The rise of Chemical Peeling in 19th-century European Dermatology: emergence of agents, formulations and treatments.

BACKGROUND: Considering the increasing number of chemical peeling applications, also the interest in the history of chemical peelings and agents, has grown in dermatology. Research ascribes the first use of phenol as a chemical peeling agent to William Tilbury Fox (1836-1879) in 1871. Furthermore, Ferdinand von Hebra (1847-1902) is said to describe the properties of various peeling agents in 1874, and Paul Gerson Unna (1850-1929) adds resorcinol and trichloroacetic acid in 1882. OBJECTIVE: To identify the first mentions of chemical peeling applications and agents in 19th-century dermatology. METHODS: Nineteenth-century dermatologists were identified by an examination of literature of the last 30 years on the history of chemical peeling. Systematic examination of the medical textbooks of Hebra, Fox and Unna was conducted. It was proved whether the mentioned agents were used for chemical peeling applications. RESULTS: The skin peeling property of phenol was already discovered by its first describer, the chemist Friedlieb Ferdinand Runge (1795-1867) in 1834. The Viennese dermatologist Hebra described phenol as a chemical peeling agent in 1860. Hebra and his associate Moriz Kaposi (1837-1902) stated that 'Lotio carbolica' was already used in London. Fox used phenol mostly as a disinfectant and not for chemical peelings since 1869. Unna described the chemical peeling property of salicylic acid in 1882 and gave the most comprehensive account of chemical peels of the 19th century in 1899. Unna also introduced the Gutta-percha plaster with salicylic acid and phenol. Around 1900, Unna was famous for his peeling paste with resorcinol in Germany. CONCLUSIONS: A new chronology of the introduction of chemical peeling in dermatology can be drawn from the results. The German-speaking dermatology pioneered the treatment of skin diseases with chemical peelings as well as for aesthetical purposes 21 years earlier than hitherto known.

[Chemical peeling for treatment of Melasma, pigmentary disorders and hyperpigmentation : Indications, effectivity and risks]. / Chemical Peelings zur Behandlung von Melasma, Pigmentstörungen und Hyperpigmentierungen : Indikationen, Effektivität und Risiken.

Pigmentary disorders and hyperpigmentation are widespread. Dark skin types in particular show a tendency to formation of melasmas and to hyperpigmentation. Light skin types have a tendency to ephelides and solar lentigines. In addition to topical treatment with lightening substances, superficial chemical peeling as well as combined procedures of topical treatment with chemical peeling play an important role in the treatment of hyperpigmentation. A strict avoidance of UV light and consequent daily application of sun protectíon factor 50+ are mandatory for successful treatment.

Katharsis of the skin: peeling applications and agents of chemical peelings in Greek medical textbooks of Graeco-Roman antiquity.

BACKGROUND: Recipes for peelings date back to medical texts of old Egypt. The oldest medical papyri contain recipes for 'improving beauty of the skin' and 'removing wrinkles' by use of agents such as salt and soda. The Egyptian Queen Cleopatra (69-30 BC) is said to have taken bathes in donkey's milk to improve the beauty of her skin. However, little is known about other agents and peeling applications in later Greek medical textbooks. OBJECTIVE: We will discover new agents and describe ancient peeling applications. First, we will have to identify ancient Greek medical terms for the modern terms 'peeling' and 'chemical peeling'. Second, on the basis of the identified terms, we will perform a systematic full-text search for agents in original sources. Third, we will categorize the results into three peeling applications: (i) cleansing, (ii) aesthetical improvement of the skin and (iii) therapy of dermatological diseases. METHODS: We performed a full systematic keyword search with the identified Greek terms in databases of ancient Greek texts. Our keywords for peeling and chemical peeling are 'smexis' and 'tripsis'. Our keywords for agents of peeling and chemical peeling are 'smégmata', 'rhýmmata', 'kathartiká' and 'trímmata'. RESULTS: Diocles (4th century BC) was the first one who mentioned 'smexis' and 'tripsis' as parts of daily cleansing routine. Criton (2nd century AD) wrote about peeling applications, but any reference to the agents is lost. Antyllus (2nd century AD) composed three lists of peeling applications including their agents. CONCLUSION: Greek medical textbooks of Graeco-Roman antiquity report several peeling applications such as cleansing, brightening, darkening, softening and aesthetical improvement of the skin by use of peeling and chemical peeling, as well as therapy of dermatological diseases. There are 27 ancient agents for what is contemporarily called peeling and chemical peeling. We discovered more specific agents than hitherto known to research.

