摘要:

The 5-lipoxygenase (5-LO) product of arachidonic acid, leukotriene (LT-)B4, is considered to play a significant role in the pathogenesis of psoriasis. In vitro LTB4 is a potent chemoat-tractant for leukocytes, and it increases DNA synthesis in human cultured keratinocytes. Intradermal injection of LTB4 into human skin in vivo results in a wheal and flare reaction, and topical application produces intraepidermal microab-scesses and induces hyperproliferation. Furthermore, LTB4 has been determined in biologically active amounts in psoriat-ic skin lesions. Despite the importance of LTB4 in psoriasis, the capacity of the human epidermis to synthesize LTB4 has remained controversial. Recently, a very limited 5-LO activity was reported in human epidermis. Thus, it was shown that human epidermis can contribute significantly to LT formation by transcellular LT synthesis. By this mechanism, LTA4 released from activated leukocytes is further transformed into LTB4 in the keratinocytes by the LTA4 hydrolase. Transcellular metabolism may be of importance in psoriasis where neu-trophils migrate into the epidermis, because in human neutro-phils the LTA4 hydrolase has been shown as the rate-limiting step in LTB4 formation. The LTA4 hydrolase was localized in the epidermis by activity determination, by inhibition of enzyme activity with known LTA4 hydrolase inhibitors, by Western blotting and by immunohistochemical staining. Moreover the enzyme was purified and further characterized from human cultured keratinocytes and human epidermis. Because of these recent results it is concluded that LTB4 is of significance in the pathogenesis of psoriasis, and it is suggested that future work should focus on developing potent LTA4 hydrolase inhibitors for treatment of psoriasis.

ISSN:1660-5527    

DOI:10.1159/000211501

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

This study defines a modification of antioxidant systems by percutaneous absorption of fluocinolone acetonide. Total antioxidant status (TAS) provides an overall indication of antioxidant status. Superoxide dismutase (SOD), a primary antioxidant, accelerates the dismutation of the toxic superoxide radical produced during the oxidative energy processes into the less harmful molecules, hydrogen peroxide and molecular oxygen. We monitored the level of SOD and TAS in 7 males with psoriasis and 6 control subjects before and after a single application of fluocinolone acetonide 0.025% ointment to 90% of the body. The results showed that the plasma level of TAS was significantly increased (p < 0.02) at 24 h posttreat-ment. The erythrocytic level of SOD was significantly decreased (p < 0.01) only at 12 h after glucocorticosteroid application. The level of TAS and SOD in patients with psoriasis was also significantly increased (p < 0.01 for both situations) as compared to healthy controls. Our study suggests that fluocinolone acetonide as a therapeutic agent may play a role in the oxidative stress in skin diseases.

ISSN:1660-5527    

DOI:10.1159/000211502

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

We investigated the antipruritic effect of a 15-min application of dimethindene maleate (Fenistil® gel) and other local analgesics (Optiderm®, EMLA®, Xylocain® ointment 5%) on subsequent focal histamine stimulus (20 mC) given by iontophoresis in 12 patients suffering from acute atopic eczema (AE). The results were compared to histamine after pretreatment with the respective placebo and to non-pretreated skin. Wheal and flare areas were planimetrically evaluated. Itch or pain ratings were performed over a 24-min period using a rating scale. The examination also comprised alloknesis, i.e. induction of a peri-focal itch sensation by a non-itching mechanical stimulus. None of the antihistaminic and anaesthetic agents reduced the itch intensity significantly. Three of the AE patients had a total lack of alloknesis. We conclude that these substances, when applied for 15 min, are not sufficiently effective in atopic skin suppressing histamine-induced reactions under experimental conditions. The diminished elicitation of alloknesis in these patients may be a result of central nervous system alterat

