RNA interference--about the reality to be exploited in cancer therapy.

The discovery of RNA interference (RNAi) in mammalian cells raises the expectations of gene therapy, especially in cancer. However, it is too early to say how great this promise may be because of many disputable problems including intracellular delivery of siRNA, the transient nature of RNAi and potential side effects after long-term treatment. The present microarray study demonstrates that the RNAi of one oncogene (encoding bcr-abl fusion protein in chronic myelogenous leukemia) triggers an overexpression of other "sleeping" oncogenes, antiapoptotic genes and factors, preserving the immortalization of bcr-abl-positive leukemia cells.

Chemiluminescent analysis of the antioxidant and immunomodulation effects of several psychotropic drugs on peritoneal macrophages.

The present study describes the application of several chemiluminescent (CL) methods for evaluation of antioxidant and immunomodulation effects of psychotropic drugs upon phagocytes: KO2-induced luminal-dependent CL for detection of superoxide anion radicals in a pure chemical system; PMA- and A23187-induced CL of peritoneal macrophages for detection of free radicals in cell suspension; and CL, produced by the luciferase-catalyzed luciferin + ATP reaction, for evaluation of cell viability before and after drug application. These methods provide also a way to investigate the location of drug action. It was found that the psychotropic drugs in fluence the 'oxidative burst' of macrophages through two mechanisms: by expression of drug antioxidant properties and/or by a direct immunomodulation effect.

Interaction of soybean agglutinin with leukemic T-cells and its use for their in vitro separation from normal lymphocytes by lectin-affinity chromatography.

A procedure for separation of leukemic T-cells from normal lymphocytes, using lectin-affinity column chromatography, is described. CNBr-activated Sepharose 6MB was used as a non-mobile phase. The gel was covalently coupled with soybean agglutinin (SBA), then served as an affinity probe for fractionation of mixture of normal lymphocytes and leukemic cells. Leukemic cell lines, derived from acute lymphoblastic leukemia (Jurkat, MOLT-4, RPMI-8402), were tested. The elution of normal lymphocytes was carried out by PBS(-). The leukemic T-cells, interacting with SBA, were removed by N-acetyl-D-galactosamine or low-concentration acetic acid. The type and viability of the separated cell fractions were analyzed by flow cytometry and fluorescent microscopy, using adequate fluorescent antibodies. The interaction of leukemic T-cells with free SBA, as well as with SBA-conjugated Sepharose beads, was examined fluorimetrically and visualized by fluorescent microscopy, using FITC-SBA as a marker. The rate of cell elution on SBA-affinity column decreased in order: normal > leukemic T-cells. Both normal lymphocytes and leukemic T-cells were removed in a mixture from SBA-free Sepharose 6MB by PBS(-) and were not fractionated discretely. The leukemic T-cells specifically interacted with SBA as well as with SBA-affinity adsorbent. In contrast, the normal lymphocytes did not interact with free SBA as well as with SBA-conjugated Sepharose beads in the concentrations applied. The method potentially combines a discrete cell fractionation with manifestation of a specific target cytotoxicity of SBA against leukemic T-cells, without any influence on normal lymphocytes.

Purification of normal lymphocytes from leukemic T-cells by lectin-affinity adsorbents - correlation with lectin-cell binding.

Utilization of leukemic T-cells from normal ones, using lectin-affinity adsorbents, is described. CNBr-activated Sepharose 6MB was covalently coupled to Soybean (SBA) or Dolichos Biflorus Agglutinins (DBA), then serves as an affinity probe for separation of leukemic T-cells from normal lymphocytes. The normal lymphocytes were removed almost completely by phosphate buffered saline (Ca(2+) and Mg(2+) free) (PBS(-)) from lectin-affinity column. More than 80% of the leukemic T-cells were retained on the lectin-affinity adsorbent, whereas another 10-15% were easily removed by PBS(-). There was a very good linear correlation between percent of cells, retained on the lectin-affinity adsorbent and percent of cells, interacting with the respective free lectin (r=0.97 for SBA, and r=0.93 for DBA). The viability of normal lymphocytes was not influenced after passing through the columns. In the case of leukemic T-cells - about 90% of the easily removed cells were dead, and another 10% were viable cells, non-interacting with DBA or SBA.