Dual anti-inflammatory and anti-parasitic action of topical ivermectin 1% in papulopustular rosacea.

BACKGROUND: Recently, therapy of rosacea with inflammatory lesions (papulopustular) has improved substantially with the approval of topical ivermectin 1% cream. It is assumed to have a dual mode of action with anti-inflammatory capacities and anti-parasitic effects against Demodex, which however has not yet been demonstrated in vivo. AIM: To find scientific rationale for the dual anti-inflammatory and anti-parasitic mode of action of topical ivermectin 1% cream in patients with rosacea. METHODS: A monocentric pilot study was performed including 20 caucasion patients with moderate to severe rosacea, as assessed by investigator global assessment (IGA score ≥3) and a Demodex density ≥15/cm2 . Patients were treated with topical ivermectin 1% cream once daily (Soolantra® ) for ≥12 weeks. The density of Demodex mites was assessed with skin surface biopsies. Expression of inflammatory and immune markers was evaluated with RT-PCR and by immunofluorescence staining. RESULTS: The mean density of mites was significantly decreased at week 6 and week 12 (P < 0.001). The gene expression levels of IL-8, LL-37, HBD3, TLR4 and TNF-α were downregulated at both time points. Reductions in gene expression were significant for LL-37, HBD3 and TNF-α at both follow-up time points and at week 12 for TLR4 (all P < 0.05). Reduced LL-37 expression (P < 0.05) and IL-8 expression were confirmed on the protein level by immunofluorescence staining. All patients improved clinically, and 16 of 20 patients reached therapeutic success defined as IGA score ≤1. CONCLUSION: Topical ivermectin 1% cream acts by a dual, anti-inflammatory and anti-parasitic mode of action against rosacea by killing Demodex spp. in vivo, in addition to significantly improving clinical signs and symptoms in the skin.

Comparison of user-friendliness and treatment cost of Loceryl® vs. Ciclopoli®--a patient's perspective.

Topical monotherapy is a valid therapeutic approach in onychomycosis. Due to its lengthy course and its non-reimbursed product status, cost and compliance are important issues and non-pharmacological properties such as over-the-counter price and ease of use should be considered when deciding which product to recommend. We investigated surrogate parameters for patient-friendliness and treatment cost in Germany in a questionnaire-based prospective, comparative, intra-individual, open-label trial of the two common topical antifungal nail lacquers Loceryl(®) (amorolfine 5%) and Ciclopoli(®) (ciclopirox 8%) in eight patients with clinically diagnosed onychomycosis. The 2.5 ml bottle of Loceryl(®) covered a treatment period of 308 days, resulting in treatment costs of €0.10 per day in comparison to the 3.3 ml bottle of Ciclopoli(®), covering 127 days at €0.21 per day, given once-daily application for Ciclopoli(®) and once-weekly application for Loceryl(®) in accordance with regulatory approval. Six out of eight patients favoured the Loceryl(®) treatment regimen. Furthermore, four out of eight patients found Loceryl(®) easier to apply, whereas three preferred Ciclopoli(®). In total, seven out of eight stated a clear preference for Loceryl(®) over Ciclopoli(®). Loceryl(®) therapy is less expensive and less time-consuming. The therapeutic period that can be covered is longer and more patients stated a clear preference for Loceryl(®) in comparison to Ciclopoli(®). The differences are statistically significant, underlining probable clinical relevance.

