Structure of Rhythms of Blood Pressure, Heart Rate, Excretion of Electrolytes, and Secretion of Melatonin in Normotensive and Spontaneously Hypertensive Rats Maintained under Conditions of Prolonged Daylight Duration.

We studied the structure of rhythms of BP, HR (by telemetric monitoring), electrolyte excretion (by capillary electrophoresis), and products of epiphyseal melatonin (by the urinary concentration of 6-sulfatoxymelatonin measured by ELISA) in normotensive Wistar-Kyoto rats and spontaneously hypertensive SHR rats maintained at 16/8 h and 20/4 h light-dark regimes. In Wister-Kyoto rats exposed to prolonged daylight, we observed changes in the amplitude, rhythm power (% of rhythm), and range of oscillations of systolic BP; HR mezor decreased. In SHR rats, mezor of HR also decreased, but other parameters of rhythms remained unchanged. Changes in electrolyte excretion were opposite in normo- and hypertensive rats. Under conditions of 20/4 h light-dark regime, daytime melatonin production tended to increase in normotensive rats and significantly increased in SHR rats. At the same time, nighttime melatonin production did not change in both normotensive and hypertensive animals. As the secretion of melatonin has similar features in animals of both lines, we can say that the epiphyseal component of the "biological clock" is not the only component of the functional system that determines the response of the studied rhythms to an increase in the duration of light exposure.

Bright Light Therapy Increases Blood Pressure and Changes the Structure of Circadian Rhythm of Melatonin Secretion in Spontaneously Hypertensive Rats.

Phototherapy (therapy with bright light) is widely used to treat seasonal affective disorders, different types of depression, sleep disorders, and other diseases; it has no significant contraindications, but its effects on functional state and biological rhythms of the cardiovascular system in hypertension are poorly studied. In experiments on Wistar-Kyoto and SHR (spontaneously hypertensive rats) rats, the effect of bright light therapy on the daily profile of BP, HR, and production of epiphyseal melatonin was investigated. Phototherapy was simulated by exposure to 9000-lux cold light at the level animal eyes over 1 h (from 10.00 to 11.00 h) with LED lamps. In freely moving rats (free access to food), daily profiles of BP and HR were studied by 24-h continuous telemetry monitoring. The production of epiphyseal melatonin was assessed by measuring urinary concentration of its stable metabolite 6-sulfatoxymelatonin (aMT6s) during the day and night. During phototherapy, systolic BP significantly increased in in animals of both lines and diastolic BP increased in SHR rats. This effect persisted after the end of phototherapy session. Bright light had no effect on HR. In Wistar-Kyoto rats, phototherapy induced a significant decrease in daily concentration of aMT6s, but its nocturnal level did not change. In SHR rats, bright light therapy significantly decreased nighttime concentration of aMT6s in the urine and had no effect on daytime concentration of this metabolite. As a result, the difference between the night and day levels of aMT6s in the urine was leveled. Phototherapy produced more pronounced and less favorable effect on animals with primary arterial hypertension.

24-Hour Profile of Blood Pressure, Heart Rate, Excretion of Electrolytes, and Locomotor Activity in Wistar-Kyoto and SHR Rats Under Conditions of Free-Run Rhythm.

We presented the results of our study of chronostructure of BP, HR, electrolyte excretion, and locomotor activity under conditions of "free-run rhythm" (light deprivation). In adult male Wistar-Kyoto (normotensive) and SHR (spontaneously hypertensive) rats, BP, biopotentials of the heart (ECG), and locomotor activity were recorded over 24 h by telemetric monitoring and the rate of excretion of electrolytes (Na+, K+, Ca2+, and Mg2+) during the nighttime and daytime hours was measured. It was found that under free-run rhythm, 24-h profiles of BP, HR, excretory function of the kidneys, and locomotor activity underwent more considerable changes in normotensive Wistar-Kyoto rats in comparison with hypertensive SHR rats. However, hypertensive rats demonstrated pronounced changes in rhythmic characteristics of HR, which can restrict adaptation reserves of the cardiovascular system.

