The effect of melatonin on antioxidant defense indicators in the blood of rats with insulin resistance Oleksandra Yu. Kushnir, Iryna Yaremii, Kyrylo Pantsiuk, Volodymyr Vivsyannuk, Inna Buzdugan, Olga Bukach, Georgiy Prodanchuk Polski Merkuriusz Lekarski, 2025 Aim: To determine the effect of melatonin on the activities of glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase and the content of reduced glutathione, glucose and insulin levels in the blood of rats with insulin resistance. Materials and Methods: Research performed in compliance with the Rules of the work using experimental animals (1977) and the Council of Europe Convention on the Protection of Vertebrate Animals used in experiments (Strasbourg, 1986). Sexually mature 18-month-old outbred white male rats were divided into groups: 1) control, 2) insulin resistant rats (dexamethasone at a dose of 0.125 mg/kg for 13 days daily), 3) insulin resistant rats ingested with metformin (200 mg/kg) daily, 4) insulin resistant rats were orally administered melatonin at a dose of 10 mg/kg daily. Measurement of fasting glucose content in the blood from the tail vein (One Touch, USA) and insulin in the blood serum (immunochemiluminescent analyzer Snibe Co., Ltd, the Maglumi test kit, China) was performer on the 14th day. Blood was taken to determine the parameters of glutathione system by using standard methods. Statistical processing was performed using the IBM SPSS Statistics 21 program. Differences were considered statistically significant at p≤0.05. Results: Melatonin ingestion as well as metformin were helpful in normalization of insulin level on the background of glucose level restoration and antioxidant system activation. Conclusions: We have established the hypoglycemic and antioxidant effects of melatonin on the background of dexamethasone-induced insulin resistance.
Effect of treatment on genetic predictors and quality of life in rheumatoid arthritis patients with type 2 diabetes, hypertension, and obesity O.P. Bukach, I.O. Buzdugan, L.O. Voloshina Miznarodnij Endokrinologicnij Zurnal, 2023 Background. Connective tissue disease, in particular rheumatoid arthritis (RA), is characterized by a progressive joint damage and polymorphism of extra-articular lesions that affect the patient’s quality of life. Although the widespread implementation of basic therapy through the use of disease-modifying antirheumatic drugs has a positive effect on social consequences, the experience gained shows the impossibility of achieving a stable remission of the disease or reducing the activity of autoimmune inflammation against the background of using these medicines in all patients for a number of reasons. One of these reasons is the presence of comorbid pathology, which requires a personalized approach to each person. The objective was to study the quality of life of patients with RA in combination with type 2 diabetes mellitus (T2DM), hypertension and obesity depending on the T-786C polymorphism of the endothelial nitric oxide synthase gene promoter. Materials and methods. A laboratory and instrumental examination involved 110 patients who were treated at the clinical base of the Department of Internal Medicine of Bukovinian State Medical University, Chernivtsi Regional Endocrinology Center, Chernivtsi Regional Clinical Hospital, and Reference Center for Molecular Genetic Research of the Ministry of Health of Ukraine. Results. When assessing the quality of life in the studied groups, a decrease in indicators on all scales was detected. Thus, in RA combined with hypertension and obesity, PF was 1.73 times lower, RP— 1.97 times, BP— 1.44 times, SF— 1.46 times, MH— 1.26 times , RE— 1.66 times, GH— 1.35 times (p<0.05) lower than in patients with isolated RA. Taking into account the T-786C polymorphism of the eNOS gene, it can be asserted that all indicators of quality of life were reduced in the carriers of the СС genotype, in contrast to the carriers of the T-allele: PF— by 2.06 (pTT<0.05) and 2.46 times (pTС<0.05); RP— by 2.0 (pTT<0.05) and 2.87 times (pTС<0.05); BP— by 1.86 (pTT<0.05) and 2.52 times (pTС<0.05); SF— by 1.55 and 2.07 times (рTС<0.05); MH— by 1.42 (pTT<0.05) and 1.53 times (pTС<0.05); RE— by 1.30 (pTT<0.05) and 1.54 times (pTС<0.05); VT— by 3.34 (pTT<0.05) and 3.72 times (pTС<0.05); GH— by 2.32 (pTT<0.05) and 2.38 times (pTС<0.05), respectively. Conclusions. When comparing the quality of life in the studied groups, it can be stated that the lowest indicators on all scales were in patients with RA combined with hypertension, obesity and T2DM and in carriers of the СС genotype of the analyzed gene, which reflected the worst physical condition and psychosocial status.
