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M Washizuka

Publications and source records attributed to M Washizuka.

At least 19 recordsLinked to original sources

Diet stimulation as a synergistic factor of aggravation in a pancreatic bile duct ligation-induced rat pancreatitis model.

We evaluated the association between aggravation of pancreatitis and multiple factors enhancing pancreatic exocrine secretion using a rat model of pancreatic bile duct ligation (PBDL)-induced pancreatitis. Under fasting and non-fasting conditions, a PBDL group, a second group treated by hepatic bile duct ligation (BDL) and a third group treated by pancreatic duct ligation (PDL) were compared in terms of serum amylase (S-amylase) activity. The S-amylase activity in the PBDL group was higher than in the sham group. In the PDL group, the increase in S-amylase activity was lower than in the PBDL group. In the BDL group, no increase in S-amylase activity was observed. Diversion of pancreatic and/or bile juice in these groups resulted in no increase of S-amylase activity. Truncal vagotomy or injection of an anticholinergic drug or a cholecystokinin (CCK)1-receptor antagonist inhibited pancreatic exocrine secretion and S-amylase activity in the non-fasting PBDL group but not in the fasting PBDL group. These results suggest that retention of pancreatic juice in the pancreatic duct is necessary for the increase of S-amylase activity, and that dietary stimulation and impaired duodenal inflow of bile and pancreatic juice commonly enhance pancreatic exocrine secretion, acting synergistically as aggravating factors in pancreatitis. CCK and the vagus nerve system appears to be involved in enhancing pancreatic exocrine secretion with diet stimulation as an aggravating factor.

Amylases↗

Cholecystokinin acts as an essential factor in the exacerbation of pancreatic bile duct ligation-induced rat pancreatitis model under non-fasting condition.

We examined the influence of 2 gut hormones involved in the enhancement of pancreatic exocrine secretion, secretin and cholecystokinin (CCK), in the exacerbation of pancreatitis. We also examined the role of the vagal system, which was considered to be a transmission route for these hormones. Our model of pancreatitis in the rat was prepared by pancreatic bile duct ligation (PBDL), which simultaneously ligated the pancreatic duct and the common bile duct. Serum amylase activity and histopathological changes in the pancreas were used as indices of pancreatitis. We also measured the volume of pancreatic juice, as well as the amylase activity and protein level of the pancreatic juice, as indices of increased pancreatic exocrine secretion. Two gut hormones were given 6 times at 1-h intervals. Administration of secretin (1-3 microg/kg, s.c.) did not influence serum amylase activity in rats with PBDL-induced pancreatitis. However, food stimulation and administration of CCK-8 (1 microg/kg, s.c.) increased serum amylase activity and promoted vacuolation of the pancreatic acinar cells in rats with PBDL-induced pancreatitis. Administration of atropine (3 mg/kg, s.c.) or a CCK1-receptor antagonist, Z-203 (0.1 mg/kg, i.v.), inhibited food-stimulated or CCK-8-induced (1 microg/kg, s.c.) enhancement of pancreatic exocrine secretion and exacerbation after the development of PBDL-induced pancreatitis. These results suggest that not secretin, which regulates the volume of pancreatic juice, but CCK, which regulates the secretion of pancreatic enzymes via the vagal system, plays an essential role in food-stimulated exacerbation after the development of pancreatitis.

Amylases↗

Fasting exacerbates acute pancreatitis by occlusion of the common bile duct in rats.

We examined the effects of fasting and non-fasting on gallstone-related acute pancreatitis by the occlusion of the common bile duct (OCD). We prepared a rat OCD-induced pancreatitis model under both fasting and non-fasting conditions, and we measured amylase activity in ascites as well as production of inflammatory cytokines and chemokines. We also examined the pathology of the pancreas, myeloperoxidase (MPO) activity in some tissues and mortality rates. In the fasted OCD group, ascites containing a large amount of amylase, interleukin 1beta (IL-1beta), interleukin 6 (IL-6), and cytokine-induced neutrophil chemoattractant-1 (CINC-1) as well as marked hemorrhage and necrosis of the pancreatic acinar cells were observed. Pulmonary MPO activity increased 3.4-fold compared to the control group. In the non-fasted OCD group, there was no development of ascites. Slight necrosis of acinar cells and slight increases in pulmonary MPO activity were observed. In addition, in the fasted OCD group, the cumulative mortality rate was 50% 6 days after ligation. However, in the non-fasted OCD group, none of the animals died. These results suggest that gallstone-related severe pancreatitis depends on fasting-related structural and/or functional changes in the pancreas. Moreover, increased production of inflammatory cytokines and chemokines in ascites under fasting condition may be involved in multiple organ failure resulting from severe acute pancreatitis.

