[Modern capabilities in diagnosis and treatment of neurotrophic keratopathy]. / Sovremennye vozmozhnosti diagnostiki i lecheniya neirotroficheskoi keratopatii.

In recent years, the problem of diagnosing and treating neurotrophic keratopathy (NK) has become relevant in view of its prevalence reaching 1.6-11.0 per 10000 people. While previously it was associated only with neuroparalytic keratitis, at present the violation of sensitive and trophic innervation of the cornea with the development of characteristic keratopathy is observed in many diseases and injuries of the organ of vision. Diagnosis of NK is based on anamnestic information and assessment of clinical and functional parameters: determination of the stability of the tear film, tear production and assessment of staining of the ocular surface with vital dyes. The main role in the diagnosis of NK belongs to corneal sensitivity determined with the Cochet-Bonnet esthesiometer. Treatment of NK is designed to restore or increase corneal sensitivity and involves tear replacement therapy, instillations of preparations derived from patient's own blood, anti-inflammatory, metabolic and antibacterial therapy. However, instillations of human erve growth factor (NGF) - the drug Cenegermin (registered in Europe in 2017 at a dose of 20 µg/ml under the name Oxervate), a recombinant form of human rhNGF from Escherichia coli bacteria - exhibit the highest pathogenetic orientation. Its «target¼ is the affected nerve fibers (specific receptors for their growth factor), which makes it possible to eliminate the violation of reparative processes in neural and epithelial cells. A high and long-term clinical efficacy of a course of six (with an interval of 2 hours) instillations of the drug for 8 weeks in the treatment of children and adults with NK has been established. Among the pathogenetically justified methods of surgical treatment, there is the so-called surgical neurotization of the cornea involving the contralateral supraorbital, supratrochlear, great auricular and other nerves, which has a long-term clinical effect.

[Influence of the DAT gene knockout on exchange of essential and toxic trace elements in rats].

The maintenance of energy homeostasis of the body according to modern data is carried out with the active participation of dopaminergic neurons of the central nervous system. The synthesis and metabolism of dopamine (DA) occurs both in the brain and in peripheral tissues. Violation of the synthesis and metabolism of DA is considered as a link in the vicious cycle which it formed during the development of diet-induced obesity. According to modern data, a number of essential and toxic trace elements, such as Cd, Al, As, Mn, Fe, Cu, Zn, are actively involved in the exchange of DA in the brain and peripheral organs and tissues. One way to assess this relationship is to compare changes in the microelement status of the organism when consuming hypercaloric diets in animals with normal and impaired DA transport. The latter can be animals with a knockout of the DAT transporter gene, which performs DA reabsorption with subsequent storage in the composition of secretory granules. The aim is a comparative study of the content of a number of essential and toxic elements in the brain, liver, and kidneys of rats that differ in the allelic variants of the DAT gene fed balanced diet and the diet with an excess of energy value. Material and methods. The study was carried out on 30 male rats of the DAT-KO knockout line (homozygotes DAT-/- and heterozygotes DAT+/-), 8-10 weeks old, and 13 males rats of the outbred Wistar line (DAT+/+) of the same age. For 62 days the animals (6 groups) received a semi-synthetic diet containing essential elements in the salt mixture or a similar high-fat-highcarbohydrate diet (HFCD) with 30% fat and 20% fructose solution instead of drinking water. The content of 16 trace elements (Fe, Mg, Cu, Mn, Co, Se, Zn, Cr, V, Cs, Ag, Al, Cd, As, Pb, Ni) were determined by inductively coupled plasma mass spectrometry in the liver, kidneys, and brain of rats with a knockout of the dopamine DAT transporter gene: homozygotes (DAT -/-) and heterozygotes (DAT+/-), as well as wild-type rats (DAT+/+) of the Wistar strain. Results and discussion. In the liver, DAT knockout led to an increase in the content of As, Cd, Co, and Cs and a decrease in Fe; in the kidneys - to an increase in the levels of Pb, As, Cd and Se, in the brain - an increase in the content of most of the studied trace elements, including Pb, As, Cs, Al and Cu. Conclusion. Against the background of consumption of HFCD, the effect of DAT knockout on the content of a number of elements was more pronounced compared with the consumption of the control diet. The revealed changes in the trace element content in DAT knockout rats are considered in terms of the effect of DA metabolism in the central nervous system and in peripheral tissues on the status of trace elements.

rs2072580T>A Polymorphism in the Overlapping Promoter Regions of the SART3 and ISCU Genes Associated with the Risk of Breast Cancer.

