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PL
Nauka staje przed nowymi problemami, z którymi na pewno sobie poradzi. Problemy te jednak należy odważnie identyfikować i likwidować w miarę możliwości.
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Content available remote Studies on correlation between structure of solutes and their retention
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EN
Quantitative structure-retention relationships (QSRRs) concern correlations between molecular structure parameters and chromatographic retention data of analytes. Of utmost importance are QSRRs describing reversed-phase high performance liquid chromatography (RP-HPLC) retention coefficients, and analyte lipophilicity expressed as the logarithm of n-octanol-water partition coefficient, log P. QSRR were used for studying retention properties of various types of stationary phase materials, like octadecyl-bonded silica (Clg), octyl-bonded silica (Cg), immobilized artificial membrane (IAM), c^-acid glycoprotein (a,-AGP), poly butadiene-coated alumina (PBCA) or porous graphitic carbon. Using QSRRs the hy-drocarbonaceous stationary phase materials were classified with respect to the nature and strength of the prevailing intermolecular interactions in the separation system. The regression coefficients of the respective QSRR equations numerically characterize the RP-HPLC stationary phases and provide a rational explanation for the differences in retention patterns on individual columns.
PL
Ilościowe zależności struktura-retencja (QSRR) dotyczą zależności pomiędzy deskryptorami strukturalnymi a parametrami retencji chromatograpficznej analitów. Niezwykle istotne z punktu widzenia bioanalityki są zależności QSRR opisujące parametr retencji chromatograficznej w funkcji lipofilności analitów, wyrażonej jako logarytm współczynnika podziału n-oktanol-woda, log P, QSRR znajduje zastosowanie w badaniach mechanizmów retencji na różnych typach materiałów stanowiących fazy stacjonarne. Analiza QSRR została zastosowana w badaniach właściwości retencyjnych różnych typów faz stacjonarnych takich jak oktadecylowana krzemionka, immobilizowana sztuczna błona biologiczna (IAM) oraz immobilizowana kwaśna c^-glikoproteina (a,-AGP), tlenek glinu pokryty polibutadienem (PBCA) i porowaty grafityzowany węgiel. Na podstawie otrzymanych równań QSRR sklasyfikowano fazy stacjonarne pod względem ich typu oraz siły dominujących oddziaływań między cząsteczkowych w tworzonych układach separacyjnych. Współczynniki regresji uzyskanych zależności QSRR w sposób ilościowy charakteryzują fazy stacjonarne do RP-HPLC i umożliwiają racjonalną interpretację różnic retencji obserwowanych na poszczególnych kolumnach.
EN
Recently, attention has been payed to the role of imidazolines in physiology of the heart. However, no systematic comparative studies were reported regarding the activity of a representative set of specific ligands towards imidazoline receptors in the heart preparations. The aim of this project was to test effects of a set of ligands on the pharmacological function of putative imidazoline receptors in isolated rat heart atria. Known imidazoline drugs with a postulated high affinity to imidazoline I1 receptor: AGN192403, rilmenidine, moxonidine and clonidine were used. The specific ligands of imidazoline I2 receptor: 2-BFI, BU239 and putative natural ligand for imidazoline I1, I2 and I3 receptors, agmatine, were tested also. The spontaneously beating right and left atria, driven electrically, were studied. Dose-response curves for amplitude and rate of the contractions of the atria were produced by administration of increasing doses of the agents. Phentolamine as 1/2 adrenergic receptors blocker and idazoxan as I2/I1/2 receptors blocker were added in order to inhibit ino- and chronotropic effects of the compounds studied. The -log EC50 parameters were calculated. The positive inotropic effect on left atria were evoked with the rank order of potency: agmatine >> clonidine > BU239 > rilmenidine moxonidine and these effects were generally diminished by idazoxan. Moxonidine produced a weak positive inotropic effect potentiated by idazoxan. Rilmenidine and moxonidine were assumed to act as partial agonists of imidazoline I1 receptor. AGN192403 did not change the amplitude of beating of left atria. The positive chronotropic effects on spontaneously beating right heart atria were with in the following order of potency: BU239 agmatine >>> clonidine > AGN192403. Idazoxan markedly antagonized chronotropic effect of both BU239 and agmatine. 2-BFI weakly diminished the rate of beating of atria; moxonidine and rilmenidine had no effect. In conclusion, imidazoline receptors of the I1 subtype may be involved in inotropic reaction of the agents studied, but this effect depends mainly on the 2/1 adrenergic receptors. Engagement of I2 imidazoline receptors, along with the 2 adrenergic ones, in chronotropic activity of isolated right atria of rat has been demonstrated.
