РАЗРАБОТКА РЕЦЕПТУРЫ И ТЕХНОЛОГИИ ПЕНООБРАЗОВАТЕЛЯ ИЗ МАСТИЧНОЙ (PISTACIA LENTISCUS L.) КАМЕДИ.

An acid fraction derived from the evergreen plant of Mastic gum(Pistacia lentiscus L., family Anacardiacae, genus Pistacis L.) has been found to have bactericidal activity against 11 strains of Helicobacter pylori. However its healing potential is significantly reduced by poor solubility and low biological penetration. Therefore, the current problem is to develop a system that provides increased penetration of the drug into the stomach through the epithelial barrier. Foams are especially interesting in this regard. Foams are light systems, they do not swell, on the contrary, they grow in volume, completely covering the mucous membrane. The foams do not require taste correction and are designed to deliver a therapeutic substance from the skin and mucous membranes and provide an effective treatment. The aim of the research was the determination of formulation and development of technology of innovative medicinal form from Mastic gum. Based on biopharmaceutical studies, the formulation of capsules containing a foaming powder composition was determined: Mastic gum 250.0; Sodium lauryl sulfate (SLS) - 9.0; Lecithin - 12.6; Xanthan 4.5; Gelatin 4.5; Isomalt 90.0; Dry egg whites - 41.0; Sodium bicarbonate - 21.0; Citric acid - 6.0; Metocell M102 - 10.0; Talc - 1,4. The technology of preparation of Mastic gum foaming powder containing capsules has been developed.Foaming capsules containing Mastic gum, in artificial gastric juice, with foam-forming ability and foam stability meet the standard requirements for foam systems.

THE MECHANISMS CONTRIBUTING TO THE DEVELOPMENT OF ARTERIAL HYPERTENSION, ADVANTAGES AND DISADVANTAGES OF THE ASSOCIATED EXPERIMENTAL MODELS (REVIEW).

Arterial hypertension is one of most common diseases in the world with variable etiologies, yet the exact cause cannot always be found. It is classified as essential (primary) or secondary hypertension. Unlike secondary hypertension, primary hypertension has no known cause. Animal models have been used to investigate the pathophysiology of the disease and for testing new treatment strategies. Using animal models to better understand the etiology, prevention, and treatment of hypertension depends on their accuracy for representing human disease. Current challenges in this field include the development of models mimicking the common hypertensive syndromes and the development of new prevention and treatment strategies. Animal models may be beneficial to address these challenges. While choosing the appropriate model of hypertension, scientists need to choose between small and large animal models. The research scope and objectives, experimental expenses, animal welfare, and practical suitability should all be considered. The advantages and disadvantages of these models need to be assessed in detail in order to select the best model. From the many models of arterial hypertension, it can be distinguish different models of essential and secondary arterial hypertension. Of the essential arterial hypertension three main methods are noteworthy, pharmacological, environmental conditions, and genetic model. As for secondary hypertension, it can be challenged by physical methods such as renal artery clipping or its microembolization.

MEDICATIONS FOR ERADICATION OF HELICOBACTER PYLORI (REVIEW).

Helicobacter pylori is a pathogenic microorganism that causes gastritis, duodenitis, peptic ulcer disease of the stomach and duodenum. Recent data confirm the close association of Helicobacter pylori with the development of gastric cancer. Due to the failure of standard H. pylori eradication regimens, intensive studies are being conducted to develop targeted local delivery and prolonging activity drug forms. Based on scientific studies, sufficient knowledge has been accumulated on the inhibitory action of biologically active substances of plant origin: peptides, polyphenols, terpenes, fatty acids on Helicobacter pylori, which allows developing an alternative treatment scheme. It is especially important today to create local and long-acting, high-density, mucoadhesive, floating and swelling systems. Unlike other forms of medicine, foam systems are interesting in this respect. They are distinguished by a large touch surface, high bioavailability and rapid therapeutic effect. Foam provides economical dosing, better contact with the mucous membrane, and give the drug a prolonged action. Under the influence of body temperature the foam increases in volume, filling all free spaces and channels. However, the foam can provide high concentrations of the medicinal substance for up to 4 hours.

