The sonographic image of inflamed inguinal lymph nodes in primary syphilis.
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Adult↗
Biomedical subjects
H C Korting
Publications and source records attributed to H C Korting.
Prospective analysis of STD related genital ulcers from Hamburg.
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Female↗
Effects of growth factors on the proliferation of human keratinocytes and fibroblasts in vitro.
Growth/differentiation factor-5 (GDF-5) is a new member of the transforming growth factor-beta (TGF-beta) superfamily of multifunctional peptide growth factors that appear to mediate many key events in cell growth and development. The effects of GDF-5 and other growth factors (epidermal growth factor, EGF; TGF-beta 1) on the proliferation of human keratinocytes and fibroblasts compared with desoximetasone and calcipotriol have been investigated. The proliferation rate was determined by a hemocytometer, MTT assay and the incorporation of [3H]-thymidine. Moreover, cell cycle analyses were performed and the influence on interleukin-1 alpha (IL-1 alpha) production in keratinocytes was measured by enzyme-linked immunosorbent assay (ELISA) because of its pronounced proinflammatory effect. In keratinocytes, GDF-5 stimulated cell proliferation to a minor extent. The drug already proved to be effective at very low concentrations (0.1 ng/ml). Growth stimulatory effects with EGF have been observed only in keratinocyte basal medium (KBM), but not in keratinocyte growth medium (KGM). TGF-beta 1 markedly inhibited the proliferation of keratinocytes at concentrations > 1 ng/ml. Calcipotriol and desoximetasone also showed a dose-dependent cell growth inhibition in epidermal cell cultures. IL-1 alpha synthesis was greatly suppressed by calcipotriol 10(-8)-10(-6) M. EGF at 10 ng/ml, in contrast, strongly stimulated IL-1 alpha production. Neither GDF-5 nor TGF-beta 1 had a significant effect on IL-1 alpha production in keratinocyte monolayer cultures. In fibroblasts, GDF-5 induced very weak antiproliferative effects. Calcipotriol and desoximetasone also inhibited cell growth in fibroblast cultures whereas proliferation and DNA synthesis were strongly stimulated by 1 ng/ml EGF. There was, however, a contradiction between TGF-beta 1 results on fibroblasts. Whereas TGF-beta 1 increased proliferation in cell number determination and in the thymidine incorporation assay, MTT assays showed slight antiproliferative effects. Due to these controversial results, in addition cell cycle analysis was employed. TGF-beta 1 led to an increased S phase, which indicates a stimulation of cell division. The different results obtained with the MTT test suggest that TGF-beta 1 may stimulate cell division of fibroblasts not only by increasing the S phase, but also by shortening the G1 phase of the cell cycle.
Cell Cycle↗
[Tinea in glabrous skin: total quality management].
Today tinea of glabrous skin still is one of the central diagnostic and therapeutic problems in dermatology. The choice of the adequate treatment is always influenced by the type of microorganism, the site of manifestation, time course and severity of the infection as well as by the immune status of the patient. Tinea has to be differentiated from other skin diseases. Thus, general guide lines for diagnostic processing are needed. Adequate treatment with various types of antimycotics either is topical or--less frequently--systemic.
Administration, Topical↗
[Cooling action of topicals--present results and testing methods in vivo and in vitro].
The cooling effect of topicals has been used in the dermatological therapy as "physical effect" on the skin for more than hundred years. This effect of dermatologicals releasing free water is widely accepted, but current knowledge does not correspond to today's possibilities of experimental thermographic tests in man. The present paper describes the results published up to now and the current testing methods in vivo and in vitro.
Animals↗
[Generalized Mycobacterium avium-intracellulare infection due to immunosuppressive therapy of paraneoplastic dermatomyositis].
The ubiquitous Mycobacterium avium-intracellulare (MAI) is the most frequent cause of disseminated atypical mycobacteriosis in AIDS patients. MAI infections may develop in patients with other acquired immune defects, such as connective tissue disorders. In adults, the gastrointestinal and respiratory systems are most frequently affected. We report a patient with dermatomyositis receiving immunosuppressive therapy in whom only the skin and the skeletal system were affected by MAI. Because it presented with polymyositis-like symptoms, the infection was initially not identified and treated. The MAI was cultured from a periarticular joint effusion from the right upper arm and from venous blood, as well as identified histologically in lesional skin. Resistance to antibiotics developed most likely because the patient failed to take oral antibiotics regularly. Because of an acute exacerbation of the tumor-associated dermatomyositis, immunosuppressive therapy was initiated, while the tuberculostatic therapy was continued. Using these therapies both diseases markedly improved. In patients with connective tissue disorders receiving longterm immunosuppressive therapy, especially when changes in symptoms and signs are observed, opportunistic infections such as MAI should be considered and included in the differential diagnosis.