We analyzed association of potentially regulatory polymorphisms (rs590352, rs11542583, rs3829202, rs207258, and rs4796672) with breast cancer. A significant association was found between this disease and rs2072580T>A (p=0.001) located in the overlapping promoter regions of the SART3 and ISCU genes. In women with AA and AT genotypes, the risk of breast cancer is higher by 6.7 times (p=0.001) and 12 times (p=0.001), respectively, in comparison with TT genotype. Under a codominant model of inheritance (AT vs AA+TT), the risk of breast cancer was increased by 4.2 times (р=0.001) for the AT genotype. Under a recessive model of inheritance (TT vs AA+TT), the risk of disease was 10-fold higher (р=0.001) for the TT genotype. It has been demonstrated that the T>A substitution affects the binding properties of transcription factors CREB1 and REST.

Putative Trace-Amine Associated Receptor 5 (TAAR5) Agonist α-NETA Increases Electrocorticogram Gamma-Rhythm in Freely Moving Rats.

Cortical gamma rhythm is involved in transmission of information (communication) between brain areas that are believed to be involved in the pathogenesis of cognitive dysfunctions. Trace amines represent a group of endogenous biogenic amines that are known to be involved in modulation of function of classical monoamines, such as dopamine. To evaluate potential modulatory influence of a specific receptor for trace amines Trace Amine-Associated Receptor 5 (TAAR5) on the dopamine system, we used HPLC measurements of dopamine and its metabolites in the mouse striatum following administration of the putative TAAR5 agonist α-NETA. Administration of α-NETA caused significant modulation of dopaminergic system as evidenced by an altered dopamine turnover rate in the striatum. Then, to evaluate potential modulatory influence of TAAR5 on the rat brain gamma rhythm, we investigated the changes of electrocorticogram (ECoG) spectral power in the gamma-frequency range (40-50 Hz) following administration of the putative TAAR5 agonist α-NETA. In addition, we analyzed the changes of spatial synchronization of gamma oscillations of rat ECoG by multichannel recording. Significant complex changes were observed in the ECoG spectrum, including an increase in the spectral power in the ranges of delta (1 Hz), theta (7 Hz), and gamma rhythms (40-50 Hz) after the introduction of α-NETA. Furthermore, a decrease in the spatial synchronization of gamma oscillations of 40-50 Hz and its increase for theta oscillations of 7 Hz were detected after the introduction of α-NETA. In conclusion, putative TAAR5 agonist α-NETA can modulate striatal dopamine transmission and cause significant alterations of gamma rhythm of brain activity in a manner consistent with schizophrenia-related deficits described in humans and experimental animals. These observations suggest a role of TAAR5 in the modulation of cognitive functions affected in brain pathologies.

[Recognizing rare cardiac diseases by electrocardiogram]. / Seltene Herzerkrankungen am Elektrokardiogramm erkennen.

A number of rare cardiac diseases can be recognized by electrocardiogram (ECG). This article illustrates the clinical importance of ECG as a key diagnostic tool to detect Wolff-Parkinson-White syndrome and channelopathies, which are frequently diagnosed late after one or more affected family members have become victims of sudden cardiac death. These channelopathies include long QT syndrome, short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. In addition, typical ECG findings are frequently present in patients with idiopathic ventricular tachycardia, arrhythmogenic right ventricular dysplasia, digitalis intoxication, hyperkalemia, acute cor pulmonale due to pulmonary embolism, as well as severe left ventricular hypertrophy as in hypertrophic cardiomyopathy.

