Streptolysin O enhances keratinocyte migration and proliferation and promotes skin organ culture wound healing in vitro

ML-05, a modified form of the hemolytic and cytotoxic bacterial toxin, streptolysin O, is currently being investigated as a treatment for collagen-related disorders such as scleroderma and fibrosis. Furthermore, ML-05 may be effective in promoting wound healing and alleviating the formation of hypertrophic scars and keloids. To investigate the effects of ML-05 on wound-healing processes, in vitro wound-healing scratch assays (using human primary epidermal keratinocytes and dermal fibroblasts) and a human skin organ culture wound model were utilized. ML-05 markedly enhanced keratinocyte migration and proliferation in wound scratch assays. ML-05 did not affect either proliferation or migration of dermal fibroblasts, indicating that ML-05's effects on cell migration/proliferation may be keratinocyte-specific. ML-05 was tested in a dose-dependent manner in a skin organ culture wound model using two different application methods: Through the culture media (dermal exposure) or direct topical treatment of the wound surface. ML-05 was found to accelerate wound healing as measured by reepithelialization, particularly after topical application. Therefore, ML-05 may have potential as a wound-healing agent that promotes reepithelialization through stimulation of keratinocyte migration and proliferation.     

Baseline characteristics and treatment preferences of oral surgery patients.

PURPOSE: Patient preferences for treatment choices may depend on patient characteristics. Using standard gamble (SG) and willingness to pay (WTP), this study compares preferences for treatment of mandibular fracture among patients in a low-income urban area. PATIENTS AND METHODS: Surveys of African-American and Hispanic adults receiving treatment at King/Drew Medical Center for either mandibular fracture (n = 98) or third molar removal (n = 105) were used to investigate differences in patient characteristics across treatment groups (third molar vs fracture) and treatment preference (wiring vs surgery). RESULTS: The fracture patients were willing to pay more to restore function without scarring or nerve damage than were the third molar patients. Patients who chose surgery were willing to accept a greater risk of possible nerve damage or scarring than those who chose wiring. Among 15 potential predictors of SG and WTP studied in 4 subgroups defined by actual treatment and treatment preference, significant predictors varied, with associations for education and clinical experience for SG and associations with income and psychosocial predictors for WTP. CONCLUSIONS: SG and WTP capture different domains of health values in patients. There is considerable heterogeneity in relationships among patient characteristics and patient preferences across subgroups defined by actual treatment and treatment preferences.     

PR05POST‐OPERATIVE HAEMATOMAS IN MICROVASCULAR FREE FLAP RECONSTRUCTION OF THE HEAD AND NECK: THE INCIDENCE,AETIOLOGY AND OUTCOME MODIFICATIONS

Background Free tissue transfer using microvascular surgery has become a safe a reliable means to repair soft tissue and/or bony defects of the head and neck. Operative success reaches 98%, however the incidence of significant post‐operative complication is also relatively high (32%). One common and often severe complication is haematoma formation at either donor or recipient sites. The incidence of recipient site haematoma is reported at 6%, however the causes and outcomes of haematomas have not been well investigated. A retrospective historical analysis of both donor and recipient site wound haematoma was performed to identify causative factors and the effect on patient outcome. Methodology A five year review was conducted for microvascular free tissue transfer to defects in the head and neck at The Royal Melbourne Hospital, for the period from February 2001 until February 2006. The medical records of these 150 patients were reviewed for donor and recipient site wound haematoma and outcomes. Results Significant factors for the development of post‐operative haematomas included lood pressure control during the first post‐operative, correlating with the likelihood of developing either a donor or recipient site haematoma (p value < 0.001), drain‐tube outputs (both high and low), smoking and the use of pre‐operative NSAIDs. Conclusion There are significant reversible factors that contribute to the development of post‐operative haematomas in head and neck surgery. Close monitoring of patient blood pressure by theatre and recovery nursing staff, close monitoring of drain outputs, and pre‐operative counselling on the use of NSAIDs and smoking may all be useful in the prevention of haematoma formation.     