Effect of phenothiazines on protein kinase C- and calcium-dependent activation of peritoneal macrophages.

The effects of some phenothiazines (promethazine, PMZ; chlorpromazine, CPZ; levomepromazine, LVPZ; thioridazine, TRDZ; trifluoperazine, TFPZ) on the activation and viability of rat peritoneal macrophages were investigated. The macrophage activation was estimated by measuring of luminol-dependent chemiluminescence, induced by phorbol-12-myristate-13-acetate (PMA) (a protein kinase C activator) or calcium ionophore A23187. The viability of macrophages was determined using ATP bioluminescence as a criterion of cell viability. It was observed that all drugs, in concentrations higher than 1 micromol/L, markedly decreased the chemiluminescent index of PMA-activated or A23187-activated macrophages. The inhibitory effect was dose-dependent. It was better expressed in the case of CPZ, followed by TFPZ and TRDZ, and less expressed in the case of PMZ and LVPZ. The suppression of chemiluminescence of PMA-/A23187-activated macrophages by phenothiazines was not a result of their cytotoxic effect. Moreover, it was found that all drugs dose-dependently enhanced the viability of macrophages, estimated by ATP production. The inhibitory effects of phenothiazines on the chemiluminescence of PMA-/A23187-activated macrophages were greater than their ability to decrease KO2-induced chemiluminescence as a result of interaction with superoxide radicals. It may be supposed that the inhibitory effect of phenothiazines on PMA-/A23187-induced chemiluminescence of macrophages is a result not only of interaction between drugs and superoxide radicals, generated during the "oxidative burst" of activated cells. Presumably the drugs have an immunomodulating effect on rat peritoneal macrophages.

Cyclooxygenase-pathway participates in the regulation of regional cerebral blood flow in response to neuronal activation under normo- and hypercapnia.

The present study was designed to investigate whether cyclooxygenase products are involved in the regulation of the regional cerebral blood flow, evoked by somatosensory activation (evoked rCBF) under normo- and hypercapnia. Indomethacin (IMC) was used as cyclooxygenase inhibitor. It was applied intravenously (i.v., 10 mg/kg/h) in two experimental protocols-before hypercapnia (i) and after hypercapnia (ii). Somatosensory activation was induced by electrical hind paw stimulation (5 Hz frequency, 5 s duration, 1.5 mA). The evoked rCBF-response was measured in alpha -chloralose anesthetized rats using laser-Doppler flowmetry. IMC abolished completely the effect of hypercapnia on the baseline level of CBF. The drug reduced significantly evoked rCBF-response also. The inhibitory effect of IMC on evoked rCBF-response is better expressed under normocapnia (approximately 70%) than that under hypercapnia (approximately 40%). After IMC application, the normalized evoked rCBF curves peaked earlier as compared to that before its application (P<0.05), although the rise time of 0.5 s was nearly constant regardless of stimulus frequency. In conclusion, the results suggest a participation of IMC-sensitive and cyclooxygenase-dependent mechanisms in the regulation of evoked rCBF, induced by somatosensory stimulation.

Fractionation of normal and leukemic T-cells by lectin-affinity column chromatography.

A method for rapid fractionation of normal and leukemic T-cells (Jurkat, RPMI-8402, MOLT-4), using lectin-affinity column chromatography, is described. CNBr-activated Sepharose 6MB was used as a non-mobile phase. The gel was covalently conjugated with Dolichos biflorus agglutinin (DBA) over 24 h. The normal cells were eluted by phosphate buffered saline (Ca(2+) and Mg(2+) free), while the leukemic T-cells, interacting with DBA, were removed by N-acetyl-D-galactosamine or by low-concentrated acetic acid as a mobile phase. The cell fractions were detected spectrophotometrically at 600 nm. The rate of cell elution decreased in the order: normal>leukemic T-cells. The viability and the type of separated T-cell fractions were characterized by flow cytometry, using adequate fluorescent antibodies. The interactions between leukemic T-cells and DBA-saturated Sepharose beads were examined by fluorescent microscopy, using fluorescent isothiocyanate-DBA as a fluorescent marker.

