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Biomedical subjects

K Takeuchi

Publications and source records attributed to K Takeuchi.

At least 1,117 records · Page 62Linked to original sources
PubMed1986

Importance of gastric motility in the pathogenesis of indomethacin-induced gastric lesions in rats.

Effects of indomethacin on gastric motility and secretion, and levels of endogenous prostaglandins (PGs) were investigated in rats, in attempts to elucidate the factors involved in the pathogenesis of indomethacin-induced macroscopic gastric lesions. Subcutaneous administration of indomethacin had no effect on the gastric mucosa at doses of 1 and 5 mg/kg, but induced visible lesions dose dependently at over 10 mg/kg within 4 hr. At 25 mg/kg, there were apparent nonhemorrhagic lesions within 1 hr, and these lesions became hemorrhagic with time. Acid secretion was not affected by this agent at either dose level, but pepsin or acid-induced HCO3- secretion was significantly increased or decreased, respectively, at a dose less than 5 mg/kg, which did not induce any lesion. Gastric motility, however, was dose dependently increased after administration of indomethacin, and its effect was significant at 10 mg/kg or greater. Time-course changes in the motility were in parallel with those of the lesion formation. PGE2 and 6-keto PGF1 alpha levels in the corpus mucosa were reduced around 80-90% for more than 4 hr from 30 min after administration of 5 mg/kg or more of indomethacin. When all the above changes caused by indomethacin were plotted for the various doses, a significant correlation (r = 0.958, P less than 0.01) was found between the lesion index and the changes in motility, but not in other factors, including PG levels. These results indicate that gastric motility may be an important factor in the pathogenetic mechanism of indomethacin-induced gastric lesions in rats. A deficiency of endogenous PGs may be a prerequisite for later extension of the lesions.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Gastric acid secretion and lesion formation in rats under water-immersion stress.

In attempts to investigate the roles of acid in the pathogenesis of stress-induced gastric lesions, gastric acid secretion was studied in pylorus-ligated and lumen-perfused rats under restraint alone (R) or restraint with additional water immersion (WI). Gastric mucosal blood flow (GMBF) was measured with the aminopyrine clearance method in acute fistula rats. Acid secretion in pylorus-ligated rats significantly decreased under R or WI of either 3.5 or 7 hr stress. In the lumen-perfused or acute-fistula rats, exposure of rats to stress for 7 hr produced a similar decrease; however, in the WI group, there was a significant increase of acid secretion for 3-4 hr during stress, but not exceeding the prestress level. Only in the WI group did GMBF exhibit similar increases to those of acid secretory activity, and these increases were significantly inhibited by intraperitoneal administration of atropine (1 mg/kg) or cimetidine (60 mg/kg). Gastric lesions developed in both groups at 3.5 hr and became extensively severe at 7 hr only in the WI group. Cimetidine failed to influence the formation of lesions at 3.5 hr but significantly inhibited the later outgrowth of lesions at 7 hr, while atropine or pylorus ligation all but completely prevented lesions induced by either 3.5- or 7-hr WI stress. These results indicate that exposure of rats to stress (R or WI) generally decreased acid secretory activity, but there was a rise in acid secretion toward normal levels during WI stress, which may play an important role in the aggravating process of stress-induced gastric lesions.

Animals↗
PubMed1986

Pathogenesis of compound 48/80-induced gastric lesions in rats.

