Oestrogen functions in skin and skin appendages

Oestrogens have significant effects on different cell types important in skin physiology, including the epidermal keratinocytes, dermal fibroblasts and melanocytes. In addition, they can also modulate skin appendages such as the hair follicle, the sebaceous gland and the apocrine glands. Oestrogens may also have important modulatory roles in events such as skin ageing, pigmentation, hair growth, sebum production and skin cancer. It is now recognised that oestrogens can modulate their actions via two distinct intracellular receptors (ERα and ERβ) or via cell surface receptors, which activate specific second messenger signalling pathways. This paper highlights the effects of oestrogens on different components of the skin and reviews some of the more recent developments in terms of receptor expression and cell signalling pathways.     

Oestrogen functions in skin and skin appendages

Oestrogens have significant effects on different cell types important in skin physiology, including the epidermal keratinocytes, dermal fibroblasts and melanocytes. In addition, they can also modulate skin appendages such as the hair follicle, the sebaceous gland and the apocrine glands. Oestrogens may also have important modulatory roles in events such as skin ageing, pigmentation, hair growth, sebum production and skin cancer. It is now recognised that oestrogens can modulate their actions via two distinct intracellular receptors (ERalpha and ERbeta) or via cell surface receptors, which activate specific second messenger signalling pathways. This paper highlights the effects of oestrogens on different components of the skin and reviews some of the more recent developments in terms of receptor expression and cell signalling pathways.     

Moxifloxacin in uncomplicated skin and skin structure infections

Moxifloxacin is a fluoroquinolone antibacterial agent which attains good penetration into peripheral tissues and inflammatory fluids. The drug shows good in vitro activity against staphylococci and streptococci. Moxifloxacin is therefore a suitable option for the treatment of uncomplicated skin and skin structure infections of bacterial origin. In clinical trials, moxifloxacin was as effective as cephalexin in the treatment of uncomplicated skin and skin structure infections in patients aged >or=18 years. Moxifloxacin 400mg once daily or cephalexin 500mg three times daily for 7 days both resulted in clinical resolution in 84% of patients during a double-blind, randomised trial in 401 patients (intent-to-treat). The main infectious agent in this study was Staphylococcus aureus. Similar results were obtained in two other randomised, double-blind trials published as abstracts. The bioavailability of moxifloxacin is substantially reduced by coadministration with antacids or iron preparations. Moxifloxacin, however, does not show pharmacokinetic interaction with theophylline or warfarin. Dosage adjustments are not required in patients with renal impairment or in patients with mild to moderate hepatic insufficiency. The most common adverse events reported during moxifloxacin treatment are gastrointestinal disturbances. The potential for photosensitivity reactions during moxifloxacin treatment is low.     

Treatment of bacterial skin and skin structure infections

Bacterial skin and skin structure infections (SSSIs) are among the most frequently seen infectious entities in the community setting and occasionally in the institutional setting. A wide variety of SSSIs exist, with cellulitis, impetigo and folliculitis being the most common. Most SSSIs are caused by aerobic staphylococci and streptococci, with aerobic Gram-negative bacilli and anaerobes being involved in more complicated infections. Systemic therapy with a variety of beta-lactams, macrolides and lincosamides (clindamycin) have been the cornerstone of SSSI therapy for many years. With the exception of mupirocin, topical therapy occupies a small therapeutic niche. Despite the emergence of antimicrobial resistance among the pathogens most commonly associated with SSSIs (for example, Streptococcus pyogenes and macrolides; Staphylococcus aureus and methicillin, vancomycin, penicillin and mupirocin), few treatment failures have been reported. The newest antimicrobials reviewed herein (linezolid, quinupristin/dalfopristin, gatifloxacin, gemifloxacin and moxifloxacin) are not a significant improvement upon older agents in the treatment of SSSIs. Perhaps this assessment will change if the penetrance of the antimicrobial resistance patterns described above reach a critical threshold and clinical failures become more widespread.     

