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A Tsuchida

Publications and source records attributed to A Tsuchida.

At least 19 recordsLinked to original sources
PubMed2007

Brain-derived neurotrophic factor enhances glucose utilization in peripheral tissues of diabetic mice.

AIMS: Repetitive subcutaneous or intracerebroventricular administration of brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and enhances energy expenditure in obese diabetic C57BL/KsJ-db/db mice. To explore the mechanism of action through which BDNF regulates glucose metabolism, we examined the effects of BDNF on glucose utilization and norepinephrine (NE) content in peripheral tissues of diabetic mice. METHODS: [(14)C]2-deoxyglucose ([(14)C]2-DG) uptake into peripheral tissues was analysed after intravenous injection of [(14)C]2-DG in db/db and normal C57BL/6 mice, and [(14)C]2-DG uptake and NE content in peripheral tissues were analysed after subcutaneous administration of BDNF (20 mg/kg) to male db/db and normal mice for 8 days. RESULTS: [(14)C]2-DG uptake in the diaphragm, heart, gastrocnemius, soleus and interscapular brown adipose tissue (BAT) of db/db mice was significantly lower than in normal mice. Repetitive administration of BDNF to db/db mice for 8 days enhanced [(14)C]2-DG uptake in the diaphragm, heart, soleus, BAT and liver. The NE content in heart, skeletal muscle, interscapular BAT and liver of db/db mice given BDNF was high compared with db/db mice given vehicle, whereas no significant change in NE content in peripheral tissues was observed in normal mice given BDNF and those given vehicle. BDNF did not affect [(14)C]2-DG uptake or NE content in the white adipose tissue of db/db mice. CONCLUSIONS: These data indicate that BDNF ameliorates glucose metabolism by enhancement of glucose utilization in muscle and BAT, with this effect caused by modulation of the central and peripheral nervous systems.

Adipose Tissue, Brown↗
PubMed2006

Combination chemotherapy with docetaxel and nedaplatin for recurrent esophageal cancer in an outpatient setting.

The purpose of this study was to address the feasibility of combination chemotherapy of docetaxel and nedaplatin for recurrent esophageal cancer patients in an outpatient setting. Patients received docetaxel (30 mg/m(2) intravenously) on day 1 and nedaplatin (40 mg/m(2) intravenously) on day 1 every 2 weeks. In total, 28 patients with recurrent esophageal cancer after the initial treatment (esophagectomy, chemotherapy and/or chemoradiotherapy) were enrolled. Each patient received six cycles of treatment and was evaluated with a computed tomography scan. The percentage of patients who completed this therapy was 60.7%. Complete response and partial response were achieved by 3.6% and 35.7% of patients, respectively. The most frequent toxicities were leukopenia and anemia; non-hematological toxicities were generally mild. There was no treatment-related death. The median survival time and 1-year survival rate were 8.5 months and 15.9%, respectively. This outpatient combination chemotherapy was useful as second-line chemotherapy for recurrent esophageal cancer.

Aged↗
PubMed2005

Puncture of solid pancreatic tumors guided by endoscopic ultrasonography: a pilot study series comparing Trucut and 19-gauge and 22-gauge aspiration needles.

BACKGROUND AND STUDY AIMS: The aim of this prospective study was to compare endoscopic ultrasonography-guided Trucut needle biopsy (EUS-TNB) with EUS-guided fine-needle aspiration biopsy (EUS-FNAB) using 19- and 22-gauge needles for biopsy from different sites in patients with solid pancreatic cancers. PATIENTS AND METHODS: Sixteen consecutive patients with masses in the uncinate process (n = 3), the head (n = 5), or the body and tail (n = 8) of the pancreas underwent both EUS-TNB and EUS-FNAB. The specimens obtained were evaluated by histopathological analysis alone RESULTS: Tissue specimens were obtained by Trucut needle, and by 19-gauge and 22-gauge aspiration needles in 69 %, 69 %, and 100 % of patients respectively. Sensitivity for malignancy was 69 % for all needles. Tissue sampling by Trucut and by 19-gauge aspiration needle from masses in the uncinate process was impossible. The sensitivity of the Trucut and 19-gauge aspiration needles was 100 % in the 11 patients with successful procedures. If Trucut or 19-gauge aspiration needles had been used for body and tail masses, and the 22-gauge aspiration needle for masses in the uncinate process and head, the sensitivity for malignancy would have been 81 %. CONCLUSIONS: EUS-TNB allows reliable tissue sampling for the diagnosis of pancreatic masses, but its use is limited to lesions in the body and tail of the pancreas. EUS-FNAB using a 22-gauge needle may be useful for accurate diagnosis in some patients with masses in the uncinate process or the head of the pancreas.