[Acute myocardial infarction in elderly and senile patients: epidemiology study according to the who program "registry of acute myocardial infarction].

The article presents results of the epidemiology study of acute myocardial infarction (AMI) among permanent Tomsk residents older than 60 years. The study was conducted in 2008-2009 according to the WHO program «Registry of Acute Myocardial Infarction¼. Data demonstrated that morbidity and mortality from AMI was higher in the above mentioned age group than in younger population. Rates of morbidity and mortality in men exceeded those in women in all age groups except population older than 80 years. The study showed high in-hospital lethality caused by high death rates in patients 60 years of age and older who were treated in non-specialized hospitals. Authors conclude that the severity of epidemiology situation with AMI is determined by the frequency of this pathology in population older than 60 years suggesting the necessity of change in the strategy of system development of medical care for AMI patients with focus on the older age groups.

Comparative morphometry of the bone structure in the dentoalveolar segments of maxillary incisors and canines.

We examined morphometric parameters of the bone tissue of 168 dentoalveolar segments that include maxillary incisors and canines regarding vertical midline. The area of dentoalveolar medial incisor segments was 1.81±0.14 cm(2); it did not differ significantly from the area of lateral incisor segments. The area of dentoalveolar segments including canines exceeded the corresponding figures in incisor segments. The thickness of the compact bone on the vestibular surface significantly increased from the cervical portion of the segment towards its base. The maximum thickness of the spongy bone on the vestibular surface was recorded in the apical part of canines dentition segments; the minimum thickness, in the middle portion of the dentoalveolar segments of lateral incisors.

[New method of conduction anesthesia in the maxilla].

There was the research aimed at improving the effeciency of intraosseous anesthesia in the maxilla by blocking the infraorbital nerve conduction along its entire length. In the experimental part of the needle puncture defined place and character of the spreading of contrast medium into the upper jaw. In the clinical part of the study shows the advantages of the proposed method of intraosseous anesthesia.

Lipid profile characterization of wastewaters from different origins.

Lipids in wastewaters are potential raw material for renewable diesel, but may complicate biological treatment of wastewaters. The lipid composition of palm oil mill effluent (POME), chemithermomechanical pulp mill (CTMP) wastewater and municipal wastewater (MWW) was studied with a combination of thin-layer chromatography and nuclear magnetic resonance. Gravimetrically determined content of extracted lipids from the solids of POME and CTMP wastewater were 8.4 ± 1.2 g/L (19.6 ± 0.8% of dry weight) and 0.17-0.23 g/L (12.4-18.5%), respectively, while MWW contained 0.021 ± 0.002 g/L (9.3 ± 1.4%) of lipids. All lipid extracts contained mono-, di- and triacylglycerols (TAGs) and free fatty acids (FFAs). In POME, lipids were mostly TAGs (11.5 ± 0.2 µmol/10 mg of lipid extract). In CTMP and MWW lipid composition was more diverse than in POME containing also sterol derivatives and fatty acid methyl esters and the main lipids were FFAs.

[Factors determining application activity for and satisfaction with medical care among able-bodied population of closed industrial city].

According to a poll results, nearly 16.5% of questioned able-bodied inhabitants of industrial city mentioned unsatisfactory health state of self, with main reasons of negative environmental influence and low availability of quality medical care. Most respondents (81.1%) are characterized by poor medical activity. Over a quarter of the questioned (25.7%) are dissatisfied with provided medical care. The main factors determining medical activity and satisfaction with medical care are age, sex, employment place and income level.

Behavioral impact of the regulation of the brain 2-oxoglutarate dehydrogenase complex by synthetic phosphonate analog of 2-oxoglutarate: implications into the role of the complex in neurodegenerative diseases.

