Parameters of Oxidative Stress and Activity of Antioxidant Enzymes in the Saliva of Patients with Type 1 Diabetes Mellitus.

Glucose concentration in the saliva is increased in type 1 diabetes mellitus. This parameter directly correlates with markers of the disease in the blood serum. Increased concentration of 8-oxo-2'-deoxyguanosine (8-OHdG) and diene conjugates, markers of oxidative stress, and reduced activities of superoxide dismutase and catalase were also observed in this pathology. Correlation analysis revealed a strong positive correlation between glucose concentration and the levels of oxidative stress markers and a negative correlation between activity of antioxidant enzymes and glucose concentration. The results indicate that the level of 8-OHdG, diene conjugates, and superoxide dismutase and catalase activities can serve as diagnostic markers of pathophysiological changes in the body in type 1 diabetes mellitus.

1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline exerts a neuroprotective effect and normalises redox homeostasis in a rat model of cerebral ischemia/reperfusion.

Ischemia is one of the main etiological factors of stroke and is associated with the development of energy deficiency, oxidative stress, and inflammation. An abrupt restoration of blood flow, called reperfusion, can worsen the effects of ischemia. In our study, we assessed the neuroprotective potential of 1-benzoyl-6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline (BHDQ) in cerebral ischemia/reperfusion (CIR) in rats. Wistar rats, divided into 4 groups were used in the study: sham-operated animals; animals with CIR caused by occlusion of the common carotid arteries and subsequent removal of the occlusions; rats treated with BHDQ at a dose of 50 mg/kg in the presence of pathology; sham-operated animals treated with BHDQ. The analysis of the state of energy metabolism in the brain, the level of the S100B protein and the histological assessment of the brain tissue were carried out. The antioxidant potential of BHDQ was assessed by measuring biochemiluminescence parameters, analysing the level of 8-isoprostane, products of lipid and protein oxidation, concentration of α-tocopherol and citrate, and aconitate hydratase activity during CIR in rats. A study of the effect of BHDQ on the regulation of the enzymatic antioxidant system and the inflammatory processes was performed. We demonstrated that BHDQ has a neuroprotective effect in CIR, reducing histopathological changes in the brain, normalizing pyruvate and lactate concentrations, and the transcripts level of Hif-1α gene. The positive effect of BHDQ was probably due to its antioxidant and anti-inflammatory activity, manifested in a decrease in the parameters of the oxidative stress, decreased mRNA of proinflammatory cytokines and NF-κB factor genes. In addition, BHDQ reduced the load on antioxidant protection enzymes, contributing to a change in their activities, decreased the level of antioxidant gene transcripts and expression of Nrf2 and Foxo1 factors toward control. Thus, BHDQ exhibited a neuroprotective effect due to a decrease in the level of oxidative stress and inflammation and the normalization of redox homeostasis on CIR in rats.

Two-color interferometer for study of dense low-ionized plasma on the target in high-power pulse linear accelerator.

A two-color infrared interferometer has been developed for the investigation of high-density weakly ionized tantalum plasma in x-ray complexes based on linear induction accelerators (1.6 kA electron beam current, 4.6 MeV energy, and 100 ns pulse duration). Simultaneous probing at two different wavelengths makes it possible to independently measure the density of neutral and electron components. The interferometer uses wavelength values of 1.064 µm (Nd:YAG laser) and 10.6 µm (CO2 laser). To attenuate the effect of sample beam refraction in inhomogeneous plasma, the interferometer used a refraction suppression scheme composed of spherical mirrors focusing the object beam into the region occupied by the plasma. In addition, the power of the sample beam transmitted through the plasma was controlled in order to analyze whether there was a distortion of the interference pattern because of strong sample beam refraction and absorption in the plasma cloud. To calibrate the initial phase shift of the probe radiation, a movable mirror mounted on a piezoelectric element and oscillating according to a harmonic law with amplitude greater than the laser wavelengths was used. In initial experiments, the parameters of target plasma registered by this interferometer are as follows: the linear density of neutrals reached 1.5 · 1017 cm-2, and the degree of ionization was of the order of 10-2. The target plasma expansion velocity is determined as ∼6 km/s.

