[Herbal extracts in hepatoprotection: antioxidant and immunomodulatory effects. A review].

The global market for herbal medicines is valued at $83 billion and continues to expand rapidly. Plant extracts, widely used due to their safety and minimal side effects, play a significant role in supporting liver function. The treatment of liver diseases, including hepatitis of various etiologies, alcoholic and non-alcoholic fatty liver disease, and cirrhosis, involves the use of effective hepatoprotective drugs. Plant extracts provide antioxidant and immunomodulatory pharmacological effects that contribute to the maintenance of liver function. The aim of this review was to analyze the mechanisms underlying the hepatoprotective effects of various herbal extracts included in the formulation of DIPANA®, focusing on their antioxidant and immunomodulatory properties. Additionally, the review aimed to present clinical study results supporting their efficacy in treating of various liver diseases. The analysis was based on available literature data and clinical studies on the use of DIPANA®. The reviewed herbal extracts and their combination (DIPANA®) demonstrate efficacy in experimental models of liver damage and clinical studies involving patients with liver diseases, including alcoholic and non-alcoholic steatohepatitis, drug-induced liver injury, and functional disorders of the gallbladder. This drug exhibits hepatoprotective, choleretic, relaxing effects and is well-tolerated by patients.

[The effectiveness of BIFIFORM KIDS in the prevention of the incidence of acute respiratory infections in children].

Probiotics are widely used as a means of dietary correction of the intestinal microbiota in patients not only with alimentary, but also with allergic and inflammatory diseases. They have systemic effects on the human organism. However, the diversity of the composition of probiotic complexes complicates the determination of the beneficial effects of specific microorganisms on the human body. These circumstances call for more research. Investigation of the effect of probiotic intake on the levels of various cytokines may explain the mechanisms of the beneficial effect of probiotic intake on the functioning of the immune system. Objective - to study the effectiveness of the probiotic Bifiform Kids for the prevention of respiratory infections in children with recurrent respiratory infections with gastrointestinal allergy symptoms. Material and methods. The prospective randomized controlled trial included 92 children aged from 4 to 5 years who suffers from more than 5 episodes of respiratory infections per year with gastrointestinal allergy symptoms. Patients from the main group (n=46) were prescribed 2 chewable tablets Bifiform Kids (Lactobacillus rhamnosus GG not less than 1×109 CFU, Bifidobacterium animalis spp. lactis not less than 1×109 CFU, thiamine mononitrate 0.40 mg, pyridoxine hydrochloride 0.50 mg in each) twice per day within 21 days. Patients from the control group (n=46) were prescribed no probiotics during the study period. The study included the measurement of blood serum levels of immunoglobulins A, M, G (by immunoturbodimetry) and E, as well as the concentration of cytokines IL-17, IL-10 (by enzyme immunoassay). Measurements were performed at the 1st day of the study, at the 21st day of the study, and 6 months after the study initiation. The microbiota composition was determined by sequencing the bacterial 16S rRNA genes in DNA preparations isolated from stool samples collected at the start of the study and after 21 days. The Shannon index was calculated for the species of detected bacteria to determine the diversity of the microbiome. The effectiveness of disease prevention was measured by calculating the prevention index and the efficiency coefficient based on the incidence of respiratory infections in both groups during the observation period (6 months). Results. In the main group, the volume of the commensal flora decreased 3 weeks after the study initiation: Enterobacter from 18.3±19.3 to 10.5±18.1%; Enterococcus from 8.7±16.1 to 3.1±10.0%; Clostridium from 3.1±8.1 to 0.5±2.2%. There was a statistically significant increase in the proportion of representatives of the genus Bifidobacterium by 2.2 times (from 16.9±26.4 to 36.5±31.5%, p=0.0017) and a decrease in the Shannon index from 1.1±2.1 up to 0.4±1.1 (p<0.05). In the control group, there were no statistically significant changes in the microbiota content. In the main group, after 21 days, the blood IL-10 level increased from 11.3±15.4 to 15.7±13.4 pg/ml, and the IL-17 concentration decreased from 8.9±7.7 to 6.5±7.1 pg/ml (p=<0.05) while maintaining this trend by the 6th month of observation. There were no changes in these indicators in children from the control group. The main group demonstrated a significant (р=<0.05) decrease in the level of IgE from 184±121 to 104±67 and 114±54 kU/l, and a significant increase in IgA from 0.73±0.45 to 1.33±0.65 and 1.21±0.57 g/l after 3 weeks and at the end of the probiotic intake, respectively. The level of IgA in the main group remained higher during the study compared to the control group. The main group demonstrated a 3-fold decrease in the incidence of respiratory infections in comparison with the control group. The efficiency index was 3.21, the therapeutic response was 69%. Conclusion. The results of the study show the effectiveness of the complex probiotic for the respiratory infections prevention in children with gastrointestinal allergy symptoms.

