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The article highlights the pathogenetic mechanisms of endometriosis outside the peritoneal cavity from the point of view of the role of bone marrow stem cells, given a possible explanation for the low efficiency of drug therapy of endometriosis outside the peritoneal cavity. The paper presents our own experience of using agonist of gonadotropin-releasing hormone intrauterine device with levonorgestrel at the same time.

Certain carbohydrates and polyols are used at various stages of the production of immunobiological preparations as stabilizers of biological activity, particularly in the production of lactoglobulin (against opportunistic pathogens) using membrane ultrafiltration. This study concerns the effect of these substances on changes in the amide content in proteins of this lactoglobulin. Lactoglobulin was incubated in near-physiological (0.9% NaCl, pH 5.5) 10% solutions of glucose, fructose, and sorbitol at 4 and 35°C for 7, 14, and 28 days. A lactoglobulin solution in 0.9% NaCl, pH 5.5, was used as the control. All substances studied suppressed the reduction of the amide group content of asparagine and, in contrast, increased the rate of amide group removal from glutamine residues in proteins of lactoglobulin preparations.

Certain carbohydrates and polyols are used at various stages of the production of immunobiological preparations as stabilizers of biological activity, particularly in the production of lactoglobulin (against opportunistic pathogens) using membrane ultrafiltration. This study concerns the effect of these substances on changes in the amide content in proteins of this lactoglobulin. Lactoglobulin was incubated in near-physiological (0.9% NaCl, pH 5.5) 10% solutions of glucose, fructose, and sorbitol at 4 and 35 degrees C for 7, 14, and 28 days. A lactoglobulin solution in 0.9% NaCl, pH 5.5, was used as the control. All substances studied suppressed the reduction of the amide group content of asparagine and, in contrast, increased the rate of amide group removal from glutamine residues in proteins of lactoglobulin preparations.

The influence of some hydrocarbons that are often used at different stages of immunobiological preparation's production as stabilizers of biological activity on the dynamics of nonenzymatic deamidation in proteins of immune whey against conditionally pathogenic microorganisms obtained by means of membrane ultrafiltration technology is investigated. Preparations of whey were incubated in 10 per cent solutions of glucose, fructose and sorbitol at the conditions similar to physiological ones (0.9% NaCl, pH 5.5) and temperature of about +4 degrees C and +35 degrees C for 7, 14 and 28 days. A sample dissolved in 0.9% NaCl (pH 5.5) without addition of hydrocarbons was used as a "control preparate". All explored substances brought about the suppressive effect on deamidation rate of asparaginyl residues whereas that of glutaminyl residues, on the contrary, was obviously increased. The possible reasons for these observations are discussed.

Free radical processes and antioxidant systems activities were studied before and after treatment in blood and saliva of 23 depressive patients with ICD-10 diagnosis--6 with depressive episode and 17 with recurrent depression. Compared to control, blood plasma Fe(2+)-rodamine induced chemiluminescence, total peroxidase and catalase activities increased and blood plasma superoxide eliminational activity as well as superoxide dismutase activity in erythrocytes decreased in patients before treatment. At the same time, total peroxidase activity, superoxide eliminational activity and catalase activity were elevated in the patient's saliva. After antidepressant treatment, positive dynamics for many parameters studied was more pronounced in responders. Saliva was shown to be potential biological material for "oxidative stress" assessment and for treatment efficacy evaluation in depression.

The intensity of free radical processes (FRP) and the activity of antioxidant (AO) systems in human blood plasma and saliva were studied under physiological emotional strain and depressive pathologies (before and after treatment). The significant alterations in the dynamics of investigative indexes under different emotional strain were revealed. These alterations in saliva were more intensive than in blood plasma. The treatment led to the stabilization of FRP intensity and the activity of AO protection. The correlation between saliva and blood plasma parametres allows to use saliva for the estimation of emotional strain and of the efficiency of therapeutics under depressive pathologies.