Specific Features of Electrolyte Excretion at the Early Stages of Arterial Hypertension in SHR Rats.

Daytime and nighttime systolic and diastolic BP was recorded in 23-week-old SHR and Wistar rats by telemetric monitoring. Urine concentrations of sodium, potassium, and calcium were determined in SHR rats during of light (07.00-19.00 h) and dark hours (19.00-07.00 h) at the age of 18, 19, 20, 21, 22, and 23 week; 23-week-old Wistar rats were used as the control. At early stages of the experiment, urine sodium concentration was elevated in SHR rats both at daytime and at night. Thereafter, this value declined and by 22-23 week was significantly lower than in normotensive Wistar rats, but only during daytime. Daytime potassium concentration significantly surpassed the control level during weeks 18-19 of the experiment, but later, a tendency to a decrease in this parameter was observed. Daytime calcium content in SHR rats did not significantly differ from the control throughout the experiment. At night, this value exceeded the control level by more than 2 times during weeks 18-19, but then returned to the level observed in normotensive animals.

[POSSIBLE ROLE OF TRANSTHYRETIN IN THE BIOLOGICAL MECHANISM OF THE REGULATORY PEPTIDE NEUROPROTECTION.]

The peptide preparation Semax has been effectively used for therapy of ischemic stroke. However, the mechanisms of its action are insufficiently understood and actively studied. The full-genome analysis of the transcriptome implemented in our recent work dem- onstrated that under conditions of focal ischemia of rat brain the Semax modified the profile of the transcription activity of many genes. In this case, the difference in the transcription levels of the gene encoding the protein transthyretin (Ttr) expression in rats under the pathological conditions of ischemia and in the presence of Semax was very high. High similarity between the effects of Ttr and coupled molecular systems with the Semax effects in ischemic stroke allowed us to suggest that the neuroprotection mechanisms of Semax (and, possibly, of other neuroprotection mechanisms of Semax) could be mediated by Ttr. In this review, we discussed the role of Ttr in CNS and its possible role in the neuroprotection mechanism of Semax.

[Effect of tripeptide Pro-Gly-Pro on rat brain transcriptome in focal ischemia].

Biologically active regulatory peptide, tripeptide Pro-Gly-Pro (PGP) was used as C-terminal fragment for peptide drugs Semax and Selank. In recent years the independent effects of PGP were observed. The question was raised, whether PGP contributes to the effects ofpeptide drugs containing PGP as a fragment. The genome-wide analysis was performed to investigate the influence of PGP on the transcriptome of ischemic rat brain cortex tissues. The gene expression alterations caused by the action of the tripeptide PGP were compared with the gene expression of the control group "ischemia" at 3 and 24 h after permanent occlusion of left middle cerebral artery. The altered expression was detected for 29 genes at 3 h and 57--at 24 h. The proteins encoded by these genes have variety of functions: cytokines, transport proteins, transcription factors, transmembrane receptors, etc. Biological processes, which are related to the genes with altered expression, were distinguished. The influence of PGP on the diversity of biological processes in different systems of the organism is demonstrated for the first time. The process "Immune response" was the most statistically notable at 24 h after occlusion. The expression of the immune system genes was predominately down regulated.

[Evaluation of biochips for the rifampin resistance detection of M. tuberculosis in strains isolated at the Novosibirsk and Tomsk regions].

