BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 EDITORIAL BOARD Editor-in-chief Scientific editors Saldan Igor Petrovich Bryukhanov Valery Mikhailovich Doctor of Medical Sciences, Professor Doctor of Medical Sciences, Professor Deputy editor-in-chief Kolyado Vladimir Borisovich Zharikov Aleksandr Yuryevich Doctor of Medical Sciences, Professor Doctor of Biological Sciences, Associate Professor Lukyanenko Natalya Valentinovna Organizing editor Doctor of Medical Sciences, Professor Kiselev Valery Ivanovich Shoikhet Yakov Nahmanovich Corresponding member of the RAS, Doctor of Medical Corresponding member of the RAS, Doctor of Medical Sciences, Professor Sciences, Professor Executive editor Responsible for translation Shirokostup Sergei Vasilyevich Khavilo Marina Vadimovna Candidate of Medical Sciences, Associate Professor Editorial board Aliev Roman Tofikovich Mamaev Andrey Nikolaevich Doctor of Medical Sciences, Professor Doctor of Medical Sciences, Professor Alyamovsky Vasily Viktorovich Momot Andrey Pavlovich Doctor of Medical Sciences, Professor Doctor of Medical Sciences, Professor Bobrov Igor Petrovich Nadeev Aleksandr Petrovich Doctor of Medical Sciences Doctor of Medical Sciences, Professor Briko Nikolai Ivanovich Neimark Aleksandr Izrailevich Academician of the RAS, Doctor of Medical Sciences, Professor Doctor of Medical Sciences, Professor Voeyvoda Mikhail Ivanovich Neimark Mikhail Izrailevich Academician of the RAS, Doctor of Medical Sciences, Professor Doctor of Medical Sciences, Professor Voitsitsky Vladimir Evgenyevich Nikonorova Marina Anatolyevna Doctor of Medical Sciences, Professor Doctor of Medical Sciences, Associate Professor Gileva Olga Sergeyevna Onishchenko Gennady Grigoryevich Doctor of Medical Sciences, Professor Academician of the RAS, Doctor of Medical Sciences, Professor Guryeva Valentina Andreevna Oreshaka Oleg Vasilyevich Doctor of Medical Sciences, Professor Doctor of Medical Sciences, Professor Dygai Aleksandr Mikhailovich Osipova Irina Vladimirovna Academician of the RAS, Doctor of Medical Sciences, Professor Doctor of Medical Sciences, Professor Elykomov Valery Anatolyevich Pavlova Natalya Grigoryevna Doctor of Medical Sciences, Professor Doctor of Medical Sciences, Professor Zlobin Vladimir Igorevich Polushin Yury Sergeyevich Academician of the RAS, Doctor of Medical Sciences, Professor Academician of the RAS, Doctor of Medical Sciences, Professor Karbysheva Nina Valentinovna Rakhmanin Yury Anatolyevich Doctor of Medical Sciences, Professor Academician of the RAS, Doctor of Medical Sciences, Professor Klester Elena Borisovna Sokolova Tatyana Mikhailovna Doctor of Medical Sciences, Professor Doctor of Medical Sciences, Professor Kokhno Vladimir Nikolaevich Tokmakova Svetlana Ivanovna Doctor of Medical Sciences, Professor Doctor of Medical Sciences, Professor Kulchavenya Ekaterina Valeryevna Fadeeva Natalya Ilyinichna Doctor of Medical Sciences, Professor Doctor of Medical Sciences, Professor Lazarev Aleksandr Fedorovich Tseimakh Evgeny Aleksandrovich Doctor of Medical Sciences, Professor Doctor of Medical Sciences, Professor Larionov Petr Mikhailovich Tsukanov Anton Yuryevich Doctor of Medical Sciences, Professor Doctor of Medical Sciences, Professor Lepilov Aleksandr Vasilyevich Chumakova Galina Aleksandrovna Doctor of Medical Sciences, Professor Doctor of Medical Sciences, Professor Lobzin Yury Vladimirovich Shapovalov Konstantin Gennadyevich Academician of the RAS, Doctor of Medical Sciences, Professor Doctor of Medical Sciences, Professor Madonov Pavel Gennadyevich Shtofin Sergey Grigoryevich Doctor of Medical Sciences, Professor Doctor of Medical Sciences, Professor
Editorial office address: 656038, RF, Altai Krai, Barnaul, Lenina Prospekt, 40, office 220 Tel.: +7(3852) 566869. E-mail: [email protected]. www.bmn.asmu.ru Registration certificate SMI PI № FS 77 – 69379 from 6th of April 2017, issued by the Federal Service for Supervision of Communications, Information Technology, and Mass Media Russian version ISSN 2541-8475 English version ISSN 2542-1336 Founder and publisher Federal State Budgetary Educational Institution of Higher Education “Altai State Medical University” of the Ministry of Health of the Russian Federation (FSBEI HE ASMU of the Ministry of Health of the Russian Federation), 656038, RF, Altai Krai, Barnaul, Lenina Prospekt, 40. www.asmu.ru The opinion of the editorial board can disagree with the opinion of the authors. The reproduction of the published materials in any form without written permission of the editorial board is forbidden. In case of republication, the reference to the journal is obligatory. The materials, marked by sigh “R” are published for publicity purposes. The content of advertising materials is beyond the responsibility of the editorial board. Print. LLC “APOSTROF”. RF, Altai Krai, Barnaul, Partizanskaja Street, 17-5. Format: 60x90 1/8. Conventional printed sheets – 10. Circulation – 500 copies. Open price. BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 СОДЕРЖАНИЕ
Health sciences Experience of the accredited scientific laboratory for measuring physical factors of the environment B.A. Balandovich, N.Yu. Tulin, A.V. Kurochkina, A.O. Pasechenko...... 3
Antiseptic bandaging materials based on sphagnum I.Kh. Garayev, I.N. Musin, L.A. Zenitova...... 7
Current trends in changes of physical development indicators of children and adolescents I.P. Saldan, S.P. Filippova, O.V. Zhukova, O.I. Shved, A.P. Pashkov, N.Yu. Potseluev, K.V. Schulz, A.S. Nagornyak... 13
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Nucleophosmin/B23 oncoprotein in the clear-celled renal tumor: interaction with clinical and anatomical prognosis factors I.P. Bobrov, M.N. Myadelets, I.V. Klimachev, A.Yu. Dolgatov, A.V. Lepilov, T.M. Cherdantseva, N.G. Kryuchkova, A.M. Avdalyan, E.L. Lushnikova, O.P. Molodykh...... 23
Features of the effect of a complex herbal product on coagulation processes in toxic hepatitis in white rats E.A. Ubeeva, S.M. Nikolaev, D.N. Olennikov, I.P. Ubeeva...... 29
Clinical medicine Morphometric assessment of the therapy efficacy in patients with moderate acne M.L. Abdukhalikova, I.O. Malova...... 33
Prognostic importance of inflammation markers (c-reactive protein and interleukin-6) in patients with arterial hypertension N.V. Vostrikova, D.V. Fyodorov, E.E. Klimova, K.M. Bishevsky...... 39
Clinical and epidemiological features of digestive diseases in patients with comorbid pathology of respiratory and cardiovascular systems E.B. Klester, I.I. Belova, A.S. Balitskaya, K.V. Klester...... 42
Optimization of physiotherapy methods in patients with chronic prostatitis with concomitant benign prostatic hyperplasia I.A. Kolmatsui, E.F. Levitsky...... 48
Parenteral viral hepatitis in people with hemophilia: ways to solve the problem M.A. Nikonorova, N.V. Karbysheva, G.M. Kozhevnikova, A.N. Mamaev, V.V. Shevchenko, O.V. Beskhlebova...... 52
The course of deep vein thrombosis of lower limbs depending on the contents of d-dimers and c-reactive protein in the acute phase A.S. Petrikov, D.V. Dudin, L.N. Popkova, I.V. Volodin, Ya.N. Shoikhet...... 57
Community-acquired pneumonia in HIV-infected patients L.V. Puzyreva, M.A. Paneva...... 63
Change in the presepsin level in hemodialysis patients with pneumonia and sepsis E.A. Titova, A.R. Eirikh, Z.A. Titova, O.G. Zhgut, S.I. Ivanova, T.N. Zateeva, D.V. Petrova, E.M. Reutskaya...... 66
Requirements for publication in the «Bulletin of Medical Science» Journal...... 69 2 Health sciences BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
UDC 614.7: 658.56 doi.org:10.31684/2541-8475.2019.1(13).3-6 EXPERIENCE OF THE ACCREDITED SCIENTIFIC LABORATORY FOR MEASURING PHYSICAL FACTORS OF THE ENVIRONMENT Altai State Medical University, Barnaul B.A. Balandovich, N.Yu. Tulin, A.V. Kurochkina, A.O. Pasechenko
The article presents the first results of the work of the accredited scientific Laboratory of Labour Conditions Hygienic Monitoring of the Institute of Occupational Health and Industrial Ecology of ASMU on carrying out the measurements of environment physical factors. Particular attention is paid to the experience of introduction of original approaches in the study of physical and radiation factors of the environment, which allows adapting generally accepted methods to the conditions of the environment and obtaining reliable and objective results, as evidenced by interlaboratory comparative tests organized by an accredited provider. Key words: accredited laboratory, physical factors, environment, measurement means, measurement procedures, interlaboratory comparative tests.
Since the entry of the Scientific Test Laboratory of the Rubtsovsk, Zarinsk, Aleysk, Yarovoye, Gorno- Institute of Occupational Health and Industrial Ecology Altaysk, and 44 villages in 18 municipalities. A of ASMU of the Ministry of Health of the Russian total of 1,557 measurements of the energy flux Federation into the Register of Accredited Persons of density of electromagnetic radiation (EFD) of the the National Accreditation System on 16.07.2018 to the radio frequency range were carried out using the present time, the priority areas of laboratory research PZ-34 electromagnetometer with the AP3-34 SHF were the assessment of the impact of electromagnetic antenna-converter of isotropic directivity, as well radiation levels (EMR) from transmitting radio as associated antennas AP3-34E USW and AP3-34N engineering objects (TREO), radiation control of USW operating on a wireless principle (“bluetooth”) scrap metal vehicles leaving the Altai Krai, industrial and designed in a complex for measurements of control of harmful physical factors in the workplaces of the electromagnetic flux density, the mean square organizations in our region, as well as expert evaluation values of vorticity of the electric and magnetic of land and buildings upon completion of construction, fields in the mode of continuous generation (Figure major maintenance and reconstruction. All these areas 1). The use of these measurement means allowed to are provided with appropriate normative methods of conduct the research in the most significant control research of physical factors of the environment and the points: habitable territories of populated areas, production environment in the area of accreditation roofs, balconies, and higher floors of residential, of the Laboratory of Labour Conditions Hygienic public administration, and industrial buildings in Monitoring. At the same time, the application of accordance with MCI 4.3.1167-02 “Determination these methods in some cases requires non-standard of the energy flux density of the electromagnetic approaches aimed at the greatest possible adaptation field in the locations of radio facilities operating of the measurement means under use to the actual in the frequency range of 300 MHz – 300 GHz” conditions of the environment. [1], as well as MCI 4.3.1677-03 “Determination of levels of the electromagnetic field created by Materials and methods radiating technical means of television, FM radio The research of physical factors in laboratory broadcasting and base stations of land mobile radio activity priority areas was carried out in communication in the range of 27-2400 MHz in their cooperation with the accredited inspection body of locations” [2]. To clarify the azimuth of directivity the Institute of Occupational Health and Industrial of the electromagnetic radiation from generating Ecology according to the implemented laboratory antennas and to search for coordinates of control test quality management system, which includes points, GPS navigator GARMIN GPSMAP 64 was 5 main block processes: obtaining a motivated used in addition to the method (Figure 2), which task for conducting laboratory tests, drawing up allowed to record the sequence and location of a research program, preparation of measurement control points for the measurement of energy flux means, direct conducting of laboratory tests, density, to navigate the selected EMR study route, analysis and evaluation of the results obtained. to determine the height and coordinates of control During the stated period, 154 radio transmission points. The Leica DISTO – D110 laser range finder facilities located in 52 populated areas of the Altai was used to determine the distance from the radio Krai and the Altai Republic have been surveyed, transmission object. including the cities of Barnaul, Novoaltaysk, Biysk,
3 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
power measurements amounting to 22740 in the cities of Barnaul and Novoaltaysk, as well as at the Ust-Talmenskaya station and the Pospelikha station. In carrying out measurements of indicators of radiation safety of examined vehicles, we used a complex of dosimeter-radiometer DRBP- 03 with blocks BDG-01 and BDBA-02 for the study of gamma, beta and alpha radiation using an extension stem with scintillation detector, as well as with additional visual and audio-diagnostics of possible radioactive sources (Figure 3). In addition, to achieve the necessary accuracy of measurements and to carry out in-laboratory control, a high-precision gamma radiation dosimeter DKS-AT1123 working in search and pulse mode was used, as well as the dosimeter-radiometer DKS-96 with the detection block BDMN- Figure 1. The PZ-34 electromagnetometer operating on a wireless 96 (Figure 4). principle, with 3 antenna-converters. According to the results of studies of indicators of radiation control of vehicles, no radiation anomalies and excess hygienic standards were revealed. During measurements, background values of the equivalent dose rate (EDR) of gamma radiation on the ground fluctuated within the range of 0.11–0.14 μSv/h, which corresponded to the long-term data of radiation condition monitoring in the Altai Krai during 2008–2018. With that, the values of EDR gamma radiation of the external surface of loaded vehicles were 0.12–0.18 μSv/h, which did not exceed the hygienic standard (0.2 μSv/h over background) in accordance with SanPiN 2.6.1.993-00 “Hygienic requirements to ensure radiation safety in the preparation and sale of scrap metal” [4]. One of the main research directions of the Institute of Occupational Health and Industrial Ecology at present is the ecological and hygienic assessment of physical environmental factors (in particular, noise) in the allocation of Figure 2. GPS navigator GARMIN GPSMAP 64 as an ancillary device land for the construction of residential, for measuring electromagnetic radiation from TREO. public and industrial buildings. In total, 288 measurements of equivalent and Results and discussion maximum noise levels were conducted One of the most important areas of the laboratory for this direction in accordance with GOST 23337- work is the radiation control of scrap metal vehicles 2014 “Noise. Methods of noise measuring in the leaving the Altai Krai and going to the largest iron- habitable territory and in the premises of residential and-steel works of the Russian Federation. During and public buildings” [5]. Measurements were the stated period of time, in accordance with the carried out both in the day (from 7-00 to 23-00) guidelines of the Federal Service for Supervision and in the night (from 23-00 to 7-00) in the cities of Consumer Rights Protection “Scrap metal of Barnaul and Novoaltaysk in the territories radiation monitoring” [3], 379 scrap metal vehicles adjacent to the railway station and the airport. For were examined (railway cars, containers, cars) with noise measurements, the integration phonometer- a total number of gamma radiation dose equivalent analyzer of the 1 class spectrum Ecophysika- 4 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
110A was used, designed for measurements of mean square, equivalent and peak sound levels, as well as for recording sound pressure levels in octave frequency bands. In order to adapt the device to the real conditions of the measurement environment and to comply with the methodology, a special tripod was applied, allowing to fix the device at a height of 1.2±0.1 m above the surface level of the measuring area of the land plot, as well as a special windproof device for the phonometer microphone due to the observed wind speed of 1.2 to 4.5 m/s (Figure 5). In analyzing the results of measurements of noise levels, it should be noted that during the day, equivalent sound pressure levels ranged from 40.5±0.7 dBA to 45.7±0.9 dBA for railway noise and from 40.6±0.8 dBA to Figure 3. The dosimeter-radiometer DRBP-03 43.9±0.7 dBA for air transport noise, which met with blocks BDG-01 and BDBA-02. hygienic standards. At the same time, during the night, equivalent noise levels exceeded the hygienic standard by 3.5–9.3 dBA for the railway transport and by 3.8–9.4 dBA for the air transport, which allowed to offer customers a complex of noise protection measures related both to the installation of noise barriers and further development of geoinformational systems of the modern city vibroacoustic emission.
Conclusion Application of certified methods of measurement of physical environmental factors in modern conditions of compliance with the laboratory test quality management system often requires non-standard approaches, which allow, on the one hand, to adapt the Figure 4. The dosimeter-radiometer DKS-96 with measurement means to the environment the neutron radiation detection block BDMN-96. objects surveyed as much as possible, and on the other hand, to ensure accuracy, traceability, objectivity, and reliability of scientific laboratory tests. The correctness of the chosen approach is confirmed by a successful round of interlaboratory comparative tests (ICT) of physical environmental factors, which the Laboratory of Labour Conditions Hygienic Monitoring passed from 18.10.2018 to 25.02.2019 with the participation of the accredited ICT provider – Ural Research Institute of Metrology. Conflict of interest. The authors declare that there is no conflict of interest.
References: 1. MCI 4.3.1167-02 “Determination of the energy flux density of the electromagnetic field in the locations of radio facilities operating in the frequency range of 300 MHz – 300 GHz”. Figure 5. Location of the Ecophysika-110A spectrum phonometer- 2. MCI 4.3.1677-03 “Determination of analyzer when measuring in the habitable territory during levels of the electromagnetic field created by the night period. radiating technical means of television, FM 5 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 radio broadcasting and base stations of land mobile trial Ecology, Altai State Medical University, Bar- radio communication in the range of 27-2400 MHz naul. in their locations”. 656038, Barnaul, Lenina Prospekt, 40. 3. MCI 2.6.1.1087-02 “Scrap metal radiation Tel.: (3852) 566898. monitoring”. E-mail: [email protected] 4. SanPiN 2.6.1.993-00 “Hygienic requirements to ensure radiation safety in the Kurochkina Anna Vladimirovna, laboratory assis- preparation and sale of scrap metal”. tant of the Laboratory of Labour Conditions Hy- 5. GOST 23337-2014 “Noise. Methods of gienic Monitoring of the Institute of Occupational noise measuring in the habitable territory and in Health and Industrial Ecology, Altai State Medical the premises of residential and public buildings”. University, Barnaul. 656038, Barnaul, Lenina Prospekt, 40. Contacts Tel.: (3852) 566898. Corresponding author: Balandovich Boris E-mail: [email protected] Anatolievich, Doctor of Medical Sciences, Associate Professor, Head of the Institute of Occupational Pasechenko Alena Olegovna, laboratory assistant Health and Industrial Ecology, Altai State Medical of the Laboratory of Industrial Ecology, Population University, Barnaul. Health Risk Hygienic Assessment and Occupation- 656038, Barnaul, Lenina Prospekt, 40. al Medicine of the Institute of Occupational Health Tel.: (3852) 566898. and Industrial Ecology, Altai State Medical Univer- E-mail: [email protected] sity, Barnaul. 656038, Barnaul, Lenina Prospekt, 40. Author information Tel.: (3852) 566898. Tulin Nikolai Yurievich, junior research associate E-mail: [email protected] of the Institute of Occupational Health and Indus-
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UDC 615.28:615.322 doi.org:10.31684/2541-8475.2019.1(13).7-12 ANTISEPTIC BANDAGING MATERIALS BASED ON SPHAGNUM Kazan National Research Technological University, Kazan I.Kh. Garayev, I.N. Musin, L.A. Zenitova
The research focuses on preclinical studies of new antiseptic surgical bandaging material with a high absorption capacity based on plant raw material — sphagnum. In folk medicine, sphagnum is known as good antiseptic material. Partisans used it particularly actively in marshy forests of Belarus saving the wounded from death during the Great Patriotic War. Despite the fame in folk medicine, until now there is no industrial production of bandaging material on its basis. The possibility of practical solution of the issue of import substitution of bandaging materials with the help of this study confirms its significance. Besides, in literature, there is virtually no information on physical and chemical characteristics of sphagnum and reasons for its antiseptic properties. In this study, the composition of compounds giving antiseptic properties to sphagnum was investigated with the use of modern instrumental methods. The content of trace elements in the sphagnum composition was determined. A prototype of bandaging material was made, its ability to show antiseptic properties towards trace elements and fungi of Staphylococcus aureus, Actinomyces sp, Candida spp., E.Сoli and Bacillus сereus was assessed. The conducted studies showed the fundamental possibility of creating new surgical bandaging materials on the basis of sphagnum with better performance characteristics in comparison with cotton-gauze bandaging materials. Key words: antiseptics, bandaging material, trace elements, analysis.
Post-operative daily wound dressing causes trace elements were found in sphagnum, including unpleasant procedures related to irritation and phosphorus, silicium, aluminium, which stimulate injury of regenerating tissues resulting in bandage growth and development of bone, connective and becoming a painful procedure for a patient. In epithelium tissues, as well as facilitate recovery this regard, it is necessary to search for bandaging and regeneration processes. materials having antiseptic properties for a long time and capable of absorbing wound effluents Materials and methods in large quantities. With the presence of such In order to find out the presence of organic bandaging materials, there is no need for their substances giving antiseptic activity to sphagnum, frequent daily replacement. it was extracted with toluene (C H -CH ), carbon
The aim of this study is to check the possibility tetrachloride (CCl4), water (Н2О), acetone (С3Н6О), ₆ ₅ ₃ of creating antiseptic bandaging materials of and ethyl alcohol (С2Н6О), and studies of the high absorption capacity based on domestic raw composition of these extracts were carried out. materials. Sphagnum plant material was used Extraction was carried out on the Soxhlet extractor as the main substance. We studied chemical at a temperature of 80–100оС for 3 hours. The ratio compositions of sphagnum extracts using organic of sphagnum to solvents amounted to 1:20 g/g. The solvents, mass-spectrometric and IR-spectrometric resulting extract was filtered through a paper filter methods. With that, the presence of various classes and used for testing. of compounds having antiseptic properties was The identification of substances extracted found. Bandaging materials were made and by the above solvents was carried out using tested for antiseptic activity towards various mass spectroscopy in combination with gas ion microorganisms. In addition, it was found that chromatography on the MAESTRO GH 7820 with long (over 10 years) storage the bandaging chromatograph [1, 2]. IR-spectrums were fixed on material does not lose its antiseptic properties. the JASCO FT/IR-6800 IR-Fourier spectrometer [3]. Test samples are made by needle punching The sphagnum extract was obtained on the method with the punch frequency of 100–120 Soxhlet extractor. The ratio of sphagnum : solvent punctures per 1 cm2 in the form of three-layer = 1:20 g/g. The extraction was conducted while cloth, the upper and lower layers of which consist boiling of solvents for 3 hours. The solution was of synthetic fibre, and the middle layer contains filtered though a paper filter and studied with mass sphagnum dried and crushed to sizes of 50–150 spectroscopy and IR-spectroscopy for the presence of µm. The method of determining the sensitivity organic substances in the studied sphagnum extracts. of microorganisms to antimicrobial compounds Then, studies on the antimicrobial effect of by the degree of their growth delay was used as pure sphagnum and experimental bandaging a method for assessing antiseptic properties of material were carried out. For this purpose, we experimental bandaging materials. The relative used methods based on the ability of antibiotics content of trace elements in sphagnum was to diffuse in the microbial environment and to determined by spectral method. In this respect, 23 delay growth or even kill microorganisms in the
7 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 antiseptic diffusion zone [4]. The microorganisms The presence of trace elements in sphagnum of Staphylococcus aureus, Actinomyces sp, Candida and their relative content were determined on the spp., E.Сoli, and Bacillus сereus were used as test SPM-35 X-ray multichannel spectrophotometer. objects. For spectral studies, samples in the amount The studies were carried out on samples made of 10 g were gradually heated for 30 minutes to by needle punching method, they consist of a temperature of 1100оС and calcinated at this three layers: the upper and lower layer made of temperature for 30 minutes in a muffle furnace. synthetic fibre, the middle layer made of shredded The resulting ash was examined for the presence sphagnum 4-5 mm thick [5]. of trace elements. To determine the effect of sphagnum on the selected test object, the following methods were Results and discussion used: streaking method, disk diffusion test, and The fine interpretation of mass spectrograms of volume displacement method. Data on growth sphagnum extracts in toluene, carbon tetrachloride, suppression in the sphagnum presence were ethyl alcohol, and water showed the presence of determined in two days at a temperature of 37°С. such substances as ethyl benzene, benzyl carbinol, The content of trace elements in sphagnum was acetophenone, phenylmethanol, benzene, phenol, identified through dividing the stems into three acetic acid, styrene, etc. in tangible quantities. sections, as shown in Figure 1. These substances contain aromatic nuclei or alcohol hydroxyl in the molecular structure, which give sphagnum antiseptic properties (Table 1). We did not consider in medical practice the presence of small amounts of hydrocarbons not being antiseptics. It can be seen that sphagnum extracts contain compounds with aromatic rings being good antiseptics in medical practice. For additional clarification of the chemical structure of macromolecular objects of sphagnum extracts, their IR-spectroscopy [3] was carried out on the FT-801 spectrometer. The frequency interpretation is presented in Table 2.
Figure 1. Division of the sphagnum stem for the studies on trace elements. Table 1 Results of mass spectroscopy of sphagnum extracts in solvents
Content of substances in solvents, % Frequency Component С6Н5СН3 CI4 H2O С2Н5ОН
8.593 6.06 – – – Ethyl benzene: C8H10
13.282 0.30 – – – Benzene, (1-methylbutyl): C11H16
617.904 0.46 – – – Acetophenone: C8H8O
18.392 5.32 – – – Phenylmethanol: C8H10O
9.708 – 0.29 – – Ethyl benzene: C8H10
19.616 – 0.26 – – Phenylmethanol: C8H10O
2.001 – – 0.03 – Phenol: C6H6O
2.208 – – 0.02 – Glycolaldehyde dimer: C4H8O4
2.302 – – 0.06 – Acetic acid: C2H4O2
2.843 – – 0.02 – Acetol: С3Н6О2 1-propanol: C H O 1.941 – – – 7.49 3 8 Styrene: C H 10.126 – – – 7.04 8 8
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Table 2 Frequencies of IR-spectrum of sphagnum extract in solvents
Frequency v, Compound classes in toluene cm-1
1740.94 Limit aliphatic -СH2 -CHO, cyclopentanone, alpha-halogen acids СН-СООН, carboxylic
acid anhydrides -СО-О-СО- vc=o,
1581.26 Polyenes, primary amines NH2, pyridines and quinolines, pyrimidines and purines 1516.20 Pyrimidines and purines, thiophenes
1463.65 Nitrosamines R2 N-N=O, boron compounds BCH3 B-Ar, 1160.27 Propionates, higher esters, phosphoric acid esters (RО)3 P++ O- 1106.86 Tertiary alcohols, aromatic acid esters, thiocarbonyl compound derivatives, benzene compounds 1023.24 Aromatic and vinylic =С-О-С-, aliphatic amines, sulfur-containing functional groups 722.78 Alkanes, sulfur-containing functional groups
Compound classes in CCl4 + 3306.80 Primary amines R-NH , secondary amines R N-H, amine salts NH , boron compounds BOH B–H-B 2 2 4 2922.63 Sulfur-containing functional groups R-SO-OH 2643.25 Boron compounds, boranes R-BH 2
1740.94 Limit aliphatic –СH2 –CHO, cyclopentanone, alpha-halogen acids СН-СООН, carboxylic acid anhydrides -СО-О-СО-v , c=o 1581.26 Polyenes, primary amines NH , pyridines and quinolines, pyrimidines and purines 2 1516.20 Pyrimidines and purines, thiophenes
1463.65 Nitrosamines R2 N-N=O, boron compounds BCH3 B-Ar, 3 + - 1160.27 Propionates, higher esters, phosphoric acid esters (RО) P + O 1106.86 Tertiary alcohols, aromatic acid esters, organic compound halogen derivatives, thiocarbonyl compound derivatives, benzene compounds, organophosphorous compounds 1023.24 Aromatic and vinylic =С-О-С-, aliphatic amines, sulfur-containing functional groups 722.78 Alkanes, sulfur-containing functional groups
The obtained data indicated that sphagnum various microorganisms. The effect of test contains in its composition a wide range of various bandaging materials on various microorganisms compound classes showing antiseptic properties was examined through different methods: towards various groups of microorganisms. These streaking method, disk diffusion test, and are organochlorine and aromatic compounds, volume displacement method [4]. The results of organophosphorous, primary and secondary characteristics of bandaging material test samples aminocompounds, various alcohols. Data of IR- are presented in Table 3. spectrums of sphagnum extracts give a wider range The made material is a composite of synthetic of qualitative composition of substances compared fibre for forming the shape and of sphagnum as the to mass spectroscopy. The results of studies show main antiseptic component with high absorption the possibility of using sphagnum as an antiseptic capacity (Table 3, exp. 1, 2). With the increase in component of bandaging materials. the content of sphagnum, its absorption capacity Using sphagnum finely crushed to the sizes of naturally increases (exp. 3–8). The made bandaging 50-150 µm, we made test samples of bandaging material was further tested for antiseptic activity, material and tested for antiseptic activity towards the results are presented in Table 4.
9 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
Table 3 Composition and physical and chemical characteristics of samples
No. of Composition, % of mass Water absorbing Density, g/ Ash content, % experiments synthetic fibre sphagnum capacity, g/g cm3 1 - 100 16–18 1400 3.14 2 100 - 3–4 1800 4.1 3 35 65 17.1 1800 - 4 45 55 14.5 1840 - 5 50 50 14.0 1810 - 6 70 30 11.0 1740 - 7 85 15 5.2 1700 - 8 90 10 4.7 1600 - Table 4 The assessment of antiseptic activity of bandaging material samples towards various microorganisms
Composition of samples, % Microorganism growth suppression, mm of mass No. of Staphyiococcus aureus Candida spp. Astinomyces sp. experi- ments syn- sphag- volume volume volume thetic disk dif- disk disk num streaking displace- streaking displace- streaking displace- fibre fusion diffusion diffusion method ment method ment method ment test test test method method method 1 35 65 45.0 63.9 16.7 13.1 31.1 14.6 10.4 83.1 86.6 2 45 55 45.0 58.9 13.7 10.8 27.5 14.1 9.8 82.8 85.5 3 50 50 45.9 56.7 15.2 9.5 25.5 13.5 9.4 80.1 85.1 4 70 30 43.2 46.8 6.2 4.7 18 12.7 4.7 76.1 83.1 5 85 15 43.2 38.7 1.5 0.7 11.1 12.7 5.7 72.9 81.5 6 90 10 41.4 36.0 0.9 0.3 9.0 12.6 5.4 72.0 81.0
With data presented in Table 4, it was revealed spp. genus shows that the activity decreases by 2-3 that through all testing methods sphagnum times. shows its antiseptic activity. Furthermore, the It was interesting to study the ability of streaking method and disk diffusion test were antiseptic action of the made bandaging material more effective against strains of Staphylococcus in the process of long-term storage and under aureus and Astinomyces sp. Growth suppression temperature. The test results are presented in Table of Staphylococcus aureus cultures was 45, 63.9, and 5. Antiseptic activity was tested towards E.Сoli and 86.6 mm respectively. The assessment of sample Bacillus сereus microorganisms. antiseptic activity towards fungi of the Candida Table 5 The assessment of antiseptic activity of long-storage samples towards E.Сoli and Bacillus сereus
Microorganism growth suppression, mm Object under study E.Сoli Bacillus сereus Sphagnum (10-year-old) 13 10 Bandaging material 15 14 Fresh sphagnum 15 15 Dried sphagnum * 12 7 * drying was made at a temperature of 100-110°C for 3 hours.
