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Case Reports 2007; 28(1): 7-10 PubMed PMID: 17277733 Citation  Keywords:  Adult, Chromosomes, Human, Pair 17:genetics, Craniofacial Abnormalities:genetics, Female, Gene Deletion, Humans, Intellectual Disability:genetics, Melatonin:physiology, Mood Disorders:diagnosis, Muscle Hypotonia:genetics, Syndrome,.   

: Smith-Magenis syndrome (SMS) is a microdeletion syndrome characterized by physical and neurobehavioural features. This report describes the case of a 27 year old female affected by SMS associated with a diagnosis, according to DSMIV criteria, of Mood Disorder N.O.S. and Intermittent Explosive Disorder. To our knowledge, the association of SMS with mood shifts has never been reported. Considering the genetic alterations that characterizes the SMS, further investigations on the region of the chromosome 17p11.2 could help produce more information on the role of melatonin in the genesis of mood disorder....

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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): 741-744 PubMed PMID: 17187016 Citation  Keywords:  Adrenal Cortex Hormones:therapeutic use, Aged, Aged, 80 and over, Anti-Infective Agents:therapeutic use, Chi-Square Distribution, Chronic Disease, Complement C3:analysis, Conjunctivitis:complications, Dry Eye Syndromes:complications, Female, Humans, Immun.   

PURPOSE: The aim of this study was a clinical analysis of patients with symptoms typical of pemphigoid.

MATERIAL AND METHODS: 21 patients were enrolled on the study within the period 1988-2004. The frequency and type of ophthalmological and extraocular symptoms and accompanying diseases were assessed. The analysis also contains immunological findings as well as administered treatment.

RESULTS: Ophthalmological changes were detected in 100% of examined patients with pemphigoid. The most frequent were dry eye syndrome and conjunctivitis. Immunohistochemical tests revealed the presence of antibodies in 68.2% of the examined cases. All patients required specific treatment--local, general and surgical. Despite the administered therapy the development of cicatricial changes was observed.

CONCLUSIONS: Chronic conjunctivitis and keratitis require diagnostics into pemphigoid. Intensive therapy is necessary in patients with ocular cicatricial pemphigoid (OCP) because of high risk of blindness. Delayed diagnostics disable immunohistochemical confirmation of disease....

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Journal Article 2006; 27(Suppl 2): 130-133 PubMed PMID: 17159797 Citation  Keywords:  Adult, Chromatography, High Pressure Liquid:methods, Dose-Response Relationship, Drug, Female, Humans, Male, Methadone:analogs & derivatives, Molecular Conformation, Opioid-Related Disorders:blood, Sensitivity and Specificity,.   

OBJECTIVES: A stereoselective HPLC method was developed to separate and quantify both enantiomers of methadone and its main metabolite EDDP in serum and urine. The method was used to establish that there is a relationship between the dose of methadone prescribed and its serum concentration as well as urine excretion of methadone and its metabolite enantiomers.

METHODS: The chiral alpha1-glycoprotein stationary phase was used for enantioseparation of (R)-methadone, (S)-methadone and (R)-EDDP (S)-EDDP. The enantiomers of methadone and EDDP were extracted from urine and serum by a simple solidphase procedure.

RESULTS: The validated method was applied to the analysis of 31 serum and urine samples obtained from methadone-maintained outpatients (65% male, age 28.8+/-4; methadone dose 146+/-47 mg). A significant correlation (Pearson) r=0.67 (p<0.001) between methadone dose and serum concentration of (R)-methadone was found. Due to the large variation in results obtained from analysis of the subjects' urine specimens, no statistically significant relationship between methadone dose and urine excretion of methadone and EDDP enantiomers was established. The rate of R/S methadone (1.38 in serum, 2.43 in urine) and R/S EDDP (0.83 in urine) confirmed stereoselectivity in methadone metabolism with high individual variability.

