Multidisciplinary, Pathology and Forensic Medicine, Multidisciplinary
13
Scopus Publications
Scopus Publications
Association between disease duration, GH-IGF-1 axis markers, and linear growth in children with type 1 diabetes mellitus: a cross-sectional study Feruzakhan Uvaidillaeva, Rustam Tukhvatshin, Valeriia Kniazeva, Baktygul Omurkulova Heart Vessels and Transplantation, 2026 Objective: This single-center cross-sectional study analyzed 250 children and adolescents (aged 5-17 years) with type 1 diabetes mellitus (T1DM) in the Kyrgyz Republic to assess the effect of T1DM duration on anthropometric parameters and key hormonal growth markers (glycated hemoglobin A1c (HbA1c), growth hormone (GH), and insulin-like growth factor 1 (IGF-1) SDS).We hypothesized that longer duration of chronic T1DM and related GH-IGF-1 axis disruption are more strongly associated with linear growth disorders than current glycemic control.Methods: Anthropometric data (SDS height/weight) and hormonal levels were compared across groups categorized by disease duration (newly diagnosed, 1-5 years, and >6 years).Results: Children with T1DM duration over 6 years exhibited markedly lower height SDS compared to both newly diagnosed (p<0.001) and 1-5-year groups (p=0.006).Mean IGF-1 SDS significantly decreased with increasing disease duration (p=0.010),indicating worsening GH-IGF-1 axis dysfunction.Although mean HbA1c improved gradually with duration, the overall level remained suboptimal (10.7%).The duration of the disease ( = -0.338;95%CI -0.204 --0.097, p < 0.001), the age of T1DM manifestation ( = 0.153; 95%CI 0.011 -0.105, p = 0.015), SDS IGF1 ( = -0.245;95% CI 0.046 -0.254, p = 0.012) and SDS weight ( = 0.524; 95% CI 0.484 -0.718, p < 0.001) had a significant effect on the SDS of height, while the other GH variables ( = 0.037; p = 0.558), HbA1c ( = -0.015;p = 0.809) did not make a statistically significant contribution.Conclusions: These findings confirm that longer disease duration is significantly associated with linear growth impairment in children with T1DM, underscoring the need for early and aggressive intervention to minimize cumulative exposure.
Histophysiology of the lungs and oxygen transport function of the blood with an exclusively fatty diet Aycholpon Israilova, Elmira Mamytova, Yusuf Shidakov, Aina Mamytova, Bolotbek Alymzhan uulu, Aigul T. Altynbekova, Rustam Tukhvatshin Heart Vessels and Transplantation, 2025 Objective: To study of the histophysiology of the lungs and the oxygen transport function o f blood in rats fed by an extreme fatty diet for 30 days.Methods: The study design is a randomized experimental study.The work was carried out on white, mongrel male rats weighing 200-250g.During the 30 days period of time, 10 animals were fed exclusively with animal fat.Then the animals were slaughtered under general anesthesia, after preliminary blood sampling for subsequent determination of the lactate level and oxygen transport function of the blood.Histological preparations of the lungs were stain ed with hematoxylin-eosin and Van Gieson.Histological analysis of lung components was performed using the application for measuring microscopic objects Tor View.For statistical analysis, the Student's criterion was applied for independent and paired samples in the SPSS 22.0 program.Results: An extreme fat diet consisting of 100% animal fat led to an increase in serum lactate level (0.79 (0.78)) vs 1.92 (0.28)) (p<0.001).Oxygen transport function decreased in animals of the dietary intervention group.Th e ratio of the rate of oxygen transport by arterial blood (VaVO2) to the rate of its consumption by tissues (VO2) in the main group decreased by 3 times (4.44 (0.47)) due to a pronounced decrease in the rate of oxygen transport by arterial blood (4.1042 (0.091)) vs. 64.4060(0.14)) (p<0.001).There was a 2-fold shift of the buffer bases towards its decrease in the animals of the main group as compared to control (4.9764 (0.81) versus 8.19 (0.22)) (p<0.001).Remodeling of the histophysiology of the bronchial tree and branches of the pulmonary artery was characterized by pronounced heterogeneity, depending on the level of division (large, medium, bronchioles) of the bronchi and the associated pulmonary and bronchial arteries.At the level of the alveolar tree , areas of atelectasis with blood deposition and emphysema of the acinar apparatus of the lungs were observed.And at the level of the microcirculatory bed intravascular, vascular, and circulatory changes were noted.Conclusions: A 30-day feeding of male rats exclusively with sheep fat led to an increase in lactic acid concentration, a decrease in the rate of oxygen transport by arterial blood and a deficiency of blood buffer bases, which were combined with microcirculatory changes, and at the alveolar level with foci of atelectasis with blood deposition, emphysema and inflammatory reaction.
