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Biomedical subjects

K Iseki

Publications and source records attributed to K Iseki.

At least 181 records · Page 10Linked to original sources
PubMed1989

Involvement of sialic acid in high-affinity binding of quaternary ammonium compounds by brush border membrane from rat intestine.

As one approach to clarify the absorption mechanisms of quaternary ammonium compounds (QACs), their binding characteristics have been studied using brush border membrane vesicles isolated from rat small intestine and liposomes composed of phospholipid and GM3 ganglioside. The binding of propantheline was significantly decreased when the vesicles were pretreated with neuraminidase. Propantheline and methochlorpromazine bound to the liposomes, the binding for the latter drug being significantly greater than that for propantheline. When GM3, isolated from rat small intestine, was incorporated into the liposomes their binding capacity for both drugs increased significantly. It is suggested that the binding of QACs to the lipid layer and sialic acid play a role in the high binding of drugs to the intestinal brush border membrane. Furthermore, a sensitive and reproducible high-performance liquid chromatographic method for sialic acid has been developed.

Animals↗
PubMed1989

Comparison of transport characteristics of amino beta-lactam antibiotics and dipeptides across rat intestinal brush border membrane.

The transport characteristics of amino beta-lactam antibiotics, ampicillin and cephradine, have been examined and compared with that of glycylglycine using brush border membrane vesicles isolated from rat small intestine. The initial rate of glycylglycine uptake was markedly stimulated in the presence of an inward H+ gradient compared with the uptake rates in the absence of an H+ gradient. With the same H+ gradient the stimulation of cephradine uptake was lower and ampicillin uptake was not altered. Cephradine uptake, however, was greater than that of glycylglycine in both vesicular conditions ((pH)i greater than (pH)o and (pH)i = (pH)o). Inhibitory effects of dipeptides, ampicillin and cephradine on the initial uptake of glycylglycine were also examined. Glycylglycine uptake was significantly decreased in the presence of L-phenylalanylglycine or carnosine. Ampicillin and cephradine did not alter the uptake of glycylglycine. These results suggest that the contribution of the inward H+ gradient to the permeation of ampicillin, cephradine and glycylglycine across the rat small intestinal brush border membranes is different for each of the substances examined.

Alanine↗
PubMed1989

[Overall clinical evaluation of cefpodoxime proxetil against infections in pediatric fields].

Dry syrup and tablet of newly developed cefpodoxime proxetil (CS-807, CPDX-PR) was investigated in the departments of pediatrics of 17 institutes and their related hospitals. 1. Pharmacokinetics of CPDX-PR in pediatrics were investigated. Peak blood levels of CPDX at dose levels of 3 mg/kg and 6 mg/kg were 2.24 +/- 0.21 and 4.68 +/- 0.54 micrograms/ml, respectively, in fasting and 1.65 +/- 0.07 and 3.71 +/- 0.41 micrograms/ml, respectively, after meal. Urinary recovery rates in 6 hours were 31.2 +/- 2.2% of dose in average. 2. Clinical efficacies of CPDX-PR on various infectious diseases were studied in 748 cases. Clinical efficacy rate in 499 cases with causative bacteria isolated was 94.6%: efficacy rates for individual infections were 96.8% (120/124) for tonsillitis, 96.0% (96/100) for urinary tract infection, 93.5% (58/62) for pneumonia, 92.4% (61/66) for impetigo, 100% (32/32) for scarler fever and 93.2% for pharyngitis or laryngitis. Bacteriological eradication rate for Gram-positive organisms was 91.0% (244/268); and for Gram-negative organisms, 89.7% (210/234). The clinical efficacy rate for cases which were non-responsive to previous antibiotic therapy was 88.1% (74/84). 3. Side effects and clinical laboratory findings were investigated in 779 cases. Two each of vomiting, loose stool and rash, 10 of diarrhea and 1 of diarrhea associated with candidiasis were reported, but no serious side effects were noted. There was no serious laboratory test abnormality except slight elevations of eosinophile, platelet, transaminase or prolongation of prothrombin time, totalling 34 occurrences.

Administration, Oral↗
PubMed1989

[Clinical and pharmacokinetic evaluation of cefpodoxime proxetil in children].

