Encapsulation of 5-fluorouracil in cholesteryl-modified cyclodextrin: thermal, spectral, and computational assessment of drug inclusion efficiency.

This research investigates the encapsulation of 5-fluorouracil (5-FU) within cholesteryl-modified ß-cyclodextrin (CD21chol) and aims to elucidate the drug inclusion efficiency through a comprehensive analysis employing both experimental and computational techniques. The study employs thermogravimetric characterization to assess the thermal stability of the encapsulated complex and infrared measurements to explore the vibrational characteristics, providing valuable insights into the physicochemical properties. Additionally, molecular simulations are employed to evaluate the interactions between 5-FU and CD21chol on the molecular-level dynamics of drug encapsulation. This integrated approach facilitates a comprehensive understanding of encapsulation, offering valuable data for developing drug delivery systems.

Electrochemical and theoretical studies of the interaction between anticancer drug ponatinib and dsDNA.

In this study, electrochemical and theoretical studies were performed to explain the interaction mechanism between ponatinib (PNT), a third generation tyrosine kinase inhibitor, and dsDNA. The electrochemical part was conducted in phosphate-buffered saline (PBS) at physiological pH of 7.4 and in acetate buffer with a pH of 4.7, using square wave voltammetry. A boron-doped diamond electrode was used in a bulk-incubated solution. The theoretical part was investigated using computational methods, such as the semiempirical method PM7 and density functional theory (DFT). Significant differences in the electrochemical behavior of PNT in the presence of DNA confirmed the occurrence of interactions. The results obtained in the acetate buffer strongly suggested the preferential interaction of PNT with guanine residues. However, at physiological pH, it can be concluded that PNT interacts with dGua and dAdo in the dsDNA molecule. These results are consistent with outcomes from the theoretical studies, where quantum-chemical calculations showed that both electrochemically detectable nucleobases form hydrogen bonds with the drug. These bonds appeared to be stronger with guanine than with adenine. According to the computational studies, the dsDNA major groove is the energetically preferred site for the complexation of PNT.

Characteristics of Oat and Buckwheat Malt Grains for Use in the Production of Fermented Foods.

Malted gluten-free cereal grains and pseudo-cereals are interesting raw materials for producing fermented foods. The aim of the work was to assess selected technological quality characteristics and antioxidant properties of special malts in terms of use in the production of fermented foods. The research material consisted of malts made from oat, buckwheat, and brewing barley. Malting was performed on a microtechnical scale according to the standard scheme for brewing barley grain. The basic quality parameters of cereal grains obtained malts, and laboratory wort were assessed according to methods applicable in brewing. Atypical brewing malts were characterized by parameters such as malt extractability, protein solubilization, diastatic force, mash filtration time, and wort viscosity. The best results, comparable to barley malt, were obtained for naked oat malt. Malted buckwheat grains turned out to be the least biochemically modified, although their use in the production of beer and/or other fermented beverages is supported by the high content of bioactive substances and antioxidant potential. As the malting process of cereal plants improves their antioxidant properties and increases their nutritional value, oat and buckwheat malts can be successfully used to produce gluten-free fermented beverages or as an addition to fermented products, e.g., in baking and confectionery.

Influence of Pre-Treatment and Drying Methods on the Quality of Dried Carrot Properties as Snacks.

The aim of the current research was to evaluate the effect of pre-treatment and drying methods on the properties of dried carrots. Carrots were blanched (B) (1 or 3 min) or osmotic dehydrated (OD) (15 or 30 min) and dried by either convection (CD), microwave-convection (MW-CD), microwave-vacuum (MVD), or freeze-drying (FD). FD carrots showed the highest dry matter content (93.6-95.8%) and the lowest water activity (0.24-0.38). MVD carrots had lower dry matter content (79.5-95.8%) and two times more water activity (0.447-0.637) than FD. The highest color difference (∆E) in relation to raw material was noted in MVD samples (22-35) and the smallest in CD and FD (7-18), mainly due to the increase in brightness of the dried carrot. In general dried MCD carrot samples were characterized by the highest max force (hardness) (21.6-42.5 N; on average 34.7 N) in the breaking test and the lowest hardness was observed in the CD (10.8 N) ones. Pre-treatment and drying caused a significant decrease in the content of carotenoids (2.0-2.7 times) and chlorophyll (2.7-4.5 times) compared to the fresh carrot but a retention or increase in the total content of phenolics and antioxidant activity, especially in microwave-vacuum-dried carrots with an increase of even 2.7-2.9 times compared to raw material. High phenolic content (195.6-277.4 mg GA/100 g d.m.) was found in pre-osmotic dehydrated samples, and lower phenolic content was found in blanched samples (110.7-189.6 mg GA/100 g d.m.). Significantly, the highest average antioxidant activity was found in microwave-vacuum-dried samples (228.9 µmol Trolox/100 g d.m.). The results of this study indicate that microwave-vacuum-drying as an alternative to freeze-drying, including in combination with thermal or osmotic treatment, is very promising for the production of dried carrot snacks.