Peculiarities of clinical signs, course and treatment of musculoskeletal system lesions in post-COVID syndrome Larysa Voloshyna, Svitlana Smiyan, Oleksandr Voloshyn, Inna Buzdugan, Olga Bukach, Natalia Voloshynovych, Oleksandra Doholich Reumatologia, 2023 IntroductionPost-COVID syndrome (PCS) is a frequent phenomenon of patients who have suffered from an acute attack of COVID-19 infection, and it is characterized by a wide range of symptoms from different organs and systems including the musculoskeletal system (MSS). However, peculiarities of MSS lesions have not been sufficiently studied to date, in particular, in the aspect of the therapeutic process. We aimed to investigate peculiarities of MSS lesions in patients with PCS.Material and MethodsObservations were carried out in 142 patients with PCS and MSS lesions. The age of patients was 36–67 years. Up-to-date methods of disease verification were used. An acute period of COVID-19 in all the patients was of moderate severity without oxygen support.ResultsMusculoskeletal system lesions in patients with PCS were found to appear 1–4 weeks after the experienced acute period of COVID-19 infection. Against the background of significant arthralgia (100%) in 93 (65.5%) patients manifestations of acute arthritis were detected, the frequency of which increased with age. Musculoskeletal system lesions were found against the background of dominating PCS manifestations from the cardiovascular and digestive systems. Deterioration of the course and results of treatment of diseases caused by an age-related polymorbid background was determined. Certain difficulties in the treatment of MSS lesions by means of non-steroidal anti-inflammatory drugs and limitation in the use of glucocorticosteroids are caused by severe gastroduodenopathy and arterial hypertension. Long-term, up to 6 months, administration of L-arginine, L-carnitine and quercetin in the rehabilitation complex improved the overall results of treatment of PCS manifestations including arthropathy.ConclusionsMusculoskeletal system lesions in patients with PCS are not the main constituent of this syndrome. Difficulties in the treatment of arthropathy are due to the signs of gastroduodenopathy and arterial hypertension. Additional administration of L-arginine, L-carnitine and quercetin is reasonable.
Analysis of the selenoprotein P (rs7579) gene polymorphism and expression in patients with chronic pancreatitis combined with hypothyroidism V.V. Ratsa, O.I. Fediv, L.P. Sydorchuk, Z.I. Rossokha, O.I. Sydorchuk, V.T. Stepan, I.O. Buzdugan Miznarodnij Endokrinologicnij Zurnal, 2023 Background. The specific role and place of genetic factors in the development of chronic pancreatitis and hypothyroidism, which determine the activity of glutathione antioxidant protection, have not been clarified. They are interconnected with changes in the fat and carbohydrate metabolism, and also affect the transport and signaling pathways of key nutrients for the work of the immune, endocrine and nervous systems. The purpose of the study is to investigate the selenoprotein P (SEPP1) (rs7579) gene polymorphism and expression in patients with chronic pancreatitis combined with hypothyroidism. Materials and methods. Forty-nine patients with chronic pancreatitis and hypothyroidism and 30 practically healthy individuals passed the screening stage. The SEPP1 (rs7579) gene polymorphism was determined by the polymerase chain reaction. Results. The study showed that out of 98 isolated alleles in patients with chronic pancreatitis and hypothyroidism and 60 alleles of the control group, the G allele of the SEPP1 gene (rs7579, 25191G/A) dominated over the A allele: in the examined patients — by 34.7 % (χ2 = 23.59; p < 0.001), in the practically healthy group — by 53.34 % (χ2 = 34.13; p < 0.001). At the same time, the relative frequency of individual genotypes, as well as wild-type and mutant alleles, probably did not differ between the experimental and control groups. The A allele of the SEPP1 gene (rs7579) slightly increases the risk of chronic pancreatitis in the studied population, but non-significantly [risk ratio (RR) = 1.43; RR 95% CI (confidence interval): 0.91–2.26; odds ratio (OR) = 1.65; OR 95% CI: 0.88–3.08; p = 0.115]. Conclusions. In patients with chronic pancreatitis who are residents of Northern Bukovyna, mutation of the SEPP1 gene (rs7579, 25191G/A) in the homozygous state occurs with a frequency of 10.2 %, while it is absent in practically healthy people. In both groups, the G allele dominates over the A allele: in the examined patients — by 34.7 % (χ2 = 23.59; p < 0.001), in controls — by 53.34 % (χ2 = 34.13; p < 0.001). SEPP1 gene polymorphism (rs7579, 25191G/A) does not determine the risk of chronic pancreatitis in the population. However, the A allele increases the risk of hypothyroidism in chronic pancreatitis patients twice [OR = 2.0; OR 95% CI: 1.09–3.66; p = 0.023], with the lowest chances of its appearance in carriers of the G allele [OR = 0.50; OR 95% CI: 0.27–0.91; p = 0.023]. Mapping of the expression quantitative trait loci on both sides of the SEPP1 gene (rs7579) transcription start site evidenced 152 statistically significant cis-variants of rs7579 of the SEPP1 gene (SELENOP) associations with the expression of 20 genes in 35 different organs and tissues and 22 phenotypic traits.