The effect of an isolated fat diet on the blood vessels of the rat´s brain (experimental randomized study) Aigul T. Altynbekova, Elmira Mamytova, Yusuf Shidakov, Aycholpon Israilova, Bolotbek Alymzhan uulu, Rustam Tukhvatshin Heart Vessels and Transplantation, 2024 Objective: Epidemiological studies show that recently there has been an increase in the number of cerebrovascular diseases and the mortality rate among the population.This trend is associated with a changing of metabolic processes in the body, in particular lipid metabolism, caused by an unbalanced high-calorie diet.The aim of the study was to investigate the effect of an isolated fat diet on lactate blood level and histomorphological changes in microcirculation of the rats` brain.Methods: The design of the study is experimental randomized.The study was conducted on sexually mature 7-8 months old lineal Wistar male rats, which were randomly divided into 2 groups -control (n=10) and experimental (n=9).The rats of the experimental group 1 ("isolated fat diet") were fed a diet consisting of fat-tailed sheep for 30 days.The control group was on a standard vivarium diet.Animal weight gain, serum lactate levels and histomorphological changes in the blood vessels of the brain regions of experimental animals were observed.Statistical processing of the results was carried out using the t-test for independent and paired samples.Results: No increase in total weight was observed in the animals of the experimental group, on the contrary, weight loss in rats was noted (p<0.001).During the experiment, a 2.1-fold increase in lactate levels was verified in animals of the experimental group (p<0.001).An unbalanced diet led to a number of pathological changes of the structural integrity of the wall of the microvessels of the rat brain, which promoted a slowdown in blood flow and blood cells aggregation and, ultimately lead to the development of blood clots. Conclusion:The obtained experimental data show changes in lipid metabolism and vascular remodeling of the microcirculatory bed of the rat brain due to increased fat intake.
Stages of the evolution of thymus atrophy in children in different cities of Kyrgyzstan Tamara Abaeva, Rustam Tuhvatshin, Masalbek Satybaldiev, Aida Ergeshova, Zarina Toichieva, Siuzana Bakytova Biomedicine India, 2023 Introduction and Aim: Thymus atrophy occurs in response to the stress of any etiology such as cold, burn, infection, trauma, pain, and psychogenic stress. The objective of the study is to evaluate the thymus gland in children aged 7–12 years from Kyrgyzstan.
 
 Materials and Methods: The present study assessed the anatomy of the thymus gland on 35 cadavers of children aged 7–12 years from 2015 to 2020. Anatomical methods including preparation, weighing, and measurement, and histological methods including hematoxylin-eosin staining were performed.
 
 Results: In children aged 7–12 years, it was found that in the thickness of the cerebral layer, there is the growth of thymic corpuscles, blood capillaries, and lymphatic slits. The level of cells in the cerebral layer is diverse, there are lymphocytes in large numbers, larger light epithelial and reticular cells, as well as macrophages. In the cortical zone, the cellular composition is mainly lymphoid cells, and mitosis was found in some of them.
 
 Conclusion: In this study, comparatively, the cortical zone prevails over the cerebral one. At this age, the thymus begins to atrophy, as well as the growth of adipose tissue.
Features of Metabolic Associated Fatty Liver Disease in the Central Asian Population in Low and High Altitudes and Nurgul Toktogulova Gaceta Medica De Caracas, 2022 Today, there is insufficient knowledge about the course of metabolically associated fatty liver disease (MAFLD) in Asian populations living at different altitudes. Our article presents the results of the study of MAFLD in individuals with different body weights in conditions of high-mountain hypoxia. To study the course of MAFLD in lean and obese patients living in the conditions of low and high mountains of Kyrgyzstan. An open comparative study of Asian patients with MAFLD with and without type 2 diabetes mellitus (DM2) living in low and high mountains was performed. In each category of patients, the lean (BMI≤23) and obese (BMI> 23) groups were considered. The anthropometric parameters and biochemical parameters of blood were determined. The liver fibrosis index was calculated using the FIB Score. It was found that residents of the high mountains with MAFLD had a lower BMI compared to the lowlanders. Low blood glucose and HbA1c levels are observed in patients with high BMI living in high altitude areas compared with lowlanders, especially in combination with DM2. In the group of obese patients with MAFLD living in highlands, low total cholesterol, low-density lipoproteins and glomerular filtration rate are observed. A high risk of fibrosis was noted in the group of lean patients in both regions. Our results indicate that the study of the effect of chronic high-altitude hypoxia on the course of MAFLD requires prospective population-based studies.
