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Biomedical subjects

K Iseki

Publications and source records attributed to K Iseki.

At least 145 records · Page 8Linked to original sources
PubMed1992

Rapid and simple method for the determination of alpha 1-acid glycoprotein in serum by column liquid chromatography.

A rapid and simple method for the determination of alpha 1-acid glycoprotein (AAG) in serum was developed by using an anion-exchange column for clean-up of serum and a hydroxyapatite column for high-performance liquid chromatography (HPLC). A good correlation was observed between this HPLC method and the conventional radial immunodiffusion method. The method may also be used to determine the AAG concentration in the serum of experimental animals.

Adult↗
PubMed1992

Uptake characteristics of polyamines into rat intestinal brush-border membrane.

The uptake characteristics of polyamines, such as spermine, spermidine and putrescine, have been investigated using brush-border membrane vesicles isolated from the small intestine of rats. The uptake of these polyamines into the membrane vesicles was high and the order of uptake was spermine greater than spermidine greater than putrescine at medium pH 7.5, respectively. The medium pH considerably affected the uptake of these polyamines and the amount of uptake increased remarkably with an increase of the medium pH (pH 7.5 or 8.0 greater than pH 5.5). An inward Na+ gradient did not stimulate the uptake rate of any of these polyamines. We have also examined the binding behaviour to the membrane lipid, phospholipids and total lipid, and there was a good correlation in the binding properties, pH-dependency and uptake activity, between the liposomes and brush-border membrane vesicles. These results suggest that the uptake of the polyamine into the vesicles consisted of rapid binding to the outside intestinal surface and slower binding to the inside membrane after permeation. Furthermore, findings from experiments concerning the mutual inhibition among these polyamines and concerning the effect of other polycations, having 2-5 amines in number, on the uptake of spermine, suggest that the number of amino groups in the polyamine molecules plays an important role in the uptake process into the brush-border membrane vesicles.

Animals↗
PubMed1992

Comparison of disposition behavior and de-coppering effect of triethylenetetramine in animal model for Wilson's disease (Long-Evans Cinnamon rat) with normal Wistar rat.

The disposition behaviors and de-coppering effect of triethylenetetramine dihydrochloride (trientine), a selective chelating agent for copper and an 'orphan drug' for Wilson's disease, have been evaluated in an animal model, Long-Evans Cinnamon (LEC) rats, and normal rats (Wistar). In LEC rats, urinary excretion of trientine was remarkably lower than that of Wistar rats. The absorption rates from the jejunal loop and in vitro metabolism in the liver S9 fraction (supernatant of 9000 x g) were approximately the same for both strains. The decline of urinary excretion of trientine in LEC rats is thought to be due mainly to the lowering of the functional activity of the kidney, because urinary excretion of creatinine and phenolsulfonphthalein were significantly lower in LEC rats than those in Wistar rats. Both acceleration of urinary excretion of copper and reduction of hepatic copper levels were observed with treatment of trientine in LEC rats aged 6 weeks. In LEC rats aged 13 weeks, however, no de-coppering effect from the liver was observed, though urinary excretion of copper was increased. These results suggest that trientine has a pharmacological effect in disease state, especially in the early stages of hepatitis.

Animals↗
PubMed1992

Absorption of acetylsalicylic acid from the rat nasal cavity.

The fate of salicylate in the plasma of rats was followed after nasal, intravenous, and oral administration of 2.0-mg doses of aspirin. Aspirin was well absorbed following nasal administration of a neutralized, nonirritating solution containing triethanolamine. The rate of absorption was slower than that of other nasally administered drugs, such as propranolol or progesterone. The bioavailability of aspirin following nasal administration was 100%, whereas the oral bioavailability was only 58.8% at the dose studied.

Absorption↗
PubMed1992

Enantioselective pharmacokinetics of homochlorcyclizine. II: Disposition and metabolism of (+)-, (-)- and racemic homochlorcyclizine after oral administration to man.

The pharmacokinetics of a single oral dose of 20 mg (+)-, (-)- and racemic homochlorcyclizine (HCZ) have been studied in humans. The formation of the quarternary ammonium-linked glucuronide was an important metabolic pathway, and the metabolic process was enantioselective as a result of differing urinary excretion rates of (+)-, (-)- and racemic glucuronide. There were significant differences between (+)-, (-)- and racemic HCZ in AUC (0-14 h) and plasma protein binding, but all HCZ enantiomers were slowly absorbed and eliminated (elimination half-lives about 11 h). The results shows help to establish a more efficient dosage regimen for HCZ therapy.

Administration, Oral↗
PubMed1992

Elevation of serum erythropoietin after subtotal parathyroidectomy in chronic haemodialysis patients.

