A new in vitro assay to test UVR protection of dermal extracellular matrix components by a flat spectrum sunscreen.

The efficacy of topical sunscreens is currently assessed by crude, costly and time consuming in vivo assays. We have previously demonstrated that components of the dermal extracellular matrix (ECM), rich in UV-absorbing amino acids, are susceptible to damage by solar simulated radiation (SSR) in vitro. Here we developed an in vitro method to test the ability of sunscreens to protect fibrillin-rich microfibrils (FRM) and fibronectin, key components of the dermal ECM from UV-induced damage. Solutions of FRM or fibronectin were irradiated without protection, in the presence of a vehicle or a commercially-available flat-spectrum sunscreen. The effect of SSR on molecular structure was determined by atomic force microscopy (FRM) and SDS-PAGE (fibronectin). Following irradiation, FRM periodicity became bi-modally distributed (peaks: 40nm & 59nm) compared to the unimodal distribution in unexposed controls (peak: 50nm). Irradiation in the presence of flat-spectrum sunscreen protected against this change, maintaining the unimodal distribution. SSR induced significant aggregation of fibronectin (p=0.005), which was abrogated by sunscreen. These results demonstrate that this in vitro assay system is sufficiently sensitive to act as an initial/additional screen of sunscreen efficacy. We conclude that sunscreen can reduce UV-mediated damage of key dermal ECM in vitro and thereby prevent remodelling associated with photoageing.

Skin aging: molecular pathology, dermal remodelling and the imaging revolution.

Skin is a multifunctional organ but, alongside every other organ system, is subject to both intrinsic (chronological) and extrinsic (environmental) aging, resulting in a loss of functional capacity. Cutaneous aging manifests as an observable change in the external appearance of the skin, the major accelerator of the aging process being our interactions with our environment, such as chronic exposure to solar irradiation (UV, IR or visible wavelengths of light). The aim of this contribution, therefore, was to provide a review of the pathological mechanisms which may play roles in the development of extrinsic, mainly photo-, aging and to review how these molecular changes impact on the structure of the organ as a whole, resulting in loss of function. Finally, we will describe the advances which are occurring in imaging techniques which may allow further characterisation of aged skin.

Presentation and management of facial swellings of odontogenic origin in children.

AIM: To determine the characteristics, aetiology and management of facial swellings of odontogenic origin in the paediatric population. STUDY DESIGN: Prospective study of children with facial swellings of odontogenic origin. METHODS: All children who presented to the Departments of Paediatric Dentistry of the Westmead Centre for Oral Health and the Children's Hospital at Westmead with a facial swelling of odontogenic origin over a 12 month period were identified and included in the study. Treating clinicians completed a standardised data collection sheet to record information relating to patient demographics, medical history, dental history, history of current episode of facial swelling of odontogenic origin, examination findings and management. Data were entered in Microsoft(®) Excel and statistical analysis carried out using Statistical Analysis Software(®) version 9.3. RESULTS/STATISTICS: Two hundred and fifty-three children were included in the study, with a mean age of 6.3 years. Sixteen percent of children were admitted for intravenous antibiotics, surgical management and supportive care. For the remaining children not admitted, a range of management approaches were undertaken. These included immediate surgical management with or without oral antibiotics, delayed surgical management following a course of oral antibiotics, or oral antibiotics alone, where the cause of the odontogenic infection had already been removed. For 2% of children, a delayed surgical management approach was unsuccessful and the children were admitted. CONCLUSIONS: Management options for children presenting with facial swellings of odontogenic origin include admission to hospital for intravenous antibiotics and acute surgical management, immediate surgical management with or without a course of oral antibiotics or initial management involving a course of oral antibiotics, with definitive dental treatment being provided after resolution of the acute odontogenic infection.

The use of bisphosphonates in children: review of the literature and guidelines for dental management.

Bisphosphonates are inhibitors of osteoclastic bone resorption with therapeutic benefit in a variety of bone disorders in both adults and children. While these agents have been routinely used in adults for the past three decades, their more recent introduction into paediatric medicine means there is a paucity of data on long-term safety and effects on dental development. There is uncertainty regarding the dental management of children treated with bisphosphonates, particularly when invasive dental procedures, such as extractions and oral surgical procedures, are required. There are limited data with which to make recommendations about the dental management of patients treated with bisphosphonates, and there are no published recommendations that specifically address paediatric patients. This paper aims to outline paediatric uses and adverse effects of bisphosphonates and present recommendations on the dental management of children receiving bisphosphonates.

Effectiveness of oral midazolam for paediatric dental care: a retrospective study in two specialist centres.

AIM: To analyse retrospectively the outcomes for children undergoing oral care under conscious sedation with oral midazolam and local analgesia at Leeds dental Institute, England and Westmead Dental Hospital, Sydney, Australia. Secondly, the study assessed the suitability of oral midazolam for paediatric dental treatment. STUDY DESIGN: Retrospective study of clinical outcomes based on dental records. METHODS: All children included in the study had been treated between September 2000 to August 2004 and full dental records were available. The dental records were examined using a standard pro forma sheet and data collected for: age, previous behaviour using the Frankl [1962] scale, units of work planned and achieved using the modified index of O'Sullivan and Curzon [1991], midazolam dosage and treatment outcome. RESULTS: The study population consisted of 101 children aged 1-11 years in both Leeds (57 children) and Westmead (44 children). There were significant differences between Leeds and Westmead with respect to age (mean +/-SD) in years 5.0+/-1.0 versus 2.9+/-1.6; number of treatment visits 1.7 versus 1.1; sedation dose used 0.5-0.7 mg/kg versus 02.-0.3; type and amount of treatment planned 8.3 units versus 3.3 and achieved 7.5 versus 2.2, for both centres respectively. There was also a difference in overall success rates of rendering the children dentally fit of 65% v. 91%, respectively. CONCLUSION: Oral midazolam was found to be a useful drug for the management of young children with behaviour problems. It was found, however, not to be effective in all cases and for the provision of all types of paediatric dentistry. The results indicate that, when using oral midazolam in children, the treatment should be restricted to simple restorations and extractions over a maximum of two visits.

Molecular basis of familial cleft lip and palate.

Cleft lip and palate (CLP) is one of the commonest congenital malformations and although the aetiology is still very unclear, a familial genetic component is considered to be an important factor in certain individuals. Molecular biology techniques are being used to identify the genes involved and this paper reviews current knowledge and the advances that have already been made. Recent evidence suggests a potential major gene on 6p, and a modifying role for transforming growth factor alpha (TGFA). Moreover retinoic acid receptor alpha (RARA) (17q), MSXI (4p), 4q and BCL3 (19q) could all be implicated in certain CLP families. In addition, the potential modifying role of various genes with the environment are considered to be important areas of research in the future. The identification of a genetic locus associated with this disease would be an important advance in CLP genetic counselling and lead to a better understanding of the genetic basis of CLP.

Efficacy of fluconazole in prophylaxis and treatment of experimental Candida endocarditis.

The efficacy of fluconazole, a bis-triazole antifungal agent, for prophylaxis and treatment of endocarditis due to Candida albicans and Candida parapsilosis is assessed in a rabbit model. Fourteen daily injections of fluconazole at doses of 20 and 10 mg/kg of body weight eradicated C. albicans and C. parapsilosis, respectively, from the cardiac vegetations in all animals tested. Amphotericin B (3 mg/kg) and flucytosine (35 mg/kg) both singly and in combination failed to achieve eradication in 100% of the animals. A two-dose prophylactic regimen of 30 mg of fluconazole/kg was consistently successful in preventing experimental endocarditis caused by C. albicans or C. parapsilosis.