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Journal Article 2007; 28(Suppl 1): 13-26 PubMed PMID: 17262010 Citation  Keywords:  Antipsychotic Agents:therapeutic use, Humans, Long-Term Care, Psychiatry, Psychotic Disorders:physiopathology,.   

: Long-term treatment of psychotic disorders requires both the general and the individual approach to the patients and their problems. Such strategies are mainly directed to solve various problems, which not solely are restricted to the medical ones. It is crucial to determine what are the principal goals for the treatment, as the requirement to resolve psychotic symptoms is not always possible to fulfil. Thus, the description of the treatment strategies should include the precise definition of treatment goals (remission, recovery, functional improvement, subjective well-being, etc.). The time of treatment needed to reach such a goal is also crucial. An important role plays the choice of antipsychotic medication, which sometimes leeds to the application of guidelines or treatment algorithms. Such widely accepted standards are valuable tools to help to identify the most appropriate treatment for psychotic conditions, being not necessary adequate to patient's expectations and needs....

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Journal Article 2001; 22(1): 53-73 PubMed PMID: 11393163 Citation  Keywords:  Adrenal Glands:physiology, Animals, Biological Clocks, Blood Pressure:physiology, Chronobiology Disorders:physiopathology, Chronobiology Phenomena, Chronotherapy, Circadian Rhythm:physiology, Drug Administration Schedule, Genomics, Homeostasis, Humans, Pi.   

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Journal Article 2006; 27(6): 807-812 PubMed PMID: 17187012 Citation  Keywords:  Animals, Cell Differentiation:physiology, Cell Line, Tumor, Cell Shape, Mice, Neuroblastoma, Neurons:cytology, Neuroprotective Agents:administration & dosage, Oxidative Stress:physiology, Stem Cells:cytology, Testosterone:administration & dosage, Tyrosine.   

OBJECTIVES: Using undifferentiated mouse neuroblastoma cells (C1300), we have previously observed that testosterone (T) exerts a neuroprotective action against oxidative stress. Nitrogen intermediates induce the production of 3-nitro-L-tyrosine (3NT), an amino acid analogue involved in many neurodegenerative disorders. The aim of our work is to investigate T capability on C1300 cell differentiation. It is also evaluated whether differentiation could mitigate the nitrosative effects of 3NT.

METHODS: The effects of both T and 3NT were studied on an undifferentiated cell line of neural origin (C1300). For this purpose, cell cultures underwent morphometric investigation, blot analyses and catalase activity assay. All data obtained were expressed as mean+/-SD and tested by one-way ANOVA or Student's t test.

RESULTS: The results were compared with those gathered by means of N6,2'-O-dibutyryl-adenosine-3',5'-cyclic-mono-phosphate (db-cAMP), a well-known differentiating agent. T-exposed cells showed an irregular shape and exhibited long branching cytoplasmic extensions, which were longer than in db-cAMP cells. Moreover, T-exposure induced an increase in the expression of tyrosinated and acetylated alpha-tubulin while 3NT-incorporation into tubulin was markedly reduced. The action of antioxidant defence systems, namely catalase activity, was enhanced in cells exposed to T.

CONCLUSION: This work highlighted the effects of db-cAMP on differentiation and neuroprotection, but even indicated that T exposure induced differentiation in C1300 cells and this process matches a significant neuroprotective effect. This action seemed to be more effective than in db-cAMP-treated cells. T is suggested, like other substances having antioxidant properties, to be of potential interest in the experimental therapy of neuropathological conditions....

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Journal Article 2006; 27(6): 799-802 PubMed PMID: 17187009 Citation  Keywords:  Adult, Catechol O-Methyltransferase:genetics, Czechoslovakia, Dopamine:metabolism, Exploratory Behavior:physiology, Female, Humans, Male, Methamphetamine, Polymorphism, Single Nucleotide, Substance-Related Disorders:enzymology,.   

OBJECTIVES: Measurable traits of human personality may mark the predisposition to psychopathology. Increased novelty seeking plays an important role in the pathogenesis of substance abuse. Novelty seeking, one of the fundamental traits of the human temperament, is related to dopamine. Catechol-O-methyltransferase (COMT) is essential for dopamine inactivation. The aim of our study was to assess whether the COMT gene Val158Met functional polymorphism in patients dependent on methamphetamine is related to their novelty seeking score.

