Temperature-Sensitive Hydrogels as Carriers for Modulated Delivery of Acetaminophen.

The purposes of this study are the polymerization of temperature-sensitive copolymers based on N-isopropyl acrylamide and 10 mol % of 2-hydroxypropylmethacrylate, characterisations of their thermal, morphological and swelling properties, as well as the analysis of potential application in drug-delivery systems. Acetaminophen, the representative of non-steroidal anti-inflammatory drugs, was used as a model drug in this study. It is a common pain relief drug, which is also used for fever treatment. However, oral administration comes with certain health risks, mainly the overdose and frequent administration of up to four times a day. The goal of applying temperature-sensitive hydrogel is to enable extended administration once a day, depending on the body temperature. The swelling behavior of the obtained poly(N-isopropyl acrylamide-co-2-hydroxypropylmethacrylate) (p(NIPA/HPMA)) hydrogels and their temperature-sensitivity, kinetics and order of swelling processes at 18 and 38 °C were analyzed. The thermal properties of these hydrogels were observed by the DSC method, and the obtained thermograms showed both melting and glass transitions. The drug delivery system of p(NIPA/HPMA) hydrogels with loaded acetaminophen was analyzed using scanning electron microscopy and Fourier transform infrared spectroscopy methods. Structural analysis of FTIR spectra indicates that non-covalent intermolecular interactions of the type of hydrogen bonds were formed among functional groups of acetaminophen and side-chains of p(NIPA/HPMA) hydrogels. The surface structure of p(NIPA/HPMA) hydrogels after drug loading indicates the acetaminophen presence into the pores of the hydrogel network, and their loading efficiency was higher than 92%. Qualitative and quantitative analysis of acetaminophen, determined by the high-pressure liquid chromatography method, showed that about 90-99% of the loaded amount was released from p(NIPA/HPMA) hydrogels within 24 h. Kinetic parameters of the acetaminophen release under simulated gastrointestinal conditions were determined. Based on obtained results, the drug delivery system of temperature-sensitive p(NIPA/HPMA) hydrogels with loaded acetaminophen could be suitable for additional investigation for modulated drug administration, e.g., for extended drug administration.

Modified Sulfanilamide Release from Intelligent Poly(N-isopropylacrylamide) Hydrogels.

The aim of this study was to examine homopolymeric poly(N-isopropylacrylamide), p(NIPAM), hydrogels cross-linked with ethylene glycol dimethacrylate as carriers for sulfanilamide. Using FTIR, XRD and SEM methods, structural characterization of synthesized hydrogels before and after sulfanilamide incorporation was performed. The residual reactants content was analyzed using the HPLC method. The swelling behavior of p(NIPAM) hydrogels of different crosslinking degrees was monitored in relation to the temperature and pH values of the surrounding medium. The effect of temperature, pH, and crosslinker content on the sulfanilamide release from hydrogels was also examined. The results of the FTIR, XRD, and SEM analysis showed that sulfanilamide is incorporated into the p(NIPAM) hydrogels. The swelling of p(NIPAM) hydrogels depended on the temperature and crosslinker content while pH had no significant effect. The sulfanilamide loading efficiency increased with increasing hydrogel crosslinking degree, ranging from 87.36% to 95.29%. The sulfanilamide release from hydrogels was consistent with the swelling results-the increase of crosslinker content reduced the amount of released sulfanilamide. After 24 h, 73.3-93.5% of incorporated sulfanilamide was released from the hydrogels. Considering the thermosensitivity of hydrogels, volume phase transition temperature close to the physiological temperature, and the satisfactory results achieved for sulfanilamide incorporation and release, it can be concluded that p(NIPAM) based hydrogels are promising carriers for sulfanilamide.

Osage orange (Maclura pomifera (Raf.) Schneid) fruit extracts: UHPLC-DAD-ESI-MS/MS analysis, antioxidant activity and in vivo skin tests.

