Vol 17, No 2 (2019)

Why do we need fullerenes today?
Piotrovsky L.B., Litasova E.V., Dumpis M.A.

The review focuses on the possibilities and prospects of the use of fullerenes and their derivatives in cosmetics, the only industrial area where fullerenes have found practical application today. Based on the literary data and the results of their own experiments, the authors substantiate the safety of using fullerene for living organisms, as well as the usefulness of introducing fullerene as antioxidant in cosmetic compositions. Other useful properties of fullerene used in cosmetics and dermatology are discussed.

Reviews on Clinical Pharmacology and Drug Therapy. 2019;17(2):5-15
Breach of ligand-receptor interaction in pathogenesis of disadaptive disorders and in pathology
Artemenkov A.A.

The review summarizes information about the effects of ligand-receptor interaction in the normal state, during maladaptation and pathology. The mechanisms of changes in the functions of the receptors of the immune system that recognize pathogen patches, interact with immunoglobulins and participate in the immune response are shown. Data on interactions within the neurotransmitter systems of the brain are presented. The properties of lectins, follicle-stimulating hormone, progesterone derivatives and calcitonin are considered. The review also summarizes information on such cellular processes as cell growth, bone regeneration and remodeling, apoptosis. The role of thiazole retinoids in the regulation of cell differentiation and signaling pathways has been shown. Particular attention is paid to angiogenesis and vascular endothelial growth factor, receptors and ligands to fibroblast growth factor, galactins involved in oncotransformation processes. It was established that phosphatase with the Src2 homology domain (SHP2) is an important component of oncogenic signaling pathways. The mechanism of multivalent interaction of bacteria and viruses with the cells of the body is discussed. The interaction of nanoparticles (graphene, fullerenes) with biological objects is considered in sufficient detail. The article discusses the problem of receptor saturation and the activity of ex-orphan receptors that can act as targets for potential drugs. The prospects of creating new drugs based on π-cation interactions are shown. It was concluded that the study of the interaction of the substance and the receptor will allow to reveal the true mechanisms of dysregulatory pathology.

Reviews on Clinical Pharmacology and Drug Therapy. 2019;17(2):17-28
Modern ideas about the effect of exogenous antioxidants on the growth of malignant tumors
Puzakov K.K., Durnova N.A., Ryzhenkova I.G.

This review analyzes the literature on the effects of certain drugs with antioxidant properties on the risk of developing malignant neoplasias, as well as on their growth and metastasis. Antioxidants are able to protect not only normal cells from the alterative effect of free radicals, but also tumor cells, thereby stimulating their survival and growth. There are data showing that in cells of certain malignant tumors, concentrations of endogenous antioxidant proteins are increasing. The synthesis of these proteins is determined by the cellular signaling pathway KEAP1/NRF2/ARE, it was revealed that oncogenes are involved in the regulation of this signaling pathway. The p53 protein, which activates apoptosis in diseased cells, can be inactivated by antioxidants, which in turn can stimulate the survival and growth of malignant tumor cells. Currently, there is a sufficient amount of information about the effect on tumor growth of certain drugs of various pharmacological groups with antioxidant properties, such as the widely used mucolytic N-acetylcysteine, antidiabetic drugs inhibitors of DPP4 (saxagliptin, sitagliptin), alpha lipoic acid used in the treatment of neuropathies of various origins, as well as vitamins A and E. development of malignant neoplasias in at-risk patients (smokers, patients with chronic obstructive pulmonary disease and diabetes mellitus ). As well as they can complicate the course of existing cancers.

Reviews on Clinical Pharmacology and Drug Therapy. 2019;17(2):29-33
Original articles
The study of the effects of the combination of Himantane and Piribedil on a model of MPTP-induced parkinsonian syndrome in C57BL/6 mice
Valdman E.A., Kapitsa I.G., Kalinina A.P., Ivanova E.A., Voronina T.A.