Bone Mineral Density Determinations by Dual-Energy x-ray Absorptiometry in the Management of Patients with Marfan Syndrome—Some Factors Which Affect the Measurement

Reduced bone mineral density (BMD) was sporadically reported in patients with Marfan syndrome. This may or may not place the Marfan patient at increased risk for bone fracture. In comparing the BMDs of our patients with those reported in the literature, it seemed that agreement between values, and hence the degree of osteoporosis or osteopenia reported, was dependent on the instrumentation used. The objective of this study was to statistically assess this impression. Bone mineral density measurements from our previously published study of 30 adults with Marfan syndrome performed on a Lunar DPXL machine were compared with studies published between 1993–2000 measured using either Lunar or Hologic bone densitometry instruments. The differences of our measurements compared with those made on other Lunar machines were not statistically significant, but did differ significantly with published results from Hologic machines (P < 0.001). Before progress can be made in the assessment of BMD and fracture risk in Marfan patients and in the evidence-based orthopedic management of these patients, standardization of instrumental bone density determinations will be required along with considerations of height, obesity, age, and sex.     

Angiogenese – therapeutische Interventionsmöglichkeiten bei rheumatischen Erkrankungen

In contrast to vasculogenesis, angiogenesis is defined as the formation of new vessels from preexisting ones. Physiologically, this multistep process occurs in adults during the reproductive cycle and during pregnancy, pathophysiologically it can be found in wound healing, inflammation and carcinogenesis. The underlying mechanisms are vasodilatation and increasing permeability, destabilization of vessel walls and degradation of extracellular matrix, followed by the proliferation and migration of endothelial cells. Migrated endothelial cells form vascular tubes at sites of ischemia and these tubes are finally stabilized by pericytes and smooth muscle cells. This process is controlled by a complex interaction of angiogenic and angiostatic factors. In contrast to carcinogenesis, the role of angiogenesis for the pathogenesis and therapy of rheumatic diseases is less understood. Two examples for pathologically disturbed angiogenesis, rheumatoid arthritis and systemic sclerosis, are discussed in this review with respect to therapeutic options.     

Genetic association studies of interleukin-13 receptor alpha1 subunit gene polymorphisms in asthma and atopy.

Interleukin (IL)-13 plays a central role in asthma pathogenesis by binding to the IL-13 receptor, which is a heterodimer composed of the IL-13 receptor alpha1 subunit (IL-13Ralpha1) and IL-4Ralpha. The genetic diversity at the IL-13Ralpha1 gene (IL13RA1) locus on chromosome Xq24 was characterised and the association of identified polymorphisms with asthma and atopy phenotypes examined. The promoter and coding region of IL13RA1 were screened for common genetic variants, and polymorphisms found were genotyped in a large cohort of 341 asthmatic Caucasian families (each containing at least two asthmatic siblings) and 182 nonasthmatic control subjects. Genetic association was determined using case-control and transmission disequilibrium test analyses. Two common polymorphisms were identified, a newly found thymidine (T) to guanine (G) transition of nucleotide -281 (-281T>G) single nucleotide polymorphism in the IL13RA1 promoter and the previously described 1365A>G variant in the IL13RA1 proximal 3' untranslated region. No significant association of either -281T>G or 1365A>G with risk of asthma or atopy phenotypes was found, apart from a suggestive association between the IL13RA1 -281T/1365A haplotype and raised total serum immunoglobulin E levels in adult female asthmatics. These findings indicate that the interleukin-13 receptor alpha1 subunit gene -281T>G and 1365A>G polymorphisms do not contribute to asthma susceptibility or severity, although the interleukin-13 receptor alpha1 subunit gene locus might be involved in the control of immunoglobulin E production.     

Stoffwechseluntersuchungen am Hund vor und nach Hypophysektomie

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