This work aimed to evaluate chemical profile, antioxidant activity and topical application safety of the raw Osage orange (Maclura pomifera (Raf.) Schneid) fruit extracts obtained by maceration using ethanol and acetone. Out of eighteen different compounds registered in the extracts, fifteen were identified by ultra-high-performance liquid chromatography-tandem mass spectrometry. Pomiferin and osajin were characteristic and representative compounds in both ethanolic and acetone extracts of the Osage orange fruit. Both extracts showed good antioxidant activity (EC50 = 0.03 mg/cm3) after 20 min of incubation. The topical administration safety of the extracts was evaluated in vivo by measuring skin biophysical parameters: electrical capacitance and erythema index, as indicators of stratum corneum hydration and irritation, respectively. Based on the results of the in vivo skin tests, it can be concluded that both of the Osage orange fruit extracts are safe for topical administration - they increased skin hydration and reduced skin irritation under the occlusion.

The Formulation of Curcumin: 2-Hydroxypropyl-ß-cyclodextrin Complex with Smart Hydrogel for Prolonged Release of Curcumin.

Curcumin comes from the plant species Curcuma longa and shows numerous pharmacological activities. There are numerous curcumin formulations with gels or cyclodextrins in order to increase its solubility and bioavailability. This paper presents the formulation of complex of curcumin with 2-hydroxypropyl-ß-cyclodextrin in a thermosensitive hydrogel, based on N-isopropylmethacrylamide and N-isopropylacrylamide with ethylene glycol dimethacrylate as a crosslinker. The product was characterized by chemical methods and also by FTIR, HPLC, DSC, SEM, XRD. The results show that synthesis was successfully done. With an increase in the quantity of crosslinker in the hydrogels, the starting release and the release rate of curcumin from the formulation of the complex with hydrogels decreases. The release rate of curcumin from the gel complex formulation is constant over time. It is possible to design a formulation that will release curcumin for more than 60 days. In order to determine the mechanism and kinetics of curcumin release, various mathematical models were applied by using the DDSolver package for Microsoft Excel application. The Korsmeyer-Peppas model best describes the release of curcumin from the gel formulation of the complex, while the values for the diffusion exponent (0.063-0.074) shows that mechanism of the release rate is based on diffusion.

Biomedical Applications of Thermosensitive Hydrogels for Controlled/Modulated Piroxicam Delivery.

The objectives of this study are the synthesis of thermosensitive poly(N-isopropylacrylamide-co-2-hydroxypropyl methacrylate), p(NiPAm-HPMet), hydrogels and the analysis of a drug-delivery system based on piroxicam, as a model drug, and synthesized hydrogels. A high pressure liquid chromatography method has been used in order to determine both qualitative and quantitative amounts of unreacted monomers and crosslinkers from polymerized hydrogels. Swelling kinetics and the order of a swelling process of the hydrogels have been analyzed at 10 and 40 °C. The copolymers' thermal properties have been monitored by the differential scanning calorimetry (DSC) method. DSC termograms have shown that melting occurs in two temperature intervals (142.36-150.72 °C and 153.14-156.49 °C). A matrix system with incorporated piroxicam has been analyzed by using FTIR and SEM methods. Structural analysis has demonstrated that intermolecular non-covalent interactions have been built between side-groups of copolymer and loaded piroxicam. Morphology of p(NiPAm-HPMet) after drug incorporation indicates the piroxicam presence into the copolymer pores. Kinetic parameters of the piroxicam release from hydrogels at 37 °C and pH 7.4 indicate that the fluid transport mechanism corresponds to Fickian diffusion. As a result, formulation of thermosensitive p(NiPAm-HPMet) hydrogels with incorporated piroxicam could be of interest for further testing as a drug carrier for modulated and prolonged release, especially for topical administration.

Occupational safety knowledge management in Slovenia, Croatia and Serbia.

This article elaborates the characteristics of knowledge management in the context of occupational safety and presents the results of research based on the assumption that there is a link between knowledge management and occupational safety performance, and that knowledge management can help in improving occupational safety performance. The research involved 645 occupational safety experts from three Balkan countries (Slovenia, Croatia and Serbia). The results showed that the knowledge management in the organization is related to all of the observed aspects of occupational safety performance: number of work-related injuries within the organization; number of lost working days due to injuries; costs caused by work-related injuries and occupational diseases; financial investments in occupational safety; assessment of the state of occupational safety. The practical implications of the article can be seen in the context of meeting the educational needs for continuous learning and improvement of knowledge/lifelong learning in the field of occupational safety.

