Матер. III съезда фармакологов России. Психофармакол биол наркол 2007 Спец Вып; 7 (Ч 1, А–Л): 1-1695–1-1696 (Тез 234)

Zharkovsky A. Neural Cell Adhesion Molecule and its Possible Roles in Depression. Proceedings of the III Congress of Pharmacology Russia, Saint-Petersburg, 23–27 September 2007. Abstr 234. Psychopharmacol Biol Narcol 2007 Sept; 7 Suppl (Pt 1, A–L): 1-1695–1-1696Recent years much attention was put on the role brain plasticity in relation to depressive state. Neural cell adhesion (NCAM) plays important roles in the structural and functional plasticity in the CNS. If the reduced neuronal plasticity is an important factor predisposing to the development of depression, than animals with reduced brain plasticity due to deficiency in NCAM should serve as a valuable model of depression. Mice deficient in NCAM molecule demonstrated signs of depression-like behavior in the tail suspension and sucrose consumption tests. This was accompanied by the impaired object recognition in the object recognition test and the reduced levels of innate anxiety. Analysis of hippocampal neurogenesis in NCAM deficient mice revealed a reduced survival of the newborn cells and their differentiation into calbindin-positive granule neurons. The NCAM-/-mice demonstrated an increased fos B expression in the basolateral nucleus of amygdala, but not in other regions like dentate gyrus of hippocampus or piriform cortex. Since BDNF signaling system plays a significant role in the mechanisms of depression and in the effects of antidepressants, we measured the levels of BDNF and the level of phosphorylation of TrkB receptor in the brain of NCAM-/-mice. Experiments demonstrated a reduced BDNF signaling in the brains of NCAM-/-mice as a reduced level of phosphorylated Trk B receptor evidenced it. The depression-like signs in NCAM-/-mice were reversed by he acute or repeated administration of NCAM-mimetic peptide FGL. In addition, repeated FGL administration tended to reduce fos B activation in the basolateral nucleus of amygdala and enhanced survival of the newly generated cells in the dentate gyrus of NCAM-/-mice. The effects of FGL on the Trk B receptor phosphorylation are currently being studied in our laboratory. Our data suggest that reduced brain plasticity due to deficiency in NCAM gene plays a role in the development of depressive state and NCAM mimetic peptide FGL might represent a new class of drugs with antidepressant activity.Zharkovsky A. Матер. III съезда фармакологов России. Психофармакол биол наркол 2007 Спец Вып; 7 (Ч 1, А–Л): 1-1695–1-1696 (Тез 234

Матер. III съезда фармакологов России. Психофармакол биол наркол 2007 Спец Вып; 7 (Ч 1, А–Л): 1-1695–1-1696 (Тез 234)

Zharkovsky A. Neural Cell Adhesion Molecule and its Possible Roles in Depression. Proceedings of the III Congress of Pharmacology Russia, Saint-Petersburg, 23–27 September 2007. Abstr 234. Psychopharmacol Biol Narcol 2007 Sept; 7 Suppl (Pt 1, A–L): 1-1695–1-1696Recent years much attention was put on the role brain plasticity in relation to depressive state. Neural cell adhesion (NCAM) plays important roles in the structural and functional plasticity in the CNS. If the reduced neuronal plasticity is an important factor predisposing to the development of depression, than animals with reduced brain plasticity due to deficiency in NCAM should serve as a valuable model of depression. Mice deficient in NCAM molecule demonstrated signs of depression-like behavior in the tail suspension and sucrose consumption tests. This was accompanied by the impaired object recognition in the object recognition test and the reduced levels of innate anxiety. Analysis of hippocampal neurogenesis in NCAM deficient mice revealed a reduced survival of the newborn cells and their differentiation into calbindin-positive granule neurons. The NCAM-/-mice demonstrated an increased fos B expression in the basolateral nucleus of amygdala, but not in other regions like dentate gyrus of hippocampus or piriform cortex. Since BDNF signaling system plays a significant role in the mechanisms of depression and in the effects of antidepressants, we measured the levels of BDNF and the level of phosphorylation of TrkB receptor in the brain of NCAM-/-mice. Experiments demonstrated a reduced BDNF signaling in the brains of NCAM-/-mice as a reduced level of phosphorylated Trk B receptor evidenced it. The depression-like signs in NCAM-/-mice were reversed by he acute or repeated administration of NCAM-mimetic peptide FGL. In addition, repeated FGL administration tended to reduce fos B activation in the basolateral nucleus of amygdala and enhanced survival of the newly generated cells in the dentate gyrus of NCAM-/-mice. The effects of FGL on the Trk B receptor phosphorylation are currently being studied in our laboratory. Our data suggest that reduced brain plasticity due to deficiency in NCAM gene plays a role in the development of depressive state and NCAM mimetic peptide FGL might represent a new class of drugs with antidepressant activity.Zharkovsky A. Матер. III съезда фармакологов России. Психофармакол биол наркол 2007 Спец Вып; 7 (Ч 1, А–Л): 1-1695–1-1696 (Тез 234

