Genetic control of cadmium tolerance in Drosophila melanogaster.

Files from a transgenic line of Drosophila melanogaster with two copies of the metallothionein allele Mtn3 were more tolerant to cadmium than strains with only one copy of the gene. However, flies with the Mtn3 allele were as tolerant as flies with the Mtn3 allele, despite the level of expression of Mtn3 being three times higher than of Mtn3. We propose that the substitution of Lys-40 (in Mtn3) for Glu-40 (in Mtn1) accounts for a reduction in binding affinity of Mtn1, which offsets the increased expression levels

Local structural studies of Ba1−x_{1-x}Kx_xFe2_2As2_2 using atomic pair distribution function analysis

Systematic local structural studies of Ba$_{1-x}$K$_x$Fe$_2$As$_2$ system are undertaken at room temperature using atomic pair distribution function (PDF) analysis. The local structure of the Ba$_{1-x}$K$_x$Fe$_2$As$_2$ is found to be well described by the long-range structure extracted from the diffraction experiments, but with anisotropic atomic vibrations of the constituent atoms ($U_{11}$ = $U_{22} \ne U_{33}$). The crystal unit cell parameters, the FeAs$_4$ tetrahedral angle and the pnictogen height above the Fe-plane are seen to show systematic evolution with K doping, underlining the importance of the structural changes, in addition to the charge doping, in determining the properties of Ba$_{1-x}$K$_x$Fe$_2$As$_2$

Gastroresistant capsular device prepared by injection molding

In the present work, the possibility of manufacturing by injection molding (IM) a gastro-resistant capsular device based on hydroxypropyl methyl cellulose acetate succinate (HPMCAS) was investigated. By performing as an enteric soluble container, such a device may provide a basis for the development of advantageous alternatives to coated dosage forms. Preliminarily, the processability of the selected thermoplastic polymer was evaluated, and the need for a plasticizer (polyethylene glycol 1500) in order to counterbalance the glassy nature of the molded items was assessed. However, some critical issues related to the physical/mechanical stability (shrinkage and warpage) and opening time of the device after the pH change were highlighted. Accordingly, an in-depth formulation study was carried out taking into account differing release modifiers potentially useful for enhancing the dissolution/disintegration rate of the capsular device at intestinal pH values. Capsule prototypes with thickness of 600 and 900 \u3bcm containing Kollicoat\uae IR and/or Explotab\uae CLV could be manufactured, and a promising performance was achieved with appropriate gastric resistance in pH 1.2 medium and break-up in pH 6.8 within 1 h. These results would support the design of a dedicated mold for the development of a scalable manufacturing process

Erodible drug delivery systems for time-controlled release into the gastrointestinal tract

In oral delivery, lag phases of programmable duration that precede drug release may be advantageous in a number of instances, e.g. to meet chronotherapeutic needs or pursue colonic delivery. Systems that give rise to characteristic lag phases in their release profiles, i.e. intended for time-controlled release, are generally composed of a drug-containing core and a functional polymeric barrier. According to the nature of the polymer, the latter may delay the onset of drug release by acting as a rupturable, permeable or erodible boundary layer. Erodible systems are mostly based on water swellable polymers, such as hydrophilic cellulose ethers, and the release of the incorporated drug is deferred through the progressive hydration and erosion of the polymeric barrier upon contact with aqueous fluids. The extent of delay depends on the employed polymer, particularly on its viscosity grade, and on the thickness of the layer applied. The manufacturing technique may also have an impact on the performance of such systems. Double-compression and spray-coating have mainly been used, resulting in differing technical issues and release outcomes. In this article, an update on delivery systems based on erodible polymer barriers (coatings, shells) for time-controlled release is presented

Non-uniform drug distribution matrix system (NUDDMat) for zero-order release of drugs with different solubility

A decrease in the drug release rate over time typically affects the performance of hydrophilic matrices for oral prolonged release. To address such an issue, a Non-Uniform Drug Distribution Matrix (NUDDMat) based on hypromellose was proposed and demonstrated to yield zero-order release. The system consisted of 5 overlaid layers, applied by powder layering, having drug concentration decreasing from the inside towards the outside of the matrix according to a descending staircase function. In the present study, manufacturing and performance of the described delivery platform were evaluated using drug tracers having different water solubility. Lansoprazole, acetaminophen and losartan potassium were selected as slightly (SST), moderately (MST) and highly (HST) soluble tracers. By halving the thickness of the external layer, which contained no drug, linear release of HST and MST was obtained. The release behavior of the NUDDMat system loaded with a drug having pH-independent solubility was shown to be consistent in pH 1.2, 4.5 and 6.8 media. Based on these results, feasibility of the NUDDMat platform by powder layering was demonstrated using drugs having different physico-technological characteristics. Moreover, its ability to generate zero-order release was proved in the case of drugs with water solubility in a relatively wide range

Quantification of asbestos and other mineral phase burden in necroscopic human lung tissues with a new method

Background: A large amount of studies on asbestos exposure reconstruction have been so far conducted digesting the lung tissues with appropriate reagents, separating the powder from the digestion liquid by filtration and analysing the residue by optical or electron microscopy. This analytical approach has good sensitivity but is not yet well standardized, the investigated portion is not representative of the bulk sample, the results are often characterized by lack of reproducibility and repeatability. Moreover, the numeric quantification of asbestos requires a time-consuming particle by particle analysis. Aim: to develop a new method for the complete quantitative characterization of asbestos and other mineral phases in human lung tissue. Methods: The new method is based on sodium hypochlorite digestion, separation and XRPD analysis. The XRPD approach needs moderate lung tissue amounts (at least 20 g of wet tissue), but allows to conduct a complete quantitative characterization of each crystalline phase in the sample giving bulk-representative results with good reproducibility, accuracy and precision. The detection limit of conventional XRPD was considerably improved by a novel instrumental setting and weight concentrations can be obtained, giving additional information to numeric ones, preferable in clinical and pathogenetic studies but probably not for the exposure reconstruction. Results: Among the analysed autoptic lung tissues, ten samples belonged to subjects occupationally exposed to asbestos and six were collected from urban area controls. Asbestos phases were detected in none of controls and in 5 of 10 occupationally exposed subjects (those with highest exposure history) indicating that this method is suitable for the reconstruction of medium and high asbestos exposures. It has been furthermore confirmed the mineral association found in previous studies: mainly composed by quartz, talc, clay minerals, micas, Fe-Al-Ti oxides and bio-minerals such Ca-phosphates, carbonates and oxalates