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Biomedical subjects

R Hori

Publications and source records attributed to R Hori.

At least 199 records · Page 11Linked to original sources
PubMed1984

Effect of aminoglycoside antibiotics on cellular functions of kidney epithelial cell line (LLC-PK1): a model system for aminoglycoside nephrotoxicity.

The effects of aminoglycoside antibiotics on cellular functions of the LLC-PK1 kidney epithelial cell line were studied as a model system for aminoglycoside nephrotoxicity. The treatment with aminoglycoside antibiotics for 3 days caused a decrease in the dome number in the confluent LLC-PK1 cells and an increase in the floating cells in the culture medium. The inhibition of dome formation was dose-dependent and the rank-order of the degree of inhibition was compatible with the rank-order of in vivo nephrotoxicity. Aminoglycosides also decreased the intracellular content of cyclic AMP, with a correlation between the alteration of dome formation and cyclic AMP content. The specific activities of N-acetyl-beta-D-glucosaminidase (marker for lysosomes), aminopeptidase and alkaline phosphatase (marker for apical membranes) and (Na++K+)-adenosine triphosphatase (marker for basolateral membranes) in the homogenate were decreased by gentamicin treatment. Lysosomal and apical membrane enzymes released into the culture medium were increased by gentamicin treatment. The ultrastructural alterations in the lysosomes of gentamicin-treated cells also were observed. Above results suggest that aminoglycoside toxicity to LLC-PK1 cells may be similar to that reported for renal tubules.

Adenosine Triphosphate↗
PubMed1983

Specific secretin binding sites in rat pancreas.

The dynamic nature of specific secretin binding sites in the pancreas was studied to simulate the interaction of secretin with its receptors in living organisms using isolated perfused rat pancreas. [125I]Secretin or [125I]-[Tyr1] secretin bound to certain binding sites in the perfused pancreas was displaced only by secretin in a dose-dependent manner, not by glucagon or vasoactive intestinal peptide, and the majority of the displaced radioactivity was demonstrated to be undegraded. On the basis of a secretin binding study with subcellular components, it was considered that the displacement would occur on the plasma membranes. These findings suggest that secretin which is distributed in the pancreas may rapidly and reversibly bind to specific binding sites or receptors on the plasma membranes with high affinity.

Animals↗
PubMed1983

Carrier-mediated transport of amino-cephalosporins by brush border membrane vesicles isolated from rat kidney cortex.

The uptake of cephalosporin antibiotics by brush border membrane vesicles isolated from rat renal cortex has been studied by a rapid filtration technique, demonstrating a carrier-mediated transport system for amino-cephalosporins such as cephalexin and cephradine. The antibiotics were taken up into an osmotically reactive intravesicular space. The uptake of cephalexin was saturable (apparent Km2.2 mM), was inhibited by structural analogues and sulfhydryl reagents, and was stimulated by the countertransport effect, although the Na+ gradient did not affect the uptake. This transport system was essentially different from the transport system for p-aminohippurate in brush border membranes. The uptake properties for cephradine in brush border membrane vesicles appeared to be similar to those for cephalexin. The present results suggest the existence of a carrier-mediated transport system for amino-cephalosporins in brush border membranes. This system may be a part of the mechanism of tubular reabsorption of these antibiotics.

Animals↗
PubMed1983

Pharmaceutical approach to subcutaneous dosage forms of insulin.

The present studies were undertaken to describe the dynamic nature of the degradation and absorption of insulin in the subcutaneous injection site and to develop agents which would stabilize this dosage form. [125I]Insulin with 0.2-U/kg of unlabeled insulin in 10 microliters of aqueous solution was injected subcutaneously in rats under the depilated skin of the back. At various times, radioactive skin tissue was extracted and assayed for insulin and/or its metabolites by gel filtration. Using these data, absorption and degradation rate constants of these substances were estimated according to a one-compartment model. Absorption rate constants of insulin and its metabolite of low molecular weight (monoiodotyrosine) were 0.021 min-1 and 0.107 min-1, respectively, while the degradation rate constant for insulin to monoiodotyrosine was 0.013 min-1. Thus, the bioavailability of insulin injected subcutaneously was lower than expected, suggesting the necessity of stabilizing methods. The protection of insulin from degradation at the site of injection was examined by the addition of various peptides. It was found that benzyloxycarbonyl-Gly-Pro-Leu-Gly was a good stabilizing agent, and remarkably inhibited insulin degradation. This inhibition was confirmed by the increase of immunoreactive insulin level and the decrease of the blood glucose level. We postulated that this peptide protects the injected insulin from degradation by inhibiting the peptidase present in subcutaneous tissue.

Animals↗
PubMed1983

Quantitative investigation on renal handling of drugs in rabbits, dogs, and humans.

