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Biomedical subjects

Masahiro Koike

Publications and source records attributed to Masahiro Koike.

7 recordsLinked to original sources

Infrared absorption change in single-walled carbon nanotubes observed by combination spectroscopy of synchrotron radiation and laser.

The Drude tail due to photo-excited carriers in single-walled carbon nanotubes (SWNTs) has been observed in the mid-infrared region by using combination spectroscopy of synchrotron radiation and Ti:sapphire laser. It is found that the density of photo-excited carriers increases as the sample temperature is raised from 12 to 300 K, and their lifetime is of the order of minutes at 300 K. These facts suggest that the movement of photo-excited carriers is largely affected by some extrinsic defect, thus resulting in the long-lasting Drude reflection in SWNTs.

Absorption↗

[Examination of three-detector high-speed-rotation SPECT acquisition under breathhold in body: clinical application of 99mTc-MAA].

In traditional pulmonary perfusion single photon emission computed tomography (SPECT), respiratory lung motion and cyclically varying changes in lung volume during image acquisition inherently degrade the image sharpness of ill-defined perfusion defects. However, because of the lack of an adequate fast imaging technique, perfusion SPECT has never been acquired under breathhold conditions, whereas breathhold images are commonly used for pulmonary magnetic resonance (MR) and computed tomographic (CT) images. Although a high-speed imaging technique combined with a multidetector SPECT system may enable SPECT images to be obtained during a short period of breathholding, image quality would be degraded owing to decreased radioactivity counts and increased statistical noise. To resolve this problem, we developed an innovative SPECT imaging technique using a triple-head SPECT system and the high-speed-detector rotation-multiplied projection (HSRMP) technique, where a single SPECT image was reconstructed from multiple respiratory dimensional breathhold projection data obtained at the same angle. HSRMP provided noiseless high-quality perfusion SPECT images by compensating for decreased radioactivity counts caused by high-speed imaging, and significantly improved image quality and perfusion defect clarity compared with traditional non-breathhold SPECT images.

Female↗

Assessment of the hepatic and intestinal first-pass metabolism of midazolam in a CYP3A drug-drug interaction model rats.

In the current study, to understand the characteristics of dexamethasone (DEX)-treated female rats as an animal model for drug-drug interactions, a double-cannulation method was applied and separately assessed for the intestinal and hepatic first-pass metabolism of midazolam. Midazolam was administered intravenously or orally to the animals, and midazolam concentrations in the portal and systemic plasma were simultaneously determined. Next, the rates of elimination from the intestine and liver were estimated using the AUC values. After oral administration of midazolam, the entire drug was absorbed without intestinal first-pass metabolism, and 93% of the administered midazolam was extracted in the liver of the DEX-treated female rats. Seven per cent of the midazolam administered reached the systemic circulation. When ketoconazole was given orally to the animals, in conjunction with midazolam, the extraction ratio in the liver decreased from 93% to 77% in the control rats, and the bioavailability of midazolam increased to 23%. On the other hand, after intravenous administration, the elimination half-life of midazolam was not changed by ketoconazole pretreatment. These results indicated that midazolam is only extracted in the liver of DEX-treated female rats and that ketoconazole inhibits the hepatic first-pass metabolism, but not the systemic metabolism. In conclusion, DEX-treated female rats can be used as a drug-drug interaction model via CYP3A4 enzyme inhibition, especially for the hepatic first-pass metabolism of orally administered drugs.

Animals↗

Mechanism of the drug interaction between valproic acid and carbapenem antibiotics in monkeys and rats.

The Ministry of Health and Welfare, Japan banned coadministration of carbapenems, such as panipenem/betamipron (PAPM), meropenem (MEPM), and valproic acid (VPA) because clinical reports have indicated that the coadministration caused seizures in epileptic patients due to lowered plasma levels of VPA. In this study, we have clarified the mechanism of the drug-drug interaction using PAPM, MEPM, and doripenem [S-4661; (+)-(4R,5S,6S)-6-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-3-[[(3S,5S)-5-[(sulfamoylamino)methyl]-3-pyrrolidinyl]thio]-1-azabicyclo[3.2.0]hept-2-ene-2-caboxylic acid monohydrate], a newly synthesized carbapenem. In vitro experiments using monkey liver slices suggested that the apparent synthetic rate of VPA glucuronide (VPA-G) increased in the presence of carbapenems. However, no such increase was observed in the experiment using monkey liver microsomes. Although no increase of uridine 5'-diphosphate D-glucuronic acid was found in monkey liver slices in the presence of carbapenems, potent inhibitory activity of carbapenems for the hydrolysis of VPA-G was found in monkey and rat liver homogenate. In vivo hydrolysis of VPA-G was clearly shown by the existence of VPA in plasma after dosing of VPA-G to rats, and its inhibition by carbapenems was also clearly shown by the negligible levels of VPA in rat plasma after coadministration of carbapenems and VPA-G. These results clearly indicate one of the important causes of drug interaction as follows: carbapenems would inhibit the hydrolytic enzyme, which is involved in the hydrolysis of VPA-G to VPA, resulting in a decrease of plasma concentration of VPA.

