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Biomedical subjects

H C Korting

Publications and source records attributed to H C Korting.

At least 289 records · Page 16Linked to original sources

Persistent oral candidosis by non-albicans Candida strains including Candida glabrata in a human immunodeficiency virus-infected patient observed over a period of 6 years.

A 38-year-old woman infected with human immunodeficiency virus (HIV) presented with persistent oral candidosis in which non-albicans Candida strains were the predominant yeasts in most of the examinations performed over a period of 6 years. Oral treatment with fluconazole had no effect on clinical signs of oral candidosis. In 8 of a total of 11 specimens, Candida glabrata, Candida parapsilosis and Candida tropicalis were at least suspected as the causative pathogens of oral candidosis. The non-response to fluconazole in our patient could be explained by in vitro resistance to fluconazole of detected Candida glabrata and Candida tropicalis isolates.

AIDS-Related Opportunistic Infections↗

Tinea mammae mimicking atopic eczema.

Tinea mammae is a dermatophyte infection of the breast. Although rarely reported in this anatomical location, it can mimic other dermatoses. In this paper we describe an 85-year-old man with an erythema at the left breast which had enlarged over the previous 3 weeks. Trichophyton rubrum was isolated. Digital 20-MHz sonography revealed a reduction in echogenicity of the corium and a widened corium. Treatment with fluconazole over 5 weeks led to clearing of the lesion at the glabrous skin. At the end of therapy no difference between the involved and uninvolved skin areas was found sonographically.

Aged↗

Antimicrobial susceptibility testing of dermatophytes--comparison of the agar macrodilution and broth microdilution tests.

Fifty dermatophyte strains, recently obtained from clinical material, belonging to 4 different species were examined for their susceptibility to 5 systemic or topical antimycotic agents using both an agar macrodilution and a broth microdilution test. Antimycotics compared were griseofulvin, itraconazole, sertaconazole, terbinafine and ciclopiroxolamine. A comparison of the minimum inhibitory concentrations (MIC) clearly showed differences between the two test methods applied. For all 5 antimycotics, MIC data were three- to seventy-fold lower in the microdilution test system. These differences, depending on the test method, have to be taken into account when comparing MIC data in the literature or when relating the in vitro data to the tissue concentrations determined in vivo.

Antifungal Agents↗

Cutaneous inflammation and proliferation in vitro: differential effects and mode of action of topical glucocorticoids.

The nonhalogenated double ester of prednisolone, prednicarbate (PC), is the first topical glucocorticoid with an improved benefit/risk ratio verified clinically and in vitro. To evaluate if this is due to unique characteristics of this steroid, a new compound created according to an identical concept, prednisolone 17-ethylcarbonate, 21-phenylacetate (PEP), and the new halogenated monoester desoximetasone 21-cinnamate (DCE) were tested and compared to PC, desoximetasone (DM) and betamethasone 17-valerate (BMV). Isolated foreskin keratinocytes served for in vitro investigations of anti-inflammatory processes in the epidermis, fibroblasts of the same origin were used to investigate the atrophogenic potential. Inflammation was induced by TNFalpha, resulting in an increased interleukin 1alpha (Il-1alpha) synthesis. As quantified by ELISA, all drugs significantly reduced Il-1alpha production. But PC and BMV appeared particularly potent, followed by DM and the two new congeners, which revealed minor anti-inflammatory activity. Glucocorticoid esters including PEP are rapidly degraded in keratinocytes (85% within 12 h). Hence, a ribonuclease protection assay of Il-1alpha mRNA was performed allowing short incubation times and thus minimizing biodegradation. This assay confirmed the anti-inflammatory potency of native PC and BMV. In contrary DCE and PEP did not reduce Il-1alpha mRNA to a significant extent. Therefore PEP acts as a prodrug only. In fibroblasts, Il-1alpha and Il-6 syntheses indicate proliferation and inflammation, respectively. Whereas PC and PEP inhibited Il-1alpha and Il-6 production in fibroblasts only to a minor extent, cytokine synthesis was strongly affected by the conventional glucocorticoids BMV and DM, but also by DCE. The minor unwanted effect of PC and PEP on fibroblasts was also reflected by their low influence on cell proliferation as derived from (3)H-thymidine incorporation. Again, more pronounced antiproliferative features were seen with the halogenated glucocorticoids. In the following, the correlation between antiphlogistic effects in keratinocytes (suppression of Il-1alpha) and antiproliferative effects in fibroblasts (suppression of Il-1alpha and Il-6; (3)H-thymidine incorporation) was analyzed. Here, PC is revealed as the only glucocorticoid with an improved benefit/risk ratio. Native PEP is shown to be almost ineffective and DCE presents exactly the opposite features of PC. It is tempting to speculate if this is due to different glucocorticoid receptor subtypes or different signaling pathways in keratinocytes and fibroblasts.

