Search

This study aimed to evaluate occult abnormalities of iron turnover in elite professional athletes. Electron paramagnetic resonance (EPR) and in vitro test for the quantitative determination of iron in human serum on "Cobas Integra 400 Plus" (CI) Roche automatic analyzer were used to evaluate the iron turnover in professional ice hockey players from four teams of the Continental Hockey League (study group, n = 110) and in two different control groups. The first group consisted of nonathletic young men (healthy controls, n = 25). The second group included male and female patients with different pathological conditions (comparison group, n = 16). The data pairs were compared using linear regression analysis, EPR data versus CI measurements. In the control and the comparison groups, EPR Fe3+ data associated with transferrin were highly correlated with CI serum iron measurements (squared correlation coefficient, r2 = 0.95). In the study group, correlation of the EPR Fe3+ measurements with CI serum iron levels in different teams of ice hockey players was statistically less powerful (r2 ranged from 0.61 to 0.78). Acute-phase copper-containing protein ceruloplasmin serum levels determined by EPR are also reported. Acute-phase responses were undetectable in most hockey players within quarterly scheduled medical examinations. The EPR spectroscopy combined with the routine biochemical serum iron measurements enable to detect occult dysmetabolic changes in iron turnover during intensive physical exercises. The results obtained support the use of EPR spectroscopy in the sports medicine because it helps to avoid misinterpretation of personalized biochemical markers and could facilitate the proper monitoring of iron-targeted interventions. [ABSTRACT FROM AUTHOR]

Based on the active ingredient of the drug Ximedon (1,2-dihydro-4,6-dimethyl-1- N-(2-hydroxyethyl)pyrimidone-2, referred below to as pyrimidine ( I), novel derivatives containing biogenic acids: succinic, L-ascorbic, para-aminobenzoic, nicotinic, and L-2-amino-4-(methylthio)butanoic (L-methionine) acids have been synthesized. The parameters of acute toxicity (LD) have been studied. The antitoxic effect of the compounds upon the injury by the hepatotropic poison carbon tetrachloride has been examined as the primary evaluation of their hepatoprotective properties. It has been found that, according to toxicological safety, the compounds synthesized belong to classes III and IV (moderately and little toxic compounds). The conjugates of pyrimidine ( I) with ascorbic acid and methionine (LD more than 5400 mg/kg) are least toxic. Pyrimidine ( I) and its derivatives possess the antitoxic activity upon acute poisoning with carbon tetrachloride; the combined injection of carbon tetrachloride with pyrimidine ( I) or its derivatives leads to an increase in the survival of animals and the normalization of the integral functional parameters, weight and body temperature, which decrease upon toxic injury. In addition, pyrimidine ( I) and some of its derivatives (conjugates with L-ascorbic, succinic, para-aminobenzoic, and nicotinic acids) decrease the weight coefficients of the liver and kidneys (the organ-to-body-weight ratio) and the activity of transaminases, the markers of hepatic cytolysis, which increase upon toxic injury with carbon tetrachloride. The area of the pathological injury of the liver by steatosis and necrosis decreases by the action of pyrimidine ( I) and its novel derivatives (conjugates with L-ascorbic, succinic, and nicotinic acids) two to three times. Advantages of pyrimidine ( I) and its novel derivatives over the hepatoprotective drug Thiotriazolin have been revealed. [ABSTRACT FROM AUTHOR]

Hepatoprotective properties of a new pyrimidine derivative - L-ascorbate 1-(2-hydroxyethyl)-4,6-dimethyl-1,2-dihydropyrimidine-2-one, synthesized on the basis Xymedon, were assessed in white rats exposed to CCl4. The compound under study administered prior to exposure to CCl reduced the deviation of biochemical parameters from reference values and severity of structural and morphological changes in liver, when compared to the control. Hepatoprotective properties of the studied compound were more pronounced than those of Xymedon. [ABSTRACT FROM AUTHOR]

The iron metabolism was studied in serum blood samples collected from 26 professional sportsmen undergoing intensive physical exercises using EPR combined with hematological and biochemical laboratory tests. Only 23% of EPR spectra ( n = 6) were practically normal while in the rest spectra additional abnormal absorption lines were detected. Presumably, the significant portion of new signals may be caused by different cytochromes. Moreover, the anisotropic signals with g ≅ 2.02; g ≅ 1.94 and g ≅ 1.86 registered in some spectra pointed to the sulfur-iron centers. There was nearly linear correlation between the concentration of Fe in transferrin (Fe-Tf) obtained from the EPR spectra and the serum iron concentration measured by absorption photometry both for sportsmen and controls (healthy individuals and patients with different diseases). At equal serum iron concentrations the Fe-Tf level was higher in sportsmen than that in controls. The Pearson correlation coefficient ( r) for Fe-Tf and serum iron values was equal to 0.89 in sportsmen versus r = 0.97 in controls. Additional new lines in serum EPR spectra of professional sportsmen prove the suitability of EPR assay for scheduled medical exams since routine biochemical and hematological tests are insufficient to discover all abnormalities in iron metabolism under intensive physical exercises. [ABSTRACT FROM AUTHOR]

