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Biomedical subjects

L Soltés

Publications and source records attributed to L Soltés.

At least 19 recordsLinked to original sources

Degradative action of reactive oxygen species on hyaluronan.

Many human diseases are associated with harmful action of reactive oxygen species (ROS). These species are involved in the degradation of essential tissue or related components. One of such components is synovial fluid that contains a high-molecular-weight polymer--hyaluronan (HA). Uninhibited and/or inhibited hyaluronan degradation by the action of various ROS has been studied in many in vitro models. In these studies, the change of the molecular weight of HA or a related parameter, such as HA solution viscosity, has been used as a marker of inflicted damage. The aim of the presented review is to briefly summarize the available data. Their correct interpretation could contribute to the implementation of modern methods of evaluation of the antioxidative capacity of natural and synthetic substances and prospective drugs--potential inflammatory disease modifying agents. Another focus of this review is to evaluate briefly the impact of different available analytical techniques currently used to investigate the structure of native high-molecular-weight hyaluronan and/or of its fragments.

Animals↗

Effect of melatonin on neurobehavioral dysfunctions induced by intrauterine hypoxia in rats.

Intrauterine hypoxia associated with oxidative stress represents an important risk factor for development of neurobehavioral dysfunctions. In the present study, we investigated the potential protective effect of melatonin (MEL) on neurobehavioral dysfunctions induced by chronic intrauterine hypoxia in rats by the anticonvulsant drug phenytoin (PHT), which is known by its teratogenic potential. Pregnant female rats (Wistar/DV) were orally treated by PHT (150 mg/kg) from day 7 to 18 of gestation. MEL was dissolved in drinking water (40 microg/ml) and administered from day 0 to 19 of gestation. Neurobehavioral development of offspring was evaluated from birth up to day 90 of postnatal life. The results of the study confirmed the high behavior-teratogenic potential of PHT. Prenatal administration of PHT resulted in delayed neuromotor and reflex development, decreased exploration in the open field, abnormal "circling" and impaired performaces in water maze. Co-administration of MEL failed to have any effect on neurobehavioral dysfunctions induced by PHT treatment. Even administration of MEL alone caused developmental alterations in offspring manifested by accelerated testes descent and delayed onset of negative geotaxia and startle reflex. The results suggest to pay increased attention to MEL concerning its exogenous use during pregnancy.

Analysis of Variance↗

Effect of melatonin and stobadine on maternal and embryofoetal toxicity in rats due to intrauterine hypoxia induced by phenytoin administration.

The aim of the present study was to test the hypothesis that the natural antioxidant melatonin (MEL) and the synthetic antioxidant stobadine (STO) could reduce the incidence of maternal and embryofoetal toxicity in rats due to intrauterine hypoxia. Chronic hypoxia was induced pharmacologically by the administration of the anticonvulsant phenytoin (PHT) during the entire period of pregnancy. PHT disturbed the normal course of pregnancy, affected reproductive parameters and increased the incidence of skeletal anomalies. MEL did not protect the PHT-induced development toxicity in rat. On the other hand, STO partially prevented PHT-induced reduction of foetal and placental weights. Administration of STO also decreased the frequency of pre- and post-implantation loss and resorptions in the PHT group. We concluded that pretreatment of pregnant rats with STO prevented to a certain extent reproductive and foetal development alterations caused by chronic intrauterine hypoxia.

Abnormalities, Drug-Induced↗

Molecular characterization of two host-guest associating hyaluronan derivatives.

Molecular characteristics were determined of two high-molecular-weight water-soluble hyaluronan derivatives, namely beta-cyclodextrin (HA-beta-CD) and N-acylurea (EDC-HA). The weight-average molecular weight (M(w)) of HA-beta-CD and of EDC-HA, determined with a multi-angle light scattering detector connected on-line to a size exclusion chromatographic system, was respectively 185.3 and 86.8 kDa. However the M(w) value determined for the equimolar mixture of the two HA derivatives equaled 556.0 kDa. Similarly, the gyration radius of the above equimolar mixture, Rg = 80.6 nm, was significantly greater than the values found for the single HA derivative, i.e. 40.2 nm for HA-beta-CD and 23.8 nm for EDC-HA. These data indicate that the two kinds of substituents, bound to the polymeric chains, form host-guest/inclusion complexes resulting in polymacromolecular associates/aggregates.

