Reliable stabilization of the pharmaceutical preparation and the active ingredient remains one of the most important problems of world pharmacy because pharmaceutical preparations are not systems which are stable without limitation. The patient must receive a quality drug and that is why the question of stability is paid grest attention to not only in research and development, industrial manufacture, but also in distribution. The measure of stability is the expiration period. Diluted solution of hydrogen peroxide (3% solution) still belongs to the most widely used and at the same time the most easily accessible disinfectants. In practice it is common both in Slovakia and abroad. It is used in several concentrations. One of its most important disadvantages is its limited stability, which markedly decreases its expiration period. The present paper investigates the stability of hydrogen peroxide solutions of routinely used concentrations (3%, 6%, and 10%) without and with a stabilizing additive (phenacetin) prepared in the pharmacy and stored under different conditions for the period of their expected usability. The content of hydrogen peroxide was assayed by the pharmacopoeial method in 7-day time intervals. All concentrations of 3%, 6%, and 10% hydrogen peroxide were found to fulfil the conditions for stability in the period of time under study. Their concentration did not fall below the limit od 90% of the content of the active ingredient, and storage under decreased temperature proved to be more suitable. Storage of hydrogen peroxide in the light is inadmissible. When the conditions of storage are observed, the required therapeutic effect of hydrogen peroxide solution can be expected for the period of three months.

• MeSH
• peroxid vodíku chemie   MeSH
• roztoky MeSH
• skladování léků MeSH
• stabilita léku MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• peroxid vodíku MeSH
• roztoky MeSH

The preparation of an amorphous solid dispersion (ASD) is a promising strategy for improving the poor oral bioavailability of many active pharmaceutical ingredients (APIs). However, poor predictability of ASD long-term physical stability remains a prevalent problem. The purpose of this study was to evaluate and compare the predictive performance of selected models concerning solid-liquid equilibrium (SLE) curve and glass-transition temperature (Tg) line modeling of ibuprofen (IBU) in cellulosic polymers (i.e., hydroxypropyl methylcellulose (HPMC) and hydroxypropyl methylcellulose acetate succinate (HPMCAS)). For SLE curve modeling, an empiricalanalyticalapproach(Kyeremateng et al., 2014)and the Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) equation of state (EOS) were chosen. Due to the unavailability of PC-SAFT parameters for both polymers, an approximation procedure for parametrization was applied. The Gordon-Taylor equation and Kwei equation were considered for Tg line determination. The impact of various computational set-ups (e.g., model parametrization or extrapolation length) on IBU solubility prediction at storage conditions was thoroughly investigated, assessed and confronted with the results from an 18-month physical stability study. IBU developed stable 20 wt% API content ASDs with both HPMC and HPMCAS.The extrapolation behavior and subsequent ASD thermodynamic stability prediction at storage conditions deduced from the aforementioned models weresignificantly different. Overall, the PC-SAFT EOS predicted higher IBU solubility in both polymers and, thus, a lower recrystallization tendency when compared to the empirical analytical approach. At higherIBU concentrations, liquid-liquid demixing inIBU-polymer systems was predicted by the PC-SAFT EOS, which was in qualitative disagreement with experimental observation.

• Klíčová slova
• Amorphous solid dispersion, Hot-melt extrusion, PC-SAFT, Phase diagram, Physical stability, Solid-liquid equilibrium,
• MeSH
• deriváty hypromelózy MeSH
• farmaceutická chemie * MeSH
• methylcelulosa MeSH
• pomocné látky * MeSH
• rozpustnost MeSH
• stabilita léku MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• deriváty hypromelózy MeSH
• methylcelulosa MeSH
• pomocné látky * MeSH

The thermal stability of pseudocyclic and cyclic N-heterocycle-stabilized (hydroxy)aryl- and mesityl(aryl)-λ3-iodanes (NHIs) through thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) is investigated. Peak decomposition temperatures (T peak) were observed within a wide range between 120 and 270 °C. Decomposition enthalpies (ΔH dec) varied from -29.81 to 141.13 kJ/mol. A direct comparison between pseudocyclic and cyclic NHIs revealed high T peak but also higher ΔH dec values for the latter ones. NHIs bearing N-heterocycles with a high N/C-ratio such as triazoles show among the lowest T peak and the highest ΔH dec values. A comparison of NHIs with known (pseudo)cyclic benziodoxolones is made and we further correlated their thermal stability with reactivity in a model oxygenation.

