Comparative analysis of the effectiveness of countermeasures in rural settlements in the long-term period after the accident at the Chernobyl AES

A comparative analysis of the strategy of countermeasures aimed at reducing exposure doses to the rural population is presented. The effectiveness of the proposed system of countermeasures assessed by criteria such as reduction factor of exposure doses and cost of averted doses. Costs of countermeasures in the rural settlements located in the affected zone are calculated for a long term after the Chernobyl NPP accident.     

Effects of the Gut microbiota on Amygdalin and its use as an anti-cancer therapy: Substantial review on the key components involved in altering dose efficacy and toxicity

Conventional and Alternative Medicine (CAM) is popularly used due to side-effects and failure of approved methods, for diseases like Epilepsy and Cancer. Amygdalin, a cyanogenic diglycoside is commonly administered for cancer with other CAM therapies like vitamins and seeds of fruits like apricots and bitter almonds, due to its ability to hydrolyse to hydrogen cyanide (HCN), benzaldehyde and glucose. Over the years, several cases of cyanide toxicity on ingestion have been documented. In-vitro and in-vivo studies using various doses and modes of administration, like IV administration studies that showed no HCN formation, point to the role played by the gut microbiota for the commonly seen poisoning on consumption. The anaerobic Bacteriodetes phylum found in the gut has a high β-glucosidase activity needed for amygdalin hydrolysis to HCN. However, there are certain conditions under which these HCN levels rise to cause toxicity. Case studies have shown toxicity on ingestion of variable doses of amygdalin and no HCN side-effects on consumption of high doses. This review shows how factors like probiotic and prebiotic consumption, other CAM therapies, obesity, diet, age and the like, that alter gut consortium, are responsible for the varying conditions under which toxicity occurs and can be further studied to set-up conditions for safe oral doses. It also indicates ways to delay or quickly treat cyanide toxicity due to oral administration and, reviews conflicts on amygdalin's anti-cancer abilities, dose levels, mode of administration and pharmacokinetics that have hindered its official acceptance at a therapeutic level.     

Strain differences in the teratogenicity induced by sodium valproate in cultured mouse embryos

Strain differences in the teratogenicity of valproic acid (VPA) have been reported in mice. Finnell and Chernoff (Proc. Grnwd. Genet. Ctr. 5:162-163, 1985) showed that 300 mg/kg of VPA twice a day on days 6-8 of gestation induced exencephaly in 82% of SWV embryos but in 0% of C57BL/6J embryos. In the present experiment, we have collected similar results and investigated this strain difference using whole embryo culture in an attempt to determine whether maternal or embryonic factors are responsible for the difference. Mouse embryos were explanted on day 8.5 (plug day 0), and embryos at the 6-8-somite stage were cultured for 48 hours in rat serum containing various doses of sodium valproate (NaVP). All the embryos died within 24 hours with 4.5-mM and higher doses of NaVP in C57BL/6NCr1BR (C57) and with 3.0-mM and higher doses in SWV. Unfused brain folds were recognized in embryos treated with 3.0-mM and higher doses in C57, and with 1.0-mM and higher doses in SWV. Irregular somite formation was observed in many embryos treated with 1.6-mM and higher doses in C57 and with 1.0-mM and higher doses in SWV. These results indicate that SWV embryos have 1.5-3 times the sensitivity of C57 embryos to the embryolethal and teratogenic effects of NaVP. Furthermore, the results suggest that the basis of the strain difference resides within the embryo rather than the mother.     