Chromatography, Gel↗

Molecular characteristics of some commercial high-molecular-weight hyaluronans.

Commercially available hyaluronan (HA) samples were investigated by the method of size exclusion chromatography (SEC). The fractions eluted from the SEC column were on-line molecularly characterized by using a multi-angle laser light scattering (MALLS) photometer. Along with the SEC-MALLS technique, the high-molecular-weight HA biopolymers were (off-line) analyzed by capillary viscometry.

Hyaluronic Acid↗

Radical degradation of high molecular weight hyaluronan: inhibition of the reaction by ibuprofen enantiomers.

The antioxidative and/or free-radical-scavenging activities of R-(-)- and S-(+)-ibuprofen enantiomers, as well as of the drug racemate, were studied in vitro on measuring the kinetics of (uninhibited or drug-inhibited) degradation of high molecular weight hyaluronan by hydroxyl radicals. The continual flux of OH radicals at aerobic conditions was maintained by the H2O2 + Cu2+ system. The kinetics of hyaluronan degradation was monitored indirectly by capillary viscometry. Under experimental conditions, with no drug addition, the relative viscosity ([eta]rel) decreased continuously, reaching 13% of the initial [eta]rel. value in 4 h. Each drug tested exhibited a dose-dependent protective effect against hyaluronan degradation, however R-(-)-ibuprofen demonstrated a slightly greater activity than the drug S-(+)-enantiomer.

Anti-Inflammatory Agents, Non-Steroidal↗

Extraction and chromatographic separation methods in pharmacokinetic studies of Stobadine--an indole-related antioxidant and free-radical scavenger.

This overview provides comprehensive information on the most relevant results of Stobadine preclinical disposition studies. In order to investigate pharmacokinetic processes of the drug in rats, dogs and in human volunteers, several bioanalytical assays based on radiometric, spectrofluorometric, as well as chromatographic determination methods were developed and implemented. In small laboratory animals, the drug absorption, distribution, metabolism and elimination were investigated by administering 3H-labeled Stobadine. Spectrofluorometry was used alternatively for the determination of cold/unlabeled Stobadine in extracts of biomaterials sampled from larger animal species. The chromatographic separation methods proved, however, to be the most advantageous for determining details of the drug disposition and fate in the body.

Animals↗

Sonication of chitin-glucan, preparation of water-soluble fractions and characterization by HPLC.

A water-insoluble chitin-glucan complex, isolated from the mycelium of Aspergillus niger, was swollen in various aqueous media and treated subsequently by high-energy sonication. The concentration of the resulting water-soluble polysaccharide fractions was dependent on the swelling medium, the amount of the chitin-glucan complex in the suspension, and on the time of sonication. The yields of water-soluble chitin-glucan were within the range 13.6 to 24.4% relative to the mass of the original chitin-glucan. The nitrogen content obtained for the samples of water-soluble chitin-glucan indicated a higher content of chitin (3.45% of nitrogen in high-molecular fraction) than in the original water-insoluble chitin-glucan sample (1.8%). The distribution of the molecular weights of the water-soluble fractions prepared was determined by high-performance liquid chromatography.

Aspergillus niger↗

Placental transfer of the antioxidant stobadine at different gestational stages in rabbits.

The distribution of [3H]-stobadine, a pyridoindole antioxidant, was investigated in New Zealand white rabbits and their fetuses on days 20 and 27 of gestation. The concentrations of [3H]-stobadine were determined in maternal and fetal organs after oral administration in a single dose of 5.0 mg/kg. The results of the study showed that during the late period of gestation the fetal organs, especially the brain and heart, were under the protective action of the antioxidant stobadine.