Chemiluminescence analysis was used to examine the yeast cell-activation of rat whole blood neutrophilic leukocytes in rats after their pre-exposure to 3-hour hypoxia (9,000 m above sea level) and two-hour hyperoxia (0.3 MPa), as well as their resultant effects. The hypoxia was found to cause a significant (42%) reduction in the length of the latent period, suggesting that it activates the phagocytic activity of neutrophilic leukocytes. At the same time hyperoxia leads to a delayed response of competent cells to yeast cell stimulation. On subsequent exposure to hypoxia and hyperoxia, drastic inhibition of drastic cellular activation occurred, which manifested itself by a 62% increase in the length of the latent period and by a 38% rise in the appearance time of luminescence peak. Thus, the findings suggest that it is essential to bear in mind the fact that phagocytosis can decrease if oxygen is overdosed during hyperbaric oxygenation and in hypoxic states.

Content of middle mass molecules (MMM) was studied in blood plasma of rats treated with pyrazidol, the known inhibitor of monoamine oxidase of the A type. A distinct increase in the MMM nonpeptide component was detected both in intact animals and in the rats kept under hypoxic conditions (9,000 m, 3 hrs) after three administrations of pyrazidol. Under conditions of intermittent hypoxia higher increase of the nonpeptide component as well as an increase of the MMM peptide component were detected. The MMM blood fraction was also elevated in the animals adapted to hypoxia. A possible role of the MMM fraction in the pyrazidol-produced adaptation effect during hypoxia is discussed.

Different regimens of oxygenation were studied in rats: acute hypoxia (9,000 m, 3 hrs), acute hyperoxia (0.7 MPa O2), which caused convulsions, and their simultaneous effects. Under these conditions the following parameters were evaluated: the rate of Fe(2+)-induced chemiluminescence, content of nitrogen and peptide catabolism products (urea, urates and middle molecule peptides) as well as total peroxidase activity, content of extraerythrocyte hemoglobin and lactic acid in blood plasma. Distinct inhibition of the chemiluminescence rate was found in all the three experimental groups studied; accumulation of uric acid, middle mass peptides, extraerythrocyte hemoglobin, lactic acid as well as an increase in the total peroxidase activity were observed in hyperoxia and in simultaneous effect of hypo- and hyperoxia; total peroxidase activity was decreased in rats with acute hypoxia. Accumulation of urates and middle mass peptides was considered according to these substances capacity to inhibit free radical oxidation in vivo.

The role of the emoxipin (Em.) (2-ethyl-6-methyl-3-oxipyridine) in the correction of the free radical oxidation and allied processes in lung tissues and blood plasma under high-pressure oxygen-prolonged action has been investigated. The studied oxygen exposure (0.3 MPa, 5h) causes the lung stage of oxygen intoxication. It is confirmed by exterior morphological assessment of the lung. The lipid peroxidation increase in lung tissue and blood plasma as well as erythrocyte membranes destabilization result from oxygen exposure. Lipid peroxidation intensity was estimated by determining of content of lipid peroxidation molecular products such as diene conjugates and Shiffs' bases. Erythrocyte membranes stability was evaluated with hemoglobin yield, total iron level and total peroxidase activity in blood plasma. Emoxipin was injected intraperitoneally in a dose 150 mg per 1 kg rats' weight just before the oxygen exposure. Emoxipin is found to improve physiological state of animals and to increase their survival; it normalizes morphology of the lungs and their state; stabilizes erythrocyte membranes injured under oxygen exposure; decreases intensity of lipid peroxidation processes in the lungs and in blood plasma which was previously increased under hyperoxia.

The authors attempted to modify the macro-method for assessment of the intensity of luminol-dependent chemiluminescence by using small volumes of capillary blood, diluted 100-fold. They have demonstrated the compatibility of two methods for blood collection, from the vein and from the finger, on the basis of the rapid test of oxygen intoxication severity and individual sensitivity of the body to hyperoxia in vitro. Use of microvolumes of the sample for analysis will facilitate the clinical application of the test for the selection of the optimal HBO schemes.

The levels of tissue antioxidant uric acid in relation to chromosomal aberrations and leaving erythrocytic chromatin were determined in the spleen, bone marrow and blood of rats exposed to toxic hyperoxia (0.7 MPa O2, convulsions). Considerable growth of the uric acid levels and the rate of chromosomal aberrations in all tissues was observed within the first hours after treatment. The article discusses mechanisms of uric acid formation, redistribution and disintegration in tissues under extreme conditions. Specificity of the uric acid metabolism in tissues was shown with the help of the correlation analysis of uric acid concentrations. Inverse relationship between uric levels and chromosomal impairments noted in some cases permits to make a supposition about genoprotective properties and adaptogenic role of uric acid during oxidative stress.

