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Biomedical subjects

A Panov

Publications and source records attributed to A Panov.

14 recordsLinked to original sources
PubMed2001

Important factors governing exposure of the population and countermeasure application in rural settlements of the Russian Federation in the long-term after the Chernobyl accident.

Rural settlements located in areas of the Russian Federation contaminated after the Chernobyl accident and exceeding an annual dose of 1 mSv a-1 have been classified according to 137Cs contamination density, internal dose and the neighbourhood of forests. It has been shown that, with the exception of the most contaminated areas, the internal doses decreased in accordance with a decline in 137Cs availability for plant root uptake. An inverse tendency was observed in areas with 137Cs contamination above 555 kBq m-2 which can be explained by a reduction or even termination of countermeasure application and by an increasing consumption of forest products in areas where restrictive countermeasures are still implemented. Twenty-seven settlements have been studied to estimate the effectiveness of countermeasures applied previously and to identify the most important factors governing the radiation exposure to the population and its change with time. It has been shown that the effectiveness of countermeasures which resulted in a decrease of up to 40% of doses has a tendency to decline in the long term. The need for continuation of remediation in rural settlements was evaluated both for selected settlements and extrapolated to the whole contaminated area and it has been shown that the application of countermeasures will be of importance at least up to the year 2045. Rather high effectiveness in terms of internal dose reduction (factor of 2-2.5) of radical improvement (disking, ploughing and reseeding) and administration of Cs binders to animals (Ferrocyn) was demonstrated for the selected settlements. It could be demonstrated that for forest-remote settlements there is a linear dependence between internal dose normalised to the density of contamination and the proportion of peat soils around settlements. For near-forest settlements, this dependence was less pronounced which can be explained by the high contribution of forest food products to the internal dose. Milk is still the major dose-forming product in rural Russian settlements (its contribution to internal dose in forest-remote settlements is above 70%); however, in near-forest settlements, the contribution of mushrooms to the internal dose is comparable to the contribution from milk.

Agriculture↗
PubMed2000

Polymorphic glutathione S-transferase M1 is a risk factor of primary open-angle glaucoma among Estonians.

Primary open-angle glaucoma, the most common form of glaucoma is a slowly progressive atrophy of the optic nerve, characterized by loss of peripheral visual function and is usually associated with elevated intraocular pressure. The etiology and genetic risk factors of primary open-angle glaucoma are mostly unknown. The aim of this study was to find out whether the polymorphism at GSTM1, GSTM3, GSTT1 and GSTP1 loci is associated with increased susceptibility to glaucoma, because these polymorphic enzymes are susceptibility candidates for several diseases, including such eye disease as cataract. The phenotype of GSTM1 and GSTT1 was determined by ELISA and the genotype of GSTM3 and GSTP1 was detected by polymerase chain reaction. Four hundred and fifty two Estonians (250 glaucomas and 202 controls) participated in a case-control study. A significant association of the GSTM1 polymorphism with glaucoma was observed. The frequency of the GSTM1 positive individuals among the glaucoma group was significantly higher than in controls (60 vs. 45.0%) with odds ratio of 1.83 (95% CI 1.26-2.66;P = 0.002). The risk among the GSTM1 positive individuals of developing glaucoma was even higher in the case of smoking: 62.7% of smokers were GSTM1 positive in the glaucoma group while only 33.3% of smokers had GSTM1 positive phenotype in controls (OR = 3.36; 95% CI 1.49-7.56;P = 0.012). An association with a lower level of significance was also found with the GSTM3 gene. Four% of the 250 patients with POAG were identified as carriers of the GSTM3 BB genotype, a proportion which was slightly higher than the 1.0% for the controls (OR = 4.17; 95% CI 0. 90-19.24;P = 0.144). The frequencies of the GSTT1 and GSTP1 genotypes in both groups were not statistically different. The present study suggests that the GSTM1 polymorphism may be associated with increased risk of development of primary open-angle glaucoma.

Adult↗
PubMed2000

Polymorphic glutathione S-transferases as genetic risk factors for senile cortical cataract in Estonians.