Adenocarcinoma↗
[Pigmentation disorders in corticoid injections].
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Administration, Topical↗
Sonographic determination of cutaneous and subcutaneous fibrosis after accidental exposure to ionising radiation in the course of the Chernobyl nuclear power plant accident.
Chronic cutaneous lesions in eight of 15 survivors of the Chernobyl nuclear energy plant accident presenting with clinical features of cutaneous radiation fibrosis were examined 6 years after exposure using high-frequency ultrasound. In all patients, lesional skin was examined using both the B- and A-modes. Similar phenomena were found in all patients. The corium was increased in thickness as well as density compared to normal skin. The increase in density was seen not only in the medium strata but also particularly at the border between corium and subcutaneous tissue. Within the subcutaneous tissue proper, isles of echo-rich spots were prominent. The number and width of echo signals in the subcutaneous tissue were increased, representing the sonographic correlate of subcutaneous fibrotic trabeculae. The thickness of epidermis plus corium was increased by more than 50% and was even doubled in some cases. According to the present findings obtained from patients with very severe exposure to ionising radiation, ultrasound analysis of cutaneous and subcutaneous radiation fibrosis shows a characteristic picture. Moreover, it was demonstrated that quantitative assessment of skin thickness is possible. As the method is simple and noninvasive, repeated examinations are possible. This provides the basis for monitoring possible treatment effects and efficient follow-up in these chronically progressive clinical conditions after exposure to ionising radiation.
Adult↗
Prednicarbate biotransformation in human foreskin keratinocytes and fibroblasts.
PURPOSE: Evaluation of skin layer-specific prednicarbate (PC) biotransformation, possibly explaining the improved benefit/risk ratio of this topical corticosteroid in atopic dermatitis (1,2). METHODS: Metabolism of PC in keratinocyte and fibroblast monolayers derived from human juvenile foreskin was evaluated. Drug concentration was determined by HPLC/UV-absorption. Accompanying cell viability tests (MTT-tests) were performed to exclude toxic drug effects. RESULTS: Keratinocytes hydrolyzed the double ester PC (2.5 x 10(-5) M) at position 21 to the monoester prednisolone 17-ethylcarbonate (P17EC) which nonenzymatically transformed to prednisolone 21-ethylcarbonate (P21EC). This metabolite was enzymatically cleaved to prednisolone (PD), the main biotransformation product at 24 hours. Fibroblasts, however, showed a distinctively lower enzyme activity. Both, PC and P17EC (or rather P21EC) were hydrolyzed to a minor extent only. The biotransformation pathway, however, was the same. When P17EC was added separately, it transformed to P21EC and again was cleaved by keratinocytes to a much higher extent. Despite of the rather high glucocorticoid concentration MTT-tests proved a non-disturbed cell viability and proliferation rate. CONCLUSIONS: Extrapolating our results to the in-vivo situation, topically applied PC may be metabolized by epidermal cells during skin penetration. A complex mixture of compounds reaches the dermis, whose fibroblasts are barely able to metabolize the steroids. Since skin atrophy is less pronounced with PC as compared to conventional halogenated glucocorticoids, less potent PC metabolites appear to be the dominant species in the dermis.
Administration, Topical↗
Prednicarbate versus conventional topical glucocorticoids: pharmacodynamic characterization in vitro.
