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Biomedical subjects

R Hori

Publications and source records attributed to R Hori.

At least 145 records · Page 8Linked to original sources
PubMed1988

Urinary excretion and diuretic action of furosemide in rats: increased response to the urinary excretion rate of furosemide in rats with acute renal failure.

A urinary excretion-response curve representing the urinary excretion rate of furosemide versus the urinary excretion rate of (Na+ + K+) was used to analyze furosemide action in rats with uranyl nitrate-induced acute renal failure (ARF) with and without dopamine coadministration. Urinary excretion of furosemide, but not its serum concentration, was the determinant for the diuretic action of furosemide. Increased diuretic response was observed in ARF rats, although the total diuretic response and urinary recovery of furosemide within 2 hr decreased. Dopamine enhanced furosemide-induced diuresis in ARF rats in terms of the total urine output and urinary electrolyte excretion, although the urinary excretion-response curves were not different. This enhancement by dopamine was found to be caused by the augmented urinary excretion of furosemide and the increased response to this drug in ARF rats. These findings suggest the contribution of decreased concentrating ability along the nephron and/or increased sensitivity of cells at the site of action to this drug.

Acute Kidney Injury↗
PubMed1988

A quantitative method of evaluating the diuretic response to furosemide in rats.

Furosemide effects are usually evaluated by measuring the urinary excretion rate of Na+ (UVNa) in humans. In the present study, however, UVNa showed a nonlinear relationship with urine flow rate after intravenous injection of furosemide in rats. In contrast, when the urinary excretion rate of (Na+ + K+) (UVNa + K) was plotted against the urine flow rate, a linear regression line was observed, with small interindividual variations in normal rats and in rats with uranyl nitrate-induced acute renal failure (ARF). Piretanide, a loop diuretic, also showed a similar relationship, while other types of diuretics revealed different slope values for the relationship. Although the urinary excretion rate of Cl- (UVCl) vs UVNa + K is expected to show a linear relationship in normal rats, the correlation coefficient of the linear regression line was smaller than that of the urine flow rate vs UVNa + K. Further, the slope of UVCl vs UVNa + K was slightly different in ARF rats. Therefore, UVNa + K provides a better quantitative measure of diuretic response to loop diuretics than UVNa or UVCl.

Acute Kidney Injury↗
PubMed1988

Regional myocardial ajmaline concentration and antiarrhythmic activity for ischaemia- and reperfusion-induced arrhythmias in rats.

1. Antiarrhythmic actions of ajmaline against ischaemia (left coronary artery occlusion for 15 min) and subsequent reperfusion-induced arrhythmias were investigated in anaesthetized rats. 2. Ajmaline (2 mg kg-1, i.v.) was effective in suppressing ischaemia-induced arrhythmias whether given pre- or post-occlusion. 3. Ajmaline diminished the reperfusion-induced arrhythmias completely when given pre-occlusion but had little effect when given post-occlusion. 4. Reperfusion-induced increases in plasma enzyme activities of lactate dehydrogenase, glutamate-oxaloacetate transaminase and creatine phosphokinase were prevented more effectively when ajmaline was given pre-occlusion rather than post-occlusion. 5. Fifteen min post-occlusion, the ajmaline concentrations in the ischaemic ventricle were 18.42 +/- 1.66 and 1.18 +/- 0.15 micrograms g-1 for pre- and post-occlusion administration, respectively. However, ajmaline concentrations in whole blood and normal ventricle were not significantly different between pre- and post-occlusion administration. 6. We suggest that the beneficial effect of ajmaline against reperfusion-induced arrhythmias is related to the ischaemic myocardial concentration of ajmaline which is markedly affected by the time of drug administration (i.e. pre- and post-occlusion).

Ajmaline↗
PubMed1988

Intestinal absorption of cephalosporin antibiotics: correlation between intestinal absorption and brush-border membrane transport.

The absorption of seven cephalosporin antibiotics from the in-situ intestinal loop at pH 7.4 and their transport by brush-border membrane vesicles in the presence of an inward H+ gradient ([pH]i = 7.5, [pH]o = 6.0) were examined. A good correlation was found between the intestinal absorption rate and the initial uptake rate by brush-border membrane vesicles. The data suggest that the transport study using intestinal brush-border membrane vesicles is useful as a model system for the intestinal absorption of beta-lactam antibiotics.

Animals↗
PubMed1988

Mechanism of action of cephalosporins and resistance caused by decreased affinity for penicillin-binding proteins in Bacteroides fragilis.