CONCLUSIONS: The enantioselective evaluation of serum methadone concentration might be an interesting tool in methadone maintenance programme. On the other hand, the urinary excretion of methadone and EDDP enantiomers is not reliable as marker of methadone compliance but could be useful for monitoring individual metabolism or for studying the stereoselectivity in pharmacokinetics and metabolism of methadone....

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Evaluation Studies 2006; 27(Suppl 2): 125-129 PubMed PMID: 17159796 Citation  Keywords:  Chromatography, Thin Layer, Forensic Toxicology:methods, Gas Chromatography-Mass Spectrometry, Hallucinogens:blood, Humans, Models, Biological, Substance Abuse Detection:methods,.   

OBJECTIVES: Until recently, routine toxicological analysis of some hallucinogens in biological material posed problems which were only resolved after the introduction of modern analytic systems into toxicological laboratories. The most frequent hallucinogens in clinical and forensic toxicology can be grouped as: cannabinoids, tropane alkaloids, N,N-dimethyltryptamine derivatives and synthetic or semisynthetic hallucinogens.

METHODS & RESULTS: There are several methods currently used for their analysis. Immunoassay analysis of abused hallucinogens is limited to the cannabinoids. Thin layer chromatography (TLC) is able to detect higher concentrations of 1-nor-delta- 9-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), tropane alkaloids (atropine and scopolamine) and ketamine (synthetic hallucinogen) in urine but for lower concentrations and for some other substances it lacks sensitivity. A reliable solution to the demand for specific and sensitive analysis of hallucinogens in biological material is gas chromatography - mass spectrometry (GC-MS). Thus, at present, analysis of cannabinoids, tropane alkaloids, ketamine as well as psilocin (N,N-dimethyltryptamine derivative) is well-managed.

CONCLUSIONS: The introduction of GC-MS systems appears to be indispensable for satisfactory qualitative and quantitative analysis of drugs of abuse, particularly hallucinogens in biological material....

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Evaluation Studies 2006; 27(Suppl 2): 121-124 PubMed PMID: 17159795 Citation  Keywords:  Amphetamines:urine, Designer Drugs:analysis, Gas Chromatography-Mass Spectrometry:methods, Humans, Reproducibility of Results, Sensitivity and Specificity, Substance Abuse Detection:methods,.   

OBJECTIVES: The purpose of this study is to evaluate the gas chromatographicmass spectrometric method (GC-MS) for assay of stimulants of amphetamine type: amphetamine (AMP), methamphetamine (MAMP), ephedrine (EPH), norephedrine (NOREPH), and the amphetamine-derived designer drugs 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA, ecstasy), 3,4-methylenedioxy-N-ethylamphetamine (MDEA) and N-methyl-benzodioxolylbutanamine (MBDB) in urine. These drugs are often encountered in forensic and clinical toxicological analysis.

METHODS: GC-MS method after mixed-mode solid-phase extraction (SPE) and derivatization with heptafluorobutyric anhydride (HFBA) is presented for quick and reliable screening as well as identification and quantification of amphetamines and amphetamine derived designer drugs in urine.

RESULTS: The measurement of calibration dependence allowed to determine the extent of linearity in the concentration range from 10 to 2,000 ng/ml for all amphetamines except AMP and for all amphetamine-derived designer drugs with correlation coefficients exceeding 0.98. Detection limits were established at 5 ng/ml and quantification limits at 10 ng/ml for all analytes, except AMP. LOD for AMP was established at 20 ng/ml and LOQ at 50 ng/ml. Extraction efficiency for all analytes at concentration levels 50 and 500 ng/ml (n=6) was established in the range 60-99%. Repeatability was measured at concentration levels 50 and 500 ng/ml (n=6), relative standard deviations (RSDs) were under 10% for all analytes.

CONCLUSIONS: The GC-MS method after mix-mode solid-phase extraction and derivatization with heptafluorobutyric anhydride is presented for screening followed by identification and quantification of AMP, MAMP, EPH, NOREPH, MDA, MDMA, MDEA, and MBDB. The applicability of the GC-MS method was proven by analyzing authentic urine samples....