Effect of immobilization, cold and cold-restraint stress on liver monooxygenase activity and lipid peroxidation of influenza virus-infected mice.

The present study provides a direct experimental evidence that the combination of influenza A/Aichi/2/68 (H3N2) infection with different models of "oxidative stress", such as immobilization, cold and cold-restraint, is associated with graduated oxidative disturbances in the liver of mice, despite the absence of virus and inflammation in this tissue. It was found that experimental influenza virus infection is accompanied with a significant increase of lipid peroxidation products, a decrease of natural antioxidants (vitamin E, glutathione) and cytochrome P-450, an inhibition of cytochrome c reductase and liver monooxygenases (analgin- N-demethylase and amidopyrine- N-demethylase). Immobilization and cold stress, applied separately or in combination (cold-restraint), did not influence significantly any of the analysed parameters compared to those of the control group of non-infected mice. Preliminary exposure of mice to immobilization or cold stress and subsequent inoculation of influenza virus resulted in a significant increase of lipid peroxidation products and a significant decrease of vitamin E and reduced glutathione, compared with levels in control (non-infected) animals. Compared to influenza virus-infected and non-stressed animals, the changes in all these parameters were negligible. Immobilization or cold stress, applied in combination with influenza virus infection, partially prevented the suppressive effect of influenza virus on cytochrome P-450 and liver monooxygenases. A tendency towards normalization of these parameters to the control levels was observed. However, after application of cold-restraint plus influenza virus infection, the level of cytochrome P-450 and activity of cytochrome c reductase stayed markedly lower than in infected and non-stressed animals. The activities of liver monooxygenases were slightly increased compared with those of infected and non-stressed animals, but stayed relatively low compared to control (non-infected) mice. Combination of cold-restraint and influenza virus infection resulted in a greater synergistic increase of lipid peroxidation products and a greater synergistic decrease of vitamin E and reduced glutathione compared to controls, as well as to influenza virus-infected and non-stressed animals.

Effect of vitamin E supplementation on lipid peroxidation in blood and lung of influenza virus infected mice.

The influenza virus infection (A/Aichi/2/68) was associated with development of oxidative stress in lung and blood of mice, accompanied by an increase in levels of lipid peroxidation products (conjugated dienes and total malondialdehyde) and a decrease in endogenous amounts of natural antioxidant vitamin E. These effects were most pronounced on the 5th day after virus inoculation, in comparison with those on the 7th. Supplementation of mice with exogenous vitamin E before virus inoculation lead to lung and blood protection against lipid peroxidation. A marked decrease in lipid peroxidation products and an increase in vitamin E content was established in blood and lung on the 5th and 7th day after virus inoculation. The stabilizing effect of vitamin E is dose-dependent in blood and dose-independent in lung, and was most pronounced on the 5th day after virus inoculation in comparison with the 7th day.

Laser-Doppler imaging of activation-flow coupling in the somatosensory cortex: normalization of signal when the baseline changes significantly.

This study describes two approaches used to normalize the laser-Doppler flowmetry (LDF) signal, corresponding to the regional cerebral blood flow (rCBF) response after electrical hind-paw stimulation. The first approach divides the LDF signal to the baseline and subsequently integrates the response curve from the rise point to the termination point (defined formally as "normalized rCBF response", and the second subtracts the baseline from the LDF signal and subsequently integrates the response curve from the rise point to the termination point (defined as "absolute rCBF response"). Both parameters are given in arbitrary units. A comparative analysis of the changes in the "normalized" and "absolute" LDrCBF response is presented both for when the baseline does not change significantly, and for when the baseline changes significantly under the influence of different factors. In summary, when the baseline changes significantly it is preferable to normalize the LDrCBF response towards the baseline by subtraction, not by division.