Quality of Life in Patients over Age 65 after Intestinal Ostomy Creation as Treatment of Large Intestine Disease.

INTRODUCTION: For patients with severe intestinal diseases, ostomy surgery can be health-preserving and even lifesaving. Unfortunately, stoma creation also results in a morbidity that patients must manage. Utilization of the correct ostomy appliances is essential for the patient to regain full daily fitness. Patients also now have access to stoma clinics and fistula support groups where they can receive education and emotional support. AIM: The aim of the study was to assess the quality of life of patients over 65 years of age with an intestinal stoma, created for treatment of severe colorectal disease. MATERIAL AND METHODS: The study involved 100 patients (52 women, 48 men) over the age of 65 with an intestinal stoma. Demographic and medical information was collected. The patients completed diagnostic surveys using the SF-36v2 questionnaire and the author's questionnaire. RESULTS: Analysis demonstrated statistically significant relationships between the quality of life of the patient population and stressors of everyday life. Furthermore, there are statistically significant relationships between quality of life and demographic factors including age, marital status, place of residence, and education. Only gender was not a statistically significant factor. CONCLUSIONS: A lengthened time interval to intestinal stoma creation is associated with an improved quality of life as well as psychological and emotional acceptance of the intestinal stoma. Support relationships with loved ones is associated with the acceptance of an intestinal stoma. There is a relationship between acceptance of an intestinal stoma and demographic factors such as marital status, place of residence, and education. Gender did not show any significant relationship. Stoma complications are not related to the acceptance of an intestinal stoma.

Factors Determining the Occurrence of Frailty Syndrome in Hospitalized Older Patients.

Frailty syndrome (FS) is a condition characterized by a decline in reserves, observed with aging. The most important consequences of the frailty syndrome include disability, hospitalization, fractures, institutionalization, and early mortality. The aim of this study was to identify the most important risk factors for FS in a group of older hospitalized patients in Poland. A total of one hundred and forty-one (78 women, 63 men) elderly patients from the Departments of Internal Medicine of the Medical University of Lodz (Poland) were recruited for this study. Frailty Instrument of the Survey of Health, Aging and Retirement in Europe (SHARE-FI), handgrip strength (HGS), depressive symptoms using the Geriatric Depression Scale (GDS), and functional ability (FA) using the Instrumental Activities of Daily Living (IADL) were assessed. According to SHARE-FI score, participants were divided into control group, frail, and pre-frail patients. Out of all 141 tested patients, FS was confirmed in 55 patients, and pre-frailty was observed in 52 patients. The occurrence of FS in the group of studied patients was related to age (p < 0.001), widowhood (p < 0.001), comorbidities (p < 0.001), heart diseases (p = 0.04), more medications taken (p < 0.001), lower FA (p < 0.001), weaker HGS, and depression (p < 0.001). The strongest positive correlations were between Share-FI score and the number of diseases (rS = 0.31), GDS (rS = 0.32), while negative correlations with IADL (rS = -0.47) and HGS (rS = -0.35). The study shows that FS is associated with age, comorbidities, number of medications taken, and widowhood. The present study has also demonstrated that FA, depression, and especially HGS are essential determinants of FS of elderly hospitalized people.

In Search of the Most Stable Molecular Configuration of Heptakis(2,6-O-dimethyl)-ß-cyclodextrin and Its Complex with Mianserin: A Comparison of the B3LYP-GD2 and M062X-GD3 Results.

Cyclodextrins are well known for their ability to form stable, highly soluble complexes with various substances, which makes them widely used as excipients in food, cosmetics, and pharmaceuticals. In this work, properties of heptakis(2,6-O-dimethyl)-ß-cyclodextrin (DM-ß-CD) in vacuo and in water, as well as its ability to bind the antidepressant drug mianserin (MIA) in aqueous solution, are investigated computationally. The results are shown to depend strongly on the density functional theory (DFT) applied. The most stable conformers of DM-ß-CD found with the B3LYP-GD2 method differ from these indicated by M062X-GD3 and other functionals. According to the latter, two crystal structures, ZULQAY and BOYFOK03, optimized in vacuo and in water, respectively, have the lowest energy. Both the B3LYP-GD2 and M062X-GD3 results show that all tested inclusion and noninclusion complexes of MIA:DM-ß-CD in stoichiometry 1:1 are stable in water. However, the structures and their energetic properties obtained with each method differ: in the most stable configurations, different aromatic rings of MIA are embedded inside DM-ß-CD, and the corresponding complexation energies (calculated with the 6-31++G(d,p) basis set and corrected for the basis set superposition error) are -29.6 (B3LYP-GD2) and -23.9 (M062X-GD3) kcal/mol. The NMR spectra of DM-ß-CD and MIA:DM-ß-CD are also compared.