Content of extra erythrocyte hemoglobin (EEH), total peroxidase activity (TPA), tseruloplasmin oxidase activity (TOA) and chemiluminescence intensity have been investigated in plasma. The dose-dependent changes of EEN, TPA, TOA are shown in experiments on the animals under hyperbaric oxygen (HBO) pressure (0.2, 0.3, 0.5, 0.7 MPa from 30 min. to 120 min.) and EEH, TPA--under hyperbaric air (1.1 MPa; 4 hours). All these parameters have been studied in patients treated with HBO for the assessment of HBO efficacy in the clinical investigations. These biochemical parameters may be used as informative tests of the functional state of the organism under HBO and hyperbaric air.

Extra-erythrocyte hemoglobin (EEH) level and total peroxidase activity (TPA) have been analysed in the blood serum and plasma of 44 patients following hyperbaric oxygenation (HBO). The levels of the parameters tested decreased after 3 HBO procedures and remained low to the end of the treatment period in the first group of patients. In the second group of patients, on the contrary, EEH and TPA levels increased after 3 HBO procedures and remained high to the end of the treatment period. In both groups of patients EEH changes correlated with TPA alterations. Possible EEH and TPA determination for the estimation and enhancement of HBO treatment efficacy is discussed.

The intensity of proteolytic processes and qualitative composition of autolysis products of the brain, liver and testicle tissues of young and old rats were studied. The gel-chromatographic analysis (Sephadex G-15 and G-50) revealed no considerable amount of high-molecular peptides (1500 Da and over) before and after autolysis. The measurement of the quantity of free amino groups in the gel-chromatographic fraction after the complete acid hydrolysis has confirmed that result. The low-molecular peptides and free amino acids, are the main products of the tissue autolysis. The intensity of proteolytic processes, determined by an increase in the amount of amino acids depends on the autolysis duration and age of animals. The total increment of amino acids in the brain and liver tissues of old animals for the first hour of autolysis has been higher by 102 and 219% as compared to young ones. The autolysis of testicles of the young and old animals after the first hour of incubation is characterized by the same intensivity. Such a regularity is not revealed when analyzing the same processes by the Lowry method.

During exposure of albino rats to oxygen under a pressure of 4 atm for 1 h (the preconvulsive state) and of 6 atm (convulsive state) an increase in the serum hemoglobin concentration was found. The total ion concentration increased at the same time. By disc electrophoresis in 7.5% polyacrylamide gel, changes in the ratio between the hemoglobin fractions in the serum were found in both stages of oxygen poisoning. An increase in the concentration of transferrins was found during hyperoxia under these conditions. If urea was administered to the animals before the session of hyperbaric oxygenation, the changes observed were less marked.

It was shown that self-fluorescence of normal human immunoglobulins prepared with the use of donor and placental raw materials lowered after incubation at 37 degrees C for 28 days and after storage under the standard conditions (4-10 degrees C) for 2 years. Dependence of thermostability of the immunoglobulins on the raw material used for their preparation and the storage period was revealed spectrofluorometrically. Resistance of the proteins to thermal denaturation lowered on storage. However, it was higher in the immunoglobulins prepared with the use of donor serum. Thermostability and lowering of self-fluorescence of the proteins depended on the level of their amidization.

gamma-Globulin from human blood serum was incubated in thermostat at 37 degrees within 15, 30, 45, 60 and 72 days. Amount of readily and poorly hydrolyzed amide groups as well as an increase in amino acid content were estimated in the protein at zero time and at these periods. The sterility of the preparation was examined in each case. Spontaneous deamidation of gamma-globulin, observed during incubation, caused an increase in negative charge and altered electrophoretic mobility of the protein molecule. gamma-Globulin was attacked by prothelin more effectively as amount of amide groups was decreased in the protein. Spontaneous deamidation appears to be one of reasons of the protein molecules ageing.

The rate of native and deamidized serum albumin in vitro splitting by the brain, liver, kidney, testicle and spleen tissue proteinases was studied at pH 3.2, 4.8, 7.2 and 8.5. The deamidized preparation of serum albumin was obtained during its incubation under sterile conditions at 37 degrees C. The amount of amide groups in the process of protein incubation decreased by 19.4% mainly due to readily hydrolyzed asparagine groups. Desamidated serum albumin is splitted by tissue proteinases more intensively than native albumin. Intensity of the splitting depends on pH of the incubation medium and proteinase source. Specific proteolytic activity to desamidated serum albumin is shown to decrease in old rats as compared to young ones.

