20.9%; P25 = 16.2%; P75 = 32.4%). In conclusion, in order to be effective, LPD must be introduced early and maintained for a long period of tune.

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Background and Objectives - Sevoflurane is an inhalational anesthetic drug with low blood/gas solubility providing fast anesthesia induction and emergence. Its ability to maintain cardiovascular stability makes it ideal for pediatric anesthesia. The aim of this study was to evaluate hemodynamic stability, consumption of inhalational anesthetics and emergence time in children with and without premedication (midazolam or clonidine) anesthetized with sevoflurane titrated according to BIS monitoring. Methods - Participated in this study 30 patients aged 2 to 12 years, physical status ASA I, undergoing elective surgeries who were divided into 3 groups: G1 - without premedication, G2 - 0.5 mg.kg-1 oral midazolam, G3 - 4 μg.kg-1 oral clonidine 60 minutes before surgery. All patients received 30 μg.kg-1 alfentanil, 3 mg.kg-1 propofol, 0.5 mg.kg-1 atracurium, sevoflurane in different concentrations monitored by BIS (values close to 60) and N2O in a non rebreathing system. Systolic and diastolic blood pressure, heart rate, expired sevoflurane concentration (EC), sevoflurane consumption (ml.min-1) and emergence time were evaluated. Emergence time was defined as time elapsed between the end of anesthesia and patients' spontaneous movements trying to extubate themselves, crying and opening eyes and mouth. Results - There were no differences among groups as to systolic and diastolic blood pressure, EC, sevoflurane consumption and emergence time. Heart rate was lower in G3 group. Conclusions - Sevoflurane has provided hemodynamic stability. Premedication with clonidine and midazolam did not influence emergence time, inhaled anesthetic consumption or maintenance of anesthesia with sevoflurane. Anesthesia duration has also not influenced emergence time. Hypnosis monitoring was important for balancing anesthetic levels and this might have been responsible for the similarity of emergence times for all studied groups.

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Iron nitroprusside Fe(II)NP was incorporated into a carbon paste electrode and the electrochemical studies were performed with cyclic voltammetry. The cyclic voltammogram of Fe(II)NP exhibits two redox couple with formal potential (E0')1 = 0.24 e (E0')2 = 0.85 V vs SCE attributed to Fe(II)/Fe(II) and Fe (II)(CN)5NO/Fe(III)(CN)5NO, respectively. The redox couple with (E0')2 = 0.85 V presents an electrocatalytic response for sulfhydryl compounds. The electrocatalytic oxidation of sulfhydryl compounds by the mediator has been used for the determination of L-cysteine and N-acetylcysteine. The modified graphite paste electrode gives a linear range from 9.2 x 10-4-2.0 x 10-2;; 9.6 x 10-4-1.4 x 10-2mol L-1 for the determination of L-cysteine and N-acetylcysteine, respectively, with detection limit of 1.9 x 10-4 mol L-1;; 1.5 x 10 -4 mol L-1 and relative standard desviations ± 5% and 1.5 x 10-3 mol L-1 ± 4% (n=3). The amperometric sensitivities are 0.024 and 0.027 μA/μmol L-1 for L-cysteine and N-acetylcysteine, respectively. The application of this electrode was tested and a commercial pharmaceutical product (Fluimucil) has been determined.

