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Background Changes in sex hormones during menopause may have detrimental effects on a woman’s sexual function and cause mood disorders. The treatment of both conditions is a challenge in gynecology. Aim To review the published literature on sexual function and mood disorders among peri- and postmenopausal women. Methods The review is based on the methodological framework of scoping reviews. We searched electronic databases including Medline (PubMed), Scopus, Embase, and Web of Science (WoS). Publications that reported data about the relationship between sexual function and mood disorders among menopausal women were included in the review. The search was not subject to any limitation in terms of time or method. Outcomes The main outcome measures used for the review were sexual dysfunction and mood disorders. Results We found 106 total records. After a full-text screening we included 19 studies from 1986 to 2020 based on various methodologies; the majority of the studies16 were cross-sectional. Investigations that addressed the symptoms of mood disorders and some domains of sexual function showed a close relationship between sexual dysfunction and mood disorders among menopausal women. Clinical implications In clinical practice, it would be appropriate to screen women for at least one mood disorder or sexual dysfunction. If a woman suffers from either, it will be necessary to assess for a further disorder as well. Strengths & Limitations The review was based on a detailed search of the published literature concerning mood disorders and sexual dysfunction among menopausal women compared to women of reproductive age. Despite the clinical importance of the subject, the number of studies eligible for inclusion in the review are rather small. Further investigation of the topic is clearly warranted. Conclusions While the association between sexual dysfunction and mood disorders appears to be bidirectional, future studies will have to investigate the specific mechanisms by which sexual dysfunction could lead to mood disorders (or vice versa). Future studies should specifically address sexual dysfunctions and attitudes of partners, BMI, family support, sleep, and multiparity.

Granular films containing Fe50Co50Zr10 alloy nanoparticles inside the ferroelectric matrix Pb0.81Sr0.04(Na0.5Bi0.5)0.15(Zr0.575Ti0.425)O3 (PZT) are characterized by a complex of functional magnetic and electrical characteristics that can be effectively controlled by an external electric or magnetic field. The formation of the necessary granular structure in the case of a PZT matrix is possible only during synthesis in an oxygen-containing atmosphere, leading to significant oxidation of metal nanoparticles. In this regard, an urgent task is to study the degree of oxidation of metal nanoparticles depending on the synthesis conditions, as well as the influence of the forming phases on the electrical properties of films.The relationship of the phase composition and electrical characteristics of granular films (FeCoZr)x(PZT)100-x (30 ≤ x ≤ 85, at.%) obtained in an oxygen-containing atmosphere at a pressure of PO in the range (2.4—5.0) ⋅ 10-3 Pa was studied by X-ray diffraction analysis, EXAFS spectroscopy (Extended X-ray Absorption Fine Structure) and four-probe electrical resistivity measurements.A comparative complex analysis of the structural-phase composition and local atomic order in films (FeCoZr)x(PZT)100-x for the first time showed the fundamental influence of oxygen pressure during synthesis on the oxidation of nanoparticles and their phase composition. It is shown that in the case of oxygen pressure up to the values of PO = 3.2 ⋅ 10-3 Pa, a transition from nanoparticles of complex Fe(Co,Zr) oxides occurs with increasing x to the superposition of complex oxides and ferromagnetic nanoparticles α-FeCo(Zr,O) (or their agglomerations). At a higher oxygen pressure PO = 5.0 ⋅ 10-3 Pa, complete oxidation of nanoparticles is observed with the formation of a complex oxide (FexCo1-x)1-δO with a wustite structure.The observed structural-phase composition allows us to explain the measured temperature dependences of the electrical resistance of granular films, characterized by a negative temperature coefficient of electrical resistance (TKR) in the entire range of film compositions at high oxygen pressure (PO = 5.0 ⋅ 10-3 Pa), and the transition to positive TKR at lower oxygen pressure (PO = 3.2 ⋅ 10-3 Pa) in the synthesis atmosphere and the value x ≤ 69 at.% in films. The transition from negative to positive TKR, indicating the presence of a metallic contribution to conductivity, is fully correlated with the detection by XRD and EXAFS methods of non-oxidized ferromagnetic nanoparticles α-FeCo(Zr,O) or their agglomerations.

Granular films containing Fe50Co50Zr10 alloy nanoparticles inside Pb0,81Sr0,04(Na0,5Bi0,5)0,15(Zr0,575Ti0,425)O3 (PZT) ferroelectric matrix possess a combination of functional magnetic and electrical properties which can be efficiently controlled by means of external electric or magnetic fields. The formation of the required granular structure in PZT matrix is only possible if synthesis is carried out in an oxygen-containing atmosphere leading to substantial oxidation of metallic nanoparticles. Thus an important task is to study the oxidation degree of metallic nanoparticles depending on synthesis conditions and the effect of forming phases on the electrical properties of the films. The relationship between the structural and phase state and electrical properties of granular FeCoZr)x (PZT)100-x films (30 ≤ x ≤ 85 at.%) synthesized in an oxygen-containing atmosphere at the oxygen pressure PO in a range of (2.4–5.0) · 10–3 Pa has been studied using X-ray diffraction, EXAFS and four-probe electrical resistivity measurement. Integrated comparative analysis of the structural and phase composition and local atomic order in (FeCoZr)x (PZT)100-x films has for the first time shown the fundamental role of oxygen pressure PO during synthesis on nanoparticle oxidation and phase composition. We show that the oxygen pressure being within PO = 3.2 · 10–3 Pa an increase in x leads to a transition from nanoparticles of Fe(Co,Zr)O complex oxides to a superposition of complex oxides and a-FeCo(Zr,O) ferromagnetic nanoparticles (or their agglomerations). At higher oxygen pressures РО = 5.0 · 10–3 Pa the nanoparticles undergo complete oxidation with the formation of the (FexCo1-x)1-δO complex oxide having a Wurtzite structure. The forming structural and phase composition allows one to explain the observed temperature dependences of the electrical resistivity of granular films. These dependences are distinguished by a negative temperature coefficient of electrical resistivity over the whole range of film compositions at a high oxygen pressure (РО = 5.0 · 10–3 Pa) and a transition to a positive temperature coefficient of electrical resistivity at a lower oxygen pressure (РО = 3.2 · 10–3 Pa) in the synthesis atmosphere and x > 69 at.% in the films. The transition from a negative to a positive temperature coefficient of electrical resistivity which suggests the presence of a metallic contribution to the conductivity is in full agreement with the X-ray diffraction and EXAFS data indicating the persistence of unoxidized a-FeCo(Zr,O) ferromagnetic nanoparticles or their agglomerations.

