Донори Н2S у створенні інноваційних лікарських засобів

Fundamental studies have identified a new group of gaseous signaling molecules – the so-called gasotransmitters – NO, CO, and H2S, which are involved in the regulation of a large number of metabolic processes. The results of these studies allowed determining a new direction in medicinal/pharmaceutical chemistry – creation of hydrogen sulfide donor compounds as potential drugs. The article presents the main achievements in the search for new H2S donors: the main stages of H2S metabolism and its biological effects; the classes of compounds that can release hydrogen sulfide based on the nature of sulfur-containing functional groups as well as the mechanism of H2S releasing. Additionally, the characteristic of the most successful direction – creation of the so-called hybrid molecules is given. The latter are compounds bearing fragments of the well known drugs covalently bounded with groups being capable to release H2S.Фундаментальные исследования выделили новую группу газообразных веществ, так называемых «газотрансмиттеров» NO, CO, H2S, которые вовлечены в процеcсы регуляции большого количества метаболических процесов. Результаты таких исследований позволили выделить новое направление в медицинской/фармацевтической химии – создание соединений доноров сероводорода как потенциальных лекарственных средств. В работе представлены главные достижения в области поиска новых потенциальных доноров H2S: основные этапы метаболизма H2S и его биологические эффекты; классы соединений способных освобождать сероводород, соответственно природы функциональных серосодержащих групп и механизма выделения H2S. Отдельно охарактеризовано наиболее успешное направление – создание так называемых «гибридных молекул», которые содержат фрагменты известных лекарственных средств, ковалентно связанных с группами, которые так или иначе способны к выделению сероводородаФундаментальні дослідження виокремили нову групу газоподібних речовин, так званих «газотрансміттерів» NO, CO, H2S, залучених до процесів регуляції великої кількості метаболічних процесів. Результати таких досліджень дозволили окреслити новий напрямок у медичній/фармацевтичній хімії – створенні сполук донорів сірководню як потенційних лікарських засобів. У роботі представлені основні досягення в галузі пошуку потенційних донорів H2S: основні етапи метаболізму H2S та його біологічні ефекти; класи сполук, здатні вивільняти сірководень відповідно до природи функціональних сульфуровмісних груп та механізму виділення H2S. Окремо охарактеризовано найбільш успішний напрямок – створення так званих «гібридних молекул», що вміщуюють фрагменти відомих лікарських засобів, ковалентно зв’язаних з групами, що в той чи інший спосіб здатні вивільняти сірководень

Corrigendum to "European contribution to the study of ROS:A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)" [Redox Biol. 13 (2017) 94-162]

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed

Heart Rate Variability and Somatization in Adolescents With Irritable Bowel Syndrome

Background/Aims Changes in autonomic regulation and psychological distress play an important role in the pathobiology of irritable bowel syndrome (IBS). The aim of the current study is to evaluate the autonomic function and to link it to the levels of somatization in adolescents with IBS.Methods We enrolled 30 adolescents with various types of IBS and 35 healthy controls. Time and frequency domain indexes of heart rate variability (HRV) were measured in supine (baseline) and standing (orthostasis) positions using short-term electrocardiographic recordings. The somatic symptoms index was assessed with the modified Screening for Somatoform Symptoms questionnaire. Results Adolescents with IBS showed no differences of HRV parameters in the supine position compared to healthy control. In orthostasis, a decrease in the standard deviation of normal RR intervals as well as main spectral index total power (TP) were observed. The reduction of TP was attributed to the reduced activities of the high-and low frequency components. Increased somatic symptoms index in IBS patients negatively correlated with TP in orthostasis (r = -0.485, P = 0.007). A subgroup analysis revealed that adolescents with IBS with TP values either 5500 msec2 in the supine position demonstrated significantly reduced activity of the low frequency component.Conclusions Adolescents with IBS showed signs of autonomic dysfunction only during the orthostatic test, which were associated with increased somatization scores. Further research is needed to establish the links between emotional wellbeing and autonomic function in this population. (J Neurogastroenterol Motil 2023;29:208-217

Interval hypoxic training in complex treatment of Helicobacter pylori-associated peptic ulcer disease

This study was aimed to demonstrate the efficacy of interval hypoxic training (IHT) in complex treatment of Helicobacter pylori-associated duodenal peptic ulcer disease (DPUD) by parameters of aerobic metabolism and indexes of heart rate variability (HRV). Eighty patients with H. pylori-associated DPUD were included into the study, mean age 32±1.8 yrs, duration of the disease up to 10 years (66.3 %). IHT was modulated using Frolov's hypoxicator (TDI-01) for 30 days after standard eradication therapy. Daily hypoxic sessions consisted of three one-minute sessions, one two-minute, and one three-minute sessions separated by one-minute intervals of room-air breathing. Use of IHT resulted in more efficient elimination of clinical symptoms, histological hallmarks of inflammation and signs of oxidative stress in glandulocytes of the gastric mucosa as determined by 4-hydroxynonenal accumulation. Moderate prooxidant activity of IHT was demonstrated by the increased level of TBARS and oxidatively modified products, normalization of hydroperoxides, middle mass molecules and atherogenic beta-lipoproteins with simultaneous increase in catalase activity and mild decline of SOD activity. Therefore, IHT appeared to be accompanied by higher intensity of redox reactions and enhanced regeneratory processes in cells and tissues. Significant increase in HRV was also noted. Such changes were associated with reduction of inflammation signs and modulation of the autonomic homeostasis in DPUD patients. In general, use of IHT in complex treatment of H. pylori in DPUD patients can be recommended to increase resistance to oxidative stress and to modulate autonomic balance and oxidative homeostasis

Corrigendum to "European contribution to the study of ROS : A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)" [Redox Biol. 13 (2017) 94-162]

No abstract available