The susceptibilities of 52 clinical isolates of Bacteroides fragilis to five monoanionic cephalosporins were examined. Cefoperazone showed the highest antibacterial activity, followed by ceftezole, cefazolin, cefamandole, and cephalothin. There were two groups of resistant strains: one group (ca. 15%), of which B. fragilis G-232 was a typical sample, was resistant to ceftezole (MIC, 100 micrograms/ml), cefazolin (MIC, 100 micrograms/ml), and cephalothin (MIC, 200 micrograms/ml) but not cefoperazone (MIC, 6.25 micrograms/ml) or cefamandole (MIC, 25 micrograms/ml). On the basis of studies of stability to beta-lactamase, outer membrane permeation, and affinity for penicillin-binding proteins (PBPs), we conclude that decreased affinity for PBP 3 may play an important role in the resistance to ceftezole, cefazolin, and cephalothin in B. fragilis G-232. Another group (also ca. 15%), of which B. fragilis G-242 was a representative, was resistant to all five cephalosporins (MIC, 100 to 400 micrograms/ml) and produced a high amount of beta-lactamase. Similar broad-spectrum resistance was seen in a mutant of strain G-232 that had a greater-than-30-fold increase in beta-lactamase production.

Bacterial Proteins↗
PubMed1988

Outer membrane permeation of Bacteroides fragilis by cephalosporins.

Outer membrane permeation of Bacteroides fragilis by cephalosporins was examined by a previously described method. The permeation parameters of cephalosporins in B. fragilis were close to 10(-5) cm3/min per microgram of cell dry weight. These values were about an order of magnitude lower than those in Escherichia coli. In B. fragilis, the permeation was not directly proportional to the hydrophilicity of cephalosporins, and the ion selectivity was weak.

Bacterial Outer Membrane Proteins↗
PubMed1988

Aminoglycoside-induced alterations in apical membranes of kidney epithelial cell line (LLC-PK1).

Aminoglycoside-induced renal cell injury was investigated using the LLC-PK1 pig kidney epithelial cell line. The development of aminopeptidase and gamma-glutamyltransferase, marker enzymes for apical membranes, was inhibited in the LLC-PK1 cells cultured with gentamicin. The inhibitory effect of gentamicin on the enzyme activities was dose dependent and was related to its accumulation within the cells. The development of Na+ -dependent active transport of alpha-methyl-D-glucoside, a nonmetabolizable hexose, was also inhibited by treatment with gentamicin. Inhibitions in apical membrane enzyme activities and Na+ -dependent transport of alpha-methyl-D-glucoside were associated with the elevation of cytosolic free calcium, determined with a fluorescent indicator fura-2. The correlation between the alterations in apical membrane functions and the increase in cytosolic free calcium concentration was also supported by the study using the calcium ionophore A23187. The present data suggest that aminoglycoside-induced alterations in apical membranes of the LLC-PK1 cells are related to the increase in cytosolic free calcium levels.

Aminoglycosides↗
PubMed1988

Increased diuretic response to furosemide in rats with glycerol-induced acute renal failure.

To clarify the diuretic response to furosemide in a diseased state, the urinary excretion of furosemide, water, and electrolytes was examined after a single intravenous injection of furosemide in control rats and rats with mild acute renal failure (ARF) induced by glycerol. The urinary recovery of furosemide was similar in the control and ARF rats. However, the diuretic response to furosemide was increased in ARF rats compared with control rats. Although the relationship between the urine flow rate (UFR) and the urinary excretion rate of (Na+ + K+) (UV Na + K) was the same in both groups, the urinary excretion rate of K+ (UV K) was decreased in ARF rats. The concentrating ability in ARF rats was also decreased compared with that in control rats. By infusion of aldosterone in ARF rats, both UV K and the concentrating ability were increased and the diuretic response to furosemide was decreased, whereas the relationship between UFR and UV Na + K was not changed. Therefore, it is concluded that the increased diuretic response to urinary excretion of furosemide in ARF rats may be caused, at least in part, by the decreased concentrating ability along the nephron.

Acute Kidney Injury↗
PubMed1988

Decreased diuretic response to furosemide in rats with acute hepatic failure.

Furosemide diuresis is occasionally reduced in cirrhotic patients with ascites. To define this phenomenon, the amounts of water, electrolytes, and furosemide excreted in urine were measured in control and CCl4-induced acute hepatic failure (AHF) rats. The diuretic action of furosemide (10 mg/kg, i.v.) was reduced in AHF rats, accompanied by increased plasma aldosterone concentration and accelerated urinary K+ excretion rate. Furosemide transiently increased the urinary inulin excretion rate (UVIN) in both control and AHF rats. Then the UVIN quickly returned to the baseline value in control rats, but rapidly dropped below the baseline in AHF rats. To clarify the contribution of aldosterone in these phenomena, AHF rats was adrenalectomized (ADX) and treated with or without exogenous aldosterone. The UVIN in ADX rats given no infusion or a low-dose aldosterone infusion was similar in pattern to that of the control group, but the UVIN in the ADX rats given a high-dose aldosterone infusion showed a pattern similar to that of the AHF rats not adrenalectomized. These findings indicate that an increase in plasma aldosterone concentration is an important factor responsible for the decreased diuretic action of furosemide, along with the reduced glomerular filtration rate.

