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Biomedical subjects

H C Korting

Publications and source records attributed to H C Korting.

At least 109 records · Page 6Linked to original sources

Liposomes for atopic dry skin: the rationale for a promising approach.

Atopic dry skin characterized by a defect of the barrier function as determined by transepidermal water-loss measurements at the ultrastructural level shows an increase in membrane-coating granules (MCGs). MCGs are lamellar, ovoid organelles appearing in the stratum spinosum and stratum granulosum. MCGs consist of stacks of small parallel disks that are extruded and fuse to continuous lamellae. Liposomes, i.e., unior multilamellar vesicles composed of alternating lipid and water phases are structurally similar. Moreover, they also can form continuous lamellae. While phospholipids are generally used for liposome production, skin lipids and in particular ceramides can also be used. These lipids also seem to be the major components of MCGs. Hence, it seems advisable to use liposomes made of such lipids in the treatment of atopic dry skin. Apart from the probable inherent effect liposomes of this type may also apply particularly well for the delivery of active components.

Body Water↗

Anti-inflammatory activity of hamamelis distillate applied topically to the skin. Influence of vehicle and dose.

The anti-inflammatory activity of hamamelis distillate has been evaluated with respect to drug concentration (0.64 mg/2.56 mg hamamelis ketone/100 g) and the effect of the vehicle (O/W emulsion with/without phosphatidylcholine (PC) in an experimental study. The effects were compared with those of chamomile cream, hydrocortisone 1% cream and 4 base preparations. Erythema was induced by UV irradiation and cellophane tape stripping of the horny layer in 24 healthy subjects per test. Skin blanching was quantified by visual scoring and chromametry. Drug effects were compared with one another and with an untreated control area, as well as with any action due to the vehicle. UV-induced erythema at 24 h was suppressed by low dose hamamelis PC-cream and hydrocortisone cream. Hydrocortisone appeared superior to both hamamelis vehicles, hamamelis cream (without PC) and chamomile cream. The latter preparation was also less potent than hamamelis PC-cream. Erythema 4 to 8 h after the stripping of the horny layer was suppressed by hydrocortisone (P < or = 0.05). Inflammation was also less pronounced following low dose hamamelis PC-cream and chamomile cream. Hamamelis PC-cream, however, appeared less potent than hydrocortisone. In general, visual scoring was more discriminatory than chromametry. The results have demonstrated an anti-inflammatory activity of hamamelis distillate in a PC-containing vehicle. A fourfold increase of drug concentration, however, did not produce an increase in activity.

Administration, Topical↗

Prednicarbate activity and benefit/risk ratio in relation to other topical glucocorticoids.

BACKGROUND: Nonhalogenated double esters of prednisolone or hydrocortisone applied topically to the skin have a low atrophogenic potential. However, activity and benefit/risk ratio and therefore the superiority over conventional topical glucocorticoids are not well defined. METHODS: The activities of cream preparations with prednicarbate (0.025% to 0.25%), hydrocortisone aceponate, and hydrocortisone buteprate (0.1%) are compared to the effects of betamethasone 17-valerate (0.1%), hydrocortisone (1%), and two drug-free vehicles in 60 healthy volunteers. Test models are the skin blanching assay (occluded and nonoccluded mode), ultraviolet-induced erythema, and an irritant (sodium dodecyl sulfate) dermatitis. The benefit/risk ratio is derived from the activity in the former models and the reduction of skin thickness as determined previously. RESULTS: Prednicarbate activity increases in a dose-dependent manner. Prednicarbate, 0.25%, and the hydrocortisone double esters appear to be equipotent to betamethasone 17-valerate in the skin blanching test and the ultraviolet-erythema test, but superior to hydrocortisone and the vehicles. Prednicarbate and its vehicle, however, do not reverse irritant dermatitis. The benefit/risk ratios of prednicarbate and hydrocortisone aceponate exceed those with betamethasone 17-valerate. CONCLUSIONS: Prednicarbate and hydrocortisone aceponate are intermediate potent glucocorticoids that are superior to betamethasone 17-valerate because of the improved benefit/risk ratio. Patients with severe atopic dermatitis and those who relapse frequently should profit from the treatment with these newer glucocorticoids.

Administration, Topical↗

Treatment of tinea unguium with medium and high doses of ultramicrosize griseofulvin compared with that with itraconazole.

