953 resultados para Drug Concentration.


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This study examines whether memory of antidepressant direct-to-consumer (DTC) prescription drug advertising is associated with the public stigma attached to depression. Results indicate that those who better remember antidepressant DTC ads tend to have a higher perceived prevalence of depression (i.e., more people suffer from depression). And, the perceived prevalence of depression is inversely associated with the public stigma toward depression. That is, those who have a higher perceived prevalence of depression report that they are more supportive of and comfortable with people who have depression. The results suggest that the perceived prevalence of depression is a mediating variable that accounts for the relationship between memory of antidepressant DTC ads and the public stigma toward depression. The implications and limitations of the study, as an exploratory investigation, are discussed.

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Particulates with specific sizes and characteristics can induce potent immune responses by promoting antigen uptake of appropriate immuno-stimulatory cell types. Magnetite (Fe3O4) nanoparticles have shown many potential bioapplications due to their biocompatibility and special characteristics. Here, superparamagnetic Fe3O4 nanoparticles (SPIONs) with high magnetization value (70emug-1) were stabilized with trisodium citrate and successfully conjugated with a model antigen (ovalbumin, OVA) via N,N'-carbonyldiimidazole (CDI) mediated reaction, to achieve a maximum conjugation capacity at approximately 13μgμm-2. It was shown that different mechanisms governed the interactions between the OVA molecules and magnetite nanoparticles at different pH conditions. We evaluated as-synthesized SPION against commercially available magnetite nanoparticles. The cytotoxicity of these nanoparticles was investigated using mammalian cells. The reported CDI-mediated reaction can be considered as a potential approach in conjugating biomolecules onto magnetite or other biodegradable nanoparticles for vaccine delivery.

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DNA vaccines or proteins are capable of inducing specific immunity; however, the translation to the clinic has generally been problematic, primarily due to the reduced magnitude of immune response and poor pharmacokinetics. Herein we demonstrate a composite microsphere formulation, composed of mesoporous silica spheres (MPS) and poly(d,l-lactide-co-glycolide) (PLGA), enables the controlled delivery of a prime-boost vaccine via the encapsulation of plasmid DNA (pDNA) and protein in different compartments. Method with modified dual-concentric-feeding needles attached to a 40 kHz ultrasonic atomizer was studied. These needles focus the flow of two different solutions, which passed through the ultrasonic atomizer. The process synthesis parameters, which are important to the scale-up of composite microspheres, were also studied. These parameters include polymer concentration, feed flowrate, and volumetric ratio of polymer and pDNA-PEI/MPS-BSA. This fabrication technique produced composite microspheres with mean D[4,3] ranging from 6 to 34 μm, depending upon the microsphere preparation. The resultant physical morphology of composite microspheres was largely influenced by the volumetric ratio of pDNA-PEI/MPS-BSA to polymer, and this was due to the precipitation of MPS at the surface of the microspheres. The encapsulation efficiencies were predominantly in the range of 93-98% for pDNA and 46-68% for MPS. In the in vitro studies, the pDNA and protein showed different release kinetics in a 40 day time frame. The dual-concentric-feeding in ultrasonic atomization was shown to have excellent reproducibility. It was concluded that this fabrication technique is an effective method to prepare formulations containing a heterologous prime-boost vaccine in a single delivery system.

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BACKGROUND The increasing cost of fossil fuels as well as the escalating social and industrial awareness of the environmental impacts associated with the use of fossil fuels has created the need for more sustainable fuel options. Bioethanol, produced from renewable biomass such as sugar and starch materials, is believed to be one of these options, and it is currently being harnessed extensively. However, the utilization of sugar and starch materials as feedstocks for bioethanol production creates a major competition with the food market in terms of land for cultivation, and this makes bioethanol from these sources economically less attractive. RESULT This study explores the suitability of microalgae (Chlorococum sp.) as a substrate for bioethanol production via yeast (Saccharomycesbayanus)under different fermentation conditions. Results show a maximum ethanol concentration of 3.83 g L -1 obtained from 10 g L-1 of lipid-extracted microalgae debris. CONCLUSION This productivity level (∼38% w/w), which is in keeping with that of current production systems endorses microalgae as a promising substrate for bioethanol production.

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DNA may take a leading role in a future generation of blockbuster therapeutics. DNA has inherent advantages over other biomolecules such as protein, RNA and virus-like particles including safety, production simplicity and higher stability at ambient temperatures. Vaccination is the principal measure for preventing influenza and reducing the impact of pandemics; however, vaccines take up to 8-9 months to produce, and the global production capacity is woefully low. With production times as short as 2 weeks, improved safety and stability, bioprocess engineering developments, and the ability to perform numerous therapeutic roles, DNA has the potential to meet the demands of emerging and existing diseases. DNA is experiencing sharp growths in demand as indicated by its use in gene therapy trials and DNA vaccine related patents. Of particular interest for therapeutic use is plasmid DNA (pDNA), a form of non-genomic DNA that makes use of cellular machinery to express proteins or antigens. The production stages of fermentation and downstream purification are considered in this article. Forward looking approaches to purifying and delivering DNA are reported, including affinity chromatography and nasal inhalation. The place that pDNA may take in the preparation for and protection against pandemics is considered. If DNA therapeutics and vaccines prove to be effective, the ultimate scale of production will be huge which shall require associated bioprocess engineering research and development for purification of this large, unique biomolecule.

