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Biomedical subjects

S Okabe

Publications and source records attributed to S Okabe.

At least 343 records · Page 19Linked to original sources

Occurrence of vestibular and facial nerve injury following cerebellopontine angle operations.

To elucidate how surgery in the cerebellopontine (CP) angle may cause vestibular and facial nerve injury, the 7th and 8th cranial nerves of dogs were manipulated as in human surgery along with monitoring of auditory evoked brain stem responses. Postoperatively, histological examinations were performed to investigate the effect of the surgical manipulations. We found that the occurrence of vestibular, facial and cochlear nerve injury was dependent on the direction of the excessive movement of the nerves in the cerebellopontine (CP) angle. Caudal-to-rostral shift of the nerve trunk most effectively avulsed the vestibular nerve. Haemorrhages were revealed between the vestibular ganglion and the fundus of the internal auditory canal. This caudal-to-rostral retraction could also damage the facial nerve in its intrapetrous labyrinthine portion. This was likely to be one of the pathophysiological mechanisms responsible for postoperative facial nerve palsy occasionally observed in human cases. Rostral-to-caudal retraction of the cerebellum damaged the cochlear nerve selectively. Although caudal-to-rostral retraction, instead of lateral-to-medial one, has been recommended to protect the cochlear nerve, this retraction was shown to be dangerous to the vestibular nerve if excessive. The clinical significance of the fragility of the vestibular nerve was discussed and the importance of preserving the vestibular nerve function is stressed.

Animals↗

Different effects of cytoprotective drugs on ethanol- and aspirin-induced gastric mucosal injury in pylorus-ligated rats.

In anesthetized rats oral administration (2 ml) of both ethanol (50% in 150 mM HCl) and aspirin (80 mM in 150 mM HCl) produced bandlike lesions in the stomach, while more generalized lesions occurred in the pylorus-ligated stomach when the irritant was given intragastrically through the fistula prepared in the rumen and the mucosal folds were removed by stomach distension. The bandlike lesions induced in the intact stomach by both irritants were significantly and dose-dependently prevented by 16,16-dimethyl PGE2 (dmPGE2: 3 and 10 micrograms/kg, subcutaneously), cysteamine (30 and 100 mg/kg, subcutaneously) or timoprazole (10 and 30 mg/kg, per os) at the doses which significantly inhibited gastric motility. In the pylorus-ligated stomach, however, neither of these agents showed any protection against the generalized lesions induced by ethanol, but such lesions caused by aspirin were significantly prevented only by dmPGE2. These agents also showed similar effects against the reduction of transmucosal PD in the pylorus-ligated stomach exposed to ethanol and aspirin. These results suggest that (1) the formation of bandlike lesions caused by ethanol and aspirin depends on the presence of mucosal folds and may be prevented by the agents that inhibit gastric motility, (2) the pathogenesis of the lesions induced by aspirin and ethanol may be different in the pylorus-ligated stomach, and (3) dmPGE2 has a unique protective ability that is not shared by usual cytoprotective agents.

16,16-Dimethylprostaglandin E2↗

Body temperature-dependent action of baclofen in rat stomach. Relation to acid secretion and ulcerogenicity.

The effect of baclofen (PCPGABA) on acid secretion, motility, and mucosa was investigated in the anesthetized rat stomach under various body temperatures (BT: 28-38 degrees C), and they were compared with those of 2-deoxy-D-glucose (2DG), an acid stimulant through cytoglycopenia. Under these conditions PCPGABA induces lesions dose-dependently (greater than 1 mg/kg, subcutaneously) in both the stomach and duodenum, and this action was dependent on BT; lowering of BT enhanced the ulcerogenicity. PCPGABA (3 mg/kg) had no effect on acid secretion at higher BT (36-38 degrees C) but produced a marked increase of acid output at lower BT (30-32 degrees C). 2DG caused a stimulation of acid output and gastric lesions without BT dependency, but the duodenal ulcerogenicity enhanced at lower BT. Gastric motility was enhanced significantly by these two agents to similar degrees, at either high or low BT. Neither PCPGABA nor 2DG affected alkaline secretion in the duodenum, while lowering of BT by itself reduced alkaline secretory responses. The above changes caused by PCPGABA and 2DG were blocked by both atropine and vagotomy. These results suggest that (1) acid stimulatory and ulcerogenic action of PCPGABA may involve a temperature-dependent process but does not relate to a cytoglycopenia, and (2) the vagus nerve mediating acid secretion and motility may be different in the temperature dependency.