Aged↗
PubMed2003

Anti-obesity and anti-diabetic effects of brain-derived neurotrophic factor in rodent models of leptin resistance.

OBJECTIVE: Obesity in rodents and humans is mostly associated with elevated plasma leptin concentrations, suggesting a new pathological concept of 'leptin resistance'. We have demonstrated that brain-derived neurotrophic factor (BDNF) can improve obesity and diabetes of C57BL/KsJ db/db (db/db) mice. In this study, we investigated whether or not BDNF is effective in two different models of leptin resistance, an acquired model and a genetic model. DESIGN: C57BL/6J mice rendered obese by consumption of a high-fat diet (diet-induced obesity (DIO) mice) were used as an acquired model and lethal yellow agouti mice (KKA(y) mice) as a genetic model of leptin resistance. Food intake and glucose metabolism were studied after acute or repetitive administration of BDNF. RESULTS: Intraperitoneal administration of BDNF (10 mg/kg, twice/day) significantly reduced cumulative food intake of DIO and KKA(y) mice, whereas they were unresponsive to leptin administration. Repetitive subcutaneous administration of BDNF (10 mg/kg daily for 6 days) reduced food intake and improved impaired glucose tolerance in DIO mice. Pair feeding of vehicle-treated DIO mice with the same amount of chow consumed by the BDNF-treated group did not improve the impaired glucose homeostasis, indicating that the antidiabetic effect is not due to decreased food intake. We also observed that BDNF is effective in improving obesity and diabetes of KKA(y) mice. CONCLUSION: This study demonstrated antiobesity and antidiabetic effects of BDNF in two different models of leptin resistance, thereby suggesting the therapeutic potential of BDNF in the treatment of leptin-resistant obesity and diabetes.

Animals↗
PubMed2002

Brain-derived neurotrophic factor ameliorates lipid metabolism in diabetic mice.

AIM: It has been reported previously that brain-derived neurotrophic factor (BDNF) regulates blood glucose metabolism in rodent obese diabetic models such as C57BL/KsJ-leprdb/leprdb (db/db) mice. BDNF further regulates energy expenditure, possibly through the central and autonomous nervous systems. In this study, we evaluated the effect of BDNF on both lipid and glucose metabolisms to clarify its action mechanism. METHODS: To control the energy intake, we used a pellet pair-feeding apparatus to synchronize food intake precisely between BDNF-treated and vehicle-treated db/db mice. BDNF (50 mg/kg/week) was subcutaneously injected to male db/db mice twice weekly for 3 weeks, and blood glucose, serum biochemical lipid parameters and tissue weights were measured. Liver triglyceride contents were measured and liver sections were histologically analysed. RESULTS: Twice weekly BDNF treatment for 3 weeks significantly lowered blood glucose compared with pellet pair-fed, vehicle-treated db/db mice (294 +/- 109 vs. 529 +/- 91 mg/dL). Serum non-esterified free fatty acid (726 +/- 72 vs. 999 +/- 220 microEq/l), total cholesterol (125 +/- 8 vs. 151 +/- 23 mg/dL) and phospholipid levels (215 +/- 13 vs. 257 +/- 36 mg/dL) of the BDNF-treated db/db mice decreased significantly. Liver weights (1.51 +/- 0.11 vs. 2.05 +/- 0.11 g), liver triglyceride contents (17.5 +/- 1.4 vs. 26.1 +/- 2.1 mg/g) and fatty liver in histological appearance were reduced with BDNF treatment. There were no significant differences in body weights and white adipose tissue weights between the two groups. CONCLUSIONS: Taken together with the accelerating effect of BDNF on energy metabolism, these findings indicate that BDNF improves glucose and lipid metabolism in obese diabetic animals without enlarging liver or adipose tissues.

