918 resultados para sustained release


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BACKGROUND AND GOAL: Patients infected with hepatitis C virus (HCV) with elevated low-density lipoprotein (LDL) levels achieve higher sustained virologic response (SVR) rates after peginterferon (PegIFN)/ribavirin treatment versus patients with lower LDL. Our aim was to determine whether SVR rates in patients with low/elevated LDL can be improved by dose intensification. STUDY: In PROGRESS, genotype 1 patients with baseline HCV RNA≥400,000 IU/mL and body weight ≥85 kg were randomized to 48 weeks of 180 μg/wk PegIFN α-2a (40 kDa) plus ribavirin (A: 1200 mg/d; B: 1400/1600 mg/d) or 12 weeks of 360 μg/wk PegIFN α-2a followed by 36 weeks of 180 μg/wk, plus ribavirin (C: 1200 mg/d; D: 1400/1600 mg/d). This retrospective analysis assessed SVR rates among patients with low (<100 mg/dL) or elevated (≥100 mg/dL) LDL. Patients with high LDL (n=256) had higher baseline HCV RNA (5.86×10 IU/mL) versus patients with low LDL (n=262; 4.02×10 IU/mL; P=0.0003). RESULTS: Multiple logistic regression analysis identified a significant interaction between PegIFN α-2a dose and LDL levels on SVR (P=0.0193). The only treatment-related SVR predictor in the nested multiple logistic regression was PegIFN α-2a dose among patients with elevated LDL (P=0.0074); therefore, data from the standard (A+B) and induction (C+D) dose arms were pooled. Among patients with low LDL, SVR rates were 40% and 35% in the standard and induction-dose groups, respectively; SVR rates in patients with high LDL were 44% and 60% (P=0.014), respectively. CONCLUSIONS: Intensified dosing of PegIFN α-2a increases SVR rates in patients with elevated LDL even with the difficult-to-cure characteristics of genotype 1, high baseline viral load, and high body weight. Copyright © 2013 by Lippincott Williams & Wilkins.

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Background: Intestinal ischemia/reperfusion (IR) injury is a serious and triggering event in the development of remote organ dysfunction, from which the lung is the main target. This condition is characterized by intense neutrophil recruitment, increased microvascular permeability. Intestinal IR is also responsible for induction of adult respiratory distress syndrome, the most serious and life-threatening form of acute lung injury. The purpose of this study was to investigate the effect of annexin-A1 protein as an endogenous regulator of the organ remote injury induced by intestinal ischemia/reperfusion. Male C57bl/6 mice were subjected to intestinal ischemia, induced by 45 min occlusion of the superior mesenteric artery, followed by reperfusion. Results: The intestinal ischemia/reperfusion evoked a high intensity lung inflammation as indicated by the number of neutrophils as compared to control group. Treatment with annexin-A1 peptidomimetic Ac2-26, reduced the number of neutrophils in the lung tissue and increased its number in the blood vessels, which suggests a regulatory effect of the peptide Ac2-26 in the neutrophil migration. Moreover, the peptide Ac2-26 treatment was associated with higher levels of plasma IL-10. Conclusion: Our data suggest that the annexin-A1 peptidomimetic Ac2-26 treatment has a regulatory and protective effect in the intestinal ischemia/reperfusion by attenuation of the leukocyte migration to the lung and induction of the anti-inflammatory cytokine IL-10 release into the plasma. The anti-inflammatory action of annexin-A1 and its peptidomimetic described here may serve as a basis for future therapeutic approach in mitigating inflammatory processes due to intestinal ischemia/reperfusion. © 2013 Guido et al.; licensee BioMed Central Ltd.