Animals↗

Possible mechanisms involved in gastric hypermotility caused by indomethacin in the rat. Role of glycoprivic response.

Pathogenesis of indomethacin-induced gastric lesions was investigated in the rat by measuring lesions, gastric motility, and terminal blood glucose levels and correlating them with each other. Subcutaneously administered indomethacin (3-25 mg/kg) dose-dependently produced lesions in the stomach with concomitant gastric hypermotility and reduction of blood glucose levels. When the lesion score and the motility were plotted against terminal glucose levels, a highly significant relationship was found among these three factors (P less than 0.01). Gastric lesions and hypermotility induced by indomethacin (25 mg/kg) were suppressed significantly by 16,16-dmPGE2 (10 micrograms/kg) with no effect on the glucose levels, while intravenous infusion of glucose (25% w/w, 1.4 ml/hr) prevented these responses and restored the reduced glucose levels above the basal values. In addition, both 16,16-dmPGE2 and glucose infusion afforded a significant protection against gastric lesions induced by indomethacin even in the acid-perfused stomach (150 mM HCl). These results confirmed gastric hypermotility as a key element in the pathogenesis of indomethacin-induced lesions and further suggested that indomethacin may sensitive gastric contractility through glycoprivic receptors by inducing hypoglycemia and PG deficiency.

16,16-Dimethylprostaglandin E2↗

Determination of gastroduodenal alkaline responses in the rat.

We set up a new system for measuring the gastroduodenal HCO3- responses using pH change and potential difference (PD) in the anesthetized rat. The stomach or the proximal duodenum was perfused at the flow rate of 0.7 mL/min with saline (pH 4.5), the pH of the perfusate and PD were continuously monitored, and HCO3- output was determined by back-titrating the perfusate and by measuring the area of pH change. In the case of the stomach, acid secretion was inhibited by omeprazole (60 mg/kg, i.p.). Output of both pH and HCO3- in these tissues was significantly increased by intravenous administration of prostaglandin (PGE2), 16, 16-dimethyl PGE2, carbachol, and YM-14673 (a thyrotropin-releasing hormone (TRH) analog), whereas the PD responded to these agents by a significant rise in the duodenum and decrease in the stomach. These parameters also responded to physiological stimulation such as mucosal acidification. When the area of pH change caused by various agents was plotted against the net amount of HCO3- output determined from back-titration, a significant relationship was found between these two factors (r = 0.98). These results indicate that this system using pH change may be useful for quantitative determination of HCO3- response in the gastroduodenal mucosa.

Animals↗

Role of accumulated gastric content in the pathogenesis of cysteamine- and mepirizole-induced duodenal ulcers in the rat.

Subcutaneous administration of cysteamine and mepirizole (at ulcerogenic and non- or weakly ulcerogenic doses) to fasted rats induced villous damage to the duodenum within 4 h. Only the damage induced by ulcerogenic doses progressed to macroscopically visible ulcers 10-12 h later. A considerable increase in gastric content was observed for more than 6-8 h after administration of the ulcerogenic dose of agents, but normal contents were noted 12 h later. The intraduodenal pH remained low for up to 16-20 h when ulcerogenic doses were given, but returned to control levels within 8-12 h when non-ulcerogenic doses were given. Histamine similarly caused villous damage to the duodenum, yet there was no progression to an ulcer. Accumulation of gastric contents and a lower intraduodenal pH with histamine persisted for only 2 h and 1 h, respectively. We conclude that prolonged accumulation of gastric contents for up to 8 h together with a decreased lower intraduodenal pH for 16-20 h are necessary for the developmental progression of villous damage to well-defined ulcers in the presence of ulcerogens.

Acid-Base Imbalance↗

The assessment of intelligence function of aged chronic schizophrenia.

The evaluation of intelligence function is required for the aged chronic schizophrenic patients under the circumstance such as long-term hospitalization. However, there have been only a few reports on the degree and quality of intelligence dysfunction in aged chronic schizophrenic patients. In the present study, using Okabe's simplified intelligence evaluation measure and GBS (Gottfries, Brane and Steen) scale, the assessment of intelligence function was examined in aged chronic schizophrenic patients hospitalized for more than 15 years. Concerning the results, in the aged schizophrenic patients, mental functions such as concentration are markedly reduced, but short-term memory is relatively well maintained. Although nearly half of them are compatible at home or to society, many problems remain to be considered on their return to society.

