PubMed Health⌕ Search

Biomedical subjects

H Yuasa

Publications and source records attributed to H Yuasa.

At least 73 records · Page 4Linked to original sources
PubMed1998

Expression of sucrase and intestinal-type alkaline phosphatase in colorectal carcinomas in rats treated with methylazoxymethanol acetate.

In this study the small-intestine phenotype in rat colonic tumors was investigated in terms of sucrase and intestinal-type alkaline phosphatase (I-ALP) activity. F344 rats were given intraperitoneal injections of methylazoxymethanol acetate at a dose level of 25 mg/kg body weight once a week for 8 weeks and were killed 40 weeks after the first injection. Sucrase and I-ALP activities in proximal and distal colon adenocarcinomas were significantly higher than those in the normal colon epithelium. In the jejunum, by contrast, normal tissue had significantly higher levels than tumors. Immunohistochemical staining of I-ALP was also strong in striated cell borders of colon adenocarcinoma cells. These data suggest that, whereas absorptive cells of the small intestine lose their own traits with tumor development, colonocytes acquire phenotypic features of the small intestine. Intestinal enzymes associated with the striated-cell border, such as sucrase and I-ALP, may be useful markers for malignant phenotypic expression in colonocytes.

Adenocarcinoma↗
PubMed1998

High-frequency color Doppler sonography of the submandibular gland: relationship between salivary secretion and blood flow.

OBJECTIVE: The purpose of this study was to evaluate the changes of blood flow of the submandibular gland in comparison with salivary secretion after gustatory stimulation through use of color Doppler sonography. STUDY DESIGN: High-frequency color Doppler sonography was performed on 30 healthy volunteers, aged 22 to 31 years. The prestimulation and poststimulation arterial blood flows were evaluated with color Doppler sonography and spectral analysis. RESULTS: The means of prestimulation maximum and minimum velocities and pulsatility index of the submandibular gland were 6.35 +/- 2.57 cm/sec, 1.79 +/- 0.93 cm/sec, and 1.53 +/- 0.42, respectively. After the stimulation, the color signals and velocities increased and the pulsatility index decreased. There was a close correlation between the increase in minimum velocity and that of salivary secretion. CONCLUSION: Color Doppler sonography is useful in analyzing changes in the blood flow of the submandibular gland caused by gustatory stimulation.

Adult↗
PubMed1998

Observer agreement in the detection of proximal caries with direct digital intraoral radiography.

OBJECTIVE: The aim of this study was to compare several values for consistency obtained by charged-coupled-device-based direct digital intraoral radiography with those obtained by conventional film-based radiography to evaluate observer agreement in determining the depth of proximal caries. STUDY DESIGN: A total of 93 proximal surfaces on radiologic images that were obtained by both the conventional film-based bite-wing technique and by direct digital intraoral radiography were evaluated by six observers. One of these observers also evaluated the same images six months after the initial evaluation. The kappa value, consistency ratio, agreement ratio, and Kendall's correlation coefficient were calculated for interobserver and intraobserver agreement. RESULTS: The overall kappa values for interobserver agreement were 0.439 and 0.424 in the direct digital system and the film-based radiography, respectively. The depth-related change of the values showed similar patterns in the two modalities for both interobserver and intraobserver agreement. CONCLUSION: The digital intraoral system resulted in no deterioration in observer agreement, and it presents no problems for clinical use with respect to the reliability of diagnosis.

Dental Caries↗
PubMed1998

Nested consent design for clinical trials.

BACKGROUND: Since random treatment allocation is hardly understood by the majority of patients, a new 'nested consent design' for clinical trials is proposed. PROPOSED DESIGN: The design consists of a two-step enrollment of study subjects. The first step is the enrollment of participants into a follow-up study, where consent to be subjects involved in the follow-up is obtained. The second step is the enrollment of randomly sampled eligible participants into a new treatment group. After the explanation of (1) treatment mode, (2) additional burdens associated with the proposed treatment and (3) expected effects and possible adverse events, written informed consent is obtained. Those who reject participation and those who are not allocated into the new treatment are treated by standard care. Endpoints are set to be the same for all follow-up study participants whether allocated into the new treatment or not, and follow-up is carried out in the same manner. Analyses are performed between those allocated to the new treatment and those non-allocated on an intent-to-treat basis. EXAMPLE: Although not a clinical trial, this design was applied in a smoking cessation program at Aichi Cancer Center Hospital for first-visit patients who answered in a questionnaire survey that they were smokers. Out of 1330 necessary participants, 324 were enrolled in the follow-up study during the first three months of enrollment. CONCLUSIONS: The design was found to be feasible for prevention trials, and possibly for clinical trials to compare a new treatment with a standard treatment. There seems to be no ethical difference between this design and the one-arm study design.