Immunophenotypes of anti-SARS-CoV-2 responses associated with fatal COVID-19.

Background: The relationship between anti-SARS-CoV-2 humoral immune response, pathogenic inflammation, lymphocytes and fatal COVID-19 is poorly understood. Methods: A longitudinal prospective cohort of hospitalised patients with COVID-19 (n=254) was followed up to 35 days after admission (median, 8 days). We measured early anti-SARS-CoV-2 S1 antibody IgG levels and dynamic (698 samples) of quantitative circulating T-, B- and natural killer lymphocyte subsets and serum interleukin-6 (IL-6) response. We used machine learning to identify patterns of the immune response and related these patterns to the primary outcome of 28-day mortality in analyses adjusted for clinical severity factors. Results: Overall, 45 (18%) patients died within 28 days after hospitalisation. We identified six clusters representing discrete anti-SARS-CoV-2 immunophenotypes. Clusters differed considerably in COVID-19 survival. Two clusters, the anti-S1-IgGlowestTlowestBlowestNKmodIL-6mod, and the anti-S1-IgGhighTlowBmodNKmodIL-6highest had a high risk of fatal COVID-19 (HR 3.36-21.69; 95% CI 1.51-163.61 and HR 8.39-10.79; 95% CI 1.20-82.67; p≤0.03, respectively). The anti-S1-IgGhighestTlowestBmodNKmodIL-6mod and anti-S1-IgGlowThighestBhighestNKhighestIL-6low cluster were associated with moderate risk of mortality. In contrast, two clusters the anti-S1-IgGhighThighBmodNKmodIL-6low and anti-S1-IgGhighestThighestBhighNKhighIL-6lowest clusters were characterised by a very low risk of mortality. Conclusions: By employing unsupervised machine learning we identified multiple anti-SARS-CoV-2 immune response clusters and observed major differences in COVID-19 mortality between these clusters. Two discrete immune pathways may lead to fatal COVID-19. One is driven by impaired or delayed antiviral humoral immunity, independently of hyper-inflammation, and the other may arise through excessive IL-6-mediated host inflammation response, independently of the protective humoral response. Those observations could be explored further for application in clinical practice.

The Use of Acrylate Polymers in Dentistry.

The manuscript aimed to review the types of acrylate polymers used in dentistry, as well as their chemical, physical, mechanical, and biological properties. Regarding their consistency and purpose, dental acrylate polymers are divided into hard (brittle), which includes acrylates for the production of plate denture bases, obturator prostheses, epitheses and maxillofacial prostheses, their repairs and lining, and soft (flexible), which are used for lining denture bases in special indications. Concerning the composition and method of polymerization initiation, polymers for the production of denture bases are divided into four types: heat-, cold-, light-, and microwave-polymerized. CAD/CAM acrylate dentures are made from factory blocks of dental acrylates and show optimal mechanical and physical properties, undoubtedly better monomer polymerization and thus biocompatibility, and stability of the shape and colour of the base and dentures. Regardless of the number of advantages that these polymers have to offer, they also exhibit certain disadvantages. Technological development enables the enhancement of all acrylate properties to respond better to the demands of the profession. Special attention should be paid to improving the biological characteristics of acrylate polymers, due to reported adverse reactions of patients and dental staff to potentially toxic substances released during their preparation and use.

Antimicrobial Properties of Silver-Modified Denture Base Resins.

