[Pharmakological characteristic of some amide local anesthetics, currently used in dental clinics].

Along with the brief history of amide local anesthetics development, their most important properties (from the viewpoint of use in clinical dental practice), are also reviewed. In particular, some properties of most commonly used local anesthetics, such as lidocaine, mepivacaine, prilocaine, bupivacaine and articaine are analysed. The most important data concerning pharmacological mechanisms of mentioned anesthetics' action, that cause certain features and peculiarities of their clinical application are given in condensed form. Besides, some precaution measures that must be taken into account in specific clinical cases together with the history and current status of each patient are mentioned as well.

[Peculiarities of metabolic syndrome and nonalcogolic fatty liver disease in menopausal women].

Correlation between menopause metabolic syndrome and nonalcogolic fatty liver disease (NAFLD) is reviewed. NAFLD refers to a wide spectrum of liver disease ranging from simple fatty liver (steatosis), to nonalcoholic steatohepatitis, to cirrhosis. The causes and pathogenetic factors of the disease are still under investigation. The risk of development of NAFLD during menopause is twice higher in comparison with fertile age and abdominal obesity and insulin resistances is more apparent. This feature is associated with deficit of estrogens during menopause, as risk of development of NAFLD is diminished with substitutive hormonotherapy. The obesity, particularly in the period of menopause, is discussed as additive, independent risk factor of metabolic syndrome and of diseases of hepatobiliare and cardiovascular systems.

[Treatment of nonalcogolic fatty disease of liver].

The experimental and clinical data concerning of treatment of nonalcogolic fatty liver disease (NAFLD) are summarized and analyzed in the review. Some aspects of pathogenetic pharmacotherapy of NAFLD have been discussed (correction of insulin resistance, obesity, dislipidemia, oxidative stress, hepatoprotectors, restoration of intestine microbiosis, replacement hormonal, syndrome and antihypertensive drugs). Medical and non - medical methods of treatment is compared. It is concluded that further study to improve methods of prevention and treatment of NAFLD are required.

[Antidiabetic activity of berberin and extract, obtained from the bark of Phellodendron lavalei, introduced in subtropic regions of Georgia, in streptozotocin induced diabetic rats].

The goal of the study was to identify antidiabetic impact of berberin and extract, obtained from the bark of Рhеllodendron lavalei, introduced in subtropic regions of Georgia. The study was conducted on Streptozotocin induced diabetic rats. Diabetes in animals was induced by single intraperitoneal injection of streptozotocin in 1M citrate buffer, pH 4.5, dose 40 mg/kg per body weight, 1 ml volume. Treatment was conducted using berberin hydrochloride dose 150 mg/kg and extract of the bark of Рhеllodendron lavalei dose 400 mg/kg per orally, on an everyday basis, once a day during 3 weeks. The following indicators were measured: weight gain during the observation period, amount of food intake g/day, food efficiency ratio (%), relative mass of internal organs and blood glucose level. Blood glucose level was measured after 3 weeks from the day experiment started, after fasting all night. It was determined that per oral administration of berberin hydrochloride dose 150 mg/kg and extract of the bark of Рhеllodendron lavalei dose 400 mg/kg, during 3 weeks caused decrease in blood glucose level in streptozotocin induced diabetic rats. The marker of this efficacy was improvement of symptoms: decrease in hyperglycemic values, decrease in polyuria and polyphagia and relative weight of kidneys and heart, improvement of food efficiency ratio and mark decrease of weight loss. It should be noted that berberins antidiabetic activity was more marked. It is suggested that medicinal plants containing studied active components can be used as a crude drug for obtaining medicinal agent of promising antidiabetic phytotherapy and along with standard treatment can be used against metabolic syndrome and prevention of diabetes type 2.

[Changes of metabolic indices caused by berberin and extract, obtained from the bark of Phellodendron lavalei, introduced in subtropic regions of Georgia, in streptozotocin induced diabetic rats].