A renal clearance method based on a computer analysis after administration of a single dose of drug was developed for measuring the renal handling of several drugs in rabbits, dogs, and humans. Secretion and reabsorption of sulfamethizole, sulfanilamide, cephalexin, and ampicillin in the nephron were analyzed quantitatively using the plasma concentration and the urinary excretion rate of the drugs. The validity of the proposed model was demonstrated. It appears that tubular secretion of sulfamethizole, cephalexin, and ampicillin depend on the active transport system which is described by Michaelis-Menten kinetics; the tubular reabsorption of these drugs is expressed by first-order kinetics. The maximum velocity of renal secretion per unit weight of these drugs was much higher in rabbits than in dogs or humans. Reabsorption showed similar values in dogs and humans. These findings suggest that an analysis of the renal handling of drugs in dogs might provide useful information when considering the appropriate therapeutic dose in humans.

Adult↗
PubMed1983

Ampicillin and cephalexin in renal insufficiency.

We analyzed the relationship between functional damage and transport processes in the kidney in patients with glomerulonephritis and renal failure by a new analytic method. In renal failure patients, there was substantial diminution of maximum transport of secretion in renal tubules. This reduction affected the urinary excretion of ampicillin and cephalexin substantially because both drugs depend on active renal tubular secretion. Our results indicate that dosage adjustment based on creatinine clearance is not appropriate for patients receiving drugs requiring active tubular secretion for urinary excretion. Our data point to a need for a prolongation of the dosage interval of cephalexin to 20 times that in normal subjects, while five times is recommended by the creatinine clearance. In these patients, it is therefore suggested that a dosage adjustment method that involves both factors--glomerular and renal tubular functions--is required.

Acute Kidney Injury↗
PubMed1982

Mechanisms of p-aminohippurate transport by brush-border and basolateral membrane vesicles isolated from rat kidney cortex.

The uptake of [3H]-labeled p-aminohippurate by brush-border and basolateral membrane vesicles isolated from rat renal cortex has been studied by a rapid filtration technique. Some characteristics of carrier-mediated transport for p-aminohippurate were demonstrated in basolateral membrane vesicles: the uptake was inhibited by probenecid or 4,4'-diisothiocyano-2,2'-disulfonic stilbene (DIDS), was saturable, was stimulated by the countertransport effect, and showed discontinuity in the Arrhenius plot. In contrast, brush-border membrane vesicles failed to display saturability of p-aminohippurate uptake and stimulation by the countertransport effect, although probenecid and DIDS reduced the uptake. Furthermore, p-aminohippurate uptake by brush-border membrane vesicles was influenced more sensitively by alteration in the membrane potential compared with that by basolateral membrane vesicles.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1982

The interaction of cephalosporin antibiotics with renal cortex of rats: accumulation to cortical slices and binding to purified plasma membranes.

The interaction of cephalosporin antibiotics with renal cortex of rats has been examined in vitro by means of cortical slice uptake and binding assay to plasma membranes and other subcellular fractions, including the comparative study with p-aminohippurate. The uptakes of cephalexin and cephaloridine by cortical slices were concentrative, and were strongly inhibited in the presence of 2,4-dinitrophenol, ouabain, nitrogen gas and probenecid. In the case of cefazolin, the degree of concentrative uptake and influence of inhibitors were low. Cephalexin, cephaloridine and p-aminohippurate specifically bound to the basolateral membranes, compared to brush border membranes and other subcellular fractions. Cefazolin binding to basolateral membranes was relatively small. These results suggest that the specificity of cephalexin and cephaloridine bindings to the basolateral membranes could be related to the interaction with the organic acid transport system at the antiluminal side. Thus, an examination of cephalosporin interaction with plasma membranes from renal cortex could offer an appropriate in vitro model system to study the renal transport of these antibiotics.

Animals↗
PubMed1982

Distribution and metabolism of secretin and aprotinin in isolated perfused rat pancreas.

The distribution and metabolism of secretin and aprotinin were studied in isolated perfused rat pancreas, which were kept under physiological conditions. At 125I-[Tyr1]secretin perfusion study the radioactivity appeared in the effluent, rapidly attaining an equilibrium with the perfusate. While the intact secretin concentration decreased to 55% of the perfusate; the distribution space of secretin was estimated to be about 0.11 ml/g pancreas. The ratio of intact secretin to degradated products in the pancreas increased concomitantly with the perfusion of 82 nM secretin. When unlabeled secretin was perfused, immunoreactive secretin concentration in the portal effluent reached also a rapid equilibrium to about 60% of the perfusate. These results suggested that pancreas might clear about 40% of the entering secretin. In the case of 125I-aprotinin perfusion, intact aprotinin fraction was predominant both in the effluent and in the pancreas. The apparent distribution space was about 40% of the volume of pancrease. Meanwhile, when 125I-reduced aprotinin or 125I-[S-carboxamidomethyl]aprotinin was perfused, the decomposed products were significantly increased. These findings indicate that the disulfide bonds in aprotinin molecule play an important role for its stability as well as its antiproteolytic activity.