PL
Badanie elastyczności metody z zastosowaniem podejścia DoE zostało pomyślnie przeprowadzone i przedstawione na przykładzie oznaczania CsA w tkankach oka królików.
EN
Acetylsalicylic acid (ASA) and α-2-pyrazylidene-α-cyano N-butyl acetamide (PD-101), a new antiaggregatory pyrazine derivative were tested for their genotoxicity in human lymphocytes in vitro using the sister chromatid exchange (SCE) technique. Both compounds were found to be inactive in inducing SCE in concentration from 1 µM up to 1000 µM. The agents displayed inhibitory effect on cell kinetics.
EN
Quantitative structure-retention relationships (QSRR) have been derived for prediction of RP-HPLC retention of peptides obtained by online digestion of myoglobin. To characterize the structure of a peptide quantitatively, and then to predict its retention time under gradient HPLC conditions, the structural descriptors used were: the logarithm of the sum of retention times of the amino acids of the peptide, log SumAA; the logarithm of the Van der Waals volume of the peptide, log VDWVol; and the logarithm of its calculated n-octanol-water partition coefficient, clog P. The predictive power of the QSRR model was checked by use of a myoglobin digest, after separation and identification of the peptides by LC-ESI-MS-MS. On-line protein digestion was performed by use of trypsin immobilized on an epoxy-modified silica monolithic support coupled on-line to LC-ESIMS -MS. The predicted gradient retention times of the peptides were related to the experimental retention times obtained after on-line digestion of myoglobin. Identification of the components of the protein digest was supported by QSRR analysis. The QSRR approach was used as an additional constraint in proteomic research to verify results from MS-MS ion search, and to confirm both correctness of peptide identifications and indications of potential false positive and false negative results. The results suggest that because of the use of QSRR for prediction of peptide retention, information derived from standard liquid chromatographic separation in proteomics research could also be useful for eventual identification of the peptides.
EN
35 physico-chemical descriptors were used to characterize all 75 congeners of chloronaphthalene in terms of their environmental stability and specific dioxin-like toxicity. A prepared basic thermodynamic and physico-chemical property data matrix of PCNs was interpreted using Principal Component Analysis (PCA). The PCA of the thermodynamic and physico-chemical data matrix created a four-dimensional model that explained 76% (58% + 9% + 5% + 4%) of the total variance. The loading plot shows that the first PC is influenced by variables describing degree of chlorination, molecular weight, polarizability and lipophilicity. The best positively correlated descriptors are: retention time, standard molar entropy, heat capacity, a first-order molecular connectivity index, logarithm of octanol-water partition coefficient, the Wiener Index, specific polarizability, a third order shape index for molecules, the sum of absolute of the charges on each atom of the molecule, molecular weight, polarizability, refractivity, solvent-accessible surface, van der Waals surface, solvent-accessible volume, van der Waals volume. Negatively correlated descriptors are: standard enthalpy of formation and energy of HOMO. The second PC is strongly influenced by energy of LUMO, while substitution pattern parameters, number of chlorine atoms at a-positions and vicinal (adjacent) carbon atoms substitution pattern are less important parameters. The third PC depends on dipole moment and the largest negative charge, and on substitution at position 2 of naphthalene nuclei, while the symmetry group parameter is determined by PC4. There are small groups consisting of compounds which have similar values of LUMO energy and substitution pattern. The congeners of CN substituted with chlorine at positions 1, 2, 3, 6 and 7 (Fv/Fv PCN congeners), and next those substituted at positions 1, 2, 3 and 6 or 7 (Fr/Fv PCB congeners) are considered to be most potent in terms of dioxin-like toxicity, and followed by those substituted at four positions (Fr[Fv), at three positions (Tr/Fv) and so on. The thermodynamic stability of the congeners of CN depends on the number of attached chlorine and structure of the molecule. Among the 75 congeners of CN only a few, like PCN nos. 42, 560, 61, 66/67, are relatively resistant to biodegradation and biomagnify in animals occupying a higher position in the marine food web, and with a particular homologue group they are characterised by the lowest absolute values of energy of LUMO.
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