Synthesis and characterization of a novel organic nitrate NDHP: Role of xanthine oxidoreductase-mediated nitric oxide formation

In this report, we describe the synthesis and characterization of 1,3-bis(hexyloxy)propan-2-yl nitrate (NDHP), a novel organic mono nitrate. Using purified xanthine oxidoreductase (XOR), chemiluminescence and electron paramagnetic resonance (EPR) spectroscopy, we found that XOR catalyzes nitric oxide (NO) generation from NDHP under anaerobic conditions, and that thiols are not involved or required in this process. Further mechanistic studies revealed that NDHP could be reduced to NO at both the FAD and the molybdenum sites of XOR, but that the FAD site required an unoccupied molybdenum site. Conversely, the molybdenum site was able to reduce NDHP independently of an active FAD site. Moreover, using isolated vessels in a myograph, we demonstrate that NDHP dilates pre-constricted mesenteric arteries from rats and mice. These effects were diminished when XOR was blocked using the selective inhibitor febuxostat. Finally, we demonstrate that NDHP, in contrast to glyceryl trinitrate (GTN), is not subject to development of tolerance in isolated mesenteric arteries.</p

Protection against tuberculosis by a single intranasal administration of DNA-hsp65 vaccine complexed with cationic liposomes

<p>Abstract</p> <p>Background</p> <p>The greatest challenges in vaccine development include optimization of DNA vaccines for use in humans, creation of effective single-dose vaccines, development of delivery systems that do not involve live viruses, and the identification of effective new adjuvants. Herein, we describe a novel, simple technique for efficiently vaccinating mice against tuberculosis (TB). Our technique consists of a single-dose, genetic vaccine formulation of DNA-hsp65 complexed with cationic liposomes and administered intranasally.</p> <p>Results</p> <p>We developed a novel and non-toxic formulation of cationic liposomes, in which the DNA-hsp65 vaccine was entrapped (ENTR-hsp65) or complexed (COMP-hsp65), and used to immunize mice by intramuscular or intranasal routes. Although both liposome formulations induced a typical Th1 pattern of immune response, the intramuscular route of delivery did not reduce the number of bacilli. However, a single intranasal immunization with COMP-hsp65, carrying as few as 25 μg of plasmid DNA, leads to a remarkable reduction of the amount of bacilli in lungs. These effects were accompanied by increasing levels of IFN-γ and lung parenchyma preservation, results similar to those found in mice vaccinated intramuscularly four times with naked DNA-hsp65 (total of 400 μg).</p> <p>Conclusion</p> <p>Our objective was to overcome the significant obstacles currently facing DNA vaccine development. Our results in the mouse TB model showed that a single intranasal dose of COMP-hsp65 elicited a cellular immune response that was as strong as that induced by four intramuscular doses of naked-DNA. This formulation allowed a 16-fold reduction in the amount of DNA administered. Moreover, we demonstrated that this vaccine is safe, biocompatible, stable, and easily manufactured at a low cost. We believe that this strategy can be applied to human vaccines to TB in a single dose or in prime-boost protocols, leading to a tremendous impact on the control of this infectious disease.</p

Trends in percutaneous coronary intervention from 2004 to 2013 according to the Portuguese National Registry of Interventional Cardiology.

INTRODUCTION AND OBJECTIVES: The aim of the present paper is to report trends in Portuguese interventional cardiology from 2004 to 2013 and to compare them with other European countries. METHODS: Based on the Portuguese National Registry of Interventional Cardiology and on official data from the Directorate-General of Health, we give an overview of developments in coronary interventions from 2004 to 2013. RESULTS: In 2013, 36 810 diagnostic catheterization procedures were performed, representing an increase of 34% compared to 2007 and a rate of 3529 coronary angiograms per million population. Coronary interventions increased by 65% in the decade from 2004 to 2013, with a total of 13 897 procedures and a rate of 1333 coronary interventions per million population in 2013. Primary percutaneous coronary intervention (PCI) increased by 265% from 2004 to 2013 (1328 vs. 3524), an adjusted rate of 338 primary PCIs per million, representing 25% of total angioplasties. Stents were the most frequently used devices, drug-eluting stents being used in 73% in 2013. Radial access increased from 4.1% in 2004 to 57.9% in 2013. CONCLUSION: Interventional cardiology in Portugal has been expanding since 2004. We would emphasize the fact that in 2013 all Portuguese interventional cardiology centers were participating in the National Registry of Interventional Cardiology, as well as the growth in primary PCI and increased use of radial access

Wetlands for wastewater treatment and subsequent recycling of treated effluent : a review

Due to water scarcity challenges around the world, it is essential to think about non-conventional water resources to address the increased demand in clean freshwater. Environmental and public health problems may result from insufficient provision of sanitation and wastewater disposal facilities. Because of this, wastewater treatment and recycling methods will be vital to provide sufficient freshwater in the coming decades, since water resources are limited and more than 70% of water are consumed for irrigation purposes. Therefore, the application of treated wastewater for agricultural irrigation has much potential, especially when incorporating the reuse of nutrients like nitrogen and phosphorous, which are essential for plant production. Among the current treatment technologies applied in urban wastewater reuse for irrigation, wetlands were concluded to be the one of the most suitable ones in terms of pollutant removal and have advantages due to both low maintenance costs and required energy. Wetland behavior and efficiency concerning wastewater treatment is mainly linked to macrophyte composition, substrate, hydrology, surface loading rate, influent feeding mode, microorganism availability, and temperature. Constructed wetlands are very effective in removing organics and suspended solids, whereas the removal of nitrogen is relatively low, but could be improved by using a combination of various types of constructed wetlands meeting the irrigation reuse standards. The removal of phosphorus is usually low, unless special media with high sorption capacity are used. Pathogen removal from wetland effluent to meet irrigation reuse standards is a challenge unless supplementary lagoons or hybrid wetland systems are used

Behaviour of a biocompatible titanium alloy during orthogonal micro-cutting employing green machining techniques

The sustainability of a process is the objective of modern industries aiming to reduce waste in production, since consumers require high quality and efficiency with fair price. Thus, a good understanding of the process should be its starting point. The manufacture of dental implants is an example in which waste reduction is important for the reduction of prices due to the demand for great quality and accuracy. This study observed the behaviour of sustainable micro-cutting applied to the Ti-6Al-7Nb titanium alloy, considering the ploughing effect on minimum quantity lubrication (MQL) and high-speed machining (HSM) conditions. When compared with dry condition and low-speed cutting in orthogonal micro-cutting, the use of HSM in dry cutting was more efficient than using MQL. The dry condition presented lower surface roughness, whilst the cooled/lubricated condition presented lower burr formation.publishe