Administration, Topical↗

Transcriptional activity of potent glucocorticoids: relevance of glucocorticoid receptor isoforms and drug metabolites.

As compared to standard glucocorticoids (GC), prednicarbate (PC) is favorable in the treatment of eczema due to its high benefit/risk ratio. The remarkable anti-inflammatory effects of PC are in strong contrast to its reported low glucocorticoid receptor (GR) binding affinity. In transfected COS-7 cells we related the transcriptional potencies of PC, its metabolites and conventional GC to their receptor binding properties. Moreover, the expression pattern of the human GR isoform hGRalpha and its mutual dominant negative inhibitor hGRbeta in skin cells have been investigated as well as the influence of hGRbeta on receptor binding and transactivation. hGRalpha mRNA and protein was largely overexpressed in skin cells. hGRbeta showed no influence on hGRalpha binding and transactivation. Concentration response curves indicated the greater transactivation potency of betamethasone 17-valerate followed by dexamethasone and prednisolone 17-ethylcarbonate. Native PC appeared almost as potent as dexamethasone. With both a strong correlation was observed between transactivation and GR binding.

Animals↗

Toxicity and antimicrobial activity of a hydrocolloid dressing containing silver particles in an ex vivo model of cutaneous infection.

In the present study we examined the effects of two hydrocolloid wound dressings (conventional silver-free Comfeel, silver-incorporating Contreet-H) on uninfected and Candida albicans- or methicillin-resistant Staphylococcus aureus-infected reconstituted human epithelium (RHE). The morphological alterations of the keratinocytes caused by infection and by treatment were analysed with light and electron microscopy. As a measure of epithelial cell damage the release of lactate dehydrogenase from epithelial cells into the surrounding medium was monitored. Application of Contreet-H or Comfeel to uninfected RHE induced no major morphological effects on epithelial cells. Both wound dressings reduced the growth of micro-organisms. Specific alterations of the infected epithelium (vacuoles, spongiosis, oedema, detachment of keratinocytes) and invasion of the epithelium were significantly reduced only by treatment with Contreet-H. At the ultrastructural level release of silver by Contreet-H and superior antimicrobial efficacy could be verified. In summary, treatment with both wound dressings reduced the number of pathogens, with the silver-based wound dressing providing a more effective antimicrobial activity. This resulted in a strong decrease of pathogen-specific alterations of the infected epithelium. We present evidence that delivering silver to infected keratinocytes in a moist healing environment improves the benefit/risk ratio as compared to silver-free wound dressings.

Anti-Bacterial Agents↗

Actinic keratosis: the key event in the evolution from photoaged skin to squamous cell carcinoma. Therapy based on pathogenetic and clinical aspects.

Skin aging is the result of intrinsic and extrinsic factors. Extrinsic aging, also called photoaging, is mainly caused by ultraviolet radiation from the sun and leads to a state which has been termed dermatoheliosis. The aim of this article is to provide an overview of photoaged skin addressing actinic keratoses (AKs) in particular. This review will describe the clinical features of photoaged skin and briefly summarize the underlying histological, photobiochemical and molecular mechanisms responsible for photoaging. The concept of the disease continuum from AK to squamous cell carcinoma will also be presented. A special focus will be on established and new therapeutic approaches to undo photoinduced skin damage.

Carcinoma, Squamous Cell↗

Tazarotene: therapeutic strategies in the treatment of psoriasis, acne and photoaging.

