On the chaotic and hyper-chaotic dynamics of nanobeams with low shear stiffness.

We construct a mathematical model of non-linear vibration of a beam nanostructure with low shear stiffness subjected to uniformly distributed harmonic transversal load. The following hypotheses are employed: the nanobeams made from transversal isotropic and elastic material obey the Hooke law and are governed by the kinematic third-order approximation (Sheremetev-Pelekh-Reddy model). The von Kármán geometric non-linear relation between deformations and displacements is taken into account. In order to describe the size-dependent coefficients, the modified couple stress theory is employed. The Hamilton functional yields the governing partial differential equations, as well as the initial and boundary conditions. A solution to the dynamical problem is found via the finite difference method of the second order of accuracy, and next via the Runge-Kutta method of orders from two to eight, as well as the Newmark method. Investigations of the non-linear nanobeam vibrations are carried out with a help of signals (time histories), phase portraits, as well as through the Fourier and wavelet-based analyses. The strength of the nanobeam chaotic vibrations is quantified through the Lyapunov exponents computed based on the Sano-Sawada, Kantz, Wolf, and Rosenstein methods. The application of a few numerical methods on each stage of the modeling procedure allowed us to achieve reliable results. In particular, we have detected chaotic and hyper-chaotic vibrations of the studied nanobeam, and our results are authentic, reliable, and accurate.

Pharmacological effects of fibroblast growth factor 21 are sex-specific in mice with the lethal yellow (Ay) mutation.

Hypothalamic melanocortin 4 receptors (MC4R) regulate energy balance. Mutations in the MC4R gene are the most common cause of monogenic obesity in humans. Fibroblast growth factor 21 (FGF21) is a promising antiobesity agent, but its effects on melanocortin obesity are unknown. Sex is an important biological variable that must be considered when conducting preclinical studies; however, in laboratory animal models, the pharmacological effects of FGF21 are well documented only for male mice. We aimed at investigating whether FGF21 affects metabolism in male and female mice with the lethal yellow (Ay) mutation, which results in MC4R blockage and obesity development. Obese C57Bl-Ay male and female mice were administered subcutaneously for 10 days with vehicle or FGF21 (1 mg per 1 kg). Food intake (FI), body weight (BW), blood parameters, and gene expression in the liver, muscles, brown adipose tissue, subcutaneous and visceral white adipose tissues, and hypothalamus were measured. FGF21 action strongly depended on the sex of the animals. In the males, FGF21 decreased BW and insulin blood levels without affecting FI. In the females, FGF21 increased FI and liver weight, but did not affect BW. In control Ay-mice, expression of genes involved in lipid and glucose metabolism (Ppargc1a, Cpt1, Pck1, G6p, Slc2a2) in the liver and genes involved in lipogenesis (Pparg, Lpl, Slc2a4) in visceral adipose tissue was higher in females than in males, and FGF21 administration inhibited the expression of these genes in females. FGF21 administration decreased hypothalamic POMC mRNA only in males. Thus, the pharmacological effect of FGF21 were significantly different in male and female Ay-mice; unlike males, females were resistant to catabolic effects of FGF21.

Nonlinear dynamics of contact interaction of a size-dependent plate supported by a size-dependent beam.

A mathematical model of complex vibrations exhibited by contact dynamics of size-dependent beam-plate constructions was derived by taking the account of constraints between these structural members. The governing equations were yielded by variational principles based on the moment theory of elasticity. The centre of the investigated plate was supported by a beam. The plate and the beam satisfied the Kirchhoff/Euler-Bernoulli hypotheses. The derived partial differential equations (PDEs) were reduced to the Cauchy problems by the Faedo-Galerkin method in higher approximations, whereas the Cauchy problem was solved using a few Runge-Kutta methods. Reliability of results was validated by comparing the solutions obtained by qualitatively different methods. Complex vibrations were investigated with the help of methods of nonlinear dynamics such as vibration signals, phase portraits, Fourier power spectra, wavelet analysis, and estimation of the largest Lyapunov exponents based on the Rosenstein, Kantz, and Wolf methods. The effect of size-dependent parameters of the beam and plate on their contact interaction was investigated. It was detected and illustrated that the first contact between the size-dependent structural members implies chaotic vibrations. In addition, problems of chaotic synchronization between a nanoplate and a nanobeam were addressed.

[COMPARATIVE CHARACTERISTICS OF EPIDEMIC SEASONS OF INFLUENZA 2015-2016AND 2009 -2010].