Intraperitoneal administration of 0.75 mg/kg of compound 48/80 (a mast cell degranulator) once daily for four days induced extensive gastric lesions in rats. Oral administration of tripelennamine (histamine H1-receptor antagonist) and cimetidine (histamine H2-receptor antagonist) twice daily for four days had little or no effect on the lesion formation. Oral administration of methysergide and cyproheptadine (serotonin antagonists) and FPL-52694 (a mast cell stabilizer) potently inhibited the compound 48/80-induced lesions. Intraperitoneal administration of histamine plus serotonin, or serotonin alone, induced gastric lesions which resembled those induced by compound 48/80. These lesions were potently inhibited by methysergide and cyproheptadine, but not by tripelennamine, cimetidine, and FPL-52694. Single or repeated administration of compound 48/80 significantly increased serum histamine and serotonin levels. After a single administration of compound 48/80, the increased histamine levels rapidly returned to normal levels, but serotonin levels remained high for 7 hr. Histamine and serotonin levels in the gastric mucosa were transiently increased after a single administration of compound 48/80, but remained normal after repeated administration. Single or repeated administration of compound 48/80 had little effect on arterial blood pressure. The compound 48/80-induced gastric lesions appear to be caused primarily by the release of serotonin, but not histamine, from extragastric sources.

Animals↗
PubMed1986

Mechanisms of protective activity of 16,16-dimethyl PGE2 and acetazolamide on gastric and duodenal lesions in rats.

16,16-Dimethyl PGE2 (16,16-dmPGE2), given orally at 10-30 micrograms/kg, had no effects on gastric acid secretion, or carbonic anhydrase activity, but did increase HCO3- secretion in both the stomach and duodenum of rats. 16,16-dmPGE2, at nonantisecretory doses, potently inhibited indomethacin- and water-immersion stress-induced gastric lesions and mepirizole-induced duodenal lesions in rats. Acetazolamide, given orally at 50 mg/kg, markedly inhibited carbonic anhydrase activity, but had no effects on gastric acid secretion and the basal and 16,16-dmPGE2-stimulated HCO3- secretion. Acetazolamide, at a nonantisecretory dose, had no effects on indomethacin-induced gastric lesions and mepirizole-induced duodenal lesions, but significantly inhibited water-immersion stress-induced gastric lesions. Combined administration of 16,16-dmPGE2 and acetazolamide did not influence the protective activity of 16,16-dmPGE2 on these lesions. The mechanism of the cytoprotective activity of 16,16-dmPGE2 may involve an increase in HCO3- secretion (nonmediated by carbonic anhydrase), while mechanisms involved in the effects of acetazolamide are apparently different.

16,16-Dimethylprostaglandin E2↗
PubMed1986

Determination of acid-neutralizing capacity in rat duodenum. Influences of 16,16-dimethyl prostaglandin E2 and nonsteroidal antiinflammatory drugs.

A model involving measurement of duodenal pH and acid-neutralizing capacity has been devised in anesthetized rats. A duodenal loop was made between the pyloric ring and the area just proximal to the outlet of the common bile duct (2 cm) and was perfused at a flow rate of 1.3 ml/min with HCl solution (1 X 10(-4) M, pH 4.0) made isotonic with NaCl. The pH of duodenal perfusate was continuously measured using a pH glass electrode of the flow type, and the amount of acid neutralized in the loop was titrated to pH 4.0 using a pH-stat method and by adding 10 mM HCl. Under normal conditions, the duodenal pH was kept around 6.0 as the result of neutralization in the loop (approximately 9 mu eq/hr). Subcutaneous administration of 16,16-dmPGE2 (10 micrograms/kg) significantly elevated the pH and increased acid-neutralizing capacity to 168.3% of normal levels. In contrast, indomethacin (5 mg/kg) and aspirin (200 mg/kg) as cyclooxygenase inhibitors or quinacrine (100 mg/kg) as a phospholipase A2 inhibitor significantly decreased both the pH and acid neutralizing capacity. After sacrifice with saturated KCl (intravenously), the pH decreased to 4.3 +/- 0.2 and the neutralizing capacity was reduced to 30% of normal values. Basal HCO3- secretion in the proximal duodenum (approximately 5 mu eq/hr), when titrated to pH 7.4, was significantly stimulated by 16,16-dmPGE2 and exposure of the mucosa for 10 min to 10 mM HCl. Neither indomethacin, aspirin, nor quinacrine had any effect on basal HCO3- secretion, but all significantly inhibited HCl-stimulated HCO3- secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

16,16-Dimethylprostaglandin E2↗
PubMed1986

Induction of duodenal ulcers in rats under water-immersion stress conditions. Influence of stress on gastric acid and duodenal alkaline secretion.