Frequency dependence of local cerebral blood flow induced by somatosensory hind paw stimulation in rat under normo- and hypercapnia.

We measured the field potential and the changes in local cerebral blood flow (LCBF) response during somatosensory activation (evoked LCBF) in alpha-chloralose--anesthetized rats by laser-Doppler flowmetry under normocapnia (PaCO(2)=34.3+/-3.8 mmHg) and hypercapnia (PaCO(2)=70.1+/-9.8 mmHg). Somatosensory activation was induced by electrical stimulation (0.2, 1, and 5 Hz with 1.5 mA for 5 s) of the hind paw. The neuronal activity of the somatosensory area of the hind paw was linear to the stimulus frequency, and there was no significant difference in the neuronal activity between hypercapnia and normocapnia. The baseline level of LCBF under hypercapnia was about 72.2% higher than that under normocapnia (p<0.01). The absolute response magnitude under hypercapnia was greater than that under normocapnia (p<0.05). The evoked LCBF under both conditions showed a frequency-dependent increase in the 0.2 to 5 Hz range, and the difference in the absolute response magnitude at the same stimulus frequency between normocapnia and hypercapnia became large with increasing stimulus frequency (p<0.05). On the other hand, after normalization to each baseline level there was no significant difference in the response magnitude of the normalized evoked LCBF between normocapnia and hypercapnia, indicating that the normalized evoked LCBF reflects neuronal activity even when the baseline LCBF was changed by the PaCO(2) level. The peak time and termination time of LCBF response curves with respect to the graded neuronal activity at 1 and 5 Hz stimulation increased significantly under hypercapnia, compared with those under normocapnia (p<0.05), although the rise time of 0.5 s was nearly constant. In conclusion, the results suggest a synergistic effect of the combined application of graded neuronal stimuli and hypercapnia on the LCBF response.

Determination of malondialdehyde in biological samples by solid-phase extraction and high-performance liquid chromatography.

An analytical procedure for determination of malondialdehyde in tissue homogenates and blood serum was developed. A reaction with 2,4-dinitrophenylhydrazine is used followed by cleaning up of the derivative by solid-phase extraction. The samples were analyzed by isocratic high-performance liquid chromatography (HPLC) using a narrow-bore HPLC-column. A good separation of the 1-pyrazole peak from that of 2,4-dinitrophenylhydrazine was observed. A high linear dependence was established by the concentration of 1-pyrazole in the range of 10-5000 ng/ml. The detection limit of the method applied for tissue homogenates and blood serum was approximately 10 ng/ml or lower, and RSD of the method was 9% (n = 8). The peak of 1-pyrazole for these samples was well separated from the other matrix peaks. Experiments carried out evaluated that the solid-phase extraction might be an effective step of the sample preparation, significantly increasing the selectivity of the analysis and the life-time of the column. The method seems to be applicable for determination of malondialdehyde in different biological samples.

Relationships between serum levels of autoantibodies against oxidized low density lipoproteins, lipid-soluble antioxidants and apolipoprotein B in patients with coronary heart disease.

