Medical perspectives (Medicni perspektivi)

10-14

Authors: Nosivets D.S.

The article deals with the issue of the biopharmaceutical interaction of L-thyroxin, diclofenac sodium and chondroitin sulfate as components of pharmacotherapy of osteoarthritis manifestations with concomitant hypothyroidism. It is known that functional insufficiency of the thyroid gland has a negative effect on all types of metabolism and in particular on the condition of the bone and cartilage tissue, leading to the development of osteoarthritis. Existing pharmacotherapeutic approaches to the medical treatment of this pathology require the use of basic hormone replacement therapy for the correction of thyroid insufficiency, and NSAIDs as drugs for the symptomatic treatment of osteoarthritis. However, to date, questions of the biopharmaceutical interaction of L-thyroxin and diclofenac sodium are not covered, and the prevention of osteoarthritis against the background of hypothyroidism with the help of chondroitin sulfate and its interaction with the components of pharmacotherapy has not been sufficiently studied. Based on the conducted research, it was established that, proceeding from the theoretical analysis of the physicochemical and chemical properties of these drugs, predominantly reversible acid-base interactions are assumed. The probability of strong and irreversible physicochemical reactions is very low and the physical mixtures of these drugs are not subject to negative interactions which can lead to profound destructive changes on the part of the dosage forms. Since L-thyroxin, diclofenac sodium and chondroitin sulfate are absorbed mainly by simple diffusion, have different transport mechanisms through biological membranes, have different degrees of binding to plasma proteins and various enzyme systems involved in their metabolism and excretion, pharmacokinetic interactions between them are excluded. At the level of pharmacological interaction, the combined and unidirectional effects of the combination of active substances L-thyroxin, diclofenac sodium and chondroitin sulfate are expected, in particular, in degenerative-dystrophic disorders due to functional insufficiency of the thyroid gland, for restoration of the structure of cartilage tissue and for a complex etiotropic and symptomatic treatment of osteoarthritis and related states.

22-32

Authors: Kolesnyk T.V., Nadiuk A.V., Kosova H.A.

Based on the cumulative data of scientific research reference values for the central blood pressure and its amplification were proposed in patients with different cardiovascular risk factors. Still, the possibility of its practical implementation in patients of different age groups has not been fully studied. There were examined 132 untreated patients (23 females and 109 males) with uncom­plicated essential hypertension, which were divided into 3 groups depending on age (WHO, 2012): I group included 47 patients of the young age, II group - 50 middle-aged patients and III group – 35 elderly patients. Measurements of central systolic blood pressure (cSBP), SBP amplification (SBP Amp), pulse wave velocity (PWV) were carried out by Arteriograph Tensioclinic (Tensiomed, Hungary). Target-organ damage included LVH which was determined by echocardiographic left ventricular mass index (LVMI), adjusted for body surface (g/m2) or height (LVMI2,7), aortic PWV>10 m/s. It was established that the use of a personalized approach in the examination of patients with arterial hypertension makes it possible to increase the efficiency of diagnosis of hypertensive-mediated subclinical organ damage. So in order to identify impairment of the vascular wall in patients of a young age with hypertension, with overweight and obesity, the reference values of PWV and cSBP in accordance with the age norm should be taken into account. It was particularly in this cohort of patients that the greatest adverse effect of vascular stiffness and body mass index (BMI) on the formation of left ventricular hypertrophy was revealed, while in elderly people it is necessary to use the reference values of cSBP, depending on the degree of hypertension.

39-45

Authors: Kravets O.V.

