[COVID-19-associated mucormycosis in ophthalmological practice in the Volgograd region]. / COVID-19-assotsiirovannyi mukormikoz v oftal'mologicheskoi praktike Volgogradskogo regiona.

The problem of fungal infections in the era of COVID-19 has acquired special significance. This infection, directly or indirectly, through the use of glucocorticoids and antibiotics in its treatment, as well as poorer self-management of chronic diseases, has led to a wide spread of risk factors for fungal diseases among people who have had a novel coronavirus infection. The article presents two cases of COVID-19-associated mycosis, more related to mucormycosis, which were diagnosed by ophthalmologists in the Volgograd region. In the first case, the severe course of rhino-orbito-cerebral form of mucormycosis required a number of surgical interventions and prolonged treatment in the intensive care unit. In the second case, the patient asked for help without signs of aggravation of the general condition, but with irreversible local manifestations. In both cases, the eyeball was removed. Morphological examination revealed aseptal ribbon hyphae of different diameters, branching mainly at right angles, more typical for fungi of the Mucorales family. Due to the severe consequences of the disease, clinicians, including ophthalmologists, need to be especially alertness in patients with the described symptoms and risk factors in the post-COVID period.

Comparison of the Size and Properties of the Cytochrome c/Cardiolipin Nanospheres in a Sediment and Non-polar Medium.

Apoptosis, as the major type of programmed cell death, plays an important role in the organism renewal and removal of defective and transformed cells, including cancer cells. One of the earliest apoptotic events is lipid peroxidation in the inner mitochondrial membrane catalyzed by a complex of cytochrome c (CytC) with the mitochondrial phospholipid cardiolipin (CL). It was shown that mixing CytC and CL solutions results in the formation of CytC/CL complexes (Cyt-CL nanospheres) with a diameter of 11-12 nm composed of the molten globule protein molecule and a CL monolayer. Using the methods of dynamic light scattering for the Cyt-CL chloroform solution and small-angle X-ray scattering for the Cyt-CL sediment, it was found that in both cases, Cyt-CL formed nanospheres with a diameter of 8 and 11 nm, which corresponded to the earlier determined lipid/protein ratios of 13-14 and 35-50, respectively. These results showed that the Cyt-CL nanospheres can form not only during crystallization but also in a hydrophobic medium. CytC in the complex exists as a molten globule, as evidenced by the emergence of tryptophan and tyrosine fluorescence (absent in the native protein) due to the Förster resonance transfer of the electron excitation energy onto the heme. At the same time, the coordinate bond between the heme iron and the sulfur atom of methionine 80 in Cyt-CL is disrupted (the absorption band at ~700 nm disappears). Similar disruption of the iron-sulfur bond in Cyt-CL was observed in 50% methanol. These changes were reversible, which corroborates the conclusion on the CytC transition to the molten globule conformation in methanol-containing solutions.

[The rationale for the conservative treatment of chronic tonsillitis in the patients of the older age groups by the «soft¼ therapy methods]. / Obosnovanie konservativnogo lecheniya khronicheskogo tonzillita u lits starshikh vozrastnykh grupp metodami «myagkoi¼ terapii.

The objective of the present study was to develop an efficient system for the treatment of chronic tonsillitis in the patients of advanced and middle age based on the application of polyvalent bacteriophages in the combination with the physical factors and herbal medicines. The study involved 65 patients (39 women and 276 men) at the age from 65 to 73 years presenting with chronic tonsillitis. The treatment included washing the tonsillar lacunae with herbal infusion consisting of a tetterwort (Choledoniummajus) extract. This procedure was followed by phonophoresiswith the use of the combined polyvalent bacteriophage preparation in the non-liquid formulation during 7-10 days. The effectiveness of such treatment was evaluated based on the results of clinical examination and the analysis of the subjective feelings reported by the patients. In addition, the rosette-forming function of lymphocytes was estimated and palatine tonsil microbiotas in different patients were compared. The effectiveness of therapy was estimated at 89.2%. The positive outcome of the proposed treatment was documented in 78.6% of the cases within 6 months after the onset of therapy. It is concluded that the treatment of chronic tonsillitis with bacteriophagal preparations and herbal infusions in combination with thetraditionallow-frequency ultrasound treatment is highly efficacious (favourable outcome in 78.6% of the patients of middle and advanced age) without the use of antibiotic medications.

