[Candidiasis of the skin].
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Candidiasis, Chronic Mucocutaneous↗
Biomedical subjects
Hans Christian Korting
Publications and source records attributed to Hans Christian Korting.
Reconstructed human epidermis for skin absorption testing: results of the German prevalidation study.
Exposure to chemicals absorbed by the skin can threaten human health. In order to standardise the predictive testing of percutaneous absorption for regulatory purposes, the OECD adopted guideline 428, which describes methods for assessing absorption by using human and animal skin. In this study, a protocol based on the OECD principles was developed and prevalidated by using reconstructed human epidermis (RHE). The permeation of the OECD standard compounds, caffeine and testosterone, through commercially available RHE models was compared to that of human epidermis and animal skin. In comparison to human epidermis, the permeation of the chemicals was overestimated when using RHE. The following ranking of the permeation coefficients for testosterone was obtained: SkinEthic > EpiDerm, EPISKIN > human epidermis, bovine udder skin, pig skin. The ranking for caffeine was: SkinEthic, EPISKIN > bovine udder skin, EpiDerm, pig skin, human epidermis. The inter-laboratory and intra-laboratory reproducibility was good. Long and variable lag times, which are a matter of concern when using human and pig skin, did not occur with RHE. Due to the successful transfer of the protocol, it is now in the validation process.
Adult↗
Receptor-selective retinoids for psoriasis: focus on tazarotene.
Topical and oral retinoids have been successfully used in antipsoriatic therapy over the last 50 years. Development of more selective agents has led to an improved efficacy and safety profile. The first topical receptor-selective retinoid to be approved for the treatment of plaque psoriasis is tazarotene. Topical tazarotene displays an onset of action and efficacy similar to those of other established antipsoriatic agents. Common adverse events of this agent such as pruritus, burning, local skin irritation, and erythema are limited to the skin and generally mild or moderate in severity. Although effective as monotherapy, evidence is accumulating that combining topical tazarotene with other established antipsoriatic therapies results in enhanced efficacy and reduced adverse events. In particular, concomitant use of topical tazarotene with a mid-potency or high-potency corticosteroid in the treatment of psoriatic plaques enhances efficacy and reduces the risk of corticosteroid-induced skin atrophy. Combination of phototherapy with tazarotene accelerates the clinical response and diminishes the cumulative UVB or psoralen plus UVA (PUVA) exposure load. Recently, an oral form of tazarotene has been developed. The results of completed phase III clinical trials of this agent indicate a beneficial effect in moderate to severe plaque psoriasis. Adverse events are generally of mild severity, and most of those observed, such as cheilitis and dry skin, are typical of hypervitaminosis A. Of note, oral tazarotene appears not to be associated with other adverse events that are typical of oral retinoids, including hypertriglyceridemia and hypercholesterolemia. However, since head-to-head trials with acitretin (the only retinoid currently approved for systemic therapy) have not been conducted, it is unclear whether tazarotene is any safer or more effective than acitretin. Moreover, the major drawback of oral tazarotene is teratogenicity, which may limit its use in female patients. Further studies evaluating long-term clinical outcomes with oral tazarotene and its use in combination therapies are awaited.
Animals↗
Human defensins.
Antimicrobial peptides are small, cationic, amphiphilic peptides of 12-50 amino acids with microbicidal activity against both bacteria and fungi. The eukaryotic antimicrobial peptides may be divided into four distinct groups according to their structural features: cysteine-free alpha-helices, extended cysteine-free alpha-helices with a predominance of one or two amino acids, loop structures with one intramolecular disulfide bond, and beta-sheet structures which are stabilised by two or three intramolecular disulfide bonds. Mammalian defensins are part of the last-mentioned group. The mammalian defensins can be subdivided into three main classes according to their structural differences: the alpha-defensins, beta-defensins and the recently described theta-defensins. Mammalian alpha-defensins are predominantly found in neutrophils and in small intestinal Paneth cells, whereas mammalian beta-defensins have been isolated from both leukocytes and epithelial cells. Recently, two novel human beta-defensins, human beta-defensin-3 (HBD-3), and human beta-defensin-4 (HBD-4) have been discovered. Similar to HBD-1 and HBD-2, HBD-3 has microbicidal activity towards the Gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli) and the yeasts Candida albicans and Malassezia furfur. In addition, HBD-3 kills Gram-positive bacteria such as Streptococcus pyogenes or Staphylococcus aureus, including multi-resistant S. aureus strains, and even vancomycin-resistant Enterococcus faecium. In contrast to HBD-1 and HBD-2, significant expression of HBD-3 has been demonstrated in non-epithelial tissues, such as leukocytes, heart and skeletal muscle. HBD-4 is expressed in certain epithelia and in neutrophils. Its bactericidal activity against P. aeruginosa is stronger than that of the other known beta-defensins. Here we present an overview of human antimicrobial peptides with some emphasis on their antifungal properties.
