Neuroprotective effect of 2-hydroxy arachidonic acid in a rat model of transient middle cerebral artery occlusion.

Stroke modifies the composition of cell membranes by eliciting the breakdown of membrane phospholipids whose products, such as arachidonic acid (AA), are released in the cytosol. The action of enzymes such as cyclooxygenases on AA leads to inflammatory stimuli and increases the cell oxidative stress. We report here the neuroprotective effect of 2-hydroxyarachidonic acid (2OAA), a cyclooxygenase inhibitor derived from AA, as a promising neuroprotective therapy against stroke. The effect of a single dose of 2OAA, administered intragastrically 1h after the ischaemic insult, in a rat model of transient middle cerebral artery occlusion (tMCAO) was tested after 24h of reperfusion. Infarct volume was measured by TTC method to evaluate the neuroprotective effect. Levels of phospholipids and neutral lipids were measured by thin-layer chromatography. The expression of cPLA2 and sPLA2 phospholipases responsible for the cleavage of membrane phospholipids, as well as the expression of antioxidant enzymes, was measured by qPCR. Lipid peroxidation was measured as the concentration of malondialdehyde and 4-hydroxynonenal. The treatment with 2OAA reduced the infarct volume and prevented ischaemia-induced increases in transcription levels of free fatty acid (FFAs), as well as in both phospholipases A2 (cPLA2 and sPLA2). The lipid peroxidation and the transcription levels of antioxidant enzymes induced by ischaemia were also decreased by this treatment. We conclude that 2OAA treatment results in a strong neuroprotective effect that seems to rely on a decrease in PLA2 transcriptional activity. This would reduce their action on the membrane phospholipids reducing reactive oxygen and nitrogen species generated by FFAs. Based on the transcriptional activity of the antioxidant enzymes, we conclude that the treatment prevents oxidative stress rather than promoting the antioxidant response. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá.

Outpatient parenteral antimicrobial therapy for infective endocarditis in patients over 80 years.

OBJECTIVE: The incidence of infective endocarditis is progressively increasing, especially in elderly patients. Outpatient parenteral antibiotic therapy (OPAT) is being an excellent alternative for treatment, but advanced age is one of the relative contraindications. The aim of this study is to compare the characteristics and prognosis of patients less or more than 80 years, treated with OPAT. METHODS: One hundred and ninety four patients were included between 1996 and 2015, 31 of them older than 80 years. RESULTS: The most frequently affected valve is the aortic one, mainly native valves. Most used antibiotics are ceftriaxone, ampicillin, cloxacillin and daptomycin. Differences in surgery (39.9% vs 9.7%, p=0.001) and use of infusion pump (55.2% vs 35.5%; p= 0.044) were observed, under 80 years and older respectively. No differences in readmissions and mortality were observed. CONCLUSIONS: OPAT could be considered an effective alternative for appropriately-selected elderly patients with infective endocarditis.