METHODS: Patients dependent on methamphetamine who had been treated at the Addiction Treatment Unit in Nechanice in 2004 and 2005 agreed to participate in the investigation. We administered the Temperament and Character Inventory (TCI) questionnaire, assessed their novelty seeking score and analysed their DNA samples for COMT Val158Met genotype.

RESULTS: The subjects were thirty-seven Czech Caucasians (women N=10) dependent on methamphetamine with an average age of 23.6+/-3.8 years. We found a significantly higher mean novelty seeking score among the patients with the Met allele (Met/Met homozygotes+Val/Met heterozygotes; N=28) than in nine Val/Val homozygotes (27.4 vs 24.1; p=0.042, Two-Sample T-Test).

CONCLUSION: The Met allele of the COMT gene Val158Met polymorphism is associated with low COMT enzyme activity and high endogenous dopamine synaptic levels in the prefrontal cortex. This leads to a decrease in dopaminergic neurotransmission in nucleus accumbens and a need for an increased activity to stimulate it. Novelty seeking behavior corresponds with this need....

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Comparative Study 2006; 27(6): 779-785 PubMed PMID: 17187008 Citation  Keywords:  Antigens, Neoplasm:immunology, Apoptosis:immunology, Decidua:immunology, Endometriosis:immunology, Female, Humans, Immune Tolerance:immunology, Immunity, Cellular:physiology, Lymphatic Metastasis:immunology, Menstrual Cycle:immunology, Metallothionein:imm.   

: Acquiring the immune-mediated apoptosis and the ability to regulate the cytotoxic immune response are the main phenomena playing fundamental roles in such situations as neoplasm survival and creation of immune tolerance during pregnancy. The aim of this study was to investigate these phenomena through the evaluation of metallothionein and RCAS1 proteins in neoplasm and its healthy environment (clear surgical margin), physiological conditions in placenta and its environment (decidua) and the comparison to non-neoplasmatic lesions originating from the environment (nasal polyps, endometriosis). We have shown that the growth of RCAS1 expression was simultaneous to the infiltration of activated immunological cells of tumor environment as well as decidua. The activity of immunological cells was in our study selectively suppressed. Metallothionein expression growth was also observed in healthy tumors stroma and in decidua probably in response to the growing cytotoxic activity and tumor spread. Alterations in RCAS1 and Metallothionein expression seem to be associated with local immune dysfunction in nasal polyps and endometriosis. In conclusion, the ability to compensate the growing cytotoxic immune response is physiologically observed in decidua, the lost of this ability in tumor environment might participate in the development of tumor spread....

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Journal Article 2006; 27(6): 795-798 PubMed PMID: 17187004 Citation  Keywords:  Adult, Female, Glycoprotein Hormones, alpha Subunit:metabolism, Humans, Male, Middle Aged, Prolactin:metabolism, Reference Values, Stimulation, Chemical, Thyroid Function Tests, Thyrotropin:metabolism, Thyrotropin-Releasing Hormone:physiology,.   

OBJECTIVE: The alpha-subunit (Alpha-SU) response to TRH was studied to examine the response of alpha-SU under TRH stimulation in normal situation.

METHODS: Thirty seven healthy individuals were included in the study. They were divided into two groups according to the data taken: A with TSH equal or more than seven fold the basal values (0: 3.14+/-1.2 microU/ml., 30 after TRH: 20.22+/-4.6 microU/ml) and B with TSH 2 to 6 fold the basal values (0: 0.5+/-0.1 microU/ml., 30 after TRH: 2.9+/-0.5 microU/ml). Both groups exhibited similar FT3 and FT4 levels.

RESULTS: In group A, prolactin displayed a 3 fold increase from the basal values, whereas alpha-SU increased 4 fold with a difference being statistically significant (p<0.001). In contrast, in group B individuals neither prolactin nor alpha-SU exhibited any significant difference from the basal values.

CONCLUSION: The expression of alpha-SU upon TRH stimulation is dependent on the TSH basal values....

