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Biomedical subjects

A I Lauerma

Publications and source records attributed to A I Lauerma.

At least 19 recordsLinked to original sources
PubMed1999

Tacrolimus ointment improves psoriasis in a microplaque assay.

Tacrolimus (FK506) is an effective and well tolerated immunosuppressant used to prevent allograft rejection. We describe the evaluation of two tacrolimus ointment formulations for treatment of chronic plaque-type psoriasis. This was a microplaque assay with randomized, double-blind design. Sixteen patients (15 men, one woman, all white and 28-69 years old) with chronic plaque-type psoriasis participated. Six different ointments were applied to discrete microplaques, 17 mm in diameter, on a descaled psoriasis lesion: these were tacrolimus ointment with diisopropyl adipate as penetration enhancer, tacrolimus ointment without diisopropyl adipate, 0.1% betamethasone 17alpha-valerate ointment, 0.005% calcipotriol ointment and, as controls, the ointment bases for tacrolimus and betamethasone. Ointments were reapplied and the area was sealed every 2-3 days during the 14-day treatment period. After 7 and 14 days, erythema and infiltration were graded on a scale of 0-4, and superficial blood flow was measured with a laser Doppler flowmeter. Epidermal thickness was measured histologically at the end of treatment. Compared with the vehicle controls, sites treated with tacrolimus ointment (with or without penetration enhancer) showed a significant reduction in erythema and infiltration (P < 0. 001), a significant reduction in superficial blood flow (P < 0.01) and a significant decrease in epidermal thickness (P < or = 0.001). Results for betamethasone and calcipotriol, when compared with the vehicle controls, were similar. These results suggest that, under conditions of descaling and occlusion, tacrolimus ointment is effective in the treatment of psoriasis.

Administration, Topical↗
PubMed1998

Topical FK506 suppresses cytokine and costimulatory molecule expression in epidermal and local draining lymph node cells during primary skin immune responses.

Recently, it has been shown that the immunosuppressive macrolide lactone, FK506, exerts good therapeutic efficacy in inflammatory skin diseases. The aim of this study was to analyze the influence of topical FK506 on molecular (IL-1alpha, IL-1beta, IL-2, IL-4, IL-12 p35, IL-12 p40, macrophage inflammatory protein-2 (MIP-2), granulocyte-macrophage CSF (GM-CSF), TNF-alpha, and IFN-gamma) and cellular (I-A+/CD80+, I-A+/CD54+, I-A+/CD69+, I-A+/B220+, and CD4+/CD25+) events in epidermal (EC) and local draining lymph node (LNC) cells during primary contact hypersensitivity responses. Cytokine mRNA levels for IL-1alpha, IL-1beta, GM-CSF, TNF-alpha, MIP-2, and IFN-gamma in EC and for IL-2, IL-4, IL-12 p35, IL-12 p40, and IFN-gamma in LNC were increased and resulted in significant LNC proliferation during oxazolone-induced contact hypersensitivity. Topical FK506 treatment dose-dependently suppressed oxazolone-induced LNC proliferation. This effect was correlated with decreased IL-1alpha, IL-1beta, GM-CSF, TNF-alpha, MIP-2, and IFN-gamma mRNA expression within the epidermis and decreased IL-12 p35 and p40 mRNA expression in LNC. Further analysis of the LNC cytokine pattern revealed that the production of both Thl (IFN-gamma and IL-2) and Th2 (IL-4) cytokines was dramatically impaired after topical FK506 treatment. Flow cytometric analysis showed that topical FK506 decreased the population of epidermis-infiltrating CD4+ T cells and suppressed the expression of CD54 and CD80 on I-A+ EC and LNC during hapten-induced contact hypersensitivity. Furthermore, topical FK506 profoundly impaired oxazolone-induced up-regulation of CD25 expression on CD4+ LNC and dramatically decreased hapten-induced expansion of I-A+/B220+ and I-A+/CD69+ LNC subsets. In conclusion, these results give new insights into the mechanisms of action of topical FK506 treatment.