AIM: Analyze epidemiologic and- clinical features of influenza epidemic seasons 2009 - 2010 and 2015 - 2016. Materials and methods Forms of federal state statistic observation No.4 , 2, 5, and 6; information from the official web-site of the Research Institute of Influenza of the Ministry of Health of Russian Federation; materials of various conferences and congresses on problems of influenza; information-analytical certificates of the Ministry of Health .of Russian Federation. RESULTS: Epidemic morbidity increases in the season 2009 - 2010. and 2015 - 2016 started at various time and had different duration. Children younger than 14 years of age predominated in the structure of patients in the 2009 - 2010 epidemic season, the main mass of patients were presented by individuals aged 45 - 59 years in the 2015 - 2016 season. The number of lethal outcomes with laboratory confirmed influenza diagnosis in 2009 - 2010 was 687-cases, and in 2015 - 2016 - 663 cases. Almost all the deceased from influenza were not vaccinated against this infection. Cardiovascular system diseases were noted in 484 individuals of the total number of deceased. Most of the deceased were late to seek medical aid. CONCLUSION: Influenza epidemic season 2015 - 2016 differs from 2009 - 2010 season by dynamics of morbidity development and a lower amount of severe forms of the disease and lethal outcomes. This may be-due to an increase of population immunity against pandemic strain A(H1N1)pdm09 via pro-epidemizing in the recent years as well as an increase of influenza vaccination coverage.

[STUDYING THE ROLE OF BRAIN MELANOCORTIN RECEPTORS IN THE SUPPRESSING OF FOOD INTAKE UNDER ETHER STRESS IN MICE].

Melanocortin (MC) system regulates food intake under the rest conditions. Stress inhibits food intake. It is not clear whether brain MC system is involved in stress-induced anorexia in mice. The aim of the work was to investigate the effect of pharmacological blockade and activation of brain MC receptors on food intake under stress. C57B1/6J male mice were subjected to ether stress (0.5 minute ether anesthesia) before the administration of saline solution or synthetic non-selective blocker (SHU9119) or agonist (Melanotan II) of MC receptors into the lateral brain ventricle. Food intake was pre-stimulated with 17 hours of fasting in all mice. Ether stress decreased food intake, increased the plasma corticosterone level and hypothalamic mRNA AgRP (natural MC receptor antagonist) level at 1 hour after the stress. Pharmacological blockade of the MC receptors weakened stress-induced anorexia and decreased mRNA AgRP level in the hypothalamus. Pharmacological stimulation of the MC receptors enhanced ether stress-induced anorexia and hypercortisolism. Thus, our data demonstrated that the central MC system was involved in the development of stress-induced anorexia in mice.

Zyklophin, a short-acting kappa opioid antagonist, induces scratching in mice.

It has been shown previously that norbinaltorphimine (norBNI) and 5'-guanidinonaltrindole (5'-GNTI), long-acting kappa opioid receptor (KOPR) antagonists, cause frenzied scratching in mice [1,2]. In the current study, we examined if zyklophin, a short-acting cyclic peptide KOPR antagonist, also elicited scratching behavior. When injected s.c. in the nape of the neck of male Swiss-Webster mice, zyklophin at doses of 0.1, 0.3 and 1mg/kg induced dose-related hindleg scratching of the neck between 3 and 15 min after injection. Pretreating mice with norBNI (20mg/kg, i.p.) at 18-20 h before challenge with zyklophin (0.3mg/kg) did not markedly affect scratching. Additionally, KOPR-/- mice given 0.3mg/kg of zyklophin displayed similar levels of scratching as wild-type animals. The absence of KOPR in KOPR-/- mice was confirmed with ex vivo radioligand binding using [(3)H]U69,593. Taken together, our data suggest that the presence of kappa receptors is not required for the excessive scratching caused by zyklophin. Thus, zyklophin, similar to the structurally different KOPR antagonist 5'-GNTI, appears to act at other targets to elicit scratching and potentially the sensation of itch.

Exaggerated anorexigenic response to restraint stress in A(y) mice is associated with elevated CRFR2 mRNA expression in the hypothalamus.

The "lethal yellow" mutation at the mouse agouti locus (A(y)) results in hyperphagia, obesity, and type 2 diabetes at rest, but helps to reduce food intake under stress. The aim of this work was to investigate mechanisms of exaggerated anorectic response to stress in A(y) mice. All parameters were measured in C57BL/6J male mice of a/a (control) and A(y)/a genotypes before, 0, 1, and 3h after a 1-h restraint. Baseline food intake and plasma insulin concentrations were higher in A(y)/a mice compared to a/a mice. Restraint reduced food intake and plasma insulin concentrations only in A(y)/a mice. Stress-induced anorexia in A(y)/a mice was independent of pathways involving hypothalamic-pituitary-adrenal axis activity and hypothalamic orexigenic neuropeptide (agouti-related peptide and neuropeptide Y) gene expressions and corticotrophin-releasing factor type 1 receptor (CRFR1). Gene expression of CRFR2 was elevated in A(y)/a mice with genotype differences particularly manifested immediately after the restraint. Hypothalamic CRFR2 is known to mediate anorectic signals from CRF-related peptides. Thus, our data suggest that stress-induced anorexia in A(y)/a mice may be associated with increased anorectic signals mediated by CRFR2 in the hypothalamus.