• Klíčová slova
• N-heterocycle, differential scanning calorimetry, hypervalent iodine, stability, thermogravimetry,
• Publikační typ
• časopisecké články MeSH

The ribosome, owing to its exceptional conservation, harbours a remarkable molecular fossil known as the protoribosome. It surrounds the peptidyl transferase center (PTC), responsible for peptide bond formation. While previous studies have demonstrated the PTC activity in RNA alone, our investigation reveals the intricate roles of the ribosomal protein fragments (rPeptides) within the ribosomal core. This research highlights the significance of rPeptides in stability and coacervation of two distinct protoribosomal evolutionary stages. The 617nt 'big' protoribosome model, which associates with rPeptides specifically, exhibits a structurally defined and rigid nature, further stabilized by the peptides. In contrast, the 136nt 'small' model, previously linked to peptidyltransferase activity, displays greater structural flexibility. While this construct interacts with rPeptides with lower specificity, they induce coacervation of the 'small' protoribosome across a wide concentration range, which is concomitantly dependent on the RNA sequence and structure. Moreover, these conditions protect RNA from degradation. This phenomenon suggests a significant evolutionary advantage in the RNA-protein interaction at the early stages of ribosome evolution. The distinct properties of the two protoribosomal stages suggest that rPeptides initially provided compartmentalization and prevented RNA degradation, preceding the emergence of specific RNA-protein interactions crucial for the ribosomal structural integrity.

• MeSH
• konformace nukleové kyseliny MeSH
• molekulární modely MeSH
• peptidy chemie   metabolismus   MeSH
• peptidyltransferasy metabolismus   chemie   MeSH
• ribozomální proteiny * metabolismus   chemie   MeSH
• ribozomy * metabolismus   MeSH
• RNA metabolismus   chemie   MeSH
• stabilita RNA MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• peptidy MeSH
• peptidyltransferasy MeSH
• ribozomální proteiny * MeSH
• RNA MeSH

The article is focused on the medium-term negative effect of groundwater on the underground grout elements. This is the physical-mechanical effect of groundwater, which is known as erosion. We conduct a laboratory verification of the erosional resistance of grout mixtures. A new test apparatus was designed and developed, since there is no standardized method for testing at present. An erosion stability test of grout mixtures and the technical solutions of the apparatus for the test's implementation are described. This apparatus was subsequently used for the experimental evaluation of the erosional stability of silicate grout mixtures. Grout mixtures with activated and non-activated bentonite are tested. The stabilizing effect of cellulose relative to erosion stability has been also investigated. The specimens of grout mixtures are exposed to flowing water stress for a certain period of time. The erosional stabilities of the grout mixtures are assessed on the basis of weight loss (WL) as a percentage of initial specimen weight. The lower the grout mixture weight loss, the higher its erosional stability and vice versa.

• Klíčová slova
• erosional stability, groundwater, grout mixtures, laboratory testing, test apparatus,
• Publikační typ
• časopisecké články MeSH

