Modulation of Biodistribution,Pharmacokinetics, and Photosensitivity with the Delivery Vehicle of a Bacteriochlorin Photosensitizer for Photodynamic Therapy

Intravenous (i.v.) formulations with various amounts of organic solvents [PEG₄₀₀, propylene glycol (PG), cremophor EL (CrEL)] were used to deliver a fluorinated sulfonamide bacteriochlorin to mice, rats, and minipigs. Biodistribution studies in mice showed that a low‐content CrEL formulation combines high bioavailability with high tumor‐to‐muscle and tumor‐to‐skin ratios. This formulation was also the most successful in the photodynamic therapy of mice with subcutaneously implanted CT26 murine colon adenocarcinoma tumors. Pharmacokinetic studies in mice and minipigs revealed that with the same low CrEL formulation, the half‐life of the photosensitizer in the central compartment was longer in minipigs. Differences in biodistribution with the various formulations, and in pharmacokinetics between the two animal species with the same formulation, are attributed to the interaction of the formulations with low‐density lipoproteins (LDLs). Skin photosensitivity studies in rats showed that 30 min exposure of the skin to a solar simulator 7 days after i.v. administration of the fluorinated sulfonamide bacteriochlorin at 1 mg kg^?1 did not elicit significant skin reactions.     

Repair of Protein Radicals by Antioxidants

In vivo, proteins are the main targets for radicals and other reactive species. Their reactions result in formation of amino acid radicals on the protein surface that often yield tryptophan and tyrosyl radicals or, in the presence of O₂, protein peroxyl radicals and hydroperoxides. All these species may propagate damage to biomolecules. Low molecular weight antioxidants, such as ascorbate, urate, and glutathione, are part of the defense system and function by repairing damaged proteins. We briefly review the existing knowledge about protein and amino acid radicals and their repair by antioxidants, including results of our investigations. The main question addressed is whether the antioxidants ascorbate, urate, and glutathione are able to repair amino acid radicals in model compounds and in proteins in vitro by pulse radiolysis. We show that ascorbate and urate repair tryptophan and tyrosyl radicals efficiently and inhibit proton-coupled electron transfer from tyrosine residues to tryptophan radicals in a number of proteins. In contrast, repair by glutathione is much slower. Ascorbate also rapidly reduces the peroxyl radicals of the N-acetylamide derivatives of glycine, alanine, and proline, whereas glutathione reduces peroxyl radicals in lysozyme. In vivo urate, ascorbate, and glutathione may prevent biological damage or, at least, reduce its rate, because they: (a) repair tryptophan and tyrosyl radicals in proteins and (b) reduce protein peroxyl radicals to the corresponding protein hydroperoxides. Most likely, in vivo, ascorbate and glutathione do not inhibit the reaction of C-centered amino acid radicals with O₂. Glutathione is less efficient that urate and ascorbate in repairing protein radicals; furthermore, the resulting glutathiyl radical is harmful. Ascorbate may be the more important repair agent in cells and tissues characterized by high ascorbate concentrations, such as the lens and brain; urate may be mainly responsible for repair in tissue compartments with higher urate concentrations, such as in plasma and saliva.     

Thermal properties of poly(pivalolactone)

Polypivalolactone (PPVL) is a highly crystalline polyester formed either by nucleophilic or electrophilic ring-opening polymerization of 2,2-dimethyl-β-propiolactone, commonly known as pivalolactone (PVL). The thermal properties and crystallization kinetics of the polymer formed under reaction injection molding (RIM) conditions were studied. The crystallization kinetics of PPVL were measured using differential scanning calorimetry (DSC), and Avrami theory was used to interpret the bulk crystallization kinetics. A comparison was made with commercially prepared PPVL. The kinetics data indicate laboratory prepared PPVL, which is of lower molecular weight, has similar crystallization rates compared to the higher molecular weight commercial material. The kinetics data also indicate the rate of crystallization is relatively rapid overall for PPVL, with low activation energies of crystallization. The calorimetric studies also utilized DSC and simultaneous ther-mogravimetric analysis/differential scanning calorimetry (TGA/DSC). Thermal analysis showed a clear difference in melting behavior between high and low molecular weight material, possibly a reflection of the presence of the α and γ-crystal forms of the polymer.     

Approximation of a multivariable sensor characteristic applied to the carbon monoxide sensor

The transducer applied in sensors and measurement systems often have non-linear characteristics, which may depend on additional factors as temperature, humidity gases flow, etc. Therefore, it is important to find the function describing the dependence between input and output values of a transducer which takes into account all the influencing factors. This paper shows a method which, basing on measured data, allows to establish a multi-variable transducer transfer function.     

