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Biomedical subjects

H Yuasa

Publications and source records attributed to H Yuasa.

At least 145 records · Page 8Linked to original sources
PubMed1994

Gastric emptying-limited oral absorption of alpha-linolenic acid administered as a milk fat-globule membrane (MFGM) emulsion in rats.

As a study to assess the potential application of milk fat-globule membrane (MFGM), which is of natural origin and expected to be a safer alternative to synthetic emulsifiers, to pharmaceutical dosage forms, the oral absorption of alpha-linolenic acid was evaluated by the analysis of gastrointestinal disposition after oral administration as an MFGM emulsion to rats. A linear model incorporated with first-order gastric emptying followed by first-order intestinal absorption was fitted to the data of the remaining fraction of alpha-linolenic acid versus time profiles for the stomach and small intestine to estimate the rate constants of gastric emptying (kg) and intestinal absorption (ka). The ka (0.045 min-1) was about 4 times larger than the kg (0.011 min-1). The kg was comparable to the apparent oral absorption rate constant estimated by the pharmacokinetic analysis of plasma concentration data. These results suggest that the oral absorption of alpha-linolenic acid administered as MFGM emulsion is gastric emptying-limited and, hence, any change in the intestinal absorption process would only modestly affect its oral absorption.

Animals↗
PubMed1994

Influence of urethane anesthesia and abdominal surgery on gastrointestinal motility in rats.

The influence of various experimental treatments on propulsive gastrointestinal motility was examined in rats, using inulin as a marker. In unanesthetized rats without any surgery, the distribution center of inulin, which was expressed as a dimensionless distance normalized by the length of the small intestine, reached 0.587 down the intestinal tract from the pylorus 60 min after the intragastric administration of inulin. However, the distribution center of inulin moved only 0.061 in 60 min in unanesthetized rats with minimial abdominal surgery for intraduodenal administration of inulin, and did not move in unanesthetized rats with cannulas for perfusion or in the rats anesthetized with urethane and treated with abdominal surgery. In urethane-anesthetized rats without surgery, almost 100% of the inulin was recovered from the stomach 60 min after intragastric administration. These results suggest that gastrointestinal motility is extensively suppressed by minimal abdominal surgery as well as by anesthesia.

Abdomen↗
PubMed1994

Inter-organ relation between salivary gland and kidney in lithium excretion. IV. Saturation of inhibitory effect of NaCl on ductal reabsorption of Li+ in beagle dogs.

The inhibitory effect of NaCl coadministration on the reabsorption of Li+ in the salivary ducts and the renal tubules was investigated in beagle dogs. Following the bolus intravenous administration of LiCl (0.145 meq/kg), 50 ml of NaCl solution (100, 200 meq/l) was administered orally each hour, and parotid saliva (Pr) and mandibular-sublingual saliva (MS) were collected under the continuous stimulation of salivation with citric acid. The renal clearance of Li+ increased with the increased concentration of administered NaCl solution. This could be a result of the competitive inhibition of the tubular reabsorption of Li+ by Na+. The salivary clearance of Li+ also tended to increase by the administration of NaCl. These results suggest the existence of a reabsorption process of Li+ in the salivary glands similar to that in the renal tubule. However, when the administered NaCl was increased from 100 to 200 meq/l, the renal clearance was further increased, but the salivary clearance was not. This suggests that the transport capacity of Li+ reabsorption is relatively small in the salivary glands, compared with that in the renal tubule, and that the inhibitory effect of NaCl on Li+ reabsorption had already reached a maximum level when 100 meq/l NaCl was administered.

Absorption↗
PubMed1994

Evaluation of milk fat-globule membrane (MFGM) emulsion for oral administration: absorption of alpha-linolenic acid in rats and the effect of emulsion droplet size.

