ОГЛЯДИ ЛІТЕРАТУРИ / LITERATURE REVIEWSthe classic manifestation of which is insulin resistance, through the formation of pro-inflammatory cytokines, which include IL-6, TNF-α, and IL-6.Conclusions.The conducted research points to the important role of systemic immunological disorders, the consequences of which are the cytokine attack of the body as a whole and periodontal tissues in particular.Studying the role of local cytokine destruction in relation to the involvement of the pituitary-adrenal system in the process, as prognostic markers, provides an opportunity to develop effective systems of primary prevention of periodontal tissue diseases in the safety of young people.

The objective: to analyze the frequency of insulin resistance (IR) in patients with systemic lupus erythematosus (SLE), study of traditional and rheumatic disease-related risk factors for the development of IR, assessment of the possibility of using of Finnish Type 2 Diabetes Risk Assessment Form (FINDRISC) to detect IR. Materials and methods. 58 patients with SLE (53 women and 5 men) without diabetes mellitus (DM) and hyperglycemia were included in the one-time study. The patients have received the inpatient treatment at the regional medical and diagnostic center of the communal enterprise “Poltava Regional Clinical Hospital named after M. V. Sklifosofsky PRC” in 2020-2023. The average age of patients was 38 [28; 43] years, the average duration of the disease is 4.0 [0.6; 6.0] years. 49 (85%) patients received glucocorticoids (GC), 20 (34%) – hydroxychloroquine, 26 (45%) – immunosuppressants, 2 (3%) persons received biological drugs. In all patients fasting glucose and insulin levels were determined, and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) index was calculated. The value of the HOMA-IR index ≥2.77 corresponded to the presence of IR. Traditional risk factors for type 2 DM and the risk of its development in the next 10 years in patients with SLE were assessed using the FINDRISC questionnaire. Results. IR was determined in 14 (24%) of 58 patients with SLE. The average value of the HOMA-IR index was 1.8 [1.3; 2,6]. The data of patients with and without IR were similar in terms of sex, age, duration and activity of SLE, therapy performed at the time of examination, frequency of traditional risk factors for type 2 DM. Body mass index (BMI), waist circumference (WC), and insulin concentration were higher in patients with IR. The HOMA-IR index was correlated with BMI (r=0.7; p<0.001), WC (r=0.6; p<0.001), risk categories for the development of type 2 diabetes according to FINDRISС (r=0.4; p=0.04), the SLEDAI-2K index (r=–0.3; p<0.02), the serum concentration of C3 complement (r=0.4; p=0.035) and the duration of GC therapy (r=0.4; p=0.02). Conclusions. IR was diagnosed in 24% of patients with SLE without a history of DM and with a normal fasting venous blood glucose level. The HOMA-IR index increased as SLE activity decreased and the duration of GC treatment increased. However, the development of IR was statistically significantly associated only with an increase in BMI and WC. The use of the FINDRISC questionnaire, which allows to assess the risk of developing type 2 DM in the general population, did not help to detect IR in patients with SLE.

The article discusses a clinical case of Wilson’s disease, a rare genetic disease characterized by impaired copper metabolism and its accumulation in various organs, particularly in the liver and brain. The complexity of the diagnostic search is described, taking into account the non‑specific symptoms that require a long and versatile diagnostic search at the onset of the disease. The complexity of the diagnosis after clinical manifestation was caused by the absence of damage to the nervous system, typical ophthalmological signs, such as Kaiser‑Fleischer rings, and changes in laboratory tests (content of «free» copper, ceruloplasmin, and copper in daily urine). The diagnostic significance of laboratory indicators of copper metabolism in blood and urine has been proven when Wilson’s disease is excluded in a patient with liver cirrhosis, even in the absence of damage to other target organs that are pathologically affected by copper. Special attention is paid to clinical manifestations, methods of laboratory and instrumental examination, as well as the importance of an interdisciplinary approach to diagnosis. This case emphasizes the importance of timely diagnosis to prevent serious complications and improve the patient’s prognosis. In addition, the problems arising from the late diagnosis of Wilson’s disease, such as the development of irreversible liver damage (cirrhosis) and neurological disorders, which can significantly impair the quality of life of patients, are considered. The role of genetic testing to confirm the diagnosis is emphasized, especially in cases where the clinical picture is ambiguous or there are concomitant diseases complicating the diagnostic process. The authors call for increased awareness among doctors about Wilson’s disease, given its rarity and the difficulty of recognizing it in the early stages. Long‑term follow‑up of patients and correction of therapy in case of changes in the clinical condition are important. Recommendations for improving diagnostic algorithms and an interdisciplinary approach in the treatment of patients with Wilson’s disease are given.

