Biomedical subjects
Hans Christian Korting
Publications and source records attributed to Hans Christian Korting.
[Dermatological guideline efforts for 2007 in perspective].
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[Candidiasis of the skin].
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[Cellulite--the greatest skin problem in healthy people? An approach].
Cellulite or so called orange peel skin affects 80-90 % of all females. It is not considered as a pathological condition but as aesthetically disturbing dimpling of the skin seen most commonly on the thighs and buttocks. Despite its high prevalence, there have been only a few scientific investigations into the pathophysiology of cellulite reflected in the medical literature. A lack of knowledge regarding specific aetiopathogenetic factors and pathogenesis at large currently limits treatment options. The preferred hypotheses about the origin of cellulite include: gender specific dimorphic skin architecture, altered connective tissue septae, vascular changes and inflammatory processes. The most widely discussed management options include: attenuation of aggravating factors, physical procedures including laser therapy and application of topical incorporating actives. The latter approach has been evidence-based with respect to caffeine liposomal cream and retinol cream.
Xerosis and callus formation as a key to the diabetic foot syndrome: dermatologic view of the problem and its management.
The diabetic foot syndrome is a major complication of diabetes mellitus. The two most important pathophysiologic factors are peripheral arterial occlusion and peripheral neuropathy. The cutaneous lesion is a plantar ulcer, often accompanied by soft tissue and bone infections which can require amputation. Triggers include poorly fitting shoes, poor foot care, or overlooked foreign bodies, often coupled with a structural foot deformity. Increased plantar pressure, especially beneath the metatarsal heads, and the resultant callus play an important role. The patients often already have xerosis of the plantar skin with scales, fissures, erosions and impaired barrier function, complicating the situation. Prompt neurologic and vascular diagnostic studies, coupled with routine examination of the feet and primary prophylactic measures are most important. The most important therapeutic goals are optimal control of the diabetes mellitus, relieving pressure points and avoiding or reducing callus formation.
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.
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.
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.
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.
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.
[Maintenance treatment and early intervention--the new paradigm in the management of atopic eczema].
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[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.
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.
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.
[Topical skin therapy with glucocorticoids--therapeutic index].
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[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.