[PHYSIOLOGY AND PHARMACOLOGICAL PROPERTIES OF NANOMATERIALS].

Literature data and results of our department studies on theoretical and practical basics of nanoscience were summarized in the article. Much attention is paid to research in the field of physical, chemical, biological, medical, physiological, pharmacological, and toxicological properties of nanomaterials with the aim of their wider implementation into practice lately. The discovery of new quantum/wave properties of nanoparticles is of particular importance. The author of the article advances an idea: wave properties of nanomaterials play greater role with a decrease in particle size. The preponderance of wave properties compared with corpuscular ones in nanostructures determines a great change in their physical. chemical properties and an increase in physical, mechanical biological, physiological, pharmacological, and toxicologica activity. The idea advanced in the article hasn't been verified by theoretical or experimental studies for now. Joined efforts of scientists of different scientific fields are needed. A confirmation of hypothesis by specific findings will be of great importance for physiology, medicine, pharmacology and promote an implementation of new efficacious preparations into clinical practice. New fundamental discoveries could be made only by multidisciplinary approach.

[STRUCTURAL AND FUNCTIONAL CHANGES MYOCARDIUM HYPERTENSIVE RATS IN APPLYING INDAPAMIDE AND ELLAGIC ACID].

The article investigates the effectiveness of antihypertensive properties of indapamide and ellagic acid in hypertensive rats. As a result of experimental studies determined the effect of drugs on blood pressure and structural recovery of the myocardium of hypertensive rats. Indapamid with ellagic acid reduces the degradation of contractile myofibrils, mitochondria lysis and swelling of the cytoplasm of cardiomyocytes. The study drug is a normalizing effect on the se parameters. The combined use of indapamid and ellagic acid enhances the structural and functional recovery of myocardium energy metabolism normalizes organelles.

[Influence of antihypertensive and metabolic drugs on fatty acids content of lipids in cardiomyocytes of rats with spontaneous hypertension].

Changes in fatty acid composition of lipids are an important factor in the development of arterial hypertension. Therefore, this is very important to research the role of fatty acid spectrum of the blood and tissues in the development of hypertension. The search for effective metabolic drugs and antihypertensive drugs which would have the additional ability to influence the fatty acid composition of lipids in cells is also important today. We have found that hypertensive rats demonstrate the essential decrease of the amount of saturated fatty acids (sFA) and high content of unsaturated fatty acids (usFA). Application of amlodipine increases the level of sFA compared with animals without treatment and the level of usFA tends to decrease. A similar pattern is observed when using bisoprolol and combination of amlodipine with bisoprolol, although the combination is characterized by more significant changes in FA composition of lipids in cardiomyocytes. Treatment with metabolic drug elgacin leads to full recovery of saturated and unsaturated fatty acids in the cardiomyocytes. During the treatment with combinations of amlodipine with elgacin and bisoprolol with elgacin the level of both types of AF was not significantly different from the elgacin action in monotherapy. This study demonstrates the modification of the FA composition of lipids in cardiomyocytes of the spontaneously hypertensive rats. The investigated drugs exhibit a normalizing influence on the ratio between sFA and usFA in cardiomyocytes of the hypertensive rats.

[NO-dependent mechanisms of cardioprotective activity of MT preparation during course administration to SHR rats].

Chronic (15 days) single daily intraperitoneal insertion of the new preparation MT (5 mg/kg) and metoprolol (10 mg/kg) into SHR rats leads to the same decrease (18%) in arterial pressure. In addition, MT exhibits a cardioprotective effect because of NO-mimetic properties, increasing NO formation in myocardium via increasing general NOS activity and eNOS expression. MT normalizes iNOS expression in myocardium mitochondria and decreases nitrotyrosine (nitrosation stress marker) formation. At the same time, the reference preparation metoprolol did not exhibit NO-mimetic properties in myocardium of SHR rats.

[The effect of amlodipine, bisoprolol on the myocardial ultrastructure of the hypertensive rats].