The performance of milk fat-globule membrane (MFGM) emulsion as an oral dosage form was evaluated in rats using [14C]alpha-linolenic acid as a lipophilic model solute. For emulsions prepared by homogenization alone, the area under the plasma concentration versus time curve (AUC) after oral administration tended to be larger for MFGM emulsion, 35.0 +/- 2.5 micrograms eq.h/ml (mean +/- S.E., n = 3), than for Tween 80 emulsion, 28.5 +/- 0.6 micrograms eq.h/ml at p < 0.1, though the peak plasma concentration (Cmax) and the time required to reach Cmax (Tmax) were not significantly different. The absorption in the intestinal loop was not significantly different between the two emulsions, either. Thus, MFGM emulsion, compared with Tween 80 emulsion, did not show an obvious advantage or enhancement in the oral and intestinal absorption of alpha-linolenic acid, except for a slight increase in AUC. However, MFGM could be a good alternative to a synthetic emulsifier for oral use, considering that it is of natural origin and may be safer. In addition, it was shown that the AUC, as well as the absorption in the intestinal loop, was decreased for a MFGM emulsion in which the droplet size was reduced by sonication, presumably because of the observed decrease in alpha-linolenic acid concentration in the water phase, which was assumed to be the result of an increased distribution of alpha-linolenic acid, due to its amphipathic nature, to the increased oil-water interface.

Administration, Oral↗
PubMed1994

Application of calcium silicate for medicinal preparation. I. Solid preparation adsorbing an oily medicine to calcium silicate.

Calcium silicate (Florite RE, FLR), a fine porous powder, was recently approved as a medicinal additive. In this study we sought to make a solid preparation by absorbing an oily medicine to FLR; tocopheryl nicotinate (TN) was used as the oily medicine. TN adsorbed to FLR powder (TN-PO) was prepared by adsorbing TN ethanol solution to FLR and granulating with hydroxypropylcellulose (HPC) in order to improve the flowability. The results were as follows. FLR showed an excellent liquid holding ability compared with other excipients, and this was attributed to the high capillarity of the pores. In the adsorbing process, FLR particles were granulated with TN overflowing from the pores or adhering to the particle surface. The angle of repose was decreased with increasing TN content, which was attributed to the process of granulation, and the angle of repose of the granules with a binder (TN-GR) was below 40 degrees at any TN content. These results show that FLR is an useful additive for the solid preparation of an oily medicine.

Adsorption↗
PubMed1994

Effects of compression pressure on physical and chemical stability of tablets containing an anticancer drug TAT-59.

(E)-4-[1-[4-[2-(Dimethylamino)ethoxy]phenyl]-2-(4-isopropyl) phenyl]-1-butenyl]phenyl monophosphate (TAT-59) is a new drug for the treatment of breast cancer. Physical and chemical stability of mixtures of TAT-59 and microcrystalline cellulose (1:9) compressed at 0, 300, 600 and 1400 kg/cm2 was evaluated by determination of water content, porosity and the amount of hydrolysis product, DP-TAT-59, formed. The water contents and porosity of these tablets scarcely changed during 57 d at 25-60 degrees C under 50% relative humidity (RH). The degradation rate of TAT-59 increased with increasing compression pressure as well as temperature. The apparent activation energy and frequency factor were determined from an Arrhenius plot of the degradation rate. Activation energy of these tablets was almost the same, while the frequency factor tended to increase with increasing compression pressure. The porosity and pore sizes in TAT-59-containing tablets decreased with increasing compressive force. We speculated from these observations that the increase in compression pressure decreased the distance and increased the contact area between TAT-59 and microcrystalline cellulose. The proximity between TAT-59 and moisture presented at the surface of microcrystalline cellulose by compression was considered to enhance the degradation of TAT-59.

Antineoplastic Agents↗
PubMed1994

Histopathological investigation on salt-loaded stroke-prone spontaneously hypertensive rats, whose biochemical parameters of renal dysfunction were ameliorated by administration of imidapril.

