Biomedical subjects

K Shuto

Publications and source records attributed to K Shuto.

At least 37 records · Page 2Linked to original sources

PubMed1996

A new sealing device (Sandwich-disc) for rapid recreation of pneumoperitoneum during laparoscopic assisted surgery.

We have developed a new device which enables rapid sealing of a minilaparotomy during laparoscopic assisted surgery to recreate an airtight condition. This device consists of a center rod and two discs (7 cm in diameter) which form an airtight condition by compressing the inner and outer surfaces of the abdominal wall. Advanced laparoscopic procedures requiring both pneumoperitoneum and minilaparotomy are facilitated with the use of this device. This new device is called the Sandwich-disc: Takasago Medical Industry Co., Ltd.

Colonic Neoplasms↗

PubMed1996

Changes in nasal cavity volume and target area of exposure to nasal drops with age in rats.

The changes in the nasal cavity volume of rats with age and the area exposed to nasal drops administered into the nasal cavity were investigated. Results indicated that the nasal cavity volume lineally increased as rats grew older. In 7-week-old rats, the exposed area in the case of an administration volume of 25 microliters, based on practice, was naso-, maxillo-, and ethmoid turbinate and this volume was enough to expose the whole area of the nasal cavity including the ethmoid turbinate. On the other hand, in 27-week-old rats, administration volumes of 10 and 25 microliters were not enough to expose the ethmoid turbinate. This indicated that the exposed area tended to become narrower in 27-week-old rats than in 7-week-old rats, but the exposed area in the case of an administration volume of 50 microliters was naso-, maxillo-, and ethmoid turbinate in 27-week-old rats. In this case, the volume was enough to spread to the ethmoid turbinate. Differences in the exposed area might be caused by differences in the volume of the nasal cavity. It was also indicated that the main exposed area was the inferior meatus in the 30 min immediately after administration. At all administration volumes, however, notice should be taken of the outflow of nasal drops into the oral cavity through the nasopalatine.

Administration, Intranasal↗

PubMed1996

A possible mechanism of increase in serum alkaline phosphatase activity in rats given granulocyte colony-stimulating factor.

Recombinant human granulocyte colony-stimulating factor (G-CSF) at a dose of 1 to 300 micrograms/kg/day was administered intravenously to rats daily for 13 weeks. Serum alkaline phosphatase (ALP) activity increased dose-dependently with leukocytosis. Most of the increased leukocytes were segmented neutrophils, and neutrophil alkaline phosphatase (NAP) scores were elevated markedly. Serum ALP activity correlated very well with the segmented neutrophil counts, and the coefficient of correlation was more than 0.97 in both sexes. Pathological examinations revealed splenomegaly and a marked increase in neutrophils in the red pulp of the spleen. In the spleen, phagocytosis of neutrophils by macrophages was observed. These data indicate that the increased ALP was of neutrophil origin. Serum ALP activity may be increased by the direct release of ALP from the high number of neutrophils into the blood, or by the leakage of ALP into the blood mainly from the spleen where many neutrophils are pooled and destroyed by the macrophage system.

Alkaline Phosphatase↗

PubMed1996

Laparoscopic splenectomy.

Laparoscopic splenectomy was carried out for the treatment of patients with splenic disorders; 20 idiopathic thrombocytopenic purpura, 1 hamartoma and 3 hereditary spherocytosis. With the patients in the right lateral position, four trocars were used. Under CO2 pneumoperitoneum with a pressure of 10 mmHg, the surrounding ligaments were divided with electrocautery. At the splenic hilum, the splenic artery and vein were exposed using ultrasonic dissector. After double ligation of these vessels, the spleen was dissected with an autostapler. The resected spleen contained in a nylon bag was fragmented with finger-fracture method and extracted through a port site extended up 2 or 3 cm in length. All the patients tolerated the procedure and no blood transfusion was required. Laparoscopic splenectomy is the preferred choice to resect the spleen because of the short hospital stay, less pain and good cosmesis.

Adolescent↗

PubMed1995

Hemodynamic and arterial blood gas changes during carbon dioxide and helium pneumoperitoneum in pigs.

