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Biomedical subjects

K Iwamoto

Publications and source records attributed to K Iwamoto.

At least 217 records · Page 12Linked to original sources
PubMed1985

Development of rabbit brain tumor model for radiologic research.

A rabbit brain tumor model using transplanted VX-2 carcinoma had an 85% rate of successful implantation. Rabbits lived 8.5 +/- 1.3 days. The tumor doubling time was 0.5 to 2.6 days. Some tumors were shown as early as four days after implantation and all tumors were seen by ten days after implantation. Two of three rabbits receiving radiation therapy to the tumor had significant extension of life. This model is a useful radiologic research tool.

Animals↗
PubMed1985

Effect of age on the hepatic clearance of propranolol in rats.

The effect of age on hepatic clearance of propranolol was investigated in male Wistar rats (3 to 104 weeks old). Pharmacokinetic analysis of the plasma propranolol data obtained after i.v. dosage (1.0 mg kg-1) indicated that both the elimination rate constant and the volume of distribution decreased with age between weeks 5 and 11, after when the distribution volume remained almost constant. The elimination rate constant was reduced consistently with age after 15 weeks. Total body clearance of the drug was reduced extensively with age between weeks 5 and 11 (94 to 43 ml min-1 kg-1) and decreased gradually thereafter. The plasma free fraction of propranolol also decreased with age, falling from more than 20% in 3 to 5 weeks-old rats to about 10% in rats of 52 to 104 weeks. In immature rats the renal clearance was approximately 5 to 12% of the total body clearance. Intrinsic hepatic clearance for unbound propranolol also decreased with age between weeks 7 and 24. As expected from the evidence that propranolol has a high extraction ratio, the extent of its hepatic clearance was significantly dependent on the liver blood flow. These data suggest that the age-dependent decrease in hepatic clearance of propranolol is largely due to a reduction of the elimination rate that might be accompanied by the age-dependent decrease in liver blood flow.

Administration, Oral↗
PubMed1985

Dose-dependent presystemic elimination of propranolol due to hepatic first-pass metabolism in rats.

Gastrointestinal first-pass elimination of propranolol and the effect of dose (1.0, 2.5, 5.0 and 10.0 mg kg-1) on its systemic availability were studied in male Wistar rats which received the drug intravenously, orally or intraportally. The plasma elimination half-life was not altered either by the route of administration or the dose. There was no gastrointestinal first-pass metabolism of propranolol, since the same systemic availability was obtained after oral and intraportal administration. Hepatic clearance was estimated to be constant at any dose. In contrast, the hepatic intrinsic clearance was found to be largely dependent on the portal dose.

Animals↗
PubMed1985

Dose-dependent disposition of fractionated 3H-heparin in rats.

To investigate the disposition of fractionated 3H-heparin, commercial 3H-heparin was fractionated by affinity chromatography on protamine-Sepharose and subsequently by Sephadex G-100 chromatography. Effect of dose on the disposition of fractionated 3H-heparin was studied. At an early stage following the intravenous administration of fractionated 3H-heparin which had either affinity or non-affinity for protamine-Sepharose, elimination of the radioactivity from plasma was delayed with increasing dose. Even at 5 h after the administration when most radioactivity in plasma disappeared, the cumulative urinary recovery was only 4.8 to 8.4% of dose (1 to 15 microCi/kg), and 61 to 43% of dose was found in liver. Therefore, it was suggested that tissue (liver) distribution of radioactivity might be a predominant factor for the dose-dependent disappearance of the radioactivity from plasma at an early stage following the administration of fractionated 3H-heparin. Plasma radioactivity levels tended to be pseudo-steady state or to increase slightly after about 1 to 2 h following the administration of fractionated 3H-heparin. Participation of entero-hepatic circulation in this tendency was rejected.

Animals↗
PubMed1985

[A case of remission of metastatic gastric cancer lesions in the chest and abdominal wall by 5'-DFUR administration].

52-year-old female was weakened and bed-ridden by metastasis of gastric cancer to the chest and abdominal wall, and peritonitis carcinomatosa 2 years after gastrectomy. One week after administration of 5'-DFUR, 1200 mg/d, p.o., a clinical effect was seen. In 3 weeks metastatic lesions had diminished in size, ascites had decreased and the patient had regained her appetite and put on weight. She recovered sufficiently to be able to do some daily work. Pathological degeneration and necrosis of cancer cells were observed. Although she died 8 months after remission, 5'-DFUR was effective in improving her condition and prolonging her life.

Abdominal Muscles↗
PubMed1985

Reduced hepatic clearance of propranolol induced by chronic carbon tetrachloride treatment in rats.

Effect of liver injury induced by chronic treatment with carbon tetrachloride for 1 to 4 months on hepatic clearance of propranolol was investigated in male Wistar rats. Plasma propranolol level after i.v. and p.o. dosing (1.0 mg/kg) was always higher in the rats which were treated for 2 and 4 months than in control (sham-injected) rats. The chronic treatment reduced hepatic clearance of propranolol significantly, yielding only approximately 30 to 50% of the control clearance value. Distribution volume of this drug was also significantly reduced by the chronic treatment but seemed to be less sensitive to the treatment than the hepatic clearance. Accordingly, the elimination rate constant was decreased slightly in the rats treated longer than 2 months. The chronic treatment for 2 and 4 months also reduced intrinsic hepatic clearance substantially. The hepatic clearance estimated for both these control and chronically treated rats was significantly dependent on the liver blood flow. Furthermore, propranolol was eliminated much more slowly in the injured liver of the rat which was treated for 2 or 4 months than in the control liver when perfused in in vitro technique. It is, therefore, suggested that the metabolic dysfunction induced by chronic treatment with carbon tetrachloride may be directly related to substantial changes in anatomical arrangement of the hepatic circulation (portasystemic shunting), which may be due to a fibrosis of the tissue.

