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Biomedical subjects

H Gollnick

Publications and source records attributed to H Gollnick.

At least 145 records · Page 8Linked to original sources
PubMed1981

[Serum triglycerides and cholesterin in patients with skin diseases during oral treatment with aromatic retinoid (author's transl)].

The serum lipid levels were repeatedly controlled in 25 patients with various skin diseases treated orally with retinoid Ro 10-9359 in different doses. In 19 cases serum lipid values before onset of treatment were taken. 6 additional patients were controlled after long-term intake of the drug over 6-8 months. Pathological elevations of triglycerides were seen in 5 patients, in 4 of them 2-12 weeks after onset of oral treatment. All patients with elevated values had additional risk factors: Manifest or asymptomatic diabetes, alcoholic abuse with fatty liver, adipositas, and/or preexisting disorders of lipid metabolism. The observed changes seemed dose-dependent. The values were lowered or returned to normal after dose reduction or after discontinuation of treatment (one case). The cholesterin levels also showed some elevated values during the time of observation, however, there was no clear relation to the administration of the drug and the daily dose. The changes were also seen preferably in patients with risk factors. Controls of serum lipid levels seem, therefore, indicated before and under administration of oral retinoid. In patients with the additional risk factors mentioned above strict indication for oral retinoid therapy is needed and lower doses should be rather administered.

Administration, Oral↗
PubMed1981

[New aspects and developments in antipsoriasis retinoid therapy].

Oral retinoids have been largely introduced in the management of psoriasis. The beneficial effect, however, differs according to the clinical type and requires an appropriate dosimetry: Pustular types respond rapidly and sufficiently to high initial doses (75 mg/d). In psoriatic erythroderma low initial doses (35 mg/d) seem indicated increasing the dose to 50 mg/d after 2-4 weeks. In chronic stationary psoriasis medium doses (50 mg/d) should be given as adjuvant treatment, combined with anthralin or UVB (SUP). In severe cases oral retinoids can be administered with systemic PUVA (RePUVA). Cheilitis, mucosal dryness and hair loss may appear temporarily as dose dependent side-effects. No hepatotoxicity was found. Interactions with serum triglycerides were seen, particularly in patients with diabetes, obesity, alcoholism and elevated triglyceride levels before treatment. Beside the compound Ro 10-9359 new synthetic derivatives are under investigation, either for topical therapy (Ro 11-1430), or for systemic therapy in lower doses (Ro 12-7554). Their mechanisms of action are still unknown. New findings suggest that retinoids may exert an immunomodulatory effect on dermal cells, in addition to their influence on keratinocytes.

Dose-Response Relationship, Drug↗
PubMed1977

[Skin wound granulation from contact with synthetic foil of teflon-polyurethane type].

When a plastic-foil consisting of teflon-polyurethan foam is applied to ulcer cruris and to polyurethan foam is applied to ulcera cruris and to combusted skin, pronounced granulation and formation of new capillaries and collagen fibers are observed in the contact area. The tightly adhering foils are tolerated by the wounds for more than 40 days with continous granulation. An adverse reaction against the foreign material and development of eosinophils and giant cells is not observed, though the polyurethan-foam of the foil was burst by the ingrowing granulation tissue. When the wound surface is clean, change of the dressing with this foil is necessary only every second or third day.

Bandages↗
PubMedDate not supplied

Optimized visualization and PCR reamplification of differentially displayed cDNA bands detected by silver staining in polyacrylamide gels as established in the model of dithranol-treated keratinocytes.

The differential display of cDNA species defined by a combination of so-called anchored and arbitrary primers has been acknowledged as a powerful complex strategy to identify differences in gene expression, and depends in its original version, inaugurated by P. Liang and A. B. Pardee in 1992, on the use of radioactive-labelled nucleotides. As a non-radioactive methodological alternative, we established the use of polyesterfilm-backed 10% polyacrylamide gels for horizontal differential-display electrophoresis under non-denaturing conditions, with subsequent detection of cDNA bands by an optimized, semi-automated silver staining omitting any fixation step. Polyacrylamide gel slices carrying the silvered cDNA species of interest were cut out, chopped, squashed and incubated in an ammonium acetate/EDTA solution at 37 degrees C overnight under vigorous shaking. This procedure resulted in a 70% average success rate for subsequent PCR reamplification with regard to the number of cDNAs harvested from the differential-display gel. Novel sequence data of three cDNA clones are communicated, which under these methodological conditions were selected to be up- or down-regulated, respectively, by antipsoriatic dithranol in cultured HaCaT keratinocytes.