Recently in Russia biochips for rifampin resistance detection of M. tuberculosis were developed. To investigate the conformity between rifampin resistance results determined both by the routinely used absolute concentration method and USING the biochips, 272 DNA samples of M. tuberculosis isolated from TB patients at Novosibirsk and Tomsk regions in 2000-2005 were analyzed. The biochip can detect 30 mutations in rpoB gene. The mutations were also tested using the single stranded conformational polymorphism method (SSCP). In addition, 60 DNAs were randomly sampled and sequenced. The results of rifampin resistance detection using biochip and absolute concentration methods were congruent in 86% cases, and were different when analyzed samples consisted of the susceptible and resistant strains of M. tuberculosis mixture. The most frequent mutations in the rpoB gene were S531 (76.2%), H526 (7%), D516 (5.6%), and L511 (5.6%). In 94% of rifampin resistant strains, there was also resistance to isoniazid. Therefore, in Siberia the rifampin resistance is the reliable marker for MDR strains of M. tuberculosis, and biochips can be used also for their detection. To hybridize with biochip the fluorescent-labeled single-stranded DNAs were routinely synthesized by two PCR, and intermediary product after the first PCR should be transferred into another tube. The last stage included high risk of cross-contamination. To exclude the risk, primer concentrations and temperature-time profile of PCR reactions were improved, and both PCR were combined in one tube. The two methods were congruent in 100%. The one tube method would be especially attractive for the routine PCR laboratory.

[Changes in lower urinary tract function in children with hyperactive urinary bladder treated with combined therapy].

Low clinical efficacy of M-cholinolytics remains a serious problem in conservative therapy of hyperactive bladder (HB). To improve treatment outcomes, combined therapy (pikamilon plus driptan) was tried in 22 boys and 25 girls aged 7 to 14 years. The children were examined with uroflowmetry, cystometry. The response to the treatment was found to depend on mean effective capacity of the urinary bladder. Duration ofurodynamic correction has a negative colleration with this capacity. Urodynamic investigations performed in different periods of therapy show that improvement of lower urinary tract function is pathogenetically important for treatment of children with urologic pathology running in the presence of hyperactive urinary bladder.

[Evaluation of reasons of the MDR M. tuberculosis strains dissemination by analysis of the rifampicin and/or isoniazid resistant isolates].

During the last years in Novosibirsk region of Russia the rate of TB patients infected by MDR strains of M. tuberculosis has been constantly increasing. This increase may occur as a result of the spontaneously mutated mycobacterium selection during treatment of patients or as a result of primary infection by the resistant M. tuberculosis, or also, as a result of both reasons in combination. If the main reason of MDR strain dissemination is selection of resistant bacterium during patient treatment, the equal apportionment of the dominated mutation into the mycobacterium genotypes would be observed. If the main reason is the primary infection by resistant M. tuberculosis, the unequal apportionment would be revealed. For deeper understanding of the main reasons of the fast MDR strains spreading in the region, the distribution of the main mutations over genotypes of strains in Novosibirsk (170 isolates) and Tomsk prison (51 isolates) was investigated. Mutations in rpoB gene associated with the rifampicin resistance and in katG (isoniazid resistance) were detected by biochips. M. tuberculosis genotypings were carried out by IS6110 PCR typing or MIRU typing, in the last method the twelve loci (MIRU 2, 4, 10, 16, 20, 23, 24, 26, 27, 31, 39, 40) have been used. The most frequent mutation in the rpoB gene was Ser531-->Leu (60-70% of the rifampicin resistant strains) and Ser315-->Thr in gene katG (80% of the isoniazid resistant M. tuberculosis). Both in Novosibirsk and in Tomsk prison the rates of clustered cases transmissions were high (69 and 63% respectively). Analysis of the distribution of the dominated mutations Ser531-->Leu (rpoB) and Ser315-->Thr (katG) revealed that all of them were detected in each clusters, but in Novosibirsk there were only two clusters, in which the percentage of strains, containing mutation Ser531-->Leu (rpoB) were higher (85.7% and 77.7% respectively, P < 0.05), then in others. Among the Tomsk prison's clusters it was revealed one in which the proportion of the Ser3 15-->Thr mutation in katGwas higher (96.4%, P < 0.05). The nonuniform distribution of the dominated mutations highlighted that the epidemic spread of drug-resistant strains of M. tuberculosis in region resulted from the selection of them during patient treatment and the subsequent transmission by TB patients.

[Molecular and genetic characterization of rifampicin- and/or izoniazid-resistent strains of M. tuberculosis, isolated in Novosibirsk and Tomsk regions].

