Manipulation of the surface pegylation in combination with reduced vesicle size of cationic liposomal adjuvants modifies their clearance kinetics from the injection site, and the rate and type of T cell response

The mechanism behind the immunostimulatory effect of the cationic liposomal vaccine adjuvant dimethyldioctadecylammonium and trehalose 6,6′- dibehenate (DDA:TDB) has been linked to the ability of these cationic vesicles to promote a depot after administration, with the liposomal adjuvant and the antigen both being retained at the injection site. This can be attributed to their cationic nature, since reduction in vesicle size does not influence their distribution profile yet neutral or anionic liposomes have more rapid clearance rates. Therefore the aim of this study was to investigate the impact of a combination of reduced vesicle size and surface pegylation on the biodistribution and adjuvanticity of the formulations, in a bid to further manipulate the pharmacokinetic profiles of these adjuvants. From the biodistribution studies, it was found that with small unilamellar vesicles (SUVs), 10% PEGylation of the formulation could influence liposome retention at the injection site after 4 days, whilst higher levels (25 mol%) of PEG blocked the formation of a depot and promote clearance to the draining lymph nodes. Interestingly, whilst the use of 10% PEG in the small unilamellar vesicles did not block the formation of a depot at the site of injection, it did result in earlier antibody response rates and switch the type of T cell responses from a Th1 to a Th2 bias suggesting that the presence of PEG in the formulation not only control the biodistribution of the vaccine, but also results in different types of interactions with innate immune cells. © 2012 Elsevier B.V.

Rapid prototyping applied to a new development in moulds for rotational moulding

Rotational moulding is a unique manufacturing technique for the production of hollow plastic parts manufacturing. Moulds for rotational moulding are generally not standardized, such as for injection moulding, so each new mould must be completely manufactured except for a few ancillary parts like screws or clamps. The aim of this work has been to adapt and apply the advantages of rapid prototyping and electroforming technologies to try to achieve an innovative mould design for rotational moulding. The new innovative design integrates an electroformed shell, manufactured starting from a rapid prototyping mandrel, with different designed standard aluminium tools. The shell holder enables mould assembly with high precision a shell in a few minutes with the advantage of changing different geometries of the electroformed shells in the same tool. The overall mould cost is significantly decreased because it is only necessary to manufacture one or two shells each time, however the rest of the elements of the mould are standard and usable for an infinite number of shells, depending on size. The rapid prototyping of the mandrel enables a significant decrease the global cost of mould manufacturing as well. © 2008 Taylor & Francis Group.

Agonistic interactions elicit rapid changes in brain nonapeptide levels in zebrafish

The teleost fish nonapeptides, arginine vasotocin (AVT) and isotocin (IT), have been implicated in the regulation of social behavior. These peptides are expected to be involved in acute and transient changes in social context, in order to be efficient in modulating the expression of social behavior according to changes in the social environment. Here we tested the hypothesis that short-term social interactions are related to changes in the level of both nonapeptides across different brain regions. For this purpose we exposed male zebrafish to two types of social interactions: (1) real opponent interactions, from which a Winner and a Loser emerged; and (2) mirror-elicited interactions, that produced individuals that did not experience a change in social status despite expressing similar levels of aggressive behavior to those of participants in real-opponent fights. Non-interacting individuals were used as a reference group. Each social phenotype (i.e. Winners, Losers, Mirror-fighters) presented a specific brain profile of nonapeptides when compared to the reference group. Moreover, the comparison between the different social phenotypes allowed to address the specific aspects of the interaction (e.g. assessment of opponent aggressive behavior vs. self-assessment of expressed aggressive behavior) that are linked with neuropeptide responses. Overall, agonistic interactions seem to be more associated with the changes in brain AVT than IT, which highlights the preferential role of AVT in the regulation of aggressive behavior already described for other species.

Flow-injection spectrophotometric determination of dipyrone in pharmaceutical formulations using ammonium molybdate as chromogenic reagent

A simple and rapid flow-injection spectrophotometric method is reported for the determination of dipyrone in pharmaceutical formulations. The method is based on the reaction of dipyrone with ammonium molybdate in acidic medium to produce blue molybdenum, which was detected spectrophotometrically at 620 nm. The analyte was determined in a single-line flow system. The calibration curve obtained was linear in the range of 5x10(-4) to 8x10(-3) mol L-1 for dipyrone concentration and the precision ( s r =1.7%) was satisfactory. The method proved to be selective and adequately sensitive. Application of the method to the analysis of pharmaceutical samples resulted in excellent accuracy; the percent mean recoveries were in the range 95.3%-101% and relative errors less than 5.0% for five pharmaceutical formulations were found.

Patient physiological status during emergency care and rapid response team or cardiac arrest team activation during early hospital admission

OBJECTIVES: The objective of this study was to examine the relationship between rapid response team (RRT) or cardiac arrest team (CAT) activation within 72 h of emergency admission and (i) physiological status in the emergency department (ED) and (ii) risk for ICU admission and in-hospital mortality.

METHODS: A retrospective matched cohort study was conducted in three hospitals in Melbourne, Australia. The exposed cohort (n=660) included randomly selected adults admitted to the medical or surgical ward through the ED who had RRT or CAT activation within 72 h of admission. Unexposed matched controls (n=1320) did not have RRT or CAT activation.

RESULTS: The exposed cohort was more likely to have physiological abnormalities fulfilling hospital RRT activation criteria during ED care (36.7 vs. 23.8%, P<0.001). After adjusting for confounders, tachypnoea (adjusted odds ratio=1.92, 95% confidence interval: 1.38-2.67) or hypotension (AOR=1.43, 95% confidence interval: 1.00-2.03), fulfilling RRT activation criteria during ED care, was associated with RRT or CAT activation within 72 h of admission. The exposed cohort had more in-hospital deaths (16.5 vs. 3.6%, P<0.001), more unexpected in-hospital deaths (2.05 vs. 0.2%, P<0.001), more ICU admissions (11.8 vs. 0.7%, P<0.001) and longer lengths of hospital stay (median=8 vs. 5 days, P<0.001).

CONCLUSION: CAT/RRT activations within 72 h of emergency admission are associated with higher mortality and increased length of stay. Factors associated with CAT/RRT activation in the wards are often identifiable when patients are in the ED. Further studies are required to determine whether early identification and intervention in patients at risk for RRT or CAT activation can improve their eventual outcomes.

Study on microwave dielectric properties of epoxy resin mixtures used for rapid product development

This paper presents a preliminary study on the dielectric properties and curing of three different types of epoxy resins mixed at various stichiometric mixture of hardener, flydust and aluminium powder under microwave energy. In this work, the curing process of thin layers of epoxy resins using microwave radiation was investigated as an alternative technique that can be implemented to develop a new rapid product development technique. In this study it was observed that the curing time and temperature were a function of the percentage of hardener and fillers presence in the epoxy resins. Initially dielectric properties of epoxy resins with hardener were measured which was directly correlated to the curing process in order to understand the properties of cured specimen. Tensile tests were conducted on the three different types of epoxy resins with hardener and fillers. Modifying dielectric properties of the mixtures a significant decrease in curing time was observed. In order to study the microstructural changes of cured specimen the morphology of the fracture surface was carried out by using scanning electron microscopy.