ORIGINAL RESEARCHES
I n t r o d u c t i o n . Despite its length and functional diversity, the small intestine is considered during surgical operations as a single organ, without a clear division into segments. The problem of intestinal anastomotic leakage has not yet been resolved, and its proportion is from 3.4 to 15.3%, with a mortality rate of up to 18.6%. Identification of the anatomical features of different segments of the small intestine and their contents is of practical importance in surgery in terms of prevention of complications.
A i m . Identification of morphological features of different segments of the small intestine and their microbiota.
M a t e r i a l s a n d m e t h o d s . An examination of 26 samples of the small intestine during autopsy was performed. The morphological features of the small intestine, its intraluminal microbiota composition, as well as leukocyte infiltration of the intestinal wall were studied at different distances from the ligament of Treitz.
R e s u l t s . The morphological characteristics of the small intestine are both individual (length) and common (changes in venous architectonics and a gradual decrease in intestinal diameter in the caudal direction). The number and cellular composition of leukocytes in the wall of the small intestine are approximately the same, which provides equal immunological protection regardless of the distance from the ligament of Treitz. The concentration of microbial communities and their qualitative composition change at different lengths of the small intestine, with a gradual increase towards the terminal segment. Changes in the qualitative and quantitative composition of the microbiota in the intestinal lumen do not lead to changes in the leukocyte reaction.
C o n c l u s i o n . When planning and performing a surgical operation, it is necessary to take into account the presence of different volumes and species composition of the bacterial load, as well as the morphological characteristics of different segments of the small intestine.
I n t r o d u c t i o n . Nowadays, the search for novel painkillers that exhibit both high efficacy and safety profiles is an essential problem of modern pharmacological research.
A i m . To study the antinociceptive activity of ten samples of new derivatives of 3-aminothieno[2,3-b]pyridine and 1,4-dihydropyridine in the classical tail immersion test.
M e t h o d s . 340 new cyanothioacetamide derivatives that were synthesized by us at the Chemex Research Laboratory (Vladimir Dahl Lugansk State University) underwent in silico screening. As a result, 10 compounds were selected that were the most promising for the pharmacological management of pain. In the experiment (tail immersion test), albino male rats were used, divided into 13 groups, 10 animals in each: the intact group, the control group (0.9% sodium chloride solution), the comparison group (metamizole sodium) and 10 experimental groups (according to the number of administered compounds). The compounds were administered intragastrically at a dose of 5 mg/kg 1.5 h before immersing the tail in hot water.
R e s u l t s . It was established that three samples with codenames AZ420, AZ331 and AZ383 showed a significant antinociceptive activity. The tail-flick time of rats in these experimental groups ranged from 31.4 s (AZ331) to 46.4 s (AZ383), while the significance of the differences p in comparison with the values of the control group ranged from 0.00073 (AZ420) to 0.00018 (AZ383).
C o n c l u s i o n s . Four new derivatives of 3-aminothieno[2,3-b]pyridine and 1,4-dihydropyridine with high analgesic activity, promising for further preclinical studies, have been identified.
I n t r o d u c t i o n . Albendazole is a broad-spectrum antiprotozoal and antihelminthic drug which also has an anti-opisthorchiasis effect. Currently, the problem of increasing the bioavailability of albendazole for the treatment of systemic helminthiasis and parasitosis is becoming urgent. One way to improve the absorption of albendazole is to increase its water solubility due to the formation of intermolecular complexes with arabinogalactan, a plant polysaccharide during mechanical treatment of their mixtures under intense mechanical treatment. The solid dispersion of albendazole with arabinogalactan, obtained by the mechanochemical method, has higher water solubility, and also increased antihelminthic, including against Opisthorchis spp. infection, pharmacological activity, without toxic effect on liver cells, compared with the officinal preparations of albendazole.
A i m . The study of physicochemical and technological characteristics of solid dispersions of albendazole with arabinogalactan obtained by the mechanochemical method.
M a t e r i a l s a n d m e t h o d s . A mixture of albendazole and arabinogalactan substances was ball milled to obtained solid dispersions, in a ratio of 1:5, 1:10, 1:20; the duration of mechanical treatment was 2, 8 and 24 hours. The shape and particle size of the parent substances and the obtained solid dispersions were determined by light and scanning electron microscopy. The particle size distribution of coarse fractions of solid dispersions was determined by sieve analysis, fi ne fractions – by dynamic image analysis of bulk materials. The determination of technological characteristics was performed using conventional pharmacopoeial methods.