ANTIHYPERTENSIVE AND CARDIOPROTECTIVE EFFECTS OF EPOXYEICOSATRIENOIC ACID ANALOGS AND SOLUBLE EPOXIDE HYDROLASE INHIBITORS (REVIEW).

In the present article is considered antihypertensive and cardioprotective action of epoxieicosatrienoic acids (EETs) analogues and soluble epoxide hydrolase (sEH) inhibitors. Being epoxygenase products of arachidonic acid metabolism EETs provide a wide spectrum of biological activity in different organs implicated in the regulation of arterial pressure, including vascular endothelium (VE), heart and kidney. EETs are acting as autocrine or paracrine agents producing vasodilation, reduction in salt and fluid retention. EETs exert vasodilatory properties by activation of the smooth muscle large conductance Ca2+ -activated K+ channels in different vascular beds. In experimental and clinical studies EETs provide beneficial influence in hypertensive states alleviating vascular endothelium function associated with reduction of inflammation and increased Na+ excretion, prevented cardiovascular and renal complications accompanied arterial hypertension (AH). In animals studies using Dahl-salt-sensitive (Dss) hypertensive rats EETs analogues displayed renoprotective effect, reducing mRNA expression of tumor growth factor-"B" as well as concomitant oxidative stress and fibrotic changes in the heart and kidneys. In cultered endothelial cells also was demonstrated anti-inflammatory action of EETs when they significantly decreased TNF-α-induced high level of monocyte chemoattractant protein-1, which was reversed by EETs antagonist. sEH is another new target for therapeutic intervention in cardiovascular diseases. In several experimental models of AH sEH inhibitors (sEHI) significantly reduce AP which was associated with their anti-inflammatory and renoprotective action. sEHI showed cardiovascular effect related to CYP2J2overexpression during myocardial ischemia-reperfusion injury. It should be noted that EETs demonstrate binding ability to PPAR receptor "Y" stimulating it's transcription process in endothelial cells facilitating by sEHI. It is suggested that EETs and sEH are involved in the regulation of the cardiovascular function playing significant role in vascular homeostasis.

THE RELATIONSHIP BETWEEN TYPE-2 DIABETES AND TUBERCULOSIS.

According to the experimental and clinical investigations, innate and adaptive immune disorders play a significant role in T2-D subjects to become more susceptible to TB. It was shown that the functions of neutrophils, macrophages, NK cells and other components of innate immunity areis markedly compromised by metabolic disorders in T2-D. The number of evidences suggests that reduction in TH1:TH2 cytokines ratios may have significant influence on susceptibility of TB infection in T2-D subjects. Hormonal changes in T2-D also may increase susceptibility to TB, including 2 hormones -ghrelin and leptin that are involved to in controlling blood glucose levels related to malnutrition during TB. According Based on the experimental and clinical results resistin, being a key molecule that links obesity and TB2-D, is considered as a protein contributing contributor to the development of insulin resistance, being a key molecule that links obesity and TB2-D. Subjects with T2-D showed higher levels of resistin in serum associated with reduced possibility of human macrophages to enhance the production of reactive oxygen species (ROS) in vitro against a challenge with TB. Immunological impairment has an important role in susceptibility to TB infection for patients with T2-D. It has been revealed that IFN-y and IL-22 markedly discriminate diabetes from nondiabetic individuals. It was also established that aside from this many cytokines such as IL-17A, IFN-B, TNFα, IL-10, IL-18, IFN-Y and IL-22 are the most significant and consequently potentially related to the effects caused by diabetes caused effects in the pathogenesis of active pulmonary TB. The endothelial system plays significant role in the pathogenesis and progression of TB infection. It was demonstrated that endothelin "B" receptor antagonist leads to vasoconstriction precluding inflammatory cell infiltration in lung tissue, suggesting that ET-1 proinflammatory action involves ET "B" receptor. It was also shown that sputum endothelin-1 level is associated with active pulmonary tuberculosis and effectiveness of treatment. Reduction ins sputum ET-1 level has significant role in the assessment of anti-tuberculosis treatment efficacy. Alterations in microbiota in T2-D subjects may influence on immunity against TB infection. As it was established the amount of bacteria producing short-chain fatty acids (SCFA) markedly decrease in T2-D, and treatment with SCFA reduced induction of TFN-α, IL-10 and IL-17 cytokines in contrast to IL-6, IFN-y and IL-22, without modification of their induction after using of SCFA. Vitamin "D" deficiency in T2-D may also play a role ion the immune response against TB. A number of evidences suggest the correlation between its diminished levels and TB or TB-T2-D. In conclusion it is suggested that different risk factors, including immunological and hormonal changes as well as alterations in different cytokine production and microbiota, endothelial dysfunction and vitamin "D" deficiency are the main contributors leading to comorbidity of T2-D and in TB.

