Effect of wheat bran and flaxseed on cadmium effects and retention in rats.

Dietary fiber can affect cadmium (Cd) absorption and toxicity, but the effect appears to depend on the type of dietary fiber. The aim of the present study was to compare the effect of dietary sources containing distinct amounts of soluble and insoluble fiber on Cd absorption, accumulation and toxicity in growing rats. The absorption of essential macrominerals (Ca, P and Mg) was also evaluated. Animals received a nutritionally balanced diet with cellulose (cel - control), wheat bran or flaxseed as the fiber source with 0 or 50 mg Cd kg(-1) diet, during 30 days. Cd exposure reduced body weight gain, feed efficiency ratio, epididymal fat relative weight and liver relative weight, and increased plasma alanine aminotransferase activity in all fiber groups. The apparent Cd absorption was similar among Cd-groups, but the flax-Cd group had a higher hepatic and renal Cd concentration. Cd decreased the absorption of Ca and P, and increased Mg absorption in the wheat bran and flaxseed groups, but not in the cel group. Although the different fiber sources investigated had no effect on Cd toxicity, the major soluble fiber source, flaxseed, increased Cd retention. Thus, caution should be taken in the intake of flaxseed by Cd-exposed populations.

[Toxic contact dermatitis from poison ivy in a private garden in Germany]. / Toxische Kontaktdermatitis auf Poison Ivy in einem Privatgarten in Deutschland.

A couple suffered for 5 years from recurrent eruptions with vesicles and bullae after contact with an unknown "climbing weed" in their private garden in Germany. After this plant was identified as poison ivy and eradicated, their skin problems were solved. This is the first report of poison ivy in this setting. Urushiols in poison ivy are not only strong allergens but also potent irritants. Negative patch tests in the husband suggest that the bullous dermatitis was a toxic reaction.

Absence of contact sensitization to Aloe vera (L.) Burm. f.

Aloe vera has been used as a cosmetic and medical remedy since ancient times and has gained increasing popularity in recent years. Despite its widespread use, reports of allergic reactions are rare. We patch tested 702 consecutive patients with an oily extract from the leaves, Aloe pulvis from the entire plant and concentrated Aloe vera gel. A specially designed questionnaire was used for the use of Aloe vera, reasons and location of application, adverse reactions, occupation, hobbies and atopy. None of the subjects showed any reaction to one of the preparations. 2 components of the plant have to be distinguished: the bark of the leaves contains anthrachinones with pro-peristaltic and potential antibiotic and anticancer properties. Constraints have been imposed due to their considerable toxic potential. Today, mostly the Aloe gel from the center of the leaves is processed. It almost exclusively consists of carbohydrates to which also many medical effects have been attributed. Carbohydrates are not likely to induce contact sensitization, which might explain the outcome of our study. However, this does not justify unrestrained promotion of Aloe products, as scientific studies investigating the claims on its constitutional effects are few in number, and the majority of them have been unable to diminish the intuitive scepticism against miracle cures, like Aloe seems to be.

Contact vitiligo following a strong patch test reaction to triglycidyl-p-aminophenol in an aircraft industry worker: case report and review of the literature.

Epoxy resin systems (ERSs) are a frequent cause of occupational allergic contact dermatitis. A 50-year-old patient developed eczematous skin lesions on the back of his hands, lower arms and eye lids, 2 months after he had started working in aircraft construction. Patch tests showed positive reactions at day 3 to nickel sulfate, epoxy resin based on diglycidyl ether of bisphenol F (DGEBF) and 1,4-butanediol diglycidyl ether (1,4-BDDGE). The chemical triglycidyl-p-aminophenol (TGPAP) applied at 1% and 0.1% induced the strongest (+++ positive) reaction. About 4 months after the patch test with TGPAP, the patient presented with 2 circular depigmented spots in the former TGPAP-patch test areas. Dermatohistopathology confirmed the diagnosis of contact vitiligo.

Fondaparinux: a suitable alternative in cases of delayed-type allergy to heparins and semisynthetic heparinoids? A study of 7 cases.

