Vol 100, No 4 (2019)

Theoretical and clinical medicine
Prognostic value of lipid peroxidation changes in acute poisoning with household drugs “bath salts”
Sumnaya D.B., Iksanov A.V., Shkarednykh V.Y., Sadova V.A., Kuleshova M.V.
Abstract

Aim. To study the state of lipid peroxidation processes in case of psychodisleptic poisoning of the “bath salt” type and to determine the clinical and biochemical markers of a favorable and complicated course of the acute period of poisoning.

Methods. In 347 patients with acute household poisoning (“bath salts”) admitted to the toxicology department of the Chelyabinsk Regional Clinical Hospital №3, the clinical and biochemical features of the acute period of psychodisleptic poisoning (“bath salts”) were studied in a favorable and unfavorable course. Blood and urine samples were taken from all patients, which later underwent chemical and toxicological studies by gas chromatography-mass spectrometry. Also, lipid peroxidation and antioxidant activity were determined in selected blood samples. Lipid peroxidation products were detected in heptane-isopropanol extracts of biological material by spectrophotometry. The intensity of Fe2+-ascorbate-induced lipid peroxidation was determined in E.I. L'vovskaya's modification. The study of patients' samples was carried out in the biochemical laboratory of the regional clinical hospital №3, at the Department of Biochemistry of the Ural state university of physical culture and the South Ural state medical university of Chelyabinsk.

Results. Patients with “bath salts” poisoning in the acute period showed an elevated content of all categories of peroxidation products in the blood serum — by 1.51–1.70 times more than in the control group of healthy people. A decrease in antioxidant activity values I and II by 1.13–1.31 times was also found. With favorable outcomes of poisoning, the level of activation of lipid peroxidation processes decreased with an adequate increase in the activity of the antioxidant system by 1.5–1.6 times. The activation of lipid peroxidation processes in the blood serum accompanied by a decrease in the activity of antioxidant system led to an unfavorable course of the disease and the development of cerebral edema in 18 patients which was fatal.

Conclusion. The clinical and biochemical features of the course of the acute period of poisoning with “bath salts” revealed by us suggest adverse outcomes of the disease with a tendency to an increase in the content of serum lipid peroxidation products in the course of the disease (instead of reducing them) along with a reduction of antioxidant activity; these indicators should be compensated by the use of antioxidant therapy.

Kazan medical journal. 2019;100(4):557–564
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The use of psychometric methods for the diagnosis of anxiety and depressive disorders in patients with a general somatic profile
Dubatova I.V., Voyakina V.G., Lepyavka S.V., Safronenko A.V., Demidov I.A.
Abstract

Aim. To identify and compare the level of anxiety and depression in therapeutic patients with somatic pathology, establish the structure of the gender distribution of anxiety and depressive disorders.

Methods. The study involved 126 people: 74 (58.73%) women and 52 (41.27%) men aged 21–59 years. 59 patients had diseases of the respiratory system (chronic bronchitis in the acute stage with an asthmatic component), 67 patients with cardiovascular diseases (40 subjects with coronary heart disease, 27 subjects with arterial hypertension). In 11 patients with coronary artery disease and 13 patients with hypertension, type I thyrotoxicosis was diagnosed. Clinical psychopathological, psychometric, psychological and statistical methods were used in the study. Psychometric tests were used: the Depression Scale of the Center for Epidemiological Research; Hospital Anxiety and Depression Scale and Taylor Anxiety Disorder Scale adapted by T.A. Nemchinova and V.G. Norakidze, adapted standardized multivariate questionnaire for personality research.

Results. According to the severity of anxiety and depressive disorders, patients were divided into the groups: group 1 with severe level, group 2 with a moderate (subclinical) level, and group 3 with mild (not exceeding the norm) anxiety and depressive disorders. Severe and moderate disorders are most characteristic for the pathology of cardiovascular system. In coronary artery disease and arterial hypertension, abnormal (severe and moderate) anxiety and depressive disorders were observed in 24/29 (82.76%) and 20/22 (90.9%) patients, respectively. In patients with abnormal anxiety and depressive disorders, the number of women prevailed over men in the subgroup with hypertension (80% versus 20%, p=0.025) as well as in combination of hypertension with type 1 thyrotoxicosis (85.7% versus 14.3%, р=0.029).

Conclusion. In patients, severe and moderate anxiety and depressive disorders are associated with the development of the pathology of cardiovascular system: coronary heart disease and arterial hypertension.

Kazan medical journal. 2019;100(4):565-570
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Daily indices of central and peripheral blood pressure in patients with chronic glomerulonephritis and arterial hypertension at different stages of chronic kidney disease
Polyakova I.V., Borovkova N.Y., Tulichev A.A., Maslova T.I., Linyova N.Y., Zubova S.Y., Maksimova I.Y.
Abstract

Aim. To study the daily indices of central and peripheral blood pressure in patients with chronic glomerulonephritis and arterial hypertension at different stages of chronic kidney disease.

Methods. 76 patients with chronic glomerulonephritis and arterial hypertension were examined: 13.2% with chronic kidney disease stage 1 (G1), 15.8% G2, 21.0% G3, 23.7% G4, 26.3% G5D. For the daily monitoring of central (in aorta) and peripheral blood pressure (in brachial artery), the BPLab monitor and the Vasotens-24 technology were used.

Results. In the examined patients central and peripheral systolic, diastolic, and pulse blood pressure increased with renal function decline. Thus, the daily systolic pressure increased from 112 [107; 129] mm Hg in the aorta and 127 [118; 131] mm Hg in the brachial artery in patients with G1 to 146 [137; 153] and 147 [138; 155] mm Hg with G5D; diastolic — from 76 [70; 83] and 78 [71; 85] to 96 [82; 104] and 97 [81; 107] mm Hg; pulse pressure — from 36 [33; 45] and 48 [42; 51] to 53 [45; 56] and 62 [50; 65] mm Hg (p <0.05). A statistically significant excess of peripheral values over the corresponding parameters of central blood pressure for systolic (in groups G1–2) and pulse (G1–4) pressure was detected. Thus, in patients with G2, the average daily systolic pressure was 132 [115; 136] mm Hg in brachial artery and 113 [110; 127] mm Hg in aorta, pulse pressure — 49 [41; 52] and 33 [30; 41] mm Hg (p <0.05). With further progression of renal failure, these differences were not reliably detected. Most patients had a defect of the daily aortic and brachial blood pressure rhythm but the dipper status of systolic and diastolic blood pressure was less common than brachial one (24 and 20% versus 39 and 35%, χ2=5.21 and 5.64; p <0.05).

