Differences in Fatty Acid Composition between Orb-Weaver Spiders Inhabiting a Riparian Zone and a Steppe Are Associated with the Consumption of Different Chironomid Taxa.

Amphibiotic insects, chironomids of the genera Glyptotendipes and Chironomus, which emerged from saline Lake Shira, differed in composition and content of fatty acids, including the essential eicosapentaenoic acid (20:5n-3, EPA), and upon flying out they were concentrated in different territories, the riparian zone and remote arid steppe zone, respectively. Potential consumers of chironomids adults, the orb-weaver spiders Larinoides suspicax, which inhabited both zones, also differed in fatty acid composition. The main difference in their biochemical composition was a significantly higher level of EPA in spiders from the riparian zone that likely to be explained by consumption of the Glyptotendipes adults enriched in this fatty acid and concentrated only within this zone. The higher level of EPA, which is deficient in terrestrial ecosystems, in orb-weaver spiders from the riparian zone of the saline lake may potentially promote a successful survival of the consumers in the arid landscape.

[Single Pill Indapamide and Perindopril Arginine Combination: Optimal Coupling of Vascular Protection and Hemodynamic Risk Factors Reduction in Patients with Essential Arterial Hypertension].

OBJECTIVE: to investigate the impact of indapamide / perindopril single-pill combination (I / P SPC) on arterial stiffness parameters, blood pressure (BP) level and BP variability (BPV) in middle-aged patients with stage II grade 1-2 essential arterial hypertension (EAH). Materials and methods. We retrospectively formed a group of patients with stage II grade 1-2 EAH who had not previously received regular antihypertensive therapy (AHT) (n=52, mean age 52.9±6.0 years). All patients were treated with I / P SPC and all of them achieved target office BP level (less than 140 / 90 mm Hg). After 12 weeks of follow-up (from the time of reaching the target BP) assessment of AHT effectiveness (general clinical data, ambulatory blood pressure monitoring [ABPM], volume sphygmography, echocardiography), and vascular stiffness evaluation were performed. RESULTS: At the end of follow-up office systolic BP (SBP), diastolic BP (DBP), pulse BP, day-time, night-time and 24­hour SBP and DBP significantly (p<0.001 for all) decreased. According to the ABPM data day-time, nighttime, and 24­hour systolic BPV significantly decreased (p=0.029, p=0.006 and p<0.001, respectively); day-time and 24­hour diastolic BPV also significantly decreased (p=0.001 and p<0.001, respectively). Day-night standard deviation (SDdn) significantly decreased too (p=0.002 and p<0.001, respectively). Volumetric sphygmography showed significant decrease of right cardio-ankle vascular index (CAVI) (from 8.20±1.29 to 7.58±1.44, p=0.001) and of left CAVI (from 8.13±1.40 to 7.46±1.43, p<0.001), as well as reduction of the number o f patients with a right- and / or left-CAVI >9.0 (from 32.7 to 11.5 %, p=0.018). According to assessment of arterial stiffness using the Vasotens24 software package, the arterial stiffness index (ASI) significantly (p<0.001) decreased from 153.5±29.9 to 138.3±20.0 (by -9.2±13.1 %). Transthoracic echocardiography data demonstrated significant decrease (p<0.001) in effective arterial elastance (from 1.82±0.43 to 1.58±0.36 mm Hg; by -11.85±16.29 %) and significant (p<0.001) increase in the arterial compliance - from 1.27±0.34 to 1.54±0.38 mm Hg / ml (+26.95±38.06 %). CONCLUSION: In AHT naive patients 40-65 years old with stage II grade 1-2 EAH therapy with I / P SPC provided effective 24­hour BP control, reduced BPV and improved arterial stiffness parameters.

[Mechanisms for the Development of Blood Pressure Variability and the Potential of Antihypertensive Drugs in Their Correction].

Blood pressure variability (BPV) is the fluctuations of blood pressure over a certain period of time under the influence of various factors. The issue of increased BPV is of particular clinical importance due to high predictive value of this parameter as a risk factor for fatal and non-fatal cardiovascular, cerebrovascular and renal events. It is proved that in the BPV increasing, the key role is played by impairments in arterial baroreflexes, which, in turn, are mediated by increased vascular stiffness, impact of angiotensin II and the sympathetic nervous system, endothelial dysfunction, nitric oxide deficiency and aging, including the vascular aging. Antihypertensive drugs that targeting largest amount of pathophysiological mechanisms in BPV increasing have a most advantages in correcting excessive pressure fluctuations. In this regard such drugs are perindopril and amlodipine, which can eliminate almost the entire spectrum of increased BPV causes and, therefore, optimally reduce the cardiovascular risk.

