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Abstract: Interleukin-2 (IL-2) is a lymphokine with a potential role in cancer therapy. Many clinical trials of recombinant human IL-2 (rhIL-2) have been conducted to treat malignant renal carcinoma, melanoma, leukemia, lymphoma, multiple myeloma. BMI Korea has developed a method to manufacture rhIL-2 in bulk using Escherichia coli as a biosimilar. Prior to conducting human clinical trials, 4-week repeated toxicity study of rhIL-2 was conducted. In this study, rhIL-2 was administered intravenously to rats at doses of 9×106, 18×106, and 36×106 IU/kg/day over a period of 4weeks. Adverse effects were observed in RBC, HGB, HCT, reticulocyte, mesenteric lymph node from middle dose, and changes of total bilirubin, femoral bone marrow, thymus, and clinical signs were observed at high dose. Local irritation was determined at low dose of female rats and at middle dose of male ones. Taken together, no observed adverse effect levels (NOAEL) was determined at dose of 9×106 IU/kg/day in male, and NOAEL was determined under the dose level in female rats. It suggests that present rhIL-2 is less toxic prior produced rhIL-2 and may be contribute more effective cancer-treatment strategy in human. [Copyright &y& Elsevier]

The Ostwald ripening phenomenon, an instability observed in essential oil emulsions, could be controlled by modifying the oil composition. Herein, this study evaluated what types of triglycerides used to modify the oil composition may be more effective in inhibiting Ostwald ripening, and also determined how the interfacial properties of the emulsions affected the efficacy of triglycerides in inhibiting Ostwald ripening. Emulsions were stabilized by emulsifiers with differently sized hydrophilic groups, which correlate to the thickness of the interfacial region, and their oil compositions were varied by mixing triglycerides. Significant increase in droplet size was observed in emulsions prepared using only orange oil during storage. Modifying oil composition by adding medium-chain triglycerides (MCT) or long-chain triglycerides (LCT; corn oil in this study) inhibited droplet growth, and adding triglycerides over 20% into the oil phase prohibited Ostwald ripening. LCT was less efficacious in inhibiting Ostwald ripening than MCT for the same content. • Ostwald ripening was affected by the emulsifier type able to attribute interfacial properties. • Incorporation of triglycerides over 20% into oil phase perfectly prevented Ostwald ripening. • Ostwald ripening was inhibited more effectively by MCT than LCT for the same content. [ABSTRACT FROM AUTHOR]

Endothelial cell injury and dysfunction caused by reactive oxygen species (ROS) are implicated in the pathogenesis of vascular diseases. ROS are generated and hypoxanthine is degraded by xanthine oxidase. Smoking and alcohol consumption are associated with an increased level of hypoxanthine. We aimed to study the direct role of hypoxanthine in endothelial dysfunction in human umbilical vascular endothelial cells (HUVECs). Hypoxanthine induced cell death and production of ROS. Furthermore, hypoxanthine induced apoptosis through regulation of protein expression related to apoptosis. When cells were pretreated with N -acetylcysteine or a pancaspase inhibitor (Z-VAD-fmk) and stimulated with hypoxanthine, Z-VAD-fmk and N -acetylcysteine prevented hypoxanthine-induced apoptosis by inhibiting the ROS production and caspase pathway. Thus, an increased extracellular concentration of hypoxanthine induces endothelial dysfunction through ROS production and regulates expression of apoptosis-related proteins in HUVECs. These effects are expected to be associated with some vascular diseases. [ABSTRACT FROM AUTHOR]