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Dynamic exercise evokes sustained cardiovascular responses, which are characterized by arterial pressure and heart rate increases. Although it is well accepted that there is central nervous system mediation of cardiovascular adjustments during exercise, information on the role of neural pathways and signaling mechanisms is limited. It has been reported that glutamate, by acting on NMDA receptors, evokes the release of nitric oxide through activation of neuronal nitric oxide synthase (nNOS) in the brain. In the present study, we tested the hypothesis that NMDA receptors and nNOS are involved in cardiovascular responses evoked by an acute bout of exercise on a rodent treadmill. Moreover, we investigated possible central sites mediating control of responses to exercise through the NMDA receptor-nitric oxide pathway. Intraperitoneal administration of the selective NMDA glutamate receptor antagonist dizocilpine maleate (MK-801) reduced both the arterial pressure and heart rate increase evoked by dynamic exercise. Intraperitoneal treatment with the preferential nNOS inhibitor 7-nitroindazole reduced exercise-evoked tachycardiac response without affecting the pressor response. Moreover, treadmill running increased NO formation in the medial prefrontal cortex (MPFC), bed nucleus of the stria teminalis (BNST) and periaqueductal gray (PAG), and this effect was inhibited by systemic pretreatment with MK-801. Our findings demonstrate that NMDA receptors and nNOS mediate the tachycardiac response to dynamic exercise, possibly through an NMDA receptor-NO signaling mechanism. However, NMDA receptors, but not nNOS, mediate the exercise-evoked pressor response. The present results also provide evidence that MPFC, BNST and PAG may modulate physiological adjustments during dynamic exercise through NMDA receptor-NO signaling. © 2013 Elsevier B.V.

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The objective of this work was to investigate the adsorption of micronutrients in humin and to verify the ability to release these elements in water. The first step was to determine the adsorption capacity of humin for several essential plant micronutrients and check the kinetic parameters. The order of adsorption was Zn < Ni < Co < Mn < Mo < Cu < Fe, whereas Zn showed maximum values of ca. 2.5 mg g-1 and Fe values of ca. 0.5 mg g-1 for systems containing 1 g of humin. Iron presented higher percentages of release (ca. 100%) and Co the lowest percentages (0.14%). The findings suggested that the use of humin enriched with micronutrients can be a promising alternative for the fertilization of agricultural soils, with the additional benefit of incorporating organic matter present in the form of humic substances into the soil and improving the agricultural productivity. © 2013 Sociedade Brasileira de Química.

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In this work, we synthesized a novel series of hydrogels composed of polyacrylamide (PAAm), methylcellulose (MC), and calcic montmorillonite (MMt) appropriate for the controlled release of fertilizers, where the components presented a synergistic effect, giving very high fertilizer loading in their structure. The synthesized hydrogel was characterized in relation to morphological, hydrophilic, spectroscopic, structural, thermal, and kinetic properties. After those characterizations, the application potential was verified through sorption and desorption studies of a nitrogenated fertilizer, urea (CO(NH2)2). The swelling degree results showed that the clay loading considerably reduces the water absorption capability; however, the hydrolysis process favored the urea adsorption in the hydrogel nanocomposites, increasing the load content according to the increase of the clay mass. The FTIR spectra indicated that there was incorporation of the clay with the polymeric matrix of the hydrogel and that incorporation increased the water absorption speed (indicated by the kinetic constant k). By an X-ray diffraction technique, good nanodispersion (intercalation) and exfoliation of the clay platelets in the hydrogel matrix were observed. Furthermore, the presence of the montmorillonite in the hydrogel caused the system to liberate the nutrient in a more controlled manner than that with the neat hydrogel in different pH ranges. In conclusion, excellent results were obtained for the controlled desorption of urea, highlighting the hydrolyzed hydrogels containing 50% calcic montmorillonite. This system presented the best desorption results, releasing larger amounts of nutrient and almost 200 times slower than pure urea, i.e., without hydrogel. The total values of nutrients present in the system show that this material is potentially viable for application in agriculture as a nutrient carrier vehicle. © 2013 American Chemical Society.

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Green chemistry is an innovative way to approach the synthesis of metallic nanostructures employing eco-friendly substances (natural compounds) acting as reducing agents. Usually, slow kinetics are expected due to, use of microbiological materials. In this report we study composites of natural rubber (NR) membranes fabricated using latex from Hevea brasiliensis trees (RRIM 600) that works as reducing agent for the synthesis of gold nanoparticles. A straight and clean method is presented, to produce gold nanoparticles (AuNP) in a flexible substrate or in solution, without the use of chemical reducing reagents, and at the same time providing good size's homogeneity, reproducibility, and stability of the composites. Copyright © 2013 Flávio C. Cabrera et al.

