Genotoxic effects of heavy metals and their salts in an experiment on Drosophila and mammals

Analysis of data on the influence of different metals (cadmium, cobalt, molybdenum) on the Drosophila melanogaster cells has revealed a considerable genotoxic effect of cadmium salts which manifests in the high percentage of cells elimination at the early stages of spermatogenesis--the premeiotic cells. The modifying effect of molybdenum in the combination with cadmium and molybdenum decreasing the percentage of the progeny fall may be induced by activation of the reparation systems. In the bone marrow cells of mice Cd ions modify cytogenetic effects of the AB preparation, intensifying its mutagenic activity in some cases.     

Concerning the mechanism of increased thermogenesis in rats treated with dehydroepiandrosterone

Dehydroepiandrosterone (DHEA) treatment of rats decreases gain of body weight without affecting food intake; simultaneously, the activities of liver malic enzyme and cytosolic glycerol-3-P dehydrogenase are increased. In the present study experiments were conducted to test the possibility that DHEA enhances thermogenesis and decreases metabolic efficiency via trans-hydrogenation of cytosolic NADPH into mitochondrial FADH₂ with a consequent loss of energy as heat. The following results provide evidence which supports the proposed hypothesis: (a) the activities of cytosolic enzymes involved in NADPH production (malic enzyme, cytosolic isocitrate dehydrogenase, and aconitase) are increased after DHEA treatment; (b) cytosolic glycerol-3-P dehydrogenase may use both NAD⁺ and NADP⁺ as coenzymes; (c) activities of both cytosolic and mitochondrial forms of glycerol-3-P dehydrogenase are increased by DHEA treatment; (d) cytosol obtained from DHEA-treated rats synthesizes more glycerol-3-P during incubation with fructose-1,6-P₂ (used as source of dihydroxyacetone phosphate) and NADP⁺; the addition of citratein vitro further increases this difference; (e) mitochondria prepared from DHEA-treated rats more rapidly consume glycerol-3-P added exogenously or formed endogenously in the cytosol in the presence of fructose-1,6-P₂ and NADP⁺.     

Short-term hypothermia activates hepatic mitochondrial sn-glycerol-3-phosphate dehydrogenase and thermogenic systems

The contribution of the sn-glycerol-3-phosphate (G-3-P) shuttle in the control of energy metabolism is well established. It is also known that its activity may be modulated by hormones involved in thermogenesis, such as thyroid hormones or dehydroepiandrosterone and its metabolites, that act by inducing de novo synthesis of mitochondrial G-3-P dehydrogenase (mGPDH). However, little is known as to the factors that may influence the activity without enzyme induction. In the present study we investigated the possible role of the G-3-P shuttle in the thermogenic response to different hypothermic stresses. It was found that a decrease of body temperature causes the liver rapidly to enhance mGPDH activity and G-3-P-dependent respiration. The enhancement, which does not result from de novo synthesis of enzymes, has the potential of increasing heat production both by decreased ATP synthesis during the oxidation of G-3-P and by activation of the glycolytic pathway.     

An overview of malaria transmission from the perspective of Amazon Anopheles vectors

In the Americas, areas with a high risk of malaria transmission are mainly located in the Amazon Forest, which extends across nine countries. One keystone step to understanding the Plasmodium life cycle in Anopheles species from the Amazon Region is to obtain experimentally infected mosquito vectors. Several attempts to colonise Ano- pheles species have been conducted, but with only short-lived success or no success at all. In this review, we review the literature on malaria transmission from the perspective of its Amazon vectors. Currently, it is possible to develop experimental Plasmodium vivax infection of the colonised and field-captured vectors in laboratories located close to Amazonian endemic areas. We are also reviewing studies related to the immune response to P. vivax infection of Anopheles aquasalis, a coastal mosquito species. Finally, we discuss the importance of the modulation of Plasmodium infection by the vector microbiota and also consider the anopheline genomes. The establishment of experimental mosquito infections with Plasmodium falciparum, Plasmodium yoelii and Plasmodium berghei parasites that could provide interesting models for studying malaria in the Amazonian scenario is important. Understanding the molecular mechanisms involved in the development of the parasites in New World vectors is crucial in order to better determine the interaction process and vectorial competence.     

Effects of polymodal rhythmic sensory influences on the human CNS state and autonomic functions

It was shown that polymodal rhythmic sensory influences (light, sound, vibratory-tactile), being a measure of neurocorrection, may be used for correction of the human psychophysiological state. The effectiveness of the method shows up in the positive influence on the mental sphere of a person, causing a decrease in the level of anxiety and improving the subjective well-being, and on the cognitive and autonomic functions. Polymodal rhythmic sensory influences are means of increasing the effectiveness of human intellectual activity, because it increases concentration in proportion to the increase in the parasympathetic activity induced by polymodal sensory stimuli.     