Malabsorption syndrome aggravates calcium homeostasis impairment in chronic kidney disease patients L. Zub, A. Shkarutyak, I. Buzdugan, V. Vivsyannik Ukrainian Journal of Nephrology and Dialysis, 2022 Recent data on the role of digestive pathology in the progression of chronic kidney disease (CKD) remain scarce. Calcium homeostasis plays an important role in the progression of renal pathology, especially in patients with malabsorption syndrome (MAS).
 The research aimed to evaluate calcium homeostasis in CKD patients with MAS.
 Methods. In this cross-sectional observational study, 99 CKD patients with MAS were enrolled. The patients were divided into 4 groups according to the CKD stage and the presence of MAS. Group I included 25 patients with CKD stages 1 and 2 without MAS; Group II consisted of 26 patients with CKD stages 1 and 2, and MAS; Group ІІІ (n = 23) and Group ІV (n = 25) included patients with CKD stage 3 without and with MAS, respectively. According to the morphological study of in vivo biopsies of the small intestinal mucosa, mild and moderate morphological changes were observed among all patients. The levels of calcium, phosphorus, parathyroid hormone, osteocalcin, and calcitonin in the blood, as well as urinary calcium levels, were detected.
 Results. Pathological changes in calcium metabolism were observed among CKD patients with MAS. The severity of calcium homeostasis disorders was more evident among patients with CKD stage 3 compared with stages 1 and 2. Urinary calcium levels were reduced in the patients of Groups III and IV. No changes were detected in phosphorus levels. Changes in parathyroid hormone and osteocalcin are caused primarily by combined renal pathology with impaired renal calcium absorption.
 Conclusion. MAS in CKD patients leads to deep violations of calcium homeostasis resulting in rapid CKD progression and bone tissue violation.
SPICES: MODERN VIEWS ON THE APPLICATION THROUGH THE PRISM OF POLY- AND COMORBIDITY OF PATIENTS AND INFECTIOUS PANDEMICS (LITERATURE REVIEW AND DISCUSSION) Larysa Voloshyna, Oleksandr Voloshyn, Bogdana Senyuk, Inna Buzdugan Wiadomosci Lekarskie Warsaw Poland 1960, 2022 The aim: To substantiate the need of wider use of species in dietician rehabilitation of patients with poly- and comorbidity, postcovid syndrome based on the analysis of the latest scientific achievements with the study of their pharmacological properties. Materials and methods: The information search in printed and electronic editions, search scientific bases with application of methods of the analysis, comparison and generalization of information data is carried out. Conclusions: New scientific data on the pharmacological properties of spices give grounds to use them more widely in the rehabilitation of patients with poly- and comorbidities and infectious processes.
Pathogenetic relationship and ways of correction of H. pylori in patients with gastric and duodenal peptic ulcers in the combination of arterial hypertension and type 2 diabetes mellitus. Treatment of patient with H. pylori in presence of toxicogenic strains and concomitant pathology I. O. Buzdugan, O. I. Fediv, S. V. Roborchuk, L. О. Voloshyna Ukrainian Therapeutical Journal, 2021 Objective — to investigate the functional state of endothelium and methods of correction of endothelial dysfunction in patients with gastric and duodenal peptic ulcers (GPU and DPU) in combination with hypertension (AH) and type 2 diabetes mellitus (DM2).
 Materials and methods. The investigation involved 100 patients, who were divided into the groups: group 1 consisted of 20 apparently healthy individuals (AHI), group 2 included 40 patients with GPU (n = 23) and DPU (n = 17) without signs of AH and DM2, group 3 involved 40 patients with GPU (n = 15) and DPU (n = 25) in combination with hypertension and DM2. The groups were sub‑divided into subgroups A and B depending on the H. pylori strains’ toxigenicity: group A included patients with CagA+ VacA+ strains’ combination, groups B — infected with H. pylori with a combination of strains of CagA+ or VacA+. All patients were administered the traditional antihelicobacter therapy (AHBT) (esomeprazole 20 mg twice daily + amoxicillin 1.0 g twice daily + clarithromycin 500 mg twice daily for 10 days). To increase the effectiveness of eradication therapy, 40 patients in addition to AHBT, received a combined probiotic (Bifidobacterium bifidum, B. lactis, Enterococcusus acidophilus, L. paracasei, L. plantarum, L. rhamnosus, L. salivarius) 1 sachet twice a day for 1 month. Eradication control was monitored 4 weeks after completion of treatment.