Animals↗

Aminoglycoside antibiotics--two decades of their HPLC bioanalysis.

Several reviews have been published on high-performance liquid chromatographic (HPLC) methods for the determination of aminoglycoside antibiotics (aminoglycosides) in biological fluids [e.g. Nilsson-Ehle, I. (1983). J. Liq. Chromat. 6: 251]. Of these, the paper by Maitra et al. [(1979a). Clin. Chem. 25: 1361.] briefly summarizes the early 2-3 years of experience on HPLC assaying of amikacin, gentamicin, netilmicin and tobramycin in body fluids. The reviews by Nilsson-Ehle, I. [(1983). J. Liq. Chromat. 6: 251] and by Miner, D. J. [(1985). Antibiotics. In Therapeutic Drug Monitoring and Toxicology by Liquid Chromatography, (Wong S. H. Y., ed.), ch. 10, p. 269. Marcel Dekker, New York and Basel.] devoted to the monitoring of antibiotics, also evaluated the first 6-8 years of the application of HPLC assays for the aminoglycosides amikacin, gentamicin, netilmicin, sisomicin and tobramycin. This report presents a great majority of the HPLC assay methods published during the last two decades for determining practically a dozen different aminoglycoside antibiotics in body fluids, particularly in the serum or plasma, and in urine.

Aminoglycosides↗

A simple chiral high-performance liquid chromatographic method to study the enantiomer-differentiating action of microorganisms. An assay with DL-tryptophan.

To investigate the 'enantiomer-differentiating' action of the microorganisms colonizing a phosphate-buffered DL-tryptophan solution, a novel chiral high-performance liquid chromatographic (HPLC) arrangement was developed and established. As the HPLC stationary phase, bovine serum albumin (BSA) bonded silica gel was used. In the function of the mobile phase, phosphate-buffered DL-tryptophan solution was applied. The composition of the eluate was monitored by an HPLC spectrophotometric detector. After injecting the assayed sample into the eluent stream, the content of each tryptophan enantiomer was evaluated either from the positive or negative responses of the HPLC detector. The validity and the performance of this novel approach were confirmed by applying another chiral HPLC device working with human serum albumin (HSA) bonded silica gel as the stationary phase and with 1-propanol containing phosphate buffer as the eluent.

Buffers↗

Pharmacokinetic study of stobadine.

The aim of this paper is to provide a brief overview of most important results of stobadine kinetic studies in rats, dogs, and human volunteers. In these studies, stobadine dihydrochloride and stobadine dipalmitate was used for intravenous and oral administration, respectively. To evaluate kinetic properties of stobadine and its metabolites, TLC, HPLC, GLC, GC-MS, radiometric, and fluorometric methods were developed and used.

Animals↗

Placental transfer of stobadine in rabbits.

Stobadine, a pyridoindole antioxidant, was investigated for its placental transfer and distribution in New Zealand white rabbits on the 27th day of gestation. The concentrations of stobadine were determined in maternal and foetal organs (plasma, brain, heart) at 30, 60, 120, and 360 minutes after oral administration of the drug in a dose of 5 mg/kg. The results obtained proved that after oral stobadine intake by rabbits at the stage of advanced pregnancy both maternal and foetal organs were under a certain drug level which could act protectively against oxidative stress--frequently occurring during late organogenesis, foetal stages and delivery, as well as during early postnatal development.

Animals↗

Reversible binding interactions between the tryptophan enantiomers and albumins of different animal species as determined by novel high performance liquid chromatographic methods: an attempt to localize the D- and L-tryptophan binding sites on the human serum albumin polypeptide chain by using protein fragments.

