Identification of antiepilepitic drug-target interactions in public databases

Epilepsy is affecting people of all age and gender. The disease is traditionally treated with application of antiepileptic drugs. The therapy choice mostly relies on the differential diagnosis which is not always easy to be deducted. The treatment guidelines and antiepileptics are diverged according to major epilepsy types – generalized and focal epilepsy. However, prospective studies of antiepileptic drug effectiveness on the European cohort have shown that pharmacoresponse is patient dependent. In this thesis the antiepileptic drug prescription trend in this cohort in generalized and focal epilepsy patients was investigated. Moreover, the use of antiepileptics in the clinics from the EpiPGX database was compared to the findings of their use in general practices in the UK. To explain the difference in patient response to therapy AED-target interactions were investigated on the level of databases. In addition, with the discovery of new genes implicated in epilepsy and success of drugs of other groups such as quinidine and fampridine in treating the symptoms, the drug-repurposing found its application in epilepsy. In this thesis, quinidine-KCNT1 and fampridine-KCNA2 interactions were investigated in order to estimate the feasibility of using public databases to select drug-target interactions for clinical application. The investigation relied mainly on the ChEMBL database. However, these genes were not found among antiepileptic drug targets in the database. Quinidine and fampridine were assay associated with other AED targets. The results suggest that the therapy choice for treatment of rare forms of epilepsy underlined by channelopathies could be significantly expanded, but that database approach requires high level of drug-target selection criteria and text mining

Supercritical foaming and impregnation of polycaprolactone and polycaprolactone-hydroxyapatite composites with carvacrol

Producción CientíficaPolycaprolactone (PCL) and polycaprolactone-hydroxyapatite (PCL-HA) scaffolds were produced by foaming in supercritical carbon dioxide (scCO2) at 20 MPa, as well as in one-step foaming and impregnation process using carvacrol as an antibacterial agent with proven activity against Gram-positive and Gram-negative bacteria. The experimental design was developed to study the influence of temperature (40 °C and 50 °C), HA content (10 and 20 wt.%), and depressurization rate (one and two-step decompression) on the foams’ morphology, porosity, pore size distribution, and carvacrol impregnation yield. The characterization of the foams was carried out using scanning electron microscopy (SEM, SEM-FIB), Gay-Lussac density bottle measurements, and Fourier–transform infrared (FTIR) analyses. The obtained results demonstrate that processing PCL and PCL-HA scaffolds by means of scCO2 foaming enables preparing foams with porosity in the range of 65.55–74.39% and 61.98–67.13%, at 40 °C and 50 °C, respectively. The presence of carvacrol led to a lower porosity. At 40 °C and one-step decompression at a slow rate, the porosity of impregnated scaffolds was higher than at 50 °C and two- step fast decompression. However, a narrower pore size distribution was obtained at the last processing conditions. PCL scaffolds with HA resulted in higher carvacrol impregnation yields than neat PCL foams. The highest carvacrol loading (10.57%) was observed in the scaffold with 10 wt.% HA obtained at 50 °C.Narodowe Centrum Nauki (Polonia) - (grant 2018/31/B/ ST8/01826)Agencia Nacional de Investigación y Desarrollo de Chile (ANID) - (project 120130)Programa de Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia - (Project AFB180001

Supercritical Fluid Applications in the Design of Novel Antimicrobial Materials

Bacterial resistance to antibiotics is one of the biggest problems in the modern world. The prevention of bacterial spreading from hospitals to the community and vice versa is an issue we have to deal with. This review presents a vast potential of contemporary high-pressure techniques in the design of materials with antimicrobial activity. Scientists from all over the world came up with ideas on how to exploit extraordinary properties of supercritical fluids in the production of advantageous materials in an environmentally friendly way. The review summarizes reported methods and results

Utilization of supercritical CO2 in bioactive principles isolation from Helichrysum italicum and their adsorption on selected fabrics

