Vol 28, No 2 (2020)
- Year: 2020
- Articles: 13
- URL: https://journals.eco-vector.com/pavlovj/issue/view/1983
- DOI: https://doi.org/10.23888/PAVLOVJ282
Original study
Significance of gene polymorphysm in development of colorectal cancer
Abstract
Aim. To determine the significance of polymorphism of MTHFR (Ala222Val), XPD (Lis751Gln), XRCC1 (Arg194Trp), XRCC1 (Arg399Gln), XRCC1 (Arg208His), APE1 (Asp148Glu), hOGG1 (ser326Ces), P53 (Pro47Ser), VEGF (C654G), EGFR(A2073T), TNF(G308A), CHEK2 (Ile157Thr), MMP1 (1607 1G>2G), TIMP1(C53CT) genes in development of colorectal cancer.
Materials and Methods. 106 Cases of colorectal cancer in patients who were on treatment in Ryazan Clinical Oncological Dispensary (Ryazan) were analyzed. Genotyping in all patients was performed using the method of isolation of DNA from leukocytes of venous blood with subsequent polymerase chain reaction (PCR) with electrophoretic detection of the result.
Results. No interrelation between the age of patients and polymorphism of any studied gene was recorded at the moment of verification of the diagnosis (р>0.05). Statistically significant relationship was identified between polymorphism of TNF (G308A) gene and the stage of cancer: its homozygous major genotype G/G more commonly occurred in the group of patients with III-IV stage (р=0.047). In the presence of allele of G/G TNF (G308A) gene together with homozygous mutant allele of MMP1 (1607 1G/2G) gene, a direct relationship with increase in the number of patients diagnosed with III-IV stage was noted. This combination of two polymorphisms showed a statistically significant difference in the studied groups (р=0.025). In 8 out of 10 patients with IV stage, the presence of G/G polymorphism in VEGF (C654G) gene was noted. This mutant homozygous variant was much more rare in patents with I (37.5%), II (40%) or III stages (37.5%) (р=0.0147).
Conclusions. The studied genes do not influence the age of manifestation of colorectal cancer and occur at the same frequency in patients of both genders irrespective of the age group. Localization and the extent of differentiation of the tumor do not depend on polymorphism of the studied genes either. The presence of G/A polymorphism of TNF (G308A) gene should be considered a favorable criterion associated with lower aggressiveness of the tumor (р<0.05), whereas identification of the major G/G genotype especially in combination with homozygous mutant allele of MMP1 (1607 1G/2G) gene is an unfavorable factor (р<0.05). The presence of G/G mutant genotype of VEGF (C654G) gene may directly correlate with rapid progression of tumor and with active metastatic spreading (р<0.05).
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A study of influence of progesterone on activity of Glycoprotein-P in vitro
Abstract
Background. Glycoprotein-P (Pgp, АВСВ1) is a transporter protein participating in pharmacokinetics of medical drugs, and also in development of resistance of tumor cells to chemotherapy.
Aim. To study the influence of progesterone on the activity of Pgp in vitro on a cell model of human small intestinal epithelium.
Materials and Methods. The work was conducted on Caco-2 cells. The activity of Pgp was evaluated by transport of fexofenadine in a special transwell-system. Concentration of fexofenadine was analyzed by HPLC method. The amount of Pgp was determined by EIA method. Four series of experiments were conducted: control – cells preincubated with clean transport medium without addition of any substances; influence of rifampicin on the activity and synthesis of Pgp in the concentration 10 µmol/l in preincubation for 3 days (induction control); influence of progesterone on the activity of Pgp in concentrations 1, 10 and 100 µmol/l in preincubation for 30 min; influence of progesterone on the activity and synthesis of Pgp in concentrations 1, 10 and 100 µmol/l in preincubation for 3 days.
Results. Progesterone in the concentrations 1 and 10 µM in incubation with cells within 30 minutes did not show any reliable influence on the activity of Pgp, however, in concentration 100 µM it reduced the activity of the transporter protein.