[CHARACTERISTICS OF THE RETINA IN CHRONIC STRESS IN LABORATORY RATS OF DIFFERENT AGE GROUPS].

The retina was studied in albino laboratory male rats of two age groups (12 and 24 months), 10 animals in each subjected to chronic combined stress. The stress was caused in animals by simultaneous exposure to pulsed light, loud sound, swinging and restriction of mobility for 7 days, 30 mm daily. The retina of intact rats of the corresponding age groups (n = 20) served as control. Enucleated eyes of stressed and control animals were processed with standard histological technique and stained with Nissl's method and hematoxylin-eosin. The retina of the stressed animals of both age groups showed the decrease in the number of cells and the disarrangement of its layers, most pronounced in the layers of photoreceptor neurons and ganglion cells. The comparative morphometric analysis demonstrated a reduction of the layer thickness and cell numerical density in the retina of stressed animals, both young (12 months) and old (24 months), as compared to that of control animals.

[The analysis of the influence of the adenoiditis treatment by different methods on the nasopharyngeal microbiocenosis in the children]. / Analiz vliianiia metoda lecheniia adenoidita na mikrobiotsenoz nosoglotki u deteĭ.

The objective of the present study was to analyze the quality of nasopharyngeal sanation during the treatment of the children presenting with exacerbations of chronic adenoiditis with the use of different methods. Another objective was to estimate the influence of individual methods on the indigenous microflora. The study has revealed the prevailing groups of microflora in the nasopharynx, nasal cavity, and palatine tonsils of 2.228 patients. The clinical examination and comparative analysis of the results of the bacteriological study of nasopharyngeal discharge involved 170 children at the mean age of 5.06±2.6 years presenting with exacerbations of chronic adenoiditis. The patients of group 1 (n=60, control group) underwent nasopharyngeal sanation by means of the low-frequency ultrasound treatment, those of group 2 (n=53) were given an oral antibiotics (amoxicillin/clavulanic acid) at an age-based dose during 7-10 days. The patients of group 3 (n=57) were treated with bacterial lysate OM-85 BV (Broncho-Vaxom) (a 3.5 mg capsule once daily in the morning hours under the fasting condition for 3 months (during 10 days of every month). The amount of anaerobic bacteria in the control cultures from the patients of group 1decreased six-fold and that of pneumococci by 3 times. In the children comprising group 2 all pathogenic species persisted despite the treatment whereas in group 3 the number of those species largely decreased whose lysates were contained in the medication. In the patients treated with Broncho-Vaxom the beneficial results of therapy 1 and 3 months after its onset were more apparent than in the children of two other groups. Moreover, this preparation did not affect the indigenous microflora.

[The effectiveness of topical antihistamine monotherapy in the patients presenting with the manifestations of seasonal allergic rhinitis]. / Éffektivnost' topicheskoĭ antigistaminnoĭ monoterapii pri manifestatsii sezonnogo allergicheskogo rinita.

The objective of the present study was to evaluate the effectiveness and safety of monotherapy with the use of allergoferon gel composed of topical recombinant human interferon-α-2ß and loratadine. A total of 105 patients at the age varying from 18 to 55 years presenting with the manifest form of seasonal allergic rhinitis were available for the examination. They were given the topical treatment in the recommended standard doses. The patients included in group 1 (n=65) were treated with allergoferon while those comprising group 3 (n=40) received mometasonefuorate (nasonex). Changes in the clinical symptoms were recorded on days 3, 7, 14, 21, and 28. The best results of the treatment were documented in the patients of group 1 on day 3 afterthe onset of therapy; this effect was attributed to the rapid beginning of the drug action that was apparent within15 minutes after the topical application of the medication. There were no significant difference between the manifestations of the symptoms on days 7 and 14 in the patients of both groups. None of the patients in group 1 refused to continue therapy up to day 28. Two patients in group 2 (5%) wished to discontinue the treatment due to side effects. It is concluded that the treatment with the allergoferon gel for the topical and external applications extends the possibilities for efficacious and safe therapy of the clinical manifestations of seasonal allergic rhinitis.

