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Biomedical subjects

Y Kurosaki

Publications and source records attributed to Y Kurosaki.

At least 19 recordsLinked to original sources
PubMed1998

Mature teratoma of the posterior mediastinum.

The vast majority of germ cell tumors in the thorax arise at or near the thymus. We report a case of a 41-year-old man with mature teratoma of the posterior mediastinum. He was asymptomatic and was incidentally found to have a posterior mediastinal mass. Computed tomography was helpful in suggesting a diagnosis of mature teratoma by demonstrating the presence of fat and calcification. The differential diagnosis included neurogenic tumors, liposarcoma, and extramedullary hematopoiesis.

Adult↗
PubMed1997

Dominant hereditary conductive hearing loss due to an ossified stapedius tendon.

Familial conductive deafness is rare. This report confirms the existence of a lineage with congenital conductive hearing loss in 3 generations. The results of otologic evaluations, including pure-tone audiometry, tympanometry, acoustic reflex test, and liquid test, in 14 patients in this family were consistent with the findings of ossicular fixation in 10 patients. Tympanotomies performed in both ears of 4 patients indicated stapes ankylosis caused by ossification of the stapedius tendon. The patients gained normal hearing levels using a simple surgical procedure.

Adolescent↗
PubMed1997

Prenatal ultrasonic diagnosis of a case of Ellis-van Creveld syndrome with a single atrium.

We present an infant with the lethal Ellis-van Creveld syndrome who was diagnosed prenatally from the sonographic detection of a narrow chest, postaxial hexadactyly of the hands and feet, short limbs and a single atrium. The postnatal radiographic features of the skeleton favoured the diagnosis of Verma-Naumoff type or Saldino-Noonan type short rib-polydactyly syndrome (SRPS). We discuss the criteria for the differential diagnosis of patients with SRPS, which can be difficult because of the overlap of the various phenotypes.

Adult↗
PubMed1997

Perfusion cells for studying regional variation in oral-mucosal permeability in humans. I: Kinetic aspects in oral-mucosal absorption of alkylparabens.

PURPOSE: To evaluate regional differences in permeability of human oral mucosa. METHODS: Newly designed perfusion cells were used for the investigation. The cells were applied to 5 different sites, i.e., dorsum of tongue, ventral surface of tongue, labial mucosa, floor of mouth and buccal mucosa of human volunteers. Model drugs used were methyl-, ethyl-, propyl- and butylparaben, which are passively absorbed from oral mucosa and have different lipophilicities. Biexponential disappearance profiles of the alkylparabens were analyzed kinetically using a two-compartment linear open model. RESULTS: Both the partitioning parameters to the oral mucosa and the absorption rate constants to the blood circulation correlated to the lipophilicities of the compounds in all mucosa. As to the former parameter, no significant difference was recognized in all mucosa. While, the latter parameter exhibited the regional difference; the absorption rate constants in buccal mucosa were approximately one-half of those estimated in other oral mucosa. A positive relation was recognized between the retention in oral-mucosal compartment and the drug lipophilicity. CONCLUSIONS: The newly designed perfusion cells used in this study were useful to examine the regional variations of drug absorption from oral mucosa in humans. The absorption rate constant, the partition to oral mucosa and the residence time in oral mucosa increased with lipophilicity of the compound. The regional difference in the drug absorption process was demonstrated; the slow absorption and the prolonged retention were demonstrated in buccal mucosa.

Administration, Oral↗
PubMed1997

Prediction of the plasma concentration profiles of orally administered drugs in rats on the basis of gastrointestinal transit kinetics and absorbability.

