Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In West Berlin in the autumn of 1975 through the following 5 months we observed 18 juvenile patients who had a toxic polyneuropathy and had sniffed a glue thinner. The neurological picture consisted of a symmetrical, progressive, ascending, mainly motor, polyneuropathy with pronounced muscle atrophy and characteristic vegetative alterations. The height of the disease was reached after 1 1/2-2 1/2 months and was characterized by tetraplegia in 7 patients. After 8 months all patients still had a motor deficit. Nerve biopsy showed paranodal axon swelling, dense masses of neurofilaments and secondary myelin retraction. The neurological and morphological data correspond to the "glue sniffer's neuropathy" and the n-hexane and MBK polyneuropathy after industrial exposure, as described in 10 cases to date. However, there was no MBK in the glue thinner. The polyneuropathies occurred in close time relation with the denaturation of the thinner with MEK (2-butanone). It is concluded from the data n-hexane and MBK have a common toxic mechanism with primary axonal changes and that there is an additional synergistic effect of MEK.
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PMID:Toxic polyneuropathies after sniffing a glue thinner. 6 97

To make clear how the n-hexane metabolism is modified by co-exposure with MEK, rats were exposed to various concentrations of MEK mixed with a fixed concentration of n-hexane. Twenty-four male Wistar rats were divided into four equal groups. Each group was exposed for 8 h to 2000 ppm n-hexane, 2000 ppm n-hexane plus 200 ppm MEK, 2000 ppm n-hexane plus 630 ppm MEK and 2000 ppm n-hexane plus 2000 ppm MEK, respectively. Free metabolites and the sum of free and conjugated metabolites of n-hexane were analyzed by gas chromatography. The main metabolite was 2-hexanol during the exposure and 2,5-hexanedione (2,5-HD) after the exposure in any group. The main metabolites, 2-hexanol and 2,5 HD, decreased in inverse proportion to the co-exposed MEK concentrations. The results suggest that augmentation of n-hexane neurotoxicity by MEK co-exposure could not be explained only by 2,5-HD. In addition, 2,5-HD is recommended as an index for biological monitoring of n-hexane exposure. However, one should be careful to evaluate the exposed n-hexane concentration by urinary 2,5-HD, because n-hexane metabolism could be largely modified by co-exposure with MEK.
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PMID:Changes in urinary n-hexane metabolites by co-exposure to various concentrations of methyl ethyl ketone and fixed n-hexane levels. 235 Feb 38

The neurotoxicity of n-hexane is thought to be caused ultimately by 2,5-hexanedione (2,5-HD), one of the n-hexane metabolites. The potentiation of n-hexane neurotoxicity by co-exposure with MEK, therefore, is suspected to be related to kinetics of 2,5-HD in blood. To clarify the kinetics of n-hexane metabolites in the mixed exposure of n-hexane and MEK, rats were exposed to 2000 ppm n-hexane or a mixture of 2000 ppm n-hexane and 2000 ppm MEK, and the time courses of serum n-hexane metabolites were determined. 2,5-HD in serum increased until 2 h after the end of exposure, when serum 2,5-HD concentration reached a peak of 16.35 micrograms/ml in the n-hexane-alone group. In contrast, 2,5-HD in the mixed exposure group increased much more slowly during and after exposure than in the n-hexane-alone group. It reached a peak of 2.12 micrograms/ml at 8 h after the end of exposure. Serum MBK, a precursor of 2,5-HD in the co-exposure group, was about half in the n-hexane-alone group during exposure. However, MBK decreased more slowly in the co-exposure group than in the n-hexane-alone group after the end of the exposure. The results suggest that co-exposed MEK might inhibit oxidation of n-hexane and decrease clearance of n-hexane metabolites. Co-exposed MEK did not increase serum 2,5-HD, which was considered a main neurotoxic metabolite. Therefore the enhancement of neurotoxicity could not be attributed to increased serum 2,5-HD in the co-exposed group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of MEK on kinetics of n-hexane metabolites in serum. 237 36