Animals↗
PubMed1984

Increased lung uptake of liposomes coated with polysaccharides.

Liposomes labeled with [14C]coenzyme Q10 in the lipid bilayer were coated with various polysaccharide derivatives, i.e., palmitoyl conjugates of pullulan, pullulan phosphate, amylopectin, amylopectin phosphate and amylopectin sulfate. The kinetics of disposition and the tissue distribution of [14C]coenzyme Q10 after intravenous injection of the liposomes into guinea pigs were investigated. Lung uptake of radioactivity after injection of the O-palmitoyl amylopectin- and O-palmitoyl amylopectin phosphate-coated liposomes was 5- and 3-times higher, respectively, at 30 min after injection than that of the conventional liposomes. For doubly labeled liposomes with [3H]inulin and [14C]coenzyme Q10, the 3H/14C ratios in the lung, spleen and heart were similar to one another. Urinary excretion of [3H]inulin encapsulated in O-palmitoyl amylopectin-coated liposomes was much lower than that of unencapsulated [3H]inulin. These observations suggest that the O-palmitoyl amylopectin-coated liposomes are rather stable in vivo and are taken up into tissues in the intact form.

Animals↗
PubMed1984

Difference in hepatic uptake kinetics of aspirin and salicylamide in rats.

Immediately after intraportal administration to rats, the ratio of liver to plasma concentrations for total aspirin was close to unity, whereas that for total salicylamide ranged from about 3 to 7. The hepatic accumulation of salicylamide appeared to be capacity-limited because the ratio decreased with increases in the dose. In vitro experiments with isolated hepatocytes indicated that aspirin was slowly transported into the hepatocytes by an apparently linear process only, while salicylamide was taken up very rapidly by both saturable and apparently linear transport processes. The cell to medium concentration ratio estimated for the initially net transported component of the unchanged drug was significantly larger with salicylamide, which give ratios from 3.5 to 19, than with aspirin which gave an almost constant value lower than 2 despite wide variations in the initial concentration. For the capacity-limited uptake process of salicylamide, the kinetic parameters were estimated as Vmax = 0.325 nmole X (mg cellular protein)-1 X sec-1 and Km = 201 microM. Among various metabolic inhibitors, 2,4-dinitrophenol (50 microM) inhibited the uptake of salicylamide most extensively. The present comparison of the in vivo and in vitro data for aspirin with those for salicylamide confirmed the previously reported difference in the hepatic first-pass effect of these two drugs.

2,4-Dinitrophenol↗
PubMed1984

pKa determination of verapamil by liquid-liquid partition.

The pKa of verapamil was determined by measuring the partition coefficient of verapamil between n-heptane and aqueous buffer solution at various pH values. The magnitude of the effects of ionic strength or temperature on the pKa of verapamil was in agreement with those reported previously. The estimated pKa of verapamil in human plasma was 8.75. The pKa of 2,4,6-trimethylpyridine measured by means of the present partition method was in good agreement with that determined by UV spectrophotometry.

Hydrogen-Ion Concentration↗
PubMed1984

Salivary excretion of urea in dogs.

The salivary excretion of urea was investigated by collecting parotid saliva (Pr) and mandibular-sublingual saliva (MS) separately in beagle dogs. (1) After intravenous administration of urea (1.5 g/kg), urea concentrations in both Pr and MS were well correlated to but were lower than those in plasma. Urea concentrations in MS were significantly lower than those in Pr (p less than 0.05), indicating that there was glandular difference in salivary excretion of urea. (2) This glandular difference was not explained by Matin's equation, even if all variation factors in this equation were considered. (3) At relatively low salivary flow rates, the increase in saliva/plasma urea concentration ratio (S/P ratio) for both Pr and MS was found in the experiments for endogenous urea. (4) At relatively low salivary flow rates, glandular difference was observed in the S/P ratios of sodium ion. (5) Salivary clearance of urea was highly dependent on salivary flow rate under stimulated condition for salivation, and mean value of the salivary clearance of urea was about 20% of its total body clearance.

Absorption↗
PubMed1984

[Clinical studies on cefoxitin in the treatment of respiratory tract infections].

The clinical effects of cefoxitin (CFX) were studied in 31 cases of respiratory tract infections. The results were as follows: As for the clinical effects, CFX was excellent in 5 cases, good in 13, fair in 8 and poor in 5 out of 31 patients; the efficacy rate was 58.1%. The efficacy rate was 57.1% in bronchopneumonia, 61.1% in pneumonia and 50.0% in acute exacerbation of chronic respiratory tract infections. The efficacy rate was 70.6% in the group of 4 g/day or less and 42.9% in the group of 6 g/day or more. The efficacy rate was 50.0% in 6 cases that had not been responded to other antibiotics previously. As for side effects, skin eruption was observed in only 1 patient. No abnormality was observed in laboratory tests due to CFX. In conclusion, CFX is a useful drug in the treatment of respiratory tract infections.

Adult↗
PubMed1983

Liposomal membranes. XIV. Fusion of liposomal membranes induced by polyisoprenoids as monitored by fluorescence quenching method.

Fusion of the single-walled liposomes of egg phosphatidylcholine as induced by the polyisoprenoids such as solanesol, trans-ethyl decaprenoate (EDP), coenzyme Q10, and dolichol has been investigated adopting the fluorescence quenching method. Relative efficiency of the polyisoprenoids employed on the induced fusion of liposomes was a sequence of solanesol less than or equal to EDP much less than CoQ10, dolichol, which was consistent with the result previously obtained by the dye-release method.

Cell Fusion↗