Treating Arterial Ageing in Patients with Diabetes: From Mechanisms to Effective Drugs

Diabetes mellitus is a major healthcare problem. It is not only characterized by hyperglycemia and chronic complications, but in longer lasting diabetes and a longer living population, it is also associated with accelerated arterial ageing, which importantly contributes to cardiovascular complications. The accelerated arterial ageing in patients with diabetes should be considered separately from arterial ageing in patients without diabetes. Basic and clinical research have allowed better insight into the mechanisms of arterial ageing. In a simplified mechanistic way, it could be considered that the three tightly connected cornerstone characteristics of arterial ageing in patients with diabetes are: phenotypic presentation as endothelial dysfunction and arterial stiffness, and the underlying basic ageing-facilitating mechanism represented as the impaired expression of genetic longevity pathways. Currently, specific drugs for preventing/treating arterial ageing are not available. Therefore, we aimed to review the capacity of available drugs, particularly antidiabetic drugs, to interfere with the arterial ageing process. In the near future, these characteristics could help to guide therapy in patients with diabetes. Overall, it appears that arterial ageing could become a new target in diabetes. The expanding knowledge regarding the capability of antidiabetic drugs and other available drugs to inhibit/delay arterial aging is therefore essential.     

A comparative study of stochastic optimization methods in electric motor design

The efficiency of universal electric motors that are widely used in home appliances can be improved by optimizing the geometry of the rotor and the stator. Expert designers traditionally approach this task by iteratively evaluating candidate designs and improving them according to their experience. However, the existence of reliable numerical simulators and powerful stochastic optimization techniques make it possible to automate the design procedure. We present a comparative study of six stochastic optimization algorithms in designing optimal rotor and stator geometries of a universal electric motor where the primary objective is to minimize the motor power losses. We compare three methods from the domain of evolutionary computation, generational evolutionary algorithm, steady-state evolutionary algorithm and differential evolution, two particle-based methods, particle-swarm optimization and electromagnetism-like algorithm, and a recently proposed multilevel ant stigmergy algorithm. By comparing their performance, the most efficient method for solving the problem is identified and an explanation of its success is offered.     

Solid phase dosing and sampling technique to determine partition coefficients of hydrophobic chemicals in complex matrixes

Determination of polymer-water and dissolved organic carbon (DOC)-water distribution coefficients of very hydrophobic chemicals (log K0w > 6) is not straightforward. Poor water solubility of the test compounds complicates the spiking and analysis of actual freely dissolved concentrations. By dosing a system via a PDMS-fiber and monitoring the depletion in the polymer, spiking and analysis of concentrations in the aqueous phase are avoided, and sorption to the polymer and other hydrophobic phases can be determined easily and accurate. In this publication we report the determination of poly(dimethyl-siloxane) (PDMS)-water, and Aldrich humic acid-water distribution coefficients for six PAHs with log K0w values varying from 4.56 to 6.85. The distribution coefficients to a PDMS fiber llog Kf) and the DOC (log KDOC) range from 3.86 to 5.39 and 4.78 to 7.43, respectively. Even for the most hydrophobic compounds, the distribution coefficients show small standard errors (< or = 0.05 log units). Therefore, this method might be applied to determine sorption coefficients of numerous, even more hydrophobic compounds, to humic acids as well as other dissolved hydrophobic matrixes.     

Tem analyses of the local crystal and domain structures in (Na(1-x)K(x))0.5Bi(0.5)TiO3 perovskite ceramics

The local crystal and domain structures of the ((Na(1-x)K(x))(0.5)Bi(0.5)TiO(3) (NBT-KBT) solid solutions were studied because of their influence on the enhanced electromechanical properties of ceramics. Based on X-ray diffraction, the morphotropic phase boundary (MPB) was determined for the composition x = 0.20, in which the rhombohedral and the tetragonal structures were observed to coexist. However, detailed domain-structure analyses using transmission electron microscopy (TEM), performed on the NBT, KBT, and five NBT-KBT solid-solution compositions, revealed some structural changes at/near the MPB. In the samples on the tetragonal side of the MPB, the grains showed a lamellar domain structure with 90° orientations of the individual domains, separated by straight domain boundaries, i.e., (011)/(101) twin planes. The rhombohedral samples on the other side of the MPB showed a typical square-net pattern with needle-like or lamellar ~71°/109° rhombohedral domains with (001) and/or (110) twin planes separating the individual domains. The domain structure at the MPB showed well-defined lamellar domains. Based on the occurrence of the superstructure reflections in the SAED patterns of various crystallographic zones, on the characteristic splitting of the reflections, and on the domain morphology observations, the crystal structure in/near the boundary region was determined to be a tetragonal structure with an in-phase oxygen octahedral tilt system (probably a(0)a(0)c(+)). It is suggested that the tetragonal polar order is partly induced from the rhombohedral structure at the MPB as a result of mechanical loading during TEM sample preparation.     

