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Biomedical subjects

H C Korting

Publications and source records attributed to H C Korting.

At least 37 records · Page 2Linked to original sources
PubMed1998

Candida sake: a relevant species in the context of HIV-associated oropharyngeal candidosis?

Candida sake is routinely identified in the oral cavity of patients infected with the human immunodeficiency virus (HIV) using the commercial identification system ATB 32 C. To establish the prevalence of C. sake and to evaluate this designation repeatedly found using the ATB 32 C system, 94 HIV-infected patients were investigated for the presence of oral candidosis based on clinical and microbiological grounds. A total of 186 Candida isolates from 62 patients were obtained. Using the assimilation assay, C. sake was suspected in 49 isolates, but only seven strains were positively identified according to ATB 32 C. With respect to antifungal susceptibility and clinical parameters the 49 strains did not differ markedly from the other strains. Only antifungal susceptibility to amphotericin B, ketoconazole, and flucytosine was increased in C. sake strains when the positively and equivocally identified strains by ATB 32 C were taken together. In addition, amplifying genomic DNA with primers T3B and AP3, C. sake could not be identified in four strains and in one strain, respectively. Therefore biochemical identification of C. sake seems to be misleading and clinical relevance may be lacking.

AIDS-Related Opportunistic Infections↗
PubMed1998

A model of human cutaneous candidosis based on reconstructed human epidermis for the light and electron microscopic study of pathogenesis and treatment.

The use of reconstructed human epidermis provided the basis for an in vitro model of human cutaneous candidosis. Candida albicans blastospores on the surface of reconstructed human epidermis provoked the following changes within 72 h: superficial keratin degradation, scaling, hyperkeratosis, parakeratosis, dyskeratosis representing hyperproliferative stress, spongiosis, and vesiculation. Great differences in the intensity of these reactions of intact reconstructed human epidermis or chemically or mechanically damaged reconstructed human epidermis illustrate the importance of the stratum corneum as a barrier. Uninfected reconstructed human epidermis showed prominent cell proliferation representing wound healing 72 h after mechanical or chemical pretreatment. These signs of repair were blocked in the presence of C. albicans and the blastospores were able to invade the stratum corneum. When desmosomes were accessible, a high affinity of C. albicans blastospores to these structures was observed. A single application of an econazole liposome dispersion decreased scaling, hyperkeratosis and dyskeratosis. Morphological alterations of C. albicans blastospores after treatment with the econazole liposome dispersion in the proposed ill vitro model were identical, as described in established animal models. This reconstructed human epidermis model of cutaneous disease may provide insight into the pathogenesis and treatment of cutaneous candidosis and may provide a substitute for animal models and investigations on humans.

Antifungal Agents↗
PubMed1998

Current antimicrobial susceptibility of cutaneous bacteria to first line antibiotics.

Antimicrobial susceptibility of common bacterial species occurring on human skin appears to be falling. Data for the antimicrobial susceptibility of major groups of bacteria isolated from human skin during routine cultures were complied and analysed over a period of 9 months. Routine diagnostics of specimens from skin lesions and normal human skin were analysed for the presence of specified groups of bacteria. The species were identified using standard methods. Anti-microbial susceptibility was determined using a broth microdilution system giving breakpoints, the Sensititre system. Of the 333 Staphylococcus aureus, 129 Streptococcaceae, 180 Enterobacteriaceae and 120 Pseudomonadaceae strains investigated more than 5% of Staphylococcus aureus strains were resistant to flucloxacillin and thus methicillin (MRSA). More than 25% of Staphylococcus aureus strains were resistant to tetracycline and erythromycin. Many MRSA strains were found multi-resistant. Gentamicin was active against a large majority of Enterobacteriaceae strains but many Pseudomonadaceae strains were resistant. Compared with previous corresponding surveys methicillin-resistant Staphylococcus aureus strains are clearly on the increase. To prevent a further increase of resistant strains a defined strategy for antibiotic use is needed in dermatology.

Anti-Bacterial Agents↗
PubMed1998

Differential expression of secreted aspartyl proteinases in a model of human oral candidosis and in patient samples from the oral cavity.