A new method based on gastrointestinal transit kinetics has been developed for estimation of the absorption profiles of drugs administered orally as aqueous solutions. The utility of the method was evaluated in rats. The gastrointestinal transit profile for each segment was estimated by in-vivo studies using phenol red, an unabsorbable marker. The gastrointestinal transit profile of phenol red was well explained by a linear gastrointestinal transit kinetic model with eight segments. We also introduced the absorption process into the gastrointestinal transit kinetic model and the plasma profile was predicted by the convolution method. The absorbability of drugs in each segment was assessed by an in-situ absorption study. The validity of the model was evaluated for model drugs with different absorption characteristics. The plasma profiles predicted for ampicillin, theophylline and cephalexin were in good agreement with those observed. The overestimated plasma profile of propranolol suggests that the low bioavailability of propranolol is a result of first-pass metabolism by the intestine wall and the liver, because the calculated absolute absorption is almost perfect. This proposed model is also suitable for estimation of segmental absorption, which is useful for the development of drug delivery systems. We have demonstrated that the plasma profile of orally administered drugs can be predicted by use of gastrointestinal transit and segmental absorbability information and that this method is especially useful for estimating separately the effect of absolute absorption and first-pass metabolism on the bioavailability of drugs.

Administration, Oral↗
PubMed1997

Biopharmaceutical studies on drug/conjugated-metabolite interactions. III. Effect of acetaminophen sulfate and its positional isomers on the pharmacokinetics of acetaminophen in rats.

The effect of three positional isomers, o-, m- and p-acetylaminophenyl sulfate (AOAPS, AMAPS and APAPS (acetaminophen sulfate), respectively), on the pharmacokinetics of acetaminophen (APAP) was investigated in rats. All of the intravenously administered positional isomers were rapidly eliminated from plasma, and approximately 80% of the dose was excreted in an unchanged form in the urine within 4 h, while biliary excretions represented a small percent of the doses. Following the intravenous bolus injection of APAP, plasma elimination of APAP was accelerated and the distribution volume of APAP was increased under a steady state concentration (about 10 microg APAP eq/ml) of AOAPS or APAPS, but not AMAPS, as compared with saline infusion. Total body clearances of APAP were increased from 18.3 ml/min/kg for the control to 23.9 and 26.9 ml/min/kg for AOAPS and APAPS coadministration, respectively. AOAPS and APAPS competitively displaced the serum protein binding of APAP, while AMAPS had little effect. The distribution volume of unbound APAP was anomalously increased by APAPS, while it was not affected by AOAPS or AMAPS. Tissue-to-plasma concentration ratios of APAP were significantly increased by APAPS in the liver, kidney and brain, while they were only slightly increased by AOAPS. It was suggested that APAPS has not only the displacing activity of serum protein binding but also other specific effectiveness on the distribution of APAP.

Acetaminophen↗
PubMed1997

Developmental changes in pharmacokinetics of recombinant human insulin-like growth factor-I in rats.

Developmental changes in pharmacokinetics of recombinant human insulin-like growth factor-I (rhIGF-I) were investigated after i.v. administration to rats aged 4 and 7 weeks, as young growing rats and adult rats, respectively. rhIGF-I in the plasma declined multi-exponentially in both groups of rats. Plasma concentrations of rhIGF-I were lower at almost all the time points examined in 4 weeks old rats than 7 weeks old rats. The values of total body clearance (CL[total]) and mean residence time (MRT) indicated that rhIGF-I disappeared more rapidly in 4 weeks old rats than 7 weeks old rats at any dosage. Dose-dependent pharmacokinetics was observed in 7 weeks old rats: the higher the dosage was, the larger the value of CL(total) came to be, but not in 4 weeks old rats. The amounts of IGF-binding proteins (IGFBPs) in the plasma were assessed by determining the endogenous IGF-I, and the levels of the 150 kDa complex, a ternary complex of IGF-I with IGFPB-3 and an acid labile-subunit, were found to be lower in 4 weeks old rats than in 7 weeks old rats. In rats at 4 weeks of age, the elimination of rhIGF-I was significantly faster than for the 7 week old rats, which would be due to the lower plasma levels of IGFBP-3 in young growing rats.

Aging↗
PubMed1997

Pharmacokinetics of recombinant human insulin-like growth factor-I in diabetic rats.