Molecular mechanisms responsible for formation of Golgi ribbon

The formation of the Golgi ribbon takes place in protists and metazoans. It is especially prominent in mammalian cells during interphase. Golgi ribbon formation represents an orchestrated sequence of events based not only on different molecular mechanisms but also on discrete cellular functions. Mechanisms responsible for the generation of the Golgi ribbon include Golgi centralization, cis- and trans-Golgins, molecular machines responsible for the fusion of cargo domains with cisternal rims, and several other less studied factors. Here, we substantiate the hypothesis that cis-Golgins function mostly not as tethering factors, but are responsible for the attachment of the cis-most cisternae to the medial Golgi stacks, whereas trans-Golgins are responsible for the attachment of the trans-most cisterna to the medial Golgi stacks. This hypothesis is tested analyzing predictions derived from it and related to molecular mechanisms responsible for mitotic fragmentation of Golgi stacks.     

Radiological assessment of protective countermeasures in the private sector of rural settlements in the Chernobyl nuclear power plant accident area

The effectiveness of countermeasures on private farms in rural settlements of the Russian Federation affected by the Chernobyl accident for the period of 1986-2005 was assessed. The averted collective doses to the residents of these settlements and the contribution of restrictive and agricultural countermeasures to dose reduction in the rural population have been estimated.     

Effective target size for the induction of bystander effects in medium transfer experiments

Although radiation-induced bystander effects are frequently observed biological phenomena, the mechanism for these effects has not been fully determined. The target-hit theory and related concepts from microdosimetry provide a convenient formalism to help identify the nature of the targets responsible for initiating the emission of diffusible factors in medium transfer experiments. We used the microdosimetric models proposed by Stewart et al. (Radiat. Res. 165, 460-469, 2006) to analyze the results of published medium transfer experiments for gamma-ray doses in the range of 0.04 mGy to 5 Gy. The analysis suggests that the effective size of the target responsible for initiating signal emission in HPV-G human keratinocyte donor cells is approximately 2 microm.     

Molecular aspects of extracorporeal photochemotherapy

8-methoxypsoralen (8-MOP), activated upon exposure to long-wavelength ultraviolet radiation, is used therapeutically to treat the diseased blood cells of cutaneous T-cell lymphoma patients. The factors responsible for the efficacy of this therapy are reviewed. Primary among these are the plasma level of 8-MOP at the time of irradiation and the effective dose of UVA. 8-MOP plasma levels determined in a series of six patients demonstrated that the drug is absorbed at a highly variable rate (122 ng/ml +/- 67). A new liquid form of 8-MOP is absorbed with a modest increase in plasma levels (170 ng/ml) but with no improvement in the variability (+/- 163). An examination of the dose-response relationship between 8-MOP concentration and UVA dose indicated that properties such as 8-MOP photoadduct formation and PHA response are proportional to the combined doses of these two factors. A new molecular target for 8-MOP photomodification, cell membrane DNA, is described.     

Analysis of axon tract formation in the zebrafish brain: the role of territories of gene expression and their boundaries

Mutant analysis in the zebrafish is revealing the genes that are expressed in the early neuroepithelium and that regulate factors responsible for the guidance of commissural axons. We review work on the developing zebrafish brain illustrating the way in which territories of regulatory gene expression influence the formation and positioning of axon pathways. Received: 20 May 1997 / Accepted: 9 June 1997     

Enzyme inhibition as a possible mechanism of the mutagenicity of dithiocarbamic acid derivatives in Salmonella typhimurium

In recent years data have accumulated regarding genotoxic properties of dithiocarbamic acid derivatives. The results from the present work indicate that the mutagenicity of these compounds depends on an indirect effect via oxygen radicals. Mutagenicity of tetramethylthiuram disulfide ( TMTD ), that was used as a model substance, was established with both frameshift and base substitution sensitive strains of Salmonella typhimurium. Addition of copper ions resulted in a decreased survival at low dithiocarbamate doses. The dose response curves seem to correlate with the formation of two types of metal dithiocarbamate complexes. At low doses charged complexes are formed, while the formation of uncharged complexes is favoured at higher dosages. The data suggest that this formation of uncharged metal complexes implies a decreased toxicity but at the same time an increased mutagenicity. The mutagenicity of both TMTD and its ethyl analogue TETD was enhanced by oxygen. Furthermore, TMTD potentiates the mutagenic action of menadione, a substance that produces O(2) and H2O2 by redox cycling with molecular oxygen. Interaction of uncharged metal dithiocarbamate complexes with both production and detoxification of reactive forms of oxygen is suggested to be responsible for the direct mutagenic effects via oxidative damage to DNA. A further enhancement of the oxygen radical content of the cells by adding microsomes that produce oxygen radicals via autoxidation of cytochrome P-450 is proposed as the mechanism for the 'metabolic activation of TMTD '.     