 Results. The increased expression of the vascular cell adhesion molecule‑1 (VCAM‑1) and the number of desquamated endothelial cells (DEK) and improvement of the oxidant‑antioxidant system have been established. Before the treatment, in comparison with the levels in AHI, levels of sVCAM exceeded in 5.88 times (р < 0.05), of erythrocytic malondialdehyde in 1.92 times (р < 0.05), and levels of the reduced glutathione was lower by 46.39 % (р < 0.05). The use of triple therapy improved the endothelial condition and the state of the oxidative‑antioxidant system, and additional application of probiotic promoted more effective correction of the indices of endothelial state and oxidative‑antioxidant system by means of maximal decrease of the levels of sVCAM and erythrocytic malondialdehyde and increase of the reduced glutathione levels.
 Conclusions. The presence of H. pylori, in particular its toxigenic strains, results in the development of endothelial disfunction in patients with GPU and DPU, combined with arterial hypertension and DM 2. When combined with hypertension and DM2, the course of GPU and DPU is accompanied with «mutual burden» syndrome resulting in the exhaustion of the antioxidant defense system and increased indexes of the glutathione system.
SECONDARY IMMUNODEFICIENCY STATES IN THE ACTIVITY OF A GENERAL PRACTITIONER – FAMILY MEDICINE AND PHYTOTHERAPEUTICWAYS OF THEIR CORRECTION (Lecture) , O Voloshуn, L Voloshyna, , B Senyuk, , I Prуsyazhnyuk, , I Buzdugan, and Phytotherapy Journal, 2021 Keywords: secondary immunodeficiency states, diagnosis, treatment, phytoimmunomodulators. Topicality. Secondary immunodeficiency states (SIS) is a fairly common phenomenon in the clinic of internal medicine as an “addition” for many diseases, which has no clear clinical signs, so it is not often diagnosed by primary care physicians. However, untimely detection and correction of SI significantly worsens the overall results of treatment and contributes to recurrence of the underlying disease.There is a prospect of further increase in the prevalence of SI, the success of correction of underlying desease due to doctors’ understanding of their clinical and pathogenetic features and knowledge of treatment strategies and tactics, including the use of phytotherapeutic agents. The aim is to highlight modern approaches to the diagnosis and treatment of SI with the use of phytotherapeutic agents. Materials and methods. Materials of the main domestic and foreign printed sources of information using methods of comparison, analysis and generalization are used. Results. Information on the classification, diagnosis, strategy and tactics of treatment and prevention of SIS depending on their severity with the use of various phytotherapeutic agents, criteria for treatment effectiveness, age and somatic aspects of rehabilitation at the outpatient stage are analyzed. The importance of timely diagnosis of secondary immunodeficiency and the use of phytotherapeutic agents in the context of the “WHO Strategy in the field of folk medicine for 2014-2023” as the latest and most effective approach in the treatment of complex pathological phenomena.
Glutathione-S-transferases genes-promising predictors of hepatic dysfunction Vasyl Prysyazhnyuk, Larysa Sydorchuk, Ruslan Sydorchuk, Iryna Prysiazhniuk, Kateryna Bobkovych, Inna Buzdugan, Valentina Dzuryak, Petro Prysyazhnyuk World Journal of Hepatology, 2021 One of the most commonly known genes involved in chronic diffuse liver diseases pathogenesis are genes that encodes the synthesis of glutathione-S-transferase (GST), known as the second phase enzyme detoxification system that protects against endogenous oxidative stress and exogenous toxins, through catalisation of glutathione sulfuric groups conjugation and decontamination of lipid and deoxyribonucleic acid oxidation products. The group of GST enzymes consists of cytosolic, mitochondrial and microsomal fractions. Recently, eight classes of soluble cytoplasmic isoforms of GST enzymes are widely known: α-, ζ-, θ-, κ-, μ-, π-, σ-, and ω-. The GSTs gene family in the Human Gene Nomenclature Committee, online database recorded over 20 functional genes. The level of GSTs expression is considered to be a crucial factor in determining the sensitivity of cells to a broad spectrum of toxins. Nevertheless, human GSTs genes have multiple and frequent polymorphisms that include the complete absence of the GSTM1 or the GSTT1 gene. Current review supports the position that genetic polymorphism of GST genes is involved in the pathogenesis of various liver diseases, particularly non-alcoholic fatty liver disease, hepatitis and liver cirrhosis of different etiology and hepatocellular carcinoma. Certain GST allelic variants were proven to be associated with susceptibility to hepatological pathology, and correlations with the natural course of the diseases were subsequently postulated.
