HCH and DDT residues in drinking water from the South of Spain, 1991-1994.
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Carcinogens↗
Biomedical subjects
M Repetto
Publications and source records attributed to M Repetto.
Biodisposition study of the organophosphorus pesticide, methyl-parathion.
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Animals↗
Influence of the cosmetic treatment of hair on drug testing.
An important issue of concern for drug analysis in hair is the change in the drug concentration induced by the cosmetic treatment of hair. The products used for this treatment are strong bases and they are expected to cause hair damage. As a result drugs may be lost from the hair matrix or, under conditions of environmental contamination, be more easily incorporated into the hair matrix. We investigated the effects of cosmetic treatment in vivo by analysing hair samples selected from people who had treated their hair by bleaching or dyeing before sample collection. All of the subjects admitted a similar drug consumption during the time period for which the strands were analysed. Samples were viewed under a microscope to establish the degree of hair damage. Treated and untreated portions from each lock of hair were then selected, separated and analysed by standard detection procedures for cocaine, opiates, cannabinoids and nicotine. In all cases the drug content in hair that had undergone cosmetic treatment decreased in comparison to untreated hair. The majority of the mean differences were in the range of 40%-60% (cocaine, benzoylecgonine, codeine, 6-acetylmorphine and THC-COOH). For morphine the mean difference was higher than 60%, and two cases (THC and nicotine) differed by approx. 30%. These differences depended not only on the type of cosmetic treatment, as bleaching produced higher decreases than dyeing, but also on the degree of hair damage i.e. the more damaged the hair, the larger the differences in the concentration levels of drugs.
Hair↗
4-Nerolidylcatechol from Pothomorphe spp. scavenges peroxyl radicals and inhibits Fe(II)-dependent DNA damage.
The total reactive antioxidant potential (TRAP) and total antioxidant reactivity (TAR) of 4-nerolidylcatechol (4-NC) and methanolic extracts of Pothomorphe umbellata and P. peltata were determined by monitoring the intensity of luminol enhanced chemiluminescence by peroxyl radicals derived from thermolysis of 2,2'-azobis(2-amidinopropane). The highest antioxidant potential was measured in the extract of P. umbellata (TRAP = 97.2 microM) while the highest reactivity was observed in the extract of P. peltata (TAR = 5.0 microM), measured as equivalents of Trolox concentration. These results were higher than those obtained for 4-NC (TRAP = 33.6 microM, TAR = 4.9 microM). DNA sugar damage induced by Fe(II) salts was also used to determine the capacity of 4-NC to suppress hydroxyl radical-mediated degradation of DNA. Calculated IC50 values for 4-NC and catechin, used as a standard, were 25 and 17 microM, respectively.
Catechols↗
Treatment of Madelung's deformity by lengthening and reaxation of the distal extremity of the radius by Ilizarov's technique.
Madelung's deformity was first described in 1878. It is characterised by a typical deformity of the carpus and not only causes pain but also impedes mobility and aesthetic appearance. Surgical correction can be effected during adolescence, the most frequently employed technique being conical osteotomy. We present a novel technique of lengthening and aligning the distal radial extremity using Ilizarov's technique. Five carpal joints were operated on in three 13-year old girls. An aesthetic effect was obvious in all the cases. Mobility improved by 30 degrees in the direction of the extension and pain always subsided directly after surgery.
Adolescent↗
A method to direct sequence cosmid LAWRIST16 clones.
We developed a new cycle condition method optimized for direct sequencing LAWRIST16 cosmid clones based on dye terminator and dye primer cycle sequencing chemistries. We report a direct comparison of the two most widely used sequencing polymerase enzymes (AmpliTaq FS and Thermosequenase). The sequencing data obtained is of high quality and we believe this method could be routinely used in large scale sequencing facilities.
Computer Communication Networks↗
Habitual, toxic, and lethal concentrations of 103 drugs of abuse in humans.
BACKGROUND: Poisoning caused by drugs of abuse or commonly used addictive medicines occurs with relative frequency and often leads, either directly or indirectly, to death. The interpretation of the blood and urine concentrations is, however, a complex and difficult problem. METHODS: We have reviewed the published data and subjected them to selection and unification on the basis of conservative criteria and our own experience. RESULTS: A compilation of the concentrations of 103 drugs of abuse in whole blood, serum/plasma, and urine, during habitual or therapeutic use and as found in toxic or lethal poisoning is given. CONCLUSIONS: The table presented can be helpful in interpretation of the drug concentrations encountered in clinical, toxicological, and forensic cases.