Antiamyloid properties of fullerene C<Subscript>60</Subscript> derivatives

A comparative estimation of the ability of complexes of fullerene C₆₀ with polyvinylpyrrolidone and fullerene C₆₀ derivatives (the sodium salt of the polycarboxylic derivative of fullerene C₆₀, sodium fullerenolate), has been carried out. The fullerenes destroyed amyloid fibrils of the Aβ(1–42) peptide of the brain and the muscle X-protein. A study of the effect of fullerenes on muscle actin showed that complexes of fullerene C₆₀ with polyvinylpyrrolidone and sodium fullerenolate did not prevent the filament formation of actin, nor did they destroy its filaments in vitro. Conversely, sodium salt of the polycarboxylic derivative of fullerene C₆₀ destroyed actin filaments and prevented their formation. It was concluded that sodium fullerenolate and complexes of fullerene C₆₀ with polyvinylpyrrolidone are the most effective antiamyloid compounds among the fullerenes examined.     

Different amyloid aggregation of smooth muscles titin in vitro

A comparative study of amyloid properties of the aggregates of smooth muscle titin (SMT) from chicken gizzard was carried out. These aggregates were formed in two solutions: 0.15 M glycine-KOH, pH 7.2–7.4 (SMT(Gly)) and 0.2 M KCl, 10 mM imidazole, pH 7.0 (SMT(KCl)). Electron microscopy data showed that SMT aggregates has an amorphous structure in both cases. The results of atomic-force microscopy demonstrated slight differences in morphology in two types of aggregates. The SMT(Gly) aggregates were represented as branching chains, composed of spherical aggregates approximately 300–500 nm in diameter and up to 35 nm in height. The SMT(KCl) aggregates formed sponge-like structures with strands of 8–10 nm in height. Structural analysis of SMT aggregates by X-ray diffraction revealed the presence of cross-β-sheet structure in the samples under study. In the presence of SMT(Gly) aggregates, thioflavine T fluorescence intensity was higher (~3-fold times) compared with that in the presence of SMT(KCl) aggregates. Congo red-stained SMT(Gly) aggregates had yellow to apple-green birefringence under polarized light, which was not observed for SMT(KCl) aggregates. Dynamic light scattering data showed the similar rate of aggregation for both types of aggregates, though SMT(KCl) aggregates were able to partially disaggregate under increased ionic strength of the solution. The ability of SMT to aggregation followed by disaggregation may be functionally significant in the cell.     

Structure based virtual screening of ligands to identify cysteinyl leukotriene receptor 1 antagonist

Montelukast and Zafirlukast are known leukotriene receptor antagonists prescribed in asthma treatment. However, these fall short as mono therapy and are frequently used in combination with inhaled glucocorticosteroids with or without long acting beta 2 agonists. Therefore, it is of interest to apply ligand and structure based virtual screening strategies to identify compounds akin to lead compounds Montelukast and Zafirlukast. Hence, compounds with structures having 95% similarity to these compounds were retrieved from NCBI׳s PubChem database. Compounds similar to lead were grouped and docked at the antagonist binding site of cysteinyl leukotriene receptor 1. This exercise identified compounds UNII 70RV86E50Q (Pub Cid 71587778) and Sure CN 9587085 (Pub Cid 19793614) with higher predicted binding compared to Montelukast and Zafirlukast. It is shown that the compound Sure CN 9587085 showed appreciable ligand receptor interaction compared to UNII 70RV86E50Q. Thus, the compound Sure CN 9587085 is selected as a potent antagonist to cysteinyl leukotriene receptor 1 for further consideration in vitro and in vivo validation.     

The detection of high-risk groups among workers in contact with heavy metals based on an analysis of chromosome aberrations and sister chromatid exchanges

Heavy metal salts, the workers from molybdenum, tungsten and cobalt plants to make in contact with, reveal their mutagenic activity. Individual sensitivity to heavy metal salts has been analyzed through the example of molybdenum. Chromosome aberrations and sister chromatid exchanges have been studied for the regularities of their formation in lymphocytes of workers depending on the length of service. Sensitivity of tests of chromosome aberrations and sister chromatid exchanges has been compared to reveal genetic consequences of these types of the effects.     

Genotoxic effects of molybdenum and its derivatives in an experiment on Drosophila and mammals]

As a result of research it is established that molybdenum shows the most pronounced genetic activity at the early stages of spermatogenesis. Genetic effects of molybdenum and its modification by vitamin S are registered in the test of dominant lethal mutations. The cytogenetic activity of molybdenum, the molybdenic candle-end and its modification by antibacterial preparation have been revealed in the cells of mammalian marrow.