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According to the results of studies, it was antiseptic activity towards this strain. Sphagnum revealed that the sensitivity of sphagnum over drying is likely to lead to the removal of some low- time (more than 10 years) towards the E.Сoli strain boiling and more volatile compounds and, as a does not weaken. Sphagnum is active towards consequence, to the decrease in antiseptic activity this strain through the non-woven material as of the bandaging material almost twice (Table 5). well as fresh moss. As for Bacillus сereus bacteria, The assessment of presence of trace elements in samples after 10-year storage show slightly less sphagnum is given in Table 6. Table 6 Results of sphagnum X-ray spectral analysis method (according to Figure 1)
Relative metal content, % Metal samples upper part middle part lower part whole stem Mg 5.84 5.80 5.70 5.90 Al 3.50 3.45 3.6 3.60 Si 29.99 18.23 3.23 19.0 P 2.30 3.07 5.28 4.50 S 2.11 3.07 4.19 6.40 Cl 0.55 3.36 2.59 3.30 K 13.29 40.13 68.34 30.0 Ca 15.11 17.86 10.04 14.0 Ti 0.91 0.47 0.16 0.50 V 0.02 0.009 0.007 - Cr 0.04 0.02 0.005 0.04 Mn 1.98 1.86 1.51 2.30 Fe 22.94 10.71 3.49 21.0 Ni 0.05 0.03 0.02 0.04 Cu 0.08 0.07 0.07 0.07 Zn 0.72 0.58 0.50 0.60 Ga 0.002 - - - Se - - 0.001 - Br 0.03 0.03 0.02 - Rb 0.07 0.16 0.38 0.1 Sr 0.15 0.12 0.09 0.2 Ba 0.19 0.16 0.05 0.5 Pb 0.12 0.06 0.02 0.09
According to the data obtained, it has been 3. It was found out that sphagnum contains found that sphagnum contains a large number of a large number of trace elements, among which trace elements that contribute to wound healing. there are such elements as phosphorus, silicium, Such elements include phosphorus, silicium, aluminum that contribute to the acceleration of aluminum, etc. regeneration of fresh tissues in wounds. Conflict of interest. The authors declare that Conclusions: there is no conflict of interest. 1. Studies have shown that sphagnum contains a sufficient amount of substances References: potentially capable of antiseptic action on various 1. Klyuev N.A., Brodsky E.S. Modern conditionally pathogenic microorganisms. methods of mass spectrometric analysis of organic 2. The possibility of manufacturing new compounds. Russian Chemical Journal. 2002; 46(4): surgical bandaging materials with antiseptic 57–63. properties and with high absorption capacity on 2. Averko-Antonovich I.Yu., Bikmullin R.T. domestic raw materials is shown. Methods of studying the structure and properties of polymers. Kazan, 2002: 604. 11 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
3. Vasiliev A.V., Grinenko E.V., Shchukin 420015, Kazan, ul. K. Marxa, 68. A.O. Infrared spectroscopy of organic and natural Tel.: (843) 2314336. compounds. SPb., 2007: 54. E-mail: [email protected] 4. GOST R ISO 20776-1-2010. Clinical laboratory tests and diagnostic test systems in Author information vitro. Study on sensitivity of infectious agents and Musin Ildar Nailevich, Candidate of Technical assessment of functional characteristics of products Sciences, Head of the Department of Medical for study of sensitivity to antimicrobial agents. Part Engineering, Kazan National Research 1. Reference method of laboratory research of activity Technological University, Kazan. of antimicrobial agents against fast-growing aerobic 420015, Kazan, ul. K. Marxa, 68. bacteria causing infectious diseases. Intr. 01. 03. 2012. Tel.: (843) 2314383. M.: Standartinform, 2012: 23. E-mail: [email protected] 5. Mandreykina A.A., Garayev I.Kh., Musin I.N., Vdovina T.V. Development of a new antiseptic surgical Zenitova Lyubov Andreevna, Doctor of Technical bandaging material based on sphagnum. Bulletin of Sciences, Professor of the Department of Synthetic Technological University. 2017; 20(23): 107-110. Rubber Technologies, Kazan National Research Technological University, Kazan. Contacts 420015, Kazan, ul. K. Marxa, 72. Corresponding author: Garayev Ilgiz Khazievich, Tel.: (843) 2314214. Doctor of Technical Sciences, Associate Professor, E-mail: [email protected] Head of the Laboratory of the Department of Medical Engineering, Kazan National Research Technological University, Kazan.
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UDC 613.955/.96 doi.org:10.31684/2541-8475.2019.1(13).13-19 CURRENT TRENDS IN CHANGES OF PHYSICAL DEVELOPMENT INDICATORS OF CHILDREN AND ADOLESCENTS Altai State Medical University, Barnaul I.P. Saldan, S.P. Filippova, O.V. Zhukova, O.I. Shved, A.P. Pashkov, N.Yu. Potseluev, K.V. Schulz, A.S. Nagornyak
The data of research literature in Russian and English in electronic search systems eLIBRARY, PubMed, international databases Scopus, Web of Science for the period of 2005–2018 are summarized and analyzed concerning the state of physical development of children and adolescents, its determinants and assessment methods in the current context. The following is presented: the age and sex standards of the physical development of children and adolescents should be regional; dependence of physical development indicators on environmental and socio-economic factors affecting the territory of residence; the need for continuous monitoring of the physical development of children and adolescents with a recheck of regional standards taking into account the ongoing processes of acceleration and deceleration. Key words: physical development, risk factors, children and adolescents, acceleration, deceleration, nutritional status, obesity, nutrition.
Physical development (PD) assessment is an and adolescents. Works with low citation rate, integral part of the study of the health status of the with a small number of references were excluded child population, as it clearly reflects the impact of from the sample group. Further, studies were environmental factors, lifestyle, and educational selected that examined the relationship between process on the body [1, 2, 3, 4, 5, 6, 7, 8, 9, 10]. the physical development indicators of children PD includes a set of indicators: somatometric, and adolescents and the factors influencing them, somatoscopic, and physiometric, among which so that the nature of identified problems could the most commonly used for the assessment are then be determined (326 works). The publications the following: body length and weight, chest were checked against the research objective, and circumference [11, 12, 13, 14]. the sample group was reduced to 151 papers. The In this case, the age and sex standards of detailed study of the materials resulted in a further PD can be only regional. Evidence in favour of reduction to 73 works, which have been included this is the research which showed statistically in this review. significant differences in schoolchildren body length and weight in five regions of Russia (the Results and discussion cities of Moscow, St. Petersburg, Rostov-on- Methods for assessing physical development Don, Arkhangelsk, Omsk). Besides, data on the of children and adolescents include the method change of body sizes of schoolchildren in Moscow of sigmal deviations, Z-score assessment, method and the boost of biological development were of assessment on regional modified scales of obtained, which probably indicates the activity of regression of body weight on body length, centile acceleration [1, 6, 9, 15]. method, as well as combined techniques [11, 14]. To All this led to the interest in studying and collect somatometric data, there are two methods: generalizing the data of research literature on the individualizing and generalizing. In order to obtain state of physical development of children and regional age and sex standards, comatometric data adolescents, factors determining it, and methods of collected by generalizing method are used [11]. assessment in the current context. In view of the fact that age and sex standards of The research objective is to generalize and physical development can be only regional, studies analyze the data of research literature on the state of often use the method of assessment on regional physical development of children and adolescents modified scales of regression of body weight on in the current context. body length [1, 6, 10, 13, 14, 15, 16, 17, 18, 19]. So, to assess the changes in PD of schoolchildren Materials and methods in the city of Kiev for the period of 1996–2008, The study was conducted on the basis of anthropometric studies were carried out, which a review of research literature in Russian and included measurement of body weight and length, English in electronic search systems eLIBRARY, chest circumference, and assessment according PubMed, international databases Scopus, Web of to Ukrainian intergroup assessment tables Science for the period of 2005–2018. The selection of (regression scales on body length) [17]. At the publications was based on key words that reflected same time, further study on this issue was carried the main trends in physical development of children out in the direction of comparative assessment of 13 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 functional systems of the organism of pupils. With As for the factors influencing the PD, the that, the study of physiometric indicators of PD of analysis of the influence of the educational process schoolchildren in Kiev and Moscow showed their organization in modern schools on the physical statistically significant differences, such as, for development of children and adolescents allowed example, the uneven rate of development of the to identify a number of intraschool environment main functional systems: muscular and respiratory factors, such as an increase in the study load through [17, 18]. the intensification of the educational process, lack When studying the dynamics over time of motor activity, psycho-emotional tension, side of somatometric indicators of 8–16 years old effects of technical training aids use [23]. schoolchildren in the city of Gomel for the In studying the quality of life of children of period from 1925 to 2010–2012, in 2010–2012, groups of medical and social risk, it was established the examination (body length and weight, chest that the weight in the majority (65.5%) does not circumference) of 8–16 years old schoolchildren correspond to height and age, insufficient weight was carried out. The data obtained by other was in the largest share of children surveyed researchers in 1925 and 1973 were used to assess (58.8%) [24]. the dynamics of studied indicators over time. It is When studying the state of health of the child found that city schoolchildren at the beginning of population in reference to the physiological full the 21 century are characterized by higher rates value condition of nutrition, it was revealed that of development of indicators in comparison with insufficient calcium intake to 40% in relation to the the peers of 1925 and 1973. Sexual dimorphism age norm is accompanied by lower indicators of during acceleration is manifested by increased body length and weight [25, 26]. body length and weight in boys and asthenization When studying the impact of actual nutrition in girls. The indicators of chest circumference of on the health of children, the indicators of PD and boys and girls surveyed at the beginning of the nutritional status in general are assessed [2, 27, 21 century are significantly higher compared to 28, 29, 30, 31, 32, 33, 34, 35, 36]. In their research, their peers of 1925. The overall increase in body Zh.Yu. Gorelova, M.I. Bakanov et al. [37, 38, 39, 40, length within the studied age range is higher 41] presented the results of the use of a specialized in the surveyed boys and girls compared to the product in school meals for the correction of data of 1925 and 1973, and in indicators of body nutritional disorders in schoolchildren (weight weight and chest circumference – in boys and girls normalization, nutritional status) during the examined in 1973 in comparison with their peers educational process. The obtained results confirm of 1925 and 2010–2012. Schoolchildren in Gomel laboratory (biochemical studies of free amino at the beginning of the 21 century demonstrated acids (AA) spectrum excretion in schoolchildren the presence of acceleration of development of before and after taking the product) and somatometric indicators compared to the peers of psychophysiological studies (assessment of 1925 and 1973 [20]. emotional state according to the method of HAM) It is important to take into account the [37, 38, 39, 40, 41]. processes of acceleration occurring from one In the studies, N.P. Setko, E.V. Bulycheva et al. decade to the next and to review the standards of [42] used and analyzed the data on nutritional status, physical development in each region in due time. functional state of musculoskeletal, respiratory, Recently, both domestic and foreign experts agree central nervous systems as the indicators to assess that the rate of acceleration is slowing everywhere. the effectiveness of implementation of the project The highest peak of acceleration in Russia was for improving school nutrition in the city of observed in the mid-70s of the last century, then (in Orenburg. As a result, it was found that measures the 80s) there was a clear tendency to stabilize the to optimize school meals led to improvement of process of acceleration of growth and development indicators of the nutritional status and functional (stagnation), later on, gradual change of it by condition of pupils [42]. deceleration occurred in certain regions and major PD indicators informatively reflect the industrial cities [21]. conformity of the diet to the needs of the body: the In the city of St. Petersburg, indicators of PD body mass index (BMI) indicator is more dependent of 7–17 years old schoolboys were studied, the on body weight than on height, and its assessment assessment of the level and harmony of PD was reveals overweight or obesity. In addition, it is conducted in accordance with the standards of recommended to measure the thickness of skin the World Health Organization (WHO) (“WHO folds of fat above triceps as an indicator of body Growth Reference 2007”). The asymmetry of body fat depot, shoulder circumference [6, 26, 29, 32, 35, length indicators with a significant representation 43, 44, 45, 46, 47, 48]. For the correct use of BMI of tall schoolchildren (1.9–10.9%) was established. in childhood, WHO recommends to use a special The surveyed schoolchildren revealed a high level method of assessing physical development of of disharmony variants of PD caused by overweight children and adolescents (BMI-for-age 5-19 years) and obesity (16.4–38.2%) [22]. [13, 14, 19, 46, 48, 49, 50, 51]. 14 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
According to L.Yu. Volkova, O.N. Komarova, and adolescents. According to studies carried out I.Ya. Kon’ [27], it is established that for mass by I.A. Makhrova, I.N. Ivashchenko, the choice of screening diagnostics of overweight and obesity in proportionate clothing corresponding to the basic the conditions of organized groups, it is expedient hygienic principles for these children is limited. to use anthropometric and somatometric methods. The study of the design features of clothing, the The works on the study of peculiarities of analysis of the properties of materials, as well as the nutritional status of children in different the lifestyle of such children are relevant [53]. environmental conditions is of interest. Studies conducted by S.K. Bermagambetova, T.K. Karimova Conclusion et al. showed that the nutritional status of children Analysis of literature sources shows, first, the has its peculiarities by indicators of physical dependence of indicators of physical development development, hemoglobin level, serum iron, and of children and adolescents on ecological, social, ferritin in different ecological regions [52]. and economic factors affecting on the territory of At present, the problem of obesity in children residence; second, the need for constant monitoring is a significant part of the literature on child and of PD of the younger generation with a recheck adolescent health. In this context, the prevalence of of regional standards every decade taking into obesity among the child population is of concern account the time trend and the ongoing divergent to both domestic and foreign experts. According acceleration and deceleration processes [19]. to numerous research, the number of overweight Thus, due to the fact that in Altai Krai tables children in Europe increases rapidly and has reached (regression scales on body length) on the research high indicators [2, 27, 44, 50, 53, 54, 55, 56, 57, 58, 59, data of Professor L.N. Klimenov of 1989 are used to 60, 61, 62, 63, 64, 65, 66, 67]. In literature, there are assess physical development of the child population indications that almost 60% of adults began obesity aged from 1 month to 14 years, it seems reasonable in childhood and adolescence [43, 66, 67, 68]. to carry out appropriate studies of anthropometric A number of works are devoted to the study indicators of children and adolescents on the of this problem in foreign literature. In Brazil, territory of Altai Krai in present. overweight among children is one of the major Conflict of interest. The authors declare that public policy issues. However, among children there is no conflict of interest. who lived and studied in rural areas, there is a lower prevalence of obesity, and none of the rural References: children were underweight. The authors note 1. Baranov A.A., Kuchma V.R., Skoblina N.A. that this may be due to low social and economic Physical development of children and adolescents at the conditions and more intense physical activity in turn of Millennium. M., 2008: 216. their daily lives [69]. According to the national 2. Baskakova E.Yu. Peculiarities of physical literature, obesity is common in 5.5% of children development, actual nutrition and metabolic disorders living in rural areas and in 8.5% of urban children in children depending on the character of feeding in in the Russian Federation [44, 55]. infancy: author’s abstract of the Candidate of In Turkey, according to a study, the prevalence Medical Sciences. 14.01.08. Nizhny Novgorod, of obesity among school-aged children was 10.3% 2012: 26. and overweight was 22.4%. Among adolescents, 3. Zul’karnaeva A.T., Povargo E.A., the number of obese boys is statistically higher Zul’karnaev T.R., Ovsyannikova L.B., Agafonov than girls. Among schoolchildren who did not have A.I. Influence of certain factors on the state of breakfast, the percentage of obesity was higher health of schoolchildren. Population Health and Life than in a group that ate regularly 3 times a day. The Environment. 2012; 8: 29-31. prevalence of obesity in adolescents who watch TV 4. Gapparov M.M., Pervova Yu.V. Influence of for more than 3 hours a day was higher than in the nutrition structure and environment on the specific rest [56]. Similar data are presented by domestic resistance of the organism of children and their authors: the absolute majority of overweight and physical development. Problems of Nutrition. 2005; obese children spend more than 3 hours a day on 1: 33-35. TV and computer [66]. 5. Kuchma V.R., Rapoport I.K. Strategy of Doctors of various specialties as the causes of WHO and review of international experience such multi-factor disease as obesity include the of prevention of diseases and promotion of role of malnutrition and lifestyle [44, 60, 66, 70, health of children and adolescents in educational 71, 72, 73]. It is noted that parents of children with institutions. Public Health and Prevention of Diseases. overweight are not sufficiently literate in matters 2008; 1: 40-45. of a healthy lifestyle and overestimate physical 6. Kuchma V.R., Skoblina N.A. Evaluation activity of children, underestimating the caloric comprehension of the children and adolescent content of consumed food [44, 56, 66]. physical growth in the course of the population Obesity problems in childhood have led to research. Current Pediatrics. 2008; 7(1): 26-28. research on clothing hygiene for obese children 15 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
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Home boys with an average body mass index compared Food Environment, Dietary Intake, and Weight with parents of boys with a high body mass index. among Overweight and Obese Children in Journal of the American Dietetic Association. 2005; Southern Appalachia. Southern medical journal. 105(9): 1411-1416. 2013; 106(10): 550-557. 46. Dietz WH, Bellizzi MC. Introduction: the use 60. Malik VS, Schulze MB, Hu FB. Intake of sugar- of body mass index to assess obesity in children. sweetened beverages and weight gain: a systematic Am. J. Clin. Nutr. 1999; 70 (1):123–125. review. Am J Clin Nutr. 2006; 84(2): 274-288.
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61. Portilla MG. Body mass index reporting 656038, Barnaul, Lenina Prospekt, 40. through the school system: Potential harm. J Am Tel.: (3852) 566800. Diet Assoc. 2011; 111(3): 442–445. E-mail: [email protected] 62. Shrewsbury V, Wardle J. Socioeconomic status and adiposity in childhood: a systematic Author information review of cross-sectional studies 1990–2005. Obesity Filippova Sofia Petrovna, Candidate of Medical (Silver Spring). 2008; 16: 275–284. Sciences, Associate Professor of the Department of 63. Triches RM. Giugliani ERJ. Obesity, eating Hygiene, Fundamentals of Ecology and Health and habits and nutritional knowledge among school Safety, Altai State Medical University, Barnaul. children. Rev Saude Publica. 2012; 56(4): 305-307. 656038, Barnaul, per. Nekrasova, 65. 64. Wang Y, Beydoun MA. The obesity epidemic Tel.: (3852) 566835. in the United States – gender, age, socioeconomic E-mail: [email protected] status, racial/ethnic, and geographic characteristics: a systematic review and meta-regression analysis. Zhukova Olga Viktorovna, Candidate of Medical Epidemiologic Reviews. 2007; 29: 6-28. Sciences, Associate Professor of the Department of 65. West F, Sanders MR. The Lifestyle Behaviour Hygiene, Fundamentals of Ecology and Health and Checklist: a measure of weight-related problem Safety, Altai State Medical University, Barnaul. behaviour in obese children. International journal of 656038, Barnaul, per. Nekrasova, 65. pediatric obesity. 2009; 4(4):266–273. Tel.: (3852) 566835. 66. Krasnoperova O.I., Smirnova E.N., Merzlova E-mail: [email protected] N.B., Baturin V.I. Role of heritable, perinatal and ambient factors in obesity in childhood. Children’s Zhved Olga Ivanovna, Lecturer of the Department Hospital. 2013; 3: 19-24. of Hygiene, Fundamentals of Ecology and Health 67. Boylan SM, Gill TP, Hare-Bruun H, Andersen LB, Heitmann BL. Associations between adolescent and Safety, Altai State Medical University, Barnaul. and adult socioeconomic status and risk of obesity 656038, Barnaul, per. Nekrasova, 65. and overweight in Danish adults. Obes Res Clin Tel.: (3852) 566835. Pract. 2014; 8(2): 115-200. E-mail: [email protected] 68. Biro FM, Wien M. Childhood obesity and adult morbidities. Am J Clin Nut. 2010; 91(5): 1499- Pashkov Artem Petrovich, Candidate of Medical 1505. Sciences, Associate Professor of the Department of 69. Horne PJ, Hardman CA, Lowe CF et al. Hygiene, Fundamentals of Ecology and Health and Increasing parental provision and children’s Safety, Altai State Medical University, Barnaul. consumption of lunchbox fruit and vegetables in 656038, Barnaul, per. Nekrasova, 65. Ireland: The Food Dudes intervention. Eur J Clin Tel.: (3852) 566835. Nutr. 2009; 63(5): 613–618. E-mail: [email protected] 70. Mazzonetto AC, Fiates GM. Perceptions and choices of Brazilian children as consumers of food Potseluev Nikolai Yurievich, Candidate of Medical products. Appetite. 2014; 78(1): 179-184. Sciences, Associate Professor of the Department of 71. Justo GF, Callo GQ, Carletti L, Molina MCB. Hygiene, Fundamentals of Ecology and Health and Nutritional extremes among school children in Safety, Altai State Medical University, Barnaul. a rural Brazilian municipality. Rural and Remote 656038, Barnaul, per. Nekrasova, 65. Health. 2012; 2: 2220. Tel.: (3852) 566835. 72. Slater SJ, Nicholson L, Chriqui J, Turner E-mail: [email protected] L, Chaloupka F. The impact of state laws and district policies on physical education and recess Shults Ksenia Viktorovna, Lecturer of the practices in a nationally representative sample of Department of Hygiene, Fundamentals of Ecology US public elementary schools. Archives of pediatrics and Health and Safety, Altai State Medical & adolescent medicine. 2012; 166(4): 311–316. University, Barnaul. 73. Trudeau F, Shephard RJ. Contribution of 656038, Barnaul, per. Nekrasova, 65. school programmes to physical activity levels and Tel.: (3852) 566835. attitudes in children and adults. Sports Med. 2005; E-mail: [email protected] 35(2): 89–105. Nagornyak Aleksei Sergeevich, Lecturer of Contacts the Department of Hygiene, Fundamentals of Corresponding author: Saldan Igor Petrovich, Ecology and Health and Safety, Altai State Medical Doctor of Medical Sciences, Rector, Head of University, Barnaul. the Department of Hygiene, Fundamentals of 656038, Barnaul, per. Nekrasova, 65. Ecology and Health and Safety, Altai State Medical Tel.: (3852) 566835. University, Barnaul. E-mail: [email protected]
18 Fundamental medicine
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UDC 615.254.7-092.4:612.398.192:616.613-003.7 doi.org:10.31684/2541-8475.2019.1(13).20-24 MORPHOFUNCTIONAL ACTIVITY OF NUCLEOLAR ORGANIZERS OF RAT NEPHROCYTES UNDER PHARMACOLOGICAL CORRECTION OF EXPERIMENTAL OXALATE NEPHROLITHIASIS BY PEPTIDE COMPLEX OF PIG KIDNEY TISSUE Altai State Medical University, Barnaul G.V. Zharikova, I.P. Bobrov, O.N. Mazko, O.G. Makarova, A.V. Lepilov, A.Yu. Zharikov
The aim of the present research is to study the influence of the peptide complex of pig kidneys tissue on the morphofunctional activity of nucleolar organizers of nephrocytes under experimental oxalate nephrolithiasis. Experiments were conducted on 24 male Wistar rats which were divided into 2 groups: a control group (6 weeks of oxalate nephrolithiasis modeling) and a test group (6 weeks of oxalate nephrolithiasis modeling + injecting the peptide complex at а dose of 15 mg). Detecting of nucleolar organizers was carried out with a modified Y. Daskal’s method. Studies revealed that with the use of the peptide complex of pig kidneys tissue an enchancement of biosynthetic processes in nephrocytes could be noticed, as an increase in morphofunctional activity of nucleolar organizers of kidney cells could be observed in comparison with a control group. An increase in activity of nucleolar cell apparatus appeared both in their increase of number of nucleoli and number of silver granules (core structures) and the increase of cell count with a large number of core structures for 1 nucleus. Key words: peptide complex of pig kidneys tissue, nephrolithiasis, nucleolar organizers.
The development of new effective and safe rodents produced by ZAO Assortiment-Agro medicines for the treatment of urolithiasis is a under the Chara trade mark. Animals were divided crucial task of modern pharmacology and urology. equally into two groups: the control one and the Nowadays, there are experimentally justified test one. Experimental oxalate nephrolithiasis prerequisites for the creation of a new anti- was modeled in the control group without lithogenic agent of peptide nature. Earlier we the introduction of pharmacologically active obtained an experimental peptide complex from substances [4]. According to the nephrolithiasis lyophilisate of pig kidney tissue, identified its amino model used, rats received the 1% ethylene glycol acid composition and tested the curative effect on aqueous solution daily in the form of the drink at the experimental model of oxalate nephrolithiasis. free access. In the same conditions of nephrolithiasis It turned out that a three-week oral administration modeling, rats of the test group received the of the obtained peptide complex at a dose of 15 mg peptide complex obtained by the method of the was accompanied by the destruction of large and acetic extraction from lyophilisate of pig kidney medium uroliths to fine dust granularity [1, 2]. tissue in the form of the starch suspension orally As is known, in the kidneys, so-called through a probe at a dose of 15 mg from day 22 to crystallization inhibitors form and function: these day 42 of the experiment. are high-molecular proteins preventing stone Chromatographic analysis of the peptide formation [3]. It is possible that the introduced complex of pig kidney tissue through the method of peptides having a nuclear orientation of action high-performance liquid chromatography (HPLC) could stimulate the formation of cellular proteins, on the Milichrom-A02 chromatograph without including crystallization inhibitors. In this regard, hydrolysis showed that its composition consists of we decided to study the impact of the peptide about 30 chromatographically significant peaks in complex of pig kidney tissue on biosynthetic the range of the retention volume from 0 to 2500 processes in nephrocytes under experimental µl. The capillary electrophoresis method on the oxalate nephrolithiasis. Thus, the aim of the CAPEL®-105M capillary electrophoresis system present research is to study the influence of the with positive high voltage polarity in hydrochloric peptide complex of pig kidneys tissue on the hydrolysate of the obtained peptide complex of pig morphofunctional activity of nucleolar organizers kidney tissue allowed to identify 14 amino acids: of nephrocytes under experimental oxalate arginine, lysine, tyrosine, phenylalanine, histidine, nephrolithiasis. leucine, isoleucine, methionine, valine, proline, threonine, serine, alanine, glycine with a total mass Materials and methods fraction of 49.778%. The study was conducted on 24 male Wistar rats After six weeks of the experiment, rats of both weighing 200–250 g, being on a standard laboratory groups were subjected to decapitation under ether diet, receiving 30–40 g of daily food for laboratory anesthesia in compliance with the requirements of
19 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 the Declaration of Helsinki of the World Medical package. In the normal distribution of data, the Association (2000). The rat kidney was the material methods of parametric statistics (Student t-test) of the study. The organ was fixed in the 10% were used while checking statistical hypotheses, formalin solution, processed according to the and if the obtained data did not meet the criteria standard method, poured into paraffin. of normal distribution (Shapiro-Wilk test W=0.89, For histological examination, kidney tissue p<0.01), the Kolmogorov-Smirnov test or Mann- was fixed in the 10% neutral formalin solution, Whitney U-test was applied. The data was processed according to the standard method and considered reliable at p<0.05. poured into paraffin. 4-5 μm thick histological sections were coloured with haematoxylin and Results and discussion eosin and with a histochemical method in order to The conducted experiments on the assessment reveal nucleolar organizers. Nucleolar organizers of the morphofunctional activity of nucleolar were revealed according to the two-stage method organizers of cells of the renal papilla collecting of Daskal Y. et al. [5] in our modification [6, 7]. tubules revealed that in the control group, the With an increase x1000 under the oil immersion number of silver granules in nucleoli per 1 nucleus of the microscope, the number of nucleoli and the amounted to 2.5±0.1, margins of fluctuations of the number of silver granules in nucleoli per 1 nucleus number of granules varied from 1 to 3 granules, were calculated, histograms of cell distribution the modal value was 3 granules. The number of by the number of granules per 1 nucleus were nucleoli in cell nucleuses averaged 2.0±0.1, margins constructed. In each case, at least 50 nephrothelium of fluctuations of the number of nucleoli ranged cells were studied. from 1 to 3 nucleoli, the modal value was 2 nucleoli Statistical processing of the material was carried (Figure 1a). out with the use of the Statistica 10.0 statistical
1a 1b Figure 1. Microphotograph of nucleolar organizers in nephrocytes (the enlarged fragment of the microphotograph is within the frame). Colouring with silver nitrate by Y. Daskal in the modification of I.P. Bobrov. Enlargement x1000. 1a – a small amount in the study control group. 1b – a large number of nucleolar organizers in the study test group.
The distribution of cell elements depending modal value made 3 granules. The number of on the number of silver granules per 1 nucleus nucleoli in this group was also reliably larger on revealed that the histogram of distribution has a the average (p=0.000035) than in the control group, left shift and is characterized by high peaks in the margins of fluctuations of the number of nucleoli cell areas having 2 and 3 granules per 1 nucleus ranged from 1 to 4 nucleoli, the model value was 3 (Figure 2). nucleoli (Figure 1b). Against this background, in the kidneys of rats The distribution of cell elements depending on of the test group, where the peptide complex of the number of silver granules per 1 nucleus in this pig kidney tissue was introduced for 3 weeks, the group revealed that the histogram of distribution evidence of a significant increase in biosynthetic has a right shift and is characterized by high peaks processes was obtained. in the cell areas having 3 and 4 granules per 1 It turned out that the test group compared to nucleus. With that, in comparison to the control the disease control showed a significant increase group, there were cells with 7 granules (2%) per 1 (p=0.0000001) to 3.4±0.1 in the average number of nucleus. There were no cells with 1 granule per 1 silver granules in nucleoli per 1 nucleus, margins nucleus, and the cell content with 2 granules was of fluctuations ranged from 2 to 7 granules, the reduced (Figure 2).
20 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
Figure 2. Histogram characterizing cell distribution by the number of silver granules in kidney cells. Note: along the x-axis – the number of silver granules, along the y-axis – the percentage of cells.
– control group;
– test group.
