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Journal Article 2010; 31(Suppl 2): 84-90 PubMed PMID: 21187824 Citation  Keywords:  Antioxidants:pharmacology, Apoptosis:drug effects, Caspase 3:metabolism, Cell Survival:drug effects, Computer Simulation, Dose-Response Relationship, Drug, Humans, In Vitro Techniques, Male, Neutrophils:cytology, Phosphorylation:drug effects, Protein Kina.   

OBJECTIVE: Pterostilbene, a naturally occurring phenolic derivative, exhibits various pharmacological effects, e.g. anti-cancerous, antioxidant, anti-inflammatory and anti-diabetic. Based on our previous study, we assessed the cellular and molecular effects of pterostilbene on human neutrophils and in cell free systems. Experimental and theoretical molecular descriptors of stilbene derivatives were also determined.r />r /> METHODS: We assessed the antioxidant properties of pterostilbene using cell free system and computational methods. The effect of pterostilbene on protein kinase C activation/phosphorylation was detected by special anti-phospho protein kinase C antibodies. Membrane associated changes determining the life span of neutrophils and human recombinant caspase-3 assay were examined.r />r /> RESULTS: Pterostilbene possessed comparable antioxidant properties as resveratrol in cell free system. Computational methods were used to establish the molecular characteristics of stilbene derivatives. The values of electronic parameters suggest a slight enhancement of electron donor properties of pterostilbene compared to resveratrol. Phosphorylation and thus activation of protein kinase C alpha/beta II in activated neutrophils was not decreased by pterostilbene. Pterostilbene in concentrations of 10-100 μM was found to inhibit the activity of human caspase-3 purified enzyme and did not influence cell viability significantly.r />r /> CONCLUSION: Pterostilbene, an analog of resveratrol, was identified as a good natural antioxidant compound. However, reducing the oxidative burst of human neutrophils during their activation in vitro with pterostilbene does not include protein kinase C phosphorylation pathway. Pterostilbene showed dose dependent activation/inhibition of caspase-3 enzyme activity....

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Case Reports 2010; 31(Suppl 2): 5-7 PubMed PMID: 21187823 Citation  Keywords:  Disease Progression, Fatal Outcome, Humans, Incidence, Infant, Newborn, Male, Metal Metabolism, Inborn Errors:complications, Molybdoferredoxin, Neurodegenerative Diseases:diagnosis, Slovakia:epidemiology,.   

OBJECTIVE: To present the case of a term newborn with rapid progression of signs of neurodegenerative disease.r />r /> RESULTS: In a case of a term newborn with numerous dysmorphic features, with seizure activity from the 3rd day of life, hypertonia and serious changes on brain parenchyma were presented. Diagnosis of molybdenum cofactor deficiency was confirmed by the decreased level of uric acid, 31 μmol/l, in serum, increased excretion of thiosulfate and S-sulfocysteine in urine, taurine (1729.3 μmol/mmol crea; normal range 30-300 μmol/mmol crea) and xanthine (276.9 μmol/mmol crea; normal range < 25 μmol/mmol crea) in urine. Sulfite oxidase activity on skin fibroblasts in culture was not detectable. The patient died at the age of 28 days of life.r />r /> CONCLUSION: Deficiency of molybdenum cofactor leads to accumulation of toxic metabolites (levels of sulfite), which causes disturbances of neurotransmitters even before delivery. Therapy is symptomatic, no effective therapy is available. Seizures are difficult to suppress. This case report is about the first patient in Slovakia....

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Journal Article 2010; 31(Suppl 2): 57-61 PubMed PMID: 21187822 Citation  Keywords:  Adipose Tissue:cytology, Animals, Blood-Brain Barrier, Brain:cytology, Female, Fluorescein:administration & dosage, Fluorescent Dyes:administration & dosage, Gastrointestinal Tract:cytology, Injections, Intravenous, Kidney:cytology, Lung:cytology, Microsc.   

OBJECTIVE: Confocal laser scanning endomicroscopy (CLSE) is a diagnostic technology that produces virtual histology of the mucosal layer using fluorescence technique. Fluorescein (FSC) is the most commonly used fluorescence agent. Fluorescence light coming from a horizontal special focal plane is detected during confocal laser endomicroscopy of the gastrointestinal tract. FSC causes intensive yellowish discoloration of tissues, including skin and mucous membranes. This pre-clinical study was aimed to evaluate the tissue distribution and pharmacokinetics of FSC after its intravenous administration.r />r /> METHODS: The study was performed in an adult experimental pig. A reversed-phase high-performance liquid chromatographic method with fluorescence detection was used for the determination of fluorescein in blood plasma and tissue samples.r />r /> RESULTS AND CONCLUSION: The pharmacokinetic study of fluorescein determined the optimum time interval for diagnostic scanning (5-10 min.) The biodistribution study of fluorescein (aimed on the potential organ accumulation) proved the high concentration in the renal system followed by levels in bile > lung > adipose tissue > all other organs (including gastrointestinal wall) and these were relatively similar to each other. Fluorescein has a significantly low distribution in the brain (contrast with the level in adipose tissue indicates the low ability to penetrate the blood-brain barrier)....