The surface quality of denture base resins allows for easy colonization by microorganisms including Candida albicans and Staphylococcus aureus, which cause major diseases of the oral cavity such as denture stomatitis. The widespread use of silver nanoparticles (AgNPs) in various fields of medicine has led to research of their possible application in dentistry, mostly in the prevention of bacterial adhesion, proliferation, and biofilm formation. The aim of the study was to synthesize cold and heat-curing denture base resins modified with AgNPs and AgCl, and evaluate the potential of the modified resins to reduce the growth of C. albicans and S.aureus. The produced material was characterized by Fourier transform infrared spectroscopy (FTIR). The antimicrobial potential of the modified material was demonstrated by the disc-diffusion method, microdilution method, and a modified microdilution method (i.e., disk-diffusion method in broth with viable counting). Spectroscopy confirmed the incorporation of biocidal materials into the structure of the denture base resins. The AgCl and AgNPs modified resins showed an antimicrobial effect. The significance of the study is in the potential therapeutic effects of the modified materials for prevention and threating staphylococci and candida in elderly patients, who are in most cases denture wearers and have a greater susceptibility to develop opportunistic infections. Modified denture base resins can significantly reduce the presence of infection at the point of contact between the denture and the mucous membrane of the prosthetic restoration. Biological tests of modified denture base resins will follow.

Electrospun Poly(lactide) Fibers as Carriers for Controlled Release of Biochanin A.

The aim of this study is to investigate the possibility of using electrospun polylactide (PLA) fibers as a carrier of the phytoestrogen biochanin A. Polylactide fibers were prepared with different contents of biochanin A by using an electrospinning method at specific process parameters. The obtained electrospun polylactide fibers, as carriers of biochanin A, were characterized by means of different methods. The presented results showed that the mechanical properties of PLA have not changed significantly in the presence of biochanin A. Scanning electron microscopy showed that the fine fiber structure is retained without visible deformations and biochanin A crystals on the surface of the fibres. The analysis by infrared spectroscopy showed that there are no strong interactions between polylactide and biochanin A molecules, which is a good prerequisite for the diffusion release of biochanin A from PLA fibers.The release of biochanin A from PLA fibers in buffer solution pH 7.4 at 37 °C was monitored by applying the HPLC method. The rate and time of the release of biochanin A from PLA fibers is in correlation with the amount of the active ingredient in the matrix of the carrier and follows zero-order kinetics. PLA fibers with biochanin A exhibit concentration-dependent activity on proliferation and migration of L929 fibroblasts in direct culture system in vitro, and proved to be suitable for a potential formulation for use in wound healing.

Curcumin: Biological Activities and Modern Pharmaceutical Forms.

Curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-hepta-1,6-diene-3,5-dione) is a natural lipophilic polyphenol that exhibits significant pharmacological effects in vitro and in vivo through various mechanisms of action. Numerous studies have identified and characterised the pharmacokinetic, pharmacodynamic, and clinical properties of curcumin. Curcumin has an anti-inflammatory, antioxidative, antinociceptive, antiparasitic, antimalarial effect, and it is used as a wound-healing agent. However, poor curcumin absorption in the small intestine, fast metabolism, and fast systemic elimination cause poor bioavailability of curcumin in human beings. In order to overcome these problems, a number of curcumin formulations have been developed. The aim of this paper is to provide an overview of recent research in biological and pharmaceutical aspects of curcumin, methods of sample preparation for its isolation (Soxhlet extraction, ultrasound extraction, pressurised fluid extraction, microwave extraction, enzyme-assisted aided extraction), analytical methods (FTIR, NIR, FT-Raman, UV-VIS, NMR, XRD, DSC, TLC, HPLC, HPTLC, LC-MS, UPLC/Q-TOF-MS) for identification and quantification of curcumin in different matrices, and different techniques for developing formulations. The optimal sample preparation and use of an appropriate analytical method will significantly improve the evaluation of formulations and the biological activity of curcumin.

Workplace stress of occupational safety specialists in Croatia and Serbia.