Thus, the results of the study conducted clarify the mechanisms of anti-lithogenic action showed that in the application of the peptide of peptide extract of pig kidney tissue. Thus, the complex of pig kidney tissue, there was an general strengthening of cellular protein synthesis increase in morphofunctional activity of nucleolar can be accompanied by an increase in the number organizers of kidney cells in comparison to the and activity of intrarenal crystallization inhibitors: control group. An increase in activity of nucleolar osteopontin, Tamm-Horsfall protein, and bikunin, cell apparatus appeared both in their increase of properties of which are well described in modern number of nucleoli and number of silver granules literature [3]. In addition, in recent years, increasing (core structures) and the increase of cell count with attention has been paid to the study of the organic a large number of core structures for 1 nucleus. matrix of kidney stone. Experiments show that As is known, the nucleolus is a dynamic the matrix can contain tens and even hundreds structure, its morphology is closely connected to the of endogenous proteins, including stimulants ribosome biogenesis: preribosomal RNA synthesis, and crystallization inhibitors [10]. Today, there is processing and migration of RNP particles into an opinion that the modification of the structure nucleoplasm and then into cytoplasm. The higher and function of stone matrix can interfere with the activity of the nucleolus and the more core lithogenesis. Comparing the previously revealed structures in it, the higher is the protein synthesis in litholytic effect of the peptide complex of pig kidney the cell and its biosynthetic activity [8]. Therefore, tissue and the results of the present study, we can the results of our experiments indicate a significant assume that an increase in protein biosynthesis increase in protein biosynthesis in nephrocytes. in nephrocytes has significant importance for On the one hand, it is in good agreement with the emergence of the anti-lithogenic effect of the modern ideas about the mechanisms of cellular peptide complex of pig kidney tissue. action of short-chain peptides and amino acids. It is believed that these substances can influence the Conclusions genetic regulation of nucleic acid synthesis and, 1. Three-week application of the peptide as a consequence, ribosomal protein synthesis complex of pig kidney tissue in experimental [8]. At the same time, the established effect can oxalate nephrolithiasis is accompanied by an 21 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 increase in the morphofunctional activity of 10. Kaneko K.,Nishii S., Izumi Y,, Yasuda nucleolar organizers of nephrocytes compared to M.,Yamanobe T., Fukuuchi T., Yamaoka N., Horie the disease control. S. Proteomic Analysis after Sequential Extraction 2. An increase in activity of nucleolar cell of Matrix Proteins in Urinary Stones Composed apparatus appeared both in their increase of of Calcium Oxalate Monohydrate and Calcium number of nucleoli and number of silver granules Oxalate Dihydrate. Analytical Sciences. 2015; 31(9): (core structures) and the increase of cell count with 935-942. a large number of core structures for 1 nucleus. Conflict of interest. The authors declare that Contacts there is no conflict of interest. Corresponding author: Zharikova Ganna Viktorovna, lecturer of the Department of General References: and Biological Chemistry, Clinical Laboratory 1. Zharikov A.Yu., Kiselev V.I., Saldan Diagnosis, Altai State Medical University, Barnaul. I.P., Zharikova G.V., Lepilov A.V., Bobrov I.P. 656038, Barnaul, Lenina Prospekt, 40. Morphological assessment of the impact of peptide Tel.: (3852) 566938. complex pf pig kidney tissue on the course of E-mail: [email protected] experimental kidney stone disease. Bulletin of Experimental Biology and Medicine. 2017; 164(8): 237- Author information 240. Bobrov Igor Petrovich, senior staff scientist of the 2. Zharikova G.V., Zharikov A.Yu., Kiselev V.I., Morphological Laboratory of the Center of Medical Mazko O.N., Makarova O.G., Kiryakova V.O. The and Biological Research, Altai State Medical influence of the peptide complex of pig kidneys on the University, Barnaul. free radical oxidation by experimental urolithiasis. 656038, Barnaul, Lenina Prospekt, 40. The Siberian Scientific Medical Journal. 2017; 37(2): Tel.: (3852) 669927. 17-21. E-mail: [email protected] 3. Zverev Ya.F., Zharikov A.Yu., Brukhanov V.M., Lampatov V.V. Modulators of oxalate Mazko Olesya Nikolayevna, Candidate of nephrolithiasis. Inhibitors’ crystallization. Biological Sciences, Senior Scientific Researcher of Nephrology. 2010; 14(1): 29-49. the Biomedical Laboratory of the Center of Medical 4. Zharikov A.Yu., Brukhanov V.M., Zverev and Biological research, Altai State Medical Ya.F., Lampatov V.V. Current methods of modeling University Barnaul. of oxalate nephrolythiasis. Nephrology. 2008; 12(4): 656038, Barnaul, Lenina Prospekt, 40. 28-35. Tel.: (3852) 669927. 5. Daskal Y., Komaromy L., Busch H. Isolation E-mail: [email protected] and partial characterization of perichromatin granules. A unique class of nuclear rnp particles. Makarova Olesya Gennadyevna, Candidate Experimental Cell Research. 1980; 126(1): 39-46. of Pharmaceutical Sciences, Senior Scientific 6. Bobrov I.P., Avdalyan A.M., Klimachev Researcher of the Biomedical Laboratory of the V.V., Lazarev A.F., Gervald V.Ya., Dolgatov A.Yu., Center of Medical and Biological Research, Altai Samuilenkova O.V., Kovrigin M.V., Kobyakov State Medical University, Barnaul. D.S. Modification of histochemical method of 656038, Barnaul, Lenina Prospekt, 40. identification of nucleolar organizers at histological Tel.: (3852) 669927. sections. Archive of Pathology. 2010; 72(3): 35-37. E-mail: [email protected] 7. Bobrov I.P., Avdalyan A.M., Cherdantseva T.M., Klimachev V.V., Lazarev A.F., Brukhanov V.M., Lepilov Aleksandr Vasilyevich, Doctor of Medical Doroshenko V.S., Gervald V.Ya., Dolgatov A.Yu., Sciences, Head of the the Department of Forensic Kovrigin M.V. Modified method of identification Medicine and Pathological Anatomy named after of argyrophilic proteins of the nucleolar organizer professor V.N. Kryukov with the Course of FVE, area at paraffin sections. Morphology. 2010; 138(5): Altai State Medical University, Barnaul. 65-67. 656038, Barnaul, Lenina Prospekt, 40. 8. Chelidze P.V. Fibrillar centres in the Tel.: (3852) 408439. nucleoli of cultured pek cells after the action of E-mail: [email protected] actinomycin D. Cytology. 1982; 24(2): 137-143. 9. Khavinson V.Kh., Soloviev A.Yu., Zharikov Aleksandr Yuryevich, Doctor of Tarnovskaya S.I., Lin’kova N.S. The mechanism of Biological Sciences, Associate Professor, Head biological activity of short peptides: penetration of the Department of Pharmacology, Altai State into a cell and epigenetic regulation of gene Medical University, Barnaul. expression. Successes of Modern Biology. 2013; 133(3): 656056, Barnaul, ul. Papanintsev, 126. 310-316. Tel.: (3852) 241859. E-mail: [email protected] 22 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
UDC 611.611:616.61-006-074 doi.org:10.31684/2541-8475.2019.1(13).25-31 NUCLEOPHOSMIN/B23 ONCOPROTEIN IN THE CLEAR-CELLED RENAL TUMOR: INTERACTION WITH CLINICAL AND ANATOMICAL PROGNOSIS FACTORS 1Altai State Medical University, Barnaul 2Altai branch of the N.N. Blokhin National Medical Research Centre of Oncology, Barnaul 3Institute of Molecular Pathology and Pathomorphology of the Federal Research Centre of Fundamental and Translational Medicine, Novosibirsk I.P. Bobrov1,2, M.N. Myadelets1, I.V. Klimachev1, A.Yu. Dolgatov1, A.V. Lepilov1, T.M. Cherdantseva1, N.G. Kryuchkova1, A.M. Avdalyan1,2, E.L. Lushnikova3, O.P. Molodykh3
Research objective. To study the nucleophosmin/B23 oncoprotein expression in cells of the clear-celled renal tumor depending on clinical and morphological parameters and postoperative survival of patients. Materials and methods. 83 kidney cancer drugs were studied. Nucleophosmin/B23 expression was revealed by immunohistochemical method, the expression severity was assessed by calculating the integral optical density of the substrate in the cell nuclei. Results. It is shown that the integral optical density of nucleophosmin/B23 in tumor cells was connected with a number of important prognostic factors: stages of the disease by TNM, the size of the tumor node, the degree of nuclear atypia by Fuhrman, the presence of metastases, and 5 year postoperative survival of patients. Conclusions. The study of the integral optical density of nucleophosmin/B23 can serve as an additional prognosis factor in clear-celled renal tumor. Key words: clear-celled renal tumor, nucleophosmin/B23, prognosis.
Finding new reliable markers of kidney cancer compared to isoforms B23.2 [9]. Hyperexpression prognosis is an urgent task of modern oncourology. of B23 protein in tumor cells is also accompanied According to modern data, nucleophosmin by the appearance of its abnormal structural (B23, NPM1, newmatrine, NO38) protein is the variants (shortened, mutant, chimeric) [10]. For main argentophilic protein of the nucleolus example, mutant nucleophosmin is localized in [1]. By chemical structure, nucleophosmin is a cytoplasm, and chimeric one, as a rule, has nuclear phosphoprotein. It is found in all mammal cells cytoplasmic localization [11]. studied to date, but most of all it is found in tumor Nucleophosmin is a polyfunctional protein cells, where its number increases more than 20 included in various intracellular processes. The times [2, 3]. The nucleophosmin protein gene main functions of this protein are: chaperonin is located on chromosome 5 in locus 5q35 [4]. activity; ribosom biogenesis stimulation; control of This gene consists of 12 functional domains and chromosomes centromere duplication; regulation of encodes several oncoprotein isoforms. In humans, the cell cycle and apoptosis; proliferation activation B23 protein exists in the form of two isoforms being and participation in the processes of the cellular the products of alternative splicing of one gene [5]. response to stress and cell malignization [12]. The dominant isoform is B23.1 (294 amino acid In the literature, there is a small number of residues, electrophoretic mobility 37-38 kDa), the works devoted to the study of nucleophosmin in minor isoform is B23.2 (257 amino acid residues, malignant neoplasms [13, 14, 15, 16, 17, 18, 19, 20]. electrophoretic mobility 35-36 kDa). Isoform B23.1 It is shown that in malignant neoplasms of the liver, localizes mainly in the nucleolus, and isoform B23.2 prostate, large bowel, urinary bladder, stomach, is contained mainly in nucleoplasm [6]. Isoform and salivary gland, nucleophosmin expression B23.2 differs from B23.1 by the absence of 35 last increases dramatically. In the literature, we found amino acids at the C-end of the molecule. Both only one foreign work where nucleophosmin isoforms function in monomeric (N-end sequence) expression in kidney cancer was investigated. Thus, and oligomeric (C-end sequence) form [7]. Sari A. et al. (2012) [21] showed that nucleophosmin In tumor cells, there is hyperexpression of expression in tumor cells correlated with the degree nucleophosmin and formation of specific forms of of nuclear atypia. The authors note that detection this protein, some of which are monomers, some are of nucleophosmin expression can be a useful oligomers, and the oligomeric state and distribution immunohistochemical marker for differential of monomeric and oligomeric forms between diagnosis between oncocytoma and chromophobe nucleoli and nucleoplasm change in the process kidney cancer. of carcinogenesis [8]. According to some authors, The research objective is to study the interaction tumor cells contain 5–10 times more isoforms B23.1 of nucleophosmin/B23 oncoprotein expression
23 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 with clinical and anatomical prognosis factors of scope, Leica EC3 digital camera (Leica Microsys- clear-celled renal tumor and postoperative survival tems AG, Germany), personal computer, and Vide- of patients. oTest-Morphologiia 5.2 software. Nucleophosmin/ B23 IOD values were expressed in relative units Materials and methods (RU). At least 25–30 tumor cells were evaluated. As the material for the study, we used 83 kidneys Statistical processing of the material was carried resected for cancer in the Altai branch of the N.N. out with the use of the Statistica 10.0 statistical Blokhin National Medical Research Centre of package. In the case of the normal distribution of Oncology of the Russian Federation, Barnaul. The data obtained, the methods of parametric statistics mean age of patients was 57.6±1.1 years. There (Student t-test) were used while checking statistical were 38 men (45.8%) and 45 women (54.2%). hypotheses, and if the obtained data did not meet In tumor grouping, according to clinical stages the criteria of normal distribution (Shapiro-Wilk (I–IV), 46 (55.4%) observations corresponded to test W=0.89, p<0.01), the Kolmogorov-Smirnov test stage I (T1N0M0); 10 (12.05%) observations to or Mann-Whitney U-test was applied. Survival stage II (T2N0M0); 17 (20.5%) observations to stage curves were constructed using the Kaplan-Meier III (T1N1M0, T2N1M0, T3N0M0, T3N1M0), and method, the statistical significance of survival 10 (12.05%) observations to stage IV (T4N0M0, curves was evaluated using the log-rank test. T4N1M0, TanyN2M1, TanyNanyM1). The degree of Correlation relationship were evaluated using the tumor malignancy was estimated by Fuhrman S.A. Pearson test. The data were considered reliable at The studied material included 35 (42.2%) tumors p<0.05. of GІ degree of anaplasia; 21 (25.3%) tumors of GІІ degree of anaplasia; 17 (20.5%) tumors of GІІI Results and discussion degree of anaplasia, and 10 (12%) carcinomas of In the study of nucleophosmin/B23 oncoprotein GІV degree of anaplasia. expression in tumor cells of clear-cell cancer, the There were 15 (18.1%) metastatic carcinomas oncoprotein had a nucleolar localization in 100% and 68 (81.9%) localized ones. The mean largest of cells, while the nuclei were painted brown size of the tumor node was 7.1±0.4 cm. Before the of varying intensity. In general, regardless of surgery, patients did not receive drug treatment. clinical and anatomical parameters of carcinomas, In the manufacture of histological preparations, quantitative analysis of nucleophosmin/B23 IOD the method of tissue matrices was used. In each showed that the median of protein IOP per 1 core case, the tumor tissue columns were taken from was 1023.6±56.7 RU, the margins of fluctuations paraffin blocks (donor blocks) after a preview of ranged from 118.9 RU to 15778.3 RU. the histological preparation with a needle puncher In correlation analysis, the connection between with an internal diameter of 2.0 mm. Then the nucleophosmin/B23 and the sex of patients was columns (10–15 pcs.) were placed in paraffin block- not found (r=0.07; p=0.50) (Table 1). In men, recipients 20x20 mm in size. Serial histological nucleophosmin/B23 protein IOD per 1 core was sections 4 μm thick were made from paraffin 1305.8±57.9 RU. In women, protein IOD did not block-recipients with the help of semi-automatic significantly differ from that in men and amounted rotor microtome and transferred to glass (to one to 1523.4±94.4 RU (p=0.06) (Table 2). glass from two paraffin blocks). There was also no correlation between Immunohistochemical detection of nucleophos- nucleophosmin/B23 protein IOD and the age of min/B23 nucleolar protein was carried out using patients (r=0.005; p=0.96) (Table 1). In the study monoclonal antibodies – nucleophosmin n/B23, of protein depending on the age of patients, the clone mouse mAb23 (Labvision firm). The integrat- lowest value of nucleophosmin/B23 IOD was noted ed optical density (IOD) of nucleophosmin/B23 in the age group from 30 to 39 years old (658.2±56.5 in nuclei was estimated using a computer image RU), and the highest one in the age from 70 to 79 analysis system consisting of a Leica DМЕ micro- years (2025.5±273.5 RU) (Table 2). Table 1 Correlation of nucleophosmin/B23 IOD with prognostic clinical and morphological parameters
Clinical and morphological parameter Correlation coefficient (r) Reliability (p) Sex of patients 0.07 0.5 Age of patients 0.005 0.96 Clinical stage 0.57 0.0001 Tumor size 0.58 0.0001 Degree of anaplasia by Fuhrman 0.70 0.0001 Presence of metastases 0.40 0.0001
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Table 2 Nucleophosmin/B23 integrated optical density depending on clinical and anatomical parameters
Nucleophosmin/B23 IOD Clinical and anatomical parameter Reliability (p) (RU) Sex: male 1305.8±57.9 female 1523.4±94.4 p=0.06 Age: 30–39 years old (1) 658.2±56.5
40–49 years old (2) 2007.7±197.9 P5-1=0.005
50–59 years old (3) 1227.6±59.3 P5-2=0.6
60–69 years old (4) 1176.8±82.5 P5-3=0.00002
70–79 years old (5) 2025.5±273.5 P5-4=0.00009 TNM stage: Stage I 956.1±31.4 Stage II 2034.6±134.3 p=0.000001 Stage III 2525.9±197.5 p=0.09 Stage IV 3825.9±521.7 p=0.009
Degree of nuclear atypia by Fuhrman: GI 728.1±19.2 GII 862.2±24.6 p=0.00002 GIII 2166.9±63.2 p=0.001 GIV 4711.7±364.7 p=0.0000001 Size of the tumor node: <7.0 cm 904.2±24.7 ≥7.0 cm 2555.5±149.2 p=0.001 Metastases: N0 1197.3±43.4 N+ 3098.3±301.0 p=0.0000001
Nucleophosmin/B23 IOD correlated with the IOD at the GIV degree of anaplasia – 4711.7±364.7 clinical stage of the disease (r=0.57; p=0.0001) (Table RU (p=0.0000001) (Figure 1, 2) (Table 2). Thus, in 1). In tumors at stage I of the pathological process, the clear-celled renal tumor, nucleophosmin/B23 the average nucleophosmin/B23 protein IOD per 1 protein IOD was interconnected with the degree of core was 956.1±31.4 RU, at stage II – 2034.6±134.3 tumor cell anaplasia. A significant increase in the RU (p=0.0000001), at stage III – 2525.9±197.5 RU content of nucleophosmin/B23 protein in cell nuclei (p=0.09), and at stage IV – 3825.9±521.7 RU (p=0.009) was revealed at the increase of tumor anaplasia. (Table 2). Thus, nucleophosmin/B23 protein IOD Nucleophosmin/B23 IOD was associated was interconnected with the clinical stage of the with metastasis of the clear-celled renal tumor pathological process. At the increase in the stage (r=0.40; p=0.0001) (Table 1). In cells of localized of the process, the content of nucleophosmin/ tumors, nucleophosmin/B23 oncoprotein IOD was B23 protein in tumor cell nuclei also significantly 1197.3±43.4 RU per 1 nucleus, and in metastatic increased. tumors, protein IOD significantly increased to Nucleophosmin/B23 IOD was associated with 3098.3±301.9 RU per 1 nucleus (p=0.0000001) (Table the size of the tumor node (r=0.58; p=0.0001) (Table 2). Thus, in the cell nuclei of metastasizing tumors 1). In tumor cells of <7cm in size, IOD was 904.2±24.7 of the clear-celled renal cancer, a significantly RU, and in tumor nodes of ≥7 cm, protein IOD larger nucleophosmin/B23 protein IOD was noted significantly increased to 2555.5±149.2 RU per 1 compared to localized tumors. nucleus (p=0.001) (Table 2). Thus, nucleophosmin/ We conducted a study of 5 year postoperative B23 protein IOD was interconnected with the survival of patients depending on nucleophosmin/ size of the tumor node. With increasing tumor B23 IOD in tumor cells. In the Kaplan-Meyer size, nucleophosmin/B23 IOD also increased by 1 survival analysis, the graph shows that when nucleus. nucleophosmin/B23 IOD in tumor cells was <1000 Nucleophosmin/B23 IOD correlated with RU, the cumulative share of survivors was 0.98 the degree of anaplasia by Fuhrman (r=0.70; (98%) by day 1800 after the operation, and when p=0.0001) (Table 1). In tumors of the GI degree of nucleophosmin/B23 IOD in tumor cells was >1000 anaplasia by Fuhrman, the mean nucleophosmin/ RU, the cumulative share of survivors was 0.60 B23 oncoprotein IOD per 1 nucleus amounted to (60%). Comparative analysis of data using the 728.1±19.2 RU, of the GII degree of anaplasia – logarithmic rank criterion revealed that differences 862.2±24.6 RU (p=0.00002), of the GIII degree of between survival curves in study groups are anaplasia – 2166.9±63.2 RU (p=0.001), and the mean reliable (log-rank; p=0.01) (Figure 3). 25 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
Figure 1. Nucleophosmin/B23 protein expression in tumor cell nuclei of GI degree of anaplasia (shown by arrows): a — coloration of the tumor with haematoxylin and eosin, increase x400; b – immunohistochemical reaction, increase x1000.
Figure 2. Nucleophosmin/B23 protein expression in tumor cell nuclei of GIV degree of anaplasia (shown by arrows): a — coloration of the tumor with haematoxylin and eosin, increase x400; b – immunohistochemical reaction, increase x1000.
Figure 3. Cumulative ratio of 5 year survival in patients with RCC depending on nucleophosmin/B23 IOD in tumor cells.
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Conclusion min protein from HeLa nuclei. Applied Biochemistry Summarizing the abovementioned, we can con- and Microbiology. 2008; 44(3): 287–295. clude that nucleophosmin/B23 nucleolar oncopro- 8. Grummitt CG, Townsley FM, Johnson CM, tein expression in the clear-celled renal tumor was Warren AJ, Bycroft M. Structural consequences of interconnected with clinical and morphological nucleophosmin mutations in acute myeloid leuke- prognostic parameters of carcinomas and 5 year mia. J. Biol. Chem. 2008; 283: 23326-23332. postoperative survival of patients. With the in- 9. Umekawa H, Chang JH, Correia JJ, Wang crease in the clinical stage, the tumor node size, the D, Wingfield PT, Olson MO. Nucleolar protein B23 degree of anaplasia, and the presence of nucleop- expression, purification, oligomerization and sec- hosmin/B23 protein IOD metastases significantly ondary structures of two isoforms. Cell. Mol. Biol. increased per 1 nucleus. In our opinion, the increase Res. 1993; 39: 635- 645. in nucleophosmin/B23 IOD significantly increases 10. Vladimirova N.M., Vol’pina O.M., the ability of tumor cells to invasive growth and Potapenko N.A., Surina E.A. Features of the struc- metastasis. Therefore, finding populations of tu- tural state of B23/nucleophosmin protein in brain mor cells with high nucleophosmin/B23 IOD per 1 cells. Biological membranes. 2014; 31(1): 57-67. nucleus in the clear-celled renal tumor may indi- 11. Shalgunov V.S., Lobanova N.V., Bulyche- cate the risk of metastases and unfavourable prog- va T.I., Deineko N.L., Volkova T.D., Filatova M.P., nosis for the course of the disease. Determination Kamynina A.V., Kim Ya.S., Vladimirova N.M., of nucleophosmin/B23 protein IOD in tumor cells Koroev D.O., Akhidova E.V., Vol’pina O.M. Anti- of primary carcinoma can be used in assessing the bodies to synthetic fragments of nucleophosmin risk of metastases at the preoperative stage, pre- for specific relief of its monomeric and oligomeric dicting the course of RCC, and planning the scope forms. Biological chemistry. 2009; 35(6): 799-807. of surgical treatment. Nucleophosmin/B23 protein 12. Sautkina E.N., Potapenko N.A., Vladimiro- IOD assessment in the clear-celled renal tumor can va N.M. State of B23/nucleophosmin and UBF nu- serve as an additional marker in determining the cleolar proteins in HeLa cells in apoptosis induced disease prognosis in combination with traditional by the tumor necrosis factor. Biochemistry. 2006; classical prognostic factors. 71(6): 786-797. Conflict of interest. The authors declare that 13. Ulanet DB, Torbenson M, Dang CV, Casci- there is no conflict of interest. ola-Rosen L, Rosen A. Unique conformation of can- cer autoantigen B23 in hepatoma: A mechanism for References: specificity in the autoimmune response. Proc. Natl. 1. Roussel P, Hernandez-Verdun D. Identi- Acad. Sci. USA. 2003; 100: 12361-12366. fication of Ag–NOR proteins, markers of prolifer- 14. Tsui KH, Juang HH, Lee T.H. Association ation related to ribosomal gene activity. Exp. Cell of nucleophosmin/B23 eith bladder cancer recur- Res. 1994; 214: 465-472. rence based on immunohistochemical assessment 2. Zenit-Zhuravleva E.G., Polkovnichenko in clinical samples. Urology. 2004; 64: 839-844. E.M., Lushnikova A.A., Treshchalina E.M., Bukae- 15. Tian QH, Yun JP, Miao J, Chen G, Fu J, va I.A., Raikhlin N.T. Nucleophosmin and nucleo- Zhang CQ, et al. High expression of nucleophos- lin: encoding genes and expression in various hu- min/B23 in hepatocellular carcinoma. Zhonghua man and animal tissues. Molecular medicine. 2012; 4: Bing Li Xue Za Zhi. 2006; 35(7): 407-411. 24-31. 16. Li S, Zhang X, Zhou Z, Huang Z, Liu L, 3. Andersen JS, Lam YW, Leung AK, Ong Huang Z. Downregulation of nucleophosmin ex- SE, Lyon CE, Lamond AI, Mann M. Nucleolar pression inhibited proliferation and induced apop- proteome dynamic. Nature. 2005; 433: 77-83. tosis in salivary gland adenoid cystic carcinoma. J. 4. Chang JH, Oison MO. Structure of the gene Oral. Pathol. Med. 2017; 46(3): 175-181. for rat nuclear protein B23. J. Bio. Chem. 1990; 265: 17. Bobrov I.P., Cherdantseva T.M., Klim- 18227-18233. achev V.V., Lazarev A.F., Avdalyan A.M., Dolgatov 5. Wang D, Baumann A, Szebeni A, Olson N. A.Yu., Samartsev N.S., Lapshtaev V.A., Popov V.A. The nucleic acid binding activity of nucleolar pro- Morphofunctional activity of nucleolar apparatus tein B23.1. Resides in its carboxyl-terminal End. J. and nucleophosmin (B23) protein in localized and Biol. Chem. 1994; 269(49): 30994-30998. metastatic kidney cancer. Fundamental research. 6. Bulycheva T.I., Deineko N.L., Vol’pina 2014; 10: 1467-1472. O.M., Vladimirova N.M. Immunocytochemical vi- 18. Bobrov I.P., Cherdantseva T.M., Myadelets sualization of monomeric and oligomeric forms of M.N., Klimachev V.V., Lazarev A.F., Avdalyan B23/nucleophosmin nucleolar protein in human A.M., Kazartsev A.V., Dolgatov A.Yu. Influence lymphocytes in the process of proliferation. Immu- condition of neoangiogenesis at expression of pro- nology. 2011; 5: 231-236. tein nucleophosminum/B23 and activity nucleolar 7. Sautkina E.N., Potapenko N.A., Bulycheva apparatus of renal cells cancer. Modern problems of T.I., Vladimirova N.M. Relief of B23/nucleophos- science and education. 2015; 5: 260.
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19. Avdalyan A.M., Kobyakov D.C., Klim- Lepilov Aleksandr Vasilyevich, Doctor of Medical achev V.V., Bobrov I.P., Lazarev A.F., Pichigina Sciences, Head of the Department of Forensic A.K., Lushnikova E.L., Nepomnyashchikh L.M. Medicine and Pathological Anatomy named after Expression of non-ribosomal nucleophosmin/B23 professor V.N. Kryukov with the Course of FVE, nucleolar protein in smooth muscle masses of the Altai State Medical University, Barnaul. uterine body. Bulletin of Experimental Biology and 656038, Barnaul, Lenina Prospekt, 40. Medicine. 2015; 8: 259-264. Tel.: (3852) 408439. 20. Raikhlin N.T., Bukaeva I.A., Karseladze E-mail: [email protected] A.I. Value of argyrophil proteins – B23/nucleop- hosmin and C23/nucleolin – in the assessment of Cherdantseva Tatyana Mikhailovna, Doctor of proliferative activity and invasive features in pros- Medical Sciences, Professor of the Department tate cancer. Journal of N.N. Blokhin Russian Cancer of Oncology and Radiation Diagnostics with the Research Centre. 2017; 28(1): 53-57. course of FVE, Altai State Medical University, 21. Sari A, Calli A, Altinboga AA, Pehlivan FS, Barnaul. Gorgel SN, Balci U, et al. Nucleophosmin expres- 656038, Barnaul, Lenina Prospekt, 40. sion in renal cell carcinoma and oncocytoma. AP- Tel.: (3852) 408439. MIS. 2012; 120(3): 187-194. E-mail: [email protected]
Contacts Kryuchkova Natalia Gennadyevna, Assistant Corresponding author: Bobrov Igor Petrovich, Professor of the Department of Forensic Medicine Senior Researcher of the Morphological Laboratory and Pathological Anatomy named after professor of the Center for Medical and Biological Research, V.N. Kryukov with the Course of FVE, Altai State Altai State Medical University, Barnaul. Medical University, Barnaul. 656038, Barnaul, Lenina Prospekt, 40. 656038, Barnaul, Lenina Prospekt, 40. Tel.: (3852) 408439. Tel.: (3852) 408439. E-mail: [email protected] E-mail: [email protected]
Author information Avdalyan Ashot Meruzhanovich, Doctor of Myadelets Mikhail Nikolaevich, pathologist, Medical Sciences, Head of the Laboratory for Postgraduate student of the Department of Forensic Research of Molecular Genetic Characteristics of Medicine and Pathological Anatomy named after Tumors, Altai branch of the N.N. Blokhin National professor V.N. Kryukov with the Course of FVE, Medical Research Centre of Oncology, Barnaul. Altai State Medical University, Barnaul. 656049, Barnaul, ul. Nikitina, 77. 656038, Barnaul, Lenina Prospekt, 40. Tel.: +7 (3852) 507399. Tel.: (3852) 408439. E-mail: [email protected] E-mail: [email protected] Lushnikova Elena Leonidovna, Doctor of Biological Klimachev Ilya Vladimirovich, pathologist, Sciences, Professor, Academician of the Russian Postgraduate student of the Department of Forensic Academy of Sciences, Director of the Institute of Medicine and Pathological Anatomy named after Molecular Pathology and Pathomorphology of professor V.N. Kryukov with the Course of FVE, the Federal Research Centre of Fundamental and Altai State Medical University, Barnaul. Translational Medicine, Head of the Department 656038, Barnaul, Lenina Prospekt, 40. of Molecular Cell Biology and Morphology, Head Tel.: (3852) 408439. of the Laboratory of Cytology and Cell Biology, E-mail: [email protected] Novosibirsk. 639117, Novosibirsk, ul. Timakova, 2. Dolgatov Andrey Yuryevich, Candidate of Medical Tel.: +7 (383) 3348003. Sciences, Associate Professor of the Department E-mail: [email protected] of Forensic Medicine and Pathological Anatomy named after professor V.N. Kryukov with the Molodykh Olga Pavlovna, Doctor of Biological Course of FVE, Altai State Medical University, Sciences, Head of the Laboratory of Mechanisms of Barnaul. Pathological Processes of the Institute of Molecular 656038, Barnaul, Lenina Prospekt, 40. Pathology and Pathomorphology of the Federal Tel.: (3852) 408439. Research Centre of Fundamental and Translational E-mail: [email protected] Medicine, Novosibirsk. 639117, Novosibirsk, ul. Timakova, 2. Tel.: +7 (383) 3348003. E-mail: [email protected]
28 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
UDC 616.36-002-092.4:615.9:615.322 doi.org:10.31684/2541-8475.2019.1(13).32-35 FEATURES OF THE EFFECT OF A COMPLEX HERBAL PRODUCT ON COAGULATION PROCESSES IN TOXIC HEPATITIS IN WHITE RATS 1Buryat State University, Ulan-Ude 2Institute of General and Experimental Biology SB RAS, Ulan-Ude E.A. Ubeeva1, S.M. Nikolaev1,2, D.N. Olennikov2, I.P. Ubeeva1
The aim of the study is to determine the hemostasis disorders in acute experimental toxic hepatitis caused by the introduction of D-Galactosamine hydrochloride in white rats and the possibility of correction with the help of the use of a new complex herbal product. The composition of the analysed phytoextract included Hypecoum erectus L. (hypecoum straight), Hedysarum dauricum (Daur sweetvetch), Glycyrhhiza uralensis Fischer (Ural licorice), Calendula officinalis (pot marigold) and Scutellaria baicalensis (Baikal skullcap). The use of phytoextract contributed to the correction of the functional state of the liver and hypocoagulation manifestations. Key words: complex herbal medicine, experimental hepatitis, hypocoagulation, hepatoprotective effect.