Acrylic Resins↗
PubMedDate not supplied

Lack of efficacy of topical capsaicin in serotonin-induced itch.

Capsaicin (CAP) has been demonstrated to be an effective topical inhibitor of cutaneous vasodilatation, pain and pruritus induced by a variety of chemical and physical stimuli. In a previous study, we showed a significantly inhibitory effect of topical CAP treatment on histamine-induced itch and cutaneous vascular reactions in healthy subjects compared to atopic eczema patients. As serotonin is proposed to play a pathophysiological role in some types of pruritus (e.g. uremic and hepatic pruritus) and CAP has been described to be successful in hemodialysis-related pruritus, we investigated the antipruritic effect of topical CAP on serotonin-induced reactions in 10 healthy volunteers in comparison to untreated skin (UPS) and placebo substance (vehicle)-treated skin (VS). On the first day, serotonin iontophoresis was performed in untreated skin. One week later, the treatments started, using either CAP 0.05% liniment or a placebo liniment (vehicle) 3 times daily over a 5-day period. On day 6, serotonin was applied by iontophoresis within the pretreated skin. After another 1-week break, the treatments were performed vice versa on the corresponding infrascapular region. Weal and flare areas were planimetrically evaluated. Itch sensations were documentated by the volunteer on a scale over a 24-min follow-up period. The examination also comprised alloknesis, which stands for induction of perifocal sensations by usually non-itching stimuli. In CAP-treated skin, serotonin-induced wheals were significantly larger post-application compared to non-pretreated skin. Wheals were significantly larger in VS than in UPS. Comparison of serotonin-induced flares in the different study arms did not reveal any significant differences. Itch sensations were not significantly reduced by topical CAP application. The areas of alloknesis were smaller in capsaicin-treated skin compared to VS and UPS, but did not reach significant value. In conclusion, topical CAP application is not effective in serotonin-induced itching in healthy volunteers. Serotonin is most unlikely to play a role in the mechanism of action of CAP.

Administration, Topical↗
PubMedDate not supplied

Age and sex variation in lipid composition of human fingernail plates.

In contrast to epidermal lipid metabolism, the lipid biochemistry of nails has yet been poorly investigated. Our purpose was to define a reference population of healthy individuals as a base for the better understanding of nail diseases and age-induced changes. Therefore, we developed a method of processing and extracting the nail plates enabling us to assess the most relevant epidermal lipid classes by HPTLC. Our study revealed that nail plate lipid composition varies with age and sex: the lipid composition of the fertile years shows distinct profiles compared to that of childhood and old age, suggesting an influence of sex hormones on nail lipogenesis. Our results open the possibility in the future of an easier comparison between healthy and diseased nails and enable us to investigate factors influencing nail lipid composition such as drugs, metabolic diseases, toxic agents, cosmetics and nail therapeutics.

Adolescent↗
PubMedDate not supplied

Tazarotene induces epidermal cell differentiation in the mouse tail test used as an animal model for psoriasis.

Disturbed epidermal proliferation and keratinization are major features of psoriatic skin lesions. The so-called mouse tail test is known as an animal model to evaluate the antipsoriatic efficacy of topical drugs with regard to the induction of orthokeratosis. The purpose of the present study was to investigate the effect of tazarotene, a novel, receptor-specific retinoid, by the mouse tail test in a direct comparison to dithranol representing a classical topical antipsoriatic compound. The tails of CFLP mice were treated with tazarotene gel (0.1%, 0.05%), dithranol ointment (1.0%), tretinoin cream (0.05%) and methylcellulose (5%) hydrogel (vehicle control) for 2 weeks. Longitudinal histological sections were prepared from the tail skin, and the degree of orthokeratosis was determined by measuring the horizontal length of the fully developed granular layer within an individual scale in relation to its total length according to a method originally described by Bosman and co-authors. The degree of orthokeratosis was significantly (p < or = 0.05) increased by 0.1% tazarotene (87+/-20%), 1.0% dithranol (75+/-26%), 0.05% tazarotene (59+/-27%), and 0.05% tretinoin (23+/-13%) as compared to untreated (11+/-6%) and methylcellulose hydrogel-treated (13+/-6%) controls. Under the conditions of the mouse tail test, tazarotene showed a strong potency to induce orthokeratosis. With regard to clinically relevant concentrations this effect was even more pronounced than that observed for dithranol.

