[Lichen planus, COVID-19 and depression: psychosomatic correlations]. / Krasnyi ploskii lishai, COVID-19 i depressiya: psikhosomaticheskie korrelyatsii.

The authors present a clinical case of a female patient with depression who developed lichen planus during the COVID-19 pandemic and describe the anamnesis, skin and mental status of the patient. The phenomenon of amplified itching in the clinical picture in the post-covid period in the framework of depressive cataesthetic hyperesthesia is considered. A comprehensive psychosomatic assessment of the condition and the inclusion of approaches of psychocorrection in basic dermatotropic therapy contributed to the normalization of mood, rapid and complete reduction of itching, improvement of the skin status and patient's quality of life.

Genome-wide SNP analysis clearly distinguished the Belarusian Red cattle from other European cattle breeds.

Local breeds can serve as an important source of genetic variability in domestic animal species. This study aimed to assess the genetic diversity and population structure of Belarusian Red cattle and their differentiation from other European cattle populations based on genome-wide SNP genotypes. Twenty pedigree-recorded non-closely related cows of Belarusian Red cattle were genotyped using the Illumina BovineHD BeadChip. Genotypes of 22 other European cattle breeds were included in the study for comparison. A total of 28 562 SNPs passed through the quality control checks and were selected for analysis. The Belarusian Red cattle displayed a moderate level of genetic variability (U HE  = 0.341, HO  = 0.368), and the highest heterozygote excess (U FIS  = -0.066), among the studied breeds; this reflects the contribution of multiple breeds to their formation. The principal component analysis, FST -based Neighbor-Net tree and Admixture clustering, clearly distinguished the Belarusian Red cattle from the other European cattle breeds. Moreover, the presence of ancestral genomic components of Danish Red and Brown Swiss breeds were clearly visible, which agrees with the breed's history and its recent development. Our study highlights the importance of maintaining the specific genomic components, which makes a significant contribution to the global genetic diversity in the modern population of Belarusian Red cattle, allowing us to consider them a valuable national genetic resource. Our research results will be useful for the development of conservation programs for this local cattle breed.

New Experimental Facts on the Influence of Secondary Immunodeficiency on the Morphology and Biological Activity of Colorectal Tumor.

Colorectal tumors were studied 5 months after carcinogen injection to outbred albino rats with secondary immunodeficiency by common histological and immunobiochemical methods with the use of monoclonal and polyclonal antibodies to Ki-67, Bcl-2, p53, and VEGF. Injection of carcinogen to intact animals led to the formation of adenocarcinomas with high and moderate cell differentiation in the colon, while injection of carcinogen to animals with immunodeficiency was associated with a 1.5-fold higher incidence of GRADE 2 and GRADE 3 adenocarcinomas with more aggressive morphological phenotype and appearance of distant metastases.

Correlation between LC50 for Adult Fish and Fish Embryos.

Testing for substance toxicity for living organisms is an important step in the development and adaptation of new drugs for various purposes. Analysis of the dependences between toxicological parameters of chemical substances for various test objects and physicochemical properties of these agents is a promising trend. Partition coefficient logP (logKow) was chosen as the key physicochemical parameter determining the toxicological parameters of the same substance for hydrobionts at different developmental stages. We found a correlation between decimal logarithm of the ratio of LCe50 for fish embryos to LCa50 for adult fish and logP. This dependence was found as a liner combination of equations obtained by drawing a trend line between experimental points and calculation of Pearson's correlation coefficient R.

[Protective action of fish muscle extracts against cellular senescence induced by oxidative stress]. / Zashchitnoe deistvie ékstraktov iz myshts ryb ot indutsirovannogo okislitel'nym stressom kletochnogo stareniia.

Muscle extracts of some fish species, i.e. pike (Esox lucius), sterlet (Acipenser ruthenus), pink salmon (Oncorhynchus gorbuscha) and, to a lesser extent, perch (Perca fluviatilis) and Russian sturgeon, (Acipenser gueldenstaedtii) prevent the development of premature senescence of the human embryonic fibroblasts induced by the sublethal concentration of H2O2. Muscle extracts of other fish species tested, i.e. coho salmon (Oncorhynchus kisutch) and zander (Sander lucioperca), have not demonstrated this feature. Cell proliferation increased after the action of the senescence-inhibiting muscle extracts. Possible mechanisms of the action of nature biologically active compounds that interfere with the development of stress-induced cell senescence are discussed.