[IS AGE-RELATED MACULAR DEGENERATION A MANIFESTATION OF ALZHEIMER'S DISEASE?].

The review conducts clinical morphological and pathogenetic parallels between Alzheimer's disease and age-related macular degeneration. The common embryology, anatomy and physiology of the brain and eye create the preconditions for the emergence of the friendly processes, including pathological aggregation of ß-amyloid and neurodegeneration. Based upon the data the authors justify the need for a thorough ophthalmic status study in the daily practice of an ophthalmologist. According to the authors this is promising for the early diagnosis and monitoring of Alzheimer's disease.

[Beta-amyloidopathy as a manifestation of proteinopathy in age-related macular degeneration].

AIM: To investigate clinical and morphological features of amyloidogenesis in age-related macular degeneration (AMD), which is thought to be associated with proteinopathy, namely beta-amyloidopathy. MATERIAL AND METHODS: A total of 111 eyes with morphological signs of AMD as well as brain samples from 56 cadavers (aged at death 60 and over) were assessed with selective methods of amyloid detection. RESULTS: Amyloid deposits were present in 39% of eyes with dry AMD and 80% of eyes with wet AMD. Combined accumulation of amyloid (that is both in eyes and the brain) was found in 50.6% of cases. CONCLUSION: The results allow to suggest that common etiopathogenetic and morphological features of AMD and Alzheimer's disease (AD) are due to the same metabolic pathway of the transmembrane amyloid precursor protein (APP) responsible for aggregation of beta-amyloid (Aß), an abnormal fibrillar protein, and the development of beta-amyloidopathy in eyes and brains. It has been demonstrated that beta-amyloidopathy is the keynote of both AMD and AD pathogenesis leading to cytotoxicity, neurodegeneration and pathological apoptosis. Such views on the problem may promote the development of neuroprotective and ophthalmic geriatric medications effective at all stages of pathogenesis, including beta-amyloid formation and aggregation.

Experimental verification of dynamic soaring in albatrosses.

Dynamic soaring is a small-scale flight manoeuvre which is the basis for the extreme flight performance of albatrosses and other large seabirds to travel huge distances in sustained non-flapping flight. As experimental data with sufficient resolution of these small-scale movements are not available, knowledge is lacking about dynamic soaring and the physical mechanism of the energy gain of the bird from the wind. With new in-house developments of GPS logging units for recording raw phase observations and of a dedicated mathematical method for postprocessing these measurements, it was possible to determine the small-scale flight manoeuvre with the required high precision. Experimental results from tracking 16 wandering albatrosses (Diomedea exulans) in the southern Indian Ocean show the characteristic pattern of dynamic soaring. This pattern consists of four flight phases comprising a windward climb, an upper curve, a leeward descent and a lower curve, which are continually repeated. It is shown that the primary energy gain from the shear wind is attained in the upper curve where the bird changes the flight direction from windward to leeward. As a result, the upper curve is the characteristic flight phase of dynamic soaring for achieving the energy gain necessary for sustained non-flapping flight.

[Alzheimer's disease and geriatric eye diseases in the aspect of amyloid genesis].

Geriatric eye diseases (age-related macular regeneration, pseudoexfoliation syndrome, pseudoexfoliative glaucoma, senile cataract) are one of the most important problems of modern ophthalmology. Meanwhile, the treatment of these diseases continues to be primarily empirically based for lack of not only valid data on their etiology, but even consensus of opinion on their pathogenesis. This review gives the current views on the commonness of the etiopathogenetic and morphological manifestations of Alzheimer's disease and age-related eye diseases in the aspect of amyloid genesis. This approach is a promising attempt to specify the mechanisms responsible for the occurrence and development of neurodegenerative diseases, their markers, and new perspectives in their treatment.

[Interaction of mutant genes Fgf5(go-Y), we, and wal changes the duration of hair growth cycles in mice].