The goal of the study was to identify changes in lipid metabolism, functional condition of liver and kidney influenced by berberin and extract, obtained from the bark of Рhеllodendron lavalei, introduced in sub tropic regions of Georgia, in streptozotocin induced diabetic rats. Diabetes in animals was induced by single intraperitoneal injection of streptozotocin in 1 M citrate buffer, pH 4.5, dose 40 mg/kg per body weight, 1 ml volume. Treatment was conducted using berberin hydrochloride dose 150 mg/kg and extract of the bark of Рhеllodendron lavalei dose 400 mg/kg per orally, on an everyday basis, once a day during 3 weeks. Afterwards the concentrations of the following agents were measured in blood: glucose, uric acid, creatinine, AST, ALT, bilirubin, triglycerides, cholesterol and high density lipoproteins. It was determined that per oral administration of berberin hydrochloride dose and extract of the bark of Рhеllodendron lavalei during 3 weeks caused decrease in blood glucose level, improved morpho-functional characteristics of liver and kidneys, and modulated lipid spectrum in streptozotocin induced diabetic rats. In conclusion we can suggest that these phytodrugs can be a valuable asset to the treatment of metabolic syndrome and prevention of diabetes type 2, associated with metabolic and systemic disorders.

[Pharmacotherapy and prevention of osteoporosis].

In the article data regarding pharmacological prevention of primary osteoporosis is reviewed. Some main aspects of the disease are underlined. The primary prevention of osteoporosis is targeted on building up and sustaining the strength of the skeleton during different periods of human life. The secondary prevention is aimed to avert the fractures in the case of developed osteoporosis. The main mechanism of fracture risk lowering is prevention of bone mineral density (BMD) reduction. The prevention is based on risk-factor modification. It is important, that success during prevention of osteoporosis may be reached, if the group with high risk of disease development will be identified in time. In the article the risk-groups for BMD determination, the WHO criteria of disease diagnostics, as well the prevention approaches--healthy life style promotion and pharmacological prevention were presented. The main group of agents acting against bone resorption: bisphosphonates (BP), calcitonin, hormone replacement therapy, selective modulators of estrogen receptors, as well as fluorides stimulating bone production and recombinant agent of parathyroid hormone--teriparatide were discussed. Bisphosphonates are most powerful inhibitors of bone resorption and are discussed as first line agents for prevention and care of osteoporosis. At present, there are a large number of antiresorptive agents, with different pharmacodynamics and pharmacokinetics and the task for physician is to define the correct treatment in each case.

Rational drug correction of systemic inflammatory response syndrome in severe experimental heart failure.

A course of adenocine (cardiotonic drug with a pronounced cardioprotective effect) for severe experimental heart failure caused by toxic allergic myocarditis (for 10 days) more effectively restored the systolic and diastolic function of the heart and arrested systemic inflammatory response syndrome than traditional therapy with angiotensin-converting enzyme inhibitors, beta-adrenoblockers, or diuretics in combination with neoton. Adenocine is characterized by a synergistic effect, and none of its ingredients alone (nicotinamide adenine dinucleotide, inosine, beta-acetyldigoxin, oxyfedrine) exhibits similar effect.

[Influence of different type beta-adrenoblockers on functional state of liver at paracetamol induced toxic hepatitis in experiment].

The aim of the present work was comparative analyze of different type beta-adrenoblockers (nonselective beta-AB-Propranolol; cardio selective beta1-AB-Bisoprolol; nonselective beta-AB with additional vasodilatory effects - carvedilol) on functional state of liver at Paracetamol induced toxic hepatitis in experiment. Experiments were carried out on 42 laboratory white rats with the body mass 180-200 g. Model of acute toxic hepatitis was created using paracetamol (peroral administration with the dose of 1000 mg/kg, once a day). Beta-adrenoblockers (beta-AB) were used with following dozes: propranolol -1,4 mg/kg; bisoprolol - 0,7 mg/kg and carvedilol - 0,9 mg/kg; beta-AB were used during 9 days (perorally), immediately after paracetamol administration. Each group consisted of 7 rats. Functional state of the liver was estimated according to blood serum concentration of aspartat-transferase (AST) and alanin-transferase (ALT) using routine method of measurement on 5th and 9th days after administration of paracetamol. Results of experiments have shown that single administration of paracetamol with the dose of 1000 mg/kg impaired functional state of the liver that was confirmed by significantly increased activation of transaminases. It was stated that non-selective beta-AB Propranolol worsens-, cardio selective beta1-AB Bisoprolol - has no effect, while nonselective beta-AB carvedilol, with additional vasodilatory and antioxidant effects - slightly improves functional state of the liver at acute toxic hepatitis caused by paracetamol. Has been suggested that hepatotoxicity is not characteristic for all types of beta-AB. According to the obtained results, it has been recommended to estimate functional tests of the liver before propranolol administration, and carry out monitoring of the liver's functional state at treatment course, especially in individuals suffering with liver malfunction. It is important to investigate detailed mechanisms of hepatotoxicity of beta-AB also.