We investigated the influence of stress on gastric acid and duodenal HCO3- secretion in rats, and examined whether duodenal ulcers develop in rats under stress conditions in the absence or presence of acid hypersecretion caused by histamine. Either restraint alone or restraint plus water-immersion stress induced lesions in the stomach but not in the duodenum. However, subcutaneous administration of histamine dihydrochloride (40 mg/kg every 2.5 h for a total of three times) to stressed rats produced macroscopically visible damage in the proximal duodenum as well as in the stomach within 8 h of exposure to stress, and the incidence of duodenal lesions was 100% in the water-immersion group (24.8 +/- 3.8 mm2, n = 8). Histamine alone had no effect on either region. These lesions in the duodenum caused by water immersion plus histamine were prevented by subcutaneously administered cimetidine (30, 100 mg/kg) or 16,16-dimethyl prostaglandin E2 (10, 30 micrograms/kg) in a dose-related manner, but not by atropine (1, 3 mg/kg). Restraint decreased acid secretion by 40%, and additional water immersion restored the decreased acid secretion to normal levels. Basal duodenal HCO3- secretion was decreased to about 70% of normal values (5-6 microEq/15 min) in the restraint group, and after additional water immersion further declined to the values of 1.5-2 microEq/15 min. An increase of HCO3- secretion caused by acid was significantly inhibited by water immersion but not by restraint. Histamine significantly increased acid secretion but did not affect duodenal HCO3- secretion. In the rats treated with both water immersion and histamine, acid secretion was significantly reduced by either cimetidine (100 mg/kg) or 16,16-dimethyl prostaglandin E2 (30 micrograms/kg), whereas duodenal HCO3- secretion was significantly increased by 16,16-dimethyl prostaglandin E2. Atropine had little effect on either acid or HCO3- secretion. These results suggest that exposure of rats to stress decreases duodenal HCO3- secretion and increases the susceptibility of the mucosa to acid emptied from the stomach, thereby inducing duodenal ulcers if acid hypersecretion is concomitantly present.

Animals↗
PubMed1986

A new model of duodenal ulcers induced in rats by indomethacin plus histamine.

We standardized a new method for producing duodenal ulcers in rats by administering indomethacin plus histamine, and investigated the pathogenesis. Indomethacin (5 mg/kg) was first given subcutaneously to rats fasted for 24 h, and subsequently histamine dihydrochloride (40 mg/kg) was given subcutaneously three times, at 2.5-h intervals, beginning 30 min after injection of indomethacin. This combined treatment induced one or two round lesions (9.8 +/- 1.4 mm2) in the proximal duodenum at an incidence of 100%, and a few lesions in the corpus and antrum of the stomach as well. Indomethacin or histamine alone had no effect on either the duodenum or the stomach. The lesions in the duodenum and antrum were inhibited by oral cimetidine (3-100 mg/kg) and 16,16-dimethyl prostaglandin E2 (dmPGE2) (3-30 micrograms/kg) in a dose-related manner, whereas those in the corpus were inhibited only by cimetidine. Indomethacin alone had no effect on gastric acid secretion, but did potentiate the increase of acid secretion caused by histamine. Histamine did not affect duodenal HCO3-secretion, whereas indomethacin slightly inhibited the basal HCO3-secretion and completely blocked the acid-stimulated HCO3-secretion. Intraduodenally administered cimetidine (30 mg/kg) or dmPGE2 (30 micrograms/kg) significantly inhibited acid secretion or increased HCO3-secretion, respectively, and both reduced the amount of acid emptied into the duodenum after treatment with indomethacin plus histamine. These results indicate that the development of duodenal lesions induced by indomethacin plus histamine in rats is due to both an increase in gastric acid secretion and an impairment of acid-induced duodenal HCO3-secretion. This newly established model will be useful for studying the pathogenesis of duodenal ulcers and for screening antiulcer agents.

