Biomedical subjects

Sanja Kezic

Publications and source records attributed to Sanja Kezic.

6 recordsLinked to original sources

PubMed2007

Analysis, interpretation, and extrapolation of dermal permeation data using diffusion-based mathematical models.

New dermal penetration data have been measured in both "infinite" and finite dose experiments on a range of compounds of varying lipophilicities. The data are analyzed, using parameter fitting, to determine the values of parameters governing the overall skin absorption processes. Two one-dimensional diffusion models are used. The first is novel, and well suited to the modeling of dermal uptake in occupational exposure scenarios. The second is an implementation of a model taken from the literature. The models are compared in a variety of exposure scenarios, and exhibit good mutual agreement. Both successfully reproduce expected features of the absorption process. Penetration parameters are determined by analyzing both infinite and finite dose data. Prediction of dermal absorption with finite dose scenarios is carried out and compared with experimental data obtained under these conditions. Parameters determined may also have an important role in improving the reliability of predictive QSARs used to estimate the extent of penetration of untested molecules.

Administration, Cutaneous↗

PubMed2006

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↗

PubMed2006

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↗

PubMed2006

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↗

PubMed2006

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↗

PubMed2004

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↗