Cationic Albumin‐Conjugated Chelating Agent as a Novel Brain Drug Delivery System in Neurodegeneration

The critical role of metal ions and in particular iron in oxidative stress and protein aggregation offers chelation therapy as a sensible pharmaceutical strategy in oxidative stress‐induced neuronal damages. In this research, we conjugated an iron‐chelating agent, deferasirox, to cationized human serum albumin molecules in order to develop a novel brain delivery system for the management of neurodegenerative disorders due to the significant role of oxidative stress‐induced neuronal injury in such diseases. Cationized albumin is known to be able to transport to brain tissue via adsorptive‐mediated transcytosis. The developed structures were molecularly characterized, and their conjugation ratio was determined. PC12 cell line was utilized to evaluate the neuroprotective features of these newly developed molecules in the presence of hydrogen peroxide neuronal damage and to identify the mechanisms behind the observed neuronal protection including apoptotic and autophagic pathways. Furthermore, a rat model of Alzheimer's disease was utilized to evaluate the impact of conjugated structures in vivo. Data analysis revealed that the conjugated species were able to hinder apoptotic cell death while enhancing autophagic process. The developed conjugated species were also able to attenuate amyloid beta‐induced learning deficits when administered peripherally.     

Randomized controlled trial of bilateral intrapleural block in cardiac surgery

The aim of this study was to determine the efficacy of bilateral intrapleural block with bupivacaine as a preemptive analgesic for postoperative pain in coronary artery bypass graft surgery. In a double-blind prospective clinical trial, 70 patients were randomly divided into a bupivacaine group (20 mL bupivacaine 0.25% and 0.5 mL adrenaline 1/200,000 each side) and a control group (20.5 mL normal saline each side). Evaluation of the severity of pain was performed using the visual analog scale at 12 and 24 h after entering the intensive care unit and again during chest tube removal. Pain scores at 12 and 24 h after intensive care unit admission were significantly lower in the bupivacaine group. There were no side-effects related to intrapleural block, such as pneumothorax or emphysema. In coronary artery bypass graft candidates, preemptive analgesia with bilateral intrapleural block using bupivacaine provided relatively less painful conditions during the first 24 h after surgery, but it did not improve the clinical outcome.     

Liver Histology Changes in Nonalcoholic Steatohepatitis after One Year of Treatment with Probucol

BACKGROUND: Probucol, a lipid-lowering agent with antioxidant effects, is effective in normalizing liver enzymes in patients with nonalcoholic steatohepatitis (NASH). We studied changes in the liver histology of patients with NASH after use of probucol for one year. METHODS: Ten patients with biopsy-proven NASH were included. Subjects were given 500 mg probucol daily. Liver biopsies were performed before treatment and after one year. RESULTS: Eight patients completed treatment. The mean alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels decreased from 94 and 55 to 41 and 26, respectively (P = 0.004 and 0.001 respectively). The scores for hepatic steatosis and necroinflammation decreased from 7.4 to 5.6 (P = 0.03). The fibrosis score changed from 1.1 to 1.3 (P = 0.79). No adverse drug effects were observed. CONCLUSION: Probucol is effective in normalizing aminotransferase levels in patients with NASH. It also significantly reduces the histology grade of steatohepatitis after one year of treatment.