PURPOSE: To investigate the possible association between glutathione S-transferase GSTM1, GSTM3, GSTT1, and GSTP1 polymorphism and the occurrence of age-related cataracts in Estonian patients. METHODS: Patients with cortical (155), nuclear (77), posterior subcapsular (120), mixed type (151) of senile cataract and control individuals (202) were phenotyped for GSTM1 and GSTT1 by enzyme-linked immunosorbent assay and genotyped for GSTM3 and GSTP1 by polymerase chain reaction. RESULTS: The frequency of the GSTM1-positive phenotype was significantly higher in the cortical cataract group (60.6%) than in the controls (45.0%) with odds ratio of 1.88 (95% CI, 1.23-2.94; P = 0.004). The cortical cataract risk associated with the GSTM1-positive phenotype was increased in carriers of the combined GSTM1-positive/GSTT1-positive phenotype (OR = 1.99; 95% CI, 1.30-3.11; P = 0.002) and the GSTM1-positive/GSTM3 AA genotype (OR = 2.28; 95% CI, 1.51-3.73; P < 0.001). The highest risk of cortical cataract was observed in patients having all three susceptible genotypes (OR = 2.56; 95% CI, 1.59-4.11; P < 0.001). Also, a significant interaction between the presence of the GSTP1* A allele and cortical cataract was found with prevalence of the GSTP1* A allele among the cortical cataract cases compared with the controls. Ninety-five percent of subjects with cortical cataract had the GSTP1 (AA, AB, or AC) genotype, whereas in controls 87% of persons had a genotype with GSTP1*A allele (OR = 3.1; 95% CI, 1.31-7.35; P = 0.007). In contrast to the GSTP1*A allele, the presence of the GSTP1*B allele in one or two copies leads to decreased cortical cataract risk (OR = 0.09 for GSTP1 BB genotype). CONCLUSIONS. The GSTM1-positive phenotype as well as the presence of the GSTP1*A allele may be a genetic risk factor for development of cortical cataract.

Adult↗
PubMed1999

Mitochondrial disease in mouse results in increased oxidative stress.

It has been hypothesized that a major factor in the progression of mitochondrial disease resulting from defects in oxidative phosphorylation (OXPHOS) is the stimulation of the mitochondrial production of reactive oxygen species (ROS) and the resulting damage to the mtDNA. To test this hypothesis, we examined the mitochondria from mice lacking the heart/muscle isoform of the adenine nucleotide translocator (Ant1), designated Ant1(tm2Mgr) (-/-) mice. The absence of Ant1 blocks the exchange of ADP and ATP across the mitochondrial inner membrane, thus inhibiting OXPHOS. Consistent with Ant1 expression, mitochondria isolated from skeletal muscle, heart, and brain of the Ant1-deficient mice produced markedly increased amounts of the ROS hydrogen peroxide, whereas liver mitochondria, which express a different Ant isoform, produced normally low levels of hydrogen peroxide. The increased production of ROS by the skeletal muscle and heart was associated with a dramatic increase in the ROS detoxification enzyme manganese superoxide dismutase (Sod2, also known as MnSod) in muscle tissue and muscle mitochondria, a modest increase in Sod2 in heart tissue, and no increase in heart mitochondria. The level of glutathione peroxidase-1 (Gpx1), a second ROS detoxifying enzyme, was increased moderately in the mitochondria of both tissues. Consistent with the lower antioxidant defenses in heart, the heart mtDNAs of the Ant1-deficient mice showed a striking increase in the accumulation of mtDNA rearrangements, whereas skeletal muscle, with higher antioxidant defenses, had fewer mtDNA rearrangements. Hence, inhibition of OXPHOS does increase mitochondrial ROS production, eliciting antioxidant defenses. If the antioxidant defenses are insufficient to detoxify the ROS, then an increased mtDNA mutation rate can result.

Animals↗
PubMed1996

Mg2+ control of respiration in isolated rat liver mitochondria.

The role of endogenous mitochondrial Mg2+ as a potential regulator of mitochondrial dehydrogenase activity, and therefore of cellular respiration, was measured in isolated mitochondria containing matrix Ca2+ and Mg2+ levels resembling those occurring in vivo. Ca2+ and Mg2+ depletion was carried out using the cation ionophore A23187 in the presence or absence of the Ca2+ uniporter inhibitor ruthenium red (RR). Divalent cation depletion inhibits the oxidation of alpha-ketoglutarate or pyruvate in states 4 and 3, slows uncoupled respiration and results in decreased membrane potential. Since the addition of Mg2+ could not restore respiration, these dehydrogenases appear not to be regulated by Mg2+. In contrast, similar cation depletion stimulates succinate dehydrogenase (or glutamate dehydrogenase) in state 4 without decreasing membrane potential. The addition of RR caused authentic uncoupling, accompanied by a decrease in membrane potential and an increase in membrane permeability. These effects could be completely reversed by Mg2+. These and other data, showing that Mg2+ depletion results in a change of respiration depending on the substrate oxidized and the metabolic state, indicate that Mg2+ removal may have direct and indirect effects on mitochondrial respiration. A clear direct effect is the stimulation of succinate or glutamate dehydrogenase by decreasing matrix Mg2+. Hence, changes in matrix Mg2+ (in addition to those of Ca2+) could be of great consequence, not only for the control of respiration but also for metabolic pathways affected by changes in concentrations of matrix substrates.

Animals↗
PubMed1996

Independent modulation of the activity of alpha-ketoglutarate dehydrogenase complex by Ca2+ and Mg2+.

