Impact of Parallel Topical Treatment with Nadifloxacin and Adapalene on Acne Vulgaris Severity and Quality of Life: A Prospective, Uncontrolled, Multicentric, Noninterventional Study.

INTRODUCTION: Daily parallel application of adapalene and nadifloxacin has been determined to be effective and well tolerated in patients with acne vulgaris in randomized, controlled clinical studies. Here, the authors report the results from a large, prospective, uncontrolled, multicentric, noninterventional study under real-life conditions in Germany. The effect of treatment on acne severity, safety, and, for the first time, health-related quality of life (HRQoL) was investigated. METHODS: Of the 292 patients (safety collective: 231 adults, 61 adolescents) who had at least grade 4 acne vulgaris on the face as per the Leeds Revised Acne Grading (LRAG), 273 (efficacy collective: 213 adults, 60 adolescents) were treated with adapalene 0.1% cream or gel and nadifloxacin 1% cream for the defined minimum of 28 days. Patients were evaluated for acne severity, acne-related facial symptoms, HRQoL, overall assessment of therapy, and safety. RESULTS: After the median treatment duration of 37 and 38 days (adults and adolescents, respectively), 93.4% and 85.0% of adults and adolescents, respectively, exhibited a sustained decrease in acne severity. The LRAG decreased by at least 3 scores in 29.1% and 24.6% of female and male adults, respectively. HRQoL improved in 67.9% and 63.5% of adults and adolescents, respectively (median improvement in the Dermatology Life Quality Index scores per patient of 3.0 [female adults], 1.0 [male adults], and 2.0 for all adolescents in the Children's Dermatology Life Quality Index). Female adults were more impaired in terms of HRQoL compared to male adults. The 2 best overall efficacy ratings were provided by physicians in 79.3% and 69.5% and by patients in 68.5% and 58.3% of adult and adolescent cases, respectively. The treatment was well tolerated, as reflected in the low number of 9 mild adverse events (AEs), all of which resolved without treatment. However, 4 patients terminated the study prematurely due to AEs. CONCLUSION: In this study, the parallel use of adapalene and nadifloxacin for at least 5 weeks resulted in a rapid improvement in acne severity, an increase in HRQoL, and a good safety profile. Therefore, it represents a promising treatment option that offers the possibility of flexible therapy adjustment.

Dermatology in Ancient Rome: Medical ingredients in Ovid's "Remedies for female faces".

BACKGROUND: In Roman medicine, face packs, plasters, unguents, and peelings were part of the therapy of dermatological diseases, but also served cosmetic purposes. Ancient medical textbooks inform us about the ingredients for these applications. Beyond medical literature, other genres contain information about dermatological applications. The Roman poet Ovid (43 BC-17 AD) wrote a didactic poem recording five recipes for topical applications for female faces (Medicamina faciei femineae). Researchers debate the relation of Ovid's poem to Roman medicine: Does the poem contain therapeutical or cosmetical information, or is it mere belles lettres? AIMS: The objective of the paper is to conduct a medico-historical classification of Ovid's poem by determining whether the ingredients of Ovid's recipes were thought to be effective by the authors of Roman medical textbooks. METHODS: First, translation and identification of the ingredients were carried out. Second, comparison of the ingredients' functions regarding the therapy of dermatological diseases in two important Roman medical textbooks was realized. For this purpose, several commentaries on the text of Ovid were used and a keyword search in Roman medical textbooks was performed. RESULTS: Ovid's five recipes contain 23 ingredients. All ingredients can be found in medical textbooks. We find that 14 of these ingredients serve cosmetic purposes, 17 serve the therapy of dermatological diseases, and 13 serve both. CONCLUSION: Ovid's recipes contain drugs that were considered effective by the authors of Roman medical textbooks. These drugs were recommended both for therapeutic and cosmetic purposes by the same authors. Therefore, Ovid's didactic poem is not mere belles lettres, but contains serious medical and cosmetical information. As far as we know, it is the first Roman text that contains dermatological recipes.