Chirped pulse propagation in a quasi-PT-symmetric medium with a broadband exceptional-point condition.

The boundary problem of dynamical Bragg diffraction of a chirped optical pulse in a dispersive quasi-PT-symmetric photonic crystal (PhC) in the Laue geometry ("on transmission") is solved by the analytical spectral method. It is shown that, in a quasi-PT-symmetric medium, in which an inhomogeneous spectral line width is much larger than the spectrum of investigated field, the exceptional-point (EP) condition is realized in a wide continuous frequency range, i.e., so-called broadband exceptional-point (BEP) condition takes place. If the Bragg condition is satisfied in a much narrower spectral range than the pulse spectrum, it leads to dramatic changes in the propagation dynamics and parameters of broadband chirped pulses in a quasi-PT-symmetric PhC. Indeed, for a positive Bragg angle of incidence in the case of diffraction in the Laue geometry, the entire spectrum of a broadband chirped pulse fulfills the BEP condition. The diffractionally reflected wave is absent in the BEP regardless of whether the Bragg condition is satisfied, and the pulse propagates as in a homogeneous conservative medium, i.e., without diffraction, gain and loss - unidirectional invisibility. When the sign of the angle of incidence changes, a unidirectional enhancement of the chirped diffracted pulse is observed in that part of it whose frequency simultaneously satisfies both the BEP condition and the Bragg condition. The rest part of the pulse, for which the Bragg condition is not satisfied, propagates as in the case of a positive angle of incidence - there is no diffracted wave. With a smooth change in the angle of incidence of the chirped pulse, a change in frequency that satisfies the Bragg condition occurs and, as a consequence, a smooth change appears in the frequency of the amplified output pulse, as well as in its duration and transverse size. It is also shown that the dispersion of the group velocity of the pulse is suppressed in the frequency range of the BEP condition. Therefore, all its frequency components propagate at a speed close to the speed of light in a conservative homogeneous medium.

[PHARMACOGENETIC ASPECTS OF TREATMENT OF PATIENTS WITH CHRONIC HEART FAILURE (REVIEW)].

This article reviews data for pharmacogenetics findings for treatment for chronic heart insufficiency of heart failure. Also, it discusses connections of genetic polymorphism with a risk of developing heart failure and how it affects the choice of a treatments medicine. The article investigates genetically determined factors of the risk of developing glycoside toxicity. One of the causes is polymorphism of the MDR1 gene encoding glycoprotein P, a transporter, that is involved in the absorption of drugs in the intestines and excretion by the kidneys. Also, the genetic characteristics of ACE in patients with heart failure are discussed. The data is presented from the study of the role of genetic liver metabolism polymorphism regarding efficacy and safety of loop diuretic torasemide. Data for genetic polymorphism of the metabolism of the main beta blocker, used in chronic heart failure metoprolosuccinate is also discussed. Data for roll ß1-AP polymorphism in the clinical use of ß-AB in patients with heart failure. Further observations are needed from longer studies, that will evaluate long-term efficacy and safety outcomes for medicines related to genetic traits.