Aged↗

Effects of TY-10957, a stable PGI2 derivative, on gastroduodenal lesions and secretory responses in the rat.

The effects of TY-10957, a stable PGI2 derivative, on gastroduodenal lesions and secretory responses were examined in rats and compared with those of ornoprostil, a PGE1 derivative. Orally administered TY-10957 dose dependently prevented gastric lesions induced by ethanol/HC1 (60% ethanol in 150 mM HCl) and duodenal ulcers induced by mepirizole (200 mg/kg); a significant effect was obtained at 3 micrograms/kg or greater in the former and at 300 micrograms/kg in the latter. Intraduodenally administered TY-10957 had minimal effects on gastric acid secretion, and at the highest dose (300 micrograms/kg) both the basal acid output and that stimulated by histamine (20 mg/kg) were significantly reduced by about 40%. TY-10957 (30-300 micrograms/kg s.c.) produced a marked increase of alkaline secretion in both stomach and duodenum of anesthetized rats, and these effects were significant at 30 micrograms/kg in the stomach and at 100 micrograms/kg in the duodenum. On the other hand, ornoprostil produced a potent and significant inhibition against ethanol/HCl-induced lesions (greater than 1 microgram/kg), but had no effect on mepirizole-induced duodenal ulcers. This PGE1 derivative had no influence on both basal and stimulated acid secretion and did not significantly affect alkaline secretion even at 100 micrograms/kg. These results suggest that TY-10957 has a protective action on both gastric and duodenal mucosa. The mechanism of duodenal antiulcer effect may involve both inhibition of acid and stimulation of alkaline secretion, while the gastroprotective action of this agent may be attributed to other factors.

Alprostadil↗

[Effects of IT-066, a new histamine H2-receptor antagonist, on gastric acid secretion and experimental gastric ulcers in rats and dogs].

We examined the effects of a new histamine H2-receptor antagonist, 3-amino-4-(4-[4-(1-piperidinomethyl)-2-pyridyloxy]-cis-2- butenylamino)-3- cyclobutene-1,2-dione hydrochloride (IT-066), on gastric acid secretion and the healing process of experimental ulcers in rats and dogs. Famotidine, a well-established H2-receptor antagonist, was used as the reference drug. Male Donryu rats (240-260 g) and Beagle dogs of both sexes (8-10 kg), having Heidenhain pouches, were used. IT-066 dose-dependently inhibited the basal gastric acid secretion of rats, and this inhibition significantly persisted for 12 hr. In addition, the agent significantly inhibited histamine-stimulated acid secretion in both normal rats and rats with acetic acid ulcers. IT-066, given p.o. twice daily for 2 and 3 weeks after ulceration, significantly accelerated both spontaneous and delayed healing (with indomethacin) of acetic acid-induced gastric ulcers in rats. The effects of IT-066 on acid secretion and ulcer healing were almost the same or slightly more potent than those observed with famotidine. IT-066, when given i.v. or p.o., dose-dependently inhibited the gastric acid secretion stimulated by histamine, pentagastrin, or carbachol in dogs. The antisecretory effects of the agent on histamine-stimulated acid secretion significantly persisted for more than 6 hr. These results indicate that IT-066 appears to be a promising antisecretory and anti-ulcer agent.

Acetates↗

[Studies on anti-ulcer effects of a new compound, zinc L-carnosine (Z-103)].

We investigated the anti-ulcer effects of zinc L-carnosine (Z-103) using several acute experimental models of gastric and duodenal lesions in rats. Effects of Z-103 on various gastric functions, e.g., antacid (in vitro), anti-pepsin (in vitro), gastric secretion, mucosal potential difference (PD) and mucus contents were also examined. Z-103 given orally prevented development of gastric lesions induced by water immersion stress, histamine, HCl-aspirin, HCl-ethanol and also duodenal ulcers induced by mepirizole in a dose-dependent manner. In vitro, Z-103 had a greater antacid effect than sodium bicarbonate; and moreover, the potency of its anti-peptic action (IC50 = 8.7 mM) was higher than those of several other drugs (sodium bicarbonate, sucrose sulfate and aceglutamide aluminum). Intragastric treatment of Z-103 (100 mg/kg alone tended to increase PD, and it also significantly inhibited the decrease in PD induced by aspirin. In addition, pretreatment with Z-103 at 10 and 30 mg/kg (p.o.) significantly prevented the decrease in mucus contents in the gastric mucosa and also mucosal lesions by oral administration of ethanol. On the other hand, Z-103 was not so effective on both basal (pylorus-ligation preparation) and histamine-stimulated gastric secretion (Heidenhain pouch preparation). These results suggest that Z-103 is useful for the treatment of gastric and duodenal ulcers in humans.