The effects of pneumoperitoneum with carbon dioxide and helium on systemic hemodynamics and arterial blood gases were investigated in pigs in an attempt to clarify the mechanisms by which pneumoperitoneum may induce organ dysfunction. A total of 16 anesthetized female pigs underwent pneumoperitoneum with carbon dioxide or helium (n = 8 each) in a stepwise fashion to intraabdominal pressures of 8, 10, 12, 16, and 20 mmHg. Changes in cardiac output; renal and hepatic blood flow; mean arterial, mean pulmonary arterial, mean pulmonary arterial wedge, inferior vena caval, and portal venous pressures; and total peripheral resistance were measured. Arterial blood samples were obtained at the same time the above parameters were determined. Urine volume was measured as an indicator of renal function. Pneumoperitoneum with either carbon dioxide or helium significantly increased venous pressures and simultaneously decreased cardiac output. These changes were associated with decreases in organ blood flow due to increased peripheral resistance. Urinary output was reduced to a similar degree in the two groups. Blood gas analysis revealed pneumoperitoneum-induced metabolic acidosis in both groups, although hypercapnia was observed only in the carbon dioxide group. These findings suggest that pneumoperitoneum-related organ dysfunction may be due to increased intraperitoneal pressure rather than to hypercapnia.

Acidosis↗

PubMed1995

The role of glucagon in the gastric hyperdynamic circulation of cirrhotic portal hypertensive rats.

The role of glucagon as a mediator of gastric hyperdynamic circulation, induced by carbon tetrachloride (CCl4), was assessed in cirrhotic rats. A selective elimination of pancreatic glucagon from the circulation was achieved by the intravenous infusion of a glucagon antiserum. Gastric blood flow was measured by laser-Doppler flowmetry. The glucagon antiserum had no effect on the blood flow in the stomach in control rats, while in cirrhotic portal hypertensive rats, the glucagon antiserum significantly reduced gastric blood flow (30%). The glucagon antiserum did not completely exclude the gastric hyperdynamic state in the cirrhotic rats. It would thus appear that glucagon contributes to a portion of the gastric hyperdynamic circulation associated with cirrhotic portal hypertension.

Animals↗

PubMed1995

Synthesis of 2-imidazolidinylidene propanedinitrile derivatives as stimulators of gastrointestinal motility--III.

Recently, we reported that a ranitidine derivative 2 (fumarate: KW-5092), which had a 2-imidazolidinylidene propanedinitrile moiety (A), showed potent gastrointestinal motility enhancing activity. We have also found that introduction of substituents such as benzyl or 4-fluorobenzyl (i.e., giving 3 or 4) at the N-3 position of the moiety (A) significantly increased this activity. In this study, novel 2-imidazolidinylidene propanedinitrile derivatives possessing a thioether 5-15 were prepared and evaluated for in vitro assays; acetylcholinesterase (AChE) inhibitory activity and potentiating action on electrically induced contractions of guinea pig ileum. Compound 5, in which a nitrogen atom of compound 2 was replaced by a sulfur atom, was more potent than 2 in these tests. Also, in a series of thioether derivatives, introduction of substituents at the N-3 position of the 2-imidazolidinylidene propanedinitrile moiety markedly influenced both activities. In particular, compounds 12 and 13, which showed an excellent potency during in vitro study (AChE IC50 = 3.6 and 2.7 nM; ES. EC30 = 2.1 and 2.5 nM, respectively), were found to be more active in the enhancement of gastrointestinal motility in anesthetized rabbits than their corresponding parent compounds 3 and 4, respectively. In addition, compounds 12 and 13 showed lower affinity for the histamine H2-receptor than ranitidine. Therefore, these compounds may be potent and selective stimulators of gastrointestinal motility.

Acetylcholinesterase↗

PubMed1995

Laparoscopic approaches in the management of patients with early gastric carcinomas.

In eight Japanese patients, three different laparoscopic procedures were used to excise an early gastric carcinoma; partial resection in four, intragastric resection of the gastric mucosa in two, and laparoscopic-assisted distal partial gastrectomy with the abdominal wall-elevating method in two patients. Histological examinations revealed that the lesions were completely resected, and there was no evidence of lymphatic metastasis. The operation time ranged from 2 to 4 h. These forms of laparoscopic gastric surgery for patients with early gastric carcinomas may be useful from the standpoint of minimal access, rapid recovery, less pain, and good cosmesis.

Aged↗

PubMed1994

Stimulating action of KW-5139 (Leu13-motilin) on gastrointestinal motility in the rabbit.