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Journal Article 2010; 31(Suppl 2): 26-35 PubMed PMID: 21187821 Citation  Keywords:  Animals, Antineoplastic Agents:metabolism, Biotransformation:drug effects, Cytochrome P-450 Enzyme System:physiology, DNA Adducts:drug effects, Ellipticines:metabolism, Kidney:metabolism, Liver:metabolism, Lung:metabolism, Male, Microsomes:drug effects, M.   

OBJECTIVE: Ellipticine is a potent antineoplastic agent exhibiting multiple mechanisms of action. This anticancer agent should be considered a pro-drug, whose pharmacological efficiency and/or genotoxic side effects are dependent on its cytochrome P450 (CYP)- and/or peroxidase-mediated activation to species forming covalent DNA adducts. The target of this study was to investigate a role of CYP and peroxidase enzymes in ellipticine oxidative activation in rats, a suitable model mimicking the fate of ellipticine in humans, in details. The contribution of pulmonary and renal CYP- and peroxidase enzymes to ellipticine metabolic activation is investigated and compared with that found in the liver.r />r /> METHODS: Ellipticine oxidation and DNA adduct formation in vitro were investigated using microsomes isolated from liver, lung and kidney of rats, either control (untreated) or treated i.p. with a single dose of 40 mg of ellipticine per kg of body weight. HPLC with UV detection was employed for the separation and characterization of ellipticine metabolites. Inhibitors of CYPs and cyclooxygenase (prostaglandin H synthase, COX) were used to characterize the enzymes participating in ellipticine oxidative activation in rat liver, lung and kidney. Ellipticine-derived DNA adducts were detected by 32P-postlabeling.r />r /> RESULTS: Using α-naphthoflavone, furafylline and ketoconazole, inhibitors of CYP1A, 1A2 and 3A, respectively, we found that the CYP1A and 3A enzymes play a major role in ellipticine activation to species forming DNA adducts in liver microsomes. Because of lower expression of these enzymes in lungs and kidneys, even after their induction by ellipticine, they play a minor role in ellipticine activation in these extrahepatic tissues. Arachidonic acid, a cofactor of COX, increased ellipticine activation in the microsomes of extrahepatic tissues. In addition, indomethacin, an inhibitor of COX, efficiently inhibited formation of ellipticine-derived DNA adduct in these microsomes. Based on these results, we attribute the higher activation of ellipticine in lung and kidney microsomes to COX than to CYP enzymes.r />r /> CONCLUSION: The results demonstrate that whereas CYP enzymes of 1A and 3A subfamilies are the major enzymes activating ellipticine in rat livers, peroxidase COX plays a significant role in this process in lungs and kidneys....

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Journal Article 2010; 31(Suppl 2): 11-15 PubMed PMID: 21187820 Citation  Keywords:  Animals, Annexin A5:metabolism, Apoptosis:drug effects, Carps:metabolism, Caspases:metabolism, Cell Survival:drug effects, Dose-Response Relationship, Drug, Immune System:cytology, L-Lactate Dehydrogenase:metabolism, Lymphocytes:cytology, Models, Animal, .   

OBJECTIVES: The aim of this study was to assess the possible in vitro apoptotic effects of anatoxin-a on the selected immune cells isolated from the blood of carp.r />r /> DESIGN: In the experiments pure anatoxin-a was used at concentrations of 0.01, 0.05, 0.1 and 1 µg/ml RPMI-1640 medium. Apoptosis or necrosis of fish leukocytes (lymphocytes and phagocytes) induced by the toxin was determined by measurement of the activity of caspases-3/7 and the analysis of phosphatidylserine on the outer leaflet of apoptotic cell-membranes using Annexin-V-Fluorescein and Propidium Iodide. Moreover, fluorescent measurement of the release of lactate dehydrogenase from the cells with damaged membranes was done.r />r /> RESULTS: The viability of the lymphocytes exposed only to the highest concentration of anatoxin-a (1 µg/ml) was significantly decreased. The exposure to the toxin at higher concentrations (0.1 and 1 µg/ml) resulted in a significant increase of caspases 3/7 activity in phagocytes and lymphocytes. Moreover, fluorescent analysis with the use of annexin-V-fluorescein and propidium iodide staining showed more cells at the apoptotic stage than necrotic cells.r />r /> CONCLUSION: Our study showed that anatoxin-a is an inducer of apoptosis in fish immune cells....

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Journal Article 2010; 31(Suppl 2): 69-72 PubMed PMID: 21187819 Citation  Keywords:  Adult, Carcinogens:pharmacology, Dose-Response Relationship, Drug, Humans, Leuzea, Male, Middle Aged, Neutrophils:drug effects, Oxidative Stress:drug effects, Phosphorylation:drug effects, Plant Extracts:pharmacology, Protein Kinase C:metabolism, Reactive.   