[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.

[Comparative characteristic of angiotensin-converting enzyme inhibitor--captopril and the angiotensin II receptor blokers--losartan action on the oxidative metabolism in experimental hyperlipidemia in rabbits].

The aim of present study--comparative characteristic of captopril and of losartan action on the oxidative metabolism in experimental hyperlipidemia. Experiments carried out on rabbits,which were divided into three groups(ten animal in each group) and orally receiving during 45 days: I control group (cholesterol 500mg/kg + methylthiouracil 100mg/kg, II group-captopril 5 mg/kg + cholesterol 500mg/kg + methylthiouracil 100mg/kg, III group-losartan 8mg/kg + cholesterol-500mg/kg + methylthiouracil 100mg/kg. Activity of superoxide dismutase, catalase, level of malonic dialdehyde, osmotic resistance of erythrocytes and resistanse of LDL to oxidation and concentration of nitric oxide in the blood have been evaluated . The administration of captopril and losartan in experimental hyperlipidemia eqivalently increased activity of SOD and catalase, osmotic resistance of erythrocytes and resistanse of LDL to oxidation, whereas decreased content of malonic dialdehyde compared to the control group . Captopril was more effective than losartan in preserving of nitric oxide. We conclude that captopril and losartan inhibited oxidative stress, which are probably associated with the inhibition of angiotensin 11. Captopril and losartan are safely used in patients during cardio-vascular disease with dyslipidemia.

[Efficacy and safety of heptral, vitamin B6 and folic acid during toxic hepatitis induced by CCL4].

The aim of this work was to evaluate of efficacy and safety of complex Heptral, Vitamin B6 and Folic Acid in experimental hepatitis therapy compared with monotherapy. Experiments were carried out on pubertal rats. Eperimental hepatitis models were induced by Tetrachlormethane. The tetrachlormethane intoxication was reproduced by subcutaneous injection of CCL(4) 1ml/kg dissolved in 1ml of olive oil. Cytochrome P450, cytochrome b5, reduced glutation,activity of glutationetranspherase and content of ATP in hepatocytes were measured by the spectrophotometric techniques,but content of homocysteine by chromophtography techniques. Under CCL(4) intoxication disturbance of liver detoxication function, energy deficit and surplus of homocysteine were observed. Treatment of the toxic hepatitis with heptral increased the level of cytochrome P450, cytochrome b5, glutation activity of glutationetranspherase glutathione and reduced content of homocysteine. Complex therapy with Heptral and B6 and folic acid reveal more expressive hepatoprotective effect and safety than monotherapy with Heptral. Complex therapy improves not only the parameters of biotransformation (metabolic and conjugation phase), but also normalizes the level of ATP and homocystein. Vitamins B6 and folic acid increases the efficacy and safety of Heptral. This complex was recomended for treatment of hepatitis.

[Antimicrobial prophylaxis in urological surgery].

The present review is dedicated to the problem of perioperative antimicrobial prophylaxis in urological surgery. There are considered modern guidelines for perioperative antimicrobial prophylaxis in urology. There are discussed; aims, timing, and duration of perioperative antimicrobial prophylaxis, risk factors of postoperative infections in urological surgery, pharmacological properties of major antimicrobial drugs, selection and route of administration of antibacterial agents. There are presented the recommendations of perioperative antimicrobial prophylaxis for the varies types of urological surgery, as well as, are given in detail the recommendations about clinical uses of antibiotics for the different types of urological interventions. There are concluded, that perioperative antimicrobial prophylaxis reduces risk of postoperative infections in urological surgery, but sometimes this prophylaxis is not effective and the problem of perioperative antimicrobial prophylaxis in urology is debatable at present. It is necessary continues search of optimal methods of of perioperative antimicrobial prophylaxis in urology. These review are designed for urologists and clinical pharmacologists.