Amidation of two protein fractions of brain, heart and liver of senite rats was found to decrease by 15--21% as compared with that of young animals. This decrease was shown to be due to unstable amide groups. Strong evidence is presented favouring the preposition that in proteins the unstable amide groups are those of asparagine and the stable ones those of glutamine. The possibility of the nonenzymatic deamidation of proteins was investigated. Deaminated proteins were found to be more easily attacked by proteinases which could be one of the possible ways of breakdown of aging proteins.

The relative effectiveness of radical formation by different concentrations of hemoglobin, hemin and Fe2+ in the reaction with H2O2 evaluated by the intensity of chemiluminescence was studied. Hemoglobin was shown to be remarkably effective at the concentrations close to those in blood plasma. It is suggested that exoerythrocyte hemoglobin and the products of its destruction up to hemin are the most effective prooxidants and potential centers of radical formation in the blood.

Changes in the total peroxidase activity (TPA) and extraerythrocyte hemoglobin (EEH) content have been studied in the blood plasma and serum of patients treated with hyperbaric oxygenation (HBO). TPA and EEH content after the 3rd HBO session increased by 38% and 257%, respectively, in the plasma and by 56% and 74%, respectively, in the serum. By the end of HBO therapy course, after the 8th session, plasma level of the parameters under study normalized, while their serum level was higher than baseline. Possible use of the parameters under study for the assessment of HBO efficacy is discussed.

The effect of different substances partly used as preservatives for the blood storage and at different stages of manufacturing of human blood preparations on the dynamics of nonenzymatic deamidation of commercial protein preparations and on their heat stability was being studied. Albumin and gamma-globulin preparations in the solutions of 60% glycerol, 60% ethylene glycol, 40% beta-alanine, aspartic and glutamic acids in physiological concentrations, 40% glucose and 40% sucrose after 2-hour thermal denaturation (100 degrees) were incubated under (or close to) physiological conditions (pH 7, 37 degrees) for 0.7; 14, 21, 28 and 90 days. The protein preparations in the saline were used as control. After precipitation of protein with TCA, the contents of free ammonia and TCA-soluble products were measured by the Lowry technique. The precipitate washed by organic solvents was used to determine the amide fractions. No reliable difference in increasing the TCA-soluble Folin-positive products was observed. All substances studied but glycerol sped up the deamidation of albumin and gamma-globulin preparations both during thermal denaturation and incubation. On the contrary, glycerol slowed down the deamidation of proteins. Possible reasons of the observed phenomena are discussed.

The in vitro and in vivo experiments show that urea inhibits the bivalent iron oxidation and as a result inhibits the lipids peroxide oxidation in homogenates of the brain and liver tissues and in suspension of rat erythrocytes.

Correlation between a pro-oxidant activity of blood, estimated by means of chemoluminescence in the system H2O2-luminol-blood plasma, and individual sensitivity of rabbits to the effect of oxygen was studied. Alterations in the blood pro-oxidant activity, as shown by treatment of the blood sample with 0.7 MPa of oxygen in vitro, correlated distinctly with the period of convulsions as well as with viability of animals during acute hyperoxia.

The number and composition of ferro-containing proteins, the total number of iron, summary peroxidase activity and peptide-hydrolase activity have been determined under different hyperbaro-oxygenation (HBO) in blood serum. It has been established that under HBO the concentration of ferro-containing proteins increases, the fraction composition of serum and erythrocyte haemoglobin changes, the activity of acid peptide-hydrolases increases and the protamine-splitting peptide-hydrolase activity lowers. The administration of urea before HBO-experiments leads to the normalization of the most biochemical indicators of blood serum. The tests of oxygen intoxication depth assessment have been suggested.

For studying the mechanism of hyperoxia toxic effect on metabolism in the rat brain localization of lysosomes enzymes - acid phosphatase, DNase II and acid peptid-hydrolases were investigated in the brain subcellular fractions under different phases of oxygen poisoning and in the in vitro experiments. Under hyperoxia redistribution of the lysosome enzymes is found between the fraction enriched with lysosomes and the soluble one. The character of redistribution evidences for disturbance of permeability in the brain lysosome membranes under hyperoxia. Urea possessing a protective effect under these conditions prevents from labilization of lysosome enzymes which is evoked by the effect of oxygen hyperoxia. When studying manifestation of the effect of lysosome hydrolases release on the substrate level there were found constancy of DNA content in the brain under hyperoxia and a decrease in polymeric property of the brain DNA an hour after the beginning of the terminal phase of oxygen poisoning.