Clinical Trials as Topic↗
PubMed1998

First-pass metabolism of 5-fluorouracil in rats.

The first-pass metabolism of 5-fluorouracil has been investigated in rats to compare systemic bioavailability after administration by different routes, the bioavailability after intravenous bolus administration being defined as unity. Bioavailability after oral administration (F(po)) was compared with that after intraintestinal administration into the closed loop (F(loop)) in conscious rats. F(po) was very low and variable (0.28 +/- 0.30, mean +/- s.d.), in agreement with earlier studies in man, but comparable with F(loop) (0.33 +/- 0.05), suggesting insignificant loss of 5-fluorouracil by degradation in the gastrointestinal lumen or by faecal excretion. The bioavailability after intraportal vein administration (F(ipv)) was compared with F(loop) in rats anaesthetized with pentobarbital, anaesthesia being used to maintain a stable portal drug infusion that mimics the sustained input of drug into the portal blood flow after intra-intestinal administration. F(ipv) was smaller than unity (0.68 +/- 0.03), suggesting significant hepatic first-pass metabolism, but higher than F(loop) (0.31 +/- 0.10), suggesting significant first-pass metabolism in the intestinal mucosa. The intestinal bioavailability for passage through the epithelial mucosa (Fi) was estimated, from the ratio of F(loop) to F(ipv) to be 0.46. The study revealed that both the liver and intestinal mucosa are responsible for the extensive first-pass metabolism of 5-fluorouracil after oral administration. This first-pass metabolism might be similar to that in man, in which the oral bioavailability is reportedly similar to that in the rats used in this study. The findings in this study should be of help in monitoring ways of improving oral 5-fluorouracil therapy.

Administration, Oral↗
PubMed1998

Natural course of untreated symptomatic temporomandibular joint disc displacement without reduction.

In some patients with disc displacement without reduction, the symptoms of pain and decreased range of motion have been observed to resolve spontaneously over time without treatment. The natural history of this condition, however, is not well-understood. Thus, to study the natural course of disc displacement without reduction, we followed 40 patients without treatment for a period of 2.5 years. The diagnosis was established by history and physical examination and confirmed with magnetic resonance (MR) imaging. After 2.5 years, 43% of the patients were asymptomatic, 33% had decreased symptoms, and 25% of the patients showed no improvement or had required treatment. MR evidence of osteoarthritis and advanced stages of internal derangement at the initial evaluation was associated with a poor prognosis. The result of this prospective cohort study indicated that approximately 40% of patients with symptomatic disc displacement without reduction will be free of symptoms within 2.5 years, one-third will improve, whereas one-quarter will continue to be symptomatic. This knowledge should be valuable for the treatment planning and evaluation of prognosis of patients with non-reducing symptomatic disc displacement.

Adolescent↗
PubMed1998

Dose dependency in the gastrointestinal absorption of cefatrizine: correlation between in vivo and in situ.

We evaluated the dose-dependent (saturable) gastrointestinal absorption of cefatrizine, an aminocephalosporin transported by peptide carriers, in rats by a physiological mechanism-based approach to clarify its absorption characteristics and to examine the in vitro (in situ)-in vivo correlation in intestinal transport. With an increase in oral dose (mumol/5 ml/kg) from 5 (low) to 50 (high), the intestinal absorption rate constant (ka), which was estimated by analysis of gastrointestinal disposition, decreased markedly, from 0.301 to 0.056 min-1. This decrease was ascribable to the saturability of intestinal membrane transport, of which the concentration dependency in the perfused intestine was similar in extent to the dose dependency in ka. However, the apparent absorption rate constant (ka'), which was estimated by analysis of plasma concentrations after oral administration, decreased only modestly from 0.037 to 0.023 min-1. This was associated with the result that, at the low dose, ka' was far smaller than ka and comparable with k(g) (gastric emptying rate constant), suggesting gastric emptying-limited absorption. At the high dose, where intestinal cefatrizine absorption was less efficient, ka' was closer to ka than k(g). It was also observed that the bioavailability was close to unity, independent of dose, suggesting that the intestinal transit time is long enough to achieve complete absorption, even at the high dose, where intestinal cefatrizine absorption is less efficient. Thus, it was found that the effect of saturability in the intestinal transport of cefatrizine is apparently attenuated in its overall gastrointestinal absorption because of the involvement of gastric emptying and intestinal transit time as additional physiological factors to define absorption. It was also found that a scaling factor is required to correlate the intestinal membrane transport between in vitro (in situ) and in vivo, though this remains to be verified to be utilized for developing oral drug delivery strategies and optimizing oral drug therapy.

