ORIGINAL RESEARCH
Introduction. Dermatological manifestations of a novel coronavirus infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are observed in the different periods of the disease, and can sometimes be the only manifestation of coronavirus disease 2019 (COVID-19). Despite the fact that at present the daily increase in new cases of coronavirus infection in the Russian Federation is small, the issues of timely diagnosis, treatment and prevention of COVID-19 remain relevant, and the experience gained during the pandemic is of invaluable practical importance.
Aim. Evaluation of dermatological manifestations associated with a novel coronavirus infection caused by SARS-CoV-2 in the acute period of COVID-19 and post-acute one.
Materials and methods. A cohort non-comparative descriptive study of 120 people aged 48–72 years (44 men, 76 women), who had COVID-19 no earlier than 12 weeks ago, was carried out.
Results. Changes in the skin and its appendages were observed in 72 (60%) patients. In 7 (9.7%) people, dermatological symptoms appeared during the acute period of COVID-19 and were represented by urticaria, pernio-like skin lesions of the feet, edematous erythema of the face and chest, itching and hyperesthesia of the skin. In two cases, skin rashes preceded the onset of respiratory signs of coronavirus infection. Dermatological manifestations of post-COVID syndrome occurred in 94.4% of patients, of which diff use alopecia was diagnosed in 60.3% of cases, skin xerosis with itching and/or paresthesia in 48.5%, onychopathy in 23.5%, new-onset dermatoses in 14.7%, and in 38.2% of cases – a combination of several dermatological disorders.
Conclusion. Among the skin lesions associated with COVID-19, we can identify symptoms typical of the acute period of the disease and signs characteristic of post-COVID syndrome. The dermatological manifestation during the acute period of COVID-19 can serve as an indicator of infection, contributing to its timely diagnosis. Knowledge of the dermatological manifestations of post-COVID syndrome will allow us to correctly conduct a diagnostic search and prescribe adequate treatment.
Introduction. The coronavirus disease 2019 (COVID-19) pandemic has been going on for more than two years and is significantly affecting routine clinical practice. Despite the numerous publications on heart damage in the acute phase of COVID-19, there is not enough data regarding the dynamics of cardiovascular system condition in coronary artery disease (CAD) patients after the infection caused by SARS-CoV-2. The influence of the long-term consequences of the disease on cardiovascular system condition of patients who have had infection requires careful study.
Aim. To assess the clinical and laboratory picture and coronary lesion nature in CAD patients with mild or moderate course of COVID-19 infection after at least 12 weeks.
Materials and methods. The analysis of clinical, laboratory parameters and coronary angiography of 118 CAD patients aged 46–67 years (mean age 60.2 ± 6.1 years) after a serologically confirmed SARS-CoV-2 infection at the lapse of 12 weeks was carried out. The patients were divided into 2 groups: group 1 included 60 patients with a mild COVID-19, group 2 included 58 patients with a moderate COVID-19 course.
Results. CAD patients with a moderate course of COVID-19 in the acute period had higher values of office blood pressure, higher incidence of uncontrolled arterial hypertension, major multivessel lesions of coronary arteries and lesions of the main vessels than CAD patients with mild COVID-19. When comparing echocardiographic parameters in patients with moderate COVID-19, the lower parameters of the left ventricular ejection fraction were found which is quite consistent with the higher NT-proBNP values in these patients.
Conclusion. CAD patients, who have had moderate COVID-19 in the acute phase of infectious process, constitute a special risk group for a subsequent more severe course of the underlying disease.
Introduction. Currently, to determine the level of social and economic well-being of individual members of society or social groups, the concept of “quality of life” is increasingly being used which is proposed to be considered as the degree of comfort of an individual, both within himself and within his society. This allows you to identify factors that either improve life or worsen it. That is why the study of quality of life, as an integral characteristic of the physical, psychological, emotional and social state of a patient, based on his subjective perception, is stated on three components: multidimensionality, which allows to differentially determine the impact of disease and treatment on the patient’s condition; variability in time depending on the patient’s condition; participation of a patient in the assessment of his condition, which is the most valuable indicator of his general state.