In incubation of Caco-2 cells with progesterone in concentrations 1, 10 and 100 µM within 3 days the activity of Pgp remained unchanged. Progesterone in concentration 100 µM in incubation within 3 days significantly increased synthesis of Pgp in enterocytes by 114.3% as compared to control, and in other used concentrations (1 and 10 µM) it produced no reliable effect.
Conclusion. In in vitro experiments on Caco-2 cells progesterone in concentration 100 µM produces a direct inhibiting effect on the activity of Pgp; however, in incubation within 3 days it increases synthesis of the transporter protein, which cancels out its inhibitory activity.
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The influence of in utero exposure to formaldehyde on newborn rat thymus structure
Abstract
Aim. To study the structure of the thymus of newborn rats born from female rats exposed to inhalation of formaldehyde during gestation.
Materials and Methods. The work was carried out on 72 white outbred rats of the first day of postnatal development. The first group consisted of newborn rats (n=37) – the offspring of six rats that were exposed to formaldehyde (FA) in concentration of 2.766 mg/m3 during the entire period of pregnancy. FA exposure was given once a day for 60 minutes in a 1 m3 exposure chamber. The second group included control animals (n=35), which were kept in conditions similar to those of the experimental groups with the exclusion of the effect of FA. In the newborn rats, the body mass and the absolute and relative mass of the thymus were determined. The structure of thymus was studied in a light optical microscope. The number of cells in the cortex and medulla of the thymus was counted over an area of 2500 μm2.
Results. The body mass and absolute mass of thymus of the newborn rats of the first group showed a statistically significant reduction against control values. The differences between the values of relative mass of thymus in the compared groups were insignificant. The number of cells in the cortex and medulla of the thymus under the influence of FA did not show any significant changes.
Conclusion. The effect of inhalation of FA on the organism of pregnant rats during the entire gestation period consists in a decrease in the body mass and in the absolute mass of the thymus of newborn rats. With this, the relative mass of the thymus did not undergo significant changes. The thymus structure in the light microscope did not show any significant changes either.
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Results of the pilot part of the cardiac drug overdoses hospital registry (storm): focus on drug-induced bradycardia
Abstract
Aim. Analysis of the relevance of drug-induced bradycardia (DIB) as a medical and social problem, its main regularities and determination of the need for further study of this issue.
Materials and Methods. The register study was performed on 01 Jan 2017-30 Jun 2018 (18 months) at the clinical base of the Ryazan Regional Clinical Cardiology Dispensary. Inclusion criteria were: 1) bradycardia/bradyarrhythmia syndrome with intake of at least one drug with a bradycardic effect (BCE), 2) signing Informed consent to the processing of personal and clinical data. No additional interventions were performed in the diagnosis or treatment of patients within the registry.
Results. During 18 months, 191 patients (age 77.0 [69.0;82.0] years, 26.7% of men) were hospitalized with a verified diagnosis of DIB, which accounted for 52.6% of all cases of hospitalization for drug overdose. During the analyzed period, there was an increase in both the total number of drug overdoses (1.7 times, p<0.001) and overdoses of drugs with BCE (1.8 times, p<0.001). Main clinical manifestations of DIB: reduced heart rate (<50 beats/min – 80.0%, <40 beats/min – 51.1%), sinoatrial (30.4%) and atrioventricular blocks (1st degree – 8.2%, 2nd degree – 10.4%, 3rd degree – 14.1%), syncope (32.6%) and cardiac pauses >3 s (7.4%). Almost all (94.8%) the patients were hospitalized by ambulance, 40.7% – to the intensive care unit; 17.8% required pacemaker implantation; hospital mortality was 5.2%. More than half (54.5%) of hospitalized patients took ≥2 drugs with BCE, 15.7% – ≥3 and 3.14% – ≥4 (both in monotherapy and as a part of a combination): beta-blockers – 68.4%, antiarrhythmic preparations – 38.9%, digoxin – 25.8%, non-dihydropyridine calcium antagonists – 10.5%, I1-imidazoline receptor agonist – 9.5%, and other drugs with BCE – 7.4%. To analyze the cause of DIB, we used clinical data of 135 patients (age 77.0 [69.0;82.0] years, 20.7% of men), who could indicate the exact dose of a taken drug with BCE. Among them, the absolute exceedance of the recommended dose of drugs with BCE was found in 14.1% of cases, while in 85.9% of cases summation/potentiation effect of several drugs with ВСЕ was observed, with intake of each in a therapeutic dose.