Twenty nine children were treated with cefpodoxime proxetil (CPDX-PR, CS-807) and the clinical efficacy and side effects were evaluated. Ages of the patients ranged from 2 months to 10 years. Dose levels of CPDX-PR ranged from 7.5 to 12.0 mg/kg/day for 5 to 12.7 days. The 29 patients included 9 tonsillitis, 2 otitis media, 5 scarlet fever, 3 bronchopneumonia, 1 lymphadenitis, 8 urinary tract infections and 1 staphylococcal scalded skin syndrome, and they were evaluated for the clinical efficacy of CPDX-PR. Results were excellent in 21 and good in 8 patients. Out of the 29 patients, 3 cases showed diarrhea and 2 cases showed elevated GOT and GPT. The pharmacokinetics of CPDX-PR was studied in 9 patients whose ages ranged from 1 to 9 years. The serum peak concentrations of CPDX in 5 patients were between 1.37 and 4.10 micrograms/ml (mean: 2.53 micrograms/ml) at 1 to 6 hours after dosing 3 mg/kg before meals. Those of 4 patients ranged 3.29 to 4.88 micrograms/ml (mean: 4.36 micrograms/ml) at 2 hours after administering 6 mg/kg before meals. Portions of CPDX excreted into urine within 6 hours ranged from 20.3 to 34.3% (mean 27.1%) in 5 patients who were given 3 mg/kg, and ranged from 24.1 to 65.7% (mean 41.1%) in 4 patients given 6 mg/kg.

Alanine Transaminase↗
PubMed1989

[Clinical and pharmacokinetic evaluation of cefteram pivoxil in children].

Twenty-six children were treated with cefteram pivoxil (CFTM-PI) and the clinical efficacy and side effects were evaluated. Ages of the patients ranged from 8 months to 9 years. Doses of CFTM-PI ranged 7.5-20.1 mg/kg/day for 4 to 19 days. The twenty-six patients including 10 patients with tonsillitis, 1 pharyngitis, 3 otitis media, 2 scarlet fever, 1 bronchopneumonia, 1 lymphadenitis, 6 urinary tract infections, 1 vaginitis and 1 staphylococcal scalded skin syndrome were evaluated for clinical efficacy. Results were excellent in 11, good in 13, and fair in 2 patients. Out of the 26 patients, one case showed elevated GOT and GPT, and another case showed elevated GOT. The pharmacokinetic study of CFTM-PI was performed in 9 fasting patients whose ages ranged from 2 to 11 years. Serum peak concentrations of CFTM were 0.92 to 1.05 micrograms/ml (mean 0.99 microgram/ml) at 1 to 2 hours after a dose of 1.5 mg/kg each to 3 patients, 1.12 to 1.38 micrograms/ml (mean 1.25 micrograms/ml) after a dose of 3 mg/kg each to 3 patients and 0.66 to 2.1 micrograms/ml (mean 1.17 micrograms/ml) after a dose of 6 mg/kg each to 3 patients. The portions of the drug excreted into urine within 8 hours were 8.9% and 14.7% in 2 patients, each given a dose of 1.5 mg/kg, from 13.0 to 23.1% (mean 18.4%) in 3 patients, each given a dose of 3 mg/kg, and 6.3% and 8.7% in 2 patients, each given a dose of 6 mg/kg.

Bacterial Infections↗
PubMed1988

Binding of organic cations to brush border membrane from rat small intestine.

The binding of six organic cations (chlorpromazine, promethazine, imipramine, diphenhydramine, methochlorpromazine and propantheline) to the brush border membrane isolated from rat small intestine has been investigated. The cations were bound to the membrane to varying extents, the order of binding being chlorpromazine greater than promethazine greater than methochlorpromazine greater than imipramine greater than propantheline greater than diphenhydramine. There was no relation between binding and the chloroform-water partition coefficient. Chlorpromazine binding was significantly decreased in the presence of imipramine, methochlorpromazine and propantheline. Anionic compounds (indomethacin and xanthene-9-carboxylic acid) did not affect chlorpromazine binding. High and low affinity binding of the cations to the intestinal brush border membrane was demonstrated with Scatchard plots and Hill plots. Imipramine and methochlorpromazine inhibited chlorpromazine binding at both binding sites. From the results, it was suggested that the organic cations tested were specifically bound to common binding sites on the brush border membrane.

Animals↗
PubMed1988

Effect of chlorpromazine on the permeability of beta-lactam antibiotics across rat intestinal brush border membrane vesicles.

