Biomedical subjects

K Iseki

Publications and source records attributed to K Iseki.

At least 109 records · Page 6Linked to original sources

PubMed1995

Enhancement by peptide histidine isoleucine of experimental carcinogenesis in the colon of rats induced by azoxymethane.

The effects of peptide histidine isoleucine (PHI) on the incidence and histology of colon tumors induced by azoxymethane (AOM), and on the labeling index of colon mucosa were investigated in Wistar rats. Rats received weekly s.c. injections of 7.4 mg/kg body weight of AOM for 10 weeks, and of 1.0 or 4.0 nmol/kg body weight of PHI until the end of the experiment in week 35. Administration of PHI at the higher, but not the lower dosage, significantly increased the incidence of colon tumors. PHI had no influence on the histology of colon tumors or adenocarcinomas. It also caused significant increase in the labeling index of colon epithelial cells. These findings indicate that PHI enhances colon carcinogenesis, and that its effect may be related to increasing proliferation of colon epithelial cells.

Adenocarcinoma↗

PubMed1995

Effect of membrane surface potential on the uptake and the inhibition of cationic compounds in rat intestinal brush-border membrane vesicles and liposomes.

The effect of membrane surface potential on the uptake of tryptamine, an organic cation, by rat intestinal brush-border membrane vesicles was investigated. In the presence of an inside-negative K(+)-diffusion potential, the manner of initial uptake of tryptamine appeared to be pH-dependent and the uptake in the acidic medium was lower than that in the neutral medium. Changes in surface potential of brush-border membrane vesicles were monitored using 8-anilino-1-naphthalenesulfonic acid (ANS) and the results suggested that the membrane surface potential (negative charge on the membrane surface) decreased in the acidic medium. A good correlation was observed between the K(+)-diffusion potential-dependent uptake of tryptamine and membrane surface potential monitored by ANS at various pH levels. The uptake of tryptamine by liposomes (large unilamellar vesicles), which contained various amounts of dipalmitoylphosphatidylserine (DPPS), was also examined. The uptake of tryptamine decreased with a decrease of DPPS content in the liposomes, and was correlated with the membrane surface potential monitored by ANS. Moreover, the effect of organic cations on the uptake of tryptamine by intestinal brush-border membrane vesicles was examined. The uptake of tryptamine was inhibited by tetracaine and imipramine. The inhibitory effect of these cations was well correlated with changes in the membrane surface potential in the presence of tetracaine or imipramine. These results suggest that the K(+)-diffusion potential-dependent uptake of tryptamine by intestinal brush-border membrane vesicles is affected by membrane surface potential, and the inhibition of tryptamine uptake originates in changes in the membrane surface potential caused by the organic cations.

Animals↗

PubMed1995

Alpha-1-acid glycoprotein concentration and the protein binding of disopyramide in healthy subjects.

Age- and gender-related changes in serum alpha 1-acid glycoprotein (AAG) concentration and the serum protein binding of disopyramide were examined after intensive medical examination. Based on the clinical chemistry tests over 51 points, 245 subjects were diagnosed as healthy and 71 subjects (22.5%) revealed an abnormal value for at least one item. In the healthy subjects, serum AAG concentration in men was significantly higher than in women (men, 0.78 +/- 0.18 mg/mL, mean +/- SD; women, 0.67 +/- 0.16 mg/mL). In contrast, there were no significant differences in the AAG concentration between age groups for men and women and in the unbound fraction of disopyramide. Gender changes AAG concentration. Age, however, does not change AAG concentration and the protein binding of the basic drug.

Adolescent↗

PubMed1995

The intestinal transport mechanism of fluoroquinolones: inhibitory effect of ciprofloxacin, an enoxacin derivative, on the membrane potential-dependent uptake of enoxacin.

