Synthesis and characterization of P(MMA-AA) copolymers for targeted oral drug delivery

This paper describes the development of pH-sensitive poly(methyl methacrylate-acrylic acid) copolymers for the enteric coating of pharmaceutical products for oral administration. To obtain the dissolution at the desired pH level, different pH-sensitive polymers are available on the market. Usually, for each desired dissolution pH, an ad hoc polymer is designed. Thus, different dissolution pH values could ask for completely different polymers. Instead, the materials proposed in this work are copolymers of the same two monomers, and the different dissolution pH was obtained by changing the volume fraction of the hydrophobic methyl methacrylate monomer to the hydrophilic acrylic acid monomer. Increasing the volumetric percentage of methyl methacrylate causes the polymer to dissolve at increasing pH, until the dissolution does not take place at all, and it is replaced by a slow swelling phenomenon. The copolymers obtained were characterized by differential scanning calorimetry, in order to evaluate their glass transition temperature, and these latter were related to %MMA. The molecular weights of the pure polymers (PAA, PMMA) were measured by intrinsic viscosity, to further validate the glass transition temperatures observed. The dissolution of the copolymers was carefully tested in buffer solutions for a dense set of pH values. A linear relationship between dissolution pH and volumetric percentage of methyl methacrylate was obtained from these measurements. As a result, for any physiological compartment, the copolymer which dissolves at the pH of interest can be easily synthesized.     

Effects of feed water temperature on inorganic fouling of brackish water RO membranes

A bench scale RO process simulator was operated in a batch concentration mode to determine the effects of product water recovery and feed water temperature on flux, rejection, and inorganic fouling by gypsum scale formation for simulated brackish water. As feed water temperature increased, salt rejection and concentration polarization decreased (reducing scale formation potential at a given recovery). However, gypsum crystal nucleation and growth rates increased with temperature. Specifically, at 15 and 25°C gypsum scale formation resulted in slow, steady flux decline at recoveries as low as 10–20%. At these temperatures, many small crystals formed over the entire membrane surface. In contrast, at 35°C flux decline was due to the increasing feed solution osmotic pressure — up to a recovery of about 70%. At this recovery, we observed a sudden, rapid loss of flux and a concomitant spike in feed water turbidity. Relatively few (in number), large crystals formed on the membrane towards the brine outlet of the RO simulator, but the entire membrane surface was covered with “needle-like” crystal fragments. The crystal fragments broke off from growing gypsum rosettes and re-deposited uniformly across the membrane forming a “cake layer” that caused the massive flux decline. These results suggest that high temperature operation of brackish water RO processes could enable higher recovery and lower energy consumption, but operating near the limiting recovery (at elevated temperature) creates an increased risk of a catastrophic fouling event.     

A lithographic approach to determine volume expansion factors during anodization: Using the example of initiation and growth of TiO2-nanotubes

The present work investigates the formation of nanotubes by anodizing titanium at 20 V in glycerol containing either 0.175 M or 0.35 M NH₄F. A photoresist-masking method of thin Ti films allows to use SEM cross-sections to directly obtain information on oxide morphology, layer thickness and metal substrate loss. Therefore not only features of the initial growth stages but also oxide expansion factors can accurately be determined. The expansion factors were found to be 2.4 for the initial formation of a barrier layer, 1.7–1.9 during pore initiation and 2.7–3.1 as the main nanotubes develop. These values (>2.6) suggest substantial contribution to steady state tube growth by a plastic oxide flow mechanism. Combined with RBS efficiency measurements the method presented here allows facile and direct investigation of the mechanism of pore/tube formation.     