Efficacy of antifungal PACT in an in vitro model of onychomycosis.

BACKGROUND: The difficulty of antifungal substances to penetrate keratin and slow nail growth limit the efficacy of topical therapy in onychomycosis. One promising alternative is photodynamic antimicrobial chemotherapy, or PACT: an irradiated photosensitizer creates singlet oxygen molecules which destroy pathogens without damaging human cells. OBJECTIVE: As PACT has demonstrated strong antifungal capabilities, we wanted to investigate its efficacy in an in vitro model of onychomycosis. METHODS: PACT was tested in a microdilution assay, in an in vitro onychomycosis model as well as in a patient. RESULTS: PACT inhibited fungal growth in the microdilution assay with no colonies of T. rubrum detectable. Fungal growth was also inhibited in an onychomycosis model, after 30 min of LED irradiation. Subsequently, a patient with distolateral onychomycosis was treated on three consecutive days and showed significant and durable improvement of nail morphology 6 months after. CONCLUSION: PACT appears to be an effective treatment of onychomycosis in vitro. The promising results need to be validated by clinical trials.  

Cream or foam in pedal skin care: towards the ideal vehicle for urea used against dry skin.

The aim of this study was to evaluate different urea-containing cosmetic preparations designed for foot care regarding skin occlusion. The primary aim was therefore to screen the short-term transepidermal water loss (TEWL) as a parameter for skin barrier function and skin occlusion and to characterize the relative role of the vehicle, i.e. cream or foam in the context of cosmetics containing urea in the 2-10% range addressing the cosmetic products urea 2% cream (GEHWOL FUSSKRAFT blau), petrolatum containing cream (GEHWOL med Schrundensalbe), urea 10% cream (GEHWOL med Lipidro-Crème), urea 10% foam (Allpresan Fuss Schaum) and vaseline (positive control) compared with an untreated area on the volar forearms of volunteers. Moreover, the short time (24 h) kinetics regarding the moisturizing effect of cream and foam formulations in diabetic patients were compared. The efficacy of a cream on reduction of skin thickness of hyperkeratotic skin in the heel region before and after a period of product application was also evaluated. In some of the trials, healthy individuals and in others, diabetic patients (type I and II) were enrolled. TEWL was determined before product application, as well as at given points of time thereafter. In this study, no excessive occlusion effects comparable with a blockage of the skin's natural water evaporation could be observed for any of the test products. To the extent to be expected, this was found neither for the cream products nor for the foam product. Slightly lowered TEWL values after application of the 10% urea cream can be interpreted as a beneficial effect in terms of an improved barrier function. Regarding skin moisture, the urea-containing cream formulation appeared equal or slightly superior to the foam formulation. The thickness of the horny layer was found reduced after application of 10 % urea-containing cream. At present it looks as if cream vehicles would still be vehicles of choice in general, when it comes to the formulation of skin care preparations for not only dry skin but also in the context of pedal skin care.

[Non-pharmacologic management of rosacea]. / Nichtmedikamentöses Management der Rosazea.

Rosacea is like no other disease a problem for patients regarding the use of skin care and cleaning products. The subjective assessment of the severity of the illness is an important factor regarding the development of depression in these patients. Inadequate skin care and cleaning products can lead to irritation and stinging of the skin. Dermatologists should address questions regarding skin care, cleaning and sun screens. Because of the higher irritability of the skin of rosacea patients, all possibly irritating cleaning products or procedures should be avoided. The water temperature is also important; it should be lukewarm to avoid the provocation of a vascular reaction. Soaps should be avoided, because they are alkaline and thus lead to a higher pH of the skin. A higher pH of the skin can lead to irritation. Appropriate make-up causes no aggravation of the skin and increases patient's satisfaction with their skin and thus leads to a higher compliance with pharmacological therapy. Laser or intense pulsed light treatment can improve telangiectasia or erythema. Operative treatment of rhinophyma is effective and well-established.

