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Journal Article 2006; 27(6): 748-754 PubMed PMID: 17187001 Citation  Keywords:  Adolescent, Attention Deficit Disorder with Hyperactivity:blood, Child, Dopamine beta-Hydroxylase:blood, Humans, Polymorphism, Genetic:genetics,.   

: Attention-deficit Hyperactivity disorder (ADHD) is a multifactorial disorder clinically characterized by inattentiveness, impulsivity and hyperactivity. The occurrence of this disorder is between 3 and 6% of the children population, with boys predominating over girls at a ratio of 3:1 or more. The research of some candidate genes (DRD4, DAT, DRD5, DBH, 5HTT, HTR1B and SNAP25) brought consistent results confirming the heredity of ADHD syndromes. Dopamine-beta-hydroxylase (DBH) is an enzyme responsible for the conversion of dopamine into noradrenaline. Alteration of the dopamine/noradrenaline levels can result in hyperactivity. The DBH protein is released in response to stimulation. DBH activity, derived largely from sympathetic nerves, can be measured in human plasma. Patients with ADHD showed decreased activities of DBH in serum and urine. Low DBH levels correlate indirectly with the seriousness of the hyperkinetic syndrome in children [19,20]. In the DBH gene, the G444A, G910T, C1603T, C1912T, C-1021T, 5 -ins/del and TaqI polymorphisms occur frequently and may affect the function of gene products or modify gene expression and thus influence the progression of ADHD. This article reviews the DBH itself and polymorphisms in the DBH gene that influence the DBH activity in the serum and the CSF level of DBH. All those are evaluated in connection with ADHD....

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Case Reports 2006; 27(6): 737-739 PubMed PMID: 17187000 Citation  Keywords:  Acute Disease, Akathisia, Drug-Induced:diagnostic imaging, Antipsychotic Agents:adverse effects, Benzodiazepines:adverse effects, Cerebellum:diagnostic imaging, Fluorodeoxyglucose F18, Humans, Male, Middle Aged, Positron-Emission Tomography:methods, Radio.   

OBJECTIVES: Akathisia is a clinical important symptom, frequently induced by neuroleptic treatment. Despite its clinical importance, less is known about its pathophysiology.r />r /> METHODS: Using [18]-FDG-PET, imaging patterns of cortical metabolic activity were obtained in a patient during olanzapine-induced akathisia and after recovery.r />r /> RESULTS: Akathisia was characterized by a reduced metabolic activity in thalamus and cerebellum. After discontinuing medication akathisia disappeared, reflected by a recovery of metabolic activity in these brain areas.r />r /> CONCLUSION: [18]-FDG-PET may be useful to identify cortical regions mediating clinical aspects of drug-induced akathisia, thereby offering a deeper insight into the pathophysiology of this serious side effect....

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Journal Article 2006; 27(6): 758-762 PubMed PMID: 17186999 Citation  Keywords:  Adult, Age Factors, Androstenedione:blood, Atherosclerosis:blood, Blood Glucose:analysis, Cholesterol:blood, Coronary Disease:blood, Estrogens:blood, Female, Gonadal Steroid Hormones:blood, Humans, Incidence, Lipoproteins, HDL:blood, Lipoproteins, LDL:blo.   

OBJECTIVES: The objectives of this study were to investigate the relationship between the incidence of coronary heart diseases in premenopausal women and plasma level of total and free testosterone, estrogen, androstenedione and sex hormone binding globulin with coronary risk factors: fasting plasma concentration of glucose, triglyceride, total cholesterol, high and low density lipoproteins.r />r /> METHODS: The study was conducted in Faculty of Medicine, Jordanian University of Science/Irbid Jordan and Technology and department of cardiology in Queen Alia Heart Institute/Amman Jordan during the period from April 2003 to March 2004. Serum sex hormones levels were measured in fifty-three premenopausal women; 25 women with coronary heart disease who had hypertension and/or diabetes mellitus and 28 women without coronary heart disease. Ages ranged from 34 to 48 years. Blood samples were collected just before performing coronary angiography and serum was obtained and frozen at -70 degrees C until use.r />r /> RESULTS: We found that the mean triglyceride, fasting blood sugar total cholesterol, and low density lipoprotein concentration were significantly higher in coronary heart disease patients than in patients with normal coronaries. We also found that the low levels of sex hormone binding globulin and high levels of free testosterone are associated with development of coronary heart disease. No significant correlation could be established between other plasma sex hormones level and coronary heart disease.r />r /> CONCLUSION: In young women, in the presence of coronary risk factors and normal level of serum estrogen, the high levels of serum free testosterone and low levels of serum sex hormone binding globulin are associated with development of atherosclerosis and increased incidence of coronary heart disease....

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Journal Article 2006; 27(Suppl 2): 183-186 PubMed PMID: 17159811 Citation  Keywords:  Acetylcholinesterase:blood, Animals, Brain:drug effects, Butyrylcholinesterase:blood, Carnitine:pharmacology, Cholinesterase Inhibitors:pharmacology, Galantamine:pharmacology, Liver:drug effects, Male, Pituitary Gland:drug effects, Rats, Rats, Wistar,.   

