[COVID-19-associated anosmia]. / COVID-19-assotsiirovannaya anosmiya.

The article is a systematic review of the literature data summarizes to date on the issue of COVID-19-associated anosmia. We mainly used full-text and abstract electronic databases (PubMed, Scopus and Web of Science). The paper discusses hypothetical mechanisms of development, clinical features, as well as methods of diagnosis and treatment of COVID-19-associated anosmia.

[Non-contact optical coherence tomography - an effective method for visualizing the exudate of the middle ear]. / Beskontaktnaya opticheskaya kogerentnaya tomografiya ­ effektivnyi metod vizualizatsii ekssudata srednego ukha.

INTRODUCTION: Otitis media with effusion (OME) accounts for 15-17% of the total number of recorded diseases of the middle ear. Surgical methods have become much more common. One of the factors affecting the tactics and effectiveness of treatment OME is the degree of viscosity of the effusion. Modern diagnostic methods do not allow to reliably identify cases of OME with high effusion viscosity. OBJECTIVE: To study the possibilities of optical coherence tomography (OCT) in the diagnosis of OME and a non-invasive study of effusion viscosity. MATERIAL AND METHODS: An analysis of the results of the examination of 29 patients who underwent surgical treatment for OME - tympanostomy. A control group of 30 patients without middle ear pathology. The study used a spectral OCT with a non-contact probe designed specifically for studies of the structural middle ear. Quantitative analysis of the results using open source ImageJ. Objectification of the degree of viscosity of the effusion was carried out by means of viscometry. A comparative analysis of the intensity of the optical signal in the external auditory canal (EAC) and in the tympanic cavity (TC) was performed, as well as a comparison of the signal from viscous and fluid effusion. RESULTS: In all patients with OME, during the OCT study, an optical signal with a higher intensity was recorded in TC than in the EAC. In all cases, in the control group in the TC, an optical signal was recorded that was identical in intensity with the signal in the EAC. When measuring the degree of viscosity of the effusion, 17 cases of OME were characterized as effusion of a low degree of viscosity, 12 cases - effusion of extreme viscosity. When comparing the average intensity of the optical signal of the OCT images of viscous and liquid effusion, a statistically significant difference was revealed, p<0.001. DISCUSSION: OCT makes it possible to detect light scattering from large scatterers - cell structures characteristic of low viscosity effusion. In addition, OCT allows you to register an optical signal from small scatterers - high molecular weight structures that are present in large quantities in viscous effusion. A correlation was found between the intensity of the optical signal in the TC and the degree of viscosity of the middle ear effusion. CONCLUSIONS: Based on OCT data, it is possible to determine the indications for surgical treatment of OME by detecting viscous exudate.

[Comparative cytological analysis of the middle ear exudate in different children's groups]. / Sravnitel'nyi tsitologicheskii analiz ekssudata srednego ukha u raznykh detskikh grupp.

The purpose: to compare the types of cytograms of exudate from the middle ear between patients with exudative otitis media (EOM) with congenital clefts of the lip/palate (CCLP) and without CCLP, determining the stages of chronic disease and the significance of surgery on the middle ear. PATIENTS AND METHODS: Two clinics was parallel conducted a cytological examination of exudate of the middle ear in children. The first group consisted of 30 patients aged 2 to 17 years with EOM without CCLP (n=54 ears). The 2nd group included 17 patients aged 1 year 4 months to 10 years with EOM with CCLP (n=34 ears). RESULTS: In the 1st group, in 61% of cases (n=33), an inflammatory-regenerative type of cytogram was detected, in 39% (n=21) - a regenerative, inflammatory type of cytogram was not detected. In the 2nd group, in 82.4% of cases (n=28), an inflammatory type of cytogram was observed, in 14.7% (n=5) - an inflammatory-regenerative type, in 2.9% (n=1 ear) - a regenerative type. CONCLUSION: With CCLP, the inflammatory nature of the cytogram of the resulting exudate from the middle ear is more common, which is characterized by signs of destruction of the mucous membrane, decay and degradation of the basal and cell membranes. Patients with CCLP often suffer from EOM. They are more likely to development of chronic purulent otitis media, including with cholesteatoma. Destructive changes in the mucous membrane of the middle ear are found in children of different ages. Taking into account the analysis of cytograms of the exudate of the middle ear with CCLP, the imposition of long-term ventilation tubes is justified.

[Overview of modern methods for the diagnosis of exudative otitis media]. / Obzor sovremennykh metodov diagnostiki ekssudativnogo srednego otita.