Calcium channel blockers and beta1-adrenoblockers are effective antihypertensive agents, but their cell protective properties are not investigated well. Spontaneously hypertensive rats received a 10 mg/kg/day amlodipine dose and 25 mg/kg/day bisoprolol dose via an orogastric tube during three months. We performed examination of the myocardium's fragments under a scanning electron microscope. Morphometric investigation of mitochondrions we performed using special program what is named "ORGANELLE". Amlodipine significantly normalizes the ultrastructure of the myocardium. This antihypertensive drug prevented the signs of over-contractility of myofibrils. Amlodipine causes the fusion mitochondrions which has compensatory character on the background of good safety of mitochondrial ultrastructures. Another feature of amlodipine is a significant increase in the number of capillaries. Bisoprolol significantly reduced over-contractility of the myofibrils, but the signs of dystrophic-destructive processes in myofibrils and mitochondrions of cardiomyocytes remained. Bisoprolol improved the condition of the endothelial cells, but the activation of the functional activity of these cells has not been observed. The combined use of two antihypertensive drugs amlodipine and bisoprolol led to a better recovery of myofibrils than their separate use, whereas the effect on mitochondrions noted similar as in the group of rats received bisoprolol and that effect was worse than during amlodipine's monotherapy. Also we didn't reveal a reason to combine these drugs after analysis of the effect of the drug combination on the conditions of blood microvessels, which number was increased compared with hypertensive rats, but significantly less than when rats received only amlodipine. These essential cell-protective effects of amlodipine and bisoprolol in spontaneously hypertensive rats could be a significant additional factor in the treatment of hypertension complicated with pathological changes in the heart.

[Quantum-pharmacological aspects of cardiovascular drugs studying].

Quantum pharmacology allows to study the mechanisms of action of cardiovascular drugs, to predict pharmacological activity and identify the most pronounced pharmacodynamic efficacy and therapeutic activity of new compounds. Calculation of quantum-pharmacological parameters for molecules of beta-blockers (propranolol, atenolol, metoprolol, carvedilol) in aqueous media, research its hydrophobic interaction with receptors allow to form a theoretical basis for the development of new generations of more effective and safe medicines for hypertension treatment. Increased hydrophobicity leads to poor solubility of carvedilol in water and high--in the lipids. The clinical pharmacology of the drug is shown by such indicators as the therapeutic dose, half-life and degree of metabolism in the liver. Due to enhanced interaction with adrenergic receptor effective dose of carvedilol is an order of magnitude lower than other beta-blockers, even with the relatively low bioavailability. Reduced bioavailability of carvedilol versus atenolol, metoprolol and propranolol is caused by elevated metabolism during the first pass through the liver, which is also due to the hydrophobicity of the drug. High solubility in lipids appears to extend the half-life of carvedilol. QSAR studies make an important contribution to the study of the properties of chemical compounds and their pharmacological activity. Software, used for computation of studied properties, has a significant role. A large number of descriptors allows a qualitative and quantitative assessment of the molecules of chemical compounds and prediction of their influence on cardiovascular system.

[Effectiveness of use of omega-3 polyunsaturated fatty acids at physical loads].

On the basis of results of quantum-chemical researches with the analysis of atomic structure of molecule, it is shown that polyunsaturated omega-3 fatty acids have the expressed antioxidant and membranoprotective properties that with bioantioxidants karotenoids--tocopherols--are similar. At application in the sportsmen of medical drug Epadol on the basis of polyunsaturated omega-3 fatty acids it is shown that it brakes the activity of lipid peroxidation simultaneously, that is represented by reduction of maintenance of malonic dialdehyde as one of his eventual foods, and assists the improvement of antioxidant defence, that it contingently the increase of concentration of recovered glutathione in the membranes of red blood cells. Under the action of this medical drug the prooxidative-antioxidative coefficient for sportsmen goes down from 2.44 to 1.34 that specifies on a presence at Epadol of antioxidant properties. At the same time sorption ability of erithrocytes, characterizing functional properties of their membranes under act of Epadol goes down from 35.04 +/- 2.23% to 25.3 +/- 1.07% that counteracts to aggregating of red blood cells. An expediency of application of Ukrainian medical drug Epadol on the basis of polyunsaturated fatty acids in practice of preparation of sportsmen for normalization of structural and functional status of cell membranes as well as of prophylaxis noncontrolled apoptosis come into question.

Wave properties of nanoparticles: the view of a problem.

