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Biomedical subjects

C M Schempp

Publications and source records attributed to C M Schempp.

At least 19 recordsLinked to original sources
PubMed2005

The UV erythema test as a model to investigate the anti-inflammatory potency of topical preparations--reevaluation and optimization of the method.

BACKGROUND: The ultraviolet (UV) erythema test is one of the most frequently used methods to investigate the anti-inflammatory potency of topical dermatological preparations in vivo. METHODS: The following questions were addressed in four separate studies with healthy persons (skin types 2 and 3): (1) the optimal localization was determined by comparing light scales on the back, buttocks and volar forearms; (2) the optimal UV-B dose was determined by comparing the 1-fold, 1.5-fold and 2-fold minimal erythema doses (MEDs); (3) hydrocortisone and prednicarbate were evaluated as positive controls, and a sample size calculation was performed, and (4) betamethasone valerate and pimecrolimus were tested as further positive controls in the optimized study model. RESULTS: The back proved to be the best localization for the UV erythema test. It showed a good correlation between the light scale and the test areas. The 1.5-fold MED was the best irradiation dose. In contrast to prednicarbate and betamethasone valerate, hydrocortisone was a rather weak positive control. However, when the sample size was > or = 40 subjects, significant results were also obtained with hydrocortisone. Pimecrolimus was not effective in the UV erythema test. CONCLUSIONS: The UV erythema test should be performed on the back with at least 40 subjects using the 1.5-fold MED. It may be useful to include a potent corticosteroid, such as prednicarbate or betamethasone valerate, in addition to hydrocortisone. The UV erythema test seems to be suitable only for substances with corticosteroid-like effects, since in this test model the calcineurin inhibitor pimecrolimus was not effective.

Administration, Topical↗
PubMed2005

[Toxic phytodermatitis caused by Euphorbia helioscopia L. (sun spurge)].

A 6-year-old patient presented with linear erythema and bullae on the face. The lesions developed after playing with plants the day before. The plant was identified as Euphorbia helioscopia L. (sun spurge). The sun spurge belongs to the Euphorbiaceae plant family. These plants produce a typical milky juice that causes toxic reactions following contact with skin and mucous membranes. In the literature several cases of toxic dermatitis caused by plants of the Euphorbiaeae family have been described. The most important differential diagnosis of these skin lesions is the bullous phototoxic dermatitis caused by psoralens. Plant-induced toxic dermatitis is of increasing importance in dermatology. The exact determination of the causative plants is a prerequisite for the diagnosis of phytodermatitis.

Blister↗
PubMed2003

[Topical treatment of atopic dermatitis with Hypericum cream. A randomised, placebo-controlled, double-blind half-side comparison study].

BACKGROUND: Recent investigations suggest an anti-inflammatory and antibacterial effect of hyperforin, which is a major constituent of Hypericum perforatum L. (Saint John's wort). OBJECTIVE: In a half-side comparison study we assessed the efficacy of a cream containing Hypericum extract standardized to 1.5% hyperforin (verum) in comparison to the corresponding vehicle (placebo) for the treatment of subacute atopic dermatitis. The study design was a prospective randomized placebo-controlled double-blind single center study. METHODS: In twenty one patients suffering from mild to moderate atopic dermatitis (mean SCORAD 44.5) the treatment with verum or placebo was randomly allocated to the left or right site of the body, respectively. The patients were treated twice daily over a period of four weeks. Eighteen patients completed the study. The severity of the skin lesions on the left and right site was determined by means of a modified SCORAD-index (primary endpoint). RESULTS: The intensity of the eczematous lesions improved on both sites of treatment. However, the Hypericum cream was significantly superior to the vehicle at all clinical visits (days 7, 14, 28) (p<0.05). Skin colonization with Staphylococcus aureus was reduced by both verum and placebo, showing a trend to better antibacterial activity of the Hypericum cream (p=0.064). Skin tolerance and cosmetic acceptability was good or excellent with both the Hypericum cream and the vehicle (secondary endpoints). CONCLUSION: Hypericum cream was significantly superior to its vehicle in the topical treatment of mild to moderate atopic dermatitis. The therapeutic efficacy of the Hypericum cream should be evaluated in further studies with larger patient cohorts, in comparison to standard therapeutic agents (i.e. corticosteroids).

Adolescent↗
PubMed2002

[St. John's wort (Hypericum perforatum L.). A plant with relevance for dermatology].