Animals↗
Oxygen accessibility and iron levels are critical factors for the antifungal action of ciclopirox against Candida albicans.
OBJECTIVES: Ciclopirox is a topical antifungal agent of the hydroxypyridone class whose mode of action is poorly understood. In order to elucidate the mechanism of action of ciclopirox, we analysed the growth, cellular integrity, biochemical properties, viability and transcriptional profile of the polymorphic yeast Candida albicans following exposure to this antifungal agent. METHODS: Multiple biochemical assays served to identify factors that were critical for antifungal activity and to identify proteins whose activities changed in drug-exposed cells. Genome-wide transcriptional profiling was used to identify genes that were up-regulated in response to the cellular effects of the drug. RESULTS: Ciclopirox inhibited growth of C. albicans yeast and hyphal cells in a dose-dependent manner. This effect was reduced (i) by the addition of iron ions or the metabolic inhibitor 2-deoxy-D-glucose to growth media, (ii) in media that lacked glucose, and (iii) for cells that were pre-incubated with hydrogen peroxide or menadione [which caused induction of proteins involved in detoxification of reactive oxygen species (ROS)]. In contrast, cells pre-cultured under poor oxygen conditions (which had decreased activity of proteins involved in ROS detoxification) were more susceptible to ciclopirox. Treatment with ciclopirox did not directly cause cell membrane damage and did not change intracellular levels of ATP. Finally, the transcriptional profiling pattern of drug-treated cells strongly resembled iron-limited conditions. CONCLUSIONS: These data indicate that metabolic activity, oxygen accessibility and iron levels are critical parameters in the mode of action of ciclopirox olamine.
Antifungal Agents↗
Lactobacilli - bacteria-host interactions with special regard to the urogenital tract.
Lactobacilli are part of the commensal human mucosal flora. Their application as probiotics in dairy products such as yoghurt has increased during the last century since a health promoting effect has been reported. Much work has been done to study the effects of these bacteria on the immune system and epithelial cells, mainly focused on the intestinal mucosa as the field of first contact. This review is aimed to present and discuss results concerning interactions of lactobacilli and immune system or epithelial cells with focus to urogenital mucosa.
Animals↗
[Maintenance treatment and early intervention--the new paradigm in the management of atopic eczema].
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Administration, Topical↗
[Comparison of activity of different topical corticosteroid creams and ointments using a vasoconstriction assay: superiority of hydrocortisone butyrate over hydrocortisone].
BACKGROUND: Topical corticosteroids are the treatment of choice for numerous inflammatory or hyperproliferative skin diseases. The vasoconstriction assay is suitable to determinate corticosteroid activity. PATIENTS AND METHODS: 60 healthy volunteers were studied. Three corticosteroids in both cream and ointment bases, as well as one corresponding vehicle, were investigated in a double-blind, randomised, intra-individual clinical study, using a vasoconstriction assay. The potencies of hydrocortisone, hydrocortisone-17-butyrate and mometasone furoate were measured, while hydrocortisone-17-butyrate was also compared to the vehicle. RESULTS: The sum score of the clinical evaluation was for Hydrocortisone 34 (cream) and 18 (ointment), for Hydrocortisone butyrate 47 (cream) and 55 (ointment) and for Mometasone furoate 57 (cream) and 50 (ointment). The chromametric values for blanching with hydrocortisone were 1.73 (cream) and 1.48 (ointment), hydrocortisone butyrate 2.87 (cream) and 3.26 (ointment) and mometasone furoate 2.98 (cream) and 2.84 (ointment). CONCLUSIONS: The clinical and chromametric evaluation of vasoconstriction showed activity for all corticosteroid formulations. Hydrocortisone butyrate was shown to be superior to hydrocortisone.
Administration, Topical↗
Peroxisome proliferator-activated receptors and their ligands: entry into the post-glucocorticoid era of skin treatment?
