Neuroprotective Effect of SGLT2 Inhibitors

Patients with diabetes are at higher risk of cardiovascular diseases and cognitive impairment. SGLT2 inhibitors (Empagliflozin, Canagliflozin, Dapagliflozin, Ertugliflozin, Sotagliflozin) are newer hypoglycemic agents with many pleiotropic effects. In this review, we discuss their neuroprotective potential. SGLT2 inhibitors (SGLT2i) are lipid-soluble and reach the brain/serum ratio from 0.3 to 0.5. SGLT receptors are present in the central nervous system (CNS). Flozins are not fully SGLT2-selective and have an affinity for the SGLT1 receptor, which is associated with protection against ischemia/reperfusion brain damage. SGLT2i show an anti-inflammatory and anti-atherosclerotic effect, including reduction of proinflammatory cytokines, M2 macrophage polarization, JAK2/STAT1 and NLRP3 inflammasome inhibition, as well as cIMT regression. They also mitigate oxidative stress. SGLT2i improve endothelial function, prevent remodeling and exert a protective effect on the neurovascular unit, blood-brain barrier, pericytes, astrocytes, microglia, and oligodendrocytes. Flozins are also able to inhibit AChE, which contributes to cognitive improvement. Empagliflozin significantly increases the level of cerebral BDNF, which modulates neurotransmission and ensures growth, survival, and plasticity of neurons. Moreover, they may be able to restore the circadian rhythm of mTOR activation, which is quite a novel finding in the field of research on metabolic diseases and cognitive impairment. SGLT2i have a great potential to protect against atherosclerosis and cognitive impairment in patients with type 2 diabetes mellitus.     

Permeability of the Perindopril Arginine under In Vitro Conditions across Caco-2 Monolayer and Biomimetic Phospholipid Membrane

Perindopril arginine (PA) as an angiotensin-converting enzyme (ACE) inhibitor is widely used in cardiovascular diseases, especially in systemic hypertension and heart failure. Although the pharmacokinetics of PA are well documented, there is no available detailed data on its permeation in in vitro conditions. The present study aimed to assess the transport of PA across both biological membranes and artificial biomimetic ones. For the determination of PA transport, the Caco-2 cell line was selected as a reliable in vitro model of gastrointestinal biological barriers. Additionally, a novel 96-well plate with phospholipid membrane PermeaPad was used to evaluate the transport of PA by passive diffusion. We confirmed that PA is relatively poorly permeable across the Caco-2 monolayer. The permeability results obtained from the non-cell-based model demonstrated higher transport of PA as compared to that of Caco-2. Thus, PA transport across the biological membranes might be suggested to be regulated by the membrane transporters.     

Simultaneous Determination of Multi-Class Pesticide Residues and PAHs in Plant Material and Soil Samples Using the Optimized QuEChERS Method and Tandem Mass Spectrometry Analysis

New analytical approaches to the simultaneous identification and quantification of 94 pesticides and 13 polycyclic aromatic hydrocarbons (PAHs) in five representative matrices (pepper, apple, lettuce, wheat, and soil) were developed. The analyses were based on gas chromatography coupled with triple quadrupole tandem mass spectrometry (GC-MS/MS). The procedure was optimized by changing the solvent used during the extraction, from acetonitrile to the acetone: n-hexane mixture at a volume ratio of 1:4 (v/v), as well as the use of a reduced amount of water during the extraction of compounds from cereals. An additional modification was the use of florisil instead of GCB in the sample cleanup step. A full method validation study was performed, at two concentration levels (LOQ and 1000 × LOQ), which showed satisfactory results for all analytes from the PAHs group, with recoveries ranging from 70.7–115.1%, and an average RSD of 3.9%. Linearity was tested in the range of 0.001–1.000 mg/kg and showed coefficients of determination (R²) ≥ 0.99 for all PAHs. Satisfactory recovery and precision parameters (LOQ and 100 × LOQ) were achieved for almost all analytes from the pesticide group in the range of 70.1–119.3% with the mean RSD equal to 5.9%. The observed linearity for all analytes in the concentration range of 0.005–1.44 mg/kg was R² ≥ 0.99, with the exception of famoxadone, chizalofop-p-ethyl, prothioconazole, spirodiclofen, tefluthrin, and zoxamid. The extended uncertainties were estimated, using a top-down approach of 9.9% (average) and 15.3% (average) for PAHs and pesticides samples, respectively (the coverage factor k = 2, the 95% confidence level). Ultimately, the method was successfully applied to determine pesticide residues in commercial samples of fruit, vegetables and grain, and soil samples for PAHs, which were collected from selected places in the Podkarpacie region. A total of 38 real samples were tested, in which 10 pesticides and 13 PAHs were determined. Proposed changes allow us to shorten the sample preparation time (by 20%) and to reduce the consumption of organic solvents (by 17%). The use of florisil for sample cleanup, instead of GCB, improves the recovery of compounds with flat particles.     

