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

BACKGROUND: Local dynamic stability (LDS) has become accepted as a gait stability indicator. The deterioration of gait stability is magnified in older adults. RESEARCH QUESTION: What is the current state in the field regarding rthe relationship between LDS and cognitive and/or physical function in older adults? METHODS: A scoping review design was used to search for peer-reviewed literature or conference proceedings published through May 2023 for an association between LDS and cognitive (e.g., Montreal Cognitive Assessment) or physical performance (e.g., Timed Up & Go Test) in older adults. Only studies investigating gait stability via LDS during controlled walking, when dealing with a subject group consisting of healthy older adults, and quantifying LDS relationship to cognitive and/or physical measure were included. We analysed data from the studies in a descriptive manner. RESULTS: In total, 814 potentially relevant articles were selected, of which 15 met the inclusion criteria. We identified 37 LDS quantifiers employed in LDS-cognition and/or LDS-physical performance relationship assessment. Nine measures of cognitive and 20 measures of physical performance were analysed. Most studies estimated LDS quantities using triaxial acceleration data. However, there was a variance in sensor placement and signal direction. Out of the 56 studied relationships of LDS to physical performance measures, sixteen were found to be relevant. Out of 22 studied relationships between LDS and cognitive measures, only two were worthwhile. SIGNIFICANCE: Considering the heterogeneity of the utilized LDS (caused by different sensors locations, signals, and signal directions as well as variety of computational approaches to estimate LDS) and cognitive/physical measures, the results of this scoping review does not indicate a current need for a systematic review with meta-analysis. To assess the overall utility of LDS to reveal a relationship between LDS to cognitive and physical performance measures, an analysis of other subject groups would be appropriate.

• Klíčová slova
• Cognition, Gait, Local dynamic stability, Physical performance,
• MeSH
• chůze (způsob) * MeSH
• chůze * MeSH
• kognice MeSH
• lidé MeSH
• senioři MeSH
• tělesná a funkční výkonnost MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• práce podpořená grantem MeSH
• scoping review MeSH

BACKGROUND: Combined infusions of propofol and sufentanil preparations are frequently used in clinical practice to induce anesthesia and analgesia. However, the stability of propofol emulsions can be affected by dilution with another preparation, sometimes leading to particle coalescence and enlargement. Such unwanted effects can lead to fat embolism syndrome after intravenous application. This study describes the physical stability of 5 commercially available propofol preparations mixed with sufentanil citrate solutions. METHODS: Two common markers of emulsion stability were used in this study; namely, the zeta potential and size distribution of the emulsion droplets. Both were measured using dynamic light scattering. The data for the pure propofol preparations and their mixtures with sufentanil citrate solution were compared. RESULTS: The absolute value of zeta potential decreased in 4 of the 5 propofol preparations after they had been mixed with sufentanil citrate. This effect indicates a lowering of repulsive interactions between the emulsion droplets. Although this phenomenon tends to cause agglomeration, none of the studied mixtures displayed a substantial increase in droplet size within 24 hours of blending. However, our long-term stability study revealed the instability of some of the propofol-sufentanil samples. Two of the 5 studied mixtures displayed a continual increase in particle size. The same 2 preparations showed the greatest reductions in the absolute value of zeta potential, thereby confirming the correlation of both measurement methods. The increase in particle size was more distinct in the samples stored at higher temperatures and with higher sufentanil concentrations. CONCLUSIONS: To ensure the microbial stability of an emulsion infusion preparation, clinical regulations require that such preparations should be applied to patients within 12 hours of opening. In this respect, we can confirm that during this period, none of the studied propofol-sufentanil mixtures displayed any physical instability that could lead to particle enlargement; thus, fat embolism should not be a risk after their intravenous application. However, our long-term stability study revealed differences between commercially available preparations containing the same active ingredient; some of the mixtures showed an increase in particle size and polydispersity over a longer period. Although our results should not be generalized beyond the particular propofol-sufentanil preparations and concentrations studied here, they do suggest that, as a general principle, a compatibility study should be performed for any preparation before the first intravenous application to exclude the risk of droplet aggregation.