Aim. Assessment of the quality of life in non-operated young patients after subarachnoid hemorrhage (SAH).
Materials and methods. The study included 165 patients with SAH (76 men, 89 women; mean age 48.82 ± 5.29 years). All patients underwent a comprehensive examination, which included the collection of complaints and anamnestic data with the identification of vascular risk factors, computed tomography (CT) and CT angiography, lumbar puncture, transcranial dopplerography, ultrasound examination of the main vessels of the head and neck, heart and abdominal organs. The vegetative state was assessed according to the A.M. Vein’s Questionnaire of Autonomic Disorders, general and mental fatigue – according to the Multidimensional Fatigue Inventory (MFI-20), cognitive ability – using a test battery, psycho-emotional status – according to the Spielberger’s State-Trait Anxiety Inventory, depressive disorders – according to the Hamilton Depression Rating Scale. Quality of life was assessed using the Nottingham Health Profile.
Results. The decrease in the quality of life as a result of SAH in young people depended on the level of stigmatization and was determined by the severity of psycho-vegetative disorders, symptomatic general and mental fatigue, state and trait anxiety, depressive disorders and cognitive impairments.
Conclusion. It is the integral assessment of quality of life that is the fundamental vector in the prospective observation of the examined patients, and, despite the absence of focal neurological symptoms and signs in most patients, there is a need to refer them to rehabilitation programs.
Introduction. The resistance of microbes to many classes of antimicrobial drugs is a global threat to human health and necessitates the search for new compounds with antimicrobial activity, with low toxicity and a potentially wide range of biological activity.
Aim. To study in vitro the ability of new xanthine derivatives (caffeine, 1-butyltheobromine and 7-butyltheophylline) to inhibit growth Staphylococcus (S.) aureus, Bacillus (B.) cereus, Escherichia (E.) coli and Pseudomonas (P.) aeruginosa.
Materials and methods. The antibacterial activity of xanthine derivatives synthesized in the Laboratory of Medicinal Chemistry of the N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry was studied in vitro using serial dilutions in a liquid nutrient medium against S. aureus, B. cereus, E. coli and P. aeruginosa cultures.
Results. Three substances, including the starting material – caffeine and 7-butyltheophylline, did not show antibacterial properties against test microbes. All xanthine derivatives studied did not inhibit the growth of E. coli and P. aeruginosa; 9 compounds containing fragments of amino acid esters or an acetylene substituent in the position of the C-8 xanthine backbone showed antibacterial activity against S. aureus and (or) B. cereus.
Conclusion. When studying the ability of natural xanthine caffeine and 12 of its derivatives to inhibit the growth of cultures of opportunistic bacteria, antibacterial properties against S. aureus and B. cereus were revealed in a number of amino acid derivatives. The best effect was shown by compounds containing fragments of alpha- and beta-amino acid esters (L-valine and beta-phenyl-beta-alanine), which determines the prospects for further research.
Introduction. Standard spine radiography is the basic method of radiodiagnosis, used for screening. X-ray imaging allows you to assess the anatomy of spinal motion segments in the cervical spine, determine the period of osteochondrosis and the tactics of further examination and treatment. Various types of dislocation of vertebrae are much more common than can be determined by spinal radiography in standard projections; as a result of dislocation, a pain syndrome occurs.
Aim. To study the effectiveness of conventional methods for diagnosis of instability in the spinal motion segment (SMS) in the cervical spine.
Materials and methods. We observed 50 patients (mean age 50.6 ± 2.19 years) who were admitted to the Clinic of the Irkutsk Scientific Center for Surgery and Traumatology (Neurosurgical Department) with a diagnosis Adult osteochondrosis of spine (ICD-10 code – M42.1). Conventional methods were used to diagnose SMS instability: plain radiography in anteroposterior and lateral projections, functional cervical spine radiography.
