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Biomedical subjects

Maarten M Verberk

Publications and source records attributed to Maarten M Verberk.

6 recordsLinked to original sources

Altered penetration of polyethylene glycols into uninvolved skin of atopic dermatitis patients.

Involved regions of the skin in atopic dermatitis (AD) patients have an altered barrier function. Whether uninvolved skin also has a diminished barrier is controversial. To assess the barrier function of uninvolved skin in AD patients, the percutaneous penetration of polyethylene glycols (PEGs) of various molecular sizes was determined in vivo in AD patients and control subjects using tape stripping of the stratum corneum (SC). The diffusion and partition coefficients were determined using Fick's second law of diffusion. The SC thickness was similar in both groups; however, the trans-epidermal water loss was higher in atopic skin. The apparent diffusion coefficient of PEGs through atopic skin was twice as high as through normal skin, and decreased with increasing molecular weight (MW) in both groups. The partition coefficient in the skin of AD patients was half of that for normal skin but as for normal skin, there was no MW dependency. Although atopic skin exhibited altered barrier with respect to diffusion and partitioning, the permeability coefficients were nearly the same for atopic and normal skin. The results support the assumption of altered skin barrier of AD patients even in the skin that is visibly unaffected by disease.

Adolescent↗

Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate.

Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels and the skin response to a single and a repeated irritation test. This study also aimed to determine changes in SC cytokine levels after repeated irritation. Transepidermal water loss (TEWL) and erythema were measured in 20 volunteers after single 24-hr exposure to 1% sodium lauryl sulfate (SLS), and during and after repeated exposure to 0.1% SLS over a 3-week period. SC cytokine levels were measured from an unexposed skin site and from the repeatedly exposed site. Interleukin (IL)-1alpha decreased by 30% after repeated exposure, while IL-1RA increased 10-fold and IL-8 increased fourfold. Baseline IL-1RA and IL-8 values were predictors of TEWL and erythema after single exposure (r = 0.55-0.61). 6 subjects showed barrier recovery during repeated exposure. Baseline IL-1RA and IL-8 levels are likely to be indicators of higher skin irritability after single exposure to SLS. Barrier repair in some of the subjects might explain the lack of agreement between the TEWL response after single and repeated irritation.

Adult↗

Increased permeability for polyethylene glycols through skin compromised by sodium lauryl sulphate.

In this in vivo human study we assessed the influence of skin damage by sodium lauryl sulphate (SLS) on percutaneous penetration of polyethylene glycols (PEGs) of different molecular weights (MW). Percutaneous penetration of PEGs was determined using tape stripping of the stratum corneum (SC). The forearm skin of volunteers was pretreated with 5% w/w SLS for 4 h, and 24 h later patches with PEGs were applied for 6 h. The penetration parameters were deduced by data regression to Fick's law for unsteady-state diffusion. The trans-epidermal water loss (TEWL) increased after SLS treatment from 6.3 +/- 2.1 to 17.9 +/- 8.7 g/m(2)/h. The diffusion coefficient for all PEGs was increased in the SLS-damaged skin. The increase was smaller for higher MW. In addition, the partition coefficient of PEGs between SC and water was larger in the SLS-compromised skin and showed a tendency to increase with MW. The permeability coefficient decreased gradually with increasing MW of PEGs in both control and SLS-compromised skin. SLS caused a threefold increase in the permeability coefficient for all MWs ranging in control skin from 0.34 to 0.70 x 10(-5) cm/h and in the SLS-compromised skin from 1.20 to 2.09 x 10(-5) cm/h for MW of 590-282 Da. The results of this study show the deleterious effect of SLS on the skin barrier for hydrophilic PEGs. A defective skin barrier will facilitate absorption of other chemicals and local skin effects.

Adolescent↗

Genetic polymorphism of metabolic enzymes modifies the risk of chronic solvent-induced encephalopathy.