Adipose Tissue↗
PubMed2001

Is frozen section effective for diagnosis of unsuspected gallbladder cancer during laparoscopic cholecystectomy?

BACKGROUND: Although frozen section is recommended to prevent tumor dissemination following laparoscopic cholecystectomy (LC) for unsuspected gallbladder cancer, there are no reports concretely demonstrating its effectiveness and outcome. METHODS: Frozen section during LC was performed in 990 patients with gallstones. The sensitivity, specificity of frozen section, and false-negative cases were evaluated in comparison with postoperative entire cross sections. RESULTS: In frozen section, 983 cases were diagnosed as benign and 7 cases as malignant. Of the benign cases, cancer was discovered in 4 patients postoperatively in which frozen section was diagnosed as regenerative epithelial severe atypia. Sensitivity was 64% and specificity was 100%. Concerning the results of frozen section by p-TNM classification, cancer was diagnosed in 40% of Tis lesions, whereas it was found in 83% of T2 or T3 lesions. CONCLUSION: Frozen section is effective in cases with T2 or greater lesions for which conversion to radical surgery should be required.

Adult↗
PubMed2001

The mechanisms by which both heterozygous peroxisome proliferator-activated receptor gamma (PPARgamma) deficiency and PPARgamma agonist improve insulin resistance.

Peroxisome proliferator-activated receptor (PPAR) gamma is a ligand-activated transcription factor and a member of the nuclear hormone receptor superfamily that is thought to be the master regulator of fat storage; however, the relationship between PPARgamma and insulin sensitivity is highly controversial. We show here that supraphysiological activation of PPARgamma by PPARgamma agonist thiazolidinediones (TZD) markedly increases triglyceride (TG) content of white adipose tissue (WAT), thereby decreasing TG content of liver and muscle, leading to amelioration of insulin resistance at the expense of obesity. Moderate reduction of PPARgamma activity by heterozygous PPARgamma deficiency decreases TG content of WAT, skeletal muscle, and liver due to increased leptin expression and increase in fatty acid combustion and decrease in lipogenesis, thereby ameliorating high fat diet-induced obesity and insulin resistance. Moreover, although heterozygous PPARgamma deficiency and TZD have opposite effects on total WAT mass, heterozygous PPARgamma deficiency decreases lipogenesis in WAT, whereas TZD stimulate adipocyte differentiation and apoptosis, thereby both preventing adipocyte hypertrophy, which is associated with alleviation of insulin resistance presumably due to decreases in free fatty acids, and tumor necrosis factor alpha, and up-regulation of adiponectin, at least in part. We conclude that, although by different mechanisms, both heterozygous PPARgamma deficiency and PPARgamma agonist improve insulin resistance, which is associated with decreased TG content of muscle/liver and prevention of adipocyte hypertrophy.

Adipocytes↗
PubMed2001

Angiotensin II type 1 receptor expression in human pancreatic cancer and growth inhibition by angiotensin II type 1 receptor antagonist.

We investigated the expression of angiotensin II type 1 receptor (AT1) in pancreatic cancer. Both AT1 mRNA and protein were expressed in human pancreatic cancer tissues and cell lines. Binding assays showed that pancreatic cancer cells have specific binding sites for angiotensin II and that binding could be eliminated by treatment with a selective AT1 antagonist in a dose-dependent fashion. Surprisingly, the growth of cancer cells was significantly suppressed by treatment with antagonist, also in a dose-dependent manner. These observations suggest AT1 plays an important role in pancreatic cancer growth. Furthermore, ligand-induced inhibition of AT1 may be a useful therapeutic strategy.

Angiotensin II↗
PubMed2001

Toxic effect of troglitazone on cultured rat hepatocytes.

We examined the cytotoxicity of troglitazone toward cultured rat hepatocytes. The drug concentration- and time-dependently decreased cell viability and increased lactate dehydrogenase leakage from the cells. Troglitazone-induced cell death was characterized by "DNA ladders", condensation of nuclei, and a positive reaction to in situ nick-end labeling. The results indicate that troglitazone can cause apoptotic cell death in cultured rat hepatocytes.