Pharmacokinetics of recombinant human insulin-like growth factor-I (rhIGF-I) was investigated after iv administration (0.32, 1.0, and 3. 2 mg/kg) to normal and streptozotocin-induced diabetic rats. rhIGF-I was eliminated from plasma biexponentially in both normal and diabetic rats. Plasma concentrations of rhIGF-I were lower at almost all the time points examined in diabetic rats than in normal rats. The pharmacokinetic parameters of total body clearance (CLtotal), mean residence time (MRT), and elimination rate constant (kel) indicated that rhIGF-I disappeared more rapidly in diabetic rats than in normal rats at any dosage. The amounts of IGF binding proteins (IGFBPs) in plasma were assessed by determining the endogenous IGF-I and. Levels of the 150 kDa complex, a ternary complex of IGF-I with IGFPB-3 and an acid-labile subunit, the 50 kDa complex, a complex of IGF-I with IGFBP-2, were found to be lower in diabetic rats than in normal rats. Fractions of rhIGF-I free and bound to the binding proteins were estimated by gel chromatographic separation of rhIGF-I in plasma after iv administration, and the pharmacokinetics of free and bound rhIGF-I was analyzed independently. Plasma concentrations of free and bound rhIGF-I were lower in diabetic rats than in normal rats, especially the concentrations of the 150 kDa complex were much lower. The reduced IGFBP-3 would be responsible for the faster elimination of rhIGF-I in diabetic rats.

Animals↗
PubMed1996

Hyperattenuating rim on noncontrast CT of the liver: probable peritumoral sparing of fatty infiltration.

CT scans showing a hyperattenuating rim within the liver were retrospectively evaluated in 10 patients to clarify the character, aetiology and clinical significance. All patients had hepatic tumours (7 cavernous haemangiomas in 6 patients, 3 metastatic tumours and 1 hepatocellular carcinoma) as well as fatty infiltration of the liver. Typical features of the hyperattenuating rim on noncontrast CT of the liver included (1) attenuation similar to that of the spleen, (2) a circular or semicircular shape, (3) a width of a few millimeters, (4) peritumoral localization and (5) loss of visualization with contrast enhancement. No such rims were noted around hepatic tumours unassociated with fatty infiltration. Peritumoral sparing of fatty infiltration was inferred. A hyperattenuating rim on noncontrast liver CT, although rare, suggests the presence of a hepatic tumour in fatty liver.

Adult↗
PubMed1996

Early squamous cell carcinoma of the lung: CT and pathologic correlation.

PURPOSE: To study the factors that influence computed tomographic (CT) visibility of early squamous cell carcinoma, which was defined as a lesion confined to the bronchial wall without lymph node metastasis. MATERIALS AND METHODS: CT was performed in 18 patients with 18 early squamous cell carcinoma lesions. The 5.0-mm or thinner sections were reviewed independently by three observers who were aware of the bronchoscopic findings, and the visibility of the lesions was correlated with histopathologic findings. RESULTS: Tumors consisted of 13 flat and five polypoid lesions. Three of the lesions were epithelial, eight were subepithelial, and seven were cartilaginous or extracartilaginous. Eleven lesions were visualized at CT as an endobronchial mass or focal bronchial wall thickening. Lesions with polypoid growth and/or cartilaginous or extracartilaginous invasion were all visualized, even on 5-mm-thick sections. Subepithelial lesions could be demonstrated when located at bronchi with craniocaudal orientation. CONCLUSION: CT is a valuable tool for diagnosis of early squamous cell carcinomas, particularly when lesions show polypoid growth and/or invade the cartilaginous layer.

Aged↗
PubMed1996

Disposition of intravenously administered adenosine 5'-phosphosulfate (APS) in rats.

The disposition of adenosine 5'-phosphosulfate (APS), an endogenous nucleotide, was investigated in rats. The degradation of APS in rat plasma was very rapid. APS was degraded in rat plasma to AMP and ATP, and these nucleotides were further degraded through adenosine. The degradation kinetics was examined. For the in vivo study, the method to protect APS from degradation in blood was examined, and it was found that the addition of EDTA to APS-containing blood and storage at 4 degrees C can protect against APS degradation. After intravenous bolus injection, APS in plasma declined rapidly and the rate of elimination was dose-dependent: the biological half-life was about 2s at the dose of 0.3 mg/kg and was longer at 3 mg/kg. When APS was administered by intravenous infusion, the plasma level rapidly reached a steady-state, which then rapidly declined after the infusion was stopped. The total body clearance of APS could not be fully explained by metabolism in plasma or glomerular filtration, therefore the contribution of other elimination processes to the total body clearance was suggested.