Development of a High-Fibre Multigrain Bar Technology with the Addition of Curly Kale.

The aim of this study was to find the effect of kale and dietary fibre (DF) on the physicochemical properties, nutritional value and sensory quality of multigrain bars. A recipe of multigrain bars was prepared with the addition of fresh kale (20% and 30%) and DF preparations (apple, blackcurrant, chokeberry and hibiscus). The bars were baked at 180 °C for 20 min. These snack bars, based on pumpkin seeds, sunflower seeds, flaxseed and wholegrain oatmeal, are a high-calorie product (302-367 kcal/100 g). However, the composition of the bars encourages consumption. In addition to the ability to quickly satisfy hunger, such bars are rich in many natural ingredients that are considered pro-health (high fibre content (9.1-11.6 g/100 g), protein (11.2-14.3 g/100 g), fat (17.0-21.1 g/100 g, including unsaturated fatty acids), carbohydrates (20.5-24.0 g/100 g), as well as vitamins, minerals and a large number of substances from the antioxidant group. The addition of kale caused a significant increase of water content, but reduction in the value of all texture parameters (TPA profiles) as well as calorific values. The content of polyphenols was strongly and positively correlated with the antioxidant activity (r = 0.92). In the bars with 30% addition of kale (422 mg GA/100 g d.m.), the content of polyphenols was significantly higher than based ones (334 mg GA/100 g d.m.). Bars with the addition of the DF were characterized by a higher antioxidant activity, and the content of carotenoids, chlorophyll A and B and polyphenols. High sensory quality was demonstrated for all (from 4.8 to 7.1 on a 10-point scale). The addition of fibre preparations was also related to technological aspects and allows to create attractive bars without additional chemicals.

Insight into lipophilicity of deoxyribonucleoside­boron cluster conjugates.

Lipophilicity was investigated for 20 2'-deoxyribonucleoside derivatives modified with electron-neutral 1,2-dicarba-closo-dodecaborane, 1,12-dicarba-closo-dodecaborane, 7,8-dicarba-nido-undecaborate anion, and metallacarborane containing Co, Fe, or Cr. The partition coefficient (P) for neutral conjugates and the distribution coefficient (D7.4) for ionic compounds were determined as a lipophilicity descriptor using a shake-flask method. All modified nucleosides had P/D7.4 values higher than those of an appropriate unmodified 2'-closo-dodecaborane and metallacarborane was found to be three orders of magnitude higher than that of its unmodified counterpart. The lowest impact on the P/D7.4 values of the conjugates was observed for the 7,8-dicarba-nido-undecaborate anion. A preliminary molecular modeling study of a thymidine-carborane conjugate with ß-cyclodextrin confirmed the ability of the components to form an inclusion complex.

The role of tannic acid and sodium citrate in the synthesis of silver nanoparticles.

We describe herein the significance of a sodium citrate and tannic acid mixture in the synthesis of spherical silver nanoparticles (AgNPs). Monodisperse AgNPs were synthesized via reduction of silver nitrate using a mixture of two chemical agents: sodium citrate and tannic acid. The shape, size and size distribution of silver particles were determined by UV-Vis spectroscopy, dynamic light scattering (DLS) and scanning transmission electron microscopy (STEM). Special attention is given to understanding and experimentally confirming the exact role of the reagents (sodium citrate and tannic acid present in the reaction mixture) in AgNP synthesis. The oxidation and reduction potentials of silver, tannic acid and sodium citrate in their mixtures were determined using cyclic voltammetry. Possible structures of tannic acid and its adducts with citric acid were investigated in aqueous solution by performing computer simulations in conjunction with the semi-empirical PM7 method. The lowest energy structures found from the preliminary conformational search are shown, and the strength of the interaction between the two molecules was calculated. The compounds present on the surface of the AgNPs were identified using FT-IR spectroscopy, and the results are compared with the IR spectrum of tannic acid theoretically calculated using PM6 and PM7 methods. The obtained results clearly indicate that the combined use of sodium citrate and tannic acid produces monodisperse spherical AgNPs, as it allows control of the nucleation, growth and stabilization of the synthesis process. Graphical abstractᅟ.

Quantum chemical study and isothermal titration calorimetry of ß-cyclodextrin complexes with mianserin in aqueous solution.