Animals↗
PubMedDate not supplied

Dithranol and dimethylfumarate suppress the interferon-gamma-induced up-regulation of cytokeratin 17 as a putative psoriasis autoantigen in vitro.

In psoriasis an etiopathogenetic vicious circle has been hypothesized in which disease manifestation is triggered by skin-specific autoantigen structures. Autoreactive T cells are supposed to mediate inflammation and hyperproliferation in the epidermopapillary compartment, positively feeding back the expression and accessibility of decisive antigen structures. Recently an epitope within cytokeratin 17 (K17) has been described as such a putative psoriasis autoantigen, which is moreover known to be up-regulated under the influence of proinflammatory interferon-gamma (IFN-gamma), which is abundantly detected in psoriatic plaques. The present study proposes an in vitro model for this presumptive IFN-gamma/K17 autoimmune loop, i.e. the incubation of hyperproliferative human HaCaT keratinocytes with 25 U IFN-gamma/ml for 72 h. This treatment led to a significant up-regulation of K17 protein expression (> or =300%) measured by flow immunocytometry as compared to the untreated control (100%, p < or = 0.05). Preincubation with a subcytotoxic and antiproliferative dithranol concentration as low as 0.3 microM for 2 h prior to the IFN-gamma exposure resulted in a K17 expression that was significantly lower than the IFN-gamma-induced K17 expression reference level. The IFN-gamma-induced K17 expression was also significantly lowered by coincubation with a subcytotoxic and nonantiproliferative concentration of 3 microM dimethylfumarate. The data indicate for dithranol and dimethylfumarate that a part of their antipsoriatic mode of action may be related to a direct down-regulation of putative psoriasis autoantigen structures.

Administration, Topical↗
PubMedDate not supplied

Perforin granule release from cytotoxic lymphocytes ex vivo is inhibited by ciclosporin but not by methotrexate.

The 70-kD plasma membrane pore-forming protein perforin is a key component of lymphocyte cytotoxicity mediated by lytic granules. It represents a major player in the regulation of various immune reactions like immunoglobulin synthesis, T-cell activation and homeostasis, and in the elimination of virus-infected and tumor cells. Dysregulation of the perforin-granule system, i.e. an increase of perforin-containing lymphocytes, was recently demonstrated in exacerbated psoriasis and generalized drug reactions. In contrast, in patients with exacerbated atopic dermatitis or unsymptomatic rhinitis allergica, a severe perforin depletion in cytotoxic T cells was demonstrated. In addition, these cells displayed a remarkable transport defect of lytic granules, i.e. a perforin hyperreleasability. Thus, the process of perforin-granule release may represent an attractive target for therapeutic immune modulation in various dermatological diseases. Ficoll isolated peripheral blood mononuclear cells (PBMCs) of healthy volunteers were preincubated with different concentrations of ciclosporin or methotrexate (MTX) for 1 h. A newly developed flow cytometry based perforin release assay was used to quantify the velocity of ionomycin/phorbol 12-myristate 13-acetate stimulated perforin-granule release in the presence or absence of pharmacological agents. The immunosuppressant MTX did not influence perforin-granule release. Ciclosporin, in contrast, was found to inhibit perforin-granule release significantly and dose dependently: whereas release from CD8(+) lymphocytes was almost maximal for the untreated control after 60 min (41% of CD8(+) perforin(+) cells at time zero), ciclosporin at 20, 4 and 2 microg/ml elevated the aforementioned parameter up to 73, 65 and 53%, respectively. Our data demonstrate that (i) perforin-granule release can be targeted efficiently by pharmacological agents which can be monitored directly in a newly developed perforin-granule release assay, and (ii) suppression of perforin-granule based cytotoxicity by ciclosporin might contribute to the beneficial therapeutic effects of this drug as an immunomodulating and immunosuppressant target.