Results. It was stated that the most common changes are characteristic of II and III periods of osteochondrosis: straightening of cervical lordosis – in 48 patients (96%), decrease in intervertebral disc height – in 46 patients (92%), anterior wedging of vertebral bodies – in 48 patients (96%), endplate sclerosis – in 37 patients (74%), presence of marginal osteophytes – in 45 patients (90%).
In maximum flexion and extension, the CII–CVI vertebrae were involved in the formation of pathological mobility of the intervertebral segments, while the CI and CVII vertebrae remained stable.
Instability in one cervical vertebra was revealed in 15 patients (30%). Most often, excessive mobility of 2 vertebrae was observed – in 22 people (44%), less often of 3 vertebrae – in 5 patients (10%). The dislocation of 4 vertebrae was quite rare – in 2 patients (4%).
When analyzing the data of functional cervical spine radiography, we have found that the SMS instability in patients with intervertebral disc degeneration develops most often in the following segments: CII–CIII – 13 people (26%), СIII–СIV – 34 people (70%), CIV–CV – 29 people (58%), СV–СVI – 12 people (24%).
Conclusion. The SMS instability still remains an urgent problem in neurology and neurosurgery. Plain radiography reveals only indirect signs of SMS instability. Diagnosis by functional spondylography made it possible to verify the SMS instability only in 36% of cases.
Introduction. An advance in understanding the biology of Hodgkin’s lymphoma (HL) and improved approaches to anticancer therapy of HL allowed increasing the survival of patients at all stages of the disease. Thus, the 5-year overall survival is more than 85% even in HL patients with III–IV stages. However, early complications and long-term effects of combined chemoradiotherapy remain an urgent problem, reducing the quality of life of patients.
Aim. To assess the quality of life of patients with HL in different periods of the disease: at the time of diagnosis of the tumor process and after multiagent chemotherapy programs.
Materials and methods. The study included 46 patients with newly diagnosed HL, hospitalized in the Hematology Departments of the City Clinical Hospital No. 2 and the Novosibirsk Regional Clinical Hospital. The control group was represented by 46 apparently healthy people without a tumor process or exacerbation of chronic diseases. The SF-36 Health Survey was used as a tool for assessing the quality of life.
Results. The quality of life of patients was significantly higher in patients at onset of the disease than after specific anticancer therapy. Compared with the control group, in patients with HL, both before the start of treatment and after chemoradiotherapy, a deterioration in the physical condition affecting daily activities was noted. Also, with an increase in the in the number of courses of anticancer therapy, the emotional and physical health of patients with HL worsened significantly, and the intensity of pain syndrome was higher in patients with advanced stages of the disease.
Conclusion. Currently, the assessment of the quality of life in patients with hematologic malignancies at onset of the disease and after anticancer therapy can help achieve optimal therapy results while maintaining a high level of quality of life.
Introduction. Altered cytokine secretion has been described in many types of cancer. Being a key mediator of intercellular interactions, they can contribute to the development of resistance to targeted therapy and cytostatic drugs in chronic myeloid leukemia (CML).
Aim. To evaluate the relationship between cytokine spectrum indicators in patients with CML and the effectiveness of targeted tyrosine kinase inhibitors (TKI) therapy.
Materials and methods. Quantitative determination of the concentration of cytokines TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-18, IFN-α in blood serum of patients with CML (n = 60) and apparently healthy blood donors (n = 22) was carried out using enzyme-linked immunosorbent assay (ELISA). The phase of the disease and the depth of molecular response were determined according to criteria of the European Leukemia Net 2020. Stratification of CML patients by risk groups was carried out according to the Sokal (1984), EUTOS long-term survival (ELTS) (2016) scores. Hematological and non-hematological toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v.5.0, 2017).