腹部皮下血管网皮瓣修复手指皮肤脱套伤

目的客观判定腹部皮下血管网皮瓣修复术治疗手指皮肤脱套伤的疗效。方法应用传统的腹部袋状皮瓣和腹部带皮下血管网皮瓣治疗手部脱套伤,并将两种方法的治疗结果进行对比。结果 手指的屈伸功能效果方面,实验组82.2,对照组46.6;治疗后的外观效果方面,实验组优良率68.9,对照组优良率37.78。结论腹部皮下血管网皮瓣修复法是一种较理想的修复手指皮肤脱套伤的治疗方法。     

Oritavancin for acute bacterial skin and skin structure infections

Introduction: Inpatient treatment of acute bacterial skin and skin structure infections (ABSSSIs) exerts a significant economic burden on the healthcare system. Oritavancin is a concentration-dependent, rapid bactericidal agent approved for the treatment of ABSSSIs. Its prolonged half-life with one-time intravenous (i.v.) dosing offers a potential solution to this burden. In addition, oritavancin represents an alternative therapy for Streptococci and multidrug-resistant Gram-positive bacteria including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus. Animal models have also shown promising results with oritavancin for other disease states including those that require long courses of i.v. therapy.

Areas covered: This review covers oritavancin’s basic chemistry, spectrum of activity, pharmacodynamics/pharmacokinetics and efficacy in clinical trials, and provides expert opinion on future directions. To compose this review, a search of PubMed was performed, and articles written in the English language were selected based on full text availability.

Expert opinion: If oritavancin is proven to be a cost-effective strategy for outpatient treatment and prevents complications of prolonged i.v. therapy, it will be sought as an alternative antibiotic therapy for ABSSSIs. In addition, further clinical data demonstrating efficacy in Gram-positive infections requiring prolonged therapy such as endocarditis and osteomyelitis could support oritavancin’s success in the current market.     

HSP27 as a biomarker for predicting skin irritation in human skin and reconstructed organotypic skin model

In vitro alternative tests aiming at replacing the traditional animal test for predicting the irritant potential of chemicals have been developed, but the assessing parameters or endpoints are still not sufficient. To discover novel endpoints for skin irritation responses, 2DE-based proteomics was used to analyze the protein expression in human skin exposed to sodium lauryl sulfate (SLS) following the test protocol of the European Centre for the Validation of Alternative Methods (ECVAM) in the present study. HSP27 was up-regulated most significantly among the eight identified proteins, consistent with our previous reports. Acid and basic chemicals were applied on human skin for further validation and results showed that the up-regulated expression of HSP27 was induced in 24 h after the exposure. Skin-equivalent constructed with fibroblasts, basement membrane and keratinocytes was used to investigate the potential of HSP27 as a biomarker or additional endpoint for the hazard assessment of skin irritation. Our skin-equivalent (Reconstructed Organotypic Skin Model, ROSM) had excellent epidermal differentiation and was suitable for the skin irritation test. HSP27 also displayed an up-regulated expression in the ROSM in 24 h after the irritants exposure for 15 min. All these results suggest that HSP27 may represent a potential marker or additional endpoint for the hazard assessment of skin irritation caused by chemical products.     

Anticoagulant-related skin reactions

Cutaneous reactions have been reported during anticoagulant therapy with coumarin derivatives, unfractionated and low molecular weight heparins, heparinoids, danaparoid and hirudins. Anticoagulant-induced skin reactions vary from local allergic manifestations to skin necrosis. In patients with allergic reactions, diagnosis and crossreactions between anticoagulants can be confirmed by intracutaneous testing. Coumarin- and heparin-induced skin necrosis are rare, but are important side effects due to their high morbidity and occasional mortality. Cutaneous tests are contraindicated in these patients. In the future, anticoagulant strategies may include direct synthetic thrombin inhibitors (argatroban and melagatran/ximelagatran) and the Factor Xa inhibitor, pentasaccharide (fondaparinux).     