Hypersensitivity to unfractionated and low-molecular-weight heparins and semisynthetic heparinoids is increasingly common. 7 female patients between 30 and 74 years with delayed-type allergy to heparins and semisynthetic heparinoids were investigated for (cross)-reactivity to fondaparinux, a new pentasaccharide with selective factor Xa inhibition. All patients showed delayed-type reactions to heparins and some additional cross-reaction to a heparinoid on intracutaneous testing. 6/7 tolerated fondaparinux on intradermal testing as well as on subcutaneous challenge testing. However, the 7th patient developed a characteristic delayed-type reaction to both skin tests with fondaparinux. Fondaparinux is a new synthetic pentasaccharide with a molecular weight of 1.728 Da. In some patients with cross-reactivity between various heparins and semisynthetic heparinoids, lepirudin, a recombinant hirudin, may be a safe and effective alternative. However, combined allergy to hirudin and heparins has been reported. Sometimes, intravenous administration of heparins or heparinoids may be tolerated. However, these patients are at risk of developing a systemic reaction. The pathogenesis of heparin hypersensitivity is not fully understood. Heparins may act as haptens by binding to dermal and/or subcutaneous structural proteins. The chemical structures of heparins and fondaparinux are different concerning their alpha- and beta-configuration and the molecular weight. However, some of their functional groups are nearly identical and therefore similar chemical and pharmacological reactivity is to be expected. Fondaparinux seems to be a valuable alternative in most cases of heparin and hirudin hypersensitivity. The clearly rare cross-reaction between fondaparinux and heparins, now confirmed by us, may be due to differences in the response to haptens.

[Epidemiologic surveillance of contact allergens. The "monitoring series" of IVDK (Information Network ofDermatologic Clinics for Detection and Scientific Evaluation of Contact Allergy]. / Epidemiologische Uberwachung von Kontaktallergenen. Der "Monitorblock" des IVDK.

The selection of the most important contact allergens is subject to a continuous change. Several factors may influence the sensitization rates and thus the decision, which substances to include in the standard series of the most frequent allergens. The Information Network of Departments of Dermatology adds substances of interest for a certain time period to the standard series in order to evaluate parameters such as sensitization rate, grade of reaction, and clinical relevance of positive reactions. In 6 testing periods starting in 1996, 13 test substances were evaluated. Due to the results, propolis, compositae mix, and bufexamac were included in the standard series in 1999, while lyral was added in 2002. Sorbitansesquioleat, dispers blue mix, and iodopropynyl butylcarbamate are under further discussion. Substances such as glutaraldehyde and p-aminoazobenzole should be tested in certain risk groups only, whereas the steroids budesonide and tixocortol should be tested when clinically suspected.

[Sensitization to tea tree oil in Germany and Austria. A multicenter study of the German Contact Dermatitis Group]. / Sensibilisierung auf Teebaumöl in Deutschland und Osterreich--Eine multizentrische Studie der Deutschen Kontaktallergiegruppe.

BACKGROUND AND AIM: Tea tree oil, a distillation product of the Australian tea tree (Melalence alternitolia) is increasingly used as an alternative remedy for various dermatological diseases. Tea tree oil contains several allergenic monoterpenes and sesquiterpenes. In this multicenter study it was evaluated, whether the increasing use of tea tree oil has lead to an increased frequency of sensitization in Germany and Austria which would justify its inclusion into the standard series. PATIENTS AND METHOD: For patch testing a standardized tea tree oil was used, dissolved 5% in diethylphtalate (DEP). Consecutive patients of 11 dermatological departments in Germany and Austria were tested. Readings were taken on day 2 and 3 according to the guidelines of the German Contact Dermatitis Research Group (DKG). RESULTS: 5% tea tree oil was positive in 36/3375 patients (1.1%). Sensitization frequencies showed great regional variations and ranged from 2.3% (Dortmund), 1.7% (Buxtehude), 1.1% (Essen), 0.7% (Graz), to 0% (Berlin, Vienna). 14/36 patients (38.9%) also showed a positive patch test reaction to oil of turpentine. CONCLUSION: Our results show that tea tree oil is an important contact allergen for some centers. It should be tested, if medical history suggests its previous use. Considering the great regional differences in frequencies of sensitization its inclusion into the standard series is not recommended yet.

The seamy side of natural medicines: contact sensitization to arnica (Arnica montana L.) and marigold (Calendula officinalis L.).