[Compatibility of Work and Family Life: Survey of Physicians in the Munich Metropolitan Area]. / Vereinbarkeit von Familie und Arztberuf ­ eine repräsentative Umfrage in München bei Ärztinnen und Ärzten unterschiedlicher Tätigkeitsbereiche.

AIM: Investigation of the compatibility of work and family life for physicians in the Munich metropolitan area. METHODS: Survey of a representative sample of 1,800 physicians using a questionnaire. RESULTS: Men were less satisfied (7% very satisfied vs. 21%) with compatibility between work and family life than women. The group least satisfied overall was hospital-based physicians (p=0.000, chi-square=122.75). Women rather than men cut back their career due to children, perceived their professional advancement as impaired, desisted from establishing private practice or quit hospital employment altogether. Respondents strove for flexible childcare and makeshift solution if the established service failed. Most did not have that at their disposal. Hospital-based physicians wished for predictable working hours, and would like to have a say in the structure of their schedule. For the majority this was not the case. While for 80% it would be important to participate in the definition of their working hours, this was only possible in 17%. 86% found the opportunity to work part-time important, but many doctors (more than 30%) did not have that option. The biggest help for office-based physicians would be an expedited procedure by the Bavarian Association of Statutory Health Insurance Physicians (KVB) when applying for a proxy. The second most important would be the ability to hand over on-call duties. 36% of respondents felt that compatibility of work and family life was best achieved outside of patient care, during residency 42% believed this to be the case. Only 6% of physicians felt the best compatibility to be achieved in a hospital. Among the physician owners of practices, 34% considered their model to be the best way to reconcile both aspects of life. CONCLUSION: More flexible options for childcare and more influence on the definition of working hours are necessary in order to better reconcile work and family life. For office-based physicians it must be made easier to find a substitute. Currently, especially women consider children as hindering their careers. Hospitals are perceived as extremely unfavorable workplaces for achieving compatibility between work and family life.

Sporicidal effect of amorolfine and other antimycotics used in the therapy of fungal nail infections.

Although topical antifungal therapies for treating onychomycosis are available, the cure rate is unsatisfactorily low with a simultaneously high risk of recurrence. One reason might be the formation of dormant fungal cells by the pathogen, known as spores, which can survive in the affected nail keratin, thereby evading the effect of antifungal drugs. In this in vitro study, the ability of amorolfine and four other antimycotics (ciclopirox, bifonazole, terbinafine and fluconazole) to kill microconidia of the dermatophyte Trichophyton rubrum, chlamydospores of the dermatophyte Epidermophyton floccosum and blastospores of the yeast Candida albicans was extensively studied as these fungi occur predominantly in onychomycosis. The effectiveness of all five antimycotics depended on the drug concentration and the incubation time: a concentration of 10-1000 times the minimum inhibitory concentration against growing hyphae cells is needed to exert a sporicidal action. Amorolfine and ciclopirox showed the same sporicidal efficacy and kinetics for all three varieties of spores. Both were more effective than fluconazole and bifonazole against microconidia and chlamydospores as well as slightly more potent against chlamydospores and blastospores than terbinafine after 4 days of incubation and at concentrations of ≥10 µg ml(-1). Finally, sporicidal activity on the tested strains was demonstrated for all five different antimycotics used for onychomycosis treatment.

Development of a specific anaerobic field test for aerobic gymnastics.

