Targeting the kynurenine pathway-related alterations in Alzheimer's disease: a future therapeutic strategy

Alzheimer's disease (AD) is a chronic neurodegenerative disorder associated with dementia as a main feature. Despite decades of thorough research in the field of AD, the pathomechanism is still not fully understood. The development of novel experimental models can help us in the discovery of both genetic and non-genetic components of disease pathogenesis. As currently available therapies in AD can provide merely moderate or only temporary symptomatic relief, there is a great demand for the development of new drugs with higher therapeutic potential. Some of the candidates would be those targeting the kynurenine pathway, the neuroactive metabolites of which are surely involved in both neurodegeneration and neuroprotection, mainly in relation with glutamate excitotoxicity and oxidative stress. Both analogs of the neuroprotective kynurenic acid and small molecule enzyme inhibitors preventing the formation of neurotoxic compounds may have potential therapeutic significance. However, there is a great need for new strategies to improve efficacy, transport across the blood-brain barrier and bioavailability, naturally with simultaneous minimization of the adverse side-effects.     

Hémovigilance et sécurité transfusionnelle en opération extérieure

The French military blood institute (FMBI) is the only military blood supplier in France. FMBI operates independently and autonomously under the Ministry of Defense's supervision, and accordingly, to the French, European and NATO technical and safety guidelines. FMBI is in charge of the collection, preparation and distribution of blood products to supply transfusion support to armed forces, especially during overseas operations. In overseas military, a primary physician is responsible for haemovigilance in permanent relation with an expert in the FMBI to manage any adverse reaction. Additionally, traceability of delivered or collected blood products during overseas operation represents a priority, allowing an appropriate management of transfusion inquiries and assessment of practices aiming to improve and update procedures and training. Transfusion safety in overseas operation is based on regular and specific training of people concerned by blood supply chain in exceptional situation.     

Soft tissue coverage using pedicled flap in combat zone:A case series

Background:Soft tissue reconstruction is typically conducted after evacuation from theater of operations.If circumstances do not allow timely evacuation,however,defect site may need to be reconstructed in the combat zone.Case presentation:A total of 41 patients with extremity soft tissue defect were treated using pedicled flaps by a single orthopedic surgeon during four deployments in Chad,Afghanistan and Mali between 2010 and 2017.The mean age was 25.6 years.A total of 46 injury sites in extremities required flap coverage:19 combat-related injuries (CRIs)and 27 non-combat related injuries (NCRIs).Twenty of the injury sites were infected.Overall,63 pedicled flap transfers were carried out:15 muscle flaps,35 local fasciocutaneous flaps and 13 distant fasciocutaneous flaps.The flap types used did not differ for CRIs or NCRIs.Mean follow-up was 71 days.Complications included deep infection (n=6),flap failure (n=1) and partial flap necrosis (n=1).Limb salvage rate was 92.7％ (38/41).Conclusions:Soft tissue defect can be managed with simple pedicled flaps in theatre of operations if needed.Basic reconstructive procedures should be part of the training for military orthopedic surgeons.Trial registration:Retrospectively registered in January2019 (2019-0901-001).     

Radio-neuroprotective effect of L-alpha-glycerylphosphorylcholine (GPC) in an experimental rat model

Ionizing radiation plays a major role in the treatment of brain tumors, but side-effects may restrict the efficacy of therapy. In the present study, our goals were to establish whether the administration of L-alpha-glycerylphosphorylcholine (GPC) can moderate or prevent any of the irradiation-induced functional and morphological changes in a rodent model of hippocampus irradiation. Anesthetized adult (6-weeks-old) male Sprague–Dawley rats were subjected to 40 Gy irradiation of one hemisphere of the brain, without or with GPC treatment (50 mg/kg bw by gavage), the GPC treatment continuing for 4 months. The effects of this partial rat brain irradiation on the spatial orientation and learning ability of the rats were assessed with the repeated Morris water maze (MWM) test. Histopathologic (HP) evaluation based on hematoxylin-eosin and Luxol blue staining was performed 4 months after irradiation. The 40 Gy irradiation resulted in a moderate neurological deficit at the levels of both cognitive function and morphology 4 months after the irradiation. The MWM test proved to be a highly sensitive tool for the detection of neurofunctional impairment. The site navigation of the rats was impaired by the irradiation, but the GPC treatment markedly decreased the cognitive impairment. HP examination revealed lesser amounts of macrophage density, reactive gliosis, calcification and extent of demyelination in the GPC-treated group. GPC treatment led to significant protection against the cognitive decline and cellular damage, evoked by focal brain irradiation at 40 Gy dose level. Our study warrants further research on the protective or mitigating effects of GPC on radiation injuries.