Unidirectional invisibility and enhanced reflection of short pulses in quasi-PT-symmetric media.

We consider the interaction of a short optical pulse with a layer with periodically modulated permittivity and a periodic gain-and-loss landscape. It is found that if the medium is quasi-parity-time (PT)-symmetric in the vicinity of the exceptional point, the propagation manifests strong unidirectional reflection and invisibility. Due to strong frequency selectivity, quasi-PT-symmetric periodic layers manifest efficient filtering of back-radiation.

Thermodynamics of Sr2NiMoO6 and Sr2CoMoO6 and their stability under reducing conditions.

The values of standard enthalpy of formation at 298.15 K and 1 atm for the double perovskites Sr2NiMoO6 and Sr2CoMoO6, measured by means of drop solution calorimetry, were found to be -2418.1 ± 12.4 and -2422.9 ± 9.6 kJ mol-1, respectively. Heat capacity of Sr2NiMoO6 and Sr2CoMoO6 was measured between 2 and 370 K using relaxation and adiabatic calorimetry, and the enthalpy increments - between 373 and 1273 K using drop calorimetry. Low-temperature magnetic and higher-temperature structural phase transformations in Sr2NiMoO6 and Sr2CoMoO6 were discussed from the thermodynamic point of view. Specific heat (Cp), standard enthalpy (ΔT0H0) and standard entropy (S0) functions were derived from the experimental data for both double perovskites. The values of Cp, ΔT0H0 and S0 at 298.15 K were determined to be 202.31 ± 0.61 J mol-1 K-1, 36.12 ± 0.18 kJ mol-1 and 231.3 ± 1.6 J mol-1 K-1 for Sr2NiMoO6, and 212.66 ± 0.64 J mol-1 K-1, 38.25 ± 0.19 kJ mol-1 and 244.4 ± 1.7 J mol-1 K-1 for Sr2CoMoO6, respectively. Additionally, using the thermodynamic data available, phase diagrams with respect to T and pO2 showing stability limits and decomposition products were calculated for Sr2NiMoO6 and Sr2CoMoO6. Though the cobaltite's stability range is wider than nickelate's both in terms of T and pO2, both complex oxides were found to be stable only at reasonably high temperatures and in oxidizing conditions, and metastable at low temperatures.

High-Resolution Thermochemical Study of Phase Stability and Rapid Oxygen Incorporation in YBaCo4- xZn xO7+δ 114-Cobaltites.

The formation thermodynamics of YBaCo4- xZn xO7+δ ( x = 0, 1, and 3) oxides was determined by high-temperature oxide melt solution calorimetry. All of the studied oxides are thermodynamically metastable due to the tendency of cobalt to increase the oxidation state under oxidizing conditions as well as to significant bond valence sum mismatch for Ba and Y in 114-oxides. Complex phase evolution in YBaCo4O7+δ at 350-400 °C upon oxygen absorption was revealed using incremental precise oxygen dosing. The calorimetric results support phase changes seen during in situ X-ray diffraction structural studies and provide high-resolution measurement of the amount and energetics of oxygen absorbed by YBaCo4- xZn xO7+δ under equilibrium conditions.

Better Understanding of Phosphoinositide 3-Kinase (PI3K) Pathways in Vasculature: Towards Precision Therapy Targeting Angiogenesis and Tumor Blood Supply.