Neuroprotective effect of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline mediated via regulation of antioxidant system and inhibition of inflammation and apoptosis in a rat model of cerebral ischemia/reperfusion.

The aim of the study was the assessment of the neuroprotective potential of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline (DHQ) and its effect on inflammation, apoptosis, and transcriptional regulation of the antioxidant system in cerebral ischemia/reperfusion (CIR) in rats. The CIR rat model was constructed using the bilateral common carotid artery occlusion followed by reoxygenation. DHQ was administered at a dose of 50 mg/kg for three days. Histological staining was performed using hematoxylin and eosin. The level of S100B protein, 8-hydroxy-2-deoxyguanosine, and 8-isoprostane was assessed using an enzyme immunoassay. The intensity of apoptosis was assessed based on the activity of caspases and DNA fragmentation. The activity of enzymes was measured spectrophotometrically, the level of gene transcripts was assessed by real-time PCR. DHQ reduced the histopathological changes and normalized levels of S100B, lactate, pyruvate, and HIF-1 mRNA in the CIR rat model. In addition, DHQ decreased the oxidative stress markers in animals with a pathology. The tested compound also inhibited inflammation by decreasing the activity of myeloperoxidase, expression of interleukins and Nfkb2. DHQ-treated rats with CIR showed decreased caspase activity, DNA fragmentation, and AIF expression. DHQ changed activity of antioxidant enzymes to the control values, decreased the expression of Cat, Gsr, and Nfe2l2, which was overexpressed in CIR, and activated the expression of Sod1, Gpx1, Gsta2, and Foxo1. DHQ showed a neuroprotective effect on CIR in rats. The neuroprotective effect involve mechanisms such as the inhibition of oxidative stress, leading to a reduction in the inflammatory response and apoptosis and the modulation of the antioxidant defense components.

[Effect of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline on the intensity of free radical processes and the activity of oxidative metabolism enzymes under toxic liver injury in rats]. / Vozdeistvie 6-gidroksi-2,2,4-trimetil-1,2-digidro-khinolina na intensivnost' svobodnoradikal'nykh protsessov i aktivnost' fermentov okislitel'nogo metabolizma pri toksicheskom porazhenii pecheni u krys.

The effect of 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline on markers of hepatocytes cytolysis (aspartate aminotransferase, alanine aminotransferase and gamma-glutamyl transpeptidase), parameters reflecting the state of oxidative status (intensity of biochemical luminescence and the content of diene conjugates), and the activity of oxidative metabolism enzymes (aconitate hydratase, glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase) was studied in rats with CCl4-induced liver injury. The results obtained in the course of the work demonstrated the ability of the test compound to reduce the severity of oxidative stress and liver cells damage, as well as to change the activity of aconitate hydratase and NADP-generating enzymes in the direction of control values. 6-hydroxy-2,2,4-trimethyl-1,2-dihydroquinoline was more effective in normalizing CCl4-induced changes of the analyzed parameters that Carsil used as a reference compound. The tendency to normalize the state of oxidative status and enzyme activity of oxidative metabolism can attributed to hepatoprotective and antioxidant properties of the tested compound.

[The effect of biguanide derivatives on oxidative stress in rats with hyperglycemia]. / Vozdeistvie biguanidinovykh proizvodnykh na razvitie oksidativnogo stressa pri giperglikemii u krys.

The effect of the synthetic biguanide derivatives N-[imino(1-piperidinyl)methyl]guanidine (NIPMG) and 1,3-dimethyl-5-[(carbamimidamidomethanimidoil) amino]benzoyl-1,3dicarboxylate (DCB) on the degree of proteins oxidative modification (POM) and the DNA fragmentation, the content of the lipid peroxidation primary products - conjugated dienes (CD), and the activity of glutathione antioxidant system in the liver and heart of rats with experimental hyperglycemia was investigated. Administration of the biguanides (15.0 mg/kg) to hypoglycemic rats promoted reduction of the free radical processes intensity in the studied tissues. Data about CD and POM level changes in hyperglycemic rats treated by NIPMG and DKB correlate with the results of DNA fragmentation degree evaluation. At the same time, the activity of antioxidant enzymes (glutathione peroxidase and glutathione reductase), and the reduced glutathione content in the liver and heart of rats changed toward control values. For metformin, which was used as a comparison drug, changes in the studied parameters in the same direction were also found. These results indicate the ability of the tested biguanide derivatives to exhibit a positive regulatory effect on free radical homeostasis, reducing the degree of oxidative stress at this pathology.