We investigated the presence of a molecular pathway from hepatic 11-βHSD-1 to brain MAO-A in the dynamics of plasma corticosterone involvement in anxiety development. During 14 days following repeated exposure of rats to predator scent stress for 10 days, the following variables were measured: hepatic 11-βHSD-1 and brain MAO-A activities, brain norepinephrine, plasma corticosterone concentrations, and anxiety, as reflected by performance on an elevated plus maze. Anxiety briefly decreased and then increased after stress exposure. This behavioral response correlated inversely with plasma corticosterone and with brain MAO-A activity. A mathematical model described the dynamics of the biochemical variables and predicted the factor(s) responsible for the development and dynamics of anxiety. In the model, hepatic 11-βHSD-1 was considered a key factor in defining the dynamics of plasma corticosterone. In turn, plasma corticosterone and oxidation of brain ketodienes and conjugated trienes determined the dynamics of brain MAO-A activity, and MAO-A activity determined the dynamics of brain norepinephrine. Finally, plasma corticosterone was modeled as the determinant of anxiety. Solution of the model equations demonstrated that plasma corticosterone is mainly determined by the activity of hepatic 11-βHSD-1 and, most importantly, that corticosterone plays a critical role in the dynamics of anxiety following repeated stress.

We have investigated the structure and electrical conductivity of carbon nanographite layers grown by chemical vapor deposition, enhanced by microwave plasma (PECVD) on an setup by IPLAS Innovative Plasma Systems GmbH (Germany). The samples were grown on fused silica substrates with deposition times of 20 and 40 min, respectively. The study of the formed layers of nanographite by the method of Raman light scattering and scanning electron microscopy showed that the surface of the nanographite sample deposited for 20 min is covered with a large number of unconnected vertical graphene nuclei with an average size of less than 10 nm. An increase in the growth time to 40 min led to an increase in the size of the nuclei to 20 –30 nm; however, their overlap does not occur. This confirmed that the samples corresponded to the initial stages of the formation of vertical graphene in the grown nanographite layers and there is no percolative structure in them. The obtained samples were used to study the temperature dependences of the sheet electrical resistance at direct current in the range of 4 –300 K and the effect on them of the number of cycles N cooling – heating (300 K – 2 K – 300 K) in an atmosphere of gaseous helium, as well as the change in the atmosphere storage of samples (by placing them in the air after warming up to room temperature). It was found that the electrical resistance of the sample deposited for 20 min is very sensitive to two technological parameters of measurement – the number of cycles N and the change in the storage atmosphere after heating. This manifested itself in the fact that after four cooling – heating cycles and one change of the atmosphere (helium – air – helium) after warming up, the resistance increased by more than 20 %, reaching saturation. The resistance of the sample, deposited for 40 min, showed less sensitivity during thermal cycling, increasing by no more than 10 %. The effect of thermal cycling we attribute to the rearrangement of defects formed at the boundaries of grains in the nanographite layer, and in the case of a change in the atmosphere, with the passivation of dangling bonds with atmospheric gases.

Background: Vitamin D3 (VD3) is involved in the pathophysiological mechanisms of affective-related disorders and controls the functional activity of various hormonal systems. The complex interaction between estrogen and VD3 creates a neurobiological basis for their participation in similar behavioral disorders. Objectives: This study aimed to evaluate whether VD3 (5.0 mg/kg, s.c.) facilitates the antidepressant-like action of fluoxetine (10.0 mg/kg, i.p.) or paroxetine (10.0 mg/kg, i.p.) by enhancing the antidepressant-like activity of these drugs in adult long-term Ovariectomized (OVX) rats subjected to Chronic Unpredictable Mild Stress (CUMS) protocol for 6 weeks. Methods: Sucrose Preference (SPT) and Forced Swim (FST) tests were performed to evaluate the anhedonia state and depressive symptoms, respectively. The Open-Field Test (OFT) was carried out to measure locomotor activity as well as grooming behavior produced by CUMS in long-term OVX rats. Corticosterone (CS)/estradiol (E2) in the serum was tested by rat ELISA kits. NF-kB, 5-HT/5-HIIA, and pro-inflammatory cytokine levels in the hippocampus were also examined by rat ELISA kits. Results: The results of this study suggest that combined treatment with fluoxetine (10.0 mg/kg, i.p.) or paroxetine (10.0 mg/kg, i.p.) along with VD3 (5.0 mg/kg, s.c.) produces distinct effects on the depression-like behavior in long-term OVX/CUMS rats. Co-administration of fluoxetine (10.0 mg/kg, i.p.) with VD3 did not facilitate the antidepressant-like effects of fluoxetine in the long-term OVX rats with CUMS. On the other hand, co-treatment with paroxetine with VD3 resulted in faster and marked antianhedonic- and antidepressant-like effects in long-term OVX rats with CUMS as compared to treatment with paroxetine alone. The co-administration of paroxetine and VD3 attenuates stress-induced modifications of CS/E2 levels in the serum, as well as- proinflammatory cytokine/NF-kB/5-HT levels in the hippocampus of long-term OVX rats exposed to CUMS. Conclusion: Supplementation of VD3 (5.0 mg/kg, s.c.)to paroxetine (10.0 mg/kg, i.p.) facilitates antianhedonic- and antidepressant-like effects of paroxetine in adult long-term OVX rats exposed to CUMS.

Electrodeposition of cobalt on monolayer graphene synthesized by chemical vapor deposition produces Co–CoO/graphene composite structures, which is accompanied by increases in the electrical resistance and magnetoresistance. We show that the observed magnetoresistance effect is caused by two competing contributions: negative (NMR) and positive (PMR) magnetoresistance. In weak magnetic fields, the NMR is described by quantum localization correction to the Drude model of conductivity in graphene. The enhancement of PMR observed in strong magnetic fields is related to the Lorentz mechanism in Co–CoO particles.