Decreased activity of the mitochondrial 2-oxoglutarate dehydrogenase complex (OGDHC) in brain accompanies neurodegenerative diseases. To reveal molecular mechanisms of this association, we treated rats with a specific inhibitor of OGDHC, succinyl phosphonate, or exposed them to hypoxic stress. In males treated with succinyl phosphonate and in pregnancy-sensitized females experiencing acute hypobaric hypoxia, we revealed upregulation of brain OGDHC (within 24 hours), with the activity increase presumably representing the compensatory response of brain to the OGDHC inhibition. This up-regulation of brain OGDHC was accompanied by an increase in exploratory activity and a decrease in anxiety of the experimental animals. Remarkably, the hypoxia-induced elevation of brain OGDHC and most of the associated behavioral changes were abrogated by succinyl phosphonate. The antagonistic action of hypoxia and succinyl phosphonate demonstrates potential therapeutic significance of the OGDHC regulation by the phosphonate analogs of 2-oxoglutarate.

[Morphometric characteristics of dentomandibular segments in cases of permanent teeth physiological occlusion].

There were determined correlations between permanent teeth size and bone tissue parameters of mandibular alveolar part and body on native preparations in people with permanent teeth physiological occlusion. Morphometric pequliarities of dentomandibular segments in cases of permanent teeth physiological occlusion were cited. The ratios between bone tissue of alveolar part and body of mandible in each mandibular segment were determined. The received data could be used in orthodontics for dentoalveolar and gnatic forms of vertical anomalies diagnostics and surgical treatment tactics determination for genioplasty for intraosseous dental implantation and implant direction choosing.

Translational strategies exploiting TNF-alpha that sensitize tumors to radiation therapy.

TNFerade is a radioinducible adenoviral vector expressing tumor necrosis factor-alpha (TNF-alpha) (Ad.Egr-TNF) currently in a phase III trial for inoperable pancreatic cancer. We studied B16-F1 melanoma tumors in TNF receptor wild-type (C57BL/6) and deficient (TNFR1,2-/- and TNFR1-/-) mice. Ad.Egr-TNF+IR inhibited tumor growth compared with IR in C57BL/6 but not in receptor-deficient mice. Tumors resistant to TNF-alpha were also sensitive to Ad.Egr-TNF+IR in C57BL/6 mice. Ad.Egr-TNF+IR produced an increase in tumor-associated endothelial cell apoptosis not observed in receptor-deficient animals. Also, B16-F1 tumors in mice with germline deletions of TNFR1,2, TNFR1 or TNF-alpha, or in mice receiving anti-TNF-alpha exhibited radiosensitivity. These results show that tumor-associated endothelium is the principal target for Ad.Egr-TNF radiosensitization and implicate TNF-alpha signaling in tumor radiosensitivity.

Neutron diffraction studies of structural and magnetic properties of niobium doped cobaltites.

Neutron powder diffraction studies of the structural and magnetic properties of the La(1-x)Sr(x)Nb(y)Co(1-y)O(3) solid solutions (x = 0.2, 0.5; y = 0, 0.075, 0.1) have been performed. Substitution of Co(2+) by Nb(5+) prevents the formation of Co(4+) and leads to stabilization of the Co(3+) ions in the high- or intermediate-spin state. This is accompanied by the significant change of the Co-O bond length as well as Co-O-Co bond angle in the CoO(6) octahedron. The obtained data are in agreement with the negative sign of the magnetic exchange interactions Co(3+)-O-Co(3+) in a relatively wide range of the Co-O-Co bond angles. Diamagnetic dilution by the niobium ions prevents long-range magnetic ordering and strongly increases magnetoresistance at low temperature.

[Level of natural autoantibodies to interferon-alpha and characteristics of interferon status during chronic hepatitis and liver cirrhosis].

Level of autoantibodies to interferon-alpha and characteristics of interferon status were studied in 118 patients with chronic diffuse liver diseases (CDLD). During formation of liver cirrhosis in patients with CDLD level of natural autoantibodies to endogenous interferon-alpha increased. During progression of CDLD, decrease of interferon-alpha level and its functional activity were observed as well as change in the ratio between active fraction of interferon-alpha and its inactivated forms towards increase of the latter. One cause of observed decrease in biological functional activity of interferon-alpha in patients with chronic hepatitis and liver cirrhosis was increased titer of interferon-alpha neutralizing autoantibodies in blood. Level of natural autoantibodies to interferon-alpha, its antiviral activity and concentration during chronic hepatitis and liver cirrhosis can be used as markers of disease severity and predictors of its outcome.