Our previous studies showed that imidapril prevented the occurrence of cerebral stroke and ameliorated biochemical parameter changes of renal dysfunction at a dose that did not inhibit the progression of hypertension in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). To confirm these findings, a histopathological investigation was conducted on the kidney of salt-loaded (from 11 to 16 weeks of age) SHRSP, which was the subject of the preceding study. Their brains and hearts were also examined. Histopathologically, renal lesions such as fibrinoid necrosis and proliferative arteritis of small calibration arteries, necrotizing glomerulitis and tubular degeneration, and cerebral hemorrhage and slight cardial hypertrophy were observed in salt-loaded control SHRSP. The occurrence of these lesions were prevented in a dose-dependent manner by the administration of imidapril (1 and 2 mg/kg/day). Especially, the preventive effects on the renal lesions were apparently noted. Enalapril also prevented these renal lesions, but its preventive effects were weaker than those of imidapril at the same dose (2 mg/kg/day). It became evident from the results of the present and previous studies that imidapril reduced renal biochemical and histopathological injuries.

Animals↗
PubMed1994

New surgical method of chordal replacement for mitral valve incompetence with echocardiographic guidance. An experimental study.

Chordal replacement with expanded polytetrafluorethylene suture has become a procedure of choice for repairing anterior leaflet prolapse among certain surgeons. However, most surgeons believe that the chordal replacement is too complicated and not reproducible. This report introduces a new method of chordal replacement using intraoperative epicardial and transesophageal echocardiography. Three dogs underwent the following procedures. One major marginal chorda of an anterior mitral leaflet was resected during cardiopulmonary bypass. A specially designed 3-0 polytetrafluoroethylene suture, having straight needles, was attached to the anterior leaflet by a mattress suture. Then the needles were brought from the root of the anterior papillary muscle to the outside of the left ventricle. After the bypass flow was reduced, both ends of the polytetrafluoroethylene suture were pulled under echocardiographic guidance until valve competence was achieved. At that point, the suture was temporarily tied. When cardiopulmonary bypass was discontinued, competence was again confirmed and the suture was tied permanently. When the procedures were completed, echocardiography showed trivial regurgitation and good pliability of the anterior leaflets in all animals. Left atrial pressures were sufficiently decreased. It appears that this new technique is reproducible for all surgeons because the optimal length of polytetrafluoroethylene chordae is determined with the valve functioning.

Animals↗
PubMed1994

Noncompetitive inhibition of cephradine uptake by enalapril in rabbit intestinal brush-border membrane vesicles: an enalapril specific inhibitory binding site on the peptide carrier.

ACE inhibitors, as well as aminocephalosporins with peptide-like structures, are transported by the intestinal peptide carrier. We investigated the transport mechanism using intestinal brush-border membrane vesicles from rabbits and observed that enalapril, an angiotensin converting enzyme inhibitor and substrate of the peptide carrier, noncompetitively inhibited the uptake of cephradine, an aminocephalosporin and substrate of the peptide carrier, with an inhibition constant (Ki) of 2.6 mM when it was present on the cis side (outside) of the vesicles. By contrast, enalaprilat, cefadroxil and GlyPro competitively inhibited cephradine transport with Ki values of 5.4, 3.8 and 5.1, respectively. These results suggest the presence of an enalapril-specific inhibitory binding site on the peptide carrier. In addition, enalapril on the trans side (inside) of the vesicles inhibited the uptake of cephradine, suggesting an apparent reduction of carrier availability by a trapping mechanism. On the other hand, cefadroxil stimulated the uptake of cephradine in the trans experiment, consistent with the concept of countertransport. These findings reveal the uniqueness of enalapril regarding its mode of interaction with the peptide carrier(s) which has been of increasing interest regarding its role in the intestinal absorption of peptide-type drugs.

Animals↗
PubMed1993

Primary structure of Tetrahymena hemoglobins.