We have systematically investigated the magnetization reversal characteristics and magnetoresistance of continuous and nanoporous [Co/Pd]5-IrMn multilayered thin films with perpendicular magnetic anisotropy at different temperatures (4-300 K). For their nanostructuring, porosity was induced by means of deposition onto templates of anodized titania with small (∼30 nm in diameter) homogeneously distributed pores. The magnetization reversal and magnetoresistance of the porous films were found to be closely related to the splitting of the ferromagnetic material into regions with different magnetic properties, in correlation with the complex morphology of the porous system. Independent magnetization reversal is detected for these regions, and is accompanied by its strong impact on the magnetic order in the capping IrMn layer. Electron-magnon scattering is found to be a dominant mechanism of magnetoresistance, determining its almost linear field dependence in a high magnetic field and contributing to its magnetoresistance behavior, similar to magnetization reversal, in a low magnetic field. Partial rotation of IrMn magnetic moments, consistent with the magnetization reversal of the ferromagnet, is proposed as an explanation for the two-state resistance behavior observed in switching between high-resistive and low-resistive values at the magnetization reversal of the porous system studied.

Novel functionalized (biofunctionalization followed by cisplatin immobilization) Fe3O4@SiO2@Au nanoparticles (NPs) were designed. The encapsulation of Fe3O4 cores inside continuous SiO2 shells preserves their initial structure and strong magnetic properties, while the shell surface can be decorated by small Au NPs, and then cisplatin (cPt) can be successfully immobilized on their surface. The fabricated NPs exhibit very strong T2 contrasting properties for magnetic resonance imaging (MRI). The functionalized Fe3O4@SiO2@Au NPs are tested for a potential application in photothermal cancer therapy, which is simulated by irradiation of two colon cancer cell lines (SW480 and SW620) with a laser (λ = 808 nm, W = 100 mW cm−2). It is found that the functionalized NPs possess low toxicity towards cancer cells (∼10–15%), which however could be drastically increased by laser irradiation, leading to a mortality of the cells of ∼43–50%. This increase of the cytotoxic properties of the Fe3O4@SiO2@Au NPs, due to the synergic effect between the presence of cPt plus Au NPs and laser irradiation, makes these NPs perspective agents for potential (MRI)-guided stimulated chemo-photothermal treatment of cancer.

The World Health Organization declared the pandemic situation caused by SARSCoV- 2 (Severe Acute Respiratory Syndrome Coronavirus-2) in March 2020, but the detailed pathophysiological mechanisms of Coronavirus disease 2019 (COVID-19) are not yet completely understood. Therefore, to date, few therapeutic options are available for patients with mildmoderate or serious disease. In addition to systemic and respiratory symptoms, several reports have documented various neurological symptoms and impairments of mental health. The current review aims to provide the available evidence about the effects of SARS-CoV-2 infection on mental health. The present data suggest that SARS-CoV-2 produces a wide range of impairments and disorders of the brain. However, a limited number of studies investigated the neuroinvasive potential of SARS-CoV-2. Although the main features and outcomes of COVID-19 are linked to severe acute respiratory illness, the possible damages on the brain should be considered, too.

The novel iron-oxide nanoparticles (NPs) stabilized with triethanolammonium oleate were produced. The specimens were divided into two groups: the top NPs (extracted from the supernatant) and the bottom NPs (nanoparticles sedimented at the bottom of the flask during centrifugation), respectively. The XRD and Mössbauer studies revealed a presence of the Fe3O4 phase in both types of nanoparticles. Furthermore, the formation of maghemite layer on the surface of nanoparticles was observed. Average particle sizes determined from TEM and XRD studies were lower than the superparamagnetic limit for the magnetite NPs. For glycerol dispersions of both types of NPs, when exposed to 100 kHz external magnetic field, a significant heat release was observed. Furthermore, the contrasts of T1- and T2-weighted MR images were significantly dependent on the concentration of NPs in their water solutions. Additionally, the reductions of the relaxation times were different for the top and the bottom NPs. The viability studies of the colon cancer cells have shown low cytotoxicity of both types of NPs due to their coating with triethanolammonium oleate, which confirm the possibility to apply the NPs for MRI-guided hyperthermia. Moreover, the presence of NPs did not cause greatest increase of the number of apoptotic cells in the human dermal fibroblasts’ culture and has stimulated proliferation of those cells, revealing great potential of the NPs in regenerative medicine. Graphical abstract

Background: Rats exposed to chronic predator scent stress mimic the phenotype of complex post-traumatic stress disorder (PTSD) in humans, including altered adrenal morphology and function. High- and low-anxiety phenotypes have been described in rats exposed to predator scent stress (PSS). This study aimed to determine whether these high- and low-anxiety phenotypes correlate with changes in adrenal histomorphology and corticosteroid production. Methods: Rats were exposed to PSS for ten days. Thirty days later, the rats’ anxiety index (AI) was assessed with an elevated plus-maze test. Based on differences in AI, the rats were segregated into low- (AI ≤ 0.8, n = 9) and high- (AI > 0.8, n = 10) anxiety phenotypes. Plasma corticosterone (CORT) concentrations were measured by ELISA. Adrenal CORT, desoxyCORT, and 11-dehydroCORT were measured by high-performance liquid chromatography. After staining with hematoxylin and eosin, adrenal histomorphometric changes were evaluated by measuring the thickness of the functional zones of the adrenal cortex. Results: Decreased plasma CORT concentrations, as well as decreased adrenal CORT, desoxyCORT and 11-dehydroCORT concentrations, were observed in high- but not in low-anxiety phenotypes. These decreases were associated with increases in AI. PSS led to a significant decrease in the thickness of the zona fasciculata and an increase in the thickness of the zona intermedia. The increase in the thickness of the zona intermedia was more pronounced in low-anxiety than in high-anxiety rats. A decrease in the adrenal capsule thickness was observed only in low-anxiety rats. The nucleus diameter of cells in the zona fasciculata of high-anxiety rats was significantly smaller than that of control or low-anxiety rats. Conclusion: Phenotype-associated changes in adrenal function and histomorphology were observed in a rat model of complex post-traumatic stress disorder.

Experimental study of current-voltage (I-V) characteristics and frequency dependences of impedance in copper-Kapton-copper structures in the temperature range 240 – 300 K were carried out. Concentration and mobility of charge carriers thermally excited from traps with exponential distribution by energy in Kapton bulk and metal-Kapton interface and injected from copper electrodes into Kapton were estimated from the fitting of experimental I-V curves within the frame of the model of the space charge limited current (SCLC). Concentration and the width of energy of localized states, arising from the disorder of the Kapton structure, are additionally estimated from the I-V characteristics.