The current investigation aimed to develop a valid specific field test to evaluate anaerobic physical performance in Aerobic Gymnastics athletes. We first designed the Specific Aerobic Gymnast Anaerobic Test (SAGAT), which included gymnastics-specific elements performed in maximal repeated sprint fashion, with a total duration of 80-90 s. In order to validate the SAGAT, three independent sub-studies were performed to evaluate the concurrent validity (Study I, n=8), the reliability (Study II, n=10) and the sensitivity (Study III, n=30) of the test in elite female athletes. In Study I, a positive correlation was shown between lower-body Wingate test and SAGAT performance (Mean power: p = 0.03, r = -0.69, CI: -0.94 to 0.03 and Peak power: p = 0.02, r = -0.72, CI: -0.95 to -0.04) and between upper-body Wingate test and SAGAT performance (Mean power: p = 0.03, r = -0.67, CI: -0.94 to 0.02 and Peak power: p = 0.03, r = -0.69, CI: -0.94 to 0.03). Additionally, plasma lactate was similarly increased in response to SAGAT (p = 0.002), lower-body Wingate Test (p = 0.021) and a simulated competition (p = 0.007). In Study II, no differences were found between the time to complete the SAGAT in repeated trials (p = 0.84; Cohen's d effect size = 0.09; ICC = 0.97, CI: 0.89 to 0.99; MDC95 = 0.12 s). Finally, in Study III the time to complete the SAGAT was significantly lower during the competition cycle when compared to the period before the preparatory cycle (p < 0.001), showing an improvement in SAGAT performance after a specific Aerobic Gymnastics training period. Taken together, these data have demonstrated that SAGAT is a specific, reliable and sensitive measurement of specific anaerobic performance in elite female Aerobic Gymnastics, presenting great potential to be largely applied in training settings.

Design, synthesis, inhibition studies, and molecular modeling of pepstatin analogues addressing different secreted aspartic proteinases of Candida albicans.

The family of secreted aspartic proteinases is known as an important virulence factor of yeast infections by Candida albicans in particular, which is the most common fungal pathogen for humans with respect to systemic disease. Due to the continuing increase of drug resistant strains, these proteinases are currently considered as promising drug target candidates. Based on the known Sap2-substrate specificity data and X-ray analyses of Sap/inhibitor complexes, three libraries of inhibitors were designed and synthesized by modifying the structure of pepstatin A, a common non-selective aspartic proteinase inhibitor, at the P3, P2, or P2' position. These novel inhibitors showed high inhibitory potencies for the isoenzymes Sap1, Sap3, Sap5 and Sap6. Then, the affinity and selectivity of the peptide ligands were investigated by molecular modeling, highlighting new key structural information for the design of potent and selective anti-virulence agents targeting Candida albicans.

A peptide derived from the highly conserved protein GAPDH is involved in tissue protection by different antifungal strategies and epithelial immunomodulation.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has an important role not only in glycolysis but also in nonmetabolic processes, including transcription activation and apoptosis. We report the isolation of a human GAPDH (hGAPDH) (2-32) fragment peptide from human placental tissue exhibiting antimicrobial activity. The peptide was internalized by cells of the pathogenic yeast Candida albicans and initiated a rapid apoptotic mechanism, leading to killing of the fungus. Killing was dose-dependent, with 10 µg ml (3.1 µM) and 100 µg ml hGAPDH (2-32) depolarizing 45% and 90% of the fungal cells in a population, respectively. Experimental C. albicans infection induced epithelial hGAPDH (2-32) expression. Addition of the peptide significantly reduced the tissue damage as compared with untreated experimental infection. Secreted aspartic proteinase (Sap) activity of C. albicans was inhibited by the fragment at higher concentrations, with a median effective dose of 160 mg l(-1) (50 µM) for Sap1p and 200 mg l(-1) (63 µM) for Sap2p, whereas Sap3 was not inhibited at all. Interestingly, hGAPDH (2-32) induced significant epithelial IL-8 and GM-CSF secretion and stimulated Toll-like receptor 4 expression at low concentrations independently of the presence of C. albicans, without any toxic mucosal effects. In the future, the combination of different antifungal strategies, e.g., a conventional fungicidal with immunomodulatory effects and the inhibition of fungal virulence factors, might be a promising treatment option.

Glycosylation of Candida albicans cell wall proteins is critical for induction of innate immune responses and apoptosis of epithelial cells.