Dependence between LD50 for Rodents and LC50 for Adult Fish and Fish Embryos.

We revealed empirical dependences between common logarithm of a ratio of rat oral LD50 to LCa50 for adult fish and lgP for 50 different chemicals; and common logarithm of a ratio of the oral LD50 in rodents to LCe50 for fish embryos and lgP for 30 different chemicals. The dependences were obtained by constructing a trend line between experimental points and calculation of Pearson's R correlation coefficient as a measure of regression significance. These dependences can show the influence of substance lipophilicity on its toxicity for aquatic organisms comparing to mammals.

Morphology and Immunohistochemical Phenotype of the Thymus in Secondary Immunodeficiency.

The thymus of outbred male rats 5 months after splenectomy (experimental secondary immunodeficiency) was studied by common histological and immunohistochemical methods using monoclonal and polyclonal antibodies to CD3, CD30, CD68, synaptophysin, to S100, p53, bcl-2, and Ki-67 proteins. Removal of the spleen led to acute involution of the thymic parenchyma, which was replaced by the adipose tissue and was associated with restructuring of the thymopoietic and nonthymopoietic components of the gland, changes in cellular composition and antigenic phenotype of the lobular cortical and medullary matter, and by reduction of cell proliferation.

[DIAGNOSTIC AND TREATMENT STRATEGY IN FOLLICULAR TUMOR OF THYROID GLAND].

The article is based on the treatment results of 44 patients with follicular tunor of thyroid gland. A staged morphological assessment of thyroid nodes was performed for all patients: in case of preoperative fine-needle biopsy, urgent intraoperative study and according to results of final histological research. The urgent histological study of surgical material was conducted for 44 patients with diagnosis "follicular tumor" according to fine-needle biopsy. The data of final histological study were matched with findings of intraoperative research. A micro-follicular adenoma was detected in 22 patients (50%) and 6 (13,6%) patients had this diagnosis combined with autoimmune thyroiditis. The general part of patients didn't changed in final study, but the rate of diagnosis "micro-follicular adenoma against the background of autoimmune thyroiditis" increased. Papillary carcinoma was revealed in 5 (11,4%) patients and follicular cancer had 4 (9,1%) patients detected in intraoperative study and 3 (6,8%) more patients according to data of final research. The histopathologic feature of colloid goiter was observed in 7 (15,9%) cases and a part of such patients reduced to 6,8% during final study. One of the patients (2,3%) had final diagnosis "oncocytoma". In case of thyroid nodules detection the needle biopsy should be carried out regardless to the size of nodule. The authors recommended performing the surgery with the urgent histological study in case of undetermined histological report. The following surgical strategy was specified by the results of the urgent histological report.

[LONG-TERM RESULTS OF SURGICAL TREATMENT OF PATIENTS WITH FOLLICULAR TUMORS OF THE THYROID].

The article analyzed an experience of treatment of 51 patients with follicular tumors. It was proved, that there weren't any complications and recurrences in case of typically performed operation and adequate replacement therapy in postoperative period. It was noted a good quality of life from 2 to 5 years.

[The role of lipid metabolism and antioxidant system changes in the development of retinal vein occlusion].