OBJECTIVE: Neutrophil leukocytes and macrophages represent professional phagocytic cells. When appropriately stimulated, they undergo dramatic physiological and biochemical changes resulting in phagocytosis, chemotaxis and degranulation with the activation of reactive oxygen species (ROS) production known as the respiratory burst.r />r /> DESIGN: In this study we analysed the effect of a crystalline complex fraction of four N-feruloyl-serotonin isomers isolated from the seeds of Leuzea carthamoides on the mechanism of oxidative burst of human neutrophils in vitro.r />r /> RESULTS: N-feruloyl-serotonin (N-f-5HT) inhibited dose-dependently oxidative burst of human whole blood and isolated neutrophils in vitro stimulated with phorbol-myristate-acetate (PMA) as measured by luminol/isoluminol enhanced chemiluminescence.In isolated neutrophils stimulated with PMA, N-f-5HT was effective against extracellular as well as intracellular reactive oxygen species. Western blot analysis documented that N-f-5HT in concentrations of 10 and 100 µM significantly decreased PMA-induced phosphorylation of protein kinase C alpha/beta II.r />r /> CONCLUSION: The results suggest that N-f-5HT represents an effective naturally occurring substance with potent effect on the oxidative burst of human neutrophils and could be further investigated for its pharmacological activity against oxidative stress in ischaemia-reperfusion, inflammation and other pathological conditions....

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Journal Article 2010; 31(Suppl 2): 120-123 PubMed PMID: 21187818 Citation  Keywords:  Adult, Ascorbic Acid:blood, Carotenoids:blood, Czech Republic, Diet, Female, Health Status, Health Surveys, Humans, Male, Military Personnel, Nutritional Status, Vitamin A:blood, Vitamins:blood, alpha-Tocopherol:blood, beta Carotene:blood,.   

OBJECTIVES: The work objective was to monitor nutritional habits in the observed group of professional soldiers with the focus on eating food with the content of antioxidant carriers. Then to show present state of health and nutrition in the group on the basis of anthropometric measurements and biochemical examinations and finally to observe the level of antioxidant vitamins in the observed group of professional soldiers.r />r /> METHODS: The group included 171 healthy individuals, 152 men and 19 women. Their average age was 34.2±7.9 years. The venous blood was taken for biochemical examinations in all individuals on a fast. Anthropometric measurements (weight, height, caliperation, waist circumferences), blood pressure and pulse were taken continually in all individuals. Simple questionnaires were administered to all participants for the complete evaluation of present health and for the registration of eating habits of the observed persons.r />r /> RESULTS: The study results show that retinol and a-tocoferol levels in the observed group were within a normal range. The average concentration of vitamin C in this group was 54 mmol/l and reached nearly the values given in other European countries. But concentrations of β-caroten and lycopen in serum were up to 50% lower in comparison with concentrations in population in the countries of West Europe. Higher vitamin C and β caroten serum levels were found in individuals who respond in a questionnaire they eat fruit and vegetables or supplements of vitamin preparations every day. Statistically lower levels of vitamin C, β karoten and lycopen in the group of obese people (compared with the group of normal weight people) show decreased level of antioxidant protection of the organism and the risk of cardiovascular diseases.r />r /> CONCLUSIONS: The results show that it is necessary to ensure optimal food not only with an energetic diet value but also with a proper input of antioxidant carriers in the form of fresh vegetables and fruit every day....

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Clinical Trial 2010; 31(5): 663-666 PubMed PMID: 21178946 Citation  Keywords:  5-Hydroxytryptophan:administration & dosage, Adaptation, Psychological:drug effects, Adult, Antidepressive Agents, Second-Generation:administration & dosage, Austria, Blood Platelets:chemistry, Brain-Derived Neurotrophic Factor:blood, Courtship:psychology.   

: This open-label trial assessed the clinical efficacy of L-5-hydroxytryptophan (5-HTP), a natural serotonin precursor, in nondepressed young subjects with high levels of romantic stress. Since both neurotrophins and serotonin have been linked to human romantic attachment, we sought to investigate the changes in serum brain-derived neurotrophic factor (BDNF) levels and platelet serotonin content in relation to the changes in romantic stress throughout the study. A total of 15 healthy subjects (11 females and 4 males, mean age: 23.3 ± 2.1 years) who experienced a recent romantic break-up or reported recent romantic problems took part in the study. The participants were treated openly for 6 weeks with L-5-hydroxytryptophan (60 mg Griffonia simplicifolia extract containing 12.8 mg 5-HTP b.i.d., Amorex, Coropharm, Villach, Austria). The subjects were evaluated at baseline, at 3 weeks and at the end of the 6-week trial using an adapted version of the Seiffge-Krenke's Problem Questionnaire. BDNF and platelet serotonin content were determined at baseline, at 3 weeks, and after the completion of the 6-week trial. We observed significant improvements in romantic stress scores from weeks 0 through 3 (p=0.007) but no further significant improvement was evident from weeks 3 through 6 (p=0.19). At 6 weeks, subjects had a significant increase from baseline in both BDNF and platelet serotonin values. Our data suggest that direct modulation of the serotonergic system may have use for the treatment of psychological suffering associated with unreciprocated romantic love....

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