[Oxidative stress during thyrotoxicosis and its correction].

Oligocrine is a preparation of vegetable origin characterized by anti-inflammatory, antioxidant, immunomodulating properties. Our study shows that administration of L-thyroxine injections (irrespective of the duration) results in elevated synthesis of thyroid hormones and intensification of oxidative stress in experimental animals. These changes are evidenced by accumulation of membrane phospholipide peroxidation products - lipid peroxides in the blood. At that we should point that while dependence of FT3 and FT4 levels on the duration of L-thyroxine administration was insignificant in the experimental model of thyrotoxicosis, intensity of lipid peroxidation increased along with prolongation of injections. Blood levels of free nitric oxide were decreased likely due to the transformation of nitric oxide into peroxinitrite. Oligocrine facilitates to the stabilization of thyroid status and restriction of NO hyperproduction, hypermetabolism and oxidative stress in the body.

Effectiveness of combined treatment with superoxide dismutase and Reamberin during skin ischemia.

Experimental skin ischemia in rats was induced by suturing a skin fold on the back with a silk thread. Combined pretreatment with superoxide dismutase (intraperitoneally) and Reamberin (intravenously) in doses of 0.01 and 6.25 mg/kg (by succinate concentration), respectively, produced a strong protective effect on the skin. The index of cytolysis decreased by 39%. The more pronounced antinecrotic effect of combined treatment with superoxide dismutase and Reamberin compared to the effect of Reamberin alone was related to a sharp increase in the reserve capacity of the antioxidant system. After combined therapy, activity of antioxidant defense enzymes not only increased, but even exceeded the normal level. The increase in activity of endogenous superoxide dismutase under the influence of combined therapy was accompanied by suppression of superoxide anion production.

Antinecrotic and antioxidant effects of superoxide dismutase during skin ischemia.

Antinecrotic activity of SOD was studied in rats with experimental skin ischemia. Treatment with SOD increased activity of endogenous SOD in skin homogenates (by 70 and 26% compared to the ischemic and intact skin, respectively). However, the rate of superoxide anion generation remained unchanged after SOD treatment. Creatine phosphate content and NAD/NADH redox potential increased by 16 and 21%, respectively, on day 3 after SOD administration. The increase in functional activity of the energy supply system and rise in the reserve capacity of the antioxidant protection system contribute to inhibition of lactate dehydrogenase and creatine phosphokinase and decrease in the cytolysis index under the influence of SOD. Our results indicate that SOD produces the antinecrotic effect and holds much promise for the therapy of skin ischemia.

[Major pathogenic links of atherosclerosis].

The experimental and clinical data concerning pathogenesis of the atherosclerosis are summarized and analyzed in this article. Major concepts that explain initiation and progressive growth of atherosclerosis such as lipid infiltrations, response to disturbing factors, "response on the keeping of particles" and inflammatory processes are discussed. These concepts are considered as base for integral theory of atherosclerosis according which the inflammatory process in atherosclerosis are the result of the universal response reaction of endothelium to the various disturbing risk factors. Chronic inflammation leads to complex cellular and molecular interactions among cells derived from the endothelium, smooth muscle and several blood cell components and causes oxidative stress, proliferation of smooth muscle cells, oxidative modification of LDL, uptake and macrophage foam cell formation, endothelium dysfunction. Major pathogenic links of atherosclerosis, such as inflammation, oxidative stress, oxidative modification of LDL, lipid infiltration, endothelial dysfunction closely interact, forming close vicious circles which leads to metabolic and morphological disturbances, re-modulation of blood vessels, cardiovascular diseases and such complication as cardiac infarction and stroke. Pathogenic peculiarities of atherosclerosis are the theoretic base to the elaboration of therapeutic strategy. Endothelium may be discussed as a new therapeutic target in atherosclerosis. So far as the leukotrienes play an important role in inflammatory processes, it is suggested that the leukotrienes may be as a potential therapeutic target in cardiovascular diseases.

[Effect of heptral and folic acid on the hepatic functions during toxic hepatitis].