Impact of phenytoin therapy on the skin and skin disease

Phenytoin (diphenylhydantoin; Dilantin), ALZA Corp.) is a highly effective and widely prescribed anticonvulsant agent used in the treatment of focal and tonic clonic generalised seizures. The side effects of phenytoin can occassionally engender significant morbidity. Phenytoin can induce generalised eruptions that include: a maculopapular exanthem, Stevens-Johnson syndrome, generalised exfoliative dermatitis, toxic epidermal necrolysis, vasculitis and fixed drug eruptions. Phenytoin is linked to a hypersensitivity syndrome that manifests with fever, rash and lymphadenopathy. Patients receiving phenytoin may develop pseudolymphoma or, rarely, malignant lymphoma and mycosis fungoides-like lesions. Rarer cutaneous side effects include drug-induced lupus, purple hand syndrome, pigmentary alterations and IgA bullous dermatosis. Phenytoin can effect clotting function and alter vitamin and mineral levels. Prenatal exposure to phenytoin may result in a spectrum of structural, developmental and behavioural changes, known as the fetal hydantoin syndrome. Patients who use phenytoin in the long-term commonly manifest with gingival hyperplasia, coarsening of the facies, and hirsutism.     

In vitro skin irritation testing with human skin cell cultures

Cultured human skin cells are a potentially useful model for skin irritancy testing. We have evaluated the effects of chemical irritants on human epidermal keratinocytes (NHEK) and on keratinocyte-dermal fibroblast (NHEK/DF) co-cultures. Cell viability in NHEK cultures, measured as incorporation of the vital dye neutral red (NR), was reduced in a dose-dependent manner in response to the chemical irritants tested. The half-maximal effective concentration (NR₅₀) values correlated with irritation scores in human patch tests with these materials. Certain materials were found to be incompatible with this test system. NHEK/DF cultures were treated with ten prototype surfactants, and were evaluated for cell viability (MTT incorporation), cytotoxicity (release of the enzymes lactate dehydrogenase and N-acetyl glucosaminidase), metabolism (glucose utilization), and inflammatory mediator (prostaglandin E₂) release. There was a close correlation of the dose-response characteristics for all the endpoints tested, and between the in vitro responses and human patch test scores for the surfactants tested. These results demonstrate the usefulness of human skin cell cultures and of cell viability, cytotoxicity, and inflammatory mediator release as endpoints, for the in vitro assessment of skin irritancy.     

Captopril-induced skin eruptions

Seven of 23 hypertensive patients treated with captopril (SQ 14,225), an orally active converting enzyme inhibitor, developed a pruritic, erythematous, macular, and papular eruption of the trunk, face, and proximal extremities. The eruption appeared one to 31 weeks after initiation of captopril therapy and was associated with diarrhea (three patients), fever (two patients), and generalized arthralgias (one patient). Six patients had an increased percentage of band cells (5 to 34 per cent) on peripheral smear without an associated leukocytosis. In one patient, the skin rash was associated with a peripheral eosinophilia (20 per cent). Coombs-positive hemolytic anemia, and acute renal failure with eosinophiluria. There were no changes in BUN, creatinine, or urinalyses in the remaining patients. Four patients showed a transient rise in plasma PGE without concomitant changes in plasma PFG2 alpha or 6-keto PGF1 alpha, and three patients had slight elevations in the erythrocyte sedimentation rate. Skin biopsies revealed a perivascular and perifollicular lymphocytic and histiocytic infiltrate with negative immunofluorescence to IgG, IgM, IgA, and beta 1 C. The skin eruption and associated symptoms resolved in all patients, even though captopril administration was continued in six of the seven patients.     

Anticoagulant-related skin reactions

Cutaneous reactions have been reported during anticoagulant therapy with coumarin derivatives, unfractionated and low molecular weight heparins, heparinoids, danaparoid and hirudins. Anticoagulant-induced skin reactions vary from local allergic manifestations to skin necrosis. In patients with allergic reactions, diagnosis and crossreactions between anticoagulants can be confirmed by intracutaneous testing. Coumarin- and heparin-induced skin necrosis are rare, but are important side effects due to their high morbidity and occasional mortality. Cutaneous tests are contraindicated in these patients. In the future, anticoagulant strategies may include direct synthetic thrombin inhibitors (argatroban and melagatran/ximelagatran) and the Factor Xa inhibitor, pentasaccharide (fondaparinux).