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Biomedical subjects

T Suwa

Publications and source records attributed to T Suwa.

At least 145 records · Page 8Linked to original sources
PubMed1987

Therapeutic effects of sofalcone on experimental gastritis.

A study was made on the therapeutic effects of sofalcone (SU-88), an antiulcer agent, on erosive and atrophic gastritis induced experimentally by 6-month administration of 5 mmol/l of sodium taurocholate (TCA) in rats. A standard meal including sofalcone of 0.25% and 1.0% shortened the total length of erosions, normalized the mucosal thickness, and reduced collagenous fibers in the gastric mucosa in one month. The doses administered were 116.3 mg and 486.1 mg/kg/week for one month. Sofalcone, thus, had a good therapeutic effect on experimental erosive and atrophic gastritis in rats.

Animals↗
PubMed1986

[Analyses of constituents of feces and the effect of a vitamin B12 fortified diet on coprophagy in the mouse].

In order to investigate coprophagy from the viewpoint of nutrition, fecal constituents were analyzed in freeze-dried samples. Feces were collected from 7:00 to 11:00 and from 19:00 to 23:00. Inorganic elements and crude fibers per unit weight were 3-4 times more concentrated in feces than in basal diet, whereas, crude proteins, crude fats and nitrogen-free extract showed various degrees of reduction. There were no differences in these tendencies with sampling time. As for some B vitamins, feces collected from 7:00 to 11:00 contained 22-92% more vitamins than feces collected from 19:00 to 23:00. In comparison with the dietary concentration, vitamin B12 was increased by 124-197 times (520-730 micrograms/100 g) in feces collected between 7:00 and 11:00. Folic acid in feces collected between 7:00 and 11:00 was 10 times greater than that in the diet. On the basis of the findings on vitamins, the effect of a vitamin B12 fortified diet (1,350 micrograms/100 g) on coprophagy was examined. Mean frequency of coprophagy per animal per day was 9.6 when animals were fed on the basal diet, whereas the frequency was immediately and significantly (p less than 0.05 approximately p less than 0.01) reduced to 4.7 after the diet had been replaced by the fortified one. However, coprophagy was not completely inhibited by vitamin B12 fortification. This indicates that some nutrient(s) in feces other than vitamin B12 might be of use to the host, and that otherwise, coprophagy might be a basically habitual form of behavior. Furthermore, under the fortified diet, the frequency of coprophagy increased gradually.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗
PubMed1985

[A pharmacokinetic study of cefoperazone during percutaneous transhepatic cholangial catheterization].

The metabolic fate of cefoperazone (CPZ) was studied in 19 cases which underwent percutaneous transhepatic cholangial catheterization (PTC-catheterization, PTCC) and were under various conditions of the liver function. The peak of bile levels of CPZ immediately after PTCC differed greatly from one case to another at 12.6-7,260 micrograms/ml with 1 g intravenous injection and 23.0-5,800 micrograms/ml with 2 g intravenous injection. The ratio of the peak of bile level to the serum level immediately after PTCC showed the highest negative correlation with the serum total bilirubin level. It also showed a significant negative correlation with GOT, GPT, Al-P and LAP. The serum CPZ level and half-life showed no significant trend except half-life showed a significant correlation with LAP. The recovery rate in urine up to 12 hours was in the range of 14.8-93.6%, showing a significant correlation with the ratio of the peak of bile levels to the serum level and the date of liver function tests. The bile level, serum level and recovery rate in urine at the time the bile outflow from the catheter has become constant after PTCC (during the course of PTCC) showed a trend almost similar to that immediately after PTCC, there being no significant difference as to each parameter during the course of PTCC and immediately after PTCC. In the cases in which the sample was collected by the cross-over technique, the ratio of the peak of bile levels to the serum level from immediately after PTCC to during the course of PTCC increased in 2 cases and decreased in 6 cases. The 2 cases that showed the increase in the ratio were the case in which the serum total bilirubin level improved almost to normal. Findings above suggest that sufficient biliary decompression can improve the movement of CPZ into bile, despite the fact that the pharmacokinetics of CPZ is affected by the liver function, particularly serum total bilirubin level, that a decrease in the movement to bile and a compensatory increase in urinary excretion are observed in jaundice and disturbance of the liver function and that the ratio of the peak of bile level to the serum level decreases during the course of PTCC rather than immediately after PTCC in some cases.

