High-content drug screening for rare diseases.

Per definition, rare diseases affect only a small number of subjects within a given population. Taken together however, they represent a considerable medical burden, which remains poorly addressed in terms of treatment. Compared to other diseases, obstacles to the development of therapies for rare diseases include less extensive physiopathology knowledge, limited number of patients to test treatments, and poor commercial interest from the industry. Recently, advances in high-throughput and high-content screening (HTS and HCS) have been fostered by the development of specific routines that use robot- and computer-assisted technologies to automatize tasks, allowing screening of a large number of compounds in a short period of time, using experimental model of diseases. These approaches are particularly relevant for drug repositioning in rare disease, which restricts the search to compounds that have already been tested in humans, thereby reducing the need for extensive preclinical tests. In the future, these same tools, combined with computational modeling and artificial neural network analyses, may also be used to predict individual clinical responses to drugs in a personalized medicine approach.

The Aquamantys® system as alternative for parenchymal division and hemostasis in liver resection for hepatocellular carcinoma: a preliminary study.

OBJECTIVE: To evaluate the clinical feasibility and safety of a new technique for liver resection using a new saline-coupled bipolar sealing device (Aquamantys®) that has shown high performance in the animal setting. PATIENTS AND METHODS: Twelve Child-Pugh A cirrhotic patients with hepatocellular carcinoma underwent partial hepatectomies using Aquamantys®. Our primary end-point was to observe occurrence of early specific surgical complications as bleeding, biliary leakage and abscess development. Our secondary end-point was to evaluate local recurrence along resection margin after a minimum follow-up of 1 year. RESULTS: One bisegmentectomy, five monosegmentectomies and six atypical resections were performed. Mean resection time was 45 minutes (range, 30-100 min). Mean blood loss was 20 mL (range 5-80 mL). Mean post-operative stay was 6 days (range 5-16 days). All specimens presented negative margins (R0) at pathological examination. No blood transfusion were required both intra-operatively and post-operatively. No mortality was observed within 30-days post-operatively. One fluid collection occurred after  6-7 bisegmentectomy and was successfully treated by ultrasound-guided percutaneous drainage. At 1 year follow-up two patients died: one because of new lesions into the liver and one because of distant metastases and multifocal new liver disease. Ten patient are alive disease free at 1 year follow-up. CONCLUSIONS: Liver resection using Aquamantys® is feasible and safe and allows to achieve almost bloodless parenchymal division with minimal necrosis and negative margins even in atipycal resection. Comparative trials are needed to confirm our preliminary results.

Effect of fish oil on neutrophil chemiluminescence induced by different stimuli in patients with rheumatoid arthritis.

Lipid composition plays an important part in the structural and metabolic functions of cell membranes. In particular the production of inflammatory mediators such as prostaglandins and leukotrienes is dependent on polyunsaturated fatty acid precursors. Neutrophil leucocytes participate in inflammatory processes by their phagocytic and killing activities which can be monitored by measuring the photon emission (chemiluminescence). Chemiluminescence was measured in a luminol dependent system after stimulation by either particulate (zymosan) or soluble (phorbol myristate acetate) stimulus in a group of 10 patients with rheumatoid arthritis before and 21 and 45 days after treatment with a diet supplemented with eicosapentaenoic and docosahexaenoic acids. Ten patients with rheumatoid arthritis continuing their usual diet were used as control subjects. A progressive reduction of chemiluminescence stimulated by zymosan and phorbol myristate acetate was found in the patients treated with fish oil supplementation. This result correlated well with the reduction in erythrocyte sedimentation rate and an improvement of clinical parameters. The effects of fish oil derived lipids on neutrophil chemiluminescence are probably due to a change of the lipid composition of the cell membrane which is dependent on the esterification of eicosapentaenoic acid and docosahexaenoic acid in cellular membrane phospholipids. The modification of membrane lipid composition seems to interact in a non-specific way with the metabolic activation of neutrophils during phagocytosis.