Administration, Topical↗
PubMed1998

Tacrolimus ointment does not affect collagen synthesis: results of a single-center randomized trial.

We conducted a randomized, double-blind, placebo-controlled trial to assess the atrophogenicity of tacrolimus ointment. In a combined group of atopic dermatitis patients (n = 14) and healthy volunteers (n = 12), 0.3% tacrolimus, 0.1% tacrolimus, betamethasone-valerate, and a vehicle control were applied in a randomized order to nonsymptomatic, 4 cm x 4 cm regions of abdominal skin. After 7 d of treatment under occlusion, the carboxy- and amino-terminal propeptides of procollagen I (PICP, PINP) and the amino-terminal propeptide of procollagen III (PIIINP) were measured from suction blister fluid with specific radioimmunoassays. In addition, ultrasound measurements of skin thickness were taken. Betamethasone-treated areas showed median PICP, PINP, and PIIINP concentrations of 17.0%, 17.6%, and 39.5% of the vehicle control at the end of the treatment period, respectively, whereas the 0.1% and 0.3% tacrolimus-treated areas showed median concentrations of approximately 100% of the vehicle control (p < 0.001). Betamethasone was also the only treatment to reduce skin thickness; the median decrease in skin thickness was 7.4% relative to 0.1% tacrolimus, 7.1% relative to 0.3% tacrolimus, and 8.8% relative to the vehicle control (p < 0.01). Results for atopic dermatitis patients and healthy volunteers were similar. These findings suggest that tacrolimus does not cause skin atrophy.

Adolescent↗
PubMed1997

A local lymph node assay to analyse immunosuppressive effects of topically applied drugs.

Topical glucocorticosteroids represent the mainstay of antiinflammatory therapy in the treatment of inflammatory skin diseases. Their clinical use, however, is limited by local and systemic side-effects. Thus, in dermatopharmacology there is a large demand for alternative non-steroidal antiinflammatories. Other than transplantation models, most of the frequently used in vivo test systems for assessment of drug-induced immunosuppression measure changes in inflammatory skin responses by means of skin erythema and edema after challenge of sensitized animals. The aim of this study was to develop an alternative mouse model to detect and analyse immunosuppressive effects of topically applied drugs. On the basis of a modified local lymph node assay, we analysed effects of topical hydrocortisone, dexamethasone, mometasone furoate and FK506 (tacrolimus) during the induction phase of contact hypersensitivity. On 4 consecutive days, NMRI mice were treated on the dorsal surfaces of both ears with increasing concentrations of test compound. During the last 3 days, the mice received in addition the contact sensitizer, oxazolone (1%). On day 5, draining auricular lymph nodes were removed in order to assess lymph node cell counts and perform flow cytometric analysis of lymph node cell subpopulations (CD4+/CD25+, Ia+/CD69+, Ia+/B220+). All test compounds proved to exert significant immunosuppressive effects after topical application, but showed differences in their immunomodulatory potential. In conclusion, the local lymph node assay serves as an appropriate model to characterize immunosuppressive effects of topically applied drugs by measuring immunologically relevant end-points.

Administration, Topical↗
PubMed1997

Absorption of topical tacrolimus (FK506) in vitro through human skin: comparison with cyclosporin A.

Cyclosporin A (CsA) is efficacious in many dermatoses as an oral but not as a topical form, while tacrolimus (FK506) has been shown to be effective in both forms. As inadequate skin absorption has been proposed as the reason for inefficacy of topical CsA, factors contributing to percutaneous absorption of FK506 and CsA were studied. Partitioning of FK506 and CsA between octanol and water, stratum corneum and water, and stratum corneum and isopropyl myristate was determined. Absorption of FK506 and CsA through dermatomed human cadaver skin was determined with in vitro flow-through cells. In partitioning experiments, CsA was more lipophilic than FK506. Both drugs were seen in comparable amounts in skin layers, but FK506 permeated the skin to a greater extent than CsA.