Adrenalectomy↗
PubMed1988

H+ coupled transport of p.o. cephalosporins via dipeptide carriers in rabbit intestinal brush-border membranes: difference of transport characteristics between cefixime and cephradine.

We demonstrated previously that aminocephalosporins, such as cephradine, possessing a alpha-amino group and a carboxyl group, are transported via H+/dipeptide carrier system in the intestinal brush-border membranes. The present study examined the transport characteristics of cefixime, a new p.o. cephalosporin with two carboxyl groups, by the rabbit intestinal brush-border membrane vesicles in comparison with those of cephradine. With an intravesicular pH of 7.5, apparent optimum extravesicular pH was 6.0 for cephradine uptake and more acidic (pH 4.5-5.0) for cefixime uptake. An inward H+ gradient [( pH]i = 7.5, [pH]o = 5.0) induced overshoot uptake of cefixime, and this uptake was reduced in the presence of carbonyl cyanide p-trifluoromethoxyphenylhydrazone, a protonophore. Cefixime uptake at pH 5.0 was trans-stimulated (countertransport effect) and cis-inhibited by dipeptides and aminocephalosporins but not at pH 7.5. Cephradine uptake at pH 7.5 was stimulated by the countertransport effect of dipeptide but not by cefixime. Cefixime and cephradine uptake at pH 5.0 was greatly inhibited by 4,4'-diisothiocyano-2,2'-disulfonic stilbene. These findings indicate that cefixime is transported by an inward H+ gradient via dipeptide carrier only in an acidic pH region, whereas cephradine is transported via dipeptide carrier in both neutral and acidic pH regions, suggesting the existence of multiple transport systems for dipeptides; a neutral pH preferring system (Type I) and an acidic pH preferring system (Type II).

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1987

Kinetics of ajmaline disposition and pharmacologic response in beagle dogs.

Pharmacokinetics and pharmacodynamics of ajmaline were studied in four healthy dogs after intravenous administration of the drug at the infusion rate of 1.0 mg/min for 45 min. Ajmaline exhibited a saturable binding to plasma protein. One kind of binding site was found in the range of observed drug concentrations and its binding capacity showed nearly threefold interindividual difference. The time course of ajmaline concentration in whole blood Cb could be described by the two-compartment open model and the unbound concentration of ajmaline in plasma Pf was estimated from Cb by using the hematocrit value and the parameters of plasma protein binding and erythrocyte partitioning. The pharmacologic responses to ajmaline were assessed by recording ECG, and the changes in PQ and QRS interval were studied in relation to ajmaline disposition. When ECG changes were related to the ajmaline concentration, a significant degree of hysteresis was observed. The relationship between the unbound drug concentration and the pharmacologic effect was analyzed by a combined pharmacokinetic-pharmacodynamic model, where the hypothetical effect compartment is connected to the Pf in the central compartment by a first-order process. This model allows estimation of the changes in PQ and QRS intervals after intravenous administration of ajmaline. By comparing the drug effect on PQ and QRS intervals, it was suggested that ajmaline distributes to the atrial and the ventricular tissue in a similar degree and causes a reduction in the conduction rate in both sites with similar activity.

Ajmaline↗
PubMed1987

Binding of basic drugs to rat lung mitochondria.

The role of the mitochondria in the accumulation of basic amine drugs in the rat lung was studied. Drug binding to the mitochondria was rapid and reached maximum levels after 2.5 min of incubation. Lipophilic basic drugs accumulated in the mitochondria more than nonlipophilic basic drugs and nonbasic drugs, and the accumulation was dose dependent. Schatchard plots revealed at least two independent sets of binding sites for basic drugs in the mitochondria. The binding was competitively inhibited by other basic drugs but not nonbasic drugs. The degree of inhibition by competing basic drugs was correlated with their lipid solubilities. These findings with isolated mitochondria agree with previous results obtained with the perfused lung preparation and indicate that the mitochondria play an important role in the accumulation of basic drugs in the lung.

Animals↗
PubMed1987

Subcellular distribution of basic drugs accumulated in the isolated perfused lung.

To clarify the mechanism by which basic drugs accumulate in the lung, the binding selectivity of drugs to different subcellular structures of the perfused rat lung was examined. Imipramine, quinine, and metoclopramide were used as examples of basic drugs. The accumulation of basic drugs was highest in the mitochondrial fraction. The drug accumulation in the lung mitochondrial fraction increased with increasing lipid solubility and was dose dependent. These results suggest the presence of specific binding sites for basic drugs in mitochondria and that mitochondria play an important role as a reservoir for basic drugs.