Adult↗
PubMedDate not supplied

Long-term stability of 8-methoxypsoralen in ointments for topical PUVA therapy ('Cream-PUVA').

8-Methoxypsoralen (8-MOP) is an established photochemotherapeutic agent for PUVA therapy. Recently, a so-called 'cream-PUVA' modality was introduced into therapy of psoriasis and other dermatoses. Little is known, however, about the stability of 8-MOP in ointments used for the topical application of this compound. Therefore, we investigated the long-term stability of 8-MOP in three different ointments, Unguentum Cordes(TM), Cold Cream Naturel(TM) and a water-containing gel on the basis of Carbopol 940. All three ointments were prepared with 8-MOP concentrations of 0.05 and 0.005%, and stored over 12 weeks at room temperature (19-20 degrees C) and at 5 degrees C. 8-MOP concentrations were measured at days 1, 8, 15, 29, 57 and 88 after preparation by thin-layer chromatography (TLC). The ointments were dissolved in an organic solvent, 10 microl were transferred onto the TLC plate and the chromatograms were developed first in toluene and then in toluene/ethyl acetate 2:1 v/v to resolve 8-MOP from the ointment constituents. The peak heights of 8-MOP were used for quantitation. The intraday variabilities are <3% for Unguentum Cordes and Cold Cream Naturel and <6% for the Carbopol 940 gel. The interday variabilities were <6.3% in all cases. In Unguentum Cordes and Cold Cream Naturel the concentrations of 8-MOP remain stable, but in Unguentum Cordes the emulsion began to break up after 8 weeks. In the Carbopol gel, only about 40% of the nominal concentrations of 8-MOP were found and they decrease significantly at storage at 5 degrees C. We conclude that the Carbopol gel seems to be unsuitable for PUVA therapy, whereas Cold Cream Naturel shows the best results.

Acrylic Resins↗
PubMedDate not supplied

Detection of enhanced monohydroxyeicosatetraenoic acid and F2-isoprostane levels in human plasma samples after extracorporeal photoimmunotherapy.

To investigate the involvement of reactive oxygen species in extracorporeal photoimmunotherapy (photopheresis), we have introduced two highly sensitive and specific techniques for the detection and quantitative measurement of oxygenated nonenzymatically formed arachidonic acid isomers [mono-hydroxyeicosatetraenoic acids (HETEs) and F2-isoprostanes] by gas chromatography-mass spectrometry/negative ion chemical ionization (GC-MS/NICI) in plasma samples of patients suffering from cutaneous T-cell lymphoma and progressive systemic scleroderma II. The analysis of HETEs involved hydrogenation, solid phase extraction on a C18 cartridge, formation of pentafluorobenzyl bromide and trimethylsilyl ether derivatives. In the case of F2-isoprostanes, the analytical procedure was similar to that of HETEs except that the hydrogenation step was omitted. In the plasma of healthy volunteers picomole amounts of 2-, 5-, 8-12-, 15-HETEs, 8-iso-PGF(2alpha) and 9alpha,11alpha-PGF(2alpha) were quantified by using 12-hydroxy-heptadecatrienoic acid and PGF(2alpha)-d4 as internal standards of HETEs and isoprostanes, respectively. Analysis of plasma samples obtained from patients before and after extracorporeal photoimmunotherapy revealed characteristic increases in both, HETE and isoprostane levels. The enhancement of indicators of lipid peroxidation is in correspondence with a moderate loss of alpha-tocopherol, the most important lipid-soluble antioxidant in human plasma. Thus, our data confirm the involvement of lipid peroxidation in extracorporeal photoimmunotherapy.

Arachidonic Acid↗
PubMedDate not supplied

Interferon-gamma-dependent in vitro model for the putative keratin 17 autoimmune loop in psoriasis: exploration of pharmaco- and gene-therapeutic effects.

