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K Ninomiya

Publications and source records attributed to K Ninomiya.

At least 37 records · Page 2Linked to original sources

Impaired adaptive cytoprotection to ethanol-induced damage in gastric mucosa of portal hypertensive rats.

Portal hypertension predisposes gastric mucosa to increased damage by noxious agents. Adaptive cytoprotection has not been studied in portal hypertensive gastric mucosa. We evaluated adaptive cytoprotection in the gastric mucosa of portal hypertensive rats by exposure to ethanol. The injury index (percent gross lesions) was significantly higher in portal hypertensive rats than in sham-operated rats. The ratio of adaptive cytoprotection, calculated as the degree of decrease in the injury index caused by pre-absolute-ethanol administration of 20% ethanol, was significantly impaired in portal hypertensive rats. Basal levels of gastric mucosal hexosamine were lower in portal hypertensive rats than in controls, and a blunted response to 20% ethanol was associated with portal hypertension. Nitric oxide inhibition (L-NAME, 5 mg/kg) reduced the ratio of adaptive cytoprotection in sham-operated but not in portal hypertensive rats. These results suggest that impaired adaptive cytoprotection in portal hypertensive gastric mucosa may be caused by blunted mucus production.

Adaptation, Physiological↗

Obesity affects expression of progesterone receptors and node metastasis of mammary carcinomas in postmenopausal women without a family history.

Possible relationships between risk factors, such as obesity and a family history of breast cancer, and prognostic factors of mammary carcinomas were investigated by examining the body mass index of patients and the expression of estrogen (ER) and progesterone receptors (PgR), c-erbB-2 and p53, grade of histology, size of tumors and nodal status of mammary carcinomas. There was no significant difference in the body mass index of premenopausal patients either with or without a family history. For postmenopausal patients, the body mass index was significantly low in patients with a family history compared with patients without a family history. In premenopausal patients with or without a family history and in postmenopausal patients with a family history, there was no significant difference in the body mass index regardless of the mammary carcinoma prognostic factor, such as expression of ER, PgR, c-erbB-2 and p53, grade of histology, size of tumors and nodal status. However, in postmenopausal patients without a family history, body mass index was significantly high for patients with mammary carcinomas that had PgR expression and node metastasis. These results suggest that obesity may affect the PgR status and nodal status of mammary carcinomas in postmenopausal patients without a family history.

Body Mass Index↗

Delayed healing of acetic-acid-induced gastric ulcer in portal hypertensive rats.

The aim of the present study was to determine the effect of portal hypertension on the healing of gastric ulcers in rats. Portal hypertension was induced by staged portal vein ligation. Sham-operated (SO) rats served as controls. Gastric ulcers were induced by application of acetic acid to the serosal surface of the stomach. Healing was assessed by determining the ulcer area on days 3, 7, and 10 after ulcer induction. Epithelial proliferation at the ulcer margin was assessed by evaluating the proliferating cell nuclear antigen labeling index. On days 3 and 7, the proliferating cell nuclear antigen labeling index was lower in portal hypertensive (PHT) rats than in SO rats. On day 10, the ulcer area in PHT rats was nearly twice that in SO rats (4.13 +/- 0.29 vs. 2.28 +/- 0.22 mm(2), p < 0.05). These results suggest that portal hypertension may delay gastric ulcer healing. Furthermore, the inhibition of epithelial proliferation at the ulcer margin may be involved in the delayed healing in portal hypertension.

Acetic Acid↗

[Imipenem/cilastatin sodium and other beta-lactams for respiratory tract infections: clinical benefit and treatment days for cure].