Urgency. The wide spread of viral hepatitis, Pharmacotherapeutic effectiveness of a CHP the increase in frequency of toxic, drug liver was determined in toxic hepatitis caused by the damage, metabolic disorders determine the need introduction of D-Galactosamine hydrochloride. to create means with hepatoprotective properties. To determine the coagulation process disorders in In determining the severity of liver disease liver damage by D-Galactosamine hydrochloride, course in the clinic, the detection of coagulation the methods generally accepted in hemostasiologу disorders is of great importance, as prothrombin were used and the level of fibrinogen was and other coagulation factors are synthesized in determined by generally accepted methods, as the liver. Clotting disorders play a significant role well as the activated partial thromboplastin time in the pathogenesis of liver damages, are able to (APTT), prothrombin index (PI), prothrombin acquire a cascade character, lead to disseminated time (PT), international normalized ratio (INR), intravascular coagulation, microcirculation prothrombin ratio (PR) in blood serum of white disorders, burden the course of pathological rats. The condition of the coagulation link of the process thus determining the outcome of diseases hemostasis system was investigated with the help [1, 2]. of a number of tests conducted using the AO Abris Medicines of plant origin attract the and Vital standard set of reagents on the Vitarei attention of researchers due to a wide range analyzer. of pharmacotherapeutic effects, low toxicity, According to researchers, D-Galactosamine possibility to potentiate the effect due to the hydrochloride causes disorders of the RNA and combination of various biologically active protein synthesis, forms acute hepatitis identical substances, especially in complex herbal products to viral human hepatitis in morphological [3, 4, 5]. and biochemical changes in the liver [7]. The research objective was to determine the D-Galactosamine liver damage was caused by a nature of changes of coagulation hemostasis in single intraperitoneal introduction to white rats at a rats under the influence of a new complex herbal dose of 400 mg/kg [7]. The CHP obtained in a form agent on the model of toxic hepatitis caused by the of a dry extract was dissolved in purified water introduction of D-Galactosamine hydrochloride. and administered intragastrically to three groups of white rats one hour before the introduction of Materials and methods hepatotoxin at doses of 100 mg/kg, 200 mg/kg, 300 The studied complex herbal product (CHP) mg/kg. In the future, the dry extract continued was a combined dry extract consisting of dry to be administered intragastrically to groups of extracts of hypecoum straight (Hypecoum erectum animals in these doses once a day for 14 days of the L.; Papaveraceae) herb, Alpine sweetvetch experiment. The comparator drug was Carsil with (Hedysarum alpinum L.; Leguminosae) herb, pot the international name Silibinin from the blessed marigold (Calendula officinalis L.; Compositae) milk thistle Silybum marianum (L.) Gaertn. Carsil flowers, Ural licorice (Glycyrrhiza uralensis Fisch.; was administered intragastrically at a dose of 100 Leguminosae) roots, and Baikal skullcap (Scutellaria mg/kg in a similar mode. The control group of baicalensis Georgi; Lamiaceae) roots in the ratio white rats was administered an equivalent amount of 5:5:4:4:2. Quantitative standardization of the of purified water in a similar mode after the product was carried out by HPLC-UV method introduction of D-Galactosamine hydrochloride. using the Milichrom A-02 microcolumn liquid The intact group of animals consisted of white rats chromatograph (Econova, Novosibirsk, Russia). 29 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 of the same age and sex receiving purified water in Results showed that the formation of the appropriate amount under this scheme. experimental hepatitis caused by D-Galactosamine Experiments were conducted on 96 white rats of hydrochloride was accompanied by significant both sexes with an initial weight of 180±20 g. Animal hemostasis disorders (Table 1, 2). On the 7th day maintenance was carried out in accordance with the of the experiment, the content of fibrinogen being “Good Laboratory Practice” (GLP) and the Order one of the most important indicators of hemostasis of the Ministry of Health of the Russian Federation was significantly reduced compared to the level No. 708Н dated 23.08.2010 “On Approval of in intact rats. In the control group of animals, the Regulations of Laboratory Practice”. Laboratory fibrinogen index remained reduced on the 14th animals meeting the requirements for inclusion day of the experiment as well, indicating the in the experiment were divided into groups preservation of hypocoagulation. In most animals according to sex, age, weight, and randomization. of the experimental group, against the background Experimental work was carried out in accordance of the introduction of Carsil, this indicator remained with “Animal Experimentation Legislations” reduced and differed from the control group by no (Appendix to the Order of the Ministry of Health of more than 10%. In the group of rats receiving CHP the USSR No. 755 dated 12.08.77), “Requirements (Table 1), the level of fibrinogen increased in 6 out of the European Convention for the Protection of 8 to 2.0 g/L and higher. of Vertebrate Animals” (Strasbourg, 1986). The The APTT indicator, one of the basic report of the study was agreed with the Ethics coagulogram indicators, depending on the Committee of the Buryat State University (No. 2 concentration of plasma factors (II, V, VIII, IX, X, dated 04.12.2016). XI, XII, and fibrinogen), allowing to evaluate the Pharmacotherapeutic effectiveness of the effectiveness of the internal path coagulation studied phytoextract was determined after 7, reflected significant changes in the coagulation 14 days from the beginning of the experiment. system in the group of experimental animals. On Statistical processing of the obtained data was the 7th day of the experiment, APTT increased by carried out on the basis of modern packages of 8.21% in the group of animals receiving Carsil, applied mathematical programs using the Student’s with the introduction of the studied polyextract t-test. The differences were considered statistically by 15.6%–18.5%, reflecting a decrease in the reliable at p<0.05. manifestations of hypocoagulation. Prothrombin index (PI) used in clinical Results and discussion conditions as an objective criterion for the severity of With the introduction of D-Galactosamine liver damage and coagulation disorders decreased hydrochloride, experimental animals in the early significantly in the formation of D-Galactosamine periods of the experiment did not show a sharp hepatitis. With the introduction of the Carsil deterioration of their state, they maintained motor reference hepatoprotector, white rats revealed an activity and appetite. The body weight of white rats increase in PI in 3 animals out of 8, averaging 9.75% in experimental groups did not change during the on the 7th day of the experiment. With the use of first week of the experiment, and in intact animals the studied phytopolyextract, the increase in the PI the weight increased by 20–25 g. In the second week, in white rats amounted to 20.6–23% at doses of 100 motor activity decreased in experimental animals, mg/kg, 200 mg/kg, 300 mg/kg on the 7th day of the appetite worsened, body weight decreased by 10– experiment. 12% compared to intact rats. Table 1 Status of blood coagulation cascade in white rats in the case of D-Galactosamine hydrochloride liver damage with the use of the complex herbal product on the 7th day of the experiment (М+о, n=8).
Experimental groups of animals (D-Galactosamine hepatitis) Biochemical Intact Experimen- No. Control + Group 1 + 100 Group 2 + 200 Group 3 + 300 indicators rats tal group + H2O mg/kg CHP mg/kg CHP mg/kg CHP Carsil 1 Fibrinogen, g/L 2.43±0.13 1.51±0.11*1 1.67±0.18 1.92±0.13*2 1.97±0.12*2 1.99±0.11*2 2 APTT, sec 23.04±1.9 34.24±1.7*1 31.4±1.53 28.9±1.4*2 28.2±1.3*2 27.89±1.25*2 3 PI, % 84.4±4.7 51.3±2.4*1 56.3±3.7 62.1±3.16*2 61.9±2.8*2 60.8±3.2*2 4 PT, sec 19.5±1.6 33.7±1.7*1 27.8±1.9 26.8±1.9*2 25.9±1.7*2 26.3±2.1*2 5 INR, RU 1.22±0.12 2.93±0.14*1 2.57±0.18 * 2.34±0.17*2 2.32±0.19*2 2.16±0.17*2 6 PR, % 1.16±0.12 2.53±0.17*1 2.17±0.19 2.05±0.112 2.02±0.13*2 2.04±0.11*2 Note. Hereinafter: *1 – differences are statistically reliable between the intact and control groups of animals at p<0.05; *2 – differences are statistically reliable between the control and experimental groups; n – number of animals in the group. 30 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
The prothrombin time (PT) indicator makes the control group in 2 animals out of 8, and an it possible to quickly assess not only the external average decrease was 14.2%. The use of the studied hemostasis system, but also the entire blood polyextract in white rats significantly reduced PR coagulation reactions cascade. The PT indicator and hypocoagulation manifestation in comparison significantly increased in D-Galactosamine liver with the control group: it was revealed in 6 animals damage in white rats, with significant differences out of 8. from the intact group remaining on the 14th day To assess the state of prothrombin complex of the experiment (Table 2). On the 7th day of the in case of liver damage by D-Galactosamine, the experiment, half of animals of the experimental indicator of the international normalized ratio group receiving Carsil showed a tendency to (INR) was used, which confirmed the development increase PT. With the use of CHP at doses of 100 mg/ of significant hypocoagulation disorders in the kg, 200 mg/kg, 300 mg/kg, a significant decrease in control group of animals. In the experimental PT was observed in groups of animals with acute group, after the introduction of Carsil to white rats, hepatitis compared to the control group (21–23%) the difference by 12% between this group and the on the 7th day of the experiment. control one was noted in the given period. When In D-Galactosamine hepatitis, prothrombin using the studied herbal product at doses of 100 ratio (PR) being the integral part of the study of mg/kg, 200 mg/kg, 300 mg/kg in groups of animals prothrombin blood complex increased significantly in the early stages of the experiment, the difference in the group of control animals. Against the of INR between this group and the control one background of the introduction of Carsil to white amounted to 20% and more. rats, there was a decrease in PR compared to Table 2 Status of blood coagulation cascade in white rats in the case of D-Galactosamine hydrochloride liver damage with the introduction of the complex herbal product on the 14th day of the experiment (М+о, n=8).
Experimental groups of animals (D-Galactosamine hepatitis) Biochemical Experimen- Group 1 + Group 2 + Group 3 + No. Intact rats Control + indicators tal group + CHP 100 mg/ CHP 200 mg/ CHP 300 mg/ H2O Carsil kg kg kg Fibrinogen, 1 2.43±0.13 1.64±0.11*1 1.85±0.19 2.01±0.10*2 2.04±0.12*2 1.99±0.11*2 g/L
2 APTT, sec 23.04±1.9 29.7±2.1*1 25.7±1.9 23.5±1.17*2 23.4±1.21*2 23.3±1.112
3 PI, % 84.4±4.7 62.1±3.4*1 75.4±6.4 79.5±3.9*2 80.7±6.2*2 79.8±5.7*2
4 PT, sec 19.9±1.6 25.9±1.2*1 23.2±1.7 21.83±1.1*2 21.6±1.3*2 21.46±1.2*2 5 INR, RU 1.22±0.12 2.13±0.15*1 1.97±0.19 1.58±0.12* 1.62±0.14*2 1.57±0.15*2 6 PR, % 1.16±0.12 1.87±0.11*1 1.48±0.13 1.41±0.12* 1.38±0.13 *2 1.37±0.10*2
On the 14th day of the experiment, in the control the intact group in most animals. At the same time, group of animals in the case of D-Galactosamine the PR and INR indicators significantly decreased, liver damage, significant differences in indicators confirming the decrease of hypocoagulation showing the violations of the coagulogram disorders in the group of animals receiving the remained (Table 2). With the introduction of CHP. Carsil, there was a tendency towards an increase in prothrombin index, fibrinogen, and APTT in Conclusion animals, but no reliable values were revealed in Experimental hepatitis caused by the this group. introduction of D-Galactosamine hydrochloride In the second week of the examination, the was characterized by the development of content of fibrinogen increased by 27–30% compared hypocoagulation disorders associated with a to the control group with the introduction of the decrease in the fibrinogen level, prothrombin studied polyextract at doses of 100 mg/kg, 200 mg/ complex factors due to the violations of the kg, 300 mg/kg in white rats. The use of the CHP synthesizing function of hepatocytes. The dynamics contributed to the increase in prothrombin index of additional indicators of coagulogram, APTT, PI, (Table 2) by 25–27% compared to the control. In the PR, and INR confirmed the coagulation disorders. second week of the experiment, the level of APTT In the severe course of the pathological process decreased by 21.5% and approached the level of in the liver, the possibility of the development of 31 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 the disseminated intravascular coagulation (DIC) 5. Lesiovskaya E.E. Scientific Phytotherapy. having a general biological orientation and capable M., 2014. of becoming cascading is of particular significance. 6. Barkagan Z.S., Momot A.P. Fundamentals of DIC, as is known, can proceed not only in the Diagnostics of Hemostasis Disorders. M., 1999: 290. pronounced clinical form, but also in the form 7. Guidance on Experimental (Preclinical) Study of compensated or subcompensated process, of New Pharmaceutical Substances. Ed. R.U. Khabriev. significantly burden the course of the pathological M., 2012: 832. process. The hypocoagulation disorders detected in the experimental animals correspond to the Contacts second phase of DIC syndrome. Corresponding author: Ubeeva Elena Hemostasis disorders in D-Galactosamine Aleksandrovna, Postgraduate student of the hydrochloride liver damage can be caused by a Department of Pharmacology, Buryat State combination of the insufficient synthetic function University, Ulan-Ude. of hepatocytes in formation of coagulation 670002, Ulan-Ude, ul. Oktyabrskaya, 36a. factors and the possibility of development of DIC Tel.: 8 (9021) 612296. syndrome. Determination of coagulation disorders E-mail: [email protected] testifies to the diagnostic value of these deviations in the assessment of severity, probable prognosis, Author information and need for correction in case of liver damage. Nikolaev Sergei Matveevich, Doctor of Medical When using the Carsil reference hepatoprotector Sciences, Professor of the Department of in a group of experimental animals with Pharmacology and Traditional Medicine, Buryat D-Galactosamine hepatitis, there is a clear tendency State University, Senior Research Scientist of IGEB to decrease in the manifestations of coagulation SB RAS, Ulan-Ude. disorders, but no significant differences were noted. 670002, Ulan-Ude, ul. Oktyabrskaya, 36a. The introduction of the CHP led to the significant Tel.: (3012) 297170. reduction of hypocoagulation, moreover, from the E-mail: [email protected] early stages of the experiment, but no distinct dose- dependent effect was revealed. Olennikov Daniil Nikolaevich, Doctor of Biological Conflict of interest. The authors declare that Sciences, Senior Researcher of IGEB SB RAS, Ulan- there is no conflict of interest. Ude. 670047, Ulan-Ude, ul. Sakhyanovoi, 6. References: Tel.: 8 (9021) 600627. 1. Infectious Diseases. National guidance. Ed. E-mail: [email protected] N.D. Ushchuk, Yu.Ya. Vengerov. M., 2010: 1056. 2. Sherlok Sh., Duli D. Diseases of the Liver and Ubeeva Iraida Polikarpovna, Doctor of Medical Biliary Tracts. Ed. Z.G. Aprosina, N.A. Mukhin. M., Sciences, Professor of the Department of Infectious 2002: 864. Diseases, Buryat State University, Ulan-Ude. 3. Nikonov G.K., Manujlov B.M. Fundamentals 670002, Ulan-Ude, ul. Oktyabrskaya, 36a. of Modern Phytotherapy. M., 2005: 520. Tel.: (3012) 297170. 4. Nikolaev S.M. Phytopharmaco-therapy and E-mail: [email protected] Phytopharmaco-prevention of Diseases. Ulan-Ude, 2012: 286.
32 Clinical medicine
BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
UDC 616.53-002.25-07:615.262 doi.org:10.31684/2541-8475.2019.1(13).36-42 MORPHOMETRIC ASSESSMENT OF THE THERAPY EFFICACY IN PATIENTS WITH MODERATE ACNE Irkutsk State Medical University, Irkutsk Regional Dermatovenerologic Dispensary, Irkutsk M.L. Abdukhalikova, I.O. Malova
In this study, we assessed the changes in facial skin morphometric indicators in the case of moderate acne against the background of systemic LIDOSE form isotretinoin therapy in 30 patients being administered isotretinoin in the LIDOSE form at the dose of 0.6–0.8 mg/kg a day until the achievement of the total course drug dose – 100–120 mg/kg of body weight. The control group consisted of 30 practically healthy people. The study showed good efficiency and tolerability of the therapy, in the course of treatment, there was a reliable positive dynamics of objective changes in skin morphometric indicators. The morphometric study carried out in dynamics reflected the positive impact of isotretinoin in the LIDOSE form on pathogenetic mechanisms of moderate acne. Key words: isotretinoin in the LIDOSE form, acne, ultrasonic scanning, sebumetry, corneometry.
Among chronic inflammatory dermatoses of objectively analyze changes in morphometric non-infectious genesis, acne vulgatis is one of the parameters of the skin during treatment [9, 10, 11]. most frequent causes of resorting to a dermatolo- High-frequency ultrasound examination of the gist. Common acne is diagnosed in 80% of the pop- skin allows the study of morphological structures ulation aged 20–30 years (aged 17 years – in 86.1%). of the epidermis and dermis. This technique can The frequency of occurrence of the disease does not be successfully applied to observe pathological depend on sex, but there is a heavier course in boys processes in the skin, as well as to objectively [1]. About 20% of patients have moderate and se- assess the effectiveness of therapeutic impact, and, vere intensity of the disease [2]. if necessary, to perform its additional correction in The disease is characterized by the progredient dermatological patients [11]. course, formation of nosogenic psychoemotional The principle of corneometry is based on disorders mainly of depressive series in about half the quantitative determination of moisture in of patients, sharply reduces the quality of life of the surface layer of the skin in the conditions of patients, and the frequency of occurrence of severe passing electric current. Electrical conductivity forms leading to significant cosmetic defects in the and current intensity between the sensor probes form of hypo- and hypertrophic scars is from 5 to directly touching the skin surface are digitalized for 15% of all cases of acne [3, 4, 5]. measurements. The higher the moisture content in It should be recognized that the most effective keratinocytes, the higher the electrical conductivity method of treatment of moderate and severe coefficient [9]. forms of acne is conducting a course of therapy The principle of photometry is used to carry with systemic isotretinoin [6]. To date, a number out sebumetry. A special synthetic tape sensitive of studies have been published demonstrating to fats is applied to the skin surface and changes the high efficacy and safety of LIDOSE form its optical density depending on the amount of isotretinoin therapy [7]. This drug allows to reduce fats. The pink surface of the paper becomes red a single dose of isotretinoin by 20%, to increase the after sebum absorption. Next, the sensor scans the safety of treatment, with that, it is cheaper than color change, the microprocessor handles the data usual forms of isotretinoin, thus, it is available received and outputs them in numerical values [9]. to more patients that determines the economic The research objective is to assess changes in viability of its application [8]. facial skin morphometric indicators in patients Currently, a large number of papers have been with moderate acne against the background of published to assess the clinical efficacy of therapy systemic LIDOSE form isotretinoin therapy. in acne patients, which includes reduced comedone formation, regression of elements, dynamics of Materials and methods postinflammatory changes. However, in modern The study was conducted on the basis of the conditions, it is necessary to focus on objective SBHI “Regional Dermatovenerologic Dispensary”, data also when the assessment due to evidence- 30 patients with moderate acne were under the based medicine is required. To do this, it is rational supervision (the main group): 18 men (aged 17–33) to use non-invasive methods of assessing the skin and 12 women (aged 17–29) who received LIDOSE condition, which include ultrasonic scanning of form isotretinoin (Acnecutan) at a dose of 0.6–0.8 the skin, sebumetry, corneometry, allowing to mg/kg per day until the total course drug dose of 100–120 mg/kg of body weight. The moisturizing 33 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 cream was used to care for the facial skin. The significance. The critical level of significance when duration of therapy of patients was 6-7 months. checking statistical hypotheses amounted to p<0.05. The control group consisted of 30 practically healthy people aged from 18 to 35. Results and discussion The duration of the disease in patients varied After completion of treatment, clinical recovery from 1 to 12 years (6.6±3.9 years). All patients noted was observed in 27 (90.0%) patients; improvement the ineffectiveness of the previously conducted in 3 (10.0%) patients; lack of effect was not traditional therapy, the occurrence of frequent registered. Against the background of treatment, relapses of the disease. In all patients, rashes were 28 (93.3%) patients registered cheilitis, 17 (56.6%) widespread and localized on the skin of the face, patients – facial dermatitis, 14 (46.6%) patients – back, upper chest, were presented by polymorphic xerosis (skin dryness). Along with the above side rashes: comedones, papules, pustules, single effects, 3 (10%) patients had nasal hemorrhage, 2 indurative and phlegmonous rashes. (6.7%) patients – blepharoconjunctivitis. Before the beginning of treatment with Morphometric skin parameters were estimated isotretinoin, 1 and 3 months after its beginning, after 1, 3 months from the beginning of therapy blood biochemical parameters were studied: and after the completion of treatment. AST, ALT, alkaline phosphatase, triglycerids, Normally, in skin ultrasonic scanning, epidermis cholesterol, creatinine (there were no deviations is represented by linear structures of high echoicity, from the norm). it is clearly delimited from the dermis with a The Aramo SG unit (ARAM HUVIS Co., Ltd, smooth contour. Two interconnected layers, the South Korea) was used to assess the facial skin papillary one and the reticular one, form dermis. morphometric parameters. Facial skin diagnostics The papillary layer is formed by loose connective on this device allows to carry out corneometry tissue, the reticular layer forms the most part of the (relative units – RU) and sebumetry (RU). dermal tissue. It consists mainly of collagen fibers Ultrasound skin examination was carried out of great diameter combining into large interweave by the DUB SkinScanner (tpm GmbH, Taberna fascicles with surrounding and branching elastic Pro Medicum, Germany) with a sensor of 22 MHz, fibers. Also in the dermis structure, hypoechogenic scanning depth of 8 mm, and resolution of 72 μm. structures of sebaceous, sweat glands, ducts, and The study was carried out on the skin of three blood vessels are visualized. In this regard, during localizations (forehead, chin, cheeks), these are ultrasonic scanning, dermis is visualized in the the areas of the most pronounced inflammation form of the different-sized acoustic reflection and maximum amount of rashes. Epidermis and structure. Due to the fact that the reticular layer is dermis thickness (μm), acoustic density (RU) were more dense, there is a stronger acoustic reflection of evaluated. the ultrasonic signal, accordingly, a brighter image The study was approved by the local Ethics of the lower dermis layers is formed. Subcutaneous Committee of the Irkutsk State Medical University. tissue is represented by hypo- and anechogenic Statistical processing of the results was carried areas clearly delimited from the dermis (Figure 1). out in the STATISTICA 6.0 program. Parametric Details of ultrasonic scanning of the skin in Student’s t-test was used to calculate the statistical patients before and after treatment are given in Table 1.
Figure 1. Ultrasonic scanning of the healthy skin in the cheek area of the participant from the control group. 34 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
Table 1 Parameters of ultrasonic scanning of the skin in acne patients before and after treatment
Control Main group before Main group group treatment after treatment Indicator p * p * p * n=30 n=30 1 n=30 2 3 M±σ M±σ M±σ Epidermis thickness, μm forehead 103.7±3.5 127.3±9.84 <0.01 81.1±6.78 <0.01 <0.01 chin 103.2±4.6 128.7±13.4 <0.01 81.1±7.4 <0.01 <0.01 cheeks 103.2±5.9 125.4±10.3 <0.01 80.7±6.09 <0.01 <0.01 Epidermis acoustic density, RU forehead 57.2±12.8 49.9±23.8 0.148 70.4±12.6 <0.01 <0.01 chin 62.3±13.7 58.8±20.3 0.433 70.6±14.6 <0.05 0.01 cheeks 63.1±6.7 45.3±10.7 <0.01 67.6±11.7 0.072 <0.01 Dermis thickness, μm forehead 1551.8±74.2 1925.5±136.3 <0.01 1800.8±137.0 <0.01 <0.01 chin 1008.9±62.8 1063.2±89.6 <0.01 1108.4±119.3 <0.01 0.102 cheeks 1532.2±67.4 1924.6±148.0 <0.01 1745.5±96.4 <0.01 <0.01 Dermis acoustic density, RU forehead 5.1±1.1 3.1±0.98 <0.01 6.4±1.3 <0.01 <0.01 chin 4.03±0.7 3.4±1.07 0.01 6.1±1.1 <0.01 <0.01 cheeks 6.4±1.07 3.2±0.89 <0.01 6.3±1.3 0.623 <0.01 Note: *р according to t-test; p1 – differences in the main and control groups before treatment; p2 – differences in the main and control groups after treatment; p3 – differences in the main group before and after treatment.
Figure 2. Ultrasonic scanning of the facial skin in the cheek area of the female patient from the main group before treatment.
In ultrasonic scanning of the skin of acne patients treatment, epidermis acoustic density in acne pa- before treatment (Figure 2), epidermis thickening tients was signifi cantly lower than the control points and uneven structure (p<0.01), as well as reduction only in the cheek area, which may be due to the fact of its acoustic density draw att ention, they are most that it is the area of the most pronounced infl amma- likely due to follicular epidermal hyperprolifera- tion and the maximum amount of rashes. Against tion, whereby the epithelium of the upper part of the the background of treatment, epidermis acoustic hair follicle, infundibulum, becomes hyperkeratotic, density increases in all studied areas (p<0.01). This keratinocytes cohesion increases [12]. In the course confi rms the impact of LIDOSE form isotretinoin on of treatment (Figure 3), epidermis thickness signifi - the strengthening and normalization of diff erentia- cantly reduces in all studied areas (p<0.01). Before tion of keratinocytes. 35 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
Figure 3. Ultrasonic scanning of the facial skin in the cheek area of the female patient from the main group after treatment.
In addition, during ultrasonic scanning of the reflection of the ultrasonic signal is visualized. skin in acne patients before treatment, dermis These changes indicate an improvement in the thickening and reduce in its acoustic density dermis structural organization and a decrease in (p<0.01) due to inflammation were noted: in the the inflammation signs, an increase in the dermis developed stage, inflammation in acne is a classic main substance. One of the main reasons for the manifestation of type IV immunological reaction. reliable dermis thickening can be the strengthening As inflammation increases in the sebaceous hair of its proliferative capabilities. Thickening and follicle, granulomatous inflammation develops leveling the dermis borders can be associated with resulting in scar formation [2]. Because of this the improvement of its structural organization, processes, uneven distribution of echo signal in primarily its fibrous structures and intercellular dermis occurs (Figure 2). substance. This is probably one of the effects After 1 month of treatment, an even greater of systemic LIDOSE form isotretinoin on the increase in the dermis thickness was recorded. These acceleration of collagen synthesis due to the impact changes can be explained by the recrudescence on the MMP expression system [13, 14, 15, 16, 17]. of the disease in patients in the 2-3 weeks of Analysis of dynamics of corneometry treatment. It is due to the fact that isotretinoin parameters revealed that initially, the skin of acne significantly reduces sebum production in the patients is overdried, most often due to the lack second week of treatment already, resulting in of rational moisturizing skin care (Figure 4). In the rapid simultaneous release of P.acnes antigens our study, before the beginning of treatment with into surrounding tissues and the following violent systemic LIDOSE form isotretinoin, we selected inflammatory reaction involving superantigens adequate moisturizing skin care for all patients, and/or Toll-like receptors. During the examination that is why even against the background of of patients after 3 months and after treatment, the treatment with retinoid, our patients showed an dermis thickness stabilization can be noticed, its improvement in the indicators of moisture in the indicators remain above the ones of the control forehead, chin skin areas (p<0.01), and in the cheek group (p<0.01). area (p<0.05). When assessing the dynamics of changes in The sebosuppressive effect of systemic LIDOSE dermis acoustic density in the course of treatment, form isotretinoin is rather pronounced, as shown there is also a significant increase in indicators in in Figure 5, which demonstrates the dynamics of all studied areas (p<0.01): there is an increase in changes in the sebumetry indicators in patients indicators to the control values in the cheek area in the forehead area, as this very area is the most and higher values in the forehead and chin areas. appropriate for the assessing the characteristics of In ultrasonic scanning of the skin of patients sebaceous glands secretion (here, the surface skin after treatment (Figure 3), thin, dense, uniform lipids are mainly secreted by sebaceous glands, and epidermis draws attention, which corresponds to the share of lipids secreted by corneocytes amounts the normalization of the cycle of cell keratinization to 3–6%). A decrease in the sebumetry indicators is and desquamation. Along with this, homogeneous, observed throughout the treatment process. dense, thickened dermis with a stronger acoustic 36 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
Figure 4. Dynamics of corneometry indicators in the forehead area against the background of LIDOSE form isotretinoin therapy.
Figure 5. Dynamics of sebumetry indicators in the forehead area against the background of LIDOSE form isotretinoin therapy.
Conclusion resulting in a curative effect on already existing Our study showed high efficacy (90% of clinical scar deformations in acne patients, also prevention recovery) and good tolerability of treatment of of new scars occurs. During acne treatment moderate acne with LIDOSE form isotretinoin. with systemic LIDOSE form isotretinoin, anti- In the course of treatment, there was a reliable inflammatory and powerful sebosuppressive effects positive dynamics of objective changes in the are observed. Besides, with properly selected and skin morphometric indicators covering all links regular use of moisturizing skin care in patients of the disease pathogenesis: strengthening and during treatment, it is possible to reduce the most normalization of differentiation of keratinocytes, common side effect of therapy, retinoid dermatitis, strengthening of dermis proliferative capabilities to minimal manifestations. Thus, the LIDOSE drug
37 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 form allows reducing the dose of isotretinoin while 11. Goryachkina M.V., Belousova T.A. Differ- maintaining high efficacy and minimal risk of side entiated approach to selection of dermatocosmet- effects. The morphometric study carried out in ic agents in complex treatment of acne in women. dynamics objectively reflected the positive impact Vestnik Dermatologii i Venerologii. 2012; 6: 96-103. of isotretinoin in the LIDOSE form on pathogenetic 12. Kang S, Cho S, Chung JH, et al. mechanisms of moderate acne. Inflammation and extracellular matrix degradation Conflict of interest. The authors declare that mediated by activated transcription factors there is no conflict of interest. nuclear factor-kappa B and activator protein-1 in inflammatory acne lesions in vivo. Am J Patol. 2005; References: 166: 1691. 1. Kungurov N.V., Kokhan M.M., O.V. 13. Baumann L. Cosmetic dermatology. Principles Shabardina O.V. Experience of therapy of patients and practice. Ed. N.N. Potekaeva. M., 2012: 688. with moderate and severe acne with isotretinoin 14. Trivedi NR, Gilliland KL, Zhao W, et al. drug. Vestnik Dermatologii i Venerologii. 2013; 1:56– Gene array expression profiling in acne lesions 62. reveals marked upregulation of genes involved 2. Akhtyamov S.N. Practical in inflammation and matrix remodeling. J Invest dermatocosmetology. Acne, scars, pitted acne scars and Dermatol. 2006; 126: 1071. acneiform dermatoses. M., 2010: 280. 15. Layton AM. Optimal management of acne 3. Adaskevich V.P. Acne vulgaris and rosacea. to prevent scarring and psychological sequelae. M., 2003. Am J Clin Dermatol. 2001; 2: 135. 4. Samgin M.A., Monakhov S.A. Acne. 16. Janssen de Limpens AM. The local Etiopathogenesis, clinic, therapy. Guidance manual treatment of hypertrophic scars and keloids with for doctors. M., 2012. topical retinoic acid. Br J Dermatol. 1980; 103: 319. 5. Masukova S.A., Sanakoeva E.G., Ilyina 17. Mizutani H, Yoshida T, Nouchi N, et al. I.V. Isotretinoin in acne therapy.Russian Journal of Topical tocoretinate improved hypertrophic scar, Clinical Dermatology and Venereology. 2012; 2: 79-85. skin sclerosis in systemic sclerosis and morphea. J 6. Eady EA, Gloor M, Leyden JJ. Dermatol. 1999; 26: 11. Propionibacterium acnes resistanse: a worldvite problem. Dermatology. 2003; 20(6): 54 -56. Contacts 7. Lehucher-Ceyrac D, Weber-Buisset MJ. Corresponding author: Abdukhalikova Maria Isotretinoin and acne in practice: a prospective Leonidovna, cosmetologist of the Cosmetology analysis of 188 cases over 9 years. Dermatology. Department, Regional Dermatovenerologic 1993; 186: 123-128. Dispensary, Irkutsk. 8. Volkova E.N., Osipova N.K., Grigorjeva 664011, Irkutsk, ul. Gusarova, 2. A.A. et al. Progressive technologies in manage- Tel.: 8 (950) 0691917. ments of patients with acne. Russian Journal of Clin- E-mail: [email protected] ical Dermatology and Venereology. 2010; 1: 74-78. 9. Panova O.S., Gubanova E.I., Lapatina N.G. Author information et al. Modern methods of assessing aquation and Malova Irina Olegovna, Doctor of Medical Scienc- biomechanical skin features. Vestnik Dermatologii i es, Professor of the Department of Dermatovene- Venerologii. 2009; 2: 80-87. reology and Cosmetology, Irkutsk State Medical 10. Sergeeva I.G., Krinitsyna V.V., Onipchen- University, Irkutsk. ko V.V. et al. Clinical and morphological charac- 664003, Irkutsk, ul. Krasnogo Vosstaniya, 1. teristics of the skin condition in acne patients in Tel.: (3952) 242313. dynamics of LIDOSE form isotretinoin therapy. E-mail: [email protected] Vestnik Dermatologii i Venerologii. 2012; 5: 120-126.
