Search

Vortex levitation can achieve non-contact handling by blowing air into a vortex cup through a tangential nozzle to generate a swirling flow. In this paper, we focused on the relationship between the sucking pressure and the flow dynamics when gap distance from the cup to a work piece changes. Then simultaneous measurement of a pressure and a flow field in the cup was performed. As a result, the mean pressure changes and the pressure fluctuation inside the cup enhances with increasing gap height. Especially, periodic pressure perturbation is observed with wide gap height and it synchronizes with an eccentric rotation of the swirling flow. It is also found that the rotation axis of swirling flow steadily inclines against the central axis of the cup for appropriate gap height., Article, JOURNAL OF VISUALIZATION. 13(4):319-326 (2010)

The objective is to confirm if the prediction of the drug-drug interaction using a physiologically based pharmacokinetic (PBPK) model is more accurate. In vivo Ki values were estimated using PBPK model to confirm whether in vitro Ki values are suitable.The plasma concentration-time profiles for the substrate with coadministration of an inhibitor were collected from the literature and were fitted to the PBPK model to estimate the in vivo Ki values. The AUC ratios predicted by the PBPK model using in vivo Ki values were compared with those by the conventional method assuming constant inhibitor concentration.The in vivo Ki values of 11 inhibitors were estimated. When the in vivo Ki values became relatively lower, the in vitro Ki values were overestimated. This discrepancy between in vitro and in vivo Ki values became larger with an increase in lipophilicity. The prediction from the PBPK model involving the time profile of the inhibitor concentration was more accurate than the prediction by the conventional methods.A discrepancy between the in vivo and in vitro Ki values was observed. The prediction using in vivo Ki values and the PBPK model was more accurate than the conventional methods.

We investigated the tissue distribution of a humanized anti-human Fas monoclonal antibody, R-125224, in SCID mice transplanted with synovial tissues from patients with rheumatoid arthritis (SCID-HuRAg mice). The binding kinetics of R-125224 was also determined, using isolated human synovial cells.Tissue distribution was assessed at 1, 24 and 168 h after intravenous administration of (125)I-R-125224 to SCID-HuRAg mice (0.4 mg/kg). The in vitro binding of (125)I-R-125224 to isolated human synovial cells was investigated.After intravenous administration of (125)I-R-125224 to SCID-HuRAg mice, the radioactivity distributed to various tissues at 1 h. Thereafter, the radioactivity in the tissues gradually decreased except for the transplanted synovial tissues, in which the radioactivity increased in a time-dependent manner, and at 168 h, the tissue/plasma concentration ratio was about 1. The in vitro binding affinity of (125)I-R-125224 to human synovial cells was high with a dissociation constant of 1.32 +/- 0.62 nM and the binding was inhibited by non-labeled R-125224 in a concentration-dependent manner.R-125224, a candidate compound for treating rheumatoid arthritis, specifically distributed to the pharmacological target site, human synovium transplanted in SCID mice, with high affinity.

Purpose. To evaluate an interaction between simvastatin and itraconazole in in vitro studies and to attempt a quantitative prediction of in vivo interaction in humans.

Despite the growing number of major surgical procedures being performed for patients on maintenance hemodialysis, few reports focus on the management and outcome of such patients, especially those undergoing major abdominal surgery. We conducted a retrospective review of 30 patients on maintenance hemodialysis who underwent abdominal surgery, 20 of whom underwent an elective operation and 10, an emergency operation. The indications of elective surgery included gastrointestinal cancer, biliary tract disease, and abdominal aortic aneurysm, while those for emergency surgery mainly involved gastrointestinal perforation or bleeding. There were no statistically significant differences between the elective group and the emergency group regarding either the mean time on hemodialysis or the preoperative clinical data. The morbidity and mortality rates were 15% and 10%, respectively, for the patients who underwent elective surgery and 50% and 70%, respectively, for those who underwent emergency surgery (P

RS-1541 is a 13-O-palmitoyl derivative of rhizoxin, an inhibitor of tubulin polymerization. RS-1541 has been shown to bind preferentially to plasma lipoproteins and to exhibit selective and sustained uptake by tumors in mice. To elucidate a mechanism of RS-1541 cytotoxicity, the cellular uptake and the cytotoxicity of a complex of RS-1541 with human low-density lipoprotein (RS-1541/LDL complex) were investigated in cultured St-4 human gastric cancer cells. Both the cellular uptake and the cytotoxicity of the RS-1541/LDL complex were greater in cells with higher LDL-receptor activities than in control cells. Excess amounts of LDL or 1 microM of monensin, a proton ionophore, significantly inhibited both the uptake and the cytotoxicity of the complex. Chloroquine, an inhibitor of lysosomal enzymes, decreased the intracellular level of rhizoxin liberated from RS-1541 and suppressed the cytotoxicity of the RS-1541/LDL complex. However, a detergent-aided solution of RS-1541 showed very low cellular uptake and cytotoxicity, irrespective of the LDL-receptor activities of these cells. These results demonstrate that the RS-1541/LDL complex is incorporated into the cells via the LDL receptor and that it manifests its cytotoxic activity after forming rhizoxin, the original antitumor agent, in the lysosomes.

RS-1541 is a 13-O-palmitoyl derivative of rhizoxin, an inhibitor of tubulin polymerization. After intravenous administration of RS-1541 to mice bearing M5076 sarcoma, the maximal inhibitory effect of RS-1541 on DNA synthesis in the tumor was observed 24 h after administration, in agreement with the Cmax of rhizoxin produced from RS-1541, but not with the Cmax of RS-1541. The inhibitory effect after RS-1541 was much higher than that after rhizoxin itself. In the spleen, thymus and bone marrow, DNA synthesis was strongly inhibited by rhizoxin but not by RS-1541. After administration of RS-1541, no significant amounts of rhizoxin were detected in the tissues, except for the tumor. In acute toxicity tests, RS-1541 appeared to be less toxic than rhizoxin. These results indicate that RS-1541 possesses a high tumor-selective effect compared with rhizoxin, because of the selective production of rhizoxin in the tumor after administration of RS-1541.

The single dose pharmacokinetics of temocapril, a prodrug type angiotensin converting enzyme (ACE) inhibitor with a thiazepin ring, were studied in nephrectomised rats and compared with those of enalapril. The nephrectomised rats had much higher serum levels of creatinine (1.1 mg/dl) and blood urea nitrogen (73.5 mg/dl) than the control rats (0.6 and 18.6 mg/dl, respectively). Concentrations of RS-5139 and enalaprilat, the active metabolites of temocapril and enalapril, respectively, in the plasma, bile and urine were measured by the ACE inhibition assay or a gas chromatography-mass spectrometry system (GC/MS). There was no significant difference in the maximum plasma concentrations (Cmax) of RS-5139 between the nephrectomised (243.3 μg/L) and control rats (342.8 μg/L). On the other hand, the Cmax of enalaprilat in nephrectomised rats was significantly higher (399.3 μg/L) than in the control group (158.6 μg/L; p