Development of New Biokinetic-Dosimetric Models for the Simulation of Iodine Blockade in the Case of Radioiodine Exposure in Man

In the case of nuclear incidents, radioiodine may be liberated. After incorporation it accumulates in the thyroid and by internal irradiation enhances the risk of cancer occurrence. By administering a large dose of non-radioactive iodine the uptake of radioiodine into the gland can be inhibited (“iodine blockade”). Biokinetic models using first order kinetics are not suited to simulate iodine blockade, as the uptake into the gland is mediated by a saturable active transport. Therefore, we integrated an uptake mechanism described by a Michaelis-Menten kinetic into a simple ICRP biokinetic model. We moreover added a total uptake blocking mechanism representing the Wolff-Chaikoff effect becoming active when the gland is saturated with iodine. The validity of the model was ascertained by comparison with IMBA software. The competition of radioiodine and stable iodine at the membrane carrier site was modeled according to the rate law for monomolecular reactions for competing substrates. Our simulations show that competition for the uptake at the membrane carrier site accounts for about 60% and the saturation of the gland with iodine for over 35% of the total protective efficacy that exceeds 95%. Following acute radioiodine exposure, it is preferable to administer a single large dose of stable iodine. In the case of continuous radioiodine exposure, a single dose of stable iodine is less effective than after an acute exposure and splitting the total available dose and shortening the dosage intervals enhance efficacy. Model-based simulations may be a useful tool to develop antidote dosage schemes for uncommon emergencies.

Reagent purification of the processing industry enterprises effluents

The article represents the results of research of the effluents purification by the reagent methods. The effluents were polluted by organic compounds of processing enterprises with small productivity. The analysis of pollution of the hydrosphere caused by the processing enterprises is carried out and the promising methods of cleaning wastewater from pollution are given. As an object of research, the streams of the production site of the fruit and vegetable juices of the Buzky Canning Factory were used. As a reagent-oxidant, sodium hypochlorite was studied. The mechanism of purification of contaminated wastewater with sodium hypochlorite is considered in detail. The task of experimental studies was to determine the flow of sodium hypochlorite where wastewater treatment is carried out to a level lower than that regulated by standards. The criterion for cleaning efficiency was two indicators of water quality: chemical oxygen consumption (COC) and dry residue. The results of the conducted studies allow us to conclude that the use of sodium hypochlorite for purification of fruit and vegetable juice from organic pollutants is promising. It is established that for effluents of the Buzky canning plant, optimal use is made for purification of effluents of hypochlorite in the ratio of 0.5 dm3/m3 of wastewater that is being purified. To ensure environmental safety from possible contamination of unreacted hypochlorite of treated wastewater, an estimation of the cost of hyprochlorite for purification and comparison of residual concentrations with normalized parameters was carried out. The kinetics of oxidation of organic impurities in effluents was also studied, which was expressed by the degree of reduction of the COC solution in the process of reacting it with sodium hypochlorite. It is proved that the kinetics of the process of oxidation of organic contaminants is described by the equation valid for monomolecular reactions. For the system under study, the rate constant of the oxidation process of organic contaminants is 0,074 1/s. The principal scheme of purification of the effluents of the Buzky canning plant by sodium hypochlorite is proposed.

Exact model reduction with delays: closed-form distributions and extensions to fully bi-directional monomolecular reactions

In order to systematically understand the qualitative and quantitative behaviour of chemical reaction networks, scientists must derive and analyse associated mathematical models. However, biochemical systems are often very large, with reactions occurring at multiple time scales, as evidenced by signalling pathways and gene expression kinetics. Owing to the associated computational costs, it is then many times impractical, if not impossible, to solve or simulate these systems with an appropriate level of detail. By consequence, there is a growing interest in developing techniques for the simplification or reduction of complex biochemical systems. Here, we extend our recently presented methodology on exact reduction of linear chains of reactions with delay distributions in two ways. First, we report that it is now possible to deal with fully bi-directional monomolecular systems, including degradations, synthesis and generalized bypass reactions. Second, we provide all derivations of associated delays in analytical, closed form. Both advances have a major impact on further reducing computational costs, while still retaining full accuracy. Thus, we expect our new methodology to respond to current simulation needs in pharmaceutical, chemical and biological research.

Nonstationary Theory of the Thermal Explosion for Monomolecular Exothermic Reactions

A new approach to the consideration of the thermal explosion macrokinetic features for monomolecular reactions in homogeneous systems based on a strict accounting of burnout during the reaction process is proposed. It is established, that the qualitative changes of the phase trajectory structure (phase portrait) on the plane: heating rate-temperature determine the characteristic modes of reaction. This approach makes it possible to go beyond the Semenov theory and allows us to consider the variety of the reaction modes. From this point of view, the theory of Semenov is a special case which is valid only for reactions of zero order. The phase trajectories analyze on the parametrical plane Semenov criterion – Todes criterion gives an opportunity to define the regions of the thermal explosion degeneration, the transition regions and the region of the thermal explosion realization. With the use of such consideration, the necessary and sufficient conditions of the thermal explosion are found.

Assays for the RNA chaperone activity of proteins

Proteins with RNA chaperone activity promote RNA folding by loosening the structure of misfolded RNAs or by preventing their formation. How these proteins achieve this activity is still unknown, the mechanism is not understood and it is unclear whether this activity is always based on the same mechanism or whether different RNA chaperones use different mechanisms. To address this question, we compare and discuss in this paper a set of assays that have been used to measure RNA chaperone activity. In some assays, this activity is related to the acceleration of monomolecular reactions such as group I intron cis-splicing or anti-termination of transcription. Hereby, it is proposed that the proteins release the RNAs from folding traps, which represent the kinetic barriers during the folding process and involve the loosening of structural elements. In most assays, however, bimolecular reactions are monitored, which include the simple acceleration of annealing of two complementary RNAs, the turnover stimulation of ribozyme cleavage and group I intron trans-splicing. The acceleration of these reactions most probably involves the unfolding of structures that interfere with annealing or folding and may in addition provoke annealing by crowding. Most assays are performed in vitro, where conditions might differ substantially from intracellular conditions, and two assays have been reported that detect RNA chaperone activity in vivo.