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Latin America and the Caribbean experienced an unexpectedly vigorous economic recovery in 2010 after the output contraction of 2009. This upturn was reflected in the region’s employment and unemployment rates, which resumed the positive trends that had been broken by the crisis, and formal wages rose slightly. The strength of the recovery and labour-market performance varied markedly across subregions and countries, however. The first part of this joint ECLAC/ILO publication on the employment situation in Latin America and the Caribbean looks at how labour markets have responded to the rapid economic upswing in 2010 and early 2011, highlighting both the significant advances achieved in the post-crisis period and the sharp differences evident across subregions and countries. As well as tapping into the improved external conditions which followed upon the Asianled global economic upturn, several Latin American countries were also able to contain the impacts of the crisis and underpin their own recovery with countercyclical policies, thanks to the leeway gained by their macroeconomic management during the run of growth from 2003 to 2008. These countries were in a position to implement expansionary fiscal and monetary policies, some of which channelled higher fiscal spending through labour-market policies or softened the impact of the crisis on employment and income, as discussed in previous ECLAC/ILO bulletins. Since the region is fairly new to the use of countercyclical policies, the second part of this document reviews the experiences arising from those policies and considers lessons for institutionalizing them. Economic growth in the Latin American and Caribbean region has historically been marked by the volatility of its economic cycles, with high-growth periods being succeeded by deep crises. Volatility has conspired against the use of production resources over extended periods and short growth horizons have impeded investment in capital and labour. In the recent international crisis, the deployment of countercyclical macroeconomic policy helped to reduce the depth and duration of the impact and to leverage a more rapid recovery. It is therefore worth looking at the fundamentals of a long-term countercyclical macroeconomic policy which would provide the tools needed to deal with future crises and pave the way for economic growth that may be sustained over time. A special factor during this crisis was that a greater effort was made to support employment and income. Several of the labour-market policy measures taken acted as vehicles for conveying increased fiscal spending to individuals, reflecting greater consideration for equality concerns. Indeed, these measures were aimed not only at stabilizing andstrengthening domestic demand per se, but also at preventing the crisis from hitting lowest-income households the hardest, as had occurred in previous episodes. And —again unlike the pattern seen in previous episodes— inflation actually fell during the crisis as the high food and fuel prices seen in the run-up to it eased as a result of both existing macroeconomic policies and global conditions. This averted the surge in inequality so often seen in previous crises. Two caveats must be added, however. First, not all the countries were in a position to deploy strong countercyclical policies. Many simply lacked the fiscal space to do so. Second, some countries took this sort of measure more as an ad hoc response to the crisis than as part of a clearly established countercyclical policy strategy. The challenge, then, is to institutionalize a countercyclical approach throughout the economic cycle. Taking up this challenge is part of making economic growth more sustainable. This year —2011— was ushered in by rapid economic growth and substantial improvements in labour indicators. With the region’s GDP projected to grow well over 4% this year, ECLAC and ILO estimate that the regional unemployment rate will fall substantially again, from 7.3% in 2010 to between 6.7% and 7.0% in 2011.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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In a large Phase III trial conducted in 10 Latin American countries, the safety and efficacy of the live attenuated monovalent rotavirus vaccine RIX4414 was evaluated in 15,183 healthy infants followed up during the first two years of life. Belém was the only site in Brazil included in this multicentre trial. The study in Belém included a subset of 653 infants who were followed up until 24 months of age for protection against severe rotavirus gastroenteritis. These subjects were randomly assigned in a 1:1 ratio to receive two doses of vaccine (n = 328) or two doses of placebo (n = 325) at approximately two and four months of age. Of the 653 enrolled infants, 23 dropped out during the study period. For the combined two-year period, the efficacy of RIX4414 was 72.3% [95% confidence interval (CI) 37.5-89.1%] against severe rotavirus-related gastroenteritis, reaching a protection rate of 81.8% (95% CI 36.4-96.6%) against circulating wild-type G9 rotavirus strains. It is concluded that two doses of RIX4414 are highly efficacious against severe rotavirus gastroenteritis in Belém during the first two years of life and provide high protection against the worldwide emergence and spread of G9P[8] strains.