38 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
UDC 616.12-008.331.1:616.15-07 doi.org:10.31684/2541-8475.2019.1(13).43-45 PROGNOSTIC IMPORTANCE OF INFLAMMATION MARKERS (C-REACTIVE PROTEIN AND INTERLEUKIN-6) IN PATIENTS WITH ARTERIAL HYPERTENSION Altai State Medical University, Barnaul N.V. Vostrikova, D.V. Fyodorov, E.E. Klimova, K.M. Bishevsky
The article describes the results of the research of 54 patients aged from 34 to 86 years having essential arterial hypertension. The results obtained reveal the increase of C-reactive protein and interleukin-6 in such patients. High frequency of revealing of abovementioned acute phase indices is noted as well, which may be of prognostic importance concerning the development and course of cardiovascular pathologies. Key words: arterial hypertension, acute phase indices.
Arterial hypertension (AH) is the leading risk alcoholism, drug addiction, diffuse connective factor for atherosclerosis and its complications tissue diseases, mental diseases, chronic heart being the cause of the apoplectic attack and failure of the III-IV functional classes of the New myocardial infarction [1, 2, 3]. According to the York Heart Association, and the presence of modern concept of atherogenesis, atherosclerosis hemodynamically significant heart defects. The is a prolonged sluggish chronic inflammation in control group consisted of 49 practically healthy the intima of the vessel [4]. This concept allows people under the age of 40. to see the connection between the mediators of The content of IL-6 and CRP in the blood serum inflammation and the risk factors of atherosclerosis. was analyzed with the immunoenzymatic method. Low-active sluggish inflammation prospectively The studies were carried out on the Uniplan device determines the risk of development of these with the help of the set of reagents Human IL-6 complications. Previously, there was evidence that ELISA produced by the Bender MedSystems, neutrophils generalize endothelium inflammatory Austria and the set of Hs-CRP ELISA produced by changes, and this activation of pro-inflammatory the Biomerica, USA. factors can be witnessed in the systemic circulation To assess the risk of the cardiovascular disease [5]. Therefore, the study of the content of the main progression, the level of CRP was used [6]. A group inflammation markers – interleukin-6 (IL-6) and with a high risk of the cardiovascular disease pro- C-reactive protein (CRP) – in patients with AH gression was formed among patients with arterial can provide information on the progression of the hypertension with a concentration of CRP being atherosclerotic process. over 3.0 mg/l. The research objective is to study the content of The statistical analysis of the results was the most important inflammation reaction markers, carried out using the SPSS 9 software package that is CRP and IL-6, in patients with essential for Windows. Results are presented in the form arterial hypertension. of: arithmetic mean (X) ± error of mean (m). The statistical significance of differences in the samples Materials and methods was assessed at p<0.05. Linear correlation analysis We examined 54 patients (12 men and 42 was used to assess the severity of the correlation of women) aged 34-86 (the mean age is 65.5±1.6). indicators. The mean duration of the AH amounted to 17±1.0 years. 22 patients had a high risk of the target Results and discussion organs damage and cardiovascular complications. The world literature compiles the great A very high risk of cardiovascular complications material, on the basis of which the unfavourable was established in 31 patients by the presence of prognostic role of CRP in relation to the associated diseases, including 15 patients with development and course of the cardiovascular arterial hypertension in anamnesis having the pathology is recognized [6, 7, 8, 9, 10]. That is why episodes of atherothrombosis (acute myocardial we considered it necessary to determine the mean infarction, acute cerebral circulation disorder). values and frequency of increase of these indicators The study did not include people with a in patients with arterial hypertension. The study of malignant form of the arterial hypertension, 54 patients with arterial hypertension revealed the symptomatic hypertension, acute inflammatory increase of the CRP level – 8.66±0.88 mg/l (p<0.001) processes and chronic ones at the stage of the compared to the similar indicators in the control recrudescence, renal and hepatic pathology, group — 1.74±0.11 mg/l. The data obtained comply hematological diseases, oncological diseases, with the results of studies of other authors which
39 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 described the increase of the CRP level in patients 4. Gogin E.E. Hypertensive disease and associat- with cardiovascular system diseases, including ed diseases of the circulatory system: basics of pathogen- arterial hypertension [11, 12, 13]. esis, diagnostics and choosing of treatment. M., 2006: Among the patients surveyed, only 4 people 254. had normal CRP values. We found a moderate 5. Koryakina L.B., Pivovarov Yu.I., Kurilska- increase in the CRP level in 11 patients. We ya T.E. et al. Vessel endothelium disfunction in ar- discovered a high risk of cardiovascular disease terial hypertension and ischemic heart disease (lit- progression (the content of CRP was over 3.0 mg/l) erature overview). Bulletin VSNC SO RAMN. 2013. in 39 patients (72%) with arterial hypertension. The 2-1 (90): 165–170. high frequency of increase of CRP indicates the 6. Gusev D.E., Ponomar’ E.G. Role of C-reac- significant role of this marker in the pathogenesis tive protein and other markers of acute inflamma- of arterial hypertension. tion phase. Clinical Medicine. 2006; 3: 25–30. The concentration of interleukin-6 in patients 7. Dmitriev V.A., Oshchepkova E.V., Titov with AH was also reliably higher than in patients V.N. C-reactive protein and arterial hypertension: of the control group and averaged 5.8±0.6 pg/ml is there a connection? Therapeutic archive. 2006; 5: and 1.3±0.08 pg/mg respectively (p<0.001). 86–89. Since interleukin-6 is a pro-inflammatory 8. Titov V.N. C-reactive protein: physical cytokine involved in the implementation of the and chemical features, methods for determination immune response in an inflammatory reaction, it and diagnostic value. Clinical laboratory diagnostics. seems that a reliable increase of this indicator is the 2004; 4: 3-9. reflection of the inflammatory process occurring 9. Antonova A.B., Shevchenko A.O., Ko- in the arterial wall in patients with arterial chetova E.V. Diagnostic value of PAPP-A and in- hypertension. flammation markers in acute coronary syndrome. The increased content of interleukin-6 (79.6%) Bulletin of RSMU. 2005; 42: 3-5. was found in 43 patients with arterial hypertension. 10. Zadionchenko V.S, Adasheva T.V., San- Earlier it was shown that IL-6 is able to activate domirskaya A.P. Endothelium disfunction and ar- the liver production of the protein of the acute phase terial hypertension: therapeutic possibilities. Rus- of the C-reactive protein inflammation, fibrinogen, sian Medical Journal. 2002; 10(1): 11–15. complement components, etc. That is why we 11. Fichtlscherer S, Rosenberger G, Walter DH. conducted a correlation analysis between IL-6 and et al. Elevated C-Reactive Protein Levels and Im- CRP levels in patients with arterial hypertension. paired Endotelial Vasoreactivity in Patients With As a result, a weak positive correlation relationship Coronary Artery Disease. Circulation. 2000; 102(9): was revealed (r=0.34; р=0.011), which confirms 1000-1006. earlier information that interleukin-6 controls 12. Shilkina N.P., Yunonin I.E., Stolyarova the CRP synthesis. The presence of a relationship S.A., Mikhailova E.V. Arterial hypertension and between the CRP and interleukin-6 levels in systemic inflammatory process: modern state of patients surveyed suggests a significant role of problem. Therapeutic archive. 2008; 5: 91–96. these inflammation markers in the pathogenesis of 13. Danesh J, Whiter JG, Hirshfeld GM. et al. arterial hypertension. C-Reactive Protein and Other Markers of Inflam- mation in the Prediction of Coronary Heart Dis- Conclusions ease. N Engl J M. 2004; 350(14):1387-1397. 1. A high level of acute phase indicators reveals in patients with arterial hypertension: CRP in 72% Contacts of cases, interleukin-6 in 79.6% of cases. Corresponding author: Vostrikova Natalya 2. There is a positive correlation relationship Vladimirovna, Candidate of Medical Sciences, between the interleukin-6 and CRP levels in Associate Professor of the Department of Nursing, patients with arterial hypertension. Altai State Medical University, Barnaul. Conflict of interest. The authors declare that 656038, Barnaul, Lenina Prospekt, 40. there is no conflict of interest. Tel.: 8 (913) 0969323. E-mail: [email protected] References: 1. Burmistrova A.L., Shmunk I.V., Suslova Author information T.A., Grigoricheva E.A. HLA and cytokines in pa- Fyodorov Dmitry Vladimirovich, Doctor of Medical tients with essential arterial hypertension. Allergol- Sciences, Professor, Head of the Department of ogy and Immunology. . 2006; 7(3): 343–344. Nursing, Altai State Medical University, Barnaul. 2. Vaulin N.A. Endothelium disfunction in 656050, Barnaul, ul. Malakhova, 53a. arterial hypertension: focus on nebivolol. Systemic Tel.: (3852) 402147. Hypertensions. 2009; 1: 11–14. E-mail: [email protected] 3. Guideline for arterial hypertension. Ed. E.I. Chazov, I.E. Chazova. M., 2005: 734. 40 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
Klimova Elena Evgenyevna, Candidate of Medical Bishevsky Konstantin Mikhailovich, Candidate Sciences, Assistant of the Department of Nursing, of Medical Sciences, Associate Professor of the Altai State Medical University, Barnaul. Department of Nursing, Altai State Medical 656038, Barnaul, Lenina Prospekt, 40. University, Barnaul. Tel.: (3852) 366128. 656038, Barnaul, Lenina Prospekt, 40. E-mail: [email protected] Tel.: (3852) 366128. E-mail: [email protected]
41 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
UDC 616.3-07-08-036: 616.12-008.331.1:616.24-008.4 doi.org:10.31684/2541-8475.2019.1(13).46-51 CLINICAL AND EPIDEMIOLOGICAL FEATURES OF DIGESTIVE DISEASES IN PATIENTS WITH COMORBID PATHOLOGY OF RESPIRATORY AND CARDIOVASCULAR SYSTEMS Altai State Medical University, Barnaul E.B. Klester, I.I. Belova, A.S. Balitskaya, K.V. Klester
Research objective. To study the frequency and features of clinical implications of concomitant diseases of the digestive organs in patients with COPD, including the cases when combined with arterial hypertension. Materials and methods. Clinical and functional disorders were analysed in 319 patients, among them, 97 were diagnosed chronic obstructive pulmonary disease (COPD) (I group), 118 patients had the combination of COPD with arterial hypertension (AH) (II group), 104 patients had AH (III group). Results. It was found that chronic gastritis is the most frequently detected digestive system disease in patients with COPD (up to 78.2% of patients), however, gastroenterological complaints are hardly expressed. HP infection ranged from 67.6% (in patients of the II group) to 83.8% (in patients of the I group). According to the morphological study, in the presence of a combined pathology, the number of patients with signs of atrophy increases, the microcirculation disorder in gastric mucosa can be observed. Conclusion. High frequency of a concomitant digestive system pathology leads to mutual burdening of diseases, requires additional examination and obligatory medication correction in patients with COPD. Key words: digestive system pathology, chronic obstructive pulmonary disease, arterial hypertension.
The combination of diseases of the digestive Materials and methods system with pathology of respiratory and circula- The study included 319 patients with COPD tory systems occurs from 8% to 80% of cases [1, 2]. diagnosed according to GOLD (2018) [12], which In addition to the genetic predisposition and the determined the formation of groups: group I – 97 presence of anatomical and functional relation- patients with COPD, group II – 118 patients with ships realized by the commonality of innervation COPD and AH, group III – 104 patients with and blood supply, the high frequency of the com- AH. The pathology of the digestive system was bination can be explained by general risk factors determined according to the Russian standards as well: smoking, old age, etc. [3, 4]. One of the (protocols) of diagnosis and treatment of patients main problems of modern medicine is the increase with diseases of the digestive system (order of the in the multiplicity of diseases, which reflects, first Ministry of Health of the Russian Federation No. of all, involution processes (multimorbidity), while 125 dated 17.04.98, taking into account standards deterministic possibility of their combination (co- of medical care according to nosology) [13]. morbidity) remains difficult to study [5, 6]. This Exclusion criteria are as follows: acute forms of problem fully refers to the pathology of the diges- IHD, blood circulation decompensation (IIB and tive tract in patients with diseases of the respira- III stage of CHF), any other combined pathology tory and cardiovascular systems, the association under decompensation. Patients were included in of which determines significant changes of clinical the study upon admission. All participants of the implications, trends, approaches to treatment, and study signed an informed consent. outcomes of each disease [7, 8]. The world litera- In estimating the distribution of patients by ture actively discusses “systemic manifestations” sex, the majority were men: in group I – 64.5±8.7%, of COPD and the relationship of heart damage in group II – 62.8±7.2%, in group III – 61.6±4.6% with the emerging and ongoing pathological pro- (p>0.05). cesses of respiratory, digestive, genitourinary, and The mean age of patients of group I was some other systems [9], arising from three leading 58.7±1.73 years, group II – 61.3±1.14, group III – mechanisms of COPD development: systemic in- 59.5±1.41 (p>0.05). flammation, oxidative stress, and neurohormonal Patients of study groups did not differ among one [10, 11]. themselves by the main clinical characteristics The research objective was a comparative study (age, sex, severity of COPD), which allowed to of the frequency of occurrence and features of compare them. For example, patients of groups clinical implications of concomitant diseases of I and II had obstructive bronchial patency the digestive system in patients with pathology of disorders, classified by the FEV1 parameter of mild respiratory and cardiovascular systems. and moderate severity, and the degree of risk B prevailed (according to GOLD, 2018, taking into account the presence of even one recrudescence
42 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 that led to hospitalization) [12], subject to relieved of anastomosis and the preserved part with the recrudescence and AH (patients of groups II and III), diagnosis of Hp (the degree of contamination of mainly of the II degree (according to the Guidelines gastric mucosa with Hp was assessed according to for the Management of Arterial Hypertension the criteria proposed by L.I. Aruin et al. [15]), and of the European Society of Cardiology and the the determination of local urease activity (Clo-test). European Society of Hypertension, 2018) [14]. The Histological changes in the gastric mucosa (GM) average FC of CHF was 2.44±0.06 in patients of were evaluated according to the modified Sydney group I, 2.86±0.07 in group II, 2.12±0.09 in group classification using a visual analog scale [15].
III (pI-II; II-III<0.05). In the summary assessment of the Statistical processing of the obtained data was clinical state of patients by RSCS, 4.48±0.11 points carried out with the help of variation statistics were determined in patients of group I, 4.97±0.13 methods using the Statistica 7.0 software package. points in group II, 4.22±0.11 points in group III (pI-II; At normal distribution, the statistical significance
II-III<0.05). of differences in average indicators was determined All patients underwent the complex clinical with the use of Student’s t-test. Non-parametric instrumental and laboratory examination with criteria were used in the analysis of distributions the analysis of anamnesis data, complaints, and different from normal ones. Qualitative differences the objective study methods with the analysis of between groups were determined using the ECG, respiratory function (RF) examination, if Fisher’s exact test (at n<5) or c2 at n>5, including medically required – clinical and X-ray studies Yates’s correction at n<50. The differences were (including gastric X-ray), methods of functional considered statistically significant at p<0.05. diagnostics (ECG, RF, Doppler echocardiography, ultrasound investigation of hepatobiliary zone Results and discussion organs), endoscopic examination (GIF-Q10, In studying the frequency of occurrence of GIF-Q20, GIF-P30 units of Olympus firm were diseases of the digestive system, the highest used) of the esophagus, stomach, and intestines frequency was revealed in group II – in 77 (65.3%) with morphological study of biopsy materials, in patients, less in group I – in 50 (51.5%) patients, and patients after stomach resection – from the area in group III – in 42 (40.4%) patients (pI-II; II-III<0.05). Table 1 Structure of diseases of the digestive system in analyzed groups of patients Group I (COPD) Group II (COPD+AH) n=77 Group III (AH) n=42 n=50 Diseases Abs Abs Abs % % р % р number number number c2=4.83; c2=4.70; GERD 29 51.8 60* 69.0 24▪ 45.3 p=0.03 p=0.03 c2=6.68; c2=3.12; Chronic gastritis 34 60.7 68* 78.2 31 58.5 p=0.01 p=0.08 c2=4.57; c2=3.74; Chronic duodenitis 27 48.2 57* 65.5 23 43.4 p=0.03 p=0.05 c2=6.42; c2=5.17; Peptic ulcer disease 15 26.8 42* 48.3 13▪ 24.5 p=0.01 p=0.02 c2=3.25; c2=2.16; Cholelithiasis 11 19.6 30 34.5 10 18.9 p=0.07 p=0.14 c2=3.13; c2=3.08; Chronic pancreatitis 10 17.9 28 32.2 8 15.1 p=0.08 p=0.08 c2=4.10; c2=3.08; Chronic hepatitis 9 16.1 28* 32.2 8 15.1 p=0.04 p=0.08 c2=2.83; c2=1.54; Liver cirrhosis 6 10.7 20 23.0 6 11.3 p=0.09 p=0.21 Chronic bowel c2=4.61; c2=3.65; 8 14.3 27* 31.0 7▪ 13.2 diseases p=0.03 p=0.03 Notes: * – statistically significant differences (p<0.05) between groups I and II; ▪ – statistically significant differences (p<0.05) between groups II and III.
All patients filled in the GerdQ questionnaire 18 (the average score of group I was 9.1±3.7; group themselves. The number of points ranged from 1 to II – 10.3±4.1; group III – 9.0±3.5; pI-II; II-III<0.05). At the
43 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 sum of points of 8 and more, GERD was diagnosed, In patients of all groups, chronic gastritis which was confirmed by the EGD data. GERD was the most frequently detected disease of the was manifested in heartburn mainly in patients of digestive system (Table 1), with gastroenterological group I (79.3%), less often in patients of groups II complaints being mildly expressed. In the analysis and III (58.3 and 33.3% respectively; pI-II; II-III<0.05), of endoscopic picture of gastric mucosa, signs which was observed in half of patients both day of inflammation more pronounced in the antral and night. Strong correlation (r=0.71) was revealed section (in 44.1% of patients) than in the fundal one between the sum of the questionnaire points and (in 14.7% of patients) were observed in patients of the EGD results. The rate of detection of GERD group I more often than in patients of groups II moderately correlates with the points by CAT and III. (r=0.48). Table 2 Histological changes of gastric mucosa in analyzed groups of patients
Group I (COPD) Group II (COPD+AH) n=68 Group III (AH) n=31 n=34 Nature of changes Abs Abs Abs % % р % р number number number Inflammation in particular: c2=2.62; c2=4.86; 11 32.3 11 16.2 12 38.7▪ mild p=0.10 p=0.03 c2=0.87; c2=0.01; 16 47.1 24 35.3 12 38.7 p=0.35 p=0.92 moderate c2=6.30; c2=4.93; 7 20.6 33 48.5* 7 22.6▪ p=0.01 p=0.03 severe Activity in particular: c2=0.01; 6 17.6 10 14.8 3 9.7 p=0.75 absent p=0.92 c2=0.45; c2=5.23; 7 20.6 9 13.2 11 35.5▪ p=0.50 p=0.02 mild c2=0.93; c2=0.14; 14 41.2 20 29.4 11 35.5 p=0.33 p=0.71 moderate c2=3.91; c2=4.09; 7 20.6 29 42.6* 6 19.3▪ p=0.04 p=0.04 severe Atrophy in particular: absent 9 26.5 5 7.4* p=0.01 8 25.8* р=0.02
mild c2=0.45; 7 20.6 9 13.2 5 16.1 p=0.76 p=0.50 c2=0.01; c2=0.18; moderate 10 29.4 22 32.3 8 25.8 p=0.94 p=0.67
c2=4.32; c2=1.35; 8 23.5 32 47.1* 10 32.3 severe p=0.04 p=0.24 Intestinal metaplasia 4 11.8 22 32.3* p=0.03 4 12.9 p=0.05 Notes: * – statistically significant differences (p<0.05) between groups I and II; ▪ – statistically significant differences (p<0.05) between groups II and III. Pangastritis was found in 41.2% of patients of depths were revealed in 44.1% of patients, among group I. Against the background of hyperemia them the “full” ones in 29.4%. The outbreaks of and edema, hemorrhages in the form of petechial atrophic changes were localized most often in the rashes and punctulate erosions were revealed (in antral section (in 50.0% of patients). 64.7% of patients). Erosive defects of different 44 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
In patients of group II, with EGD, diffuse denal localization of ulcers prevailed (in 40% of stomach lesion was more often revealed in the patients). Hp was found in 10 (66.7%) patients of presence of large areas of pale mucous membrane group I. with thinning or complete loss of gastric folds, Localization of ulcerative process in the stomach hyperemia and edema of mucous membrane in the prevailed in patients of group II. The stomach body and antral section, contact bleeding. ulcer was characterized by large size, its formation In endoscopic examination of patients of group against the background of mucous membrane III, gastritis with predominant antral lesion was ischemia, the detection of Helicobacter pylori in diagnosed in 22.6%, common gastritis – in 71.0%, 19 patients (45.2%). In assessing the results of while isolated lesion in the body and gastric fundus endoscopic examination in patients of group III, was observed in only 6.4% of patients. According to ulcers were also more often located in the stomach the data of the complex application of cytological, than in the duodenum and often (in 31%) were histological, and urease tests, the infection of the multiple. Нelicobacter pylori (Hp) ranged from 67.6% (in As COPD course worsened, the proportion of patients of group II) to 83.8% (in patients of group stomach ulcers increased: the ratio of stomach and I), indicating a high degree of association of the duodenal ulcers increased from 1:4.2 (CHF I FC) to studied diseases with the Hp. 1:2 (CHF III FC). 80.3% of patients with combined The results of the morphological study showed pathology were characterized by chronic recurrent that the activity of inflammation (neutrophil course of PUD. infiltration) of various degrees of severity was According to the criteria proposed by A.A. revealed in almost all infected patients (94–100%), Ilchenko [18], cholelithiasis (CL) was found in while active gastritis was less likely in uninfected 19.6% of patients of group I, 34.5% of patients of patients. The frequency of occurrence of intestinal group II, 18.9% of patients of group III, which metaplasia (27.9%) prevailed in patients of group II. exceeds the population level ranging from 10% The obtained results conform to the data of to 15% [19]. Of these, stage I was more likely to other researchers, which showed that in 10–40% be found in patients of group I (45.45%). Stage II of cases, foci of complete and incomplete intestinal was diagnosed without statistically significant metaplasia in GM are found in persons with differences in all groups (27.3%; 30.0%; 30.0% chronic gastritis [16, 17]. respectively). Half (50.0%) of patients of group II In patients with nonatrophic gastritis, the were determined by stage III of CL. There were no level of colonization of the mucous membrane patients with stage IV among the examined ones. of Np correlated with indicators of activity and Diagnosis of chronic pancreatitis (CP) was inflammation degree. At the same time, the based on clinical and laboratory indicators and moderate (p=0.44) direct correlation was found in data obtained from transabdominal ultrasound patients of group I, and the average one (p=0.70; examination, computer and magnetic resonance p=0.61) was found in patients of groups II and III. tomography. CP was diagnosed as defined in 17.9% In patients with atrophic gastritis, the moderate of patients of group I, 32.2% of patients of group direct correlation was found between atrophy and II, and 15.1% of patients of group III. According activity, inflammation degree. Feedback was found to the classification of CP [20], taking into account between atrophy and degree of colonization of Np morphological changes of the pancreas gland, the (in patients of group I, p=-0.61; in patients of group parenchymatous variant of CP was most often II, p=-0.76; in patients of group III, p=-0.53). determined (in 60.0%, 67.9%, 62.5% of patients of Chronic duodenitis was secondary in all groups I, II, III respectively). examined patients. Chronic hepatitis (CH) was found in 16.1% Comparative analysis of inflammatory and of patients of group I, 32.2% of patients of group atrophic changes of the mucous membrane of the II, 15.1% of patients of group III. Among them, gastroduodenal zone showed that in the presence viral CH was found mainly in patients of groups of a combined pathology, the number of patients I (66.7%) and III (62.5%), less often in patients of with signs of atrophy was greater, dystrophic group II (42.9%). In the distribution of patients by processes were found both in the cells of the glands the type of viral liver lesion, CH B was diagnosed and in the cells of the cover epithelium, as well as in about half of patients without statistically microcirculation disorder in the gastric mucosa was significant differences in groups. The risk factors observed. According to the morphological study, for the development of viral CH were surgical these changes were much more common than interventions (from 65.6% to 72.2% of patients). in the visual examination during the endoscopic Liver cirrhosis (LC) was diagnosed in 10.7% of examination. patients of group I, 23.0% of patients of group II, The ulcer anamnesis averaged to 18.4±7.8 years 11.3% of patients of group III. in patients of group I, 25.3±8.5 years in patients of Functional disorders of the intestine were group II (pI-II<0.05), 21.7±5.9 years in patients of diagnosed in accordance with the criteria of the group III (pII-III<0.05). In patients of group I, duo- Rome consensus IV in 108 (33.8%) patients, among 45 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 them, with a predominance of constipation — 3. Park HJ, Leem AY, Lee SH. et al. Comorbidities 13.3%, with diarrhea — 21.7%, mixed — in 65.0% in obstructive lung disease in Korea: data from of patients of groups I and II mainly. Inflammatory the fourth and fifth Korean National Health dystrophic changes of the colon mucous membrane and Nutrition Examination Survey. Int .J. Chron. with disorders of its function were revealed in 38 Obstruct. Pulmon. Dis. 2015; 10: 1571-1582. (12.8%) patients. Of these, 7 patients were diagnosed 4. Barnes PJ. Senescence in COPD and Its with ulcerative colitis and 1 patient with Crohn’s Comorbidities. Annu Rev. Physiol. 2017;79: 517-539. disease. The diagnosis is verified by the data of 5. Pirogowicz I, Patyk M, Popecki P. et al. Lung clinical, laboratory, instrumental, and histological function in patients with gastro-esophageal reflux methods of research. By localization of nonspecific disease and respiratory symptoms. Adv. Exp. Med. ulcerative colitis lesion, the following was revealed: Biol. 2013; 788: 161-166. left sided – in 28.6%, total – in 14.3%, distal – in 6. Cazzola M, Calzetta L, Rinaldi B. et al. 57.1%. By severity (Truelove and Witts), the results Management of Chronic Obstructive Pulmonary are as follows: mild – in 42.8%, average – in 42.8%, Disease in Patients with Cardiovascular Diseases. heavy – in 14.2% of patients. Inflammatory changes Drugs. 2017; 77(7): 721-732. were detected mainly in the rectum and the blind 7. Smirnova L.E., Smirnova E.N., Egorov intestine. Changes in the mucosa were most often E.N. Disruption of immune status and intestinal represented by hyperemia – in 60.5%, erosions – in microbiota in chronic obstructive pulmonary 42.1%, hemorrhages – in 34.2%, contact bleeding – disease in combination with arterial hypertension. in 50.0%; pseudopolyps – in 15.8%, microabscesses Experimental and Clinical Gastroenterology. 2016; (6): – in 7.9%, granulomas – in 2.6%. The obtained 56-59. results agree with the data of foreign researchers 8. Agarwal SK, Heiss G, Barr RG. et al. Airflow who presented the pathogenetic mechanism of obstruction, lung function, and risk of incident heart cross-influence of pathology of respiratory and failure: the Atherosclerosis Risk in Communities digestive systems [21, 22]. (ARIC) study. Eur. J. Heart Fail. 2012; 14(4): 414-422. 9. Cavaillès A, Brinchault-Rabin G, Dixmier A. Conclusion et al. Comorbidities of COPD. Eur. 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The highest frequency 23(2): 277-285. of complicated course of peptic ulcer disease 12. GOLD Report, Global Strategy for the in patients of group III can be attributed to the Diagnosis, Management, and Prevention of characteristics of the digestive system pathology. COPD. Updated February 2018. Available from There is a mutual burden of symptoms of the https://goldcopd.org/wp-content/uploads/2016/04/ disease, especially in the presence of a worsened GOLD-2018-WMS.pdf. course of COPD. The presence of clinical signs of 13. Standards (protocols) of diagnosis and gastrointestinal pathology in patients with COPD treatment of patients with diseases of the digestive requires additional examination and obligatory system. Attachment to the Order of the Ministry drug correction. of Health of the Russian Federation No. 125 dated Conflict of interest. The authors declare that 17.04.1998. Healthcare Service. 1998; 7. there is no conflict of interest. 14. 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Helicobacter pylori eradication with gastric cancer 46 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 and gastric mucosal histological changes: a 10-year 656038, Barnaul, ul. Lyapidevskogo, 1. follow-up study. Chin. Med. J. (Engl). 2014; 127(8): Tel.: (3852) 689880. 1454-1458. E-mail: [email protected] 17. Courillon-Mallet A. Follow-up of patients after Helicobacter pylori eradication. Rev. Prat. Author information 2014; 64(2): 211-214. Belova Irina Ivanovna, Candidate of Medical 18. Ilichenko A.A. Classification of cholelithiasis. Sciences, Associate Professor of the Department of Therapeutic Archive. 2004; 2: 75-78. Hospital Therapy and Endocrinology, Altai State 19. Di Ciaula A, Wang DQ, Garruti G. et al. Medical University, Barnaul. Therapeutic reflections in cholesterol homeostasis 656050, Barnaul, ul. Malakhova, 53. and gallstone disease: a review. Curr. Med. Chem. Tel.: (3852) 402529. 2014; 21(12): 1435-1447. E-mail: [email protected] 20. Guidlines of Russian Gastroenterological Association on diagnosis and treatment of chronic Balitskaya Aleksandra Sergeevna, Postgraduate pancreatitis. Russian Journal of Gastroenterology, student of the Department of Faculty Therapy Hepatology, Coloproctology. 2014; 4: 70-97. and Occupational Diseases, Altai State Medical 21. Rodriguez-Roisin R, Bartolome SD, Huchon University, Barnaul. G, Krowka M. Inflammatory bowel diseases, 656038, Barnaul, ul. Molodezhnaya, 20. chronic liver diseases and the lung. Eur Respir J. Tel.: (3852) 201279. 2016; 47(2): 638-650. E-mail: [email protected] 22. Keely S, Hansbro PM. Lung-gut cross talk: a potential mechanism for intestinal dysfunction in Klester Karolina Vladimirovna, Resident of the patients with COPD. Chest. 2014; 145(2): 199-200. Department of Therapy and Family Medicine, Altai State Medical University, Barnaul. Contacts 656045, Barnaul, ul. Lyapidevskogo, 1. Corresponding author: Klester Elena Borisovna, Tel.: (3852) 689811. Doctor of Medical Sciences, Associate Professor, E-mail: [email protected] Senior Researcher of the Central Research Laboratory, Altai State Medical University, Barnaul.