Helichrysum italicum (Roth) G. Don fil., Asteraceae, possesses numerous secondary plant metabolites with a wide range of biological activities. Yet, data on the potential of supercritical fluid extraction (SFE) in their isolation are scarce. This study provides analyses of the chemical profiles of extracts obtained by SFE with or without ethanol as a cosolvent using GC-FID, GC-MS, HPLC, and UHPLC-MS techniques. Among the compounds with proven biological activity identified, the presence of arzanol was confirmed. In the next step, the integrated process of supercritical fluid extraction and impregnation was applied to deliver active compounds to cotton gauze and polypropylene fabric for possible topical applications. The analytical procedures results showed a considerable affinity of both textile materials for incorporating active components present in the H. italicum. The study indicated the high-pressure techniques applied as very efficient in the isolation of bioactive components from H. italicum and their adsorption on selected carriers

INDeLER: eLearning Personalization by Mapping Studentâ??s Learning Style and Preference to Metadata

This paper presents the process of developing Student profile by mapping students categories explored with Felder- Solomanâ??s ILS questionnaire to the appropriate value of the personalization vector XYZ, and by deriving vector's values from the acquired studentâ??s answers on Preference test. Obtained values for XYZ vector form the PeLCoM metadata which provide recommendations for creating personalized eLearning experience. The architecture of Personalized eLearning System INDeLER is presented. INDeLER system derives studentâ??s profile, provides sequencing of personalized eLearning sessions and supports scenario for designing lessons content tailored to the individual student needs. Further, we describe how the personalization system INDeLER includes teacher's influence to the eLearning experience by composing different pedagogical aspects and corresponding didacticsâ?? and methodicâ?? processes to the unique way of teaching tailored to the particular student needs. The example of INDeLER personalization process is also shown

Modified approach to PROMETHEE for multi-criteria decision-making

This paper presents a modification of PROMETHEE for multi -criteria decision- making. The authors of PROMETHEE have defined six generalised preference functions in order to express their preferences for particular criteria. A modified approach to PROMETHEE is based on the Universal preference function which replaces the six proposed functions and generates an unlimited number of other preference functions. By applying this method, we can express all the complexity of selecting preference functions in the problems of optimisation by PROMETHEE

Comparative analyses of diffusion coefficients for different extraction processes from thyme

This work was aimed to analyze kinetics and mass transfer phenomena for different extraction processes from thyme (Thymus vulgaris L.) leaves. Different extraction processes with ethanol were studied: Soxhlet extraction and ultrasound-assisted batch extraction on the laboratory scale as well as pilot plant batch extraction with mixing. The extraction processes with ethanol were compared to the process of supercritical carbon dioxide extraction performed at 10 MPa and 40°C. Experimental data were analyzed by mathematical model derived from the Fick’s second law to determine and compare diffusion coefficients in the periods of constant and decreasing extraction rate. In the fast extraction period, values of diffusion coefficients were one to three orders of magnitude higher compared to those determined for the period of slow extraction. The highest diffusion coefficient was reported for the fast extraction period of supercritical fluid extraction. In the case of extraction processes with ethanol, ultrasound, stirring and extraction temperature increase enhanced mass transfer rate in the washing phase. On the other hand, ultrasound contributed the most to the increase of mass transfer rate in the period of slow extraction

Comparative analysis of mathematical models for supercritical extraction simulation from industrially valuable lamiaceae herbs

The present study was aimed to compare different mathematical models used to simulate process of supercritical extraction from commercially important Lamiaceae herbs. Supercritical extractions with carbon dioxide from rosemary, sage, thyme and lavender originated from the southern Balkan region were performed at 10MPa and 40 degrees C. Obtained extraction curves were simulated by the model based on the heat transfer analogy, Sovova's model and the model on the micro-scale. The models were used to analyse mass transfer phenomena and to quantify mass transfer parameters in the fluid and/or solid phase as well as the solubility of the solute in supercritical phase