R e s u l t s . During the study, experimental data were collected on the physical (shape and size of particles, particle size distribution) and pharmacotechnological properties (powder flowability, bulk density and tapped density of powders, Hausner’s ratio and Carr’s index) of albendazole and arabinogalactan, as well as their solid dispersions obtained by mechanochemical solid-phase synthesis.
C o n c l u s i o n . According to the results of the study, a sample of solid dispersion of albendazole and arabinogalactan (ratio 1:5, mechanical treatment time 2 hours) with appropriate physicochemical and technological properties was determined for use in the technology of further oral dosage form obtaining. The revealed rather low technological parameters of the rest solid dispersions of albendazole with arabinogalactan determine the need to select the optimal composition of excipients during further pharmaceutical development.
I n t r o d u c t i o n . The oversaturation of large cities with pharmacies and their consolidation into networks leads to increased competition between them, while at the same time, in rural settlements, the population often does not have the opportunity to purchase medications in their places of residence, since there are no pharmacies. In these conditions, it is necessary to optimize the location of pharmacies which is not regulated by law.
A i m . An assessment of the pharmaceutical market concentration in the Russian Federation and analysis of the pharmacy location in municipalities of the Novosibirsk region in 2021.
M a t e r i a l s a n d m e t h o d s . We used data of the Unified Register of Licenses of the Federal Service for Surveillance in Healthcare, as well as reports from the DSM Group, statistical data of the Medical Information and Analytical Center of the Novosibirsk region, data on the number of pharmacies from the 2GIS app for 10 municipalities of the Novosibirsk region and separately for 10 districts of the city of Novosibirsk. Research methods: content analysis, normative and index methods, economic and statistical, and regression analyses.
R e s u l t s . The Herfindahl-Hirschman index calculated for 2021 – 427.69 – allowed us to establish that the Russian pharmaceutical market is low-concentrated, no single pharmacy network has a dominant position in the market, therefore, at present, norms of antimonopoly regulation of the market are not applicable. The average value of the actual number of population per pharmacy in 10 districts of Novosibirsk was 26.26 thousand people. The smallest number of people per pharmacy is observed in the Central district of the city; the profitability of their work is ensured by a high consumer traffic on weekdays and the close location of office buildings. Based on the data obtained, it was established that in each of the districts of Novosibirsk, the number of population per pharmacy is 10–15 times less than the standards calculated according to the Guidelines of the Ministry of Health of the Russian Federation. The actual number of population per one pharmacy in the municipalities of the Novosibirsk region was 15.321 thousand people. Among the municipalities of the Novosibirsk region, only in the worker’s settlement Koltsovo there is a correspondence between the number of pharmacies and the number of residents; in other areas there is an excess of pharmacies and an imbalance in their location. It was also found that in the central district hospitals of the Novosibirsk region, pharmaceutical activities are carried out via 1013 separate structural divisions.
C o n c l u s i o n . An increase in the amount of pharmacies and an enhancement of their uneven distribution have been revealed, namely, an excess of parmacies – in urban municipalities and a shortage – in rural settlements, which leads to difficulties in provision of medicines and a paradoxical price increase. Most pharmacies in the Novosibirsk region belong to pharmacy networks; optimization of the pharmacy location is necessary to increase the accessibility of medicines.
I n t r o d u c t i o n . The analysis of metals in pharmaceutical practice uses both for the quantification of an active ingredient and for assessment of elemental impurities. For metal-containing drugs, the analytical methods must be specific and free from the interference of elemental impurities.
A i m . To study the influence of elemental impurities on the quantification of the pharmaceutical substance bismuth subsalicylate.
M a t e r i a l s a n d m e t h o d s . As a test sample the active pharmaceutical substance bismuth subsalicylate was used obtained by two different ways. Standard samples of elemental impurities of copper, lead and silver were prepared in concentrations with the maximum impurity content according to the European Pharmacopoeia. The analysis was carried out by stripping voltammetry.
R e s u l t s . The addition of solutions of elemental impurities of copper, lead and silver, either separately or as a mixture of all three solutions, does not cause the appearance of a signal on the voltammogram corresponding to the bismuth peak. When quantifying the pharmaceutical substance bismuth subsalicylate and comparing the peak height values, the ratio of the indicators turns out to be equal or close to 100%.