Blood Chemical Analysis↗
Therapeutic, toxic, and lethal concentrations in human fluids of 90 drugs affecting the cardiovascular and hematopoietic systems.
BACKGROUND: Drugs affecting the cardiovascular and hematopoietic systems are frequently involved in poisoning. As a continuation of our previously published study about the concentrations of drugs of abuse, we have compiled published data about these drugs and subjected them to selection and unification on the basis of conservative criteria and our own experience. RESULTS: A compilation of the concentrations of 90 drugs affecting heart, circulation, blood or hematopoietic organs, in whole blood, serum/plasma, and urine, corresponding to therapeutic, toxic or lethal concentrations is given. Although the interpretation of the concentrations is a complex and difficult problem, the presented table can be helpful in interpretation from the actual concentrations of this group of drugs encountered in clinical, toxicological and forensic cases.
Cardiovascular Agents↗
Tricompartmental kinetics of the organophosphorous pesticide dimethoate.
We present a study on the distribution and persistence of the organophosphorous pesticide, dimethoate, in the Wistar rat. Dimethoate's levels in blood and tissues were determined using gas chromatography with a NPD detector. The toxicokinetic profile was estimated by non-linear regression using the software program PCNONLIN, which concluded that a tricompartmental model best described dimethoate's behavior in the rat body.
Adipose Tissue↗
Oxidative stress in blood of HIV infected patients.
The oxidative stress in human erythrocytes was studied in asymptomatic and symptomatic patients infected by the human immunodeficiency virus (HIV), and patients with the acquired immunodeficiency syndrome (AIDS). tert-Butyl hydroperoxide initiated chemiluminescence, superoxide dismutase and catalase activities, and total glutathione were evaluated in the erythrocytes and the total antioxidant capacity in the plasma of control, patients infected with HIV that have not yet developed acquired immunodeficiency syndrome, and patients in the later stage of AIDS. tert-Butyl hydroperoxide initiated chemiluminescence was increased by 33% in asymptomatic (stage A1) and symptomatic patients (stage B2) infected with HIV and 82% for patients with AIDS (stage B3) (P < 0.05). While catalase activity did not show any difference between patients and controls, other indices showed differences that, in some cases, reached statistical significance. Superoxide dismutase activity was increased by 24% in stages A1 and B2 of HIV infection and 65% in patients in stage B3 (P < 0.05). Glutathione was decreased by 20% in stages A1 and B2, and by 32% in stage B3 patients (P < 0.05). Total plasma antioxidant capacity was increased in 30 and 57% for the asymptomatic and AIDS patients groups, respectively (P < 0.05). The data indicate that erythrocyte's oxidative stress is associated with the progressive development of HIV disease. Parameters indicating oxidative stress could be an interesting form to screen the evolution of these patients and their response to anti-oxidant therapies.
Adult↗
The antioxidant enzymatic blood profile in Alzheimer's and vascular diseases. Their association and a possible assay to differentiate demented subjects and controls.
A study of several elements of the antioxidative system: Cu-Zn superoxide dismutase (SOD), catalase (CAT), glutathione system (GLU), chemiluminescence (CHE), and antioxidant capacity (AOX), was conducted in 20 demented probable Alzheimer's (DAT), and 15 vascular demented (VD) patients, 19 control (C) subjects, and 11 relatives (F) of one DAT patient. A significant association was found between the variables of the antioxidant system, measured in blood samples, and the neurological pathologies VD and DAT: Kruskal-Wallis test; p = 0.0006 (p = 0.014 when the analysis did not include SOD). This demonstrated that VD and DAT diseases are accompanied by oxidative disorders. The VD and DAT diseases are differentially distinguishable by changes in blood profiles. A graphical method for classification, the Principal Components Analysis (PCA), distinguished between demented and non-demented subjects on the basis of their laboratory variables. A numerical method, Discriminant Functions (DF), constructed to separate the clinical groups on the basis of the same variables, obtained relatively high percentages of success: 92% of demented were detected against healthy subjects; of the latter 82% have been correctly identified as non-demented. Discrimination between VD and DAT patients was achieved for 100% of VD and 86% of DAT patients. DF were similarly successful in detecting the healthy condition of DAT relatives. Possible different mechanisms involved in H2O2 elimination in DAT and VD patients are proposed, where CAT is the responsible enzyme of this reaction in DAT patients, while in VD this function would be achieved mainly through the action of GLU. It seems that SOD levels are stable, at least, within one year. Variations appear to be linked with clinical changes.