Ability of Lactobacillus gasseri K 7 to inhibit Escherichia coli adhesion in vitro on Caco-2 cells and ex vivo on pigs' jejunal tissue

The ability of Lactobacillus (Lb.) gasseri K 7 to inhibit adhesion of Escherichia coli O8:K88 to intestinal mucosa was studied on cultured Caco-2 cells and ex vivo on pigs' small intestinal tissue. Lactobacilli were added simultaneously with E. coli, before E. coli and after E. coli for competition, exclusion and displacement assays. The concentration of lactobacilli on fully differentiated Caco-2 cells was 4.5+/-0.3 x 10(8) cfu/well, while the concentration of E. coli varied from 1.5 x 10(6) to 4.3 x 10(8) cfu/well. The number of E. coli adhered to Caco-2 monolayer (cfu/well) was lineary correlated (R(2)=0.97) to the concentration of added cells. In the assay simulating exclusion, E. coli adhesion was reduced by Lb. gasseri K 7 strain by 0.1 to 0.6 log cfu/well. The binding of E. coli was inhibited even more when incubated simultaneously with lactobacilli, particularly at the lowest concentration of E. coli (ratio E. coli/lactobacilli 1:248), where five-times reduction (or 0.7 log) was observed. When adhesion to tissue derived from pigs' jejunum was tested, concentration of E. coli was constant (6.9+/-0.14 x 10(7) cfu/ml), while the concentration of Lb. gasseri K 7 was 5.9 x 10(7) and 1.3 x 10(7) cfu/ml in two independent experiments, respectively. The adhesion of E. coli and Lb. gasseri K 7 cells to jejunal mucosa was similar (1.0+/-0.17 x 10(6) and 1.54+/-0.10 x 10(6) cfu/cm(2)) when the concentrations of single strains in suspensions were approximately the same. No significant competition, exclusion or displacement of E. coli by lactobacilli was observed on jejunal tissue. In conclusion, Lb. gasseri K 7 was found to be effective in reducing E. coli adhesion to Caco-2 enterocytes, but it was not able to do so in ex vivo conditions tested for pig jejunal tissue.     

Fatty acid composition of eggs produced by the Slovenian autochthonous Styrian hen

The fatty acid composition of eggs produced by the autochthonous Styrian hen reared in two rearing systems was determined. Eggs were collected four times during the year. The fatty acid composition was determined by the in situ transesterification method and gas chromatography–flame ionisation detection (GC–FID). Eggs of the Styrian hen from free range contained significantly more α-linolenic, eicosapentaenoic (EPA), docosapentaenoic (DPA) and docosahexaenoic acid (DHA), as well as more total n−3 fatty acids. On the other hand, eggs from caged hens contained significantly more linoleic, arachidonic, as well as total polyunsaturated fatty acids (PUFA) and n−6 PUFA. The n−6/n−3 ratio was better from the nutritional point of view in eggs from free range. The fatty acid content is expressed in wt.%, as well as mg/100 g of yolk and mg/100 g of fresh egg, to better understand how much each of fatty acid is consumed with an edible portion.     

Mathematical modelling of the solubility of supercritical CO2 in poly(l-lactide) and poly(d,l-lactide-co-glycolide)

Two mathematical models, Sanchez–Lacombe equation of state and the Perturbed-Chain Statistical Associating Fluid Theory were applied for modelling the phase equilibrium for the poly(l-lactide)–CO₂ and poly(d,l-lactide-co-glycolide)–CO₂ systems. Aspen Polymer Plus software was used. The results were compared with previously obtained experimental values for solubility. The solubility of scCO₂ in the two biodegradable polymers was calculated for three different temperatures (308, 313 and 323 K) in the pressure range (10–30 MPa). The characteristic parameters for the components and the binary interaction parameters for the models were optimized in order to obtain the best fit between the estimated and the experimental gas solubility data. The results suggest that both SL EOS and PC-SAFT are reliable models in describing the phase equilibrium of the PLLA–CO₂ and PLGA–CO₂ systems at the proposed working conditions.     

Attachment of Cancer Urothelial Cells to the Bladder Epithelium Occurs on Uroplakin-Negative Cells and Is Mediated by Desmosomal and Not by Classical Cadherins

Urinary bladder cancer is often multifocal; however, the intraluminal dissemination of the urothelial cancer cells is poorly understood. The involvement of N-cadherin in the adhesion of the cancer urothelial cells to the urothelium had not previously been studied. Therefore, we herein explore the possibility of the intraluminal dissemination of the urothelial cancer cells by evaluating the role of classical cadherins in the adhesion of urothelial cancer cells to the urothelium. We used E-cadherin negative T24 cells and established a T24 Ncad^low cell line with an additionally decreased expression of N-cadherin in the plasma membrane and a decreased secretion of proform of metalloproteinase 2. The labelled T24 and T24 Ncad^low cells were seeded onto urothelial in vitro models. After 24 h in co-culture, unattached cancer cells were rinsed and urothelia with attached cancer urothelial cells were processed for fluorescence and electron microscopy. Both the T24 and T24 Ncad^low cells attached to the urothelium, yet only to the uroplakin-negative urothelial cells. The ultrastructural analysis showed that T24 and T24 Ncad^low cells adhere to poorly differentiated urothelial cells by desmosomes. To achieve this, they first disrupt tight junctions of superficial urothelial cells. This study indicates that the lack of E-cadherin expression and decreased expression of N-cadherin in the plasma membrane of T24 cells does not interfere with their adhesion to the urothelium; therefore, our results suggest that intraluminal dissemination of cancer urothelial cells along the urothelium occurs on uroplakin-negative cells and is desmosome-mediated.     

Solubility and diffusivity of CO2 in carboxylated polyesters

The solubility of CO₂ in saturated polyester resins at different temperatures (306 and 343 K) and pressures (0.1-30 MPa) has been measured using a magnetic suspension balance. The solubility data were used for estimating the binary diffusion coefficients. The results show a good solubility of CO₂ in polymers, up to 0.64 g CO₂/g polymer. The diffusion coefficients of supercritical CO₂ in polymers have generally high values and are in the range from 0.156 × 10⁻⁸ to 10.38 × 10⁻⁸ cm²/s. DSC and XRD analyses of the semi-crystalline polymer samples indicate that amorphous degree of polymers after exposure to CO₂ is increased. The observed structural effects are dependent on pressure, temperature and time of exposure to CO₂.