Effects of Gly-His-Lys-D-Ala Peptide on Skin Wound Regeneration Processes.

We evaluated the effects of the Gly-His-Lys-D-Ala peptide in a dose 0.5 µg/kg on skin wound regeneration in male Wistar rats (n=80) after initial surgical debridement when administered intracutaneously around the site of injury. Histological (severity of the inflammatory reaction, formation of granulation tissue, and epithelialization terms) and morphometric (number of fibroblastic cells, macrophages, granulocytes, and lymphocytes) studies were performed on autopsy specimens on days 3, 7, 10, and 30 of the experiment. Daily intracutaneous injection of the peptide resulted in an increase in the number of fibroblastic cells and macrophages, as well as in a decrease in the number of granulocytes against the background of active wound contraction on day 30 of the experiment. Thus, Gly-His-Lys-D-Ala alleviated the inflammatory reaction and promoted the regenerative processes.

Reparative and Antioxidant Effects of New Analogues of Immunomodulator Thymogen in Experimental Model of Liver Damage.

We studied the reparative and antioxidant effects of Thymogen and its new structural analogues obtained by binding amino acid D-Ala to the N- or C-end of the peptide molecule in acute toxic hepatopathy. Intragastric administration of carbon tetrachloride for 5 days caused the development of fat degeneration of hepatocytes, a decrease in catalase activity, and an increase in malondialdehyde concentration. Administration of peptides suppressed oxidative peroxidation and stimulated reparative regeneration of hepatocytes; Thymogen analogues produced more pronounced hepatotropic and antioxidant effects than Thymogen. Inclusion of D-Ala enhanced the effect of Thymogen on the processes of regeneration in hepatocytes and the antioxidant effect under conditions of acute carbon tetrachloride hepatopathy. The highest efficiency was achieved when the amino acid was added to the C-end of the molecule.

[Symbolism of the white coat in the medical profession].

It has long been a tradition for doctors to dress professionally in white coats - a universal symbol of belonging to the medical profession. This tradition dates back to the time of Hippocrates, but during the XIX-XXI centuries, the symbolism of the white coat was criticized in connection with research on the spread of infections through tissue. Currently, many doctors refuse to use the oldest symbol of the profession, and the practice of medical activity is replete with new variants of the uniform of a medical worker (both in style and in color palette. However, it should be noted that the white coat symbolizes another important part of the medical education of students, the standard of professionalism and care, as well as a symbol of the trust they must earn from patients.

Two-dimensional terahertz spectroscopy as a tool for revealing nonlinear interactions in media.

Usually, the presence of multiple eigenstates (magnons and phonons) in a system makes it difficult to analyze the coupled excitation mechanism using conventional single-pulse terahertz (THz) spectroscopy. On the contrary, 2D THz spectroscopy reveals energy flows between these states, which facilitates the identification of the coupled dynamics. In this article, we provide a theoretical description of this advanced technique and an experimental demonstration of its performance in antiferromagnet CoF2. Here, 2D THz spectroscopy shows that the THz pulse induces energy transfer from the magnon mode to the Raman-active phonon mode via a nonlinear excitation pathway.

[DEVELOPMENT OF TELEMEDICINE TECHNOLOGIES: OVERVIEW OF FOREIGN PRACTICE].

The article discusses the development of telemedicine technologies. It is noted that throughout history, technological revolutions have destroyed the workforce, creating new forms and models of work, making others obsolete and leading to broader changes in society, and digital technologies have developed faster than any innovation in recent history. By the method of content analysis of thematic publications, a review of the country practice of implementing telemedicine technologies in national health systems was carried out. It is concluded that telemedicine is an excellent tool for use in the health sector, reducing inequality and providing access to medical services. Where the construction of hospital facilities can take months, telemedicine uses improvised technologies to provide and maintain remotely.

[The National Consensus statement on the management of adult patients with non-alcoholic fatty liver disease and main comorbidities].