Metabolic syndrome (MS) is a group of interrelated metabolic disorders such as high blood pressure, central obesity, insulin resistance (IR), dyslipidemia. The main mechanisms that indicate a metabolic disorder and contribute to its development are IR and a large amount of circulating free fatty acids. In turn, tissue IR is often combined with other abnormalities including disorders of uric acid metabolism, changes in the hemostasis system, endothelial dysfunction, increased levels of C-reactive protein. At the same time, metabo­lic disorders are a risk factor for hyperuricemia. MS occurs in 25–60 to 90 % of all gout patients. About 50 % of patients with hyperuricemia have symptoms of MS. Hyperuricemia as a component of MS is a predictor of cardiovascular mortality, development of diabetes mellitus, hypertension and nephrolithiasis. Hyperuricemia is closely related to diabetes, obesity, coronary heart disease, hypertension. On the example of a clinical case, the main components of MS are considered, as well as the issue of the relationship between hyperuricemia, gout and the components of MS. The main idea behind the creation of the MS concept is to select a population of patients at a high cardiovascular risk in whom preventive measures such as lifestyle modification and the use of adequate drugs can significantly affect the main health indicators. The goal of managing patients with MS is to minimize cardiovascular risk and mortality as much as possible. Accordingly, the therapeutic strategy should include optimal ways to modify the lifestyle; lowering blood pressure to the target level and treating comorbid conditions; reducing low-density lipoprotein cholesterol according to the risk profile: > 50 %, and < 70 mg/dL (1.4 mmol/L) in patients at a very high cardiovascular risk; > 50 %, and < 100 mg/dL (1.8 mmol/l) in high-risk patients; reducing fasting serum glucose < 126 mg/dl (7 mmol/l) or glycated hemoglobin < 7 % (53 mmol/mol); maintaining uric acid level < 6.5 mg/dL (0.387 mmol/L), in patients with gout — below 6 mg/dL (0.357 mmol/L). Thus, according to the results of the research, a causal relationship was found between insulin resistance and serum uric acid levels in patients with metabolic syndrome. The strategy for managing patients with metabolic syndrome should include screening and correction of hypertension, carbohydrate purine metabolism, dyslipidemia, and prevention of cardiovascular events.

Introduction: Human chemerin is an adipokine that regulates chemotaxis, inflammation, and glucose metabolism. In addition, accumulating evidence suggests that chemerin promotes apoptosis, autophagy, and pyroptosis. However, there are no data on its impact on eryptosis. The current study aimed to analyze the effects of human active Glu21-Ser157 chemerin on eryptosis in vitro. Materials and Methods: Human chemerin 0-2-10-50 µg/mL was incubated for 24 h with human erythrocytes (hematocrit 0.4%) obtained from eight healthy individuals. Flow cytometry-based determination of phospholipid scrambling, reactive oxygen species (ROS) production, and intracellular Ca2+ levels was performed. To supplement data on ROS and Ca2+ signaling in chemerin-mediated eryptosis, incubation in the presence or absence of antioxidants vitamin C and N-acetylcysteine and Ca2+-binding agent EGTA was carried out, respectively. Confocal microscopy-based techniques were used to detect reactive nitrogen species (RNS) generation, involvement of caspase-3 and caspase-8, as well as the state of lipid order in cell membranes of erythrocytes exposed to human Glu21-Ser157 chemerin. Results: Our observations suggest that human Glu21-Ser157 chemerin had no impact on eryptosis parameters at 2 µg/mL. However, chemerin stimulated phosphatidylserine externalization, ROS production, and Ca2+ accumulation at higher concentrations suggesting activation of eryptosis. Ca2+ uptake turned out to be at least partly required for chemerin-mediated eryptosis. Chemerin-mediated erythrotoxicity was additionally mediated by RNS, caspase-3, and caspase-8. Moreover, Glu21-Ser157 chemerin promoted reduction in the liquid-ordered phase of cell membranes in erythrocytes. Conclusions: The present study first discloses that human chemerin can induce eryptosis via Ca2+-dependent mechanisms at concentrations noticeably exceeding circulating levels. Thus, chemerin-induced eryptosis can hardly contribute to eryptosis-mediated anemia in diseases associated with enhanced levels of chemerin in blood.