PURPOSE: To clarify the absorption-structure relationship for the fluoroquinolones from the point of view of inhibitory behavior. METHODS: The inhibitory effects of ciprofloxacin on the transport process of enoxacin across the rat intestinal brush-border membrane was examined. RESULTS: Ciprofloxacin, which has a similar structure to enoxacin, exhibited a pH-dependent interference with enoxacin absorption from rat jejunal loops. The uptake experiments using BBM vesicles showed that ciprofloxacin significantly reduced not only the initial binding of enoxacin to the membrane surface, but also the K(+)- or H(+)-diffusion potential-dependent transport across the membrane. Furthermore, an H(+)-diffusion potential (interior negative) also exhibited a stimulative uptake of ciprofloxacin. CONCLUSIONS: These results suggest that the inhibition behavior of ciprofloxacin from the jejunal loop was closely related to the ionic diffusion potential-dependent uptake of enoxacin across the brush-border membrane.

Animals↗

PubMed1995

Transport mechanism of ceftibuten, a dianionic cephem, in rat renal brush-border membrane.

The uptake mechanism of ceftibuten by rat renal brush-border membrane vesicles was investigated. Uptake was found to be independent of a Na+ gradient and partially dependent on an inwardly directed H(+)-gradient. Competition experiments between ceftibuten and several compounds demonstrated that the peptide-like structural features of inhibitors are more essential than their charge properties for inhibiting uptake. Anionic compound, such as p-aminohippuric acid, also inhibited ceftibuten uptake by renal brush-border membrane vesicles in the presence of an H(+)-gradient. We conclude that ceftibuten, in spite of its anionic structure, is transported via the dipeptide transport systems, rather than the organic anion transport system.

Animals↗

PubMed1995

Changes in the binding capacity of alpha-1-acid glycoprotein in patients with renal insufficiency.

The elevation of alpha-1-acid glycoprotein (AAG) concentration and the binding characteristics of disopyramide (DP) to AAG in patients with renal insufficiency were investigated. The serum AAG concentration and protein binding of DP in patients were significantly greater than those in healthy subjects. However, in both the serum and the purified AAG, Scatchard analysis showed that the number of binding sites per molecule of AAG in patients was significantly lower than that in healthy subjects, although there was no difference in the dissociation constant (Kd). These results suggest that the AAG induced in renal insufficiency is qualitatively different from normal AAG. Moreover, the change of the unbound DP fraction when DP concentration was increased was larger in the patients than in the healthy controls. Therefore, monitoring of the unbound DP would be important for therapeutic drug monitoring in patients with renal insufficiency.

Adult↗

PubMed1995

Improving the oral bioavailability of sulpiride by sodium oleate in rabbits.

To improve the limited oral bioavailability of sulpiride, a dosage form containing sodium oleate as an absorption enhancer was developed and evaluated using gastric-emptying-controlled rabbits in a cross-over manner. In addition to the known properties of sodium oleate with respect to modifying the permeability of biomembranes, it was found to be capable of improving the physicochemical properties of sulpiride toward a higher lipophilicity (by ion-pair association) and a higher solubility (by micellar solubilization). Nonetheless, the incorporation of sodium oleate with sulpiride as a mixture filled in hard gelatin capsules failed to increase intestinal absorption, whereas the use of enteric capsules, instead of the hard gelatin capsules resulted in a significant increase (P < 0.05) in the oral bioavailability.

Administration, Oral↗

PubMed1995

Transport mechanisms of enoxacin in rat brush-border membrane of renal cortex: interaction with organic cation transport system and ionic diffusion potential dependent uptake.

The mechanism of the renal transport of enoxacin (ENX) has been investigated using brush-border membrane vesicles (BBMVs) isolated from the rat renal cortex. The initial rate and time-course of ENX uptake were quite dependent upon the medium pH (pH 5.5 > pH 7.5). The pH dependence was in accordance with the degree of cationic form. Carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) affected the transient uphill transport of ENX across the renal brush-border membrane in the presence of an outward-directed H(+)-gradient. The initial uptake was saturable, and transport kinetic parameters were given for a Km and Vmax of 0.59mM and 1.37nmol/(mg protein)/30s, respectively. On the other hand, an outward H(+)-gradient (pHin = 5.5, out = 7.5) dependent uptake of ENX was partially decreased by the voltage-clamped BBMVs. Furthermore, a valinomycin-induced K(+)-diffusion potential (interior negative) was found to increase the uptake of ENX at pH 5.5, which is cationic form-rich. These results suggest that ENX uptake participates in not only the H+/organic cation antiport system for organic cation secretion but also the ionic diffusion potential (interior negative) dependent permeation through the membrane.