Animals↗
PubMed1987

Clinical and ultrastructural studies in duodenal pseudomelanosis.

Nine patients with duodenal pseudomelanosis are described: seven had endstage renal failure while one other patient had undergone renal transplantation. Eight of the nine had been on oral iron supplements. The pigment stained positively with Perls' stain for iron in five patients, positively with the Masson-Fontana method normally used to identify melanin in one, and positively with both methods in three. Electron probe x-ray analysis of the pigment on samples from six patients showed iron to be present in all six, while sulphur was present in five. Varying sulphur content of the pigment in different patients could account for differences in histochemical characteristics. Iron was also shown in the duodenal biopsies of 34 of 48 uraemic patients on oral iron supplements, but was present in only 22 of 120 patients endoscoped for miscellaneous conditions (p less than 0.001). We postulate that the pigment of duodenal pseudomelanosis is derived from iron absorbed from the lumen.

Adolescent↗
PubMed1987

Effect of sulfhydryl reagents on tetraethylammonium transport in rat renal brush border membranes.

Effect of sulfhydryl reagents on the transport of tetraethylammonium, an organic cation, has been studied in brush border membrane vesicles isolated from rat renal cortex. H+ gradient-dependent uptake of tetraethylammonium by the vesicles was inhibited by various sulfhydryl reagents in a dose-dependent manner, and the potency of the reagents was followed in the order of HgCl2 greater than p-chloromercuribenzoate, p-chloromercuribenzene sulfonate (PCMBS) greater than N-ethylmaleimide. In the absence of H+ gradient, tetraethylammonium uptake and efflux also were inhibited by p-chloromercuribenzoate and PCMBS. The sulfhydryl reagents did not affect the dissipation rate of H+ gradient across the membranes. Pretreatment of brush border membranes with PCMBS resulted in an inhibition of tetraethylammonium uptake in the presence and absence of H+ gradient, and this inhibition was reversed by subsequent treatment of the vesicles with thiols such as dithiothreitol, glutathione and cysteine. The inhibitory effect by PCMBS pretreatment was protected in the preincubation with unlabeled tetraethylammonium. These results suggest that sulfhydryl reagents inhibit the transport of tetraethylammonium by their specific interaction with the active sites of the carrier, and that sulfhydryl groups are essential for organic cation transport system in renal brush border membranes.

4-Chloromercuribenzenesulfonate↗
PubMed1986

H+ coupled uphill transport of aminocephalosporins via the dipeptide transport system in rabbit intestinal brush-border membranes.

The transport characteristics of aminocephalosporin antibiotics, possessing an alpha-amino group and a carboxyl group, in brush-border membranes isolated from rabbit small intestine have been studied by a rapid filtration technique. The uptake of cephradine by brush-border membrane vesicles was stimulated by the countertransport effect of dipeptides, which indicates the existence of a common carrier transport system. An inward H+ gradient ([pH]i = 7.5 to 8.4, [pH]o = 6.0) stimulated cephradine uptake against a concentration gradient (overshoot phenomenon), and this stimulation was reduced when the H+ gradient was subjected to rapid dissipation by the presence of carbonyl cyanide p-trifluoromethoxyphenylhydrazone, a protonophore. A valinomycin-induced K+ diffusion potential (interior-negative) stimulated H+ gradient-dependent cephradine uptake without altering the equilibrium value. The uptake of other aminocephalosporins (cefadroxil, cefaclor, cephalexin) was also stimulated in the presence of an inward H+ gradient, while the uptake of cephalosporins without the alpha-amino group (cefazolin, cefotiam) was not changed in the presence or absence of the H+ gradient. These results suggest that the transport of aminocephalosporins can be driven actively by an inward H+ gradient via the dipeptide transport system in the intestinal brush-border membranes, and that the process results in the transfer of a positive charge.

Animals↗
PubMed1986

Specific binding of atrial natriuretic polypeptide to renal basolateral membranes in spontaneously hypertensive rats (SHR) and stroke-prone SHR.

The binding of alpha-human atrial natriuretic polypeptide (alpha-hANP) to basolateral membranes isolated from renal cortex of spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHR-SP) was measured at 0 degree C and compared with that of Wistar-Kyoto rats (WKY). The binding of 125I-alpha-hANP in SHR and SHR-SP at 14-15 weeks old demonstrated different binding profiles compared with that in WKY, though there were no apparent differences of the profiles among WKY, SHR and SHR-SP at 5 weeks old. For the high affinity binding sites, the apparent dissociation constant and the maximal binding capacity in SHR and SHR-SP were significantly decreased in comparison with those in WKY. The present data suggest that the altered characteristics of specific receptors for atrial natriuretic polypeptide in SHR and SHR-SP may be involved in the development or maintenance of genetic hypertension.

Age Factors↗