Lipid metabolism in non-alcoholic fatty liver disease in patients with different body weights in mid-mountain conditions Nurgul A. Toktogulova, Roza B. Sultanalieva, Rustam R. Tuhvatshin, Turarbek K. Kaliev Terapevticheskii Arkhiv, 2022 Aim. To study the peculiarities of lipid metabolism disorders in non-alcoholic fatty liver disease in lean and obese patients in medium altitude conditions.Materials and methods. The study was carried out within the framework of the project Etiopathogenetic features and rates of development of non-alcoholic fatty liver disease (NAFLD) in the conditions of Kyrgyzstan (№ of state registration MHN/TZ-2020-3). An open comparative study of patients with two forms of NAFLD: fatty liver and non-alcoholic steatohepatitis (n=236) living in low mountains (Bishkek, altitude above sea level 750800 m; n=111) and middle mountains (At-Bashy district , Naryn region, height above sea level 20462300 m; n=125) Kyrgyzstan. The average age of the patients was 55.70.95 years. Given that genetic factors may play a role in the development of NAFLD, we analyzed a population represented only by ethnic Kyrgyz. Patients in each group were divided into lean (BMI23) and obese (BMI23) groups. To determine physical activity, a physical activity questionnaire was used, which was compiled on the basis of the materials of the International Physical Activity Prevalence Study www.ipaq.ki.se. Physical examination included measurement of anthropometric parameters (height, body weight, waist circumference), calculation of body mass index (BMI), skeletal muscle mass index (SMM), percentage of body fat. According to the grades of the WHO, the degree of obesity was assessed by BMI for Asians. Blood samples were taken for research in the morning on an empty stomach after at least 12 hours of fasting. The following indicators were determined: glucose, lipid spectrum (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides), alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels. The BARD scale was used as a predictor for assessing the development of liver fibrosis in patients with NAFLD. The scoring system included three variables: BMI, AST/ALT, and the presence of DM 2. The diagnosis of NAFLD made on the basis of history, laboratory tests, ultrasound examination of the liver, and exclusion of other liver diseases. The results were analyzed using the SPSS 16.0 statistical software package for Windows. A p-value0.05 was considered statistically significant at the 95% confidence level.Results. It was found that the inhabitants of the middle mountains with NAFLD are represented by a lower BMI relative to the inhabitants of the low mountains. In women, the levels of SMM and the percentage of fat are significantly and statistically significantly correlated (r=-0.971; p0.001), while in men these two indicators are not related. Men showed a trend towards higher percentages of fat, regardless of body weight and region of residence. For women, this indicator was within acceptable limits and did not exceed 31%. There was found a statistically significant difference in total cholesterol levels between low and middle mountain people in the group of obese patients (p0.001) suffering from NAFLD. Statistically significant low ALT indices were revealed in the group of obese patients living in mid-mountain conditions.Conclusion. Taken together, our results suggest that chronic mid-mountain hypoxia may slow down the course of overweight-induced NAFLD.
Genetic and clinical characteristics of BRCA-associated hereditary breast cancer in the West region of Kazakhstan Marzhan A Aitmagambetova, Gaziza A Smagulova, Rustem R Tuhvatshin, Azhar N Zheksenova, Ainur Amanzholkyzy Carcinogenesis, 2022 Breast cancer is the most common cancer in women and is cause mortality in many countries. The purpose of this article is to determine the BRCA1 BRCA2 gene mutation polymorphisms, as well as to determine the clinical, histopathological and prognostic characteristics in patients with breast cancer in the western region of Kazakhstan. A study was conducted on the genotyping of 278 patients in the MC ZKMU Marat Ospanov with an established diagnosis of breast cancer, which revealed that out of 278 patients, of three cases were identified. In the age category up to 50 years, 70 cases were detected (25.1%) after 50 years 208 cases were identified (74%). Number of patients in stage I was 20 (7.1%) in stage second 204 (73%) and in stage third 54 (19%). By tumor size, 30 (10%) cases were T1, 194 (69%) cases were T2, 35 (12.5%) cases were T3 and 19 cases were T4 (6.8%). According to metastasis of the lymph nodes, no lymph nodes were detected in 107 (38%) cases, 1-3 l/n (Lymph Nodes) in 95 (34%) cases, 4-9 l/n in 12 (4%) cases, 10 l/n in 4 (1.4%) cases and unknown cases was 60 (21%). In 99.6% of patients no distant metastases was detected. According to the molecular classification of the tumor, Luminal type A is most found in this study 147 (52.8%), then Luminal type B 57 (20.5%), HER-2 positive 26 (9.3%) and Triple negative 48 (17.2%). By ethnicity the Kazakh race is 182 (65%) the Caucasian race was 96 (34%). Large population screening studies involving all BRCA1/2 polymorphisms are required to confirm the penetrance, frequency and significance of a wide range of variations of BRCA1/2 genes in the Kazakh population.