Mutant gene wallhaarig (wa) was acting as a modifier of the mutant gene waved alopecia (wal), substantially increasing hair loss rate in mice, as was previously shown in our laboratory. The current paper is devoted to a study of mutant gene angora- Y(Fgf5(go-Y)), which had extended anagen stage of the first and second generations hair growth cycles in triple heterozygotes (Fgf5(go-Y)/Fgf5(go-Y) we/we wal/wal). First generation guard hair in triple homozygotes had their anagen stage 4 days longer than the same stage in double homozygotes (+/+ we/we wal/wal). Hair loss started at a catagen stage in double homozygotes, while it started in triple homozygotes at the end of the same stage or even in a telogen. Such mutant gene interaction in hair follicle morphogenesis led to a partial recovery of a body hair coat in triple homozygotes.

Targeting pancreatic and ovarian carcinomas using the auristatin-based anti-CD70 antibody-drug conjugate SGN-75.

BACKGROUND: CD70 is an ideal target for antibody-based therapies because of its aberrant high expression in renal carcinomas and non-Hodgkin lymphomas and its highly restricted expression in normal tissues. The expression profiling of CD70 in carcinomas has been limited because of the lack of a CD70-specific reagent that works in formalin-fixed paraffin-embedded (FFPE) tissues. METHODS: We generated murine monoclonal antibodies (mAbs) specific for CD70 and validated their specificity by western blot analysis and developed a protocol for immunohistochemistry on FFPE tissues. CD70+ tumour cell lines were used for testing the anti-tumour activity of the anti-CD70 antibody-drug conjugate, SGN-75. RESULTS: We report novel detection of CD70 expression in multiple cancers including pancreatic (25%), larynx/pharynx (22%), melanoma (16%), ovarian (15%), lung (10%), and colon (9%). Our results show that pancreatic and ovarian tumour cell lines, which express high levels of endogenous or transfected CD70, are sensitive to the anti-tumour activity of SGN-75 in vitro and in vivo. CONCLUSION: Development of murine mAbs for robust and extensive screening of FFPE samples coupled with the detection of anti-tumour activity in novel indications provide rationale for expanding the application of SGN-75 for the treatment of multiple CD70 expressing cancers.

Insight of scent: experimental evidence of olfactory capabilities in the wandering albatross (Diomedea exulans).

Wandering albatrosses routinely forage over thousands of kilometres of open ocean, but the sensory mechanisms used in the food search itself have not been completely elucidated. Recent telemetry studies show that some spatial behaviours of the species are consistent with the 'multimodal foraging strategy' hypothesis which proposes that birds use a combination of olfactory and visual cues while foraging at sea. The 'multimodal foraging strategy' hypothesis, however, still suffers from a lack of experimental evidence, particularly regarding the olfactory capabilities of wandering albatrosses. As an initial step to test the hypothesis, we carried out behavioural experiments exploring the sensory capabilities of adult wandering albatrosses at a breeding colony. Three two-choice tests were designed to investigate the birds' response to olfactory and visual stimuli, individually or in combination. Perception of the different stimuli was assessed by comparing the amount of exploration directed towards an 'experimental' display or a 'control' display. Our results indicate that birds were able to perceive the three types of stimulus presented: olfactory, visual and combined. Moreover, olfactory and visual cues were found to have additional effects on the exploratory behaviours of males. This simple experimental demonstration of reasonable olfactory capabilities in the wandering albatross supports the 'multimodal foraging strategy' and is consistent with recent hypotheses of the evolutionary history of procellariiforms.

[The angora gene weakens the effect of interaction of the mutant genes wellhaarig and waved alopecia in mice].

The interaction of the mutant genes wellhaarig (we) and waved alopecia (wal) in mice was earlier demonstrated in our laboratory. The we gene significantly accelerates the appearance of alopecia in double we/wewal/wal homozygotes as compared to that in single +/+ wal/wal homozygotes. It has been found in this work that the mutant gene angora-Y (Fgf5(go-Y)) weakens the effect of interaction of the we and wal genes. The first signs of alopecia appear in mice of the we/wewal/wal genotype at the age of 14 days, in triple FgfS(go-Y)/Fgf5(go-Y) we/wewal/wal homozygotes alopecia is observed seven days later, i. e., in 21-day-old animals. The progression of alopecia in triple homozygotes is expressed to a lesser degree than in double +/+ we/wewal/wal homozygotes. A single dose of the Fgf5(go-Y) gene also decreases the effect of interaction of the we and wal genes, but less than a double dose of this gene. The first signs of alopecia in mice of the +/Fgf5(go-Y) we/wewal/wal genotype appear only three days later than in double +/+ we/wewal/wal homozygotes. The data obtained demonstrate that the Fgf5(go) gene is a powerful modifier of mutant genes determining the process of alopecia.