High affinity IgG autoantibodies against oxidized low density lipoproteins (oxLDLs), apolipoprotein B and lipid-soluble antioxidants--alpha-tocopherol and beta-carotene, were tested in patients with coronary heart disease. Correlation relationships between these parameters were analysed. Fifty one patients with coronary heart disease (37 males/14 females) defined as Q-wave myocardial infarction and/or stenosis of more than 50%, and 51 healthy blood donors (34 males/17 females) as controls participated in this study. LDLs were isolated by density gradient ultracentrifugation and oxidized with Cu2+. OxLDLs or native LDLs (nLDLs) were used as antigens in enzyme immunoassay (ELISA) to detect IgG autoantibodies in the serum. The contents of alpha-tocopherol and beta-carotene were measured by HPLC. Apolipoprotein B was determined by immunoturbidimetry. Correlation analysis of the parameters was carried out by Spearmann's test. Alpha-tocopherol was decreased significantly in the serum of patients with coronary heart disease (2.96+/-1.63 nmol/mg serum protein vs 6.23+/-2.28 nmol/mg serum protein in Control group) (p < 0.01). Also, the serum level of beta-carotene was decreased in patients with coronary heart disease (174.0+/-95.7 pmol/mg serum protein vs 313.2+/-141.5 pmol/mg serum protein in Control group) (p < 0.01), while apolipoprotein B was increased significantly (1.20+/-0.34 g/l in patients with coronary heart disease vs 0.86+/-0.23 g/l in Control group) (p < 0.001). In a previous study we established that the mean serum level of IgG autoantibodies against oxLDLs (expressed in optical density units) was about 2.5 times higher in patients with coronary heart disease as compared to control subjects (p < 0.001). A good positive linear correlation was observed between alpha-tocopherol and apolipoprotein B levels in Control group (r = 0.78, p < 0.001), as well as in the group of patients with coronary heart disease (r = 0.42, p < 0.001). Poor nonsignificant correlations were established between all another measured parameters. In conclusion, the lipid-soluble antioxidants--alpha-tocopherol and beta-carotene, are not informative with respect to the susceptibility of the serum to oxidative modifications and as to the extent of the subsequent humoral immune response. Presumably, the reduction of the correlation coefficient between apolipoprotein-B and alpha-tocopherol in patients with coronary heart disease in comparison with control subjects could provide indirect information on modifications of apolipoprotein-B and on a decrease of its susceptibility to interact with this major lipid-soluble antioxidant in atherogenesis.

Effect of vitamin E on lipid peroxidation and liver monooxigenase activity in experimental influenza virus infection.

Influenza virus infection was associated with development of oxidative stress in liver of mice, viz. increase in amount of lipid peroxidation products, decrease in cytochrome P-450 and NADP. H-cytochrome c-reductase activity, and inhibition of liver monooxygenases (aniline hydroxylase, ethylmorphine-N-demethylase, amidopyrine-N-demethylase and analgin-N-demethylase). These effects were most pronounced on the 7th day after virus inoculation as compared to the 5th one. Supplementation of mice with vitamin E before virus inoculation leads to liver protection against oxidative stress and toxicosis. A marked decrease of lipid peroxidation products and an increase of cytochrome P-450 and activities of monooxygenases was established. The stabilizing effect of vitamin E was dose-dependent and was most pronounced on the 5th day after virus inoculation as compared to the 7th one.

Pharmacodynamic of the antioxidant action of alpha-tocopherol and its derivatives in liver, brain, heart and skeletal muscles.

The aim of the present work was to determine the pharmacodynamics of antioxidant effect of alpha-tocopherol and its derivatives (alpha-tocopheryl esters and chromanols with different chain-length) in the animal tissues, as well as the role of cytochrome P-450 in biotransformation of these compounds. Alpha-tocopherol and its derivatives were injected intraperitoneally in rats or mice in a single dose of 100 mmol per kg b.w. The animals were sacrificed at different time intervals (0, 1, 2, 4, 8, 12, 24, 36 hours) and the liver, heart, brain and skeletal muscles were removed, homogenized and incubated with lipid peroxidation (LPO) inducers (Fe2+ + ascorbate). LPO was evidenced by the generated malone dialdehyde (MDA). Data were expressed as percentage of LPO inhibition by alpha-tocopherol or its derivatives as compared to control group. The kinetic curves of the inhibitory action of alpha-tocopherol and its derivatives on LPO were characterized by three phases: a phase of increasing antioxidant activity, a phase of maximal antioxidant activity (about 60-95% LPO inhibition), and a phase of decreasing antioxidant activity. Alpha-tocopheryl esters possessed dynamics of antioxidant action the same as alpha-tocopherol. Therefore the hydrolysis of alpha-tocopheryl esters in animal organism is not a limiting factor for their antioxidant effect. The alpha-tocopherol derivatives with short chain-length (C1, C6) had a shorter half-life in animal tissues as compared to alpha-tocopherol or its esters. In vitro experiments showed that C1 and C6 are substrates of cytochrome P-450. In contrast, alpha-tocopherol and its esters did not bind to cytochrome P-450 even at concentrations as high as 10 mmol/l. Apparently, C1 and C6 underwent biotransformation and were excreeted more quickly from the organism.

