[Pancreatic exocrine function in rats treated with oral 1-phenyl-1-hydroxy-n-pentane (author's transl)].
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Biomedical subjects
Publications and source records attributed to S Baba.
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Tumor development was examined sequentially in the nasal cavity of male F344 rats given 0.01% 1,4-dinitrosopiperazine (DNP) in their drinking water for various periods. Rats were sacrificed at 10-week intervals for up to Week 50. On continuous DNP administration, simple hyperplasia of the nasal cavity epithelium was observed from Week 10, papillary hyperplasia, nodular hyperplasia, and papilloma was observed from Week 20, and carcinoma was observed from Week 30. Carcinoma was observed in 100% of the animals given DNP for 50 weeks. The carcinomas were adenocarcinomas (86%), adenosquamous cell carcinomas (10%), and undifferentiated carcinomas (4%). Simple hyperplasia was distributed evenly in the nasal cavity. Seventy % of the nodular hyperplasias and 81% of the carcinomas were located in the ethmoturbinate and about 75% of the papillary hyperplasias and papillomas were located in the nasoturbinate and maxilloturbinate. These findings suggest that nodular hyperplasia is very important as a precursor of carcinoma in the nasal cavity of rats treated with DNP and that papilloma is less important in relation to carcinoma development.
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The distribution of antimicrobial agents in infected target tissues would be essential for their application to treat the sites of infection. Taking accounts of the view point, we had reported the distribution of 3 nalidixic acid analogs in tissues which are related to otorhinolaryngology by macro-autoradiography and radiometry. We investigated here in the distribution of a nalidixic acid analog OPC-7241. This agent is 9-fluro-5-methyl-8-(4-methyl-1-piperaginyl)-6, 7-dihydro-1-oxo-1H, 5H-benzo [ij]quinoligine-2-carboxylic acid supplied by Otsuka Pharmaceutical Co., Ltd. Autoradiography was performed 30 minutes after intravenous administration of 14C-OPC-7241 in 2.96 MBq(80.0 microCi)/12.5mg/kg to New Zieland White rabbit. Radiometry was performed 30 minutes, 1 hour and 3 hours after intravenous administration of 14C-OPC-7241 in 740 kBq (20.0 microCi)/10.0 mg/kg to NZW rabbits. Such care was taken in filling the carboxymethyl cellulose paste into the paranasal cavity, nasal cavity, oral cavity and external ear canal not to damage mechanically. Horizontal frozen sections parallel to mandibular basis were cut in 50 microns thickness in a cryostadt. Blackening of 14C-OPC-7241 was most significant in soft palate and its expanse which is apparently the same gland-like tissues as soft palate when stained with hematoxylin and eosin. Significant radioactivity was recognized in tonsils, the cartilage of external ear canal, septal cartilage, periodontal membrane, dental pulp, muscle and concha nasalis ventralis. The levels was low in ethmoid cells, mucosa of tympanic cavity, cochlea, maxillary sinus and bone. Quantitatively, the levels of 14C-OPC-7241 radioactivity were high in soft palate, mandibular gland and tonsils. Radioactivity was significant in tongue and concha nasalis ventralis. The levels were low in turbinates, ethmoid cells, maxillary sinus, septal cartilage, septal mucosa, cochlea, brain, optic nerve and lens. Thus radiometric results agreed with the above autoradiographic findings. Macro-autoradiography can be one of useful means for the evaluation chemotherapeutic agents for possible clinical application.
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The mode of inhibition of a new complex oligosaccharide that inhibits the alpha-glucoside hydrolase activity of pancreatic and salivary alpha-amylase was studied. Kinetic analysis revealed a non-competitive type of inhibition with a Ki of 1.47 +/- 0.03 micrograms when tested against human pancreatic alpha-amylase and 3.89 +/- 0.08 micrograms against human salivary alpha-amylase. The inhibitory action of alpha-glucoside hydrolase inhibitor (alpha-GHI) on pancreatic amylase was observed over a wide range of pH (6.0--7.9), whereas the inhibition of salivary amylase was optimal at pH 6.5. Column chromatographic investigations suggested the possible formation of an enzyme-inhibitor complex because the mixture of alpha-GHI and pancreatic alpha-amylase was eluted as a single component through a Sephadex G200 column. However, this enzyme-inhibitor complex was easily separated into each component and the enzyme activity was fully recovered after electrophoresis.
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Determination of urinary metabolites of orally administered rutin and rutin-2',5',6'-d3 in humans was carried out by TLC and GLC-mass spectrometry. In human urine, 3-hydroxyphenylacetic acid, 3-methoxy-4-hydroxyphenylacetic acid, 3,4-dihydroxyphenylacetic acid, 3,4-dihydroxytoluene, and beta-m-hydroxyphenylhydracrylic acid were identified as rutin metabolites. Unchanged rutin and quercetin were not present in urine.