[Day-by Day Blood Pressure Variability: Methodological Aspects, Prognostic Value, Effects of Antihypertensive Therapy].

In this article we present problems of prognostic value of day-by-day blood pressure (BP) variability, its role in development and progression of damage of target organs in arterial hypertension, and impact on risk of cardiovascular, cerebral-vascular complications, and mortality. We also discuss methodological aspects of assessment of day-by-day BP variability. The article contains literature data on effects of antihypertensive therapy on variability of home BP, and consideration of evidence base of possibilities of the fixed amlodipine/perindopril combination for lowering day-by-day BP variability.

[Blood Pressure Variability. Visit-to-Visit Blood Pressure Variability].

The article is devoted to the modern state of the problem of blood pressure variability (BPV). Along with discussion of classification and methods of diagnosis it contains data on prognostic value of visit-to-visit BPV. We have also reviewed effect on BPV of various regimens of antihypertensive therapy and presented evidence base supporting ability of amlodipine/perindopril fixed dose combination to lower visit-to-visit BPV.

[24­Hour Arterial Pressure Variability: Prognostic Significance, Methods of Evaluation, Effect of Antihypertensive Therapy].

We discuss in this article problems of prognostic significance of 24­hour arterial pressure variability (24hAPV), as well as the role of 24hAPV in development and progression of various target organs damage by arterial hypertension. We also present literature data on impact of various regimens of antihypertensive therapy on 24hAPV, and on ability of fixed-dose perindopril/amlodipine to lower 24­hAPV.

[A change in adrenal responsiveness in sotalol-treated patients with paroxysmal atrial fibrillation depending on autonomic nervous system tone].

AIM: To evaluate the efficacy of sotalol depending on the magnitude of changes in adrenal responsiveness and autonomic nervous system tone in patients with paroxysmal atrial fibrillation (AF). SUBJECTS AND METHODS: Twenty-six patients with paroxysmal AF in the presence of coronary heart disease (CHD) and hypertension were examined. Sinus rhythm variability and sympathicotonic and vagotonic disorders were studied in patients with paroxysmal AF before and during sotalol treatment. A commercial Beta-ARM-Agat kit was used to estimate the adrenal responsiveness of erythrocyte membranes (ß-APM), which can judge the body's individual sensitivity to ß-adrenoblockers. RESULTS: Sotalol used in the average therapeutic doses of 160-240 mg did not reduce ejection fraction or increase atrioventricular conduction up to abnormal values. In patients with borderline and mild hypertension, the drug lowered blood pressure statistically significantly (p=0.01) and was well tolerated. The drug increased the sensitivity of ß-adrenoblockers in patients with adrenergic AF. CONCLUSION: The effect of sotalol on the autonomic nervous system manifested in the higher power of a high-frequency spectral component of heart rate variability than in that of a low-frequency one. Long-term sotalol administration significantly reduced ß-APM, increasing the sensitivity of adrenoceptors.

FOR EXTRAINTESTINAL MANIFESTATIONS OF INFLAMMATORY BOWEL DISEASE IN CHILDREN.

Inflammatory bowel disease (IBD) are systemic diseases with different intestinal and extra-intestinal manifestations (ElM). This fact can determin an examination plan and the disease course and prognosis. Up to 8.4% of children with IBD have ELM like the first symptom of the disease. The range of ElM of iBD in children is differ from that one of adult patients: rarer arthropathy and arthritis, skin and liver diseases, an extremely rare eye disease. The physical development disorder is a typical children's manifestation of the IBD, the "failure of the weight curve" is an early symptom of the IBD debut (82% of examined children), especially ulcerative colitis. The article discusses the clinical features and therapy of the most frequent extraintestinal manifestations of IBD in children: skin, mucous, eye diseases, axial and peripheral arthropathies, primary scierosing cholangitis, physical, sexual development disorders, decreased bone mineral density. Most often, we observed patients with arthritis and primary scierosing cholangitis - up to 12.5% of patients with active disease. A growth failure was observed in 20% of children with IBD debut, and remained in 9.7% children despite adequate anti-inflammatory therapy. Decreased bone mineral density in children with IBD observed in 30% cases (ISCD-recommendations). Extraintestinal manifestations are very important to make the early diagnosis of IBD without any intestinal symptoms. The pediatrician can suspect a systemic diseases course. ElMs adversely impact upon patientsquality of life and some can be life-threatening.

