We investigated the utility of three-dimensional (3D) spheroid cultures of human hepatocytes in discovering drug metabolites. Metabolites of acetaminophen, diclofenac, lamotrigine, midazolam, propranolol and salbutamol were analyzed by liquid chromatography-tandem mass spectrometry (LC/MS/MS) to measure enzyme activities in this system cultured for 2 and 7 days. Sequential metabolic reactions by Phase I and then Phase II enzymes were found in diclofenac [CYP2C9 and UDP-glucuronyltransferases (UGTs)], midazolam (CYP3A4 and UGTs) and propranolol (CYP1A2/2D6 and UGTs). Moreover, lamotrigine and salbutamol were metabolized to lamotrigine-N-glucuronide and salbutamol 4-O-sulfate, respectively. These metabolites, which are human specific, could be observed in clinical studies, but not in conventional hepatic culture systems as in previous reports. Acetaminophen was metabolized to glucuronide and sulfate conjugates, and N-acetyl-p-benzo-quinoneimine (NAPQI) and its metabolites were not observed. In addition, mRNA of drug-metabolism enzymes [CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, UGT1A1, UGT2B7, sulfotransferase 1A1 (SULT1A1) and glutathione S-transferase pi 1 (GSTP1)], which were measured by qRT-PCR, were expressed in the human hepatocyte spheroids. In conclusion, these results suggest that human hepatocyte spheroids are useful in discovering drug metabolites.

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We investigated ship navigation records known as Automatic Identification System (AIS) data near the source region of the 2011 Tohoku, Japan, tsunami. The AIS data of 16 ships in the offshore navigation could be compiled by about 40 min after the tsunami generation. Most of the AIS data showed notable deviation of the ship heading from the course over ground during the tsunami passage. There was good agreement in terms of amplitude/phase between the ship velocity and the simulated tsunami velocity in the direction normal to the ship heading. An equation of motion due to wave drag and inertia forces was examined for an offshore movable floating body. We explain that the ship movement in the direction normal to the heading immediately responds to the tsunami current, and relative velocity between the ship and the tsunami current asymptotically become zero. This indicates the movement velocity of navigating ships in the direction normal to the heading derived from AIS data will work as an offshore tsunami current meter. We examined the AIS data during the 2011 Tohoku tsunami and showed these data could be useful for tsunami source estimation and forecast. The AIS data in the current framework will possibly be a crowd-sourced tool for monitoring offshore tsunami current and tsunami forecast.

This study demonstrates that boronic acid-containing polymers coated onto solid support function as synthetic mitogens for mouse lymphocytes. The polymer was synthesized by radical copolymerization of 3-acrylamidophenylboronic acid with dimethylacrylamide (poly(AAPBA-DMAA)). The boronic acid in the trigonal form in the copolymer activated lymphocytes, probably by crosslinkage to glycoprotein moieties on the plasma membrane surface, as in the case of lectin stimulation. A higher concentration of phenylboronic acid on the copolymer surface resulted in greater activation of lymphocytes, suggesting that the number of phenylboronic acid residues per unit area may be a crucial factor in lymphocyte proliferation. The proliferative response of lymphocytes was also affected by the surface wettability, probably due to a difference in the flexibility of polymer strands at the cell-polymer interface.