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.
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.
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.
Discussing aesthetic issues and their management with patients is a growing area of dermatologic practice. Sometimes treatment options within ones 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 ones 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 mans face are controversial. Clear male signals such as a strong chin are likely not to increase attractiveness.
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.
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.
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.
The synthetic route to pepstatin derivatives by a solid phase peptide synthesis using either O-protected or O-unprotected statine as a building block has been investigated. Statine was prepared according to a modified literature procedure, whereas protection of its 3-hydroxyl moiety using tert-butyldimethylsilylchloride (TBSCl) provided the novel O-TBS-protected statine building block. The O-tert-butyldimethylsilyl (TBS)-protected statine approach provides an improved synthetic strategy for the preparation of statine-containing peptides as demonstrated by the synthesis of the pepstatin analogue iva-Val-Leu-Sta-Ala-Sta.
In the recent past, we have found ourselves in need of truly novel antifungal drugs as drug resistance in fungi has been evolving. Moreover, effective therapy has become particularly important as the number of immuno-compromised patients with life-threatening fungal infections increases. Fortunately, during the last few years, virulence factors of fungi and their inhibitors have, at least to some extent, been discovered and characterized. This should provide new options for the development of potential antifungal therapeutics. Inhibitors of the secreted aspartic proteinase of Candida albicans might turn out to be particularly rewarding.
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.
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.
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.
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??g?ml (3.1??M) and 100??g?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??M) for Sap1p and 200?mg?l(-1) (63??M) 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.
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