This review provides contemporary insights into the direct and indirect pathogenetic connections between purine compound metabolism and biochemical processes within the cells of the gastrointestinal system. A thorough analysis of recent publications from 2000 to 2024, sourced from databases including Scopus, PubMed, eLIIBRARY, and Google Scholar, was conducted. Uric acid serves as the end product of purine-containing compound catabolism. Its concentration is intricately regulated through the collaboration of the kidneys and gastrointestinal organs, namely the small intestine and liver. Gout, a chronic condition, emerges from the interplay between molecular genetic factors and external influences. Elevated levels of urates in the blood serum (hyperuricemia) and the deposition of sodium urate crystals in organs and tissues set off a cascade of inflammatory and fibrotic processes within mucosal, smooth muscle, parenchymal, and endothelial cells, including those within the gastrointestinal tract. Normally, a person excretes about 1.5 g of uric acid per day. Under physiological conditions, two-thirds of uric acid is excreted from the body by the kidneys, one-third through the intestines, and a small part is excreted with bile. The hypothesis that links the pathogenesis of hyperuricemia with “renal overload” suggests that the disease may develop as a result of impaired renal excretion with insufficient elimination of uric acid through the intestines. Part of uric acid transport systems actively works in hepatocytes and enterocytes, which determines its formation and clearance. Uric acid transporter proteins are divided into two categories: urate reabsorption transporters and urate excretion transporters, their expression is regulated by transcription factors, hormones and metabolites of intestinal microflora. The influence of intestinal microbiota on uric acid metabolism is related to its participation in purine metabolism, decomposition and elimination of uric acid with metabolites of intestinal flora and inhibition of gouty inflammation and is evaluated as a new therapeutic potential in gout and hyperuricemia, which allows to avoid kidney damage and urolithiasis.

The study presents data on the relationship between clinical manifestations and signs of enthesitis, synovitis, and tendinitis detected during ultrasonography in patients with the cutaneous form of psoriasis and psoriatic arthritis. 56 patients with widespread psoriasis whom dermatologists first referred to a rheumatologist for joint and muscle pain were examined. The period of musculoskeletal pain in patients did not exceed 10 months. In addition to general clinical and laboratory examinations, all patients underwent ultrasonography of swollen and/or painful joints, tendons and ligaments. The study demonstrated the diagnostic capabilities of ultrasound to detect foci of inflammation in patients with psoriatic arthritis and identify groups of patients with isolated enthesitis and a combination of enthesitis with synovitis for differentiated anti-inflammatory therapy.

This article provides a thorough analysis of new and promising pharmaceuticals for the treatment of gout, encompassing anti-inflammatory and urate-lowering therapies. It covers drugs that have already received regulatory approval and are in active clinical use, as well as those in various stages of implementation and clinical research, showcasing their notable efficacy and safety. Additionally, the article discusses contemporary gout treatment approaches in alignment with international and domestic clinical guidelines. Emphasis is placed on the safety and efficacy of colchicine in gouty arthritis and its cardioprotective properties for patients with gout and comorbid cardiovascular disease. The article provides the information on the effectiveness of canakinumab, a new anti-inflammatory agent for the symptomatic therapy of gout. The effectiveness and safety of anakinra makes it possible to consider it as a promising alternative to the traditional approach to the anti-inflammatory therapy of gout. Rylonacept allows physicians to develop more effective treatment algorithms for those patients with gout who unsatisfactory respond to conventional therapy. The article provides a historical perspective on the use of adrenocorticotropic hormone as an anti-inflammatory agent for gout. It also highlights existing, new, and potential anti-inflammatory drugs, with a primary focus on the safety and effectiveness of febuxostat, supported by recent large randomized clinical trial results. Additionally, the article describes other medications aimed at reducing uric acid levels in the bloodstream, including uricosuric agents (such as probenecid, benzbromarone, sulfinpyrazone, lesinurad, verinurad, dotinurad, and archalofenate), xanthine oxidase inhibitors (allopurinol and topiroxostat), and pegylated uricase drugs, which may hold promise for future use in combination with primary urate-lowering therapies.