Animals↗

PubMed1995

Preparation and biological activity of 24-epi-26,26,26,27,27,27-hexafluoro- 1 alpha,25-dihydroxyvitamin D2.

A new fluorinated analog of vitamin D2, 24-epi-26,26,26,27,27,27-hexafluoro- 1 alpha,25-dihydroxyvitamin D2, was efficiently synthesized starting from (R)-4-isopropyl-3-propionyl-2- oxazolidinone with high stereochemical control. In all four physiological test systems, the fluorinate vitamin D2 analog was found to be slightly less active than 1 alpha,25-dihydroxyvitamin D3.

Animals↗

PubMed1995

Handedness trends across age groups in a Japanese sample of 2316.

Hand-preference data of 2316 Japanese were analyzed by age groups, sex, and familial sinistrality. Right-hand preference increased across age groups at least up to 30 years for men, while women showed relatively stable and stronger preference for right-hand use. Unlike some Western studies, no linear trends across age groups were found for both sexes. Declining cultural censorship against left-handedness would not be responsible for the trends, since there was no evidence indicating such a decline in Japan. Hypotheses of reduced longevity and life-long adaptation to the right-handed world are not satisfactory either, since both hypotheses assume a linear trend spanning the entire life span. Thus, it seems that a single-factor hypothesis which explains all the results by resorting to a single cause does not account for the complex results found in this and other studies.

Adolescent↗

PubMed1994

Inhibition of HT-29 human colon cancer growth under the renal capsule of severe combined immunodeficient mice by an analogue of 1,25-dihydroxyvitamin D3, DD-003.

An analogue of 1,25-dihydroxyvitamin D3, 22(S)-24-homo-26,26,26,27,27,27-hexafluoro-1 alpha,22,25-trihydroxyvitamin D3 (DD-003), showed 10-fold greater inhibiting effect than 1,25-dihydroxyvitamin D3 on the growth of HT-29 human colonic adenocarcinoma cells in culture. To examine the anticancer activity of DD-003 in vivo, a fibrin clot of HT-29 cells was prepared with fibrinogen and thrombin and implanted under the renal capsule of the severe combined immunodeficient mouse. Starting 7 days after implantation of HT-29 tumor, mice were given 3 micrograms/kg body weight of DD-003 or the vehicle i.p. every other day for 5 times. The HT-29 tumor grew rapidly in control mice; malignant growth was clearly observed with mitosis, massive tumor angiogenesis, and invasion into normal kidney tissue. Tumors in DD-003 treated mice were smaller with less invasion compared to the control. Administration of DD-003 inhibited growth of HT-29 tumor by 63%. Serum calcium concentrations and body weights of the treated mice were similar to those of the control. DD-003 inhibited growth of HT-29 tumor in a dose-dependent manner over the range of 0.1-10 micrograms/kg body weight, with no increase of serum calcium concentration observed at any dose level. When DD-003 was withdrawn after 2 weeks of treatment, tumor growth resumed. Since chemosensitivity tested by the subrenal capsule assay correlates well with clinical response, DD-003 may be clinically applicable in procedures such as postsurgical chemotherapy of colon cancer.

Animals↗

PubMed1994

Effect of membrane surface potential on the uptake of anionic compounds by liposomes.

The effect of membrane surface potential on the uptake of several anionic compounds by liposomes (large unilamellar vesicles), which contain various amounts of dipalmitoylphosphatidylserine (DPPS), was investigated. The uptake amount of four tested anionic compounds (cefixime, benzyloxyindoleacetic acid (BOIAA), ceftibuten and S-1006) decreased with an increase in the DPPS content of liposomes, and was correlated with the membrane surface potential monitored using a fluorescent dye, 8-anilino-1-naphthalene sulfonate (ANS). Moreover, for all of the tested anionic compounds, a good correlation was observed between the ratio of the uptake value (5 min) by each of the liposomes comprising various amounts of DPPS to the uptake value by liposomes containing 10% DPPS and a relative membrane surface potential monitored by ANS. On the other hand, the uptake of zwitterionic compounds (enoxacin, cephradine and benzyloxytryptophan (BOTP)) was independent of DPPS content. These results suggest that the uptake of tested anionic compounds by large unilamellar lipid vesicles is dependent on the membrane surface potential which originates in the surface negative charge.