The stereoselectivity of the reversible binding interactions between the D- and L-tryptophan enantiomers and serum albumins of different animal species and fragments of human serum albumin (HSA) was investigated by applying three novel high performance liquid chromatographic (HPLC) arrangements. The separations were performed by means of 1) an achiral (diol-bond), 2) a chiral (bovine serum albumin-bond) silica gel sorbent, and 3) a column switching technique which uses both the diol- and HSA-bond HPLC stationary phases. A polarimetric detector and/or an ultraviolet (UV) spectrophotometer were used to monitor the separation process. HPLC arrangement 3 allowed the evaluation of enantioselective binding for D- and L-tryptophan to different albumins and albumin fragments. At present, column switching can be considered the technique of the broadest applicability for investigating the reversible binding interactions between a protein and drug enantiomers.

Animals↗

High-molecular-weight hyaluronan--a valuable tool in testing the antioxidative activity of amphiphilic drugs stobadine and vinpocetine.

The antioxidative activity of stobadine and vinpocetine was studied in vitro by measuring their inhibition effect on the depolymerization of the high-molecular-weight hyaluronan by hydroxyl radicals. The radicals were generated by the Cu(2+)-H2O2 system. Hyaluronan depolymerization was monitored by means of size exclusion chromatography. The antioxidative activity of stobadine and vinpocetine was compared to that of D-mannitol. A 50% inhibition of hyaluronan depolymerization was reached at stobadine and vinpocetine concentrations of 1.7 x 10(-6) and 3.0 x 10(-7) mol l-1, respectively, while a D-mannitol level of 2.6 x 10(-3) mol l-1 was needed to achieve the same inhibitory effect.

Antioxidants↗

Propafenone binding interaction with human alpha 1-acid glycoprotein: assessing experimental design and data evaluation.

Binding data on racemic RS-propafenone as well as individual R- and S-drug enantiomers interacting reversibly with human alpha 1-acid glycoprotein, as obtained by a high-performance liquid chromatographic method, are evaluated according to three different approaches introduced, respectively, by Scatchard, Bjerrum, and by Tobler and Engel. A non-linear curve-fitting procedure was applied to compute the binding parameters exclusively for the binary system comprising the examined protein and R- and S-propafenone, individually. The exactness of the study design rather than the numerical values were the focus of attention in the evaluation of the data found.

Chromatography, Affinity↗

Cronobiologic analysis of abortions in two related populations of teenager girls during two decades.

STUDY OBJECTIVE: To identify and compare the time dynamics of artificial abortions in two (Czech and Slovak) ethnically, historically and socially closely related populations. DESIGN: Data have been taken separately for 12-15 and 16-18 year age girls from official exhaustive statistical sources and processed by advanced procedures of time series analysis. SETTING: Czech and Slovak Republics. PARTICIPANTS: All girls of the given age. INTERVENTIONS: Legislative liberalization of abortions 1987. MAIN OUTCOME MEASURES: Estimated starting values of relative numbers of abortions by 1971, increasing linear trends, period lengths of fluctuation, coefficients of determination and those of cross-correlation. Level of significance alpha = 0.05. RESULTS: The Czech figures are significantly higher than the Slovak. Thus, estimated abortion percentage (from pregnancies) for 1971 was for younger Czech girls 53%, and for those from Slovakia 29%. All estimated trends were increasing significantly in all cases for the Czech population (by 1.5% per year in the younger group) and in one case for Slovakia. The estimated period lengths were usually 10-12 years. Czech and Slovak data display significant positive mutual cross-correlation, the delay being 1-3 years in Slovak girls. Surprisingly, all data significantly cross-correlate with the geomagnetic index value Ap, acting as lead-lag, with 3-6-year delay for abortions. CONCLUSIONS: Despite living in the same federal state--the former Czechoslovak Republic, both Czech and Slovak populations do differ in starting values and general trends of abortions in teenagers. This can be due to historical, racial and religious peculiarities as well as a more advanced process of industrialization in the western part--the Czech Republic. The latter hypothesis is corroborated by strong dynamism of changes and by the time delay in Slovakia. The periodicity exhibits a frequency resembling that known for solar motion round barycenter of solar system, for sunspots and geomagnetism.

Abortion, Legal↗