The aim of study was to evaluate effectiveness of heptral (S-Adonosylmethionine-Adomet) and folic acid during the acute toxic damage of the liver induced by carbon tetrachloride. Experiments have been carried out on pubertal rats. The carbon tetrachloride intoxication was performed by subcutaneous injection of CCL(4) 1 ml/kg dissolved in 1 ml of olive oil. The activity of aspartat-and alaninaminotransferases, alkaline phosphatase, the content of free and total billirubine in the blood, as well as total oxidant and antioxidant activity of the blood, were measured by the spectrophotometric techniques. Oxidative stress, cytolyses of the hepatocytes and cholestasis were observed during CCL(4) intoxication. Heptral, and in less degree, folic acid improved liver function during the acute toxic damage, but complex therapy with heptral and folic acid revealed more expressive hepatoprotective effect. It is suggested that better positive effect of complex therapy with heptral and folic acid compared with monotherapy by each drug is probably associated with resynthesis of methionine from homocystein (toxic metabolite of adenosylmethionine) by folate. This combination allows reducing the side effects of heptral induced by homocysteine.

Antihypoxic and antinecrotic effect of mexidol in skin ischemia.

Course treatment with mexidol in a dose of 25 mg/kg for 3 days decreased activities of aspartate transaminase and creatine phosphokinase in the plasma on day 3 after the incidence of skin ischemia (by 1.3 and 1.66 times, respectively). Under these conditions the index of cytolysis decreased by 1.3 times. Therefore, mexidol prevented progression of necrotic processes in the skin. Mexidol therapy of animals with skin ischemia restored the reserve capacity of systems for energy supply and antioxidant defense. The systems of NADH-ubiquinone reductase and succinate-ubiquinone reductase served as the targets for the action of mexidol. Mexidol significantly decreased the damaging effect of reactive oxygen species. Dermatoprotective properties of mexidol were associated with its influence on the energy supply system (regulation of enzyme activity in the electron transport chain, ubiquinone metabolism) and antioxidant defense.

[Pharmacological correction of hyperactivity of renin-angiotensin-aldosterone system].

Reference data on the function of renin-angiotensin-aldosterone system (RAAS) and pharmacological correction of its hyperactivity are summarized and analyzed in the paper. RAAS plays important role in the development and worsening of hypertension, facilitates proliferation of smooth muscle and heart cells. The hyperactivity of RAAS promotes the development of cardiovascular complications, such as myocardial infarction, stroke, increases cardiovascular mortality and morbidity. Pharmacological correction of RAAS hyperactivity decreases hypertension, prevents occlusion of heart and blood vessels, provides anti-ischemic action, vascular and cardiac protection, improves life style, prevents cardiovascular mortality, such as fatal stroke, myocardial infarction and sudden death. b-blocker inhibitors, angiotensin converting enzyme (ACE) inhibitors, angiotensin AT1-receptors blockers are reviewed as first line therapy of essential hypertension and congestive heart failure. ACT inhibitors, AT1- receptor blockers decrease total cholesterol, LDL, but increase HDL, beta-blockers decrease HDL. AT1-blockers are alternative drugs for treatment of cardiovascular diseases in those cases where ACE inhibitors are contraindicated or intolerance exists.

[Comparison of an aceclidine tremor with arecoline and nicotine ones in rats of different ages]. / Sopostavlenie atseklidinovogo tremora s arekolinovym i nikotinovym u krys raznogo vozrasta.

A comparative characterization of a tremor produced by aceclidine (0.5--200 mg/kg), arecoline (1--30 mg/kg) and nicotine (0.1--8 mg/kg) in rats of different age is given and the influence on the tremor of atropine sulphate (1--100 mg/kg) and scopolamine hydrobromide hydrobromide (2.5 mg/kg) described. The common character of effects produced by aceclidine and arecoline was ascertained. The tremor develops in rats aged 7--8 days and its maximum duration is in rattlings of junior and medium age. M-cholino-lytics either prevent or alleviate the tremor, lacrimation and salivation induced by aceclidine or arecoline in rats of all age categories. The aceclidine model is recommended for studying the central and peripheral M-cholinergic processes in rats of various age groups.