The results of studies on nanopharmacology have made conditions to develop a hypothesis: from the standpoint of quantum mechanics an increase in pharmacological properties of nano- particle based medications is driven by the preponderance of wave properties over corpuscular ones. According to results obtained the changes of spin states in molecules is one of the es- sential properties of living matter, which is characterized by self-organization. Self-organiza- tion is also common in nanostructur-es. Therefore, the quantum wave properties of nanopar- ticles with their high ability to change spin states determine pronounced pharmacological effect of nanoparticle based medications. At this stage of research the scientific facts received do not rise to the possibility to experimentally or mathematically justify the assumptions made, so pleasetake them for granted. I am convinced that this article will be the 'nanomotor' that will attract world's scientists to continue research in order to prove current hypothesis - the wave properties of nanoparticles determine their high activity - experimentally.

[Capillaries of living systems: natural nanomechanisms of the functioning].

This article summarizes the literature and research data that concerns role of capillaries in the functioning of natural nanomechanisms in living systems. Physiologically active substances the body--essential and non-essential amino-acids, neurotransmitters (epinephrine, norepinephrine, acetylcholine), vitamins (retinol, ergocalciferol, etc.), albumin, ATP, DNA, RNA, fibrinogen and others--are at the nanoscale size. Natural nanostructures are ion channels of biological membranes, colloidal solutions of the body (blood, interstitial fluid). Only in recent years, scientists have begun to more actively explore the role of capillaries in the functioning of organs and body with position of natural nanomechanisms. To the nanomechanisms in functioning capillaries in the body of living systems maybe contribute: wall capillaries, vascular endothelium, as nanostructures, capillary forces, biological nanomotors, ion channels, surface tension and surface energy of nanoparticles, and such processes and phenomena as nanohydrophobic shift or "lotus-effect" double electric layer, entropy that occur in the structures of the body. The significance of water flow processes in capillaries studied enough. Establishing nanomechanisms in functioning capillaries in living systems requires an interdisciplinary approach involving different specialists in physics, chemistry, biology, physiology, pharmacology and toxicology.

[Carbonology: pharmacochemical aspect and research prospects].

The paper is devoted to the new direction of science - carbonology. Carbon is the base of organic compounds. Compounds of carbon with metals are known. The article gives a brief description of the three allotropic forms of carbon (soot, graphite, diamond), and various types of hybridization in organic structures, describes the role of biogenic carbon. At the end of the twentieth century new carbon nanostructures were discovered: fullerenes and carbon nanotubes. Scientists all over the world study physical, chemical, pharmacological and toxicological properties of the allotropes of carbon structures, which are promising for nanochemistry, nanopharmacology and nanotoxicology. The main characteristics of fullerenes are the high electrical conductivity, antiviral, antioxidant properties and possible use for targeted drug delivery. Carbon nanotubes have strong adsorption properties, high electrical conductivity, strength, are used for targeted drug delivery and the production of biosensors. In order to introduce carbon nanoparticles in the practical medicine it is necessary to intensify research to biosafety.

[Quantum-chemical basics of pharmacokinetics (literary review and own investigations)].

The work is devoted to the use of quantum-pharmacological approaches in pharmacokinetic investigations. The main objective of the pharmacological researches is to find new, more active and less toxic drugs. To date, such a search is carried out empirically. The current approach can not fully meet the needs of medicine in the new drugs, requires considerable time and financial costs and does not meet modern standards of bioethics. Quantum pharmacology leads to the synthesis of drugs with desired properties is much faster and more efficient. Computer prediction of pharmacokinetic and biopharmaceutical properties of biologically active substances can make 50-70% more effective development of original drugs.

[Natural nanotechnologies in living cell: view on the problem].