Administration, Topical↗
PubMed1996

Delayed-type hypersensitivity in palmoplantar pustulosis: effect of cyclosporin A treatment on skin testing with recall antigens.

Delayed-type hypersensitivity reactions to skin antigens are an indirect measure of cellular immune response. We studied in a double-blind manner whether clinically effective doses of cyclosporin A in palmoplantar pustulosis would diminish delayed-type hypersensitivity reactions in vivo. For testing delayed-type hypersensitivity, we applied intradermally a standardized panel of seven recall antigens and a vehicle control in 30 patients with palmoplantar pustulosis, and 28 were tested both at baseline and after 4 weeks. For 4 weeks 14 patients were treated with 2.5 mg/kg/day cyclosporin A and 14 patients with placebo. Cyclosporin A but not placebo caused a significant decrease in clinical disease parameters. In contrast, no significant differences in delayed-type hypersensitivity reactions between treatment groups were observed. The results do not support the view that the efficacy of low-dose cyclosporin A in dermatological disorders can be entirely explained by cyclosporin A's inhibitory actions on effector T-cells.

Adult↗
PubMed1996

Effect of topical cis-urocanic acid on local lymph node activation during contact sensitization in mouse, rat and guinea-pig.

Cis-urocanic acid (cUCA) has been suggested as a mediator of impairment of contact hypersensitivity induction by ultraviolet B (UVB) irradiation. We ascertained whether topical cUCA influences local lymph node activation during induction of contact hypersensitivity. Topical cUCA or vehicle was applied during the local lymph node assay to oxazolone. Local lymph node weight and cell number were assessed in all animals. Additionally, cell proliferation rate was studied in Hartley guinea-pigs and CBA/Ca mice, whereas activation of antigen-presenting cells was quantified in NMRI mice and Wistar rats. Topical cUCA suppressed all parameters of local lymph node activation due to oxazolone application in guinea-pigs. No effect, with the exception of a suppression of antigen-presenting cell activity, was seen in mice. No effect was seen in rats. The study shows that topical cUCA may suppress local lymph node activation during contact sensitization and suggests that differences between the effect of cUCA in different animal species may exist.

Animals↗
PubMed1995

A local lymph-node assay validation study of a structure-activity relationship model for contact allergens.

A structure-activity relationship model for prediction of contact allergenic potential of chemicals had previously been developed. The model had been shown to be able to classify known allergens and nonallergens using data on physicochemical and reactivity parameters of functional groups by discriminant two-value multiple regression analysis. To investigate the model, six selected chemicals which had not been previously investigated for allergenicity were studied with both the model and a murine local lymph-node assay. The same compounds were predicted to be allergens (3-bromo-2-coumaranone, 1-nitrocyclohexene and alpha-acryloyloxy-beta, beta-dimethyl-beta-butyrolactone) and nonallergens (1-carbethoxy-4-piperidone, 6,7-dimethoxy-2-tetralone and 9-acetylanthracene) by both the model and the local lymph-node assay.

Allergens↗
PubMed1995

Topical cis-urocanic acid suppresses both induction and elicitation of contact hypersensitivity in BALB/C mice.

Cis-urocanic acid, converted from trans-urocanic acid in stratum corneum by ultraviolet B irradiation, has been shown to impair contact hypersensitivity induction. To study whether topical cis-urocanic acid also alters contact hypersensitivity elicitation, as well as immediate hypersensitivity and acute irritation, we treated mice with 1% topical cis-urocanic acid or vehicle prior to induction or elicitation of hypersensitivity to contact allergen oxazolone or respiratory allergen trimellitic anhydride or prior to acute irritation from croton oil. Topical cis-urocanic acid suppressed both induction and elicitation of contact hypersensitivity to oxazolone. However, no effect by cis-urocanic acid on induction or elicitation of trimellitic anhydride allergy or croton oil irritation was seen. The possible efficacy of topical cis-urocanic acid as a treatment of inflammatory skin diseases responsive to ultraviolet B irradiation may be worthwhile to investigate.