PURPOSE: To compare changes in lipid metabolism and antioxidant status in patients with retinal vein occlusion (RVO) with that in patients with a history of ischemic stroke and in patients with no clinical manifestations of atherosclerosis. MATERIAL AND METHODS: A total of 111 patients were enrolled in the study. Group 1 included 80 patients with RVO and grade 2-3 stage II-III essential hypertension, group 2-11 patients with grade 3 stage III essential hypertension, high cardiovascular risk and a history of ischemic stroke. The control group included 20 patients with no clinical manifestations of atherosclerosis. All patients underwent a standard ophthalmic examination, fluorescent retinal angiography, lipid metabolism and redox system assessment. RESULTS: The levels of low-density lipoproteins (LDL) and cholinesterase were higher in study groups than in controls regardless the type of RVO. A statistically proven increase in oxidized LDL (oxLDL) was found in patients with complicated hypertension and ischemic RVO. A direct correlation was determined between the level of anti-oxLDL IgG and lipid peroxidation activity (LP) (R = 0.376; p = 0.136) as well as the levels of glutathione peroxidase (GPx) (R = 0.529; p = 0.029) and GPx per gram of hemoglobin (R = 0.543; p = 0.024) in patients with branch RVO. Redox system assessment showed a decrease of thiols and an increase of LP metabolites. CONCLUSION: The results demonstrated that retinal vein occlusions develop under disorders of lipid metabolism similar to those in patients with a history of ischemic stroke. The correlation between the level of anti-oxLDL IgG and LP points to the redox system involvement in the intricate pathogenesis of RVO.

[Comparative study of pharmacokinetics of ofloxacin in a free and niosomal forms in experiments on white mice when administered per os].

AIM: To study features of pharmacokinetics of ofloxacin as a part of anion PEGylated niosomes on a basis of sorbitan monostearate (Span 60) to experimental white mice per os. MATERIALS AND METHODS: Ofloxacin was entrapped in niosomes consisting of Span 60, cholesterol, PEG 4000 and dicetylphosphate. Sizes of niosomes estimated by means of probe microscopy. Efficiency of inclusion of an antibiotic in niosomes defined after removal of free drug by a centrifugation. The analysis of the quantitative contents of ofloxacin in samples carried out a method of a high performance liquid chromatography. RESULTS: We studied the main pharmacokinetic parameters of ofloxacin when used free and niosomal forms of antibiotic to experimental white mice per os. It is shown that use of oral niosomal forms leads to decrease of maximal concentration in serum and increase of ofloxacin half-life by 7,4 times in average compared to the free form. It is determined that bioavailability of ofloxacin in the niosomal form is 154% relative to the free form of the antibiotic. CONCLUSIONS: Niosomal microcontainers are perspective technology of encapsulation and the directe transport of antibacterial preparations through biological barriers. Using of niosomal formulation of ofloxacin is able to afford to increase considerably efficiency of treatment in comparison with a free form and significantly decrease negative effects of antibiotic therapy.

[Pathogenesis of retinal vein occlusions].

Retinal vein occlusion (RVO) is a multifactorial disease and its pathogenesis is still not fully understood. Mechanical, hemodynamic, rheological, coagulation, biochemical, and immunological factors are involved. Two currently prevalent theories of RVO pathogenesis are the mechanical theory and the "coagulopathic" theory. The latter implies an imbalance between thrombogenic factors and antithrombogenic protection. According to some authors, endothelial dysfunction plays a large part in thrombosis development, neoangiogenesis, vascular remodeling, intravascular activation of platelets and leucocytes. In recent studies increasing emphasis is being placed on investigation of immune-mediated mechanisms of vein occlusions. RVO can also be associated with combined hypoxic and free radical tissue damage.

[Study on pharmacokinetics of cefuroxime by dynamics of its distribution in oral fluid of patients with sinusitis].

A method for quantitative determination of cefuroxime in mixed saliva of patients with sinusitis by using spectrophotometer Shimadzu UV-1800, combined with the IBM PC is described. The conditions of the determination were the following: λ = 266 nm, a quartz cuvette, the analysis time of 10 minutes. The method for determination of cefuroxime is characterized by high specificity, accuracy, use of small amounts of oral fluid and expressivity. The method may be recommended for the use in the clinical practice for optimizing cefuroxime therapy in patients. The pharmacokinetics of cefuroxime was investigated by the dynamics of its distribution in the oral fluid of patients with various infectious-somatic disorders.

[Characteristic of the complement system in patients with ischemic heart disease with moderate and marked hemolysis after operations with cardiopulmonary bypass].