Saint John's wort (Hypericum perforatum L.) is a herbal remedy that is effective in the treatment of mild to moderate depression. In traditional folk medicine, oily extracts of St. John's wort are used for topical treatment of wounds, burns and myalgia. The lipophilic phloroglucin-derivative hyperforin has antibacterial and antiinflammatory effects. These effects could be of relevance in topical treatment of infected wounds and other dermatoses, but no studies have been conducted so far. The naphtodianthrone hypericin is a photodtodynamic active substance that kills tumor cells via the induction of apoptosis. Hypericin also displays antiviral activity in vitro. In vivo, intravenous or oral treatment with hypericin of HIV-infected subjects did not result in a reduction of the virus load. Most of the patients treated with hypericin experienced phototoxicity. Similar phototoxic symptoms ("hypericism") have been observed in grazing animals ingesting large amounts of St. John's wort. In contrast, antidepressant medication with St. John's wort usually does not produce phototoxic symptoms. Recent pharmacokinetic studies suggest that the phototoxic threshold level of hypericin is not reached with dosages used for the oral treatment of depression. However, very recent reports demonstrated interactions of St. John's wort with other drugs such as digoxin, indinavir and cyclosporin. Blood levels of these drugs were dramatically decreased by St. John's wort. This should be considered in the treatment of skin conditions with antiviral drugs or cyclosporin.

Depressive Disorder↗
PubMed2002

[Plant-induced toxic and allergic dermatitis (phytodermatitis)].

Herbal products are being used increasingly for medical or cosmetic purposes. Many cosmetics contain plant extracts for fragrance. Sensitizing plants in cosmetics are tea tree oil, arnica, chamomile, yarrow, citrus extracts, common ivy, aloe, lavender, peppermint, and others. However, the sensitizing potential of these plants varies. Most of the sensitizing substances are sesquiterpene lactones or terpenes. The present paper reviews the various forms of phytodermatitis, including irritant plant dermatitis, phototoxic and photo-allergic dermatitis, allergic dermatitis, and airborne contact dermatitis.

Dermatitis, Allergic Contact↗
PubMed2001

Soluble CD44 inhibits melanoma tumor growth by blocking cell surface CD44 binding to hyaluronic acid.

Proteolytic cleavage of the extracellular domain of CD44 from the surface of cells has been observed recently in different cell types. In cell culture supernatants of human melanoma cell lines a 70 kDa soluble CD44 protein (solCD44) was detected at concentrations of 250-300 ng/ml. Protease inhibitor studies revealed that serine proteases and metalloproteases are involved in the cleavage of CD44 from the surface of melanoma cells. To analyse a possible function of soluble CD44 a human malignant melanoma cell line was stably transfected with cDNAs encoding either wild type soluble CD44s or mutated forms with defective HA binding properties (CD44sR41A and CD44sR150A/R154A). Soluble CD44s almost completely inhibited hyaluronic acid binding by melanoma cells, whereas soluble CD44 mutated in the HA binding domain had no effect. When cultivated on hyaluronic acid, melanoma cell proliferation was induced by 30% for both the parental and the control transfected cells. This increase in proliferation was blocked completely in solCD44s-secreting transfectants, whereas solCD44sR41A and solCD44sR150A/R154A-secreting cells again showed hyaluronic acid-induced cell proliferation. These cell lines were subcutaneously injected into MF1 nu/nu mice to compare their growth as tumors in vivo. Compared to tumors derived from parental and control transfected cells, we observed a dramatic reduction of primary tumor growth with solCD44s expressing MM cells. Transfectants expressing solCD44s mutated in the HA binding domain in contrast developed fast-growing primary tumors. These results provide strong evidence that direct solCD44 interactions with hyaluronic acid interfere competitively with processes induced by hyaluronic acid binding to surface CD44. Autocrine, or drug-induced secretion of solCD44 by human melanoma cells may thus exert potent antitumoral effects in vivo.

Animals↗
PubMed2001

Hypericin photo-induced apoptosis involves the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and activation of caspase-8.

Hypericin (HYP) is a photosensitizing pigment from Hypericum perforatum that displays cytotoxic effects in neoplastic cell lines. Therefore, HYP is presently under consideration as a new anticancer drug in photodynamic therapy. Here, we investigated the mechanism of action of HYP photo-induced apoptosis of Jurkat cells compared to the cytostatic drug paclitaxel (PXL). Both photoactivated HYP and PXL similarly increased the activity of caspase-8 and caspase-3, and drug-induced apoptosis of Jurkat cells was completely blocked by inhibitors of caspase-8 (Z-IETD-FMK) and caspase-3 (Z-DEVD-FMK). The involvement of death receptors was analyzed using neutralizing monoclonal antibodies against Fas (SM1/23), FasL (NOK-2) and TNF-R1 (MAB225), and a polyclonal rabbit anti-human TNF-related apoptosis-inducing ligand (TRAIL) antiserum. TRAIL antibody blocked TRAIL-induced and HYP photo-induced, but not PXL-induced apoptosis of Jurkat cells. In contrast, PXL-induced, but not HYP-induced apoptosis was blocked by the SM1/23 and NOK-2 antibodies. Anti-TNF-R1 antibody had no effect. These findings suggest that HYP photo-induced apoptosis of Jurkat cells is mediated in part by the TRAIL/TRAIL-receptor system and subsequent activation of upstream caspases.