BACKGROUND: Numerous studies have shown that work often causes stress in employees and even in occupational safety experts. Occupational stress can lead to serious health consequences for employees. As the job of occupational safety experts is very responsible, they are more exposed to workplace stress and more vulnerable to its consequences. This study resulted with expertise on the work related stress of safety experts in Croatia and Serbia. OBJECTIVE: This study examined workplace stress of occupational safety experts in Croatia and Serbia. METHODS: Surveys were used to collect original data and statistical methods were used for data processing and analysis. RESULTS: There was a correlation between the level of stress on safety expert's jobs and stress levels related to the status of safety experts as dependent variables and the organization profile related with safety experts' employment as independent variables. Stress of safety experts related to activities and the status of safety experts were of medium level. CONCLUSION: There is a need for preventive protection from stress in this profession. Continuous education of safety experts plays a key role in stress prevention, not only for the safety experts but it also plays a key role in stress management throughout the organization.

Semi-Crystalline Copolymer Hydrogels as Smart Drug Carriers: In Vitro Thermo-Responsive Naproxen Release Study.

In this study, poly(N-isopropylacrylamide-co-2-hydroxypropyl methacrylate) hydrogels were synthesized using free radical initiated copolymerization method. Four hydrogels with different cross-linker concentrations were prepared. Semi-crystalline, cross-linked copolymer networks were confirmed by FTIR, SEM and XRD analysis. Variation of swelling behaviour was monitored gravimetrically and thermo-responsiveness has been noticed. An application of synthesized thermo-responsive hydrogels as carriers for the modulated release of anti-inflammatory model drug was investigated. Moreover, naproxen loading into these hydrogels was also determined using FTIR, SEM and XRD techniques and release was analyzed using HPLC method at simulated physiological conditions. Swelling kinetic and mechanism of water transport, as well as diffusion of naproxen through the hydrogels were analyzed. Thus, the aim of this work was to study various compositions of obtained hydrogels and their possibility of application as a thermo-responsive carrier for prolonged naproxen release in order to evaluate as a potential candidate for drug carrier in future pharmaceutical applications.

Modified Biochanin A Release from Dual pH- and Thermo-Responsive Copolymer Hydrogels.

The temperature- and pH-responsive poly(N-isopropylacrylamide-co-acrylic acid), p(NIPAM-co-AA), copolymer was synthesized by free radical polymerization and examined as a carrier for modified release of biochanin A. Biochanin A is a biologically active methoxylated isoflavone which exhibits estrogenic and other pharmacological activities. Due to its poor aqueous solubility and extensive first-pass metabolism, biochanin A has low bioavailability. The aim of this work was to incorporate biochanin A into the synthesized p(NIPAM-co-AA) copolymer and to examine its release at the body temperature and pH values that correspond to pH values of vaginal and rectal cavities. The amount of released biochanin A was monitored by the ultra-visible spectroscopy (UV-Vis) method. The structure of synthesized p(NIPAM-co-AA) copolymer and copolymer with incorporated biochanin A were characterized by using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) methods. The content of residual monomers in the synthesized copolymer was analyzed by using the high-pressure liquid chromatography (HPLC) method. The swelling behavior of p(NIPAM-co-AA) copolymer was monitored in relation to the temperature and pH values of the surrounding medium. For modelling the process of p(NIPAM-co-AA) copolymer swelling, the full three-level factorial design was applied.

Amino-modified hollow alumina spheres: effective adsorbent for Cd2+, Pb2+, As(V), and diclofenac removal.

A simple sol-gel method and external gelatinization method of hollow alumina spheres synthesis were developed in this study. The spheres were modified with polyethyleneimine (PEI) producing PEI-Al2O3 via (3-glycidyloxypropyl)trimethoxy-silane, GLYMO, linker. Characterization results, obtained using XRD and SEM microscopy revealed spherical geometry with a hollow core of PEI-Al2O3 adsorbent. Introduction of a large number of the amino group, 6.9 mmol g-1, contributes to achieving high adsorption capacities, qm, of 95.6, 124.9, 61.3, and 125.9 mg g-1 for Cd2+, Pb2+, As(V), and DCF, respectively, which is obtained by using the Langmuir model. Thermodynamic studies indicated feasible adsorption and higher spontaneity with temperature increase. The kinetic study conveniently modeled using pseudo-second-order (PSO) and Weber-Morris kinetic model, as well as single resistance mass transfer model, indicated a change of the contribution of diffusional processes during adsorption with a dominance of intra-particle diffusion. The fixed-bed column adsorption data, fitted using Bohart-Adams, Clark, Yoon-Nelson, and Thomas models, showed lower capacity in comparison to batch study, and thus clear potential applicability of PEI-Al2O3 was deduced even at a high loading of feed water.

