Improved Controlled Release and Brain Penetration of the Small Molecule S14 Using PLGA Nanoparticles

Phosphodiesterase 7 (PDE7) is an enzyme responsible for the degradation of cyclic adenosine monophosphate (cAMP), an important cellular messenger. PDE7’s role in neurotransmission, expression profile in the brain and the druggability of other phosphodiesterases have motivated the search for potent inhibitors to treat neurodegenerative and inflammatory diseases. Different heterocyclic compounds have been described over the years; among them, phenyl-2-thioxo-(1H)-quinazolin-4-one, called S14, has shown very promising results in different in vitro and in vivo studies. Recently, polymeric nanoparticles have been used as new formulations to target specific organs and produce controlled release of certain drugs. In this work, we describe poly(lactic-co-glycolic acid) (PLGA)-based polymeric nanoparticles loaded with S14. Their preparation, optimization, characterization and in vivo drug release profile are here presented as an effort to improve pharmacokinetic properties of this interesting PDE7 inhibitor.     

Detection of beeswax adulterations using concentration guide‐values

The concentrations of 102 chemical compounds (saturated and unsaturated hydrocarbons, palmitates, total and free acids, total hydroxyacids, total and free alcohols, acidic monoesters and monoesterified 1,2,3‐propanetriols) have been determined by GC/FID on white and yellow comb beeswax of Apis mellifera from different regions of Spain. Guide‐value ranges are proposed for its characterization and to discriminate adulterated foundation beeswax sheets. The concentrations of many compounds resulted to be statistically different for white and yellow beeswaxes, while the observation of concentrations out of normal in some marketed foundation beeswax sheets suggested their adulteration. However, the measurement of anomalous concentrations in foundation beeswax sheets did not imply necessarily their rejection by the bees.     

Simultaneous determination of neonicotinoid insecticides in sunflower-treated seeds (hull and kernel) by LC-MS/MS

A validated analytical method to determine seven neonicotinoids (dinotefuran, nitenpyram, thiamethoxam, clothianidin, imidacloprid, acetamiprid and thiacloprid) in sunflower seeds (hull and kernel) using HPLC coupled to electrospray ionisation mass spectrometry (ESI-MS) is presented. Sample clean-up based on a solid–liquid extraction, and the removal of lipid fraction, in the case of kernels, is proposed and optimised. Low limits of detection and quantification were obtained, ranging from 0.3 × 10^–3 to 1.2 × 10^–3 µg g^–1 and from 1.0 × 10^–3 to 4.0 × 10^–3 µg g^–1, with good precision, and recovery values ranged from 90% to 104% for hulls and kernels. The method was applied for the analysis of five thiamethoxam-dressed sunflower seeds and four non-treated seeds, where, besides thiamethoxam, residues of the other neonicotinoid, clothianidin, were also detected and confirmed via tandem mass spectrometry (LC-ESI-MS/MS). Finally, the presence of residues of thiamethoxam and clothianidin in collected sunflower seeds (hulls) coming from coated seeds confirmed the translocation of these neonicotinoids through the plant up to these seeds.     

Bactericidal effect of saffron (Crocus sativus L.) on Salmonella enterica during storage

The presence of pathogenic bacteria in spices represents a public health risk as a possible cause of food contamination. Salmonella has been found in several spices and it has been involved in food-borne outbreaks, but this bacterium has not been reported as a contaminant of saffron (Crocus sativus L.). We examined a possible antibacterial effect of saffron using samples from Iran, Greece and Spain which were artificially contaminated with clinical isolates belonging to five different serovars of Salmonella. We detected a loss of viability during the room-temperature storage of the saffron samples, with bacteria being undetectable at day 16 except in the case of the DT104 strain of the Typhimurium serovar, in all of the samples, and of the Hadar serovar in the Iranian sample, both of which gave negative culture at day 32. The laboratory strain LT2 of the Typhimurium serovar was undetectable at day 4. To gain an insight into the basis for this bactericidal effect, we measured the inhibitory and bactericidal concentrations of safranal and crocin, the main compounds responsible for the flavouring and colouring capabilities of saffron. They were in the order of 8–16 mg/mL and 64–128 mg/mL for safranal and crocin, respectively. These data suggest that these compounds, and probably their chemical relatives, are involved in the antibacterial activity of saffron, and that this effect can significantly reduce the risk of food contamination with Salmonella by this spice.     