A study of the complement system in cardiosurgical patients with moderate (40 patients) and marked (18 patients) hemolysis after coronary artery bypass grafting in conditions of cardiopulmonary bypass was carried out. Before and after operation the content of D35+-, D55+-erythrocytes and reticulocytes in blood, free hemoglobin in blood plasma, indicators of the functional state of classical, lectin and alternative pathways of complement activation as well as concentration of its terminal complex in blood serum were analyzed. It was established that development of marked hemolysis was associated with higher (compared with moderate hemolysis) content of terminal complement complex and reticulocytes in blood before operation as well as deficiency of D55+- erythrocytes and low activity of alternative pathway.

Distribution of the Vasotocin Subtype Four Receptor (VT4R) in the Anterior Pituitary Gland of the Chicken, Gallus gallus, and its Possible Role in the Avian Stress Response.

The neurohormone arginine vasotocin (AVT) in non mammalian vertebrates is homologous to arginine vasopressin (AVP) in mammals. Its actions are mediated via G protein-coupled receptors that belong to the vasotocin/mesotocin family. Because of the known regulatory effects of nonapeptide hormones on anterior pituitary functions, receptor subtypes in that family have been proposed to be located in anterior pituitary cells. Recently, an avian vasotocin receptor subtype designated VT4R has been cloned, which shares 69% sequence homology with a human vasopressin receptor, the V1aR. In the present study, a polyclonal antibody to the VT4R was developed and validated to confirm its specificity to the VT4R. The antibody was used to test the hypothesis that the VT4R is present in the avian anterior pituitary and is specifically associated with certain cell types, where its expression is modulated by acute stress. Western blotting of membrane protein extracts from pituitary tissue, the use of HeLa cells transfected with the VT4R and peptide competition assays all confirmed the specificity of the antibody to the VT4R. Dual-labelling immunofluorescence microscopy was utilised to identify pituitary cell types that contained immunoreactive VT4R. The receptor was found to be widely distributed throughout the cephalic lobe but not in the caudal lobe of the anterior pituitary. Immunoreactive VT4R was associated with corticotrophs. Approximately 89% of immunolabelled corticotrophs were shown to contain the VT4R. The immunoreactive VT4R was not found in gonadotrophs, somatotrophs or lactotrophs. To determine a possible functional role of the VT4R and previously characterised VT2R, gene expression levels in the anterior pituitary were determined after acute immobilisation stress by quantitative reverse transcriptase-polymerase chain reaction. The results showed a significant increase in plasma corticosterone levels (three- to four-fold), a significant reduction of VT4R mRNA and an increase of VT2R mRNA (P < 0.05) in acutely immobilised chicks compared to controls. The data suggest a role of the VT4R in the avian stress response.

[The application of resort factors for the treatment of gastroesophageal reflux disease].

The application of SMT-phoresis chloride-iodine-bromine brine for the treatment of gastroesophageal reflux disease (GERD) had positive influence on its clinical course and improved the motor-evacuative function of the stomach. Also, the psychoemotional conditions of the patients improved. It is concluded that SMT-phoresis of the chloride-iodine-bromine brine applied at the Uva health resort can be used either as monotherapy or included in the combined treatment of gastroesophageal reflux disease

Co-purified gelatinases alter the stability and biological activities of human plasma fibronectin preparations.

BACKGROUND AND OBJECTIVE: Fibronectin (FN) is an important cell adhesion molecule that is used widely to characterize cell behavior. Preparations of FN purified from human plasma by gelatin-Sepharose affinity chromatography typically also contain gelatin-binding gelatinases that may cleave FN, reduce its stability and alter its biological activities. Available methods for separating gelatinases from FN are resource demanding. Therefore, our objective was to devise a time- and cost-efficient protocol for purification of gelatinase-free FN. MATERIAL AND METHODS: Experiments tested the elution profiles for FN and gelatinases from gelatin-Sepharose using a concentration range (1-7%) of dimethyl sulfoxide (DMSO) and 4 m urea as eluants. Subsequently, we explored the sequential application of those eluants for differential elution of gelatinases and FN using a single affinity column. Finally, experiments characterized the stability of purified FN with or without contaminating gelatinases, as well as the effects of FN degradation on cell attachment and migration. RESULTS: Assay optimization demonstrated that pre-elution with 3% DMSO efficiently eliminated gelatinases but not FN from gelatin-Sepharose, whereas subsequent elution with 4 m urea released FN. Sequential elutions with DMSO and urea produced gelatinase-free FN, which was more stable than FN eluted by urea only. Fibronectin degradation did not affect human gingival fibroblast attachment, but increased cell migration significantly. CONCLUSION: The present experiments devised a time- and cost-efficient protocol for eliminating gelatinases during purification of human plasma FN. Gelatinase-free FN preparations had greater stability, which may be essential for experiments because FN fragments have altered biological activities compared with intact FN.