MicroRNAs (miRNAs) are small RNA molecules, which act as post-transcriptional regulators of a gene expression, with important functions within the cell physiology. Whilst many authors have focused on the study of miRNA expression in physiological and pathological processes, various technical variables related to miRNA isolation have simultaneously emerged and the stability of the stored miRNA samples has been questioned. A robust method for RNA isolation is essential for reproducible results and miRNAs instability in the stored samples would make for an alarming situation for most expression studies. Here these issues are discussed and we investigate the stability of miRNAs isolated from clinical samples of B lymphocytes (chronic lymphocytic leukemia) by the most commonly utilized method based on a Trizol/TRI-Reagent solution (RNAs stored at -80 degrees C). To assess the stability of miRNAs, a Real Time-PCR analysis was performed for a panel of 29 miRNAs from a freshly isolated RNA sample and after 14 days storage at -80 degrees C. Furthermore, a Real Time-PCR analysis was repeatedly performed for a stored RNA sample over a period of approximately 10 months. We observed high stability of isolated miRNAs and respective cDNAs. The reproducibility and efficiency of the Trizol/TRI-Reagent isolation method was also tested and compared to the mirVana Isolation kit (Ambion) and RNeasy kit (Qiagen). In conclusion, Trizol/TRI-Reagent based isolation is a robust reproducible method, and obtained miRNA samples do not show any tendency to degradation when properly stored and handled.

• MeSH
• B-lymfocyty chemie   MeSH
• chronická lymfatická leukemie diagnóza   MeSH
• fenoly chemie   MeSH
• guanidiny chemie   MeSH
• lidé MeSH
• mikro RNA chemie   izolace a purifikace   MeSH
• odběr biologického vzorku MeSH
• polymerázová řetězová reakce MeSH
• reprodukovatelnost výsledků MeSH
• roztoky MeSH
• stabilita RNA * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• fenoly MeSH
• guanidiny MeSH
• mikro RNA MeSH
• roztoky MeSH
• trizol MeSH Prohlížeč

Thermodynamical arguments are known to be useful in the construction of physically motivated Lyapunov functionals for nonlinear stability analysis of spatially homogeneous equilibrium states in thermodynamically isolated systems. Unfortunately, the limitation to isolated systems is essential, and standard arguments are not applicable even for some very simple thermodynamically open systems. On the other hand, the nonlinear stability of thermodynamically open systems is usually investigated using the so-called energy method. The mathematical quantity that is referred to as the "energy" is, however, in most cases not linked to the energy in the physical sense of the word. Consequently, it would seem that genuine thermo-dynamical concepts are of no use in the nonlinear stability analysis of thermodynamically open systems. We show that this is not the case. In particular, we propose a construction that in the case of a simple heat conduction problem leads to a physically well-motivated Lyapunov type functional, which effectively replaces the artificial Lyapunov functional used in the standard energy method. The proposed construction seems to be general enough to be applied in complex thermomechanical settings.

• Klíčová slova
• Lyapunov functional, nonlinear stability, thermodynamically open systems, thermodynamics,
• Publikační typ
• časopisecké články MeSH

Human phosphoglycerate kinase 1(hPGK1) is a key glycolytic enzyme that regulates the balance between ADP and ATP concentrations inside the cell. Phosphorylation of hPGK1 at S203 and S256 has been associated with enzyme import from the cytosol to the mitochondria and the nucleus respectively. These changes in subcellular locations drive tumorigenesis and are likely associated with site-specific changes in protein stability. In this work, we investigate the effects of site-specific phosphorylation on thermal and kinetic stability and protein structural dynamics by hydrogen-deuterium exchange (HDX) and molecular dynamics (MD) simulations. We also investigate the binding of 3-phosphoglycerate and Mg-ADP using these approaches. We show that the phosphomimetic mutation S256D reduces hPGK1 kinetic stability by 50-fold, with no effect of the mutation S203D. Calorimetric studies of ligand binding show a large decrease in affinity for Mg-ADP in the S256D variant, whereas Mg-ADP binding to the WT and S203D can be accurately investigated using protein kinetic stability and binding thermodynamic models. HDX and MD simulations confirmed the destabilization caused by the mutation S256D (with some long-range effects on stability) and its reduced affinity for Mg-ADP due to the strong destabilization of its binding site (particularly in the apo-state). Our research provides evidence suggesting that modifications in protein stability could potentially enhance the translocation of hPGK1 to the nucleus in cancer. While the structural and energetic basis of its mitochondrial import remain unknown.