Aged↗
Comparative effects of the metabolic inhibitors 2,4-dinitrophenol and iodoacetate on mouse neuroblastoma cells in vitro.
The toxic effects of two metabolic inhibitors, dinitrophenol and iodoacetic acid, were compared. Mouse neuroblastoma cell cultures (Neuro-2a) were exposed to different concentrations of the toxic compounds for 24, 48 and 72 h to study basal toxicity effects (cell proliferation by quantification of total protein content (PR) and relative neutral red uptake (RNRU) by lysosomes). The following biochemical indicators assessed in the in vitro test system were: cytosolic phosphofructokinase (PFK) and enolase (ENL) activities in glycolysis; mitochondrial succinate dehydrogenase (SDH) activity in the citric acid cycle; lysosomal beta-galactosidase (GAL) activity; and neuronal acetylcholinesterase (AChE) activity. The effects of the two metabolic inhibitors on the various indicators differed. Iodoacetic acid was found to be far more toxic than dinitrophenol to neuroblastoma cell proliferation at 24 h exposure. Though 2,4-dinitrophenol and iodoacetic acid both inhibited cell proliferation of the neuroblastoma cells, their effects on the other endpoints were opposite. Dinitrophenol was a general activator of the metabolism, particularly affecting lysosomal function. Iodoacetic acid did not significantly alter general metabolism, but considerably modified lysosomal function and AChE activity. The modification of lysosomal function of Neuro-2a cells by the two compounds was quite different: dinitrophenol increased RNRU and GAL activity, and iodoacetic acid decreased both parameters.
2,4-Dinitrophenol↗
Neutrophil function, nitric oxide, and blood oxidative stress in Parkinson's disease.
We studied nitrogen radical nitric oxide (.NO) release and reactive oxygen species (ROS) production by isolated neutrophils after phorbol myristate acetate (PMA) stimulation in 12 newly diagnosed and nine treated Parkinson's disease (PD) patients and 10 age-matched healthy controls. Neutrophils of both groups of PD patients had an elevated PMA-activated release of .NO [61 and 57%, respectively, higher than that of controls (p < 0.05)]. In contrast, H2O2 release was only significantly increased by 56% in chronically treated patients. In agreement, the maximum rate of luminol-dependent chemiluminescence, which partly represents O2- H2O2- .NO interactions, was increased only in the treated group. When other blood markers of oxidative stress were compared, only erythrocyte catalase activity was decreased in both PD patient series by 33 and 39%, respectively (p < 0.05), whereas plasma antioxidant capacity and erythrocyte superoxide dismutase activity levels were decreased only in treated PD patients. This study suggests that neutrophils express a primary alteration of .NO release in PD patients, whereas H2O2 and oxidative-stress parameters are more probably related to the evolution of PD or to effects of treatment with L-dopa.
Antiparkinson Agents↗
Changes in antioxidative activities induced by Fe (II) and Fe (III) in cultured Vero cells.
The toxicity of iron (II) and iron (III) chlorides was studied at different biochemical and cellular levels, including antioxidative and metabolic enzymes and two general indicators of cytotoxicity in Vero monkey kidney cells after 24-h exposure. Iron (II) was fourfold more toxic than Fe (III) in cell proliferation, with EC50 of 5.5 and 22 mM, respectively. Metabolic markers were far more sensitive than cytotoxicity assays at these concentrations. At the highest concentrations of toxicant tested [10 mM Fe(II) and 50 mM Fe(III)], both species produced nearly total inhibition of the relative uptake of neutral red (RNRU) and phosphofructokinase activity (PFK), and stimulated intracellular specific lactate dehydrogenase activity (LDH). Succinate dehydrogenase (SDH) and hexosaminidase (HEX) activities were reduced in dose-dependent manner, as was the antioxidative enzyme glucose-6-phosphate dehydrogenase (G-6-PDH) with both forms of iron. Glutathione reductase (GOR) and glutathione-S-transferase (GST) activities were stimulated by Fe (II) but were inhibited by the higher Fe (III) concentrations. In conclusion, the experimental model may be useful for the study of different metabolic effects induced by the two oxidation states of iron.
Animals↗
Long-range sequence analysis in Xq28: thirteen known and six candidate genes in 219.4 kb of high GC DNA between the RCP/GCP and G6PD loci.