Glucocorticoids have remained one of the most frequently used classes of drugs for the treatment of skin diseases since their introduction more than 50 years ago. As a result of the discovery of new members of the nuclear hormone receptor (NR) superfamily, alternative therapeutic interventions that target retinoid and vitamin D receptors have been developed. Peroxisome proliferator-activated receptors (PPARs) comprise another important NR subfamily, consisting of three different isotypes: PPARalpha, PPARdelta (PPARbeta) and PPARgamma. These NRs are activated by a variety of natural and synthetic ligands such as fatty acids, eicosanoids, and antidiabetic and antihyperlipidaemic agents. While these receptors are established as regulators of gene expression in lipid and glucose homeostasis, evidence is now accumulating that PPARs also play a crucial role in cutaneous biology. Results from in vitro and in vivo studies have indicated the involvement of PPARs in epidermal maturation, proliferation and differentiation, as well as in immune and inflammatory responses, carcinogenesis, hyperpigmentation and skin wound healing. Furthermore, treatment of psoriatic patients with PPARgamma activators (thiazolidinediones) has been shown to induce beneficial effects. However, the effects of PPAR ligands should be carefully evaluated to determine whether they are in fact mediated via PPAR-dependent mechanisms. Nonetheless, PPARs seem to have significant potential as therapeutic targets in skin inflammatory disorders.
Animals↗
Toll-like receptors and innate antifungal responses.
The mammalian Toll-like receptors (TLRs) are homologues of Drosophila Toll and constitute a novel protein family involved in the mediation of innate immunity and the activation of adaptive immunity. Analysis of infection with human pathogenic fungi Candida albicans and Aspergillus fumigatus implicated TLR2 and TLR4 in elicitation of immune responses. Cryptococcus neoformans is recognized by a process that uses TLR4. C. albicans induces immunostimulation through causative agents, such as mannan or its structural derivatives (e.g. phospholipomannan), which are recognized by the immune system as pathogen-associated molecular patterns and are located in the cell wall of fungi. Secreted aspartic proteinases represent a key virulence factor that contributes to the ability of C. albicans to cause mucosal and disseminated infections, and might be a further potential stimulator of TLRs. Simultaneous activation of other pattern recognition receptors collaborating with TLRs illustrates the cooperation of various chains within ligand-specific receptor complexes for the recognition of fungal pathogens and their cell wall components.
Animals↗
[Topical skin therapy with glucocorticoids--therapeutic index].
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Administration, Topical↗
[Use of Lactobacillus as a probiotic factor to treat urogenital and intestinal infections as well as to prevent and treat allergic diseases].
Lactobacilli are probiotic micro-organisms that are part of the oral, intestinal and urogenital commensal flora. The beneficial effect of these bacterial strains, especially the eradication of or protection against pathogenic bacteria and yeasts, was shown by several studies. The preventive and therapeutic effect of lactobacilli applies to diarrhoea and urogenital infections in particular. Lactobacilli also seem to have a protective influence on the development and treatment of atopic disease.
Female Urogenital Diseases↗
Toll-like receptors as key mediators in innate antifungal immunity.
The Toll protein of Drosophila is a transmembrane receptor involved in dorsoventral polarization during embryonic development and recognition of infection. In mammals, Toll-like receptors (TLRs) constitute a novel protein family involved in innate immunity and respond to a wide spectrum of microorganisms, including fungi, bacteria, viruses, and protozoa. Specific agonists for nine of the ten members of the human TLR family have been described to date. TLRs as well as the TLR-associated adaptor molecule MyD88 have been implicated in the recognition of the fungal pathogens Candida albicans, Aspergillus fumigatus, Cryptococcus neoformans and Pneumocystis carinii. Moreover, several pathogen associated molecular patterns (PAMPs) located in the cell wall or cell surface of fungi have been identified as potential ligands. Yeast zymosan activates TLR2/ TLR6 heterodimers, whereas Saccharomyces cerevisiae- and C. albicans-derived mannan seems to be detected by TLR4. Phospholipomannan, present in the cell surface of C. albicans has been shown to be recognized by TLR2, while TLR4 mainly interacts with glucuronoxylomannan, the major capsular polysaccharide of C. neoformans. MyD88 has been implicated in TLR signalling of linear (1 --> 3)-beta-D-glucan, and of beta-glucan from P. carinii. These data point towards the ability of the innate immune system to utilize TLRs that are specific to different types and components of pathogenic fungi. Recent evidence further suggests that TLRs cooperate with other immune receptors involved in fungal recognition and that the selective induction of adaptor proteins finally leads to distinct signalling events upon fungal challenge.
Adaptor Proteins, Signal Transducing↗
[Grover's disease following hemodialysis in a patient with renal failure].