The primary structure of hemoglobins of Tetrahymena thermophila and T. pyriformis was determined by peptide and cDNA sequence analysis. Their sequences were 83.5% identical to each other and homologous to other protozoan and cyanobacteria hemoglobins, but not to proteins of the globin family. An intron was not present in the T. thermophila hemoglobin gene.

Amino Acid Sequence↗
PubMed1993

Ultrasonic diagnosis of 3,2'-dimethyl-4-aminobiphenyl induced tumors in the urogenital organs of F344 rats.

The usefulness of transabdominal ultrasonography in the diagnosis of 3,2'-dimethyl-4-aminobiphenyl- and testosterone propionate-induced tumors of the urogenital organs was evaluated in F344 rats. Seven mass lesions (1 ventral prostate, 1 dorsolateral prostate, 3 seminal vesicles, and 1 kidney) in the urogenital organs could easily be diagnosed concerning size and localization by ultrasound. Histological examination revealed a lesion in the ventral prostate to be an abscess and the other tumors to be malignant. Three hydronephroses by tumor invasion to the ureter, and six tumors in organs other than the urogenital organs could be detected by ultrasound. The threshold of malignant tumor detection by ultrasound was 7 mm in actual length. The size of the mass lesion estimated by ultrasound correlated well with the direct measurement (r = 0.96). Transabdominal ultrasonography is useful for diagnosing the localization of experimental tumors and accurately measuring their size in the urogenital organs of rats.

Adenocarcinoma↗
PubMed1993

Two cases of Graves' disease with presentation of unilateral diffuse uptake of radioisotopes.

We present two cases of Graves' disease whose initial thyroidal scintiscan with 99mTcO4- (Case 1) and 123I (Case 2) showed unilateral diffuse uptake of radioisotopes. Initial diagnosis was possibility of malignancy in Case 1 and Graves' disease or Plummer's disease in Case 2. Both cases underwent right hemithyroidectomy. Histopathology of the resected thyroid gland in both showed hyperplastic columnar epithelium and infiltrative lymphocytes which was compatible with Graves' disease. Twenty seven (Case 1) and eight months (Case 2) after operation, both presented with thyrotoxic symptoms associated with enlarged left lobe, increased serum free thyroid hormone concentrations, suppressed TSH concentration, increased thyroidal 123I uptake in the remaining left lobe, and positive thyrotropin receptor antibodies. Both cases were successfully treated with methimazole. It was concluded that initial radioisotope uptake as well as scintigram in rare subgroup of patients with Graves' disease could be similar with that of non-autoimmune autonomous goiter (Plummer's disease).

Animals↗
PubMed1993

Biodegradable poly(DL-lactic acid) formulations in a calcitonin delivery system.

A synthetic analogue of eel calcitonin, [Asu1, 7]-ECT, was incorporated into biodegradable poly(DL-lactic acids) with number-average molecular weights (Mn) of 1400-4400 by the melt-pressing technique. The in vitro release of drug from a parabolically degradable poly(DL-lactic acid) with Mn = 1400 showed an initial burst release and completed the release in 3 d from the start of the test. The drug release from a Mn = 4400 polymer with an S-type degradation pattern was kept at 14 +/- 5 units/d for an experimental period of 24 d.

Amino Acid Sequence↗
PubMed1993

Influence of anesthetic regimens on intestinal absorption in rats.