C. albicans is one of the most common fungal pathogen of humans, causing local and superficial mucosal infections in immunocompromised individuals. Given that the key structure mediating host-C. albicans interactions is the fungal cell wall, we aimed to identify features of the cell wall inducing epithelial responses and be associated with fungal pathogenesis. We demonstrate here the importance of cell wall protein glycosylation in epithelial immune activation with a predominant role for the highly branched N-glycosylation residues. Moreover, these glycan moieties induce growth arrest and apoptosis of epithelial cells. Using an in vitro model of oral candidosis we demonstrate, that apoptosis induction by C. albicans wild-type occurs in early stage of infection and strongly depends on intact cell wall protein glycosylation. These novel findings demonstrate that glycosylation of the C. albicans cell wall proteins appears essential for modulation of epithelial immunity and apoptosis induction, both of which may promote fungal pathogenesis in vivo.

Alternative approaches to antifungal therapies.

The expansive use of immunosuppressive medications in fields such as transplantational medicine and oncology, the higher frequency of invasive procedures in an ageing population and the HIV/AIDS pandemic have increased the frequency of systemic fungal infections. At the same time, increased resistance of pathogenic fungi to classical antifungal agents has led to sustained research efforts targeting alternative antifungal strategies. In this review, we focus on two promising approaches: cationic peptides and the targeting of fungal virulence factors. Cationic peptides are small, predominantly positively charged protein fragments that exert direct and indirect antifungal activities, one mechanism of action being the permeabilization of the fungal membrane. They include lysozyme, defensins and cathelicidins as well as novel synthetic peptides. Among fungal virulence factors, the targeting of candidal secreted aspartic proteinases seems to be a particularly promising approach.

Treatment of ocular rosacea with 40 mg doxycycline in a slow release form.

BACKGROUND: About 30-50 % of rosacea patients have ocular involvement. The symptoms range from a foreign-body sensation to conjunctivitis or blepharitis and may even include severe corneal ulcerations. Systemic treatment is generally with tetracycline. Side effects can occur with the usual antimicrobial dose. PATIENTS AND METHODS: In a retrospective study, seven patients were evaluated who had been treated for ocular rosacea with a sub-antimicrobial dose of doxycycline 40 mg in a slow-release form (Oraycea). The responses were evaluated on the basis of clinical findings. RESULTS: Seven patients with an average age of 63 took slow release doxycycline 40 mg every day for at least two months. In five patients, other systemic drugs had already failed. All patients experienced a clear improvement in their ocular rosacea after an average of 2.29 months of treatment. One patient had complete clearance and another had almost complete clearance. None of the patients experienced side effects. CONCLUSIONS: A sub-antimicrobial dose of slow release doxycycline 40 mg daily is an effective long-term therapy for ocular rosacea. It is not associated with the side effects of long-term antibiotic therapy or the risk of resistance.

Direct detection of five common dermatophyte species in clinical samples using a rapid and sensitive 24-h PCR-ELISA technique open to protocol transfer.

Identification of dermatophytes is usually based on morphological characteristics determined by time-consuming microscopic and cultural examinations. An effective PCR-ELISA method has been developed for rapid detection of dermatophyte species directly from clinical specimens within 24 h. Isolated genomic DNA of skin scrapings and nail samples from patients with suspected dermatophyte infections is amplified with species-specific digoxigenin-labelled primers targeting the topoisomerase II gene. The subsequent ELISA procedure with biotin-labelled probes allows a sensitive and specific identification of the five common dermatophytes -Trichophyton rubrum, T. interdigitale, T. violaceum, Microsporum canis and Epidermophyton floccosum. PCR-ELISA, based on the new polyphasic species concept, was assessed using 204 microscopy-positive samples in two university mycological laboratories in Munich and Tübingen, and 316 consecutive specimens - regardless of mycological findings - in a dermatological practice laboratory in Neu-Ulm. One of the five dermatophytes was confirmed by PCR-ELISA in 163 of 204 (79.9%) of the clinical samples from the university hospitals found positive using microscopy. Culture was positive for dermatophytes in 59.8% of the same cases. A significant difference between these two methods could be demonstrated using the McNemar test (P < 0.005). Analysis of specimens from Neu-Ulm confirmed the results in a dermatological practice laboratory as 25.0% of the specimens had positive PCR results, whereas only 7.3% were positive according to culture. Direct DNA isolation from clinical specimens and the PCR-ELISA method employed in this study provide a rapid, reproducible and sensitive tool for detection and discrimination of five major dermatophytes at species level, independent of morphological and biochemical characteristics.