1. The gastrointestinal motor stimulating action of the motilin analogue, KW-5139 (Leu13-motilin), was investigated both in the anaesthetized rabbit and in rabbit isolated smooth muscle tissues. 2. KW-5139 (0.3-10 micrograms kg-1, i.v.) produced motor stimulating actions in the gastric antrum, ileum and descending colon, the excitatory responses of which were initiated at the same time but declined with different time courses. The rank order of the excitatory response was: descending colon > or = gastric antrum >> ileum. 3. Atropine (1-3 mg kg-1, i.v.) or naloxone (1 mg kg-1, i.v.) completely suppressed the excitatory response to KW-5139 in the gastric antrum, but only partially attenuated that in the descending colon. This suggests that the mechanism of the excitatory response is different in the gastric antrum and the descending colon, and that cholinergic neural pathway is involved in the response of the gastric antrum. 4. KW-5139 (0.1 nM-1 microM) caused concentration-dependent contractions of the gastric antrum, duodenum, jejunum, ileum and the descending colon in vitro. In the rabbit intestine, the contractile response to KW-5139 was strongest in the duodenum and weakest in the ileum. 5. The contractile response to KW-5139 in the intestinal segments were not affected by tetrodotoxin, but were decreased by verapamil, or pretreatment with a high concentration of porcine motilin, confirming the involvement of motilin receptors in the response to KW-5139. 6. The present results suggest that the rabbit is a suitable species for the investigation of motilin on gut motility, because of the high responsiveness of the descending colon as well as the upper gastrointestinal tract.

Animals↗

PubMed1994

Effect of vinconate on long-term potentiation in a mossy fiber-CA3 system of guinea pig hippocampal slices.

We investigated the effect of vinconate on the long-term potentiation of population spikes following the stimulation of mossy fibers in the CA3 pyramidal layer of hippocampal slices from guinea pig brain. Vinconate (10(-7) and 10(-6) M) dose-dependently augmented the long-term potentiation in the mossy fiber-CA3 system. This effect was reduced by treatment with scopolamine at a concentration of 10(-6) M, which showed no significant change in the long-term potentiation in a mossy fiber-CA3 system. These results suggest that vinconate may augment long-term potentiation in the mossy fiber-CA3 system partly via activation of the cholinergic system.

Animals↗

PubMed1994

[Effect of KW-5805 on gastric mucus changes induced by water immersion-restraint stress and aspirin in rats].

The effects of 5-[2-(diethylamino)ethyl]amino-5,11-dihydro[1]benzoxepino[3,4- b]pyridine trihydrochloride (KW-5805) on the changes of gastric mucus induced by stress and aspirin were studied in rats. Water immersion-restraint stress time-dependently decreased the gastric adherent mucus content and induced gastric ulcers. Aspirin, administered orally at 200 mg/kg, reduced the gastric adherent mucus level and produced gastric erosions. The diminution of gastric mucus reached a maximum at 3 hr, and a gradual return to the non-treatment value was observed subsequently. Pretreatment with KW-5805, given orally at 3, 10 or 30 mg/kg, dose-dependently prevented stress- and aspirin-induced mucus depletion and gastric ulceration. Gastric mucus glycoprotein levels, indicated by the contents of hexose and hexosamine, were also decreased by aspirin. KW-5805 pretreatment (30 mg/kg, p.o.) significantly inhibited the diminution of mucus glycoproteins. KW-5805 also increased the gastric adherent mucus content and the amount of glycoproteins in normal rats. These results suggested that the stimulating effects of KW-5805 on the secretion and storage of gastric mucus may account for some of its antiulcer properties.

Animals↗

PubMed1994

[Effect of 5-[2-(diethylamino)ethyl]amino-5,11- dihydro[1]benzoxepino[3,4-b]pyridine trihydrochloride (KW-5805) on the biosynthesis of rat gastric mucus].

The effect of 5-[2-(diethylamino)ethyl]amino-5,11- dihydro[1]benzoxepino[3,4-b]pyridine trihydrochloride (KW-5805) on the activity of an enzyme regulating gastric mucous aminosugar metabolism was studied in rats. Restraint and water-immersion stress decreased the gastric mucosal glucosamine synthetase activity and induced gastric ulcers. The decrease of the enzyme activity reached a maximum at 1 hr and then returned to the non-stressed value. Pretreatment with KW-5805 at oral doses of 3 and 30 mg/kg inhibited the decrease of the enzyme activity and the gastric adherent mucus content and gastric ulceration induced by the stress. KW-5805 (30 mg/kg, p.o.) increased the enzyme activity in normal rats and also prevented the decrease of gastric mucosal N-acethylglucosamine kinase activity in the stressed rats. KW-5805 stimulated the activities of gastric mucosal. UDP-N-acethylglucosamine 4-epimerase and UDP-galactosyltransferase in in vitro. These results suggested that the antiulcerogenic effect of KW-5805 might be due to the activation of an enzyme regulating the biosynthesis of gastric mucus resulting in the reinforcement of gastric mucosal defensive mechanisms.