The intracellular PI3K-AKT-mTOR pathway is involved in regulation of numerous important cell processes including cell growth, differentiation, and metabolism. The PI3Kα isoform has received particular attention as a novel molecular target in gene therapy, since this isoform plays critical roles in tumor progression and tumor blood flow and angiogenesis. However, the role of PI3Kα and other class I isoforms, i.e. PI3Kß, γ, δ, in the regulation of vascular tone and regional blood flow are largely unknown. We used novel isoform-specific PI3K inhibitors and mice deficient in both PI3Kγ and PI3Kδ (Pik3cg(-/-)/Pik3cd(-/-)) to define the putative contribution of PI3K isoform(s) to arterial vasoconstriction. Wire myography was used to measure isometric contractions of isolated murine mesenteric arterial rings. Phenylephrine-dependent contractions were inhibited by the pan PI3K inhibitors wortmannin (100 nM) and LY294002 (10 µM). These vasoconstrictions were also inhibited by the PI3Kα isoform inhibitors A66 (10 µM) and PI-103 (1 µM), but not by the PI3Kß isoform inhibitor TGX 221 (100 nM). Pik3cg(-/-)/Pik3cd(-/-)-arteries showed normal vasoconstriction. We conclude that PI3Kα is an important downstream element in vasoconstrictor GPCR signaling, which contributes to arterial vasocontraction via α1-adrenergic receptors. Our results highlight a regulatory role of PI3Kα in the cardiovascular system, which widens the spectrum of gene therapy approaches targeting PI3Kα in cancer cells and tumor angiogenesis and regional blood flow.

Photoluminescence polarization in strained GaN/AlGaN core/shell nanowires.

The optical polarization properties of GaN/AlGaN core/shell nanowire (NW) heterostructures have been investigated using polarization resolved micro-photoluminescence (µ-PL) and interpreted in terms of a strain-dependent 6 × 6 k·p theoretical model. The NW heterostructures were fabricated in two steps: the Si-doped n-type c-axis GaN NW cores were grown by molecular beam epitaxy (MBE) and then epitaxially overgrown using halide vapor phase epitaxy (HVPE) to form Mg-doped AlGaN shells. The emission of the uncoated strain-free GaN NW core is found to be polarized perpendicular to the c-axis, while the GaN core compressively strained by the AlGaN shell exhibits a polarization parallel to the NW c-axis. The luminescence of the AlGaN shell is weakly polarized perpendicular to the c-axis due to the tensile axial strain in the shell.

Transient diffusion and thermal processes in a finite one-dimensional harmonic crystal.

In this paper, an instant homogeneous thermal perturbation in the periodic one-dimensional harmonic crystal is studied. The exact solution for thermal and diffusive characteristics is obtained, namely, particle velocity dispersion (kinetic temperature) and particle displacement dispersion. It is found that thermal and diffusion processes demonstrate a quasi-periodic recurrence. The recurrence interval is equal to the time it takes the sound wave to travel the half-length of the crystal. The 'thermal echo' (sharp peaks in kinetic temperature) occurs in the system with the specified periodicity. Diffusion characteristics reveal large-scale time changes with a nearly complete return to the initial state at each quasi-period. It is also shown that the spatial mean squared displacements of particles are significantly different from the ensemble mean squared displacements.

In vitro effect of Knotolan, a new lignan from Abies sibirica, on the growth of hormone-dependent breast cancer cells.

Here we present antiestrogenic effects of Knotolan, a new dietary lignan from Abies sibirica raw material. Knotolan abolished growth-stimulating effects of 17ß-estradiol on hormone-dependent MCF-7 cells.

[Episiotomy--obstetrics operation with strict indications or iatrogenic injury of the female pelvic floor].

Episiotomy is the most common operation in obstetrics, which took its place in the obstetric's practice a long ago. According to hospital protocols or doctor's habits nowadays form 9.5 to 95% of delivering woman will have episiotomy. These results are not based on difference of process or mechanism of delivery. And in that case it seems that the true is at least somewhere between both results. Unfortunately the indications about episiotomy, described in obstetrics books, are not according "evidence-based" medicine results, but only supposing positive and negative results for the pregnant woman. Current indications for performing the episiotomy, based on the lot of researches, are fetal distress syndrome, complicated vaginal delivery (instrumental, breech or occipito-posterior delivery) and scar from poor-healed old 3rd or 4th degree rupture of the perineum.

Thermal echo in a finite one-dimensional harmonic crystal.