In the present study, we investigate whether genetic polymorphism in enzymes involved in the metabolism of organic solvents influences susceptibility to chronic solvent encephalopathy (CSE), which is one of the major effects of long-term exposure to organic solvents. Polymorphisms in the genes encoding CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1 and GSTP1 enzymes were determined in a group of male CSE patients (N=97) and controls (N=214). The selection of the patients was based on a standard diagnostic protocol, including interviews, neuropsychological tests and questionnaires directed to somatic, cognitive and mood symptoms and exposure, in combination with well-defined decision rules. As controls, healthy workers of similar socio-economic background, without memory problems and with no known exposure to organic solvents, were included in the study. Comparing patients and controls, higher frequencies of the variant *5B allele of the CYP2E1 gene (OR: 5.8; 95% CI: 1.8-18.8) and of the variant GSTP1*C allele (OR: 0.40; 95% CI: 0.17-0.94) were found. Homozygous carriers of the exon 4 EPHX1 Arg139 variant allele had a lower risk (OR: 0.25; 95% CI: 0.06-1.13). The present study indicates that genetic polymorphism of CYP2E1, EPHX1 and GSTP1 modify the risk of developing CSE.

Adult↗

Percutaneous absorption of m-xylene vapour in volunteers during pre-steady and steady state.

Percutaneous absorption of m-xylene (XYL) was determined in volunteers exposed to 29.4 microg cm(-3) XYL vapour on the forearm and hand for 20, 45, 120 and 180 min. The internal exposure was assessed by measuring the concentration of XYL in exhaled air. The systemic kinetics were determined using a reference exposure by inhalation. The dermal permeation rate and the cumulative absorption of XYL as a function of time were calculated using mathematical deconvolution. From these relationships, the average flux into the skin throughout the exposure (J(skin, average)) and the maximal flux into the blood (J(blood, max)) were derived. Both fluxes were dependent on the duration of exposure, approaching each other at longer exposure durations. The values of J(skin, average), adjusted to a concentration of 1 microg cm(-3), were 0.091 microg cm(-2) h(-1) during 20-min exposure falling to 0.072, 0.066 and 0.061 microg cm(-2) h(-1) for 45, 120 and 180 min, respectively. The values of J(blood, max) showed an opposite trend, gradually increasing from 0.034 microg cm(-2) h(-1) at an exposure duration of 20 min to 0.042, 0.059 and 0.063 microg cm(-2) h(-1) for 45, 120 and 180 min of exposure durations, respectively.

Administration, Inhalation↗

Visual evoked potentials in workers with chronic solvent encephalopathy.

OBJECTIVES: Two promising variations of visual evoked potentials (VEPs) were studied in solvent-exposed workers: the effect of a low-contrast stimulus in comparison with the usually applied high contrast, and the ability of pattern-onset VEP to reveal damage to specific visual cortical areas. In addition, we studied disturbances of a visual event-related potential (P300). METHODS: Thirty male patients (48 +/- 9 years of age) with solvent-induced chronic encephalopathy, and 41 controls (46 +/- 8 years) without solvent exposure, participated. Pattern-reversal checkerboards with low (11%) contrast and with high (93%) contrast between the checks were used. For onset VEPs two dedicated stimulus patterns were used. P300 was elicited with an "oddball" paradigm. RESULTS: At low contrast the N75-P100 peak-to-peak amplitude in the controls was 9.6 +/- 4.9 microV, i.e. 57% of the amplitude at high contrast (16.3 +/- 7.2 microV). In the patients the response at low contrast was only 48% of that at high contrast; the corresponding amplitudes were 7.5 +/- 3.5 microV and 15.8+/-4.9 microV. For the pattern-onset VEPs no effect of exposure was found. With regard to the P300, the patients missed more targets (average 3.6%) than did the controls (average 0.5%). Patients had a smaller P300 amplitude (8.8 +/- 4.5 microV) than the controls (11.5 +/- 5.3 microV), and a longer latency (390 +/- 34 ms compared to 376 +/- 24 ms). CONCLUSION: The results point to a physiological basis for the solvent-induced decrease of visual contrast sensitivity as found by others by means of psychophysical methods. The results also suggest that the neurophysiological examination of the visual system in persons who have undergone exposure to toxins might be benefited by the addition of low-contrast stimuli.

Adult↗