Fluid disorders always accompany acute pathology of abdominal organs. To conduct comparative analysis of efficiency of the goal-directed and restrictive regimens of infusion therapy of replenishment of volume depletion in high surgical risk patients with acute abdominal pathology 80 patients, operated by urgent laparotomy were studied. Patients were divided into two groups. In the first group (n=40) a goal-directed infusion therapy was conducted, in the second (n=40) – restrictive. Rheographic method was used to investigate the performance of water sectors of the organism, daily and cumulative water balances were defined, the percentage of excessive fluid was determined and estimated. In patients of the first group an increase in plasma volume by 11% (p<0.05), exceeding of the volume of interstitium by 14% (p<0.05) and the volume of extracellular fluid by 7% (p<0.05) on the 1st and 2nd day were noted. From the 3 to 7th day a reduction in extracellular fluid to 91.5% (p<0.05) of the norm was noted. Recovery of all the studied parameters was detected on the 10th postoperative day, when the percent of excessive fluid reached 9.6%. In patients of the second group there was restoration of plasma volume to normal in reduced by 10% (p<0.05) – 12% (p<0.05) from the norm of the interstitium volume, respectively to the 1st and 2nd day after surgery. From the 3d day there was a significant restoration to normal of all the studied parameters, which coincided with the “zero” values of the daily water balance and sufe limits of the percent of excess fluid, which reached 6.1% on the 10th day of treatment. Thus, the goal-directed infusion therapy allows to perform the correction of volume depletion in high surgical risk patients with acute abdominal pathology by increasing intravascular volume to excessive and increase of interstitium volume on 1st and 2nd day, development of a mild volume depletion from the 3d to 5th day, maintainance of the percentage of excessive fluids within safe borders. Restrictive mode of infusion therapy normalizes fluid balance of water sectors due to restoration of plasma volume in 6 hours of treatment and maintains it within the limits of the norm during all the postoperative period, preventis the development of interstitial oedema, ensures the "zero" daily water balance and limits the postoperative growth of the percentage of excess fluid.

53-57

Authors: Bashkirova N.S., Vуsochina I.L.

The role of the initial hormonal profile disorders of the system “pituitary – thyroid” in the emergence of a bronchospasm in response to exogenic stimuli has not been finally determined. The aim of our research was to investigate the character and degree of the relationship between bronchial hypersensitivity in children exposed to smoking and the functional activity of the thyroid gland. The research involved 74 patients aged 10 to 17 years. Sixteen children were not exposed to tobacco smoke, 50 children were passive smokers, and 8 of the children surveyed smoked actively. To investigate the level of bronchial sensitivity, a bronchial provocation test with a non-specific stimulus – bronchoconstrictor acetylcholine was carried out. We assayed the functional state of the thyroid gland by the level of free triiodothyronine (FT3), free thyroxin 4 (FT4) and thyroid stimulating hormone (TSH), identified by Enzyme-linked Immunosorbent Assay (ELISA) (Alkor Bio, Russia). Indicators of hormones of a thyroid gland in most of the examined children did not differ from standard values for healthy children. Analysis of the results of the inhaled bronchial provocation test with acetylcholin showed that the state of non-specific bronchial hypersensitivity was observed in 2 active smokers and in none of the passive smokers and non-smokers (χ2=15,4>χ201=9,21 або р<0,01). According to our data, in children with hypothyroidism, under the effect of tobacco smoke, changes in the functional state of sensitive bronchial receptors do not occur. Among 2 children who had an increased activity of the thyroid gland (hyperthyroidism), one child from the group of smokers had an increased bronchial sensitivity by the results of the acetylcholine test (p>0.05). According to our data, changes in the functional status of sensitive bronchial receptors (cholinergic receptors) resulting from exposure to tobacco smoke in children exposed to tobacco smoke, active or passive, do not depend on the functional state of the thyroid gland (Рχ2>0,05).

67-73

Authors: Dytiatkovsky V.O., Abaturov O.E., Naumenko N.V., Pinayeva N.L., Alifirenko O.O.

The paper presents data of the firstly conducted in Ukraine own study of associations of the single nucleotide polymorphism (SNP) rs7216389 of orsomucoid-1-like protein 3 gene (ORMDL3) variants’ with atopic diseases in children. Aim: to detect clinical significance of the SNP rs7216389 ORMDL3 in genesis of atopic diseases in children. We examined 153 children aged 3 to 18 years. The main group consisted of 119 children with clinical manifestations of atopic diseases with elevated total serum immunoglobulin E, confirmed by immunofluorescence assay method. The comparison group consisted of 34 children with a non-aggravated individual or family allergic anamnesis in whom there was detected the absence of any clinical syndromes and symptoms of atopic diseases and, mostly, physiological parameters of the serum total immunoglobulin E by immunofluorescence assay method. All the children were genotyped by ORMDL3 gene using polymerase chain reaction in real time with a restricted fragment length polymorphism. The genotype T/T within SNP rs7216389 of ORMDL3 gene significantly prevails among the children with atopic diseases and is associated with an increased incidence risk of seasonal allergic rhinoconjunctivitis (SARC) by 4.11 times (95% CI 1.55; 16.61), perennial allergic rhinitis (PAR) by 5.07 times (95% CI 1.22; 13.90) times and bronchial asthma (BA) by 10.31 times (95% CI 2.50; 42.62). Children with genotype T/T in locus rs7216389 of the ORMDL3 gene are the increased risk group for developing the atopic diseases. Children with genotype C/C in locus rs7216389 of the ORMDL3 gene are the decreased risk group for the development of atopic dermatitis.