Medical remedies of plant origin have gained increasing popularity in recent years. Both anaphylactic and eczematous allergic reactions are on the rise, accordingly. Arnica and marigold, both of the Compositae family, are in widespread use, but only limited data are available on their allergenic potential. We tested 443 consecutive patients, in addition to the European standard and other series, with Compositae mix, sesquiterpene lactone mix, arnica, marigold, and propolis. 5 subjects ( approximately 1.13%) reacted to arnica, 9 ( approximately 2.03%) to marigold. The Compositae mix was positive in 18 cases ( approximately 4.06%). Among them were 3 out of 5 individuals with a sensitization to arnica, and 4 out of 9 who reacted to marigold. Sensitization to arnica and marigold was often accompanied by reactions to nickel, Myroxylon Pereirae resin, fragrance mix, propolis, and colophonium. We conclude that Compositae allergy contributes significantly to the epidemiology of contact dermatitis and that sensitization to arnica and marigold cannot be assessed by testing with the Compositae or sesquiterpene mix alone. As extracts of these plants are frequently used in occupational and cosmetic products, patch testing with additional plant extracts or adjustment of the commercial Compositae mix to regional conditions is recommended.

Coadministration of either cyclosporine or steroids with humanized monoclonal antibodies against CD80 and CD86 successfully prolong allograft survival after life supporting renal transplantation in cynomolgus monkeys.

BACKGROUND: Recent studies have shown some efficacy using monotherapy with monoclonal antibodies (mAb) against CD80 and CD86 receptors after life-supporting renal transplantation in non-human primates. Our study was designed to evaluate the efficacy of combinations of the same mAbs with either microemulsion cyclosporine (CsA) or steroids. METHODS: Unilateral renal transplantation was performed in 16 blood group-matched and MLR-mismatched cynomolgus monkeys that were assigned to four different treatment groups. All monkeys in groups I, II, and IV were treated with the combination of a CD80 (h1F1) and CD86 (h3D1) mAb given at 20 mg/kg each preoperatively, then 5 mg/kg at weekly intervals starting postoperative (po) day 0 until poday 56 (9 doses). In group I the animals (n=4) were treated with mAbs only. In group II (n=4) mAbs were combined with a CsA regimen adjusted daily to maintain target 24 hr trough levels of 150-300 ng/ml CsA for poday 0 to poday 56. In group III (n=4) the animals received CsA monotherapy according to the same regimen as group II. In group IV methylprednisone was administered at 2 mg/kg IV on poday 0-2, then at 0.5 mg/kg/day prednisone per gavage that was and tapered to 0.2 mg/kg/day on which they were maintained until poday 56. All animals were off all immunosuppressive treatment after poday 56 and were then followed until poday 119. RESULTS: The mean survival of groups I-IV was 74 (range 9-119 days), 113 (96-119 days), 39 (22-71 days), and 79 days (6 to 119), respectively. All animals in group I showed clinical evidence of acute severe rejection (fever, creatinine increase, anuria) within the first week posttransplant, including those that retained renal function until poday 119. Only one animal in group II had a moderate clinical rejection during the treatment period and three of four animals survived the intended follow-up period. All animals in group III had multiple biopsy proven or severe clinical rejection episodes within the first 21 days and only one animal survived beyond poday 40. Moderate or severe acute rejection was diagnosed in three of four animals of group IV within the first 28 days post transplant and only one animal survived until poday 119. CONCLUSION: Our data show that combining a calcineurin inhibitor or prednisone with mAbs designed to block costimulatory signals does not antagonize the immunosuppressive efficacy of these mAbs. In addition, combining CsA with mAbs directed against the CD80 and CD86 receptors significantly prolongs graft survival when compared to CsA monotherapy. Therefore clinical trials of humanized mAbs to CD80 and CD86 used in combination with conventional immunosuppression can be considered.

Sensitization and cross-reaction patterns in Danish Compositae-allergic patients.