ENDOCANNABINOIDS RECEPTORS MEDIATED CENTRAL AND PERIPHERAL EFFECTS (REVIEW).

The present article is devoted to the action of endocannabinoids via stimulation of their corresponding receptors. It is well established the existence of three type of endocannabinoids (ECS) such as anandamide (AA), 2-arachidonoylglycerol (2-AG) and palmitoylethanolamide (PE) providing their effects by activation of CB1 and CB2 ECS receptors. AA is a partial agonist for both receptors, having more affinity for CB1 receptors, while 2-AG reveals an equal agonistic properties to both of them in contrast to PE, which may bind to a unidental "CB2-like" receptors. CB1 receptors are distributed in the central and peripheral nervous system being identified in the greater amounts in the brain cortex, basal ganglia, spinal cord, cerebellum, hippocampus and olfactory areas, owing for the modulatory action of ECS on cognitive function, memory, behaviour, emotion and locomotor activity. Their location in the periaqueductal grey matter and dorsal spinal cord may explain their involvement in pain sensation and modulation. Colocallization of the CB1 receptors with the oroxinergic projection system in the lateral hypothalamus is responsible for their implication in feeding behaviour. CB2 receptors were found in the cells of immune system (spleen, macrophages). It should be noted that ECS may also play a role in the regulation of fertility and pre-and postnatal development. The stimulation of ECS receptors is associated with the activation of MAPK, PI/PKB and MEK/ERK signalling pathways with increased activity of different transcription factors. CB1 receptors are involved in neuronal exitability by decreasing synaptic input, implying retrograde transmission and presynaptic inhibition resulting in reduction of neurotransmitter release. In the article it is also described an ionic mechanisms of release of ECS and the steps of their synthesis as well as participation of a transporter in ECS uptaken process in neurons and astrocytes. Aside from this it is proposed the mechanisms of analgesic action of ECS especially concerning reduction in neuropathic pain in comparison to opioids and possible involvement of α2-adrenoceptors in antinociceptive activity of ECS. Some analgesic properties of ECS is due to their inhibitory action on cyclooxygenase-2 (COX-2). Recent evidences showed that regarding antinociceptive action of ECS along with CB1 receptors most significant receptors are PPAR-alpha and TRPV receptors. There are controversial data concerning the influence of ECS on cognitive function. Knockout mices with the absence of CB1 receptors have showed improved memory and long-term potentiation proofing the significant role of ECS in the disorders of "old memories". Some data suggests that genetic or pharmacological inhibition of COX-2 activity may reduce disorders in hippocampal long-term synaptic plasticity and fear memory, as well as supports improving effects of tetrahydrocannabinoids (THC) on neurodegenerative processes such as Alzheimer's disease, because THC facilitates to marked expression of an important endopeptidase neprilysin for degradation of AB proteins. A number of evidence indicates the possible involvement of ECS in schizophrenia and major depressive disorders. Assumingly such beneficial effect of ECS is associated with M1/M2 microglial polarization process. In conclusion it is suggested that ECS as natural ligand for their corresponding receptors provide wide spectrum of pharmacological effects may become an interesting targets for future therapeutic intervention.