Administration, Oral↗
PubMed1998

Fractional absorption of L-carnitine after oral administration in rats: evaluation of absorption site and dose dependency.

We evaluated the fractional absorption of L-carnitine, a gamma-amino acid essential cofactor for the transfer of long-chain fatty acids, in rats in vivo after oral administration to determine its absorption behavior. At both low (0.05 micromol/rat) and high (100 micromol/rat) doses, L-carnitine was recovered only from the region of the cecum and below at 10 h after administration. During a major shift in distribution from cecum at 10 h to feces at 24 h, there was no significant change in the total recovery at each dose, suggesting that L-carnitine absorption is negligible in the cecum and the large intestine (colon and rectum). However, the recovery of L-carnitine was incomplete and the fraction recovered was larger at the high dose than at the low dose. The fractions absorbed were estimated to be 96.7 and 33.0% for the low and high doses, respectively, as these were the fractions that disappeared from the gastrointestinal tract. These values were comparable with 100 and 42%, respectively, of bioavailability values by the pharmacokinetic analysis of plasma concentration data in our preceding study [Matsuda et al., Biopharmaceutics & Drug Disposition, in press]. These results suggest that L-carnitine is significantly absorbed only in the small intestine, without undergoing first-pass degradation, and in a dose-dependent manner presumably due to the involvement of saturable transport by L-carnitine carriers. Consistent with the suggestions in vivo, L-carnitine absorption in the closed intestinal loop in situ was concentration-dependent in the small intestine but not in the large intestine, and the apparent membrane permeability in the large intestine was smaller by an order of magnitude than that of passive transport in the small intestine. These findings support our preceding kinetic modeling strategy assuming the small intestine to be the sole absorption site, and should be of help in guiding studies on development of more efficient oral L-carnitine delivery strategies.

Administration, Oral↗
PubMed1998

Studies on development of dosage forms for pediatric use (V) oral mucosal irritation study of gummi drugs in hamster cheek pouch.

In the present study we investigated irritation of the oral mucosa and the safety of gummi drugs containing acetaminophen (AAP). The oral mucosae of hamsters were macroscopically examined for any evidence of irritation after gummi drugs were inserted into the cheek pouch and left there for 1 h. The cheek pouch tissue was also macroscopically and microscopically examined 24 h after gummi drugs were withdrawn from the cheek pouch. As a result, no evidence of irritation was found macroscopically 1 h after insertion, or macroscopically and microscopically 24 h after the withdrawal of the gummi drugs or placebos as compared with negative controls (saline). Considering these results, the gummi drugs administered in the present study produced no irritation to the oral mucosa.

Acetaminophen↗
PubMed1998

First-pass metabolism of 5-fluorouracil in the perfused rat small intestine.

