[Cell-Free and Concentrated Ascites Reinfusion Therapy for Malignant Intractable Ascites from Colorectal Cancer].

Malignant intractable ascites worsens not only patient symptoms but also their daily activities. It often leads to a patient discontinuing or postponing chemotherapy. In the present study, we introduced cell-free and concentrated ascites reinfusion therapy(CART)for malignant intractable ascites from colorectal cancer. Six patients underwent 12 CART treatments using AHF-WMO as the ascites filterand AHF-UP as the concentrator(Asahi Kasei Medical Co., Ltd.)from January 2014 to January 2017. The patients included 2 men and 4 women aged 67-89 years. Primary locations were 3 rectums, 1 transverse colon, 1 descending colon, and 1 cecum. Five patients had peritoneal dissemination, and 1 patient had liver metastasis. All the patients were administrated diuretics, but they were all refractory to the treatment. The median punctured ascites volume was 3,850 mL, and the ascites reinfusion after CART was 485 mL, the median concentration was 7.5. Only one patient had a fever. Performance status(PS)improved significantly after the treatment, and appetite score also improved. One patient was fit to undergo chemotherapy after the treatment. In summary, we found that CART is a safe and acceptable procedure for malignant intractable ascites in colorectal cancer patients.

Cremophor EL, a non-ionic surfactant, promotes Ca(2+)-dependent process of cell death in rat thymocytes.

Cremophor EL, a surfactant for pharmaceutical products, augments the cytotoxicity of hydrogen peroxide in rat thymocytes [Iwase, K., Oyama, Y., Tatsuishi, T., Yamaguchi1, J., Nishimura1, Y., Kanada, A., Kobayashi, M., Maemura, Y., Ishida, S., Okano, Y., 2004. Cremophor EL augments the cytotoxicity of hydrogen peroxide in lymphocytes dissociated from rat thymus glands. Toxicol. Lett. 154, 143-148]. The effect of cremophor EL on Ca(2+)-dependent process of cell death has been examined using a flow cytometer since hydrogen peroxide increases intracellular Ca2+ concentration. Cremophor EL at clinically-relevant concentrations greatly increased the population of dead cells in rat thymocytes simultaneously treated with A23187, a calcium ionophore increasing intracellular Ca2+ concentration. Removal of Ca2+ from external solution diminished the cremophor EL-induced increase in the dead cell population. Result suggests that Ca(2+)-dependent process is involved in the cremophor EL-induced decrease in the cell viability in the simultaneous presence of A23187. The population of cells with hypodiploidal DNA was not increased by the application of cremophor EL and A23187 although the cell viability was greatly decreased, indicating that the type of cell death is necrosis. It is suggested that cremophor EL at clinically-relevant concentrations augments the Ca(2+)-dependent process of necrosis.

Extract of Ginkgo biloba leaves attenuates kainate-induced increase in intracellular Ca2+ concentration of rat cerebellar granule neurons.

In order to reveal one of possible mechanisms for neuronal protective action of extract of Ginkgo biloba leaves (EGBL), the effect of EGBL on kainate- and KCl-induced increases in intracellular Ca(2+) concentration ([Ca(2+)]i) of rat cerebellar neurons was examined using a confocal laser microscope with appropriate fluorescent probes. EGBL at 3 microg/ml started to attenuate kainate-induced increase of [Ca(2+)]i and further increase in EGBL concentration (up to 30 microg/ml) concentration-dependently and significantly inhibited the kainate response. The complete inhibition by EGBL was observed in some neurons when the concentration was 10-30 microg/ml. The kainate-induced increase in [Ca(2+)]i was mainly due to Ca(2+) influx through voltage-dependent Ca(2+) channel opened by membrane depolarization via activation of kainate receptor-channel. However, the increase in [Ca(2+)]i by KCl was not significantly affected by EGBL at concentrations where the kainate response was greatly inhibited. EGBL consisting of flavone glycosides and terpene lactones is known to be an antioxidant. Furthermore, in this study, it is shown that EGBL exerts an inhibitory action on kainate receptor (a subtype of glutamate receptor). Since some of neurodegenerative diseases are due to cell death induced by glutamate excitotoxicity and oxidative stress, EGBL may be very suitable for preventing and/or treating such diseases.