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Biomedical subjects

A A Konradov

Publications and source records attributed to A A Konradov.

At least 19 recordsLinked to original sources

Correlations of life-span variation parameters in 128 successive generations of Drosophila melanogaster with changes in atmospheric pressure and geomagnetic activity.

Correlations between the parameters of life-span (LS) distribution of Drosophila melanogaster, including mean LS (MLS) and the time of 10 and 90% population mortality, and some geophysical parameters that are usually beyond the control of researchers dealing with laboratory cultures, including atmospheric pressure, solar activity indices (Wolf's sunspot numbers and 2,800-MHz radio flux), and geomagnetic activity (planetary index, K(p)), were studied. Geophysical data were obtained from free-access official web sites of the National Oceanic & Atmospheric Administration of the US Department of Commerce and the Institute of Terrestrial Magnetism and Radiowave Propagation of the Russian Academy of Sciences. The geophysical parameters were calculated only for the period corresponding to 10 days of preimaginal development of the flies from egg to imago. Canonical correlation analysis, calculation of the non-parametric Spearman rank-order correlation coefficients, and graphical data analysis were used. Highly significant correlations between parameters of LS distribution in males and females and environmental factors, such as the atmospheric pressure on the 4th and 5th day of development and geomagnetic activity indices (K(p)) on the 6th and 10th day of development were found, with correlation coefficients varying from 0.31 to 0.37 (P<0.02). Assuming a causal relationship between geophysical factors and LS, it may be hypothesized that energetically weak environmental factors determine the formation of LS oscillatory dynamics in laboratory populations. The possible mechanisms underlying the contribution of these environmental factors to the LS variation in successive generations are discussed.

Animals↗

[Historical dynamics of life-span distribution of Man].

In this activity the historical dynamics of life-span distribution parameters of the people was investigated in 12 developed countries encompassing the period of 1750-1998 years, it is treated about 1200 life tables. The approximately of a linear segment of a curve of age-specific death rate by the Gompertz function allows getting an analytical view of the life-span distribution. It is shown that the decreasing of the lower age range since 35 years till 10 years a little bit augments an approximation error. The Stehler-Mildvan correlation parameters are computed for each country, for each year during all indicated period. Estimations of the average life, modal age, dispersion etc. are obtained. It draws a conclusion about the limitation and stabilization of modal age at preservation of existing regularity in dynamics of the life-span distribution parameters.

Adult↗

The phenomenology and possible mechanisms of a new experimental method for accelerating postirradiation restoration of hemopoietic stem cell potential.

Extraction of bone marrow from one or several bones immediately after irradiation, with or without subsequent incubation for a short period under suitable conditions, and subsequent reimplantation into the same organism can reduce the lethal effect of irradiation in a number of species. Extraction plus a period of incubation is referred to as the reimplantation method. The effectiveness is roughly relative to the amount of bone marrow extracted and transplanted. This effect has been demonstrated by assays of 30-45-day survival and of hemopoietic stem cell potential. The effectiveness of the reimplantation method has been tested in a dose range of 6.5 to 8.5 Gy and was found to be 1.2-1.06 in terms of dose reduction factors assayed by bone marrow row cellularity 9 days after exposure and 1.18-1.09 for survival of bone marrow colony-forming units. The favorable effect of incubating irradiated bone marrow with cycloheximide on the stem cell potential has been proven by experiments using a donor-recipient method. The positive effect of the reimplantation procedure and the partial extraction procedure on the stem cell potential in irradiated mice can be shown as soon as 2 h after exposure and the procedures. The results suggest that ther exist some reserves that can be stimulated to accelerate hemopoietic restoration in a heavily irradiated organism. The recruitment of these reserves seems to be related to the response of the structures producing cytokines after lethal irradiation. In addition, repair processes may be involved in the rescue of lethally irradiated hemopoietic stem cells.

Animals↗

31P NMR in vivo study of rat brain energy metabolism after frontal cortex injury. A method based on convoluted correlation matrices of the spectral data.