The activity of alpha-ketoglutarate dehydrogenase complex (KGDHC), an important enzyme regulating several metabolic pathways, could be regulated by changes in the environment within the mitochondrial matrix. It has been postulated that the activity of this and other dehydrogenases in vivo could be modulated by changes in the intramitochondrial concentrations of Ca2+ or Mg2+. Using a purified alpha-ketoglutarate dehydrogenase from pig hearts, the effect of Ca2+ and/or Mg2+ on the enzyme activity was investigated. Either Ca2+ or Mg2+ increased enzyme activity, and the effects were additive if the concentrations of free divalent cations were below 0.1 and 1 mM for Ca2+ and Mg2+, respectively. In the presence of 1 mM alpha-ketoglutarate and other cofactors, the KM for Mg2+ was 25 microM and less than 1 microM for Ca2+. The KM for alpha-ketoglutarate was a function of the divalent cation(s) present: 4 +/- 1.1 mM in the absence of Ca2+, with or without Mg2+; 2.2 mM in the presence of 1.8 microM Ca2+ alone; and 0.3 mM in the presence of both Ca2+ and Mg2+. Mg2+ increased KGDHC activity only in the presence of thiamine pyrophosphate (TPP) indicating that KGDHC requires both TPP and Mg2+ for enzyme's maximal activity. The affinity of KGDHC for NAD+ is significantly changed by either Mg2+ or Ca2+. The conclusions are that changes in both Ca2+ and Mg2+, in concentrations possibly occurring within mitochondria, could control KGDHC activity and that thiamine pyrophosphate is required for maximal enzyme activity.

Animals↗
PubMed1991

Interstrain differences in organization of metabolic processes in the rat liver--I. The dynamics of changes in the contents of adenine nucleotides, glycogen and fatty acyl-CoAs in the course of short-term starvation in the livers of rats of Wistar, August and WAG strains.

1. The metabolic patterns in the livers of rats of the Wistar, August and Wag strains were evaluated 4, 8, 12 and 24 hr after food withdrawal. 2. In the fed state (4 hr) there were large differences in the liver's contents of ATP, phosphate potential values, glycogen contents and blood FFA. These distinctions disappeared in the fasted state (12 hr). 3. There are large differences between the strains in the dynamics of transition of the liver metabolic patterns from the fed to the starved states. 4. The results obtained show that the three strains of the laboratory animals strongly differ in the organization of the liver energy metabolism.

Acyl Coenzyme A↗
PubMed1983

Enzyme activity pattern in developing mouse brain in situ in embryonic brain aggregated cells at 37 degrees C and 0 degree C.

In aggregates of nervous tissue, cultivated for 1--7 days at 0 degree C and 37 degrees C, respectively, the activities of seven enzymes of energy liberating metabolism were estimated, in order to evaluate their metabolic "profiles" and changes during cultivation. The enzymes used as markers of different pathways of energy liberation from substrates were: lactate dehydrogenase - LDH - (EC 1.1.1.27), triose-3-phosphate dehydrogenase - TPDH - (EC 1.2.1.12), glycerol-3-phosphate dehydrogenase - GPDH - (EC 1.1.1.8), hexokinase - HK - (EC 2.7.1.1.), malate:NAD dehydrogenase - MDH - (EC 1.1.1.37), citrate synthase - CS - (EC 4.1.3.7), and 3-hydroxyacetyl CoA dehydrogenase - HOADH - (EC 1.1.1.35). During the cultivation, some changes in the metabolic "profiles" were observed. Although some of these changes as well as the differences between the cultivation at 0 degree C and 37 degrees C, were statistically significant, they were not greater than the variations between different samples of any tissue taken at different times. They were not, therefore considered to be of major significance. However, all the aggregates exhibited "profiles" characteristic for the nervous tissue, with relatively very high activity of HK, high activity of MDH and CS (carbohydrate breakdown) and low activity of GPDH and HOADH (lipid catabolism).

Animals↗
PubMedDate not supplied

Dietary sugar and salt represent real risk factors for cataract development.

Dietary sugar and salt represent etiological risk factors of human cataract. To verify etiological data on the basis of histological findings, 9 pigs with a body weight of 40 kg, 3 months of age, in groups of 3 were continuously fed with 5% of refined dietary sugar (sucrose - C(12)H(22)O(11)), 0.5% of salt (NaCl) and a sugar-salt mixture (2.5 + 0.25% accordingly) in their crude (unboiled) meal food during 3 months, which resulted in minor cataractous changes in the lens. In the second experiment, 10 weight- and age-matched animals were fed a chronic sugar and intermittent salt diet during 6 months; the other 10 animals served as controls. During the second experiment, crystallin leakage into the aqueous humor of the lens was detected, and a marked swelling of the lens fibers and fiber tips was noticed, indicating that excessive amounts of dietary sugar and salt are risk factors for the development of cataract in normal (nondiabetic) animals.

Animals↗