[Physical treatment methods for acne. Light, laser, photodynamic therapy and peeling]. / Physikalische Therapieverfahren bei Akne. Licht, Laser, photodynamische Therapie und Peeling.

The medical treatment of acne is generally sufficient to meet the expectations of acne patients. However, in a number of situations additional therapeutic approaches may be advisable. There are a wide variety of useful physical methods. They range from electromagnetic waves, usually light, to peeling and manual therapy. Phototherapy of acne includes not just visible light but also laser and flash lamp therapy. The present review provides an overview on the evidence. Visible light, in particular blue light, provides an effective option for treatment of inflammatory acne. Photodynamic therapy also is efficacious; however, it should not be used because of an unfavorable risk-benefit ratio. UV treatment of acne is obsolete. Newer studies on the use of a variety of laser systems and flash lamps have demonstrated in part rewarding results.

[Acne vulgaris. Role of cosmetics]. / Acne vulgaris. Rolle der Kosmetik.

Appropriate cosmetics for skin cleansing are capable of contributing to a reduction of especially inflammatory lesions in acne-prone patients and to support pharmacological intervention in patients with manifest acne. Cleansing of acne-prone skin should employ acidified synthetic cleansers with a pH of 5.5 rather than soap. Furthermore, the ingredients of certain skin care products, i.e. nicotinamide, lactic acid, triethyl acetate/ethyllineolate, and prebiotic plant extracts, affect different mechanisms of acne pathogenesis and therefore may contribute to a decrease in acne lesions. At least some of these ingredients underscore the concept of evidence-based cosmetics. In contrast, the problem of acne lesions caused by comedogenic ingredients in cosmetics today is negligible.

In a study for acne vulgaris, sequence-based HLA typing showed a novel DPB1 allele, DPB1*2402.

In this paper, we characterize the novel human leucocyte antigen (HLA)-DPB1*2402 allele that we found in a patient suffering from acne vulgaris. In comparison to the closest related allele DPB1*0401, HLA-DPB1*2402 has a single nucleotide exchange at position 115 (202), T replaces G. In consequence, codon 39 (68) TAC encodes for tyrosine in the novel allele instead of aspartic acid 39 (68) GAC in DPB1*0401.

Modes of action of the new arylguanidine abafungin beyond interference with ergosterol biosynthesis and in vitro activity against medically important fungi.

BACKGROUND: In contrast to the increasing numbers of agents for the treatment of invasive fungal infections, discoveries of new antifungal agents with therapeutic value in dermatomycoses are reported only rarely. METHODS: Abafungin (chemical abstracts service registry No. 129639-79/8) is the first member of a novel class of synthetic antifungal compounds, the arylguanidines. It was first synthesized at Bayer AG, Leverkusen, Germany, and its antifungal action was discovered during the screening of H(2)-receptor antagonists based on the structure of famotidine. To obtain insight into its mode of action and antifungal activity, various tests were carried out with different fungal pathogens in vitro. RESULTS: Abafungin was found to have potent antifungal activity. Furthermore, mode-of-action studies suggested that abafungin exerts its antifungal activity regardless of whether the pathogens are growing or in a resting state. One target of abafungin was found to be the inhibition of transmethylation at the C-24 position of the sterol side chain, catalyzed by the enzyme sterol-C-24-methyltransferase. A second action of abafungin seems to be a direct effect on the fungal cell membrane. CONCLUSION: The observed characteristics of abafungin indicate that abafungin might be a promising antifungal agent defining a new class of antimycotics.

Activity of different desoximetasone preparations compared to other topical corticosteroids in the vasoconstriction assay.