Animals↗

Study on the practical use of quantitative whole-body auto-radioluminography.

The practical use of quantitative radioluminography (RLG) using reading system BAS 2000 (Fuji Photo Film Ltd., Tokyo, Japan) and STORM 820 (Molecular Dynamics, USA) was examined using a chemical matrix as an internal standard, which offers the benefits of being preservative, inexpensive, and easy to handle. The results were as follows: 1. As the water content is within the range of 65-80% for most organs and tissues, we selected a chemical matrix, Tissue-TEK containing 85% water, as a base for the preparation of a standard curve. 2. The calibration curve prepared using Tissue-Tek as the internal standard was compared with the calibration curve using liver paste preparations as the internal standard. The results showed good linearity in both cases, with almost no difference in the slopes of the two calibration curves. 3. The PSL-BG or MD counts/pixel-BG values of the lowest radioactivity concentration measured for small areas of the region of interest (ROI) showed large fluctuations with both BAS 2000 and STORM 820, but the fluctuation became less than 15% at above 25 mm(2) of ROI. 4. The value of dpm/g calculated using the calibration curve prepared from Tissue-Tex internal standards showed a very good correlation with the values of dpm/g obtained by scraping off the tissue from the remaining block and conducting measurements with a liquid scintillation counter.

Animals↗

[Significance of the visual evaluation method using the two-visit method (two-sample preference test suggested by Ferris)].

To increase the accuracy of the visual evaluation method, we studied the significance of the two-sample preference test using the two-visit method, as proposed by Ferris. Advantages of this method include not only its ability to estimate whether the image quality of the sample is statistically the same but also its ability to distinguish the difference between samples more clearly than when using the conventional two-sample preference test or paired-comparison method. However, a disadvantage is that this method involves two observations of the same sample. When using chest images, even if a difference between the samples is not recognizable by the conventional method, a significant difference can be elicited with this method. The data obtained by this method can be evaluated with the paired-comparison method, so some samples may be ranked as well. Therefore, we verified that the two-sample preference test, which Ferris formulated, is useful in visual evaluations.

Humans↗

Liver-specific distribution of rosuvastatin in rats: comparison with pravastatin and simvastatin.

Rosuvastatin is a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. The liver is the target organ for the lipid-regulating effect of rosuvastatin; therefore liver-selective uptake of this drug is a desirable property. The aim of this study was to investigate, and compare with pravastatin and simvastatin, the tissue-specific distribution of rosuvastatin. Bolus intravenous doses (5 mg/kg) of radiolabeled rosuvastatin, pravastatin, and simvastatin were administered to rats, and initial uptake clearance (CL(uptake)) in various tissues was calculated. Hepatic CL(uptake) of rosuvastatin (0.885 ml/min/g tissue) was significantly (p < 0.001) larger than that of pravastatin (0.703 ml/min/g tissue), and rosuvastatin was taken up by the hepatic cells more selectively and efficiently than pravastatin. Hepatic CL(uptake) of simvastatin (1.24 ml/min/g tissue) was significantly larger than that of rosuvastatin (p < 0.01) and pravastatin (p < 0.001). However, adrenal CL(uptake) of simvastatin (1.55 ml/min/g tissue) was larger than hepatic CL(uptake), and simvastatin was distributed to other tissues more easily than rosuvastatin. Microautoradiography of the liver, spleen, and adrenal was undertaken 5 min after administration of the study drugs; distribution was quantified by counting the number of silver grains. After administration of rosuvastatin and pravastatin, silver grains were distributed selectively in the intracellular space of the liver, but more rosuvastatin (3.3 +/- 1.0 x 10(5) particles/mm(2)) than pravastatin (2.0 +/- 0.3 x 10(5) particles/mm(2)) tended to distribute to the liver. Simvastatin was less liver-specific (it also distributed to the spleen and adrenal). The results of this study indicated that rosuvastatin was taken up by hepatic cells more selectively and more efficiently than pravastatin and simvastatin.

Algorithms↗