Animals↗
PubMed2001

Mitochondrial ATP-sensitive K+ channels play a role in cardioprotection by Na+-H+ exchange inhibition against ischemia/reperfusion injury.

OBJECTIVES: The possible role of the ATP-sensitive potassium (KATP) channel in cardioprotection by Na+-H+ exchange (NHE) inhibition was examined. BACKGROUND: The KATP channel is suggested to be involved not only in ischemic preconditioning but also in some pharmacological cardioprotection. METHODS: Infarction was induced by 30-min coronary occlusion in rabbit hearts in situ or by 30-min global ischemia in isolated hearts. Myocardial stunning was induced by five episodes of 5-min ischemia/5-min reperfusion in situ. In these models, the effects of NHE inhibitors (cariporide and ethylisopropyl-amiloride [EIPA]) and the changes caused by KATP channel blockers were assessed. In another series of experiments, the effects of EIPA on mitochondrial KATP (mito-KATP) and sarcolemmal KATP (sarc-KATP) channels were examined in isolated cardiomyocvtes. RESULTS: Cariporide (0.6 mg/kg) reduced infarct size in situ by 40%, and this effect was abolished by glibenclamide (0.3 mg/kg), a nonselective KATP channel blocker. In vitro, 1 microM cariporide limited infarct size by 90%, and this effect was blocked by 5-hydroxydecanoate (5-HD), a mito-KATP channel blocker but not by HMR1098, a sarc-KATP channel blocker. Infarct size limitation by 1 microM EIPA was also prevented by 5-HD. Cariporide attenuated regional contractile dysfunction by stunning, and this protection was abolished by glibenclamide and 5-HD. Ethylisopropyl amiloride neither activated the mito-KATP channel nor enhanced activation of this channel by diazoxide, a KATP channel opener. CONCLUSIONS: Opening of the mito-KATP channel contributes to cardioprotection by NHE inhibition, though the interaction between NHE and this KATP channel remains unclear.

Animals↗
PubMed2001

Preoperative diagnosis of intraductal papillary-mucinous tumors of the pancreas with attention to telomerase activity.

BACKGROUND: It has been reported that, in patients with intraductal papillary-mucinous tumor (IPMT) of the pancreas, it is difficult to distinguish adenoma from carcinoma preoperatively. Recently, it has also been reported that telomerase activity was detected in many patients with carcinoma. In this report, the authors used the method of telomerase repeat amplification protocol (TRAP) assay on pancreatic juice retrieved by endoscopic retrograde pancreatic juice aspiration (ERP aspiration). METHODS: Pancreatic juice was collected from 28 patients (13 with intraductal carcinoma and 15 with adenoma) using ERP aspiration at either Hiroshima University Hospital or its affiliated hospitals. Two samples of pancreatic juice were collected from each patient. Each sample was examined by cytology for Papanicolaou staining and TRAP assay. RESULTS: Four of 13 IPMT patients (31%) with intraductal carcinoma were diagnosed accurately by cytology. Seven of nine patients who were classified with benign tumors by cytologic assessment had tumors that expressed telomerase activity. Overall, 11 of 13 IPMT patients (85%) with intraductal carcinoma were diagnosed correctly by cytology associated with telomerase activity. All of the IPMT patients with adenoma were classified with benign tumors by cytologic assessment, and telomerase activity was not expressed. CONCLUSIONS: In this study, the authors found that telomerase activity was expressed with a comparatively high probability in intraductal carcinoma. These results suggest that telomerase activity in pancreatic juices may be used as an adjunct to cytologic diagnosis and may aid further in distinguishing between benign IPMT and malignant IPMT of the pancreas preoperatively.

Adenocarcinoma, Mucinous↗
PubMed2001

The effects of brain-derived neurotrophic factor on insulin signal transduction in the liver of diabetic mice.