80-86

Authors: Kalbus O.I., Shastun N.P., Makarov S.O., Bukreyeva Yu.V., Somilo O.V.

Myasthenia gravis is a relatively rare autoimmune disease with an undetermined aetiology which affects neuromuscular junctions. Currently, the following approaches to the treatment of myasthenia gravis are mainly distinguished: symptomatic treatment with anticholinesterase inhibitors (AChEIs), immunomodulatory therapy (“basic” therapy) with glucocorticoids, cytostatics, monoclonal antibodies; surgical treatment — thymectomy; short-term treatment with plasmapheresis and intravenous administration of immuno­globulin. The efficiency of treatment approaches to myasthenia gravis in Ukraine remains insufficiently studied. The purpose of this work is to analyse the therapeutic approaches in patients with myasthenia gravis depending on the clinical form and severity of the disease. Between 2014 and 2017, 182 patients with myasthenia gravis have been examined, out of which 147 (80.8%) were the patients with the generalized form of the disease and 35 (19.2%) — with its ocular form. The clinical neurological examination included the collection of complaints, an anamnesis of disease and life as well as a neurological examination. In all the patients, the level of antibodies to acetylcholine receptors (AchR) and to muscle-specific tyrosine kinase (MuSK) has been measured, in terms of quantity as well, using the enzyme-linked immunosorbent assay (ELISA), and the presence of antibodies to titin and SOX1 has also been detected by means of indirect immunofluorescence. Of the total sample, less than a third (28.0%) of the patients examined received basic therapy; among them, there were no patients with the ocular form and only 34.7% — with the generalized form (p<0.001). Basic therapy is found more often among the patients with class II myasthenia gravis (51.9%), with a statistically significant (p<0.001) higher share of the patients receiving such a therapy than in classes III and IV (26.6% and 22.6% respectively). The structure of therapy in patients with classes III and IV has not shown any statistically significant difference (p=0.658), with symptomatic treatment being the predominant type of therapy. Undergoing basic therapy reduces the chances of a severe clinical course of myasthenia gravis (the QMG score of 17 and higher) — OR=0.52 (95.0% CI 0.14-0.90), p=0.032; fatal cases of the disease — OR=0.36 (95.0% CI 0.02-0.70), p=0.049. When basic therapy is used, the survival rate of the patients (Figure 2) is 42.0 years on average (95% CI 42.0-42.7) which is considerably higher (p=0.021) compared to that of the patients receiving symptomatic treatment only — 33.0 years (95% CI 30.9-36.7). Immunomodulatory therapy was prescribed for only 28% of the patients in the total sample, for none of the patients with the ocular form of myasthenia gravis, and for 34.7% of the patients with the generalized myasthenia gravis. The prescription of immunomodulatory therapy reduces relative risks of a severe clinical course of myasthenia gravis — OR=0.52 (95.0% CI 0.14-0.90), p=0.032. The prescription of immunomo­dulatory therapy decreases the probability of a fatal outcome of the disease — OR=0.36 (95.0% CI 0.02-0.70), p=0.049). With the use of immunomodulatory therapy, the patient survival rate rises considerably reaching an average of 42.0 years (95% CI 42.0-42.7), which is much higher compared to that in the group of the patients receiving symptomatic treatment only — 33.0 years (95% CI 30.9-36.7), p=0.021.

96-101

Authors: Zakharov S.V., Zakharov V.K., Gorbuntsov V.V.