Anthracenes↗
PubMed2000

Effect of topical application of Hypericum perforatum extract (St. John's wort) on skin sensitivity to solar simulated radiation.

St. John's wort (Hypericum perforatum) is a tradional folk remedy that is used for the topical treatment of superficial wounds, scars and burns. A characteristic metabolite of St. John's wort is the photodynamic active plant pigment hypericin. It is known that hypericin may cause a severe photodermatitis called hypericism when higher amounts of St. John's wort are ingested orally. To date, no reports on the photosensitizing capacity of topical application of St. John's wort are available. Here, we investigated the effects of Hypericum oil (hypericin 110 microg/mL) and Hypericum ointment (hypericin 30 microg/mL) on skin sensitivity to solar simulated radiation. Sixteen volunteers of the skin types II and III were tested on their volar forearms with solar simulated radiation for photosensitizing effects of Hypericum oil (n=8) and Hypericum ointment (n=8). The minimal erythema dose (MED) was determined by visual assessment, and skin erythema was evaluated photometrically. With the visual erythema score, no change of the MED could be detected after application of either Hypericum oil or Hypericum ointment (P>0.05). With the more sensitive photometric measurement, an increase of the erythema-index after treatment with the Hypericum oil could be detected (P< or =0.01). The results do not provide evidence for a severe phototoxic potential of Hypericum oil and Hypericum ointment, detectable by the clinically relevant visual erythema score. However, the trend towards increased photosensitivity detected with the more sensitive photometric measurement could become relevant in fair-skinned individuals, in diseased skin or after extended solar irradiation.

Administration, Cutaneous↗
PubMed2000

Topical application of St John's wort (Hypericum perforatum L.) and of its metabolite hyperforin inhibits the allostimulatory capacity of epidermal cells.

St John's wort (Hypericum perforatum) is a traditional herbal medicine that is used for the topical treatment of superficial wounds, burns and dermatitis. The characteristic metabolites of St John's wort are the photodynamic active plant pigment hypericin and the phloroglucin-derivative hyperforin. To date, no studies on immunomodulatory properties of topical preparations of St John's wort have been performed. Here, we investigated the alloantigen presenting function of human epidermal cells (EC) exposed to Hypericum ointment in vivo in a mixed EC lymphocyte reaction (MECLR). The effect of Hypericum ointment was compared with the immunosuppressive effect of solar-simulated radiation (SSR). Subsequently, we tested purified hyperforin in vivo and in vitro in a MECLR to evaluate its possible contribution to the effect of the Hypericum ointment. Furthermore, we assessed the effect of hyperforin on the proliferation of peripheral blood mononuclear cells (PBMC) in vitro. Compared with untreated skin, treatment with Hypericum ointment resulted in a significant suppression of the MECLR (P </= 0.001) that was similar to the effect of SSR. The combination of Hypericum ointment plus SSR was not significantly different from either treatment alone. EC isolated from skin treated with the hyperforin containing ointment also showed a reduced capacity to stimulate the proliferation of allogeneic T cells (P </= 0.001). Similarly, in vitro incubation of EC with hyperforin suppressed the proliferation of alloreactive T cells (P </= 0.001). Furthermore, hyperforin inhibited the proliferation of PBMC in a dose-dependent manner, without displaying pronounced toxic effects as determined by Trypan blue staining. The results demonstrate an inhibitory effect of Hypericum extract and of its metabolite hyperforin on the MECLR and on the proliferation of T lymphocytes that may provide a rationale for the traditional treatment of inflammatory skin disorders with Hypericum extracts.

Adjuvants, Immunologic↗
PubMed2000

Magnesium ions inhibit the antigen-presenting function of human epidermal Langerhans cells in vivo and in vitro. Involvement of ATPase, HLA-DR, B7 molecules, and cytokines.