The first-pass intestinal metabolism of 5-fluorouracil (5-FU) was investigated by single-pass perfusion of the rat small intestine. At the low concentration of 0.06 mg/ml, the fraction of 5-FU absorbed into (i.e., appeared in) the mesenteric venous blood (Fa,b) was about 50% smaller than the fraction absorbed (disappeared) from the intestinal lumen (Fa), indicating the first-pass extraction of 5-FU in the intestinal mucosa. By addition of uracil (6 mg/ml), the Fa of 5-FU was reduced presumably by competition for the pyrimidine carrier at the process of intestinal uptake (entry into the mucosa). The Fa,b was also reduced, but to a lesser extent, resulting in insignificant first-pass extraction. These results suggest that the extraction of 5-FU in the absence of uracil is caused by metabolism and that uracil is a competitor for this pathway. When 5-FU concentration was raised from 0.06 to 0.6 mg/ml in the absence of uracil, the Fa was reduced by about 50%, consistent with the suggestion of the involvement of saturable uptake by the pyrimidine carrier, and thereafter remained unchanged at 6 mg/ml. However, since Fa,b was also reduced by a similar extent, the intestinal availability (FI=Fa,b/Fa) was unchanged at about 0.5, indicating that the intestinal first-pass extraction of 5-FU is independent of concentration with the extraction ratio (difference between unity and FI) of about 0.5 over the wide range of concentration from 0.06 to 6 mg/ml. Thus, the present study demonstrates that the significant first-pass metabolic extraction of 5-FU occurs in the mucosa of the small intestine, supporting our previous suggestion that 5-FU undergoes first-pass metabolism not only in the liver but also in the small intestine after oral administration. Considering that the oral bioavailability of 5-FU in the human (28%) is reportedly comparable with that in the rat (28%), it is likely that intestinal first-pass metabolism may be significant also in the human. Intestinal first-pass metabolism should be taken into account to explore more efficient and controlled oral 5-FU therapy.

Animals↗
PubMed1998

Development of emulsion type new vehicle for soft gelatin capsule. I. Selection of surfactants for development of new vehicle and its physicochemical properties.

Screening of surfactants was carried out to develop an oil in water (o/w) emulsion type new vehicle for a soft gelatin capsule (SGC), using polyethyleneglycol 400 (PEG 400) as hydrophilic phase and medium chain triglyceride (Miglyol 810), propyleneglycol dicaprylate (Sefsol 228) or soybean oil as hydrophobic phase (PEG 400: hydrophobic phase: surfactant = 87:10:3) and by means of simple homogenization. Polyoxyethylene (20) cetylether (BC-20TX), which can form homogeneous and viscous white gels using the above hydrophilic and hydrophobic phase combination, was selected as a model surfactant for developing the new vehicle. Using Miglyol 810 as hydrophobic phase, a model new vehicle formulation (PEG 400:water:Miglyol 810: BC-20TX = 77:10:10:3) was prepared, and its physicochemical properties were evaluated. The particle size distribution of the new vehicle, after diluting about 3000 times with water, ranged from about 0.5 to 50 microns. Furthermore, the new vehicle had thixotropic property at room temperature (about 25 degrees C) and temperature-dependent gel-sol transforming property with the transformation temperature of about 37 degrees C. These properties meet the requirement for encapsulation of the new vehicle in SGC and suggest that it can be expected to form the o/w emulsion state in the aqueous environment in the stomach. The rheological properties would also make it advantageous for use in other dosage forms such as suppository, cataplasm or liniment.

Capsules↗
PubMed1998

Formation of water-insoluble gel in dry-coated tablets for the controlled release of theophylline.

Sodium alginate (ALNa) of a natural polysaccharide is known to form a water-insoluble gel when combined with a bivalent metal. In this study, we prepared tablets containing ALNa and calcium gluconate (GLCa) as a bivalent metal, and studied the application of the water-insoluble gel involving the controlled release of a test drug by permeation of water. Dry-coated tablets containing theophylline (TP) as a model drug, ALNa and GLCa were prepared by the dry power compression method. The controlled release of TP was evaluated by the dissolution test according to JP XIII. The release rate was extremely high for the tablets which contained only TP and GLCa. A zero order or sigmoidal release profile was observed for the tablets that contained only TP and ALNa. On the other hand, the lowest dissolution rate and a sigmoidal release profile were observed for the tablet containing TP and GLCa in its core and ALNa in its outer phase. These results suggest that dry-coated tablets containing ALNa and GLCa and prepared by the direct powder compression method would be useful for the controlled release of drugs.

Alginates↗
PubMed1998

[Anesthetic management of a patient with dilated cardiomyopathy using olprinone].