In vitro models for human skin disease.

Modern tissue culture technology has made it possible to generate human skin equivalents that represent either epidermis or epidermis plus dermis (full-thickness skin) in vitro. Commercially available skin equivalents and in-house models are used for safety analysis of cosmetics and toxicity screening of various pharmaceutical compounds. Recently, tissue culture technology has also been used to develop in vitro models of skin disease, in particular to promote cutaneous drug research while sparing experimental animals. The spectrum of model diseases available covers a range from inflammatory disease to cancer. It has, thus, been possible to gain more insight into the role of active pharmaceutical ingredients of various dermatologically relevant drug classes as well as conventional and innovative formulations.

[S2k-guideline for therapy of acne]. / S2k-leitlinie zur therapie der akne.

To optimize the treatment of acne in Germany, the German Society of Dermatology (DDG) and the Association of German Dermatologists (BVDD) initiated a project to develop consensus-based guidelines for the management of acne. The Acne Guidelines focus on induction therapy, maintenance therapy and treatment of post-acne scarring. They include an evaluation of the most commonly used therapeutic options in Germany. In addition, they offer detailed information on how to administer the various treatments and on contraindications, adverse drug reactions, and drug interactions, taking into account gender and special conditions such as pregnancy and lactation. The Acne Guidelines were developed following the recommendations of the Association of Scientific Medical Societies in Germany (AWMF). The treatment recommendations were developed by an expert group and finalized by an interdisciplinary consensus conference. The first choice treatments for acute acne according to acne type are as follows: 1) comedonal acne: topical retinoids; 2) mild papular/pustular acne: fixed or sequential combinations of BPO and topical retinoids or of BPO and topical antibiotics; 3) moderate papular/pustular acne: oral antibiotic plus BPO or plus topical retinoid, or in a fixed combination 4) acne papulo-pustulosa nodosa and acne conglobata: oral antibiotic plus topical retinoid plus BPO or oral isotretinoin. For maintenance treatment: topical retinoid or its combination with BPO. Particular attention should be paid to compliance and quality of life. Additional treatment options are discussed in the main body of the text.

"Beauty lies in the eye of the beholder"? Aspects of beauty and attractiveness.

Discussing aesthetic issues and their management with patients is a growing area of dermatologic practice. Sometimes treatment options within one's own discipline are rapidly discussed, without a clear idea of the various aspects of the face which all combine to produce beauty and attractiveness. We review various features leading to the impression of beauty and attractiveness. Familiarity with these concepts should facilitate a broader discussion with the patient on the aspects of beauty and attractiveness beyond the borders of one's own discipline and also lead to multidisciplinary treatment options. We also examine the question how much the personality of the beholder himself is involved in the perception of attractiveness and beauty (of the person sitting opposite to him). The "ideal" face has an average profile with slightly protrusive and full lips. Attractiveness increases with average features and symmetry. Moreover, particular features such as the scheme of childlike characteristics combined with aspects of maturity and expression make a female face appear especially beautiful. Which attributes contribute to attractiveness of a man's face are controversial. Clear male signals such as a strong chin are likely not to increase attractiveness.