Results of aimed patch testing with constituents of sesquiterpene lactone (SL) mix, Compositae mix (CM) and other Compositae extracts and allergens in 190 Compositae-allergic patients detected in an 8-year period are presented. Feverfew of CM elicited positive reactions most frequently, followed by tansy, wild chamomile, yarrow and arnica, whereas dehydrocostus lactone of SL was the most frequent elicitor of positive reactions, followed by alantolactone and costunolide. Chrysanthemum (Dendranthema) and marguerite (Argyranthemum frutescens) were the most important suspected sensitizers in both occupationally and nonoccupationally exposed, and cross-reactions between chrysanthemum and feverfew/tansy/chamomile may partly explain the high prevalence of positive reactions to the 3 last mentioned. In the nonoccupationally sensitized group, garden plants such as feverfew, blanket flower (Gaillardia), elecampane (Inula helenium), large yellow ox-eye (Telekia speciosa) and cosmea (Cosmos) were additional important allergenic plants. The 3 last mentioned were picked up by SL mix. Most of the lettuce-sensitized persons were CM-positive. 19% of the occupationally sensitized group were negative to both SL and CM, making very aimed patch testing necessary, notably when suspecting rare sensitizers such as Gerbera and star of the veldt (Osteospermum). The significance of the weeds dandelion, dog fennel and ox-eye daisy as sensitizers is not clarified, but they are probably less important than cultivated plants.

Viral serine proteinase inhibitor (SERP-1) effectively decreases the incidence of graft vasculopathy in heterotopic heart allografts.

BACKGROUND: Graft vascular disease (GVD) is the most common cause of late graft failure in solid organ transplantation. Recent studies have shown good efficacy of a novel nontoxic viral-derived serine proteinase inhibitor (SERP-1) in preventing postangioplasty restenosis. The current study was designed to test whether short-term treatment with SERP-1 was effective in reducing the incidence of GVD in a solid organ transplant. METHODS: Piebald-Virol-Glaxo (PVG) donor hearts were transplanted into August-Copenhagen-Irish (ACI) recipients and observed for 90 days. All recipients (n=60) were treated with microemulsion cyclosporine (CsA) 7.5 mg/kg per gavage from day 0 to day 9 and randomized into 4 groups. SERP-1 was given intravenously. Group I received CsA monotherapy; group II, CsA+SERP-1 1 ng/g (postoperative days 0-9); group III, CsA+SERP-1 10 ng/g (postoperative days 0-9); and group IV, CsA+SERP-1 10 ng/g (postoperative days 0-9, 30, and 60). Graft viability was monitored by palpation, and GVD was assessed by morphometry. RESULTS: Two animals in group I rejected their allografts on postoperative days 7 and 14, 1 animal in group II rejected the allograft (postoperative day 31), and none in group III and IV rejected the allografts. At 90 days postoperative, 23.8% of all coronary vessels showed evidence of GVD in group I, 18.4% in group II, 12.9% in group III, and 11.8% in group IV. The difference in incidence of GVD was significant between groups I and III (P<0.05) and groups I and IV (P<0.05). Treatment with SERP-1 was well tolerated, and all animals regained weight quickly postsurgery. CONCLUSIONS: Treatment of allograft recipients with SERP-1 in combination with CsA early after transplantation significantly decreases the incidence of GVD when compared to grafts treated with only CsA. These results demonstrate the clinical potential for this novel serine protease inhibitor to prevent GVD in solid organ transplantation.

An 8-year experience with routine SL mix patch testing supplemented with Compositae mix in Denmark.

Routine patch testing with sesquiterpene lactone (SL) mix, supplemented with Compositae mix (CM) and other Compositae extracts and allergens where appropriate, was evaluated over an 8-year period. 190 of 4386 patients tested (4.3%) were Compositae-sensitive, 143 females (mean age 51.5 years) and 47 males (mean age 55 years), and 83% of reactions considered clinically relevant. 22% were suspected of occupational sensitization/dermatitis. 62% had a contact allergy to 2 or more compounds, most often to nickel, fragrance and colophonium. SL mix detected 65%, CM 87% of Compositae-allergic patients, and the overall detection rate with both mixes was 93%. Few irritant reactions and no cases of clear-cut active sensitization were recorded with the mixes, but our results emphasize the importance of differentiating late-appearing reactivation reactions from patch test sensitization. The weakly positive CM reactions could reflect some irritancy, but as they were associated with fragrance and/or colophonium allergy to a higher degree than weakly positive SL mix reactions, they probably represented cross-reactions. In conclusion, the detection rate with SL mix was high enough to support its continued use as a screening mix and it was very well and rather safely supplemented by aimed testing with CM.