Conclusion. The study confirmed high medical and social significance of the problem of DIB, which requires attention of practitioners, pharmacologists and clinical pharmacologists, health care providers, and also continuation of its study.
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Dynamics of parameters of psychological status of patients with stable ischemic heart disease and coronary artery bypass surgery
Abstract
Aim. Assessment and analysis of parameters of psychological status of patients with coronary heart disease (CHD) referred for coronary artery bypass surgery (CABG).
Materials and Methods. A study of parameters of psychological status, in particular, of the attitude to illness, coping strategies, and lifelong orientations was conducted in 58 male patients aged 40 to 74 years with a stable form of CHD before and after CABG surgery. The parameters were evaluated by a clinical psychologist in 2-3 days after admission of the patient to the hospital and in 7-8 days after CABG. Clinical and psychological diagnostics was carried out using the following questionnaires: TOBOL (L.I. Wasserman, et al.), «Life-Purpose Orientations» (D.A. Leontiev), «Coping Behavior Strategies» (R. Lazarus, adapted version of T.A. Kryukova). Statistical analysis was performed with use of computer Statistica 10.0 software program.
Results. After CABG patients with coronary artery disease show a significant reduction of the parameters of the anxious variant of the internal picture of the disease on the basis of TOBOL questionnaire, of the «positive re-evaluation» coping strategy on the basis of evaluation of stress-coping behavior and of the level of «Aim» scale on the basis of evaluation of the level of neurotization using the «Life-Purpose» test.
Conclusion. The results of the study indicate reduction of the level of adaptation to the disease in patients with coronary artery disease after CABG in result of behavioral disorders and difficulties in setting further aims for recovery. To increase postoperative adaptation, the psychocorrection measures may be «targeted» to the coping strategy for «positive re-evaluation» and assistance in setting aims in the postoperative stage of CABG.
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Variability of heart rhythm in patients with myocardial infarction with Q wave with standard therapy and nutritive support with organic selenium
Abstract
Aim. Assessment if the interrelation of the levels of selenium, parameters of heart rate variability (HRV), biochemical and rheological characteristics of blood in patients with Q-myocardial infarction (Q-MI) taking standard medicinal therapy and dietary correction with organic selenium in different stages of the disease.
Materials and Methods. An open comparative clinical study was conducted with involvement of 90 patients (the average age 58.3±1.4, of them 71 men and 19 women) diagnosed with acute coronary syndrome with elevation of Q-segment with outcome into Q-MI. The patients were divided to two comparable groups: control group that received standard therapy, and the main group that additionally received dietary product enriched with organic selenium. In acute, subacute and cicatrization stages, the dynamic series of RR intervals were recorded and mathematically analyzed on Varicard 2.51 complex, some biochemical parameters of blood, selenium status, rheological properties of blood were assessed.
Results. In the stage of hospital treatment, reduction of the heart rate (from 68.8±1.7 to 64.0±1.3 beat/min; p<0.05) was recorded in the main group. The initial level of SDNN in both groups was within the critical range (25.0±1.3 msec), and stress index (SI) several time exceeded the norm (1356.2±390.6 conv.un.); by the end of the observation both parameters did not achieve normal values in both groups. The coefficient of variation (CV) stayed below normal values throughout the whole treatment period, although in the dynamics it showed some tendency to growth. The spectrum power of the curve enveloping the dynamic series of RR intervals (HF) almost twice increased in the control group (р<0.05). Correlation analysis of the interrelation of biochemical parameters of blood, coagulogram and selenium of blood serum with different parameters of mathematical analysis of the heart rhythm revealed interrelations of different levels and direction.
Conclusion. Use of dietary product rich in selenium having a positive effect on the trophotropic functions of an organism, in complex with standard therapy, reduces tension of adaptation mechanisms and enhances adaptation potential of an organism that improves the prognosis and reduces risks.
