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Biomedical subjects

M Sano

Publications and source records attributed to M Sano.

At least 685 records · Page 38Linked to original sources

Inhibition of development of methylnitrosourea-induced rat colonic tumors by peroral administration of indomethacin.

The nonsteroid antiinflammatory drug indomethacin, a prostaglandin synthesis inhibitor, inhibited the development of carcinogen-induced large bowel carcinomas in rats. CD-Fischer rats were given carcinogenic pretreatment with intrarectal instillation of 2 mg of methylnitrosourea 3 times a week from the 1st to the 5th week, in order to produce large bowel tumors. Thereafter, peroral administration of a high or low dose of indomethacin dissolved in drinking water (20 micrograms or 10 micrograms indomethacin/ml tap water) for 15 weeks was started at the 11th week, before the tumors developed. At autopsy in the 26th week just after the completion of the 15-week treatment, the incidence of developing large bowel tumors was significantly reduced in treated rats, compared to untreated control rats; 17% or 14% vs. 67%. However, at autopsy in the 36th week, 10 weeks after cessation of the treatment, the development of tumors in treated rats was significantly increased. Thus, indomethacin inhibited the development of methylnitrosourea-induced large bowel tumors in rats. The effectiveness of peroral administration of indomethacin was comparable to that of intraperitoneal administration. It is postulated that treatment with this drug may effectively prevent the development of large bowel cancer in patients at high risk.

Animals↗

Is glucagon present in the human gastric fundus?

The presence of pancreatic type glucagon in the fetal and adult human gastric fundus was examined by radioimmunoassay and by an indirect immunofluorescence technique using specific antiserum against pancreatic glucagon. Although pancreatic type glucagon-containing cell (glucagon-positive cell) were demonstrated in the fetal gastric fundus in 16th, 18th, 23rd and 29th week's gestation, they were not detected in the adult gastric fundus. This immunohistochemical finding was supported by radioimmunoassay study for glucagon in gastric fundus in which there was 52 pg/mg of glucagon in the fetal gastric fundus at 20th week's gestation while glucagon was negligible in the adult gastric fundus. The findings, therefore, suggest that glucagon-positive cells in the human gastric fundus may play an important role in the maintenance of fetal life. Moreover, one fourth of glucagon-positive cells in the fetal gastric fundus reached the gut lumen with their cytoplasmic processes. In view of the finding that none of the canine glucagon-positive cells in the gastric fundus had contact with the gut lumen, the morphological feature of glucagon-positive cells in the human, fetal gastric fundus suggests that the function of glucagon-positive cells in the human, fetal gastric fundus may be somewhat different from that in other mammals.

Adult↗

Properties of detergent-dispersed adenylate cyclase from cerebral cortex. Presence of an inhibitor protein.

Adenylate cyclase was solubilized from washed particulate fraction of rabbit cerebral cortex with the nonionic detergent Lubrol 12A9 and subjected to either gel filtration on Ultrogel AcA 34 or chromatography on DEAE Bio-Gel A. By both procedures the enzyme was resolved into two components, one insensitive to guanyl 5'-yl imidodiphosphate [Gpp(NH)p] and NaF but stimulated by Ca2+ and calmodulin, and another that was sensitive to Gpp(NH)p and NaF but relatively insensitive to Ca2+ and calmodulin. The data support the possibility that two independent forms of adenylate cyclase exist in cerebral cortex, one regulated by guanine nucleotide regulatory protein and another by Ca2+-calmodulin. Fractions containing the guanylnucleotide-sensitive activity were found to contain a factor that inhibited basal and Ca2+-stimulated adenylate cyclase in the Ca2+-sensitive fraction. The inhibitor was inactivated by heating at 60 degrees C and by incubation with trypsin. Inhibition was not time-dependent, and it was not due to destruction of cAMP by phosphodiesterase or of ATP by ATPase. Inhibitory action was not reversed by calmodulin and therefore it does not appear to be a calmodulin binding protein. Sucrose density gradient sedimentation indicated a sedimentation coefficient of 4S for the inhibitor; by this technique it co-sedimented with the adenylate cyclase sensitive to Gpp(NH)p and NaF.

3',5'-Cyclic-AMP Phosphodiesterases↗

Disposition of timiperone, 4'-fluoro-4-[4-(2-thioxo-1-benzimidazolinyl)piperidino]butyrophenone, a neuroleptic, in the rat on repeated oral dosage.

1. The metabolic disposition of [14C]timiperone was studied in male Wistar strain rats receiving an oral dose of 0.5 mg/kg consecutively daily for 21 days. 2. Blood concentrations of 14C indicate that absorption of [14C]timiperone on repeated dosage may be similar to that after a single dose. 3. Tissue levels of 14C after repeated doses were increased to up to double those after a single dose, but the decline of tissue concentrations after the 21st dose was similar to that after a single dose. Thus, no rat tissue show accumulation. 4. Repeated administration did not affect the metabolism of timiperone. 5. Excretion of 14C on the third day of repeated medication was urine, 44.7% and faeces 52.4% of the cumulative dose, and total daily excretions were more than approx. 97% of the cumulative dose in days 3-21 of the repeat dosage schedule.

Administration, Oral↗

A simple and rapid method of dissociating hepatocytes from fixed liver of the mouse.

