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Biomedical subjects

A Kamiya

Publications and source records attributed to A Kamiya.

At least 199 records · Page 11Linked to original sources
PubMed1985

Microcirculatory responses to carotid sinus nerve stimulation at various ambient O2 tension in the rabbit tenuissimus muscle.

To quantify the integrated effects of local and central control mechanisms through tissue metabolites and the autonomic nervous system on the peripheral vascular beds, microcirculatory responses to the carotid sinus nerve stimulation at various levels of ambient oxygen tension (PO2) were measured in the rabbit tenuissimus muscle suffused with oxygenated Tyrode solution, using a microscope-TV system. The statistical analysis of the experimental data exhibited that both capillary red cell velocity and perfused capillary density at the control state were significantly decreased as PO2 was elevated (P less than 0.01) and that the stimulation also significantly augmented their values (P less than 0.01) except for the peak velocity data. Regression analysis indicated that both the velocity and density responses to PO2 changes during stimulation were less sensitive than those at the control state. For instance, the vasodilating effect of stimulation on density at PO2 20 mm Hg was enhanced by about four-fold at 80 mm Hg, although the effect on velocity was increased only by 16% with the same PO2 change. From these results, it was concluded that the microcirculatory changes due to the arteriolar smooth muscle contraction evoked by unit sympathetic discharge was significantly influenced by the ambient PO2 level. Such synergistic interaction of the local and central control mechanisms like a series-coupled gain control system was suspected to play an important role in the overall regulation of the microcirculation.

Animals↗
PubMed1985

A new dosing regimen in renal insufficiency: application to cephalexin.

We describe a new method of drug dosage adjustment. The method simultaneously considers glomerular and tubular functions as parameters, because nonparallel decreases in both functions limit the use of the conventional endogenous creatinine clearance (CLCR) method for dosage adjustment. In the new method, CLCR and the 15-minute phenolsulfonphthalein (PSP15') test were used and applied to patients with renal insufficiency with cephalexin (CEX) as a model drug for renal tubular secretion. The results clearly demonstrate good control of plasma CEX concentrations by the CLCR-PSP15' method, whereas there were marked changes in plasma CEX levels with the CLCR method alone. Our method appears to be more useful for patients with renal impairment than the conventional CLCR method for CEX, which is mainly excreted in urine by renal tubular secretion. A nomogram for the CEX dosing interval is proposed for application to clinical practice.

Absorption↗
PubMed1985

Endothelial surface of the blood flow loaded canine carotid artery. A scanning and transmission electron microscopical study.

In order to study the ultrastructural changes of the endothelial surface induced by blood flow change, an arterio-venous shunt was constructed between the common carotid artery and the external jugular vein in 10 dogs. Blood flow rate was measured before anastomosis, after anastomosis, and after 1 week. After the final measurement (1 week), the arteries were fixed under normal pressure by 2.5% glutaraldehyde solution in phosphate buffer (pH 7.4) and were examined with scanning and transmission electron microscopes. Protrusion of nucleic parts of the endothelial cells, microvilli-like surface projections, and disturbance of pinocytotic vesicles predominated in the shunted arteries exposed to elevated blood flow. No significant ultrastructural changes could be defined in the intercellular junction of the endothelial cells which supported the increased permeability through the junction. It was suggested that the wall shear stress exerted a reactive change on the endothelial cells as well as a direct mechanical deformative effect in the endothelial plasma membrane.

Animals↗
PubMed1984

Effects of nephrotoxic compounds on active uptake of drugs in isolated renal tubules in rabbits.

The uptake of sulfonamides and phenolsulfonphthalein (PSP) was examined in vitro using isolated renal proximal tubule suspension, and the effects of nephrotoxic compounds on the uptake of sulfamethizole (SMZ) were studied. The uptake of SMZ and PSP was energy dependent and was inhibited competitively by iodopyracet (IP), which is transported actively by the p-aminohippurate mechanism. The uptake of sulfamethoxazole was also reduced by IP but that of sulfanilamide was negligible. The present results correspond well with those of in vitro experiments reported previously. Nephrotoxic compounds, mercuric chloride, neomycin, viomycin and kanamycin, decreased the uptake of SMZ non-competitively. The inhibitory action of the three antibiotics corresponds with in vivo potency, suggesting that this renal tubule preparation may provide a simple method for predicting the nephrotoxicity of drugs.

Animals↗
PubMed1984

Pharmacokinetics of nitroglycerin after parenteral and oral dosing in the rat.