Therapeutic efficacy and the treatment days for cure of imipenem/cilastatin sodium (IPM/CS) in treatment of pulmonary infections were prospectively determined in comparison with those of beta-lactams other than carbapenems mainly ceftazidime (CAZ) or sulbactam/cefoperazone (SBT/CPZ). The overall response rate was 84.9% (62/73) in the IPM/CS group and 74.7% (56/75) in the beta-lactam group, the difference not being significant. In the subjects having underlying respiratory diseases, the response rate was 91.1% (41/45) and 73.9% (34/46) in the IPM/CS and beta-lactam groups, respectively. In patients with infections secondary to chronic respiratory disease, the rate was 91.2% (31/34) in the former group and 66.7% (24/36) in the latter group, respectively. The differences were significant for both stratified analyses. The treatment days for cure judged by the attending physician were 12.9 +/- 0.6 days in the IPM/CS group, and 14.5 +/- 0.7 days in the beta-lactam group. The difference was not, however, significant. In patients with mild to moderate infections, the treatment days for cure was 12.0 +/- 0.6 days (n = 64) in the IPM/CS group and 14.3 +/- 0.7 days (n = 70) in the beta-lactam group. In patients with underlying respiratory disease, the treatment days for cure were 11.8 +/- 0.7 days (n = 45) and 14.7 +/- 0.9 days (n = 46) in the IPM/CS and beta-lactam groups, respectively. In patients with infections secondary to chronic respiratory disease, the days were 11.1 +/- 0.7 days (n = 34) and 14.7 +/- 1.1 days (n = 36), respectively. Thus, IPM/CS therapy significantly reduced the number of treatment days until cure. There was, however, no significant difference between the two therapy groups in treatment of the patients with severe infections, those without underlying respiratory disease, or those with pneumonia and/or lung abscess. The treatment days for cure were also assessed by the members of review committee taking into consideration of body temperature, leukocyte count, and C-reactive protein. As the result, it was 6.9 +/- 0.5 days in the IPM/ CS and 10.3 +/- 0.7 days in the beta-lactam groups; respectively, and the difference was significant. Time (days) until cure was also compared between the two groups using survival time analysis, confirming a more rapid response in the IPM/CS group. Although IPM/CS therapy was associated with a shorter response time as assessed by both the attending physicians and the review committee, there were considerable differences between the results of these judgements. Thus, the duration of treatment with injectable antibiotics requires reevaluation in the future. No significant differences were observed between the groups with respect to parameters indicating side effects and laboratory abnormalities. There were no severe symptoms or laboratory findings, and symptoms and changes in laboratory values, if any resolved during the course of therapy or after the withdrawal of treatment. In conclusion, IPM/CS seems to be very useful as first-line therapy for respiratory tract infections and for shortening the duration of treatment.

Adult↗

Hepatoprotective, superoxide scavenging, and antioxidative activities of aromatic constituents from the bark of Betula platyphylla var. japonica.

The 50% aqueous methanolic extract from the bark of Betula platyphylla SUKATCHEV var. japonica (MIQ). HARA was found to show potent inhibitory activity on the liver-injury induced by CCl4 or D-galactosamine (D-GalN)/lipopolysaccharide as well as O2- scavenging and antioxidative activities. From the 50% aqueous methanolic extract, two new diarylheptanoids named betulaplatosides Ia (1) and Ib (2) and a new arylbutanoid named betulaplatoside II (3) were isolated together with seventeen known aromatic constituents. 1, 2, and two known diarylheptanoids [(5S)-5-hydroxy-1,7-bis-(4-hydroxyphenyl)-3-heptanone 5-O-beta-D-apiofurano-syl-(1-->6)-beta-D-glucopyranoside (6) and aceroside VIII (7)] showed protective activity against D-GalN-induced cytotoxicity in primary cultured rat hepatocytes. Furthermore, several aromatic constituents exhibited potent O2- scavenging and antioxidative activities.

Animals↗

Hepatoprotective and nitric oxide production inhibitory activities of coumarin and polyacetylene constituents from the roots of Angelica furcijuga.

The methanolic extract from the roots of Angelica furcijuga KITAGAWA was found to exhibit protective effects on liver injury induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS). From the methanolic extract, seventeen coumarins, two phenylpropanoids, and two polyacetylenes were isolated and examined their in vitro and in vivo hepatoprotective effects and inhibitory activity of NO production in macrophages. A acylated khellactone, isoepoxypteryxin, showed protective activity against D-GalN-induced cytotoxicity in primary cultured rat hepatocytes. On the other hand, six acylated khellactones (hyuganins A, B, C, and D, anomalin, isopteryxin) and two polyacetylenes [(-)-falcarinol and falcarindiol] strongly inhibited NO production induced by LPS in cultured mouse peritoneal macrophages, and also other acylated khellactones (isoepoxypteryxin, pteryxin, and suksdorfin) and a coumarin glycosides (praeroside II) were found to show the activity. By comparison of the inhibitory activities for acylated khellactones with those for other coumarins, acyl groups were found to be essential to exerting potent activity.

Acetylene↗

Inhibitory effect and action mechanism of sesquiterpenes from Zedoariae Rhizoma on D-galactosamine/lipopolysaccharide-induced liver injury.