Anthropogenic impacts in North Poland over the last 1300 years — A record of Pb, Zn, Cu, Ni and S in an ombrotrophic peat bog

Lead pollution history over Northern Poland was reconstructed for the last ca. 1300 years using the elemental and Pb isotope geochemistry of a dated Polish peat bog. The data show that Polish Pb-Zn ores and coal were the main sources of Pb, other heavy metals and S over Northern Poland up until the industrial revolution. After review of the potential mobility of each element, most of the historical interpretation was based on Pb and Pb isotopes, the other chemical elements (Zn, Cu, Ni, S) being considered secondary indicators of pollution. During the last century, leaded gasoline also contributed to anthropogenic Pb pollution over Poland. Coal and Pb-Zn ores, however, remained important sources of pollution in Eastern European countries during the last 50 years, as demonstrated by a high ²⁰⁶Pb/²⁰⁷Pb ratio (1.153) relative to that of Western Europe (ca. 1.10). The Pb data for the last century were also in good agreement with modelled Pb inventories over Poland and the Baltic region.     

Novel Antitumor L‐Arabinose Derivative of Indolocarbazole with High Affinity to DNA

Novel indolocarbazole derivative 12‐(α‐L ‐arabinopyranosyl)indolo[2,3‐α]pyrrolo[3,4‐c]carbazole‐5,7‐dione (AIC) demonstrated high potency (at submicromolar concentrations) against the NCI panel of human tumor cell lines and transplanted tumors in vivo. In search of tentative targets for AIC, we found that the drug formed high affinity intercalative complexes with d(AT)₂₀, d(GC)₂₀ and calf thymus DNA (binding constants (1.6×10⁶) M ^?1≤K_a≤(3.3×10⁶) M ^?1). The drug intercalated preferentially into GC pairs of the duplex. Importantly, the concentrations at which AIC formed the intercalative complexes with DNA (C≤1 μM ) were identical to the concentrations that triggered p53‐dependent gene reporter transactivation, the replication block, the inhibition of topoisomerase I‐mediated DNA relaxation and death of HCT116 human colon carcinoma cells. We conclude that the formation of high affinity intercalative complexes with DNA is an important factor for anticancer efficacy of AIC.     

New Al2O3:C,Mg crystals for radiophotoluminescent dosimetry and optical imaging

Optical and dosimetric properties of a new radiophotoluminescent material based on aluminum oxide doped with carbon and magnesium (Al2O3:C,Mg) and having aggregate oxygen vacancy defects are presented. The Al2O3:C,Mg crystals are characterized by several new optical absorption and emission bands. It is suggested that the main optical properties of this material are due to the formation of aggregate defects composed of two oxygen vacancies and two Mg-impurity atoms. Radiation-induced optical absorption bands are centered at 335 and 620 nm and produce fluorescent emission at 750 nm with a 75 +/- 5 ns lifetime. The dose measurements are performed by illumination of the Al2O3:C,Mg crystal with 335 nm or 650 nm light and by measuring the intensity of the 750 nm fluorescence. The detector material is insensitive to room light before and after the irradiation and the traps are stable up to 600 degrees C. A dose measurement range between 5 mGy and 200 Gy, suitable for therapeutic radiology applications, was demonstrated. The short luminescent lifetime and nondestructive readout is favorable for imaging applications.     

A new method for determination of transverse isotropic orientation and the associated elastic parameters for intact rock

This paper presents the development of an analytical method to determine the parameters of orientation and deformability of transversely isotropic cylinders of rock using the Council for Scientific Industrial Research (CSIR) triaxial cell under isotropic biaxial loading. The mathematical formulation is based upon the elastic and anisotropic constant transformation presented by Lekhnitskii (in: JJ. Brandstatter (Ed.), Theory of Elasticity of an Anisotropic Elastic Body, Holden-Day Series in Mathematical Physics, Holden Day Inc., San Francisco, 1963, 404p). By using three rosettes with four gages each, the method herein proposed permits the determination of the global tridimensional deformability characteristics of a rock cylinder, using only the local bidimensional deformation measurements provided by the rosette's gages. The new analytical method gives the direction and dip of the isotropy plane together with the magnitude of anisotropic elastic constants for transversely isotropic rocks of Class A (rocks with no visible symmetry planes) and Class B (with visible symmetry planes). No restrictions on the direction of the symmetry planes are imposed. This determination is obtained from strains measured in only one biaxial compression test performed with the CSIR cell on the overcore obtained from in situ stress test.     