16,16-Dimethylprostaglandin E2↗
PubMed1986

Three-dimensional CT reconstructions of tongue and airway in adult subjects with obstructive sleep apnea.

The interaction between airway and tongue structures in a sample of 25 adult men with obstructive sleep apnea was quantified on the basis of a series of preoperative CT slices obtained for each subject. Tracings were completed for tongue, and right and left nasal, nasopharynx, oropharynx, and hypopharynx structures; computer graphics were used to obtain superior and lateral three-dimensional reconstructions of all structures for each subject. In addition, cross-sectional areas of specific sites of airway constriction, surface area, volume, and ratio calculations were completed. The majority of the constrictions occurred in the oropharynx (0.52 +/- 0.18 cm2), but six subjects had two constrictions--one in the oropharynx and one in the hypopharynx. The airway had a mean volume of 13.89 +/- 5.33 cm3, whereas tongue volume ranged from 44.03 to 99.56 cm3 with a mean of 71.96 +/- 13.41 cm3. Subjects with more severe obstructive sleep apnea tended to have larger tongue and smaller airway volumes. The more obese subjects showed larger tongue surface areas and smaller airway surface areas. To determine the structural relationships between airway and tongue variables, a series of logarithmic plots was determined. An isometric relationship characterized tongue surface area and tongue volume. A logarithmic plot of oropharyngeal airway vs. tongue volume showed a negative allometric relationship. Tongue volume increased more rapidly than airway volume in subjects with obstructive sleep apnea. Subjects with large tongue volumes were observed to experience significant complications at the time of surgical treatment. Quantification of the volume of the oropharynx and its relationship to tongue volume provide an overview of the interaction between these structures.

Adult↗
PubMed1986

Variations of gastric transmucosal potential difference and lesion formation during hemorrhagic shock in the rat.

We measured transmucosal potential difference (PD) of the stomach in anesthetized rats before, during, and after hemorrhagic shock, and investigated the effects of various drugs on the PD and gastric lesion during this period. After hemorrhagic shock, there was a decrease of PD and an increase of luminal pH in the saline-perfused stomach, the degree of these changes being dependent on a fall in the arterial blood pressure. The graded reduction of PD in response to hemorrhagic shock was similarly observed in the acid-perfused stomach as in the saline-perfused one. However, gastric lesions developed only in the former, and a significant correlation was found between the lesion index and the fall in blood pressure, the reduction in PD, or the concentration of HCl as the perfusate. Subcutaneously administered propantheline bromide (30 mg/kg) or cimetidine (100 mg/kg) had no effect on gastric lesion and PD reduction caused by hemorrhagic shock. These lesions were significantly inhibited by 16,16-dimethyl prostaglandin E2 (10 micrograms/kg) or sulindac (100 mg/kg), a scavenger of OH., and aggravated by indomethacin (1 mg/kg), with less effect on the PD reduction. Intravenous infusion of NaHCO3 (0.5 M) also significantly prevented the lesion with a concomitant suppression of the PD reduction in response to hemorrhagic shock, but these effects were significantly reversed by pretreatment of the animals with acetazolamide (50 mg/kg). These results indicate that during hemorrhagic shock the PD may largely reflect the impairment of mucosal blood flow and may be used as an indicator of mucosal vulnerability to acid, gastric lesions develop only in the presence of exogenous acid, and production of prostaglandins and superoxide radicals may be involved in the pathogenesis of gastric lesions.

Acetazolamide↗
PubMed1986

Effects of ouabain on blood pressure regulation in rats.