The structure and electrical properties of (FexOy)10 (ZnO)90 ceramics (0 ≤ x ≤ 3; 1 ≤ y ≤ 4) synthesized in air by one− and two−stage method were studied. To dope ZnO, powders of FeO, α−Fe2O3, and Fe3O4 or a mixture (α−Fe2O3 + FeO) were used. On the basis of X−ray diffraction analysis, gamma−resonance spectroscopy and Raman spectroscopy, it was established that at fixed average iron concentrations of 1—3 at.% in ceramic samples, at least three phases are formed: solid solution Zn1−δFeδO with wurtzite structure and residual iron oxides FexOy, used as doping agents. Scanning electron microscopy and energy−dispersive X−ray analysis have shown that, in the studied ceramics, the grain sizes of the wurtzite phase decreased from several tens of micrometers using one−step synthesis to the submicron level for the case of two−step synthesis. It was found that the incorporation of iron into ZnO leads to a contraction of the crystal lattice in the wurtzite phase and the stronger, the higher the proportion of oxygen in the doping iron oxides FexOy. The study of the temperature dependences of the electrical resistivity have shown that deep donor centers with an activation energy of about 0.35 eV are formed in the wurtzite phase Zn1−δFeδO. The temperature dependences of the electrical resistivity in the undoped ZnO in the temperature range of 6—300 K and in the doped ceramics (FexOy)10(ZnO)90, obtained by the one−step synthesis method, at temperatures below 50 K, are characterized by a variable activation energy, which indicates a strong disordering of their structure.

To evaluate the role of central subfield thickness (CST), cube average thickness (CAT), and cube volume (CV) as imaging biomarkers for severity of diabetic retinopathy within the ETDRS-based grades of retinopathy using spectral domain optical coherence tomography (SD-OCT). This study aims to evaluate the role of macular CST, CAT, and CV on SD-OCT as imaging biomarkers for severity of DR. One hundred ninety-four consecutive cases of type 2 diabetes mellitus were divided according to ETDRS classification: diabetes mellitus without retinopathy (No DR; n = 65), nonproliferative diabetic retinopathy (NPDR; n = 66), and proliferative diabetic retinopathy (PDR; n = 63). Sixty-three healthy controls were included. CST, CAT, and CV were analyzed using SD-OCT. Data were analyzed statistically. Analysis of variance revealed a significant increase in levels of CST, CAT, CV, and LogMAR visual acuity with the increase in severity of DR. Independent t-test revealed significant difference in CST, CAT, and CV between cases with DME and cases without DME. On multivariate linear regression analysis, increase in CST, CAT, and CV were found to indicate the increase in severity of DR. SD-OCT-based imaging biomarkers CST, CAT, and CV are effective tools for documenting the severity of diabetic retinopathy. These imaging biomarkers serve as significant indicators of severity of disease.

A paradoxical reduction in anxiety levels in chronic predator stress paradigm (PS) in Sprague–Dawley rats has recently been shown in previous works. In this paper, we studied the possible neurobiological mechanism of this phenomenon. We segregated PS-exposed Sprague–Dawley rats into the high- and low-anxiety phenotypes. The long-lasting effects of PS on corticosterone levels, blood flow speed in the carotid arteries, diffusion coefficient, and 1H nuclear magnetic resonance spectra in the hippocampus were compared in the high-anxiety and low-anxiety rats. In addition, we evaluated the gene BDNF expression in the hippocampus which is considered to be a main factor of neuroplasticity. We demonstrated that in low-anxiety rats, the corticosterone level was decreased and carotid blood flow speed was increased. Moreover, in the hippocampus of low-anxiety rats compared to the control group and high-anxiety rats, the following changes were observed: (a) a decrease in N-acetyl aspartate levels with a simultaneous increase in phosphoryl ethanol amine levels; (b) an increase in lipid peroxidation levels; (c) a decrease in apparent diffusion coefficient value; (d) an increase in BDNF gene expression. Based on these findings, we proposed that stress-induced anxiety reduction is associated with the elevation of BDNF gene expression directly. Low corticosterone levels and a rise in carotid blood flow speed might facilitate BDNF gene expression. Meanwhile, the decrease in apparent diffusion coefficient value and decrease in N-acetyl aspartate levels, as well as an increase in the lipid peroxidation levels, in the hippocampus possibly reflected destructive changes in the hippocampus. We suggested that in Sprague–Dawley rats, these morphological alterations might be considered as an impetus for further increase in neuroplasticity in the hippocampus.

The use of vitamin D3 along with traditional therapy opens up new prospects for increasing the adaptive capacity of nerve cells to the effects of a wide range of stress factors, including hypoxia-ischemic processes. However, questions about prophylactic and therapeutic doses of vitamin D3 remain controversial. The purpose of our study was to analyze the effects of vitamin D3 at different concentrations on morpho-functional characteristics of neuron–glial networks in hypoxia modeling in vitro. We showed that a single administration of vitamin D3 at a high concentration (1 µM) in a normal state has no significant effect on the cell viability of primary neuronal cultures, however, it has a pronounced modulatory effect on the functional calcium activity of neuron–glial networks and causes destruction of the network response. Under hypoxia, the use of vitamin D3 (1 µM) leads to total cell death of primary neuronal cultures and complete negation of functional neural network activity. In contrast, application of lower concentrations of vitamin D3 (0.01 µM and 0.1 µM) caused a pronounced dose-dependent neuroprotective effect during the studied post-hypoxic period. While the use of vitamin D3 at a concentration of 0.1 µM maintained cell viability, preventive administration of 0.01 µM not only partially preserved the morphological integrity of primary neuronal cells but also maintained the functional structure and activity of neuron–glial networks in cultures. Possible molecular mechanisms of neuroprotective action of vitamin D3 can be associated with the increased expression level of transcription factor HIF-1α and maintaining the relationship between the levels of BDNF and TrkB expression in cells of primary neuronal cultures.