MEDICAL BASIS OF DIABETIC NEUROPATHY FORMATION (REVIEW).

Nowadays, chronic diseases are leading cause of death worldwide. One of popular chronic disease of 21 century is Diabetes Mellitus (DM) that affected 422 million people around the world in 2014; its prevalence is expected to increase to 592 million by the year 2035. Diabetic neuropathy (DN) seems to be the most common and least understood complication being present in over 50% of chronic diabetics. As the latest date explain the pathogenesis of DN is not fully understood. Therefore, considering the widespread of DN, severity of its consequences, it is vital to investigate details of its pathophysiology and find therapeutic strategies to improve patients' condition. Generally two mechanisms have been suggested to be involved in the pathogenesis of diabetic neuropathy. The first mechanism is the activation of the Renin Angiotensin Aldosterone System (RAAS) in the presence of hyperglycemia with increased tissue level of Angiotenzin II (Ang II). Ang II stimulates Nicotin Adenine Dinucleotide (Phosphate) (NAD (P)) oxidase which enhances oxidative stress and vascular damage and leading to DN. The other mechanism is linked with disturbance in the metabolism and vasculature of nerve tissue in the presence of excessive uptake of glucose. Conclusion: In our review we have discussed different mechanisms involved in formation of DM and DN. Based on the latest research studies the main component in the big picture of DN formation is hyperglycemia.The list of mechanisms are associated with high glucose level leading inflammation, oxidative stress, hypoxia and apoptosis through the activation of several pathogenic pathways induced by Tumor Necrosis Factor alfa (TNFa), AgII, (pro)renin, Protein Kinase C (PKC), glycolysis intermediated products, Cyclooxygenase 2 (COX2) and reactive nitrogen species (RNS). Therefore to use drugs linked with above discussed pathological processes would be effective solution in the treatment of DM and its complications.

NICORANDIL EFFICACY IN THE TREATMENT OF ISCHEMIC HEART DISEASE (REVIEW).

Nicorandil is an antianginal agent with a dual mechanism of action. It belongs to ATP-senitive potassium channel openers which has the beneficial effect in angina pectoris, playing an significant role in the dilation of arteries, veins and coronary artery. It leads to the relaxation of vascular smooth muscle and causes vasodilatation of major epicardial vessels. This effect is crucial for reducing risks of further damage in cases when percutaneous coronary intervention (PCI) is necessary. Relevant new studies concluded that Nicorandil has antiarrhythmic and cardioprotective effects by improving reperfusion, ultimately leading to a reduction in microvascular damage caused by PCI. Furthermore, Nicorandil addition to the standard therapy of paitents with ischemic heart disease has demonstrated improved quality of life.

[Possible mechanism of hyperemia in the skin caused by non-painful mechanical pressure].

It is believed that hyperemia in the skin, resulting from applied weak mechanical pressure delays the development of ischemia, and that it is a defensive neurovascular reaction against the local pressure, which can be considered as a critical point in terms of prevention of ischemia and, respectively, the risk for development of bedsores. Taking into account that nitric oxide can be released from autonomic nerves and make a significant contribution to the functioning of the mechanism of neurogenic vasodilation in different tissues, and the fact that the same role can also play the calcitonin gene-related peptide, the aim of this study was to clarify the role of each of these factors in the development of local hyperemia caused by non-painful, mechanical pressure on the skin. In experiments on white rats with a quantitative measurement of the intensity of skin blood flow, it was confirmed that in case of non-painful pressure acting on the skin, two-phase reaction of local blood flow appears - at first there is an increase in its level, and then an exponential decrease with stabilization at a level below the initial one. Analysis of received data allow to make conclusion that in relization of this phenomenon the role of trigger element belongs to nitric oxide, and the role of the executing unit - to calcitonin gene-related peptide. The effectiveness of this combined mechanism is limited by development of dominance of pressor-induced mechanical compression of cutaneous vessels over its vasodilator effect.