Results. It was found that the serum concentration of a number of cytokines in the group of patients with CML was significantly higher compared to the control group: TNF-α – 2.80 and 0.70 pg/ml, p < 0.001, IL-6 – 3.10 and 0.70 pg/ml, p < 0.001, IL-18 – 296.40 and 122.10 pg/ml, p < 0.001, IL-10 – 5.15 and 0.95 pg/ml, p < 0.001, IFN-α – 5.60 and 4.00 pg/ml, p = 0.006, respectively. Among patients with CML, the level of cytokines varied depending on the level of molecular response and the type of TKI. Patients who did not achieve a major molecular response (MMR) were characterized by a significantly greater increase in the secretion of TNF-α, IL-6 and IL-1β (6.65 and 2.30 pg/ml, p = 0.004, 9.40 and 2.80 pg/ml, p < 0.001, 3.69 and 0.88 pg/ml, p = 0.004, respectively) compared with patients with MMR. However, only IL-6 was a statistically significant prognostic factor influencing the achievement of MMR (odds ratio 1.131, confidence interval 1.015–1.260, p = 0.025). Among patients receiving imatinib therapy, the level of TNF-α was lower compared to patients receiving nilotinib, dasatinib and bozutinib (2.10, 4.00, 6.85 and 4.25 pg/ml, respectively, p = 0.013).
Conclusion. The results of the research demonstrated increased secretion of TNF-α, IL-6, IL-18, IL-10, and IFN-α in CML patients, which may indicate an important role in the pathogenesis of CML. TNF-α, IL-6, and IL-1 levels were higher in patients who did not achieve MMR, and IL-6 was a statistically significant predictor the achievement of MMR.
Introduction. Under conditions of chemical damage to the cornea, its cellular structure is significantly disrupted, requiring emergency highly differentiated regeneration without an expressed proliferative component of inflammation and expansion of immunocompetent cells to gain an antimicrobial potential. For the purpose of pharmacological initiation of these processes, the study of the topical administration of anti-inflammatory enzyme preparations, such as subtilisin and hyaluronidase, is pathogenetically justified.
Aim. To study the effect of hyaluronidase and subtilisin, PEGylated (polyethylene glycol – PEG) using the technology of electron beam synthesis on the number of immunocompetent cells in the area of the corneal chemical injury during their subconjunctival and topical administration.
Materials and methods. An experimental study of the effect of PEGylated hyaluronidase and subtilisin enzymes, on the cellular composition of the corneal chemical injury was performed on 28 rabbits. Corneal injury was modeled using the Obenberger alkali burn technique. PEG-subtilisin or PEG-hyaluronidase was applied topically or subconjunctivally into the right eye of the animal, depending on the group, the left eye of the animal was used as a control – it was treated with 0.9% NaCl. After the experiment, enucleation was performed. The biomaterial obtained was used to prepare tissue specimens for morphological examination.
Results. The total count of cells in the groups of topical and subconjunctival administration of PEG-subtilisin was 43 (40; 52) and 73 (33; 92), and subconjunctival injection of PEG-hyaluronidase – 46 (37; 61), which was higher than the count of cells when using 0.9% NaCl in these groups (p < 0.01) and higher (p < 0.0001) cell numbers in the group of topical administration of PEG-hyaluronidase. The total count of cells with topical application of PEG-hyaluronidase was 15 (13; 16), with topical application of 0.9% NaCl of this group – also 15 (14; 18) (p = 0.38). The neutrophil count with the use of PEG-subtilisin was 1 (1; 2) with topical and 0 (0; 1) with subconjunctival administration, and with the use of PEG-hyaluronidase – 0 (0; 0) both with topical and subconjunctival administration.
Conclusion. The administration of PEG-hyaluronidase subconjunctivally and PEG-subtilisin both topically and subconjunctivally leads to an increased migration of immunocompetent cells to the area of the corneal chemical injury, while the migration of neutrophils is insignificant. It is completely absent when PEG-hyaluronidase is injected subconjunctivally. Topical administration of PEG-hyaluronidase does not induce a pronounced cellular response of immunocompetent cells in the area of the corneal chemical injury, and the effect of the application is comparable to that of 0.9% NaCl.