ISSN:1660-5527    

DOI:10.1159/000211503

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Lipid-soluble psychotropics are often used to treat skin diseases with psychosomatic indications. Although these drugs are known to exert their effects through the central nervous system, relatively little is known about their mechanism of action in skin. In this communication, several lipid-soluble psychotropic drugs have been examined for their ability to inhibit protein kinase C (PKC)-catalyzed phosphorylation of exogenous substrates and endogenous skin proteins. Phosphorylation of three discrete skin protein substrates at 64, 42 and 28 kDa and a group crowded together at 15-18 kDa was prevented by the antidepressants/antipsychotics. Inhibition was more pronounced in a phospholipid (PL) dependent system, but both drug-PL and drug-PKC interactions seem to be important in the mechanism of action of these drugs. In addition to the tricyclic nucleus, the propanamine side chain or its N-methyl form may influence the interaction of these drugs with PKC and its substrate(s). Chlorpromazine, imipramine, fluoxetine, doxepin, amitriptyline and hydroxyzine used in the practice of dermatology may exert their therapeutic effects by modulating skin PKC activity.

ISSN:1660-5527    

DOI:10.1159/000211504

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Ginkgo bilobα studies have focused on the anti-inflammatory effects of the major components, ginkgolide and bilobalide, whereas little is known about their effect on fibroblasts. This study demonstrated the enhancing effects of Ginkgo L. extracts, especially the fiavonoid fractions: quercetin, kaempfe-rol, sciadopitysin, ginkgetin, isoginkgetin, on the proliferation of normal human skin fibroblast in vitro measured by MTT (3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyl-tetrazolium bromide) assay and direct hemocytometer cell count. Furthermore, increased production of collagen and extracellular fi-bronectin were documented by radioisotope (2,3-3H-proline) incorporated collagen assay, procollagen type I C-peptide assay and by immunoturbidimetric assay. These proliferative effects suggest another useful pharmacologic application of Ginkgo L. extracts in addition to their well-known anti-inflammatory effect

ISSN:1660-5527    

DOI:10.1159/000211505

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

Minoxidil is the most used drug with proved effects in the treatment of androgenetic alopecia (AGA), but little is known about its pharmacological activity and target cells in hair follicles. As AGA is characterized by follicle atrophy, accelerated hair cycles and hair fiber thinning, we postulated that kerati-nocyte proliferation/differentiation is affected and we tested Minoxidil’s effects on those parameters. Normal human keratinocytes (NHK) of follicular or epidermal origin were cultured in the presence of Minoxidil (0, 0.1, 1, 10, 100, 1,000 μM) during 5-8 days in various media (high-/low-calcium content, with or without serum). Proliferation was assessed by mitochondrial dehydrogenase activity (XTT), BrdU incorporation, lysosome numeration (neutral red incorporation) and total protein dosage. Drug-induced cytotoxicity was measured by lactate dehydrogenase release in culture supernatant, and pro-differentiating effects were evaluated by relative involucrin expression (ELISA dosage). On this basis, we showed that Minoxidil had biphasic effects on the proliferation and differentiation of NHK: Minoxidil stimulated NHK proliferation at micromolar doses, while antiproliferative, pro-differentiative and partially cyto-toxic effects were observed with millimolar concentrations. We can hypothesize that Minoxidil hypertrichotic activity in vivo is possibly mediated by the maintenance of proliferative potential in follicular keratinocytes precociously committed to differentiati

ISSN:1660-5527    

DOI:10.1159/000211506

出版商:S. Karger AG    

年代:1997

数据来源: Karger

摘要:

We examined the influence of melatonin, serotonin and tryptophan on the basal and δ-aminolevulinic acid (ALA)-induced porphyrin content in HaCaT, SKMel-23 and HepG2 cells. ALA-preincubated and ALA-free cells were fed with medium containing 1 mM melatonin, serotonin or tryptophan. After 24 h the porphyrin content in the cells and in the culture medium was measured. In the three cell lines the inbucation with 1 mM HaCaT cells. In HepG2 cells, neither melatonin, serotonin nor tryptophan influenced ALA-induced porphyrin concentrations significantly, but all three indoles depressed the porphyrin levels in SKMel-23 and HaCaT cells. The indoles may decrease the ALA uptake in HaCaT or SKMel-23 cells. Another mechanism could be the inhibition of enzymes converting ALA into porphyrins

ISSN:1660-5527    

DOI:10.1159/000211507

出版商:S. Karger AG    

年代:1997

数据来源: Karger