Polyurethane Composites Reinforced with Walnut Shell Filler Treated with Perlite,Montmorillonite and Halloysite

In the following study, polyurethane (PUR) composites were modified with 2 wt.% of walnut shell filler modified with selected mineral compounds–perlite, montmorillonite, and halloysite. The impact of modified walnut shell fillers on selected properties of PUR composites, such as rheological properties (dynamic viscosity, foaming behavior), mechanical properties (compressive strength, flexural strength, impact strength), dynamic-mechanical behavior (glass transition temperature, storage modulus), insulation properties (thermal conductivity), thermal characteristic (temperature of thermal decomposition stages), and flame retardant properties (e.g., ignition time, limiting oxygen index, heat peak release) was investigated. Among all modified types of PUR composites, the greatest improvement was observed for PUR composites filled with walnut shell filler functionalized with halloysite. For example, on the addition of such modified walnut shell filler, the compressive strength was enhanced by ~13%, flexural strength by ~12%, and impact strength by ~14%. Due to the functionalization of walnut shell filler with thermally stable flame retardant compounds, such modified PUR composites were characterized by higher temperatures of thermal decomposition. Most importantly, PUR composites filled with flame retardant compounds exhibited improved flame resistance characteristics-in all cases, the value of peak heat release was reduced by ~12%, while the value of total smoke release was reduced by ~23%.     

Oligomerization and Nitration of the Grass Pollen Allergen Phl p 5 by Ozone,Nitrogen Dioxide,and Peroxynitrite: Reaction Products,Kinetics, and Health Effects

The allergenic and inflammatory potential of proteins can be enhanced by chemical modification upon exposure to atmospheric or physiological oxidants. The molecular mechanisms and kinetics of such modifications, however, have not yet been fully resolved. We investigated the oligomerization and nitration of the grass pollen allergen Phl p 5 by ozone (O₃), nitrogen dioxide (NO₂), and peroxynitrite (ONOO^–). Within several hours of exposure to atmospherically relevant concentration levels of O₃ and NO₂, up to 50% of Phl p 5 were converted into protein oligomers, likely by formation of dityrosine cross-links. Assuming that tyrosine residues are the preferential site of nitration, up to 10% of the 12 tyrosine residues per protein monomer were nitrated. For the reaction with peroxynitrite, the largest oligomer mass fractions (up to 50%) were found for equimolar concentrations of peroxynitrite over tyrosine residues. With excess peroxynitrite, the nitration degrees increased up to 40% whereas the oligomer mass fractions decreased to 20%. Our results suggest that protein oligomerization and nitration are competing processes, which is consistent with a two-step mechanism involving a reactive oxygen intermediate (ROI), as observed for other proteins. The modified proteins can promote pro-inflammatory cellular signaling that may contribute to chronic inflammation and allergies in response to air pollution.     

TP53-Induced Glycolysis and Apoptosis Regulator (TIGAR) Is Upregulated in Lymphocytes Stimulated with Concanavalin A

The glycolytic modulator TP53-Inducible Glycolysis and Apoptosis Regulator (TIGAR) is overexpressed in several types of cancer and has a role in metabolic rewiring during tumor development. However, little is known about the role of this enzyme in proliferative tissues under physiological conditions. In the current work, we analysed the role of TIGAR in primary human lymphocytes stimulated with the mitotic agent Concanavalin A (ConA). We found that TIGAR expression was induced in stimulated lymphocytes through the PI3K/AKT pathway, since Akti-1/2 and LY294002 inhibitors prevented the upregulation of TIGAR in response to ConA. In addition, suppression of TIGAR expression by siRNA decreased the levels of the proliferative marker PCNA and increased cellular ROS levels. In this model, TIGAR was found to support the activity of glucose 6-phosphate dehydrogenase (G6PDH), the first enzyme of the pentose phosphate pathway (PPP), since the inhibition of TIGAR reduced G6PDH activity and increased autophagy. In conclusion, we demonstrate here that TIGAR is upregulated in stimulated human lymphocytes through the PI3K/AKT signaling pathway, which contributes to the redirection of the carbon flux to the PPP.