Vol 17, No 4 (2019)

The purpose of the review was to analyze the neurochemical and neurophysiological mechanisms of the orexin system and the role of orexin in body functions and behavior. The focus is on the participation of orexin in the mechanisms of reinforcement and the formation of addictive behavior. At the beginning of the review a history of the first works on the field of orexin and its receptors are described. Hypothalamic orexin-producing cells and effects on brain functions are described. The effects of orexins and their receptors on eating behavior, wakefulness and positive reinforcement are described. Then, the effects of orexins on narcolepsy was analyzed. The participation of orexins in the mechanisms of reinforcement and dependence and the key role of orexins in the development of addictive behaviors is described. The special role of orexin in the formation of ethanol dependence is shown. Next, the issue of the action of orexins under stress was considered. Orexins have been shown to play an important role in the regulation of the nervous and humoral mechanisms mediating the formation of emotional memory associated with negative experience. It is concluded that orexin can modulate the estimation of stress and probability for reaching stimulus. In this regard, orexin antagonists can be considered as possible promising means of preventing and treating disorders of the anxiety-phobic spectrum, as well as disorders associated with the use of addictive drugs caused by stress and environmental stimuli.

Mitochondrial dysfunctions (an impaired energy metabolism in the mitochondria) are essential in a pathogenesis of many diseases.

Aim. The analysis of various mitochondrial dysfunction (MD) type study, as well as evaluation of drugs with an antihypoxic effect in their treatment.

Methods. Collection, systematization and analysis of experimental and clinical data of current scientific research about the problem.

Results. The mitochondrial dysfunctions can be caused by genetic disorders of the mitochondrial or nuclear genome (the primary MD or the mitochondrial diseases), as well as structural, functional and biochemical defects of mitochondria caused by other diseases (the secondary MD). MD are characterized by impaired tissue respiration, ATP synthesis deficiency and decreased energy metabolism. The clinical implications of MD are polysystemic and polymorphic. One of the biochemical sign of MD is the lactic acidosis. There are certain difficulties with the early diagnosis of primary MD. It is suggested to use complete exome sequencing among patients with a clinical suspicion on mitochondrial disease. The energotropic pharmacotherapy including drugs with an antihypoxic effect is used for MD treatment. It is more rational to use the drug combination that influences different stages of energy production. The combinations of L-carnitine, coenzyme Q10, cytochrome C and succinate-containing drugs are frequently used for MD. However, the usage of energotropic and antihypoxic drugs is not able to cure the patients and stop the progression of all disease displays.

Conclusion. MD are a multidisciplinary problem, therefore, doctors of any speciality must be competent in the MD diagnosis and treatment. The use of energotropic agents in the MD treatment requires further research. Numerous issues remain open (daily drug doses choice, treatment duration, rational combinations). The phenotype variability and the uniqueness of diagnosed cases, clinical and genetic differences between patient groups with mitochondrial diseases fail to create homogeneous samplings for therapy effectiveness and safety analysis. The literature data are the results of different degrees of reliability. The international efforts are needed to unify studies of related mitochondrial disorders, which, in combination with a constant improvement of MD pathogenesis knowledge will allow to develop more effective treatment regimens.

The experimental work analyzes the evaluation of the pharmacological efficacy of 3 experimental samples of the anti-osteoporosic preparation, created on the basis of salts of succinic acid in comparison with the comparison drug. On the experimental model of osteoporosis, according to the application of atomic absorption spectroscopy and flame photometry of the femur, the high efficiency of the new drug in the correction of induced pathology has been proved. The data obtained indicate that when acid salts of the natural conformer of succinic acid are used, it is possible to achieve sufficient saturation of bone tissue with calcium without overloading the body with excess calcium.

Purpose. In experiments on rats, we studied the self-stimulation reaction of the lateral hypothalamus and the conditioned reaction of place preference upon activation (orexin) and blockade of the orexin receptor by SB-408124 or Orexin B_18-28 in rats.

Methods. As behavioral methods, self-stimulation of the lateral hypothalamus and a conditioned reaction of place preference were chosen. Orexin and its antagonists SB-408124 or Orexin B_18-28 (Sigma, USA) were used for pharmacological analysis. All preparations were used in 3 dosages: 0.1, 1.0, 10 µg, injecting into the lateral ventricle of the brain (i.v.) through the implanted cannula.

Results. It has been shown that peptide substances of orexin and its antagonists modulate the conditional and unconditional reinforcing properties of the brain. The studied orexin antagonists showed a dose-dependent (0.1-1-10 μg, i.v.) inhibitory effect on the self-stimulation of the lateral hypothalamus, activated by indirect adrenergic agonist amphetamine (β-phenylisopropylamine). The inhibitory effect of orexin antagonists also manifested itself in relation to the generation and expression of a preference for amphetamine place, especially when using high doses of the peptide (10 μg i.v.).