We compared the influence of anesthetic regimens using urethane (U), pentobarbital (P), ether (E), and ketamine/midazolam (K) on the intestinal absorption of several probes using a single-pass perfusion technique in rats. The selected probes were D-glucose (1 mM) for the resistance of the unstirred water layer (UWL), D-glucose (100 mM) for the capacity of carrier-mediated D-glucose transport, L-glucose, and urea for membrane-limited passive transport, and tritiated water (3H2O) for blood flow at the absorption site. The absorbed fraction of D-glucose (1 mM) was the smallest for U and the largest for P, suggesting that the resistance of UWL is the largest for U and the smallest for P. The absorbed fraction of D-glucose (100 mM) was the largest for P (U = E = K < P), suggesting a higher capacity of carrier-mediated D-glucose transport for P. The absorbed fraction of urea was similar for all anesthetics, while that of L-glucose was the smallest for K (U = P = E > K). Although the results for these two markers of membrane-limited passive transport were inconsistent, the passive permeability of the intestinal membrane may be lower when treating with K. The intestinal absorptions of D-glucose (1 and 100 mM), L-glucose, and urea were, in general, lower with any of the anesthetics than under nonanesthesia (N), suggesting increased resistance of UWL and decreased intestinal membrane permeability by carrier-mediated and passive transport under anesthesia. The only exception was the absorption of D-glucose (100 mM) under P, which was comparable to that under N.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗
PubMed1993

Peptide carrier-mediated transport in intestinal brush border membrane vesicles of rats and rabbits: cephradine uptake and inhibition.

The uptake kinetics of cephradine, an amino-beta-lactam antibiotic, were studied in rat and rabbit intestinal brush border membrane vesicles preparations using both the Ca2+ and the Mg2+ methods of preparation, in the presence of an inward proton gradient. The Ca2+ method demonstrated greater uptake of cephradine in intestinal brush border vesicles prepared from both rat and rabbit and was used for these studies. The transport was observed to be of Michaelis-Menten carrier-mediated type with a passive transport component. The kinetic parameters obtained were as follows: for rat and rabbit, respectively, Km, 1.6 and 1.9 mM; Jmax', 1.7 and 20.7 nmol/mg/min; Pc' (= Jmax'/Km), 1.1 and 10.9 microL/mg/min; and Pm', 0.4 and 0.8 microL/mg/min. The kinetic parameters for the rat vesicles are consistent with those from our previous perfusion study using a conversion factor of 0.71 cm2/mg protein. The rabbit vesicles exhibited a similar Michaelis constant and a 10-fold larger maximal transport velocity, suggesting a quantitative advantage for the study of carrier-mediated transport in the rabbit compared to rat vesicles from the intestine. Cephradine uptake was inhibited by phenylpropionylproline, a proline derivative, and enalapril, an ACE inhibitor, which do not have an alpha-amino group, as well as dipeptides, tripeptides, and amino-beta-lactam antibiotics in both rat and rabbit vesicles. These results support the suggestion that they share the same peptide carrier pathway for oral absorption and that the vesicles may be a useful tool in developing orally effective peptide-type drugs.

Alkaline Phosphatase↗
PubMed1993

Induction of glandular stomach cancers in C3H mice treated with N-methyl-N-nitrosourea in the drinking water.

Establishment of an animal model of stomach carcinogenesis in mice was attempted using N-methyl-N-nitrosourea (MNU) in the drinking water. One hundred and forty-eight male 6-week-old C3H mice were given MNU in their drinking water at a concentration of 120 ppm (group 1), 60 ppm (group 2), 30 ppm (group 3) or 0 ppm (group 4) for 30 weeks. At the end of this time, dose-related induction of adenomatous hyperplasias was found. From weeks 31 to 54 adenocarcinomas developed in a dose-dependent manner in groups 1, 2 and 3. In total, 6 well differentiated and 5 poorly differentiated adenocarcinomas as well as 6 signet ring cell carcinomas arose in 15 stomach cancer-bearing animals in group 1, 4 well differentiated and 2 poorly differentiated adenocarcinomas with one signet ring cell carcinoma in 5 mice of group 2 and one well differentiated adenocarcinoma in group 3. In the forestomach, only one squamous cell carcinoma was found at week 54 in group 1 along with a single well differentiated adenocarcinoma in the duodenum. Thus, MNU in the drinking water selectively induced neoplastic lesions in the glandular stomach epithelium of mice.

Adenocarcinoma↗