The effectiveness of hemantane, an original adamantane derivative, in combination with the dopamine receptor agonist piribedil on the model of acute parkinsonian syndrome induced by a single intraperitoneal injection of 30 mg/kg neurotoxicin-1, induced by a single intraperitoneal injection of 30 mg/kg neurotoxin 1-methyl-4-phenyl-tetrahydropyridine (MPTP) in C57BL/6 mice. Rigidity was assessed by stride length, oligokinesia and impaired coordination in the “rotarod test’’, effect on the catalepsy model caused by 0.1 mg/kg haloperidol. It has been established that the combination of hemantane and piribedil reduces the manifestations of parkinsonian syndrome, significantly exceeding in efficiency of each of the drugs separately.

Reviews on Clinical Pharmacology and Drug Therapy. 2019;17(2):35-40
Cholinergic mechanisms of regulation of free radical oxidation of the liver lipids in cold adaptation in rats
Tikhanov V.I., Shabanov P.D.

The effects of administration of cholinotropic agents (neostigmine, hexamethonium, pilocarpine, atropine, nicotine) on liver tissue after the 5 days period of cooling of rats were compared. The analysis of the conditions inducing lipid peroxidation (LPO), the analysis of the substrate components of the LPO in liver, and the evaluation of the LPO products content in the 5 days period of cold loads were made. The data obtained indicate on the contradirectory effects when pilocarpine and nicotine were administered to animals, as well as after administration of atropine and hexamethonium to animals. There was the similar effects after administration of both pilocarpine and hexamethonium and both nicotine and atropine in conditions of activated LPO assessed by substrate components of LPO in the liver after 5 days cooling. On the basis of these results, a hypothesis of reciprocity between muscarinic and nicotinic cholinoreceptors located on the plasma membrane of hepatocytes in the LPO processes of the liver during the period of cold loads has been formulated.

Reviews on Clinical Pharmacology and Drug Therapy. 2019;17(2):41-48
Comparative effectiveness of Molixan and Glutoxim in the model of toxic liver lesions with anti-tuberculosis drugs
Bugaev P.A., Basharin V.A., Antushevich A.E.

Due to the high frequency of liver lesions caused by anti-tuberculosis drugs, the possibility of using compounds based on oxidized glutathione for hepatoprotection is shown.

Purposes and tasks. The purpose of the study was to conduct a comparative assessment of the hepatoprotective properties of molixan and glutoxim in liver lesions with anti-tuberculosis drugs. To achieve this goal, it was necessary to perform the following tasks: on the model of toxic liver damage caused by anti-tuberculosis drugs (isoniazid, rifampicin, pyrazinamide) to study the effectiveness of glutoxin and molixan by biochemical and morphological parameters; on the basis of the data to determine the most effective scheme of application.

Materials and methods: the study was conducted on 90 white male not inbred rats. Antituberculosis drugs (AD) were administered to animals daily for 14 days in the following doses: isoniazid – 50 mg/kg intraperitoneal, rifampicin – 250 mg/kg and pyrazinamide – 45 mg/kg intragastrically. Glutoxim and molixan were administered daily for 14 days at doses: 20 and 40 mg/kg – glutoxim, 30 mg/kg – molixan, intraperitoneal for 2 hours before the introduction of anti-tuberculosis drugs. The animals were divided into 5 groups of 18 rats each. Group 1 – intact animals, 2 – control AD, 3 – AD + glutoxim 20 mg/kg, 4 – AD + glutoxim 40 mg/kg, 5 – AD + molixan 30 mg/kg. In the study on day 15, biochemical parameters of blood were determined, the liver was taken for morphohistological study and the level of LPO in its homogenates was determined by the concentration of diene conjugates and malondialdehyde.

Results and conclusions. As a result of the experimental study, it was noted that the more pronounced hepatoprotective effect was exerted by molixan.

Reviews on Clinical Pharmacology and Drug Therapy. 2019;17(2):49-54
Effect of altered thyroid status on the incidence of colon tumors induced by methylnitrosourea in rats
Glushakov R.I., Tolkach P.G., Kurbanov R.A., Semenov A.L., Tchizh G.A., Reynyuk V.L., Basharin V.A., Kotiv B.N.

Aim. The present study was designed to determine whether medically induced hyper- and hypothyroidism effect on incidence of colon tumors induced by methylnitrosourea (MNU) burden in rats.