In 1999, A.S. Gudmundsdottir et al. have envisaged an epitope on keratin 17 (K17) as a putative psoriasis major autoantigen recognized by T cells. In a HaCaT keratinocyte model, we now demonstrate that IFN-gamma and to a less extent also TNF-alpha and TGF-alpha are able to induce K17 protein expression, in contrast to IL-1alpha, IL-1beta, IL-6, IL-8 and IL-18. This supports our hypothesis of an existing proinflammatory cytokine/K17 autoimmune loop as a presumptive positive feedback mechanism driving psoriasis etiopathogenesis. K17 overexpression was now found to also coincide with suppression of keratinocyte proliferation, e.g. induced by NF-kappa B inhibitors (Bay 11-7082 and Bay 11-7085), and thereby correlated hyperapoptosis to be encountered in psoriatic epidermis. Acitretin as an established antipsoriatic drug and the tyrosine kinase inhibitor imatinib decreased, whereas hydrocortisone as well as dexamethasone increased the IFN-gamma-induced K17 overexpression. The latter might be another mechanism explaining the well-known rebound phenomena after abrupt withdrawal of corticosteroids in psoriasis treatment. Finally, we defined a K17-directed and effective antisense oligodesoxynucleotide which may hold promise for future gene-therapeutic approaches in psoriasis.

Acitretin↗
PubMedDate not supplied

Up-regulated perforin expression of CD8+ blood lymphocytes in generalized non-anaphylactic drug eruptions and exacerbated psoriasis.

Perforin expressed in CD8+ cytotoxic T cells is known to mediate the lysis of target cells carrying microbial as well as tumor-associated antigens, and to be involved in autoimmune and transplant reactions. The aim of the present investigation was to study the role of perforin- and CD8-expressing effector lymphocytes from peripheral blood in patients with generalized inflammatory skin diseases. Mononuclear cells were separated from peripheral venous blood and permeabilized by 0.1% saponin. The co-expression of cytoplasmatic perforin and cell membrane-residing CD8 was determined in lymphocytes by immuno-flow cytometry. Patients affected by generalized macular-papular drug eruptions (n = 14), drug-unrelated acute urticaria (n = 10) and drug-independently exacerbated psoriasis (n = 11, PASI scores ranging from 25 to 35), as well as control individuals not affected by any inflammatory skin disease (n = 10) were enrolled. Additionally, n = 5 patients with drug-induced Stevens-Johnson syndrome (SJS) were included. The average proportion of CD8+ peripheral lymphocytes co-expressing perforin in generalized drug eruptions (68.8+/-24.9%) and exacerbated psoriasis (67.2+/-17.1%) differed significantly from the controls (43.5+/-11.6%; p 0. 05), whereas no significant difference for acute urticaria (58.2+/-23.1%) could be measured. In each of the 5 SJS patients treated by high dose systemic steroids the parameter substantially declined during the first 7 days after admission from an average value of 81. 6% down to 33.0%. Thus, as compared to controls we observed an increased perforin+ proportion of CD8+ lymphocytes in generalized drug eruptions and in exacerbated psoriasis but not in acute urticaria. Therefore the parameter showed some specificity as a marker of distinct inflammatory skin disorders, and proved to be useful in monitoring the disease activity of SJS under anti-inflammatory medication. Furthermore, the findings point to a possible crucial role of CD8+ lymphocytes in the pathogenesis of psoriasis.

Adult↗
PubMedDate not supplied

Photodynamic therapy in dermatology.

Application of non-ionising radiation with or without photosensitizers is rather common in dermatology. Though the method itself was described in ancient times, its routine use in medicine based on scientific research started in the second half of the 20th century. Light can be used in three different patterns: phototherapy (UV-A or UV-B light), photochemotherapy (combination of psoralens with UV-A light) and photodynamic therapy (combination of photosensitizers with UV- and/or visible light). The following article deals with the photodynamic therapy or PDT. Using PDT implies the understanding of light dosimetry and calculation of light dose using different light sources and photosensitizers. The number of PDT sensitisers under investigation is rapidly increasing. The PDT itself, being a relatively new modality, quickly spreads its list of applications covering new indications in different areas of medicine. Though the main part of this list is made up of dermatological conditions, the use of PDT in other disciplines is also discussed to make dermatologists familiar with different aspects of the issue. PDT, like any treatment modality, has its benefits and adverse effects. The future of PDT is closely related to teamwork in physical, biochemical and clinical research which could provide better understanding of underlying mechanisms and help to create protocols for higher therapeutic efficacy.

Dermatology↗