PHARMACEUTICAL ACTIVATORS OF ATP-DEPENDENT POTASSIUM CHANNELS AS POTENTIAL NEPHROPROTECTORS AGAINST GLOMERULAR AND TUBULAR DAMAGE TO THE NEPHRON (REVIEW).

Considering the incidence, high risk of progression and severe consequences of renal pathology, a preventive therapy as well as correction of kidney dysfunction are issues of a great importance today. An essential condition for an improvement of nephroprotection is a determination of new mechanisms of disturbances and restoration of homeostatic kidney processes. A unique physiological role of ATP-dependent potassium (KATP) channels and their participation in adaptive-compensatory reactions substantiate the feasibility of search for effective nephroprotectors among pharmacological modulators of their activity. The goal of research - to generalize available scientific data concerning the influence of KATP channels activators on kidneys for prospective administration of these pharmacological class representatives in nephroprotection. Analysis of renal effects of KATP channels activators allows stating a fact of perspectivity of the further studies of these pharmacological class representatives as the potential nephroprotectors in glomerular and tubular damage of the nephron.

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.

[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.

Addictive potential of Tianeptine - the threatening reality.

A total of 24 patients (male volunteers), consumers of opiates in the past and suffering from Tianeptine abuse, were under clinical observation. The age range of patients was from 21 to 33 years. Tianeptine consumption history was 5 months duration on the average. The daily dose of preparation was 40 tablets (500 mg intravenous injections on the average). Patients used Tianeptine in combination with antihistamines (Promethazine, Suprastin). Research was carried out with the use of clinical, psychological and laboratory methods. Has been used Ch. Spilberger's scale of anxiety and T. Balashov's scale of depression. Comparison of withdrawal syndrome developed after cessation of Tianeptine and opiates consumption has shown that in case of Tianeptine, in the dynamic of withdrawal syndrome predominates well expressed high-level of anxiety and depression, while at opiates consumption - withdrawal syndrome is characterized by algesic events and vegetodysfunctions. Supposedly, Tianeptine, in contrast to other anti-depressants, stimulates release of neurotransmitter dopamine in nucleus Accumbens, that probably determine addictive potential of this drug. High level of anxiety, excitability and vegetodysfunctions, presumably could be explained by activation of the NMDA (glutamate receptors) receptor system in Locus coeruleus, and in vegetative ganglion. In the present article potential threat that may develop at Tianeptine consumption, especially in former opiate consumers, without medical purposes has been emphasized.

Mechanisms of lead-induced poisoning.

Lead is a ubiquitous environmental toxin that is capable of causing numerous acute and chronic circulatory, neurological, hematological, gastrointestinal, reproductive and immunological pathologies. The mechanism of lead induced toxicity is not fully understood. The prime targets to lead toxicity are the heme synthesis enzymes, thiol-containing antioxidants and enzymes (superoxide dismutase, catalase, glutathione peroxidase, glucose 6-phosphate dehydrogenase and antioxidant molecules like GSH). The low blood lead levels are sufficient to inhibit the activity of these enzymes and induce generation of reactive oxygen species and intensification oxidative stress. Oxidative stress plays important role in pathogenesis of lead-induced toxicity and pathogenesis of coupled disease. The primary target of lead toxicity is the central nervous system. There are different cellular, intracellular and molecular mechanisms of lead neurotoxicity: such as induction of oxidative stress, intensification of apoptosis of neurocites, interfering with Ca(2+) dependent enzyme like nitric oxide synthase. Population studies have demonstrated a link between lead exposure and subsequent development of hypertension and cardiovascular disease. The vascular endothelium is now regarded as the main target organ for the toxic effect of lead. Lead affects the vasoactive function of endothelium through the increased production of reactive oxygen species, inactivation of endogenous nitric oxide and downregulation of soluble guanylate cyclase by reactive oxygen species, leading to a limiting nitric oxide availability, impairing nitric oxide signaling. This review summarizes recent findings of the mechanism of the lead-induced toxicity and possibilities of its prevention.

Effects of carvedilol, losartan and trimetazidin on functional parameters of isolated heart of rats at oxidative stress.