Anions↗

PubMed1994

Changes in the permeation rate of organic anions through the intestinal brush-border membrane with membrane surface potential.

The effects of membrane surface potential on the uptake of anionic compounds by rat intestinal brush-border membrane vesicles were investigated. The uptake amount of all tested anionic compounds (ceftibuten, cefixime, benzylpenicillin, s-1006 and rentiapril) in the neutral medium (pH 7.5) was lower than that in the acidic medium (pH 5.5). Changes in surface potential of brush-border membrane vesicles were monitored using a fluorescence dye, 8-anilino-1-naphthalenesulfonate (ANS), and the results suggested an increase of a negative charge on the membrane surface proportional to the increase of the pH of medium. A good correlation was observed between the initial uptake rate of all tested anionic compounds and relative membrane surface potential monitored by ANS. Moreover, the uptake of cefixime by artificial liposome made from PC containing various amount of DPPS was measured. The uptake value of cefixime was decreased in proportion to an increase of DPPS content. These results suggest that the permeation of anionic compounds across intestinal brush-border membrane is dependent on surface potential originate in the surface negative charge.

Anilino Naphthalenesulfonates↗

PubMed1994

An epidemiologic analysis of end-stage lupus nephritis.

We analyzed 566 patients (515 females and 51 males) with systemic lupus erythematosus who were treated in Okinawa, Japan, from 1972 to 1991 and followed until April 1993. One hundred four patients (95 females and 9 males) died, and 51 were considered to have end-stage lupus nephritis. The annual incidence and prevalence, per million population in each sex, were increased from 16.0 and 66.0 in 1972 to 46.7 and 683.9 in 1991 in the female patients, and from 4.2 and 8.3 in 1973 to 8.3 and 70.0 in 1991 in the male patients, respectively. Cox proportional hazard analysis was done to determine the effects of several covariates on patients and renal survival. The patients' survival rate improved, as the hazard ratio (HR) was decreased to 0.69 (year of diagnosis, 1982 to 1986) and to 0.48 (year of diagnosis, 1987 to 1991) when the HR in patients diagnosed before 1981 was taken as 1.00. Similarly, we examined renal survival by using the Cox proportional model. For this analysis, the date of start of dialysis therapy was regarded as the time of renal death. Male patients had significantly poor renal survival; the HR was 3.64 (95% confidence interval, 1.89 to 6.98) when the HR in the females was taken as 1.00. However, age at diagnosis and year of diagnosis did not significantly affect renal survival. The cumulated incidence of end-stage lupus nephritis from the time of diagnosis of systemic lupus erythematosus was 3.1% at 5 years, 9.4% at 10 years, 15.5% at 15 years, and 21.0% at 20 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Enantioselective pharmacokinetics of homochlorcyclizine: disposition of (+)- and (-)-homochlorcyclizine after intravenous and oral administration of racemic homochlorcyclizine to rats.

Concentrations of homochlorcyclizine enantiomers in blood, urine, and tissues of the liver, lung, kidney, brain, heart, spleen, intestine and stomach of rats after drug administration were determined by high-performance liquid chromatography on a chiral stationary phase. After intravenous administration (10 mg kg-1), homochlorcyclizine was rapidly distributed in many tissues, with the highest concentration in lung. No differences were found between enantiomers in blood concentrations. After oral administration (50 mg kg-1), the concentrations of the (+)-isomer in nearly all tissues were higher than those of the (-)-isomer. The AUC0-infinity values of the (+)- and (-)-isomers differed significantly. The absorption of racemic homochlorcyclizine from rat small intestine was not enantioselective. These results suggested that the different concentrations between enantiomers after oral administration were not caused by enantioselective absorption or distribution but rather by preferential first-pass metabolism of the (-)-isomer in the liver. The enantioselectivity of metabolism was also demonstrated by in-vitro experiments.

