903 resultados para Antitubercular Agents


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The aim of this study was to evaluate the antimicrobial activity and pH changes induced by Portland cement (PC) alone and in association with radiopacifiers. Methods. The materials tested were pure PC, PC + bismuth oxide, PC + zirconium oxide, PC + calcium tungstate, and zinc oxide and eugenol cement (ZOE). Antimicrobial activity was evaluated by agar diffusion test using the following strains: Micrococcus luteus, Streptococcus mutans, Enterococcus faecalis, Pseudomonas aeruginosa, and Candida albicans. After 24 hours of incubation at 37°C, inhibition of bacterial growth was observed and measured. For pH analysis, material samples (n=10) were placed in polyethylene tubes and immersed in 10 mL of distilled water. After 12, 24, 48, and 72 hours, the pH of the solutions was determined using a pH meter. Results. All microbial species were inhibited by the cements evaluated. All materials composed of PC with radiopacifying agents promoted pH increase similar to pure Portland cement. ZOE had the lowest pH values throughout all experimental periods. Conclusions. All Portland cement-based materials with the addition of different radiopacifiers (bismuth oxide, calcium tungstate, and zirconium oxide) presented antimicrobial activity and pH similar to pure Portland cement.

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Introduction & Objectives: Thrombosis of the renal allograft is expected to occur in 1–6% of kidney transplants, and graft loss is expected in almost all cases. Anticoagulant and anti-platelet agents could serve as an adjunctive preventive measure, but sound evidence of benefits are still lacking, in this setting. We therefore assessed the efficacy and safety of anticoagulant and anti-platelet agents, in reducing the rate of renal allograft thrombosis. Methods: A review of the literature was carried out in major databases (MEDLINE, EMBASE and LILACS), with a comprehensive search strategy, to locate all available case series studies of anticoagulant and/or anti-platelet prophylaxis of thrombosis in renal transplantation. The date of the last search was 11 August 2014. We pooled all case series in a proportional meta-analysis. Statistical significance was achieved if the 95% confidence intervals obtained for each intervention did not overlap. Results: Our search strategy retrieved 7160 titles, from which 21 case series were chosen for analysis. A total of 3246 patients were identified (1718 treated with antiplatelet and/or anticoagulant agents, and 1528 non-treated control subjects). Allograft thrombosis occurred in 7.24% (95% CI 3.45 to 12.27%) of the patients receiving no intervention, compared to 3.38% (95% CI 1.45 to 6.1%), 1.2% (95% CI 0.6 to 2.1%) and 0.47% (95% CI 0.001 to 1.79%), in the anticoagulant, aspirin, and aspirin + anticoagulant groups, respectively. Bleeding complication rates were 28.0% (95% CI 15.4 to 42.7%) for anticoagulants, compared to 12.13% (95% CI 0.8 to 33.93%) for aspirin + anticoagulant, 0.31% (95% CI 0.0001 to 1.32%) for aspirin, and 6.1% (95% CI 2.2 to 11.7%) for the control group. Conclusions: Aspirin is more effective in reducing allograft thrombosis, after kidney transplantation, whether alone or in association with an anticoagulant, when compared to no drug prophylaxis, and without higher haemorrhagic complication rates. Anticoagulants, when used alone, do not show a beneficial effect on thrombosis rates, additionally yielding higher bleeding rates.

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

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Objectives: To evaluate the anti-erosive potential of solutions containing sodium fluoride (NaF, 225 ppm F) and different film-forming agents.Methods: In Phase 1, hydroxyapatite crystals were pre-treated with solutions containing NaF (F), linear sodium polyphosphate (LPP), sodium pyrophosphate tetrabasic (PP), sodium tripolyphosphate (STP), sodium caseinate (SC), bovine serum albumin (BSA), stannous chloride (Sn) and some combinations thereof. Deionized water was the control (C). The pH-stat method was used to evaluate hydroxyapatite dissolution. In Phase 2, the most effective solutions were tested in two independent experiments. Both consisted of an erosion-remineralization cycling model using enamel and dentine specimens with three solution treatments per day. In Phase 2a, the challenge was performed with 0.3% citric acid (pH = 3.8). In Phase 2b, 1% citric acid (pH = 2.4) was used. Hard tissue surface loss was determined profilometrically. Data were analyzed with two-way ANOVA and Tukey tests.Results: In Phase 1, F, LPP, Sn and some of their combinations caused the greatest reduction in hydroxyapatite dissolution. In Phase 2a, C showed the highest enamel loss, followed by LPP. There were no differences between all other groups. In Phase 2b: (F + LPP + Sn) < (F + LPP) = (F + Sn) < (F) = (LPP + Sn) < (LPP) < (Sn) < C. For dentine, in both experiments, only the fluoride-containing groups showed lower surface loss than C, except for LPP + Sn in 2a.Conclusions: F, Sn, LPP reduced enamel erosion, this effect was enhanced by their combination under highly erosive conditions. For dentine, the F-containing groups showed similar protective effect.Clinical significance: The addition of LPP and/or Sn can improve the fluoride solution protection against erosion of enamel but not of dentine. (C) 2015 Elsevier Ltd. All rights reserved.