OBJECTIVES: The alkaloid galantamine (GAL), which exhibits a combined anticholinesterase and direct parasympathomimetic mechanism of action, is employed in conjunction with therapeutic interventions in the stimulation of central cholinergic transfer in cognitive diseases. We attempted to achieve pharmacologically-induced enhancement of the parasympathomimetic activity of GAL in the key areas of rat brain, using an interactive combination of the alkaloid with the transmembrane enhancer L-carnitine (CAR).r />r /> METHODS: We investigated activities of acetylcholinesterase (AChE) in brain areas (frontal cortex, basal ganglia, septum and hippocampus) and the hypophysis, and that of butyrylcholinesterase (BuChE) in plasma and liver.r />r /> RESULTS: Following administration of the highest of the GAL doses used (2.5; 5; 10 mg/kg i.m.), AChE activity decreased mainly in the frontal cortex, hippocampus and hypophysis. In the interaction of GAL and CAR, AChE inhibition was stronger but without any statistical significance. The peripheral inhibition of BuChE was found to be dose-dependent. Premedication by CAR led to a slight change in the values of the activities monitored.r />r /> CONCLUSIONS: CAR in terms of positive modulation of GAL targeting to the central nervous system had no statistically significant effect....

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Journal Article 2006; 27(Suppl 2): 180-182 PubMed PMID: 17159810 Citation  Keywords:  Animals, Copper:pharmacology, Fatty Acids, Unsaturated:metabolism, Lipoxygenase:metabolism, Lipoxygenase Inhibitors:pharmacology, Models, Biological, Organometallic Compounds:pharmacology, Rats,.   

OBJECTIVES: Lipoxygenases (EC 1.13.11.12, LOX) catalyze the hydroperoxidation of polyunsaturated fatty acids (PUFA). This reaction leads to the production of conjugated hydro peroxide dienes of PUFA. In animals, LOX generate leukotriens (LT) and lipoxins, which belong to inflammatory mediators. It is believed that restricting LT synthesis by inhibition of LOX would have therapeutic utility for the treatment of a variety of inflammatory conditions (e.g. asthma, rheumatoid arthritis, psoriasis).r />r /> METHODS & RESULTS: The process of production and elimination of radical intermediates in vitro can be monitored by determination of LOX activity. We assessed the concentration of PUFA hydroperoxides in our system with LOX-catalyzed enzyme reaction spectrophotometrically. The inhibition of LOX activity (LOX from cytosol fraction of rat lungs) with selected N-salicylideneaminoalkanoatocopper(II) complexes was tested. In our experiments, all compounds tested showed an inhibitory effect on LOX catalyzed hydroperoxidation of PUFA. Cu(II) (from CuSO(4).5H(2)O dilution) ions also inhibited this enzyme reaction, but all compounds studied had a 10 times higher anti-LOX activity. The most effective of these complexes was monohydrate aqua-(N-salicylidene-L-a-alaninato)copper(II) complex [Cu(sal-L-alpha-ala)(H(2)O)].H(2)O with IC(50) 1.86 x 10(-4) mol/l.r />r /> CONCLUSIONS: These complexes are known for their anti-phlogistic and radioprotective properties and they can be classified as potential anti-radical compounds. The structure of these complexes is similar to the active site of Cu,Zn-SOD (superoxide dismutase) and superoxide radical scavenger activity of these complexes is known. We found that these copper complexes were capable to inhibit LOX activity, which may be related with their anti-radical properties....

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Evaluation Studies 2006; 27(Suppl 2): 176-179 PubMed PMID: 17159809 Citation  Keywords:  Animals, Antibodies, Monoclonal:adverse effects, Antibodies, Monoclonal, Humanized, Antineoplastic Agents:adverse effects, Bevacizumab, Cardiomyopathies:chemically induced, Chemokine CCL2:metabolism, Cyclophosphamide:adverse effects, Doxorubicin:adverse e.   

OBJECTIVES: Although the mechanisms responsible for the occurrence of congestive heart failure after anti-cancer therapy are largely unknown, both the formation of free radicals in the myocardium and inflammatory cytokines with resultant production of neurohormones could be operative. The common manifestations of cardiovascular toxicity after anti-cancer therapy may include cardiac ischemia, ST-segment elevation, or depression, serious hypotension and bradyarrhythmias with resultant cardiac depression and congestive heart failure, or hyper-tension, serious ventricular tachycardia, cardiac edema, QT prolongation and thrombo-embolism.r />r /> METHODS & RESULTS: The mechanisms of cardiotoxicity of four representative anti-cancer agents 1) anthracycline doxorubicin, 2) and 3) alkylating agents cyclophosphamine and streptozotocin and 4) the new humanized monoclonal antibody bevacizumab (directed solely against myocardial and vascular endothelial growth factors), were investigated in chronic experiments on rodents for the occurrence and intensity of early electrocardiographic signs of cardiotoxicity, for late biochemical markers, and for the late production of congestive heart failure. Our results suggested a sneaking ascension of long-term multifactorial cardiotoxicity of the four anti-cancer agents tested. Of these quasi-selective bevacizumab (Avastin) that binds to and inhibits endothelial growth factor and thus neoangiogenicity in rats showed unexpectedly high overexpression of inflammatory cytokines and monocyte chemoattractant protein (mcp-1), both in plasma and in the myocardium.r />r /> CONCLUSIONS: Thus, suddenly increased and coincidental expression of inflammatory cytokines, neurohormones and chemoattractants in plasma during anti-cancer therapy could be the long-awaited markers of imminent cardiotoxicity....