Adult↗
PubMed1984

Effect of 2'-carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy)chalcone (SU-88) on prostaglandin metabolism in hog gastric mucosa.

SU-88 [2'-carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy)chalcone] inhibited the activity of the prostaglandin (PG)-metabolizing enzyme, 15-hydroxy-PG-dehydrogenase (15-OH-PG-DH), in a cytoplasmic fraction of gastric mucosa. This compound had no effect on the PG synthetase of bovine seminal vesicle microsomes and lactate dehydrogenase in rat liver. The 15-OH-PG-DH activity of gastric mucosa was not influenced by a specific inhibitor of alcohol dehydrogenase, 4-methylpyrazole. Carbenoxolone (CBX) also inhibited 15-OH-PG-DH activity. The IC50 values for SU-88 and CBX were approximately 20 and 40 microM respectively. SU-88 inhibited 15-OH-PG-DH activity uncompetitively or competitively according to whether PGE1 or NAD was used as substrate. CBX inhibited competitively the activity of this enzyme for both substrates. After the addition of SU-88 or CBX to the incubation medium of gastric mucosa, the PGE2 level of the medium was increased significantly while that of the tissue remained unchanged. These results indicate that SU-88 specifically inhibited 15-OH-PG-DH activity and suggest that 15-OH-PG-DH activity regulates the level of PGs in gastric mucosa and may have an anti-ulcer influence.

Animals↗
PubMed1984

The studies on the role of gastric glycoproteins with reference to cytoprotection: protective effect of prostaglandin E2 and sofalcone on ethanol-induced necrosis.

The gastric cytoprotective action of prostaglandin E2 (PGE2) and sofalcone was studied in rats. The in vitro incorporating activity of 3H-glucosamine into the gastric macromolecular glycoproteins was examined when PGE2 (0.1 mg/kg, p.o.) or sofalcone (100 mg/kg, i.p.) was administered 5, 15 or 30 min before the oral administration of absolute ethanol. The cytoprotective effect of PGE2 against gastric mucosal damage was demonstrated 5 min after PGE2 was given orally. The cytoprotective effect by sofalcone was seen after 15 min. However, during this period, the decrease in gastric macromolecular glycoprotein synthesis induced by the ethanol damage could not be restored by pretreatment with PGE2 or sofalcone. On the other hand, the reduction in the content of the gastric macromolecular glycoproteins by the ethanol damage was found to be prevented to a significant extent by pretreatment with PGE2. The same phenomenon was also observed in the administration of sofalcone. Accordingly, PGE2 has stimulating effect on the gastric glycoproteins biosynthesis, but this effect can not be considered as the mechanism responsible for cytoprotection, if indeed a single mechanism exists. Thus, it is suggested that the adhesion or maintenance of secreted macromolecular glycoproteins to the gastric tissue is closely related to cytoprotection.

Animals↗
PubMed1984

Effect of an anti-ulcer agent, 2'-carboxymethoxy-4, 4'-bis (3-methyl-2-butenyloxy) chalcone (SU-88), on the biosynthesis of gastric sulfated mucosubstances in restrained and water-immersed rats.

2'-Carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy) chalcone (SU-88) has an anti-ulcer effect which is considered to increase the resistant factors of the gastric mucosa. In order to clarify the mechanism of the action of SU-88, the biosynthesis of gastric sulfated mucosubstances (SMS) in vivo and in vitro was investigated in rats with gastric erosion induced by restraint and water-immersion. The incorporation of 35S-sulfate into gastric SMS was significantly reduced 18 hr after the onset of stress. Pretreatment with SU-88 (500 mg/kg, p.o., X 10 days) prevented a reduction in the incorporation of 35S-sulfate due to stress when 35S-sulfate was administered in vivo. On the contrary, the incorporating activity of 35S-sulfate into the SMS in the isolated rat gastric mucosa with erosion was significantly increased 12 hr after the onset of stress, as compared with that of the control group in vitro. The incorporation of 35S-sulfate into the SMS was still further increased by the oral administration of SU-88. The mode of action of SU-88 on the biosynthesis of SMS was discussed.