Acute Disease↗

[Effect of liver hydrolysate on hepatic proliferation in regenerating rat liver].

The effect of liver hydrolysate (LH) derived from bovine liver on rat liver regeneration after partial hepatectomy (PH) were investigated. Oral administration of LH increased rat liver weight dose-dependently at 24 h after PH. Hepatic ornithine decarboxylase (ODC) activity and proliferating cell nuclear antigen (PCNA) labeling index were measured in regenerating rat liver as markers of cell proliferation. ODC activities at 4 and 24 h after PH were significantly increased by LH administration. PCNA labeling index at 24 h after PH were also increased by LH administration. These results suggest that LH stimulates liver regeneration in partially hepatectomized rats.

Animals↗

Chromophobe cell renal carcinoma in childhood.

We report the first case of chromophobe cell renal carcinoma in childhood. A 12-year-old boy presented gross hematuria following minor trauma. He was diagnosed as having a left renal tumor 45-mm in diameter. Radical nephrectomy was performed. One year later the boy was well.

Carcinoma, Renal Cell↗

[Effect of liver hydrolysate on ethanol- and acetaldehyde-induced deficiencies].

Since it has been reported that amino acids have alleviating effects on ethanol- and acetaldehyde-induced toxicity, we investigated the effect of liver hydrolysate derived from bovine liver on ethanol- or acetaldehyde-induced toxicity and deficiency models of mice and rats in the present study. Liver hydrolysate improved the deficiencies of beam walking and food intake of mice in a dose-dependent fashion when challenged with ethanol at the dose of 5 ml/kg, p.o. According to the analysis using selective inhibitors for alcohol dehydrogenase and acetaldehyde dehydrogenase, it has been suggested that this improvement effect of liver hydrolysate is mainly due to the reduction of acetaldehyde toxicity. No effect of liver hydrolysate was found in coma and death produced by orally treated ethanol at 10 ml/kg. In contrast, liver hydrolysate dose-dependently decreased the coma and death of mice administered acetaldehyde at 1.8 ml/kg, p.o. Furthermore, an increase in serum GPT activity, which was caused by twice oral administration of acetaldehyde at 1.2 ml/kg at interval of 1 hr, was inhibited by liver hydrolysate. These results suggest that liver hydrolysate has a protective effect against ethanol- and acetaldehyde-induced toxicity.

Acetaldehyde↗

Evidence for a depressive-like state induced by repeated saline injections in Fischer 344 rats.

We investigated the behavioral changes induced by mild stress in animals that may be relatively susceptible to a depressive-like state, the Fischer 344 rat strain. The mild stress of repeated handling and intraperitoneal (i.p.) injections with saline (2 ml/kg, twice a day for 14 days) elicited a moderate suppression of body weight gain, a decrease in open field activity, and a prolonged immobility during the tail suspension test in Fischer 344 rats compared with Sprague-Dawley rats. Chronic treatment of Fischer 344 rats with imipramine (10 mg/kg i.p., twice a day for 14 days) effectively suppressed open field activity and prolonged immobility. These results suggest that repeated saline injections may be a mild stressor in these rats. In the Fischer 344 strain, which may be vulnerable to the effects of mild stressors, repeated saline injections might induce a depressive-like state and could presumably represent an experimental model for depression.

Animals↗

Protective effect of citalopram against the attenuation of the alpha 1-potentiation of cAMP formation in Fischer 344 strain rats.