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Journal Article 2006; 27(Suppl 2): 172-175 PubMed PMID: 17159808 Citation  Keywords:  Animals, Arthritis, Experimental:enzymology, Biomarkers:analysis, Body Weight:drug effects, Joints:enzymology, Male, Mannans:pharmacology, Rats, Rats, Inbred Lew, Spleen:enzymology, gamma-Glutamyltransferase:metabolism,.   

OBJECTIVES: To assess glucomannan and pyridoindole derivatives for possible antioxidant therapy of rheumatoid arthritis (RA) by using the model of adjuvant arthritis (AA). We evaluated the association between clinical markers of the adjuvant arthritis model used - increase of hind paw volume (HPV), changes of body mass (CBM), and tissue gamma-glutamyl transferase (GGT) activity assessed in the spleen and the joint.r />r /> METHODS: AA was induced in Lewis rats by a single intradermal injection of Mycobacterium butyricum. The two independent experiments included healthy animals as reference, arthritic animals without any drug administration and arthritic animals with pyridoindole administration in one dose tested or glucomannan administration in two different doses. The pyridoindoles (PI) studied were stobadine dipalmitate and its derivatives SMe1.2HCl and SMe1EC2.HCl. We monitored CBM and HPV twice a week. Parameter of inflammation - GGT in the spleen and the joint from the hind paw (cartilage and soft tissue without bone) was determined on day 28. The correlation coefficient of GGT activity with CBM and with HPV was calculated.r />r /> RESULTS: The antioxidants tested were effective in slowing down the progress of adjuvant arhritis. The association between tissue GGT activity and the clinical marker of adjuvant arthritis - CBM was higher in the spleen than in the joint. The other clinical marker assessed - HPV, gave a better association with GGT activity measured in the joint than in the spleen.r />r /> CONCLUSIONS: It may be concluded that GGT activity in tissues as the spleen and the joint could provide a simple and inexpensive marker for AA and RA development at systemic as well as local level; all the antioxidants studied were effective in slowing down the progress of adjuvant arhritis....

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Journal Article 2006; 27(Suppl 2): 168-171 PubMed PMID: 17159807 Citation  Keywords:  Acetylcholine:pharmacology, Animals, Diabetes Mellitus, Experimental:complications, Diabetic Angiopathies:etiology, Hyperglycemia:complications, Male, Phenylephrine:pharmacology, Rats, Rats, Wistar, Reactive Oxygen Species:adverse effects, Streptozocin, V.   

OBJECTIVES: In the present study, the relationship between diabetes-induced hyperglycemia, reactive oxygen species production and endothelium-mediated arterial function was examined. The effect of antioxidant on the reactive oxygen species induced damage was tested.r />r /> METHODS: Diabetes was induced by streptozotocin (STZ), 3 x 30 mg/kg i.p., administered on three consecutive days. After 10 weeks of diabetes, the functional state of the endothelium of the aorta was tested, endothelemia evaluation was performed and systolic blood pressure was measured. Reactive oxygen species (ROS) formation in blood and the aorta was measured using luminol-enhanced chemiluminescence (CL). Levels of reduced glutathione (GSH) were determined in the aorta, kidney, and plasma. To study the involvement of hyperglycemia in functional impairment of the endothelium, aortal rings incubated in solution with high glucose concentration were tested in in vitro experiments.r />r /> RESULTS: After 10 weeks of diabetes, endothelial injury was observed, exhibited by diminished endothelium-dependent relaxation of the aorta, increased endothelemia and by elevated systolic blood pressure. Using luminol-enhanced CL, a significant increase of ROS production was found in arterial tissue and blood. GSH levels were significantly increased in the kidney, while there were no GSH changes in plasma and the aorta. Incubation of aortic rings in solution with high glucose concentration led to impairment of endothelium-dependent relaxation. The synthetic antioxidant SMe1EC2 was able to restore reduced endothelium-mediated relaxation.r />r /> CONCLUSIONS: Our results suggest an important role of hyperglycemia-induced ROS production in mediating endothelial dysfunction in experimental diabetes, confirmed by CL and the protective effect of the antioxidant SMe1EC2....

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