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An effective means of facilitating DNA vaccine delivery to antigen presenting cells is through biodegradable microspheres. Microspheres offer distinct advantages over other delivery technologies by providing release of DNA vaccine in its bioactive form in a controlled fashion. In this study, biodegradable poly(D,L-lactide-coglycolide) (PLGA) microspheres containing polyethylenimine (PEI) condensed plasmid DNA (pDNA) were prepared using a 40 kHz ultrasonic atomization system. Process synthesis parameters, which are important to the scale-up of microspheres that are suitable for nasal delivery (i.e., less than 20 μm), were studied. These parameters include polymer concentration; feed flowrate; volumetric ratio of polymer and pDNA-PEI (plasmid DNA-polyethylenimine) complexes; and nitrogen to phosphorous (N/P) ratio. PDNA encapsulation efficiencies were predominantly in the range 82-96%, and the mean sizes of the particle were between 6 and 15 μm. The ultrasonic synthesis method was shown to have excellent reproducibility. PEI affected morphology of the microspheres, as it induced the formation of porous particles that accelerate the release rate of pDNA. The PLGA microspheres displayed an in vitro release of pDNA of 95-99% within 30 days and demonstrated zero order release kinetics without an initial spike of pDNA. Agarose electrophoresis confirmed conservation of the supercoiled form of pDNA throughout the synthesis and in vitro release stages. It was concluded that ultrasonic atomization is an efficient technique to overcome the key obstacles in scaling-up the manufacture of encapsulated vaccine for clinical trials and ultimately, commercial applications.

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Background The adsorption of bovine serum albumin (BSA) onto mesoporous silica spheres (MPS) synthesized from silica colloids was studied employing real time in situ measurements. The stabilities of the BSA at different pH values, their isoelectric points and zeta potentials were determined in order to probe the interactions between the protein and the mesoporous silica. Results The pore size of MPS was designed for protein, and this, coupled with an in depth understanding of the physico-chemical characteristics of the protein and MPS has yielded a better binding capacity and delivery profile. The adsorption isotherm at pH 4.2 fitted the Langmuir model and displayed the highest adsorption capacity (71.43 mg mL-1 MPS). Furthermore, the delivery rates of BSA from the MPS under physiological conditions were shown to be dependent on the ionic strength of the buffer and protein loading concentration. Conclusion Economics and scale-up considerations of mesoporous material synthesized via destabilization of colloids by electrolyte indicate the scaleability and commercial viability of this technology as a delivery platform for biopharmaceutical applications.

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The creation of a commercially viable and a large-scale purification process for plasmid DNA (pDNA) production requires a whole-systems continuous or semi-continuous purification strategy employing optimised stationary adsorption phase(s) without the use of expensive and toxic chemicals, avian/bovine-derived enzymes and several built-in unit processes, thus affecting overall plasmid recovery, processing time and economics. Continuous stationary phases are known to offer fast separation due to their large pore diameter making large molecule pDNA easily accessible with limited mass transfer resistance even at high flow rates. A monolithic stationary sorbent was synthesised via free radical liquid porogenic polymerisation of ethylene glycol dimethacrylate (EDMA) and glycidyl methacrylate (GMA) with surface and pore characteristics tailored specifically for plasmid binding, retention and elution. The polymer was functionalised with an amine active group for anion-exchange purification of pDNA from cleared lysate obtained from E. coli DH5α-pUC19 pellets in RNase/protease-free process. Characterization of the resin showed a unique porous material with 70% of the pores sizes above 300 nm. The final product isolated from anion-exchange purification in only 5 min was pure and homogenous supercoiled pDNA with no gDNA, RNA and protein contamination as confirmed with DNA electrophoresis, restriction analysis and SDS page. The resin showed a maximum binding capacity of 15.2 mg/mL and this capacity persisted after several applications of the resin. This technique is cGMP compatible and commercially viable for rapid isolation of pDNA.

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Improved biopharmaceutical delivery may be achieved via the use of biodegradable microspheres as delivery vehicles. Biodegradable microspheres offer the advantages of maintaining sustained protein release over time whilst simultaneously protecting the biopharmaceutical from degradation. Particle samples produced by ultrasonic atomization were studied in order to determine a feed stock capable of producing protein loaded poly-ε-caprolactone (PCL) particles suitable for nasal delivery (i.e., less than 20 μm). A 40 kHz atomization system was used with a 6 mm full wave atomization probe. The effect of solids percent, feed flow rate, volumetric ratio of the polymer stock to the protein stock, and protein concentration in the protein stock on particle size characteristics were determined. It was shown that feed stocks containing 100 parts of 0.5 or 1.0% w/v PCL in acetone with one part 100 mg ml -1 BSA and 15 mg ml -1 PVA produced particles with a mass moment diameter (D[4,3]) of 13.17 μm and 9.10 μm, respectively in addition to displaying high protein encapsulation efficiencies of 93 and 95%, respectively. The biodegradable PCL particles were shown to be able to deliver encapsulated protein in vitro under physiological conditions.

