UDC  616.375-008.64-07-053.2

Abstract. Cardiac autonomic neuropathy (CAN) is closely associated with an approximately five-fold increase in the risk of cardiovascular mortality in patients with diabetes mellitus (DM). Impaired autonomic function of the cardiovascular system in DM, which leads to the development of CAN, can be accompanied by coronary artery ischemia, heart rhythm disturbances, “silent” myocardial infarction, severe orthostatic hypotension, and sudden cardiac death syndrome. The article provides an analysis of literature data on the impact of glycemic variability (GV) on diabetic CAN development. This review analyzed the possible relationships between GV in people with diabetic CAN. In particular, the issues related to glycemic control and CAN, the link between GV and CAN in diabetes were analyzed. Unsatisfactory glycemic control and uncontrolled glycemic status are considered the main risk factors for chronic complications of DM, in particular CAN. An increase of GV is associated with a higher risk of chronic complications of DM, cardiovascular risk, all-cause mortality and morbidity. The clinical trial results demonstrated that time in range might be a promising metric for assessing glycemic control and prognosis of diabetic complications. This review is based on a search in PubMed and MEDLINE, Scopus, BIOSIS, EMBASE, Google Scholar and Springer Online Archives Collection. The following keywords were used: glycemic variability, cardiac autonomic neuropathy and diabetes mellitus. Research findings missed by the web search have been identified through a manual search of the bibliography of publications. CAN is one of the frequent long-term complications of DM, and reasonable control of GV may be necessary for its prevention. Determination of GV may have advantages for predicting future complications of DM in clinical trials and practice. The association of autonomic dysfunction and glucose levels, insulin resistance, and HbA1c variability suggest further research to reduce chronic complications development. Further investigation is needed to study the mechanisms of GV and evaluate them as therapeutic targets in the treatment of patients with T2DM.
Keywords: diabetes mellitus; cardiac autonomic neuropathy; glycemic variability

UDC: 611.37.018.72:615.212.7].08

Use of narcotic drugs in clinical practice for the purpose of obtaining analgesic and anti-inflammatory effects requires a comprehensive morphological study of the peculiarities of structural arrangement of organs under the conditions of exposure to opioids. The aim of our study was to establish the peculiarities of restructuring of the structural components of the pancreas under the conditions of long-time exposure to opioids in the experiment. The study included 24 adult laboratory white male rats. The test animals were divided into 2 groups, the experimental and control ones. The experimental animals were daily administered narcotic analgesic nalbuphine intramuscularly (once a day in the same interval) for four weeks, and the control animals were administered saline solution. The following research methods were used: bloodstream injection followed by translucence of sections of the pancreas and their
photographing, morphometry of the vessels of the pancreatic hemomicrocirculatory bed, histological, histochemical studies and electron microscopy of the pancreas, blood biochemistry test; statistical processing of the study results using a software package. After four weeks of opioid exposure, lesion of the pancreatic parenchyma microstructure was observed, manifested by swelling and infiltration by lymphocytes and macrophages of the pancreatic connective tissue stroma, disorganization of the exo- and endocrine parts of the parenchyma, deep destructive changes in the excretory ducts, as well as in the vessels of the hemo- and lympho-microcirculatory bed of the pancreas. At the ultrastructural level, deep dystrophic changes of exo- and endocrinocytes of the pancreas were identified, in particular, loss of regular shape, karyopyknosis and karyorrhexis of the nuclei, swelling and clearing of cytoplasm, development of microcystic degeneration of cells, loosening and disorganization of the basement membrane, which can result in impairment of exocrine function of the pancreas and complication of the process of secretory granules excretion into the lumen of the intercalated ducts. A significant decrease, compared to the control group, in the diameter of arterioles, density of exchange vessels network, as well as increase in the diameter of venules, the indicator of trophic activity of the tissue, are the evidence of destructive changes in the hemomicrocirculatory bed of the pancreas under the effects of nalbuphine. Significant changes in blood biochemistry parameters (alanine aminotransferase, aspartate aminotransferase) after a four-week administration of nalbuphine are illustrative of the process of pancreatic tissue destruction. Therefore, four-week administration of opioid leads to profound changes in the micro- and ultrastructure of the pancreas, vessels of its hemomicrocirculatory bed, and blood biochemistry parameters in experimental white rats.
Keywords: pancreas, structural changes, opioid, experiment.