PURPOSE: Pharmacodynamic characterization of topical glucocorticoids as prednicarbate (PC), its metabolites prednisolone 17-ethylcarbonate (PEC) and prednisolone (PD), betamethasone 17-valerate (BMV), betamethasone (BM) and desoximetasone (DM) by evaluating their effects on epidermal and dermal cells. Synopsis of pharmacokinetic and pharmacodynamic studies, possibly explaining the improved benefit-risk ratio of prednicarbate. METHODS: Isolated foreskin keratinocytes were used to investigate the influence on epidermal inflammatory processes, dermal fibroblasts of the same origin to study antiproliferative activities of glucocorticoids. Interleukins were measured by ELISA-assay, the influence on II-1 alpha-production also on mRNA-level by RNAse protection assay. Proliferation was assessed by 3H thymidine incorporation and biodegradation by HPLC/UV-absorption. Cell viability was controlled by MTT assay. RESULTS: In keratinocytes, inflammation was induced by TNF alpha, resulting in an increased II-1 alpha synthesis. This cytokine was particularly suppressed by PC and BMV, whereas PEC, PD, DM and BM were less potent (p < or = 0.05). Since, however, the double ester PC is rapidly degraded in keratinocytes, a RNAse-protection assay of II-1 alpha mRNA was performed allowing short incubation times and thus minimizing biodegradation effects. In agreement with the previous experiment, the antiinflammatory potency of native PC was confirmed. In fibroblasts, II-1 alpha and II-6 synthesis indicate proliferation and inflammation respectively. Whereas PC inhibited II-1 alpha and II-6 production in fibroblasts to a minor extent only, it was strongly reduced by the conventional glucocorticoids and PEC (p < or = 0.05). The minor unwanted effect of PC on fibroblasts was also reflected by its low influence on cell proliferation as assayed by 3H thymidine incorporation. More pronounced antiproliferative features were observed with BM, PEC and especially BMV. CONCLUSIONS: Correlating antiphlogistic effects in keratinocytes (suppression of II-1 alpha) with antiproliferative effects in fibroblasts (suppression of II-1 alpha and II-6), the improved benefit-risk ratio of PC compared to conventional glucocorticoids does not result only from distinct drug metabolism in the skin but also from a specific influence on the cytokine network.
Administration, Topical↗
The hydroxypyridones: a class of antimycotics of its own.
The hydroxypyridones chemically form a class of antimycotics not related to others. For a long time ciclopirox olamine has been the only compound to be used clinically. Recently, ciclopirox as a free acid and rilopirox have also been considered. The congeners are active against a broad spectrum of medically relevant fungi including dermatophytes, yeasts and moulds in vitro. According to investigations based on animal and in vivo models for fungal disease, this also applies in vivo. Low toxicity in the experimental animal has made topical applications in man possible. Clinical experience relates, in particular, to dermatophytosis and vaginal candidosis, but rarer conditions have also been investigated. High tolerability corresponds to efficacy in major dermatomycological conditions. Today, interest mainly focuses on ciclopirox lacquer for onychomycosis. Here as in general, the relative role of hydroxypyridones will have to be finally established in comparative trials.
Antifungal Agents↗
Direct evidence for uptake of intact liposomes encapsulating silver sulfadiazine by cultured human keratinocytes based on combined transmission electron microscopy and X-ray microanalysis.
Cultured human keratinocytes were exposed to liposomally encapsulated silver sulfadiazine, free silver sulfadiazine, silver sulfadiazine cream, and a corresponding vehicle for 5 min to 24 h. Phagocytosis of intact liposomes by keratinocytes was demonstrated in vitro by combined X-ray microanalysis and electron microscopy. Silver as an active part of the antimicrobial served as an electron-dense marker.
Anti-Infective Agents, Local↗
Immunohistochemical investigations of genital ulcers caused by Haemophilus ducreyi.
To gain information on the specific composition of the inflammatory infiltrate of genital ulcers caused by Haemophilus ducreyi, biopsies of 6 genital ulcers which were diagnosed as chancroid on clinical and microbiological grounds were subjected to immunohistochemical investigations after conventional haematoxylineosin staining. A variety of antibodies reactive against B- and T-cells, plasma cells and granulocytes were used with each tissue sections. The lymphocytic infiltrate of chancroid ulcers consisted of both B- and T-lymphocytes and showed a cluster-like formation. B-lymphocytes were preferentially localized perivascularly in the middle layer, T-lymphocytes mainly in the deep layer of the inflamed oedematous tissue. Results stress the importance of both B- and T-cell mediated immune responses in Haemophilus ducreyi infection.
Antibodies, Bacterial↗
Light and electron microscopic findings in human epidermis reconstructed in vitro upon topical application of liposomal tretinoin.
The topical application of tretinoin is a well-established approach to the treatment of acne vulgaris. However, induced inflammation, clinically addressed as a "flare-up", is a major drawback. Recently, clinical and experimental investigations have hinted at a better tolerability, with equal efficacy, if the active compound is liposomally encapsulated. Using epidermis reconstructed in vitro, we compared the morphological changes upon topical application of a liposomal form (0.05% and 0.025%) and conventional form (0.05%) light and electron microscopically. After 24 h several remarkable changes of the stratum corneum with all treatment modalities, representing inhibition of keratinisation wanted in acne vulgaris, were seen. When preparations of equal strength, i.e. 0.05%, were compared, the changes representing toxic dermatitis in the epidermis were more marked with the conventional form. Epidermis reconstructed in vitro treated with the liposomal forms showed no significant differences due to either concentration. It is suggested that these changes correspond to the flare-up on clinical grounds. The in vitro findings further corroborate the hypothesis that liposomal encapsulation can increase the benefit/risk ratio of an active compound applied to the skin.