Serum level of IgG autoantibodies against oxidized low density lipoproteins and lag-phase of serum oxidation in coronary heart disease--inverse correlation.

High affinity IgG autoantibodies (ABs) against oxLDLs and lag-phase of serum oxidation were tested in patients with coronary heart disease (CHD). Fifty one (37 M/14 F) patients with CHD defined as Q-wave myocardial infarction and/or stenosis of more than 50% and 51 (34 M/17 F) healthy blood donors as controls participated in this study. LDLs were isolated by gradient ultracentrifugation and oxidized with CuSO4. The modified LDLs (oxLDLs) or native LDLs (nLDLs) were used as antigens in an enzyme immunoassay (ELISA) to detect IgG ABs in both groups. The serum was oxidized by CuSO4 and the oxidation was monitored spectrophotometrically at lambda = 234 nm to follow the formation of conjugated diens. The lag-phase (in minutes) is the interval between the addition of CuSO4 to the serum and the beginning of extensive oxidation (increasing absorbance at 234 nm). The concentrations of total cholesterol, triglycerides, HDL-cholesterol, apo-A and apo-B were measured as well. The mean level of ABs against oxLDLs (expressed as optical density units) was 0.590 +/- 0.330 in CHD-patients vs 0.244 +/- 0.200 in controls (p < 0.001). The lag-phase in minutes was 47.00 +/- 27.19 in CHD-patients and 80.23 +/- 26.30 in controls (p < 0.001). A negative correlation between ABs levels and lag-phase was established in CHD-patients (r = -0.69, p < 0.001) and controls (r = -0.62, p < 0.001). A poor correlation was established between ABs levels or lag-phase, on one hand, and other measured parameters. In conclusion, the lag-phase of serum oxidation by Cu2+ could be informative for LDL susceptibility to modification and the extent of consequent humoral immune response.

Lipid peroxidation in rat lung induced by neuroleptanalgesia and its components.

The aim of the present work was to determine the likelihood of lipid peroxidation in the lungs of rats subjected to neuroleptanalgesia and its components. In particular, the effect of fentanyl, droperidol, a nitrous oxide/oxygen mixture when used separately or in combination, on the lung level of lipid peroxidation was investigated. The in vitro antioxidant properties of fentanyl and droperidol were also tested. Lipid peroxidation was evidenced by the endogenously generated conjugated dienes and fluorescent products of lipid peroxidation and the decrease in lung vitamin E content. It was found that fentanyl and droperidol, used separately or in combination, did not induce lipid peroxidation in the rat lung, while the exposure of rats for 120 min to a nitrous oxide/oxygen mixture (2:1 v/v) led to well-expressed peroxidation. The (N2O + O2)-pro-oxidant action was significantly inhibited in rats previously injected with fentanyl and/or droperidol. The results show that the application of fentanyl, droperidol and (N2O + O2), as in neuroleptanalgesia, ensures minimal lipid peroxidation in the lung. In addition, we found that fentanyl and droperidol were able to inhibit the Fe(2+)-catalysed lipid peroxidation in lung homogenate. We speculate that the inhibitory effect of fentanyl and/or droperidol on the (N2O + O2)-induced lipid peroxidation in the rat lung may be caused directly by their antioxidant properties. However, another explanation seems to be possible. The free radicals that are produced during the metabolism of fentanyl and droperidol may react with the radicals generated during the one-electron reduction of nitrous oxide. Such reactions will obviously reduce the free radical concentration in the organism and, hence, the likelihood of initiating lipid peroxidation.