Animals↗

Effects of orally administered human epidermal growth factor on natural and delayed healing of acetic acid-induced gastric ulcers in rats.

We examined the effects of orally administered human epidermal growth factor (hEGF) on healing of acetic acid-induced gastric ulcers in rats. hEGF, given twice daily at 30 and 100 micrograms/kg for 2 weeks or at 100 micrograms/kg for 4 weeks to rats with ulcers, had no effect on natural healing or the gastric secretion, delayed one caused by indomethacin. Oral hEGF had no effect on basal histamine-stimulated gastric secretion, and stomach weight. These results indicate that oral hEGF has no biological activity on the pathophysiology of the stomach.

Acetates↗

Determination of bicarbonate output using pH deflection in the rat duodenum: influences of prostaglandins and cholinergic agents.

We set up a system to measure the luminal pH, potential difference (PD) and bicarbonate output in the anesthetized rat duodenum, and investigated these responses caused by prostaglandins (PGs) and cholinergic agents. When the proximal duodenum (1.7 cm) was perfused at a flow rate of 0.7 ml/min with saline adjusted to pH 4.5, the duodenal pH, PD and HCO3- output were 5.5 to 6.0, -4 to -6 mV and 1.2 to 1.6 muEq/10 min, respectively; they were markedly reduced by i.v. injection of saturated KCl. Both natural (PGE1, PGE2) and synthetic (PGE2, PGl2) PGs, given either s.c. or i.v., significantly elevated all these parameters, while indomethacin (s.c.) decreased the pH as well as the PD. Small but significant increases of the pH were observed after i.v. administration of cholinergic agents (carbachol, bethanechol), a GABAergic agent (baclofen) and an analogue of thyrotropin releasing hormone (YM-14673), with a temporal elevation of the PD; the degree of net HCO3- output caused by these agents was 20-50% of the values obtained with PGE2 (100 micrograms/kg, i.v.), and they were significantly reduced in the presence of atropine. These results suggest that (a) the system using pH deflections can be used to sensitively detect HCO3- output in the rat duodenum, and (b) duodenal acid neutralizing capacity may be regulated by central and peripheral cholinergic systems as well as endogenous PGs.

Alprostadil↗

Effects of KB-5492, 1-(3,4,5-trimethoxybenzyl)-4-((4-methoxyphenyl)oxycarbonylmethyl) p iperazine monofumarate monohydrate, on gastric lesions and gastric secretion in rats.

Effects of a newly synthesized compound, KB-5492, on gastric lesions and gastric secretion were studied in rats. Oral KB-5492 inhibited the lesions induced by HCl.ethanol, HCl.aspirin, water-immersion stress, indomethacin, histamine and prednisolone at 30-300 mg/kg. The ED50 values varied from about 35 to 98 mg/kg. KB-5492 had no effect on gastric acid secretion even at 300 mg/kg. KB-5492 appeared to have a much more potent protective effect than a known anti-ulcer drug, sofalcone, against acute gastric lesions.

Animals↗

Stimulation by prostaglandin E2 of alkaline secretion in the rat duodenum: comparative study with hypertonic NaCl.