Introduction. Nasal administration is the optimal way to administer the drug to achieve maximum bioavailability in the topical treatment of nasal and paranasal sinus diseases. Due to the ease of administration and the possibility of dosing, nasal sprays have become the preferred way of active pharmaceutical substances delivery. In this regard, the composition and technology of a new nasal spray for the allergic rhinitis treatment based on fexofenadine hydrochloride and glycyrrhizic acid derivative was developed.
Aim. To conduct the pharmaceutical and technological tests for the previously proposed nasal spray composition for the treatment of allergic rhinitis and to develop a process flow diagram for its manufacturing.
Materials and methods. The substances used were fexofenadine hydrochloride and ammonium glycyrrhizinate. The weight uniformity of the nasal spray dose and the number of doses in the package were determined according to the corresponding article of the State Pharmacopoeia; the contact angle, the spray plume, and the spray angle were determined according to the methods from the literature data.
Results. During the experimental determination of the characteristics of the contact angle and the spray plume, an actuator manufactured by Coster Tecnologie Speciali S.p.A. (Italy) was selected which provided the best distribution of drops of the preparation and created the maximum area of the spray plume – 392.13 ± 28.075 mm2. As a result of tests to determine the average dose weight and the uniformity of dosing, compliance with the requirements of the current pharmacopoeia monograph was established. Comprehensive research enabled the development of a process flow diagram for the manufacturing of anti-allergic nasal spray.
Conclusion. The conducted research made it possible to determine a number of pharmaceutical and technological indicators characterizing nasal spray, and to propose the optimal process flow diagram for its manufacturing.
Introduction. On the basis of the Chemex Scientific Lab of the Vladimir Dahl Lugansk State University we have synthesized and selected 4 samples of partially hydrogenated pyridine derivatives via in silico screening, containing a furan fragment in the fourth position (codenamed cv-150, cv-140, cv-083 and jen09-039), the effect of which on the course of dexamethasone-induced diabetes mellitus (DM) is of interest.
Aim. To study the morphological parameters of the liver of dexamethasone-induced diabetic rats during a period of pronounced senile changes in the setting of pharmacological treatment with new partially hydrogenated pyridines, cyanothioacetamide derivatives.
Materials and methods. The experiment was carried out with 92 18-month-old albino male rats, by administering per os 4 samples of 1,4-dihydropyridine at a dose of 1 mg/kg to each individual group of animals with dexamethasone-induced diabetes mellitus. Simultaneously, a control group (dexamethasone-induced diabetes) and a group of intact animals (without steroid-induced diabetes) were used. Dexamethasone was administered for 13 days. The intact and control group of animals consisted of 12 individuals. Four experimental groups of animals consisted of 17 individuals in each group. Animals of the experimental groups received one of the study compounds cv-150, cv-140, cv-083 and jen09-039 via gastric tube at a dose of 1 mg/kg body weight for 21 days.
Results. During the experiment, 10 animals died from late complications of DM. Death was recorded in the control and experimental groups treated with cv-083 and jen09-039 compounds. The most pronounced hepatomegaly was found in animals of the control group, the absolute liver weight averaged 16.43 g (3.4% of body weight) with indicators in intact animals group of 14.44 g (2.8% of body weight). The liver weight of rats treated with the cv-150 compound was 12.90 g (2.74% of body weight). The minimal number of pathological changes of the liver was detected in animals receiving partially hydrogenated pyridine cv-083 – 28.6%. The maximum number of pathological changes was registered in control animals receiving dexamethasone without pharmacological treatment – 88.9%. No liver changes were detected in intact rats.
Conclusion. Positive metabolic and psychosomatic changes were observed during the experiment in groups of animals treated with cv-150 and cv-140 compounds. There was no mortality in these experimental groups. According to necroptic study, hepatoprotective activity was found in these compounds. The result of using the cv-083 compound is questionable. The jen09-039 compound did not have any positive effect on the course of dexamethasone-induced diabetes.