Intelligent Poly(N-Isopropylmethacrylamide) Hydrogels: Synthesis, Structure Characterization, Stimuli-Responsive Swelling Properties, and Their Radiation Decomposition.

Poly(N-isopropylmethacrylamide) (p(NiPMAm)) is one of the lesser known homopolymers that has significant potential for designing new "intelligent" materials. The aims of this work were the synthesis a series of cross-linked p(NiPMAm) hydrogels by the free radical polymerization method and the application of gamma-ray radiation for additional cross-linking. The synthesized p(NiPMAm) hydrogels were structurally characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The amount of unreacted monomers was analyzed using high pressure liquid chromatography (HPLC) to evaluate conversion of monomers into polymers. The swelling behavior was monitored in dependence of pH and temperature changes. The previous aim of gamma-ray radiation was the further the cross-linkage of the obtained hydrogel sample in the gelatinous, paste-like state, but the gamma-ray radiation caused decomposition. After absorbing irradiation doses, they transformed into the liquid phase. The results obtained by the gel permeation chromatography (GPC) method indicated that only oligomers and monomers were present in the irradiated liquid material, without molecules with a higher average molar mass, i.e., that the decomposition of the hydrogels occurred. Additionally, the irradiated liquid material was analyzed using the static headspace gas chromatography mass spectrometry (HSS-GC/MS) and gas chromatography/flame ionization detection (HSS-GC/FID) methods. The presence of unchanged initiator molecule and a dominant amount of four new molecules that were different from homopolymers and the reactant (monomer and cross-linker) were determined.

Educational needs of employees in work-related stress management.

BACKGROUND: Dynamic and intense socio-economic, scientific and technological development has both positive and negative effects on the business world. Due to increasing problems of work-related stress, the issue of stress management has arisen. Primary stress management and proactive interventions in work-related stress prevention are specifically activated. In this regard, the issue of educational needs of employees for the prevention of work-related stress is of particular importance. OBJECTIVE: The basic concern that has drawn our attention is whether employees generally show the desire and need to adopt the knowledge in the field of work-related stress prevention and relief and whether they are supported by the management of their business organization. METHODS: We used several methods to conduct this research: survey, scaling and comparative method. The comparative method was used for the analysis of legal documents in the field of occupational safety and health in six Balkan countries with the aim of determining the legal obligations of employers in managing workplace stress. The research population consisted of employees in small and medium-sized enterprises in the city of Kraljevo (the Republic of Serbia), while the research sample was determined by a random sampling method and included 450 respondents. RESULTS: Despite the recommendations of international organizations, the employers in most countries are not legally bound to deal with work-related stress management. The results have shown that there is a correlation between work-related risks/stressors and educational needs of employees for learning or acquiring knowledge in the field of work-related stress prevention. Employees express the desire to become acquainted with the possibilities of overcoming work-related stress. CONCLUSION: Employees' education and training have an invaluable role and considerable importance in primary, work-related stress management. The knowledge about the causes and mechanisms of work-related stress development is an important step towards its prevention. The research has shown that employees express the need for acquiring knowledge to prevent stress at work. In this regard, it is necessary to provide legally binding support of the manager in order to undertake the activities of work-related stress management. Interventions should target work-related stress at its source with a focus on prevention rather than an individual approach whose long-term benefits are uncertain.

Chemical Analysis of Selected Seaweeds and Seagrass from the Adriatic Coast of Montenegro.