C o n c l u s i o n . The presence of elemental impurities of copper, lead and silver does not interfere with the quantification of the pharmaceutical substance bismuth subsalicylate by stripping voltammetry.
I n t r o d u c t i o n . Anticoagulants are included in the treatment protocols for several cardiovascular diseases. Nonea rossica Steven is of scientific interest as a source of biologically active compounds with the properties of an indirect anticoagulant.
A i m . Study of anticoagulant activity of total extracts from Nonea rossica Steven herb.
M a t e r i a l s a n d m e t h o d s . A dry extract was obtained from the herb using 70% ethanol, then the extractant was removed. The anticoagulant effect was studied in vivo (36 male Wistar rats) using a prothrombin time test. As a reference drug, warfarin was used in doses recommended by the patient information leaflet.
R e s u l t s . The extract studied at a dose of 1.7 g/kg showed anticoagulant activity comparable to the reference drug (prothrombin time is 31.3 ± 1.27 and 33.42 ± 1.33 s, respectively).
C o n c l u s i o n . Nonea rossica Steven is a promising plant for practical as an indirect anticoagulant.
I n t r o d u c t i o n . Current clinical and laboratory methods for assessing the intrauterine growth of a fetus are indirect and often have a low prognostic significance. Meanwhile, the determination of risk factors of antenatal death of a full-term fetus with the assessment of their prognostic significance and the possible preventability of adverse perinatal outcome will identify ways to reduce the stillbirth rate.
A i m . Determine the clinical and anamnestic risk factors for antenatal death of a full-term fetus in the Chelyabinsk region.
M a t e r i a l s a n d m e t h o d s . A retrospective analysis of the medical records of all cases with antenatal fetal death at 37 weeks 0 days – 41 weeks 6 days of pregnancy, registered in the territory of the Chelyabinsk region from 2019 to 2021, was carried out. Two groups were assigned: group 1 – women with antenatal death of the full-term fetus (158 patients), group 2 – women with live full-term births (50 patients).
R e s u l t s . Women with antenatal death of the full-term fetus statistically significantly more often lived in the city of Chelyabinsk and big cities of the Chelyabinsk region, had secondary vocational education and used to smoke tobacco; they had first or second pregnancy and first delivery. Among these women, female pelvic inflammatory diseases, hypertension, endocrine system diseases and specific infectious diseases (HIV infection, hepatitis C and tuberculosis) were statistically more common. These women had statistically more pregnancy-related complications such as hypertension without significant proteinuria; diabetes mellitus arising in pregnancy; gestational edema; false labour up to 37 full weeks of pregnancy; placental disorders; maternal care for poor fetal growth; acute respiratory infections. The following factors have a direct impact on antenatal death at full-term pregnancy: a history of hypertension, moderate pre-eclampsia, placental disorders, and fetal growth retardation.
C o n c l u s i o n . In the presence of risk factors directly affecting the occurrence of antenatal death of a full-term fetus, we consider it appropriate to deliver at 37 weeks 0 days – 38 weeks 0 days of pregnancy in order to reduce the risk of an adverse outcome of pregnancy.
I n t r o d u c t i o n . After on-pump coronary artery bypass grafting (CABG) surgery, the problem of prevention of bypass graft thrombosis, following the development of the phenomenon of induced aspirin resistance (Ar) remains unresolved.
A i m . To study the clinical and laboratory signs associated with the development of Ar, as well as to assess the significance of this phenomenon in the risk of cardiovascular complications (CVC) in patients with coronary artery disease (CAD) which who underwent on-pump CABG surgery, using mathematical modeling.
