[Synergistic effects of terbinafine and itraconazole antimycotics].
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Biomedical subjects
Publications and source records attributed to H C Korting.
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Isoforms of aspartyl proteinase (Sap), which are encoded by at least nine related SAP genes, have been implicated to be a major virulence factor of the opportunistic yeast Candida albicans in experimental infections. Although it is generally assumed that proteinases are important for infections, detailed information on the pathogenetic role of Saps is still lacking. The same applies to the question whether the genes and corresponding isoforms of the enzyme are expressed during oral infection. For in vivo investigations, parts of the lesional oral epithelium were collected from three HIV-infected patients with oropharyngeal candidiasis. Immunoelectron microscopy was performed (pre- and post-embedding gold labeling with silver enhancement) using an anti-Sap murine monoclonal antibody directed against the gene products Sap1-3. It was possible to demonstrate expression of Sap antigens in each of the three samples of human oral candidiasis. This suggests that at least one of the genes SAP1-3 was expressed at the time of sample collection. Furthermore, a possible role of the enzymes during the interaction of yeast cells and mucosal cells is suggested: the majority of Sap antigens is secreted by those C. albicans cells that adhere directly to the epithelial surface. Sap immunoreactivity can be detected in particular at the site of close contact between C. albicans and epithelial cells, suggesting a pathogenetic role of the Saps in host-fungal interaction. Thus, inhibition of the enzyme might prove to be an important alternative in the prevention and treatment of candidiasis.
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Today quality is not only in the economy but also in medicine a prime parameter in the evaluation of goods and services. To guarantee quality in a comprehensive way not only quality control but also quality assurance or even quality management are needed. One has to focus on its integral aspects which are structure, process and result. With laboratory analysis a preanalytic phase has to be distinguished from an analytic and a postanalytic one. According to the notion of the Deutscher Arztetag quality assurance is a common task of all physicians. A variety of organisations provide support. Guidelines of various types are pivotal. Some concerning dermatology have already been released by Deutsche Dermatologische Gesellschaft; others are in the process of formulation. A comprehensive monograph is under way.
Seborrhoic dermatitis is an erythematosquamous condition of unknown etiology with a prevalence of approximately 2.5%. Frequently difficult to treat, it may respond to the application of low doses of dithranol, a substance which can induce a pustular dermatitis as an adverse side effect depending on the applied concentration and individual susceptibility. We describe a pustular dermatitis after the application of a preparation containing dithranol at an erroneously high concentration in a 30-year-old patient with seborrhoic dermatitis.
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.
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.
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.
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.
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.
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.
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.
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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.