[Pulmonary larval paragonimiasis mimicking lung cancer]. / Legochnyi larval'nyi paragonimoz, imitiruiushchii rak legkogo.

Larval paragonimiasis is a parasitic disease caused by lung fluke larvae. Unlike the classic form of paragonimiasis, the larval form occurs with a large number of clinical manifestations. However, this fact only complicates the diagnosis of larval paragonimiasis, for the abundance of clinical manifestations results in the misdiagnosis of other diseases. Another feature of this form of paragonimiasis is the tendency to generalize and mimic the clinical presentation of malignant neoplasms. The performed diagnostic measures failed to give an accurate view of the nature of the disease, therefore diagnostic thoracoscopy was carried out and biopsy specimens were taken from the subpleural region of dissemination, followed by urgent histologic examination suggestive of glandular cancer. This circumstance became the reason for atypical resection of the affected portion, which was done; however, the patient died from pulmonary thromboembolism on postoperative day 2. The main diagnosis of chronic pulmonary generalized paragonimiasis (cystic and pneumosclerotic phases) with neoplastic syndrome was posthumously made.

[Intensity of apoptotic processes, aconitate hydratase activity and citrate level in patients with type 2 diabetes mellitus complicated steatohepatitis under application of epifamin at basic therapy].

DNA fragmentation, caspase-1 and caspase-3, aconitate hydratase (AH) activities, and citrate content have been investigated in the blood of patients with type 2 diabetes mellitus complicated by steatohepatitis. These indicators of apoptotic processes intensity and oxidative stress development were estimated after basic treatment and a combined therapy including epifamin. Before treatment DNA fragmentation blood leukocytes, decrease of AH activity and increase of caspases activities in the serum of patients were detected. Treatment with epifamin provided more pronounced changes in the investigated parameters towards control values as compared to basis therapy. Epifamin caused a positive effect on the citrate content in the serum of patients. Epifamin inclusion to the basic therapy was accompanied by a more pronounced changes towards the normal values of such biochemical parameters as ALT, AST, b-lipoproteins, cholesterol, fasting glucose and postprandial glucose levels. All these changes may be obviously attributed to epifamin-induced correction of the melatonin level and manifestation of adaptogenic properties and antioxidant effects of the hormone.

[EFFECTS OF MELATONIN ON THE ACONITATE HYDRATASE ACTIVITY, CONTENT OF LIPID PEROXIDATION PRODUCTS AND SOME NON-ENZYMATIC ANTIOXIDANTS IN THE BLOOD OF PATIENTS WITH TYPE 2 DIABETES MELLITUS COMPLICATED BY STEATOHEPATITIS].

Type 2 diabetes mellitus complicated by steatohepatitis is accompanied by a decrease in aconitate hydratase activity, increase in the content of diene conjugates, decrease in the concentration of α-tocopherol, and change in the citrate level in the blood serum of patients, which is evidence of the development of oxidative stress as a result of the intensification of free radical oxidation of biosubstrates and decreasing degree of antioxidant defense of the organism. Combined therapy with melaxen provided a more significant change of the investigated parameters toward the norm (on the average by 36%, p 0.05) in comparison with basic treatment. This result was evidently associated with implementation of the antioxidant effect of melatonin, the level of which is corrected under the action of the drug employed.

[Effect of melaxen and valdoxan on free radical processes intensity, aconitate hydratase activity and citrate content in rats tissues under hyperthyroidism].

The influence of melaxen and valdoxan on the biochemiluminescence parameters, aconitate hydratase activity and citrate level in rats heart and liver during development of experimental hyperthyroidism has been investigated. Administration of these substances promoted a decrease of biochemiluminescence parameters, which had been increased in tissues of rats in response to the development of oxidative stress under hyperthyroidism. Aconitate hydratase activity and citrate concentration in rats liver and heart, growing at pathological conditions, changed towards control value after administration of the drugs correcting melatonin level. The results indicate the positive effect of valdoxan and melaxen on oxidative status of the organism under the development of experimental hyperthyroidism that is associated with antioxidant action of melatonin.