An instant homogeneous thermal perturbation in the finite harmonic one-dimensional crystal is studied. Previously it was shown that for the same problem in the infinite crystal the kinetic temperature oscillates with decreasing amplitude described by the Bessel function of the first kind. In the present paper it is shown that in the finite crystal this behavior is observed only until a certain period of time when a sharp increase of the oscillation amplitude is realized. This phenomenon, further referred to as the thermal echo, occurs periodically, with the period proportional to the crystal length. The amplitude for each subsequent echo is lower than for the previous one. It is obtained analytically that the time-dependence of the kinetic temperature can be described by an infinite sum of the Bessel functions with multiple indices. It is also shown that the thermal echo in the thermodynamic limit is described by the Airy function.

[Unlicensed and off label usage of some drugs in obstetric practice].

Off label usage refer with prescribing of some drugs outside indications licensed by the regulatory organs of the country or is in conflict with the product information. During pregnancy there are cases, when the health of the mother is a priority and the obstetrician has no alternative, except off label using the medication. The examples, which we show, include usage of different drugs in Bulgaria with their unlicensed indications, age group, dosage and duration of the curing course. Unlicensed usage is not illegal, because of necessity to meet the special needs of the patient. Such prescribes can not be accepted as an experiment, if there are based over publications in scientific magazines or/and presented in international congresses and consensuses. That question is covered by EC Pharmaceutical Directive 89/341 EEC.

[Cognitive and emotional disorders in university students and teachers: the possibility of treatment with recognan (citicoline)]. / Kognitivnye i psikhoémotsional'nye narusheniia u uchashchikhsia i prepodavatelei vuzov: vozmozhnosti korrektsii s pomoshch'iu preparata rekognan (tsitikolin).

AIM: To study the efficacy of recognan (citicoline) in treatment of cognitive, emotional, autonomic, asthenic disorders in university students and teachers. MATERIAL AND METHODS: Fifty-eight subjects (17 men and 41 women), mean age 27.75±12.05 years, including who 42 students and 16 teachers were studied. The sample was randomized into 2 groups (29 each): the main sub-group received oral therapy with recognan for 30 days, while the daily dosage was 500 mg (5 ml). In the control group, no drug therapy was performed. Patient's state was assessed with a large battery of psychological tests and psychometric scales. The follow-up period was 30 days. All participants were examined three times (initially, in the middle of the study (day 15), in the end of the study (day 30)). RESULTS AND CONCLUSION: Asthenic state was detected in 69%, autonomic dysfunction in 82.7%, sleep disorders in 75.8% of subjects. A high level of state anxiety was revealed in 22.2%, trait anxiety in 29.8%, a high level of stress was determined in 6,9%. It is shown that the use of recognan (citicoline) has a positive effect on compensation of autonomic and asthenic disorders, improves cognitive status, corrects psycho-emotional disorders, when used as a short (2 week) and month course.

The defect structure and chemical lattice strain of the double perovskites Sr2BMoO6-δ (B = Mg, Fe).

The defect structure of B-site ordered double perovskites Sr2BMoO6-δ was analyzed. The defect structure model was proposed and successfully verified using data on oxygen nonstoichiometry of Sr2MgMoO6-δ and Sr2FeMoO6-δ. As a result, equilibrium constants of the defect reactions involved were estimated. Fe and Mo in Sr2FeMoO6-δ were found to be in the mixed oxidation state close to +2.5 and +5.5, respectively. Chemical strain of the Sr2FeMoO6-δ double perovskite lattice was studied by in situ high temperature XRD at 1100 °C depending on pO2. Parameter a of the Sr2FeMoO6-δ cubic cell was found to increase with decreasing pO2 because of lattice chemical expansion. The tetragonal polymorph of Sr2FeMoO6-δ was shown to exhibit transversal isotropy with respect to chemical expansion. It was also found that its crystal lattice expands in the ab-plane and simultaneously contracts along the c-axis when the oxygen content in the double perovskite decreases. In order to describe the degree of anisotropy of chemical strain a new phenomenological coefficient was introduced. This coefficient was shown to affect both the magnitude and change direction of an oxide cell volume caused by its reduction/oxidation. Excellent agreement between the chemical expansion along the a-axis calculated for both polymorphs of Sr2FeMoO6-δ according to the model recently developed and that measured experimentally was shown. Chemical contraction observed along the c-axis with a decreasing oxygen content in the tetragonal polymorph was also found to coincide completely with that calculated using the approach developed in the present study.