The National Consensus was prepared with the participation of the National Medical Association for the Study of the Multimorbidity, Russian Scientific Liver Society, Russian Association of Endocrinologists, Russian Association of Gerontologists and Geriatricians, National Society for Preventive Cardiology, Professional Foundation for the Promotion of Medicine Fund PROFMEDFORUM. The aim of the multidisciplinary consensus is a detailed analysis of the course of non-alcoholic fatty liver disease (NAFLD) and the main associated conditions. The definition of NAFLD is given, its prevalence is described, methods for diagnosing its components such as steatosis, inflammation and fibrosis are described. The association of NAFLD with a number of cardio-metabolic diseases (arterial hypertension, atherosclerosis, thrombotic complications, type 2 diabetes mellitus, obesity, dyslipidemia, etc.), chronic kidney disease and the risk of developing hepatocellular cancer were analyzed. The review of non-drug methods of treatment of NAFLD and modern opportunities of pharmacotherapy are presented. The possibilities of new molecules in the treatment of NAFLD are considered: agonists of nuclear receptors, antagonists of pro-inflammatory molecules, etc. The positive properties and disadvantages of currently used drugs (vitamin E, thiazolidinediones, etc.) are described. Special attention is paid to the multi-target ursodeoxycholic acid molecule in the complex treatment of NAFLD as a multifactorial disease. Its anti-inflammatory, anti-oxidant and cytoprotective properties, the ability to reduce steatosis an independent risk factor for the development of cardiovascular pathology, reduce inflammation and hepatic fibrosis through the modulation of autophagy are considered. The ability of ursodeoxycholic acid to influence glucose and lipid homeostasis and to have an anticarcinogenic effect has been demonstrated. The Consensus statement has advanced provisions for practitioners to optimize the diagnosis and treatment of NAFLD and related common pathogenetic links of cardio-metabolic diseases.

Free-carrier generation dynamics induced by ultrashort intense terahertz pulses in silicon.

We report the results of experimental studies and numerical simulation of the dynamics of the electron-hole pairs formation in silicon under the action of a two-period terahertz pulse with a maximum electric field strength of up to 23 MV/cm. It is shown that an inhomogeneous distribution of the charge carrier concentration over the depth of the silicon sample is formed, which persists for several microseconds. This inhomogeneity is formed due to a sharp increase in the rate of filling the conduction band with free carriers in the subsurface input layer of the silicon wafer, which occurs at a field strength above 15 MV/cm.

Comparative Morphological Study of the Formation of Reparative Regenerate during Skin Wound Healing in Rats under the Effect of Drugs and Bone Marrow.

We studied the formation of the reparative regenerate of the skin wound in rats under the effect of drug products based on keratan and secretome of bone marrow mesenchymal stem cells (MSC), as well as bone marrow cells (native and exposed to laser radiation with a wavelength of 1.56 µm). Due to the biological affinity for the dermal tissue, keratan preparations being applied to the skin stimulate regeneration of the wound defect. This substance in the form of a gel is characterized by high diffusion capacity, penetrates into the deeper layers of the dermis, and promotes the growth of the granulation tissue. Application of an ointment prepared on the basis of MSC secretome promotes quick transition of the healing process from the inflammatory to the regenerative stage. Thus, bone marrow cells were successfully used for skin wound healing. The results of the use of bone marrow cells for the healing of skin wounds were successful; bone marrow exposed to laser radiation demonstrated high efficiency in promoting reparative processes.

["Ictal" Bradyarrhythmias in Patients with Drug-Resistant Epilepsy: Results of Long-Term Heart Rhythm Monitoring].

Aim      To determine the type and incidence of ictal bradyarrhythmias in patients with drug-resistant types of epilepsy by long-term electrocardiogram (ECG) monitoring.Material and methods  Subcutaneous ECG monitors programed for recording pauses >3 sec and episodes of bradycardia ≤45 bpm were implanted in 193 patients with persistent epileptic seizures without organic pathology of the myocardium. Recording was activated by the patient/family at the onset of epileptic seizure. The follow-up period was 36 months with visits to the clinic every three months.Results For 36 months of monitoring, 6494 ECG fragments were recorded. Ictal bradycardia was observed in 6.7 % of patients, including ictal asystole in 2.6 % of patients. Episodes of bradycardia and asystole during epileptic seizures were transient and developed significantly more frequently in men, patients with long duration of the disease, bilateral tonic-clonic or focal seizures with disorder of consciousness, during sleep, on the background of treatment with several antiepileptic agents, mostly from the group of potassium channel blockers.Conclusion      Bradyarrhythmias accompanying epileptic seizures are transient and reproducible from seizure to seizure. They reflect functional changes in the myocardium and do not determine the life prediction for patients with epilepsy without organic pathology of the heart.