In this study, we consider a technological approach to obtain a high perpendicular magnetic anisotropy of the Co/Pd multilayers deposited on nanoporous TiO2 templates of different types of surface morphology. It is found that the use of templates with homogeneous and smoothed surface relief, formed on silicon wafers, ensures conservation of perpendicular anisotropy of the deposited films inherent in the continuous multilayers. Also, their magnetic hardening with doubling of the coercive field is observed. However, inhomogeneous magnetic ordering is revealed in the porous films due to the occurrence of magnetically soft regions near the pore edges and/or inside the pores. Modeling of the field dependences of magnetization and electrical resistance indicates that coherent rotation is the dominant mechanism of magnetization reversal in the porous system instead of the domain-wall motion typical of the continuous multilayers, while their magnetoresistance is determined by electron-magnon scattering, similarly to the continuous counterpart. The preservation of spin waves in the porous films indicates a high uniformity of the magnetic ordering in the fabricated porous systems due to a sufficiently regular pores array introduced into the films, despite the existence of soft-magnetic regions. The results are promising for the design and fabrication of future spintronic devices.

Lymph nodes (LNs) play a very important role in the spread of cancer cells. Moreover, it was noticed that the morphology and chemical composition of the LNs change in the course of cancer development. Therefore, finding and monitoring similarities between these characteristics of the LNs and tumor tissues are essential to improve diagnostics and therapy of this dreadful disease. In the present study, we used Raman and Fourier transform infrared (FTIR) spectroscopies to compare the chemical composition of the breast cancer tissues and LNs collected from women without (I group-4 patients) and with (II group-4 patients) recurrence. It was shown that the similarity of the chemical composition of the breast tissues and LNs is typical for the II group of the patients. The average Raman spectrum of the breast cancer tissues from the I group was not characterized by vibrations in the 800&ndash, 1000 cm&minus, 1 region originating from collagen and carbohydrates, which are typical for tumor-affected breast tissues. At the same time, this spectrum contains peaks at 1029 cm&minus, 1, corresponding to PO2&minus, from DNA, RNA and phospholipids, and 1520 cm&minus, 1, which have been observed in normal breast tissues before. It was shown that Raman bands of the average LN spectrum of the II group associated with proteins and carbohydrates are more intensive than those of the breast tissues spectrum. The intensity of the Raman spectra collected from the samples of the II group is almost three times higher compared to the I group. The vibrations of carbohydrates and amide III are much more intensive in the II group&rsquo, s case. The Raman spectra of the breast cancer tissues and LNs of the II group&rsquo, s samples do not contain bands (e.g., 1520 cm&minus, 1) found in the Raman spectra of the normal breast tissues elsewhere. FTIR spectra of the LNs of the I group&rsquo, s women showed a lower level of vibrations corresponding to functional group building nucleic acid, collagen, carbohydrates, and proteins in comparison with the breast cancer tissues. Pearson&rsquo, s correlation test showed positive and more significant interplay between the nature of the breast tissues and LN spectra obtained for the II group of patients than that in the I group&rsquo, s spectra. Moreover, principal component analysis (PCA) showed that it is possible to distinguish Raman and FTIR spectra of the breast cancer tissues and LNs collected from women without recurrence of the disease.

Cardiovascular complications are a side effect of cancer therapy, potentially through reduced blood vessel function. ONC201 (TIC10) is currently used in phase 2 clinical trials to treat high-grade gliomas. TIC10 is a phosphatidylinositol 3-kinase (PI3K)/AKT/extracellular signal-regulated kinase (ERK) inhibitor that induces apoptosis via upregulation of TNF-related apoptosis-inducing ligand, which via stimulation of FOXO and death receptor could increase eNOS upregulation. This has the potential to improve vascular function through increased NO bioavailability. Our aim was to investigate the role of TIC10 on vascular function to determine if it would affect the risk of CVD. Excised abdominal aorta from White New Zealand male rabbits were cut into rings. Vessels were incubated with TIC10 and AS1842856 (FOXO1 inhibitor) followed by cumulative doses of acetylcholine (Ach) to assess vessel function. Vessels were then processed for immunohistochemistry. Incubation of blood vessels with TIC10 resulted in enhanced vasodilatory capacity. Combination treatment with the FOXO1 inhibitor and TIC10 resulted in reduced vascular function compared to control. Immunohistochemical analysis indicated a 3-fold increase in death receptor 5 (DR5) expression in the TIC10-treated blood vessels but the addition of the FOXO1 inhibitor downregulated DR5 expression. The expression of DR4 receptor was not significantly increased in the presence of TIC10; however, addition of the FOXO1 inhibitor downregulated expression. TIC10 has the capacity to improve the function of healthy vessels when stimulated with the vasodilator Ach. This highlights its therapeutic potential not only in cancer treatment without cardiovascular side effects, but also as a possible drug to treat established CVD.

Novel functionalized (biofunctionalization followed by cisplatin immobilization) Fe