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The reactions of the precursor [Pd(N,C-dmba)(MeCN)2](NO 3) (1) (dmba = N,N-dimethylbenzylamine), with the proligands 3,5-dimethylpyrazole (Hdmpz), 2-quinolinethiol (qnSH) and 1,1′- bis(diphenylphosphine)ferrocene (dppf) afforded the compounds [Pd(N,C-dmba)(Hdmpz)(ONO2)]0.5CH2Cl2 (2), [Pd(N,C-dmba)(qnSH)(ONO2)] 0.5CH2Cl2 (3) and [Pd(N,C-dmba)(dppf)](NO3) (4), respectively. The mononuclear species 2,3 and 4 were characterized by elemental analysis, infrared spectroscopy, NMR and thermogravimetric analysis. The IR spectra show bands which are consistent with terminal monodentate nitrate group for 2-3 and ionic nitrate for 4. The 1H and 13C NMR data confirm that coordination of the organic ligands has occurred and the 31P{1H} NMR data for 4 clearly evidences the occurrence in solution of three cyclopalladated species with the dppf acting as a bridging ligand in two cases and as a chelate in one. The thermal behavior of compounds 1-4 suggests that complex 2 is the most stable. The X-ray diffractometry results show the formation of PdO from 1 and 2, Pd2OSO4 from 3, and of a mixture of PdO and Fe 2(PO4)3 from 4, as final decomposition products.

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Molecular hybridization is a new concept in drug design and development based on the combination of pharmacophoric moieties of different bioactive substances to produce a new hyrid compound with improved affinity and efficacy, when compared to the parent drugs. Additionally, this strategy can results in compounds presenting modified selectivity profile, different and/or dual modes of action and reduced undesired side effects. So, in this described several example of different strategies for drug design, discovery and pharmacomodulation focused on new innovative hybrid compounds presenting analgesic, anti-inflammatory, platelet anti-aggregating, anti-infections, anticancer, cardio- and neuroactive properties.

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Aims: The effect of exercise training (ET) on vascular responsiveness in diabetes mellitus has been largely well studied. However, limited studies have investigated the effects of ET on functional responses of the corpus cavernosum (CC) in diabetic animals. Therefore, the aim of this study was to investigate whether prior ET prevents the impairment of erectile function in streptozotocin-induced diabetic rats. Main methods: Rats were exercised for four weeks prior to the induction of diabetes, and then again for another 4 weeks thereafter. Concentration-response curves to acetylcholine, sodium nitroprusside, Y-27632, BAY 412272 and phenylephrine (PE) were obtained in CC. The excitatory and inhibitory effects of electrical-field stimulation were also evaluated. Key findings: Plasma SOD levels were markedly decreased in the sedentary diabetic group (D-SD) as compared to control sedentary animals (C-SD), approximately 53% (P < 0.05) and this reduction was restored in trained diabetic animals. Physical training restored the impairment of endothelium-dependent and -independent relaxation responses seen in the D-SD group. The potency values for Y-27632 in the CC were significantly reduced in the D-SD group, which was reversed by physical training. The impairment of electrical-field stimulation (EFS)-induced relaxation seen in the D-SD group was restored by physical training. On the other hand, both EFS-induced contractions and concentration-response curves to PE in cavernosal strips were not modified by either diabetes or physical training. Significance: Practice of regular physical exercise may be an important approach in preventing erectile dysfunction associated with diabetes mellitus by re-establishment of the balance between NO production and its inactivation. © 2010 Elsevier Inc. All rights reserved.

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A biomimetic sensor based on a carbon paste electrode modified with the nickel(II) 1,4,8,11,15,18,22,25-octabutoxy-29H,31H-phthalocyanine complex was developed as a reliable alternative technique for the sensitive and selective analysis of the herbicide diuron in environmental media. The sensor was evaluated using cyclic voltammetry and amperometric techniques. The best amperometric responses were obtained at 750 mV vs. Ag/AgCl (KClsat), using 0.1 mol L-1 phosphate buffer solution at pH 8.0. Under these conditions, the sensor showed a linear response for diuron concentrations between 9.9 × 10-6 and 1.5 × 10-4 mol L -1, a sensitivity of 22817 (±261) μA L mol-1, and detection and quantification limits of 6.14 × 10-6 and 2 × 10-5 mol L-1, respectively. The presence of the nickel complex in the carbon paste improved selectivity, stability, and sensitivity (which increased 700%), compared to unmodified paste. The applicability of the sensor was demonstrated using enriched environmental samples (river water and soil). © 2012 Elsevier B.V. All rights reserved.