• MeSH
• anestetika intravenózní aplikace a dávkování   chemie   MeSH
• chemické jevy * MeSH
• fixní kombinace léků MeSH
• intravenózní infuze MeSH
• lidé MeSH
• propofol aplikace a dávkování   chemie   MeSH
• stabilita léku MeSH
• sufentanil aplikace a dávkování   chemie   MeSH
• velikost částic MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• anestetika intravenózní MeSH
• fixní kombinace léků MeSH
• propofol MeSH
• sufentanil MeSH

This study presents an innovative approach that utilizes polymers with different topologies and properties as potential matrices for the poorly water-soluble active pharmaceutical ingredient piribedil (PBD). We investigated amorphous solid dispersions (ASDs) as well as micellar systems composed of PBD and (i) the commercial amphiphilic copolymer Soluplus, (ii) self-synthesized hydrophilic linear PVP (linPVP), and (iii) self-synthesized hydrophilic star-shaped PVP (starPVP). Differential scanning calorimetry, X-ray diffraction, Fourier-transform infrared, and broadband dielectric spectroscopy were applied to gain comprehensive insights into the thermal and structural properties, intermolecular interactions, global molecular dynamics, and recrystallization of the API from the amorphous PBD-polymer ASDs. The primary objective was to evaluate the impact of the type and topology of macromolecules, as well as the composition of binary formulations, on the physical stability of PBD in the amorphous form, phase transition temperatures, the API's recrystallization rate, and ultimately, the release of drug in the prepared ASDs and micelles. Most importantly, our research led to the discovery of new polymorphic form (II) of PBD that has not been previously described in the scientific literature. We also revealed that ASDs containing hydrophilic PVP polymers exhibit the best performance in stabilizing the amorphous form of the API, with the starPVP systems showing the highest stabilization effect. In contrast, for micellar systems, Soluplus turned out to be the most suitable candidate in terms of forming the self-assembles of the lowest size distribution among all systems. The long-term stability of the amorphous drug in PBD-Soluplus micelles was higher compared to PBD-starPVP ASD. Moreover, an improvement in the bioavailability of the API contained in all tested formulations (binary and micellar systems) was observed, with PBD-starPVP micelles exhibiting the most desirable drug release profile within the polymer matrix, as well as the highest concentration of released drug. The obtained data highlight the crucial role of the type and topology/architecture of the polymer in the design of novel pharmaceutical formulations.

• Klíčová slova
• Soluplus copolymer, amorphous solid dispersions, bioavailability, drug delivery system, micellar systems, piribedil, polyvinylpyrrolidone, solubility, topology of polymers,
• MeSH
• biologická dostupnost MeSH
• diferenciální skenovací kalorimetrie metody   MeSH
• difrakce rentgenového záření metody   MeSH
• farmaceutická chemie metody   MeSH
• hydrofobní a hydrofilní interakce MeSH
• krystalizace MeSH
• micely MeSH
• piribedil * chemie   MeSH
• polyethylenglykoly chemie   MeSH
• polymery chemie   MeSH
• polyvinyly chemie   MeSH
• příprava léků metody   MeSH
• rozpustnost MeSH
• spektroskopie infračervená s Fourierovou transformací metody   MeSH
• stabilita léku MeSH
• uvolňování léčiv MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• micely MeSH
• piribedil * MeSH
• polyethylenglykoly MeSH
• polymery MeSH
• polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer MeSH Prohlížeč
• polyvinyly MeSH

We investigated the soluble forms of the earliest activation antigen of human leukocyte CD69. This receptor is expressed at the cell surface as a type II homodimeric membrane protein. However, the elements necessary to prepare the soluble recombinant CD69 suitable for structural studies are a matter of controversy. We describe the physical, biochemical and in vivo characteristics of a highly stable soluble form of CD69 obtained by bacterial expression of an appropriate extracellular segment of this protein. Our construct has been derived from one used for CD69 crystallization by further optimization with regard to protein stability, solubility and easy crystallization under conditions promoting ligand binding. The resulting protein is stable at acidic pH and at temperatures of up to 65 degrees C, as revealed by long-term stability tests and thermal denaturation experiments. Protein NMR and crystallography confirmed the expected protein fold, and revealed additional details of the protein characteristics in solution. The soluble CD69 refolded in a form of noncovalent dimers, as revealed by gel filtration, sedimentation velocity measurements, NMR and dynamic light scattering. The soluble CD69 proved to be remarkably stable in vivo when injected into the bloodstream of experimental mice. More than 70% of the most stable CD69 proteins is preserved intact in the blood 24 h after injection, whereas the less stable CD69 variants are rapidly taken up by the liver.