1. Male Fischer-344 rats were given methyl ethyl ketone (MEK; 1.87 ml/kg), a potentiator of the neurotoxicity of n-hexane, by gavage for 4 days prior to a single inhalation exposure to n-hexane (1000 ppm). 2. Samples of blood, liver, testis and sciatic nerve were obtained and analysed for n-hexane, MEK and their metabolites by g.l.c.-mass spectrometry. 3. Pretreatment with MEK increased the concentrations of 2,5-hexanedione (2,5-HD; the proximal neurotoxin) in blood, sciatic nerve and testis relative to concentrations in the tissues in sham-treated controls. 4. Concentrations of 2,5-dimethylfuran, a metabolite of 2,5-HD, were increased in all four tissues tested. 5. After 1-7 days treatment with MEK, the activity of 7-ethoxycoumarin O-deethylase was increased (up to 500%), but benzphetamine N-demethylase activity was virtually unaffected. 6. Hence, the potentiating effects of MEK on the neurotoxicity of n-hexane appear to arise, at least in part, from the activating effects of MEK on selected microsomal enzymes responsible for n-hexane activation.
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PMID:Effects of methyl ethyl ketone pretreatment on hepatic mixed-function oxidase activity and on in vivo metabolism of n-hexane. 277 8

The effects of the solvents n-hexane, butanone (methyl-ethyl-ketone, MEK) and a mixture of both in the intrapulmonary nerve system of rats were studied by light and electron microscopy. The alteration in the fine structures of the tissue consisted in a disseminated swelling of axons due to a striking multiplication of neurofilaments. Nonspecific axonal alterations could be demonstrated as well. The latter consisted in clusters of phospholipid material within the axoplasm of nerve fibers and the cytoplasm of Schwann cells plus an accumulation of glycogen granules in the axoplasm. Additionally, single degenerative changes of Schwann cells were observed. An enzyme-associated metabolic damage with a concomitant impairment of axonal flow is discussed as a possible underlying pathomechanism.
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PMID:Ultrastructural alteration of intrapulmonary nerves after exposure to organic solvents. A contribution to 'sniffers disease'. 652 43

It is well known that n-hexane produces peripheral neuropathy, and 2,5-hexanedione, one of the metabolites of n-hexane, is thought to be the main causative agent. Recently, the metabolites of n-hexane in urine have been measured by gas chromatography, and 2,5-hexanedione was proved to be useful for the biological monitoring of n-hexane exposure. In the present experiment, we intended to clarify the change of n-hexane metabolites in the urine of rats exposed to various concentrations of n-hexane and to its mixture with toluene of MEK. In the first experiment, five separate groups of five rats each were exposed to 100, 500, 1000, or 3000 ppm of n-hexane, or fresh air respectively in an exposure chamber for 8 h a day. Urinary samples were gathered during exposure, 16, 24, and 40 h after exposure. Half of each sample was analyzed by gas chromatography after hydrolysis with acid and enzymes, and the other half was analyzed without hydrolysis. 2,5-Dimethylfuran, MBK, 2-hexanol, 2,5-hexanedione, and gamma-valerolactone could be identified as n-hexane metabolites in the urine. The main metabolites were 2-hexanol and 2,5-hexanedione. 2-Hexanol was mostly excreted during exposure, while most of the 2,5-hexanedione was excreted after the end of exposure. The amount of metabolites in the urine correlatively increased with the concentration of n-hexane from 100 to 1000 ppm, but the amount of metabolites scarcely increased when the concentration of n-hexane increased from 1000 to 3000 ppm.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes of n-hexane metabolites in urine of rats exposed to various concentrations of n-hexane and to its mixture with toluene or MEK. 665 98