Possible involvement of increased mucosal permeability in the stimulation by prostaglandin E2 (PGE2) of duodenal HCO3- secretion was investigated in rats. PGE2 (0.3, 1 mg/kg, s.c.) dose-dependently increased HCO3- secretion in the duodenum with a significant elevation of transmucosal potential difference (PD); the PD was increased from -4.5 +/- 0.3 mV to -10.0 +/- 1.5 mV (mucosa negative) at 1 mg/kg. These responses caused by PGE2 were abolished by sacrificing the animals with saturated KCl (i.v.). Although a significant increase of HCO3- output was observed after exposure of the mucosa to 1 M NaCl (0.5 ml), this response was accompanied by a significant reduction of PD and was not abolished after KCl injection. The mucosal permeability determined by Evans blue (1%, i.v.) was not affected by PGE2, while 1 M NaCl markedly elevated the amount of extravasated dye in both the luminal content and the mucosa. Stimulation of HCO3- output by PGE2 was significantly mitigated by ouabain (3 mg/kg, s.c.) or prior exposure of the mucosa to 1 M NaCl. These results suggest that stimulation by PGE2 of duodenal HCO3- secretion is not simply due to the increased mucosal permeability, but depends rather on both the Na/K ATPase activity and the intact perfusion of the organ. The HCO3- response as induced by 1 M NaCl may result from the increased permeability and is accompanied by a marked reduction of PD.

Animals↗

Effects of topical application of KT1-32 on transmucosal potential difference and acid secretion in the rat stomach.

Effects of intragastric application of azuletil sodium (KT1-32), a novel antiulcer drug, on transmucosal potential difference (PD) and acid secretion were investigated in the rat stomach. The stomach was mounted on a Lucite chamber and perfused with saline before and after exposure to KT1-32 for 10 min. KT1-32 (3-30 mg/kg) produced an elevation of PD in a dose-dependent manner with a rise of the luminal pH. The increased PD response caused by KT1-32 (10 mg/kg) persisted after removal of the agent from the stomach, but this PD generating effect was significantly mitigated by pretreatment with omeprazole (60 mg/kg, i.p.). KT1-32 raised PD under basal conditions, but did not significantly affect the reduced PD response caused by 30% ethanol. In addition, topical application of KT1-32 significantly reduced acid secretion caused by histamine (4 mg/kg/hr, i.v.) and carbachol (20 micrograms/kg/hr, i.v.). In the in vitro study, KT1-32 at 3.9 x 10(-4) M showed 50% inhibition of the H/K ATPase activity prepared from the hog gastric mucosa. These results suggest that KT1-32 exerts locally antisecretory and PD generating effects. The latter may be accounted for by the antisecretory action, which is probably related to the H/K ATPase inhibition.

Administration, Topical↗

Effects of a crude extract of a marine dinoflagellate, containing dimethyl-beta-propiothetin, on HCl.ethanol-induced gastric lesions and gastric secretion in rats.

A crude extract of Crypthecodinium cohnii and its main component, dimethyl-beta-propiothetin, significantly and dose-dependently protected the gastric mucosa against HCl.ethanol-induced lesions in rats. Since indomethacin pretreatment reduced the protective effect to some extent, endogenous prostaglandins might be partly involved in the mechanism of action. Both the crude extract and dimethyl-beta-propiothetin significantly increased gastric secretion.

Animals↗

Effect of omeprazole on delayed healing of acetic acid-induced gastric ulcers in rats.

Omeprazole, a gastric mucosal proton pump inhibitor, significantly and dose-dependently prevented the delayed healing of acetic acid-induced gastric ulcers in response to repeatedly administered indomethacin to rats. Both basal and histamine-stimulated gastric acid secretions in rats with acetic acid-induced ulcers that were given indomethacin were markedly and persistently (greater than 24 hr) inhibited after 4 weeks treatment with omeprazole. The prevention of delayed ulcer healing by omeprazole appears to be due to its long-lasting antisecretory activity.

Acetates↗

Distinguishing normal and abnormal tracheal breathing sounds by principal component analysis.

Expired and inspired tracheal breathing sounds (BS) were recorded from 10 normal subjects and 8 patients with respiratory diseases, including bronchial asthma, sarcoidosis, fibrosing lung disease, chronic bronchitis, and radiation pneumonitis. Frequency spectra were generated using Fast Fourier Transform (FFT), and we observed considerable differences between BS spectra of normal subjects and patients. The frequency of peak amplitude and mean frequency of the BS spectra of patients were significantly higher than those of normal subjects. Spectral features were extracted by dividing each spectra into equal frequency bands--each feature being the mean amplitude of each FFT element within a frequency band. We used Principal Component Analysis to compare spectral feature sets and found a clear separation between normal and abnormal tracheal BS for 10, 20, and 40 features/spectra. We conclude that Principal Component Analysis of BS could become a new method of diagnosing respiratory disease in an automated fashion.

Adult↗