[Manifestations of polymorphism of ß1-adrenoreceptors in patients with newly diagnosed cardiac rhythm disorders].

Individual peculiarities of the receptor apparatus of cardiomyocytes may determine pathological features of heart activity and susceptibility to pharmaceuticals. The possible role of beta-adrenoreceptor polymorphism in the development of cardiac rhythm disturbances is assessed by PCR. Special attention is given to A145G polymorphism of the ADRB1 gene in 127 patients with primary cardiac rhythm disorders. It was shown that AJ45G polymorphism (Ser49Gly) at DNA sites encoding for the amino acid sequence of beta-1 adrenoreceptors can influence the development of sex-specific cardiac rhythm disorders.

A Complex of Pyrosequencing-Based Methods for Detection of Somatic Mutations in Codons 600 and 601 of the BRAF gene.

The aim of the study is to develop methods for the differentiation of mutations in the BRAF codon 600 and to increase the sensitivity of the K601E mutation detection. Materials and Methods: The nucleotide sequence of the BRAF codons 592-602 was identified using the PyroMark Q24 genetic analysis system. The mutations search in codon 600 was conducted using the 600-S primer in line with the following order of adding nucleotides: GCTGTCАTCTGCTAGCTAGAC (corresponding to nucleotides 1799-1786). The K601E mutation was detected using the 601-S primer in line with the following order of nucleotide addition: GCTACTCACTGTAG (corresponding to nucleotides 1801-1793). The analytical characteristics of the proposed methods for somatic mutations' detection were determined using dilutions of plasmid DNA samples containing the BRAF gene region without mutations or with one of the following mutations: V600E, V600R, V600K, V600M, and K601E. Validation was performed on 132 samples of biological material obtained from the thyroid nodules. Results: The developed methods allow to determine 2% of the V600E or V600M mutations, 1% of the V600K and V600R mutations, and 3% of the K601E mutations in samples with high DNA concentration; it is also possible to confidently detect at least 5% of the mutant allele for all mutations in low concentration samples (less than 500 copies/PCR). During biological material testing, 53 samples with the V600E mutation were detected; the proportion of the mutant allele was 4.9-50.0%. Conclusion: A complex of methods for determination of the nucleotide sequence of the BRAF codons 592-601 and the algorithm for testing samples and analyzing mutations in the BRAF codons 600-601 was developed. The method provides sufficient sensitivity to detect frequent mutations in codons 600 and 601 and allows them to be precisely differentiated.

[Cognitive functions, emotional status, MRI measurements in treatment-naïve middle-aged patients with uncomplicated essential arterial hypertension]. / Kognitivnye funktsii, émotsional'nyi status i pokazateli magnitno-rezonansnoi tomografii u nelechenykh patsientov srednego vozrasta s neoslozhnennoi arterial'noi gipertenziei.

AIM: To study cognitive functions, anxiety and depression levels, 24-hour blood pressure (BP) profile, cerebral blood flow (CBF) perfusion in treatment-naive middle-aged patients with uncomplicated essential arterial hypertension (EAH) depending on the white matter hyperintensities (WMH) burden. MATERIAL AND METHODS: Forty-one hypertensive patients (mean age 46.2±4.6 years) and 41 healthy volunteers (mean age 50.3±6.7 years) were enrolled to the study. All subjects underwent brain MRI (MAGNETOM Skyra 3.0T, T1, T2 FSE, T2 FLAIR, T1 MPRAGE, ASL), Montreal cognitive assessment (MoCa), 10-word learning task, verbal fluency test, trail making test, Stroop color and word test, anxiety and depression assessment with Hamilton rating scales, 24-hour blood pressure monitoring (ABPM). RESULTS: WMH were found in 22 (53.7%) hypertensive patients and in 3 (7.3%) healthy volunteers (p=0.0002). Hypertensive patients had the significantly lower CBF compared to controls (p<0.001). CONCLUSION: WMH were identified in treatment-naive middle-aged patients with uncomplicated mild to moderate EAH. There was an association between WMH and lower CBF in the cortical plate of frontal lobes, SBP variability and worse cognition. Cerebral hypoperfusion can cause cognitive impairment even in the earliest stages of EAH, which increases due to emotional disorders.

[Metabolic activity of peripheral blood neutrophils during treatment of children with acute lymphoblastic leukemia].

Neutrophilic metabolic activity was studied in 21 children with lymphoblastic leukemia during chemotherapy. After one-year chemotherapy, reduced cell activities of catalase and glutathione reductase were observed in children with septic complications during a follow-up in the presence of lower neutrophilic lactate levels. There was a direct correlation between lactate levels and catalase activity. Since the reduction in the levels of lactate in the neutrophils is attended by their apoptosis, this suggests that there is an association of delayed cell death with a fall in the phagocytic antioxidative defense potential.