[Premature ageing in metallurgical industry workers depending on the behavioral risks existence.]

The purpose of the study is to determine the role of behavioral risks in increasing biological age indicators. A new formula for calculating the biological age (BA) was plotted, based on the data obtained for 499 employees using the V.P.Voytenko's method. It was found, that the maximum difference between biological and chronological (CA) ages are observed in workers with the lowest level of physical activity (0,54±0,3 years). In addition, there is a maximum number of health complaints in this group. With an increase in BMI by one kg/m2, the difference between biological and chronological ages grow by 0,16 of the year. We conducted a two-factor analysis of variance in order to figure out the combined effect of behavioral risks on the BA-CA value. At the maximum level of smoking and the lowest level of physical activity, the highest difference values between BA and CA are observed.

Morphological Changes in the Large Intestine of Rats Subjected to Chronic Restraint Stress and Treated with Selank.

We studied the effects of Selank on the condition of the colon wall in Wistar male rats subjected to restraint stress. Selank was injected intraperitoneally in doses of 80, 250, and 750 µg/kg 15 min before stress exposure. In rats subjected to stress, signs of atrophy, inflammatory reaction, and changes in the number and functional activity of mast cells were observed against the background of increased corticosterone level. Selank administration led to a decrease in corticosterone levels, reduced pathomorphological manifestations of stress exposure, and accelerated adaptation. These effects were presumably realized due to multifunctional biological effects of Selank.

Second harmonic generation in the bulk of silicon induced by an electric field of a high power terahertz pulse.

The experimental findings on the second harmonic generation (SHG) in centrosymmetric crystal silicon are reported. The SHG is induced by extremely high electric field (up to 15 MV/cm) parallel to the crystal surface of a short terahertz (THz) pulse while probing by an infrared femtosecond optical pulse. The SHG under such unique conditions is reported for the first time. At the electric field amplitude above 8 MV/cm, the quadratic dependence of the SHG yield integrated over the THz pulse duration on the electric field is violated and SHG yield is not changed with a further increase of the THz field. Saturation of SHG intensity at high electric fields is explained in terms of carrier density increase due to impact ionization and destructive interference of electric-field induced and current induced nonlinear polarizations.

Structural Dynamics of the Fibrous Basis of Reparative Regenerate during Spontaneous Healing of the Skin Wound.

Structural dynamics of the fibrous basis of the reparative regenerate during spontaneous skin wound healing comprises multiple stages, it successively transforms from one organization level to another more complex level, forms a multilevel 3D structure including molecular, supramolecular, fibrillar, fiber, and tissue elements. The formed reparative regenerate is integrated with the preserved skin, together they have common fibrous basis consisting of three parts that are different in organization of fibrous structures: atypical (central), tissue organospecific (peripheral), and transitional.

Strong thermo-induced single and two-photon green luminescence in self-organized peptide microtubes.

Diphenylalanine peptide nano- and microtubes formed by self-assembly demonstrate strongly enhanced and tunable single-photon and two-photon luminescence in the visible range, which appears after heat- or laser treatment of these self-organized peptide microtubes. This process significantly extends the functionality of these microstructures and can trigger a new interest in the optical properties of structures based on short peptides.

Bioinspired peptide nanotubes: deposition technology, basic physics and nanotechnology applications.

Synthetic peptide monomers can self-assemble into PNM such as nanotubes, nanospheres, hydrogels, etc. which represent a novel class of nanomaterials. Molecular recognition processes lead to the formation of supramolecular PNM ensembles containing crystalline building blocks. Such low-dimensional highly ordered regions create a new physical situation and provide unique physical properties based on electron-hole QC phenomena. In the case of asymmetrical crystalline structure, basic physical phenomena such as linear electro-optic, piezoelectric, and nonlinear optical effects, described by tensors of the odd rank, should be explored. Some of the PNM crystalline structures permit the existence of spontaneous electrical polarization and observation of ferroelectricity. The PNM crystalline arrangement creates highly porous nanotubes when various residues are packed into structural network with specific wettability and electrochemical properties. We report in this review on a wide research of PNM intrinsic physical properties, their electronic and optical properties related to QC effect, unique SHG, piezoelectricity and ferroelectric spontaneous polarization observed in PNT due to their asymmetric structure. We also describe PNM wettability phenomenon based on their nanoporous structure and its influence on electrochemical properties in PNM. The new bottom-up large scale technology of PNT physical vapor deposition and patterning combined with found physical effects at nanoscale, developed by us, opens the avenue for emerging nanotechnology applications of PNM in novel fields of nanophotonics, nanopiezotronics and energy storage devices.