ß-Cyclodextrin (ß-CD) is studied as a carrier of the drug mianserin (MIA). ß-CD with MIA adducts with 1 : 1 and 2 : 1 stoichiometry are investigated in vacuo and in water using quantum chemical methods: PM6 and B3LYP/6-31G(d,p). An effect of the dispersion correction GD2 and the basis set superposition error on the complexation energies is also evaluated. Additionally, the interaction between MIA hydrochloride and ß-CD in aqueous solution at 298.15 K is examined experimentally by isothermal titration calorimetry. Interaction parameters, such as the binding constant, enthalpy, entropy and Gibbs free energy, are presented. Analysis of the obtained data led to the following conclusions: the interaction of MIA with ß-CD is rather strong; there is no significant energetic difference between the 1 : 1 complexes of ß-CD with S-MIA and R-MIA enantiomers; the 2 : 1 (ß-CD : MIA) adduct is energetically more favorable than 1 : 1; the complex formation of MIA + ß-CD is enthalpy and entropy driven.

Simulations of Adiabatic Electrochemical Reduction of the CF3I Molecule-Assessment of Different Models.

The kinetics and mechanism of electrochemical reduction of the CF3I molecule are studied using molecular dynamics simulations. The potential energy surface used in the simulations is based on the Newns-Anderson-Schmickler Hamiltonian and on the analytical potentials fitted to points obtained from quantum calculations for the CF3I neutral molecule and anion. Two different sets of points were used for fitting: the first obtained in vacuo1 and the second in dimethyl sulfoxide,2 which yields two models, named respectively "VAC" and "SOLV." Additionally, each model was tested with two different values of the solvent reorganization energies: λ = 0.624 eV and λ = 1 eV. The results show that both models provide results which are qualitatively similar but differ quantitatively, mainly due to a shift in the overpotential η. The electron transfer coefficient is found to vary linearly at a certain range of overpotentials, but this relation changes for larger η, where it takes a parabolic-like form. The transfer coefficient is very sensitive to the λ value: at T = 298 K and η = 0.9 V, we report values α = 0.204 obtained for λ = 0.624 eV and α = 0.28 for λ = 1 eV.

Solvent effect on the potential energy surfaces for the one-electron reduction of CF3X (X = Cl, Br, I) molecules: a DFT PCM study.

In this article, an effect of solvent on potential energy surfaces, constructed at the PBE1PBE/aug-cc-pVTZ level vs C-X distances for the neutral molecules CF(3)X (X = Cl, Br, I) and the corresponding radical anions CF(3)X¯, is studied using the polarizable continuum model (PCM). The properties and energy changes in these compounds in the presence of argon, acetonitrile (ACN), and dimethyl sulfoxide (DMSO) are compared to the results obtained earlier in vacuo. The presence of solvent very weakly influences the neutral molecules, but it significantly changes properties of radical anions, such as structural parameters and partial charges on atoms. The effect of solvent is manifested also in strong modification of the potential energy surfaces, on which the minima corresponding to the locally stabilized forms of CF(3)X¯ are shallower in argon, and in ACN and DMSO, they almost disappear. This in turn results in much higher energy barriers (by about 0.2-0.3 eV) for the reductive cleavage of C-X bonds in polar solvents than in vacuo. Despite different dielectric constants of ACN and DMSO, the potential energy surfaces obtained in these two solvents are very similar, and the activation energies equal, respectively, 0.635 and 0.637 eV for CF(3)Cl; 0.479 and 0.481 eV for CF(3)Br; and 0.336 and 0.337 eV for CF(3)I.

Rosiglitazone treatment in nondiabetic subjects with nonalcoholic fatty liver disease.

INTRODUCTION: Pharmacological treatment options for nonalcoholic fatty liver disease (NAFLD) are limited. It has been suggested that thiazolidinediones may be useful in NAFLD treatment. OBJECTIVES: An open-label prospective study was conducted to assess the efficacy and safety of rosiglitazone treatment in nondiabetic subjects with NAFLD. PATIENTS AND METHODS: A total of 27 subjects (mean age 44 ± 11 years, body mass index 29.2 ± 3.1 kg/m2), with biopsy-confirmed NAFLD and no other complaints, were treated with rosiglitazone 4 mg daily for 6 months. RESULTS: No adverse events were observed during a 6-month treatment with rosiglitazone. Liver enzymes gradually decreased (alanine transaminase from 101 ± 59 to 58 ± 39 IU/l, aspartate transaminase from 52 ± 24 to 37 ± 15 IU/l; P <0.001). Plasma insulin levels decreased significantly by 30% to 50% in each time point of the oral glucose tolerance test. The homeostatic model assessment index decreased from 3.73 ± 1.89 to 2.06 ± 1.68 (P <0.001). No significant changes in plasma glucose were noted. Plasma adiponectin increased from 2198 ± 1853 to 5734 ± 1999 ng/ml (P <0.001). There were no statistically significant changes in body weight, glycated hemoglobin A1c, plasma lipids, or leptin. CONCLUSIONS: Rosiglitazone treatment in patients with NAFLD is safe, well-tolerated and leads to a significant improvement in liver function and insulin sensitivity, without adversely affecting the lipid profile.