Influence of inheritance and fostering on sensitivity to effects of morphine on nociception and locomotor activity in two inbred rat strains.

There are differences between individuals in their pain threshold, locomotor activity, and sensitivity to drugs of abuse which affect these processes. We have investigated the role of genetic differences and fostering in determining sensitivity to the action of morphine on nociception and locomotor activity in two strains of rats [Fischer-344 (F) and WAG/G (W)], using methods of reciprocal cross and cross-fostering. Nine-week old rats were used in the experiments. It was found that FF rats were more sensitive to the action of morphine on locomotor activity in open field apparatus than WW rats. Both types of F1 hybrids inherited a low sensitivity to the depressive action of morphine, their activity significantly differed from FF activity and had no distinction from that of WW rats. However, there was a strong maternal effect: if WW rats were fostered by a FF mother, the depression of their locomotor activity was similar to that of FF inbred rats, and vice versa. There were significant differences between normal and cross-fostered rats in all groups. WW rats had a higher sensitivity to thermal stimuli than FF rats. Both types of hybrids had intermediate nociceptive latencies. The strain difference between WW and FF rats in the baseline latencies of tail withdrawal disappeared after crossfostering-the latencies in FF rats were significantly decreased. Administration of morphine produced greater antinociception in FF rats than in WW. Cross-fostering of FF rats by WW mothers dramatically decreased their sensitivity to the analgesic action of morphine, while WW rats fostered by FF mothers did not change their resistance to morphine induced antinociception. Thus, the sensitivity of young rats to morphine-induced analgesia or depression of locomotor activity is mostly determined by fostering during the first 21 days.

Differences in morphine reinforcement property in two inbred rat strains: associations with cortical receptors, behavioral activity, analgesia and the cataleptic effects of morphine.

The purpose of the current study was to investigate genetic differences between two inbred strains of rats, Fisher-344 (F344/N) and Wistar Albino Glaxo (WAG/GSto), in a number of drug-naive and drug-related behaviors, including oral and intravenous morphine self-administration. F344/N and WAG/GSto rats differed in drug-naive behaviors such as nociception, rearing and sensitivity to lick suppression tests but did not differ in locomotor activity, ambulation or grooming behavior. F344/N rats were less sensitive to thermal stimuli as measured via tail-flick response, and more sensitive to the suppressive effects of intermittent shock in a lick suppression test. The F344/N rats demonstrated a significantly greater amount of rearing in open field tests but did not differ from WAG/GSto rats in locomotor activity, ambulation or grooming behavior. In addition to the behavioral results, naive F344/N and WAG/GSto rats were found to differ in mu and alpha 2 receptor concentrations (F344/N > WAG/GSto) and in 5HT2 and D2 affinity constants (WAG/GSto > F344/N). These two inbred rat strains also differed in drug-related behaviors. F344/N rats showed significantly greater depression of locomotor activity at morphine 3 mg/kg than WAG/GSto rats. In addition, F344/N rats consumed significantly greater amounts of morphine in a two-bottle choice procedure and morphine maintained significantly greater amounts of behavior during intravenous self-administration sessions. Importantly, drug maintained behavior was significantly greater than with vehicle only in the F344/N rats during operant self-administration sessions.

Evaluation of Wistar rats' individual sensitivity to the development of physical dependence on morphine.

Behavioral and physiological indices which could be symptoms of individual Wistar rats' sensitivity to the development of physical dependence on morphine, were studied. This state was induced in three different ways: (1) by i.p. injection of increasing doses of the drug; (2) by i.p. injection of morphine as a reward of a rat's visit to a certain compartment of the Y-maze; (3) by voluntary drinking a morphine solution. Animals with high sensitivity to the development of dependence induced by the first way initially demonstrated intensive ambulation and low rearing in the open field and low nociception in the tail flick test. In the second case the 'predisposed' animals had initially higher ambulation also in comparison with the 'resistant' ones, but did not demonstrate significant withdrawal symptoms. The rats imbibing morphine solution exhibited a withdrawal syndrome, low level of initial nociception and received more electrocutaneous stimuli in the Vogel test. Thus, marked differences of sensitivity to the development of morphine dependence are correlated with some initial behavioural and physiological indices and may be genetically and neurochemically determined.

Biochemical resistance to development of morphine-dependence in rats: biogenic amines, its receptors and antibodies.

