Oxaliplatin is widely used as a key drug in the treatment of colorectal cancer. However, its administration is associated with the dose-limiting adverse effect, peripheral neuropathy. Platinum accumulation in the dorsal root ganglion (DRG) is the major mechanism responsible for oxaliplatin-induced neuropathy. Some drug transporters have been identified as platinum complex transporters in kidney or tumor cells, but not yet in DRG. In the present study, we investigated oxaliplatin transporters and their contribution to peripheral neuropathy. We identified 12 platinum transporters expressed in DRG with real-time PCR, and their transiently overexpressing cells were established. After exposure to oxaliplatin, the accumulation of platinum in these overexpressing cells was evaluated using a coupled plasma mass spectrometer. Octn1/2-and Mate1-expressing cells showed the intracellular accumulation of oxaliplatin. In an animal study, peripheral neuropathy developed after the administration of oxaliplatin (4 mg/kg, intravenously, twice a week) to siRNA-injected rats (0.5 nmol, intrathecally, once a week) was demonstrated with the von Frey test. The knockdown of Octn1 in DRG ameliorated peripheral neuropathy, and decreased platinum accumulation in DRG, whereas the knockdown of Octn2 did not. Mate1 siRNA-injected rats developed more severe neuropathy than control rats. These results indicate that Octn1 and Mate1 are involved in platinum accumulation at DRG and oxaliplatininduced peripheral neuropathy.

The entrapment of α-chymotrypsin (α-CT) within 70-140 nm liposomes formed from POPC (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) leads to an unexpected and remarkable increase in the thermal stability of the enzyme. This finding is based on the observation that heating aqueous suspensions of α-CT-containing POPC liposomes to 80 °C for 30 minutes resulted in partial enzyme inactivation, whereas the same treatment of aqueous solutions of free α-CT inactivated the enzyme completely. The stabilizing effect of enzyme confinement in the attoliter volumes of the liposomes was found to increase with decreasing numbers of α-CT molecules per liposome. Single-enzyme confinement was particularly effective, as intermolecular interactions between heat-denatured α-CT molecules (causing irreversible inactivation) are not possible.

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This study investigated the local characteristics of void-fraction distribution and heat transfer around tubes in two-phase flows under adiabatic conditions using vertical duct test sections with inner dimensions of 90 × 90 mm 2. Two kinds of test sections, in-line and staggered tube bundles, each containing five columns and eight rows, were employed for the measurements. The tube diameter of each was 15 mm, and the pitch-to-diameter ratio was 1.5 for both bundles. The working fluids were air and water, and the experiments were performed under atmospheric pressure in a temperature range of 20-25 ºC. Superficial liquid velocity, J L , and gas velocity, J G , ranged from 0.1 to 0.3 m/s and 0.03 to 1.19 m/s, respectively. Two-dimensional void-fraction distributions were obtained using X-ray radiography and the local heat-transfer coefficients were measured using a platinum wire electrode placed on a tube that could be rotated. In the experiments, the time-averaged void fraction increased at the maximum and vertical minimum gaps for the in-line tube bundle, whereas the void fraction increased upstream of the tubes for the staggered tube bundle. In the bubbly flow condition, enhancement of the heat transfer by bubbles motion clearly occurred between ±90 and 180° for the in-line tube bundle, and increased all over the pipe for the staggered tube bundle. The increase in the local heat transfer coefficients by bubbles motion was more apparent for the in-line tube bundle. The average heat transfer coefficient in the staggered tube bundle was higher than that in the in-line tube bundle in the bubbly flow regime, whereas the results were opposite in the intermittent flow regime.

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