Administration, Oral↗

PubMed1994

The stimulative effect of diffusion potential on enoxacin uptake across rat intestinal brush-border membranes.

Evidence of a membrane potential dependence for enoxacin uptake by rat intestinal brush-border membrane vesicles has been found. The transient overshooting uptake of enoxacin disappeared in the voltage-clamped brush-border membrane vesicles in the presence of an outward H(+)-gradient. Momentary dissipation of the H(+)-gradient itself by carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) did not affect the uptake of enoxacin. In contrast, enoxacin uptake was depressed by an interior positive K(+)-diffusion potential induced by valinomycin. Furthermore, not only the outward H(+)-gradient but also an inward Cl(-)-gradient caused a stimulating effect on enoxacin uptake, and the stimulation by the Cl(-)-gradient was dissipated by using voltage-clamped membrane vesicles. These results indicate that enoxacin transportation across the brush-border membrane is dependent on the ionic diffusion potential. On the other hand, neither Gly-Gly nor guanidine had any effect on enoxacin uptake by the membrane vesicles in the presence of an inward (for Gly-Gly) or outward (for guanidine) H(+)-gradient as a driving force for each transport system. Therefore, it seems that enoxacin transport through the intestinal epithelia does not participate in the carrier-mediated transport systems for Gly-Gly and guanidine.

Animals↗

PubMed1994

The inhibitory effects of cephalosporin and dipeptide on ceftibuten uptake by human and rat intestinal brush-border membrane vesicles.

The types of inhibitory effects caused by compound V (an analogue of ceftibuten) and alanylproline (dipeptide) on the uptake of ceftibuten by brush-border membrane vesicles (BBMV) prepared from human and rat small intestine were analysed. In the presence of an inward H(+)-gradient, the initial uptake rate of ceftibuten by both human and rat intestinal BBMV was concentration-dependent with apparent Km and Vmax values of 0.35 mM and 2.052 nmol (mg protein)-1 min-1 for human BBMV, and 0.50 mM and 3.056 nmol (mg protein)-1 min-1 for rat BBMV, respectively. For both human and rat BBMV, kinetic analysis by Dixon and Lineweaver-Burk plots demonstrated that the uptake of ceftibuten was competitively inhibited by compound V, whereas inhibition by alanylproline was noncompetitive or partially competitive. These results suggest that there is a stereospecific transport system which is common to ceftibuten and compound V, and that this system is not identical to the carrier system for the dipeptide, alanylproline.

Animals↗

PubMed1994

Effect of renal diseases and comorbid conditions on survival in chronic dialysis patients.

International and geographical differences in the survival rates of chronic dialysis patients can be explained by differences in primary renal disease, in the acceptance rate of elderly patients, and in predialysis comorbid conditions. Several studies have shown the effects of these factors on survival. However, in most studies, a large number of patients may leave for renal transplantation or transfer to other centers, so that precise analysis becomes impossible. Although the number of patients in our registry is not so large (n = 1,982), we have few such problems and were able to examine the effects of the above-mentioned factors on patient survival using the Cox proportional hazard model. Hazard ratios (HR) and 95% confidence intervals were 0.739 and 0.366-1.491 in patients with polycystic kidney disease (n = 38), 2.669 and 1.513-4.708 in patients with systemic lupus erythematosus (n = 39), 1.245 and 0.935-1.660 in patients with nephrosclerosis (n = 122), 1.815 and 1.447-2.229 in patients with diabetes mellitus (n = 374), and 1.595 and 1.201-2.117, respectively, in patients with other renal diseases (n = 146) when the HR in patients with chronic glomerulonephritis (n = 1,263) was taken as 1.00. HR and 95% confidence intervals were 1.222 and 1.016-1.470 in patients with one comorbid condition (n = 217) and 1.494 and 1.033-2.160, respectively, in patients with two comorbid conditions (n = 24) when the HR of patients with no predialysis comorbid conditions (n = 1,741) was taken as 1.00. Our data demonstrate the effects of renal diseases and number of predialysis comorbid conditions on the survival in chronic dialysis patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