The pharmacokinetics of nitroglycerin was characterized in detail using venous plasma after different intravenous bolus doses (0.15-2.48 mg/kg), intra-arterial infusion (8.2 micrograms/min over 5 h), and oral doses (7-100 mg/kg). Venous plasma clearance was found to be approximately 650 mL/kg and was independent of the intravenous or intra-arterial dose. This confirmed earlier reports that the venous plasma clearance of nitroglycerin in rats exceeded the value of normal cardiac output. A terminal half-life of approximately 15 min was observed after high intravenous bolus doses of nitroglycerin. This slow disappearance phase was likely rate limited by redistribution of drug back into the plasma. The bioavailability of oral nitroglycerin (F) showed an apparent Michaelis-Menten dependency on dose. F was less than 5% at doses less than 20 mg/kg, but increased to a plateau of approximately 20% from 50-100 mg/kg. First-pass metabolism of nitroglycerin is thus apparently controlled by at least two systems (sites or enzymes). Coadministration of mannitol hexanitrate, a potential competitive inhibitor of first-pass metabolism, did not increase F.

Administration, Oral↗
PubMed1984

Quantitative investigation of renal handling of drugs in dogs with renal insufficiency.

A quantitative analytical method for studying renal handling of drugs in dogs with mild renal impairment is described. Renal damage was induced experimentally by pretreatment with mercuric chloride or neomycin. Analytical results of renal handling in those animals indicated a reduction in maximum transport of secretion, while the affinity of drugs to secretion site and reabsorption showed slight or no change. These results were consistent qualitatively with other renal function test values which demonstrated the state of glomerular or proximal renal tubular function. Evidence for the applicability of the proposed analytical method for quantitative validation of functional changes in the nephron in renally impaired animals, as well as the precise determination of the site of damage, was demonstrated. This work holds considerable promise for the study of dosage adjustments in patients with renal disease.

Acute Kidney Injury↗
PubMed1984

Blood vessel uptake and metabolism of organic nitrates in the rat.

Recent reports have suggested that the unusual pharmacokinetics observed for nitroglycerin (NTG) and isosorbide dinitrate (ISDN) may be partially explained by extensive uptake and/or metabolism of these drugs by vascular and other extrahepatic tissues. Using the rat as an animal model, this hypothesis was examined by in vivo intravessel NTG and [14C]ISDN infusion and injection into various vessel segments, viz. the femoral vein, inferior vena cava [IVC: lower, middle and upper) and the aorta. NTG and [14C]ISDN concentrations were determined in these blood vessels and in plasma. Blood vessel segments nearest the input site had the greatest amounts of nitrate, whereas segments further away from the input site had progressively less nitrate, with the exception of aorta, which appeared to take up NTG less extensively, on a per weight of vessel basis, than the IVC. Blood vessel NTG concentrations (nanogram per gram) were generally higher (10-fold) and declined about twice as slowly as NTG plasma concentrations (nanograms per milliliter). [14C]NTG and [14C]ISDN were also incubated with cofactors in IVC, aorta, abdominal muscle, lung and liver. The amounts of nitrate metabolites formed from parent drug were larger in each extrahepatic tissue incubation than in the controls (P less than .05). The results are consistent with the hypothesis that vascular and other extrahepatic tissues can take up and/or metabolize organic nitrates. The data appear to provide a partial explanation for the large systemic clearance seen with nitrates and appear consistent with existing mechanistic hypotheses for the vascular action of these compounds.

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

Rectal absorption of nitroglycerin in the rat: avoidance of first-pass metabolism as a function of rectal length exposure.

Nitroglycerin administered orally undergoes substantial presystemic elimination. It was shown recently that first-pass hepatic metabolism of high clearance drugs can be substantially avoided via rectal administration. In applying this concept to nitroglycerin in rats, it was found that unrestricted rectal instillation of nitroglycerin (at 3.5-mg/kg dose) gave a mean +/-SD bioavailability of 26.7 +/- 7.0% (n=6) compared to 1.8 +/- 0.9% (n=5) from oral dosing. This mode of dosing did not lead to complete avoidance of first-pass metabolism of nitroglycerin in rats. When the rectal exposure length to nitroglycerin was restricted to 3.5 cm from the anus, the mean +/-SD bioavailability increased to 83.5 +/- 74.5% (n=14). However, the variability in bioavailability was extremely large. When the rectal exposure length was restricted to 2.0 cm from the anus (at 1.75-mg/kg dose), nitroglycerin bioavailability was estimated at 91.2 +/- 30.4% (n=6). The plasma nitroglycerin concentrations (greater than 5 min) obtained after this mode of administration were similar to those achieved after intravenous dosing. The data showed that substantial avoidance of presystemic nitroglycerin metabolism can be achieved via rectal administration. This avoidance can be nearly complete if nitroglycerin is limited in exposure to only the lower rat rectum. It was also demonstrated that sustained (at least 24 hr) nitroglycerin delivery via the rat rectal route was feasible with an experimental osmotic minipump. This delivery system also produced nearly complete bioavailability for nitroglycerin in the rat.

Animals↗