Toenail tinea is a very recalcitrant dermatosis. Griseofulvin at > or = 500 mg/day is the current medication of choice, but it is minimally successful. In a controlled open trial ultramicrosize griseofulvin (UMSG) at doses of 660 and 990 mg/day was compared with itraconazole at 100 mg/day in 109 patients. At 4-week intervals, the patients were evaluated for their clinical and mycological statuses and adverse reactions. Treatment was given for up to 18 months. Compliance was checked by tablet counting. Response (cure, partial cure, marked improvement) was analyzed by the intent-to-treat method. Cured and partially cured patients were followed up. Except for one early dropout, the toenails (mean, 6 to 7) were involved. Cure or partial cure was found in 6% (UMSG at 660 mg), 14% (UMSG at 990 mg), and 19% (itraconazole at 100 mg) of patients (P = 0.2097); marked improvement was found in 36, 44, and 39% of patients in the three treatment groups, respectively. Most patients had to be treated for 18 months. Failure was related to short medication periods (adverse drug reactions, dropout). While stable cure was not obtained with UMSG at 660 mg, the higher dose of UMSG and itraconazole gave stable cures in the other patients. Side effects of nausea, diarrhea, and headache were found in 20, 26, and 11 patients, respectively (P = 0.0028), and the numbers in whom medication had to be discontinued differed, too (P = 0.0137). While there was no major difference with glutamic-pyruvic transaminase and gamma-GT, total and low-density lipoprotein cholesterol levels declined slightly in the itraconazole group (P = 0.0357 and P = 0.0639, respectively, at 3 months). More than 70% of the patients had an average compliance of > or = 90%; four patients (two dropouts) were poor compliers. In conclusion, it appears questionable whether griseofulvin can continue to be considered the "gold standard" in the treatment of toenail tinea. At present, itraconazole at 100 mg shows better efficacy and is better tolerated.

Adult↗

Mechanisms of adherence of Candida albicans to cultured human epidermal keratinocytes.

We established an in vitro adherence model with primarily cultured human keratinocytes as target cells which allows for the investigation of the molecular mechanisms that are responsible for Candida albicans host cell attachment in the initiation of cutaneous candidosis. The extent of C. albicans binding to cultured human keratinocytes was dependent on the yeast inoculum size and the incubation temperature. Heat and paraform-aldehyde treatment of yeasts completely abolished the binding activity of C. albicans. Of the different Candida species tested, C. albicans was by far the most adhesive species. C. albicans adherence was blocked by the acid protease inhibitor pepstatin A and the metabolic inhibitor sodium azide. The latter, however, was much less effective when yeasts were preincubated, suggesting that sodium azide was mainly acting on the keratinocytes. The extracellular matrix protein fibronectin was slightly inhibitory, whereas the fibronectin-derived peptides RGD and RGDS were not able to prevent attachment. PepTite-2000, another RGD-containing synthetic peptide, reduced C. albicans adherence by a margin of 25% (P < 0.005). CDPGYIGSR-NH2, which is a synthetic adhesive peptide derived from the laminin B chain, was much more efficient in its inhibitory activity than the RGD peptides and reduced C. albicans adherence to cultured human keratinocytes up to 76% (P < 0.001). Laminin itself and the synthetic pentapeptide YIGSR were less active. A dose-dependent reduction in adherence was also observed with collagen type III. Additionally, saccharides were tested for their potential to inhibit C. albicans attachment to keratinocytes. The most potent competitive saccharide inhibitors of C. albicans adherence to human keratinocytes were the amino sugars D-(+)-glucosamine and D-(+)-galactosamine with one isolate of C. albicans (4918) and D-(+)-glucosamine and alpha-D-(+)-fucose with another C. albicans isolate (Sp-1). Collectively, our data suggest the existence of multiple molecular mechanisms such as protein-protein, lectin-carbohydrate, and yeast-yeast coaggregational interactions that are responsible for optimal C. albicans attachment to cultured human keratinocytes.

Amino Acid Sequence↗

Erythema multiforme-like eruption in association with severe headache following pyritinol.

A 46-year-old woman presented with an unusual erythema multiforme-like eruption and severe headache 10 days after treatment with pyritinol for cerebral concussion. Histopathologic findings were consistent with erythema multiforme. Skin lesions and headache cleared after withdrawal of the drug. According to neurological examination and magnetic resonance imaging of the brain, the headache may have resulted from a slight, pyritinol-induced vasculitis. Previous reports on severe pyritinol-induced side effects and possible pathogenetic mechanisms are reviewed. Since pyritinol cannot be considered as an essential drug for cerebral concussion, adverse effects as described here raise doubts as to its general use in the given indication.

Brain↗

[Skin lipids in seborrhea- and sebostasis-associated skin diseases].

Recent studies suggest that epidermal skin lipids play an important role in the pathogenesis of skin diseases associated with seborrhoea or sebostasis. Depending on the state of the skin, various lipids are found in varying quantities and proportions. In some sebostatic diseases, in particular, altered enzyme activities relevant to the synthesis of lipids have been identified, which may account for alterations in epidermal lipid fractions. This concept represents a substantial modification of earlier ones, according to which sebostatic or seborrhoeic skin diseases were attributed solely to decreased or increased sebum lipids, respectively. This provides an important rationale for a new approach to the therapy of certain skin diseases with specific lipid fractions, such as ceramides.

Ceramides↗

Treatment of atopic eczema with evening primrose oil: rationale and clinical results.