Objective – to study the concentration of pro- and anti-inflammatory cytokines in patients with early latent syphilis before and after treatment. The study was conducted in 112 patients with early latent syphilis (52 men and 60 women) and 15 healthy persons of the control group – all aged 18-43. Serological tests were used: the classical complex of serological reactions (CSR), ELISA, the reaction of passive hemagglutination (RPGA), immunofluorescence reaction with absorption (RIF-abs) and RIF-200. Using ELISA, the levels of cytokines IL-2, IL-6, IL-10, TNFα, and INFγ were determined in serum (in patients with latent syphilis, before and after treatment). The analysis of the received data was carried out with application of the program package Statistics 6.0. To identify the relationships between the indices, Friedman's nonparametric variance analysis with the definition of χ2 was used. The concentration of IL-10 before treatment in patients with early latent syphilis was significantly increased by 3.7 (14.9±0.9 pg/ml compared to the control group 4.11±0.5 pg/ml). The dependence of the content of this cytokine on the period of infection was established. It was found that one year after treatment concentration of IL-10 remained 1.8 times higher. The concentration of IL-6 was increased by 6.5 times in patients with latent early syphilis and was also dependent on the period of the infection, and also even 1.5-2 years after treatment the IL-6 content remained elevated. It was also found that in patients with latent early syphilis the concentration of IL-2 was increased by 2.3 times and it did not normalize in 24.5% of patients even two years after treatment. In patients with latent early syphilis, the concentration of TNFα was increased by 3.6 times. After treatment, the concentration of TNFα decreased, but exceeded the control values by 1.55 times. Further analysis of the concentration of TNFα revealed that, with a disease period of up to one year, the concentration of this cytokine was normal during ten months after treatment, and in patients with the disease period of more than one year, after treatment normalization of the TNFα level was absent in 64.5% even after 18 months. It was found that the concentration of INFγ in patients with early latent syphilis before treatment was increased by 3.8 times in comparison with the control group. After treatment, almost 25 % of patients with the duration of the infection more than one year revealed no normalization of INFγ and it was increased by 1.5 times. In patients with latent early syphilis there was a significant increase in the concentration of cytokines TNFα and INFγ, an imbalance of IL-2, IL-6, IL-10 as well as. The dependence of the cytokine concentration on the period of infection is noted. Based on the study of the cytokine status in patients with early latent syphilis with periods of infection of more than one year, the use of immunomodulatory therapy may be recommended. Increasing the concentration of such cytokines as TNFα, IL-6, IL-10 after treatment can be used as prognostic tests of serological resistance.

106-112

Authors: Antonenko A.M., Vavrinevych O.P., Omelchuk S.T., Shpak B.I.

This work is the first part of our study to develop alternative experimental mathematic models for predicting toxicity of insecticides. In the first stage, calculations will be carried out and the most reliable models will be proposed. In the second – a statistical analysis and comparative estimation of the toxicometric parameters obtained experimentally and calculated according to the proposed equations. The purpose of the research is the scientific substantiation of the calculation models for predicting toxicity of insecticides of different classes. Data on the physico-chemical properties and toxicometry parameters of fungicides are taken from the PPDB pesticides database. Insecticides of such chemical classes as derivatives of tetram and tetronic acids, benzoylureas, carbamates, neonicotinoids, pyrethroids, organophosphorus compounds, avermectins were selected for analysis. It has been established that there is a significant positive correlation between NO(A)EL in the chronic experiment of all insecticides, the median lethal doses at oral administration (LD50 per os) of pyrithoids and neonicotinoids, and the molecular weight (at p<0.05). There is a significant negative correlation between the toxicometry parameters of all insecticides and their individual groups (pyrithoids, neonicotinoids, organophosphorus compounds) and melting temperature and the octanol-water partition coefficient, log Po/w (at p<0.05). It is proved that the proposed calculation models for predicting insecticide hazards are adequate according to Fisher's criterion, and the coefficients of regression equations are reliable according to Student's criterion (p<0,05).

122-129

Authors: Chopchik V.D.

The purpose of this study was to analyze the state, problems and ways to improve the organization of the work of the Dental Medical Center (SMC) of A.A. Bogomolets National Medical University on the basis of a sociological survey of dentists. A sociological survey was conducted among 101 dentists of DMC. A specially designed questionnaire was used. According to the dentists’ opinion, the main directions for improving the organization of the SMC are the introduction of mechanisms for the economic motivation of staff (71.3±4.5%); modern dental technologies (82.2±3.8%); equipping the center with modern medical and diagnostic equipment (88.1±3.2%); improving the quality of postgraduate training of dentists (96.0±1.9%); introduction of a system for monitoring the quality of medical care (58.4±4.9%); improving the efficiency and quality of dental services through program initiatives of the departments of DMC (52.5±5.0%); an increase of the economic and legal independence of the dental center (76.2±4.2%); organizational, academic and financial autonomy of the center (88.1±3.2%); introduction of public-private partnership mechanisms in the DMC (75.2±4.3%). The conducted sociological research allowed to establish that the main parameters of the organization and management of the DMC do not correspond to the economic realities of time and require modernization, as well as determining the main directions of development of the DMC.