Cr(III) and Cr(VI) in leather and elicitation of eczema

The aim of the present study was to investigate the relation between the content of Cr(VI) and soluble Cr(III) in leather and the ability of the leather to elicit eczema in chromium allergic patients. An array of chromium-tanned leather samples was analysed for the content of total Cr(VI) and soluble Cr(III) using the DIN 53314 and the DS/EN 420 methods. Subsequently, a group of 15 patients with a history of foot eczema and leather exposure was exposed to a selection of 14 chromium- and 1 vegetable-tanned leather sample on the upper back for 48 hr. In addition, one leather sample was used for a prolonged 14-day exposure study. In total, 4 of the 15 patients reacted to at least one leather sample, and 5 of the 14 leather samples elicited a reaction in at least 1 patient. The prolonged exposure study demonstrated that an extended exposure period may reveal allergenic potential of a leather sample not otherwise identified using an ordinary 48-hr exposure period. No relation was observed between the measured content of Cr(VI) and soluble Cr(III) in the leather and the elicitation of eczema. Thus, in order to evaluate the quality of chromium-tanned leather in relation to preventing allergic skin reactions, other more clinical relevant methods reflecting the actual bioavailable Cr(III) and Cr(VI) fractions should be developed.     

Chromium allergy: significance of both Cr(III) and Cr(VI)

Most studies investigating chromium allergy have been performed with Cr(VI). However, real exposure to chromium from leather products includes both Cr(III) and Cr(VI). We have determined and compared the minimum elicitation threshold (MET) concentration for Cr(III) and Cr(VI) in Cr(VI)-sensitive patients. In addition, reactions to combinations of Cr(III) and Cr(VI) were compared to reactions elicited by Cr(III) and Cr(VI) alone. Dilution series of Cr(III) and Cr(VI) were applied in Finn Chambers on the back of 18 patients. The patches were left for 2 days and readings were done on days 2, 3 and 7. The MET10% for Cr(III) and Cr(VI) was calculated from the dose-response curves to be 0.18 microg/cm2/48 h (6 p.p.m.) and 0.03 microg/cm2/48 h (1 p.p.m.), respectively. No significant differences in the response to combined Cr(III) and Cr(VI) solutions versus single solutions were found. Cr(III) was concluded to play an important role in chromium allergy, because Cr(III) and Cr(VI) were both capable of eliciting eczema at low concentrations. Rather than regarding chromium dermatitis as a result of Cr(VI) allergy alone, it may be more correct to consider it as a result of a combined Cr(III) and Cr(VI) allergy.     

Cr(III) reactivity and foot dermatitis in Cr(VI) positive patients

Chromium allergy has become synonymous with Cr(VI) allergy. However, real exposure to chromium from leather products may include both Cr(III) and Cr(VI). In this study, we investigate the reactivity to both Cr(VI) and Cr(III) in consecutive patients to analyse the relation between foot eczema/leather exposure and reactivity to Cr(III). From March 2002 to December 2004, 2211 consecutive patients with suspected allergic contact dermatitis were patch tested with 0.5% potassium dichromate (Cr(VI)) and 13% chromium trichloride (Cr(III)). A total of 71 (3.2%) patients had a positive reaction to Cr(VI), of which 31 also had a positive Cr(III) reaction. No Cr(VI) negative patients had a positive reaction to Cr(III). An increased risk of foot dermatitis was found in Cr(VI) positive patients with a concomitant positive or doubtful reaction to Cr(III) compared with Cr(VI) positive patients with no reactions to Cr(III). The increased risk was not due to a higher degree of sensitivity to Cr(VI). Leather was reported most frequently as the suspected cause of chromium dermatitis (54%). However, Cr(VI) allergics having foot eczema and positive or doubtful Cr(III) reactions often had positive reactions to other shoe allergens. Thus, Cr(III) allergy is part of a multiple shoe allergy pattern.     

Differentiation of normal human keratinocytes influences hexavalent chromium uptake and distribution and the ability of cells to withstand Cr(VI) cytotoxicity

The degree of differentiation of normal human keratinocytes determines the biology of the cells to a large extent. We have previously documented that keratinocytes from different donors differ significantly in their ability to withstand hexavalent chromium [Cr(VI)]-induced cytotoxicity. Several factors may contribute to this differing donor sensitivity to Cr(VI). The aims of this study were to investigate to what extent keratinocyte differentiation might influence Cr(VI) uptake and the ability of cells to withstand Cr(VI)-induced cytotoxicity. Keratinocytes from different donors were cultured under identical conditions and exposed to Cr(VI) (as potassium dichromate) at different points during their maturation process. The degree of differentiation of the cells was assessed using a quantitative assay for involucrin and related to the Cr(VI) cytotoxicity experienced by the cells. Chromium content was measured in whole cell, cytosolic and particulate fractions. While proliferative keratinocytes exposed to Cr(VI) showed a high degree of cytotoxicity to dichromate exposure, the more differentiated cells showed significantly less cytotoxicity but a higher uptake of the metal ion into the cells. The relative percentage of cytosolic chromium was high in the proliferative cells and decreased as the cells matured, suggesting that differentiated cultures were binding most of the chromium to the particulate fraction. Total chromium also increased during differentiation. The use of the channel-blocking agent 4, 4'-diisothiocyanate-2-2'-stilbenedisulphonic acid confirmed the spatial differences of chromium accumulation in the phenotypically different cultures, in that it prevented Cr(VI) entry into the proliferative cells and attenuated dichromate cytotoxicity in these cultures, but had no effect on the Cr(VI) uptake in differentiated cells, nor did it reduce its cytotoxicity. These data support the hypothesis that the upper differentiated layers of the epidermis are able to offer considerable physical protection to the lower proliferative layers from chemical pro-oxidants.     