Analysis of the contribution of forest pathways to the radiation exposure of different population groups in the Bryansk region of Russia

The experience gained in the aftermath of serious radiation accidents shows that forests are an important source of external and internal exposure of the affected population. This paper presents the results of an assessment of the major radiological consequences for forests of Russia, most heavily contaminated after the Chernobyl nuclear power plant (ChNPP) accident. Illustrated in the Novozybkovsky district of the Russian Federation, the significance of different forest exposure pathways is estimated and the doses resulting from forest pathways are compared with the doses from agricultural products. It has been found that the contribution of mushrooms and berries to the internal doses of the population, relative to the doses from agricultural products, varied from 10–15% in 1987 to 40–45% in 1996. The results indicate large differences in internal exposure of members of the ”critical groups” and ”normal population”, increasing with time after deposition. Data are presented that give information on the contribution of forests to the collective doses of inhabitants of the area under consideration. It has been shown that for 10 years after the accident (1987–1996), the contribution of forest products to the collective dose of the rural population living in contaminated forests of the Novozybkovsky district, amounts to about 20% (213 person Sv) of the total collective dose of internal and external exposures. However, a potential impact of these products including the dose from exported products is much higher and might reach 659 person Sv. It has been found that in the long-term after the ChNPP accident, serious attention should be given to forest countermeasures, and restoration strategies should be selected on the basis of a combined analysis of the effectiveness of forest and agricultural countermeasures. Received: 16 March 2000 / Accepted: 10 September 2000     

The use of computer system in the introduction of countermeasures in agriculture after the Chernobyl accident

In the development of strategies for countermeasures aimed at the rehabilitation of contaminated areas, essential is to identify criteria for assessing their effectiveness and factors influencing the priority of the criteria chosen. A method is suggested for assessing effectiveness of countermeasures in agriculture based on a multicriterium analysis of radiologic, economic, regulatory and socio-psychological indicators characterizing the use of countermeasures. Rating of countermeasures strategies is presented depending on financing of works on the rehabilitation of the Chernobyl affected areas.     

Extrapolations are the Achilles heel of risk assessment

This Reflections article considers the problems associated with the various extrapolations that are required for the estimation of human cancer risks from exposure to environmental carcinogens at low doses. These include extrapolation between species (particularly rodent to human), from responses at high doses to those at low doses, and among different stages of life. Reductions in uncertainty in risk estimates are closely coupled to the ability to conduct reliable extrapolations. The best way forward appears to be the use of data on mechanisms of carcinogenesis to develop bioindicators of responses related to the pathway to tumor formation. Such an approach is proposed based on the phenotypes represented by the six acquired characteristics forming the Hanahan-Weinberg model for carcinogenesis (The Hallmarks of Cancer). In addition, approaches can be established that use the Hanahan-Weinberg model as the basis for the collection and/or analysis of microarray or similar data. The reduction in reliance on default options and safety factors in the risk assessment process is a real possibility.     