M a t e r i a l s a n d m e t h o d s . A study included 260 men aged 45 to 70 years (58.2 ± 6.8 years) with a diagnosis of CAD (stable angina pectoris of II–IV functional class (FC) (234 people) and silent myocardial ischemia of II–IV FC (26 people)). All patients received conventional therapy, including beta-blockers, angiotensin-converting enzyme inhibitors, nitrates, statins and acetylsalicylic acid (ASA). Myocardial revascularization was performed by on-pump CABG. Blood sampling for the assessment of laboratory risk factors (RF) of Ar was carried out at three stages: 1) at the prehospital stage – before CABG; 2) at the early postoperative period – 2 days after CABG surgery; 3) in the long-term postoperative period – 1 year after CABG surgery. At baseline, during the preoperative period, all 260 patients were aspirin sensitive (AS). Systemic inflammatory response to surgical intervention was assessed by the level of interleukin-6 (IL-6) and highly sensitive C-reactive protein (HSRP) in the blood serum, and endotheliopathy was assessed by the level of endothelin-1 (ET-1). Platelet aggregation activity (PAA) was also studied. We classified as aspirin resistant (AR) patients, those individuals whose PAA did not reach target values while they were taking ASA at a dose of 100 mg/day, and decreased by less than 50% compared with the baseline parameters. To analyze the impact of various factors (predictors) on PAA, the linear stepwise regression analysis with inclusions was used. Binary logistic regression was used to assess the influence of Ar on the risk of developing CVC, and linear discriminant analysis – to assess the relationship of clinical and laboratory predictors with the risk of developing specific types of CVC. Recurrence of angina pectoris, myocardial infarction (MI), decompensation of heart failure (HF) and sudden cardiac death were considered as CVC.
R e s u l t s . Ar was detected in 122 people (46.9%) on the 2nd day after CABG. This cohort of patients constituted the main group. The comparison group included 138 people (53%) who remained aspirin sensitive (AS). A year after surgery (and taking ASA at a dose of 100 mg/day this year), the proportion of AR patients decreased to 62 people, amounting to 24% of AS patients at baseline in the preoperative period. In two groups of patients, we compared such indicators as IL-6, HSRP, ET-1, PAA at all three stages of the study, while the cardiopulmonary bypass time (CBT) and the number of coronary bypass grafts (NBGs) – immediately after the CABG. In the main group (AR patients), much higher levels of the studied parameters were revealed than in the comparison group (statistically significant) both on the 2nd day and 1 year after CABG. CVC were detected in 53 out of 260 people (20.4%) during one year follow-up. They were distributed as follows: recurrence of angina pectoris – 37 people (14.2%); MI – 7 people (2.7%); decompensation of HF – 5 people (1.9%); sudden cardiac death – 4 people (1.5%). A mathematical model was developed to predict the risk of CVC after CABG in order to improve the long-term prognosis after surgery. As a result of the regression analysis, we got a set of five predictors that are statistically significantly related to PAA: ET-1, IL-6, HSRP, CBT, NBGs. The regression equation, which allows predicting the value of PAA on the 2nd day after CABG, had the form: PAA = 34.40 + 0.45 · IL-6 + 0.92 · ET-1 + 0.25 · CBT + + 0.73 · HSRP + 0.13 · NGBS, where 34.40 is the absolute term of the equation. Thus, according to the calculated PAA value, it will be possible to concluded the presence of either As or Ar for a particular individual. When assessing the relationship of Ar with the risk of CVC in patients after on-pump CABG, using binary logistic regression, it was determined that PAA is a statistically significant prognostic factor for CVC (χ2 = 21.0; p = 0.013). Using discriminant analysis, a mathematical model has been created to evaluate the probability of developing certain types of CVC in patients after on-pump CABG.
C o n c l u s i o n . The grade of systemic inflammatory response to on-pump CABG affects the development of induced Ar. The persistence of a systemic inflammatory reaction is associated with the prolongation of Ar in the long-term postoperative period. The regression analysis revealed an important role of systemic inflammatory response markers and endotheliopathy (IL-6, HSRP, ET-1) in the development of the phenomenon of Ar in patients undergoing on-pump CABG. The mathematical model, created by utilizing discriminant analysis, makes it possible to predict with the accuracy of 87% the probability of developing CVC (recurrence of angina pectoris, MI, decompensation of HF, sudden cardiac death) in patients who underwent on-pump CABG. Significant risk factors for CVC include: CBT, the levels of PAA, IL-6, HSRP and ET-1. Correction of these factors’ parameters will improve the long-term prognosis in patients with CAD after CABG.
I n t r o d u c t i o n . A variety of treatment regimens for bacterial vaginosis (BV) pose to the clinician the question of choosing appropriate therapy for this disease.
A i m . Improving the results of combination treatment of reproductive-age women with bacterial vaginosis by topical application of polyvalent bacteriophages.