Administration, Topical↗
PubMed1994

Topical FK506: suppression of allergic and irritant contact dermatitis in the guinea pig.

Topical FK506 has recently been shown to have an anti-inflammatory effect in vivo in humans. In this study its effects in contact dermatitis were studied in the guinea pig model. Topical FK506 suppressed both irritant and allergic patch-test reactions. The most prominent suppressive effect was seen when skin sites were pretreated with FK506. Topical FK506 did not impair the induction of contact allergy as assessed by challenges, although it suppressed local lymph node cell accumulation during contact allergy induction. Topical FK506 may hold promise as a treatment for skin disorders that respond to oral FK506 or cyclosporin A.

Administration, Topical↗
PubMed1994

Topical FK506--clinical potential or laboratory curiosity?

Cyclosporine A (CsA) is an immunosuppressant that is efficacious in several inflammatory skin disorders. Its use is, however, limited due to systemic side-effects. Topical forms of CsA have been tried but they do not seem to be effective presumably due to insufficient penetration to skin. Tacrolimus (FK506) is another immunosuppressant that has almost similar effects on the cellular level as CsA. FK506 is 10-100 times more potent than CsA and it has lower molecular weight. Recent studies suggest that topical FK506 penetrates human skin in amounts exceeding those of topical CsA. Topical FK506 also seems to suppress skin inflammation in man. These findings prompt for further clinical studies of efficacy and safety of topical FK506.

Administration, Cutaneous↗
PubMed1993

Contact allergy to corticosteroids.

Recent evidence shows that contact allergy to topical corticosteroids is more frequent than earlier believed. This review summarizes the current knowledge of this condition, including methods for clinical diagnosis.

Administration, Topical↗
PubMed1993

Contact hypersensitivity to hydrocortisone-free-alcohol in patients with allergic patch test reactions to tixocortol pivalate.

It has been suggested that contact allergy to hydrocortisone alcohol is a frequent phenomenon. A recent study showed that all patients with allergic patch reactions to tixocortol pivalate reacted to intradermal hydrocortisone sodium phosphate. We studied patients with positive patch test reactions to tixocortol pivalate but negative to hydrocortisone alcohol, with penetration enhancers in hydrocortisone alcohol patch tests and oral challenges with hydrocortisone alcohol. Additionally, prick and intradermal tests with hydrocortisone sodium succinate were used. Using penetration enhancers and oral challenges enabled detection of more contact allergies to hydrocortisone alcohol compared to conventional patch testing alone. 9/12 patients with allergic reactions to tixocortol pivalate reacted to intradermal hydrocortisone sodium succinate. No immediate reactions were seen in prick or intradermal tests, suggesting that hydrocortisone contact hypersensitivity is probably not associated with immediate allergy to hydrocortisone. The present study suggests that allergic patch test reactions to tixocortol pivalate are caused by hypersensitivity to hydrocortisone alcohol itself or to one of its metabolites in the skin.

Anti-Inflammatory Agents↗
PubMed1993

Intradermal testing in the diagnosis of allergic contact dermatitis. A reappraisal.

Contact hypersensitivity may be diagnosed with patch testing or intradermal testing. Although these methods have been used earlier in parallel, patch testing has gradually become the only method in routine diagnosis of contact allergy. Recent findings in corticosteroid contact hypersensitivity have shown that patch testing is not always an optimal method, especially when poor penetrants are used. Therefore, a reappraisal of intradermal testing is presented, based on the literature. Studies employing both patch and intradermal testing are reviewed and the advantages and disadvantages of intradermal tests as compared to patch tests in contact allergy diagnostics are discussed. We find that it might be worthwhile to evaluate whether contact allergy to compounds other than corticosteroids may be easier to detect with intradermal than patch test.

Adrenal Cortex Hormones↗