Rotator cuff tears are among the most frequent upper extremity injuries. Current treatment strategies do not address the poor quality of the muscle and tendon following chronic rotator cuff tears. Hypoxia-inducible factor-1 alpha (HIF-1α) is a transcription factor that activates many genes that are important in skeletal muscle regeneration. HIF-1α is inhibited under normal physiological conditions by the HIF prolyl 4-hydroxylases (PHDs). In this study, we used a pharmacological PHD inhibitor, GSK1120360A, to enhance the activity of HIF-1α following the repair of a chronic cuff tear, and measured muscle fibre contractility, fibrosis, gene expression, and enthesis mechanics. Chronic supraspinatus tears were induced in adult rats, and repaired 28 days later. Rats received 0 mg/kg, 3 mg/kg, or 10 mg/kg GSK1120360A daily. Collagen content, contractility, fibre type distribution and size, the expression of genes involved in fibrosis, lipid accumulation, atrophy and inflammation, and the mechanical properties of the enthesis were then assessed two weeks following surgical repair.Objectives
Methods
High-intensity narrow-spectrum (HINS) light is
a novel violet-blue light inactivation technology which kills bacteria through
a photodynamic process, and has been shown to have bactericidal
activity against a wide range of species. Specimens from patients
with infected hip and knee arthroplasties were collected over a
one-year period (1 May 2009 to 30 April 2010). A range of these
microbial isolates were tested for sensitivity to HINS-light. During
testing, suspensions of the pathogens were exposed to increasing
doses of HINS-light (of 123mW/cm2 irradiance). Non-light exposed
control samples were also used. The samples were then plated onto
agar plates and incubated at 37°C for 24 hours before enumeration.
Complete inactivation (greater than 4-log10 reduction)
was achieved for all of the isolates. The typical inactivation curve
showed a slow initial reaction followed by a rapid period of inactivation.
The doses of HINS-light required ranged between 118 and 2214 J/cm2.
Gram-positive bacteria were generally found to be more susceptible
than Gram-negative. As HINS-light uses visible wavelengths, it can be safely used
in the presence of patients and staff. This unique feature could
lead to its possible use in the prevention of infection during surgery
and post-operative dressing changes. Cite this article:
The stress response to trauma is the summation of the physiological response to the injury (the ‘first hit’) and by the response to any on-going physiological disturbance or subsequent trauma surgery (the ‘second hit’). Our animal model was developed in order to allow the study of each of these components of the stress response to major trauma. High-energy, comminuted fracture of the long bones and severe soft-tissue injuries in this model resulted in a significant tropotropic (depressor) cardiovascular response, transcardiac embolism of medullary contents and activation of the coagulation system. Subsequent stabilisation of the fractures using intramedullary nails did not significantly exacerbate any of these responses.