Preparation and characterization of potassium, rubidium and ammonium tetrachlorouranate(III) trihydrates

The synthesis and characterization of a new series of hydrated uranium(III) complex chlorides of the general formula M¹UCl₄-3H₂O (M¹K, Rb or NH₄) are reported. The compounds crystallize in the monoclinic system. Unit cell parameters were determined from X-ray powder diffraction data. The magnetic susceptibilities of the complex chlorides were measured by the Faraday method in the 4.2–300 K range. The compounds exhibit Curie-Weiss paramagnetism in the 100–300 K range, with the derived effective magnetic moments ranging from 3.57μ_B to 3.71μ_B. Solid state electronic and IR spectra were recorded in the 4000–30 000 and 80–4000 cm⁻¹ ranges, respectively and discussed. Non-static high vacuum thermal dehydrations enabled us to obtain the anhydrous compounds KUCl₄, RbUCl₄ and UCl₃.     

Regional Planning and Economic Development in the South West Region,Western Australia

Abstract

The paper examines the influence of a regional planning and development authority (the South West Development Authority) on economic growth in the South West Region of Western Australia. Employment and population changes are analysed along sectoral and spatial criteria. The findings show that between 1983 and 1989, the Authority's influence on the creation of employment opportunities was limited, being confined mostly to some gains in the public sector and to the promotion of the region and the city of Bunbury as tourist destinations. This ineffectiveness is associated with a lack of power to attract private and direct public investment to the region.     

A Two-Stage Method for an Approximate Calculation of Statically Indeterminate Trusses

The paper presents the principles of a method, which in two simple stages makes possible to carry out the statically calculation of values of forces acting in the fiat static indeterminate trusses. In each stage, it is considered the static determinate truss, scheme of which is obtained after remove the suitable number of members from the basic static indeterminate truss. The both intermediate statically determinate trusses are of the same clear span and they are loaded by forces of half values applied to the corresponding truss nodes. The method applies one of the typical procedures of calculation of the statically determinate trusses and then it is applied in an appropriate way the rule of superposition for obtaining the final values of forces acting in particular members of the basic truss. The values of forces calculated in this way are of a very close approximation to the force values determined in the special and complex ways being considered as the exact calculation methods. The proposed method can be useful mostly but not only for the initial structural design of such systems. The simplicity of the two-stage method justifies an assumption that it can be relatively easy and worthy to adjust to the requirements of the computer aided technology of statically calculation of the complex forms of trusses.     

Anti-proliferative,pro-apoptotic and anti-oxidative activity of Lactobacillus and Bifidobacterium strains: A review of mechanisms and therapeutic perspectives

Abstract

Lactobacillus and Bifidobacterium strains, their isolated constituents and substances that they secrete exert various anti-cancer actions, resulting from their anti-proliferative, pro-apoptotic and anti-oxidant properties. They can express and secrete anti-oxidant enzymes, bind reactive oxygen species, release small molecular weight anti-oxidants and chelate transition metals, preventing detrimental actions of many carcinogens. Lactobacillus and Bifidobacterium can interact with proteins regulating the cell cycle inhibiting proliferation of cancer cells, which often are intrinsically resistant to apoptosis. Lactobacilli and bifidobacteria can break this resistance through activation of pro-caspases and downregulation of the anti-apoptotic Bcl-2 and upregulation of pro-apoptotic Bax proteins. Anti-cancer effects of these bacteria can be also associated with their multi-pathways action in the microbiota. However, exact mechanism of their anti-cancer action is poorly known and needs further studies, which are justified by the important role of these bacteria in cancer biology as well as their potential preventive and therapeutic use.     

Liquid-liquid and vapour-liquid behaviour of oleyl alcohol applied to extractive fermentation processing

Investigations into the product recovery step of the extractive ethanol fermentation through partition experiments for ethanol-water-Adol^r? 85 NF ternary systems were undertaken. Experimental liquid-liquid equilibrium data for this ternary system were compared with numerical predictions based on the UNIFAC method. The influence of salts on distribution coefficients for ethanol extraction was also examined. An improvement in extraction characteristics was observed for ternary systems with salts. Flash vaporisation was used to subsequently examine the effect of liquid-liquid ternary compositions on vapour-liquid partitioning. The UNIFAC model was found to be very useful for semi-quantitative analysis of such liquid extraction systems.