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Biomedical subjects

K Shiratori

Publications and source records attributed to K Shiratori.

At least 73 records · Page 4Linked to original sources

Intravascular ultrasound imaging--in vitro and vivo validation.

Intravascular ultrasound imaging is a new technique for visualizing arterial structures. The purpose of this study was twofold; first, to assess the ability of this intravascular ultrasound catheter to generate cross-sectional images of human artery segments in vitro and second, to determine the reliability of intravascular ultrasound technique in the evaluation of human arteries in vivo. For the vitro study, ultrasound images of the arteries were presented as a two-dimensional, 360 degrees display of vessel cross-section perpendicular to the long-axis of the probe. The ultrasound scanning provided an accurate description with high resolution of lumen structure and lumen-intima interface in all vessel specimens. There was a good correlation between the planimetric luminal area on the ultrasound images and the area obtained from histologic images (r = 0.92). There was also a good correlation in the plaque thickness between ultrasound and histological examination (r = 0.88). In the in vivo study, the ultrasound catheter was easily introduced, readily manipulated, and images were successfully obtained in all patients. No untoward effects were noted during manipulation of the catheter. There was a good correlation in the arterial dimension between ultrasound and angiographic measurements (r = 0.93). Thus, intravascular ultrasound imaging appears to be useful for characterizing and quantitating arterial lesions.

Carotid Arteries↗

Secretin as a potential mediator of antiulcer actions of mucosal protective agents.

Recently, we have reported that several nonacid agents including phenylpentol, methanol extract of licorice root (FM 100), plaunotol, and teprenon stimulate release of endogenous secretin in humans, dogs, and rats. The latter three are antiulcer agents developed in Japan that have a protective effect on the gastric mucosa. We have clearly shown that plaunotol inhibits postprandial gastrin release and gastric acid secretion that parallel the increase in plasma secretin concentration. It has also been recently demonstrated that the secretin-induced inhibition of gastric acid secretion in rats is completely blocked by indomethacin, a potent inhibitor of prostaglandin synthesis. It appears that the inhibitory action of secretin on gastric acid secretion is mediated mainly by endogenous prostaglandins. Because the three antiulcer agents FM 100, plaunotol, and teprenon have been shown to increase the content of endogenous prostaglandins in the gastric mucosa, endogenous secretin released by these agents may play a significant role in their mucosal protective action. It is concluded that the antiulcer effect of these drugs could in part be attributable to their unique ability to release endogenous secretin, and that secretin is a potential mediator of the antiulcer actions of mucosal protective agents.

Animals↗

Somatostatin analog, SMS 201-995, inhibits pancreatic exocrine secretion and release of secretin and cholecystokinin in rats.

We studied the effect of a synthetic octapeptide somatostatin analog, SMS 201-995 (sandostatin), on pancreatic exocrine secretion and on plasma secretin and cholecystokinin (CCK) levels in vivo in anesthetized rats. The exocrine pancreas was stimulated by either intravenous infusion of both secretin (0.06 CU/kg/h) and cholecystokinin octapeptide (CCK-8) (0.03 micrograms/kg/h) or intraduodenal infusion of oleic acid (pH 6.5) in a dose of 0.25 mmol/h. Intravenous administration of SMS 201-995 in three different doses of 100, 200, and 400 ng/kg/h resulted in dose-related inhibition of pancreatic secretion in terms of volume, bicarbonate, and amylase stimulated by exogenous secretin and CCK. Intraduodenal oleic acid stimulated pancreatic secretion, including volume, bicarbonate, and amylase, and this was accompanied by a significant elevation in the plasma concentrations of secretin and CCK. Intravenous administration of SMS 201-995 in the three different doses described above caused dose-dependent suppression of the increase in pancreatic exocrine secretion as well as the plasma concentration of secretin and CCK induced by intraduodenal infusion of oleic acid. It is concluded that SMS 201-995 inhibits pancreatic exocrine secretion and the release of endogenous hormones, such as secretin and CCK, in rats.

Amylases↗

Fecal isoamylase activity in patients with pancreatic diseases.