We investigated the effects of citalopram, a selective serotonin reuptake inhibitor (SSRI), using an animal model for a depressive state. In Fischer 344 rats, known as emotional animals, repeated stress by twice-daily intraperitoneal (i.p.) saline injections for 14 days elicited a depressive state characterized by a decreased open-field activity and a prolonged immobility during the tail-suspension test. Concomitantly, suppression of norepinephrine (NE)-induced cAMP formation was found in the cerebral cortical slices of the stress-exposed rats without changes in adrenergic alpha 1- or beta-receptors. The difference in cAMP formation between the intact and the stress groups was totally abolished under the blockade of the alpha 1-receptor system or by the stimulation with isoproterenol or forskolin, whereas the suppressed response in the stress group was also observed in combination with isoproterenol and phenylephrine. From these results, we confirmed that the potentiation of the beta-receptor-stimulated cAMP formation by the alpha 1-receptor is attenuated following repeated stress. Chronic i.p. administration of citalopram dissolved in saline improved both the suppressed open-field activity and the prolonged immobility in the tail-suspension test. The animals treated with citalopram exhibited a comparable alpha 1-potentiation effect as observed in the intact rats. However, another SSRI, paroxetine, was less effective on the attenuation of the alpha 1-potentiation in spite of its behavioral improvement in the depressive state. These findings suggest that citalopram has a protective effect against the repeated stress-induced depressive state by mechanisms besides the serotonin reuptake inhibition.

Adrenergic Uptake Inhibitors↗

An attenuated alpha-1 potentiation of beta adrenoceptor-stimulated cyclic AMP formation after repeated saline injections in Fischer 344 strain rats.

We investigated the behavioral and neurochemical features of Fischer 344 strain rats in which a depressive state was induced by repeated handling and saline injections as a mild stressor. The repeated intraperitoneal injections of saline (2 ml/kg, twice a day for 14 days) elicited a moderate suppression of body weight gain, a decrease in their open field activity and a prolonged immobility in the tail suspension test. In the stress-exposed rats, the tissue content of norepinephrine (NE) was increased in the cerebral cortex and hypothalamus, whereas that of dopamine or serotonin was not affected. Although the stress exposure did not affect the binding properties of either the alpha-1 or beta adrenoceptors, it suppressed cAMP formation stimulated by NE, but not by isoproterenol or forskolin, in the cerebral cortical slices. In the presence of prazosin or phorbol ester, the difference in NE-stimulated cAMP formation between the control and the stress groups was totally abolished. Phenylephrine enhanced isoproterenol-stimulated cAMP formation in the control but not in the stress group. From these results, it is postulated that the alpha-1 potentiation of beta adrenoceptor- stimulated cAMP formation was attenuated in the stress group. These findings suggest that the manipulation of mild stressor with repeated handling and saline injections to Fischer 344 rats elicits a depressive state characterized by the behavioral changes and the attenuated alpha-1 potentiation in the cerebral cortex, and that this manipulation might be available for the study of the stress-induced depressive state as a generally acceptable mild stress model.

Animals↗

Hippocampal serotonin 5-HT1A receptor enhances acetylcholine release in conscious rats.

We investigated changes in the extracellular levels of acetylcholine (ACh) following local application of serotonergic agents to the dorsal hippocampus of freely moving rats by means of perfusion using a microdialysis technique. Perfusion of serotonin (5-HT; 10 microM, for 30 min at a rate of 3 microliters/min), dissolved in Ringer's solution containing 10 microM eserine, showed no marked effect on the extracellular levels of ACh. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 20 microM), a 5-HT1A agonist, increased ACh levels, whereas 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline (CGS-12066B; 100 microM), a 5-HT1B agonist, decreased it. Clomipramine (2 microM), an uptake inhibitor of 5-HT, had no effect on ACh levels. Following perfusion of 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN-190; 10 microM), which is a selective 5-HT1A antagonist, the effect of 8-OH-DPAT was totally abolished, whereas CGS-12066B decreased extracellular ACh levels. 5-HT, as well as clomipramine, had a decreasing effect on ACh levels after pretreatment with NAN-190. These results indicate that the 5-HT1A receptor, which exists in the dorsal hippocampus, enhances the spontaneous ACh release, and that the mechanism of serotonergic modulation of ACh release partly depends on both the stimulatory control via the 5-HT1A receptor and the suppressive one via the 5-HT1B receptor in the dorsal hippocampus of rats.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Differential effects of intracerebroventricular AF64A injection, nucleus basalis of Meynert lesion, and scopolamine on place navigation and open-field behavior of rats.