Candida albicans, an opportunistic pathogen in humans, secretes secretory aspartyl proteinases (Saps), which have been correlated with virulence. We examined the temporal regulation of the mRNA expression of seven known members of the SAP gene family by reverse transcription polymerase chain reaction (RT-PCR) in (i) an in vitro model of oral candidosis based on reconstituted human epithelium (RHE); and (ii) clinical samples from patients with oral candidosis. SAP1 and SAP3 transcripts were first detected 42 h after inoculation of RHE, while at the same time, slight morphological alterations in the epithelium were documented by light microscopy. SAP6 expression occurred 6 h later concomitantly with germ tube formation of some infecting Candida cells and severe lesions of the epithelial tissue. SAP2 and SAP8 RT-PCR products were first detected 60 h after infection, while SAP4 and SAP5 transcripts were never discovered. Thus, a temporal progression of SAP expression in the order SAP1 and SAP3 > SAP6 > SAP2 and SAP8 was observed at the same time as increasing RHE damage occurred. At the protein level, Sap antigen was found within the C. albicans yeast cells and the epithelial cells by immunoelectron microscopy using an anti-Sap murine monoclonal antibody directed against the gene products Sap1-3. Expression of SAP1-3 and 6 was also detected by RT-PCR in samples from patients suffering from oral candidosis. Our results suggest that the pathogenesis of experimental and clinical oral candidosis is associated with the differential and temporal regulation of SAP gene expression.

Adult↗
PubMed1998

Tinea barbae due to Trichophyton mentagrophytes related to persistent child infection.

The case of a 42-year-old father is presented with 6 weeks' history of a painful kerion-like sycosis barbae. His two children had suffered from tinea manus 3 months previously, also caused by the zoophilic fungus Trichophyton mentagrophytes probably acquired from guinea-pigs. Seemingly ignoring the pathogenetic link, oral antibacterial treatment had been the first therapeutic attempt initiated by the family physician. Finally, successful treatment was performed by means of oral application of fluconazole 50 mg daily for a period of 6 weeks.

Adult↗
PubMed1998

[Investigations on the regulation of secreted aspartyl proteases in a model of oral candidiasis in vivo].

By means of RT-PCR and specific primers the expression of SAP1-6 and SAP8 was investigated with respect to the time course in an in vitro candidosis model based on reconstituted human mucosal epithelium. Corresponding morphological alterations of the epithelium were documented by light microscopy. The detection of Sap was performed immunoelectron microscopically using a monoclonal antibody. In the oral candidosis model SAP1 and SAP3 transcripts were detected 42 h after inoculation corresponding to first histopathological changes. Additional SAP6 expression was observed six hours later concomitantly with germ-tube formation. Later on SAP2 and SAP8 transcripts were found after 60 h. On protein level it was possible to demonstrate Sap antigens within Candida and markedly deteriorated epithelial cells. Initial experiments with proteinase mutants and proteinase inhibitors showed reduction of histological damage. In a clinical specimen obtained from a twenty nine-year-old female patient suffering from acute oral candidosis SAP1, 3 and 6 could be demonstrated corresponding to the findings in vitro after 48 h. Investigating a clinical specimen obtained from a lesion of chronic oral candidosis in an HIV-infected patient also showed SAP2 expression. On the basis of our results a relationship between the expression on of particular SAP genes and the turn up of lesions looks as probable as a relevant contribution to the in vivo infection.

Adult↗
PubMed1998

Aquarium dermatitis: cercarial dermatitis in an aquarist.

A 33-year-old man presented with very itchy red papules on the back of his hands and forearms. These papules appeared about 90 min after he had cleaned his aquarium in which he kept native fish and watersnails. He had obtained the watersnails some weeks before from a nearby pond. Examination of water from the aquarium revealed cercariae. The clinical diagnosis of cercarial dermatitis was corroborated. Cercarial dermatitis has repeatedly been seen in swimmers but not in aquarists keeping fish in a home aquarium.

Adult↗
PubMed1998

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↗
PubMed1998

[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↗
PubMed1998

[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↗
PubMed1997

[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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