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Comparison of cytotoxicity of vascular prostheses in vitro
Abstract
Aim. To study and compare cytotoxicity of the main types of synthetic prostheses used in arterial reconstructive surgery, including polytetrafluoroethylene (PTFE) and polyethylene-terephthalate (Dacron).
Materials and Methods. On the culture of human umbilical vein endothelial cells (HUVEC) of the 3rd passage, MTS test was conducted that is used in laboratory examinations with attraction of cellular technologies to study cytotoxicity of medical drugs and medical products. The test
implies use of MTS reagent that is 3-(4,5-dimethylthiazol-2-il)-5-(3-carboxymethoxyphenyl)-2-
(4-sulfophenyl)-2H-tetrazolium; additionally phenazine methosulfate (PMS) was used that plays the role of electron-binding reagent. In the experiment, cells were incubated with PTFE and Dacron within 24 hours at 37ᵒC with 5% CO2. For control, HUVEC cultured in the standard growth
medium, were used. In the presence of PMS, MTS was reduced by mitochondrial dehydrogenases of endothelial cells to formazan staining blue. Supernatant of cell cultures was evaluated by
photocolorimetric method on Stat Fax 3200 analyzer (microplate reader) of Awareness technology Inc. Palm City Fl. (USA).
Results. The lowest mean values were noted in Dacron group – 0.21 (0.20-0.22) optical density units, the highest values were noted in the control group – 0.36 (0.35-0.38); parameters in PTFE group were 0.35 (0.33-0.36). In comparison of the groups statistically significant differences were found between the control group and Dacron group (р<0.001), control and PTFE group (р=0.037), Dacron and PTFE (р<0.001). Incubation with Dacron led to suppression of metabolic activity of cells by 41.7% as compared to the control group (р<0.001). Metabolic activity of cells exposed to PTFE, approached that of the control group, that is, it corresponded to the optimal conditions of culturing of endothelial cells in vitro.
Conclusion. In comparison with polyethylene-terephthalate (Dacron), polytetrafluoro-ethylene (PTFE) showed the least suppression of metabolic activity of endothelial cells in vitro.
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Research of physical and mechanical characteristics of suture material in experiment in operations on liver
Abstract
Taking into account the peculiarities of the blood supply to the liver and the structure of its parenchyma, and, as a result, considerable difficulties in providing reliable hemostasis without additional traumatization, a surgeon needs to be careful when performing a surgical manipulation. Despite a large number of modern methods for stopping parenchymal bleeding, many practi-tioners give preference to classic methods of hemostasis, including ligation of bleeding vessels in the bulk of the organ using specialized sutures. One of the most serious complications of the use of suture material is cutting of organ tissue, which leads to enhanced bleeding and expansion of the area of damage. At the moment, the tactics of choosing suture material for surgical procedures is empirical. In this context, the aim of this study was to assess the physico-mechanical properties of suture material regarding its structure, and to develop a criterion for choosing surgical sutures for surgical procedures. For the study, the liver was removed out of corpses of males of 35 to 40 years of age, after which separate sections of 7.5×7×4 cm in size were obtained from it. Then a wound 3 cm long and 2 cm deep was made. The wound was sutured with a simple interrupted suture without tightening, but with application of one simple half-node. For suturing, catgut, twisted capron and polyglycolide thread were used. Attention was paid to the maximal force applied at the moment of cutting (Fmax) and the degree of pulling the thread at the moment of cutting (Lu). The analysis of the data was based on comparison of Fmax and Lu parameters. This method permits to refuse from the empirical approach to the choice of suture material for operations on the liver, and to develop a criterion for choosing surgical sutures.
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Methods for improving the results of using a synthetic prosthesis in the popliteal-tibial segment in critical limb ischemia
Abstract
Aim. Analysis of immediate and long-term results of using a synthetic prosthesis for femoral-distal-popliteal and tibial bypass grafting in patients with critical lower limb ischemia.