Fecal isoamylase activity was studied in 93 consecutive patients (26 in the recovery stage of acute pancreatitis, 24 with chronic pancreatitis, 13 with pancreatic cancer, and 30 with other gastrointestinal diseases) and compared with fecal chymotrypsin activity and the results of the secretin test. Seventy-six healthy subjects were studied as controls. Both pancreatic (p)-type and salivary (s)-type isoamylase activities in stool were determined by inhibitor assay as well as cellulose acetate electrophoresis. The mean fecal amylase activity in healthy subjects was 757 +/- 88 IU/g (p-type isoamylase: 77 +/- 2%, s-type isoamylase: 23 +/- 2%). There was a good correlation between fecal p-type isoamylase and chymotrypsin activities (r = 0.625, p less than 0.001). Fecal p-type isoamylase activity in patients with chronic pancreatitis and pancreatic cancer was significantly lower than in healthy subjects (p less than 0.001). Patients with moderate and severe exocrine pancreatic insufficiency as determined by the secretin test had significantly lower fecal p-type isoamylase activity. Daily fat intake did not affect fecal amylase or isoamylase activities. Fecal s-type isoamylase activity in patients with hypoacidity was significantly higher than in patients with hyperacidity, but no difference in fecal p-type isoamylase activity was observed. It is concluded that analysis of fecal isoamylase activity is useful in the assessment of pancreatic function.

Acute Disease↗

Potentiating effect of CCK and secretin on rat exocrine pancreas and its cholinergic dependence.

We investigated whether physiological doses of cholecystokinin (CCK) potentiate the stimulating effect of a physiological dose of secretin on exocrine pancreatic secretion, and the effect of atropine on this potentiating action in rats. Pure pancreatic juice was collected from anesthetized rats prepared by pancreatic duct and bile duct cannulation. Intravenous infusion of CCK-8 in three different doses, 0.03, 0.06, and 0.12 micrograms/kg/h, significantly increased pancreatic juice volume and amylase output, dose-dependently. Simultaneous infusion of CCK-8 in graded doses with secretin in a dose of 0.03 CU/kg/h, produced a dose-related increase in pancreatic secretory response significantly greater than the response to CCK-8 alone (p less than 0.05) and greater than the sum of the response to secretin alone and CCK-8 alone. The incremental pancreatic secretion, including juice volume and amylase output, in response to intravenous infusion of CCK-8 with secretin, was significantly suppressed by intravenous administration of atropine in a dose of 100 micrograms/kg/h (p less than 0.01). Thus, it is concluded that CCK-8 and secretin in physiological doses potentiate each other's stimulatory action on exocrine pancreatic secretion and this potentiating action appears to be cholinergic-dependent.

Amylases↗

Infective endocarditis--analysis of 116 surgically and 26 medically treated patients.

We have reviewed 116 cases of bacterial endocarditis treated surgically and 26 cases treated medically since 1973. There were 123 patients with native valve endocarditis and 19 patients with prosthetic valve endocarditis. Overall, the left-sided valves were infected most frequently. There were 10 cases with right-sided valves involved. Multiple valves were infected in 6 patients. There were 6 perioperative deaths in the surgical group. The most common cause of death was multi-organ failure associated with uncontrollable sepsis. The overall operative mortality for active endocarditis was 7.7% (4/55), and for healed endocarditis, 3.3% (2/61). For active native valve endocarditis, the mortality was 4.2% (2/48), for healed native valve endocarditis, 3.6% (2/55), for active prosthetic valve endocarditis, 28.6% (2/7), and for healed prosthetic valve endocarditis, 0%. There was no difference in the operative mortality between active native valve endocarditis and healed native valve endocarditis. The mortality of active prosthetic valve endocarditis was significantly higher than that of active native valve endocarditis (p less than 0.01). Of the 26 patients treated medically, 7 died during the initial hospitalization. The major factor related to mortality in the medically treated patients was persistent sepsis (four patients), and congestive heart failure (three patients). The overall mortality of the medical group for active valve endocarditis was 15% (3/20), and for active prosthetic valve endocarditis, 67% (4/6). We conclude that patients with infective endocarditis with significant valve lesions who are unresponsive to medical therapy should be considered for urgent surgery.

Aortic Valve↗

Sex difference in the stereoselective metabolism of a new dihydropyridine calcium channel blocker, in rat studies in vivo and in vitro.