Conclusion. The features of the peripheral and central blood pressure daily indices at different stages of chronic kidney disease in patients with chronic glomerulonephritis and arterial hypertension determine the relevance of their further study to compare the effect on cardiovascular risk and renal failure progression.

Kazan medical journal. 2019;100(4):571-577
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Evaluation of the effect of breastfeeding duration on child health
Yur'ev V.K., Moiseeva K.E., Alekseeva A.V., Harbediya S.D.
Abstract

Aim. To conduct an objective and subjective assessment of the impact of breastfeeding duration on children's health.

Methods. For a subjective assessment, a survey with random sampling of 476 mothers of children under the age of 1 year was conducted. For an objective assessment of health, the copying of data from the form 112/u “Case history of child's development” was used. The representativeness of this sample was tested by the method of Professor A.M. Merkov, with the error not exceeding 4%.

Results. The majority of women participating in the survey indicated that after discharge from the obstetric hospital, they continued breastfeeding for up to 3 months (21.8%) and up to 6 months (25.3%). The study revealed a statistically significant relationship between the subjective assessment of children's health and the duration of breastfeeding. The highest subjective health score was in children who received breast milk up to 6 and 12 months (4.2±0.09 and 4.3±0.07), the lowest — in children who were formula-fed (3.1±0.10). The performed analysis of the dependence of the proportion of healthy children on the duration of breastfeeding demonstrated the direct strong correlation between the indicators (rxy=0.88). The presence of an inverse strong correlation was established between the proportion of children with chronic diseases and the duration of breastfeeding (rxy=–0.88). In addition, the longer the period of feeding the baby with breast milk, the lower the incidence of acute diseases during the first year of life (rxy=–0.85).

Conclusion. Assessment of the child's health, both subjective and objective, depends on the duration of breastfeeding; infants who are breastfed longer during the first year are less likely to get sick and generally have better health.

Kazan medical journal. 2019;100(4):578-582
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Vascular endothelial growth factor in tumor cells in platinum-containing chemotherapy of advanced ovarian cancer
Gening S.O., Dolgova D.R., Antoneeva I.I., Abakumova T.V., Kolodiy I.O., Gening T.P.
Abstract

Aim. Study of the relationship of vascular endothelial growth factor expression in tumor cells of ascites and primary tumor in patients with ascitic form of ovarian cancer undergoing neoadjuvant chemotherapy according to the AP scheme (doxorubicin + cisplatin).

Methods. The level of vascular endothelial growth factor messenger ribonucleic acid (mRNA) was assessed using PCR-RT in epithelial cells of ascites and primary tumor tissue obtained intraoperatively after 2–4 courses of neoadjuvant chemotherapy according to the AP scheme from 25 patients with a verified diagnosis of ovarian cancer (serous adenocarcinoma) at stage III–IV according to the International Federation of Gynecology and Obstetrics. Processing of the results was performed using the software package Statistica 10.

Results. An increase in the expression of vascular endothelial growth factor mRNA in epithelial cells of ascites in 60% of samples was established. In the intraoperatively obtained tumor tissue after 2–4 courses of neoadjuvant chemotherapy according to the AP scheme, vascular endothelial growth factor expression was increased in 73% of the samples. At the same time, the increase of relative expression in the tumor after neoadjuvant chemotherapy did not depend on the degree of therapeutic pathomorphosis but was related to early relapse and increased level of cancer antigen-125 (CA-125). Median of relapse-free survival in vascular endothelial growth factor-positive ovarian cancer was less than 5 months.

Conclusion. Neoadjuvant chemotherapy according to the AP scheme increases the expression of vascular endothelial growth factor in the tumor tissue in advanced ovarian cancer; the degree of vascular endothelial growth factor overexpression in ovarian tumor is related to the presence of early relapse and an increase in the serum CA-125 level.

Kazan medical journal. 2019;100(4):583-588
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Disorders of hemostasis as the main pathogenetic mechanism in the development of menopausal abnormal uterine bleeding
Chechulina O.V., Kurmanbaev T.E., Tukhvatullina L.M., Khairullina E.A., Mustafin I.G.
Abstract

The article presents our own clinical observations of cases of abnormal uterine bleeding in postmenopausal women, where the main cause was the pathology of hemostasis: a patient after liver transplantation for cirrhosis with chronic viral hepatitis C, and a patient with primary idiopathic thrombocytopenic purpura which manifested at a later age. Among the most common causes of abnormal uterine bleeding in postmenopausal women are hyperplasia and endometrial cancer, leiomyoma, are adenomyosis are distinguished. Pathology of the hemostasis system as the main cause of abnormal uterine bleeding, prevails in the pubertal and reproductive period. In the literature available we did not find any publications concerning uterine bleeding in postmenopausal patients against the background of the pathology of the blood coagulation system. This article illustrates the significance of hemostasis disorders both secondary and primary in the origin of abnormal bleeding in postmenopausal period. Careful collection of anamnesis, an indication of the occurrence of petechial rash, gingival bleeding should alert the doctor. It should also be remembered that “suddenly arisen” immune cytopenias and late-onset thrombosis are often manifestations of the hematological paraneoplastic syndrome and require the exclusion of neoplasia, first of all, of the hematopoietic system. These clinical observations allow recommending a mandatory examination of the hemostatic system in patients with postmenopausal bleeding.

Kazan medical journal. 2019;100(4):589-594
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Microanatomy of vitreoretinal interactions in macular and paramacular areas
Lyskin P.V.
Abstract

Aim. To refine microanatomy of vitreoretinal interactions in central areas of retina and to obtain additional information on vitreoretinal interactions regarding theoretical possibility of collagen synthesis in the vitreous body of adult humans and mechanisms of vitreoretinal adhesion.

Methods. Scanning electron microscopy study was performed in central areas of human retina after removal of vitreous base from its surface.