The level of norepinephrine (NE), epinephrine (E) and dopamine (DA) in hypothalamus and blood plasma along with antibodies to NE, DA and serotonin (5-HT) and characteristics of alpha 1-, alpha 2-adrenergic, D2-dopaminergic and S2-serotoninergic receptors in synaptic brain membranes were studied in two groups of rats predisposed or resistant to the formation of physical morphine dependence. The resistant animals were characterized by a significant elevation of DA levels in blood plasma, elevation of antibodies to NE, and by higher concentration of alpha 2-adrenergic receptors in the brain cortex and of D2-receptors in striatum. The affinity of D2-receptors to dopamine in resistant rats also was higher than in predisposed animals. The other parameters studied did not differ significantly between the two groups. These findings suggest that the increased activity of DA and NE neurotransmitter systems can be a cause for the genetic resistance of some individuals among Wistar rats to the formation of physical dependence on morphine.

Pentagastrin modulation of sensitivity of neurons of the lateral hypothalamus to noradrenaline and dopamine.

The chemical sensitivity of neurons of the lateral hypothalamus of hungry and fed rabbits to pentagastrin (PG) and to the mediators, noradrenaline (NA) and dopamine (DA), was investigated utilizing indices which permit the assessment of the structural-functional organization of the impulse stream of nerve cells. It was demonstrated that the neurons of the lateral hypothalamus possess varied chemical sensitivity in the presence of alimentary motivation and during the satisfaction of the corresponding need. The microiontophoresis of PG changes the sensitivity of cells in hungry animals to a higher degree to DA (60%) than to NA (30%), while in fed animals, to a higher degree to NA (48%) than to DA (23%). The administration of NA against the background of the action of PG to fed rabbits decreased the percent of neurons with spike train complex activity. The number of cells in the deprived animals with impulse activity of a similar character decreased following the microiontophoresis of DA alone and DA against the background of the action of PG. It is concluded that PG exerts a modulating influence on the effects of NA and DA on the impulse activity of the neurons, and that the character of the effect of PG depends on the initial state of the animal.

[Gram-negative virulent bacterial lipopolysaccharide: role in infection and immunity]. / Lipopolisakharidy gramotritsatelnykh virulentnykh bakterii i ikh rolv infektsii i immunitete.

The paper discusses the data available in the literature on the studies on lipopolysaccharides (LPS) of bacteria which show their different virulence. A comparative study of the chemical composition and structure of LPS of the bacteria fails to detect any great difference, but they differ in their biological, especially immunobiological properties. It is suggested that the differences are associated with LPS conformation, chiefly its lipid moiety and ion-coordinating processes and free radical reactions are involved in the conformation. Examining just these phenomena may made advances in further studies of virulent bacterial LPS and possibilities of its use while designing new-generation vaccines.

[Immunosuppressive effects of pathogenic gram-negative bacteria]. / Immunosupressivnoe deistvie patogennykh gramotritsatel'nykh bakterii.

The review deals with the Immunosuppressive effects of virulent gram-negative bacteria (Salmonella, Shigela, Pseudomonas aeruginosa), with the importance of these effects for the bacteria to survive in the infected body. The above bacteria affect the immunity system in a different way, yet have common features. They are characterized by the occurrence of endotoxin shock, by the suppression of the phagocytic system and cell-mediated immunity. A significant role in suppressing a cellular immune response is played by the lipopolysaccharide of virulent bacteria that greatly differs from that of nonvirulent strains. The immunosuppressive activity of the bacteria and their lipopolysaccharide is closely related to their virulent properties.

[Neuromediator sensitivity of neurons of the reticular formation and orbital cortex in hungry and satiated rabbits]. / Neiromediatornaia chuvstvitel'nost' neironov retikuliarnoi formatsii i orbital'noi kory u golodnykh i nakormlennykh krolikov.

In conditions of stereotaxic fixation, noradrenaline microionophoresis and stimulation of the lateral hypothalamus acted in the same sense on impulse activity of 35 and 37% of the neurones in the reticular formation of satiated rabbits, in joint action increasing the number of cells with distribution of intervals characteristic of alimentary motivational excitation. Microionophoresis of acetylcholine to the neurones of the orbital cortex in freely behaving rabbits reshaped the impulse activity of 57% of cells in accordance with the pattern of discharge activity characteristic of alimentary motivational excitation. Such excitation, natural as well as artificially evoked, widens polychemical properties of the neurones of the reticular formation and, on the contrary, narrows polychemical properties of the nerve cells of the orbital cortex.