1. After oral dosing with a new racemic dihydropyridine calcium channel blocker (I), plasma levels of (+/-)-I, the 3-desisopropyl metabolite (M-2), the pyridine metabolite (M-3) and the 5-desmethyl metabolite (M-10) in female rats were higher than in males, and plasma levels of (+)-I were higher than those of the (-)-enantiomer in both sexes. 2. Plasma levels of M-2 after oral dosing with (-)-I were much higher than those after dosing with (+)-I, in both male and female rats. 3. Stereoselective metabolism of I by rat liver microsomes was shown in the formation of the 3-(2'-hydroxy-1'-methylethyl) ester metabolite (M-1), and metabolites M-2 and M-10. 4. Marked sex differences were seen in the formation of M-1 and M-3 in adult rats (7 weeks of age), but not in immature rats (3 weeks of age). 5. In liver microsomes of rats pretreated with phenobarbital, the formation of M-1 was decreased in adult male rats, and formation of M-2 and M-3 was increased in adult rats of both sexes.

Animals↗

Plaunotol inhibits postprandial gastrin release by its unique secretin-releasing action in humans.

Plaunotol, an acrylic diterpene alcohol, is a new antiulcer agent derived from the "plau-noi" plant and has been reported to stimulate the release of endogenous secretin in humans. We investigated the effect of plaunotol on postprandial gastrin release, comparing it to the effect of exogenous secretin in a physiological dose in eight healthy volunteers. Four sets of experiments were performed in each volunteer: (1) meal alone, (2) meal after intravenous ranitidine (50 mg), (3) meal after oral administration of plaunotol (320 mg) in addition to ranitidine, and (4) meal after ranitidine with simultaneous intravenous infusion of secretin (0.03 CU/kg/hr). The postprandial increase in plasma secretin concentration was significantly reduced by ranitidine, while postprandial gastrin release was markedly exaggerated. Plaunotol in combination with ranitidine significantly increased secretin release and inhibited gastrin release after a meal. Intravenous infusion of secretin resulted in significant suppression of postprandial gastrin release exaggerated by ranitidine. The present study indicates that plaunotol inhibits postprandial gastrin release by its unique secretin-releasing action.

Adult↗

Role of secretin and cholecystokinin in oleic acid-stimulated pancreatic secretion in rats.

We investigated the possible role of endogenous secretin and cholecystokinin (CCK) on oleic acid-stimulated pancreatic exocrine secretion in anesthetized rats. Intraduodenal infusion of oleic acid (pH 6.5) in three different doses (0.06, 0.25 and 1 mmole/hr) resulted in dose-related increases in pancreatic juice volume, bicarbonate and amylase outputs (r = 0.665, 0.736 and 0.517, respectively) (P less than 0.001). Plasma secretin and CCK concentrations also elevated significantly in response to oleic acid, in a dose-related manner (r = 0.721 and 0.546, respectively) (P less than 0.001). There were statistically significant correlations between plasma secretin concentrations and bicarbonate outputs, and between plasma CCK concentrations and amylase outputs in response to oleic acid (P less than 0.01). Potent CCK antagonist, CR 1409 (5 mg/kg.hr) administered intravenously suppressed completely increase in amylase output induced by oleic acid, and partially in juice volume and bicarbonate output. It is concluded that both endogenous secretin and CCK play important roles on oleic acid-induced pancreatic secretion in rats.

Amylases↗

Value of transesophageal color Doppler echocardiography in the evaluation of coronary artery anatomy and blood flow.

The purpose of this study was to test the efficacy of newly developed biplane transesophageal color Doppler and two-dimensional echocardiography in the evaluation of coronary artery anatomy and blood flow. Using these two techniques, high quality images of the entire main left coronary artery (from the left coronary ostium to the bifurcation of the left anterior descending and circumflex coronary arteries), adequate for assessment of luminal diameter and percent stenosis, were obtained in 34 (89%) out of 38 patients. Transesophageal color Doppler echocardiography visualized coronary blood flow in 32 (84%) of the 38 patients. Transesophageal two-dimensional echocardiography clearly showed significant (50% of greater) narrowing of the coronary lumen in 10 out of 12 patients (sensitivity; 83%) and insignificant narrowing or no abnormalities of the coronary lumen in 23 of 26 normal individuals (specificity; 88%). This preliminary study suggests that biplane transesophageal color Doppler and two-dimensional echocardiography are feasible, noninvasive techniques for imaging the main left coronary artery and blood flow.

Adult↗

[Influence of gastric juice on human amylase activity].