Hepatoprotective sesquiterpenes were isolated from the aqueous acetone extract of Zedoariae Rhizoma, the rhizome of Curcuma zedoaria ROSCOE (Zingiberaceae). Principal sesquiterpenes, furanodiene, germacrone, curdione, neocurdione, curcumenol, isocurcumenol, aerugidiol, zedoarondiol, and curcumenone and curcumin were found to show potent protective effect on D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced acute liver injury in mice. Plausible action mechanisms for their hepatoprotective activity were clarified on the basis of the inhibitory effect on D-GalN-induced cytotoxicity in primary cultured rat hepatocytes, LPS-induced NO production in cultured mouse peritoneal macrophages, and D-GalN/tumor necrosis factor-alpha (TNF-alpha)-induced liver injury in mice.

Animals↗

Vasopressin antagonist improves renal function in a rat model of pneumoperitoneum.

Pneumoperitoneum (PP) is associated with oliguria and increased plasma arginine vasopressin (AVP) levels. This study investigated the role of AVP in the pathogenesis of oliguria due to PP. Anesthetized and ventilated rats (n = 12) were subjected for 1 h to carbon dioxide PP with an intra-abdominal pressure of 8 mmHg or, as control, at 0 mmHg, before the determination of plasma AVP level. Another group of rats (n = 48) subjected to PP or control conditions was pretreated with the AVP V2 receptor antagonist, OPC-31260 (5 mg/kg), or vehicle, and their renal parameters were measured. Glomerular filtration rate (GFR) was determined by inulin clearance in an additional group of rats (n = 12) subjected to PP with or without pretreatment with OPC-31260. Rats subjected to PP had higher plasma AVP levels than did controls (17.3 +/- 8.1 pg/ml vs 1.5 +/- 0. 6 pg/ml, P < 0.05). In rats pretreated with vehicle, PP decreased urine output, excretion of water, and urea nitrogen, leading to reduced serum osmolality and serum sodium levels as well as elevated blood urea nitrogen levels. OPC-31260 pretreatment improved urine output, excretion of water, and urea nitrogen, thereby preventing changes in serum osmolality, serum sodium levels, and blood urea nitrogen levels. OPC-31260 pretreatment did not affect GFR. Results suggest that plasma AVP contributes to the oliguria due to PP. OPC-31260 may be useful in treating the water retention associated with PP.

Animals↗

Phase II trial of combination chemotherapy with cisplatin, carboplatin and etoposide in stage IIIB and IV small-cell lung cancer. Fukuoka Lung Cancer Study Group.

PURPOSE: A phase II trial combining cisplatin, carboplatin and etoposide was conducted in previously untreated patients with stage IIIB and IV small-cell lung cancer, in an attempt to increase response rates and prolong survival. METHODS: Previously untreated patients with small-cell lung cancer, with measurable disease, aged < or = 72 years, performance status < or = 2, and adequate hematologic, hepatic and renal function were enrolled in the study. They were treated with 80 mg/m2 cisplatin on day 1, 100 mg/m2 carboplatin on days 2, 3 and 8, and 50 mg/m2 etoposide on days 1, 2, 3 and 8. RESULTS: A total of 46 patients (20 with stage IIIB and 26 with stage IV disease) were enrolled in the study. A total of 186 courses of chemotherapy were given, and the dose was reduced in 27 courses (15%). The chemotherapy was repeated for four or more courses in 30 patients. There were 10 complete responses and 32 partial responses, for a total response rate of 91% (95% confidence interval, 79% to 98%). The median survival time and 2-year survival rates were 18 months and 22% for stage IIIB disease, and 14 months and 15% for stage IV disease. Major side effects were hematologic: leukopenia, anemia, and thrombocytopenia of grade 3 or more occurred in 48%, 46%, and 43% of patients, respectively. CONCLUSIONS: The three-drug regimen of cisplatin, carboplatin and etoposide is feasible and active against small-cell lung cancer.

Aged↗

Comparison of pneumoperitoneum and abdominal wall lifting as to hemodynamics and surgical stress response during laparoscopic cholecystectomy.