Tazarotene is a member of the new generation of receptor-selective, synthetic retinoids for the topical treatment of mild to moderate plaque psoriasis, acne vulgaris and photoaging. Though they are effective in monotherapy, clinical studies with a focus on novel combination treatments and a comparison of different agents for these skin disorders are accumulating. The concomitant use of tazarotene with a mid-potency or high-potency corticosteroid enhances the efficacy in psoriatic plaques and reduces the risk of steroid-induced skin atrophy. Combining phototherapy with adjunctive tazarotene accelerates the clinical response and reduces the cumulative UVB or PUVA exposure load. Tazarotene applied once daily is superior to adapalene monotherapy in acne vulgaris and is efficacious in the treatment of photodamage. Novel therapeutic regimens such as short-contact therapy have been developed for both acne and psoriasis in order to diminish the major adverse events like pruritus, burning, local skin irritation and erythema.

Acne Vulgaris↗

Hyaluronic acid in the treatment and prevention of skin diseases: molecular biological, pharmaceutical and clinical aspects.

The glycosaminoglycan hyaluronic acid (HA), or hyaluronan, is a major component of the extracellular matrix of skin, joints, eye and many other tissues and organs. In spite of its simple structure, HA demonstrates remarkable rheological, viscoelastic and hygroscopic properties which are relevant for dermal tissue function. Biological activities in skin, however, are also due to its interaction with various binding proteins (hyaladherins). Due to an influence on signaling pathways, HA is involved in the wound-healing process and scarless fetal healing. Increased HA concentrations have been associated with inflammatory skin diseases. In clinical trials, topical application of HA improved wound healing; in particular, acute radioepithelitis, venous leg ulcers or diabetic foot lesions responded to HA treatment. Moreover, as a topical drug delivery system for diclofenac, an HA gel has recently been approved for the treatment of actinic keratoses. Finally, chemical modifications led to new HA derivates and biomaterials, which may be introduced into therapy in the future. Therefore, ongoing research offers new horizons for the therapeutic use of this glycosaminoglycan which has been regarded as an inert structural component until recently.

Animals↗

Penciclovir cream--improved topical treatment for herpes simplex infections.

Human herpesviruses can be found worldwide and cause many viral infections in immunocompetent as well as in immunocompromised patients. Herpes simplex virus (HSV) diseases can be the cause of life-threatening disease, especially in neonates. After initial infection, HSV persists latently in host neurons with the risk of periodical reactivation over a lifetime. The development of acyclovir, a potent and specific nucleoside inhibitor of the herpes DNA polymerase, was a milestone in the history of antiviral drugs in the late 1970s. During the last decades a better understanding of the replication and disease-causing state of HSV types 1 and 2 has been achieved enabling the development of new and potent antiviral compounds. In the mid-1990s, for example, valacyclovir and famciclovir were launched as prodrugs of acyclovir with improved bioavailability. Despite the numerous drugs available for the systemic treatment of HSV infections, the topical application of a cream containing an antiviral agent is still the most convenient method of treating herpes simplex labialis/facialis in the general population. For some time, the topical standard treatment for recurrent HSV infections has been acyclovir cream, despite the fact that the evidence for efficacy in recurrent episodes has been equivocal. Penciclovir, a novel acyclic nucleoside analogue, has demonstrated efficacy against HSV types 1 and 2 and seems to have a pharmacological advantage due to a prolonged half-life of its active form in HSV-infected cells. This review discusses and compares the topical treatment modalities available for HSV infections. As a conclusion, different studies are available that have shown that it is possible to reduce viral replication and hasten lesion resolution with 1% penciclovir treatment beyond the prodromal phase of the HSV infection. Comparing data of topical treatment with acyclovir and penciclovir revealed a superiority for penciclovir cream showing a significant decrease in time to lesion healing, lesion area and pain. While systemic acyclovir or valacyclovir may be valid drugs especially for HSV prophylaxis, 1% penciclovir cream should be preferred as topical treatment since there are good therapeutic results independent of the phase of development of herpetic eruptions.

Acyclovir↗

Safety and efficacy of fluticasone propionate in the topical treatment of skin diseases.