After successful subtotal parathyroidectomy (PTX) in 10 chronic haemodialysis patients, significant elevation of Epo was observed, from 48.4 +/- 17.8 mU/ml(M +/- SEM) at preoperative state to 103.3 +/- 34.7 mU/ml at 6 h and 163.4 +/- 50.2 mU/ml at 12 h after PTX. Significant reductions in both PTH-m and ionized calcium (iCa) were confirmed. Since Epo did not increase in the cases with an inadequate PTX and ovariectomy, an abrupt reduction in PTH with a decrease in iCa may play some role in the elevation of Epo.

Adult↗
PubMed1992

The pH dependent uptake of enoxacin by rat intestinal brush-border membrane vesicles.

The mechanism of the intestinal transport of enoxacin, an orally active fluoroquinolone antibiotic, has been investigated using brush-border membrane vesicles isolated from rat small intestine. The initial rate and time-course of enoxacin uptake were considerably dependent upon the medium pH (pH 5.5 greater than pH 7.5) and upon the percent ionization of the carboxyl group (pKa 6.2, anionic charge), namely, the degree of uptake of cationic form was higher than that of the zwitterionic form. There was evidence of transport into the intravesicular space as shown by the effect of extravesicular medium osmolarity on enoxacin uptake at steady state (30 min). This transport across the brush-border membrane was stimulated by the valinomycin-induced K(+)-diffusion potential (interior negative) and an outward H(+)-diffusion potential. Furthermore, changing the pH of the medium from 5.5 to 7.5 significantly decreased the effect of valinomycin-induced K(+)-diffusion potential on the enoxacin uptake. These results suggest that the uptake behaviour of the cationic form of enoxacin plays an important role in the intestinal absorption process of enoxacin.

Animals↗
PubMed1992

Transport characteristics of cephalosporin antibiotics across intestinal brush-border membrane in man, rat and rabbit.

The uptake of orally active cephalosporins, ceftibuten and cephradine, by intestinal brush-border membrane vesicles isolated from man, rat and rabbit was studied. In the presence of an inward H+ gradient, ceftibuten but not cephradine was taken up into intestinal brush-border membrane vesicles of man and rat against the concentration gradient (overshoot phenomenon). In rabbit jejunal brush-border membrane vesicles, the uptake of both cephalosporins in the presence of an inward H+ gradient exhibited the overshoot phenomenon. In human and rat vesicles, the initial uptake of ceftibuten was strongly inhibited by compound V, an analogue of ceftibuten, but the uptake of cephradine was not affected by any of the cephalosporins tested, whereas in the rabbit brush-border membrane vesicles, initial uptake of both ceftibuten and cephradine were markedly inhibited by all cephalosporins and dipeptides used. These results suggest that the transport characteristics of human and rat intestinal brush-border membrane for cephalosporins are comparable, and that rabbit is an inadequate animal for investigating the transport characteristics of beta-lactam antibiotics.

Administration, Oral↗
PubMed1992

Chronic hypovolemia associated with accelerated hypertension and orthostatic hypotension in a patient on continuous ambulatory peritoneal dialysis.

We report a patient with nondiabetic end-stage renal disease on continuous ambulatory peritoneal dialysis (CAPD) associated with chronic hypovolemia. Despite the administration of nilvadipine, the patient showed accelerated hypertension and concomitantly orthostatic hypotension. Plasma renin activity was markedly high, and blockade of angiotensin II action by captopril or an angiotension II antagonist decreased the supine blood pressure. This indicated that the enhanced activity of the renin-angiotensin system was the principal cause of the supine hypertension. The plasma concentration of norepinephrine was also very high. After correction of hypovolemia by blood transfusion, the enhancement of the renin-angiotensin system and high plasma norepinephrine level were reduced, and symptomatic orthostatic hypotension disappeared. The accelerated hypertension was easily controlled by the administration of low-dose captopril and nilvadipine. These findings suggest that chronic hypovolemia related to the intractable supine hypertension as well as orthostatic hypotension. Hypovolemia-induced enhancement of the renin-angiotensin system and sympathetic nerve activity may cause vasoconstrictive hypertension in patients on CAPD.

Blood Volume↗
PubMed1992

Method for optical resolution of racemic homochlorcyclizine and comparison of optical isomers in antihistamine activity and pharmacokinetics.

A method was developed for semi-preparative scale enantioseparation of racemic homochlorcyclizine (HCZ) by high performance liquid chromatography (HPLC) on Chiralcel OD column. The best resolution was achieved using an eluent composed of n-hexane plus 0.2 M isopropylamine. By this method, about 5.0 mg of racemic HCZ could be resolved completely in one run. The optical purity of the enantiomers were both greater than 99.9%. The studies of antihistamine activity on guinea pig ileum demonstrated that l-HCZ is significantly more potent than d- and racemic HCZ. The pharmacokinetics of d- and l-HCZ after oral administration to rats also differed. The successful resolution of racemic HCZ permits comparison of the pharmacokinetics and antihistamine activity of the enantiomers.

