Search

Chemotherapy-induced peripheral neurotoxicity is a common dose-limiting side effect of several cancer chemotherapeutic agents, and no effective therapies exist. Here we constructed a systems pharmacology model of intracellular signaling in peripheral neurons to identify novel drug targets for preventing peripheral neuropathy associated with proteasome inhibitors. Model predictions suggested the combinatorial inhibition of TNFα, NMDA receptors, and reactive oxygen species should prevent proteasome inhibitor-induced neuronal apoptosis. Dexanabinol, an inhibitor of all three targets, partially restored bortezomib-induced reduction of proximal action potential amplitude and distal nerve conduction velocity in vitro and prevented bortezomib-induced mechanical allodynia and thermal hyperalgesia in rats, including a partial recovery of intraepidermal nerve fiber density. Dexanabinol failed to restore bortezomib-induced decreases in electrophysiological endpoints in rats, and it did not compromise bortezomib anti-cancer effects in U266 multiple myeloma cells and a murine xenograft model. Owing to its favorable safety profile in humans and preclinical efficacy, dexanabinol might represent a treatment option for bortezomib-induced neuropathic pain.

Background: Increased costs and mortality associated with inappropriate blood transfusions have led to investigations about blood request and blood transfusion techniques. We investigated the transfusion status in patients who underwent orthopedic surgery in Poursina Hospital (Rasht, Iran) to optimizing blood usage and determine if a scheduled transfusion program for every orthopedic surgery could improve blood transfusion management., Method: In this descriptive-prospective study, all orthopedic surgeries in Poursina Hospital, Rasht, between April to June 2013 were reviewed. All patient information was recorded, including: demographics, type of surgery, hemoglobin level, cross-match test, duration of surgery, and blood loss, and transfusion. Based on the one-way ANOVA and independent samples test analysis, cross-match to transfusion ratio and transfusion possibility, the transfusion index, and maximal surgical blood order schedule were calculated to determine blood transfusion status., Results: Among 872 selected orthopedic surgery candidates, 318 of them were cross-matched and among those, 114 patients received a blood transfusion. In this study, the cross-match to transfusion ratio was 6.4, transfusion possibility 36.47%, transfusion index 0.6, and maximal surgical blood order schedule 0.9., Conclusion: We found that blood ordering was moderately higher than the standard; so it is highly recommended to focus on the knowledge of evidence based on transfusion and standard guidelines for blood transfusion to avoid over-ordering.