[Atorvastatin and oxidative stress in coronary heart disease with obesity].

The aim of the work was to study the role of atorvastatin in the correction of oxidative stress manifestations in patients with coronary heart disease and dyslipidemnia (DLP). It included 122 patients with stable forms of CHD and 20 practically healthy subjects. Plasma lipids and products of lipid peroxidation (dienic conjugates and compounds reacting with 2-thiobarbituric acid), eryhrocyte antioxidative enzymes glutathione peroxidase and superoxide dismutase were determined by standard methods; activity of the ceruloplasmin/transferrin antioxidant system) was measured by electron paramagnetic resonance. The patients underwent 24 hr ECG Holter monitoring. Atorvastatin at a dose of 20 mg/d given during 6 months exerted antioxidative and antiperoxidative effects in 90% of the patients. It normalized parameters of lipid peroxidation and antioxidant protection thereby improving the clinical course of CHD.

Pregnancy and lactation have anti-obesity and anti-diabetic effects in A(y)/a mice.

AIM: Dominant 'yellow' mutation at the mouse agouti locus (A(y)) results in obesity. Pregnancy and lactation are characterized by large energy demand. The aim of this study was to investigate whether obesity would develop in pregnant and suckling A(y) mice. METHODS: Body weight and food intake in pregnancy, lactation, and after weaning, plasma leptin, insulin, corticosterone and blood glucose concentrations on days 7, 13 and 18 of pregnancy, days 1, 10, 21 and 80 postpartum, glucose and insulin tolerance on pregnancy days 7 and 18 were measured in C57Bl/6J mice of a/a (normal metabolism) and A(y)/a genotypes. The same parameters were also measured in age-matched virgin females. RESULTS: Virgin A(y)/a females exhibited hyperphagia, enhanced body weight, glucose intolerance and normal blood parameters at the mating age. With age, they developed obesity, hyperleptinaemia, hyperinsulinaemia and hyperglycaemia. Obesity did not develop in mated A(y)/a mice; during suckling, they had equal food intake and body weight as a/a mice. During pregnancy, glucose tolerance was enhanced in A(y)/a mice and became equal in both genotypes. In both genotypes, concentrations of hormones increased, and glucose decreased from pregnancy day 7 to day 18 and returned to normal values after parturition. A(y)/a mice did not differ from a/a in corticosterone, insulin and glucose levels during pregnancy and lactation, in leptin levels during suckling; however, A(y)/a mice had two times higher leptin levels than a/a during pregnancy. After weaning, A(y)/a mice began to eat and weigh more than a/a exhibiting normal metabolic parameters for 50 days. CONCLUSION: Pregnancy and lactation retard obesity and diabetes development in A(y) mice.

Function of the hypothalamo-hypophyseal-adrenal system in mice with ectopic hyperproduction of the agouti protein.

The agouti protein is known to compete with the melanocortin hormones (ACTH, melanocyte-stimulating hormone) at melanocortin receptors, which in turn are involved in controlling the central and peripheral components of the hypothalamo-hypophyseal-adrenal system. The aim of the present work was therefore to assess the effects of the dominant mutation Agouti yellow (A(y)/a), which induces ectopic hyperproduction of the agouti protein and yellow coat color, on the function of the hypothalamo-hypophyseal-adrenal system. Experiments were performed on male A(y)/a mice of the C57BI/6J line. Controls consisted of mice of the same line bearing the recessive mutation nonagouti (a/a), which leads to the absence of agouti protein and black coat color. The experimental results showed that mice with different agouti genotypes had identical basal corticosterone levels, though yellow mice, as compared with black mice, had increased corticosterone levels after restriction stress (p < 0.02), along with decreased stress reactivity after treatment with dexamethasone (p < 0.0007), and increased adrenal sensitivity to small doses of activity, both in vitro and in vivo.

Elevated basal activity of tryptophan oxygenase in alcohol-preferring C57BL mice.

Tryptophan oxygenase activity in alcohol-preferring C57Bl mice and control CBA and DBA/2 mice was studied under nonstressful conditions and after glucocorticoid-induced stress. Elevated basal tryptophan oxygenase activity in C57Bl mice is probably responsible for reduced brain content of tryptophan and serotonin associated with alcohol preference.