The combination of seawater baths and solar radiation at the Dead Sea is known as an effective treatment for patients with psoriasis and atopic dermatitis. Dead Sea water is particularly rich in magnesium ions. In this study we wished to determine the effects of magnesium ions on the capacity of human epidermal Langerhans cells to stimulate the proliferation of alloreactive T cells. Twelve subjects were exposed on four subsequent days on the volar aspects of their forearms to 5% MgCl2, 5% NaCl, ultraviolet B (1 minimal erythemal dose), MgCl2 + ultraviolet B, and NaCl + ultraviolet B. Epidermal sheets were prepared from punch biopsies and were stained for ATPase and HLA-DR. Compared with untreated skin, the number of ATPase+/HLA-DR+ Langerhans cells was significantly reduced after treatment with MgCl2 (p = 0.0063) or ultraviolet B (p = 0.0005), but not after NaCl (p = 0.7744). We next questioned whether this reduced expression of ATPase and HLA-DR on Langerhans cells bears a functional relevance. Six subjects were treated on four subsequent days with 5% MgCl2, ultraviolet B (1 minimal erythemal dose), and MgCl2 + ultraviolet B. Epidermal cell suspensions from treated and untreated skin were assessed for their antigen-presenting capacity in a mixed epidermal lymphocyte reaction with allogeneic naive resting T cells as responder cells. Treatment with MgCl2, similarly to ultraviolet B, significantly reduced the capacity of epidermal cells to activate allogeneic T cells (p = 0.0356). Magnesium ions also suppressed Langerhans cells function when added to epidermal cell suspensions in vitro. The reduced antigen-presenting capacity of Langerhans cells after treatment with MgCl2 was associated with a reduced expression by Langerhans cells of HLA-DR and costimulatory B7 molecules, and with a suppression of the constitutive tumor necrosis factor-alpha production by epidermal cells in vitro. These findings demonstrate that magnesium ions specifically inhibit the antigen-presenting capacity of Langerhans cells and may thus contribute to the efficacy of Dead Sea water in the treatment of inflammatory skin diseases.

Adenosine Triphosphatases↗
PubMed1999

[Bullous phototoxic contact dermatitis caused by Ruta graveolens L. (garden rue), Rutaceae. Case report and review of literature].

A patient developed severe bullous phototoxic contact dermatitis caused by Ruta graveolens L. (garden rue) which belongs to the Rutaceae family. To date only a few cases of phototoxic reactions to the garden rue have been reported. The phototoxic components of Ruta graveolens L. are the fouranocoumarins 5-methoxypsoralen (bergapten) and 8-methoxypsoralen (xanthotoxine), and the furanoquinoline dictamnine whose phototoxic properties were recently discovered. Since the garden rue is frequently cultivated, it should be considered in the differential diagnosis of phototoxic phytodermatitis.

5-Methoxypsoralen↗
PubMed1999

[Comparison of balneophototherapy and UVA/B mono-phototherapy in patients with subacute atopic dermatitis].

In a controlled prospective study we compared the efficacy of combined salt water bath and UVA/B phototherapy to a UVA/B mono-phototherapy in patients with subacute atopic dermatitis (AD). The patients in the balneophototherapy group (n=16) were treated with baths containing 3-5% of the synthetic salt Psori-sal(trade mark), followed immediately by UVA/B irradiation, while the other treatment arm (n=12) received UVA/B phototherapy alone. After 20 treatments the balneophototherapy group showed a statistically significant (p</=0.0015) reduction of the SCORAD score from 69.5 before to 36.8 after therapy. No statistically significant reduction in the SCORAD score could be observed in the UVA/B phototherapy group (50.6 before to 44.3 after therapy). The cumulative UVB dose was significantly lower in the balneophototherapy group (0.9 J/cm2) as compared to the UVA/B monotherapy group (2.0 J/cm2). Balneophototherapy was well tolerated by patients with atopic dermatitis and no side effects were observed. We conclude that balneophototherapy expands the therapeutic options for patients with subacute atopic dermatitis.

Adult↗
PubMed1999

In vitro and in vivo activation of hypericin with the incoherent light source PDT 1200 SOA (520-750 nm) and with solar simulated radiation (290-2500 nm).

The photodynamic active plant pigment hypericin is a possible new photosensitizer for photodynamic therapy. Hypericin shows absorption maxima in the ultraviolet (330 nm) and visible light range (550 and 588 nm). The present study compared the photoactivation of hypericin with the incoherent light source PDT 1200 SOA (520-750 nm) to that with a 1000 watt solar simulator (290-2500 nm). Hypericin displayed dose and time dependent phototoxic effects in the keratinocyte cell line HaCaT in vitro and after intracutaneous in vivo application with both light sources. In vivo, delayed (48 h) photosensitivity in hypericin-sensitized skin was observed. With intracutaneous application of 100 ng/ml hypericin, no phototoxic reaction could be produced. The PDT 1200 SOA was about four times more effective in vitro and about ten times more effective in vivo when compared to the solar simulator. Since the PDT 1200 SOA allows homogenous irradiation of large areas, we conclude that the PDT 1200 SOA is an effective and convenient light source for in vitro and in vivo studies using hypericin.

Anthracenes↗