Autoimmune hepatitis is considered a rare autoimmune inflammatory disease of the liver, which has a high mortality in the absence of therapy.A feature of autoimmune hepatitis is a wide range of clinical symptoms, from asymptomatic (in 25-37% of patients) for several years to an acute course of the disease, which complicates the timely diagnosis of such patients.In addition, the course of autoimmune hepatitis in 14-44% of cases is complicated by other concomitant autoimmune diseases, such as autoimmune thyroiditis or type I diabetes.The complexity of managing patients with autoimmune hepatitis is often due to overlap syndromes with primary biliary cholangitis or primary sclerosing cholangitis.Histological examination and diagnostic markers of autoimmune hepatitis, which has an overlap syndrome with primary biliary cholangitis, play the most important role in the verification of the diagnosis, especially in case of simultaneous manifestation of diseases.This paper presents a clinical case of a patient with a crossover course of autoimmune hepatitis and primary biliary cholangitis, which had an asymptomatic onset and required a liver biopsy to confirm the overlap syndrome.We aimed to investigate the possibilities of management and prevention of complications in a patient with autoimmune hepatitis who had an overlap syndrome with primary biliary cholangitis.Using the example of this clinical case, the tactics of preventing the progression of the disease and the possibility of preventing the appearance of side effects of therapy in a patient with the overlap syndrome of autoimmune hepatitis and primary biliary cholangitis are highlighted.The presented research data may interest family doctors, therapists, gastroenterologists and doctors of other specialties.

A clinical case is presented of delayed diagnosis of primary hyperaldosteronism (PHA) due to aldosterone-producing adenoma. Suspicion of PHA arises in case of persistent combination of hypertension with hypokalemia of various severity, a specific neuromuscular syndrome, as well as a high risk of cardiomyopathy, heart failure, and deterioration of kidney function, which are not typical for banal hypertension. Unsatisfactory blood pressure control with a standard combination of pharmacotherapy, an unexpected positive effect of mineralocorticoid receptor antagonists, high blood pressure in young people, as well as a family history of early high blood pressure or stroke at a young age, paroxysmal course of hypertension itself increases the risk of PHA. For a long time, a disease in our patient was considered a banal hypertension, although the diagnostic hypothesis of PHA should appear immediately after severe neuromuscular syndrome, rapid progression of cardiomyopathy and clinically significant heart failure began to dominate in the clinical picture. A 44-year-old female patient came to the attention of rheumatologists with suspicion of inflammatory myopathy due to frequent episodes of muscle weakness whose origin remained unclear. Key complaints of pronounced paroxysmal generalized muscle weakness, especially in the limbs, numbness and paresthesias in the extremities, calf muscle cramps against the background of hypertension were regarded as a neuromuscular syndrome specific to PHA. The PHA hypothesis was supported by the presence of cardiomyopathy, heart failure, clinically significant hypokalemia, and elevated aldosterone level. Computed tomography of the retroperitoneal space confirmed the presence of adrenal adenoma. Unfortunately, with a delay, after 13 years of hypertension, the diagnosis of PHA against the background of aldosterone-producing adenoma was confirmed. Consultation with a surgeon endocrinologist was suggested, as well as administration of eplerenone 50 mg daily in combination with lercanidipine 20 mg daily. Already after 6 weeks of pharmacotherapy, a positive therapeutic effect was obtained regarding the control of hypertension, heart failure, and the severity of neuromuscular syndrome. The differential diagnosis of secondary endocrine hypertension can be successful only with the possession of skills for early clinical detection of endocrine pathology, even in subclinical disease presentation. The diagnosis of PHA makes it possible to offer a patient radical surgical treatment, as well as to choose optimal approaches to pharmacotherapy.