Animals↗
PubMed1992

A case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) with low plasma concentrations of antidiuretic hormone.

A 66-year-old Japanese man presented with persistent hyponatremia without polydipsia and polyuria. Laboratory examination showed serum sodium of 117 mEq/l, plasma osmolality 239 mosm/kg, urine sodium 108 mEq/l, urine osmolality 577 mosm/kg, and normal levels (less than 2.0 pg/ml) of serum antidiuretic hormone (ADH). ADH release was regulated normally with changes in plasma osmolality. No obvious cause for the syndrome of inappropriate secretion of ADH (SIADH) could be detected. However, 20 months later, the patient had bouts of hematuria and was found to have cancer of the urinary bladder. Increased renal sensitivity to ADH was suspected as the underlying mechanism of SIADH.

Aged↗
PubMed1991

Spermine uptake by rat intestinal brush-border membrane vesicles.

The uptake of spermine by isolated rat intestinal brush-border membrane vesicles was studied. Uptake was biphasic, with an initial rapid uptake followed by a prolonged slower phase. Spermine uptake was not affected by a Na+ electrochemical gradient. The equilibrium uptake of spermine was considerably dependent upon the medium pH. At pH 7.5 the degree of uptake was higher than that at pH 6.5 and was inversely proportional to the extravesicular osmolarity with a relatively high binding, which was estimated by extraporation to infinite extravesicular osmolarity (zero intravesicular space), while the uptake at pH 6.5 was not altered under the various medium osmolarities. A kinetic analysis of the initial uptake rate of spermine at 37 degrees C gave a Km of 24.2 microM and Vmax of 206.1 pmol/mg protein per min. Furthermore, the uptake at 4 degrees C was nonlinear, providing evidence for saturability. These findings suggest that spermine was associated with intestinal brush-border membrane vesicles in two ways, by binding to the outside and inside of membrane vesicles. The interaction of spermine and the apical membrane can be a contributory factor in the accumulation of this polyamine in the intestine of the intact animal.

Animals↗
PubMed1991

Transport characteristics of ceftibuten, cefixime and cephalexin across human jejunal brush-border membrane.

The transport characteristics of orally active cephalosporins, ceftibuten, cefixime and cephalexin have been examined using brush border membrane vesicles isolated from human jejunum. In the initial uptake of ceftibuten, the stimulation and overshoot phenomena were observed in the presence of an inward H+ gradient. Effects of H+ gradient on the uptake of cefixime and cephalexin were low and no overshoot was observed. These transport characteristics, especially uphill transport phenomena, were in agreement with previous results obtained from rat intestinal brush-border membrane vesicles and suggest that these beta-lactam antibiotics are absorbed by different transport systems, despite their similar molecular structures.

Biological Transport, Active↗
PubMed1991

Gastrointestinal absorption of quaternary ammonium compounds correlated to their binding to small intestinal brush border membrane in rat.

The relationship between absorption of quaternary ammonium compounds (QACs) from rat intestine and their in-vitro binding to isolated brush-border membrane has been examined, using a series of n-alkyltrimethylammoniums. The binding of these QACs gradually increased with each extension of unbranched hydrocarbon chain from octyltrimethylammonium to tetradecyltrimethylammonium. However, hexyltrimethylammonium and heptyltrimethylammonium failed to bind to the membrane. On the other hand, the disappearance of these QACs from rat jejunal loop also increased with the length of hydrocarbon chain over the range of 8.9 to 71.3%. A good correlation was found between binding to the brush-border membrane and disappearance from jejunal loop. From these results, it was suggested that the size of the hydrophobic part of a QAC molecule was a principal determinant of both absorption and membrane binding, and that the absorption of QACs with an appropriate sized hydrophobic part, was closely associated with the degree of binding to the membrane.

Animals↗
PubMed1991

H+ coupled transport of orally active cephalosporins lacking an alpha-amino group across brush-border membrane vesicles from rat small intestine.

The effect of an inwardly directed H+ gradient' on the transport characteristics of ceftibuten, cefixime and analogues of ceftibuten in rat intestinal brush-border membrane vesicles have been investigated. In the presence of a transmembrane H+ gradient, ceftibuten and its analogues exhibited a peak to equilibrium overshoot and an accumulation in the vesicles against the concentration gradient. However, the uptake of cefixime and S-1006 [(6R, 7R)-(7-[(Z)-2-(2-aminothiazol-4-yl)-2-pentenoylamino]-8-oxo- 3- carbamoyloxy-methyl-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxyl ic acid), which lacks a carboxyl group at position 4 of carboxyethylidene structure, exhibited no overshoot, although the equilibrium uptake was increased by a H+ gradient. The equilibrium uptake was dependent on the pH of the final incubation medium and the H+ gradient. These data suggested that the orally active cephalosporins were transported into rat intestinal brush-border membrane by the transmembrane H+ gradient and the pH of the medium.

Animals↗