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Comparative Study 2006; 27(Suppl 2): 65-68 PubMed PMID: 17159782 Citation  Keywords:  Asphyxia Neonatorum:blood, Delivery, Obstetric, Glutathione Peroxidase:blood, Humans, Infant, Newborn, Malondialdehyde:blood, Oxidative Stress, Stress, Physiological:blood, Superoxide Dismutase:blood, Term Birth:blood,.   

OBJECTIVES: In healthy term newborns (HTN) to determine on the 1st and 5th day of life the activity of total antioxidant capacity (TAS), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPX) and to compare the values with the group of asphyxiated term newborns (ATN).

PATIENTS/METHODS: The series consisted of 15 HTN and 24 ATN. In both groups TAS, MDA, GPX and SOD were investigated.

RESULTS: Reference values in HTN (1st/5th day of life) for TAS were 0.52+/-0.03/0.49+/-0.04 mmol/l, for MDA 0.72+/-0.07/1.08+/-0.09 micromol/l, for SOD 594.20+/-16.47/591.23+/-14.14 Ug/Hb and for GPX 25.48+/-1.32/25.98+/-1.20 Ug/Hb. In a group of ATN the obtained values were (1st/5th day of life): TAS 1.1+/-0.08/0.98+/-0.08 mmol/l, MDA 2.08+/-0.22/2.21+/-0.34 micromol/l, SOD 509.18+/-26.8/564.49+/-36.4 Ug/Hb and GPX 30.2+/-1.9/32.45+/-2.69 Ug/Hb.

CONCLUSIONS: Statistically significant differences were found on the 1st and 5th day of life between the two groups investigated in values of MDA (**p<0.01) and TAS (**p<0.01). Increased values of MDA in the group of ATN on the 1st and 5th day of life confirmed the presence of lipoperoxidation. The obtained values of TAS on the 1st and 5th day of life in the group of ATN were surprisingly higher than in HTN. The increase of TAS in ATN could point to a certain ability of ATN to prevent the damage of balance between overproduction of MDA and antioxidants. The results of SOD and GPX activity were not statistically significant, yet they are indicative of the biochemical reaction of the organism of term newborns to asphyxia....

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Journal Article 2006; 27(Suppl 2): 35-39 PubMed PMID: 17159775 Citation  Keywords:  Animals, Coloring Agents:pharmacokinetics, Cytochrome P-450 CYP1A1:metabolism, Cytochromes b5:physiology, DNA:metabolism, DNA Adducts:metabolism, Humans, Male, Metabolic Detoxication, Phase I, Models, Biological, Naphthols:metabolism, Rabbits, Rats, Rats,.   

OBJECTIVES: Modulation of the cytochrome P450 (CYP) 1A1-mediated oxidative activation and detoxication of carcinogenic Sudan I by the heme-protein cytochrome b(5) (b(5)) was investigated. Another aim of the study was to examine the formation of Sudan I-DNA adducts in vivo.

METHODS: High performance liquid chromatography (HPLC) with ultraviolet (UV) detection was employed for the separation of Sudan I metabolites formed by human recombinant CYPs and rat CYP1A1. The (32)P-postlabeling technique was utilized to determine Sudan I-DNA adducts.

RESULTS: The capabilities of the most efficient CYP enzymes oxidizing Sudan I, human and rat recombinant CYP1A1, as well as of human recombinant CYP1A2, 2A6 and 3A4 were significantly increased by b(5), while reactions catalyzed by human CYP1B1, 2C8, 2C9 and 2E1 were insensitive to this heme protein. Sudan I oxidation catalyzed by CYP2B6, 2C19 and 2D6 was even decreased by b(5). The stimulation of the CYP1A1-mediated Sudan I oxidation was dependent on concentration of b(5). Likewise, the increase in CYP1A1-mediated formation of Sudan I-DNA adducts by b(5) was concentration dependent. Other proteins containing heme such as cytochrome c or myoglobin were without this effect. The major Sudan I-DNA adducts formed in vitro are also generated in vivo, in livers of rats treated with Sudan I.

CONCLUSIONS: The data are the first report on the stimulation of CYP1A1-mediated oxidative reactions by b(5). In addition, the results demonstrating covalent binding of Sudan I to rat liver DNA in vivo indicate a genotoxic mechanism of Sudan I carcinogenicity in rats....

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