During incubation of gamma-globulin preparations under conditions similar to physiological ones within 28 days (0.9% NaCl, pH 7.0, 37 degrees) as well as during storage at 3-10 degrees within 36 months gradual nonenzymatic deamidation of the protein occurred mainly due to hydrolysis of readily accessible amide groups (asparagine). Fluorescence of the preparations decreased gradually in the course of deamidation; it constituted for 82% of the initial value after incubation during 28 days. Immunological activity of the gamma-globulin, which lost 19.6% of amide groups, was decreased by 34%; alteration in the amidation by 45.1% was accompanied by a decrease in active antibodies concentration by 92.3%. Nonenzymatic deamidation may be responsible for conformational alterations and inactivation of gamma-globulin.

Rates of autolysis and degree of amidation of tissue proteins were studied in rats under conditions of ageing and after starvation during 7 days. Proteins with decreased content of amide groups accumulated in brain, liver tissues and skeletal muscles. This phenomenon occurred apparently due to decrease in the rate of protein autolysis observed in ageing. In testes, where the rate of protein autolysis was similar both in young and old animals, the protein amidation was not altered on the course of ageing. Under conditions of severe starvation activation of proteolysis was observed in cells. At the same time, the amide content was restored in liver and muscle proteins of old rats up to the level, estimated in tissues of young animals. These data suggest stimulation of selective degradation of the deamidated proteins. The activation of autolysis and normalization of the protein amide groups content were not observed in brain of old animals under conditions of starvation.

A rise of hemoglobin concentration accompanied by an increase of the total iron in the blood serum of white mice was found under oxygen pressure of 4 atm for an hour (preconvulsive state) and 6 atm (convulsive state). Changes in correlations of hemoglobin fractions in the blood serum were detected in both stages of oxygen poisoning by disc-electrophoresis in 7.5% polyacrylamide gel. A rise of transferrin concentration under these conditions (hyperoxia) was observed. The deflections occurred were less pronounced following administration of urea to the animals before hyperbaric oxygenation.

Olfactory mucosa of the frog was stimulated with odours of amylacetat , butanol, alcohol, naphthalene, acetic acid in air and oxygen media under normal and high oxygen pressure (0.2 MPa and 0.7 MPa). The electroolfactogram (EOG) amplitude was higher in oxygen due, probably, to the olfactory mucosa oxygen saturation on concentration gradient as well as to the activation of processes related to the EOG generation. 0.2 MPa pressure as well as 0.7 MPa pressure applied for 60 min decreased the EOG amplitude.

The amide content of total proteins and protein fractions (alpha-, beta-, gamma-cristallins and albuminoid) from cortex and nuclear lens zones of cattle has been investigated. The amide content in proteins of cortex and nuclear lens of young animals (1,5-2 years old) is the same. The decrease of the amide content in the proteins of nuclear lenz zone of old animals (6-12 years old) is due to fraction of readily hydrolysed amides. The data obtained prove the posttranslational desamidation of lens proteins at ageing. beta-Cristallines--the proteins with the highest amides content is exposed to posttranslational desamidation most of all.

The rate of lipid peroxidation (by content of the lipid peroxide transformation end product--malonic dialdehyde) in homogenates of rat brain was studied as affected by hyperoxia and with a protective effect of urea in experiments in vivo and in vitro. In both cases an increase is observed in the malonic aldehyde yield with the effect of oxygen under higher pressure. Urea in physiological concentrations lowers the yield under the effect of hyperoxia in vitro. In experiments in vivo introduction of urea also evokes a decrease in the rate of peroxidation. It is established that hyperoxia and urea affect mainly the ascorbate-dependent system of peroxidation. The compositon of phospholipids in the rat brain was studied under the effect of hyperoxia and urea. No changes were found in the number of fractions under the effect of 6at oxygen, only quantitative changes are observed. With introduction of urea before hyperoxia there occurs a normalization in the phospholipid composition. The authors suppose the protective effect of urea to be due to its influence on membranes.