BACKGROUND: Impairments in hemodynamics during pneumoperitoneum (PP) have been noted. This study compared changes in hemodynamics and surgical stress response with PP and abdominal wall lifting (AWL) during laparoscopic cholecystectomy. METHODS: Twenty patients with symptomatic cholecystolithiasis were assigned to PP (n = 10) or AWL (n = 10). Cardiac output (CO), stroke volume (SV), and ejection fraction (%EF) were measured by transesophageal echocardiography. Clearances of para-aminohippurate (CPAH) and sodium thiosulfate (CSTS) were determined as measures of renal function. Levels of interleukin-6, C-reactive protein, white cell count, and neutrophil elastase were evaluated as indicators of surgical stress. RESULTS: In the PP group, CO, SV, and %EF were depressed significantly during pneumoperitoneum. Immediately after and 15 min after insufflation, the CPAH and CSTS were decreased by 78.0% and 73.8%, respectively. None of the hemodynamic parameters changed significantly in the AWL group. Surgical stress response was not different significantly between the two groups. CONCLUSIONS: In contrast to pneumoperitoneum, AWL did not alter cardiac function or renal hemodynamics. AWL may be useful in patients with cardiovascular or renal disorders.

Abdominal Muscles↗

Laparoscopic cholecystectomy in patients undergoing anticoagulant therapy.

We recently performed a laparoscopic cholecystectomy on three patients receiving preoperative oral anticoagulant therapy. The patients requiring anticoagulants for pre-existing cardiac conditions have the following risks at surgery: thromboembolism, hemorrhage, endocarditis, and cardiopulmonary dysfunction. In patients receiving anticoagulant therapy, one must thus maintain a balanced international normalized ratio of the prothrombin time to prevent thromboembolism or hemorrhage. Warfarin sodium was discontinued preoperatively in all patients. Heparin sodium was individualized according to each patient's risk of thromboembolism. As a result, these patients all underwent a laparoscopic cholecystectomy without complications. Attention was paid to achieve hemostasis in the operative field and the trocar inserted sites during the procedure. The administration of warfarin sodium was resumed on the first postoperative day in all patients. Restarting warfarin sodium early also helps to simplify postoperative management. A broad spectrum of antibiotic therapy was also used to reduce the risk of endocarditis. Each patient's cardiopulmonary function was carefully monitored. The minimal invasion experienced during a laparoscopic cholecystectomy may thus facilitate the management of gallstones in patients receiving systemic anticoagulation treatment based on the findings of this limited series.

Adult↗

Laparoscopic enucleation of a pancreatic insulinoma: report of a case.

We report herein the case of a 48-year-old Japanese woman in whom a pancreatic insulinoma was successfully treated by laparoscopic enucleation. The patient presented after developing episodic neurohypoglycemic symptoms, and an insulinoma in the pancreatic tail, 1.0 cm in diameter, was diagnosed by the results of biochemical and radiological examinations. A laparoscopic intraoperative ultrasonogram demonstrated a solitary hypoechogenic tumor in the pancreatic tail. After the tail and body of the pancreas with the spleen were mobilized, laparoscopic enucleation was performed without any complications. The total operative time was 225min and the estimated blood loss was 20 ml. Serial blood sugar measurements demonstrated a sharp rise in blood sugar levels at the time of enucleation. The patient's postoperative course was uneventful, and she was discharged on the seventh postoperative day. She has remained well for 33 months following surgery without any hypoglycemic symptoms.

Female↗

Interleukin 6 and its relationship to clinical parameters in patients with malignant pleural mesothelioma.

The relationship between interleukin 6 (IL-6) levels and clinical parameters was studied in 25 patients with malignant pleural mesothelioma. The serum levels of IL-6, C-reactive protein, alpha1-acid glycoprotein and fibrinogen were significantly higher in mesothelioma than in lung adenocarcinoma with cytology-positive pleural effusion. Serum IL-6 levels correlated with the levels of the acute-phase proteins. We demonstrated a high incidence of thrombocytosis (48%) and a significant correlation between platelet count and the serum IL-6 level. The level of IL-6 in the pleural fluid of patients with mesothelioma was significantly higher than in the pleural fluid of patients with adenocarcinoma, and was about 60-1400 times higher than in the serum. However, even higher levels of IL-6 in the pleural fluid and of thrombocytosis were found in patients with tuberculous pleurisy. These results indicate that large amounts of IL-6 from the pleural fluid of patients with mesothelioma leak into the systemic circulation and induce clinical inflammatory reactions. These profiles are not specific to mesothelioma as similar profiles are found in patients with tuberculous pleurisy. However, the detection of a markedly increased level of IL-6 in pleural fluid argues against a diagnosis of adenocarcinoma.