УДК 616.36-004-06+616.149-008.341.1+616.24-008-092

Резюме. Портопульмональна гіпертензія визначається як розвиток легеневої артеріальної гіпертензії на тлі портальної. Точну її поширеність важко визначити через відсутність рутинного скринінгу у пацієнтів з портальною гіпертензією. Гемодинамічні зміни, пов’язані з портальною гіпертензією, включно з гіпердинамічним станом, портосистемними шунтами та спланхнічною вазодилатацією, викликають значні порушення в легеневому судинному руслі та відіграють ключову роль у патогенезі захворювання.
Без лікування портопульмональна гіпертензія призводить до прогресуючої правосерцевої недостатності з поганим прогнозом. Незважаючи на те, що допплерівська ехокардіографія є найкращим інструментом початкового скринінгу для симптомних пацієнтів і кандидатів на трансплантацію печінки, катетеризація правих відділів серця залишається золотим стандартом для діагностики захворювання. Лікування пацієнтів з портопульмональною гіпертензією спрямоване на поліпшення серцевої функції, зменшення легеневого судинного опору, оптимізацію функціональної здатності. ЛАГ-специфічна терапія, яка включає агоністи простацикліну і його рецепторів, антагоністи рецепторів ендотеліну, інгібітори фосфодіестерази та стимулятори гуанілатциклази, відіграє ключову роль у лікуванні пацієнтів з портопульмональною гіпертензією. Невеликі неконтрольовані та нещодавні поодинокі рандомізовані контрольовані дослідження повідомили про багатообіцяючі результати вазодилататорної терапії щодо клінічного та гемодинамічного поліпшення хворих, що дозволило певній частині пацієнтів провести трансплантацію печінки. У цьому огляді обговорюються епідеміологія, підхід до діагностики та лікування хворих із портопульмональною гіпертензією. Для пошуку літературних джерел використовували базу даних MedLine на платформі PubMed і бібліотеку Cochrane за ключовими словами: portopulmonary hypertension, portal hypertension, lung arterial hypertension, liver cirrhosis, pulmonary complications.
Ключові слова: портопульмональна гіпертензія; легенева артеріальна гіпертензія; гемодинаміка; трансторакальна ехокардіографія; катетеризація серця; лікування; трансплантація печінки

Colorectal cancer is influenced by genetic mutations, lifestyle factors, and diet, particularly high fat intake, which raises bile acid levels in the intestinal lumen. This study hypothesized that bile acids contribute to tumorigenesis by disrupting ion transport and ATPase activity in the intestinal mucosa. The effects of 3-sulfo-taurolithocholic acid (TLC–S) on ATPase activity were investigated in colorectal cancer samples from 10 patients, using adjacent healthy tissue as controls, and in rodent liver function. ATPase activity was measured spectrophotometrically by determining inorganic phosphorus (P_i) in postmitochondrial fractions. Ca²⁺ dynamics were assessed in isolated mouse hepatocytes with fluorescence imaging, and rat liver mitochondria were studied using polarographic methods to evaluate respiration and oxidative phosphorylation. TLC–S increased Na⁺/K⁺ ATPase activity by 1.5 times in colorectal cancer samples compared to controls (p ≤ 0.05). In healthy mucosa, TLC–S decreased Mg²⁺ ATPase activity by 3.6 times (p ≤ 0.05), while Mg²⁺ ATPase activity in cancer tissue remained unchanged. TLC–S had no significant effect on Ca²⁺ ATPase activity in healthy colon mucosa but showed a trend toward decreased activity in cancer tissue. In rat liver, TLC–S decreased Ca²⁺ ATPase and Na⁺/K⁺ ATPase activities while increasing basal Mg²⁺ ATPase activity (p ≤ 0.05). Additionally, TLC–S induced cytosolic Ca²⁺ signals in mouse hepatocytes, partially attenuated by NED-19, an NAADP antagonist (p ≤ 0.05). TLC–S also reduced the V3 respiration rate of isolated rat liver mitochondria during α-ketoglutarate oxidation. These findings suggest that TLC–S modulates ATPase activity differently in cancerous and healthy colon tissues, playing a role in colorectal cancer development. In rat liver, TLC–S affects mitochondrial activity and ATPase function, contributing to altered cytosolic calcium levels, providing insight into the mechanistic effects of bile acids on colorectal cancer and liver function.