Modern methods for diagnosis of exudative otitis media (EOM) have great potential, however, the problem of diagnosis of EOM is still relevant. The article describes the methods of modern diagnostics that are widely used in the daily practice of an otolaryngologist. The basic principles, advantages and disadvantages of generally accepted diagnostic methods for EOM are presented. The method of optical coherence tomography (OCT) is described as a method of studying biological tissues, which is used in many fields of medicine. Information is provided on the possibilities of OCT in the diagnosis of diseases of the ENT organs and, in particular, of the middle ear. The results of studies of the tympanic cavity structures in various inflammatory conditions, the possibilities of intrasurgery use of OCT, as well as the possibilities and perspectives of introducing OCT into the practice of an otorhinolaryngologist in the diagnosis of exudative otitis media are described.

A case report of Ramsay Hunt syndrome in a patient with HIV treated by dual-wavelength photodynamic therapy.

In this paper we report on the application of dual-wavelength photodynamic therapy with a topical chlorin-based photosensitizer for treatment of Ramsay Hunt syndrome in a patient with HIV. Traditional treatment approach (combination of acyclovir and a glucocorticosteroid) failed to provide a significant outcome, while photodynamic therapy resulted in fast positive dynamics. No recurrence was observed in a 5-month-long follow-up.

Structural Features of Actin Cytoskeleton Required for Endotheliocyte Barrier Function.

Cytoplasmic actin structures are essential components of the eukaryotic cytoskeleton. According to the classic concepts, actin structures perform contractile and motor functions, ensuring the possibility of cell shape changes during cell spreading, polarization, and movement both in vitro and in vivo, from the early embryogenesis stages and throughout the life of a multicellular organism. Intracellular organization of actin structures, their biochemical composition, and dynamic properties play a key role in the realization of specific cellular and tissue functions and vary in different cell types. This paper is a review of recent studies on the organization and properties of actin structures in endotheliocytes, interaction of these structures with other cytoskeletal components and elements involved in cell adhesion, as well as their role in the functional activity of endothelial cells.

The Centrosome as the Main Integrator of Endothelial Cell Functional Activity.

The centrosome is an intracellular structure of the animal cell responsible for organization of cytoplasmic microtubules. According to modern concepts, the centrosome is a very important integral element of the living cell whose functions are not limited to its ability to polymerize microtubules. The centrosome localization in the geometric center of the interphase cell, the high concentration of various regulatory proteins in this area, the centrosome-organized radial system of microtubules for intracellular transport by motor proteins, the centrosome involvement in the perception of external signals and their transmission - all these features make this cellular structure a unique regulation and distribution center managing dynamic morphology of the animal cell. In conjunction with the tissue-specific features of the centrosome structure, this suggests the direct involvement of the centrosome in execution of cell functions. This review discusses the involvement of the centrosome in the vital activity of endothelial cells, as well as its possible participation in the implementation of barrier function, the major function of endothelium.

Femtosecond Nanostructuring of Glass with Optically Trapped Microspheres and Chemical Etching.

Laser processing with optically trapped microspheres is a promising tool for nanopatterning at subdiffraction-limited resolution in a wide range of technological and biomedical applications. In this paper, we investigate subdiffraction-limited structuring of borosilicate glass with femtosecond pulses in the near-field of optically trapped microspheres combined with chemical postprocessing. The glass surface was processed by single laser pulses at 780 nm focused by silica microspheres and then subjected to selective etching in KOH, which produced pits in the laser-affected zones (LAZs). Chemical postprocessing allowed obtaining structures with better resolution and reproducibility. We demonstrate production of reproducible pits with diameters as small as 70 nm (λ/11). Complex two-dimensional structures with 100 nm (λ/8) resolution were written on the glass surface point by point with microspheres manipulated by optical tweezers. Furthermore, the mechanism of laser modification underlying selective etching was investigated with mass spectrum analysis. We propose that the increased etching rate of laser-treated glass results from changes in its chemical composition and oxygen deficiency.

[Endothelial cell cytoskeleton reorganization during functional monolayer formation in vitro].