Работа посвящена микроскопическим синхротронным исследованиям морфологии, атомного и электронного строения массива пор субмикронного размера в слое SiO2 на кремнии, cформированного с использованием ионно-трековой технологии в комбинации с последующим за облучением химическим травлением. Методом исследования являлась фотоэмиссионная электронная микроскопия с использованием синхротронного излучения высокой интенсивности. Метод использовался в двух режимах. Использование химически селективной электронноймикроскопии позволило получить морфологическую информацию об изучаемом массиве пор. Рентгеноспектральный режим спектроскопии ближней тонкой структуры края синхротронного излучения рентгеновского диапазона позволил получить информацию о специфике локального окружения атомов заданного сорта от микроскопических областей нанометровых и субмикронных участков полученных микроскопических изображений. Поры имеют достаточно резкие границы, без переходного слоя. Дном пор является подложка - кристаллический кремний, покрытый естественным оксидом, толщина которого составляет величины около 2-3 нм. Облучение ионами ихимическое травление не оказывают существенного влияния на структурно-фазовые характеристики пористой матрицы оксида кремния. Не наблюдается существенного разупорядочения в кремнии, доступном на дне отдельных пор. Технологические загрязнения отсутствуют. Показана эффективность использования ионно-трековой технологии в комбинации с последующим за облучением химическим травлением для формирования массивов обособленных пор близких размеров субмикронного диапазона. Полученные результаты демонстрируют эффективность в применении метода фотоэмиссионной электронной микроскопии с использованием синхротронного излучениявысокой интенсивности для изучения с высокой точностью и в микроскопическом масштабе широкого ряда объектов композитной структурно-фазовой природы поверхности. ЛИТЕРАТУРА Sinha D., Petrov A., Fink D., Fahrner W. R., Hoppe K., and Chandra A. Tempos structures with gold nanoclusters. Radiation Effects and Defects in Solids. 2004;159(8–9): 517–533. DOI: https://doi.org/10.1080/10420150412331304187 Kaniukov E. Yu., Ustarroz J., Yakimchuk D. V., Petrova M., Terryn H., Sivakov V., Petrov A. V. Tunable nanoporous silicon oxide templates by swift heavy ion tracks technology. Nanotechnology. 2016;27(11): 115305. DOI: https://doi.org/10.1088/0957-4484/27/11/115305 Ivanou D. K., Streltsov Е. A., Fedotov A. K., Mazanik A. V., Fink D., Petrov A. Electrochemical deposition of PbSe and CdTe nanoparticles onto p-Si(100) wafers and into nanopores in SiO2/Si(100) structure. Thin Solid Films. 2005;490(2): 154–160. DOI: https://doi.org/10.1016/j.tsf.2005.04.046 Ivanova Yu. A., Ivanou D. K., Fedotov A. K., Streltsov Е. A., Demyanov S. E., Petrov A. V., Kaniukov E. Yu., Fink D. Electrochemical deposition of Ni and Cu onto monocrystalline n-Si(100) wafers and into nanopores in Si/SiO2 template J. Materials Science. 2007;42(22): 9163–9169. DOI: https://doi.org/10.1007/s10853-007-1926-x Fink D., Alegaonkar P. S., Petrov A. V., Wilhelm M., Szimkowiak P., Behar M., Sinha D., Fahrner W. R., Hoppe K., Chadderton L. T. Electrochemical deposition of Ni and Cu onto monocrystalline n-Si(100) wafers and into nanopores in Si/SiO2 template. Nucl. Instr. Meth B. 2005;236(1–4): 11–20. DOI: https://doi.org/10.1016/j.nimb.2005.03.243 Mosier-Boss P. Review of SERS substrates for chemical sensing. Nanomaterials. 2017;7(6): 142. DOI: https://doi.org/10.3390/nano7060142 Jahn M., Patze S., Hidi I. J., Knipper R., Radu A. I., Muhlig A., Yuksel S., Peksa V., Weber K., Mayerhofer T., Cialla-May D., Popp J. Plasmonic nanostructures for surface enhanced spectroscopic methods. Analyst. 2016;141(3): 756–793. DOI: https://doi.org/10.1039/c5an02057c Turishchev S. Yu., Parinova E. V., Pisliaruk A. K., Koyuda D. A., Yermukhamed D., Ming T., Ovsyannikov R., Smirnov D., Makarova A., Sivakov V. Surface deep profile synchrotron studies of mechanically modifi ed top-down silicon nanowires array using ultrasoft X-ray absorption near edge structure spectroscopy. Scientifi c Reports. 2019;9(1): 8066. DOI: https:// doi.org/10.1038/s41598-019-44555-y Liu L., Sham T. K. The effect of thermal oxidation on the luminescence properties of nanostructured silicon. Small. 2012;8(15): 2371–2380. DOI: https://doi.org/10.1002/smll.201200175 Barranco A., Yubero F., Espinos J.P., Groening P., Gonzalez-Elipe A. R. Electronic state characterization of SiOx thin fi lms prepared by evaporation. J. Appl. Phys. 2005;97(11): 113714. DOI: https://doi.org/10.1063/1.1927278 Паринова Е. В., Федотов А. К., Коюда Д. А., Федотова Ю. А., Стрельцов Е. А., Малащенок Н. В., Ovsyannikov R., Турищев С. Ю. Изучение особенностей формирования композитных структур на основе столбиков никеля в матрице диоксида кремния с помощью синхротронных XANES исследований в режиме регистрации выхода электронов или фотонов. Конденсированные среды и межфазные границы. 2019;21(1): 116–125. DOI: https://doi.org/10.17308/kcmf.2019.21/726 Kleineberg U., Haindl G., Hutten A., Reiss G., Gullikson E.M., Jones M.S., Mrowka S., Rekawa S. B., Underwood J. H. Microcharacterization of the surfaceoxidation of Py/Cu multilayers by scanning X-ray absorption spectromicroscopy. Appl. Phys. A. 2001;73(4): 515–519. DOI: https://doi.org/10.1007/s003390100801 Шмаль Г., Рудольф Д. Рентгеновская оптика и микроскопия. Пер. с англ. М.: Мир: 1987. 464 с. Polishchuk I., Bracha A. A., Bloch L., Levy D., Kozachkevich S., Etinger-Geller Y., Kauffmann Y., Burghammer M., Giacobbe C., Villanova J., Hendler G., Chang-Yu Sun, Giuffre A. J., Marcus M. A., Kundanati L., Zaslansky P., Pugno N. M., Gilbert G. P., Katsman A., Pokroy B. Coherently aligned nanoparticles within a biogenic single crystal: a biological prestressing strategy. Science. 2017;358(6368): 1294–1298. DOI: https://doi.org/10.1126/science.aaj2156 Kalegowda Y., Chan Y-L., Wei D-H., Harmer S. L. X-PEEM, XPS and ToF-SIMS characterisation of xanthate induced chalcopyrite fl otation: Effect of pulp potential. Surface Science. 2015;635: 70–77. DOI: https://doi.org/10.1016/j.susc.2014.12.012 Турищев С. Ю., Паринова Е. В., Кронаст Ф., Овсянников Р., Малащенок Н. В., Стрельцов Е. А., Иванов Д. К., Федотов А. К. Фотоэмиссионная электронная микроскопия массивов субмикронных столбиков никеля в матрице диоксида кремния. ФТТ. 2014;56(9): 1851–1860. DOI: https://doi.org/10.1134/S1063783414090297 Турищев С. Ю., Паринова Е. В., Федотова Ю. А., Мазаник А. В., Федотов А. К., Апель П. Ю. Характеризация массивов субмикронных столбиков никеля в матрице диоксида кремния микроскопическими методами. Конденсированные среды и межфазные границы. 2013;15(1): 54–58. Режим доступа: https://journals.vsu.ru/kcmf/article/view/878 Kasrai M., Lennard W. N., Brunner R. W., Bancroft G. M., Bardwell J. A., Tan K. H. Sampling depth of total electron and fl uorescence measurements in Si L- and K-edge absorption spectroscopy. Appl. Surf. Science. 1996;99(4): 303–312. DOI: https://doi.org/10.1016/0169-4332(96)00454-0 Зимкина Т. М., Фомичев В. А. Ультрамягкая рентгеновская спектроскопия. Ленинград: Изд-во ЛГУ; 1971. 132 c. Stohr J. NEXAFS Spectroscopy. Berlin: Springer, 1992. 403 p. DOI: https://doi.org/10.1007/978-3-662-02853-7 Brown F. C., Rustgi O. P., Extreme ultraviolet transmission of crystalline and amorphous silicon. Phys. Rev. Let. 1972;28(8): 497–500. DOI: https://doi.org/10.1103/PhysRevLett.28.497 Turishchev S. Yu., Terekhov V. A., Parinova E. V., Korolik O. V., Mazanik A. V., Fedotov A. K. Surface modifi cation and oxidation of Si wafers after low energy plasma treatment in hydrogen, helium and argon. Materials Science in Semiconductor Processing. 2013;16(6): 1377–1381. DOI: https://doi.org/10.1016/j.mssp.2013.04.020 Domashevskaya E. P., Terekhov V. A., Turishchev S. Yu., Khoviv D. A., Parinova E. V., Skryshevskii V. A., Gavril’chenko I. V. Peculiarities of electron-energy structure of surface layers of porous silicon formed on p-type substrates. Inorganic Materials. 2012;48(14): 1291–1297. DOI: https://doi.org/10.1134/S0020168512140063