The effect of chlorpromazine on the membrane permeability of beta-lactam antibiotics (benzylpenicillin, ampicillin, cephradine and cephalexin) and actively transported substances (glycylglycine and D-glucose) has been studied using rat intestinal brush border membrane vesicles. Except for cephalexin, the initial uptakes at 25 degrees C of these antibiotics were significantly enhanced in the presence of chlorpromazine. In contrast, the transport of glycylglycine and D-glucose was significantly inhibited. These results suggest that the two groups, drugs and actively transported substances, have a different permeation process. The effect of chlorpromazine concentration on membrane lipid fluidity, as assessed by the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-anilino-8-naphthalene sulphonate (ANS), was also examined. The fluorescence polarization of ANS decreased with increasing concentration of chlorpromazine, while that of DPH increased suggesting an increase of membrane surface fluidity might affect the permeation of beta-lactam antibiotics and actively transported substances in a different manner.

Animals↗
PubMed1988

Does 1 alpha(OH)D3 treatment affect blood pressure levels in maintenance hemodialysis patients?

Forty-eight chronic hemodialysis patients were divided comparably into two groups (24 patients in each). Two micrograms of 1 alpha(OH)D3 was administered to one group for 3 months and its placebo to the other group. In the 1 alpha(OH)D3-treated group, serum total calcium increased from 7.82 +/- 0.11 (mean +/- SEM) to 9.70 +/- 0.27 mg/dl (p less than 0.001) which was significantly higher (p less than 0.001) than control values of 8.86 +/- 0.06 mg/dl from normal volunteers. Systolic, diastolic and mean blood pressures, however, did not change significantly throughout the study. Even in the 9 patients who had a substantial increment of serum calcium of more than 2 mg/dl with hypercalcemia (greater than 10 mg/dl) at 3 months, no significant changes in blood pressure were found. Serum iPTH decreased from 2.83 +/- 0.28 to 0.98 +/- 0.23 ng/ml (p less than 0.001) at 3 months of treatment. Furthermore, a significant inverse correlation was obtained between the changes in serum calcium and iPTH. In the placebo group there were no significant changes in serum calcium, iPTH and blood pressure during the 3-month treatment period. The present study indicates that a substantial increase in serum calcium or a chronic hypercalcemia induced by 1 alpha(OH)D3 treatment in maintenance hemodialysis patients does not accompany a rise in blood pressure, probably due to a concomitant suppression of PTH. The results also suggest that the hypocalcemic state found in hemodialysis patients is not associated with any significant change in blood pressure. The importance of PTH in blood pressure regulation was discussed.

Adult↗
PubMed1988

An evaluation of serum ferritin determination in chronic hemodialysis patients with persistent low serum iron concentration.

Low serum iron concentration is not rare in chronic hemodialysis patients. Therefore it is important to differentiate true iron deficiency from reactive low serum iron concentration. We have evaluated the utility of determining serum ferritin concentration to differentiate iron deficiency in chronic hemodialysis patients with persistent low serum iron concentration. Parenteral iron therapy (40 mg/week, group 1, n = 12) for 3 months caused a 3.0% increase in hematocrit level compared to a group 2 (n = 12; p less than 0.05). Serum ferritin concentration in logarithmic scale was significantly correlated with serum iron concentration (r = 0.671; p less than 0.05). The change in hematocrit level was significantly correlated with that in serum iron concentration (r = 0.648; p less than 0.05), but not with the change in serum ferritin concentration. Persistent low serum iron concentration may be an indication for iron supplement even though the serum ferritin concentrations are in the normal range.

Adult↗
PubMed1987

Binding of amino beta-lactam antibiotics to soluble protein from rat intestinal mucosa--I. Purification of drug-binding protein.

Several amino beta-lactam antibiotics, including ampicillin, amoxicillin, cyclacillin, cephalexin, cephradine and cefadroxil, were found to bind in vitro to specific components in 105,000 g supernatant of homogenate obtained from rat intestinal mucosa. The major binding component (fraction b) was purified by chromatography on DEAE-cellulofine and by gel filtration on Sephadex G-50. The molecular weight of fraction b was determined by SDS polyacrylamide gel electrophoresis (15,000 Da). The binding behaviour of these amino beta-lactam antibiotics to fraction b were estimated by equilibrium dialysis. There were significant high affinities of all tested amino beta-lactam antibiotics which were well absorbed from intestine, but there was not a good correlation between binding and absorption of these drugs. It was also found that poorly absorbed cephalosporins which lack aminobenzyl group in their structure, cefazolin and cephaloridine, did not bind to fraction b.