INTRODUCTION: We report on a double-blind, vehicle-controlled, single-center confirmatory study with random assignment. The purpose of the study was to investigate the topical bioavailability of different topical corticosteroid formulations in healthy human beings focussing on desoximetasone (DM). MATERIALS AND METHODS: Two DM 0.25% formulations [ointment (DM-o) and fatty ointment (DM-fo, water-free); class III corticosteroids], the corresponding active ingredient-free vehicles and three comparators of different strength [clobetasol propionate 0.05% (CP 0.05%), fatty ointment, class IV; hydrocortisone (HC) 1%, fatty ointment, class I, and betamethasone (BM) 0.05%, fatty ointment, class III] were tested using the vasoconstriction assay. The degree of vasoconstriction (blanching) in the treatment field was compared to the one found in untreated control fields using chromametric measurements and clinical assessment. RESULTS/CONCLUSION: DM-o 0.25%, DM-fo 0.25% and BM 0.05% showed similar vasoconstrictive potential, i.e., clear blanching. In fact, both DM preparations were proven to be noninferior to BM 0.05%, while CP 0.05% was found a little less active. HC 1.0% and the DM vehicles showed no clear-cut vasoconstrictive effect. No adverse events related to the study medications were observed. Good topical bioavailability of both DM formulations was detected by chromametric measurement and clinical assessment.

[Conventional and molecular diagnosis of cutaneous mycoses]. / Konventionelle und molekulare Diagnostik bei Dermatomykosen.

The clinical presentation of fungal infections of the skin, hair, and nails is varied and sometimes presents a confusing clinical picture. The main objective is to rapidly institute diagnostic measures to avoid delays in therapy with potential expansion of the infection. A variety of laboratory tests are required. Classical methods are based on microscopy, different culture procedures, and histologic examination. Genotypic approaches to detection and identification of fungal pathogens have become very rapid and sensitive, making them additional options for routine diagnosis.

[Characterization of the interaction between Candida albicans and host cells: In vitro model using reconstituted human skin and mucosa]. / Charakterisierung der Interaktion zwischen Candida albicans und Wirtszellen. In-vitro-Modelle auf der Basis von rekonstituierter humaner Haut/Schleimhaut.

Basic research on the biology and immunology of microbial infection requires appropriate model systems. Currently most such studies involve animal studies which are a focus of ethical controversy. Possible alternatives, especially for localized infections, are provided by models using in vitro reconstituted human epithelium or epidermis (RHE). In recent years, these model systems have been successfully established to evaluate the effectiveness of topical anti-infectives, to characterize the role of fungal virulence factors, and to study the immune responses during localized Candida albicans infections. Most recently, these models have been supplemented with immune cells such as lymphocytes, polymorphonuclear leukocytes, mast cells or dendritic cells, to study their role during the course of infection and to characterize the interaction between the skin barrier and accessory immune cells. Although the most experience is with Candida albicans RHE infections, such model systems can also be used to study infections with other fungi or bacteria.

Dermasence refining gel modulates pathogenetic factors of rosacea in vitro.

BACKGROUND: Over the counter cosmetics sold for local treatment of slight to moderate rosacea often state the claim of actively modulating rosacea pathogenesis. Factors involved in the pathogenesis of this common yet complex skin disorder include kallikrein-related peptidase 5 (KLK5), LL-37, as well as protease-activated receptor 2 (PAR2) and vascular endothelial growth factor (VEGF). OBJECTIVE: The objective was to prove the modulating effect of the cosmetic skin care agent Dermasence Refining Gel (DRG) on factors involved in rosacea pathogenesis. METHODS: We analyzed the effect of DRG on the expression of KLK5, LL-37, PAR2, and VEGF in an in vitro skin model of human reconstituted epidermis. RESULTS: The expression of CAMP (LL-37 gene, fold change -4.19 [±0.11]), VEGFA (fold change -2.55 [±0.12]) and PAR2 (-1.33 [±0.12]) was reduced, KLK5 expression increased (fold change 2.06 (±0.08)) after 18 h of treatment with DRG in comparison to treatment with the matrix gel only. The reduction in CAMP expression was significant (P<.01). The protein expression of all four inflammatory markers was markedly reduced after 18 hours of DRG treatment in comparison to baseline (0 hour), by measure of fluorescence intensity. CONCLUSION: We show evidence explaining the anti-inflammatory effect of Dermasence Refining Gel in rosacea pathogenesis in vitro. The adjunctive use of DRG in mild to moderate rosacea as a topical cosmetic seems medically reasonable.