Recently a defect in the function of the enzyme delta-6-desaturase has been discussed as a major factor in the development of atopic eczema. Delta-6-desaturase is responsible for the conversion of linoleic acid to gamma linolenic acid. Several plants, including evening primrose, are known to be fairly rich in gamma linolenic acid. Hence, substitution of gamma linolenic acid in patients prone to developing atopic eczema seems like a feasible concept. During the last few years different clinical trials have been performed. Controlled trials following a parallel study design showed marked improvement in atopic eczema. Patients treated with the drug showed less inflammation, dryness, scaling and overall severity compared to controls. Although these findings have been supported by meta-analysis, there is still conflicting evidence in trials based on a crossover design alone, demonstrating a decrease in itching. At present, evening primrose oil in doses used for the treatment of atopic eczema is considered safe. However, still more trials addressing both efficacy and safety are needed to make a final decision.

Administration, Oral↗

0.25% prednicarbate cream and the corresponding vehicle induce less skin atrophy than 0.1% betamethasone-17-valerate cream and 0.05% clobetasol-17-propionate cream.

The atrophogenic potential of medium-potent topical glucocorticoids is still controversial. In a double-blind controlled trial 24 healthy volunteers either applied 0.25% prednicarbate cream or the corresponding vehicle to one and 0.1% betamethasone-17-valerate cream or 0.05% clobetasol-17-propionate cream to the other forearm twice daily. Skin thickness was regularly assessed during the six week period of application and for further three weeks thereafter, using both the B- and A-mode of a 20 MHz ultrasound scanner. Both betamethasone-17-valerate and clobetasol-17-propionate cream significantly reduced skin thickness as compared to cream base while prednicarbate cream did not. Given that 0.1% betamethasone-17-valerate- and 0.25% prednicarbate cream are reported to be about equipotent in the treatment of atopic eczema the latter preparation shows an increased ratio between its desired anti-inflammatory and its unwanted atrophogenic effect.

Adult↗

Topical glucocorticoids with improved benefit/risk ratio: do they exist?

Topical glucocorticoids are still among the dermatologicals most frequently used. This is due to their undebatable potency in inflammatory skin disease. Their use is limited by the fear of side effects both systemic and topical, especially skin atrophy. Hence, congeners with an increased benefit-risk ratio are urgently needed and research on new drugs no longer focuses on more active drugs but safer ones. Only recently, evidence has been forwarded that the goal is realistic. Some new glucocorticoids, especially the nonfluorinated double-ester type such as prednicarbate, appear promising. In fact, they seem to affect fibroblast growth in vitro as well as skin thickness in vivo less than equipotent conventional glucocorticoids. Pertinent findings in humans have been obtained with the use of ultrasound equipment. The relevant aspects of chemistry, pharmacology, clinical benefits, and toxicology of the various glucocorticoids old and new are reviewed, as are potential future alternatives.

Administration, Topical↗

Lack of immunoglobulin A1 protease production by Haemophilus ducreyi.

A collection of 20 strains of Haemophilus ducreyi including freshly isolated, low-passage and multi-passage reference strains was examined for immunoglobulin A1 protease production by SDS-PAGE and immunoblotting. None of the strains demonstrated IgA1 protease activity despite the fact that different culture media were used. By direct immunofluorescence testing, binding of IgA to Haemophilus ducreyi organisms could be demonstrated.

Blotting, Western↗

Comparative atrophogenicity potential of medium and highly potent topical glucocorticoids in cream and ointment according to ultrasound analysis.

24 healthy volunteers with no history of skin disease were entered in a 6-week double-blind randomized study to compare the atrophogenicity potentials of both cream and ointment forms of triamcinolone acetonide and clobetasol propionate. The atrophogenicity potential of cream preparations turned out to be greater than that of ointment preparations containing identical amounts of the same glucocorticoid. This result proves both the reproducibility of the assay and the general character of the phenomenon in view of the limited previous evidence.

Administration, Topical↗

Topical glucocorticoids of the non-fluorinated double-ester type. Lack of atrophogenicity in normal skin as assessed by high-frequency ultrasound.

With the advent of non-fluorinated double esters the spectrum of topical dermatotherapy with glucocorticoids seems to have broadened to include safer congeners. To assess the atrophogenicity potential of glucocorticoids, high-frequency ultrasound has been proposed. In a comparative trial using the DUB 20 system, 24 healthy volunteers applied hydrocortisone aceponate, the corresponding vehicle, prednicarbate ointment and betamethasone-17-valerate ointment over a period of 6 weeks. While both hydrocortisone aceponate and prednicarbate ointment induced no significant reduction in skin thickness, the onset of epidermal-dermal thinning with betamethasone-17-valerate was early and the extent marked. These findings imply an increased therapeutic index with the non-fluorinated double esters.

Administration, Topical↗

Atypical presentation of co-existent Haemophilus ducreyi and Treponema pallidum infection in an HIV-positive male.

A 25-year-old homosexual black male presented with asymmetrical perianal ulceration of uncertain clinical origin. Indepth microbiological examination revealed the combined presence of Haemophilus ducreyi and Treponema pallidum. The atypical clinical appearance may have been due to the changed immunological status of the host's being infected with Human Immunodeficiency Virus.

Adult↗