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Background: Activation of GABAB receptors with baclofen into the lateral parabrachial nucleus (LPBN) induces ingestion of water and 0.3 M NaCl in fluid replete rats. However, up to now, no study has investigated the effects of baclofen injected alone or combined with GABAB receptor antagonist into the LPBN on water and 0.3 M NaCl intake in rats with increased plasma osmolarity (rats treated with an intragastric load of 2 M NaCl). Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used.Results: In fluid replete rats, baclofen (0.5 nmol/0.2 μl), bilaterally injected into the LPBN, induced ingestion of 0.3 M NaCl (14.3 ± 4.1 vs. saline: 0.2 ± 0.2 ml/210 min) and water (7.1 ± 2.9 vs. saline: 0.6 ± 0.5 ml/210 min). In cell-dehydrated rats, bilateral injections of baclofen (0.5 and 1.0 nmol/0.2 μl) into the LPBN induced an increase of 0.3 M NaCl intake (15.6 ± 5.7 and 21.5 ± 3.5 ml/210 min, respectively, vs. saline: 1.7 ± 0.8 ml/210 min) and an early inhibition of water intake (3.5 ± 1.4 and 6.7 ± 2.1 ml/150 min, respectively, vs. saline: 9.2 ± 1.4 ml/150 min). The pretreatment of the LPBN with 2-hydroxysaclofen (GABAB antagonist, 5 nmol/0.2 μl) potentiated the effect of baclofen on 0.3 M NaCl intake in the first 90 min of test and did not modify the inhibition of water intake induced by baclofen in cell-dehydrated rats. Baclofen injected into the LPBN did not affect blood pressure and heart rate.Conclusions: Thus, injection of baclofen into the LPBN in cell-dehydrated rats induced ingestion of 0.3 M NaCl and inhibition of water intake, suggesting that even in a hyperosmotic situation, the blockade of LPBN inhibitory mechanisms with baclofen is enough to drive rats to drink hypertonic NaCl, an effect independent of changes in blood pressure. © 2013 Kimura et al.; licensee BioMed Central Ltd.

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The stimulation by Mg2+, Na+, K+, NH 4 +, and ATP of (Na+, K+)-ATPase activity in a gill microsomal fraction from the freshwater prawn Macrobrachium rosenbergii was examined. Immunofluorescence labeling revealed that the (Na +, K+)-ATPase α-subunit is distributed predominantly within the intralamellar septum, while Western blotting revealed a single α-subunit isoform of about 108 kDa M r. Under saturating Mg2+, Na+, and K+ concentrations, the enzyme hydrolyzed ATP, obeying cooperative kinetics with V M = 115.0 ± 2.3 U mg-1, K 0.5 = 0.10 ± 0.01 mmol L-1. Stimulation by Na+ (V M = 110.0 ± 3.3 U mg-1, K 0.5 = 1.30 ± 0.03 mmol L -1), Mg2+ (V M = 115.0 ± 4.6 U mg -1, K 0.5 = 0.96 ± 0.03 mmol L-1), NH4 + (V M = 141.0 ± 5.6 U mg -1, K 0.5 = 1.90 ± 0.04 mmol L-1), and K+ (V M = 120.0 ± 2.4 U mg-1, K M = 2.74 ± 0.08 mmol L-1) followed single saturation curves and, except for K+, exhibited site-site interaction kinetics. Ouabain inhibited ATPase activity by around 73 % with K I = 12.4 ± 1.3 mol L-1. Complementary inhibition studies suggest the presence of F0F1-, Na+-, or K +-ATPases, but not V(H+)- or Ca2+-ATPases, in the gill microsomal preparation. K+ and NH4 + synergistically stimulated enzyme activity (25 %), suggesting that these ions bind to different sites on the molecule. We propose a mechanism for the stimulation by both NH4 +, and K+ of the gill enzyme. © 2013 Springer Science+Business Media New York.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)