Atorvastatin treatment is effective when used in combination with mefloquine in an experimental cerebral malaria murine model

<p>Abstract</p> <p>Background</p> <p>One of the major complications of <it>Plasmodium falciparum </it>infection is cerebral malaria (CM), which causes one million deaths worldwide each year, results in long-term neurological sequelae and the treatment for which is only partially effective. Statins are recognized to have an immunomodulatory action, attenuate sepsis and have a neuroprotective effect. Atorvastatin (AVA) has shown in vitro anti-malarial activity and has improved the activity of mefloquine (MQ) and quinine.</p> <p>Methods</p> <p>The efficiency of 40 mg/kg intraperitoneal AVA, alone or in association with MQ, was assessed in an experimental <it>Plasmodium berghei </it>ANKA rodent parasite model of CM and performed according to different therapeutic schemes. The effects on experimental CM were assessed through the evaluation of brain histopathological changes and neuronal apoptosis by TUNEL staining.</p> <p>Results</p> <p>AVA alone in the therapeutic scheme show no effect on survival, but the prophylactic scheme employing AVA associated with MQ, rather than MQ alone, led to a significant delay in mouse death and had an effect on the onset of CM symptoms and on the level of parasitaemia. Histopathological findings show a correlation between brain lesions and CM onset. A neuronal anti-apoptotic effect of AVA in the AVA + MQ combination was not shown.</p> <p>Conclusions</p> <p>The combination of AVA and MQ therapy led to a significant delay in mouse mortality. There were differences in the incidence, time to cerebral malaria and the level of parasitaemia when the drug combination was administered to mice. When used in combination with MQ, AVA had a relevant effect on the in vivo growth inhibition and clinical outcome of <it>P. berghei </it>ANKA-infected mice.</p

Fulminant adult-onset subacute sclerosing panencephalitis: a case report

We present the case of a young adult who developed acute encephalopathy with severe status epilepticus and rapid deterioration to vegetative state and death within 6 weeks. Although the clinical picture, MRI and EEG findings were atypical, the hypothesis of subacute sclerosing panencephalitis (SSPE) was suggested by markedly increased intrathecal IgG synthesis in the cerebrospinal fluid, and diagnosis was confirmed by the presence of high antimeasles antibodies in cerebrospinal fluid and brain biopsy findings. Acute SSPE is an exceptionally rare and little-known form of SSPE with protean symptomatology, and this case is to our knowledge the first observation of SSPE presenting with status epilepticus in adults. Our case reinforces the need to include, even in developed countries, SSPE as a diagnostic possibility in unexplained acute encephalopathies

The Masquelet induced membrane technique: towards the biological understanding of the clinical failure

International audienc

The Masquelet induced membrane technique: towards the biological understanding of the clinical failure

International audienc

Towards Understanding Therapeutic Failures in Masquelet Surgery: First Evidence that Defective Induced Membrane Properties are Associated with Clinical Failures

International audienceThe two-stage Masquelet induced-membrane technique (IMT) consists of cement spacer-driven membrane induction followed by an autologous cancellous bone implantation in this membrane to promote large bone defect repairs. For the first time, this study aims at correlating IMT failures with physiological alterations of the induced membrane (IM) in patients. For this purpose, we compared various histological, immunohistochemical and gene expression parameters obtained from IM collected in patients categorized lately as successfully (Responders; n = 8) or unsuccessfully (Non-responders; n = 3) treated with the Masquelet technique (6 month clinical and radiologic post-surgery follow-up). While angiogenesis or macrophage distribution pattern remained unmodified in non-responder IM as compared to responder IM, we evidenced an absence of mesenchymal stem cells and reduced density of fibroblast-like cells in non-responder IM. Furthermore, non-responder IM exhibited altered extracellular matrix (ECM) remodeling parameters such as a lower expression ratio of metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinases (TIMP-1) mRNA as well as an important collagen overexpression as shown by picrosirius red staining. In summary, this study is the first to report evidence that IMT failure can be related to defective IM properties while underlining the importance of ECM remodeling parameters, particularly the MMP-9/TIMP-1 gene expression ratio, as early predictive biomarkers of the IMT outcome regardless of the type of bone, fracture or patient characteristics

Meningeal chondroblastic osteosarcoma: case report and review of the literature

International audiencePrimary meningeal osteosarcomas are exceedingly rare. We report a case of a 51-year-old man with a chondroblastic osteosarcoma treated with pre-operative embolization, surgical removal, followed by adjuvant chemotherapy and radiation therapy. Patient is alive without any recurrence 43 months after diagnosis