Impact of Interface Model on Simulation Results of a Radial Pump at Part Load and Shut-Off Conditions

Computational Fluid Dynamics (CFD) is a well-known tool for predicting and analyzing performance in a variety of engineering branches, including turbomachinery, allowing engineers to partially replace physical experiments with their virtual analog. Nevertheless, numerical analysis should be used carefully regarding possible deviation between simulated and experimental results due to multiple reasons (including but not limited to applied simplifications in the numerical model). These deviations usually have their minima close to the Best Efficiency Point (BEP). The paper deals with analyzing the outcome of steady-state simulations for a radial pump at strong part load and shut-off conditions by switching between three simulation types (steady-state with mixing plane, steady-state with frozen rotor, transient with sliding mesh). A comparison of velocity profiles on the interface surfaces is made, showing how the chosen interface model affects the structures being formed at part load conditions. These effects show particular impact on performance parameters (first of all, head production), which is discussed in the paper. The information provided could be helpful for adjusting the simulation parameters and finding an appropriate compromise between simulation reliability and demand for computational time thereby

Effects of nitrendipine, chlordiazepoxide, flumazenil and baclofen on the increased anxiety resulting from alcohol withdrawal

Male hooded Lister rats were fed a liquid diet containing 10% absolute ethanol for 4-5 weeks. Control rats received the liquid diet in amounts controlled to produce equal weight gain. The rats were tested 7.5 h after withdrawal of ethanol and 30 min after i.p. injection with nitrendipine, chfordiazepoxide or baclofen or 20 min after i.p. injection with flumazenil. Nitrendipine (25-100 mg/kg) was unable to reverse the anxiogenic responses detected on withdrawal from ethanol_, but the highest dose did reduce withdrawal tremor. Chiordtazepoxide (IO mg/kg), flumazenil (4 mg/kg) and bacIofen (I .2$ mgfkg) significantly reversed the anxiogenic response detected on withdrawal from ethanol. These reversals of ethanol withdrawal responses are similar to the reversal of the increased anxiety detected on withdrawal from chronic treatment with benzodiazepines. The mechanisms and clinical implications of these drug-induced reversals are discussed

Concurrent treatment with verapamil prevents diazepam withdrawapl-induced anxiety, in the absence of altered calcium flux in cortical synaptosomes

Rats, chronically treated with diazepam (4 mg/kg/day) for 28 days, displayed increased anxiety when tested in the elevated plus-maze, 42 hr after the last dose. This anxiogenic withdrawal response was entirely prevented by the concurrent administration of the calcium channel antagonist, verapamil. No anxiolytic effect of chronic administration of verapamil was observed in vehicle-treated rats. To investigate the possibility that increased calcium function in nerve terminals might underlie diazepam withdrawal-induced anxiety, the uptake by cortical synaptosomes of 45Ca2 + was studied. Both fast (3-sec) and slow (60-sec) phase uptake were measured. No changes in basal (5 mM), potassium-stimulated (55 mM) or net uptake were observed during either fast or slow phase uptake. It is concluded that increased calcium influx in nerve terminals in the cortex does not underlie the anxiogenic effect of withdrawal of the benzodiazepine but that further studies must be carried out in other regions of the brai

Analysis of potential interactions between warfarin and prescriptions in Estonian outpatients aged 50 years or more

In Estonia, warfarin is widely prescribed by general practitioners to prevent and treat thromboembolic diseases. To date, there has been no systematic analysis of the potential risk of warfarin interactions with other drugs in the outpatient population.Objective: The aim of the study was to analyze the incidence of potential interactions in prescription schemes in Estonia in a cohort of outpatients receiving warfarin treatment.Methods: The retrospective study population included 203,646 outpatients aged 50 years or older of whom 7,175 received warfarin therapy. Patients who had used at least one prescription drug for a minimum period of 7 days concomitantly with warfarin were analyzed. Potential drug interactions were analyzed using Epocrates online, Stockley’s Drug Interactions and domestic drug interaction databases.Results: The average number of drugs used concomitantly with warfarin was 4.8 (SD=1.9) (males: 4.7 SD=2.0, females: 4.9 SD=2.0). No potential interactions in treatment regimens were found in 38% of patients, one potential interaction was observed in 29% and two or more potential interactions were observed in 33% of patients. The mean number of all potential interactions was 1.2 per patient and about the same in men and women. Potential interactions were associated with the number of drugs. Warfarin-related interactions were detected in 57% of patients, and the number of interactions related to warfarin per patient varied from 1 to 5. Most frequent were use of warfarin with NSAIDs (14%), followed by simvastatin (9%) and amiodarone (7%).Conclusion: This study shows that 57% of outpatients in Estonia receiving warfarin have drugs potentially interacting with warfarin in their treatment schemes. Most interactions (14%) with warfarin are associated with the prescription of NSAIDs