Pigmented villonodular synovitis is a rare proliferative disease of the synovial membrane, which most often affects the knee joints. Being a benign disease, at the same time, this pathology is often aggressive, and in some cases spreads to the soft tissues outside the joint. There are two forms of monoarticular damage: localized and diffuse. The diffuse form gives frequent relapses. To date, there are no standards for the management of this disease, just as there are no early markers for the detection of pigmented villonodular synovitis. This joint lesion has a long asymptomatic course, or it has symptoms of non-specific recurrent arthritis, so the patients can later be referred for magnetic resonance imaging, which is the only non-invasive method of diagnosing this pathology. At the same time, in modern conditions, most patients with recurrent synovitis will undergo an ultrasound examination of the joint according to the diagnostic standards. Ultrasonography made for abovementioned synovitis is insufficiently described in the medical literature. The aim of our study was to highlight the current data on the diagnosis and management of patients with pigmented villonodular synovitis and to describe our own clinical case. A feature of our clinical case was the detection of characteristic symptoms using ultrasonography. Irregular thickening of the synovial membrane with nodular forma­tions and villous growths, with the length of villi up to 7 mm near the patella with single loci of blood flow, was revealed by ultrasound examination and power Doppler mapping. Shear wave elastometry of the synovial membrane was performed. It demonstrated a significant increase in the stiffness of the synovial membrane, which can be a patho­gnomonic symptom of this pathology. The diagnosis of villonodular synovitis was confirmed histologically after surgical treatment. Subsequently, the patient had a recurrence of the pigmented villonodular synovitis, which was also detected by ultrasound diagnostics. Thus, pigmented villonodular synovitis of the knee joint is a rather rare pathology that requires differential diagnosis with inflammatory joint diseases. The final diagnosis is based on histological exa­mination. MRI and ultrasound diagnostics are non-invasive methods that can detect this pathology with high accuracy. The advantage of ultrasonography is its availability and non-invasiveness. The increase in stiffness of the synovial membrane along with its proliferation, which we found, can serve as an additional criterion of villonodular synovitis, and, according to the data available to us, has not been described in the literature so far.

This article covers a case of a rare genetic disorder – Wilson’s disease. It is an autosomal recessive inherited disorder that attracts the close attention of scientists since the disease affects many organs and systems of a patient and can develop both in children and in adults. Wilson’s disease occurs with similar frequency throughout the world. It is caused by mutations in the ATP7B gene identified on the long arm of the 13th chromosome, as well as by the heterozygous carriage. The copper metabolism disorder determined by the genetic changes plays a major role in the development of Wilson’s disease. The excess copper accumulates in the liver parenchyma, nervous tissue and in the peripheral cornea (so-called Kayser-Fleischer rings) which results in subsequent organ damage. Since there is no unified examination that could confirm or rule out Wilson’s disease, it is necessary that doctors are able to define the symptoms of this disease. The early detection of symptoms and diagnostic studies can improve the disease prognosis. The aim of our research was to study the debut of Wilson’s disease in a 39-year-old patient with comorbid pathology. We also analyzed the difficulties of managing patients with Wilson’s disease in the example of this clinical case. We considered different mechanisms of the disease development and peculiarities of the diagnosis of atypical symptoms using international recommendations and protocols. The difficulty of our clinical case was that the symptoms of the disease with a comorbid pathology were atypical at the early stage of the illness. We did not detect damage to the nervous system, as well as ophthalmological features, and changes in the amount of free copper, ceruloplasmin levels and rate of 24-hour urinary copper excretion. It was proven that detection of these biochemical markers in blood and urine is important in ruling out Wilson’s disease in a patient with cirrhosis of the liver even if the other organs that were usually affected by copper were not damaged. Prompt diagnosis of the markers of Wilson’s disease and corresponding treatment can prevent the progression of the disease and its complications in such patients. Our research can be useful for gastroenterologists, neuropathologists, family physicians, and doctors of other specialties.