Changes in Fe-transferrin (Fe-Tf) and Cu-ceruloplasmin (Cu-Cp) concentrations in venous blood sampled from anemic patients with urinary bladder and kidney cancer of stages I-IV were assessed using EPR spectroscopy. In malignancy-associated anemia, the paramagnetic Fe concentration in Tf proved to be below the norm, while in anemic non-oncology patients the Tf iron saturation was normal. Moreover, in patients with malignancy-associated anemia the Cu-Cp on average was nearly twice higher than in healthy volunteers ( p < 0.01). Thus, simultaneous EPR measurement of protein-borne paramagnetic centers (such as Fe-Tf and Cu-Cp) in the blood of anemic patients can be used as an express biomarker for urological cancer even at early stages of malignant growth. [ABSTRACT FROM AUTHOR]

The magnitude of transmembrane potential Δψ in cells of Escherichia coli K12 was determined by the method of flow cytofluorometry for different phases of growth. It was large in the log phase, whereas in the lag and stationary phases, the population was shown to consist of two subpopulations with low and large values of Δψ in cells. In the presence of 200 mg/l of 2,4,6-trinitrotoluene (TNT), this bimodal distribution of Δψ over the population was observed during the entire growth period until TNT was almost completely eliminated from the cultivation medium (to a concentration of 18–20 mg/l). The mean value of Δψ in cells of the population grown in the presence of TNT was substantially smaller than that in controls due to the larger fraction of the subpopulation with a low value of Δψ. Upon elimination of TNT, the distribution of Δψ in cells of the culture became unimodal and close to that in the control culture in the early log phase of growth. These findings are discussed from the standpoint that considers heterogeneity of the culture of Escherichia coli K12 as a mechanism of its adaptation to the presence of xenobiotics. [ABSTRACT FROM AUTHOR]

The possibility of inducing apoptosis in K562 myelogenic erythroleukemia cells, A549 lung carcinoma cells, and normal human lymphocytes was studied for Bacillus intermedius RNase (binase) and its mutants Lys26 Ala and His101 Glu with impaired catalytic activity. Selective induction of apoptosis in leukemic blood cells by binase was demonstrated for the first time. Binase did not exert an antiproliferative or proapoptotic effect on peripheral blood lymphocytes of healthy donors. Low-molecular-weight (less than 50 kb in size) oligonucleosomal DNA fragments, which are early markers of apoptosis, were observed in human solid-tumor cells treated with binase. Studies with the binase mutants showed that a decrease in catalytic activity to 2.5% of the level characteristic of the wild-type enzyme deprives binase of its proapoptotic effect. The selective proapoptotic effect of binase on malignant cells provides evidence that bacterial RNases are promising for designing alternative antitumor drugs. [ABSTRACT FROM AUTHOR]

Apoptosis (from the Greek apoptosis, i.e., falling of leaves) is the phenomenon of programmed cell death, which plays an important role in the normal embryonic development and maintenance of the homeostasis of the differentiated tissues of adult organisms. Completion of the apoptosis process is accompanied by specific morphological and biochemical changes in the involved cells. Various disturbances in the control of apoptosis underlie various neurodegenerative diseases, the formation of malignant tumors, autoimmune disturbances, and developmental abnormalities. A deficit of neurotrophic factors leads to apoptosis of neurons. The survival of specific cell populations of neurons is controlled by neurotrophic factors and their combinations. Oncogene bcl-2, a repressor of cell death, belongs to the better-studied factors controlling apoptosis. The terminal stages of cell death, including the death of neurons, depend on the activation of caspases, specifically caspase-1 (interleukin-1β-converting enzyme). Ca2+and reactive forms of oxygen play an important role in the initiation of apoptosis by changing the mitochondrial permeability. Neuregulin, a factor of neuronal origin, is the main controlling factor in apoptosis of Schwann cells, and this process determines the size of their definitive population. Fibroblast growth factor b diminishes the apoptosis of Schwann cells in regenerating nerve fibers. [ABSTRACT FROM AUTHOR]

High radioprotective activity of xymedon was shown in mice. Radioprotective effects of this preparation were accompanied by restoration of the delayed-type hypersensitivity response and Ca2+-ATPase activity in splenocytes which were inhibited by γ-irradiation (3 Gy). At concentrations of 10−3 and 10−6 M xymedon stimulated the activity of DNA topoisomerase-I of splenocyte nuclei. Here we discuss a mechanism of radioprotective effects of pyrimidine derivatives associated with the inhibition of apoptosis of lymphoid cells and the stimulation of proliferation and differentiation of lymphoid precursor cells. [ABSTRACT FROM AUTHOR]

The pyrimidine derivatives xymedone and diucifon decrease the activity of adenylate cyclase, as shown in experiments on thymocytes and lymphocytes of guinea pig lymph nodes and human peripheral blood lymphocytes. Inhibition of the enzyme depends on the subpopulation and species appurtenance of immunocompetent cells. The relationship between the results and effects of pyrimidine derivatives in experiment and clinical setting is discussed. [ABSTRACT FROM AUTHOR]