[THE ROLE OF NITRIC OXIDE AND BLOOD RHEOLOGICAL PROPERTIES IN THE MAINTENANCE OF A TEMPERATURE HOMEOSTASIS IN THE BRAIN TISSUE].

The problem of temperature regulation in the brain tissue in conditions of whole body hyperthermia was investigated in experiments on white rats. The received results revealed that the brain is provided with a highly efficient system for temperature autoregulation against the changes in environmental temperature. According to our data the upper limit of this autoregulation (for rats, at least) is about the 450C of environmental temperature. The important role in functioning of this autoregulatory system belongs to Nitric Oxide. It is revealed also that the increase in the index of red cells aggregability may significantly hinder (among other things) maintaining of the temperature homeostasis in the brain.

[Study of anxiety level and passive avoidance response in rats that in neonatal period undergo the prolonged dexamethasone treatment].

The decrease in locomotor activity and the number of crossed sectors in open field, has been shown in the group of animals, which for four days in the neonatal period received dexamethasone treatment. Based on these data we decided in the same experimental conditions to study the animals' state of anxiety and the behavior in passive avoidance chamber. The newborn male pups were divided on four groups. The first group was left intact, the pups of the second group were injected by saline, the third group - by dexamethasone and the fourth group - with combination of dexamethasone and L-arginine. The received results show, that deficiency of nitric oxide in the early neonatal period caused by administration of dexamethasone led to statistically significant increase of anxiety level, but statisticaly significant changes in their behavior in a passive avoidance chamber was not observed.

[Possible role of nitric oxide in newborns weight gain disorder caused by prolonged dexamethasone therapy (experimental study)].

Experimental studies on rats revealed that the newborns growth retardation, caused by long-term treatment with Dexamethasone in the neonatal period, can be prevented by the simultaneous with dexamethasone administration of the nitric oxide donor--L-arginine. This indicates that the mentioned Dexamethasone-induced growth disorder is caused by inhibition of Nitric Oxide Synthases activity.

Mechanism of cardioprotective effect of adenocine and non-glycoside cardiotonic drugs during experimental chronic cardiac insufficiency.

The therapeutic action of adenocine during cardiac insufficiency (heart failure) caused by ischemic (stenosis) or reperfusion (removal of ligature) injury to the myocardium prevents depletion of ATP, the major energy source for myocytes in the right and left ventricles, and a drop in NAD/NADH ratio. The development of energy shortage during heart failure cannot be eliminated by ß-acetyldigoxin, levosimendan, or milrinone: the content of ATP in the right and left ventricular myocardium remained below the normal level by 28 and 29%, 37 and 33%, 32 and 28%, respectively; the NAD/NADH ratio of the energy supply system in cardiomyocytes did not return to normal. Adenocine increased the content of NAD to the normal level in both the right and left ventricles, while it remained below the normal level after administration of ß-acetyldigoxin (by 24 and 19.5%, respectively), levosimendan (by 27 and 29%), and milrinone (by 26 and 24%). In contrast to ß-acetyldigoxin, levosimendan, and milrinone, adenocine inhibited activity of poly(ADP-ribose) polymerase in both ventricles. It is concluded that adenocine directly inhibits the key enzyme triggering apoptosis; we also hypothesized that this drug activates the regulatory and signal mechanisms arresting apoptotic alterations in the myocardium during heart failure.

Comparative therapeutic efficacy of adenocin and non-glycoside cardiotonic drugs in chronic heart failure at rest and under conditions of heart overload.