Although it is well established that amylase activity is inactivated by acid, little is known about the influence of native gastric juice on amylase activity. We investigated the effect of gastric juice, acid, and pepsin on both pancreatic (P-) and salivary (S-) isoamylase activities in vitro. S- and P-isoamylase activities were completely inactivated by HCl (10 mEq/l), but 20% of each isoamylase activity remained when bovine serum albumin (BSA) (3%) was added. However pepsin (0.2 tyrosine mg/ml/min) inactivated both isoamylase activities even though BSA was added. When saliva or pancreatic juice was mixed with gastric juice, both isoamylase activities were detected until the mixing ratio was 3:7 (gastric juice:saliva or pancreatic juice, v/v). It is suggested that some of both isoamylase activities could survive after exposure to gastric juice in the stomach and duodenum, depending on the concentrations of acid and protein in gastric juice, and mixing ratio to gastric juice.

Amylases↗

Effect of pancreatic juice and trypsin on oleic acid-stimulated pancreatic secretion and plasma secretin in dogs.

We have investigated a negative feedback mechanism in the intestinal phase of pancreatic exocrine secretion in dogs with gastric cannulas and Thomas duodenal cannulas in whom pancreatic juice was collected by cannulation of the main pancreatic duct. Intraduodenal infusion of oleic acid emulsion in a dose of 18 mmol/h resulted in a significant increase in pancreatic secretion of water, bicarbonate, and protein, which was accompanied by increased plasma concentrations of both secretin and cholecystokinin. Infusion of pancreatic juice or bovine trypsin into the duodenum significantly inhibited the oleic acid-stimulated pancreatic secretion. This inhibition coincided with a significant decrease in plasma secretin level, whereas plasma cholecystokinin concentration was not affected by either pancreatic juice or trypsin. Neither pancreatic secretion nor plasma secretin concentration was affected by intraduodenal administration of NaHCO3 solution. The trypsin-induced suppression of pancreatic secretion was prevented by intravenous administration of secretin in a dose that achieved a plasma secretin level comparable to that during the oleic acid administration. This study indicates that a negative feedback mechanism is operative in the intestinal phase of pancreatic exocrine secretion in dogs, and endogenous secretin plays a significant role in the mechanism.

Animals↗

Postprandial plasma gastrin and secretin concentrations after a pancreatoduodenectomy. A comparison between a pylorus-preserving pancreatoduodenectomy and the Whipple procedure.

Based on the observation that patients given a pylorus-preserving pancreatoduodenectomy maintain higher gut hormonal levels than do patients who have received the classic Whipple surgical procedure, which seems most likely due to a postoperative difference in the remaining digestive tract, the postprandial plasma gastrin and secretin concentrations in patients who have received either surgery have been evaluated to examine this difference more fully. The subjects were 20 patients treated by a pylorus-preserving operation and 27 patients treated by the Whipple procedure whose concentrations were compared with those of 8 healthy control patients. The postprandial plasma gastrin concentrations were found to be similar in patients given the pylorus-preserving operation and the controls and were significantly lower in patients who underwent the Whipple procedure (p less than 0.05). Similarly, the postprandial plasma secretin concentrations did not differ in these two groups, whereas patients who underwent the Whipple procedure showed significantly lower concentrations at 60, 90, and 120 minutes (p less than 0.05). The above findings, as well as supportive data in the literature, indicate that the duodenal bulb and the gastric antrum, which are resected in the Whipple procedure and are kept in the pylorus-preserving operation, seem to play important roles in the gut hormonal release and that the pylorus-preserving operation is the superior surgical technique in terms of gastrin and secretin release.

Duodenum↗

Effect of plaunotol on release of plasma secretin and pancreatic exocrine secretion in humans.

Plaunotol, an acyclic diterpene alcohol is a new antiulcer agent derived from the leaves of the plau-noi plant. We investigated the effect of plaunotol on the release of endogenous secretin with radioimmunoassay and exocrine pancreatic secretion, using a dye dilution technique with polyethylene glycol 4,000 as a nonabsorbable marker in eight human volunteers. Intrajejunal administration of plaunotol (pH 6.5) in three different doses (80, 160, and 320 mg/30 min) resulted in significant increases in both plasma secretin concentration and pancreatic bicarbonate secretion in a dose-related manner (r = 0.819 and 0.701, p less than 0.001, respectively). Bicarbonate outputs produced by plaunotol correlated well with plasma secretin concentrations (r = 0.727, p less than 0.001). Amylase output was also increased significantly by plaunotol. However, the response was not dose-dependent from that of bicarbonate output. These results indicate that endogenous secretin is released by plaunotol in humans and suggest that the increased pancreatic bicarbonate secretion can be attributed to the increased plasma secretin concentration.