47 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
UDC 616.65-002:616-006.55:615.849.11 doi.org:10.31684/2541-8475.2019.1(13).52-56 OPTIMIZATION OF PHYSIOTHERAPY METHODS IN PATIENTS WITH CHRONIC PROSTATITIS WITH CONCOMITANT BENIGN PROSTATIC HYPERPLASIA Federal Siberian Research Clinical Centre under the Federal Medical Biological Agency, Tomsk I.A. Kolmatsui, E.F. Levitsky
A method of complex treatment of patients with chronic prostatitis with concomitant benign prostatic hyperplasia (BPH) has been developed depending on the degree of prostate hyperplasia, severity of inappropriate urination, predominance of obstructive or irritative symptoms. Treatment complexes included the differentiated use of combined physiotherapeutic factors: low-energy light-magnetotherapy, magneto-pelotherapy (or micro-enemas of mineral water in combination with magnetotherapy), electrostimulation (or ultrasonic therapy), iodine-bromine baths. The use of optimized methods of physiotherapeutic impact combined with medicinal treatment in chronic prostatitis in combination with BPH allowed to expand the indications for its prescription, increased efficiency, provided a good profile of therapy tolerance, increased the period of remission, and did not cause the progression of prostate hyperplasia, symptoms of the lower urinary tract and risk of acute urination delay. Key words: chronic prostatitis, BPH, differentiated physiotherapy, optimization.
Chronic prostatitis (CP) is observed in were observed. Depending on the severity of lower most (67–97%) patients with benign prostatic urinary tract symptoms (LUTS), patients were di- hyperplasia (BPH), which burdens the course of vided into two groups: a group with mild LUTS the disease and reduces the quality of life [1, 2]. (S) IPSS <12 points (76 persons) and a group with Physiotherapy occupies a significant place in the moderate LUTS (S) IPSS 12–19 points (65 per- complex treatment of patients with CP, but with sons). These groups were distributed into the main concomitant BPH, the factors of influence causing groups (1A, 2A) and experimental groups (1B, 2B) endogenous thermal reactions are not applied by random sampling. The groups under study [3]. In patients with BPH in combination with CP, were comparable in the main baselines. it is possible to use the magnetic laser therapy in Study inclusion criteria are as follows: informed the period before and after surgical treatment, consent, verified diagnosis of CP/CPPS (IIIA, IIIB which effectively reduces the irritative symptoms, category; NIH, 1999) and I, II stage BPH, mild and the number of inflammatory complications and moderate LUTS (S) IPSS <19 points, age of patients shortens the rehabilitation period [4, 5]. The use of not more than 65 years old. Exclusion criteria low-level laser radiation, permanent magnetic field are the following: high risk of BPH progression: (PMF), electrical stimulation, and colour rhythm Vpg>40 cm3, PSA total>1.6 ng/ml; presence of signs therapy leads to the improvement of indicators of infravesicular obstruction (IVO): Qmax<10 ml/ of prostate secretion, uroflowmetry, PSA level, sec, Vru>50 ml; presence of acute urinary retention prostate gland volume (PG), IPSS symptom index, (AUR) in the anamnesis; presence of intravesical QoL and significantly increases the effectiveness component of the PG average fraction (according of treatment in the complex treatment of patients to pelvic organs transrectal US) of more than 5 ml. with BPH with concomitant CP [6]. According to Verification of the diagnosis of CP/CPPS and A.A. Ushakov et al. (1999), the use of ultrasound therapy (UST), impulse magnetic therapy, BPH and evaluation of treatment effectiveness electrical stimulation provides a pronounced anti- were carried out on the basis of questionnaires inflammatory effect, improves urination and a (NICH-CPSI, QoL, IPSS), urination diary, prostate sexual function, with that, it does not stimulate the digital investigation, microscopy, microbiological growth of prostatic hyperplasia in these patients and PCR studies of prostatic secretion (PS), [7]. In general, however, research on this issue is transrectal US (echography) of pelvic organs, not sufficient and results are often contradictory. urofluometry. The degree of tension of non- The research objective was to increase the specific adaptation mechanisms was determined effectiveness of complex treatment in patients by the type of adaptation reaction and the level of with CP with concomitant BPH by optimizing the reactivity according to L.H. Harkavy et al. (1998). methods of physiotherapeutic influence. Treatment effectiveness evaluation was determined by the integral indication (V.F. Kazakov et al., Materials and methods 2004) constituting “improvement” (20.1–30%) and 141 patients with CP/chronic pelvic pain syn- “significant improvement” (over 30.1%) [8]. The drome (CPPS) with concomitant I, II stage BPH results of the treatment were evaluated immediately 48 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 after the end of the treatment course and 4 weeks significant decrease in the total score on the IPSS after its end (prostatic secretion microscopy), the scale, QoL quality of life index was observed during long-term results of the treatment were evaluated treatment. Imperative symptoms decreased more after 1 year. dramatically in the main groups, with patients in the Patients of the main groups (1A, 2A) received main group 2A showing a statistically significant LED therapy (infrared and blue bands) intrarectally decrease compared to the experimental group to the prostate projection in combination with 2B (Table 1). The improvement of the copulative PMF magnetic therapy, sapropelic tampon (t 37- function was manifested by the increase in the total 38°C) in combination with PMF exposure, SMC score of the MIEF-5 questionnaire from 16.2±2.2 electrostimulation (1A group) or micro-enemas to 19.8±1.1 (p<0.05) only in patients of the main of mineral water (t 37-38°C) in combination with group 1A, which was due to the lower severity of PMF exposure, and ultrasound (US) therapy (2A the disorders and more directed physiotherapeutic group). Patients of the experimental groups (1B, effects. Prostate digital investigation of patients of 2B) were treated with LED therapy (infrared and the main groups (1A, 2A) as a result of treatment red bands), sapropelic tampons (t 37-38°C) (1B revealed a decrease in painfulness and improved group), or micro-enemas of mineral water (t 37- consistency, more pronounced in patients of the 38°C) (2B group). main group 1A (Table 1). The examination of PS more Photomagnetotherapy was carried out by objectively reflected the dynamics of effectiveness a cavitary emitter intrarectally to the prostate 4 weeks after the treatment. Thus, the number of projection by means of a device generating LED leukocytes in the prostatic secret was increased in radiation of red (660 nm) and infrared (840–950 38.5% and 31.1% of cases respectively immediately nm) bands or blue (420–450 nm) and infrared after the course of treatment in the main groups bands with a total power density of 5 mW/cm² and (1A, 2A), which was due to the improvement of the a value of magnetic induction of 30–40 mT. PMT drainage function of acini and was accompanied therapy was conducted by the 3 and 4 operation by normalization of PG palpatory parameters modes (5 min each), modulation frequency 100 (painfulness and consistency). Normalization (150) Hz, modulation depth 25 (50) %, half-period of the content of leukocytes occurred a month duration 1:1.5 s per the course of 10 procedures. after treatment in 90.4% and 88.9% of patients of The ultrasound therapy (UST) was carried out on the main groups (1A, 2A) respectively. During the lumbar area (L1-L3), paravertebrally, urinary treatment, normalization of adaptive reactivity bladder and perineum, radiation power 0.2 (0.4) occurred relatively more often in patients of the W/cm2, libale, 3-4 min per zone, the course of 10 main groups (1A, 2A), which testified to good procedures. tolerability of treatment and was manifested by In the treatment complex, all patients received an increase in the number of patients with a calm iodine-bromine baths for the course of 10 activation reaction and a decrease in the number procedures and basic drug therapy including of patients with a high activation reaction at a a-adrenergic blockers. high level of reactivity. In the patients of the main SРSS 15.0 statistical package was used for groups, one month after the treatment, the PSA statistical processing (Nasledov A.D., 2008). The level did not exceed the initial values of indicators normality of distribution of features was checked and indicators in the experimental groups. using Kolmogorov–Smirnov and Shapiro–Wilk According to urofluometry, there was an increase tests. The data are presented as “mean ± standard in Qmax and the effective capacity of the urinary deviation” (M ± σ). If the data were presented in bladder only in patients of the main groups, and scores, Wilcoxon T test was applied. If the sample Qmax was significantly different from that in the distribution was different from normal or the data experimental groups (Table 1). In PG ultrasound was presented in scores, the non-parametric Mann– examination, there was a slight decrease in its size Whitney U-test was applied. The significance due to decreased edema, improved echostructure, critical level was assumed to be 0.05 (Glantz S.A., and statistically significant decrease in residual 1999). urine volume more pronounced in the main groups of patients (р<0.01) (Table 1). In the course Results and discussion of physiotherapy, pathological reaction in the form As a result of the treatment, pain and dysuric of increased pain, dysuria, painfulness in DRI was symptoms were relieved in most patients. not observed. The integral indicator of evaluation However, in patients of the main groups (1A, 2A), of treatment effectiveness (“improvement” and the positive dynamics was more pronounced, “significant improvement”) in patients of the main which was manifested by a more significant groups (1A, 2A) and the experimental groups (1B, decrease in the total score on the NIH-CPSI scale 2B) was 90.4%, 86.7% and 61.5%, 57.7% respectively (Table 1). In patients of these groups, a more (p<0.01). 49 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
Table 1 Comparative dynamics of indicators in the study groups (М±σ)
Main Experimental Main Experimental group (1A) group (1B) group (2A) group (2B) Indicator n=52 n=24 n=45 n=20 b/t a/t b/t a/t b/t a/t b/t a/t NIH-CPSI (S) 14.7±2.2 8.1±1.5*# 14.4±2.1 11.2±1.4* 18.5±2.4^ 10.3±2.2*# 18.3±2.3 14.8±2.0* NIH-CPSI (QoL) 3.7±0.3 2.1±0.2*# 3.5±0.4 2.7±0.2* 4.5±0.3^ 2.6±0.2*# 4.4±0.3 3.2±0.2* IPSS (S) 10.3±1.4 6.4±1.3** 10.2±1.3 8.1±1.2* 16.2±2.3^ 9.1±1.7** 15.9±2.2 11.4±1.6* storage 5.1±0.6 3.5±0.5** 5.0±0.6 4.0±0.4* 8.7±0.6^ 4.9±0.4**# 8.6±0.5 5.8±0.3* symptoms (questions 2, 4, 7) DRI, 2.8±0.2 1.7±0.3**# 2.7±0.3 2.3±0.2 2.7±0.3 1.9±0.3* 2.7±0.2 2.4±0.2 painfulness (score) DRI, 2.9±0.2 1.9±0.2**# 2.8±0.2 2.6±0.1 2.9±0.3 2.3±0.2* 2.8±0.2 2.6±0.2 consistency (score) PS leukocytes 25.2±9.5 7.9±3.4**# 24.6±8.4 17.4±5.3 24.8±9.7 8.2±3.8** 23.8±8.2 15.9±4.8 (number per HPF)
Qmax (ml/s) 17.3±2.0 22.7±1.2**# 17.5±1.8 18.8±1.1 13.1±1.4^ 16.9±1.1**# 13.4±1.3 15.5±1.0 V (ml) 278.4±22.7 328.2±18.3* 285.3±21.5 296.3±17.6 236.3±20.3^ 282.7±18.4* 242.3±20.1 263.8±16.4 RU volume 14.8±5.4 4.7±2.6** 14.3±5.7 9.6±2.9 28.2±4.6^^ 15.4±3.7** 28.5±4.2 18.2±3.5* (ml) Note: * – criterion of significance of differences within groups at p<0.05; ** – at p<0.01; # – criterion of significance of differences with the experimental group at p<0.05; ^ – criterion of significance of differences between the main groups at p<0.05; ^ ^ – at p<0.01. PS – prostatic secret, RU – residual urine, V – urination volume, HPF – high power field, DRI – digital rectal investigation, PG – .on the IPSS scale – ٭ ,prostate gland, b/t – before treatment, a/t – after treatment
In the analysis of remote treatment results, it was volume amounted to 27.9±3.1 and 36.9±3.2 cm3 found that the frequency of relapses of CP during respectively and did not differ significantly from the year was observed in 9 (17.3%) and 8 (17.8%) the experimental groups (p>0.05). The PSA level patients of the main groups and in 11 (45.8%) and 8 did not significantly increase in patients of the (40%) patients of the experimental groups (2.6 and main groups and the experimental groups (Table 2.2 times more often respectively, p<0.01). Dynamic 2). Patients of the main groups (1A, 2A) maintained observation did not reveal the stimulating effect of positive dynamics of LUTS according to the IPSS the performed complex treatment on the growth questionnaire, Qmax, and Vru (Table 2). The of PG hyperplasia and the IVO progression (Table studied patients did not have episodes of AUR and 2). In patients of the main groups (1A, 2A), the PG progression of disease symptoms during the year. Table 2 Remote treatment results in the study groups (М±σ)
Main Experimental Main Experimental group (1A) group (1B) group (2A) group (2B) Indicator n=52 n=24 n=45 n=20 b/t rem. res. b/t rem. res. b/t rem. res. b/t rem. res. n=52 n=44 n=24 n=18 n=45 n=38 n=20 n=17 IPSS (S) 10.3±1.4 9.4±1.2 10.2±1.3 9.6±1.1 16.2±2.3^ 15.3±1.9 15.9±2.2 15.5±2.0
Qmax (ml/s) 17.3±2.0 22.3±1.6 17.5±1.8 19.1±1.4 13.1±1.4^ 16.3±1.3 13.4±1.3 15.1±1.4 PG volume 27.1±3.2 27.9±3.1 26.5±3.1 27.4±3.4 35.9±2.5^^ 36.9±3.2 35.5±2.3 36.6±3.1 (cm3) RU volume 14.8±5.4 6.4±2.5* 14.3±5.7 12.3±3.3 28.2±4.6^^ 18.7±3.0* 28.5±4.2 25.3±3.2 (ml) PSA 0.9±0.2 1.0±0.2 0.8±0.2 0.9±0.2 1.2±0.3 1.4±0.2 1.2±0.3 1.4±0.3 (ng/ml) Note: * – criterion of significance of differences within groups at p<0.05; ^ – criterion of significance of differences between the main groups at p<0.05; ^ ^ – at p<0.01. RU – residual urine, PG – prostatic gland, b/t – before treatment, rem. res. – remote treatment results. 50 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
The therapeutic effect of low-energy LED papers of the 1st Professional Russian Andrologist therapy causes anti-inflammatory, trophic and Association congress. M., 2001: 25. microcirculation improving impact. Compared to 2. Trapeznikova M.F., Pozdnyakov K.V., the red spectrum, the blue spectrum of radiation Morozov A.P. Drug therapy of chronic prostatitis in more pronouncedly suppresses the alterative and patients with benign prostatic hyperplasia. Difficult exudative phases of inflammation, stimulates Patient. 2006; 4(8): 15–19. phagocytosis, improves blood circulation and 3. Physiotherapy and spa medicine. Book II. Ed. rheological blood properties, has a bactericidal B.M. Bogolubov. M., 2008: 312. effect [9]. The magnetic field significantly reduces 4. Loran O.B., Markov A.V., Lukyanov I.V. the absorption of electromagnetic oscillations, Complex therapy of irritative urination disorders increasing the light penetration depth and reducing after transurethral prostatic resection and the reflection coefficient, thereby potentiating the adenomectomy. Urologiia. 2007; 4: 41-44. effects [10]. In CP in elderly patients, including 5. Neimark B.A., Neimark A.I., Snegirev the combination with the I stage BPH, rectal I.V. Transrectal magnetic therapy of benign sapropel tampons are carried out at a temperature prostatic hyperplasia on the Intramag apparatus of therapeutic mud 37-38°С, but at the same time, in prevention post-surgery complications after there is a decrease in the rectal mucosa permeability transurethral benign prostatic hyperplasia for biologically active substances, decrease in resection. Urologiia. 2006; 2: 75-79. the action of chemical factors, which causes an 6. Golubchikov V.A., Kochetov A.G., Sitnikov insufficient anti-inflammatory effect. Therapeutic N.V., Perekhodov S.N., Rojuk R.V. Physiotherapy efficiency of sapropel and micro-enemas of mineral in treatment of I st. benign prostatic hyperplasia water in combination with PMF significantly with concomitant chronic prostatitis. Men’s Health increases, making it possible to use them at a conference materials. M., 2005: 173-174. temperature of 37-38°С, excluding the thermal 7. Ushakov A.A., Bronnikov I.Yu. Analysis influence factor [11]. Optimized parameters of PMT of effectiveness of use of some physical methods stimulate the contractile function of detrusor and in complex treatment of chronic prostatitis and PG, therefore they are recommended for detrusor benign prostatic hyperplasia. Lechaschii Vrach hyporeflexia and contraindicated for detrusor Journal. 1999; 6: 50-53. hyperactivity against the background of IVO [3, 8. Kazakov V.F., Serebryakov V.G. 12]. US therapy has mainly an anti-inflammatory Balneotherapy of ischemic heart disease. M., 2004: 256. and antispasmatic effect and is used for detrusor 9. Phototherapy. Guidance for doctors. Ed. hyperreflexia [12]. Artificial iodine-bromine baths N.R. Paleev. M., 2001: 390. have a regulatory effect on the hypothalamus- 10. Ulashchik V.S., Lukomsky I.V. General pituitary system, reduce the dynamic component physiotherapy. Minsk, 2003: 510. of IVO (reduce sphincter hypertonia) and detrusor 11. Levytsky E.F., Kuz’menko D.I., Laptev hyperactivity [12]. B.I. Complex use of natural medical factors and fields of permantent magnets in the experiment and clinic. Conclusion Tomsk, 2001: 150. Optimization of physiotherapeutical influence 12. Private physiotherapy. Ed. G.N. in patients with CP in combination with BPH Ponomarenko. M., 2005: 744. was carried out by using the blue spectrum of LED radiation and combined methods of PMF Contacts magnetic therapy: photomagnetotherapy and Corresponding author: Kolmatsui Igor magnetopelotherapy. Anatolievich, Candidate of Medical Sciences, The use of optimized methods of physiotherapy Senior Researcher of the Advisory Group of the in patients with CP in combination with BPH Department of Prevention and Rehabilitation allowed to conduct differentiated treatment Treatment of Professional Diseases, Federal depending on the severity of LUTS, the prevalence Siberian Research Clinical Centre under the Federal of obstructive or irritative symptoms, and the Medical Biological Agency, Tomsk level of prostatic hyperplasia, which increased the 634009, Tomsk, ul. Rosy Luxembourg, 1. treatment effectiveness, increased the remission Tel.: (3822) 906511; 8 (913) 8060158. period and provided a good safety profile. E-mail: [email protected] Conflict of interest. The authors declare that there is no conflict of interest. Author information Levytsky Evgeny Fedorovich, Doctor of Medical References: Sciences, Professor, Honoured Worker of Science 1. Mikhailichenko V.V., Tiktinsky O.L., of the Russian Federation, Tomsk. Fesenko V.N. et al. Chronic prostatitis in patients 634009, Tomsk, ul. Rosy Luxembourg, 1. with benign prostatic hyperplasia. Theses of scientific Tel.: (3822) 512005. E-mail: [email protected] 51 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
UDC 616.36-002-004:616.151.514-07(571.15) doi.org:10.31684/2541-8475.2019.1(13).57-61 PARENTERAL VIRAL HEPATITIS IN PEOPLE WITH HEMOPHILIA: WAYS TO SOLVE THE PROBLEM 1Altai State Medical University, Barnaul 2Peoples’ Friendship University of Russia, Moscow M.A. Nikonorova1, N.V. Karbysheva1, G.M. Kozhevnikova2, A.N. Mamaev1, V.V. Shevchenko1, O.V. Beskhlebova1
Clinical and laboratory examination of 80 patients with hemophilia aged 16-59 living in the Altai Krai was car- ried out. From childhood, all patients have repeatedly received cryoprecipitate or fresh frozen plasma. In 50 of 80 patients with hemophilia (62.5%), chronic viral hepatitis (CVH) was diagnosed: CVH B and C in 1 patient (2%), CVH B in 2 (4%) and CVH C in 47 patients (94%). The mean age of patients with hemophilia and CVH is 38.4 (22–59 years). All patients have no data on the prior acute hepatitis B or C. In 30%, we noted an increase of ALT (in 30%), AST (in 20.4%), GGT (in 26.6%), ALP (in 13.3%). The obtained biochemical data indicate the presence of a minimal degree of activity of chronic hepatitis. Key words: hemophilia, hepatitis C, hepatitis B, liver cirrhosis.
Parenteral viral hepatitis B and C are one of the binant factors, coagulation factor concentrates for most urgent problems of both global and domes- “home treatment”. However, in urgent situations, tic health care. These infections are associated with in this patients it is possible to use blood prepara- lethal outcomes in patients with acute hepatitis, as tions that have not passed reliable procedures for well as with the cases of development of chronic virus inactivation. Before 2006, blood preparations liver diseases including cirrhosis and primary liver were very widely used without quarantine and cancer [1, 2]. According to the World Health Or- without viral inactivation procedures, which led to ganization (WHO), around 50 million people are the widespread of viral hepatitis in this groups of infected with hepatitis B annually, and up to 2 mil- patients [5, 6]. Thus, according to many research- lion people die. From 100 to 200 million people are ers, the rate of detection of hepatitis virus markers carriers of hepatitis C virus. According to WHO remains high to date and reaches 60% in adult pa- forecasts, in the next 10–20 years, a number of pa- tients and 4.7% in children under 18 [7, 8, 9, 10]. tients with liver cirrhosis can increase by 60%, pa- Clinical implications of chronic hepatitis in pa- tients with cancer by 68%, and the mortality from tients with hemophilia are most often absent for liver diseases can increase twice [3]. In 2015 alone, many years or expressed in the least, which makes 1,34 million people died of viral hepatitis, which diagnosis difficult and causes the development of may be compared to deaths from tuberculosis and sluggish chronic inflammatory process. Regular HIV infection. Most of deaths from viral hepatitis in transfusions of blood components and prepara- 2015 were related to chronic liver diseases (720,000 tions (fresh frozen plasma, erythrocyte concen- deaths due to complications of liver cirrhosis) and trate, coagulation factors concentrates, etc.), as well primary liver cancer (470,000 deaths due to hepa- as toxinemia, the frequency of which significantly tocellular carcinoma). Globally, in 2015, about 257 increases in the presence of other complications, million people lived with chronic HBV infection such as resorption of hematomae, are the starting and 71 million people with chronic HCV infection mechanism of activation of autoimmune process- [2]. es enhancing cytolytic syndrome. In this regard, It is widely recognized that blood and blood morphological signs of liver parenchyma damage preparations are the most important factors in in- may be very deep and often nonreversible. As a fection contamination with hepatitis viruses with rule, these processes in this category of patients parental transmission mechanisms. Patients with occur gradually and asymmetrically; in addition, hemophilia receiving regular treatment with blood they can cause the formation of hepatocellular car- preparations belong to the group of increased risk cinoma [6, 11]. However, despite the ease of the of infection with hepatitis viruses [4]. course, the frequency of chronic liver diseases and All known to date antihemophilic drugs filling associated mortality is 17 times higher in patients the deficiency of plasma coagulation factors VIII with hemophilia, and hepatocellular carcinoma is 6 and XI (FVIII and FXI) in patients with hemophilia times more frequent than in the population on the can be divided into 3 groups: non-virus inactivat- whole [12, 13]. Complications of chronic hepatitis ed, virus inactivated, and recombinant. In recent С, liver cirrhosis (e.g. esophagus variceal hemor- years, significant progress has been made in pro- rhage, hepatic encephalopathy), and hepatocellu- viding patients with hemophilia living in the Rus- lar carcinoma are the second most frequent cause sian Federation with virus inactivated and recom- of death in patients with hemophilia [14, 15, 16]. 52 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
Dynamics of progression of chronic liver dis- Table 1 ease depends on many factors: age, sex, HCV % of pa- Indicator N=80 genotype, inflammation activity, mixed infection tients of hepatitis B virus (HBV) or human immunodefi- ciency virus (HIV), other infections associated with ALT (0.0–40.0 U/L) 49–92.7 30% blood transfusion, presence of metabolic disorders AST (0.0–37.0 U/L) 61.2–129.6 20.4% (diabetes, obesity, fatty hepatosis, increased con- Bilirubin (8.55–20.5 10.9–16.9 N centration of iron in serum), and smoking [17, 18, µmol/L) 19, 20]; in general, this comorbid pathology affects Cholesterol (3.24–5.17 psychosomatic features and quality of life of these 5.91–7.65 6% mmol/L) patients [21, 22, 23, 24]. Total protein (65.0– The research objective is to determine the fea- 66.2–82.9 N tures of the course of viral hepatitis in patients with 87.0 g/L) hemophilia living in Altai Krai and further tactics AP (270 U/L) 286–452 13.3% of patient management. GGT (11.0–61.0 U/L) 72.8–91.5 26.6%
Materials and methods The obtained biochemical data indicate the Currently, in Altai Krai, 107 patients with he- presence of a minimal degree of activity of chronic mophilia aged from 16 to 59 (the mean age is 25.9 hepatitis. According to various researchers, clini- (16–33)) are on record in the Polyclinic Department cally expressed forms of liver pathology develop in of the Regional Clinical Hospital, among them 65% no more than 10% of patients with hemophilia [25]. are residents of Altai Krai districts and 35% are Chronic hepatitis C in patients with hemo- residents of Barnaul. 73 patients have hemophilia philia, long-term infected since early childhood, A (92%), 7 patients have hemophilia B (8%). 4 pa- is characterized by the low-symptomatic course, tients have light hemophilia course, 8 patients are low biochemical activity in the form of a minimal observed with severe hemophilia, and 68 patients increase in ALT level (1.3 times) in the absence of are with moderate hemophilia. All patients have significant changes in other indicators of impaired repeatedly received cryoprecipitate or fresh frozen liver function, as well as by the predominance of lb plasma. genotype of the causative agent (56.9%) and high Clinical and laboratory examination included: viral load (58.5%), occurs with less clinical and medical history, clinical examination, laboratory laboratory manifestations regarding the amount tests (general blood test, biochemical blood test of complaints, the frequency of liver increase, the with determination of total bilirubin and its frac- severity of cytolytic and immunoinflammatory tions, aminotransferase activity, etc.), ultrasound syndromes than in people without hemophilia. diagnostics of the liver, elastometry of the liver, With that, clinical and laboratory manifestations of detection of antibodies to HCV by enzyme immu- chronic hepatitis C are not related to the severity of nodetection method, detection of viral replication hemophilia by the main indicators of hemostasis, with the help of polymerase chain reaction of HCV while the relative independence of HCV-infection RNA, genotyping of HCV and determination of vi- course from the severity of congenital coagulopa- ral load of HCV RNA in blood serum. thy confirms the main importance of the impact of infection in early childhood on the severity of the Results and discussion manifestation and the rate of viral hepatitis C pro- In 50 of 80 patients with hemophilia (62.5%), gression. chronic viral hepatitis was diagnosed: chronic vi- The study is currently in progress. In the ral hepatitis B and C in 1 patient (2%), chronic vi- examined patients, 1b genotype of hepatitis C virus ral hepatitis B in 2 patients (4%), and chronic viral and the initial stages of fibrosis (0-2) on a scale hepatitis C in 47 patients (94%). The mean age of prevail. patients with hemophilia and chronic viral hepati- According to the international guidelines tis is 38.4 (22–59 years). (EASL) for the treatment of patients with CHC, it In the history of all patients with hemophil- is extremely important to provide antiviral therapy ia, there is no data on past acute hepatitis B or C, for CHC in all patients with hemophilia regardless which indicates probable infecting in childhood. of the stage of the disease (severity of fibrosis), Such subjective manifestations of a disease as as- duration of infection, hepatitis activity (levels of thenia and manifestations of dyspeptic character ALT and AST), level of viremia and virus genotype. were rather rare. In laboratory examination (Table The sooner the therapy is carried out and the 1) of patients, 30% were noted to have an increase elimination of the virus from the body is achieved, in ALT, 20.4% in AST, 26.6% in GGT activity, 13.3% the faster the complete structural and functional in alkaline phosphatase (AP). recovery of the liver will occur. Sustained virologic response (SVR) after the course of antiviral therapy reduces the risk of adverse outcome in persons with 53 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 hemophilia [27]. The results of double antiviral hepatitis C in patients with hemophilia and therapy (interferon + ribavirin, pegasys + ribavirin, other hereditary coagulopathies; 4) to initiate the 24–48 weeks) showed high effectiveness of AVT in professional community to develop federal clinical young people with 3a and 2a genotypes and lack recommendations (treatment protocol) of medical of effect in elderly people with 1b genotype [28]. care for patients with hemophilia and other Antiviral therapy with ledipasvir-sofosbuvir direct hereditary coagulopathies with chronic hepatitis C, antiviral drugs for patients with HCV infection as well a standard of specialized medical assistance genotype 1 or 4 or sofosbuvir-ribavirin for patients to patients with hemophilia and other hereditary with genotype 2 or 3 shows a sustained virologic coagulopathies with chronic hepatitis C [32]. response in 12 weeks after treatment being 99% Conflict of interest. The authors declare that (98/99) in patients with infection genotype 1 or 4; there is no conflict of interest. 100% (5/5) in patients with cirrhosis with infection genotype 1 who received treatment; 100% (10/10) in References: patients with genotype 2; and 83% (5/6) in patients 1. World Health Organization. Monitoring with infection genotype 3. High efficiency and and evaluation for viral hepatitis B and C: good tolerance among patients with hemophilia recommended indicators and framework was noted [29]. [electronic resource]. Technical report. April EASL recommendations (2015, 2016) noted 2016. 40 p. URL:http://www.who.int/hepatitis/ that the rate of progression of liver disease to the publications/guidelines-hepatitis-c-b-testing/en/. terminal stage in patients with hemophilia is the 2. World Health Organization. Global same as in HCV-positive persons in the general hepatitis report, 2017. April 2017. 83 p. URL: population. In chronic liver diseases, examination http://www.who.int/hepatitis/publications/global- of patients with hemophilia is the same as in hepatitis-report2017/en/. persons without hemophilia. For patients with 3. Ott JJ, Horn J, Krause G, Mikolajczyk RT. hemophilia, transjugular liver biopsy is a safer Time trends of chronic HBV infection over prior procedure. Non-invasive methods can be used to decades - A global analysis. J Hepatol. 2017;66(1):48- monitor the progression of the disease. Hepatic 54. doi:10.1016/j.jhep.2016.08.013. insufficiency in HCV-positive persons is considered 4. Morfini M. The History of Clotting Factor to be one of the most common causes of death Concentrates Pharmacokinetics. J. Clin. Med. in patients with hereditary blood coagulation 2017;6(3). pii: E35. doi: 10.3390/jcm6030035. disorders. The tactics of management of patients 5. Makeev A.B., Selivanov E.A., Vecherko with CHC and hemophilia are the same as in the A.V., Popova N.N., Zhiburt E.B. On some factors population not suffering from hemophilia, except determining the state of donation at the present for the impossibility of histological examination of time. Transfusiology. 2001; 2: 20-27. the liver. New DAA drugs can be used in patients 6. Mamaev A.N. Coagulopathies. Guidance. with hemophilia for the treatment of CHC [30]. M., 2012: 264. In May 2016, at the meeting “Croit IV”, as a result 7. Davis GL, Esteban-Mur R, Rustgi V, Hoefs of discussions among experts from 36 European J, Gordon SC, Trepo C, et al. Interferon alfa-2b alone countries, recommendations were summarized or incombination with ribavirin for the treatment concerning hemophilia therapy, which stated that of relapse of chronic hepatitis C. International the treatment of hepatitis C should be provided to Hepatitis Interventional Therapy Group. N Engl J all people with hemophilia as a matter of priority Med. 1998;339(21):1493-1499. by direct action antiviral agents [31]. 8. Makris M, Konkle BA. Hepatitis C in In April 2016, a round table of experts in the haemophilia: time for treatment for all. Haemophilia. field of hemophilia treatment “Achievements and 2017; 23(2):180-181. doi: 10.1111/hae.13183. problems in the treatment of hemophilia” was 9. Yatsenko E.A., Mazurin A.V., Yakunina held, at which a resolution was made on the need to L.N., Reizis A.R., Plakhuta T.G., Soskov G.I. implement the following measures: 1) to maintain Frequency and clinical features of viral hepatitis the system of centralized provision of patients C in children with hemophilia. Hematology and with hereditary coagulopathy by concentrates Transfusiology. 