Oxidation of low density lipoproteins leads to disturbance of their binding with alpha-tocopherol.

The dynamics of binding of exogenous alpha-tocopherol (alpha-T) added to native or oxidatively modified LDLs (LDLs or oxLDLs) were investigated. Venous blood from 31 clinically healthy blood donors (15 males and 16 females) was used. LDLs were isolated by density gradient ultracentrifugation. LDLs were oxidized in vitro by CuSO4. LDLs or oxLDLs were enriched with exogenous alpha-T (initial concentrations: 0; 10; 20; 50; or 100 nmol per mg protein). The contents of alpha-T in LDLs or in oxLDLs were measured by HPLC. Lag-phase of LDL oxidation before or after saturation with alpha-T was recorded. Correlation analysis of the lag-phase of LDL oxidation and alpha-T content in LDLs was carried out by the method of Esterbauer et al. The experimental results demonstrated that: (i) alpha-T was incorporated into native LDLs to a higher extent as compared to oxLDLs. (ii) A saturation of LDLs and oxLDLs with alpha-T was observed. (iii) A positive correlation was observed between the duration of the lag-phase of LDL oxidation in vitro and the content of alpha-T in LDLs. (iv) Based on LDL saturation with alpha-T, the persons could be classified in two groups: LDLs from group I of 26 persons were found to incorporate exogenous alpha-T to the extent of 1.8 to 3 times its initial concentration; LDLs from group II of 5 persons incorporated little or no exogenous alpha-T. In the first group, oxidation of LDLs lead to a considerable decrease in alpha-T dependent variable k and to a moderate reduction of alpha-T-independent variable alpha in the equation of Esterbauer et al.: lag-phase = k.[alpha-tocopherol]+alpha. In the second group, oxidation of LDLs lead to insignificant changes in k, as well as in a. (v) According to the levels of k and a the native LDLs from the second group of 5 persons were very close to oxLDLs from the first group of 26 persons. Presumably, native LDLs from the second group of persons were initially oxidatively modified, and probably this will be a risk group in relation to atherogenic disorders.

[The induction of lipid peroxidation in the serum of patients with acute peritonitis]. / Induktsiia na lipidna pereoksidatsiia v seruma na patsienti s ostur peritonit.

The level of lipid peroxidation products in the sera of patients with acute peritonitis and clinically healthy blood donors are studied. An increase in the level of TBA-reactive substances is documented in the acute peritonitis group--twice as high as compared to clinically healthy blood donors. Changes in the patients in toxic and terminal phases of peritonitis are rather significant. Following hemofiltration, the serum lipid peroxidation products are decreased in comparison with the pre-hemofiltration state.

Interrelationship between cortisol levels in plasma and the circadian rhythm of temperature, pulse and blood pressure in depressed patients with good and disturbed sleep.

Cortisol levels in plasma were measured in 122 depressed patients at 8:00 a.m. and 11:00 p.m. on the first day and at 8:00 a.m., 4:00 p.m. and 11:00 p.m. on the second day after oral administration of dexamethasone. Some of the patients were studied before and after medication so the total number of plasma cortisol level examinations came to 173. All patients had to describe the state of their sleep with the help of a questionnaire. The temperature and pulse of 92 patients were taken hourly from 7:00 a.m. to 11:11 p.m. for two consecutive days where the total measurements came to 34. 27 patients out of these had their blood pressure taken. A control group of 65 healthy persons without somatic and psychic disorders was tested at the same time. We found out that plasma cortisol levels in patients with disturbed sleep were higher compared to the group with good sleep. It was also noticed that younger patients and males had higher plasma cortisol level. Patients with disturbed sleep had higher Mesors (midline-estimating statistic of rhythm, 'Mesor') of temperature, pulse and systolic blood pressure. Healthy persons had significantly lower pulse Mesors compared to patients with good and disturbed sleep. The percentage distribution of suppressors and nonsuppressors showed no differences by sex, age and sleep disturbances.