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The maturing of the biotechnology industry and a focus on productivity has seen a shift from discovery science to small-scale bench-top research to higher productivity, large scale production. Health companies are aggressively expanding their biopharmaceutical interests, an expansion which is facilitated by biochemical and bioprocess engineering. An area of continuous growth is vaccines. Vaccination will be a key intervention in the case of an influenza pandemic. The global manufacturing capacity for fast turn around vaccines is currently woefully inadequate at around 300 million shots. As the prevention of epidemics requires > 80 % vaccination, in theory the world should currently be aiming for the ability to produce around 5.3 billion vaccines. Presented is a production method for the creation of a fast turn around DNA vaccine. A DNA vaccine could have a production time scale of as little as two weeks. This process has been harnessed into a pilot scale production system for the creation of a pre-clinical grade malaria vaccine in a collaborative project with the Coppel Lab, Department of Microbiology, Monash University. In particular, improvements to the fermentation, chromatography and delivery stages will be discussed. Consideration will then be given as to how the fermentation stage affects the mid and downstream processing stages.

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We show that the cluster ion concentration (CIC) in the atmosphere is significantly suppressed during events that involve rapid increases in particle number concentration (PNC). Using a neutral cluster and air ion spectrometer, we investigated changes in CIC during three types of particle enhancement processes – new particle formation, a bushfire episode and an intense pyrotechnic display. In all three cases, the total CIC decreased with increasing PNC, with the rate of decrease being greater for negative CIC than positive. We attribute this to the greater mobility, and hence the higher attachment coefficient, of negative ions over positive ions in the air. During the pyrotechnic display, the rapid increase in PNC was sufficient to reduce the CIC of both polarities to zero. At the height of the display, the negative CIC stayed at zero for a full 10 min. Although the PNCs were not significantly different, the CIC during new particle formation did not decrease as much as during the bushfire episode and the pyrotechnic display. We suggest that the rate of increase of PNC, together with particle size, also play important roles in suppressing CIC in the atmosphere.

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As negative employee attitudes towards alcohol and other drug (AOD) policies may have serious consequences for organizations, the present study examined demographic and attitudinal dimensions leading to employees’ perceptions of AOD policy effectiveness. Survey responses were obtained from 147 employees in an Australian agricultural organization. Three dimensions of attitudes towards AOD policies were examined: knowledge of policy features, attitudes towards testing, and preventative measures such as job design and organizational involvement in community health. Demographic differences were identified, with males and blue-collar employees reporting significantly more negative attitudes towards the AOD policy. Attitude dimensions were stronger predictors of perceptions of policy effectiveness than demographics, and the strongest predictor was preventative measures. This suggests that organizations should do more than design adequate and fair AOD policies, and take a more holistic approach to AOD impairment by engaging in workplace design to reduce AOD use and promote a consistent health message to employees and the community.

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The study sought to explore the initial impact of the ACT's implementation of roadside oral fluid drug screening program. The results suggest that a number of individuals reported intentions to drug drive in the future. The classical deterrence theory variables of certainty of apprehension, severity and swiftness of sanctions were not predictive of intentions to drug drive in the future. In contrast, having avoided apprehension and having known of others that have avoided apprehension were predictive of intentions to drug drive in the future. Increasing perceptions of the certainty of apprehension, increased testing frequency, and increased awareness of the oral fluid drug screening program could potentially lead to reductions of drug driving and result in safer road environment for all ACT community members.

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The New South Wales (NSW) Centre for Road Safety (CRS) called for research services to conduct a review of international policy and practice to address drug-driving. The project sought to provide Transport for NSW (TfNSW) with a comprehensive review of current and emerging international practices in this area1. This report is submitted by the Centre for Accident Research and Road Safety – Queensland (CARRS-Q)...

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Alcohol-related mortality and morbidity represents a substantial financial burden on communities across the world. Adolescence and young adulthood is a peak period for heavy episodic alcohol consumption, with over a third of all people aged 14-19 years having been at risk of acute alcoholrelated harm at least once in the previous 12 months (Australian Institute of Health and Welfare [AIHW], 2011). Excessive alcohol consumption has long been seen as a male problem; however, a gradual shift towards a social acceptance of female drunkenness has narrowed the gap in drinking quantity and style between men and women (Grucza, Bucholz, Rice, & Bierut, 2008). The presented data point to the vulnerability of women to the consequences of acute alcohol intoxication and indicate that alcohol-related offending by women is on the rise. Taken together, these findings reveal that alcohol-related harms and aggression for young women are becoming more prevalent and problematic. This report addressed these issues from a policing perspective...