The purpose of the work was to study rifampicin- and izoniazid-resistent strains of M. tuberculosis, circulating in Western Siberia, by VNTR and IS6110 typing. The authors also studied genetic causes of resistance to these antibiotics and undertook a search of new VNTR loci, displaying polymorphism in genomes of closely related clonally-disseminated variants of Mycobacterium tuberculosis in W-Beijing family model analysis.

[Photochemotherapy in the treatment of acute pneumonias]. / Ispolzovanie fotogemoterapii v lechenii ostrykh pnevmonii.

The application of photochemotherapy in acute pneumonia is based on pneumonia pathogenesis and the mechanism of ALIB- (autotransfusion of laser irradiated blood) and AUVBI- (autotransfusion of ultraviolet blood irradiation) techniques. The ALIB is preferable since the technique requires no device sterilization. The complex treatment of acute pneumonia with ALIB and AUVBI was found to enhance therapeutic efficacy, to decrease the severity of the disease course, to reduce its duration and hospital stay in inpatients. No considerable impact of ALIB on the duration of pneumonia was observed, but X-ray examination revealed a definite reduction in pulmonary microcirculatory disorders. Laser therapy promotes the normalization of functional T-lymphocytic activity. ALIB should be applied individually and in relation to the severity of the disease, to the distribution of an inflammatory pulmonary process and to the duration of the disease course.

[Use of metaiodobenzylguanidine for assessing status of ends of myocardial sympathetic nerves in myocardium of patients with bronchial asthma]. / Ispol'zovanie metaiobenzilguanidina dlia otsenki sostoianiia okonchanii simpaticheskikh volokon v miokarde bol'nykh bronkhial'noi astmoi.

AIM: To evaluate sympathetic nervous system activity of the heart in patients with bronchial asthma (BA) given beta-adrenomimetics (BAM). MATERIAL AND METHODS: 27 patients with moderate BA (13 patients in an acute phase and 14 patients in remission) treated with BAM and 13 healthy people were examined by using 123I-metaiodobenzylguanidine (MIBG) myocardial planar scintigraphy and estimating the washout rate, early (15-min) and late (240-min) uptake; single-photon emission computed tomography; assessment of MIBG distribution in the left ventricular myocardium, catecholamine excretion with urine. RESULTS: It was found that the MIBG washout rate was significantly higher in asthmatic patients especially in the acute period. The cardiac MIBG uptake was significantly lower in the group of patients with impaired cardiac sympathetic activity. More inhomogeneous myocardial MIBG uptake also occurred in the asthmatic group. Norepinephrine and epinephrine excretion was significantly higher in patients with bronchial asthma and cathecholamine and MIBG excretions correlated. CONCLUSION: Cardiac functional sympathetic activity impairment in asthmatic patients was shown by increased MIBG washout rate and reduced myocardial MIBG uptake, more inhomogeneous substance distribution in the left ventricular myocardium and higher catecholamine excretion levels reflecting sympathetic nervous activity intensification.

Moving nonradiating kinks in nonlocal φ4 and φ4-φ6 models.

We explore the existence of moving nonradiating kinks in nonlocal generalizations of φ(4) and φ(4)-φ(6) models. These models are described by nonlocal nonlinear Klein-Gordon equation, u(tt)-Lu+F(u)=0, where L is a Fourier multiplier operator of a specific form and F(u) includes either just a cubic term (φ(4) case) or cubic and quintic (φ(4)-φ(6) case) terms. The general mechanism responsible for the discretization of kink velocities in the nonlocal model is discussed. We report numerical results obtained for these models. It is shown that, contrary to the traditional φ(4) model, the nonlocal φ(4) model does not admit moving nonradiating kinks but admits solitary waves that do not exist in the local model. At the same time the nonlocal φ(4)-φ(6) model describes moving nonradiating kinks. The set of velocities allowed for these kinks is discrete with the highest possible velocity c(1). This set of velocities is unambiguously determined by the parameters of the model. Numerical simulations show that a kink launched at the velocity c higher than c(1) starts to decelerate, and its velocity settles down to the highest value of the discrete spectrum c(1).