AIM/HYPOTHESIS: We previously reported that repeated subcutaneous or intracerebroventricular injection of brain-derived neurotrophic factor (BDNF) reduces blood glucose concentrations in obese diabetic C57BL/KsJ-db/db mice. In this study, we assessed the effects of BDNF on insulin action in peripheral tissues of diabetic mice. METHODS: First, brain-derived neurotrophic factor (20 mg/kg) was subcutaneously given to male db/db mice for 14 days and then the insulin-stimulated tyrosine phosphorylation of insulin receptors and insulin-stimulated phosphatidylinositol (PI) 3-kinase activity in peripheral tissues was assessed. Second, we examined the effects of a single subcutaneous or intracerebroventricular brain-derived neurotrophic factor injection on insulin responsiveness in liver and skeletal muscle of streptozotocin (STZ)-induced diabetic mice. Third, the effects of brain-derived neurothrophic factor on insulin action were also examined in cultured cells. RESULTS: Repeated injection of BDNF to db/db mice for 14 days enhanced insulin-stimulated tyrosine phosphorylation of insulin receptors in liver and insulin-stimulated PI 3-kinase activity in liver, skeletal muscle and interscapular brown adipose tissue. We then examined the rapid effect of BDNF on insulin signalling in vivo. A single subcutaneous or intracerebroventricular injection of BDNF rapidly increased insulin-stimulated tyrosine phosphorylation of insulin receptors and PI 3-kinase activity in liver of STZ-mice. No direct effect of brain-derived neurothrophic factor was observed on insulin signalling in primary cultured hepatocytes, L6 muscle cells or 3T3-L1 adipocytes. Brain-derived neurothrophic factor did not affect either glucose uptake or gluconeogenesis in these cells. CONCLUSION/INTERPRETATION: These data indicate that brain-derived neurothrophic factor rapidly enhances insulin signal transduction in liver and shows hypoglycaemic action in diabetic mice.

3T3 Cells↗
PubMed2001

Contribution of both the sarcolemmal K(ATP) and mitochondrial K(ATP) channels to infarct size limitation by K(ATP) channel openers: differences from preconditioning in the role of sarcolemmal K(ATP) channels.

The roles of sarcolemmal ATP-sensitive K+ (sarcK(ATP)) and mitochondrial ATP-sensitive K+ (mitoK(ATP)) channels in the cardioprotection induced by K(ATP) channel openers remain unclear, though the mitoK(ATP) channel has been proposed to be involved as a subcellular mediator in cardioprotection afforded by ischemic preconditioning (PC). In the present study, selective inhibitors of the sarcK(ATP) and mitoK(ATP) channels were used to examine the role of each channel subtype in infarct size limitation by KATP channel openers. Isolated rabbit hearts were perfused in the Langendorff mode with monitoring of the activation recovery interval (ARI) and subjected to 30-min global ischemia/2-h reperfusion to induce infarction. Before ischemia, hearts received 10 microM pinacidil, 100 microM diazoxide, or PC with or without preceding infusion of a sarcK(ATP) channel-selective blocker (5 microM HMR1098) or a mitoK(ATP) channel-selective blocker (100 microM 5-hydroxydecanoate, 5-HD). ARI, an index of action potential duration, was shortened from 118+/-3 ms to 77+/-5 ms after 10 min of ischemia in untreated control hearts. Pinacidil shortened ARI before ischemia from 113+/-2 ms to 78+/-5 ms and enhanced the ARI shortening during ischemia. Diazoxide did not affect ARI before ischemia but accelerated ischemia-induced shortening of ARI. Infarct size as a percentage of the left ventricle (%IS/LV) was reduced by pinacidil and diazoxide from the control value of 47.2+/-4.0% to 4.5+/-1.5% and 5.2+/-1.2%, respectively. HMR1098 significantly inhibited the shortening of ARI by ischemia, pinacidil and diazoxide and partially blocked infarct size limitation by these K(ATP) channel openers (%IS/LV=32.6+/-4.2% and 23.4+/-5.3%, respectively). Infusion of 5-HD did not modify the change in ARI caused by the K(ATP) channel openers but completely abolished cardioprotection (%IS/LV=46.0+/-6.2% with pinacidil and 57.2+/-7.0% with diazoxide). PC with two episodes of 5-min ischemia limited %IS/LV to 21.6+/-4.0%, and this protection was not inhibited by HMR1098. Neither HMR1098 nor 5-HD alone modified infarct size. In conclusion, both sarcK(ATP) and mitoK(ATP) channels may contribute to the anti-infarct tolerance afforded by pinacidil and diazoxide.