In order to test the hypothesis that a circulating inhibitor of the sodium-potassium ATPase pump may cause a concomitant rise in blood pressure and increased sodium excretion, we studied chronic effects of continuous infusion of ouabain, an inhibitor of sodium-potassium ATPase, for up to 6 days on systolic blood pressure and urinary sodium excretion in conscious rats. We also evaluated the effect of this substance in rats with hypertension induced by chronic infusion of norepinephrine. Continuous infusion of ouabain (1.2 mg/kg per day) into the jugular vein by an osmotic minipump did not induce any changes in systolic blood pressure and urinary sodium excretion in intact rats on regular diets. Furthermore it did not cause a change in systolic blood pressure in rats drinking 1% NaCl, and in unilaterally nephrectomized rats drinking 1% NaCl, when compared with vehicle-infused animals. When the same dose of ouabain was administered simultaneously with 1.8 mg/kg per day norepinephrine infused intraperitoneally by another osmotic minipump in conscious rats, systolic blood pressure rose on day 1 to only 129.3 +/- 2.8 mmHg compared with the rist to 145.0 +/- 2.0 mmHg when norepinephrine alone was infused (P less than 0.01). The antihypertensive effect of ouabain was sustained for the entire experimental period lasting for 6 days and was not associated with any changes in urinary sodium excretion. The administration of ouabain to rats made hypertensive by a 3-day infusion of norepinephrine, returned the blood pressure to control levels, and the antihypertensive effect was sustained throughout the experimental period lasting a further 3 days and was not associated with any changes in urinary sodium excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Gilles de la Tourette's syndrome and schizophrenia.

A Gilles de la Tourette's syndrome (TS) patient is described who experienced a schizophrenic episode 11 years after TS onset. Analogies and differences between the two syndromes are reviewed, leading to the conclusion that TS is a definite entity independent from schizophrenia, but that they share some common features of symptomatology and pathophysiology and have closely related anatomical lesions.

Adolescent↗
PubMed1986

Structural analysis of p28 adult T-cell leukaemia-associated antigen.

The 28,000 mol. wt. polypeptide (p28) of adult T-cell leukaemia-associated antigen encoded by the 24S defective human T-cell leukaemia virus (HTLV-I) is associated with protein kinase activity. We have determined the nucleotide sequence of this defective HTLV-I provirus and found that it contains a portion of the gag gene (p19 and part of p24), the pX region, and two long terminal repeats, one at each end. The predicted p28 gag-pX fused protein consists of 190 amino acids and its mol. wt. was calculated as 21,055. The results of peptide mapping analysis showing that p28 contains p19 supported the nucleotide sequence data. That p28 was encoded by this defective provirus was also demonstrated by transient expression of p28 polypeptide in COS 7 cells transfected with a recombinant plasmid containing a simian virus 40 early promoter and the p28-coding region of the 24S HTLV-I.

Adult↗
PubMed1986

camR, a negative regulator locus of the cytochrome P-450cam hydroxylase operon.

A 4.27-kilobase insert from a HindIII DNA library of Pseudomonas putida carrying the CAM plasmid allowed coordinate expression of genes camD and camC under control of camR, an upstream regulator. The camC gene specifies cytochrome P-450cam, and camD specifies the 5-exo-alcohol dehydrogenase. A 1.38-kilobase deletion from the insert results in the constitutive expression of genes camC and camD; transformation in trans restores the substrate control, indicating that camR is a negative regulator.

Alcohol Dehydrogenase↗
PubMed1986

Endogenous prostaglandins in gastric alkaline response in the rat stomach after damage.