To investigate the antiandrogenic action of cimetidine in vivo, prostatic androgen uptake and metabolism, spermatogenesis, morphology of the prostate and testes, and plasma hormone levels were studied using Sprague-Dawley rats, and the results were compared with the effects of cyproterone acetate or castration. Cimetidine and cyproterone acetate caused significant reduction in the weights of the ventral prostate and testes. The changes of ventral prostate were accompanied by a dose-related epithelial atrophy. No adverse effect on spermatogenesis was observed after treatment with cimetidine at daily doses of 50 mg/kg or cyproterone acetate of 10 mg/kg. Although cimetidine treatment induced a significant decrease in plasma testosterone levels, the uptake of testosterone-3H and its conversion to DHT of the ventral prostate were not inhibited by cimetidine.
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Portal plasma immunoreactive secretin (IRS) concentrations, pancreatic juice flow, and amylase output were simultaneously measured in response to intraduodenal infusion of 1-phenyl-1-hydroxy-n-pentane (PHP), as well as infusion of hydrochloric acid (HCl). These data were compared with those obtained from intravenous bolus injections of synthetic porcine secretin in anesthetized rats. The intraduodenal infusion of PHP or HCl at a rate of 2 ml/min for 2 min produced a dose-related increase in portal plasma secretin concentrations, pancreatic juice flow, and amylase output. However, the mechanism of secretin release by PHP seems to differ from that of HCl. The secretin response to 0.1 N HCl infused at a rate of 0.1 ml/min for 30 min was complete after 10 min, despite continued infusion, while PHP stimulated a secretin release which persisted for 10 min after cessation of infusion. The pH in the second portion of the duodenum, following PHP infusion, remained consistently greater than 6.3. PHP-stimulated pancreatic exocrine secretions were only partially suppressed by somatostatin, while secretin release was almost completely inhibited. However, intraduodenal PHP may stimulate the release of secretin along with other gastrointestinal hormones, and the endogenous release of these hormones may not be inhibited by somatostatin.
Amylase-creatinine clearance ratio (ACCR) and amylase isoenzyme clearance were determined simultaneously in patients with chronic renal failure. ACCR in patients with compensated renal failure (3.5 +/- 0.4%) was not significantly different from normals (2.6 +/- 0.2%), while that in patients with non-compensated renal failure (6.7 +/- 0.4%) was significantly higher than that in normals. Clearance ratio of pancreatic isoamylase (Amylase-1) relative to creatinine clearance (CAmy . 1/Ccr) in patients with both compensated (5.9 +/- 1.0%) and non-compensated (6.8 +/- 0.4%) renal failure was as high as that in patients with acute pancreatitis (6.6 +/- 0.5%). On the other hand, clearance ratio of salivary isoamylase (Amylase-3) relative to creatinine clearance (CAmy . 3/CCr) in patients with compensated renal failure (1.5 +/- 0.3%) was almost the same as that in normals (2.1 +/- 0.1%), while that in patients with non-compensated renal failure was 5.9 +/- 0.7%, which was significantly higher than that in normals. The present study revealed that elevated ACCR in patients with severely impaired renal function was due to the increase of the clearance ratio for both pancreatic and salivary amylase. These facts suggested that glomerular permeability and tubular reabsorption for pancreatic and salivary amylase might play an important role on ACCR in patients with severely impaired renal function.
Pancreatic juice flow and amylase output, and the concentrations of immunoreactive secretin in portal and peripheral blood were simultaneously determined in anesthetized rats in response to intraduodenal instillation of 1-phenyl-1-hydroxy-n-pentane (PHP), a phenyl carbinol derivative induced from one of the constituents of Curcuma. PHP stimulated both pancreatic juice flow and amylase output and increased portal and jugular plasma secretin levels in a dose-related fashion. During intraduodenal instillation of PHP the pH in the second portion of the duodenum remained consistently above 6.3. Infusion of cyclic somatostatin at a dose of 5 microgram/kg/h significantly suppressed the PHP-induced secretin release, though pancreatic flow rate and amylase output were only slightly and insignificantly suppressed. These observations suggest that PHP release secretin by an acid independent mechanism but also stimulates the exocrine pancreas by a mechanism independent of secretin.
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Plasma insulin and glucagon responses to oral glucose loading were examined in rats with islet cell tumors induced by a single intravenous injection of streptozotocin (30 or 40 mg/kg body weight). Twenty-four macroscopic and six microscopic tumors occurred in 21 rats. In 15 of 21 tumor-bearing rats, there was exaggerated insulin release in response to oral glucose. Plasma glucose levels did not rise with the oral glucose load and were comparable to those seen in normal animals. Hence these rats are described as having "responsive tumors." In six rats with "nonresponsive tumors" there was no insulin response and the plasma glucose levels rose. No significant differences in plasma levels were observed between the two groups. Nonresponsive tumors as well as responsive tumors contained a significant amount of extractable insulin (17.68 +/- 8.60 and 35.07 +/- 10.05 mg/g wet weight, respectively) and detectable amounts of immunoreactive glucagon (1.47 +/- 0.61 and 2.24 +/- 0.67 micrograms/g wet weight, respectively). These results suggest that a small dose of streptozotocin produces two types of islet cell tumors. One is insulin producing and insulin secreting whereas the other is insulin producing but not insulin secreting.