Three seaweeds (Halimeda tuna, Codium bursa and Cystoseira barbata) and one seagrass (Cymodocea nodosa) were collected from the Coast of Montenegro, Gulf of Boka Kotorska and their chemical analysis was performed. In seagrass C. nodosa, three phenolic compounds were identified (diosmetin 7-sulfate, caftaric and coutaric acid). The content of ß-glucan, fatty acids, sterols and micro- and macro-elements were investigated among all samples. The highest content of ß-glucan was detected in C. nodosa seagrass (13.04±0.42 g/100 g). The highest polyunsaturated fatty acids (PUFAs) level was reported in C. barbata, the brown alga (7.157 mg/g), which also had the significant sterol content (fucosterol, 21.76±0.1 µg/g). Green algae, C. bursa and H. tuna, showed the highest level of sterols (ß-sitosterol, 95.21±0.16 µg/g and 73.90±0.08 µg/g, respectively). H. tuna had the highest content of calcium (Ca) in amount of 55125 µg/g. In C. bursa, C. barbata and C. nodosa, the Na/K ratio was low (0.43, 0.46 and 0.69, respectively).

The effect of complexation with cyclodextrins on the antioxidant and antimicrobial activity of ellagic acid.

PURPOSE: The aim of the paper was to develop the simple procedures for preparation of inclusion complexes of ellagic acid (EA) with cyclodextrins (CDs) and to investigate their antioxidant and antimicrobial activity. METHODS: The structural characterization was carried out using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and nuclear magnetic resonance (NMR) methods. The phase solubility technique was used to investigate the interactions between 'host' and 'guest' molecules and to estimate the molar ratio between them. The antioxidant and antimicrobial activity of EA and inclusion complexes were determined. RESULTS: The apparent stability constants were found to be 117 dm3 mol-1 for the complex with ß-CD and 161 dm3 mol-1 for the complex with (2-hydroxypropyl)-ß-cyclodextrin (HP-ß-CD). The results of phase-solubility studies showed that EA formed the inclusion complexes with CDs in the molar ratio of 1:1. The calculated half-maximal inhibitory concentration was 41.18 µg cm-3 for butyl hydroxy toluene, 1.96 µg cm-3 for EA, 0.88 µg cm-3 for inclusion complex with HP-ß-CD, and 1.27 µg cm-3 for inclusion complex with ß-CD. CONCLUSION: The stability constants indicated the rapid release of EA from the inclusion complexes in the aqueous medium at 25 °C. The antioxidant activity of EA was increased, while the antimicrobial activity was preserved after complexation with CDs.

Is it possible to improve prognostic value of NCCN-IPI in patients with diffuse large B cell lymphoma? The prognostic significance of comorbidities.

The prognostic value of the International Prognostic Index (IPI) has been re-evaluated in the rituximab-treated diffuse large B cell lymphoma (DLBCL) patients. Accordingly, National Comprehensive Cancer Network-IPI (NCCN-IPI) has been introduced to estimate prognosis of DLBCL patients. However, comorbidities that frequently affect elderly DLBCL patients were not analyzed. The aim of this study was to evaluate the prognostic significance of comorbidities using Charlson Comorbidity Index (CCI) in 962 DLBCL patients. According to CCI, majority of patients (73.6%) did not have any comorbidity, while high CCI (≥ 2) was observed in 71/962 (7.4%) patients, and in 55/426 (12.9%) of the elderly patients aged ≥ 60 years. When the CCI was analyzed in a multivariate model along with the NCCN-IPI parameters, it stood out as a threefold independent risk factor of a lethal outcome. Also, we have developed a novel comorbidity-NCCN-IPI (cNCCN-IPI) by adding additional 3 points if the patient had a CCI ≥ 2. Four risk groups emerged with the following patient distribution in low, low-intermediate, high-intermediate, and high group: 3.4, 34.3, 49.4, and 12.5%, respectively. The prognostic value of the new cNCCN-IPI was 2.1% improved compared to that of the IPI, and 1.3% improved compared to that of the NCCN-IPI (p < 0.05). This difference was more pronounced in elderly patients, in whom the cNCCN-IPI showed a 5.1% better discriminative power compared to that of the IPI, and 3.6% better compared to the NCCN-IPI. The NCCN-IPI enhanced by the CCI and combined with redistributed risk groups is better for differentiating risk categories in unselected DLBCL patients, especially in the elderly.