Results. On the surface of retina we found a thin layer of epiretinal vitreous body most strongly bound to the retina. Thickness of paramacular epiretinal vitreous is 3–5 µm and it is formed mainly by thin densely packed fibrils. Its surface layer facing the vitreous cavity consists of the thickest (1 µm) and longest (250 µm) fibrils loosely packed. These fibrils look like “pearl threads” and exhibit signs of newly formed fibrils. Epiretinal layer of the vitreous in the fovea is thinner, its thickness is about 2 µm. Top layer of fibrils is least densely packed with the thickness of the fibrils of about 0.2 µm. The closer to internal limiting membrane, the thinner the fibrils, the denser their packing. The discovered layer can be interpreted as an additional anatomic structural unit of the vitreous body — epiretinal vitreous.

Conclusion. We detected indirect signs of lifetime synthesis of newly formed fibrils in the vitreous of adult human; newly formed collagen may be localized in epiretinal vitreous which may be the main binding component providing vitreoretinal adhesion.

Kazan medical journal. 2019;100(4):595-600
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Laser treatment of chronic central serous chorioretinopathy with a point of leakage in the subfoveolar zone without fluorescein angiography
Samoylov A.N., Korobitsin A.N.
Abstract

Aim. Develop a methodology and evaluate the clinical results of laser treatment of patients with chronic central serous chorioretinopathy in the presence of a leakage point in the foveola zone.

Methods. The results of patients (32 eyes) with central serous chorioretinopathy after laser exposure in the avascular area were analyzed. The best-corrected visual acuity in these patients before treatment was 0.7 to 1.0 (average 0.78±0.15) with a height of neuroepithelial detachment of 162 to 328 μm according to optical coherence tomography. No signs of choroidal neovascularization was detected in angio mode on optical coherence tomography. The treatment was performed with an Ellex Integre Pro Scan 561 nm. The follow-up examination was performed in 1 and 6 months.

Results. In 1 month, positive dynamics of both functional and anatomical parameters was noted in all eyes. According to the optical coherence tomography, a complete attachment of the neuroepithelium in the central zone of the retina occurred, detachment of the neuroepithelium was absent. Best-corrected visual acuity in 1 month after treatment increased to 0.89±0.08, in 6 months to 0.92±0.04. The study revealed a correlation between visual acuity and the central thickness of the retina in the fovea, there were no complaints about the appearance of scotomas after laser treatment in the foveola zone.

Conclusion. The developed techniqe of laser exposure on the foveola zone in case of chronic central serous chorioretinopathy with a 561 nm laser demonstrated high clinical efficacy and safety and can be recommended to all patients with central serous chorioretinopathy.

Kazan medical journal. 2019;100(4):601-605
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Use of autologous conditioned platelet-rich plasma in the surgery of rhegmatogenous retinal ­detachment with large and multiple breaks, abruption from the dentate line
Arsyutov D.G.
Abstract

Aim. To evaluate the effectiveness of surgical treatment of rhegmatogenous retinal detachment with large and multiple breaks, abruption from the dentate line with the use of 25, 27 Ga subtotal vitrectomy, pneumoretinopexy or silicone tamponade with blocking of retinal defects with the use of autologous conditioned platelet-rich plasma without endolaser coagulation around retinal defects.

Methods. The surgery included 25, 27 Ga vitrectomy, posterior hyaline membrane removal, pneumoretinopexy, instillation of 2–3 layers of autologous conditioned platelet-rich plasma deprived of leukocytes and containing 1.5–2 times more platelets than in whole blood into the area of retinal detachment, its break or along the edge of retinotomy till the retinal defect is totally covered. A total of 27 patients with visual acuity 0.03 to 0.9 were treated.

Results. In the early postoperative period 93% of patients had total retinal reattachment, in whim retinal detachment was blocked; 2 patients were reoperated. In the late postoperative period (1–12 months) 4 recurrent retinal detachments were registered, which also required reoperation. Visual acuity of the operated patients in the late postoperative period was 0.1–1.0.

Conclusion. 25, 27 Ga vitreoretinal surgery of rhegmatogenous retinal detachment with large retinal breaks, abruption from the dentate line, including retinotomy and retinal defects blockage with the use of autologous conditioned platelet-rich plasma without the use of endolaser coagulation is a method which allows achieving total reattachment of retina, better function of the operated eye in most cases.

Kazan medical journal. 2019;100(4):606-610
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Modern optimizing techniques of surgical treatment of proliferative diabetic retinopathy
Stebnev V.S., Stebnev S.D., Malov I.V., Malov V.M., Eroshevskaya E.B.
Abstract

Aim. To evaluate the clinical efficacy of microinvasive vitrectomy and three-dimensional digital imaging in patients with proliferative diabetic retinopathy.

Methods. The clinical treatment results were studied in 62 patients (62 eyes) with proliferative diabetic retinopathy complicated by tractional retinal detachment who underwent vitreoretinal surgery with the use of microinvasive techniques and three-dimensional digital imaging. There were 38 (61%) women, 24 (39%) men, mean age 57±5.2 years. The duration of diabetes mellitus was 6 to 13 years (an average of 11.7 years). Of the 62 patients, 11 had insulin-dependent diabetes mellitus, and 51 had non-insulin-dependent diabetes.

Results. Final anatomical result (the elimination of the zones of proliferation and adhesion of the retina) was reached in 59/62 (95.1%) of the eyes: in 54/62 (87%) eyes after the first intervention, in 8/62 eyes after additional surgical intervention. The maximum corrected visual acuity increased in 55/62 (88.7%) eyes from 0.01±0.12 to 0.22±0.11 (p <0.05); in 3/62 (4.8%) eyes remained the same; 4/62 (6.5%) eyes had visual impairment. Complications were diagnosed in 14 (22.6%) of the eyes: retinal tears (10), hemophthalmus (2), subchoroid hemorrhage (1), detachment of the choroid (1). Postoperative control of intraocular pressure demonstrated the following: 36 (58.1%) eyes had normal intraocular pressure (11–22 mm Hg), 20 (32.3%) — increased intraocular pressure (≥22 mm Hg), 6 (9.7%) — reduced intraocular pressure (≤10 mm Hg). In the postoperative period (up to 1 month after surgery) additional surgical interventions were performed on 8/62 (12.9%) eyes.

Conclusion. In patients with proliferative diabetic retinopathy, the use of microinvasive vitreoretinal technologies and digital imaging system provide high anatomical (95.1% of patients) and functional results (88.7% of patients).

Kazan medical journal. 2019;100(4):611-615
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Behavioral risks of student dental health
Safarov D.A.
Abstract

Aim. To increase the effectiveness of treatment and prevention of periodontal diseases in smoking students.