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Comparative Study 2006; 27(Suppl 2): 100-103 PubMed PMID: 17159790 Citation  Keywords:  Asbestos:toxicity, Asbestosis:genetics, Epoxide Hydrolases:genetics, Gene Frequency, Genetic Predisposition to Disease, Glutathione S-Transferase pi:genetics, Glutathione Transferase:genetics, Health, Humans, Micronuclei, Chromosome-Defective:chemically i.   

OBJECTIVES: As asbestos presents a direct genetic hazard for humans, a small-scale molecular epidemiological study was conducted to monitor 61 subjects long-term exposed to asbestos in comparison with 49 town controls and 21 control subjects from administration of the same factory.

RESULTS: Asbestos exposed workers had significantly higher numbers of chromosomal aberrations compared with both control groups (P=0.003). Clinical examination showed that 44.3% of exposed workers developed symptoms of asbestosis. We were interested in the relationship between the risk of asbestos-coupled diseases and individual variability in biotransformation enzymes, especially in glutathione S-transferases and microsomal epoxide hydrolase. GSTP1*105Val allele appeared less in the group of workers with asbestosis compared to those without asbestosis (18.5% vs 34.7%, P=0.044), and in subjects with developed asbestosis coupled with bronchitis compared to those without bronchitis (0% vs 25%, P=0.048). Similarly, the genotype corresponding to low activity of microsomal epoxide hydrolase was significantly decreased in workers with fibrotic plaques compared to those without plaques (26.7% vs 56.3%, P=0.045).

CONCLUSIONS: Our results suggest that GSTP1*105Val allele and low EPHX1 activity genotype may be protective for people occupationally exposed to asbestos. However, more extensive studies are needed to confirm our results....

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Journal Article 2006; 27(Suppl 2): 57-60 PubMed PMID: 17159780 Citation  Keywords:  Adult, Antineoplastic Agents:toxicity, Chromosomes, Human, DNA Damage, DNA-Binding Proteins:genetics, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Male, Medical Staff, Hospital, Middle Aged, Occupational Diseases:chemically induced, .   

OBJECTIVES: Medical workers in oncological units have chronically been exposed to low doses of cytostatics (C) with potential consequences on DNA and chromosomal integrity. Our study addresses relationships between chromosomal aberrations (CAs), chromosome (CSA), and chromatid (CTA) types and polymorphisms in DNA repair genes XRCC1 and XRCC3.

METHODS: The study was conducted on 72 exposed individuals from hospitals in Martin (HMT; 28 individuals), Ruzomberok (HRK; 31 medical workers) and in Trstená (HTS; 13 individuals), and on 34 unexposed individuals. Conventional cytogenetic analysis was employed for the detection of CAs. XRCC1 and XRCC3 polymorphisms were assayed for by Taqman SNP genotyping assays ("Assay-by-Demand") using Real-Time allelic discrimination on AB 7 500 equipment (all from Applied Biosystems, Foster City, USA).

RESULTS: Higher frequencies of CAs were detected in exposed individuals than in controls (1.78% versus 1.32%, respectively). The frequency of aberrant cells (Ab.c.) was highest among workers from HRK (1.97%), followed by those from HMT and HTS (1.54% and 1.85 %, respectively). In the exposed group a moderately higher frequency of CTA (0.93%) in comparison with CSA (0.85%) was detected. Higher CAs were detected in individuals with homozygous variant polymorphism in XRCC1 exon 10 gene than in those with wild-type genotype (1.87% versus 1.60%). Variant T allele in XRCC3 exon 7 was also associated with higher CAs (1.71% and 1.74%) as compared to the wild-type C allele (1.45%).

CONCLUSIONS: The detection of individuals with increased susceptibility to genotoxic agents enables to take preventive measures during the working process....

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