Agouti locus may influence reproduction under food deprivation in the water vole (Arvicola terrestris).

The effect of 16-hr food deprivation on day 3 and again on day 5 of pregnancy on the fecundity of female water voles homozygous (ae/ae) or heterozygous (A/ae) for, an allele at the Agouti (A) locus, non agouti extreme (ae) was studied. 63 A/ae females (mated to ae/ae males) produced 115 food-deprived and 115 control pregnancies, and 52 ae/ae females (mated to A/ae males) produced 55 food-deprived and 57 control pregnancies. Regardless of the experimental group, pregnant ae/ae females weighed less than A/ae females. The effect of food deprivation on fecundity depended on the Agouti-locus genotype of the female. In food-deprived A/ae females, fecundity was diminished due to fewer successful pregnancies (P < 0.001) and lower survival of the young (P < 0.05). In food-deprived ae/ae females, reproductive performance was not changed; a somewhat reduced rate of successful pregnancies was compensated for by significantly increased (P < 0.002) postnatal survival of the young. In progeny weaned from food-deprived mothers, the frequency of A/ae females was diminished. Resistance of ae/ae females to the negative effect of nutritional stress, and predominance of ae/ae young in progeny produced by food-deprived mothers, may favour the maintenance of polymorphism for the Agouti-locus in natural populations of the water vole.

Effects of food deprivation in early pregnancy on the development of ovaries and adrenals in female progeny of the water vole (Arvicola terrestris).

The effects of maternal food deprivation for 16 hr on day 3 and again on day 5 of pregnancy on the development of adrenals and ovaries in the female offspring during postnatal life (8, 21, 30 and 60 days after birth) were examined. Experimental and control groups consisted of 6-15 animals. On day 8, the daughters of the deprived mothers had lower body weight than the control animals. Later, the differences between the groups disappeared. Maternal food deprivation alters the prepubertal dynamics of adrenal progesterone production in vitro, and in mature experimental females adrenal progesterone production is significantly (P < 0.05) lower than in the control. In deprived mothers' offspring, the postnatal development of the endocrine function of the ovaries was disturbed: on day 8, the ovarian progesterone production was 3.3 times less (P < 0.001) and ovarian estradiol production was 3.2 times less (P < 0.05) than in the control, and on day 30, a prepubertal peak in ovarian estradiol production in vitro was absent. Maternal food deprivation causes alterations in the prepubertal dynamics of blood concentrations of corticosterone, progesterone and estradiol and reduction in blood concentrations of progesterone (P < 0.05) and estradiol (P < 0.001) in mature individuals. It was concluded that maternal food deprivation before implantation disturbs the normal course of postnatal maturation of the ovarian endocrine functions and adrenal progesterone secretion in daughters.

The study of properties of immunoreactive estradiol secreted by adrenals and ovaries of immature female rats.

Some properties of immunoreactive estradiol secreted by adrenals and ovaries of immature female rats were studied. It was shown that adrenals and ovaries of 15-day-old animals secrete approximately equal amounts of immunoreactive estradiol, with thin-layer chromatogram of immunoreactive material being identical for both glands. Adrenal- as well as ovarian-derived estradiol can bind to uterine cytosol estradiol receptors with the formation of complexes, which can be activated in the cell-free system. The removal of either adrenals or ovaries causes a decrease of cytosol estradiol receptor levels in the uterus 6 hours after the operation. From these results and previously reported data, nothing suggests that immunoreactive estradiol secreted by the adrenals of immature rats should be regarded as "spurious" hormone.

Opiate binding sites and endogenous opioids in Bufo viridis oocytes.

Binding sites with high affinity for [3H]naloxone, but not for [3H]morphine and [3H] (D-Ala2, D-Leu5) enkephalin, have been found in membranes of Bufo viridis oocytes. The binding is reversible and saturable. Bound [3H]naloxone is easily displaced both by unlabeled naloxone and bremazocine, much worse by morphine and SKF 10,047; (D-Ala2, D-Leu5) enkephalin and beta-endorphin practically fail to displace [3H]naloxone. Scatchard analysis is consistent with the existence of two classes of binding sites with Kd 15 nM and 10(3) nM. The number of binding sites with high affinity for naloxone is 16 pmol/mg protein of homogenized oocytes which is 20-50-fold higher than in, toad or rat brain. Oocyte extract displaces [3H]naloxone bound with oocytes' membranes and inhibits electrically evoked contractions of the rabbit vas deferens. This inhibition is reversed by naloxone. It is suggested that compounds similar to opiate kappa-agonists exist in oocytes. It cannot be ruled out that they participate via specific receptors in the regulation of oocyte maturation and egg development.