Administration, Oral↗

PubMed1994

Enhancement by KW-5092, a novel gastroprokinetic agent, of the gastrointestinal motor activity in dogs.

KW-5092 ([1-[2-[[[5-(piperidinomethyl)-2- furanyl]methyl]amino]ethyl]-2-imidazolidinylidene) propanedinitrile fumarate) is a novel gastroprokinetic agent with acetylcholinesterase (AChE) inhibitory activity and acetylcholine (ACh) release facilitatory activity. The present study examined the effects of KW-5092 on gastrointestinal (GI) motor activity in dogs. In anesthetized dogs, KW-5092 at 0.03 to 1 mg/kg, i.v. dose-dependently enhanced the gastric antral and the colonic motor activity. Neostigmine, an AChE inhibitor, enhanced the motor activity at 0.03 and 0.1 mg/kg, i.v. Ranitidine, a histamine H2-receptor antagonist with AChE inhibitory activity and ACh release facilitatory activity, enhanced the motor activity but decreased blood pressure at 1 to 10 mg/kg, i.v. In conscious dogs, KW-5092 at 0.03 to 1 mg/kg, i.v. or 1 to 10 mg/kg, p.o. dose-dependently enhanced the gastric antral, duodenal, ileal and the colonic motor activities. Neostigmine at 0.1 mg/kg, i.v. or 3 mg/kg, p.o. enhanced the duodenal, ileal and colonic motor activities, but induced excitement, slavering, vomiting and diarrhea. Ranitidine at 3 mg/kg, i.v. enhanced the gastric antral and colonic motor activities, but induced collapse or akinesia. The present results suggest that KW-5092 enhances the GI motor activity in a wide range from the gastric antrum to the colon and does not induce behavioral and cardiovascular side effects. KW-5092 may be a useful drug for the treatment of GI motility dysfunctions.

Acetylcholine↗

PubMed1994

Effects of KW-5805, a new antiulcer agent, on experimental gastric and duodenal ulcers, gastric mucosal lesions by necrotizing agents and gastric acid secretion.

Effects of KW-5805, a new antiulcer agent, on various experimental ulcers, necrotizing agent-induced gastric lesions and gastric acid secretion in rats were compared with those of pirenzepine and cimetidine. KW-5805 showed antiulcer activities against experimental gastric and duodenal ulcers (ED50 = 1.2-10.0 mg/kg, p.o.). KW-5805 effectively inhibited gastric lesions induced by various necrotizing agents (ED50 = 4.5-39.8 mg/kg, p.o.). In addition, the cytoprotective effect of KW-5805 was not affected by indomethacin, but reserved by N-ethylmaleimide. These antiulcer and cytoprotective effects of KW-5805 were more potent than those of pirenzepine and cimetidine. In pylorus-ligated rats, intraduodenal KW-5805 administration at 30 mg/kg showed a weak antisecretory effect, which was 3-10 times less potent than those of pirenzepine and cimetidine. In rats with acute gastric fistula, intravenous injection of KW-5805 reduced methacholine-stimulated gastric acid secretion at doses of 10 and 30 mg/kg and inhibited tetragastrin-induced acid secretion at 30 mg/kg. These results indicate that KW-5805 has potent and broad antiulcer properties, which are probably exerted by its potent cytoprotective effect in addition to its antisecretory effect.

Animals↗

PubMed1993

Synthesis of 2-imidazolidinylidenepropanedinitrile derivatives as stimulators of gastrointestinal motility.

Ranitidine (1), the histamine H2-receptor antagonist, has been previously reported to increase gastric emptying and gastric motility by inhibition of acetylcholinesterase (AChE) and enhancement of acetylcholine (ACh) release. In order to obtain potent gastroprokinetic agents, a new series of ranitidine derivatives (5-32) possessing a nitrogen atom instead of a sulfur atom (B) was synthesized and their AChE inhibitory activity and potentiating action on electrically evoked contractions of guinea pig ileum were evaluated. Modification of substituents R1 and R2 markedly influenced the activities. In particular, compound 19, (1-[2-[[[5-(piperidinomethyl)-2-furanyl]methyl]amino]-ethyl]-2- imidazolidinylidene)propanedinitrile fumarate, showed 20 and 100 times more potent AChE inhibitory activity and potentiating action on the ileal contraction, respectively, than ranitidine. Furthermore, compound 19 (KW-5092) enhanced gastrointestinal motility in anesthetized rabbits along with a negligible histamine H2-receptor blocking activity.