Animals↗
PubMed1984

Cytoprotective effect of SU-88, an anti-ulcer agent, in the rat.

The gastric cytoprotective action of SU-88, an anti-ulcer agent, was studied in rats. SU-88 dose-dependently prevented the formation of gastric lesions induced by absolute ethanol as observed by PGE2. The efficacy of SU-88 when given i.p. was more potent than the p.o. administration. Indomethacin (5mg/kg, p.o.) given 30 min prior to SU-88 dosing blocked this protective effect, whereas it was not affected when indomethacin was given 30 min after the SU-88 dosing. Cimetidine, on the other hand, failed to exert a protective effect against the ethanol-induced lesions and caused a significant increase in the lesions induced by 0.6N HCI. Pretreatment with SU-88 prior to cimetidine resulted in a marked reduction in the lesions. SU-88 was found to increase the synthesis of gastric glycoproteins and to prevent the reduction of glycoprotein synthesis caused by the administration of absolute ethanol. However, no increase in the synthesis was observed 5 min after the SU-88 dosing, although the lesion was significantly suppressed at that time. These findings indicate that SU-88 possesses a cytoprotective effect and that this effect seems to be mediated by the increase in endogenous PG.

Animals↗
PubMed1984

[Clinical studies on preoperative abdominal arterial infusion of anticancer agents].

Operable patients with gastrointestinal cancer were injected once with MMC 0.4 mg/kg, ADM 0.8 mg/kg or KW 2083 1 mg/kg through the abdominal artery 7 to 15 days before operation. Biopsy was made on liver tissues during operation, and changes of serum biochemical test values were observed before and after operation. In 7 cases of MMC 20 mg arterial infusion, 7 cases of ADM 40 mg and 6 cases of KW 2083 50 mg liver biopsy showed fibrosis around the central vein. Eosin bodies, neutrophils or necrotic lesions were observed in some other cases. Serum biochemical test values were transiently affected with anesthesia, but these changes will have no unfavorable influence on the results of operation and following treatment.

Abdomen↗
PubMedDate not supplied

Comparison of stepwise and simultaneous estimations of population pharmacokinetics and pharmacodynamics of TS-943.

The prediction performances of population pharmacokinetic-pharmacodynamic analysis of the two methods (a stepwise and a simultaneous estimations) were evaluated with respect to their accuracies and precisions. A study was designed to investigate the safety and efficacy of TS-943 by a 4 hours constant infusion in 36 healthy male subjects. Population analysis was performed using pharmacokinetic and pharmacodynamic models with NONMEM. The mean of the prediction error (MPE) and the root mean squared error (RMSE) served as a measure of accuracy and precision. In addition, a bootstrap validation was also performed. The results indicate that those population pharmacokinetic-pharmacodynamic parameters for the two methods were comparable. The results of simultaneous estimations are similar to those obtained using a stepwise estimation. The mean parameter estimates obtained with the additional 200 bootstrap replicates of data were within 15% of those obtained with the final model in both methods. The present results demonstrated that the accuracy of pharmacodynamic evaluations using a stepwise end a simultaneous estimations was comparable.

Adult↗
PubMedDate not supplied

A retrospective analysis of background lesions and tissue accountability for male accessory sex organs in Fischer-344 rats.

Because the paired lobes (ventral, dorsal, lateral, and anterior) of the rat prostate have not been consistently sampled in many carcinogenicity and toxicity studies, comparison among different investigations has been compromised. The lack of specific site identification for prostatic lesions further lessens the value of incidences reported. We present here the lobe-specific incidences and degree of severity of background prostatic, seminal vesicular, and ampullary glandular lesions in 1768 control Fischer-344 rats from 35 recent National Toxicology Program 2-year carcinogenicity and toxicity studies conducted in 4 laboratories. The dorsal and lateral lobes were combined and considered the dorsolateral lobe where inflammation, epithelial degeneration, mucinous cysts, and edema were observed. Inflammation in the dorsolateral lobes was significantly associated with pituitary gland adenoma whose prolactin was suggested to play an important role in pathogenesis of prostatic inflammation. Epithelial degeneration, epithelial hyperplasia, inflammation, edema, and adenoma were conspicuous in the ventral lobes. Inflammation and edema occurred in the anterior lobes (coagulating glands). Inflammation, dilatation, epithelial hyperplasia, edema, and adenoma were observed in the seminal vesicles. Inflammation was also present in the ampullary glands. We suggest an optimal embedment and trimming method in rat prostate and seminal vesicle to ensure adequate, consistent sampling.