A 54-year-old woman with polycystic renal disease and renal failure developed Grover's disease while undergoing renal dialysis. Grover's disease or transitory acantholytic dermatosis is characterized by intensely pruritic, hyperkeratotic, succulent papules and plaques located on the trunk. The pathogenesis is unknown; genetic factors and actinic damage have been implicated. Medications, heat or immunosuppression can worsen the disease. Associations with atopic dermatitis, contact dermatitis and asteatotic dermatitis have also been described. Differential diagnostic considerations include folliculitis, scabies and dermatitis herpetiformis. Therapeutic options include moisturizing agents and phototherapy, as well as topical and systemic retinoids. There are only few case reports in the literature describing Grover's disease occurring during hemodialysis treatment. All such previous patients have been men; ours is the first woman.
Acantholysis↗
Ciclopirox olamine treatment affects the expression pattern of Candida albicans genes encoding virulence factors, iron metabolism proteins, and drug resistance factors.
The hydroxypyridone ciclopirox olamine belongs to the antimycotic drugs used for the treatment of superficial mycoses. In contrast to the azoles and other antimycotic drugs, its specific mode of action is only poorly understood. To investigate the mode of action of ciclopirox olamine on fungal viability, pathogenicity, and drug resistance, we examined the expression patterns of 47 Candida albicans genes in cells grown in the presence of a subinhibitory concentration (0.6 micro g/ml) of ciclopirox olamine by reverse transcription-PCR. In addition, we used suppression-subtractive hybridization to further identify genes that are up-regulated in the presence of ciclopirox olamine. The expression of essential genes such as ACT1 was not significantly modified in cells exposed to ciclopirox olamine. Most putative and known virulence genes such as genes encoding secreted proteinases or lipases had no or only moderately reduced expression levels. In contrast, exposure of cells to ciclopirox olamine led to a distinct up- or down-regulation of genes encoding iron permeases or transporters (FTR1, FTR2, FTH1), a copper permease (CCC2), an iron reductase (CFL1), and a siderophore transporter (SIT1); these effects resembled those found under iron-limited conditions. Addition of FeCl(3) to ciclopirox olamine-treated cells reversed the effect of the drug. Addition of the iron chelator bipyridine to the growth medium induced similar patterns of expression of distinct iron-regulated genes (FTR1, FTR2). While serum-induced yeast-to-hyphal phase transition of C. albicans was not affected in ciclopirox olamine-treated cells in the presence of subinhibitory conditions, a dramatic increase in sensitivity to oxidative stress was noted, which may indicate the reduced activities of iron-containing gene products responsible for detoxification. Although the Candida drug resistance genes CDR1 and CDR2 were up-regulated, no change in resistance or increased tolerance could be observed even after an incubation period of 6 months. This was in contrast to control experiments with fluconazole, in which the MICs for cells incubated with this drug had noticeably increased after 2 months. These data support the view that the antifungal activity of ciclopirox olamine may at least be partially caused by iron limitation. Furthermore, neither the expression of certain multiple-drug resistance genes nor other resistance mechanisms caused C. albicans resistance to this drug even after long-term exposure.
2,2'-Dipyridyl↗
Improved differentiation of benign and malignant lymphadenopathy in patients with cutaneous melanoma by contrast-enhanced color Doppler sonography.
OBJECTIVE: To evaluate whether administration of a D-galactose-based signal enhancer is useful in color Doppler sonography (CDS) for better detection of vascularity patterns, which may help to differentiate malignant from benign lymph nodes in patients with cutaneous melanomas. DESIGN: Comparison of B-mode sonography, native CDS, and signal-enhanced CDS. SETTING: Department of Dermatology and Allergology, Ludwig-Maximilians-University, Munich, Germany. PATIENTS: Twenty examinations in 19 patients (median age, 60 years; 10 men) who presented with echo-poor structures suggestive of lymphadenopathy in B-mode sonography during follow-up for cutaneous melanomas. INTERVENTIONS: Histopathologic and follow-up examinations; documentation by color prints. MAIN OUTCOME MEASURES: Frequency of detection and description of different lymph node vascularity patterns in signal-enhanced CDS. RESULTS: Signal-enhanced CDS revealed additional information about vascularization of lymph node metastases, reactive lymph nodes, hematomas, and seromas, which was helpful for the differential diagnosis in 15 of 20 examinations. For lymph node metastases, signal enhancement facilitated the detection of accessory peripheral vessels in most investigations. Concerning reactive lymph nodes, hilar vessels in part with branching to the lymph node periphery could be identified only after application of the contrast enhancer in most patients. Quantitative variables could not be measured in all cases and did not help to differentiate between malignant and reactive lymph nodes. CONCLUSIONS: Administration of a D-galactose-based signal enhancer for CDS in patients with cutaneous melanomas can help to differentiate malignant from reactive lymph nodes, hematomas, or seromas. However, these promising results require confirmation in a prospective multicenter study.
Adult↗