Analysis of Variance↗
PubMed2001

Critical timing of mitochondrial K(ATP) channel opening for enhancement of myocardial tolerance against infarction.

OBJECTIVE: The present study was designed to assess the relationship between the timing of a mitoK(ATP) channel opener, diazoxide, and its infarct size-limiting effect. METHODS: In isolated rabbit hearts, infarction was induced by 30 min of global ischemia and 2 h of reperfusion, and infarct size was determined by tetrazolium staining and expressed as a percentage of the left ventricle (%IS/LV). Diazoxide, a mitoK(ATP) channel selective opener, and/or 5-hydroxydecanoate (5-HD), a mitoK(ATP) channel blocker, were infused before or after the onset of ischemia. When these agents were infused during the ischemic period, they were dissolved in a hypoxic buffer at concentrations 10-fold higher than those in the pre-ischemic period, and the infusion rate was set at 2% of the pre-ischemic coronary flow. RESULTS: In untreated controls, %IS/LV was 53.2+/-4.1 (SE). Pretreatment with diazoxide (100 microM) with a 10-min washout period reduced %IS/LV to 7.8+/-2.4 and this protection was abolished by co-infusion of 5-HD (50 microM). Pre-ischemic infusion of diazoxide without a washout period reduced %IS/LV to 7.3+/-1.4, and infusion of diazoxide from 10 min after the onset of ischemia also limited %IS/LV to 14.9+/-4.6. However, diazoxide infusion from 25 min after the onset of ischemia failed to reduce infarct size (%IS/LV = 54.5+/-7.2). Furthermore, pretreatment with 5-HD (50 microM) also completely abolished the protection afforded by early post-ischemic diazoxide infusion (%IS/LV = 48.3+/-6.5). Neither infusion of 5-HD nor the anoxic vehicle alone during ischemia modified %IS/LV. CONCLUSION: These findings suggest that opening of mitoK(ATP) channels before ischemia and during early ischemia, but not that upon reperfusion, is important for enhancement of myocardial tolerance against infarction.

Animals↗
PubMed2001

Ultrastructure of NADPH diaphorase-positive nerve fibers and their terminals in the rat cerebral arterial system.

To investigate how perivascular NO synthase (NOS)-containing nerves in the cerebral arterial system are involved in controlling the cerebral circulation, we observed the ultrastructure of NOS-containing nerve fibers and their terminals by means of nicotinamide adenine dinucleotide hydrogen phosphate-diaphorase (NADPH-d) histochemistry. We also observed the correlation between NADPH-d stained perivascular nerves and the perivascular sympathetic nerves, by means of double staining with NADPH-d histochemistry and tyrosine hydroxylase (TH) immunohistochemistry at the light microscopic level. NADPH-d-positive nerve fibers showed dense distribution mainly in the rostral portion of the circle of Willis and proximal portions of its main branches, where some of the NADPH-d-positive fibers coexisted with TH-positive fibers in a single nerve bundle. NADPH-d-positive nerve fibers were unmyelinated and had close contact with NADPH-d-negative myelinated and unmyelinated nerve fibers in a single nerve bundle, and NADPH-d-positive nerve terminals also existed closely with NADPH-d-negative nerve terminals. The number of NADPH-d-positive nerve terminals and their ratio to all other terminals were significantly higher in the rostral portion of the circle of Willis and the proximal portion of its branches, than the caudal portion of the circle of Willis and the distal portion of its branches. Nerve terminals were observed to locate within 250 nm from the basal lamina of arterial smooth muscle cells in the rostral portion of the circle of Willis and proximal portion of its branching arteries. The present observation confirmed that NOS-containing nerve fibers truly innervate the smooth muscle cells of the arterial wall in the circle of Willis and its main branches. Close contact between NADPH-d-positive and -negative nerve fibers and terminals in these arterial portions may indicate that NOS-containing perivascular nerves may work to modulate the rest of the other perivascular nervous system, such as the sympathetic nerves, to regulate the homeostasis of the arterial tonus.

Animals↗