Stimulation of Suicidal Erythrocyte Death by the Antimalarial Drug Mefloquine.

BACKGROUND: The antimalarial drug mefloquine has previously been shown to stimulate apoptosis of nucleated cells. Similar to apoptosis, erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include oxidative stress, increase of cytosolic Ca2+-activity ([Ca2+]i), and ceramide. METHODS: Phosphatidylserine abundance at the cell surface was estimated from annexin V binding, cell volume from forward scatter, reactive oxidant species (ROS) from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, [Ca2+]i from Fluo3- fluorescence, and ceramide abundance from specific antibody binding. RESULTS: A 48 h treatment of human erythrocytes with mefloquine significantly increased the percentage of annexin-V-binding cells (≥5 µg/ml), significantly decreased forward scatter (≥5 µg/ml), significantly increased ROS abundance (5 µg/ml), significantly increased [Ca2+]i (7.5 µg/ml) and significantly increased ceramide abundance (10 µg/ml). The up-regulation of annexin- V-binding following mefloquine treatment was significantly blunted but not abolished by removal of extracellular Ca2+. Even in the absence of extracellular Ca2+, mefloquine significantly increased annexin-V-binding. CONCLUSIONS: Mefloquine treatment leads to erythrocyte shrinkage and erythrocyte membrane scrambling, effects at least partially due to induction of oxidative stress, increase of [Ca2+]i and up-regulation of ceramide abundance.

Experiences in surgery of primary malignant brain tumours in the primary sensori-motor cortex practical recommendations and results of a single institution.

OBJECTIVE: Tumour resection in the Rolandic region is a challenge. Aim of this study is to review a series of patients malignant glioma surgery in the Rolandic region which was performed by combinations of neuronavigation, sonography, 5-aminolevulinic acid fluorescence guided (5-ALA) surgery and intraoperative electrophysiological monitoring (IOM). METHODS: 29 patients suffering malignant gliomas in the motor cortex (17) and sensory cortex (12) were analyzed with respect to functional outcome and grade of resections. RESULTS: Improvement of motor function was seen in 41.5% one week after surgery, 41.5% were stable, only 17% deteriorated. After three months patients had an improvement of motor function in 56%, of Karnofsky Score (KPS) 27% and sensory function was improved in 8%. Deterioration of motor function was seen in 16%, in sensory function 4% and in KPS 28% after three months. 25% showed no residual tumour in early post surgical contrast enhanced MRI. 10% had less than 2% residual tumour and 15% had 2-5% residual tumour. CONCLUSIONS: Preoperative functional neuroimaging, neuronavigation for planning the surgical approach and resection margins, intraoperative sonography and 5-ALA guided surgery in combination with the application of IOM shows that functional outcome and total to subtotal resection of malignant glioma in the Rolandic region is feasible.