• Klíčová slova
• cancer, ligand binding, phosphoglycerate kinase, protein phosphorylation, protein stability,
• MeSH
• adenosindifosfát metabolismus   MeSH
• cytosol * metabolismus   MeSH
• fosfoglycerátkinasa * metabolismus   genetika   chemie   MeSH
• fosforylace MeSH
• kinetika MeSH
• lidé MeSH
• ligandy MeSH
• mutace MeSH
• nádory * genetika   metabolismus   patologie   MeSH
• simulace molekulární dynamiky * MeSH
• stabilita proteinů MeSH
• termodynamika MeSH
• vazba proteinů * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adenosindifosfát MeSH
• fosfoglycerátkinasa * MeSH
• ligandy MeSH

Diglycolamides (DGA) form one of the most promising groups of organic ligands used in bio-inspired solvent extraction processes of lanthanide and actinide ions. Continuous experimental and theoretical research is still performed in order to further improve their application properties including their chemical stability in the real extraction environment. This work provides results of our theoretical approach focused on inclusion of an acid influence on the DGAs chemical structure, treated in frame of the density functional theory. Three different models describing the acid action are proposed and investigated in attempt to increase the resulting accuracy of the chemical stability predictions based on verified theoretical descriptors. The procedure is applied and tested on the set of selected hydrophilic DGA representatives. Comparison of the model results obtained with and without acid action shows that two types of protection effects may occur: a 'direct' protection, accompanied by an explicit change of the ligand stability indicators, and an 'indirect' one consisting in reaction of acid molecules with radicals preceding the contact of latter with the extracting ligands. The possibility of the direct acid protection route is supported by the significant decrease of the Fukui charges found with the acid models included. On the other hand, there is in general no significant difference of trends in the calculated chemical stability descriptors suggesting that an indirect mechanism must be also considered in order to explain the experimentally observed protective role of acids on the chemical stability of investigated DGA derivatives.

• Klíčová slova
• acid influence, density functional theory, diglycolamides, hydrophilic DGA, radiolytic stability,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Telomeres are indispensable for genome stability maintenance. They are maintained by the telomere-associated protein complex, which include Ku proteins and a telomerase among others. Here, we investigated a role of Ku80 in Leishmania mexicana. Leishmania is a genus of parasitic protists of the family Trypanosomatidae causing a vector-born disease called leishmaniasis. METHODOLOGY/PRINCIPAL FINDINGS: We used the previously established CRISPR/Cas9 system to mediate ablation of Ku80- and Ku70-encoding genes in L. mexicana. Complete knock-outs of both genes were confirmed by Southern blotting, whole-genome Illumina sequencing, and RT-qPCR. Resulting telomeric phenotypes were subsequently investigated using Southern blotting detection of terminal restriction fragments. The genome integrity in the Ku80- deficient cells was further investigated by whole-genome sequencing. Our work revealed that telomeres in the ΔKu80 L. mexicana are elongated compared to those of the wild type. This is a surprising finding considering that in another model trypanosomatid, Trypanosoma brucei, they are shortened upon ablation of the same gene. A telomere elongation phenotype has been documented in other species and associated with a presence of telomerase-independent alternative telomere lengthening pathway. Our results also showed that Ku80 appears to be not involved in genome stability maintenance in L. mexicana. CONCLUSION/SIGNIFICANCE: Ablation of the Ku proteins in L. mexicana triggers telomere elongation, but does not have an adverse impact on genome integrity.

• MeSH
• antigen Ku genetika   metabolismus   MeSH
• genom protozoální MeSH
• Leishmania mexicana genetika   metabolismus   MeSH
• leishmanióza kožní parazitologie   MeSH
• lidé MeSH
• nestabilita genomu * MeSH
• protozoální proteiny genetika   metabolismus   MeSH
• telomery genetika   metabolismus   MeSH
• Trypanosoma brucei brucei genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigen Ku MeSH
• protozoální proteiny MeSH