Conclusion. The effect of orexin antagonists can be used in the development and study of antinarcotic drugs.

In the present study, influence of the complex use of concentrate of polyunsaturated fatty acid (PUFA) from a fat of Baikal seal and cortexin on cognitive functions in rats with cerebral ischemia was evaluated. Cognitive impairments are early signs of cerebrovascular insufficiency, which are based on the development of pathobiochemical reactions that cause damage to the lipid and protein structures of cell membranes. It has been suggested that the administration of PUFA and cortexin will have a nootropic effect due to the synergy of their actions. The aim of the study was to determine the effect of PUFA and Cortexin on cognitive function in rats with cerebral ischemia. The study was performed on Wistar rats of both sexes. A model of cerebral ischemia was reproduced by occlusion of the left common carotid artery under ether anesthesia. Animals received PUFA (20 mg/kg) intragastrically once day for 14 days before surgery and for the next 10 days after in combination with administration of cortexin (4 mg/kg, i.p). For a comparative evaluation of the therapeutic efficacy of the complex use of PUFA and cortexin, three groups of animals were used: piracetam and monotherapy with PUFA, and Cortexin. Behavioral activity and cognitive functions in rats were determined using the methods: “open field”, “elevated plus maze”, “Morris water maze”. It has been established that combined use of PUFA and Cortexin stimulated locomotor and exploratory activity, reduced anxiety in animals and had a more effective nootropic effect as compared with monotherapy.

Daptomycin is the first representative of the class of cyclic polypeptides, reached the application in clinical practice. Unlike most antibiotics, it has rapid bactericidal activity, including against microbial cells in biofilms. The spectrum of activity of daptomycin includes almost all clinically significant gram(+) bacteria, including strains resistant to other classes of antimicrobials. Currently, in the Russian Federation, daptomycin is registered for two indications: complicated skin and soft tissue infections at a dose of 4 mg/kg 1 time per day and blood flow infections caused by S. aureus, including bacteremia and right-sided endocarditis, at a dose of 6 mg/kg 1 time per day.

The literature review shows that standards for the treatment of purulent diseases to date include antiseptic and disinfectants, but do not include agents that dilute and/or dissolve thick pus. It is shown that the pharmacodynamics of antiseptic and disinfectants consists in the local disinfecting effect of these agents. With local interaction with the surface of living and non-living tissues, these agents are able to sterilize it. It was found that for disinfection of the selected surfaces, these agents are used in solutions that contain these agents in concentrations that provide a denaturing effect. It is shown that denaturing action of antiseptic and disinfectants is a special case of dependence of local action of solutions of all medicines and chemical compounds on their concentration. The fact is that increasing the concentration of chemical compounds in solutions sooner or later turns that solutions into a liquid medium that is not compatible with life. Therefore, this liquid kills all cells of the micro-and macroworld. That is why the use of solutions with denaturing action provides a detrimental effect on the cells of all microorganisms and cells of the macroorganism. With local interaction with the tissues of the macroorganism, the drugs cause the following pharmacological effects: local sterilizing, irritating (local inflammatory) and cauterizing (necrotic) action. Thus solutions with denaturing concentration of one means increase the hardness, other means do not change the hardness, and the third means decrease the hardness of biological tissues, including purulent masses. From this it is concluded that today in the treatment of purulent diseases are used means, detrimental effect on all forms of life, and not means, unidirectionally acting on purulent masses. At the same time, it is shown that some of the modern antiseptic and disinfectants can change the properties of purulent masses in the “right” direction and optimize their removal by diluting and dissolving the thick pus. It is established that the leaders in the solvent action on thick and sticky pus are sodium bicarbonate solutions in combination with hydrogen peroxide. It is shown that solutions that effectively dissolve thick pus have special physical and chemical properties: all of them have moderate alkaline, temperature, boiling and osmotic activity. Preparations that most effectively dissolve thick pus and most quickly and completely remove it out of the purulent cavities, additionally contain carbon dioxide gas or oxygen gas under excessive pressure. In chronological order are recipes invented hygiene products with special physical and chemical properties, providing them with the ability to quickly and effectively liquefy, dissolve and remove the thick pus out of the purulent cavities. It is shown that a new group of hygiene products was discovered in Russia and was called “Solvents of pus”. The most effective and safe solvents of pus are warm (heated to a temperature of 42 °C) solutions containing 2–4% sodium bicarbonate and 0.5–3% hydrogen peroxide.