2001; 46(1): 28-29. of coagulation factors, which has proved its 10. Ignatyev S.V., Ivashkina E.P., effectiveness and rationality; 2) public health Vorozhtsova S.I., Nazarova E.L., Timofeeva M.A. bodies are to pay special attention to the treatment Hemostasiological and biochemical indicators in of posttransfusion hepatitis with the use of modern patients with hemophilia with posttransfusion antiviral drugs. Taking into account the specifics hepatitis. Bulletin of blood supply service of Russia. of the main disease, consider it appropriate to 2012; 3: 45-49. use non-interferon treatment schemes for CHC 11. Ignatyev S.V., Ivashkina E.P., Vorozhtsova in patients with hemophilia and other hereditary S.I., Tarasova L.N., Chernova T.A., Timofeeva coagulopathies; 3) to develop financial provision M.A. Dynamics of biochemical blood indicators of diagnostics and antiviral therapy of chronic in patients with hemophilia with posttransfusion 54 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 hepatitis receiving hepatotrophic therapy with 25. Snegireva-Davydenko I.B., Plushch O.P. heptral. Clinical laboratory medicine. 2014; 59(6): 4-6. Parenteral viral hepatitis B, C, G and TT in patients 12. Makris M, Preston F, Rosendaal F, et with hemophilia: extention, features of the course al. The natural history of chronic hepatitis C in and therapy. Hematology and Transfusiology. 2002; 3: haemophiliacs. Br J Haematol. 1997; 96: 875-876. 20–23. 13. Telfer P, Sabin C, Devereux H, et al. The 26. Strel’tsov A.G. Features of the course of progression of HCV-associated liver disease in a viral hepatitis C in patients with hemophilia: author’s cohort of haemophilic patients. Br J Haematol. 1994; abstract of the Candidate of Medical Sciences: 87: 555-561. 14.00.10, 14.00.29. Saint Petersburg, 2006: 20. 14. Plug I, Van Der Bom JG, Peters M, et al. 27. Holmström M, Nangarhari A, Öhman J, Mortality and causes of death in patients with Duberg A-S, Majeed A., Aleman S. Long-term liver- hemophilia, 1992-2001: A prospective cohort study. related morbidity and mortality related to chronic J Thromb Haemost. 2006; 4: 510-516. hepatitis C virus infection in Swedish patients with 15. Quraishi MN, Khan F, Tripathi D. How we inherited bleeding disorders. Haemophilia. 2016; 22: manage variceal hemorrhage in cirrhotic patients. e494–e501. doi:10.1111/hae.13020. Key practical messages from the British Guidelines. 28. Tentsova I.A., Plushch O.P., Polyanskaya Pol Arch Med Wewn. 2016; 126(3): 174-184. T.Yu., Zorenko V.Yu. Treatment of hepatitis C 16. Musialik J, Chwist A, Baron J, Mędrecki in patients with hemophilia. Hematology and D, Waluga M, Hartleb M. An unusual cause of Transfusiology. 2012; 57(S3): 139-140. hepatic encephalopathy. Pol Arch Med Wewn. 29. Walsh CE, Workowski K, Terrault NA, 2015;125(4):303-304. Sax PE, Cohen A, Bowlus CL et al. Ledipasvir- 17. Harris HE. Clinical course of hepatitis C sofosbuvir and sofosbuvir plus ribavirin in patients virus during the first decade of infection: cohort with chronic hepatitis C and bleeding disorders. study. BMJ. 2002; 324: 450-450. Haemophilia. 2017; 23(2): 198-206. doi: 10.1111/ 18. Hourigan LF, Macdonald GA, Purdie hae.13178. D, et al. Fibrosis in chronic hepatitis C correlates 30. EASL Recommendations on Treatment of significantly with body mass index and steatosis. Hepatitis C. Journal of Hepatology. 2018; 69(2): 461– Hepatology. 1999; 29: 1215-1219. 511. 19. Thomas DL, Astemborski J, Rai RM, et al. 31. Giangrande PLF, Peyvandi F, O’Mahony B, The natural history of hepatitis C virus infection: Behr-Gross ME, Hilger A, Schramm W, Mannucci host, viral, and environmental factors. JAMA. 2000; PM. Kreuth IV: European consensus proposals for 284: 450-456. treatment of haemophilia with coagulation factor 20. Kucharska M, Zaleska-Dorobisz U, concentrates. Haemophilia. 2017; 23(3): 370-375. doi: Szymczak A, Inglot M, Rymer W, Zalewska M, et 10.1111/hae.13211. al. Stage of liver fibrosis in patients with congenital 32. Shestakova I.V., Zozulya N.I., Zhulyov bleeding disorders and infected with hepatitis C Yu.A., Borisov S.V. Resolution of a round table virus. Pol Arch Intern Med. 2017; 127(6):412-417. doi: of experts “Achievements and problems in the 10.20452/pamw.4027. treatment of hemophilia”. Moscow, 14 April 2016. 21. Lychev V.G., Babushkin I.E., Nikulina M.A. URL: http://hemophilia.ru/rhs/rhs-events/659- Psycological features of patients with hemophilia, v-den-bolnyh-gemofiliey-eksperty-obsudyat- chronic renal insufficiency and ICP. Collection of obespechennost-lekarstvami-i-borbu-s-epidemiey- theses of the I International Congress “Psychosomatic gepatita-c-sredi-bolnyh-gemofiliey.html. (Date of medicine - 2006”. SPb., 2006: 127-128. access 1.09.2018) 22. Babushkin I.E., Nikulina M.A., Lychev V.G., Kudinova I.Yu. Psychosomatic aspects of Contacts viral hepatitis in patients with hemophilia in the Corresponding author: Nikonorova Marina comparative aspect. Preventive and Clinical Medicine. Anatolyevna, Doctor of Medical Sciences, Associate 2011; 2-2(39): 318. Professor of the Department of Infectious Diseases 23. Babushkin I.E., Lychev V.G., Momot and Phthisiology, Altai State Medical University, A.P., Kudinova I.Yu., Nikulina M.A. Quality of Barnaul. life in patients with multidirectional hemostasis 656038, Barnaul, Lenina Prospekt, 40. pathology: hemophilia and thrombophilia. Tel.: (3852) 566888. Preventive and Clinical Medicine. 2011; 2-2(39): 319. E-mail: [email protected] 24. Salomon T, Chaves DG, Brener S, Martins PR, Mambrini JV, Peixoto SV. Determining the Author information health-related quality of life in individuals with Karbysheva Nina Valentinovna, Doctor of Medical haemophilia in developing economies: results Sciences, Professor, Head of the Department of from the Brazilian population. Haemophilia. Infectious Diseases and Phthisiology, Altai State 2017;23(1):42-49. doi: 10.1111/hae.13130. Medical University, Barnaul. 656045, Barnaul, Zmeinogorsky Tract, 75. 55 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
Tel.: (3852) 268342. E-mail: [email protected] Shevchenko Valery Vladimirovich, Candidate of Medical Sciences, Associate Professor of the Kozhevnikova Galina Mikhailovna, Doctor of Department of Epidemiology, Microbiology and Medical Sciences, Head of the Department of Virology, Altai State Medical University, Barnaul. Infectious Diseases with courses of Epidemiology 656024, Barnaul, ul. Lyapidevskogo, 1, office 710. and Phthisiology, Peoples’ Friendship University of Tel.: (3852) 689471. Russia, Moscow. E-mail: [email protected] 117198, Moscow, ul. Miklikho-Maklaya, 8. Tel.: (495) 3654753. Beskhlebova Olga Vasilyevna, Candidate of E-mail: [email protected] Medical Sciences, Assistant of the Department of Infectious Diseases and Phthisiology, Altai State Mamaev Andrey Nikolaevich, hemostasiologist, Medical University, Barnaul. Senior Researcher, Altai State Medical University, 656045, Barnaul, Zmeinogorsky Tract, 75. Barnaul. Tel.: (3852) 268342. 656038, Barnaul, Lenina Prospekt, 40. E-mail: [email protected] Tel.: (3852) 566888. E-mail: [email protected]
56 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
UDC 616.151.511:616.15-008.1-07-08 doi.org:10.31684/2541-8475.2019.1(13).62-67 THE COURSE OF DEEP VEIN THROMBOSIS OF LOWER LIMBS DEPENDING ON THE CONTENTS OF D-DIMERS AND C-REACTIVE PROTEIN IN THE ACUTE PHASE 1Altai State Medical University, Barnaul 2Diagnostic Center of Altai Krai, Barnaul 3City Hospital No. 5, Barnaul A.S. Petrikov1,2, D.V. Dudin1,3, L.N. Popkova3, I.V. Volodin1,3, Ya.N. Shoikhet1,3
The article concentrates on the evaluation of the course and progression of deep vein thrombosis of lower limbs (DVT of lower limbs) in the acute phase, taking into account the dynamics of clinical and laboratory blood values against a background of anticoagulant therapy. It also studies the odds ratios of development of proximal and distal DVT of lower limbs depending on the contents of the markers of coagulation hemostasis and inflammation – D-dimers and C-reactive protein (CRP). Key words: proximal and distal deep vein thrombosis of lower limbs, acute phase, course of venous thrombosis, D-dimers, C-reactive protein, inflammation.
The development of deep vein thrombosis ability to resist thrombocyte aggregation and fibrin of lower limbs (DVT of lower limbs) remains a formation [14]. significant problem of medicine and is one of In recent years, there have been works the main causes of mortality and disability of the on determining the content of acute phase population [1, 2, 3, 4, 5], so timely diagnosis of inflammation proteins and coagulation hemostasis DVT of lower limbs determining the nature of the markers, as well as on evaluation of associative disease and the possible risk for the patient is of relationships in the acute phase in DVT of lower paramount importance. Today, in the diagnosis limbs [9, 14, 15, 16, 17, 18, 19]. However, the issue of of DVT of lower limbs, along with ultrasonic the course of venous thrombosis in the acute phase techniques, laboratory tests are widely used, among remains insufficiently studied taking into account which the detection of D-dimers is important [5, 6, the dynamics of D-dimers and CRP content 7]. It is known that D-dimers are products of fibrin depending on the prevalence of thrombotic process. decay and integral indicators of activation of the Analysis of the interrelations of inflammatory and coagulation hemostasis system, and their high hemostatic reactions in the acute phase in patients concentration in blood plasma is an indispensable with DVT of lower limbs may allow to determine indicator of thrombotic state [8]. At the same time, the prognostic course of thrombosis against the the content of D-dimers can be a prognostic sign of background of the studied clinical and laboratory the course of venous thrombosis [9]. markers and conducted ACT. All of the above was Many researchers in the pathogenesis of a prerequisite for determining the quantitative venous thromboembolic complications (VTEC) content of D-dimers and CRP in the blood serum in development assign a significant role to systemic the acute phase, studying the relationships between and local inflammation along with multidirectional them and their associative influence on the course disorders in the hemostasis system [10, 11, 12]. of DVT of lower limbs against the background of A significant marker of inflammatory response treatment. is C-reactive protein (CRP), which belongs to the The research objective is to study the odds group of acute phase proteins [12]. E.A. Thomas, ratio of development of DVT of lower limbs, the M.J. Cobby et al. proved that CRP is highly sensitive character of the lesions and its course depending and reliable acute phase protein contributing to the on the content of D-dimers and CRP in the acute diagnosis of DVT of lower limbs [13]. It was found phase against the background of anticoagulant that the use of CRP in the diagnosis of venous therapy. thrombosis has 100% sensitivity (95% CI; 78–100%) with the method specificity of 52% (95% CI; 34– Materials and methods 70%). According to modern ideas, the content of The comparative prospective study from CRP can reflect local inflammation in the vessel November, 2015 to May, 2017 included 62 patients intima and prospectively determine the risk of with documented DVT of lower limbs, aged from vascular complications. Its increased content in the 25 to 69 years (the mean age was 55.1±1.5), being blood serum can also affect endothelium and lead treated in the Department of Vascular Surgery of to its destruction, loss of thromboresistance, loss of RSBIH City Hospital No. 5, Barnaul – it is a clinical base of the Department of Faculty Surgery, Hospital
57 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
Surgery with the course of FVE of FSBEI HE ASMU with superficial vein thrombosis (SVT) was found of the Ministry of Health of the Russian Federation. in 1 patient (2.7%). In 18 patients of the first group, Depending on the nature of damage of the deep long thrombosis of the femoral vein in combination veins, patients were randomized into 2 groups. with lesions of the popliteal and pedidial veins The first group consisted of 37 patients – 27 men (48.7%) prevailed. 13 patients showed thrombosis (73.0%) and 10 women (27.0%) with proximal DVT of the iliofemoral popliteal pedidial segment of lower limbs (the mean age was 55.9±1.8 years). (35.1%), and 6 patients (16.2%) had iliofemoral The second group consisted of 25 patients – 14 men popliteal phlebothrombosis. In the second group, (56.0%) and 11 women (44.0%) with distal deep isolated distal DVT of lower limbs was found in vein thrombosis (the mean age was 53.9±2.6 years). 20 patients (80.0%), the combination of distal DVT There were no statistically significant differences of lower limbs with PATE was found in 2 patients between the analyzed groups of patients by sex (8.0%), and the combination with SVT was found and age (p˃0.05). in 3 patients (12.0%). Thrombosis with lesion of the In the first group, isolated proximal thrombosis popliteal pedidial segment was diagnosed in 18 was diagnosed in 30 patients (81.1%), the patients (72.0%), and isolated lesion of the pedidial combination of DVT of lower limbs with PATE was segment was diagnosed in 7 patients (28.0%) found in 6 patients (16.2%), and the combination (Table 1). Table 1 The nature of clinical implications in patients with DVT of lower limbs
Nature of First group (n=37) Second group (n=25) clinical Abs Abs p ˃ % % implications number number Isolated DVT of lower limbs 30 81.1 20 80.0 0.05 DVT of lower limbs + PATE 6 16.2 2 8.0 0.05 DVT of lower limbs + SVT 1 2.7 3 12.0 0.05 Total: 37 100.0 25 100.0 -
Inclusion criteria are as follows: deep vein basic biochemical indicators, APTT, MNO, PTI, thrombosis of lower limbs documented by SFMC, fibrinogen), according to standard methods, ultrasound angiography (USAG), age from 25 to on the 1–3, 5–7, and 12–14 days of hospitalization, 69, duration of the disease no more than 14 days. blood was taken from the cubital vein to quantify Exclusion criteria are the following: oncology the content of CRP and D-dimers. Evaluation of diseases, acute infections, skeletal traumas and CRP concentration in blood serum was carried fractures, operative interventions, prolonged out by immunoturbidimetric method using the immobilization, air travels, age under 25 and over automatic biochemical analyzer Sapphire 400 69, presence of contraindications to the use of (Hirose Electronic System, Japan) with a set of anticoagulant therapy (ACT), severe concomitant CRP reagents – Vital of DAC – SpectroMed firm. diseases of the kidneys, liver, and heart in the stage Determination of D-dimers content in blood serum of decompensation. was carried out by chemiluminescent two-stage A control group was formed by the case-control immunoenzymatic method on the automatic method, it included 74 relatively healthy people coagulometer Instrumentation Laboratory ACL (45 men and 29 women) with no signs of any Elite Pro (USA) using D-Dimer, HemosIL reagents. disease, aged between 23 and 67 years (the mean The mean content of D-dimers in serum in the age was 52.2±1.7 years). Study inclusion criteria are control group was 143.2±9.2 ng/ml, and the content as follows: absence of acute vascular events in the of CRP was 1.4±0.2 mg/l (Table 2). anamnesis (venous or arterial thrombosis, PATE, In the acute phase, treatment of patients was myocardial infarction, apoplectic attack, etc.), carried out according to Russian clinical recom- absence of pathology of bronchopulmonary and mendations [5]. All patients were prescribed un- cardiovascular systems, joint diseases, oncology fractionated heparin (UFH) as a starting drug. Fur- diseases, skeletal traumas, and prolonged ther, 8 patients (12.9%) were transferred to vitamin immobilization. There were no statistically K antagonists (VKA), and 54 patients (87.1%) were significant differences between the analyzed transferred to new oral anticoagulants (NOAC). In groups of patients and the control group by sex the first group, 6 patients (16.2%) were selected a and age (p>0.05). dose of warfarin, 29 patients (78.4%) were trans- In the in-patient hospital, along with the ferred to dabigatran etexilate (DE) at a dose of 150 generally accepted clinical and laboratory blood mg 2 times a day from day 5, and 2 patients (5.4%) indicators (indicators of general blood analysis, were assigned rivaroxaban. In the second group, 58 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 warfarin was assigned to 2 patients (8.0%), DE to noted taking into account the drug used in the an- 21 patients (84.0%), and rivaroxaban to 2 patients alyzed groups. (8.0%). No statistically significant differences were Table 2 Dynamics of D-dimers and CRP content in patients with DVT of lower limbs in acute phase
Dynamics of D-dimers content (ng/ml) period of first group second group control group p < p < p < observation (n=37) (n=25) (n=74) 1-2 1-c 2-c 1–3 days 2809±346.7 1564±202.8 0.01 0.01 0.01 5–7 days 2331±391.3 1186±200.5 0.01 0.01 0.01 12–14 days 1514±221.3 448±79.5 0.01 0.01 0.01 143.2±9.3 p (1–3) – p (5–7) >0.05 <0.05
p (1–3) – p (12–14) <0.01 <0.01 – – –
p (5–7) – p (12–14) <0.01 <0.01 Dynamics of C-reactive protein content (mg/l) period of first group second group control group p < p < p < observation (n=37) (n=25) (n=74) 1-2 1-c 2-c 1–3 days 58.0±6.4 28.4±7.4 0.01 0.01 0.01 5–7 days 33.0±7.1 14.4±2.6 0.01 0.01 0.01 12–14 days 17.2±4.3 6.0±0.7 0.01 0.01 0.01 1.4±0.2 p (1–3) – p (5–7) <0.01 <0.01
p (1–3) – p (12–14) <0.01 <0.01 – – –
p (5–7) – p (12–14) <0.01 <0.01
Statistical processing of the obtained data on days 5–7 – by 1043 ng/ml (p<0.01), and on days was carried out using licensed programs 12–14 – 305 ng/ml (p<0.01). MicrosoftOffice and Statistica, version 10 (USA), In intragroup comparison, it was found that in which included an assessment of the statistical patients with proximal DVT of lower limbs against significance between two compared data groups: the background of ACT on days 12–14 the average for parametric variation series – Student’s t-test, for content of D-dimers was statistically significantly dichotomous (qualitative) data – Z-test, as well as lower by 1295 ng/ml (p<0.01) compared to days1–3, calculation of the Pearson’s correlation coefficient and by 817 ng/ml compared to days 5–7 (p<0.001). (r). To estimate the normality of the distribution, There was also a statistically significant decrease a visual evaluation of the frequency distribution in the average content of D-dimers on days 12–14 (histogram and normality graph) was applied with in patients with distal DVT of lower limbs by 1116 the subsequent use of the Shapiro-Wilk W test. mg/ml (p<0.01) compared to days 1–3, and by 378 Differences were considered statistically significant ng/ml (p<0.05) compared to days 5–7. at p<0.05. On days 1–3 from hospitalization, the content of D-dimers in patients of the first group was Results and discussion statistically significantly higher than in patients of It was found that the average content of CRP and the second group by 1245 ng/ml (p<0.01), on days D-dimers in patients with DVT of lower limbs and 3–5 – by 1145 ng/ml (p<0.01), and on days 12–14 – PATE in the acute phase in both proximal and distal by 1066 ng/ml (p<0.01). thrombosis was statistically significantly higher On days 1–3 from hospitalization, the average than in the control group (Table 2). The average content of CRP in patients with proximal thrombosis content of D-dimers in patients of the first group of the group was statistically significantly higher on days 1–3 from hospitalization was statistically than in the control group by 56.6 mg/l (p<0.01), on significantly higher than in the control group by days 5–7 – by 31.6 mg/l (p<0.01), and on days 12– 2666 ng/ml (p<0.01), on days 5–7 – by 2188 ng/ml 14 – by 15.8 mg/l (p<0.01). In patients with distal (p<0.01), and on days 12–14 – 1371 ng/ml (p<0.01). DVT of lower limbs, the level of CRP on days 1–3 In patients of the second group, the concentration from hospitalization was statistically significantly of D-dimers on days 1–3 from hospitalization was higher than the control data by 27.0 mg/l (p<0.01), statistically significantly higher than the mean on days 5–7 – by 13.0 mg/l (p<0.01), and on days values of the control group by 1421 ng/ml (p<0.01), 12–14 – by 4.6±0.7 mg/ml (p<0.01). 59 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
In intragroup comparison, it was found that in to VKA (warfarin) at a daily dose of 5 mg. During patients of the first group against the background the acute phase, there was a tendency to increase of ACT, there is a statistically significant decrease in the content of CRP (more than 50 mg/l) and in the average content of CRP on days 5–7 by D-dimers (more than 3000 ng/ml) by days 12–14. 25.0 mg/l (p<0.01), and on days 12–14 by 40.8 Four months after release against the background mg/l (p<0.01) in comparison with days 1–3. There of taking warfarin, the patient was hospitalized was also a statistically significant decrease in the again with an acute recurrent femoropopliteal average content of CRP in patients with distal DVT pedidial phlebothrombosis on the left. of lower limbs – by 14.0 mg/l (p<0.05) on days 5–7, The influence of different levels of CRP and and by 22.4 mg/l (p<0.01) on days 12–14 compared D-dimers in blood serum on the odds ratio (OR) of to days 1–3. development of DVT of lower limbs was studied. It On days 1–3 from hospitalization, the content of was found that serum CRP content up to 5.0 mg/l CRP in patients of the first group was statistically was not accompanied by an increase in the odds significantly higher than in patients of the second ratio of development of distal [OR=0.104; 95% CI: group by 29.6 mg/l (p<0.01), on days 3–5 – by 18.6 0.382–6.735, p>0.05] and proximal DVT of lower mg/l (p<0.01), and on days 12–14 – by 11.2 ng/ml limbs [OR=0.021; 95% CI: 0.721–3.774, p>0.05]. (p<0.01). The CRP concentration in the range from 5.01 to Thus, the average content of D-dimers and CRP 10.0 mg/l also did not affect the increase in the in blood serum in patients with proximal DVT of OR of development of distal [OR=1.612; 95% CI: lower limbs was statistically significantly higher 0.133–37.260, p>0.05] and proximal thrombosis than in distal venous thrombosis, which indicates [OR=1.672; 95% CI: 0.251–33.071, p>0.05], whereas more significant and long lesion of the venous bed. CRP content in the blood serum of more than 10.0 In the first group, the correlation analysis es- mg/l is associated with the OR of development of tablished the presence of associative relations of distal thrombosis by 8.7 times [OR=8.7; 95% CI: average strength between the content of D-dimers 4.031–18.576, p<0.05] and proximal thrombosis by and CRP on days 5–7 (r=0.55; p=0.012) and on days 16.8 times [OR=16.8; 95% CI: 5.592–50.545, p<0.05]. 12–14 (r=0.46; p=0.0042). In patients of the second It was found that the content of D-dimers in group, the correlation of the average strength be- blood serum ranging up to 250 ng/ml was not tween the content of D-dimers and CRP was estab- accompanied by an increase in the odds ratio of lished on days 1–3 (r=0.58; p=0.0092) and on days development of both distal [OR=0.022; 95% CI: 12–14 (r=0.53; p=0.0204). 0.001–0.087, p>0.05] and proximal [OR=0.007; In the acute phase in patients with DVT of 95% CI: 0.001–0.055, p>0.05] DVT of lower limbs. lower limbs against the background of ACT, there The D-dimers concentration from 251 to 500 ng/ was a tendency to decrease in both the average ml also did not affect the OR of development of content of D-dimers and the mean concentration distal [OR=0.207; 95% CI: 0.026–1.676, p>0.05] and of CRP on days 5–7 and 12–14 in comparison with proximal [OR=0.132; 95% CI: 0.017–1.055, p>0.05] the initial indicators (p<0.01). In the first group, on thrombosis, while an increase in the D-dimers days 12–14, a synchronous decrease in the content content of more than 500 ng/ml was associated of D-dimers and CRP was observed in 27 patients with an increase in the OR of development of distal (73.0%), a decrease in one indicator was observed thrombosis by 35.9 times [OR=35.9; 95% CI: 9.11– in 8 patients (21.6%), and a synchronous increase 141.17, p<0.05] and proximal thrombosis by 36.5 in D-dimers and CRP in 2 patients only (5.4%). times [OR=36.5; 95% CI: 9.27–143.3, p<0.05]. Among them, a 45-year-old man with acute occlusal Thus, the increase in the content of D-dimers in femoropopliteal pedidial phlebothrombosis on the blood serum of more than 500 ng/ml is associated left, who was transferred to VKA, died of PATE on with the increase in the OR of development of both the 13th day of hospitalization. At the same time, distal and proximal DVT of lower limbs by 35.9 there was a significant increase in the content of and 36.5 times respectively. The increase in CRP CRP on days 5–7 and 12–14 (100 mg/l and more) concentration of more than 10.0 mg/l is associated against the background of treatment, the level of with the increase in the OR of development of distal D-dimers was sharply increased (7500 ng/ml and thrombosis by 8.7 times and proximal thrombosis more) during the entire period of hospitalization. by 16.8 times. In the second group, on days 12–14, a synchronous decrease in the content of D-dimers Conclusion and CRP was observed in 23 patients (92.0%), a Determination of D-dimers and CRP content decrease in D-dimers against the background of in patients with DVT of lower limbs allows to CRP growth was observed in 1 patient (4.0%), and a assess its course and prognosis, as well as the synchronous increase in D-dimers and CRP in only effectiveness of ACT in the acute phase. The use of one woman aged 35 (4.0%). She was diagnosed with adequate ACT in the acute phase, accompanied by acute popliteal pedidial phlebothrombosis on the a synchronous decrease in the content of D-dimers left. After UFH therapy, the patient was transferred and CRP by days 12–14 from the moment of 60 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 hospitalization, testifies to the favorable course of 7. Jezovnic MK, Poredos P. Idiopathic ve- DVT of lower limbs. At the same time, the increase nous thrombosis is related to systemic inflamma- in laboratory markers on days 5–7 and 12–14 against tory response and to increased levels of circulating the background of the use of anticoagulants, in markers of endothelial dysfunction. Int. Angiol. particular, D-dimers and CRP, can be considered as 2010; 29(3): 226-231. a prognostically unfavorable sign of the course of 8. Reber G, de Moerloose P. Standardization DVT of lower limbs with the development of lethal of D-dimer testing. In: Quality in laboratory hemosta- outcome or the progression of thrombosis. sis and thrombosis. Willey-Blackwell, Sheffield, UK. It was established that the content of D-dimers 2009: 99-109. in serum of more than 500 ng/ml is associated with 9. Petrikov A.S., Shoikhet Ya.N., Dudin D.V. the increase in the OR of development of proximal The course of deep vein thrombosis and pulmo- and distal DVT of lower limbs by 36.5 and 35.9 nary artery thromboembolia in the acute phase de- times respectively. The increase in the CRP level in pending on the content of D-dimers and C-reactive serum of more than 10 mg/l is associated with the protein against the background of treatment. Medi- increase in the OR of development of proximal and cal Herald of the South of Russia. 2017; 3: 78-79. distal thrombosis by 16.8 and 8.7 times respectively. 10. Wang MF, Yang LH, Yang XL. et al. Cor- It was revealed that in patients with proximal and relation of inflammatory marker and coagulation distal DVT of lower limbs in the acute phase during factors with deep vein thrombosis. Zhongguo Shi days 12–14, the average content of D-dimers and Yan Xue Ye Xue Za Zhi. 2010; 18(3):753-756. CRP in blood serum is statistically significantly 11. Lippi G, Favaloro EJ, Montagnana M, higher than in healthy people. In the acute period, Franchini M. C-reactive protein and venous throm- the average values of D-dimers and CRP in boembolism: causal or casual association? Clinical proximal thrombosis are statistically significantly Chemistry and Laboratory Medicine. 2010; 48(12): higher compared to distal thrombosis. There is 1693–1701. a moderate correlation between the content of 12. Kunutsor SK, Seidu S, Blom AW, Khunti K, D-dimers and CRP in serum on days 5–7 and 12–14 Laukkanen JA. Serum C-reactive protein increases of hospitalization in patients with proximal DVT of the risk of venous thromboembolism: a prospective lower limbs, on days 1–3 and 12–14 in patients with study and meta-analysis of published prospective distal DVT of lower limbs against the background evidence. European Journal of Epidemiology. 2017: 32: of ACT. 657-667. Conflict of interest. The authors declare that 13. Thomas EA, Cobby MJ, Rhys Davies E, there is no conflict of interest. Jeans WD. Whicher Liquid crystal thermography and C reactive protein in the detection of deep ve- References: nous thrombosis. J.T.B.M.J. 1989; 299: 951-952. 1. Othieno R, Okpo E, Forster R. Home versus 14. Petrikov A.S., Shoikhet Ya.N., Belykh V.I. in-patient treatment for deep vein thrombosis. The Multivariant analysis of risk of vein thrombosis of lower Cochrane Database of Systematic Reviews. 9.01.2018. limbs, pulmonary artery thromboembolia basing on the DOI:10.1002/14651858. markers of inflammation, hemostasis, and endothelial 2. Kearon C, Akl АE, Comerota AJ. et al. disfunction. Barnaul, 2015: 262. Antithrombotic Therapy for VTE Disease: CHEST 15. Zacho J, Tybjaerg-Hansen A, Nordest- Guideline and Expert Panel Report. Chest. 2016; gaard BG. C-reactive protein and risk of venous 149(2): 315-352. doi: 10.1016/j.chest.2015.11.026. thromboembolism in the general population. Ar- 3. Lutsey PL, Horvath KJ, Fullam L. et al. An- teriosclerosis, Thrombosis and Vascular Biology. 2010; ticoagulant Preferences and Concerns among Ve- 30(8): 1672–1678. nous Thromboembolism Patients. Thrombosis and 16. Petrikov A.S., Belykh V.I., Karbyshev I.A., Haemostasis. 2018;118 (3): 553-561. Shoikhet Ya.N. Correlation of C-reactive protein 4. Kahn SR, Springmann V, Schulman S. et with venous thromboembolic complications. Prob- al. Management and adherence to VTE treatment lems of Clinical Medicine. 2015; 1(35): 41-45. guidelinesin a national prospective cohort study 17. Folsom AR, Lutsey PL, Astor BC, Cush- in the Canadian outpatientsetting. The Recovery man M. C-reactive protein and venous thrombo- Study. Thromb Haemost. 2012; 108: 493-498. embolism. A prospective investigation in the ARIC 5. Andriyashkin A.V., Arutyunov G.P., Brit- cohort. Thrombosis and Haemostasis. 2009; 102(4): ov A.N. et al. Russian clinical recommendations on 615–619. diagnostics, treatment and prevention of venous 18. Petrikov A.S., Shoikhet Ya.N., Dudin D.V., thromboembolic complications (VTEC). Journal of Karbyshev I.A., Belykh V.I. Assessment of the Venous Disorders. 2015; 4(2-2): 10-17. course of venous thromboembolic complications in 6. Potu KC, Ketineni S, Lamfers R. A Primer the acute phase depending on the content of mark- on Diagnostic and Financial Implications of D-di- ers of hemostasis and inflammation.Materials of the mer Testing. S D Med. 2016; 69(9): 414-417. All-Russia Research and Practical Conference “Imme-
61 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 diate and Emergency Medical Aid – 21 century”. Bar- Popkova Lyubov Nikitichna, Head of the naul, 2017: 212-215. Laboratory, Doctor of Clinical Laboratory Medicine, 19. Olson NC, Cushman M, Lutsey PL. et al. City Hospital No. 5, Barnaul. Inflammation markers and incident venous throm- 656045, Barnaul, Zmeinogorsky Tract, 75. boembolism: the reasons for geographic and racial Tel.: (3852) 268277. differences in stroke (REGARDS) cohort. Thrombo- E-mail: [email protected] sis and Haemostasis. 2014; 12: 1993-2001. Volodin Ilya Vladimirovich, Doctor of Clinical Contacts Laboratory Medicine, City Hospital No. 5, Barnaul. Corresponding author: Petrikov Aleksei 656045, Barnaul, Zmeinogorsky Tract, 75. Sergeevich, Doctor of Medical Sciences, Associate Tel.: (3852) 268277. Professor of the Department of Faculty Surgery E-mail: [email protected] named after Professor I.I. Neimark, Hospital Surgery with the course of FVE, Altai State Medical Shoikhet Yakov Nakhmanovich, Doctor of Medical University, Barnaul. Sciences, corresponding member of RAS, Head of 656045, Barnaul, Zmeinogorsky Tract, 75. the Department of Faculty Surgery named after Tel.: (3852) 685144. Professor I.I. Neimark, Hospital Surgery with E-mail: [email protected] the course of FVE, Altai State Medical University, Barnaul. Author information 656045, Barnaul, Zmeinogorsky Tract, 75. Dudin Denis Valeryevich, Assistant (ext. part- Tel.: (3852) 685023. timer), Regional Clinical Hospital, Barnaul. E-mail: [email protected] 656024, Barnaul, ul. Lyapidevskogo, 1. Tel.: (3852) 268233. E-mail: [email protected]
62 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
UDC 616.24-002:616.98:578.828HIV:616.89-008.441.33 doi.org:10.31684/2541-8475.2019.1(13).68-71 COMMUNITY-ACQUIRED PNEUMONIA IN HIV-INFECTED PATIENTS Omsk State Medical University, Omsk L.V. Puzyreva, M.A. Paneva
Community-acquired pneumonia is one of the causes of respiratory diseases in HIV-infected patients, especially in injecting drug users. To assess the studies of clinical implications of community-acquired pneumonia in patients being the injecting drug users, 69 cases of diseases were analysed in retrospect. Reliable differences in complaints of patients, general blood analysis and X-ray changes in pulmonary tissue in patients being injecting drug users were revealed. Key words: community-acquired pneumonia, HIV infection, injecting drug users.
