Establishment of international legal regulation on the criminal-legal combat against domestic violence

The issue of combating domestic violence is one of the most important in today's conditions, both in Ukraine and throughout the world, because violence (including domestic violence) is recognized as violating human rights. In order to improve the situation and implement mechanisms for combating domestic violence at the international level, a system of the international legal protection of the rights of victims of domestic violence and combating domestic violence has been created. The purpose of the work is to assess and study the provisions of international legal acts aimed at combating domestic violence. The research methodology is a complex of methods: historical, comparative-legal, descriptive, systemic-structural, dogmatic, sociological and modeling, induction and deduction, and philosophical method. An analysis of the features of the emergence and development of international legal regulation in the field of combating domestic violence was carried out, in particular, the system and features of individual international acts regarding the detection and response to cases of domestic violence are considered. Also, the criminal law regulations regulating the fight against domestic violence were analyzed. Attention is drawn to the development and experience of the criminal-legal response to domestic violence in the international community and its transformation in modern conditions. The possible directions of the development of international legal regulation regarding the criminal legal response to domestic violence in Ukraine and the world have been determined

Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis

peer reviewedBackground: Thiamine diphosphate (ThDP), an indispensable cofactor for oxidative energy metabolism, is syn- thesized through the reaction thiamine + ATP ⇆ ThDP + AMP, catalyzed by thiamine pyrophosphokinase 1 (TPK1), a cytosolic dimeric enzyme. It was claimed that the equilibrium of the reaction is in favor of the for- mation of thiamine and ATP, at odds with thermodynamic calculations. Here we show that this discrepancy is due to feedback inhibition by the product ThDP. Methods: We used a purified recombinant mouse TPK1 to study reaction kinetics in the forward (physiological) and for the first time also in the reverse direction. Results: Keq values reported previously are strongly underestimated, due to the fact the reaction in the forward direction rapidly slows down and reaches a pseudo-equilibrium as ThDP accumulates. We found that ThDP is a potent non-competitive inhibitor (Ki ≈ 0.4 μM) of the forward reaction. In the reverse direction, a true equi- librium is reached with a Keq of about 2 × 10− 5, strongly in favor of ThDP formation. In the reverse direction, we found a very low Km for ThDP (0.05 μM), in agreement with a tight binding of ThDP to the enzyme. General significance: Inhibition of TPK1 by ThDP explains why intracellular ThDP levels remain low after administration of even very high doses of thiamine. Understanding the consequences of this feedback inhibition is essential for developing reliable methods for measuring TPK activity in tissue extracts and for optimizing the therapeutic use of thiamine and its prodrugs with higher bioavailability under pathological conditions

2-Hydroxy­amino-2-oxoacetohydrazide

In the title compound, C2H5N3O3, the hydroxamic group adopts an anti orientation with respect to the hydrazide group. In the crystal, mol­ecules are connected by N—H⋯O and O—H⋯N hydrogen bonds into zigzag chains along the c axis