Materials and Methods. Patients with symptoms of chronic arterial ischemia of the lower extremities in the stage of critical ischemia (n = 109) were operated at the university surgical clinic on the base of D.D. Pletnev City Clinical Hospital, Moscow, in the period from 2009 to 2017. All the patients underwent the operation of femoral-distal popliteal or femoral-tibial bypass grafting using a synthetic explant (PTFE). Shunting with a synthetic prosthesis was performed in 33 (30.3%) patients, and in 76 (69.7%) cases a combination of an explant with a section of autovein was used in the form of a combined shunt in 44 patients (40.4%) (synthetic prosthesis + autovein) or a patch- or cuff plasty of distal anastomosis in 32 patients (29.3 %). In 14 (12.8%) patients of both groups, the intervention was supplemented by intraoperative balloon angioplasty of the lower leg arteries. Long-term results were evaluated within the period up to 5 years after surgery. Kaplan-Meyer survival analysis was used for the calculation of results.
Results. The cumulative 5-year patency of the synthetic prosthesis was 42.9%. However, use of the prosthesis in combination with the autovein section in the form of a combined shunt or plastic surgery of the distal anastomosis significantly improved the values of cumulative patency (54.5%) and limb retention (83.6%).
Conclusions. The results obtained make it possible to recommend the use of a synthetic prosthesis in combination with an autovenous plastic surgery of a distal anastomosis or by combining a prosthesis with a small section of an autovein in the absence of a complete autovein. Regular monitoring of such shunts in the long-term period and timely follow-up interventions are necessary for improving long-term results.
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Methods of pharmacological correction of intrauterine growth restriction syndrome
Abstract
Aim. Comparative analysis of the effectiveness of pharmacological correction of intrauterine growth restriction syndrome (IGRS) by monotherapy with diosmin and dipiridamol.
Materials and Methods. Retrospective and prospective examination of 80 pregnant women with singleton pregnancy with gestational age from 28 to 36 weeks with confirmed diagnosis of IGRS of 1 or 2 degree asymmetric form was conducted. 75.0% Of pregnant women that participated in the study, were of the average reproductive age (23-29 years of age). The share of young first-time-mother in I group was 10.0%, in II group – 15.0%, the share of age first-time-mothers was 17.5 and 10.0%, respectively. Extended history taking and history analysis, general clinical and obstetric-gynecological examination were conducted, laboratory and ultrasound methods were used. Newborns were evaluated on Apgar scale at birth and in 5 minutes. In the early neonatal period, inborn and transient pathological syndromes were evaluated.
Results. In patients receiving diosmin (n=40), reduction of the resistance index of the right and left uterine arteries to 0.440±0.004 and 0.460±0.004, respectively, and of the umbilical artery to 0.56±0.02 was achieved, that is lower than in the group of patients taking dipiridamol (n=40). A positive influence of diosmin on the intrauterine condition of the fetus was found that was manifested by its increased compensatory capacities for adaptation to chronic hypoxia in reliably higher percent of cases as compared to dipiridamol. After pharmacological correction, a tendency to normalization of the main parameters of the system of hemostasis was found in higher percent in women taking diosmin. This, in turn, produced a favorable influence on the volume of blood loss in physiological deliveries. Thus, in I group the average amount of blood loss was 180±15 ml, while in II group it was 265±15 ml (р<0.05). However, in operative delivery no such differences were obtained. In I group immediately after deliveries 10.0% of newborns were transferred to the resuscitation and intensive care unit, in II group transfer to resuscitation department was required in 37.5% of infants (<0.05). All the rest of children immediately after birth in the satisfactory condition were placed to one ward with mother, and they did not require resuscitation measures.
Conclusion. Increase in the compensatory capacities of the fetus was shown in the conditions of chronic intrauterine hypoxia in a reliably higher percent of cases after pharmacological correction with diosmin. This, in turn, produced a favorable influence on perinatal outcomes, birth of children with a higher parameters of mass and height and health index.