Effects of sublethal dose of chlorfluazuron on testicular development and spermatogenesis in the common cutworm, Spodoptera litura

This paper describes the physiological mechanism of action of chlorfluazuron on testicular development and spermatogenesis when sublethal doses (LD₁₀: 1.00 ng/larva or LD₃₀: 3.75 ng/larva) are applied topically to the cuticle of newly moulted fifth instars of the common cutworm Spodoptera litura (F.) (Lepidoptera, Noctuidae). These doses disrupt the growth and development of testes by decreasing the volume and weight of testes and thickness of testes sheath as compared with that of the controls. Sublethal doses of chlorfluazuron also significantly reduce the protein content of the testis, but do not affect the carbohydrate and lipid contents in newly emerged treated males when measured in μg/mg of testis as compared with that of the controls. Additionally, such doses disrupt spermatogenesis by reducing the number and size of eupyrene and apyrene sperm bundles in the testis. Very few or no eupyrene sperm bundles are observed in vas deferens of pre‐ and newly moulted adults compared with controls. This result shows that the transfer of sperm bundles from testes to vas deferens is delayed in treated males. The effects of chlorfluazuron on testicular development and spermatogenesis is thought to be one of the factors responsible for the reduction in fecundity, fertility and hatchability caused by sublethal doses of chlorfluazuron.     

Electron microscopy of the stacked disk aggregate of tobacco mosaic virus protein. II. The influence of electron irradiation of the stain distribution

Optical and computer analysis of bright field electron micrographs of the same negatively stained stacked disk specimens subjected to different electron doses shows that the stain migrates and redistributes itself over the protein surfaces during irradiation. The analysis suggests that the main factors responsible for this migration are the contraction of the stain inevitably brought about by the irradiation, and associated surface energy effects. The morphology of the protein has a strong influence on the path of the migration.A major consequence of these changes in stain distribution is that conventional bright field micrographs taken under normal dosage conditions tend to give a somewhat misleading representation of the specimen's original structure.Migration of the stain under the electron beam is likely to be a fairly general phenomenon and it therefore seems important to take bright field micrographs of negatively stained specimens using the smallest possible electron doses.     

Development of a low-dose anti-resorptive drug regimen reveals synergistic suppression of bone formation when coupled with disuse.

Safe and effective countermeasures to spaceflight-induced osteoporosis are required to mitigate the potential for mission-critical fractures and ensure long-term bone health in astronauts. Two anti-resorptive drugs, the bisphosphonate zoledronic acid (ZOL) and the anti-receptor activator of NF-kappaB ligand protein osteoprotegerin (OPG), were investigated to find the minimum, comparable doses that yield a maximal increase in bone quality, while minimizing deleterious effects on turnover and mineralization. Through a series of five trials in normally loaded female mice (n = 56/trial), analysis of trabecular volume fraction and connectivity using microcomputed tomography, along with biomechanical testing, quantitative histomorphometry, and compositional analysis, was used to select 45 microg/kg ZOL and 500 microg/kg OPG as doses that satisfy these criteria. These doses were then examined for their ability to mitigate bone loss following short-term unloading through hindlimb suspension (HLS). Seventy-two mice were prophylactically administered ZOL, OPG, or PBS and assigned to loaded control or 2-wk HLS groups (n = 12 for each of 6 groups). Both anti-resorptives were able to preserve trabecular microarchitecture and femoral elastic and maximum force in HLS mice (+30-40% ZOL/OPG vs. PBS). In HLS mice, anti-resorptive dosing reduced resorption perimeter at the femoral endocortical surface by 30% vs. PBS. In loaded control mice, anti-resorptives produced no change in bone formation rate; however, reductions in bone formation rate brought about by HLS were exacerbated by anti-resorptive treatment, suggesting synergistic inhibition of osteoblasts during disuse. Refined anti-resorptive dosing will tend to target countermeasures to the period of disuse, resulting in faster recovery and less adverse effects for astronauts.     

The hypothesis of the least constraint and the lognormal distribution of individual sensitivity

The connection between factors and individuals can be characterized by integral parameter and rigidity (constraint). Lognormal distribution of individual sensitivity in population has been substantiated on the basis of probabilistic entropy and evolutionary biology. The connection between heterogeneity of populations and natural selection has been demonstrated. A method for estimation of doses of harmful factors that influenced formation of populations during evolution.