The endothelium lining the inner surface of blood vessels regulates vascular permeability, permitting the exchange between the blood circulating in vessels and tissue fluid, and performs thereby the barrier function. Endothelial cells cultured in vitro retain the ability to perform a barrier function that is inherent in vascular endothelial cells in vivo. Endothelial monolayer in vitro is a unique model system that allows studying the interaction of cytoskeletal and adhesive structures of endothelial cells from the earliest stages of its formation. In this paper we describe and characterize quantitatively the changes in the cytoskeleton of endothelial cells from the time of endothelial cells spreading on the glass and formation of the first contacts between neighboring cells un- til the formation of a functional confluent monolayer. The main type of intermediate filaments of endothelial cells were vimentin filaments. The location of vimentin filaments and their number did not change at different stages of the endothelial monolayer formation, they occupied more than 80% of the cells. The system of actin filaments in endothelial cells was represented by the cortical actin at the cell periphery and bundles of actin stress fibers arranged in parallel. Upon the formation of contacts with neighboring cells the number and thickness of actin filaments increased. In addition, the formation of the endothelial monolayer led to changes in microtubule network, which was evident from the increase in the number of microtubules at the cell edge. Further, at all stages of assembling the endothelial monolayer, the number of microtubules formed at the cell margin in the area of cell-cell contacts exceeded the number of microtubules in the area of the free lamellae.

Optical coherence tomography monitoring for laser surgery of laryngeal carcinoma.

BACKGROUND AND OBJECTIVES: The goal of this study is to apply a new bioimaging modality, the Optical Coherence Tomography (OCT), for intraoperative control in laser surgery of laryngeal carcinoma. STUDY DESIGN/MATERIALS AND METHODS: We studied 26 patients with laryngeal carcinoma in situ and in T(1), T(2) stage. We used an endoscopic OCT device for imaging at a wavelength of 0.83 microm with the acquisition rate of approximately 0.5 frames/s for a single (200 x 200 pixel) tomogram. All patients were operated with a surgical YAG:Nd laser at two switchable wavelengths of 1.44 microm and 1.32 microm by laryngofissure, direct microlaryngoscopy, and fibrolaryngoscopy. RESULTS: Information on structural alterations in laryngeal mucosa to the depth of 2 mm, obtained by OCT, makes it possible to precisely locate tumor borders, thus giving an opportunity to control the surgical treatment of laryngeal carcinoma. The YAG:Nd laser scalpel with wavelengths of 1.32 microm and 1.44 microm is successful in surgical procedures both in open and closed larynx due to efficient coagulation and minimization of collateral tissue damage area. Combination of the two wavelengths in the single laser unit and intraoperative OCT monitoring result is a new modality for minimally invasive larynx surgery. CONCLUSIONS: OCT is promising to become a new diagnosing method of laryngeal carcinoma and a tool for laser treatment monitoring.

Expression profiling in knockout mice: lymphotoxin versus tumor necrosis factor in the maintenance of splenic microarchitecture.

Expression profiling provides a powerful approach to define the underlying molecular mechanisms in disease. Several techniques referred collectively to as gene profiling may be also helpful in the analysis of the phenotype of mice with targeted mutations, especially if applied to distinct histological compartments, to specific cell types or to evaluate the effect of specific challenges, such as infection. Here we review several of the existing techniques applicable to genetic knockout studies, and share our experience from the study of mice with tumor necrosis factor (TNF) and lymphotoxin (LT) deficiencies, with specific emphasis on the distinction between TNF- and LT-mediated signalling pathways in vivo. Gene expression profiling analysis of TNF/LT-deficient mice supports the notion that TNF and LT, originally discovered as distinct biological activities, manifest both distinct and redundant functions in vivo.

[X-Ray upper airway changes in individuals suffering from obstructive respiratory disorders during sleep]. / Rentgenologicheskie izmeneniia verkhnikh dykhatel'nykh putei u lits, stradaiushchikh obstruktivnymi rasstroistvami dykhaniia vo vremia sna.

Obstructive respiratory disorders during sleep present an important medical and social problem. Serious dysfunctions of cardiovascular, nervous, endocrine and other vital systems of the body reduce longevity and life quality. On the other hand, load nocturnal snore and abnormal diurnal sleepiness cause great damage to family life, reduce working capacity and induce accidents. X-ray visualization of the upper airways is essential in diagnosing obstructive upper airway states and selecting patients for surgical treatment. The paper presents the authors' own experience in using various X-ray diagnostic methods in patients with chronic snore and obstructive sleep apnea-hypopnea syndrome.

Gene profiling approach in the analysis of lymphotoxin and TNF deficiencies.

Mice with combined lymphotoxin-alpha (LTalpha) and tumor necrosis factor (TNF) deficiencies show defects in the structure of peripheral lymphoid organs such as spleen, lymph nodes, and gut-associated lymphoid tissues. To identify genes associated with this defective phenotype in spleen, we applied a gene profiling approach, including subtractive cloning and gene array hybridizations, to mice with combined TNF/LT deficiency. The differentially expressed genes identified by these techniques was then evaluated by Northern blot analysis for splenic expression in knockout mice with single LTalpha or single TNF deficiency. Most of the genes detected in this analysis are directly or indirectly associated with disrupted LT and not TNF signaling.