Methods. Female rats (n = 88) were randomly divided into four groups: I (euthyroid-control), II (hyperthyroid caused by liothyronine), III (hyperthyroid caused by L-thyroxine) and IV (hypothyroid caused by propylthiouracil (PTU), also 11 rats were intact control. Colon carcinogenesis was induced with a four intrarectal instillation of MNU (4 mg in 0.5 ml saline solution) one time per week. Liothyronine (100 ± 10 µg per 100 g of animal weight 1 time per day), L-thyroxin (100 ± 10 µg per 100 g of animal weight 1 time per day) and propylthiouracil (PTU, 2,0 ± 0,15 mg per 100 g of animal weight 1 time per day) were administered intragastrically through an atraumatic probe daily, starting from the day of the last intrarectal instillation of MNU. Rats were sacrificed at 216 days after experiment beginning, and the total colon were excised, fixed for histology and analyzed.

Results. Drug inhibition of thyroid hormone function by PTU resulted in a decrease in the incidence of MNU-induced colon tumors and amounted to 27.3%. The incidence of colon tumors in the hyperthyroid group caused by L-thyroxine was 70.0% (F-test – 0.012, χ2 – 7.67; p < 0.05 compared with the hypothyroid group).

Reviews on Clinical Pharmacology and Drug Therapy. 2019;17(2):55-62
Adaptogenic effect of phlojodicarpus sibiricus extract on cerebral ischemia
Gulyaev S.M., Taraskin V.V., Urbanova E.Z.

The aim of the study was to determine the adaptogenic effect of the extract from the roots of Phlojodicarpus sibiricus during ischemic influence on the left hemisphere of the brain. Experiments were conducted on Wistar rats of both sexes weighing 200-220 g. Unilateral cerebral ischemia was induced by permanent occlusion of the left common carotid artery under ether anesthesia. Adaptogenic anti-ischemic effect of Ph. sibiricus was determined by the number of desquamated endotheliocytes, nitrogen oxide metabolites – nitrites in the blood, by the content of lipid peroxidation products – malondialdehyde (MDA) and the activity of the antioxidant defense system in the brain tissue. It is established that Ph. sibiricus has an anti-ischemic effect, reduces the number of endotheliocytes desquamated, increases the level of nitric oxide in the blood (p ≤ 0.05), stimulates SOD and catalase activity, reducing the intensity of lipid peroxidation and the accumulation of MDA in the brain during ischemic exposure (p ≤ 0.05). Preventive administration of Ph. sibiricus extract has an adaptogenic effect in unilateral cerebral ischemia, which consists in reducing desquamated endotheliocytes, increasing the production of nitric oxide by endothelium, increasing the antioxidant defense system and reducing the intensity of oxidative reactions in the brain. Adaptogenic effect of Ph. sibiricus extract is caused by endothelium protective and antioxidant effects.

Reviews on Clinical Pharmacology and Drug Therapy. 2019;17(2):63-66
The influence of Fencarole and Zaditen on intestinal microflora of rats in the stages of passive anaphylactic reaction
Ismoilov S.R.

It was experimentally established that in the conditions of passive anaphylactic reaction more distinct dysbiotic shifts occurred in the microflora of the large intestine of rats on the 6th day of sensitization and on the 3rd day of food anaphylaxis. And in the study of the effect of antihistamines on these disorders revealed their ambiguous effect, although fencarole and zaditen did not have sufficient protective effect on intestinal dysbiotic changes.

Reviews on Clinical Pharmacology and Drug Therapy. 2019;17(2):67-72
Clinical pharmacology
Aldosterone antagonists in cardiology practice
Danilov A.I., Kozlov S.N., Evseev A.V.

In review presents the patological effects of aldosterone, clinical pharmacology of aldosterone antagonists and their role in countering the development of cardiovascular diseases are highlighted. The results of clinical studies have demonstrated high clinical efficacy and safety of spironolactone and eplerenone in a wide range of cardiovascular risk. However, the potential adverse drug reactions associated with these drugs limit their use in some categories of patients. However, adequate monitoring of these reactions, including hyperkalemia and acute kidney injury, can be avoided. In situations where there are indications for the use of spironolactone or eplerenone, the latter is the drug of choice due to the lower risk of gender adverse reactions. The frequency of other adverse drug reactions, in particular hyperkalemia, spironolactone and eplerenone are comparable.