Adult↗

Effect of fatty acid on secretin release and cholinergic dependence of pancreatic secretion in rats.

We investigated the effects of oleic acid in the duodenum on pancreatic exocrine secretion and plasma secretin, and determined the role of cholinergic dependence on pancreatic secretion and secretin release in response to oleic acid in anesthetized rats. Oleic acid emulsion (pH 6.5) in three different doses of 0.06, 0.25, and 1 mmol/h was infused intraduodenally for 1 h with or without intravenous administration of atropine in a dose of 100 micrograms/kg/h. Intraduodenal administration of oleic acid resulted in significant increases in pancreatic juice volume and bicarbonate output, in a dose-related manner (p less than 0.001). Plasma secretin concentration caused dose-dependent elevation (p less than 0.001) by oleic acid, which correlated very well with bicarbonate output in response to oleic acid (p less than 0.001). Atropine inhibited pancreatic secretion including juice volume and bicarbonate output stimulated by oleic acid in each dose, statistically significantly (p less than 0.05-0.01), but did not affect plasma secretin concentration. Thus, we conclude that oleic acid in the duodenum stimulates pancreatic secretion and endogenous secretin release in rats, and that secretin release is not influenced by the cholinergic tone, although pancreatic secretory response is inhibited significantly.

Animals↗

Effect of CCK antagonists CR 1409 and CR 1505 on rat pancreatic exocrine secretion in vivo.

The action of cholecystokinin (CCK) antagonists CR 1409 and CR 1505 on pancreatic exocrine secretion stimulated by exogenous and endogenous CCK was studied in vivo in anesthetized rats, and compared with proglumide. Intravenous administration of CR 1409 and CR 1505 in graded doses between 0.04 and 25 mg/kg/h resulted in a dose-dependent inhibition in pancreatic juice volume and amylase output stimulated by intravenous infusion of CCK-8 in a dose of 0.06 microgram/kg/h. CR 1409 is 1,000 times and CR 1505 is 267 times more potent than proglumide, based on the ED50 (effective dose for half-maximal inhibition) for CCK-8-stimulated amylase secretion. Intraduodenal administration of casein in a dose of 400 mg/h caused significant increases in plasma CCK concentration and pancreatic secretion of juice volume and outputs of amylase and trypsin. Both CR 1409 and CR 1505 in a dose of 5 mg/kg/h suppressed the increases in pancreatic juice volume and both amylase and trypsin outputs induced by casein given intraduodenally. These results indicate that CCK antagonists including CR 1409, CR 1505, and proglumide inhibit pancreatic exocrine secretion stimulated by not only exogenous, but also endogenous CCK in rats.

Animals↗

Plaunotol stimulates endogenous secretin release and exocrine pancreatic secretion in rats.

The effect of the new antiulcer agent plaunotol on the release of endogenous secretin and the pancreatic exocrine secretion was investigated in anesthetized rats. In 48 rats with pancreatic and biliary diversion, continuous intraduodenal infusion of plaunotol in 3 graded doses (5, 20 and 80 mg/h/rat) resulted in significant increases in both circulating plasma secretin concentration and pancreatic exocrine secretion, including volume and bicarbonate output, in a dose-dependent manner (r = 0.655, p less than 0.001; r = 0.598, p less than 0.001; r = 0.436, p less than 0.01, respectively). The pancreatic bicarbonate output was closely correlated to plasma secretin concentrations (r = 0.631, p less than 0.001). Amylase output also increased after plaunotol administration, but not in a dose-dependent manner (r = 0.092, n.s.). These findings suggest strongly that the increase in pancreatic secretion of fluid and bicarbonate output was mainly due to increased endogenous secretin release resulting from plaunotol administration.

Amylases↗

Study of the structure-activity relationships of new dihydropyridine derivatives.

The effects of structure around the 3- and 5-alkoxycarbonyl groups and the 2-carbamate groups of 4-(2,3-dichlorophenyl)-2-carbamoyloxymethyl dihydropyridine derivatives were investigated, concerning their vasodilating action, plasma level, hypotensive action and acute toxicity. High negative linear correlation was found between the plasma levels and the number of C atoms in esterifying alkyl groups in 3- and 5-positions of the dihydropyridine ring. High plasma levels and effective hypotensive action were found in compounds having lower alkyls as esterifying groups of 3- and 5-carboxyl groups, among 2-unsubstituted derivatives.

Animals↗