A simple and rapid method of dissociating hepatocytes of fixed liver tissue is described. Mouse liver was fixed by vascular perfusion with sodium phosphate buffered 2% formaldehyde-2% glutaraldehyde solution containing 0.02% picric acid and then osmicated in 2% OsO4 in phosphate buffer by immersion. Hepatocytes are easily dissociated by tapping the fixed tissue blocks in distilled water with a glass rod or by ultrasonics. This method results in very low cell fragility and a high yield of well preserved hepatocytes in suspension. For light microscopic examination the separated cells may be uniformly spread on a slide glass coated with Mayer's egg albumen and stained. Electron microscopic evaluation of the dispersed cells indicated that they have intact cell membranes and retain the integrity of their cytoplasm and nuclei well. This method is most suitable for accurate determination of the nuclear content and size of individual liver cells, as well as of the number of mitotic cells, and is potentially useful for gathering other information on the morphometric cytology of the liver.

Animals↗

[Studies of the effects of cis, cis and trans, trans-octadecadienoic acids on lipid metabolism in essential fatty acid deficient rats (author's transl)].

The effect of an essential fatty acid [EFA] deficiency in male Sprague-Dawley rats and its excerbation by inclusion of trans fatty acids in the diet were observed from the level and composition of serum lipoproteins. Male Sprague-Dawley rats were fed from weaning diet containing all essential nutrients and 10% of a fat supplement as safflower oil (SAFF] or hydrogenated coconut oil [HCO] for 28 weeks. At the end of 28 weeks, the blood was withdrawn from the retro-ocular plexes of 4 animals of each group, and lipoprotein lipid and fatty acids were analyzed. Another 5 animals of each group were switched to a 5% supplement of ethyl linolelaidate [TRANS]. In addition, the remaining 5 animals of HCO group were switched to SAFF diet. Lipoprotein lipid and fatty acid analyses were performed on the pooled serum in each group at 3, 7 and 14 days after switching the diet, and after 21 days serum was analyzed on the individual animal of each group. The results obtained were as follows: [1] With the development of an EFA deficiency in HCO group, there was a decrease in the high density lipoprotein [HDL] and increase in the very low density lipoprotein [VLDL] plus low density lipoprotein [LDL] fraction. [2] In a switching group from the SAFF to the TRANS supplement, the level of arachidonate in the serum lipid was decreased with a corresponding decrease in HDL, whereas linoleate, at least for the initial 3 weeks, decreased only in triglyceride fraction. [3] In a EFA deficient rat [HCO group] after switched to the TRANS supplement, HDL was further decreased and increase o VLDL-LDL was progressed. Consequently, the HDL: VLDL-LDL ratio was lowered strikingly. These changes in the EFA deficiency were accompanied by a large increase in monoenoic acids and a decrease in eicosatrienoic acid converted from oleic acid. [4] The administration of SAFF diet to the EFA deficient group induced a rapid increase in arachidonate in HDL, and decrease in eicosatrienoic acid and oleic acid. These changes were accompanied by a marked decrease in VLDL-LDL. It is suggested that the normal HDL might play an important role on catabolism of VLDL-LDL. These results suggest that polyunsaturated fatty acid, especially arachidonic acid rather than linoleic acid is essential to the formation and the function of HDL in the rats.

Animals↗

Effect of acetylcholine and catecholamines on the enterochromaffin-like cells of the stomach.

Small pieces of fundic mucosa from rats were incubated for 15 minutes at 3 degrees C. in tissue culture medium, and the effects of acetylcholine, epinephrine and norepinephrine on the enterochromaffin-like cell were studied by electron microscopy with a morphometric study of the secretory granules. The addition of acetylcholine and norepinephrine did not cause significant changes in the secretory granules of the cell, while the addition of epinephrine caused a significant increase in the volume density of the secretory granules. This increase was associated with a significant decrease in electron opaque components within the secretory granules of the cell. The results suggest that the activity of the cells in rats is under direct adrenomedullary influence.

Acetylcholine↗

Determination of ethambutol in plasma using selected ion monitoring.

The determination of ethambutol in plasma is described. Using ethambutol-d4 as an internal standard, ethambutol and the internal standard were extracted with chloroform under alkaline conditions, and converted into their trifluoroacetyl derivatives with trifluoroacetic anhydride in benzene-pyridine (4:1). Selected ion monitoring was carried out by monitoring the peaks at m/z 294 and 296 corresponding to the fragment ion [M/2]+ of the derivatives. Ethambutol was determined by use of the peak height ratio of the peak at m/z 294 against that at m/z 296. The method was utilized for studying the bioavailability and pharmacokinetics of the drug.

Animals↗

Sensitive and selective method for the determination of chlormezanone in plasma by electron-capture gas chromatography.

A sensitive and selective determination method of chlormezanone in plasma has been divised. Chlormezanone in plasma was extracted with toluene at pH 4.5, and converted into p-chlorobenzaldehyde in 0.1 N NaOH. Using p-bromobenzaldehyde as an internal standard, the hydrolysis product and the internal standard were extracted with n-hexane, and the extract was concentrated in vacuo in the presence of isoamyl alcohol to prepare the sample solution. The sample solution was submitted to electron-capture gas chromatography. Chlormezanone was determined by use of the peak height ratio of p-chlorobenzaldehyde against the internal standard. The method was utilized successfully for pharmacokinetic studies of chlormezanone in plasma.

Benzaldehydes↗