Literature and research data concerning natural nanotechnology in living systems is summarized in this article. Over millions of years, nature has evolved complex processes controlling the functioning of living organisms. Using the principles of nature to create new tools and technologies is the current direction in the development of "smart" materials and systems. Physiologically active substances (amino acids, neurotransmitters, vitamins, albumin, ATP, fructose, DNA, RNA, fibrinogen, glutathione and others) are nano in size. Biological membranes, ion channels, nanopores, colloidal solutions of the body (blood, interstitial fluid) are nanostructures. The basic principle of nature reads: small tools make great work. In biological materials natural principle of high efficiency and minimum energy consumption is carried out due to the existence of natural nanotechnology that needs more study. In efficient energy-consuming processes during the evolution gradually disappeared and were replaced by more effective. The study and experimental proof of natural nanotechnology will bring a better understanding of the laws of physiological functioning of organs and those of metabolic processes that maintain life. The ability to reproduce biological form with nanoscale precision will find application in tissue engineering, drug delivery, modeling and development of sensory and immune systems, visualization and diagnostic tools. Natural nanotechnology is highly effective, low energy-consuming, causes a rapid flow of vital processes in the body, the ability to quickly response to external positive and negative factors. Not all data presented in this paper is experimentally confirmed, it may be controversial and require further extensive research by specialists of different areas to determine the role of nanotechnology and nanomechanisms in physiological, biochemical, immunological, genetic and other processes in living systems.

The prospects of medical application of metal-based nanoparticles and nanomaterials.

Current studies, dedicated to metallic (gold, silver, iron, and copper) nanomaterials are reviewed in this paper. This metals own unique physical and chemical properties which determine their application. The medical application of metallic nanomaterials includes therapy and prophylaxis of diseases, development of new drugs and improvement of conventional ones, nanodiagnostics. Nevertheless some aspects concerning the introduction of the nanometals into medical practice need further profound research.

[Compressive therapy of lymphedema].

Lymphedema is a simple complication after mastectomy. On current data there are two main methods of treatment of this disease that include different physical exercises, massage, compression of the edematous tissue and limb bandaging. One of this methods is based on the serial compression of the limb with an intermittent pump that is followed by physical exercises. Another method is known as the complex decongestive therapy (CDP) by Földi. Individual treatment program is worked out for each woman. The positive effect of treatment can be reached after a year of strict adherence to the program.

[Structure and function of biomembranes: influence of nanoparticles].

The up-to-date view on a biomembrane structure and functions and the role of lipid, protein and carbohydrate biomembrane components in maintenance of a cell vital activity is summarized in this article. The up-to-date model of a biomembrane structure as a nanocompartmentalized fluid in which lipids and proteins undergo anomalous diffusion is examined. An attention is paid to lipid rafts existence as nanoscaled membrane domains. The analysis of literature and research results concerning the nanonature of ion channels and the mechanism of influence of nanoparticles on a biomembrane is carried out. It is shown that the data on structure and functions ofa biomembrane and the nature of influence of nanoparticles on it is necessary to create new high-performance therapeutic agents, diagnostic tools and to study nanoobjects' toxicological properties.

[Pharmacological and pharmaceutical foundation of nanodrugs].

Literary data and results of own investigations about pharmacological and pharmaceutical grounds of nanodrugs are analyzed in the article. Main requirements to nanodrugs are summarized. (1) To have much more expressed effect in comparison with drugs used in a medicinal practice. (2) New nanodrug mustn't have adverse reactions. (3) Nanodrugs must decrease adverse effects of other drugs. (4) Nanodrugs mustn't negatively influence on clinic-pharmacological properties of drugs used in medicinal practice forthe treatment of different disorders. (5) One of the requirements to nanodrugs is positive pharmacoeconomic parameters. (6) Medicinal form of nanodrug must be usable for different ways of drug administration. (7) Technology of drug production should be inexpensive, without negative influence on ecology. Comprehensive experimental researches of nanoparticle pharmacodynamics and pharmacokinetics in the human body and its influence on environment should be done. A new technology of obtaining nanoparticles of iron oxide, silver, copper and their composites has been developed in the laboratory of electron-beam nanotechnology of nonorganic materials for medicine. It was shown, that nanoparticles of iron and silver oxide have more significant antimicrobial activity than oxides of these metals in normal size.

[Using nanotechnology and nanomaterials in ophthalmology].

