Objective: Methodology development for quality control of optically active pharmaceutical substances based on water isotopologues.Methods: Solutions of L-ascorbic acid, glucose, galactose and valine stereoisomers were prepared using deuterium depleted water (DDW-«light» water, D/H=4 ppm), natural deionized high-ohmic water (BD, D/H=140 ppm), heavy water (99.9% D2O). The optical rotation was observed using an automatic polarimeter Atago POL-1/2. The size distribution of giant heterogeneous clusters (GHC) of water was recorded by low angle laser light scattering (LALLS) method.Results: The infringement of Biot’s Law was found for solutions of ascorbic acid, expressed in the absence of a constant value of the specific optical rotation at a concentration of below 0.1%, depends on the D/H ratio. The inequality was established in absolute values of optical rotation for L-and D-isomers of valine in solutions with different ratios of hydrogen isotopologues. The mutarotation of glucose confirmed the first-order kinetics, and the activation energies were statistically distinguishable for BD and DDW. The mutarotation of the natural galactose D-isomer proceeded with a lower energy consumption compared to the L-isomer. In heavy water, the mutarotation of monosaccharides had different kinetic mechanisms. Polarimetric results correlated with the number and size of GHC, which confirmed the possibility of chiral solvent structures induction by optically active pharmaceutical substances.Conclusion: In the optically active pharmaceutical substances quality control there should be considered the contribution of induced chiral GHC of water to the optical rotation value that depends on the isotopic D/H ratio, the substance nature and the form of its existence at a given pH.

The literature review covers an analysis of the typical protective and adaptive reaction mechanisms that develop in small rodents that spontaneously hibernate under the cold snap, together with warm-blooded animals and humans during circadian fall of the body temperature at night time and in a course of a slow-wave sleep, along with induced artificial therapeutic hypothermia. The general features of neuroprotection states development in natural endogenous and induced hypothermia are highlighted, which include metabolic, epigenetic and biophysical reactions that ensure the formation of nonspecific tolerance of the brain to potentially damaging effects. Significant attention has been devoted to the participation of hibernation proteins, opioids and antioxidant systems in the processes of safe exit from state of torpor in animals and in implementation of sleep restoration functions. Taking into account the circadian nature formation of endogenous brains hypothermia at night and in the phases of slow sleep, it is suggested that periodic temperature exposure on the cerebral cortex can be applied in order to restore the disturbed circadian rhythms. From the standpoint of common mechanisms of endogenous and induced hypothermia, selective hypothermia of the cerebral cortex can be considered as a nature-like technology. Based on the extensive experimental material indicating a significant neuroprotective potentials of low temperatures during hibernation, diurnal hypothermia as well as artificially induced hypothermia, it was stated that implementation of the technology for selective hypothermia of the cerebral cortex in order to prevent the negative consequences of cerebral catastrophes are a perspective trend.

BACKGROUND: In patients with osteoarthritis, the long course of synovitis changes the nature of the inflammatory process, it becomes more resistant and resistant to a number of therapeutic techniques. In the arsenal of a practicing doctor, there are no reliable and affordable therapeutic methods that reliably provide relief of synovitis in the knee joint and objectively monitor the effectiveness of the therapy. Among the numerous methods of application in the treatment of diseases and injuries of the musculoskeletal system, low-molecular technologies with anti-inflammatory and analgesic effects are distinguished. One of these methods is local deep hypothermia. AIM: To substantiate the use of different low-temperature modes of local deep hypothermia in patients with knee osteoarthritis aggravated by synovitis, to study clinical efficacy and safety. MATERIALS AND METHODS: The study included 90 patients with osteoarthritis of the knee joints, burdened with synovitis. To determine the therapeutic parameters of local deep hypothermia, all patients were divided into three groups of 30 people. The effectiveness of the performed local deep hypothermia was assessed by the dynamics of the algofunctional Leken index, the intensity of joint pain on a 100-point Visual Analogue Scale (VAS) in millimeters and a decrease in the need for nonsteroidal anti-inflammatory drugs (NSAIDs). RESULTS: Technical and clinical parameters have been developed for carrying out the local deep hypothermia technique: area, cooling depth, rate of heat removal from the joint, duration of reproduction and number of procedures. Against the background of the performed local deep hypothermia, patients in three groups showed significant positive dynamics on the VAS and algofunctional Leken index, and in all three groups the difference between the initial and final values of these parameters was statistically significant (p 0.001). The use of local deep hypothermia allowed a significant part of patients to refuse to take NSAIDs, or to reduce the need to 50 mg and take episodically according to need. In our study, we did not record a recurrence of synovitis in all three groups during the first 3 months, which was 100%. After 12 months, the duration of remission in group I was 10.0%, in group II patients 73.3% and in group III patients 86.6%. CONCLUSION: Local deep hypothermia improves the effectiveness of synovitis treatment and can be recommended as an independent method for the treatment of patients with osteoarthritis of the knee aggravated by synovitis. The recommended local deep hypothermia exposure is 90 min, which allows for the longest period of remission of synovitis in the knee joint.

Objective: The aim of this study was to demonstrate that chiral switching should be recognized as a widespread phenomenon that extends beyond the production of pure enantiomeric drugs. Methods: To investigate the optical activity of substances from various chemical classes, enantiomers of chiral compounds (Sigma-Aldrich, USA) were chosen: valine and its racemic form (D-valine, L-valine, and racemic valine with optical purity ≥ 99%), L-ascorbic acid (content ≥ 99%), carbohydrates (D-glucose, D-galactose, L-galactose, contents ≥ 99.5%). Solutions were prepared using deuterium-depleted water (DDW–"light" water, D/H=4 ppm), natural deionized high-ohmic water (BD, D/H=140 ppm), and heavy water (99.9% D2O; Sigma-Aldrich). Optical activity was measured using the Atago POL-1/2 polarimeter. Results: One of the components in the racemic medication mixture can act as an inert agent, exhibit toxicity, or undergo undesirable biotransformation mechanisms, resulting in the formation of products with unknown properties. It has been established that a change in the deuterium/protium (D/H) ratio in water leads to a change in the equilibrium and kinetic characteristics of optically active compounds across various chemical classes, such as amino acids, carboxylic acids, and carbohydrates. An inequality was observed in the absolute values of the optical rotation of the L-and D-isomers of valine and galactose, depending on the D/H isotope ratio. The impact of chiral water clusters on optical rotation accounts for the sudden shift in the specific rotation of dilute solutions (less than 0.5%) of L-ascorbic acid in water, based on the D/H ratio. The influence of the isotopic composition of water was confirmed by studying the temperature-dependent mutarotation kinetics of D-glucose and L-and D-galactose in Arrhenius coordinates. The mutarotation process in natural high-resistivity water is characterized by an activation energy (Ea) of 40.8±1.4 kJ mol-1, while in deuterium-depleted water, Ea = 63.6±3.5 kJ mol-1. This results in a kinetic isotope effect for deuterium (KIED) of 1.6. Conclusion: Methodological approaches have been developed to control chiral switching based on the isotopic composition of water in vivo and in vitro. The study of changes in the optical activity of hierarchical structures in the human body, the influence of solvent properties on the mechanisms of optical rotation, as well as the use of KIED values, can be utilized to monitor various chiral transitions in vitro and living organisms.