Adenocarcinoma↗

Effects of loxiglumide on pancreatic exocrine secretion stimulated by cholecystokinin-8 in conscious dogs.

The effects of loxiglumide (CAS 107097-80-3, CR 1505), a novel cholecystokinin-A(CCK-A) receptor antagonist, on pancreatic exocrine secretion stimulated by exogenously administered CCK-8 were examined in conscious dogs with chronic pancreatic fistula. Pancreatic exocrine secretion in dogs was significantly increased by intravenous infusion of CCK-8 at a dose of 0.06 microgram/kg/h. Loxiglumide inhibited CCK-8-augmented outputs of pancreatic protein, trypsin and amylase at intravenous doses of 1, 3, 10 mg/kg/h (p < 0.05 or 0.01), and inhibited pancreatic juice volume at a dose of 10 mg/kg/h (p < 0.05). These results demonstrated that the selective CCK-A antagonist loxiglumide inhibited the increase of pancreatic exocrine secretion stimulated by CCK-8 based on selective blockade of receptor binding of CCK in dogs.

Amylases↗

Effects of loxiglumide on pancreatic exocrine secretion stimulated by meal in conscious dogs.

The effects of loxiglumide (CAS 107097-80-3, CR 1505), a novel cholecystokinin-A(CCK-A) receptor antagonist, on pancreatic exocrine secretion stimulated by meal were examined in conscious dogs with chronic pancreatic fistula. Pancreatic exocrine secretion was stimulated by intraduodenal infusion of a liquid test meal and postprandial plasma CCK levels were apparently elevated. Loxiglumide inhibited the meal-stimulated outputs of pancreatic protein, amylase and bicarbonate at an intravenous dose of 10 mg/kg/h (p < 0.05). However, loxiglumide did not show apparent inhibition of pancreatic juice volume and trypsin output. These results show that the selective CCK-A antagonist loxiglumide may inhibit the increase of pancreatic exocrine secretion based on selective blockade of receptor binding of CCK endogenously induced by meal in dogs.

Amylases↗

The significance of esophageal variceal pressure in patients with cirrhosis.

We measured the portal circulatory hemodynamic parameters in 10 cirrhotic patients with portal hypertension and esophageal varices to determine the significance of esophageal variceal pressure. In 4 patients (group I), the temporary portal vein occlusion produced significant elevations in both the esophageal variceal pressure and the portal venous pressure. The results of the portal circulatory hemodynamic assessment in this group were consistent with the predominance of the backward flow mechanism. In the remaining 6 patients (group II), however, portal vein clamping resulted in a slightly increased esophageal variceal pressure with an enormous increase in the portal pressure. The forward flow mechanism thus appeared to be predominant in group II. In other words, the results of the pressure measurements were consistent with the functional separation of the hemodynamics in the esophageal varices and portal trunk in group II and the functional hemodynamic continuity in group I. This functional separation between the esophageal varices and the portal trunk in group II might therefore have resulted from the increased blood flow in the lesser splanchnic region.

Blood Pressure↗

Effects of escins Ia, Ib, IIa, and IIb from horse chestnut, the seeds of Aesculus hippocastanum L., on acute inflammation in animals.

We investigated the effects of escins Ia, Ib, and IIb isolated from horse chestnut, the seeds of Aesculus hippocastanum L., and desacylescins I and II obtained by alkaline hydrolysis of escins on acute inflammation in animals (p.o.). Escins Ia, Ib, IIa, and IIb (50-200 mg/kg) inhibited the increase of vascular permeability induced by both acetic acid in mice and histamine in rats. Escins Ib, IIa, and IIb (50-200 mg/kg) also inhibited that induced by serotonin in rats, but escin Ia didn't. Escins Ia, Ib, IIa, and IIb (200 mg/kg) inhibited the hind paw edema induced by carrageenin at the first phase in rats. Escin Ia (200 mg/kg) and escins Ib, IIa, and IIb (50-200 mg/kg) inhibited the scratching behavior induced by compound 48/80 in mice, but escin Ia was weakest. Desacylescins I and II (200 mg/kg) showed no effect. With regard to the relationship between their chemical structures and activities, the acyl groups in escins were essential. Escins Ib, IIa, and IIb with either the 21-angeloyl group or the 2'-O-xylopyranosyl moiety showed more potent activities than escin Ia which had both the 21-tigloyl group and the 2'-O-glucopyranosyl moiety.

Acute Disease↗