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

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Lung cancer is a leading cause of death in developed countries. Although smoking cessation is a primary strategy for preventing lung cancer, former smokers remain at high risk of cancer. Accordingly, there is a need to increase the efficacy of lung cancer prevention. Poor bioavailability is the main factor limiting the efficacy of chemopreventive agents. The aim of this study was to increase the efficacy of cancer chemopreventive agents by using lipid nanoparticles (NPs) as a carrier. This study evaluated the ability of lipid NPs to modify the pharmacodynamics of chemopreventive agents including N-acetyl-L-cysteine, phenethyl isothiocyanate and resveratrol (RES). The chemopreventive efficacy of these drugs was determined by evaluating their abilities to counteract cytotoxic damage (DNA fragmentation) induced by cigarette smoke condensate (CSC) and to activate protective apoptosis (annexin-V cytofluorimetric staining) in bronchial epithelial cells both in vitro and in ex vivo experiment in mice. NPs decreased the toxicity of RES and increased its ability to counteract CSC cytotoxicity. NPs significantly increased the ability of phenethyl isothiocyanate to attenuate CSC-induced DNA fragmentation at the highest tested dose. In contrast, this potentiating effect was observed at all tested doses of RES, NPs dramatically increasing RES-induced apoptosis in CSC-treated cells. These results provide evidence that NPs are highly effective at increasing the efficacy of lipophilic drugs (RES) but are not effective towards hydrophilic agents (N-acetyl-L-cysteine), which already possess remarkable bioavailability. Intermediate effects were observed for phenethyl isothiocyanate. These findings are relevant to the identification of cancer chemopreventive agents that would benefit from lipid NP delivery.

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

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Despite the resistance developed by the Mycobacterium tuberculosis (MTb) strains, isoniazid (INK) has been recognized as one of the best drug for treatment of Tuberculosis (Tb). The coordination of INH to ruthenium metal centers was investigated as a strategy to enhance the activity of this drug against the sensitive and resistant strains of MTb. The complexes trans-[Ru(NH3)(4)(L)(INH)](2+) (L = SO2 or NH3) were isolated and their chemical and antituberculosis properties studied. The minimal inhibitory concentration (MIC) data show that [Ru(NH3)(5)(INH)](2+) was active in both resistant and sensitive strains, whereas free INK (non-coordinated) showed to be active only against the sensitive strain. The coordination of INH to the metal center in both [Ru(NH3)(5)(INH)](2+) and trans-[Ru(NH3)(4)(SO2)(INH)](2+) complexes led to a shift in the INH oxidation potential to less positive values compared to free INH. Despite, the ease of oxidation of INH did not lead to an increase in the in vitro INH activity against MTb, it might have provided sensitivity toward resistant strains. Furthermore, ruthenium complexes with chemical structures analogous to those described above were synthesized using the oxidation products of INK as ligands (namely, isonicotinic acid and isonicotinamide). These last compounds were not active against any strains of MTb. Moreover, according to DFT calculations the formation of the acyl radical, a proposed intermediate in the INH oxidation, is favored in the [Ru(NH3)(5)(INH)](2+) complex by 50.7 kcal mol(-1) with respect to the free INH. This result suggests that the stabilization of the acyl radical promoted by the metal center would be a more important feature than the oxidation potential of the INH for the antituberculosis activity against resistant strains. (C) 2015 Elsevier B.V. All rights reserved.

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

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In the search for new therapeutic tools against tuberculosis and to further address the therapeutic potential of pyridine-2-thiol 1-oxide (Hmpo) metal complexes, two new octahedral [M(III)(mpo)3] complexes, with M = Ga or Bi, were synthesized and characterized in the solid state and in solution. Attempts to crystallize [Ga(III)(mpo)3] in CH2Cl2 led to single crystals of the reaction product [GaCl(mpo)2], where the gallium(III) ion is in a square basis pyramidal environment, trans-coordinated at the basis to two pyridine-2-thiolato 1-oxide anions acting as bidentate ligands through their oxygen and sulfur atoms. The biological activity of the new [M(III)(mpo)3] complexes together with that of the previously reported Fe(III) analogous compound and the pyridine-2-thiol 1-oxide sodium salt (Na mpo) was evaluated on Mycobacterium tuberculosis. The compounds showed excellent activity, both in the standard strain H37Rv ATCC 27294 (pan-susceptible) and in five clinical isolates that are resistant to the standard first-line anti-tuberculosis drugs isoniazid and rifampicin. These pyridine-2-thiol 1-oxide derivatives are promising compounds for the treatment of resistant tuberculosis.

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The surface free energy of conditioned-dentin is one of the factors that interfere with monomeric infiltration of the interfibrillar spaces. Saturation of the tooth matrix with different substances may modulate this energy and, consequently, the wettability of the dentin. To evaluate the influence of different substances used to saturate conditioned-dentin on surface free energy (SFE) of this substrate. Dentin blocks (4 × 7 × 1 mm, n = 6/ group), obtained from the roots of bovine incisors, were etched using phosphoric acid for 15 seconds, rinsed and gently dried. The surfaces were treated for 60 seconds with: ultra-purified water (H20-control); ethanol (EtOH), acetone (ACT), chlorhexidine (CHX), ethylenediaminetetraacetic acid (EDTA); or sodium hypochlorite (NaOCl). The tooth surfaces were once again dried with absorbent paper and prepared for SFE evaluation using three standards: water, formamide and bromonaphthalene. Analysis of variance (ANOVA) and Dunnet's tests (a = 0.05) were applied to the data. Ethylenediaminetetraacetic acid was the only substance that caused a change to the contact angle for the standards water and formamide, while only EtOH influenced the angles formed between formamide and the dentin surface. None of the substances exerted a significant effect for bromonaphtha-lene. In comparison to the control, only EDTA and NaOCl altered both polar components of the SFE. Total SFE was increased by saturation of the collagen matrix by EDTA and reduced when NaOCl was used. Saturation of the collagen matrix by EDTA and EtOH changed the surface free energy of the dentin. In addition, the use of NaOCl negatively interfered with the properties evaluated. The increase of surface free energy and wettability of the dentin surface would allow higher penetration of the the adhesive system, which would be of importance to the clinical success of resin-dentin union.

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

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