Methods. A comprehensive dental examination and survey was conducted among 380 students 180 of whom were smokers, and the other 200 students were not tobacco smokers. The students were comparable by age (mean age 21.1±0.09 and 21.4±0.10 years, p=0.1009) and the initial state of the oral cavity. To assess the effectiveness of treatment and preventive measures, smoking students with inflammatory changes in periodontium were divided into the groups. The first group (52 subjects) was divided into three subgroups: 1a (n=15) — removal of plaque by the piezoelectric ultrasound apparatus Vector; 2a (n=20) — use of the Air-Flo C2 air-abrasive apparatus; 3a (n=17) — use of Gracey curette. The second group (n=32) was divided into two subgroups: control (n=15) where only conventional therapy was applied, including professional oral hygiene (removal of supra- and subgingival dental deposits) and the main one (n=17), where, unlike the control group, additional supportive therapy was introduced with Antitobacco Chamomile-Sage conditioner. Repeated clinical examinations were carried out 1 and 6 months after the completion of treatment using periodontal and hygienic indices.

Results. Students were found to have caries and periodontal inflammation but it was more pronounced in patients with a bad smoking habit in history: 4.37±0.12 and 3.98±0.09 — the intensity of caries in smokers and non-smokers, respectively (p <0.05). Among the smoking students in relatively rare cases a healthy periodontium was detected: 2.78±1.22, versus 9.0±2.02 in the group of non-smoking students (p <0.05). With the inclusion of Antitobacco Chamomile-Sage conditioner in the complex therapy, the values of OHI-S and papillary marginal attachment indices were significantly lower than in the control group 1 and 6 months after treatment. A comparative analysis of the data obtained in another treatment group, divided into three subgroups, revealed that with the use of Gracey curette a more pronounced positive shift in the indices was observed.

Conclusion. Favorable dynamics in the reduction of hygienic and periodontal indices at all stages of the research, indicating improvement of oral hygiene and periodontal condition, was recorded when using periodontal Gracey curette and “Antitobacco Chamomile-Sage” herbal conditioner in the complex treatment.

Kazan medical journal. 2019;100(4):616-621
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Osteometry of the human spine at the age of maturity in the Ural region
Men’shchikova I.A.
Abstract

Aim. To reveal the patterns of the changes of osteometric characteristics of the adults living in the Ural region.

Methods. 56 cadavers of human beings at the age of maturity were analyzed (28 women aged 21 to 55 years, and 28 men aged 22 to 60 years) being the residents of the Ural region. The scheme recommended by the Symposium on Age Periodization at the Institute of Age Physiology in 1969, was used for distribution by age groups. Osteometry and statistical method were used.

Results. In the cervical spine, the greatest sagittal size was determined in the spinal process of the VII cervical vertebra (30.9±1.79 mm), in the thoracic spine — in the VII thoracic vertebra (41.5±2.4 mm), and in lumbar spine — in the III lumbar vertebra (36.4±0.95 mm). The frontal size of vertebral bodies increased from overlying vertebrae to underlying ones, however, the decrease in the frontal size of vertebral bodies was noted from the I thoracic to the VI thoracic vertebra, and starting from the VII thoracic vertebra its further increase was observed. The sagittal size of vertebral body increased only from the II cervical vertebra to the III lumbar one. The sagittal size of the bodies of the III–V vertebrae was within the range of 32–34 mm. The sizes of vertebral arch pedicle allow conducting the transpedicular fixation at the level of all vertebrae, but it should be taken into account that in V and VI thoracic vertebrae frontal size of arch pedicle is the least as compared to other levels. The frontal sizes of spinal canal were more than sagittal ones at the levels of all vertebrae, with the exception of atlas and the V thoracic vertebra.

Conclusion. The results can serve as the basis for performing any surgical interventions on the spine and as the norm for evaluation of its pathological changes.

Kazan medical journal. 2019;100(4):622-628
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Experimental medicine
Effect of endocrine disrupting chemicals bisphenol A and triclosan on semen quality
Chigrinets S.V., Bryukhin G.V.
Abstract

Aim. To establish a relationship between the concentration of endocrine disruptors (bisphenol A, triclosan) in testicular tissues or seminal fluid and semen quality in men and experimental animals.

Methods. 53 samples of seminal fluid were investigated from men with normo- and pathozoospermia. In seminal fluid the level of bisphenol A and triclosan were determined by gas chromatography-mass spectrometry. The spermiological study was carried out according to the World Health Organization guidelines (2010). The experimental part of the study was performed on adult male lab Wistar rats (n=28). The amount of spermatozoa per 1 ml of sperm was determined with the calculation of their motility and atypical forms. The concentration of bisphenol A and triclosan in the testicles was measured by gas chromatography-mass spectrometry.

Results. Bisphenol A and triclosan were detected in 100 and 84.9% of the ejaculate samples with a median concentration of 0.15 (0.06–0.31) ng/ml and 0.13 (0.05–0.22) ng/ml, respectively. With the Spearman's rank correlation coefficient, statistically significant correlation was found between the concentration of endocrine disruptors and ejaculate parameters: between bisphenol A and the total count of spermatozoa, their concentration, the proportion of progressively motile spermatozoa, the proportion of spermatozoa with normal morphology and degree of sperm DNA fragmentation. Triclosan concentration correlated with the proportion of spermatozoa with normal morphology and the degree of sperm DNA fragmentation. The experimental part of the study demonstrated that bisphenol A reduced the total number of spermatozoa with an increase in the proportion of atypical forms of spermatozoa and a violation of the proportion of fertile spermatozoa compared to the group of intact animals. Triclosan reduced the proportion of progressively motile spermatozoa.

Conclusion. Bisphenol A and triclosan have a negative effect on sperm quality in men and experimental animals.

Kazan medical journal. 2019;100(4):629-635
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Effect of bromfenac on free radical oxidation in model systems
Galimova E.F., Khaibullina Z.G., Enikeev D.A., Bortsova Y.L., Mochalov K.S., Galimova S.S., Travnikov O.Y., Asadullina T.S., Aver’yanova K.S.
Abstract

Aim. The study of free radical oxidation processes in an experiment on model systems using the anti-inflammatory drug bromfenac (nakwan) widely used in ophthalmology for the treatment of infectious and inflammatory diseases of the anterior chamber of the eye.

