Influence of Liposomes’ and Lipoplexes’ Physicochemical Characteristics on Their Uptake Rate and Mechanisms by the Placenta

Pregnant women are still considered as drug orphans. Developing new medications for pregnancy complications is an urgent need. Nanomedicines seem to be a promising approach to control the biodistribution of drugs to ensure both the mother’s and the fetus’ safety. Understanding the interaction between nanoparticles and the placental barrier is a key factor to the success of the development of nanomedicines for pregnant women. In this study, we evaluated the behavior of fluorescent PEGylated liposomes and lipoplexes in human placental tissue using in vitro and ex vivo models, BeWo cell culture and suspended villous placental explants, respectively. Fluorescent based analytical tools such as Fluorescence activated cells sorting (FACS), confocal microscopy and HPLC coupled to fluorescence detection were used to assess liposomes penetration and their endocytosis mechanisms in the placenta. First, no influence of the PEGylation density was observed on the cellular internalization of liposomal formulations using both models. The comparison between neutral and cationic liposomes exhibits a significant higher internalization of the cationic formulation compared to the neutral ones. In addition, the HPLC quantification of the fluorescent liposomes in human villous explants demonstrated an increase of cationic liposomes uptake with increasing incubation concentrations. Similar uptake of cationic liposomes and lipoplexes, containing the same cationic lipid, the DMAPAP but with an overall neutral surface charge, was observed and evidenced the higher effect of composition than charge surface on trophoblast penetration. Moreover, both cationic liposomes and lipoplexes exhibited an endocytosis mechanism of internalization via pathways implicating dynamin. These data highlight the key role of the liposome’s lipid composition and the possibility to modulate their internalization in the placenta by adjusting their design.     

Modelling the long-term feed-to-fillet transfer of leuco crystal violet and leuco malachite green in Atlantic salmon (Salmo salar)

Leuco crystal violet (LCV) and leuco malachite green (LMG) are the main metabolites of two dyes that are forbidden for use in food production, but can be present at low background concentration in novel Atlantic salmon feed ingredients such as processed animal proteins (animal by-product [ABP]). In this study, the potential transfer of dietary LCV or LMG to the fillet of farmed Atlantic salmon was investigated. The uptake and elimination rate kinetics were determined in seawater-adapted Atlantic salmon (initial weight 587 ± 148 g) fed two levels of either LCV- or LMG-enriched diets (~500 and 4000 µg kg^?1, respectively) for 40 days, followed by a 90-day depuration period with feeding on control diets (<0.15 μg kg^?1 LCV and LMG). A three-compartmental model was developed, based on a fillet fat, fillet muscle and a central body compartment comprising all other tissues. Model calibrations showed a good fit with measured values during overall uptake and elimination period; however, the model poorly predicted the short-term (days) peak measured values at the end of the exposure period. The model was used to simulate the long-term (>16 months) LCV and LMG feed-to-fillet transfer in Atlantic salmon under realistic farming conditions such as the seasonal fluctuations in feed intake, growth and fillet fat deposition. The model predictions gave highest expected LCV and LMG fillet concentrations of approximately 0.12 and 0.45 μg kg^?1, depending on the dietary levels of ABP and background level of LCV and LMG contamination. These levels are under the reference point for action of 2 µg kg^?1 for the sum of MG and LMG that EFSA assessed as adequate to protect public health. However, for LCV, the predicted highest levels exceed the analytical decision limit (CCα) of 0.15 µg kg^?1 for the method used in this paper.     

Prevalence of Salmonella in grade A whole shell eggs in the island of Ireland

Following the emergence of Salmonella Enteritidis as a widespread contaminant of eggs and the role of eggs in the transmission of human salmonellosis, control measures were introduced to curb the spread of infection. Two approaches to Salmonella control are currently used by egg producers in Ireland, because Northern Ireland producers, like those in the rest of the United Kingdom, widely adopted a vaccination regime, whereas the Republic of Ireland does not permit vaccination but introduced controls based on routine monitoring for specific Salmonella serovars and subsequent culling of infected flocks. To compare the efficacy of these two approaches and determine the prevalence of salmonellae in eggs produced for retail sale in the island of Ireland, a major survey of approximately 30,000 grade A eggs was undertaken. Egg shells and contents were analyzed separately for salmonellae by procedures based on International Organization for Standardization methodology. The survey yielded only two positive samples, with Salmonella Infantis and Salmonella Montevideo isolated from shells; no egg contents yielded salmonellae. There was no statistically significant difference in the prevalence of salmonellae between eggs produced in Northern Ireland and those from the Republic of Ireland; hence, both regimes appeared to be equally effective in controlling salmonellae. The prevalence was also significantly lower than that found in a recent major United Kingdom survey. Hence, shell eggs produced in the island of Ireland are unlikely to be a source of human salmonellosis.     