DNA comprising 219 447 bp was sequenced in nine cosmids and verified at > 99.9% precision. Of the standard repetitive elements, 187 Alus make up 20.6% of the sequence, but there were only 27 MERs (2.9%) and 17 L1 fragments (1.6%). This may be characteristic of such high GC (57%) regions. The sequence also includes an 11.3 kb tract duplicated with 99.2% identity at a distance of 38 kb. The region is 80-90% transcribed and 12.5% translated. Thirteen known genes and their exon-intron borders are all accurately predicted at least in part by GRAIL programs, as are six additional genes. From centromere to telomere, the orientation of transcription varies among the first eight genes, then runs centromeric to telomeric for the next five, and is in the opposite sense for the last six. Eighteen of the 19 genes are associated with CpG islands. Two islands are exact copies in the 11.3 kb repeat units, and could thus give rise to double dosage levels of an X-linked gene. Another island is associated with two genes transcribed in opposite directions. From the sequence data, three genes and their exon structure are inferred. One of them, previously associated with HEX2, is shown to be a different gene unrelated to hexokinases; a second gene, previously known by an EST, is plexin, from its 65.5% identity with the Xenopus analog; and a third is a subunit of a vacuolar H-ATPase, and is named VATPS1.
Base Sequence↗
Homozygosity and heterozygosity for the transthyretin Leu64 mutation: clinical, biochemical and molecular findings.
Transthyretin gene point mutations cause hereditary amyloidosis with an autosomal dominant pattern of inheritance. The disease usually manifests itself in heterozygous patients, although a few homozygotes have been reported. We describe two unrelated patients carrying the Leu64 mutation, one of whom presents a homozygous genotype (Family B). Homozygosity was confirmed by sequence analysis, RG-PCR and double one-dimensional electrophoresis of the plasma protein. Although the clinical picture of the homozygous patient of Family B was more severe than that shown by the heterozygous members of Family A, the variability often displayed by FAP patients does not allow any firm conclusion about the role of homozygosity in the seriousness of the disease.
Aged↗
Method for the simultaneous quantification of n-hexane metabolites: application to n-hexane metabolism determination.
1. The described analytical procedure permits the simultaneous determination of the main n-hexane metabolites in urine. 2-Hexanone, 2-hexanol, 2, 5-hexanediol and 2, 5-hexanedione, were chosen to dose the rats used in this study. All urine samples were collected and analysed on a daily basis, before and after acidic hydrolysis (pH 0.1) by GC/MS. 2-Hexanone, 2, 5-dimethylfurane, gamma-valerolactone and 2, 5-hexanedione were determined before hydrolysis: 2-hexanol and 2, 5-hexanediol, after hydrolysis; and 5-hydroxy-2-hexanone and 4, 5-dihydroxy-2-hexanone were calculated by the difference between gamma-valerolactone and 2, 5-hexanedione with and without hydrolysis, respectively. 2. A metabolic scheme was proposed reflecting the biotransformations undergone by the four compounds assayed. We consider 2, 5-dimethylfurane as a "true metabolite' because the quantities detected were always greater before hydrolysis. 3. It has been reported that human and rat n-hexane metabolism follow a similar pattern. Therefore, as a practical application and without increasing either sample or time requirements, the simultaneous quantification of the different metabolites and their excretion profile could provide better information about the metabolic situation of exposed workers than the determination of 2, 5-hexanedione alone. According to our experimental results, 4, 5-dihydroxy-2-hexanone itself would be a good toxicity indicator.
Animals↗
The genomic organization of the human transcription factor 3 (TFE3) gene.
We have determined the exon-intron structure of the human TFE3 gene located on Xp11.22-23. By designing PCR primers, we were able to amplify various segments of the TFE3 genomic region, thus establishing that this gene is composed of seven exons, the first six of which are small (from 56 to 159 nt). The 5' UT region is contained entirely in the first exon, while the 3' UT region is contained in the seventh exon. The comparison of the genomic and the published cDNA versions revealed that the deduced amino acid sequence of TFE3 in the C-terminus region is 125 amino acids shorter than previously reported. This eliminates most of the putative proline- and arginine-rich domain and makes the human sequence more similar to its mouse homolog. The activation domain at the N-terminus is contained in exon 2, as has been described for the mouse. The basic helix-loop-helix (BHLH) motif is spread over exons 4 to 6, while the leucine zipper (LZ) is almost all contained in the last portion of exon 6. This split BHLH is different from other BHLH-LZ genes whose genomic structures have been determined up to now.
Animals↗