Safety and efficacy of sertaconazole nitrate cream 2% in the treatment of tinea pedis interdigitalis: a subgroup analysis.

Sertaconazole nitrate is a broad-spectrum antifungal agent indicated in the United States for the treatment of tinea pedis interdigitalis. The objective of this subgroup analysis was to evaluate the safety and efficacy of sertaconazole nitrate cream 2%, specifically in participants with tinea pedis interdigitalis (ie, fungal skin disease of the toe web) of dermatophyte origin. A total of 92 participants were included in this analysis. The primary end points were eradication of the pathogen (confirmed by fungal culture results) and reduction in total clinical score (TCS) of at least 2 points. Secondary end points included reducing signs and symptoms and reporting adverse events (AEs). After 4 weeks of treatment, 88.8% (79/89) of evaluable participants achieved success on the primary end points. Most participants also demonstrated substantial improvement in signs and symptoms after 4 weeks of treatment: 63.7% (58/91) were free of erythema, 33.0% (30/91) were free of desquamation, and 91.2% (83/91) were free of itch. The rate of reported AEs was low (8.7% [8/92]), and none were considered serious. These findings indicate that sertaconazole nitrate cream 2% is highly safe and effective in the treatment of tinea pedis interdigitalis.

Susceptibility testing of amorolfine, bifonazole and ciclopiroxolamine against Trichophyton rubrum in an in vitro model of dermatophyte nail infection.

Antimycotic nail lacquers are effective and safe for the treatment of onychomycosis. To assess the efficacy of three topical agents we studied the minimum inhibitory and fungicidal concentration of amorolfine, bifonazole and ciclopiroxolamine. Amorolfine showed the most effective fungistatic and fungicidal activity in vitro against seven clinical Trichophyton rubrum nail isolates, followed in descending order by ciclopiroxolamine and bifonazole. To mimic a nail infection more appropriately, the nail minimum fungicidal concentration (Nail-MFC) was determined in an onychomycosis model. Amorolfine and ciclopiroxolamine had Nail-MFCs ranging from 2-32 microg/ml and 16-32 microg/ml, respectively. In contrast, bifonazole was unable to kill T. rubrum in this model. Statistical analyses of the results show a significant difference between the two treatments with amorolfine and ciclopiroxolamine (P<0.001). For amorolfine a mean concentration of 12.28 microg/ml (95%-CI=[8.66, 17.41]) was sufficient to kill all strains, while for ciclopiroxolamine about twice that concentration was needed, i.e., 24.13 microg/ml (95%-CI=[17.06, 34.13]). The individual sensitivity of six of the seven T. rubrum strains was higher for amorolfine. These data demonstrate that both amorolfine and ciclopiroxolamine effectively kill T. rubrum growing on nail powder and suggest a better cidal action for amorolfine. Further investigation would be required to determine if these in vitro data can partially explain the clinical observation of significantly higher cure rates in onychomycosis following a therapy with an amorolfine-containing nail lacquer formulation.

Treatment of disseminated granuloma annulare with low-dose fumaric acid.

While localized variants of granuloma annulare are typically self-limited, disseminated granuloma annulare tends to be chronic and often therapy-resistant. Treatment with fumaric acid esters is effective for severe forms of psoriasis. Disseminated granuloma annulare has also been reported to respond to fumaric acid esters. We treated 8 patients (mean age 64.2 years; 4 men, 4 women) with low-dose fumaric acid esters for 1-18 months. One patient showed complete clearance, 4 marked improvement, one slight to moderate improvement and one no response. One patient discontinued treatment due to nausea after one month and another stopped it after 18 months. Five out of 8 patients tolerated the treatment well. Six patients developed transient, mild leucopaenia and one eosinophilia. None of these blood abnormalities necessitated discontinuation of therapy. Low-dose fumaric acid esters significantly improve disseminated granuloma annulare in approximately 63% of patients. Larger, controlled, prospective studies are needed to evaluate its efficacy and safety in this setting.