Methods. The antioxidant capacity of the drug was evaluated by chemiluminescence registration and analysis of model systems that generate reactive oxygen species and reproduce lipid peroxidation processes using the chemiluminomer CL-003. The following parameters of spontaneous and induced chemiluminescence were determined: light sum and maximum luminescence amplitude, duration of latent period, amplitude of fast and slow flash.

Results. When tested in vitro in two different model systems, a high antioxidant activity of the studied drug was established, up to complete suppression of chemiluminescence when 90 μg of bromfenac was added to the incubation medium, which characterizes the inhibition of the generation of reactive oxygen species. A significant increase in total antioxidant activity with bromfenac was also demonstrated, which is reflected by the integral parameter of chemiluminescence — light sum which decreased with the introduction of 10 μg of the drug by 1.2 times, and with 90 μg by 1.5 times. A comparative analysis of the antioxidant properties of various nonsteroidal anti-inflammatory drugs used in ophthalmic practice demonstrated a more pronounced efficacy of bromfenac compared to ketorolac, the use of which was not accompanied by statistically significant changes in chemiluminescence. A very important mechanism of the positive effect of bromfenac is the direct dependence of the action on its quantity in the reaction medium, which opens up prospects for the controlled correction of free radical phenomena and the excessive activation of lipid peroxidation in the imbalance of the pro- and antioxidant processes in biological systems.

Conclusion. It is suggested that the protective effects of the drug in various infectious-inflammatory lesions of the eye can be determined, along with previously known properties, its antioxidant activity, restriction of increased production of reactive oxygen species and oxidative stress phenomena.

Kazan medical journal. 2019;100(4):636-641
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Reaction of the hemostatic system in response to hypercapnic hypoxia of maximum intensity ­depending on different types of preconditioning
Moskalenko S.V., Shakhmatov I.I., Kovalev I.V., Shakhmatova K.I., Vdovin V.M.
Abstract

Aim. To study the adaptation reactions of the hemostasis system to hypercapnic hypoxia of maximum intensity in rats subjected to preliminary multiple exposure to ethylmethylhydroxypyridine succinate and hypercapnic hypoxia of submaximal intensity.

Methods. In the experiment, Wistar male rats (80 individuals) were used. Training cycles: 30-fold daily exposure to hypercapnic hypoxia of submaximal intensity (20 minutes — 9.0±0.5% O2, 7.0±0.5% CO2); administration of ethylmethylhydroxypyridine succinate (50 mg/kg) to animals for 30 days; combined effects of the two described modes. Tested experimental exposure was simulated as a single hypercapnic hypoxia of maximum intensity (20 minutes — 5.0±0.5% O2, 5.0±0.5% CO2) at the end of each of three 30-day training cycles.

Results. Preliminary 30-day exposure to both isolated hypercapnic hypoxia of submaximal intensity and combined exposure to ethylmethylhydroxypyridine succinate contributes to hypocoagulation shift in the hemostasis system and reduces the level of the markers of pre-thrombotic state in response to a single hypercapnic hypoxia of maximum intensity. The state of the hemostasis system after 30-day cycle of isolated use of an antihypoxant is characterized by the inhibition of the vascular-platelet system of the hemostasis system and preserved hypercoagulation shifts in its plasma unit. The obtained results suggest that both preliminary isolated effect of hypercapnic hypoxia of submaximal intensity and the combined effect of hypercapnic hypoxia and ethylmethylhydroxypyridine succinate increase the resistance of the hemostasis system in experimental animals to acute hypercapnic hypoxia of maximum intensity compared to rats of the control group. This was confirmed by the inhibition of the vascular-platelet system, hypocoagulation in the plasma unit, decrease in the level of thrombotic readiness markers and increase in the anticoagulant activity of the blood system compared to the control. At the same time, isolated course administration of ethylmethylhydroxypyridine succinate did not cause the same amount of adaptive changes to maximum intensity hypercapnic hypoxia, since only platelet suppression of the hemostasis and hypocoagulation via the internal coagulation pathway were registered.

Conclusion. Isolated exposure of hypercapnic hypoxia of submaximal intensity and its combined exposure with ethylmethylhydroxypyridine succinate increase the resistance of the hemostasis system to acute hypercapnic hypoxia of maximum intensity; isolated course administration of ethylmethylhydroxypyridine succinate does not cause the same amount of adaptive changes.

Kazan medical journal. 2019;100(4):642-649
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Determination of felodipine in biological fluids
Kvachakhiya L.L., Shormanov V.K., Kononenko N.S.
Abstract

Aim. Development of methods for the determination of felodipine in blood and plasma.

Methods. The study object was felodipine [3-ethyl-5-methyl-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate]. The experiments were carried out on model mixtures of felodipine with blood and human blood plasma. Acetone was proposed as an isolating agent for the extraction of felodipine from biological fluids. To identify and quantify felodipine in extracts from blood and plasma, the methods of thin-layer chromatography, spectrophotometry and gas-liquid chromatography in combination with mass spectrometry were proposed.

Results. The possibility of using acetone as an isolating agent to extract felodipine from biological fluids is demonstrated. The optimal conditions for the extraction of felodipine with acetone were found to be achieved already at 2-fold infusion of a biological object with an isolating agent, if the mass ratio of isolating liquid and biological material at each infusion stage is at least 2:1, and the infusion time is at least 30 minutes. Optimal felodipine purification conditions were achieved in a macrocolumn (15×1 cm) of Silasorb S-18 sorbent of 30 μm with elution of the substance with the polar eluent acetonitrile-water (7:3). The methods of determining felodipine in the blood and plasma were developed. With the content of felodipine of 25 mg in 25 g of biological fluid, the developed methods allow determining 86.01–87.86% in blood and 95.64–96.18% of the substance in blood plasma. The values of the detection limit of felodipine in the blood and plasma by the developed methods are 200 μg/100 g and 150 μg/100 g, respectively.

Conclusion. Methods for the determination of felodipine in biological fluids were developed based on isolating with acetone and purification in the Silasorb S-18 sorbent column; use of these methods allows determining up to 87.86% of the analyte in the blood and up to 96.18% in the blood plasma.