We have systematically investigated the magnetization reversal characteristics and magnetoresistance of continuous and nanoporous [Co/Pd]

Gestational methylazoxymethanol acetate (MAM) treatment produces offspring with adult phenotype relevant to schizophrenia, including positive- and negative-like symptoms, cognitive deficits, dopaminergic dysfunction, structural and functional abnormalities. Here we show that adult rats prenatally treated with MAM at gestational day 17 display significant increase in dopamine D3 receptor (D3) mRNA expression in prefrontal cortex (PFC), hippocampus and nucleus accumbens, accompanied by increased expression of dopamine D2 receptor (D2) mRNA exclusively in the PFC. Furthermore, a significant change in the blood perfusion at the level of the circle of Willis and hippocampus, paralleled by the enlargement of lateral ventricles, was also detected by magnetic resonance imaging (MRI) techniques. Peripubertal treatment with the non-euphoric phytocannabinoid cannabidiol (30 mg/kg) from postnatal day (PND) 19 to PND 39 was able to reverse in MAM exposed rats: i) the up-regulation of the dopamine D3 receptor mRNA (only partially prevented by haloperidol 0.6 mg/kg/day); and ii) the regional blood flow changes in MAM exposed rats. Molecular modelling predicted that cannabidiol could bind preferentially to dopamine D3 receptor, where it may act as a partial agonist according to conformation of ionic-lock, which is highly conserved in GPCRs. In summary, our results demonstrate that the mRNA expression of both dopamine D2 and D3 receptors is altered in the MAM model; however only the transcript levels of D3 are affected by cannabidiol treatment, likely suggesting that this gene might not only contribute to the schizophrenia symptoms but also represent an unexplored target for the antipsychotic activity of cannabidiol.

Novel coronavirus disease (COVID-19) pandemic caused by SARS-CoV-2, for which there is no effective treatment except employing prevention strategies, has already instituted significant number of deaths. In this review, we provide a scientific view on the potential role of vitamin D in SARS-CoV-2 virus/COVID-19 disease. Vitamin D is well-known to play a significant role in maintaining the immune health of an individual. Moreover, it induces antimicrobial peptide expression that can decrease viral replication and regulate the levels of pro-inflammatory/anti-inflammatory cytokines. Therefore, supplementation of vitamin D has the potential to reduce the incidence, severity and the risk of death from pneumonia resulting from the cytokine storm of many viral infections including COVID-19. We suggest that supplementation of subjects at high risk of COVID-19 with vitamin D (1.000 to 3.000 IU) to maintain its optimum serum concentrations may be of significant benefit for both in the prevention and treatment of the COVID-19.

We have studied the interconnection between structure (grain sizes, chemical and phase composition, porosity) and some electric properties (resistivity, Hall and Seebeck coefficients, as well as power factor, concentration and mobilities of carriers) in composite ceramics (ZnO)z[(TM)xOy]1-z (TM = Fe and Co – transition metals, 0 ≤ x ≤ 3; 1 ≤ y ≤ 4, 0.5 ≤ z ≤ 10 wt%), prepared by one-step and/or two-step annealing on air of powder mixtures of ZnO and TM oxides. The structure of ceramic samples was studied by X-ray diffraction (XRD), Mossbauer (MS) and Raman (RS) spectroscopies, scanning electron microscopy (SEM), energy-dispersive X-ray (EDX) analysis and magnetometry. It was proved that phase composition of (ZnO)z[(TM)xOy]1-z ceramics depends on the type of doping agents. Addition of CoO to ZnO results in the formation of solid solutions with wurtzite structure after two-step annealing independently on Co concentration z ≤ 10 wt%. Addition of FexOy to ZnO results in the formation of the samples with three phase components after synthesis: submicron grains of wurtzute-like structure with large grains of ZnFe2O4 ferrite with spinel structure and residual oxides FexOy used as dopant in powder mixture. SEM measurements evidence that size of the wurtzite phase grains decreases from several tens of micrometers when using the one-step synthesis to a submicron level for the case of the two-step technology. Temperature dependences of electrical resistivity ρ(Т), as well as Hall and Seebeck coefficients in the undoped ZnO in th range of 6–500 K have shown a competition of the Mott and Shklovsky-Efros variable range hopping conductance (due to disordering), percolative one (due to formation of large-scaled potential relief) and a standard electron transport by C band. It was found that C band contribution to the carrier transport in ceramic samples (ZnO)z[(TM)xOy]1-z above 100 K was provided by both low and deep donor centers which have been formed in the wurtzite phase Zn1-δ(TM)δO. For example, in the TM doped samples we observed intrinsic shallow levels with ionization energies of about ΔE1 = (0.04–0.05) eV as well as extrinsic deep levels with ΔE2 = (0.24–0.37) eV. The iron doping of ZnO-based ceramic samples increased the room temperature Seebeck coefficient S(300 K) in average. In so doing, the S(300 K) dependence on electron concentration n of the studied samples (ZnO)z(FexOy)1-z approached maximal values (up to 1000 µV/K) at n = 1021 m−3. At the same time ZnO doping with Co resulted in more weak increase (up to 1.3–1.5 times) of S(300 K) values. Practically threefold growth of S(300 K) doe to Fe doping was attributed by us to the influence of particles of ferrite) formed in wurtzite matrix. The power factor P = (S2/ρ), estimated for the studied samples, evidenced that for both dopants it’s the highest values ( = 10−5 W/K·m) were approached in the (ZnO)z[(TM)xOy]1-z ceramics with the lowest resistivity values.