Die percutane Resorption von 3- und 6wertigem Chrom (Cr51)

Zusammenfassung An Meerschweinchen wurde die percutane Resorptionsquote von Radiochrom (Cr⁵¹) in wäßriger Lösung als Cr₆-Anion mit und ohne Nalaurylsulfat-Zusatz sowie als Cr₃-Kation nach etwa 19 Std und 4–5 Tagen ermittelt. Ferner wurde die Verteilung von resorbiertem Radiochrom auf die subcutanen Lymphknoten, Milz, Leber, Nieren, Blutelemente (Serum, Erythrocyten, Leukocyten) und Ausscheidungen nach (3,7) 18–24 Std sowie auch nach 4,5 und 8 Tagen gemessen. Die an 26 von insgesamt 32 verwertbaren Tieren erhobenen Befunde wurden im einzelnen diskutiert. Hervorhebung verdient im Hinblick auf die Pathogenese des Kontaktekzems insbesondere die Beobachtung, daß nach Permeation durch intakte Epidermis der relativ größte Teil des Radiochroms sich in den subcutanen Lymphknoten nachweisen läßt (regionärkontralateral>homolateral und diagonal). Bei traumatisierter Epidermis tritt diese primäre Anreicherung von Cr⁵¹ in den Lymphknoten bei Angebot als Cr₆ ⁵¹-Anion in den Hintergrund.Herrn Prof. Dr. A. Marchionini zum 60. Geburtstag gewidment.Die Arbeit wurde aus Mitteln des Ministeriums für Atomkernenergie und Wasserwirtschaft durchgeführt.     

Chromium- and nickel-induced cytotoxicity in normal and transformed human keratinocytes: an investigation of pharmacological approaches to the prevention of Cr(VI)-induced cytotoxicity

Summary Chromium and nickel compounds cause irritancy but can also induce allergic contact dermatitis. The aims of this study were to characterize the direct cytotoxic effects of Cr(VI), Cr(III) and Ni(II) salts on keratinocytes, and to investigate pharmacological strategies to protect cells against Cr(VI)-induced cytotoxicity. Normal human keratinocytes and the HaCaT keratinocyte cell line were used. Cell viability was assessed by neutral red dye uptake, the 3-[4,5-dimethylthiazol-2-yl]-2.5- diphenyltetrazolium bromide (MTT) eluted stain assay and measurement of lactate dehydrogenase (LDH) activity in the medium. The assays varied slightly in their sensitivities (neutral red > MIT > LDH) although all three gave similar results. In both cell types, the relative order of cytotoxicity of the salts was Cr(VI)≫ Ni(II) > Cr(III). There were no major differences between chromium salts of a common valency. Normal human keratinocytes showed a much greater variability in their response to Cr(VI) and Ni(II) salts than HaCaT cells and were generally more resistant to Cr(VI)- and Ni(II)-induced cytotoxicity.
Several drugs were screened for their potential to protect both cell types against the cytotoxic effects of Cr(VI). specifically the reducing agents ascorbic acid, cysteine and glutathione. and the Cr(VI) cellular uptake inhibitors 4.4'-diisothiocyanato-2.2'-stilbenedisulphonic acid (DIDS) and 4-acetamido-4'-isothiocyanato-2.2'-stilbenedisulphonic acid (SITS). All five drugs provided concentration-dependent protection against Cr(VI)-induced cytotoxicity but only ascorbic acid offered complete protection. Several of these pharmacological approaches to the prevention of Cr(VI) cytotoxicity confirm previous clinical studies on the inactivation of Cr(VI), while the clinical potential of others has yet to be investigated.     

Incidence rate of mycosis fungoides in Isfahan (Iran)

Mycosis fungoides (MF) is an extranodal non‐Hodgkin’s lymphoma with primary involvement of the skin. The aim of the present study was to determine the incidence rate of MF in Isfahan (Iran) and to compare the results with other reports. We collected our data from the MF clinic of Alzahra Hospital which is the main center for treatment of MF patients in Isfahan (2007–2008). Eleven cases were reported to the MF clinic of Alzahra during the study, seven of which were diagnosed as MF. The incidence rate of MF in Isfahan in 2007–2008 was 3.91/1 million persons. The age spectrum was 28–80 years and the mean 43.14 years. The male : female ratio was 3:4. In conclusion, the incidence rate of MF in Isfahan (Iran) is similar to other areas. However, the male : female ratio is opposite to that of other studies     

信号传导与转录激活因子-3与银屑病

信号传导与转录激活因子-3是一种重要的核转录因子,能被白介素-6、表皮生长因子等细胞因子和生长因子激活,参与细胞增殖、存活、转化、迁移等过程.在银屑病皮损中,角质形成细胞中的信号传导与转录激活因子-3几乎都呈激活状态,它能通过调节银屑病相关发病基因和细胞因子的表达,参与角质形成细胞的增殖、分化和存活以及皮损中血管发生,是银屑病发病中重要的信号传导与转录激活因子.