The effect of melaxen on the activity of caspases and the glutathione antioxidant system in toxic liver injury.

A comparative study of the activity of caspase-1 and caspase-3, the glutathione antioxidant system and NADPH-generating enzymes (glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase) and a study of DNA fragmentation in the blood serum of patients with chronic alcoholic hepatitis during basic treatment and combination therapy including melaxen have been carried out. It was found that the blood serum level of reduced glutathione, which decreases in pathology, increased more significantly in patients receiving melaxen as compared to the group of patients receiving the standard treatment. More significant changes in the activity of caspase-1 and caspase-3, glutathione reductase, glutathione peroxidase, glutathione-S-transferase, glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase toward the control values were observed during the combination therapy. The correction in the melatonin level under the influence of melaxen apparently had a positive effect on the free-radical homeostasis in patients, which resulted in more pronounced changes in the investigated parameters towards the normal values as compared to the basic treatment. KEY WORD S chronic alcoholic hepatitis; glutathione peroxidase; glutathione reductase; reduced glutathione; glutathione-S-transferase; caspases; melaxen.

Development of a negative ion-based neutral beam injector in Novosibirsk.

A 1000 keV, 5 MW, 1000 s neutral beam injector based on negative ions is being developed in the Budker Institute of Nuclear Physics, Novosibirsk in collaboration with Tri Alpha Energy, Inc. The innovative design of the injector features the spatially separated ion source and an electrostatic accelerator. Plasma or photon neutralizer and energy recuperation of the remaining ion species is employed in the injector to provide an overall energy efficiency of the system as high as 80%. A test stand for the beam acceleration is now under construction. A prototype of the negative ion beam source has been fabricated and installed at the test stand. The prototype ion source is designed to produce 120 keV, 1.5 A beam.

[The use of melatonin in combined therapy of drug-induced hepatitis].

Combined treatment including melatonin resulted in the improvement of general conditions in 81.7% of the patients with drug-induced hepatitis compared with 66.5% after standard therapy including hepatoprotectors. Normalization of biochemical characteristics was more pronounced after treatment with melatonin that caused no side effects as shown by laboratory and instrumental studies.

Photon neutralizer as an example of an open billiard.

A simple photon cavity consisting of three flat mirrors is considered, which provides a model for a photon neutralizer of negative ion beams to be used in a neutral beam injector for plasma heating in fusion devices. Treating the system as an open mathematical billiard, the mechanism of photon scattering on the sharp boundary between two mirrors is described. Assuming a balance between the continuous injection of the photons into the device and their loss through its open ends, the stationary angular distribution of the photons in the trap is computed in closed form and an estimate for the confinement time of the photons in the neutralizer is provided.

[Effects of melaxen and valdoxan on the activity of glutathione antioxidant system and NADPH-producing enzymes in rat heart under experimental hyperthyroidism conditions].

The effects of melaxen and valdoxan on the activity of glutathione antioxidant system and some NADPH-producing enzymes have been studied under conditions of experimental hyperthyroidism in rat heart. Under the action of these drugs, reduced glutathione (GSH) content increased as compared to values observed under the conditions of pathology. It has been established that the activities of glutathione reductase (GR), glutathione peroxidase (GP), glucose-6-phosphate dehydrogenase, and NADP isocitrate dehydrogenase (increased under pathological conditions) change toward the intact control values upon the introduction of both drugs. The influence of melaxen and valdoxan, capable of producing antioxidant effect, leads apparently to the inhibition of free-radical oxidation processes and, as a consequence, the reduction of mobilization degree of the glutathione antioxidant system.

[The activity of glutathione antioxidant system at melaksen and valdoxan action under experimental hyperthyroidism in rats].