Refinement of the (NH4)3H(SO4)2 crystal structure: II. X-ray and neutron single-crystal diffraction from phase II at room temperature

The crystal of (NH₄)₃H(SO₄)₂ is of special interest due to the possible influence of ammonium ion on the series of phase transitions: I↔II↔ III↔IV↔V↔VII. Earlier, the x-ray single-crystal diffraction study of phase II of the (NH₄)₃H(SO₄)₂ crystal showed that the crystal structure of this compound had two crystallographically independent groups of the ammonium ions NH₄(1) and NH₄(2) but orientational positions of these ammonium ions were not determined exactly. The refinement of the NH₄(1) and NH₄(2) orientational positions in phase II was carried out by the x-ray and neutron single-crystal diffraction study. The analysis of difference Fourier maps of electron charge density and nuclear density suggested the possibility of disordering of NH₄(2) ammonium ions. The text was submitted by the authors in English.     

A note on a theorem of Perles concerning non-crossing paths in convex geometric graphs

During the last decade a Turán-type result of Perles about the length of the longest non-crossing paths in convex geometric graphs has been receiving some attention in the community studying geometric graphs. In this note we prove that it implies a theorem of Merino, Salazar and Urrutia about the length of the longest alternating paths for a multicoloured point set in convex position. We also give an alternative proof of Perles's theorem based on some ideas from the Merino et al. paper.     

Polarized emission of doped ZnS crystals

Polarization of light emitted in various spectral ranges was studied in two single crystals ZnS:Cu, Cl and ZnS:Ag, Cu, Al. The G-Cu, B-Cu and a small amount of S-A centers have been identified in the ZnS:Cu, Cl crystal by the spectral and polarization methods. The B-Ag band was found in the spectrum of the ZnS:Ag, Cu, Al crystal and its polarization properties investigated. This emission appears to be always polarized perpendicular to the [111]_c axis of the stacking faults independently of the polarization of the exciting light. The symmetry of the B-Ag center is not lower than that of the host lattice. Analogy with G-Cu centers suggests a model for the B-Ag center in which the polarization comes from the symmetry properties of the Ag²⁺ orbitals in the trigonal field of stacking faults.     

Red luminescence of ZnS: Fe crystals

In order to elucidate the nature of the red emission band at 660 nm in ZnS: Fe crystals, the equilibrium luminescence, the thermoluminescence and the photoinduced EPR signals were measured, using UV, or the simultaneous UV + IR excitations. In addition, the polarization properties and the light-pressure shift of the red luminescence were studied. On the basis of the obtained results and of the data reported in the literature and concerning the red and IR emissions in ZnS: Fe a donor-acceptor model is proposed, in which the transition Cl^2?→Fe³⁺ would give rise to the 660 nm band.     

Kinetics of luminescence in ZnS crystals as studied by centers discrimination

It was shown, by alternating the unpolarized and polarized UV-excitation of ZnS crystals, that the excited S-A centers accumulated during the rise of luminescence do not contribute to the steady emission.     

The Influence of Temperature Differences in Smoking Chamber and Furnace and Smoking Time on the Quality of Medium-Ground Sausages

The aim of the work was to determine the impact of two variants (A and B) of smoking (differing in temperature values, furnace, top and bottom of the smoking chamber and the length of smoking time) in the sausage technological process carried out in a traditional smoking chamber with an indirect furnace. The research material consisted of medium-ground sausages: Country, Home and Bieszczady sausages. The research showed that, as the temperature in the smoking chamber and the smoking time changed, the following texture parameters decreased: cycle hardness 1 and 2, springiness, gumminess and chewiness. In addition, there were shown statistically significant differences (p < 0.05) in the chemical composition of Country sausage between the applied smoking variants. It was also found that the temperature of the furnace, upper and lower smoking chamber and the length of smoking time did not have a statistically significant influence on the share of red (a*) and yellow (b*) in the analysed sausages.