Effects of carvedilol, lozartan and trimetazidin on functional parameters of isolated heart (heart rate and volume speed of coronary blood flow) of rats at oxidative stress have been studied with the use of Langendorf's method. Experiments have been carried out on 32 pubertal white rats (with body mass 220-250 g). Oxidative stress was induced through perfusion of hydrogen peroxide (with concentration - 4.10 -5 M). Obtained results were analyzed statistically according to the Student's t criterion. Studies have shown that carvedilol and trimetazidin have well expressed antioxidant and cardio protective effects at oxidative stress provoked by hydrogen peroxide compared to lozartan. Moreover, effect of carvedilol on HR and VsCBf was especially obvious than effects of Trimetazidin. Antioxidant and positive treatment effects of carvedilol could be explained by its wide range of pharmacological ability: as nonselective beta-adrenoblocker (via inhibition of adenylatecyclase and decreasing cyclic adenosinemonophosphate), alpha 1-adrenoblocker (decreasing activation of phospholipase C and concentration of inositoltriphosphate, diacylglicerole and Ca(++)) and antioxidant. It is suggested that positive effects of carvedilol on HR and VsCBf at oxidative stress are related with wide range of pharmacological mechanisms of preparation. Cardio protective effects of carvedilol at oxidative stress (revealed in our experiments) along with other positive cardio - hemodynamic peculiarities perhaps is very important and could be used successfully at treatment of cardio-vascular system diseases.

The environmental contexts of early human occupation of Georgia (Transcaucasia).

The hominid mandible and a third metatarsal found in Dmanisi (Republic of Georgia) are accompanied by a rich faunal assemblage and a core-chopper stone tool industry. The mandible represents a somewhat isolated morphological type of Homo erectus that appears, given the combination of its primitive and advanced traits and specific dental morphology, to be a forerunner of both late H. erectus and early archaic H. sapiens. The faunal assemblage mostly consists of Villafranchian mammals, with the majority of the species assigned to an early phase of the Upper Villafranchian (Late Villanian and Early Biharian). Faunal and paleobotanical evidence as well as the depositional nature of the site indicate that hominid occupation took place in a mosaic environment of open steppe and gallery forests. Both the concentration of resources and the warm climatic conditions in the Dmanisi region at the beginning of the early Pleistocene were favorable for hominid occupation. It is possible that hominids reached the Caucasus through the Levantine corridor, and that the environment of this region allowed them to establish a stronghold and later colonize adjacent areas.

Earliest Pleistocene hominid cranial remains from Dmanisi, Republic of Georgia: taxonomy, geological setting, and age.

Archaeological excavations at the site of Dmanisi in the Republic of Georgia have uncovered two partial early Pleistocene hominid crania. The new fossils consist of a relatively complete cranium and a second relatively complete calvaria from the same site and stratigraphic unit that yielded a hominid mandible in 1991. In contrast with the uncertain taxonomic affinity of the mandible, the new fossils are comparable in size and morphology with Homo ergaster from Koobi Fora, Kenya. Paleontological, archaeological, geochronological, and paleomagnetic data from Dmanisi all indicate an earliest Pleistocene age of about 1.7 million years ago, supporting correlation of the new specimens with the Koobi Fora fossils. The Dmanisi fossils, in contrast with Pleistocene hominids from Western Europe and Eastern Asia, show clear African affinity and may represent the species that first migrated out of Africa.

A Plio-Pleistocene hominid from Dmanisi, East Georgia, Caucasus.

Archaeological excavations at the mediaeval site of Dmanisi (East Georgia) revealed that the town was built on a series of deposits yielding Late Villafranchian mammalian fossils and led to the discovery in late 1991 of a well preserved early human mandible. Dmanisi, where excavations are being carried out by a joint expedition of the Archaeological Research Centre of the Georgian Academy of Sciences and the Römisch-Germanisches Zentralmuseum (Mainz, Germany), is located southwest of Tbilisi, at about 44 degrees 20'N, 41 degrees 20'E (Fig. 1). The fossils date to the latest Pliocene (or perhaps to the earliest Pleistocene), probably between 1.8 and 1.6 million years ago (Myr). Here we identify the mandible as belonging to the species Homo erectus, of which it is the earliest known representative in western Eurasia. It shows a number of similarities to the African and Chinese representatives of this species.