SPLASH (PLA2IID), a novel member of phospholipase A2 family, is associated with lymphotoxin deficiency.

Lymphotoxin (LT) deficient mice have profound defects in the splenic microarchitecture associated with defective expression on certain gene products, including chemokines. By using subtraction cloning of splenic cDNA from wild-type and LT alpha or TNF/LT alpha double deficient mice we isolated a novel murine gene encoding a secretory type phospholipase A2, called SPLASH. The two major alternative transcripts of SPLASH gene are predominantly expressed in lymphoid tissues, such as spleen and lymph nodes. SPLASH maps to the distal part of chromosome 4, to which several cancer-related loci have been also mapped.

Mice with a targeted mutation in lymphotoxin-alpha exhibit enhanced tumor growth and metastasis: impaired NK cell development and recruitment.

Mice deficient in lymphotoxin (LT)-alpha lack peripheral lymph nodes and Peyer's patches and have profound defects in development of follicular dendritic cell networks, germinal center formation, and T/B cell segregation in the spleen. Although LTalpha is known to be expressed by NK cells as well as T and B lymphocytes, the requirement of LTalpha for NK cell functions is largely unknown. To address this issue, we have assessed NK cell functions in LTalpha-deficient mice by evaluating tumor models with known requirements for NK cells to control their growth and metastasis. Syngeneic B16F10 melanoma cells inoculated s.c. grew more rapidly in LTalpha-/- mice than in the wild-type littermates, and the formation of experimental pulmonary metastases was significantly enhanced in LTalpha-/- mice. Although LTalpha-/- mice exhibited almost a normal total number of NK cells in spleen, they showed an impaired recruitment of NK cells to lung and liver. Additionally, lytic NK cells were not efficiently produced from LTalpha-/- bone marrow cells in vitro in the presence of IL-2 and IL-15. These data suggest that LTalpha signaling may be involved in the maturation and recruitment of NK cells and may play an important role in antitumor surveillance.

Endoscopic applications of optical coherence tomography.

We report results of application of our endoscopic optical coherence tomography (EOCT) system in clinical experiments to image human internal organs. Based on the experience of studying more than 100 patients, we make first general conclusions on the place and capabilities of this method in diagnosing human mucous membranes. It is demonstrated that EOCT can serve for several clinical purposes such as performing directed biopsy, monitoring functional states of human body, guiding surgical and other treatments and monitoring post-operative recovery processes. We show that applications of OCT are more informative in the case of internal organs covered by epithelium separated from underlying stroma by a smooth basal membrane and therefore concentrate on the results of the EOCT study of three internal organs, namely of larynx, bladder, and uterine cervix. Finally, we report first examination of internal organs in abdomen with the use of laparoscopic OCT.

In vivo endoscopic OCT imaging of precancer and cancer states of human mucosa.

First results of endoscopic applications of optical coherence tomography for in vivo studies of human mucosa in respiratory, gastrointestinal, urinary and genital tracts are presented. A novel endoscopic OCT (EOCT) system has been created that is based on the integration of a sampling arm of an all-optical-fiber interferometer into standard endoscopic devices using their biopsy channel to transmit low-coherence radiation to investigated tissue. We have studied mucous membranes of esophagus, larynx, stomach, urinary bladder, uterine cervix and body as typical localization for carcinomatous processes. Images of tumor tissues versus healthy tissues have been recorded and analyzed. Violations of well-defined stratified healthy mucosa structure in cancered tissue are distinctly seen by EOCT, thus making this technique promising for early diagnosis of tumors and precise guiding of excisional biopsy.

Interferon-gamma enhances tumor necrosis factor-alpha production by inhibiting early phase interleukin-10 transcription.