Kazan medical journal. 2019;100(4):650-656
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Experimental study of the effectiveness of 6-methyl-3-(thietane-3-yl)uracil-containing eye ­ointment in the treatment of corneal thermal burns
Gabdrakhmanova A.F., Meshcheryakova S.A., Gaynutdinova R.F., Kil’diyarov F.K., Kurbanov S.A., Khuzhamberdiev A.K.
Abstract

Aim. To evaluate the effectiveness of wound healing eye ointment with 6-methyl-3- (thietane-3-yl) uracil in the treatment of corneal thermal burn in the experiment.

Methods. The study was conducted on 6 rabbits of the chinchilla breed. The results of treatment and histomorphological studies of the rabbits’ cornea are presented after experimental thermal burn by instillation of water with a temperature of 80–85 °C with 20-second exposure to the cornea. In the experimental group (right eyes of rabbits) the animals were treated with developed 6-methyl-3-(thietane-3-yl)uracil eye ointment, in the control group (left eyes of rabbits) 20% gel of solcoseryl was applied. Animals were observed daily for 14 days. The condition and the morphological changes of the cornea were compared on days 1, 3, 7, 10, and 14 after the experimental thermal burn.

Results. The features of reparative processes after corneal thermal burn depending on used treatment were determined. The study revealed that 6-methyl-3-(thietane-3-yl)uracil improved trophics more repidly, increased cell growth and cell reproduction, stimulated the regeneration process in damaged corneal tissues, accelerated wound and burn healing, and also provided anti-inflammatory effect. Positive dynamics was registered on days 4–5 in the experimental group, and by the 7th day in the control group. With 6-methyl-3-(thietane-3-yl)uracil no toxic reactions in the form of destruction of the collagen skeleton, maceration, pronounced edema and hyperemia were observed. On day 14 of follow-up, the microscopic picture of rabbits’ cornea had the usual normal structure.

Conclusion. Treatment with 6-methyl-3-(thietane-3-yl)uracil resulted in faster and more structured and anatomically correct healing of corneal thermal burn compared to the treatment with alternative medication solcoseryl in the control group.

Kazan medical journal. 2019;100(4):657-661
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Reviews
Endometrial cancer: modern concepts of screening
Protasova A.E., Sobivchak M.S., Bayramova N.N., Glushakov R.I., Tapil’skaya N.I.
Abstract

Currently endometrial cancer remains a pressing issue for public health worldwide. Every year there is a steady increase in morbidity rates, which is associated with an increase in the prevalence of risk factors for the disease among which “non-steroid triad” is prevalent: obesity, diabetes, metabolic syndrome. Other significant risk factors for endometrial cancer include the long-term use of tamoxifen and the presence of Lynch syndrome, which makes it possible to carry out selective screening of the disease in these groups of patients. Endometrial cancer is a symptomatic disease, the main clinical manifestation of which is the bleeding from the genital tract on the background of postmenopause. In this case, with timely diagnostic measures, the disease is diagnosed in more than 80% of cases in the early stages of the tumor process, in which the results of treatment are satisfactory. However, despite years of research, questions remain about the relevance and feasibility of population and selective screening for uterine cancer, the ultimate goal of which is to reduce mortality from this disease in a population. Endometrial biopsy and ultrasound of the pelvic organs are considered as the main screening methods, however, the effectiveness of these methods as a population screening is limited. Unreasonable tests lead to overdiagnosis of the disease, invasive interventions increase the risk of the development of predictable complications. This review of the literature contains current information on factors that increase and decrease the risk of endometrial cancer and the results of scientific research on endometrial cancer screening. This information will allow the doctor to choose a rational tactic for managing each particular patient with various risk factors for endometrial cancer and to avoid unnecessary invasive interventions.

Kazan medical journal. 2019;100(4):662-672
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Capabilities of cytostatic agents usage in ophthalmology
Belousova N.Y., Poltanova T.I.
Abstract

Antineoplastic drugs are increasingly used in the treatment of diseases of the vision organ. However, practicing ophthalmologists often deal with lack of information about the choice of drugs with anticancer effect, their mechanism of action, dosage, route of administration, potential side effects including their prevention. Mechanism of action is presented for the most commonly used immunosuppressants in ophthalmology (such as metabolic antagonists, alkylation agents, antineoplastic antibiotics, monoclonal antibodies). Efficiency and routes of administration are described for cytostatics used for the treatment of intraocular tumors (retinoblastoma), for prevention and treatment of proliferative syndrome in ophthalmosurgery complicating the surgery for glaucoma, pterigium and refractive corneal procedures, and presenting the pathogenetic basis of proliferative vitreoretinopathy and posterior lens capsule opacity. Possible local side effects of immunosupressors in ocular surgery are presented (epithelial and suture defects, hemorrhagic choroidal detachment, cataract progression, endophthalmitis, malignant glaucoma, toxic effect on the ciliary body, keratopathy, hypertensive maculopathy). Also, the issue of the use of cytostatics and immunodepressants for acute and chronic inflammatory eye diseases is discussed (for example, for uveitis, filamentary ke­ratitis, allergic blepharoconjunctivitis, allergic conjunctivitis and spring ophthalmia, adenoviral keratoconjunctivitis, rosacea keratitis, ocular pemphigoid, recurrent chalazion, scleritis, episcleritis, painful bullous keratopathy, state after keratoplasty and refractive surgery of ocular fibrous capsule). Special attention was paid to the eye neovascularization and common use of intravitreal injections of monoclonal antibodies (ranibizumab, aflibercept) for premature infants’ retinopathy, choroidal neovascularization of various origin (in trauma, myopia, histoplasmosis), neovascular form of age-related macular dystrophy, secondary neovascular glaucoma, proliferative diabetic retinopathy and diabetic macular edema. Need for search of new more effective and safe medicines with antineoplastic and immunodepressive action is emphasized for ophthalmology, eye surgery and medicine in general.