Respiratory diseases are one of the main causes processed using Statistica 6 software. Due to the of morbidity and mortality worldwide, with pneu- presence of a distribution other than normal, meth- monia taking the lead. The problem of pneumonia ods of descriptive statistics with the calculation of has always been of great scientific and practical non-parametric Pearson’s χ2 test and Mann–Whit- interest. Recently, it has attracted even greater at- ney U-test were applied. The data of the Me medi- tention due to the spread of ARVI, influenza, and an were used. The results were considered signifi- acquired immunodeficiency disorders contribut- cant at p<0.05. ing to the increase in the proportion of pneumonia In both study groups, patients were comparable in the population total morbidity [1]. by sex, age, social status (p>0.05). Bacterial pneumonia is the main cause of mor- bidity and mortality among HIV-infected people, Results and discussion and its probability is 25 times higher than among Most often the patients of the main study group the general population [2, 3, 4, 5]. In Europe, the entered the in-patient hospital through EFR – 87.5% development of recurrent bacterial pneumonia in- (p=0.044) against 60.4% in the experimental group. creased threefold (from 1.5% to 4.6%) after the be- At the time of admission, patients in both groups ginning of ART in AIDS patients [6]. complained of weakness, ailment, decreased ap- It is known that community-acquired bacterial petite, febrile temperature, cough, mostly wet, pneumonia pathogenesis is closely associated with and dyspnea on exertion. However, patients in the use of injecting drugs, which is one of the main the main group often complained of muscle ache, explanations for the changes in pulmonary tissue. joint ache (37.5%; p<0.001), lack of appetite (25.0%; In this group of patients, changes on the valves of p<0.001), discomfort and chest pain, mostly on the the heart are often found; in the anamnesis, data on left (25.0%; p=0.009), edema of legs (31.3%; p=0.06), the past angiogenic sepsis are not rare. A frequent and diarrhea (37.5%; p<0.001) (Table 1), which is causative agent of pneumonia is Staphylococcus often recorded in IDUs in the development of the aureus, Haemophilus influenzae, and other micro- clinic of septic inflammation [9]. organisms. The mortality rate from pneumonia in In the analysis of the clinical stages of HIV in- patients being the injecting drug users (IDUs) is fection at the time of admission to the in-patient 33.7%, while the average in Russia among young hospital, the prevalence of patients from the main patients is 1–3% [7, 8]. group in the stages of acute HIV infection with The research objective is to compare clinical im- secondary diseases (2B) and subclinical stage 3 plications of community-acquired pneumonia in amounted to 75.0%, and the number of patients in patients being the injecting drug users. the control group in the stages of secondary diseas- es made 50.9% (p>0.05). Materials and methods We calculated the experience of HIV infection 69 cases of community-acquired pneumonia in from the moment of its registration to the day of HIV-infected patients treated in the in-patient hos- treatment. In the main group and the experimental pitals of Omsk were analyzed retrospectively. group, it amounted to 6 years in IU (U=414; p=0.88). The patients were compared in two groups de- According to the results of immunological pending on the presence of signs of bacteriologi- studies, in experimental groups, there are no sta- cal endocarditis and angiogenic sepsis – it was the tistically significant differences, except for the ab- main group (n=16). The experimental group (n=53) solute number of CD4+ lymphocytes, the number consisted of patients with no signs of bacteriologi- of which is smaller in the experimental group (in cal endocarditis. IU, 288 cl/µl, in the main group – 371 cl/µl; U=270.0; The work performed did not infringe on rights, p=0.02), which corresponds to the clinical stages of did not endanger patients. The obtained data are HIV infection. 63 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
Table 1 Characteristics of complaints in patients of study groups, abs (%)
Sign The main group (n=16) The control group (n=53) χ2 / р Weakness, ailment 14 (87.5) 41 (77.4) 1.045 / 0.307 Decreased appetite 4 (25.0) 20 (37.7) 0.879 / 0.349 lack of appetite 4 (25.0) 0 (0.0) 14.06 / 0.001 Muscle and joint ache 6 (37.5) 0 (0.0) 21.768 / 0.001 Cough 16 (100.0) 45 (84.9) 2.732 / 0.099 dry 5 (31.1) 11 (20.8) 0.76 / 0.384 wet 11 (68.8) 34 (64.2) 0.115 / 0.735 Dyspnea on exertion 9 (56.3) 20 (37.7) 1.729 / 0.189 at rest 3 (18.8) 10 (18.9) 0.00 / 0.992 Chest pain 8 (50.0) 9 (17.0) 7.216 / 0.008 on the left 4 (25.0) 2 (3.8) 6.974 / 0.009 on the right 2 (12.5) 4 (7.5) 0.38 / 0.538 with no clear localization 2 (12.5) 3 (5.7) 0.855 / 0.356 Headache 1 (6.3) 4 (7.5) 0.031 / 0.861 Vertigo 1 (6.3) 8 (15.1) 0.848 / 0.358 Nausea 0 (0.0) 2 (3.8) 0.622 / 0.431 Vomiting 1 (6.3) 3 (5.7) 0.008 / 0.93 Increased temperature 15 (93.8) 48 (90.6) 0.157 / 0.693 Edema of legs 5 (31.3) 3 (5.7) 7.852 / 0.006 Diarrhea 6 (37.5) 0 (0.0) 21.76 / 0.001
More than 80.0% of HIV-infected patients did In the general blood test, the value of hemoglo- not take antiretroviral therapy when applying to bin in IU in the main group amounted to 100 g/l, in a health facility because of complaints, which may the experimental group 110 g/l (U=387.0; p=0.598). have led to the development of secondary diseases The level of erythrocytes in the study groups was (p>0.05). 2.6х1012/l (U=379.5; p=0.521). Leukocytes in the main At admission to the in-patient hospital, each sec- group were 9.5x109/l, in the experimental group – ond patient was more likely to have the moderate 6.4x109/l (U=284.0; p=0.04). In both groups, eryth- severity state, and almost every fourth patient was rocyte sedimentation rate amounted to 42 mm/h in critical condition in study groups (p>0.05). The (U=391.5; p=0.644). skin cover was pale in patients of the main group in In the leukogram and in the biochemical blood 75.0%, in the experimental group in 52.8% (p>0.05). test, there are no significant differences in study In the case of respiratory auscultation, either rigid or groups (p>0.05). rigid weakened breath in patients in study groups During the X-ray examination of chest organs, was listened. In rare cases, vesicular one was listened the following changes were revealed. The presence in the experimental group (p>0.05). In auscultation of infiltrative changes was revealed in all patients, of mediastinal organs, clear rhythmic tones were both one- and bilateral (p>0.05). It was found that listened in more than 70.0% of patients, and in case the lesion of the middle right fraction was much of palpation of abdominal organs, painlessness was more frequent in patients of the main group (43.8%; diagnosed in more than 60.0% of patients in study p<0.01). Also, in IDUs with community-acquired groups. Half of the patients in each group showed pneumonia, destruction cavities in the pulmonary an increase in the liver to 4 cm from the edge of the tissue were recorded in 56.3% of cases (p<0.01). costal arch (p>0.05). Both groups described the expansion of roots When admitted to the in-patient hospital, the of lungs due to the increase in intrathoracic lymph body temperature in patients was 38.7°C in IU in nodes. One in four patients showed hydrothorax. both groups (U=404.0; p=0.78). The frequency of re- In the study of sputum for secondary microflo- spiratory movements at admission (IU 20 and 18 per ra, Staphylococcus aureus was verified in IDUs with minute; U=405.0; p=0.78) and the pulse on the radial community-acquired pneumonia in 68.8% of cases artery (IU 98 and 90; U=305.5; p=0.09) did not differ (p<0.01) (Table 2). In the control group, Klebsiella significantly. pneumonia was revealed in sputum in 22.6% (p<0.05). 64 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
Table 2 Data on the bacteriological study of sputum in patients of study groups, abs (%)
The causative agent The main group (n=16) The control group (n=53) χ2 / р Staphylococcus aureus 11 (68.8) 6 (11.3) 21.83 / 0.001 Pneumocystis jirovecii + 1 (6.25) 1 (1.9) 0.831 / 0.362 Staphylococcus aureus Escherichia coli. 1 (6.25) 1 (1.9) 0.831 / 0.362 Klebsiella pneumonia 0 (0.0) 12 (22.6) 4.385 / 0.037 Klebsiella pneumonia + 0 (0.0) 1 (1.9) 0.306 / 0.58 Staphylococcus aureus Haemophilus influenzae 0 (0.0) 5 (9.4) 1.627 / 0.203 Pneumocystis jirovecii + undefined 0 (0.0) 8 (15.1) 2.732 / 0.09 Streptococcus viridans 0 (0.0) 1 (1.9) 0.306 / 0.58 Undefined 3 (18.8) 18 (34.0) 1.343 / 0.247
Mainly, patients of both groups spent approxi- 4. Feikin DR, Feldman C, Schuchat A, Janoff mately the same number of bed-days in the in-pa- EN. Global strategies to prevent bacterial pneumo- tient hospital: 17 and 18 days (U=411.0; p=0.85), nia in adults with HIV disease. Lancet Infect Dis. and mortality was observed in 18.8% and 35.8% 2004; 4: 445–455. (χ2=1.611; р=0.199) in the main group and control 5. Zimina V.N., Astafyev A.V. Communi- group respectively. ty-acquired pneumonia in adult HIV-infected pa- tients: features of the course and treatment, pre- Conclusion vention. Pulmonology. 2016; 4(26): 488-497. Thus, the study of patients being IDUs with 6. Puro V, Serraino D, Piselli P, Boumis E, community-acquired pneumonia revealed the fol- Petrosillo N, Angeletti C, et al. The epidemiology lowing differences. Among the complaints, bone of AIDS associated recurrent bacterial pneumo- ache, muscle ache, lack of appetite, discomfort, nia in Europe in the pre- and post-HAART peri- chest pain, often on the left, edema of the legs, and ods [abstract 295]. In: Program and abstracts of 8th diarrhea predominated. These patients admitted Conference on Retroviruses and Opportunistic Infection the in-patient hospital through EFR, which indi- (Chicago). Alexandria, 2001: 131. cates the intensity of complaints and the severity 7. Ed. A.G. Chuchalin, A.I. Sinopalnikov. of their condition. In the general blood test, leuko- Clinical guidelines. Community-acquired pneumonia in cytosis and lymphopenia were observed, and de- adults. M., 2005: 200. struction cavities, infiltrative changes in the middle 8. Androsova N.A., Bykonya I.N., Pudova right fraction were determined using X-ray. Staph- A.N. et al. Clinicoradiological features of pneumo- ylococcus aureus was verified in sputum in 68.8%. nia in drug addicts. Journal of radiology and nuclear Therefore, when entering the in-patient hospi- medicine. 2001; 2: 4-9. tal, it is necessary to determine the patient’s predis- 9. Uteshev D.B., Karabinenko A.A., Filatova E.N., position to the injecting drug use, which will help Storozhakov G.I. Infectious and septic complications in in the choice of tactics of management and treat- drug addicts. Lechaschii Vrach Journal. 2001; 1: 28-31. ment of the patient. Conflict of interest. The authors declare that Contacts there is no conflict of interest. Corresponding author: Puzyreva Larisa Vladi- mirovna, Candidate of Medical Sciences, Head of References: the Department of Infectious Diseases, Omsk State 1. Chuchalin A.G., Abrosimov V.N., Medical University, Omsk. Avdeev S.N. Pulmonology. National guide. Ed. A.G. 644099, Omsk, ul. Lenina, 12. Chuchalin. M., 2016: 800. Tel.: (3812) 532666. 2. Gebo KA, Moore RD, Keruly JC, Chaisson E-mail: [email protected] RE. Risk factors for pneumococcal disease in hu- man immunodeficiency virus-infected patients. J Author information Infect Dis. 1996; 173: 857–862. Paneva Marina Aleksandrovna, Candidate of Med- 3. Tumbarello M, Tacconelli E, de Gaetano ical Sciences, Associate Professor of the Depart- Donati K, Ardito F, Pirronti T, Cauda R, et al. Bac- ment of Hospital Therapy, Endocrinology, Omsk terial pneumonia in HIV-infected patients: analysis State Medical University, Omsk. of risk factors and prognostic indicators. J. Acquir 644099, Omsk, ul. Lenina, 12. Immune Defic Syndr Hum Retrovirol. 1998;18: 39–45. Tel.: (3812) 359362. E-mail: [email protected] 65 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
UDC 616.24-002:616.94:616.15-073.27 doi.org:10.31684/2541-8475.2019.1(13).72-76 CHANGE IN THE PRESEPSIN LEVEL IN HEMODIALYSIS PATIENTS WITH PNEUMONIA AND SEPSIS 1Altai State Medical University, Barnaul 2Regional Clinical Hospital, Barnaul E.A. Titova1, A.R. Eirikh2, Z.A. Titova1, O.G. Zhgut2, S.I. Ivanova2, T.N. Zateeva2, D.V. Petrova2, E.M. Reutskaya2
The research objective is to study presepsin as an inflammation marker to improve diagnosis of severe pneumonia and sepsis in patients on hemodialysis. Materials and methods. 42 patients with severe pneumonia, sepsis, chronic glomerulonephritis and nephropathy aged from 17 to 77 years were examined. Among them, 18 patients received hemodialysis. Presepsin level was quantified on immunochemiluminiscent analyzer Pathfast (Mitsubishi Chemical Medience Corporation, Japan). Results. Рresepsin level in hemodialysis patients with severe pneumonia was 4431.2±2448.41 pg/ml. In hemodialysis patients with pneumogenic sepsis, рresepsin was 7256.1±1547.14 pg/ml. Рresepsin in hemodialysis patients with chronic glomerulonephritis and nephropathy was 2204.0±240.75 pg/ml. There was no difference between the presepsin level in patients with severe pneumonia, pneumogenic sepsis and hemodialysis patients with chronic glomerulonephritis and nephropathy. Presepsin in hemodialysis patients with pneumogenic sepsis was higher than in hemodialysis patients with chronic glomerulonephritis and nephropathy. Conclusion. High presepsin level is an indication of an active infection process and/or an effect of hemodialysis. Possible underestimation of the progression of severe pneumonia and sepsis in hemodialysis patients should be taken into account. Pneumogenic sepsis in hemodialysis patient may be considered if presepsin level is three times higher than the original one. Key words: presepsin, pneumonia, sepsis, hemodialysis.
Presepsin (PSP) is used as a biomarker of with pneumogenic sepsis (n=9, 21.4%), the third bacterial infection [1]. It is known that PSP is group – with chronic glomerulonephritis (CGN), secreted by kidneys and increases when their nephropathy (n=4, 9.5%). Patients in groups 1–3 functions are impaired [1, 2]. received hemodialysis. Patients with pneumogenic At the same time, the diagnosis of pneumonia sepsis (n=4, 9.5%) were treated with hemodialysis and sepsis in hemodialysis patients causes on urgent indications due to the acute renal difficulties in general and depending on the damage. The fourth and fifth groups consisted of identification of biomarkers. Further research is patients with severe pneumonia and pneumogenic needed to determine the role of PSP in the diagnosis sepsis who did not receive hemodialysis (n=13, of pneumonia, sepsis in hemodialysis patients. 31.0% and n=11, 26.2%). The research objective is to study PSP to The PSP level was quantified with the use of improve the effectiveness of diagnosis of severe the immunochemiluminiscent analyzer Pathfast pneumonia and sepsis in hemodialysis patients. (Mitsubishi Chemical Medience Corporation, For this purpose, the PSP level was determined Japan). The measurement results are presented in the following groups: 1) hemodialysis patients in picograms per milliliter, pg/ml. PSP was with pneumonia, sepsis, 2) hemodialysis patients determined at admission. Patients were managed in without infectious complications, 3) patients with accordance with existing clinical recommendations pneumonia, sepsis. and standards. Statistical processing of the data was carried Materials and methods out using the Statistica V. 10.0 software package. 42 patients were examined. The patients To determine statistically significant differences, were treated in the Department of Pulmonology, Mann–Whitney U-test was used. The differences Department of Nephrology, Department of were considered significant at p<0.05. Resuscitation and Intensive Care of the Regional Clinical Hospital in the period from 2014 to 2018. Results and discussion The age of patients varied from 17 to 77 years, The PSP level in patients with severe pneumonia the mean age was 53.5±2.40 years (±m). Among and chronic hemodialysis patients with severe them, there were 25 men (59.5%) and 17 women pneumonia is presented in Table 1. In patients (40.5%). All patients were divided into 5 groups. with severe pneumonia, the PSP level was lower The first group consisted of patients with severe than in chronic hemodialysis patients with severe pneumonia (n=5, 11.9%), the second group – pneumonia. 66 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
Table 1 PSP in patients with severe pneumonia and chronic hemodialysis patients with severe pneumonia
Patients with severe Chronic hemodialysis pa- pneumonia tients with severe pneumonia р Indicator (1) (2)
X ±m X ±m 1-2 362.6±76.29 4431.2±2448.41 р=0.010 PSP at admission n=13 n=5 Note: PSP is for presepsin. The PSP level in patients with pneumogenic patients with pneumogenic sepsis, the PSP level sepsis and chronic hemodialysis patients with was lower than in chronic hemodialysis patients pneumogenic sepsis is presented in Table 2. In with pneumogenic sepsis. Table 2 PSP in patients with pneumogenic sepsis and chronic hemodialysis patients with pneumogenic sepsis
Patients with pneumogenic Chronic hemodialysis patients sepsis with pneumogenic sepsis р Indicator (1) (2)
X ±m X ±m 1-2 1415.6±297.83 7062.0±1046.08 PSP at admission р=0.002 n=11 n=5
PSP in hemodialysis (chronic and on urgent CGN, and nephropathy. PSP in hemodialysis indications) patients with severe pneumonia, patients with pneumogenic sepsis was higher pneumogenic sepsis, CGN, and nephropathy is than in hemodialysis patients with CGN and presented in Table 3. There was no difference in nephropathy. Data on the PSP level can indicate an the PSP level in patients with severe pneumonia increase of the PSP level in hemodialysis patients and hemodialysis (chronic and on urgent with pneumogenic sepsis compared to chronic indications) patients with pneumogenic sepsis, hemodialysis patients with CGN and nephropathy. Table 3 PSP in hemodialysis patients with severe pneumonia and pneumogenic sepsis compared to patients with CGN and nephropathy
Hemodialysis Hemodialysis Hemodialysis pa- patients patients with tients with CGN with severe pneumogenic р and nephropathy Indicator pneumonia sepsis (3) (1) (2)
X ±m X ±m X ±m 1-2 1–3 2-3 PSP at admis- 4431.2±2448.41 7256.1±1547.14 2204.0±240.75 р=0.142 р=0.713 р=0.037 sion n=5 n=9 n=4
PSP in only chronic hemodialysis patients with There was no difference between the PSP level in severe pneumonia, pneumogenic sepsis, CGN, and chronic hemodialysis and hemodialysis on urgent nephropathy is presented in Table 4. There was no indications patients with pneumogenic sepsis and difference in the PSP level in patients with severe the PSP level in only chronic hemodialysis patients pneumonia and only chronic hemodialysis patients with pneumogenic sepsis (p=0.841). with pneumogenic sepsis, CGN, and nephropathy. We obtained data on the higher PSP level PSP in only chronic hemodialysis patients with in chronic hemodialysis patients with severe pneumogenic sepsis was higher than in chronic pneumonia and pneumogenic sepsis compared to hemodialysis patients with CGN and nephropathy. patients with severe pneumonia and pneumogenic Data on the PSP level can indicate an increase of sepsis. These data may indicate the effect of chronic the PSP level in chronic hemodialysis patients hemodialysis on the PSP level in severe pneumonia with pneumogenic sepsis compared to chronic and pneumogenic sepsis. hemodialysis patients with CGN and nephropathy. 67 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019
Table 4 PSP in chronic hemodialysis patients with severe pneumonia and pneumogenic sepsis compared to patients with CGN and nephropathy
Indicator Chronic Chronic Chronic hemo- р hemodialysis hemodialysis dialysis patients patients patients with with CGN and with severe pneumogenic nephropathy pneumonia sepsis (3) (1) (2) 1-2 1–3 2-3 X ±m X ±m X ±m PSP at admis- 4431.2±2448.41 7062.0±1046.08 2204.0±240.76 р=0.144 р=0.711 р=0.019 sion n=5 n=5 n=4
The literature data on changes of the PSP level After hemodialysis, the PSP level decreased from in chronic hemodialysis patients with pneumonia, 1510 (1280–1670) pg/ml to 753 (542–1210) pg/ml. pneumogenic sepsis are limited. The results obtained by the authors suggested An increase of the PSP level in sepsis and acute that PSP is filtered in hemodialysis. The increase renal damage (ARD) to 1523 (293-16764) pg/ml is in PSP in hemodialysis patients is due to reduced known [1]. clearance and/or increased PSP production. Nakamura Y. et al. studied PSP in patients with and without ARD, with and without sepsis [3]. Conclusions Authors determined that the PSP median value 1. The presepsin level in hemodialysis increases with an increase in the severity of ARD in patients with pneumonia, pneumogenic sepsis the groups of patients with and without sepsis. In made 5469.5±2862.58 pg/ml and 7256.1±1547.14 the group without ARD, the PSP border level was respectively. Рresepsin in hemodialysis patients 670 pg/ml, in patients with ARD, the PSP level was with chronic glomerulonephritis and nephropathy higher by 864 pg/ml. The researches concluded that was 2204.0±240.75 pg/ml. High presepsin level is the PSP level can be used to determine sepsis in an indication of an active infection process and/or patients with less severe forms of ARD. However, an effect of hemodialysis. with a significant decrease in renal functioning, 2. There was no difference between the PSP can be unreliable. presepsin level in patients with severe pneumonia, In their study, Takahashi G. et al. determined the pneumogenic sepsis and hemodialysis patients PSP border level to diagnose sepsis accompanying with chronic glomerulonephritis, nephropathy. ARD, which was detected by various indicators [4]. Thus, it is possible to assume the underestimation In ARD being determined by lipocalin associated of the development of severe pneumonia, sepsis in with neutrophil gelatinase (NGAL), the PSP border hemodialysis patients. level amounted to 828 pg/ml. 3. Pneumogenic sepsis in hemodialysis patients The data obtained in our study show an increase may be considered if the presepsin level is three in the PSP level in hemodialysis or only chronic times higher than the original one. hemodialysis patients with pneumogenic sepsis Conflict of interest. The authors declare that compared to hemodialysis patients not having there is no conflict of interest. infectious complications. Nagata T. et al. in their study determined the References: PSP levels in patients with reduced glomerular 1. Velkov V.V. The use of Presepsin biomarker for filtration rate (GFR) depending on the stage of early and highly specific diagnosis of sepsis. Clinical chronic kidney disease (CKD, KDIGО, 2012) and guidelines. M.; 2014. Available at: http://www. in chronic hemodialysis patients with anuria fedlab.ru/upload/medialibrary/e5e/kochetov-ag.- (excluding patients with an infection, cancer, liver klin-rek.-kld.-presepsin_-dek-2014.pdf. The link is diseases, autoimmune disorders, using steroids and active on 26.12.2018. immunodepressants) [5]. With reduced GFR and 2. Saito J, Hashiba E, Kushikata T, Mikami A, no infection, the PSP levels increased depending on Hirota K. Changes in presepsin concentrations in the stage of CKD to a maximum of 251.0 (213–297.5) surgical patients with end-stage kidney disease pg/ml at stage 5 of CKD. The PSP median value in undergoing living kidney transplantation: a pilot hemodialysis patients made 1160.0 (1070.0–1400.0) study. J Anesth. 2016; 30 (1): 174-177. DOI: 10.1007/ pg/ml. After obtaining these results, the PSP level s00540-015-2065-1. was measured in hemodialysis patients before, 3. Nakamura Y, Ishikura H, Nishida T, Kawano immediately after and in 2 days after hemodialysis. Y, Yuge R, Ichiki R, Murai A. Usefulness of
68 BULLETIN OF MEDICAL SCIENCE 1 (13) 2019 presepsin in the diagnosis of sepsis in patients with 656038, Barnaul, Lenina Prospekt, 40. or without acute kidney injury. BMC Anesthesiology. Tel.: (3852) 366091. 2014. 14:88: DOI: 10.1186/1471-2253-14-88. E-mail: [email protected] 4. Takahashi G, Shibata S, Fukui Y, Okamura Y, Inoue Y. Diagnostic accuracy of procalcitonin Zhgut Olga Georgievna, Candidate of Medical and presepsin for infectious disease in patients Sciences, Head of the Department of Nephrology, with acute kidney injury. Diagnostic Microbiology Regional Clinical Hospital, Barnaul. and Infectious Disease. 2016. 86 (2): 205-210: 656024, Barnaul, ul. Lyapidevskogo, 1. DOI:10.1016/j.diagmicrobio.2016.07.015. Tel.: (3852) 689872. 5. Nagata T, Yasuda Y, Ando M, Abe T, Katsuno E-mail: [email protected] T, Kato S, Tsuboi N, Matsuo S, Maruyama S. Clinical impact of kidney function on presepsin Ivanova Svetlana Aleksandrovna, Board Certified levels. PLoS One. 2015. 10(6). DOI:10.1371/journal. of the Department of Nephrology, Regional Clinical pone.0129159. Hospital, Barnaul. 656024, Barnaul, ul. Lyapidevskogo, 1. Contacts Tel.: (3852) 689872. Corresponding author: Titova Elena E-mail: [email protected] Aleksandrovna, Doctor of Medical Sciences, Professor of the Department of Therapy and Zateeva Tatyana Nikolaevna, Board Certified of General Medical Practice with the Course of the Department of Nephrology, Regional Clinical Further Vocational Education, Altai State Medical Hospital, Barnaul. University, Barnaul. 656024, Barnaul, ul. Lyapidevskogo, 1. 656038, Barnaul, Lenina Prospekt, 40. Tel.: (3852) 689872. Tel.: (3852) 366091. E-mail: [email protected] E-mail: [email protected] Petrova Dina Vladimirovna, Candidate of Medical Author information Sciences, Head of the Department of Pulmonology, Eirikh Andrei Rudolfovich, Head of the Express Regional Clinical Hospital, Barnaul. Diagnostics Laboratory, Regional Clinical Hospital, 656024, Barnaul, ul. Lyapidevskogo, 1. Barnaul. Tel.: (3852) 689684. 656024, Barnaul, ul. Lyapidevskogo, 1. E-mail: dinа[email protected] Tel.: (3852) 689989. E-mail: [email protected] Reutskaya Elena Mikhailovna, Deputy Chief Physician for Treatment, Regional Clinical Titova Zoya Aleksandrovna, Candidate of Hospital, Barnaul. Medical Sciences, Associate Professor of the 656024, Barnaul, ul. Lyapidevskogo, 1. Department of Anesthesiology, Resuscitation Tel.: (3852) 689812. and Clinical Pharmacology with the Course of E-mail: [email protected] Further Vocational Education, Altai State Medical University, Barnaul.
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