The ability of cytokine synthesis inhibitory factor or interleukin-10 (IL-10) and interferon-gamma (IFN-gamma) to modulate the production of tumor necrosis factor (TNF-alpha) induced by lipopolysaccharide (LPS) was examined in mouse bone marrow-derived macrophages (BMDM). IFN-gamma profoundly enhances LPS-stimulated TNF-alpha production, whereas IL-10 is markedly inhibitory, demonstrating the opposing effects of IFN-gamma and IL-10 on BMDM. Early neutralization of endogenously produced, LPS-stimulated IL-10 markedly enhanced short term TNF-alpha production, an effect further amplified by the absence of IFN-gamma priming. The regulatory effects of IFN-gamma and IL-10 apparently occurred at the translational (or post-translational) level, with TNF-alpha mRNA steady-state levels remaining unchanged. Furthermore, IFN-gamma exerts its enhancing effect on TNF synthesis by the transcriptional inhibition of IL-10. This in vitro finding was also confirmed in vivo. In the absence of LPS, IFN-gamma was not capable of inducing TNF-alpha production in BMDM, indicating that LPS or other signals are necessary for transcriptional activation. Reduced but significant TNF-alpha production in LPS-injected IFN-gamma receptor -/- mice suggests that IFN-gamma is not an absolute requirement and that other cytokines or cell types contribute in a secondary fashion to the priming of LPS-induced TNF-alpha production in vivo.

Correction or transfer of immunodeficiency due to TNF-LT alpha deletion by bone marrow transplantation.

BACKGROUND: Mice with inactivated tumor necrosis factor (TNF) and lymphotoxin alpha (LT alpha) genes have profound abnormalities of the immune system including lymphocytosis, lack of lymph nodes, undifferentiated spleen, hypoimmunoglobulinaemia, and defective Ig class switch. Here, we asked whether this phenotype is due to incompetent lymphohemopoietic progenitors or to a defective environment. MATERIALS AND METHODS: Lethally irradiated TNF-LT alpha-deficient and wild-type mice received bone marrow cells from either TNF-LT alpha-deficient or wild-type mice. The reconstitution and transfer of the phenotype was followed by morphological and functional analyses. RESULTS: Bone marrow cells from wild-type mice restored the synthesis of TNF and LT alpha, corrected the splenic microarchitecture, normalized the lymphocyte counts in the circulation, and repopulated the lamina propria with IgA-producing plasma cells of TNF-LT alpha-deficient mice. Furthermore, the formation of germinal centers in the spleen and the defective Ig class switch in response to a T-cell dependent antigen was corrected, while no lymph nodes were formed. Conversely, the TNF-LT alpha phenotype could be transferred to wild-type mice by bone marrow transplantation after lethal irradiation. CONCLUSIONS: These data demonstrate that most TNF- and LT alpha-producing cells are bone marrow derived and radiosensitive, and that the immunodeficiency due to TNF-LT alpha deletion can be corrected to a large extent by normal bone marrow cell transplantation. The genotype of the donor bone marrow cells determines the functional and structural phenotype of the TNF-LT alpha-deficient adult murine host, with the exception of lymph node formation. These findings may have therapeutic implications for the restoration of genetically defined immunodeficiencies in humans.

Role of interferon-gamma in interleukin 12-induced pathology in mice.

Interleukin 12 (IL-12) activates natural killer (NK) and T cells with the secondary synthesis and release of interferon-gamma (IFN-gamma) and other cytokines. IL-12-induced organ alterations are reported for mice and the pathogenetic role of IFN-gamma is investigated by the use of mice deficient in the IFN-gamma receptor (IFN-gamma R-/-). IL-12 caused a rapid infiltration of liver and splenic red pulp with activated macrophages; this and increased NK cells resulted in a fivefold increase of splenic weight in wild-type mice. Splenomegaly was associated with myelosuppression and decreasing peripheral leukocyte counts. IL-12-induced changes in wild-type mice were associated with markedly increased IFN-gamma serum levels and up-regulation of major histocompatibility complex (MHC) class I and II expression in various epithelia. IL-12 induced a qualitatively similar macrophage infiltration in IFN-gamma R-/- mice, less marked splenomegaly (to 2 x normal), and no MHC upregulation. Strikingly increased vascular endothelial intercellular adhesion molecule-1 expression was apparent in both IFN-gamma R-/- and IFN-gamma R+/+ mice. Restricted to mutant mice was a severe, invariably lethal, interstitial, and perivascular pulmonary macrophage infiltration with diffuse pulmonary edema. Extensive quantitative reverse transcriptase polymerase chain reaction analysis revealed an increase of only IL-6 and IL-10 pulmonary gene transcripts in IFN-gamma R-/- mice compared with wild-type mice. IL-12-induced myelosuppression is due to IFN-gamma-release from NK cells and T cells, and is associated with macrophage activation and distinct MHC class I and II antigen upregulation. The pulmonary pathology in IFN-gamma R-/- mice, however, reveals a toxic potential for IL-12 and suggests that endogenous IFN-gamma plays a protective role in preventing fatal pulmonary disease in these mice.