The paper deals with the role of flow cytometry in assessing the biocompatibility and safety profiles of nanomaterials. Flow cytometry is a powerful tool to characterize the impact of various exogenous factors on different cell populations due to its ability to register optical and fluorescence characteristics of cells analyzing multiple parameters simultaneously. An overview of flow cytometry application for evaluating the redox state of cells, viability and cell death modes (apoptosis, necrosis, necroptosis, pyroptosis, autophagy), and pro-inflammatory effects of nanoparticles is provided. Flow cytometry offers rapid, informative, quite cost-effective and multi-angled analysis of safety profiles of nanomaterials taking into account the key mechanisms of their toxic action. Recent advances in flow cytometry technologies and the availability of commercial automated cell counters make flow cytometry a convenient research tool for in vitro nanotoxicology. However, the field requires the development of standardized flow cytometry protocols for nanotoxicity testing.

Gout is one of the most common inflammatory diseases of the joints, which is often accompanied by comorbid pathology, most often diseases of the cardiovascular system and metabolic disorders. This fact reflects the influence of hyperuricemia and the lack of compensation for purine metabolism disorders. Most researchers explain the lack of effective control of purine metabolism in gout with patients’ low adherence to treatment. This idea led to the formation of the concept of insufficient use of hypouricemic therapy and, as a result, to the lack of control over the course of the disease and the possibility of preventing the deterioration of the general state of the patient’s health, which is largely due to the progression of concomitant pathology. Many retrospective studies demonstrate a low frequency of timely appointment of hypouricemic therapy, inefficient dosage, which does not allow to reach target levels of SC in blood serum and effectively control the disease. Febuxostat is an effective means of reducing the level of SC in the blood serum in this disease. The literature provides data on the serious advantages of febuxostat over other hypouricemic agents. The purpose of this work was to study the possibility of obtaining a clinical and laboratory effect in a short time after the start of febuxostat therapy (up to 3 months) in patients with gouty nephropathy who have concomitant pathology. A study of the efficacy and safety of febuxostat (tablets of 80 or 120 mg) was conducted in gout patients with concomitant diseases. The observation period was 3 months, during which time the possibility of patients achieving the target level of SC (≤360 μmol/l) was evaluated. 6 patients reached the target SC level within 1.5 months of treatment. In 19 (30%) patients, the SC level decreased to ≤360 μmol/L after 3 months of therapy. Exacerbations of gout were noted in the first 2 months of therapy in individual patients and were characterized by less activity of joint syndrome. It is known that hyperuricemia is one of the main risk factors for endothelial dysfunction, which, in turn, contributes to the development of arterial hypertension and damage to target organs. Regardless of hypertension, an increase in the level of SC in the blood serum affects the cells of the endothelium and vascular smooth muscle, leading to the formation of microvascular damage to the kidneys. According to our data, the presence of CKD, DM and/or hypertension significantly reduces the speed of reaching the target levels of SC and increases the frequency of new cases of gout attacks, each of which increases the severity of inflammation, as well as the risk of cardiovascular disasters and death. Achieving the target level of SC in 6 patients 1.5 months after starting febuxostat and in a quarter of patients after 3 months. therapy demonstrates its powerful hypouricemic effect, which provides an early response to treatment.

At the current stage of medical science, the effectiveness of treatment depends not only on the professionalism of physicians, but also on the responsibility of the patients themselves. Low adherence has been proven to be a significant cause of the reduced therapy effectiveness and quality of life, increased risk of complications and treatment costs, worsening of disease prognosis, and reduced patient life expectancy. According to WHO reports, more than 250 factors can influence the adherence to the treatment. Until now, no "gold standard" has been developed for the assessment of adherence to treatment. Patients with psoriasis typically face social stigmatization and rejection, with subsequent profound effects on self-confidence, self-esteem, and feeling of psycho-emotional discomfort. Comorbidity of arthritis affects the psycho-emotional status of patients even more seriously. The purpose of the study is to analyze the psycho-emotional state, adherence to treatment, medical support and recommendations for lifestyle modification in patients with erosive form of psoriatic arthritis comorbidity. 60 patients with a reliable diagnosis of psoriatic arthritis and comorbid pathology were included in the study. Patients with psoriatic arthritis and comorbidity had mainly an average level of adherence to medication, medical support, and a low level of adherence to recommendations for lifestyle modifications. Taking oral glucocorticosteroids was associated with high adherence to drug therapy, while low adherence to medical care was associated with psychoemotional disorders such as anxiety and depression.