Kazan medical journal. 2019;100(4):673-679
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Proteomic technologies in the development of new vaccines based on serotype-non-specific protein antigens of Streptococcus pneumoniae
Tyuri Y.A., Zaripova A.Z., Isaeva G.S., Mustafin I.G., Bayazitova L.T.
Abstract

The review presents a modern strategy to improve the means of vaccine prevention of streptococcal infections aimed at finding and developing new vaccines for immunization of people belonging to risk groups. It should be noted that pneumococci (S. pneumoniae) are members of gram-positive bacteria (diplococci) and become the main cause of various nosological forms of human infectious diseases (such as pneumonia, otitis media, sinusitis, bacteremia and meningitis). Existing pneumococcal vaccines (conjugate and polysaccharide) have some important limitations, for example, serotype dependence, loss of effectiveness due to a change in the serotype landscape, insufficient protective effect from non-invasive forms of pneumococcal infections and high production costs associated with the development of these products. The main part of the review presents the most important research papers that used modern proteomic technologies in the study of the S. pneumoniae proteomic profile. These works allow us to evaluate at the molecular level the importance of bacterial proteins as candidates for creating new combination vaccines that can effectively protect against the full range of pneumococcal serotypes circulating in the human population. So, in particular, the data are provided on the new methodology for the analysis of the proteome of extracellular S. pneumoniae bacterial microvesicles to identify immunoreactive protein antigens, potential candidates for inclusion into vaccines. As a result of these studies, 15 immunoreactive proteins were discovered, 7 of which are cytosolic and 8 proteins are bound to the cell surface (MalX, ABC transporter or substrate binding transport protein, AmiA, AliA, LytC, IgA1 protease, PspA and the putative precursor of β-galactosidase). These are possible candidates for developing combination vaccines. Additionally, the review presents data on the role of significant virulence factors of the protein nature of S. pneumoniae strains in nasopharyngeal colonization, increased infectivity, as well as on overcoming reactions of the host's immune response.

Kazan medical journal. 2019;100(4):680-688
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Somatic disorders in autism as one of the factors of behavioral and social interaction disorders
Ivanova D.V., Semina I.I., Ziganshin A.U.
Abstract

Autism is a pressing global problem in a number of medical and related scientific disciplines. For autism, a polysystemic feature is typical, and neurological changes are usually accompanied by somatic ones, most often affecting the intestine, pancreas, and often lungs, pelvic organs, kidneys, adrenal glands and other organs. It is not surprising that the mortality from somatic causes in such children exceeds the mortality of healthy children of the same age groups by 3–10 or more times (depending on the severity of autism). Many studies report a high prevalence of gastrointestinal symptoms in autistic people. The most common of these is chronic constipation (22% on average). The functional interaction of the gastrointestinal tract and the central nervous system is due to the presence of various connections and includes the autonomic nervous, immune and neuroendocrine systems. Of particular importance in gastrointestinal disorders and the pathogenesis of autism is the intestinal microbiota, a complex bacterial community located in the gastrointestinal tract. Under the influence of external and internal factors, the microbiota changes the permeability of the intestinal and blood-brain barriers, and the metabolites produced by the altered microbiota can enter the bloodstream and the central nervous system, disrupting its functioning. It was proven that there are pronounced differences between the intestinal microbiota of healthy children and autistic children, and directed individual correction often leads to normalization or significant improvement in social and communicative behavior and other deviations typical of children with autism. Thus, violations in the somatic sphere can increase the severity of the clinical presentation of autism, causing various behavioral and communication disorders. Identification of the spectrum of these disorders, as well as the study of the mechanisms of their development and interrelationship, is an urgent problem, the solution of which may be important for determining the tactics of complex therapy of patients with autism spectrum disorders.

Kazan medical journal. 2019;100(4):689-694
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Social hygiene and healthcare management
Analysis of pathologies among workers of a large enterprise of housing and communal services based on the results of periodic medical examinations
Bendyuk G.Y., Dokhov M.A., Sidorov A.A.
Abstract

Aim. The determination of age-specific coefficients of pathologies in the team of SUE “Vodokanal of St. Petersburg” for 2015–2017.

Methods. The study was conducted in the Medical unit of SUE “Vodokanal of St. Petersburg” in 2015–2017. 8600 people were followed up for 3 years. During the study, extensive indicators of the structure of the pathological process and intensive indicators characterizing its prevalence were calculated.

Results. As a result of the study, it was found that the first place (27.1%) in the structure of pathologies both in men and women is occupied by diseases of the eye and its adnexa. At the second ranked place (25.7%) there were diseases of the circulatory system. As a result of the study, age groups with a high rate of increase in morbidity were identified. Thus, the rate of increase in the detection of pathology of the circulatory system at the transition from the age group below 25 years to the age group 25–29 years was 73.7% among men and 80.4% among women. It was found that diseases of the ear and mastoid process were more common among men, and the greatest increase in the incidence was recorded in the age group 25–29 years. At the same time, diseases of the genitourinary system were more common in women, and the highest incidence rate was revealed in the age group 40–44 years.

Conclusion. Тhe results indicate the need for a differentiated approach to planning the volume of preventive work in different age groups of employees of the housing and communal services enterprise.

Kazan medical journal. 2019;100(4):695-700
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Results of a comprehensive study of expert opinion and social hygienic aspects of doctors of draft boards of the subjects of the Russian Federation
Sogiyaynen A.A.
Abstract

Aim. Examination of expert opinions and social and hygienic aspects of the activities of draft board doctors of the subjects of the Russian Federation.

Methods. The results of an anonymous continuous survey of medical specialists of the military-medical commissions of the military commissariats of the subjects of the Russian Federation (n=646) are presented, who directly conduct military-medical examination of the studied contingent.

Results. When interviewing experts, significant factors were found that affect the health of citizens of draft age and the quality of military medical expertise. Thus, experts assessed the state of health of modern young men as satisfactory in 84% of cases, and in 3.6% as unsatisfactory. 46.5% of medical specialists noted a positive trend in the level of moral and psychological training of the contingent. Over 14% of respondents noted a negative trend in the health status of young men of draft age over the past 5 years. 9.8% of specialists assess the level of treatment and preventive measures among persons of draft age as unsatisfactory, 25.3% of experts consider it necessary to expand the list of mandatory diagnostic studies when preparing citizens for military service. The reasons for the unsatisfactory work of the system for the prevention of diseases among citizens before being drafted for military service, according to medical specialists, are formalism in carrying out activities for the prevention of diseases, lack of subspecialists in health care organizations, especially in remote areas, and the elimination of adolescent service. The state of the regulatory framework governing the relationship of the parties during the medical provision of training and conscription to the military forces of the Russian Federation adversely affects the work of 43.6% of doctors.

Conclusion. An expert opinion of the medical specialists of the military medical commissions of the military commissariats indicates that the main reserves for improving the quality of measures to prepare citizens for military service are the expansion of diagnostic and treatment and prophylactic measures carried out before military conscription.