Experiments were performed on the model of chronic heart failure. Functional capacity of myocardial structures under conditions of maximum pressure overload was within the upper limit of normal after treatment with Adenocin. The myocardial functional reserve and potential capacity index were shown to increase to normal under these conditions. Dobutamine, levosimendan, and milrinone increased functional capacity under conditions of maximum pressure overload. Treatment with adenocin restored diastolic function of the heart under conditions of maximum pressure overload. The end-diastolic pressure increased, but remained 1.7 times below the level observed in heart failure. After treatment with dobutamine and milrinone, the end-diastolic pressure (8th episode of ligation) did not differ from the level observed in heart failure, while after administration of levosimendan this parameter decreased by 31%. Contraction-relaxation coupling was completely restored under the influence of Adenocin in all episodes of ligation both before and after removal of the ligature. Nearly all animals with heart failure were resistant to 8 episodes of ligation after treatment with Adenocin (89 vs. 96% under normal conditions). Under these conditions, the survival rate of animals after administration of levosimendan, milrinone, and dobutamine was 65, 60, and 61%, respectively, (the mortality rate of animals with heart failure was 75%). Adenocin, a cardiotonic drug with cardioprotective properties, in contrast to other cardiotonic drugs, has a modulatory effect on the system of cell energy supply, restores myocardial reserves, and improves myocardial function under conditions of overload.

[Possible mechanism of behavioral disorders in rats under long term treatment with dexamethasone in neonatal period].

Despite the fact that the side effects of prolonged treatment with dexamethasone are well known, information about its effects on the central nervous system is very limited. Experimental study of long-term effects of dexamethasone administration in the neonatal period on behavioral activity of rats in the open field was conducted. Four groups of newborn males were selected from the offspring of pregnant rats. The first group was left intact, the animals of second group were injected saline solution, the third group - with the dexamethasone and the fourth group - along with dexamethasone received L-arginine. Tests in an open field for all groups of animals were carried out on the 45th (first test) and 60th (second test) days after birth. The results showed that the decrease in motor activity of animals and in the number of sectors crossed in the open field with a high statistical significance was observed only in the group of animals, which for four days in the neonatal period underwent dexamethasone treatment. At the same time, another group of animals, which was also injected dexamethasone in the same doses, but additionally was injected L-arginine, the behavior in the open field did not differ from the intact animals or animals which were injected (as a control) saline solution. It was concluded that it is the lack of nitric oxide in the early neonatal period, which occurs as a result of dexamethasone treatment that causes observed changes in animals' behavior.

Effect of combination of zafirlukast and quercetin on baroreflex sensitivity and endothelin production in rats with myocardial infarction.

The purpose of this study was to evaluate the influence of zafirlukast (Z), quercetin (Q) and their combination on baroreflex sensitivity (BRS), endothelin-1 (E1) plasma concentration and the severity of ventricular arrhythmias (VA) occurring during myocardial infarction (MI). In anaesthetized Wistar rats, MI was induced by ligation of the left anterior descending coronary artery (CAL). Animals were divided into the five groups: I--sham-operated (SO); II--CAL; III--CAL+Z (0.25 mg/kg intraperitoneally 1 hour prior and 12-24 hour after CAL); IV--CAL+Q (1.5 mg/kg by i.v. injection after anesthesia and every 24 hour during 72 hour); V--CAL+Z+Q as above. CAL after 1 hour was accompanied by high incidence of VA associated with a significant mortality (68% at 72 hour) as compared with SO rats. In survived rats BRS was greatly attenuated (0.44 +/- 0.08 ms/mmHg) vs. SO animals (0.92 +/- 0.14 ms/mmHg, p < 0.05) that correlated to increase E1 plasma concentration (9.2 +/- 0.6 pg/ml) vs. SO rats (2.9 +/- 0.4 pg/ml, p < 0.001). Q did not influence markedly on the severity of VA or rats mortality, while Z and Z+Q decreased mortality in rats in compare to II group of animals (from 68%-42% and 30%), increased the reduced BRS resulting from MI (+38.5% and +55.4%, p < 0.05) and blunted the increase of E1 (-34.8% and -43.5% respectively, p < 0.05). Our results suggested a possible beneficial combine action of Z and Q on MI.

[The role of seasonal circadian rhythms in hemodynamic regulation].