Improved cancer detection in automated breast ultrasound by radiologists using Computer Aided Detection.

OBJECTIVE: To investigate the effect of dedicated Computer Aided Detection (CAD) software for automated breast ultrasound (ABUS) on the performance of radiologists screening for breast cancer. METHODS: 90 ABUS views of 90 patients were randomly selected from a multi-institutional archive of cases collected between 2010 and 2013. This dataset included normal cases (n=40) with >1year of follow up, benign (n=30) lesions that were either biopsied or remained stable, and malignant lesions (n=20). Six readers evaluated all cases with and without CAD in two sessions. CAD-software included conventional CAD-marks and an intelligent minimum intensity projection of the breast tissue. Readers reported using a likelihood-of-malignancy scale from 0 to 100. Alternative free-response ROC analysis was used to measure the performance. RESULTS: Without CAD, the average area-under-the-curve (AUC) of the readers was 0.77 and significantly improved with CAD to 0.84 (p=0.001). Sensitivity of all readers improved (range 5.2-10.6%) by using CAD but specificity decreased in four out of six readers (range 1.4-5.7%). No significant difference was observed in the AUC between experienced radiologists and residents both with and without CAD. CONCLUSIONS: Dedicated CAD-software for ABUS has the potential to improve the cancer detection rates of radiologists screening for breast cancer.

[Working hours and job satisfaction among physicians in hospitals and general practice in Munich. Results of an anonymous questionnaire]. / Arbeitszeit und Arbeitszufriedenheit angestellter und beamteter Arzte in München. Ergebnisse einer anonymen Befragung.

PURPOSE: In autumn 2004 the local association of physicians (Arztlicher Kreis- und Bezirksverband München) performed a survey among employed physicians in Munich on working hours and working conditions. The aim of the study was to assess the extent to which the German law on working hours is actually implemented in employed physicians, and to obtain information about their work satisfaction. METHODS: A questionnaire was sent to all employed physicians in hospitals and medical practices. Participants were asked to give anonymous information and send it back per mail. RESULTS: In total, 2450 out of 5461 physicians took part in the survey. 45% reported that their working hours do not meet the German law on working hours of 1994. 44.4% stated that overtime is not fully recognized by their employers. 43.5% think the job would become more attractive if the law was implemented. 63.3% expect an income loss with the implementation. 53.7% are thinking about quitting their job. For 59.9% the burden of long working hours is an important reason for this. Women are more likely to be given a limited employment contract than men, and their overtime is more rarely recognized in full. CONCLUSION: Many employed physicians in Munich are dissatisfied with their job. The high burden of long working hours is a main reason for this.

Current state of three-dimensional characterisation of antifungal targets and its use for molecular modelling in drug design.

The alarming rise in life-threatening systemic fungal infections due to the emergence of drug-resistant fungal strains had produced an increased demand for new antimycotics, especially those targeting novel antifungal structures. Drug discovery has developed from screening natural products and chemical synthesis to a modern approach, namely structure-based drug design. Whilst many antifungal agents currently in use were discovered more than 30 years ago, characterisation of various drug targets has only been achieved recently, contributing immensely to understanding the structure-activity relationships of antifungals and their targets. Three-dimensional characterisation has become a well established tool for modern antifungal drug research and should play an important role in investigations for new antifungal agents.