Animals↗
PubMedDate not supplied

Correlation between human hepatocyte growth factor and interleukin-6 concentrations after surgery.

BACKGROUND/AIMS: The aim of this study was to determine whether the production of human hepatocyte growth factor (hHGF) occurs in injured tissue following surgery in conjunction with interleukin-6 (IL-6) synthesis, and independently of liver resection. METHODOLOGY: The post-operative concentrations of hHGF and IL-6 in the serum and local exudative fluid were measured in 33 patients following abdominal (n = 20) or thoracic surgery (n = 13) (non-HTX), and in 7 undergoing a partial hepatectomy (HTX). RESULTS: Concentrations of two cytokines in the fluid were much higher than those in the serum (p < 0.001) in all patients. The maximum serum levels of hHGF were significantly correlated with those of IL-6 (p < 0.05), intra-operative blood loss (p < 0.005), and operating time (p < 0.005) in patients undergoing non-HTX. In these patients, the fluid levels of hHGF were also significantly correlated with those of IL-6 (p < 0.001). In serum and fluid, the hHGF/IL-6 ratios were markedly higher after HTX than after non-HTX (p < 0.05). CONCLUSIONS: These results suggests that hHGF may be produced in conjunction with IL-6 in injured tissue following surgery, but the production of hHGF may predominate over that of IL-6 in the liver following partial hepatectomy.

Aged↗
PubMedDate not supplied

Serum interleukin-6 levels in patients with biliary obstruction.

BACKGROUND/AIMS: The clinical significance of the interleukin-6 (IL-6) response in patients with biliary obstruction was studied. METHODOLOGY: This study included 30 patients who had biliary obstruction and underwent percutaneous transhepatic biliary drainage. Cases complicated by cholangitis were excluded. The serum levels of IL-6 and standard liver function tests were examined before and after biliary drainage. RESULTS: Serum IL-6 levels were significantly higher in patients with biliary obstruction compared to control subjects (p<0.05). After drainage, serum IL-6 levels decreased significantly (p<0.01). The patients with serum IL-6 levels exceeding 10 pg/ml were characterized by lower hepaplastin values, lower serum levels of total protein and albumin, higher mean age, and more frequently positive cultures of bile compared to those with serum IL-6 levels of less than 10 pg/ml. Serum IL-6 levels were correlated negatively with hepaplastin values and serum levels of total protein and albumin (p<0.05). CONCLUSIONS: These results suggest that subclinical biliary infection, liver dysfunction and advanced age promote the IL-6 response in patients with biliary obstruction. Such a cytokine response may disturb the physiologic immune response after the ensuing major operation and may be related to some post-operative complications.

Aged↗
PubMedDate not supplied

Epidermal growth factor receptor-dependent cytotoxic effect of anti-EGFR antibody-ribonuclease conjugate on human cancer cells.

We have conjugated the murine monoclonal antibody (528) against the human epidermal growth factor receptor (EGFR) to mammalian pancreatic ribonuclease (RNase) via N-succinimidyl-3-(2-pyridyldithio) propionate (SPDP) and 2-iminothiolene (2-IT). The conjugate showed dose-dependent cytotoxicity against EGFR-producing squamous cancer cells (A431, TE8, TE5, Ca9-22) and no detectable cytotoxicity against EGFR-deficient small-cell lung cancer cells (H69). The cytotoxicity of the conjugate was positively correlated with the EGFR numbers of each cell line. The addition of excess 528 antibody to the medium protected A431 cells from the conjugate cytotoxicity. This immunoconjugate might be useful for targeted treatment of squamous cell carcinomas hyperexpressing EGFR.

Animals↗