Contact allergy to balsam of Peru. II. Patch test results in 102 patients with selected balsam of Peru constituents.

BACKGROUND: In Switzerland, Germany, and Austria, allergic reactions to balsam of Peru (BP) have now made it the third most common contact allergen. OBJECTIVE: A series of 20 single BP constituents (including resorcinol monobenzoate), established in 1995, was used for patch tests in patients with a positive reaction to BP in the standard series. MATERIALS AND METHODS: Between 1995 and 1998, 2,273 patients were tested with the standard series, including BP, fragrance mix (FM), and propolis. Patients positive for BP were requested to participate in a further test using the 19 compounds of the BP constituents and resorcin monobenzoate (BP series); 102 patients agreed and were patch tested. The results of the 72-hour reading were used for the evaluation. RESULTS: A total of 93 patients reacted to 1 or more of the BP series compounds. Positive reactions were seen, in decreasing order, to cinnamic alcohol, cinnamic acid, coniferyl benzoate, benzoic acid, cinnamyl cinnamate, eugenol, resorcinol monobenzoate, coniferyl alcohol, and benzyl alcohol. There were no positive reactions to vanillin or ferulic acid. A correlation between skin lesions and frequent consumption of sweets was found in 7 patients with major positive test reactions to coniferyl benzoate and benzyl alcohol. Most of the reactions to eugenol and isoeugenol had less to do with BP itself than with a primary sensitization to fragrances. Although resorcin monobenzoate (RMB) has up to now not been detected in BP, 16 patients reacted distinctly to this compound. Eleven were strong smokers; the remaining ones had contact with plastic materials that have been reported to contain RMB. RMB is used frequently as an antioxidant in synthetic material. When these patients stopped smoking, the skin lesions cleared. However, consumption of sweets caused recurrences. CONCLUSION: The evaluation of reactions to single constituents of BP by testing with the special BP series facilitates understanding how sensitization may be acquired. The allergen may prove to be BP itself or 1 or more of its constituents. Testing for the constituents of this series may provide patients with a more specific allergen diagnosis and may facilitate improved therapy. BP may function as an important indicator for contact allergy to RMB.

[Contact allergy caused by poison ivy (Toxicodendron spp]. / Kontaktallergie auf Poison ivy (Toxicodendron spp.).

Within 3 days two female patients presented with an eruption featuring erythema, edema, vesicles and bullae. We suspected poison ivy allergy which was subsequently proven by history and positive patch tests. In Germany the risk of specific hypersensitivity to Toxicodendron species is low, since the distribution of such plants is confined to botanical gardens. Other species belonging to the family of Anacardiaceae contain urushiols as well (e.g., mango, cashew) and may cause allergic contact dermatitis.

Contact allergy to Disperse Blue 106 and Disperse Blue 124 in German and Austrian patients, 1995 to 1999.

Between 1995 and 1999, 1986 patients were tested in the 31 participating centres of the Information Network of Departments of Dermatology (IVDK), all of them members of the German Contact Dermatitis Research Group, with a textile dyes series containing Disperse Blue (DB) 106 and 124, and since 1997 also with a mix of both. 86 patients (4.3%) reacted positively to DB 106 and/or DB 124; with good concordance between the 2 allergens (Cohen's weighted kappa 0.72), and the single allergens and the mix (kappa=0.75 in both cases), which had been tested in parallel in 969 and 975 patients, respectively. In contrast, concordance between DB 106/124 and p-phenylenediamine and p-aminoazobenzene, respectively, was poor. Some 70% of positive reactions to DB 106/124 had current clinical relevance. Furthermore, a significant increase in the proportion of DB 106/124-positive patients among those tested was found from 1995 to 1999. Hence, DB 106/124 are important allergens deserving close monitoring. The use of a mix of DB 106 and DB 124 seems justified in view of the close chemical similarity of both compounds. If possible, the presence of the allergen(s) in individual textiles considered causative should be checked by thin layer or column chromatography.