[Immunohistochemical characteristics of the spleen under the effect of various types of stressors].

The effect of different types of stressors (physical and psychoemotional) on the splenic immunoarchitecture in prepubertal Sprague-Dawley rats was evaluated using the quantitative immunohistochemical methods. Rats aged 1 month were exposed to chronic stress for 5 hours daily during 7 consecutive days. After the last stress session, animals were sacrificed, spleen was obtained for weighing and processed for routine histology and immunohistochemistry (CD3, CD8, CD90, CD20, ED1, PCNA, caspase-3) with subsequent computer image analysis. The results obtained demonstrated that the range of stress-induced immunosuppressive changes in the splenic compartments was associated with the type of stressor. Chronic exposure to purely psychological stress resulted in the decreased volume of the splenic white pulp associated mainly with the reduction of T-cell subcompartments with the decrease in their cellularity and the reduction of volume density of CD90+ and CD8+ cells in them compared to those in age-matched control animals, while the physical stressor affected both T- and B-subcompartments of the white pulp causing the reduction of lymphoid nodule volume, marginal zone width and volume density of CD20+ cells. Hypoplasia of the splenic B-zones was mainly associated with increased splenocyte apoptotic rate while that of the T-zones--with decreased proliferation rate and attenuated traffic of the recent thymic immigrants into the spleen.

[Survival of transgenic mouse embryos carrying different genetic constructs].

The survival of transgenic mouse embryos was studied as a function of the transgene structure. The data obtained indicate that the introduction of a chromosomal DNA fragment providing for the anchoring of interphase chromosomes on the nuclear envelope increases the efficiency of transgenesis in mice threefold due to their increased viability.

CD133/prominin-1 is a potential therapeutic target for antibody-drug conjugates in hepatocellular and gastric cancers.

CD133/prominin-1 is a pentaspan transmembrane glycoprotein overexpressed in various solid tumours including colorectal and glioblastomas. CD133 was found here to be highly expressed in >or=50% of pancreatic, gastric and intrahepatic cholangiocarcinomas. Quantitative flow cytometric analysis showed that a panel of established hepatocellular, pancreatic and gastric cancer cell lines expressed CD133 at levels higher than normal epithelial cells or bone marrow progenitor cells. A murine anti-human CD133 antibody (AC133) conjugated to a potent cytotoxic drug, monomethyl auristatin F (MMAF), effectively inhibited the growth of Hep3B hepatocellular and KATO III gastric cancer cells in vitro with IC(50) values of 2-7 ng ml(-1). MMAF induced apoptosis in the cancer cells as measured by caspase activation. The anti-CD133-drug conjugate (AC133-vcMMAF) was shown to internalise and colocalised with the lysosomal marker CD107a in the sensitive cell lines. In contrast, in the resistant cell line Su.86.86, the conjugate internalised and colocalised with the caveolae marker, Cav-1. Addition of ammonium chloride, an inhibitor of lysosomal trafficking and processing, suppressed the cytotoxic effect of AC133-vcMMAF in both Hep3B and KATO III. Anti-CD133-drug conjugate treatment resulted in significant delay of Hep3B tumour growth in SCID mice. Anti-CD133 antibody-drug conjugates warrant further evaluation as a therapeutic strategy to eradicate CD133+ tumours.

[Gene angora as a modifier of the mouse hairless gene].