A 51-year-old man with dilated cardiomyopathy, who had been treated with medication for five years, was scheduled for abdomioperineal resection of the rectum. Preoperative echocardiography demonstrated left ventricular dilation and hypertrophy, with an ejection fraction of 0.34. Anesthesia was induced with ketamine 40 mg and fentanyl 0.5 mg intravenously. Endotracheal intubation was facilitated by administration of vecuronium 10 mg. Anesthesia was maintained with nitrous oxide-oxygen-sevoflurane and fentanyl. In order to regulate myocardial contractility and after-load, use of a phosphodiesterase III inhibitor was considered, although phosphodiesterase III inhibitors are known to induce arrhythmias, which should be avoided in dilated cardiomyopathy patients. We chose olprinone, because its inotropic action is not associated with arrhythmogenecity. Before infusing olprinone, cardiac output was 4.5 l.min-1 and systemic vascular resistance was 1306 dynes.sec.cm-5. When olprinone was continuously infused for one hour, cardiac output increased to 5.2 l.min-1 and systemic vascular resistance decreased to 958 dynes.sec.cm-5. Some premature ventricular contractions occurred, but they were easily controlled by administration of 50 mg lidocaine. These clinical data demonstrate that olprinone enhanced myocardial contractility, and decreased after-load and arrhythmogenecity in a dilated cardiomyopathy patients. In conclusion, olprinone is useful in the perioperative cardiovascular management of surgical patients with dilated cardiomyopathy.

Anesthesia↗
PubMed1998

[Evaluation of preincisional mexiletine administration to alleviate postoperative pain].

Mexiletine, an antiarrhythmic agent, was preincisionally administered intravenously for the purpose of reducing postoperative pain. Twenty-eight female patients for mastectomy were studied. The patients were divided into three groups. Group 1 received no mexiletine. Group 2 received bolus administration of mexiletine 1 mg.kg-1 with additional continuous administration of 1 mg.kg-1.hr-1 for 75 minutes. Group 3 received bolus administration of mexiletine 2 mg.kg-1. The requirement of butorphanol as a postoperative analgesic within 1 hour after mastectomy in Group 3 was significantly lower than that in Group 1 (P < 0.05), but butorphanol requirement in Group 2 was not significantly lower than that in Group 1. Plasma mexiletine concentration was slightly higher in Group 3 (1.7 micrograms.ml-1) than that in Group 2 (1.0 microgram.ml-1) immediately after the intravenous mexiletine administration, although there was no significant difference. The results indicate that mexiletine 2 mg.kg-1 as preoperative bolus administration maintains its plasma concentration above 1.7 micrograms.ml-1, and is clinically effective for reducing the postoperative pain after mastectomy.

Adult↗
PubMed1997

Cca3, the mRNA level of which transiently decreases before initiation of DNA synthesis in regenerating rat liver cells.

Kinetics of cca1, cca2, cca3 and rat gas1 mRNA levels were compared with those of DNA synthesis level in regenerating rat liver cells after partial hepatectomy. A transient decrease of cca3 mRNA level and an increase of rat gas1 mRNA level were observed before initiation of DNA synthesis, followed by a rapid decrease of rat gas1 mRNA level. By molecular cloning and nucleotide sequencing, cca3 cDNA was found to consist of 4514 nucleotides with a large open reading frame of 3027 nucleotides, encoding a protein of 1009 amino acids with three copies of an ankyrin repeat-like sequence.

Adaptor Proteins, Signal Transducing↗
PubMed1997

Carcinogenesis in accessory sex organs of rats induced by 3,2'-dimethyl-4-aminobiphenyl: response to androgen deprivation.

It is generally accepted that early human prostate cancers reveal higher androgen dependency than do advanced ones. In the present study, we examined whether the animal model of prostate cancer has already lost androgen dependency at the early stages of carcinogenesis. At experimental week 46, androgen deprivation was induced in rats and the incidences of atypical hyperplasia and cancer were examined in the ventral, dorsolateral prostate, coagulating glands, and seminal vesicles. Androgen deprivation significantly lowered the incidence of atypical hyperplasia in all four organs. As for the incidence of cancer, no significant differences were observed in the coagulating glands and seminal vesicles. Regarding atypical hyperplasia, androgen deprivation significantly decreased the proliferative cell nuclear antigen labeling index in the coagulating gland and seminal vesicles. The presence of cancer was also decreased in the coagulating gland but not in the seminal vesicles. With control group specimens, more intense staining of androgen receptor was observed in atypical hyperplasias than in cancers. Compared with the atypical hyperplasias, the cancers revealed low androgen dependency at the early stages of carcinogenesis. The cancers in the seminal vesicles also revealed higher androgen independency than did those in the coagulating gland.

Aminobiphenyl Compounds↗