[Effects of different methods of physical therapy on the course of autonomic dysfunction syndrome].

A comparative randomized controlled trial was made of efficacy of vegetative disorders correction with drugs and physiotherapeutic factors. A total of 120 patients with vegetative vascular dystonia entered this trial. Its results demonstrated that addition of physiotherapy to the rehabilitation complex allows differential functional changes in the autonomic nervous system. This can be used for optimization of rehabilitation programs.

Changes in serum levels of growth factors in healthy individuals after living related liver donation.

INTRODUCTION: To obtain better insight into the kinetics of hepatic growth factors following partial hepatectomy for living related liver donation, we investigated the postoperative changes in serum levels of hepatocyte growth factor (HGF), epidermal growth factor (EGF), vascular epidermal growth factor (VEGF), and transforming growth factor-alpha (TGF-alpha). PATIENTS AND METHODS: Eighteen healthy donors undergoing right hepatectomy for living related donation were enrolled in this study. Serum levels of HGF, EGF, VEGF, and TGF-alpha were measured using enzyme-linked immunosorbent assay kits before surgery, at 2 hours after resection, and daily during 5 days postoperatively. RESULTS: Mean preoperative HGF serum levels in healthy adults were 778 +/- 64 pg/mL. Within 2 hours after operation, they significantly increased to 9608 +/- 3111 pg/mL afterward decreasing to 2726 +/- 241 at day 1 and 2283 +/- 250 pg/mL at day 2. Hereafter HGF serum levels stabilized at increased levels until day 5 (2109 +/- 138, 2047 +/- 219, 2283 +/- 336 pg/mL, respectively). At all time points, the differences between pre- and postoperative HGF levels were significant (P < .01). In contrast, VEGF and EGF serum levels showed no significant differences between pre- and postoperative levels at all time points. TGF-alpha was not detected using a commercially available test with a detection limit of 10 ng/mL, suggesting only low TGF-alpha serum levels following liver resection. CONCLUSION: Significantly increased HGF serum levels after hepatectomy demonstrate its crucial role among the other investigated growth factors in regeneration of the remnant liver tissue during the early period after the operation.

[ACE and AGTR1 genes polymorphisms in left ventricular hypertrophy pathogenesis in humans]. / Polimorfizm genov ACE i AGTR1 v patogeneze gipertorofii levogo zheludochka serdtsa u cheloveka.

The role of A2350G polymorphism in exon 17 of the ACE gene and A1166C - in 3'-UTR of the AGTR1 in the pathogenesis of left ventricular hypertrophy was studied in patients with essential hypertension (EH) and arterial hypertension combined with diabetes mellitus type 2 (AH + DM2). Patients with EH and AH + DM2 did not differ from the control sample of healthy individuals by allele or genotype frequencies. However, an association of both polymorphisms with LVH was detected in EH patients. The frequency of 1166C allele was higher in patients with LVH (33.6% vs 20.7% without LVH). A1166C polymorphism determined the magnitude of left ventricular mass index (LVMI) in EH patients as well (p = 0.007). 2350G allele frequency of the ACE gene was in 1.5, and GG genotype--in 3.5-fold higher in EH patients with LVH, as compared without LVH. LVMI was significantly higher in patients with GG genotype as compared with heterozygotes and AA homozygotes (p = 0.002). Thus the presence of 1166C allele of AGTR1 and 2350G allele of ACE can be considered as predisposing factors for LVH development in EH. In contrast, association of studied polymorphisms with presence or LVH degree was not detected in patients with arterial hypertension combined with DM2. This may indicate another structure of genetic component of predisposition to LVH in different causes.