Disturbances of energy metabolism in rat brain after frontal lobectomy and post-traumatic effects of monosialic ganglioside GM1 on brain energy metabolism were studied by 31P NMR in vivo. Frontal lobectomy caused the statistically significant reversible decrease of ATP and increase of ADP during the compensatory period. In a presence of GM1 these post-operational effects were not observed. The mean value of normalized correlation coefficients between NMR-measured phosphomonoesters, P(i), pH, phosphocreatine, gamma-ATP + beta-ADP, alpha-ATP + alpha-ADP +NAD/NADH + diphosphodiesters and beta-ATP for a given group of animals (Z-index) was used to estimate brain energetic status. It has been shown that the variation of the Z-index correlates with the dynamics of locomotor activity during the compensatory period. The Z-index increased by more than 100% for the subgroup with an increased moving activity and only by about 20% for the subgroup with a decreased activity. Moreover, the compositions of these subgroups were almost the same as those from the solution of the reverse task, i.e., the studied group was divided into two subgroups by the Z-index. The Z-index is proposed as a possible criterion of pathology detection in brain energetics.

Animals↗

31P NMR in vivo study of the acute effects of different doses of gamma-radiation on rat brain phosphate metabolism.

Changes in relative levels of brain phosphates and intracellular pH at selected time intervals after total gamma-irradiation of a rat at a single dose of 6.5 or 300 Gy were studied by 31P NMR in vivo. Irradiation yielded only minor changes in the spectra. Irradiation at a dose of 6.5 Gy caused a reversible decrease in Pi and an alkaline pH shift of 0.2 units after day 1, with no change in ATP. The signal, which consisted of alpha-ATP, alpha-ADP, NAD+/NADH and diphosphodiesters, declined after day 6, possibly due to a fall in NAD+/NADH concentration. Irradiation at a dose of 300 Gy led to an increase in ATP from 10 to 13% of total phosphates after day 1. Homeostasis of brain energy metabolism was characterized by the Z-index (normalized sample correlation coefficients averaged over the correlation matrix for NMR-measured phosphomonoesters, Pi, pH, phosphocreatine, gamma-ATP+beta-ADP, alpha-ATP+alpha-ADP+NAD+/NADH+diphosphodiesters and beta-ATP). The Z value rose from -0.18 +/- 0.02 to -0.02 +/- 0.02 by day 6 or from -0.19 +/- 0.02 to -0.07 +/- 0.02 by day 1 after irradiation at a dose of 6.5 or 300 Gy, respectively. This may indicate a pathological state of brain energetics as a system and a decrease in its stability.

Animals↗

[Changes in energy metabolism in the brain in experimental cerebral ischemia of different degree of severity (nuclear magnetic resonance-spectroscopic study)].

The peculiarities of brain energy metabolism were studied in male rats before and during cerebral ischemia of various severity elicited by bilateral common carotid arteries ligation. A multidimensional analysis was applied. In the rats which died after the ischemia, the NAD + NADH+/phosphocreatine (PCr) ratio and ATP content before ligation were higher than those in the surviving group. Also the strength of relationships between parameters of NMR spectra in each correlation matrix were 10 times higher and the variability of elements in each matrix was significantly lower in victims than those in the surviving group. The development of severe ischemia and the animals death were accompanied by an increase in the inorganic phosphate content, decrease in pH and stepwise disappearing of PCr and ATP. In animals surviving the same brain ischemia model, the changes in 31P spectra parameters pointed to some increase in the ratio of NAD + NADH+ only to ATP + ADP but not to PCr, and to an increase in summarized strength of correlation between 31P spectra parameters with the variability of elements decreased within each correlation matrix. Detection of these changes can be helpful in the diagnosis of mild ischemia without neurological deficit which already needs preventive therapy against more severe ischemia.

Animals↗

[The pharmacokinetics of the antitumor preparation of dimetinur].