Animals↗

PubMed1993

Effect of vinconate against regional age-related changes in the gerbil brain.

We investigated age-related changes in the binding sites of muscarinic acetylcholine, forskolin, adenosine 3',5'-cyclic monophosphate (cAMP), and of a voltage-dependent L-type calcium channel blocker in the gerbil brain using receptor autoradiography. [3H]Quinuclidinyl benzilate (QNB), [3H]forskolin, [3H]cAMP, and [3H]PN200-110 were used to label muscarinic receptors, adenylate cyclase, cAMP-dependent protein kinase, and L-type calcium channels, respectively. In middle-aged animals (16-month-old gerbils), [3H]QNB, [3H]PN200-110, [3H]forskolin, and [3H]cAMP binding sites were elevated in the hippocampal region compared with that of young gerbils (4 weeks old). Further, a significant elevation in [3H]forskolin binding was seen in the nucleus accumbens. In contrast, [3H]QNB, [3H]PN200-110, and [3H]forskolin binding sites were reduced in the cerebellum, neocortex and thalamus, and hypothalamus in middle-aged animals, respectively. [3H]cAMP binding was not altered in other regions except for an elevation in the hippocampus. Thus, the age-related alterations in receptor binding may proceed by different mechanisms in various brain regions. Chronic vinconate treatment partly modulated the age-related alterations in [3H]QNB, [3H]forskolin, and [3H]cAMP binding in the hippocampus, but not that of [3H]PN200-110. Vinconate also regulated the age-related changes in [3H]forskolin binding in the nucleus accumbens. These results indicate that the age-related alterations in the binding sites of muscarinic acetylcholine, forskolin, cAMP, and L-type calcium channel blocker occur in particular in the hippocampus. Further, they suggest that a novel vinca alkaloid derivative, vinconate, can partly modulate age-related changes in these binding sites.

Acetylcholine↗

PubMed1993

Effect of OM-853, a cerebral metabolic ameliorator, on ambulatory activity and passive and active avoidance responses in mice and Mongolian gerbils.

Behavioral effects of OM-853 were investigated in both mice and Mongolian gerbils. In mice, OM-853 alone produced no marked change in the ambulatory activity, although it tended to lower it at 100 mg/kg, and this drug (5-100 mg/kg, p.o.) reduced the ambulation-increasing effect of scopolamine (0.5 mg/kg, s.c.) in a dose-dependent manner. Moreover, OM-853 (50 and 100 mg/kg, p.o.) prolonged the latency times shortened by scopolamine under the passive avoidance. On the other hand, in the discrete avoidance situation, OM-853 facilitated the acquisition of shuttle avoidance at 10 and 25 mg/kg, p.o. and lever-press avoidance at 25 and 50 mg/kg, p.o. in the pre-training administration schedule, and the former at 25-100 mg/kg, p.o. and the latter at 10 and 25 mg/kg, p.o. in the post-training administration schedule. In gerbils, OM-853 (50 mg/kg, i.p.) ameliorated the learning deficit of the lever-press avoidance response induced by forebrain ischemia. The present results suggest that OM-853 has beneficial actions on some types of learning and memory in normal, scopolamine-treated and ischemic animals. The possible mechanisms involved are discussed.

Animals↗

PubMed1993

Effects of OM-853, a novel indolonaphthyridine derivative, on behavioral responses in the forced swim test in rats.

Effects of OM-853 on behavioral responses in the forced swim test were studied. OM-853 significantly reduced the duration of immobility without any change in the exploratory activity. Imipramine also reduced the duration of immobility, but idebenone did not. On the other hand, vinpocetine enhanced the duration with a suppressive effect on ambulation. The anti-immobility effect of OM-853 was reversed by pretreatment with haloperidol. These results demonstrate that the effect of OM-853 on the swim test is different from that of idebenone and vinpocetine. Furthermore, the present results suggest that OM-853 may exert its anti-immobility activity through facilitated transmission of the dopaminergic and/or adrenergic systems.

Animals↗