Administration, Topical↗
The role of Candida albicans secreted aspartic proteinase in the development of candidoses.
Although Candida albicans infections in humans are increasingly frequent, our understanding of the host-parasite relationship is limited. The secreted aspartic proteinase of C. albicans was first described in 1965 and has proved to be a major factor in virulence. This enzyme belongs to the class of aspartic proteinases which includes pepsin and renin in humans. Although found in some fungi, secreted aspartic proteinase is rare in these organisms. While the existence of several isoenzymes may not be fully established, it is now obvious that at least seven different genes encode for secreted aspartic proteinase. Within Candida cells it is located in membrane-bound vesicles. Upon fusion of these subcellular structures within the plasma membrane, the enzyme is released to the environment. In the context of human mucosal diseases it is responsible both for adhesion and invasion. Strains from HIV-infected patients with oral candidosis generally exhibit higher enzymatic activity than control strains. In future secreted aspartic proteinase may prove a prime target for new types of antimycotics.
Amino Acid Sequence↗
0.05% clobetasol 17-propionate cream and ointment but not the corresponding 0.1% triamcinolone acetonide preparations increase skin surface roughness: a possible dissociation of unwanted epidermal and dermal effects.
Repeated open application of clobetasol 17-propionate cream and ointment to normal skin over a period of 6 weeks induced an increase in skin surface roughness as assessed by profilometry (p < 0.05), while 6 weeks' application of triamcinolone acetonide cream and ointment did not. The increase in skin roughness with clobetasol 17-propionate cream turned out to be greater than with ointment containing identical amounts of clobetasol 17-propionate (p < 0.05). A clear-cut correlation between increase of skin surface roughness and skin thickness as assessed by high-frequency ultrasound could be demonstrated only with clobetasol 17-propionate cream and ointment.
Administration, Topical↗
Coal tar, pine tar and sulfonated shale oil preparations: comparative activity, efficacy and safety.
BACKGROUND: Tar and sulfonated shale oil preparations are used in the treatment of a variety of inflammatory skin diseases, including psoriasis vulgaris; due to the high polycyclic aromatic hydrocarbon (PAH) content of tars, a possible relationship with cancer in humans has been postulated. On the other hand, the purity of sulfonated shale oils concerning PAHs guarantees a good tolerability during dermatologic therapy. AIM: In this review, it is attempted to compare activity, efficacy and safety of coal tar, pine tar and sulfonated shale oil preparations which currently play a role in dermatologic treatment. RESULTS AND CONCLUSIONS: Primary sources of PAHs in the normal human environment are forest fires, cigarette smoke and combustion of fossil fuels for heating and energy. Thermal processing of fossil substances is also required for the production of tars and sulfonated shale oils. Due to individual manufacturing techniques, tars and sulfonated shale oils differ completely in their chemical composition. Still, sulfonated shale oils are often falsely grouped as tars because of their related origin and similar dermatologic indications. There is at least limited evidence of the activity and efficacy of various tars as well as sulfonated shale oil preparations in different frequent inflammatory skin diseases. This includes psoriasis vulgaris and atopic eczema of glabrous as well as hairy skin. There is still some concern about the long-term tolerability of tar preparations at least in some contexts. This, however, does not apply to sulfonated shale oil preparations. Consequently, at least their use should still be considered a rational drug treatment in dermatology.
Animals↗
The hyperkeratotic variant of porokeratosis Mibelli is a distinct entity: clinical and ultrastructural evidence.
An isolated case with the hyperkeratotic variant of porokeratosis Mibelli (PM) is reported. The 62-year-old woman developed multiple brown macules with well demarcated large keratotic nodules on both legs. Histopathological studies revealed the presence of a cornoid lamella characteristic of porokeratosis. Ultrastructural investigations revealed dyskeratotic as well as edematous, swollen keratinocytes; autophagocytotic vacuoles were visible. The clinical and ultrastructural peculiarities of the hyperkeratotic variant of PM suggest the possibility of a separate entity.
Administration, Topical↗