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Reviews
Epidemiological safety as a component of the operational management unit of the infocenter in introduction of lean manufacturing in a medical organization that provides primary health care
Abstract
Currently, the primary health care system is undergoing active reformation. Lean manufacturing technologies are being introduced into the activities of medical organizations that help reduce the loss of medical and auxiliary processes. One of the main methods of lean production is visualization, which is implemented in the operational management of a medical organization in the form of creating information centers (InfoCenters) that reflect the main parameters of the activity of a medical organization in the SQDCM system: safety, quality, order execution, costs and a comfortable environment. Criteria of safety of medical activity most relevant for the national healthcare system are parameters of epidemiological safety. A parameter most difficult for indication, but necessary for reflection of epidemiological diagnostics in the InfoCenter is the accident rate at work.
Aim. Generalization of literature data on the possibility of including epidemiological safety parameters into the operational assessment of the InfoCenter.
Epidemiological studies conducted in our country in medical organizations of various profiles show an increasing rate of emergency situations among the medical personnel. With this, the system of indication and identification of all emergency cases still remains imperfect, and medical personnel often hide cases of emergency situations.
Conclusion. Introduction of criteria of epidemiological safety into the practical activity of a medical organization as a component of the operational management unit of the InfoCenter will contribute to the formation of functioning and constantly improving system of analysis of the activity of medical organizations, to the control of provision of medical care, and to standardization of invasive procedures to ensure epidemiological safety. The key tasks of the InfoCenter are: focusing the attention of medical organization employees on problems, prompt response to emerging problems and risks, and also ensuring effective communication of all participants of operational meetings in a single information space.
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Disadaptive genetic-evolutionary processes in human populations of industrial cities
Abstract
Aim. Generalization of literature and proprietary data on genetic-physiological and evolutionary processes occurring in human populations in environmentally neglected industrial cities.
In the review information is given about damage to the genetic apparatus of cells of a human organism under influence of unfavorable environmental factors and disadaptations of different
genesis. To denote the totality of alterations induced by the given exposure, a new term is introduced – ‘genetics of disadaptations’. The information of mutagenic factors of the environment of industrial cities associated with growth of oncological diseases and of malformations resulting from chromosomal aberrations in cells is generalized. The problem of genetic burden of human populations
in environmentally neglected territories and of the influence of disadaptive factors on this process is discussed. Information of the ecological situation and morbidity of the population in Cherepovets industrial city is given. A role of disadaptations in genetic-evolutionary processes occurring in
human populations is shown. The cause of different manifestations of disadaptation in the population is stated to be divergence of traits. A hypothesis is proposed and evidences are given in favor of the existence of natural selection for a disadaptive trait in human populations. It is suggested that being accumulated in a human organism, disadaptive disorders may be transmitted to the next
generations reducing vital ability of organisms and inducing different diseases.
Conclusion. Within the topic, examples of different prophylactic measures for improving the health of the population of industrial cities are given to prevent unfavorable alterations of human genome under the influence of unfavorable ecological and related disadaptive factors.
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Consanguineous marriage as socio-medical problem
Abstract
Despite the availability of a large amount of scientific data on the negative impact of consanguineous marriages on the health of children born in such families, the significance of this problem is not decreasing in a number of countries.
Aim. Analysis of the modern scientific base on the problem of consanguineous marriages, assessment of their impact on the development of a particular pathology in children.
The article reflects the position of modern clinical recommendations, the results of recent studies, and some controversial and unresolved issues. Despite the emerging trend of declining consanguineous marriages in recent decades, this problem involves at least 20% of the population and dozens of countries around the world. The prevalence of consanguineous marriages in the world varies significantly, ranging from 0.1-0.4% in the United States and European countries to more than 50% in North Africa, the Middle East and West Asia. The most common form of consanguineous marriage is a marriage between first cousins. In general, rural residents who have a lower level of education are more likely to enter into consanguineous marriages.
Conclusion. Despite a number of positive social and economic aspects of consanguineous marriages, from the point of view of genetics and medicine, it is necessary to take into account the negative impact of consanguineous marriages, which consists in an increased genetic risk to offspring and a high incidence of congenital pathology in newborns. An assessment of the socio-demographic aspects of consanguineous marriages shows that their greater prevalence is often due to poor economic conditions, lack of education, and low social security.
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Media Registry Entry of the Federal Service for Supervision of Communications, Information Technology and Mass Communications (Roskomnadzor) PI No. FS77-76803 dated September 24, 2019.