Functional transient receptor potential vanilloid 1 and transient receptor potential vanilloid 4 channels along different segments of the renal vasculature.

AIM: Transient receptor potential vanilloid 1 (TRPV1) and vanilloid 4 (TRPV4) cation channels have been recently identified to promote endothelium-dependent relaxation of mouse mesenteric arteries. However, the role of TRPV1 and TRPV4 in the renal vasculature is largely unknown. We hypothesized that TRPV1/4 plays a role in endothelium-dependent vasodilation of renal blood vessels. METHODS: We studied the distribution of functional TRPV1/4 along different segments of the renal vasculature. Mesenteric arteries were studied as control vessels. RESULTS: The TRPV1 agonist capsaicin relaxed mouse mesenteric arteries with an EC50 of 25 nm, but large mouse renal arteries or rat descending vasa recta only at >100-fold higher concentrations. The vasodilatory effect of capsaicin in the low-nanomolar concentration range was endothelium-dependent and absent in vessels of Trpv1 -/- mice. The TRPV4 agonist GSK1016790A relaxed large conducting renal arteries, mesenteric arteries and vasa recta with EC50 of 18, 63 nm and ~10 nm respectively. These effects were endothelium-dependent and inhibited by a TRPV4 antagonist, AB159908 (10 µm). Capsaicin and GSK1016790A produced vascular dilation in isolated mouse perfused kidneys with EC50 of 23 and 3 nm respectively. The capsaicin effects were largely reduced in Trpv1 -/- kidneys, and the effects of GSK1016790A were inhibited in Trpv4 -/- kidneys. CONCLUSION: Our results demonstrate that two TRPV channels have unique sites of vasoregulatory function in the kidney with functional TRPV1 having a narrow, discrete distribution in the resistance vasculature and TRPV4 having more universal, widespread distribution along different vascular segments. We suggest that TRPV1/4 channels are potent therapeutic targets for site-specific vasodilation in the kidney.

Malignant tumours of the spermatic cord with contribution of a rare case of lymphosarcoma.

A detailed survey is given to the problem of malignant tumours of the spermatic cord. The authors present their own case of lymphosarcoma of the spermatic cord. They found only three cases of lymphosarcoma of the spermatic cord in the accessible literature. In the treatment of these malignant tumours they prefer to make radical operation - hemicastration with total extirpation of the spermatic cord - followed by radiotherapy.

Enzymes and cytomorphological sperm alterations in some diseases of the male reproductive system.

In this work the alterations of some acrosomal enzymes and gamma-GT were studied in diseases of the male genital tract. Thirty-two patients with vascular diseases, seven with inflammatory diseases and twenty-four controls were investigated. In all patients the sperm morphology was studied and the following enzymes were assayed: beta-glucuronidase, beta-galactosidase, beta-glucosidase and gamma-GT. In all patients with vascular and inflammatory diseases we found severe hypokinesis and decreased number of spermatozoa. The activity of all four enzymes in both pathological groups was decreased in comparison with the controls, and this decrease was significant for all enzymes in males with vascular diseases and for beta-galactosidase and beta-glucosidase in cases with inflammatory diseases. Our data show that the decrease of spermatozoal count was accompanied by a decreased enzyme activity. The role of decreased sperm plasma enzyme activity, the decreased production of spermatozoa and quantitative changes in structure and acrosome enzyme content are discussed.