The review analyzes the possible role of multioscillatory circadian system in the seasonal circadian variability of basic indices of cardiovascular system and probable mechanisms of development of changes in diurnal rhythms of the organism. It was postulated the close relationship between hemodynamic parameters and homeostatic mechanisms of circulation. The destruction of relationship may initiate the development of pathologic condition - desynchronizes. Studies suggest a potential role of relationship between circadian rhythms and secretion of vasoactive peptides, such as angiotensine, endothelins, sodium uretic peptide, endothelial relaxing factor and enkephalins, the circadian rhythmicity of receptor. It is suggested the necessity of investigation of circadian hemodynamic rhythms during desinchronoses formation in purpose of rational pharmacotherapy of different cardiovascular diseases.

[The perspectives of using lectins in immunodiagnostic and gene therapy].

In this article review diagnostic value of protein group-lectins for practical oncology are presented. It is indicated, that with some carbohydrate structures lectins revealed the possibility of reversible and selective action and with earlier elaborated methods, which are based on identification of antigen determinants with antibodies, they can significantly increase of tumour diagnostic sensitivity and specificity. It is consider the mechanisms of relationship between so-called mannan-binding lectins and mannans or carbohydrate structures, which are formed from the mannose residue. The presense of such mannose-enrich structures is connecting with the process of blastomic transformation. It was shown experimentally, that mannan-bindig lectins are interacting with the carbohydrate chains of the markers of blastomic transformation, particularly with the cancer-embryonic antigen. It was established the markedly increase of lectins gene expression in transformated cells. The gene therapy, which comprises the deliver of therapeutic genes to cells and tissues by virus vectors and nonvirus systems is also analysed. The last of them are the most widely using ligands containing oligosaccharides, because on the surface of many animal origin cells were identified lectins-protein receptors. It is suggested the perspectives of using oligosaccharide probes, which are the ligands for endogenous receptors-lectins in tumour diagnostic and guiding transport of medicinal products.

[Imidazoline receptors].

An increasing number of studies suggest that the pharmacology and therapeutic potential of a family of imidazoline receptors continues to generate substantial interest of investigators. This review analyzes the functional role of imidazoline receptors, their subpopulation, distribution in the central and peripheral nervous system and action of related ligands. Besides to their brainstem location where I1-receptor sites play a significant role to regulate and modulate blood pressure, they also are found in different parts of brain with the highest densities in the striatum, pallidum, hippocampus, amygdala, substantia nigra, while I3-receptor sites were revealed in pancreas which enhances insulin secretion, I2-receptors are widely distributed in interpeduncular nucleus, arcuate and pineal gland and take a part in monoamine turnover. It is conclusion that imidazoline receptor in near future can become a therapeutic target in the treatment of diabetes, stroke, mood disorders and hyperalgesic condition.

The mechanisms of neurodegenerative processes and current pharmacotherapy of Alzheimer's disease.

An increasing number of studies suggest that current pharmacotherapy used in Alzheimer's disease (AD), in addition to having a symptomatic effect, also may interact with the ongoing neuropathological processes in the brain. The oldest hypothesis explain the cause of the AD is the "cholinergic hypothesis", which states, that AD begins as a deficiency in the production of acetylcholine (ACh). Interactions between the cholinergic and serotoninergic systems are believed to play a role in the mechanism underlying AD. The activation of NMDA receptors and increase in intracellular Ca(++) concentration play key role in the development of neurodegenerative processes. Potassium channels may also be involved in several other steps within the cascade that leads to neurodegeneration. In the development of AD a great role play an imbalance between anabolism and catabolism causes an accumulation of amyloid beta-peptide (Abeta), which is a proposed trigger of the onset of AD. There are various therapeutic strategies in current pharmacotherapy of AD. Major group is inhibitors of acetylcholinesterase--donepezil, galantamine, physostigmine. The new effective treatments of AD are NMDA glutamate receptor antagonist-memantine and potassium channel openers such as retigabine. Experimental study suggest, that neprilisin, a rate-limiting peptidase, decreases neurodegeneration.