Features of the course of non-alcoholic fatty liver disease in experimental animals at high altitudes Nurgul Toktogulova, Rustam Tuhvatshin Open Access Macedonian Journal of Medical Sciences, 2021 Background: Nearly 25% of adults worldwide are affected by non-alcoholic fatty liver disease (NAFLD). taged changes in the liver from steatosis progress to non-alcoholic steatohepatitis (NASH) and its complicated forms such as fibrosis, cirrhosis, and hepatocellular carcinoma. There are very few data in the literature on the development of NAFLD in conditions of high altitude. There are no data on the state of pro- and anti-inflammatory cytokines in NAFLD in high altitude conditions. Thus, simulating NAFLD on animals in artificial highlands will help find answers to these questions.Aim: to study the features of the course of non-alcoholic fatty liver disease (NAFLD) in experimental animals in artificial high-mountain conditions.Material and methods: The study was carried out on 180 male Wistar rats. 7 groups of experimental animals were formed, which were divided into control and experimental groups. The rats of the control group were on a standard diet. Non-alcoholic fatty liver disease was modeled by keeping animals on a diet (Ackermann et al., 2005) rich in fructose and fat in low and high mountain conditions (in a pressure chamber 6000 m above sea level) for 35 and 70 days. In all groups of animals, the following was determined: the concentration of total bilirubin (TB), the activity of the enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), the level of total cholesterol (TC), low-density lipoprotein cholesterol (LDL), the total protein content in plasma (TP), pro- and anti-inflammatory cytokines.Results: In animals on a diet enriched with fructose and fat, it equally led to the inhibition of the synthetic function of the liver, both in high altitude and in low altitudes. Liver enzyme levels were uncertain. AST levels were high in all major groups, with a similar upward trend at 5 and 10 weeks on the fructose-fortified diet. The greatest shift was observed on the part of ALT in animals under conditions of hypobaric hypoxia, the growth of which was statistically significantly lower than in the low- altitude groups. The opposite picture was observed in pigment metabolism. Indicators of total cholesterol and LDL increased almost twofold in the main high- altitude groups, and were significantly higher than the indicators of low- altitude animals with p <0.001. The activity of pro- and anti-inflammatory cytokines in the main group, when the animals were raised in the pressure chamber, statistically significantly increased after 5 weeks compared to the low-altitude group by more than 2 times and statistically significantly correlated with cytolysis syndromes, hypercholesterolemia and impaired synthetic function against the background of liver hypoergosis.Conclusion: Non-alcoholic fatty liver disease in animals on a special diet enriched with fructose under conditions of hypobaric hypoxia is characterized by deeper violations of pigment metabolism, pro- and anti-inflammatory cytokines and lipid spectrum with simultaneously statistically significant low alanine aminotransferase indices compared to low-altitude groups on an identical diet.
Dynamics of pro- and anti-inflammatory cytokines in experimental animals with non-alcoholic fatty liver disease under conditions of hypobaric hypoxia Nurgul Toktogulova, Rustam Tukhvatshin, Elmira Mainazarova Open Access Macedonian Journal of Medical Sciences, 2021 AIM: The aim of the study was to study the level of pro- and anti-inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), and interleukin 4 (IL-4), on a model of non-alcoholic fatty liver disease (NAFLD) in experimental animals under conditions of low mountains and hypobaric hypoxia. METHODS: The study was carried out on 180 male Wistar rats, which were divided into control and experimental groups. The rats of the control group were on a standard diet. NAFLD was modeled by keeping animals on a diet (Ackermann et al., 2005) rich in fructose and fat in conditions of low mountains and hypobaric hypoxia (in a pressure chamber 6000 m above sea level) for 35 and 70 days. Total cholesterol (TC) and lipid spectrum, pro- and anti-inflammatory cytokines were determined in all groups of animals. RESULTS: The activity of pro- and anti-inflammatory cytokines in the main group during the rise of animals in the pressure chamber increased statistically significantly on the 35th day in comparison with the low-altitude group by more than 2 times, and on the 70th day of staying at the high-altitude did not have convincing differences from the low-altitude group. The cytokine index (TNF-α/IL-4) of animals in conditions of hypobaric hypoxia on a fructose enriched diet increased by more than 1.5 times after 5 weeks, staying at an altitude for 10 weeks led to a decrease of TNF-α/IL-4 in relation to the low-mountain group, in which the opposite picture was observed - a tendency towards an increase in TNF-α/IL-4. IL-4 and TNF-α _levels were statistically significantly correlated with lipid metabolism disorders. CONCLUSION: NAFLD in animals on a special diet enriched with fructose under conditions of hypobaric hypoxia leads to deeper disturbances in the system of pro- and anti-inflammatory cytokines and the lipid spectrum.