Magnetic nanostructures revealing the exchange bias (EB) effect have attracted much interest in recent years due to their promising applications in spintronics, magnetic sensing and recording devices with various functionalities. In this paper, we report on the perpendicular exchange bias effect in a multilayered thin film composed of [Co/Pd] ferromagnetic multilayers exchange-coupled to an antiferromagnetic IrMn. The film was deposited on a porous anodized titania template. Influences of the films’ surface morphology as well as the order of layers deposited on the EB effect were studied. The enhancements of the EB field HEB (up to 30%) and the coercive field HC (two times) were achieved in the nanoporous films relative to their continuous film counterparts, which could be attributed to the specific morphology of the porous surfaces.

Composite nanoparticles (NPs) of FeCo-Ag and FeCo-Au fabricated by the redox-transmetalation technique are characterized by transmission electron microscopy (TEM), X-ray diffractometry (XRD), Mossbauer spectroscopy and magnetometry. TEM images prove the formation of agglomerated quasi-spherical NPs with mean value of diameter about 28 nm. As indicated by XRD and Mossbauer spectroscopy composite NPs constitute cores containing Fe3+Co-based oxides with smaller contribution of bcc α-FeCo alloy and shells representing well crystallized Ag and Au. Mean value of diameters of magnetic cores (≈10 nm) and non-magnetic shells (≈18 nm) in composite NPs are estimated by complementary analysis of TEM images, broadening of XRD reflections and approximation of hysteresis curves M(H) with Langevin function.

The paper reports on the first successful fabrication of Co-graphene composites by electrochemical deposition of Co nanoparticles (NPs) on the sheets of twisted graphene. Characterization of the surface morphology and element mapping of twisted graphene decorated with Co NPs by transmission and scanning electron microscopy in combination with the energy-dispersive X-ray spectroscopy reveals the formation of isolated quasi-spherical oxidized Co NPs with the mean diameter 〈 d〉 ≈ 220 nm and core-shell structure. X-ray photoelectron spectroscopy indicates that the core of deposited NPs consists of metal Co while the shell is CoO. Composite Co-graphene samples containing core-shell NPs reveal an exchange bias field up to 160 Oe at 4 K as detected by vibrating sample magnetometry after the field cooling procedure.

For the first time, nanoporous Al2O3 templates with smoothed surface relief characterized by flattened interpore areas were used in the fabrication of Co/Pd and Co/Pt multilayers (MLs) with strong ...

This study was designed to examine an anxiety-like behavior in the adult gonadectomized (GDX) male rats subjected to testosterone propionate (TP) treatment alone or in combination with 8-OH-DPAT, a 5-HT1A receptor agonist, or with NAN-190, 5-HT1A receptor antagonist. Two weeks after gonadectomy, GDX rats were subjected by treatments with the solvent, TP (0.5mg/kg, s.c.), 8-OH-DPAT (0.05mg/kg, s.c.), NAN-190 (0.1mg/kg, i.p.), TP in combination with 8-OH-DPAT or NAN-190 during 14days. Anxiety behavior was assessed in the elevated plus maze (EPM) and the open field test (OFT). 8-OH-DPAT treatment failed to modify the anxiety-like behavior of GDX rats in the EPM as compared to the GDX rats given with oil solvent. NAN-190 injected alone or in combination with TP to GDX rats resulted in a significant anxiolytic-like effect as compared to the GDX given with oil solvent or TP application. Our data indicate that the combination of NAN-190 and TP is more effective than TP alone in GDX rats inducing a more profound anxiolytic-like effect in the EPM. Thus, the results of this study suggest that effects of 5-HT1A receptor agonist/antagonist can modify anxiety level in opposite direction in male rats after gonadectomy.

We studied the structure and magnetic properties of porous multilayered Co/Pd films deposited on the templates of anodized Al2O3 with a specific surface morphology that is characterized by a cellular–porous structure with several pores inside each cell. X-ray diffraction analysis and reflectometry are used to study the peculiarities of the formation of phases in deposited films. The effect of morphological features of porous Co/Pd films on their magnetoanisotropic properties and magnetization reversal processes (magnetization reversal mechanisms, domain structure of films, and coercive field H c ) is revealed by SQUID magnetometry and magnetic force microscopy.

We used porous nanotubular templates of TiO 2 for fabrication of Co/Pd antidot arrays with strong perpendicular magnetic anisotropy. The morphology of porous multilayers followed the features of the initial template demonstrating a pronounced relief consisting of the cells with periodic pores with small inclination. We confirmed the formation of Co 0.4 Pd 0.6 alloy at the Co/Pd interface. We observed the conservation of perpendicular magnetic anisotropy in the Co/Pd porous film with coercive field H C = 2.7 kOe, enhanced with respect to the continuous film due to the pinning of magnetic moments on the nanopore edges. From angular dependence of the coercive field H C we deduced the change of the magnetization reversal mechanism from domain wall motion in the continuous film to the predominantly coherent rotation mechanism in the porous film.

Background:Vitamin D can be one of the candidate substances that are used as additional supplementation in the treatment of anxiety-related disorders in women with estrogen imbalance.Materials and methods:The aim of the present study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg/day, s.c.) on the anxiety-like behavior and monoamines levels in the rat hippocampus following ovariectomy in female rats. Cholecalciferol was given to ovariectomized (OVX) rats and OVX rats treated with 17β-estradiol (17β-E2, 0.5 μg/rat, s.c.). The anxiety-like behavior was assessed in the elevated plus maze (EPM) and the light-dark tests (LDT), locomotor and grooming activities were assessed in the open-field test (OFT).Results:Cholecalciferol in high doses alone or in combination with 17β-E2-induced anxiolytic-like effects in OVX and OVX rats treated with 17β-E2as evidenced in the EPM and LDT tests, and increased grooming activity in the OFT test. We found that DA and 5-HT levels increased while 5-HT turnover in the hippocampus decreased in these groups of OVX rats.Conclusion:Our results indicate that cholecalciferol in high doses has a marked anxiolytic-like effect due to an increase in the monoamines levels in the experimental rat model of estrogen deficiency.