Using an activated carbon felt (ACF, KF-1600), the applicability of an ACF passive sampler in monitoring organic vapors was evaluated. The evaluated results of the ACF passive sampler were compared with those of a 3 M (Model 3500) passive sampler. At low-humidity condition (8 +/- 3% RH), the sampling rates of the ACF passive sampler for volatile organic vapors were within the range of +/-25% from the results of a charcoal tube, which was the reference method recommended by NIOSH. However, at high humidity condition (90 +/- 5% RH), even though the sampling rates for toluene, MIBK, and PCE were within the range of +/-25%, the sampling rates of ACF sampler for n-hexane and MEK decreased steeply with time after being high at the beginning of the exposure time. Under this condition, the sampling rate of the 3 M passive sampler for MEK was also high at the beginning of the exposure time. In case of the ACF passive sampler, the sampling rates of the relatively strong adsorbates such as toluene, MIBK, and PCE were much less affected by humidity than those of n-hexane and MEK which were weak adsorbates.
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PMID:Evaluation of an activated carbon felt passive sampler in monitoring organic vapors. 924 26

In vitro assessment of organic solvents can be problematic as the volatile nature of these compounds makes maintaining a constant exposure level difficult. However, a stable exposure level must be maintained if reliable dose response data are to be obtained. Here we describe a gas-tight glass exposure system which allows prolonged exposure of cultured cells to constant concentrations of volatile organic solvents. The system permits convenient sampling of gas and liquid phases for reliable quantification of solvent concentration. We determined medium/air partition coefficients (K) for toluene, n-hexane and methyl ethyl ketone which can be used to calculate liquid phase solvent exposure levels in an in vitro system specifically designed for organic solvent exposure. Cultured cells were exposed to these compounds for five days and toxicity assessed by trypan blue exclusion. Headspace gas chromatography was used to determine K in RPMI-1640 and EMEM tissue culture medium at 37 degrees C. The presence of cells in the system at levels normally used in in vitro exposure systems did not significantly alter solvent partitioning. Equilibrium liquid phase solvent concentrations were measured by gas chromatography for two of the compounds to confirm that exposure levels calculated using K were correct. Results show that sub-chronic exposure to volatile organic solvents causes a dose dependent decrease in Jurkat T-cells and SH-SY5Y viability. Solvent potency increased with lipophilicity (n-hexane>toluene>MEK).
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PMID:Validation of a method for acute and subchronic exposure of cells in vitro to volatile organic solvents. 1704 55

This study measured inhalation exposure to 13 volatile organic compounds (VOCs) among workers in the leatherwear industry in Spain, examined the changes in those exposures over a 5-year period, and documented local exhaust ventilation practices that affected exposure. In collaboration with an occupational risk prevention company, air samples were collected from 849 workers' personal breathing zones using personal air pumps with activated charcoal tubes. VOCs were analyzed using a GC/MS-optimized method modified in our laboratory from that proposed by Spanish authorities (INSHT). Airborne concentrations were compared with occupational exposure limit (OEL) values from the European authorities. The most frequently detected VOCs were acetone (98.1%), toluene (94.8%), n-hexane (71.2%) and other C6-C7 branched alkyl hydrocarbons (97.5%). Other frequently detected VOCs were MEK (64.9%), ethylacetate (60.7%), and cyclohexane (29.3%). Benzene was detected in 24.6% of samples. Although all the samples were taken while workers performed tasks judged to have the highest VOC exposure potential, only 14% of samples showed excessive aggregate exposure, and chemical-specific OELs were exceeded in a relatively small number of cases: 7.2% for n-hexane, 2.8% for toluene, 0.6% for acetone, and 0.4% for hexane isomers. Over the study period, a diminished use of n-hexane in solvent formulations and an increased use of branched hexane and heptane isomers were observed. Six factors relating to work location conditions and types were evaluated. Most high-exposure cases were associated with three task types. The presence of local exhaust ventilation was an important exposure control, but significant exposures despite the use of local exhaust were observed. Although n-hexane exposures significantly decreased over the study period, the overall level of VOC exposure did not decrease. More effective exposure prevention measures need to be implemented.
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PMID:Characterization and evolution of exposure to volatile organic compounds in the Spanish shoemaking industry over a 5-year period. 2301