[The role of endothelial dysfunction in the pathogenesis of combined cardiopulmonary diseases].

The aim of the study was to evaluate the endothelial function in patients with coronary heart disease and an exacerbation of chronic obstructive pulmonary disease (COPD), and the role of endothelial dysfunction (ED) in the pathogenesis of reciprocal exacerbation syndrome in cases of combined cardiovascular pathology. The subjects were 366 patients with single or combined cardiovascular diseases, in whom non-invasive evaluation of the endothelial regulation of the vascular tone was performed, and serum levels of NO were measured. The study revealed the biggest number of cases with an altered endothelium-dependent vasodilatation, and the most prominent decrease in NO level in patients with CHD and COPD. All the patients were followed up during two years in order to compare clinical manifestations of single and combined cardiovascular pathology. The results show that ED may be considered a predictor of complicated clinical course of COPD in patients with CHD.

Photoluminescence studies of oligothiophene self-assembled monolayers at low excitation energy.

Photoluminescence spectroscopy studies have been performed on self-assembled monolayers (SAMs) on Au(111) of thiophene oligomers with the number of thiophen rings N=3 and N=4. Photoluminescence spectra of SAMs reveal excitonic behavior with different band resolution and temperature dependence. These differences are attributed to different SAMs structure (degree of ordering).

Frequency-domain interferometric second-harmonic spectroscopy.

We report a new spectroscopic technique to measure simultaneously the intensity and the phase of second-harmonic (SH) radiation over a broad spectral range without laser tuning. Temporally separated SH pulses from two sources, excited by the same broad-bandwidth 15-fs Ti:sapphire fundamental pulse, interfere in a spectrometer to yield frequency-domain interference fringes. We demonstrate the technique by measuring the strongly bias-dependent phase of SH radiation from a Si/SiO(2)/Cr metal-oxide-semiconductor capacitor in the spectral range of the SiE(1) critical point.

Population pharmacokinetics of sirolimus in kidney transplant patients.

OBJECTIVE: To characterize the dose-related pharmacokinetics of the immunosuppressant agent sirolimus (formerly rapamycin) in kidney transplant patients by use of two-stage and nonlinear mixed-effect model population methods. METHODS: Patients (n = 36) from three centers (Germany, the United Kingdom, and Sweden) who received steady-state oral doses of cyclosporine (ciclosporin) were assessed after single oral administration of sirolimus at doses of 3, 5, 10, and 15 mg/m2. Plasma and whole blood sirolimus samples were analyzed by a high-performance liquid chromatographic/mass spectrophotometric method. Simultaneous fitting used biexponential functions with intercept/slope or clearance/volume terms, as well as first-order absorption (ka) and a lag-time. RESULTS: The nonlinear mixed-effect model method (P-Pharm) provided a better characterization of sirolimus kinetics, especially for the absorption and distribution phases where fewer data were available per patient. Sirolimus distribution between whole blood and plasma was concentration-independent, with a mean blood/plasma ratio (coefficient of variation) of 30.9 (48.5%). Elimination was not influenced by dose, as shown by estimates of the terminal half-life of 63 hours (27.5%) and apparent oral blood clearance of 8.9 L/hr (38.2%). Sirolimus distribution parameters were influenced by body weight and surface area. Sirolimus was rapidly absorbed, as shown by the absorption lag-time of 0.27 hour (35.1%), and ka of 2.77 hr-1 (48.4%). The concomitant administration of sirolimus and cyclosporine did not reveal any pharmacokinetic interactions. CONCLUSION: This report provides an initial population pharmacokinetics of sirolimus in kidney transplant recipients receiving cyclosporine concurrently. Sirolimus blood and plasma pharmacokinetics were biexponential and linear for doses from 3 to 15 mg/m2. No pharmacokinetic interaction was found between sirolimus and cyclosporine.