Biomedical subjects

Hiroshi Sekiya

Publications and source records attributed to Hiroshi Sekiya.

8 recordsLinked to original sources

PubMed2006

Effects of pomegranate juice on human cytochrome P450 2C9 and tolbutamide pharmacokinetics in rats.

In this study, we investigated whether pomegranate juice could inhibit CYP2C9 activity. The ability of pomegranate juice to inhibit the diclofenac 4'-hydroxylase activity of human CYP2C9 was examined using human liver microsomes. Pomegranate juice was shown to be a potent inhibitor of human CYP2C9. The addition of 25 microl (5% v/v) of pomegranate juice resulted in almost complete inhibition of human CYP2C9 activity. In addition, we investigated the effect of pomegranate juice on the pharmacokinetics of tolbutamide (substrate for CYP2C9) in rats. Relative to the control group, the area under the concentration-time curve was approximately 1.2-fold greater when pomegranate juice (3 ml) was injected p.o. 1 h before the p.o. administration of the tolbutamide (20 mg/kg). The elimination half-life of tolbutamide was not altered by pomegranate juice administration. These results suggest pomegranate juice ingestion inhibits the intestinal metabolism of tolbutamide without inhibiting the hepatic metabolism in rats. Thus, we discovered that pomegranate juice inhibited human CYP2C9 activity and furthermore increased tolbutamide bioavailability in rats.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2006

Contextual interference in implicit and explicit motor learning.

The purposes of this study were to examine the contextual interference effect in implicit learning and to compare implicit and explicit learning. Thirty-two participants performed a pursuit-tracking task for 60 acquisition and ten retention trials. The middle segment of target pathways had only two patterns whereas other segments had random patterns. A combination of awareness and practice order for the middle segment created four acquisition conditions: implicit-blocked, implicit-serial, explicit-blocked and explicit-serial. A questionnaire and a recognition test revealed that implicit groups were unaware of the repetition. Results showed no contextual interference effect in either implicit or explicit learning. Acquisition and retention performances were better for the middle segment than the other segments regardless of awareness. No difference between the implicit and explicit groups was found, suggesting that the implicit learning condition led to learning equivalent to the explicit learning condition.

Adolescent↗

PubMed2005

Excited-state double-proton transfer in the 7-azaindole dimer in the gas phase. 3. Reaction mechanism studied by picosecond time-resolved REMPI spectroscopy.

The excited-state double-proton-transfer (ESDPT) reaction in the jet-cooled 7-azaindole dimer (7AI2) has been investigated with picosecond time-resolved resonance-enhanced multiphoton ionization spectroscopy. The observed decay profiles of 7AI2 by exciting the origin and the intermolecular stretch fundamental in the S1 state are well reproduced by single-exponential functions with time constants of 1.9 +/- 0.9 ps and 860 +/- 300 fs, respectively. This result provides clear evidence of the concerted mechanism of ESDPT in 7AI2.

Gases↗

PubMed2005

Excited-state double-proton transfer in the 7-azaindole dimer in the gas phase. 2. Cooperative nature of double-proton transfer revealed by H/D kinetic isotopic effects.

The dispersed fluorescence (DF) spectra of the 7-azaindole dimer (7AI2) and deuterated dimers 7AI2-hd and 7AI2-dd, where hd and dd indicate the deuteration of an imino proton and two imino protons, have been measured in a supersonic free jet expansion. The undeuterated 7AI2-hh dimer exhibits only the tautomer fluorescence, but both the normal and tautomer fluorescence have been detected by exciting the origins of 7AI2-h*d, 7AI2-hd* and 7AI2-dd in the S1-S0 region, where h* and d* indicate the localization of the excitation on 7AI-h or 7AI-d moiety. The DF spectra indicate that 7AI2-h*d and 7AI2-hd* undergo excited-state proton/deuteron transfer (ESPDT), while excited-state double-deuteron transfer (ESDDT) occurs in 7AI2-dd. The H/D kinetic isotopic effects on ESDPT have been investigated by measuring the intensity ratios of the normal fluorescence to the tautomer fluorescence. The ESPDT rate is about 1/60th of the ESDPT rate, and the ESDDT rate is about 1/12th of the ESPDT rate, where ESPDT rate is an average of the rates for 7AI2-h*d and 7AI2-hd*. The observed H/D kinetic isotope effects imply that the ESDPT reaction of 7AI2 has a "cooperative" nature; i.e., the motion of the two moving protons strongly couples each other through the electron motions. The difference in the estimated ESPDT reaction rates, 9.8 x 10(9) and 6.9 x 109 s(-1) for 7AI2-h*d and 7AI2-hd*, respectively, is consistent with the concerted mechanism rather than the stepwise mechanism.