A role of endogenous prostaglandins in gastric alkaline response (an increase of luminal pH) and functional recovery was investigated in the rat stomach after damage with acidified taurocholate (TC, 20 mM) or aspirin (ASA, 40 mM). Exposure of the stomach to TC or ASA similarly produced a transmucosal potential difference (PD) reduction and enhancement of H+ backdiffusion. The PD was restored gradually with time, and this process was much faster in the case of TC compared with ASA. After exposure to TC, acid secretion ceased and bicarbonate (0.5-1 mu eq/10 min) appeared in the lumen, whereas acid secretion persisted in the stomach exposed to ASA. However, in the presence of cimetidine (8 mg . kg-1 . h-1), these two agents produced a similar degree of luminal alkalinization (approximately 1 mu eq/10 min of HCO3-). Pretreatment with indomethacin (5 mg/kg, sc) significantly inhibited luminal alkalinization and PD recovery seen after exposure to TC. Concurrent administration of 16,16-dimethyl prostaglandin E2 (3 micrograms/kg, sc) antagonized the effects of indomethacin in stomachs exposed to TC and also unmasked luminal alkalinization and expedited the PD recovery in stomachs exposed to ASA. The levels of PGE2 and 6-keto-PGF1 alpha in the corpus mucosa were significantly increased in stomachs exposed to TC, but decreased in those exposed to ASA. These results indicate that luminal alkalinization of the stomach after damage with TC results from both an inhibition of acid secretion caused by endogenous prostaglandins and an increased appearance of HCO-3, and may play a role in functional recovery of the damaged mucosa. Gastric alkalinization seems to be a common phenomenon after exposure to mucosal damaging agents unless they have an inhibitory effect on prostaglandin biosynthesis.

16,16-Dimethylprostaglandin E2↗
PubMed1986

Mechanisms of irritative activity of compound 48/80 on rat gastric mucosa.

A single intraperitoneal injection of compound 48/80 (48/80) (0.5-3 mg/kg) into anesthetized rats caused a dose-dependent reduction of the transmucosal potential difference (PD) and intraluminal pH (pH), and induced gastric lesions within 2 h. These same changes were seen with an intraperitoneal injection of histamine, but not with serotonin. There was a significant correlation between the lesion index and the PD reduction, although the integrity of the resting gastric mucosal barrier remained unaltered. The PD reduction caused by 48/80 was dose-dependently inhibited by tripelennamine (H1-antagonist) and FPL-52694 (mast cell stabilizer) and partially suppressed by methysergide (serotonin antagonist), but the changes in pH were prevented by FPL-52694 and cimetidine (H2-antagonist). The reduction of PD and pH induced by histamine was inhibited by tripelennamine or cimetidine, respectively, but these responses were not inhibited by FPL-52694 or methysergide. Gastric lesions induced by 48/80 were potently inhibited by tripelennamine and FPL-52694, and partially by cimetidine, whereas those induced by histamine were significantly prevented by tripelennamine and cimetidine, but not by FPL-52694. Methysergide had no effect on the development of gastric lesions in response to 48/80 or histamine. These results suggest that a single injection of 48/80 reduced the PD and stimulated acid secretion, thereby producing gastric lesions. These effects of 48/80 may be due to activation of H1- and H2-receptors by acutely released endogenous histamine.

Animals↗
PubMed1986

Effect of cell proliferation on healing of gastric and duodenal ulcers in rats.

The healing of acetic acid-induced gastric and duodenal ulcers was examined together with the biochemical indices of growth in gastric and duodenal mucosa in the following three groups of rats: (a) chow-fed, (b) fed an isocaloric liquid diet, (c) fed the liquid diet plus pentagastrin injections (250 micrograms/kg, 3 times/day). Animals received the diet regimen for 10 days from 1 day after induction of ulcer (day 0). Following the feeding regimens, serum gastrin levels, oxyntic gland mucosal DNA synthesis, and gastric secretory function were significantly lowered in the rats fed liquid diets. DNA synthesis in the duodenal mucosa was not different from the pre-ulcer levels. Pentagastrin significantly restored the DNA synthetic and gastric secretory activity of the liquid diet-fed rats toward the levels in the chow-fed group. In the latter group, a significant increase in DNA synthesis and levels of serum gastrin was found at day 6 (after 5 days feeding), which corresponded with a rapid, spontaneous healing of ulcers. Feeding rats liquid diet significantly delayed the healing of gastric, but not duodenal ulcers. Repeated administration of pentagastrin accelerated gastric ulcer healing in the liquid diet group toward the rate observed in the chow-fed group, but had no effect on the healing of duodenal ulcers. These results indicate that cell proliferation is an important factor in the healing of gastric ulcers.

Animals↗