Kazan medical journal. 2019;100(4):701-705
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Clinical observations
Clinical case of destructive pulmonary tuberculosis combined with laryngeal tuberculosis
Naumov A.G., Boronin K.A., Bokova K.V., Zherebyat'eva N.S., Zhukova E.V., Konygina K.S., Sukhova O.A.
Abstract

Timely detection of tuberculosis among the population, both pulmonary and, especially, extrapulmonary, is a priority task of domestic and foreign health care. Often, extrapulmonary forms of tuberculosis mask various other pathologies. For example, laryngeal tuberculosis may be masked as a malignant neoplasm or occur as a nonspecific lesion. The purpose of the article is to attract the attention of medical specialists to the problem of diagnosing tuberculosis on the example of a clinical case of a patient with combined pulmonary and laryngeal tuberculosis. In accordance with the obtained clinical, laboratory and instrumental data, we concluded that when patients are admitted to a non-specialized medical organization with complaints from the larynx (dysphonia, aphonia) or oropharyngeal organs (dysphagia), complete diagnostic minimum is required including chest X-ray, complete blood count, otolaryngology consultation and microbiological monitoring (sputum microscopy) for the purpose of integrated examination of the patient and further routing to antituberculous institution. An example is given of successful treatment of a patient with a combination of pulmonary and extrapulmonary tuberculosis (laryngeal tuberculosis) identified due to the presence of symptoms in the larynx.

Kazan medical journal. 2019;100(4):706-709
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Clinical experiences
Justification for preservation of the projected skin flap above the tumor during surgical treatment of primary resectable breast cancer
Khamitov A.R., Ismagilov K.K.
Abstract

Aim. Improvement of the aesthetic outcomes of reconstructive plastic surgery for nodular breast cancer due to the scientific rationale of conservation of the projected skin flap and moving the postoperative scar to aesthetically acceptable zones.

Methods. Data of clinical and instrumental methods of investigation of 240 patients with primary resectable breast cancer were analyzed. The probability of involvement of the front layer of the superficial fascia in the projection of a malignant tumor depending on its clinical and topographic anatomical figures was estimated.

Results. The study revealed that the fascia involvement does not depend on the skin flattening. The skin flatte­ning is an indirect sign of superficial tumors having a probability of intimate adherence of the tumor to the fascia of 31.8±0.401%. In turn, the intimate adherence of the tumor to the front layer of the superficial fascia with a pro­bability of its involvement of 39.3±0.41% is a significant risk factor for the projected skin flap involvement. It was also found that involvement of the fascia studied does not depend neither on the size of the tumor, nor on the nodal status, nor on the biological subtype. The key risk factor is the depth of the tumor.

Conclusion. The indication for the projection skin flap preservation is the location of a malignant tumor at a depth of more than 1.05 cm, at which the probability of affecting the fascia is statistically insignificant and is 1.7±0.1%, which requires placing the subcutaneous tissue resection line in the tumor projection from the side of preserved skin flap.

Kazan medical journal. 2019;100(4):710-718
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History of medicine
Professor Zaynab Khabibullovna Karimova — a bright representative of Kazan school of ­microbiologists (on the 110th anniversary)
Isaeva G.S., Khabirova G.Z., Akberov A.R.
Abstract

The article was prepared for the 110th anniversary of the head of the department of microbiology at Kazan State Medical University, Professor Zaynab Khabibullovna Karimova. The article presents the main milestones of her biography, highlights the historical aspects of the formation of Kazan school of microbiologists, which she represented. The article was prepared using primary sources — scientific articles and monographs published during the period of her activity (20–70s of the 20th century), colleagues’ memories, archival materials of the department of microbiology named after V.M. Aristovskiy of Kazan State Medical University, as well as the family archive. The main scientific achievements of Z.H. Karimova and her scientific contribution to the development of microbiology are described, especially the study of spirochetosis. A description of experimental studies on the creation of nutrient media for the isolation of pure culture of Treponema pallidum and the search for diagnostic methods for syphilis is presented. Studies of searching for the etiological factor of jaundice of unknown origin in the Republic of Tatarstan in the 30–40s of the last century, of the detection of sources and factors of transmission of leptospirosis, the development of new methods for the diagnosis of leptospirosis and other aspects of the scientific activity of Z.H. Karimova are described.

Kazan medical journal. 2019;100(4):719-726
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Cochrane Review Summaries
Long-term antibiotics for preventing recurrent urinary tract infection in children
 
Abstract

В чем суть проблемы? Инфекции мочевого пузыря и почек (инфекции мочевой системы — ИМС) распространены у детей, особенно у девочек. Они приводят к развитию вызывающего дискомфорт заболевания, которое может включать рвоту, лихорадку и слабость/утомляемость. У некоторых детей может возникнуть повреждение почек, а также повторные эпизоды заболевания. При повторных инфекциях риск повреждения почек возрастает. Некоторые врачи назначают долгосрочный приём антибиотиков, чтобы предотвратить повторение инфекций, но это может стать причиной ухудшения самочувствия ребёнка за счёт других симптомов (вызванных использованием антибиотиков), например рвоты.

Что мы сделали? Мы провели поиск в электронных базах данных и списках ссылок на литературные источники для выявления и обобщения результатов всех рандомизированных контролируемых испытаний, в которых лечение низкими дозами антибиотиков, назначаемых в течение не менее 2 мес, сравнивали с отсутствием лечения или с плацебо у детей с риском развития ИМС. Мы также нашли исследования, в которых сравнивали различные виды и дозы антибиотиков.

Kazan medical journal. 2019;100(4):727
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Adverse events in people taking macrolide antibio­tics versus placebo for any indication
 
Abstract

Вопрос обзора. Мы хотели выяснить, испытывают ли люди, принимающие антибиотики-макролиды, больше неблагоприятных событий, чем те, кто принимают плацебо.

Актуальность. Антибиотики-макролиды являются группой антибиотиков, которые обычно используются для лечения острых и хронических инфекций. Четырьмя наиболее часто используемыми макролидами являются азитромицин, кларитромицин, эритромицин и рокситромицин. Люди, принимающие антибиотики-макролиды, имеют риск проявления неблагоприятных событий, таких как тошнота, диарея и сыпь.

Kazan medical journal. 2019;100(4):727-728
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