Regulation of androgen receptor transcriptional activity by rapamycin in prostate cancer cell proliferation and survival.

The mTOR (mammalian target of rapamycin) inhibitor rapamycin caused growth arrest in both androgen-dependent and androgen-independent prostate cancer cells; however, long-term treatment induced resistance to the drug. The aim of this study was to investigate methods that can overcome this resistance. Here, we show that rapamycin treatment stimulated androgen receptor (AR) transcriptional activity, whereas suppression of AR activity with the antiandrogen bicalutamide sensitized androgen-dependent, as well as AR-sensitive androgen-independent prostate cancer cells, to growth inhibition by rapamycin. Further, the combination of rapamycin and bicalutamide, but not the individual drugs, induced significant levels of apoptosis in prostate cancer cells. The net effect of rapamycin is determined by its individual effects on the mTOR complexes mTORC1 (mTOR/raptor/GbetaL) and mTORC2 (mTOR/rictor/sin1/GbetaL). Inhibition of both mTORC1 and mTORC2 by rapamycin-induced apoptosis, whereas rapamycin-stimulation of AR transcriptional activity resulted from the inhibition of mTORC1, but not mTORC2. The effect of rapamycin on AR transcriptional activity was mediated by the phosphorylation of the serine/threonine kinase Akt, which also partially mediated apoptosis induced by rapamycin and bicalutamide. These results indicate the presence of two parallel cell-survival pathways in prostate cancer cells: a strong Akt-independent, but rapamycin-sensitive pathway downstream of mTORC1, and an AR-dependent pathway downstream of mTORC2 and Akt, that is stimulated by mTORC1 inhibition. Thus, the combination of rapamycin and bicalutamide induce apoptosis in prostate cancer cells by simultaneously inhibiting both pathways and hence would be of therapeutic value in prostate cancer treatment.

A 90 kDa fragment of filamin A promotes Casodex-induced growth inhibition in Casodex-resistant androgen receptor positive C4-2 prostate cancer cells.

Prostate tumors are initially dependent on androgens for growth, but the majority of patients treated with anti-androgen therapy progress to androgen-independence characterized by resistance to such treatment. This study investigates a novel role for filamin A (FlnA), a 280 kDa cytoskeletal protein (consisting of an actin-binding domain (ABD) followed by 24 sequential repeats), in androgen-independent (AI) growth. Full-length FlnA is cleaved to 170 kDa (ABD+FlnA1-15) and 110 kDa fragments (FlnA16-24); the latter is further cleaved to a 90 kDa fragment (repeats 16-23) capable of nuclear translocation and androgen receptor (AR) binding. Here, we demonstrate that in androgen-dependent LNCaP prostate cancer cells, the cleaved 90 kDa fragment is localized to the nucleus, whereas in its AI subline C4-2, FlnA failed to cleave and remained cytoplasmic. Transfection of FlnA16-24 cDNA in C4-2 cells restored expression and nuclear localization of 90 kDa FlnA. Unlike LNCaP, C4-2 cells proliferate in androgen-reduced medium and in the presence of the AR-antagonist Casodex. They also exhibit increased Akt phosphorylation compared to LNCaP, which may contribute to their AI phenotype. Nuclear expression of 90 kDa FlnA in C4-2 cells decreased Akt phosphorylation, prevented proliferation in androgen-reduced medium and restored Casodex sensitivity. This effect was inhibited by constitutive activation of Akt indicating that FlnA restored Casodex sensitivity in C4-2 cells by decreasing Akt phosphorylation. In addition, FlnA-specific siRNA which depleted FlnA levels, but not control siRNA, induced resistance to Casodex in LNCaP cells. Our results demonstrate that expression of nuclear FlnA is necessary for androgen dependence in these cells.