Introduction. To date, it has been established that risk factors for the development of a novel coronavirus infection (NCI), in addition to advanced age and chronic obstructive pulmonary disease (COPD), are metabolic diseases such as obesity, diabetes mellitus, arterial hypertension (AH), non-alcoholic fatty liver disease (NAFLD), united by the notion of “metabolic syndrome” (MS). At the same time, NCI contributes to the onset and aggravation of the clinical manifestations of MS. Similar to the restoration of respiratory function in subjects who had NCI, it seems relevant to analyze the disorders of carbohydrate and lipid metabolism in the long-term period after acute NCI in COPD patients.
Aim. To study in a comparative aspect the dynamics of clinical and functional characteristics of the metabolic syndrome in COPD patients who had NCI.
Materials and methods. We observed for 12 months in the Therapeutic Department of the City Health Centre No. 9, Barnaul, 385 COPD patients, which were divided into 2 groups: group I – 55 patients without MS, group II – 330 patients with MS. When assessing the distribution of patients by sex, the majority were men. The mean age of patients in group I was 65.2 ± 11.1 years; in group II – 63.7 ± 9.8 years (рI–II > 0.05). Group III (comparison) consisted of 120 patients with MS without COPD, comparable in age and gender. Complaints, anamnestic data of all patients were collected. Physical examination, laboratory (assessment of carbohydrate, lipid metabolism, liver and kidney function) and clinical (electrocardiography, echocardiography) examinations were carried out. Demographic indicators, smoking habit, duration of COPD, presence of complications and comorbidities were assessed.
Results. NCI was detected in 15 (27.3%) patients of group I, in 169 (51.2%) patients of group II (рI–II < 0.05). In the comparison group, NCI was diagnosed in 52 (43.3%) patients (pII–III > 0.05). Post-COVID syndrome (NICE, 2020) was diagnosed in 6.7% of patients in group I, in 34.3% of patients in group II (p < 0.05), and in 18.4% of patients in group III (p > 0.05). A direct strong correlation was found between the occurrence of post-COVID syndrome and the severity of carbohydrate metabolism disorders according to the values of the visceral adiposity index (VAI) and the insulin resistance index (HOMA-IR) (r = 0.74 and 0.72, respectively; p < 0.05). For most clinical and laboratory indicators, the negative dynamics persisted until the 6th month with improvement by the 12th month: the levels of high-density lipoprotein cholesterol and glucose decreased, the fat free mass index (FFMI) increased (p < 0.05), however, the number of patients with high normal blood pressure and AH increased statistically significantly by the 12th month after NCI, reaching 92.4% in group II (p < 0.05).
Conclusion. NCI is more often diagnosed in patients with MS in combination wih COPD, in the presence of risk factors: advanced age, COPD, obesity, AH. Post-COVID syndrome was detected in every third patient with MS and COPD with the positive dynamics of carbohydrate and lipid metabolism disorders by the 12th month of the follow-up. AH with the development of complications (diastolic dysfunction, abdominal obesity, and associated NAFLD) was characterized by an unfavorable, progredient course in patients with MS in combination with COPD in the long-term period after NCI, which necessitates early initiation of therapy for comorbidities.
REVIEW
Echinococcosis is a serious problem for modern mankind. This disease has no specific clinical manifestations, but its complications can be fatal. Echinococcus granulosus is endemic for the Astrakhan Region. Every year, the number of cases of human infection with Echinococcus granulosus is increasing on the Astrakhan Region territory. Most often Echinococcus granulosus cysts are found in the liver (85%) and lung (up to 15%). The heart (only 0.4–2%), spleen, kidneys, and brain are damaged much less frequently (1–5% for all locations). The article presents a clinical case of a patient with echinococcosis of the heart and aorta, brain caused by Echinococcus granulosus.