Fluticasone propionate - the first carbothioate corticosteroid - has been classified as a potent anti-inflammatory drug for dermatological use. It is available as 0.05% cream and 0.005% ointment formulations for the acute and maintenance treatment of patients with dermatological disorders such as atopic dermatitis, psoriasis and vitiligo. This glucocorticoid is characterized by high lipophilicity, high glucocorticoid receptor binding and activation, and a rapid metabolic turnover in skin. Although skin blanching following fluticasone propionate exceeds that of corticosteroids of medium strength, several clinical trials demonstrate a low potential for cutaneous and systemic side-effects, even in difficult-to-treat areas like the face, the eyelids and intertriginous areas. Even among paediatric patients with atopic dermatitis, fluticasone propionate proved to be safe and effective. These pharmacological and clinical properties are reflected by the high therapeutic index of this glucocorticoid.

Administration, Cutaneous↗

Glucocorticoids for human skin: new aspects of the mechanism of action.

Topical glucocorticoids have always been considered first-line drugs for inflammatory diseases of the skin and bronchial system. Applied systemically, glucocorticoids are used for severe inflammatory and immunological diseases and the inhibition of transplant rejection. Owing to the progress in molecular pharmacology, the knowledge of the mechanism of action has increased during the last years. Besides distinct genomic targets, which are due to the activation of specific cytoplasmatic receptors resulting in the (trans-) activation or (trans-) repression of target genes, there are non-genomic effects on the basis of the interference with membrane-associated receptors as well as with membrane lipids. In fact, various glucocorticoids appear to differ with respect to the relative influence on these targets. Thus, the extended knowledge of glucocorticoid-induced cellular signalling should allow the design and development of even more specifically acting drugs - as it has been obtained with other steroids, e.g. estrogens for osteoporosis prevention.

Administration, Topical↗

Efficacy of ceftizoxime in the treatment of incubating syphilis in rabbits.

While ceftizoxime given as a single intramuscular shot cures uncomplicated gonorrhoea in almost every case, its efficacy against Treponema pallidum in cases of concomitant incubating syphilis is less clear. To analyse this question, the rabbit orchitis model was used. After initial experiments defining appropriate inocula and doses, ceftizoxime was compared to penicillin G with its well-known activity against the organism in vitro and in vivo. According to the final experiment, ceftizoxime applied in doses corresponding to the ones used in humans for uncomplicated gonorrhoea cures rabbit orchitis due to T. pallidum about as effectively as penicillin. Hence there seems to be no need to refrain from using the third-generation cephalosporin ceftizoxime to cure gonorrhoea for fear of masking concomitant syphilis.

Animals↗

The suppressive effect of serum samples from patients with chancroid on human mononuclear cells correlates with the clinical picture and is interleukin-2-dependent.

Plasma samples from patients with chancroid diagnosed both on clinical and microbiological grounds were assessed for their ability to inhibit mitogen-induced proliferation of human lymphocytes from healthy donors. All serum samples analysed suppressed phytohaemagglutinin A (PHA) blastogenic response. A significant difference in the observed extent was seen when serum samples from patients with and without associated lymphadenopathy were compared (P < 0.05). Using an interleukin-2 (IL-2)-dependent cell line it could be demonstrated that the addition of patients' plasma to cultured cells markedly depressed mitogen-induced IL-2 synthesis. Results presented suggest that cell-mediated mechanisms play a role in the pathogenesis of infection due to Haemophilus ducreyi.

Cell Line↗

Evidence for the phagocytosis of intact oligolamellar liposomes by human keratinocytes in vitro and consecutive intracellular disintegration.

While there is evidence for the use of liposomes as drug carriers upon topical application to the skin, the underlying mechanisms are far from being clear. Therefore human keratinocytes grown in vitro were exposed to large oligolamellar liposomes. After attachment and invagination these particles can be found unchanged within the cytoplasm both inside and outside of lysosomes. If incorporated into lysosomes the structural lipids can be disintegrated and spread within the entire phagolysosome. Gold labeling adds further to the hypothesis of intact uptake of liposomes by the living cells of the human epidermis.

Cells, Cultured↗

[Contact urticaria with transition to protein contact dermatitis in a cook with atopic diathesis].

Protein contact dermatitis is a rare disease within the group of occupational dermatoses. However, it is of some importance to people in food handling occupations. Skin symptoms usually manifest as immediate-type reactions (type-I-reaction according to Coombs and Gell), but changes to type IV-reactions are known. This applies especially to people with atopic eczema who have contact to fish proteins. This can be derived from a case presented here and a few similar observations described in the literature.

Animals↗