The present study was conducted to compare the behavioral effects of intracerebroventricular AF64A injection, electrolytic lesion of the nucleus basalis of Meynert (NBM), and systemic scopolamine treatment, all of which are typical experimental models of central cholinergic system dysfunction, on place navigation performance and open-field behavior in rats. The animals were trained in a circular pool to escape from opaque water onto the hidden platform fixed at a particular location for 5 days. Significant performance deficits were observed in all the models tested. However, it is of importance that any impairments relating to information storage within a day or across days were not obtained. Choline acetyltransferase activity was decreased in the hippocampus of AF64A-injected rats and in the cortex of NBM-lesioned rats, respectively, but those changes did not simply associate with the reductions of the performance. These results suggest that the central cholinergic system is only partially involved in cognitive process. In the open-field test, ambulation, rearing, defecation, and urination were measured for 5 min. Patterns of changes in the open-field behavior were clearly different among the 3 models, indicating variability of the effects of these cholinergic manipulations on motor activities and emotionality.

Animals↗

[Apparently bladder origin signet ring cell carcinoma: a case report].

A 72-year-old woman with signet-ring cell carcinoma of the urinary bladder treated with total cystectomy is described. The bladder yielded linitis plastica pattern of infiltration similar to that seen in the gastric cancer, i.e., cancer tissue extended almost whole bladder deeply to the serosa, whilst the mucosal surface was only minimally invaded. She received no adjuvant therapy and she is alive without recurrence 8 months after the operation. We review the reported cases and shortly discuss the prognosis and treatment of primary signet-ring cell carcinoma of the urinary bladder.

Adenocarcinoma, Mucinous↗

[Adrenal myelolipoma: two case reports].

We report 2 cases of adrenal myelolipoma which were suspected preoperatively and confirmed by surgical resection. As with most cases previously reported, the lesions were found in obese, middle-aged persons. Laboratory tests of adrenal function revealed values within the normal level. Excretory urography showed radiolucent masses in the suprarenal area displacing the kidney inferiorly. Computerized tomography revealed well-defined masses consisting of fat density areas and higher density areas. Ultrasonography demonstrated hyperechoic, heterogeneous tumors. The tumors were shown to be hypovascular and adrenal in origin on the angiogram. An operation was performed because of complaint of flank pain in the first case and hypertension associated with elevated plasma renin activity in the second case. The pathological study disclosed typical adrenal myelolipoma with a mixture of hematopoietic and adipose tissue. Adrenal myelolipoma is clinically unusual and only 41 cases with premortem diagnosis have been reported in English literature. We herein report the 14th and 15th cases in Japan. As computerized tomography and ultrasonography become more widely used, we believe that the number of cases difficult to differentiate from a malignancy will increase.

Adrenal Gland Neoplasms↗

Sequential instillation therapy with mitomycin C and adriamycin for superficial bladder tumors.

From October 1983 to September 1985, 84 patients with superficial bladder tumor (Ta, Tl, Tis) were treated with sequential instillation of mitomycin C (MMC) and adriamycin (ADM). Doses of 20 mg MMC on day 1 and 40 mg ADM on day 2 were instilled into the bladder and retained for at least 2 h; this was repeated once a week for 5 consecutive weeks. Patients who achieved complete response (CR), were randomized and underwent prophylactic treatment taking the form of either intermittent instillation of MMC or daily oral administration of 5-fluorouracil. Of 79 evaluable patients, 72 (91%) had received prior treatment for superficial bladder tumors, 69 (87%) had high-grade tumors, and 18 (23%) had non-papillary Tis. The overall response rate was 68%, made up of CR in 43 patients (54%) and partial response (PR) in 11 (14%). Patients with either five or more tumors or tumors larger than 1 cm showed a significantly lower response rate than those with fewer than five tumors and tumors smaller than 1 cm, respectively. There was no correlation between tumor growth pattern, tumor grade and response rate, though non-papillary Tis appeared to respond better than papillary tumors. A history of prior instillation therapy or of toxicity to this treatment had no significant influence on the response rate. Although no systemic toxicity was observed, 62 patients (74%) experienced cystitis and the treatment had to be discontinued within 4 weeks in 13 of 33 cases with severe symptoms. The preliminary conclusion of prophylactic treatment was that intermittent instillation of MMC was superior to 5-FU medication in reducing the recurrence rate for at least 2 years after the treatment.

Administration, Intravesical↗