• MeSH
• CD antigeny krev   chemie   MeSH
• diferenciační antigeny T-lymfocytů krev   chemie   MeSH
• dimerizace MeSH
• konformace proteinů MeSH
• krystalizace MeSH
• lektiny typu C MeSH
• lidé MeSH
• myši MeSH
• rekombinantní proteiny MeSH
• rozpustnost MeSH
• stabilita proteinů * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CD antigeny MeSH
• CD69 antigen MeSH Prohlížeč
• diferenciační antigeny T-lymfocytů MeSH
• lektiny typu C MeSH
• rekombinantní proteiny MeSH

• MeSH
• azosloučeniny * MeSH
• koncentrace vodíkových iontů MeSH
• kontaminace léku * MeSH
• kyseliny MeSH
• stabilita léku * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• azosloučeniny * MeSH
• kyseliny 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

INTRODUCTION: The study investigates the association between circadian phenotype (CP), its stability (interdaily stability - IS) and physical activity (PA) in a weight loss (WL) programme. METHODS: Seventy-five women in WL conservative treatment (BMI ≥ 25 kg/m2) were measured (for about 3 months in between 2016 and 2018) by actigraphy. RESULTS: We observed a difference in time of acrophase (p = 0.049), but no difference in IS (p = 0.533) between women who lost and did not lose weight. There was a difference in PA (mesor) between groups of women who lost weight compared to those who gained weight (p = 0.007). There was a relationship between IS and PA parametres mesor: p0.001; and the most active 10 h of a day (M10): p < 0.001 - the more stable were women in their rhythm, the more PA they have. Besides confirming a relationship between PA and WL, we also found a relation between WL and CP based on acrophase. Although no direct relationship was found for the indicators of rhythm stability (IS), they can be considered very important variables because of their close connection to PA - a main factor that contributes to the success of the WL programme. DISCUSSION: According to the results of the study, screening of the CP and its stability may be beneficial in the creation of an individualized WL plan.

• Klíčová slova
• Actigraphy, Circadian rhythm, Obesity, Physical activity, Sleep, Stability of the rhythm,
• Publikační typ
• časopisecké články MeSH

Physical fitness and dynamics of cardiovascular adaptation to the physical load were evaluated in research workers aged 40-55 years. After a special conditioning program for 19 months. The improvements concerned particularly the economy of hemodynamics and reduction of CHD risk score according to Hall. Three years after the termination of regular exercise program some volunteers were retested and the actual state of physical activity level, fitness and CHD risk score were evaluated again. 50% of the group recently examined, still performed regular sport activity, although at a lower intensity. In the group with a physical activity higher level of physical fitness, lower CHD risk score and lower incidence of coronary insufficiency symptoms was found. According to EPI a higher level of stability and middle level of extraversion was characteristic for their personality profile. Physical activity adequate to the actual health state may be supposed as important primary prevention of coronary heart disease.

• MeSH
• extrasystoly prevence a kontrola   MeSH
• koronární nemoc prevence a kontrola   MeSH
• lidé středního věku MeSH
• lidé MeSH
• osobnost MeSH
• riziko MeSH
• spotřeba kyslíku MeSH
• srdeční frekvence MeSH
• tělesná námaha * MeSH
• tělesná výkonnost * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Evidence has shown that higher levels of physical fitness (PF) in youth have beneficial effects on adult health-related outcomes. However, the tracking of separate PF components during adolescence has been less studied. Since PF often starts to rapidly decline during adolescence, it is necessary to provide information regarding critical time-point for interventions. This study aimed to analyze the extent of tracking the components of PF through PF tests. METHODS: In this longitudinal study, we recruited 240 adolescent girls with recoded data at 2 time-points (15 y and 17 y). PF included body composition (fat mass), explosive power of lower extremities (standing broad jump), muscle endurance of the trunk (sit-ups in 60 s), flexibility (sit-and-reach test), muscle endurance of lower extremities (squats in 60 s), aerobic endurance (the 800 m run test) and speed endurance (the 400 m run test). Tracking coefficients were calculated using generalized estimating equations. Tertiles (high, moderate and low) were calculated for each fitness component. RESULTS: The highest tracking coefficients between the two time-points were found for explosive power of lower extremities (β = 0.98), followed by flexibility (β = 0.89), body composition (β = 0.88), speed endurance (β = 0.86), aerobic endurance (β = 0.75), muscle endurance of lower extremities (β = 0.65), and muscle endurance of the trunk (β = 0.51). Tertile ratings remained stable across the two time-points. CONCLUSIONS: Moderate to high tracking of PF in adolescent girls suggests that interventions aiming to increase the level of PF should probably begin in early adolescence.

• Klíčová slova
• Generalized estimating equations, Performance, Secondary school, Stability, Youth,
• MeSH
• cvičení * fyziologie   MeSH
• dospělí MeSH
• lidé MeSH
• longitudinální studie MeSH
• mladiství MeSH
• následné studie MeSH
• složení těla MeSH
• tělesná výkonnost * fyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH