Post-ischaemic silencing of p66Shc reduces ischaemia/reperfusion brain injury and its expression correlates to clinical outcome in stroke.

AIM: Constitutive genetic deletion of the adaptor protein p66(Shc) was shown to protect from ischaemia/reperfusion injury. Here, we aimed at understanding the molecular mechanisms underlying this effect in stroke and studied p66(Shc) gene regulation in human ischaemic stroke. METHODS AND RESULTS: Ischaemia/reperfusion brain injury was induced by performing a transient middle cerebral artery occlusion surgery on wild-type mice. After the ischaemic episode and upon reperfusion, small interfering RNA targeting p66(Shc) was injected intravenously. We observed that post-ischaemic p66(Shc) knockdown preserved blood-brain barrier integrity that resulted in improved stroke outcome, as identified by smaller lesion volumes, decreased neurological deficits, and increased survival. Experiments on primary human brain microvascular endothelial cells demonstrated that silencing of the adaptor protein p66(Shc) preserves claudin-5 protein levels during hypoxia/reoxygenation by reducing nicotinamide adenine dinucleotide phosphate oxidase activity and reactive oxygen species production. Further, we found that in peripheral blood monocytes of acute ischaemic stroke patients p66(Shc) gene expression is transiently increased and that this increase correlates with short-term neurological outcome. CONCLUSION: Post-ischaemic silencing of p66(Shc) upon reperfusion improves stroke outcome in mice while the expression of p66(Shc) gene correlates with short-term outcome in patients with ischaemic stroke.

Quantitative morphometric patterns in cartilage and bone from the humeral heads of end-stage osteoarthritis patients.

OBJECTIVE: The purpose of this work is to investigate in a quantitative manner, the gross and regional structural patterns in cartilage and bone from the humeral head of end-stage OA patients, with the goal of identifying patterns of disease. Since the prevalence of primary OA of the shoulder is increasing as the population ages and the non-traumatic degenerative changes leading to this disease are poorly understood, a site-specific morphometric analysis speaks to the structure-function remodelling relationship of the pathological anatomy. METHODS: Humeral heads were harvested from twenty-one patients undergoing shoulder arthroplasty for end-stage primary OA. The samples were scanned with micro-computed tomography and magnetic resonance imaging (MRI), and registered to provide reconstructed 3D datasets of the cartilage, cortical and trabecular bone tissues. Gross visual examination of the datasets allowed samples to be classified as OA-like, osteoporosis (OP)-like or OA/OP-like. RESULTS: Volumes of interest (VOI) separating the OA-like samples into five distinct regions showed positive correlations between bone and cartilage morphometric parameters; specifically in areas where more cartilage has been lost, the underlying subchondral cortical bone was more porous and thicker, while the subchondral trabecular bone was more dense, including more connections and trabeculae. These differences were site-specific, where the central humeral head saw the greatest destruction of cartilage and bone sclerosis, followed by the anterior aspects. CONCLUSION: The ability to correlate bone and cartilage changes is valuable, as these structural cues may allow a more targeted diagnostic approach and a better classification of the disease, leading to improved therapies.

[Bilateral fractures of the humerus after hypoglycemic seizure]. / Bilaterale Humerusfrakturen nach Hypoglykämie.

HISTORY: An 87 year-old woman with insulin dependent diabetes was referred to our hospital because she had sustained a generalized tonic-clonic seizure. Initial blood sugar concentration before hospital admission was 1.1 mmol/l. INVESTIGATIONS: Conventional radiography and computed tomography of both shoulders confirmed the diagnosis of bilateral proximal fractures of the humerus with posterior dislocation. The cause of the seizure was found to be iatrogenic because timing of application of the dual-acting insulin medication had been wrongly changed, and the patient had developed severe hypoglycemia. TREATMENT AND COURSE: After administration of glucose and a 7-day course of antibiotics for aspiration pneumonia, both fractures were treated surgically with hemiarthroplasty. After a four-week stay in hospital the patient was discharged to her nursing home, requiring much more care than before. CONCLUSION: The presentation of simultaneous bilateral fractures of the humerus is a rare but severe and almost pathognomonic complications of generalized tonic-clonic seizures, for example in the context of marked hypoglycemia. Appropriate monitoring and treatment of blood sugar levels in diabetics must be emphasized.

[Avulsion fracture of the calcaneal tuberosity in athletes]. / Avulsionsfraktur der Tuberositas calcanei bei Athleten.

Avulsion fractures of the calcaneal tuberosity are rare injuries. Several surgical treatment options have been described. The size of the calcaneal fragment is the limiting factor in choosing the method for restoration. Finding the right type of fixation modality remains challenging in this rare kind of injury. In the case presented one Mitek Super Anchor was used to reattach the small fragment of the tuberosity to the calcaneus. Stable fixation with bony reunion and excellent functional outcome were achieved by this technique within 10 weeks. Therefore, we recommend the use of an anchor system for the treatment of small fragment calcaneal avulsion fractures.