Reviews on Clinical Pharmacology and Drug Therapy. 2019;17(2):73-77
Medicines in pharmaceutical form “solution for injection” and the injection of drugs: advantages and limitations
Urakov A.L.

The literature review shows that today any substance, and hence any drug, can be in such physical states as solid, liquid, gas and plasma. The classification of pharmaceutical forms of drugs, from which it follows that presently the drugs are produced in solid, liquid, soft and gaseous “dosage forms”. It is shown that the modern quality standards of drugs do not guarantee the presence of a single aggregate physical properties of all drugs produced in the same dosage forms. It is established that modern quality standards of drugs allow the production of drugs in the same pharmaceutical forms, but with different concentrations of all ingredients and with different physical and chemical properties. The ranges of concentration values of the dissolved ingredients and indicators of acid (alkaline) and osmotic activity of high-quality drugs from different pharmacological groups produced by different pharmaceutical companies in the form of “Solutions for injection” are given. From the above examples, it follows that at present qualitative “Solutions for injections” have an acidity value in the range of pH 2-12 and an osmotic activity value in the range of 0-3900 mOsmol/l of water. In addition to this, it is shown that modern drugs prepared in the pharmaceutical form “Solutions for injection” and considered to be of high quality, have a concentration of dissolved ingredients in the range of 0.01-100 %. Therefore, almost all modern medicines produced in the dosage form “Solutions for injection” have different mechanical, physical, chemical and/or physico-chemical properties that can change their pharmacological activity. Examples are given of how different concentrations of ingredients and osmotic activity of certain drugs in the dosage form “Solutions for injections” affect the severity of their local action on tissues in the range from short-term inflammation of tissues to their necrosis. It is proved that modern “solutions for injections” do not guarantee the safety of local interaction with viable tissues of the human body. The technologies of improving the safety of injection of modern “Solutions for injection” and technology to prevent tissue necrosis with “wrong” injections of drugs (by accident, ignorance, ignorance, mistake) are listed.

Reviews on Clinical Pharmacology and Drug Therapy. 2019;17(2):79-84
Creating the new Russian vaccines as an example of import substitution in pediatrics
Sklyarova E.V., Berkihanova D.B., Pashaev S.V., Yusupov M.G., Glushakov R.I., Nurmagomedov М.N., Davudov I.G., Proshin S.N.

In the modern economy the import substitution is an exceptional and temporary measure in the modern term. All states use or have used protectionist policies in their history due to the fact that there is a positive relationship between protectionism measures and the growth of gross national income. Active course on import substitution taken in Russia in 2014 after the introduction of Russian and anti-Russian economic sanctions. On August 4, 2015, at a meeting of the Government of the Russian Federation the decision was made to establish a Government Commission on Import Substitution. Resolution of the Government of the Russian Federation of August 4, 2015 No. 785 “On the establishment of a government commission on import substitution”, in which the composition of the commission is approved, were signed by the Prime Minister Dmitry Medvedev. Analysis of the current state of the pharmaceutical and medical industry indicates its lag behind similar industries of economically developed countries in the range of products. While maintaining this trend the health of citizens of the Russian Federation as the most important component of the national security of the Russian Federation becomes dependent on foreign economic conditions. In this regard the innovative development of the domestic pharmaceutical and medical industry, especially for the production of drugs that are actively used in pediatrics, including neonatology, is one of the priorities of the modernization of the economy of the Russian Federation.

Conclusion. Pneumococcal infection causes most severe cases of pneumonia, sepsis, meningitis, and otitis, especially dangerous for those for one reason or another weakened immune system. In this regard WHO recommends vaccination as the most effective way to prevent infectious diseases, including those caused by pneumococcal infection.

Reviews on Clinical Pharmacology and Drug Therapy. 2019;17(2):85-88

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