Amylases↗
PubMed1982

[Parenteral administration of diphenylhydantoin in the pre- and post-operative course on plasma level measurement].

In the neurosurgical care, postoperative convulsion, the especially in the early postoperative course, is one of major complications because it can spoil an otherwise good surgical result. The present study was intended to investigate the prophylactic use of anticonvulsants on chemical measurement of their plasma levels. Parenteral diphenylhydantoin (DPH) given just before craniotomy failed to maintain high level of DPH in the postoperative course even with pretreatment of oral DPH. On the other hand, preoperative oral phenobarbital administration maintained fairly high level in spite of no prescription on the operative day. Intravenous DPH of 250 mg immediately after craniotomy resulted in fairly high level of DPH throughout the early postoperative course in cases of pretreatment of oral DPH. In reviewing the pharmacokinetics of anticonvulsants, the prophylactic use of anticonvulsants in the early postoperative course was discussed.

Adult↗
PubMed1981

A simple method for the isolation of basolateral plasma membrane vesicles from rat kidney cortex. Enzyme activities and some properties of glucose transport.

A procedure for preparing basolateral membrane vesicles from rat renal cortex was developed by differential centrifugation and Percoll density gradient centrifugation, and the uptake of D-[3H] glucose into these vesicles was studied by a rapid filtration technique. (Na+ + K+)-ATPase, the marker enzyme for basolateral membranes, was enriched 22-fold compared with that found in the homogenate. The rate of D-glucose uptake was almost unaffected by Na+ gradient (no overshoot).

Alkaline Phosphatase↗
PubMed1980

Tissue distribution and metabolism of drugs V: effect of secretin and pancreozymin on drug transport in rabbit pancreas.

The effect of secretin and pancreozymin on the tissue distribution and penetration of drugs in the rabbit pancreas was studied to clarify hormonally regulated drug distribution. Drugs with high liquid solubility were distributed easily within the pancreas even during secretin or pancreozymin treatment, and these hormones had little effect on drug distribution from the blood to the pancreas. However, secretin increased the concentration ratio of dimethadione in the pancreatic juice (J) to plasma unbound dimethadione (Pf), probably because the pancreatic juice during secretin infusion is alkaline relative to the control. Secretin had no effect on the J/Pf of isonicotinamide and sulfanilamide. Secretin decreased the J/Pf of drugs with low lipophilicity or large molecular weight because the penetration rates of these drugs from cell water to pancreatic juice were not rapid enough to reach equilibrium. Pancreozymin was unable to change the J/Pf of any drug tested. These results suggest that the barrier between the blood and the pancreas or the barrier between the pancreas and the pancreatic juice is unchanged by secretin or pancreozymin.

Animals↗
PubMed1980

Tissue distribution and metabolism of drugs VI: Effect of second drugs on pancreatic distribution and insulin-releasing activity of sulfonylureas in perfused rat pancreas.

The distribution of sulfonylureas and their insulin-releasing potency as a pharmacological response were studied in isolated perfused rat pancreas. Sulfonylurea concentrations in the perfused pancreas in the presence or absence of a second drug were determined after perfusion for 15 min. Sulfonylureas could be distributed throughout the pancreas readily, and the tissue sulfonylurea concentration was reduced by the addition of sulfaphenazole, sulfadimethoxine, and salicylic acid. The insulin secretion rate stimulated by tolbutamide also was reduced by these three drugs; sulfanilamide, which could not displace the tolbutamide distribution, did not affect the tolbutamide-mediated secretion of insulin. These results document the importance of drug concentration in the tissue or receptor site with regard to insulin secretion and show that the sulfonylurea-mediated secretion of insulin can be modified easily by concomitant perfusion of a second drug that displaces sulfonylurea in the pancreas. These findings suggest that the drug interaction at the target organ or receptor site should be understood to provide adequate drug therapy.

Animals↗
PubMed1979

The accumulation of manganese from the environmental medium by the egg of Oryzias latipes.

The manganese content of the egg and embryo of the Medaka, Oryzias latipes was determined by activation analysis. A remarkable increase in the amount of manganese in the egg was observed within one hour after fertilization. The rate of increase was reduced by the gastrula stage and the concentration of manganese remained unchanged at a later stage. The accumulation of manganese by the Oryzias egg was discussed in relation to the effect of manganese on respiratory enzyme systems.

Animals↗