Biomedical subjects

N Dimitrova

Publications and source records attributed to N Dimitrova.

16 recordsLinked to original sources

PubMed2006

Metabolic activation of chemicals: in-silico simulation.

The role of metabolism in prioritising chemicals according to their potential adverse health effects is extremely important given the fact that innocuous parents can be transformed into toxic metabolites. Our recent efforts in simulating metabolic activation of chemicals are reviewed in this work. The application of metabolic simulators to predict biodegradation (microbial degradation pathways), bioaccumulation (fish liver metabolism), skin sensitisation (skin metabolism), mutagenicity (rat liver S-9 metabolism) are discussed. The ability of OASIS approach to predict metabolism (toxicokinetics) and toxicity (toxicodynamics) of chemicals resulting from their metabolic activation in a single modelling platform is an important advantage of the method. It allows prioritisation of chemicals due to predicted toxicity of their metabolites.

Animals↗

PubMed2005

Base-line model for identifying the bioaccumulation potential of chemicals.

The base-line modeling concept presented in this work is based on the assumption of a maximum bioconcentration factor (BCF) with mitigating factors that reduce the BCF. The maximum bioconcentration potential was described by the multi-compartment partitioning model for passive diffusion. The significance of different mitigating factors associated either with interactions with an organism or bioavailability were investigated. The most important mitigating factor was found to be metabolism. Accordingly, a simulator for fish liver was used in the model, which has been trained to reproduce fish metabolism based on related mammalian metabolic pathways. Other significant mitigating factors, depending on the chemical structure, e.g. molecular size and ionization were also taken into account in the model. The results (r(2)=0.84) obtained for a training set of 511 chemicals demonstrate the usefulness of the BCF base line concept. The predictability of the model was evaluated on the basis of 176 chemicals not used in the model building. The correctness of predictions (abs(logBSF(Obs)-logBCF(Calc))=0.75)) for 59 chemicals included within the model applicability domain was 80%.

Animals↗

PubMed1994

As(III) removal from aqueous solutions using non-stoichiometric coprecipitation with iron(III) sulphate and filtration or flotation.

A study of As(III) removal from aqueous solutions was carried out, using iron (III) sulphate as a coprecipitation agent. When the initial As(III) concentration was 3775 mg l(-1), maximum As(III) removal was achieved at pH 9 and with a molar ratio of Fe(III)/As(III) equal to 11. Under these conditions the formed precipitates showed highest stability, relative to the fixation of As(III). Flotation, which can be applied as a subsequent solid/liquid separation method, was found to be particularly effective for solutions containing low As(III) concentrations (</= 10 mg(-1)).

Journal Article↗

PubMed1988

Mathematical modelling of intra- and extracellular potentials generated by active structures with short regions of increased diameter.

The Hodgkin-Huxley (1952) model was used to calculate intracellular potentials by the method of Joyner et al. (1978). Extracellular potentials were estimated on the basis of a mathematical model proposed by us. It has shown that, irrespective of practical isopotentiality of the membrane of a local inhomogeneity, the latter affects extracellular potentials in two ways: 1) through changes in the potential profile in the region of the structure before the inhomogeneity; 2) through its own potential profile. The first effect is considerably greater than the second one, but the second is greater than the effect of the equal portion of the thin fibre. Increase in the diameter or length of an inhomogeneity is combined with such changes in the potential profile, that the effect of the inhomogeneity on the extracellular potential amplitude is practically independent of its actual size. The extracellular potential waveform substantially depends on the ratio of the diameters of the two parts of the structure and on the position of the inhomogeneity in relation to the sealed structure end. Registration of the positive-negative potentials having a large positive phase should not be considered as an indication of passive properties of the structure.

Extracellular Space↗

PubMed1988

Theoretical study of transmembrane and extracellular potentials under propagation block due to geometrical inhomogeneity.

A mathematical model was used to study transmembrane and extracellular potentials produced by active geometrically inhomogeneous excitable structures under conditions of propagation block. The structures were electrical analogues of intact or damaged unmyelinated nerve fibres, of the soma to axon transition, or of branching axons or dendrites. It was shown that: (1) damage to a cell is equivalent to the presence of a geometrical inhomogeneity, namely of a region of increased diameter; (2) propagation block caused by a geometrical inhomogeneity, results in; (a) a sharp decrease in the calculated transmembrane potential amplitude not only for the blocked region but also before it; (b) a considerable increase in the amplitude of both the negative phase of extracellular potentials at the points of the volume conductor preceding the blocked region and the first positive phase at points in the proximity of the region; (c) a more pronounced increase in the first positive phase amplitude at small radial distances, if the geometrical inhomogeneity is short compared with the length constant (gamma); (3) the membrane damage results in recording of potentials resembling "giant" ones.

Cell Membrane↗

PubMed1987

Mathematical modelling of intra- and extracellular potentials generated by active structures: effects of a step change in structure diameter.

A mathematical model developed in our laboratory is used to estimate and analyse extracellular potentials generated in a volume conductor by a geometrically inhomogeneous structure with a step increase or a step decrease in its diameter. The transmembrane potentials were calculated using the model of Hodgkin and Huxley (1952) and the method of Joyner et al. (1978). Variations in waveforms of the transmembrane and extracellular potentials were described and discussed. Differences in waveforms of the extracellular potentials and in declines of their components are due to changes in the source which generates these potentials. In case of a propagation block the peak-to-peak amplitude of the extracellular potentials calculated over the area of the block may be higher than that over the area of propagation of action potentials. The possible applications of the results to the analysis of extracellular potentials recorded around actual motoneurons during their orthodromic or antidromic activation are discussed.

Action Potentials↗

PubMed1982

[Various biochemical properties of Salmonella strains isolated from animal food products].

Studied were a total of 488 Salmonella strains isolated from food products and washings from productional surfaces for the presence of variants, with the use of tests of producing gas from glucose and hydrogen sulfide and the coincidence of the two properties. It was found that 7 species only had biochemical variants. Most frequent were the variants with S. cholerae suis. Biochemical variants were found in 24.79 per cent of the typed Salmonellae, these of the S. cholerae suis species being 19.26 per cent -- 7.58 per cent were gas-negative, 6.14 per cent were hydrogen sulfide-negative, and 5.53 per cent were simultaneously gas- and hydrogen sulfide-negative. The coincidence was 5.53 per cent, i.e., it lower than the values average for the biochemical variants as cited in the literature. Of all investigated strains of Salmonellae 12.6 per cent were gas-negative, 6.55 per cent--hydrogen sulfide-negative, and 6.35 per cent -- gas- and hydrogen sulfide-negative. The lower values found -- as compared to those of Ewing and Ball -- could be explained by the fact that 77.68 per cent of all biochemical variants belong to Salmonella cholerae suis.

Animals↗

PubMed1980