M a t e r i a l s a n d m e t h o d s . A prospective study involving 120 female patients from 18 to 45 years old with complaints of abnormal vaginal discharge, diagnosis of BV confirmed by the Amsel criteria was performed. The patients were divided into 4 groups of 30 people, depending on the treatment regimen for BV: group 1 – metronidazole (gel) intravaginally + preparation Phagogyn (gel), polyvalent bacteriophage (PVB) for topical application; group 2 – clindamycin (cream) intravaginally + Phagogyn for topical application; group 3 – chlorhexidine gluconate (vaginal tablets) + Phagogyn for topical application; group 4 – Elzhina (ornidazole 500 mg, neomycin 65 000 U, prednisolone 3 mg, econazole 100 mg) + Phagogyn for topical application.
R e s u l t s . 10–14 days after the treatment, the effectiveness of metronidazole for vaginal application in combination with Phagogyn according to the Amsel criteria was 60.00%, clindamycin intravaginally in combination with Phagogyn – 73.33%, chlorhexidine gluconate intravaginally with Phagogyn – 43.33%, Elzhina + Phagogyn – 96.67%.
C o n c l u s i o n . The combination of Elzhina with Phagogyn is feasible for use in clinical practice to achieve better results in the treatment of BV, since this combination turned out to be the most effective.
I n t r o d u c t i o n . The 1,4-benzodiazepin-2-one derivative (codenamed PAV-0056), in a wide range of low doses 0.1–10 mg/kg has a pronounced analgesic effect as bradykinin receptor type 1 antagonist. Preclinical study of the pharmacokinetics of a new potential analgesic with different routes of administration in appropriate doses seems to be relevant.
A i m . To evaluate the pharmacokinetic parameters, bioavailability and transmembrane transport of the 1,4-benzodiazepin-2-one derivative PAV-0056.
M a t e r i a l s a n d m e t h o d s . PAV-0056 at doses of 0.1, 1 and 10 mg/kg was administered in a 1% aqueous solution of polyvinylpyrrolidone into the stomach and vein of male Sprague Dawley rats (age 1.5–3 months) weighing 250–300 g. We determined the plasma concentration of PAV-0056 in the blood of rats at discrete time intervals using mass spectrometry. The pharmacokinetic parameters and absolute bioavailability of PAV-0056 were studied. The permeability of PAV-0056 through a cell monolayer was studied on a 21-day cell culture originated from of colorectal carcinoma (Caco-2).
R e s u l t s . The absolute bioavailability of the 1,4-benzodiazepin-2-one derivative PAV-0056 after administration into the stomach of rats at a dose of 0.1 mg/kg is 10.1 ± 6.1%, at a dose of 1 mg/kg – 2.2 ± 0.1%, at a dose of 10 mg/kg – 6.4 ± 0.8%. Systemic exposure AUC and maximum plasma concentration Cmax change linearly with increasing dose of PAV-0056 from 0.1 to 10 mg/kg (coefficients of determination R2 are 0.9767 and 0.9976, respectively). PAV-0056 is absorbed from the small intestine within 1 h and eliminated from plasma within 5 h. After intravenous administration, PAV-0056 is eliminated within 0.5 h. The analgesic has a total clearance (ClT) of 83.16 l/kg/h and is not a P-glycoprotein substrate.
C o n c l u s i o n . The lipophilic derivative of 1,4-benzodiazepin-2-one, PAV-0056 after administration into the stomach is absorbed from the small intestine by passive diffusion with a bioavailability of no more than 10.1 ± 6.1%. Linear pharmacokinetics and no interaction with P-glycoprotein allow PAV-0056 to be positioned as a non-opioid analgesic with a good safety profile.
CLINICAL CASE
The article presents an expert case of electrical injury from technical electricity in water (the corpse of a girl with signs of a thermal burn was found in the bathroom, nearby there was a telephone connected to the electrical network). A forensic histological examination of the damaged tissues was carried out. The authors studied the histological picture of the electrical mark and changes in the dermis caused by electrical current in water. It was revealed that, firstly, the morphological picture of the electrical mark in water is determined by both the electrochemical damaging effect associated with the development of electrolytic processes in tissues and thermal exposure; secondly, not only the skin and subcutaneous fat, but deeper tissues are subject to massive traumatic effects which should be taken into account when the treatment of patients with non-fatal electrical injuries.