Deuterium↗

PubMed2005

Excited-state double-proton transfer in the 7-azaindole dimer in the gas phase. 1. Evidence of complete localization in the lowest excited electronic state of asymmetric isotopomers.

The fluorescence excitation and UV-UV hole-burning spectra are measured for deuterated 7-azaindole dimers (7AI2), 7AI2-(h(N)h(C))-(h(N)d(C)), 7AI2-(d(N)h(C))-(h(N)d(C)), 7AI2-(h(N)h(C))-(d(N)h(C)), and 7AI2-(h(N)h(C))-(d(N)d(C)), where h and d indicate the H and D atoms, respectively, and the subscripts N and C designate the imino N-H (or N-D) and C-H (or C-D) bonds at the 3-position. The transitions of the isotopomers have been consistently assigned. It has been found that the excitation is completely localized on one monomer unit in the lowest excited electronic state of asymmetrical 7AI2 dimers except for 7AI2-(d(N)h(C))-(h(N)d(C)) in which the excitation is delocalized over the dimer. This indicates that the undeuterated 7AI2 dimer and its isotopomers that belong to the C2h symmetry point group should be treated by the weak coupling limit of the exciton theory.

Journal Article↗

PubMed2005

Gene cloning and properties of the RND-type multidrug efflux pumps MexPQ-OpmE and MexMN-OprM from Pseudomonas aeruginosa.

We cloned two operons for putative RND-type multidrug efflux pumps from Pseudomonas aeruginosa by a PCR method. We designated the genes in one operon mexPQ(-opmE) and in another operon mexMN. Introduction of the mexPQ-opmE into drug hypersensitive cells resulted in elevated MICs of macrolides, fluoroquinolones and some other drugs. Introduction of the mexMN into the hypersensitive cells possessing oprM, but not into cells not possessing oprM, resulted in elevated MICs of chloramphenicol and thiamphenicol. Thus, we conclude that MexPQ-OpmE and MexMN-OprM are functional multidrug efflux pumps when expressed in P. aeruginosa.

Bacterial Outer Membrane Proteins↗

PubMed2004

Ultrafast excited-state dynamics in photochromic N-salicylideneaniline studied by femtosecond time-resolved REMPI spectroscopy.

Ultrafast processes in photoexcited N-salicylideneaniline have been investigated with femtosecond time-resolved resonance-enhanced multiphoton ionization spectroscopy. The ion signals via the S(1)(n,pi( *)) state of the enol form as well as the proton-transferred cis-keto form emerge within a few hundred femtoseconds after photoexcitation to the first S(1)(pi,pi( *)) state of the enol form. This reveals that two ultrafast processes, excited-state intramolecular proton transfer (ESIPT) reaction and an internal conversion (IC) to the S(1)(n,pi( *)) state, occur on a time scale less than a few hundred femtoseconds from the S(1)(pi,pi( *)) state of the enol form. The rise time of the transient corresponding to the production of the proton-transferred cis-keto form is within 750 fs when near the red edge of the absorption is excited, indicating that the ESIPT reaction occurs within 750 fs. The decay time of the S(1)(pi,pi( *)) state of the cis-keto form is 8.9 ps by exciting the enol form at 370 nm, but it dramatically decreases to be 1.5-1.6 ps for the excitation at 365-320 nm. The decrease in the decay time has been attributed to the opening of an efficient nonradiative channel; an IC from S(1)(pi,pi( *)) to S(1)(n,pi( *)) of the cis-keto form promotes the production of the trans-keto form as the final photochromic products. The two IC processes may provide opposite effect on the quantum yield of photochromic products: IC in the enol form may substantially reduce the quantum yield, but IC in the cis-keto form increase it.

Journal Article↗

PubMed2003

Functional cloning and characterization of a multidrug efflux pump, mexHI-opmD, from a Pseudomonas aeruginosa mutant.

We isolated mutant YM644, which showed elevated resistance to norfloxacin, ethidium bromide, acriflavine, and rhodamine 6G, from Pseudomonas aeruginosa YM64, a strain that lacks four major multidrug efflux pumps. The genes responsible for the resistance were mexHI-opmD. Elevated ethidium extrusion was observed with cells of YM644 and YM64 harboring a plasmid carrying the genes. Disruption of the genes in the chromosomal DNA of YM644 made the cells sensitive to the drugs.

Anti-Bacterial Agents↗