Adenosine Phosphosulfate↗
PubMed1996

Pharmacokinetics of acetaminophen sulfate after oral administration in rats: analysis of plasma profiles exhibiting a non-linear second peak.

The pharmacokinetics of the two-peak plasma profiles of orally administered acetaminophen sulfate (APAPS), a major conjugated metabolite of acetaminophen (APAP), in rats was examined by a two-compartment model having two delivery routes with individual time lags: a direct delivery route of APAPS absorbed in an unchanged form and an indirect one where APAPS was absorbed as APAP after deconjugation in the lower intestine. Pharmacokinetic parameters were estimated by a non-linear least squares program, MULTI(FILT), based on the fast inverse Laplace transform algorithm. Plasma APAPS concentration profiles after oral doses were simulated satisfactorily. In a dose escalation study, the peroral availability of APAPS derived from the direct route was not changed significantly with the doses. However, that from the indirect route was decreased with the dose escalation, suggesting the contribution of a capacity-limited deconjugation of APAPS to APAP by the intestinal microflora to the non-linear pharmacokinetics of orally administered APAPS. The absorption of peroral APAPS in rats at a dose range of 30 to 120 mg APAP eq/kg could be summarized as follows: (1) approximately 25% (22 to 32%) of orally administered APAPS are absorbed from the gastrointestinal tract in an unchanged form; (2) more than 50% (50 to 98%) are deconjugated to APAP in the lower intestinal tract; and (3) the latter plays a significant role as an indirect and non-linear APAPS delivery system because considerable amounts of APAP thus absorbed are rapidly reconjugated to APAPS in the systemic circulation, which gives the second plasma APAPS peak.

Acetaminophen↗
PubMed1996

Oral administration of insulin as poly(vinyl alcohol)-gel spheres in diabetic rats.

The oral administration of insulin in poly(vinyl alcohol)-gel spheres (PVA-GS), an oral dosage form with prolonged residence time in the ileum, was examined in streptozotocin-induced diabetic rats. Intragastric administration of PVA-GS containing insulin and a protease inhibitor, aprotinin or bacitracin, caused a significant and prolonged reduction of blood glucose levels, suggesting insulin absorption. The bioavailability of insulin estimated from the hypoglycemic effect was about 2% in the presence of either protease inhibitor. The release profiles of insulin and the protease inhibitors from the PVA-GS could be explained by Higuchi's plot, and the rates were similar to each other. The site dependency of insulin absorption in the intestinal tract was examined by an in situ loop method. Insulin absorption estimated by plasma insulin levels was larger in the ileum and the large intestine than in the jejunum. The prolonged residence time of PVA-GS in the absorption site, the lower intestine, and the synchronous release of insulin and the protease inhibitors from the PVA-GS are the two major explanations for the improved bioavailability of insulin administered as PVA-GS containing a protease inhibitor.

Administration, Oral↗
PubMed1996

Pharmacokinetics of glycyrrhizin in rats with D-galactosamine-induced hepatic disease.

The pharmacokinetic behavior of glycyrrhizin (GZ) was examined in D-galactosamine-intoxicated (GAL) rats. When GZ was administered intravenously, the apparent volume of distribution (Vdss) and the total body clearance (CLtotal) were more significantly decreased in GAL rats than those in normal rats. When GZ was administered orally, the area under the plasma concentration-time curve (AUC), the mean residence time (MRT) and the time to reach the maximum plasma concentration (Tmax) for GZ were higher, but the maximum plasma concentration (Cpmax) in GAL rats was lower than that in normal rats. The bioavailability of GZ, however, was not significantly changed. On the other hand, the AUC for glycyrrhetic acid (GA), a main metabolite of GZ, after oral administration of GZ was higher in GAL rats than in normal rats, although there was no significant difference in MRT or Tmax, Cpmax or the bioavailability for GA between GAL and normal rats. The reasons for these differences in GAL rats would be changes in the absorption rate (reduced gastric emptying rate) and reduction of the hepatic elimination rates (biliary excretion of GZ and hepatic metabolism of GA).

Administration, Oral↗