Animals↗
PubMed1987

Binding of amino beta-lactam antibiotics to soluble protein from rat intestinal mucosa--II. Mutual inhibition of binding among amino beta-lactam antibiotics and binding characteristics.

The characteristics of binding of amino beta-lactam antibiotics including ampicillin, amoxicillin, cephalexin and cephradine to fraction b obtained from the 105,000 g supernatant of rat small intestinal mucosa was investigated. The mutual inhibition of binding among these antibiotics was observed, and these were dependent on the concentration of inhibitors. It was found that dipeptides such as L-carnosine and glycylglycine significantly reduced the binding of cephalexin to fraction b, but the binding of cephradine was only slightly decreased by these dipeptides. Furthermore, the binding of cephalexin and cephradine was not influenced by amino acids (L-phenylalanine, glycine). Although ANS(1-anilino-8-naphthalenesulfonic acid magnesium salt), which is a hydrophobic probe, bound to the fraction b, there was no competitive inhibition in binding between ANS and amino beta-lactam antibiotics. The Scatchard plot of binding data of cephalexin gave two dissociation constant (Kd) values (1.37 and 15.7 microM). On the other hand, one Kd value (11.2 microM) was obtained for ampicillin.

Ampicillin↗
PubMed1987

[Development of intestinal flora in neonates].

The development of faecal bacterial flora was studied using quantitative anaerobic and aerobic culture methods to determine the differences between various types of feeding. Enterobacteria first colonized predominantly in neonatal intestine, and their viable counts on the first day of life were between 10(8)-10(10) per gram faeces. In the breast-fed group, enterobacteria decreased gradually and their level on the 6th day of life was about 10(6) per gram faeces. Bifidobacteria began to increase after 2 or 3 days of life and outnumbered other bacteria, amounting to about 10(10) per gram faeces on the 6th day. In the bottle-fed group, enterobacteria maintained their high counts despite the increase of bifidobacteria, and their counts (10(9.3 +/- 1.1)/g) on the 6th day still exceeded those of bifidobacteria (10(8.4 +/- 1.6)/g). At 1 and 3 months of age, bifidobacteria were the most prevalent organisms in all feeding groups. However, the numbers of other bacteria such as enterobacteria were significantly greater in the bottle-fed infants than in the breast-fed infants. In the breast-fed formula supplemented group, bacterial colonization of the intestine was in the middle range between the breast-fed group and the bottle-fed group. In addition to the microbiological study, physicochemical properties of faeces and milk (i.e. pH and buffering capacity) were examined to explore their effects on the faecal bacterial flora. Faeces from breast-fed infants had a lower pH and lower buffering capacity than those from bottle-fed infants. The buffering capacity of formula was almost twice as much as that of human milk. It is postulated therefore, that low buffering capacity of human milk seems to produce an acidic environment in the intestine, which is favourable for the growth of bifidobacteria and unfavourable for the growth of potential pathogenic bacteria such as enterobacteria. These results suggest that breast feeding is beneficial for protection against intestinal and/or systemic infection.

Bifidobacterium↗
PubMed1986

Effects of hypercalcemia and parathyroid hormone on blood pressure in normal and renal-failure rats.

Hypertension is common in primary hyperparathyroidism, but the mechanisms are not clear. Significant hypercalcemia induces elevation in blood pressure (BP), whereas excessive parathyroid hormone (PTH) lowers BP. However, in chronic renal failure (CRF) and secondary hyperparathyroidism, the hypercalcemia-induced hypertension is more severe. We examined the interaction between PTH and calcium on BP in normal rats and in those with CRF. Calcium caused a dose-related rise in serum calcium and a rise in mean arterial pressure (MAP). For a comparable rise in serum calcium, the increment in MAP in parathyroidectomized (PTX) rats (7 +/- 3 mmHg) was significantly lower (P less than 0.05) than in sham PTX rats (19 +/- 7.3 mmHg). In PTX rats receiving PTH, the MAP response to calcium infusion (17 +/- 2.4 mmHg) was similar to that in the sham PTX rats. The infusion of similar amounts of calcium in CRF rats caused a greater rise in serum calcium. In CRF-PTX rats, the changes in MAP during calcium infusion were significantly lower (P less than 0.05) than in CRF-sham PTX animals, despite similar rise in serum calcium. For a comparable rise in serum calcium, the rise in MAP in CRF rats was greater than in normal rats. These data suggest that the presence of PTH plays an important permissive role for the hypertensive action of the hypercalcemia.

Animals↗