Peculiarities of anatomy, histology and physiology of eyes, do not allow to create an effective concentration of a medication in damaged tissues by traditional methods. Therefore, effective remedy delivery to a pathological focus is an current issue for ophthalmologists, pharmacologists and pharmacists. One of the perspective ways to solve this problem is nanotechnology. The use of nanomaterials (nanoparticles, dendrimers, cyclodextrins, liposomes, niosomes, diskomes), medicine formulations (microemulsions, hydrogel systems, nanosuspenisons) and ways of medicine delivery and nanomaterials (contact lenses, microneedles, intraocular implants, iontophoresis), open new possibilities in the treatment of serious eye diseases, such as glaucoma, diabetic retinopathy, macular degeneration, uveitises of different etiology. It will establish new high level therapy standards in ophthalmology in future. Aspects of possible complications and long-term effects of application of these technologies are still poorly explored and need further development and improvement. Despite of it, this new direction of the treatment in ophthalmology is very important and perspective.

[Lymphedema: clinic-therapeutic aspect].

Lymphedema may be presented in mild or less severe form. Nowadays, accurate diagnosis and effective therapy are available. Wearing surgical bandage, massage, exercise, and pumps form the core program for most patients with lymphedema. The application of pharmacological therapies has been notably absent from the management strategies for lymphatic vascular insufficiency states but lately some progress has been made by applying wobenzym in the treatment. Surgical approaches to improve lymphatic flow through vascular anastamosis have been, in large part, unsuccessful, but controlled liposuction affords lasting benefit in selected patients.

[Physiological processes in organism: nanomechanism].

Physiologically active substances by nanosizes are divided into 4 groups. The first group includes substances up to 100 nm: leukocytes, erythrocytes, cell components (nucleus, mitochondria), cancer cells, bacteria and bacteriophages. The second group consists of nanoparticles with size from 10 to 100 nm. These are antibody, ribosomes, glycogen granules, liposomes, and others. The third group of substances has sizes from 10 to 1 nm. This group includes: albumin, hemoglobin, membrane cells, fibrixogen, receptors (serotonin, beta-adrenergic receptor and others), insulin, fat soluble vitamins (ergocalciferol, retinol), folic acid, drugs (digoxin, quetcitin), chlorophyll plants, fullerenes. The fourth group consists of matter smaller than 1 nm, in particular: ATP, fructose, mediators (acetyl-choline, adrenaline, noradrenaline), phenylephrine, amino acids, water molecules, CO2, NO, oxygen atoms, hydrogen. The existence in the body of physiological processes based on natural nanotechnology may be proved by the following facts. 1. Physiologically active substances have nanosizes. 2. Cell membranes, the capillary wall have also nanosizes, promoting effective physiological processes involving biologically active substances with nanosizes. 3. Due to the small size of nanoparticles can penetrate through cell membranes and be distributed in the body. 4. From the position of modern nanoscience functioning organs, cells, subcellular structures, calcium channels, sodium-potassium pump is under the laws of natural nanomechanisms. 5. Summarising the literature data and own research, we can argue that the body's physiological processes based on natural nanomechanisms require more detailed, in-depth research. Nanophysiology studies peculiarities of the physiological processes in the body from the position of nanoscience and the impact of nanoparticles on the function of cells and organs. The author accepts the fact that not all ideas reported in this article have experimental confirmations, discussion is necessary for further comprehensive research, specialists of different directions to discover the role of nanomechanismes in physiological processes in the body.

[Nanoparticles: properties and application prospects].

A new trend of scientific-technical and medical researches has been formed which unites nanoscience, nanotechnology, nanomedicine, nanopharmacology. Nanoparticles are the main product of nanotechnologies. Nanoparticles are organic and inorganic structures, their size being less than one hundred nanometers (nano from Greece nanos--a dwarf; particle is a separate unit which is separated from the whole). Prefix nano means 10(-9) m. Nanosizes are values from 1 to 100 nanometers, micro-sizes--from 100 to 1000 nanometers, and above 1000 nanometers--are macrosizes. By the data of Internet for 1.08.20.2008 there are 18512 papers in the world scientific literature (8663 of them were published during the last 2.5 years), where properties of nanoparticles which are obtained by different nanotechnological methods are described. Actually, quantity of works concerning nanoparticles is much more because not all publications are cited in Internet. The first publication concerning a characteristic of nanoparticles was published in 1978. The survey generalized the data of scientific literature and author's investigations which concern sizes of nanoparticles of biologic molecules and their properties.