An evaluation of process specific information resources,aimed at hazard analysis,in Small and Medium Enterprises in food manufacturing

Food borne illness continues to be a major global concern, with approximately 76 million cases in the US and 70,000 in the UK annually. The adoption of a food safety management system based upon Codex HACCP principles became a legal requirement in the UK on January 1st 2006 but some companies are inexperienced and fail to implement it correctly. Barriers to HACCP include time, money and expertise, particularly for SMEs and microbusinesses. Lack of expertise is a particular problem when constructing the hazard analysis component of HACCP. A sector specific information resource, using simple language with no technical terms or jargon, was developed to assist SMEs with hazard analysis. One hundred and twenty three SME food manufacturers were recruited and intervention and control groups were assigned, with the intervention group receiving the resource. Evaluation visits were performed after four months. Each company was assessed against a specific tool that determined knowledge, behavior and attitude to food safety. The resource was well received but there was no significant improvement in knowledge, behavior or attitude when comparing the intervention and control group scores. Significant differences in the behavior of SMEs and microbusinesses were evident with SMEs scoring higher in all sections of the resource than the microbusinesses. SMEs also had a significantly higher total knowledge score than microbusinesses but there were no significant differences in attitudes. It is apparent action must be taken to assist SMEs with hazard analysis and full HACCP implementation, but provision of a single resource without additional support is not enough.     

Effectiveness of speed indicator devices: An observational study in South London

Speed indicator devices (SIDs) are vehicle activated signs displaying the real-time speeds of passing vehicles. They are part of the array of road safety measures for managing speeds on local authority roads in the United Kingdom. This paper documents an evaluation of the effectiveness of SIDs that was carried out in South London in 2008. SIDs were installed at 10 sites in South London for periods of between one and three weeks. The overall effect of the SIDs being installed was a reduction in vehicle speeds of 1.4 mph and a significant reduction in the proportion of vehicles exceeding the speed limit.The research also investigated the distance over which the SIDs are effective and the effect on vehicle speeds once the SID is removed. The results showed that a speed reduction occurred over a distance of up to 400 m and that once the SID is removed then, in general, the mean vehicle speeds returned to pre-SID levels by the end of the first week.     

Inhibition of angiotensin converting enzyme (ACE) activity by polyphenols from tea (Camellia sinensis) and links to processing method

The focus of this study was to investigate Angiotensin Converting Enzyme (ACE) inhibiting activity across 34 teas (Camellia sinensis) produced by 5 different processing methods including green (GT), oolong (OT), white (WT), black (BT) and dark (DT) teas. In vitro ACE inhibitory activity was affected by the tea processing method with IC(50) values for ACE inhibition: green < oolong < white < black < dark teas. Substrate-dependence of the reaction kinetics was studied for GT and BT polyphenolic size fractions either < or > 3 kDa and also Green Tea Polyphenolic Isolate (GTPI), and revealed that enzyme velocity curves fitted allosteric, not Michaelis-Menten, relationships. Inhibition was weakly dependent on substrate concentration for GT fraction >3 kDa and independent of substrate concentration for all other GT and BT size fractions and GTPI. Furthermore, evidence for direct inactivation of ACE by GTPI was demonstrated. Overall, the results suggest that tea polyphenolics exert a mixed mode of in vitro inhibition of ACE, mostly of a kinetically uncompetitive type. The results are discussed in the context of in vivo and epidemiological evidence for regulation of blood pressure by tea consumption.     

Entrance effects in solar storage tanks

A theoretical and experimental analysis of water jets entering a solar storage tank is performed. CFD calculations of three inlet designs with different inlet flow rates were carried out to illustrate the varying behaviour of the thermal conditions in a solar store. The results showed the impact of the inlet design on the flow patterns in the tank and thus how the energy quality in a hot water tank is reduced with a poor inlet design. The numerical investigations were followed by experiments. A test solar store, similar to the store investigated by numerical modelling was constructed with cylindrical transparent walls so that the flow structures due to the inlet jets could be visualized. With the three inlets, nine draw-off tests with different inlet flow rates were carried out and the temperature stratification in the tank was measured during the draw-offs. The experimental results were used in an analysis using the first and second law of thermodynamics. The results showed how the entropy changes and the exergy changes in the storage during the draw-offs influenced by the Richardson number, the volume draw-off and the initial tank conditions.     

Using Symmetries in the Index Calculus for Elliptic Curves Discrete Logarithm

In 2004, an algorithm is introduced to solve the DLP for elliptic curves defined over a non-prime finite field \(\mathbb{F}_{q^{n}}\) . One of the main steps of this algorithm requires decomposing points of the curve \(E(\mathbb{F}_{q^{n}})\) with respect to a factor base, this problem is denoted PDP. In this paper, we will apply this algorithm to the case of Edwards curves, the well-known family of elliptic curves that allow faster arithmetic as shown by Bernstein and Lange. More precisely, we show how to take advantage of some symmetries of twisted Edwards and twisted Jacobi intersections curves to gain an exponential factor 2 ^ω(n?1) to solve the corresponding PDP where ω is the exponent in the complexity of multiplying two dense matrices. Practical experiments supporting the theoretical result are also given. For instance, the complexity of solving the ECDLP for twisted Edwards curves defined over \(\mathbb{F}_{q^{5}}\) , with q≈2⁶⁴, is supposed to be ～ 2¹⁶⁰ operations in \(E(\mathbb{F}_{q^{5}})\) using generic algorithms compared to 2¹³⁰ operations (multiplications of two 32-bits words) with our method. For these parameters the PDP is intractable with the original algorithm. The main tool to achieve these results relies on the use of the symmetries and the quasi-homogeneous structure induced by these symmetries during the polynomial system solving step. Also, we use a recent work on a new algorithm for the change of ordering of a Gröbner basis which provides a better heuristic complexity of the total solving process.