The pharmacological disposition of 1,3-dimethyl-1-nitrosourea (dimetinur) in intact rats and animals with Walker carcinosarcoma, glioma 2211, colon adenocarcinoma was studied by the colorimetric assay using an oral drug dose of 100 mg/kg. Computer analysis of data was based on a single-compartment model using the area under the concentration-time curve (S) and the intact drug half-life (t1/2) as main pharmacokinetic parameters. The highest level of the drug (S) was observed in tumour and brain tissues on an equality with drug distribution between blood, spleen, kidney and lungs. The half-life of the dimetinur removal from blood exceeds the known values for certain active NAM type. The antitumour activity of the drug against the studied tumours correlates positively with pharmacokinetic parameters for the tumours (S and 1/tmax).

Animals↗

[Secretion of immunoglobulins in malignant melanoma of the skin].

The study was concerned with the dynamics of correlations between IgA, IgM and IgG levels involved in pigmented neoplasm development in 154 cancer patients and 75 healthy subjects. The dynamics was found to represent stages of tumor development rather than changes in absolute indexes of serum immunoglobulin concentrations. The nature of changes in the structure of correlations suggested a possible switch from IgM to IgG and IgM to IgA secretion, i.e. disturbances in B-lymphocyte differentiation. Said changes were observed at a certain stage of melanoma progression, namely, during metastatic spreading.

Humans↗

[Inoculability and threshold effects in transplantation of experimental tumors].

Inoculability of various experimental tumors (spontaneous, chemically-induced, solid, ascitic and leukemic) versus the amount of inoculated tumor cells (10(0)-10(7)) was studied. With small amounts of cells (10(2)-10(3)), inoculability of some tumors appeared to be nil, while in certain long-passaged neoplasms, particularly, leukemia, as few as 5-10 cells were enough. The data obtained pointed to a threshold in experimental tumor transplantation. However, quantitative analysis failed to establish one in the tumors under study. To assure transplantation, much larger study groups, e. g. of no less than 1500 animals for a breast cancer study, are required, which is hardly practicable.

Cell Count↗

[Dynamics of the chromosomal damages to Ehrlich ascitic cancer and bone marrow cells of mice by the antitumor preparation dimetinur].

The dimetinur effect upon chromosomes of the Ehrlich ascite carcinoma and bone marrow cell populations was analyzed by the cytogenetic method for 10 days after i.p. and i. v. drug administration in doses from 50 to 150 mg/kg. Kinetic regularities of changes in a fraction of cells with chromosome breakages and in the number of broken chromosomes per cell as well as "dose-effect" relations are determined. A linear correlation is established between the level of residual chromosome damages in a population of tumour cells and the coefficient of activity chi* characterizing the antitumour effect of dimetinur. Selectivity of the dimetinur mutagenic action expressed as a more deep and prolonged damage of the genetic system of tumour cells as compared to bone marrow cells of tumour-bearing animals is shown under conditions of a pronounced therapeutic activity.

Animals↗

Assessment of lethal and cytostatic effects of alkylnitrosoureas on the cells of experimental tumors.

The action of a number of active anticancer agents belonging to the alkylnitrosoureas (MNU, DMNU, ADEKO, BCNU, CCMU, MeCCNU), as well as the effectiveness of a combined use of DMMU and ADEKO with cyclophosphamide was assessed on experimental tumors transplanted by inocula of different size. A mathematical model of the connection between survival of tumor-bearing animals with the kinetics of tumor growth was proposed to analyze the treatment effect. The contribution of lethal and cytostatic factors to the resultant effect of the drugs was evaluated. A combination of DMNU and cyclophosphamide was found to possess an additive effect. The synergism of the therapeutic action shown in a combined application of ADEKO and cyclophosphamide was stipulated by the potentiation of the lethal effect of these drugs on tumor cells.

Alkylation↗

[Physical criteria of pathological processes. III. Structure of the correlation between the level of steady brain potential with serum complement proteins in rheumatic diseases].

The activity of serum complement proteins and the level of steady brain potential in patients with systemic lupus erythematosus and rheumatoid arthritis were determined. The statistical analysis indicated that there is a correlation between the parameters of the complement system and neurophysiological characteristics. The differences between rheumatoid arthritis and systemic lupus erythematosus are observed in the mean values of activity of complement proteins and the steady potential, their dispersions, and the structure of correlations between immunological and neurophysiological parameters.

Arthritis, Rheumatoid↗