Solid-phase microextraction applied to the analysis of pesticide residues in honey using gas chromatography with electron-capture detection

The possibilities of using solid-phase microextraction to determine residues of pesticides in honey have been examined. For this purpose, three types of fiber have been assayed: polyacrylate of 85 microns thickness, and polydimethylsiloxane of 7 and 100 microns thickness. They have been applied to the extraction of 21 pesticides of different chemical families. The effects of the temperature, extraction time and ionic strength on the microextraction have been studied, proposing the most adequate for each fiber. Under optimized conditions, precision, intervals of linearity and detection limits were evaluated.     

Pharmacokinetics of intravitreal vancomycin in normal and infected rabbit eyes

The purpose of this study was to determine the pharmacokinetics governing the distribution and elimination of intravitreally injected vancomycin in normal and infected rabbit eyes. Two groups each of 36 pigmented animals were used. Group 1 served as control. In Group 2, experimental endophthalmitis was induced in the right vitreous by inoculation with Staphylococcus aureus. Once endophthalmitis developed, a vancomycin solution was injected. Four animals from each group were killed at nine time points post-injection, the vitreous and aqueous were removed, and blood samples were taken for HPLC analysis. Data analysis was performed using the RSTRIP program. The half-lives were 69 hours in normal vitreous and 14.53 hours in infected vitreous. Therapeutic drug levels were present in the vitreous 84 hours post-injection in all eyes; they were detected from 2 to 48 hours in normal aqueous but at lower levels in the infected ones. Kv and Ca/Cv ratios suggested that the primary route of elimination was across the retina and the anterior chamber in normal eyes, and via the retina in infected eyes. Results indicate that pharmacokinetic parameters change in pathological conditions, which may help establish better treatment guidelines for endophthalmitis.     

Load balancing in a heterogeneous world: CPU-Xeon Phi co-execution of data-parallel kernels

Heterogeneous systems composed by a CPU and a set of different hardware accelerators are very compelling thanks to their excellent performance and energy consumption features. One of the most important problems of those systems is the workload distribution among their devices. This paper describes an extension of the Maat library to allow the co-execution of a data-parallel OpenCL kernel on a heterogeneous system composed by a CPU and an Intel Xeon Phi. Maat provides an abstract view of the heterogeneous system as well as set of load balancing algorithms to squeeze the performance out of the node. It automatically performs the data partition and distribution among the devices, generates the kernels and efficiently merges the partial outputs together. Experimental results show that this approach always outperforms the baseline with only a Xeon Phi, giving excellent performance and energy efficiency. Furthermore, it is essential to select the right load balancing algorithm because it has a huge impact in the system performance and energy consumption.

     

Effect of Temperature and Light Exposure on the Detection of Total Intact Glucosinolate Content by LC-ESI-MS in Broccoli Leaves

Total intact glucosinolate content in broccoli leaf extracts (Ramoso calabrese cultivar) has been determined by liquid chromatography coupled to tandem mass spectrometry with the aim of detecting potential differences in this value due to the effects of the drying temperature or the working and storage conditions (temperature and light exposure). Those broccoli leaf extracts were obtained with two different sample treatments based on heating the sample (microwave or oven), and using boiling water as extraction solvent. Significant differences were observed in the total intact glucosinolate content depending on the drying temperature and light exposure under typical working conditions. Meanwhile, those differences were less remarkable when the extracts were stored at low temperature and protected from light exposure.     

Optimized Formation,Extraction, and Determination of Sulforaphane in Broccoli by Liquid Chromatography with Diode Array Detection

A new method has been developed to determine sulforaphane in broccoli florets, stems, and leaves using liquid chromatography coupled to diode array detection. The hydrolysis reaction, required to convert glucoraphanin to its breakdown product, sulforaphane, and the extraction procedure, based on solvent extraction with methyl t-butyl ether followed by solid phase extraction with silica cartridges, were optimized for the three broccoli matrices; the resulting recovery values ranged from 92 to 102 % in all cases. A fast separation was performed on a C₁₈ analytical column with a mobile phase composed of ammonium formate (20 mM) in water and acetonitrile (55:45, v/v) in isocratic elution mode. This method was fully validated and was found to be selective, linear from 2.5 to 800 mg/kg, and precise (percent relative standard deviation values below 5 %). Moreover, the limits of detection and quantification were 0.8 and 2.5 mg/kg, respectively. Finally, the proposed method has been applied to the analysis of sulforaphane in broccoli samples of two different cultivars (Parthenon and Marathon).