Investigation of glutathione antioxidant system activity and diene conjugates content in rats liver and blood serum at the influence of melaksen and valdoxan under experimental hyperthyroidism (EG) has been revealed. It has been established that the activities of glutathione reductase (GR), glutathione peroxidase (GP) and glutathione transferase (GT), growing at pathological conditions, change to the side of control value at these substunces introduction. Reduced glutathione content (GSH) at melaxen and valdoxan action increased compared with values under the pathology, that, obviously, could be associated with a reduction of its spending on the detoxication of free radical oxidation (FRO) toxic products. Diene conjugates level in rats liver and blood serum, increasing at experimental hyperthyroidism conditions, under introduction of melatonin level correcting drugs, also approached to the control meaning. Results of the study indicate on positive effect of melaxen and valdoxan on free radical homeostasis, that appears to be accompanied by decrease of load on the glutathione antioxidant system in comparison with the pathology.

[Effect of combined therapy with melaxen on lipid peroxidation rate and citrate content in blood serum of patients with drug-induced hepatitis diagnosis].

A combined therapy with melaxen led to a decrease in the activity of gamma-glutamyl transpeptidase and the level of diene conjugates in blood serum of patients with the drug-induced hepatitis developing on the background of administration of antituberculous preparations. These changes are indicative of pronounced antioxidant and hepatoprotective properties of the drug. In addition, there was a decrease in the content of citrate and a change in the activity of aconitate hydratase toward a normal level, which reflects a decrease in the degree of pathologic oxidative stress development and is evidence of the antiradical effect of melaxen.

[Peculiar properties of glutathione system and NADPH-generated enzymes functioning in blood of patients with drug-induced hepatitis under combined treatment with epifamin].

Activity of the glutathione antioxidant system has been studied in patients with drug-induced hepatitis treated with standart base therapy and combined with epifamin therapy. In blood serum of patients before treatment the decrease of reduced glutathione (GSH) level and the increase of glutathione peroxidase (GP) and glutathione reductase (GR) activities versus control were observed. Combined treatment with epifamin changed GSH level to the normal values. Treatment with epifamin was accompanied by pronounced increase in GP and GR activities compared with standard therapy. Activities of the NADPH-generated enzymes, glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase, which decreased at this pathology, also demonstrated a more significant increase than standart treatment.

[Intensity of free radical oxidation and superoxide dismutase activity in patients with drug hepatitis in combination therapy with melaxen or epifamin].

Intensity of free radical oxidation processes and superoxide dismutase activity at patients with drug-induced hepatitis at the combined therapy with melaxen or epifamin. Free radical homoeostasis state at patients with drug-induced hepatitis being on standard treatment, including hepatoprotectors, and the combined therapy with melaxen or epifamin has been investigated. Biochemiluminescence parameters in blood serum point out to intensification of free radical processes and inhibition of antioxidant defense of organism, at this time superoxide dismutase activity in blood serum increased. After leading of standard therapy a decline of oxidative stress expression was observed. Incorporation to base treatment of melaxen or epifamin accompanied by correction of antioxidant status of organism and provided more expressed antioxidant effect, that confirmed by changing of biochemiluminescence parameters and superoxide dismutase activity. Obviously, it is related to antiradical properties of melatonin the level of which is corrected under the action of these preparations.

[Antioxidant status of patients with thyrotoxicosis syndrome treated with the combined regimen containing epifamin].

The work purpose was research of degree of free-radical processes intensity and catalase activity in blood serum of patients with a thyreotoxicosis syndrome at traditional treatment and the combined therapy with epifamin. Patients (n=25) have been divided into 2 groups: the first group of patients--12 persons who are on traditional treatment (antithyreoid drugs, beta-adrenoblockers); the second group--13 persons, are padding to basic therapy received epifamin on 1 tablet (10 mg) 3 times a day 10-15 minutes prior to meal within 7 days. Patients with thyreotoxicosis syndrome had an intensification of free-radical oxidation that was traced at measurement of biochemiluminescence parameters in blood serum. At the combined therapy with epifamin less expressed intensity of free-radical processes, and also increasing of the general antioxidant activity of an organism that did not descend at traditional treatment was observed. At carrying out of standard therapy of thyreotoxicosis syndrome, including application of antithyreoid drugs and beta-adrenoblockers, catalase activity decreased, that unfavorable affected antioxidant potential of an organism. At the combined therapy with epifamin level of catalase activity, on the contrary, increased, that could influence positively on antioxidant protection of an organism.