Na tropie środków przydatnych w terapii lub profilaktyce choroby Alzheimera

Mimo olbrzymich inwestycji kadrowych i finansowych, próby pozyskiwania nowych przełomowych leków okazują się coraz trudniejsze, a w przypadku choroby Alzheimera wręcz nieskuteczne. Farmakoterapia choroby Alzheimera i innych chorób, w których obserwuje się tworzenie fibryli białka amyloidowego, nie rokuje całkowitego wyleczenia czy poprawy funkcjonowania chorych. Rutynowo stosuje się leczenie paliatywne, objawowe lub substytucyjne. W fazie eksperymentalnej jest terapia skojarzona, z użyciem środków działających plejotropowo oraz substancji, które mają hamować zwyrodnienie neurofibrylarne. Obserwacje epidemiologiczne, kojarzone z paleniem tytoniu, skierowały uwagę badaczy na podjednostkę α7 neuronowego receptora cholinergicznego typu nikotynowego (α7nAChR). Najbardziej obiecujące i racjonalne wydają się jednak próby ingerencji farmakologicznej w proces agregacji amyloidu czy rozpuszczania jego złogów. Istnieją doniesienia o takim działaniu dla różnych środków, szczególnie przyjmowanych długotrwale. Obok nikotyny i pochodnych wchodzących w skład etnograficznie charakterystycznych używek, wskazuje się także na niektóre składniki prawidłowej diety, w tym kwasy tłuszczowe omega-3. W badaniach zainicjowanych w Katedrze Biofarmacji i Farmakodynamiki Gdańskiego Uniwersytetu Medycznego, mierzono nową metodą elektrochemicznospektroskopową powinowactwo wielu związków pirydynowych i piperydynowych, zwłaszcza alkaloidów występujących w używkach i przyprawach, do amyloidu β(1–42). Wykazano silne właściwości wiązania amyloidu z wieloma wytypowanymi do badań związkami. Szczególnie obiecująco z punktu widzenia profilaktyki choroby Alzheimera przedstawia się alkaloid trigonellina, charakterystyczny dla powszechnie spożywanych w Azji (także jako składnik curry) i znanych w Polsce nasion kozieradki, która należy do surowców roślinnych uwzględnionych w obowiązującej Farmakopei Europejskiej

Affinity Chromatography Method for Determination of Binding of Drugs to Melanin and Evaluation of Side Effect Potential of Antipsychotic Agents

The extrapyramidal side effect parameters of typical and atypical antypsychotics were correlated with affinity chromatographic data determined on the melanin-based column. The chromatographic study was performed according to the hypothesis that extrapyramidal symptoms (EPS) as side effects of the use of antipsychotic drugs at clinically effective doses are correlated to the affinity of these drugs to neuromelanin. For that aim the polymerization product of L-DOPA (melanin) was immobilized onto aminopropyl silica and the binding efficiency of melanin towards antipsychotics has been determined. The results indicate that melanin based-column can be used to evaluate the risk of EPS of drug candidates to antipsychotic drug therapy

Ionic Liquids as Mobile Phase Additives for Feasible Assay of Naphazoline in Pharmaceutical Formulation by HPTLC–UV–Densitometric Method

A specific and reliable High-Performance Thin Layer Chromatography (HPTLC) with densitometry detection method has been developed for determination of naphazoline nitrate in nasal drops. The best separation of basic analyte, without spot tailing, was achieved using the mobile phase composed of acetonitrile:water (60:40,v/v) with 1.5 % (v/v) imidazolium-class ionic liquid added and the plates covered with stationary phase based on the RP-18 with F254S (10cm x 20cm). The presented results confirm that imidazolium tetrafluoroborate ionic liquids are efficient suppressors of free silanols, which are considered to be responsible for troublesome and irreproducible chromatographic determinations of basic compounds. The developed chromatographic system was found to be convenient in use and at the same time providing a repeatable assay of naphazoline nitrate in nasal drops, which could not be obtained with the use of standard silanol suppressing mobile phase additives, like triethylamine (TEA) or dimethyloctylamine (DMOA)

Partial Least Square and Hierarchical Clustering in ADMET Modeling: Prediction of Blood - Brain Barrier Permeation of alpha-Adrenergic and Imidazoline Receptor Ligands

PURPOSE. Rate of brain penetration (logPS), brain/plasma equilibration rate (logPS-brain), and extent of blood-brain barrier permeation (logBB) of 29 alpha-adrenergic and imidazoline-receptors ligands were examined in Quantitative-Structure-Property Relationship (QSPR) study. METHODS. Experimentally determined chromatographic retention data (logKw at pH 4.4, slope (S) at pH 4.4, logKw at pH 7.4, slope (S) at pH 7.4, logKw at pH 9.1, and slope (S) at pH 9.1) and capillary electrophoresis migration parameters (mu(eff) at pH 4.4, mu(eff) at pH 7.4, and mu(eff) at pH 9.1), together with calculated molecular descriptors, were used as independent variables in the QSPR study by use of partial least square (PLS) methodology. RESULTS. Predictive potential of the formed QSPR models, QSPR(logPS), QSPR(logPS-brain), QSPR(logBB), was confirmed by cross- and external validation. Hydrophilicity (Hy) and H-indices (H7m) were selected as significant parameters negatively correlated with both logPS and logPS-brain, while topological polar surface area (TPSA(NO)) was chosen as molecular descriptor negatively correlated with both logPS and logBB. The principal component analysis (PCA) and hierarchical clustering analysis (HCA) were applied to cluster examined drugs based on their chromatographic, electrophoretic and molecular properties. Significant positive correlations were obtained between the slope (S) at pH 7.4 and logBB in A/B cluster and between the logKw at pH 9.1 and logPS in C/D cluster. CONCLUSIONS. Results of the QSPR, clustering and correlation studies could be used as novel tool for evaluation of blood-brain barrier permeation of related alpha-adrenergic/imidazoline receptor ligands

The state-of-the-art determination of urinary nucleosides using chromatographic techniques “hyphenated” with advanced bioinformatic methods

Over the last decade metabolomics has gained increasing popularity and significance in life sciences. Together with genomics, transcriptomics and proteomics, metabolomics provides additional information on specific reactions occurring in humans, allowing us to understand some of the metabolic pathways in pathological processes. Abnormal levels of such metabolites as nucleosides in the urine of cancer patients (abnormal in relation to the levels observed in healthy volunteers) seem to be an original potential diagnostic marker of carcinogenesis. However, the expectations regarding the diagnostic value of nucleosides may only be justified once an appropriate analytical procedure has been applied for their determination. The achievement of good specificity, sensitivity and reproducibility of the analysis depends on the right choice of the phases (e.g. sample pretreatment procedure), the analytical technique and the bioinformatic approach. Improving the techniques and methods applied implies greater interest in exploration of reliable diagnostic markers. This review covers the last 11 years of determination of urinary nucleosides conducted with the use of high-performance liquid chromatography in conjunction with various types of detection, sample pretreatment methods as well as bioinformatic data processing procedures

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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