The interactions between mouse angora-Y (Fgf5go-Y) and hairless (hr) genes have been studied. Homozygous mutant gene Fgf5go-Y increases hair length starting on day 14 after birth. We obtained mice with genotypes +/+ hr/hr F2, +/Fgf5go-Y hr/hr and Fgf5go-Y/Fgf5go-Y hr/hr. Both +/Fgf5go-Y hr/hr and +/+ hr/hr mice began to loose hair from their heads on day 14. This further extended on the whole body. On day 21 the mice were completely deprived of hair. Therefore a single dose of gene Fgf5go-Y does not affect alopecia mice homozygous for hr. However in double homozygotes Fgf5go-Y/Fgf5gO-hr/hr alopecia started 4 days later, namely on day 18. It usually finished 10-12 days after detection of first bald patches. On days 28-30 double homozygotes have lost all the hair. Hair loss in double homozygous mice was 1,5-fold slower than in +/+ hr/hr mice. This resulted from a significant extension of anagen phase induced by a mutant homozygous gene Fgf5go-Y in morphogenesis of the hair follicle. In contrast, hr gene was expressed only at the transmission phase from anagen to catagen. Our data shows that the angora gene is a modifier of the hairless gene and this results in a strong repression of alopecia progression in double homozygous mice compared to +/+ hr/hr animals.

[Gene angora enhances the effects of gene waved alopecia in mice].

Interaction between the mutant gene angora-Y (Fgf5(go-Y)) and the mutant gene waved alopecia (wal) in mice has been studied. Gene Fgf5(go-Y) in a homozygous state increases the length of hair of all types, whereas the homozygotes at wal gene display a waved hair with subsequent development of partial alopecia. Crosses between Fgf5(go-Y)/Fgf5(go-Y) and wal/wal mice gave the animals displaying the genotypes +/Fgf5(go-Y) wal/wal and Fgf5(go-Y)/Fgf5(go-Y) wal/walas well as F2 +/+ wal/wal mice. The first signs of alopecia in F2 +/+ wal/wal appear at the same time as in the mutant wal/wal BALB/c mice. This demonstrates that the genetic background has no effect on the expression of mutant gene wal. A single dose of gene Fgf5(go-Y) in +/Fgf5(go-Y) wal/wal mice causes a considerably earlier appearance of the first signs of alopecia compared with the +/+ wal/wal single homozygotes. The signs of alopecia in double homozygotes Fgf5(go-Y)/Fgf5(go-Y) wal/wal appear even earlier than in the mice +/Fgf5(go-Y) wal/wal. By the end of the first month after birth, the majority of double homozygotes have a virtually bold back with preserved scarce long hairs, guard hairs. Alopecia covers also the sides and belly. However, the head retains its hair and the regions of thinned long hairs remain on the limbs and near the tail base. The data obtained demonstrate that gene Fgf5(go-Y) is a modifier of gene wal, as it enhances considerably the effect of gene wal. This appears in an earlier development of alopecia and its more pronounced progress in the mice with genotypes +/Fgf5(go-Y) wal/wal and, particularly, Fgf5(go-Y)/Fgf5(go-Y) wal/wal.

cAMP response element-binding protein content is a molecular determinant of smooth muscle cell proliferation and migration.

We hypothesized that cAMP response element-binding protein (CREB) could function as a molecular determinant of smooth muscle cell fate. In arterial sections from the systemic and pulmonary circulation, CREB content was high in proliferation-resistant medial subpopulations of smooth muscle cells and low in proliferation-prone regions. In vessels from neonatal calves exposed to chronic hypoxia, CREB content was depleted and smooth muscle cell (SMC) proliferation was accelerated. Induction of quiescence by serum deprivation in culture led to increased CREB content. Highly proliferative SMC in culture were observed to have low CREB content. Exposure to proliferative stimuli such as hypoxia or platelet-derived growth factor decreased SMC CREB content. Assessment of CREB gene transcription by nuclear run-on analysis and transcription from a CREB promoter-luciferase construct indicate that CREB levels in SMC are in part controlled at the level of transcription. Overexpression of wild type or constitutively active CREB in primary cultures of SMC arrested cell cycle progression. Additionally, expression of constitutively active CREB decreased both proliferation and chemokinesis. Consistent with these functional properties, active CREB decreased the expression of multiple cell cycle regulatory genes, as well as genes encoding growth factors, growth factor receptors, and cytokines. Our data suggest a unique mode of cellular phenotype determination at the level of the nuclear content of CREB.