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Biomedical subjects

N Harada

Publications and source records attributed to N Harada.

At least 181 records · Page 10Linked to original sources
PubMed1999

Antithrombin reduces ischemia/reperfusion injury of rat liver by increasing the hepatic level of prostacyclin.

We investigated whether antithrombin (AT) can reduce ischemia/reperfusion (I/R)-induced injury of rat liver by promoting prostacyclin release from endothelial cells. Although intravenous administration of AT (250 U/kg) markedly reduced hepatic injury, neither dansyl-Glu-Gly-Arg-chloromethyl ketone-treated factor Xa (DEGR-Xa), a selective inhibitor of thrombin generation, nor Trp49-modified AT, which lacks affinity for heparin, had any effect. Hepatic levels of 6-keto-PGF1, a stable prostacyclin (PGI2) metabolite, were increased significantly after I/R of the rat liver. AT significantly increased the hepatic level of 6-keto-PGF1, whereas neither DEGR-Xa nor Trp49-modified AT increased it. Hepatic tissue blood flow was markedly reduced after I/R. Although AT significantly increased the hepatic tissue blood flow after I/R, neither DEGR-Xa nor Trp49-modified AT increased the blood flow. Hepatic levels of cytokine-induced neutrophil chemoattractant (CINC) and myeloperoxidase (MPO) were significantly increased after hepatic I/R. The levels of these two indicators were reduced by AT but were unaffected by either DEGR-Xa or Trp49-modified AT. Pretreatment of animals with indomethacin (IM) completely inhibited the protective effects of AT on the I/R-induced hepatic damage and the leukocyte activation as well as the AT-induced increase in hepatic 6-keto-PGF1 levels after I/R. Iloprost, a stable analog of PGI2, exhibited effects similar to those of AT and also significantly inhibited the exacerbation of liver injury, the decrease in hepatic tissue blood flow, and the increases in hepatic CINC and MPO levels seen in rats subjected to I/R but pretreated with IM. These findings suggest that AT may prevent I/R-induced hepatic injury by increasing the hepatic levels of PGI2 through the interaction of AT with cell-surface glycosaminoglycans, thus increasing hepatic tissue blood flow and inhibiting leukocyte activation in animals subjected to I/R.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Tumor of the ampulla of Vater: experience with local or radical resection in 171 consecutively treated patients.

HYPOTHESIS: This study was designed to evaluate prospectively oncological factors determining survival after resection of tumors of the papilla, comparing local and radical oncological resection. We hypothesized that, in malignant lesions of the ampulla, the T and N stages are major determinants of the patient's long-term outcome. BACKGROUND DATA: The frequency of malignant lesions in adenomas of the papilla is about 26%. Villous adenoma of the ampulla is considered a premalignant lesion. Local excision has been recommended for benign adenoma and pancreatoduodenectomy for malignant lesions. PATIENTS AND METHODS: From January 1, 1982, through June 30, 1997, 171 patients with tumors of the ampulla of Vater were surgically treated. Demographics, intraoperative factors, tumor pathological findings, and postoperative short- and long-term follow-up data were documented prospectively. Of the patients, 45 had adenoma of the papilla and 126 had malignant lesions of the ampulla. RESULTS: Local resection was performed in 40 of the 45 patients with adenoma. In 98 of the 126 patients with malignant lesions, a radical Kausch-Whipple resection or pylorus-preserving pancreatoduodenectomy was used. Of the patients with benign adenoma, 40 had local resection and 5 had pylorus-preserving pancreatic head resection, with a hospital mortality of 0%. Thirty of 35 patients had villous adenoma, 9 (30%) of the 30 with severe dysplasia. Of the 126 patients with malignant lesions, 98 had partial pancreatoduodenectomy and 10 had ampullectomy, with an overall hospital mortality of 3.1% for patients who underwent resection. Seventy-eight of the 98 patients had an R0 resection. The 5-year survival probability for all patients who underwent resection was 84% for cancer stage I, 70% for stage II, and 27% for stage III. In 8 patients with villous adenoma and carcinoma in situ and in 10 patients with cancer in the adenoma, ampullectomy with local lymph node dissection was performed. In 4 of the patients who had villous adenoma and a carcinoma in stage pT1 N0, an R0 resection was performed, resulting in cure of cancer. On the basis of a multivariate regression analysis, the prognosis after oncological resection of cancer of the ampulla is determined by the absence of lymph node metastasis (P<.05), the absence of infiltration into the pancreatic head tissue (P<.05), and the application of an R0 resection. CONCLUSIONS: In patients with villous adenoma of the ampulla, ampullectomy was an adequate surgical treatment. In patients with a low-risk cancer in stages pTis and pT1 N0 M0, G1 or G2, a local resection with ampullectomy including local lymph node dissection is justified. An oncological resection of cancer of the ampulla by means of a pylorus-preserving partial pancreatoduodenectomy or the Kausch-Whipple resection is the surgical procedure of choice; the 3- and 5-year survival rates were 72% and 52%, respectively, in patients with R0 resections.

Adenoma↗
PubMed1999

A minireview of studies conducted in japan using finger-skin temperature during cold-stress tests for the diagnosis of hand-arm vibration syndrome.

For the diagnosis of the hand-arm vibration syndrome, cold-stress tests using different water temperatures and periods of hand immersion have been investigated in Europe, North America, and Japan. In recent years, peripheral circulation and sensory tests, including finger-skin temperature measurement involving immersion of one hand in cold water at 10 degrees C for 10 min, have been widely accepted in Japan. On the other hand, standardization of the vascular assessment method is under discussion at the International Organization of Standardization. We reviewed research findings from Japan concerning finger-skin temperature measurement during the cold-stress test, especially factors influencing the test results and the diagnostic significance. For establishment of the cold-stress test for epidemiology studies of the hand-arm vibration syndrome, standardization of the environmental factors influencing the test results and reporting of its sensitivity and specificity are needed.

Arm↗
PubMed1999

Assessment of autonomic nervous activity in hand-arm vibration syndrome patients using time- and frequency-domain analyses of heart rate variation.

OBJECTIVES: The aim of the present study was to non-invasively assess autonomic nervous activity, using time- and frequency-domain analyses of heart rate variation (HRV), and to investigate the relationship between indices of HRV and duration of exposure to vibration (DEV), time since retirement from work involving vibration (TR) and time undergoing treatment (TT) in a group of patients with hand-arm vibration syndrome (HAVS). SUBJECTS AND METHODS: Twenty one HAVS patients who were no longer exposed to vibration and were undergoing standard treatment for HAVS, and 10 healthy control subjects, similar to the patients in age, height, weight and number of current smokers and drinkers, volunteered for this study. Indices of HRV [time-domain indices (the mean of R-R intervals, standard deviation and coefficient of variation) and normalized units of frequency-domain indices [low frequency (LF) and high frequency (HF) components], indicating parasympathetic nervous activity, were calculated from 2 min electrocardiographic data recorded during spontaneous breathing by subjects in supine rest. RESULTS: The LF and HF components of the patients were significantly lower than those of the healthy controls (P < 0.05). When Pearson correlation analysis was applied for the patient group, using indices of HRV with age, weight, height, DEV, TR and TT, the LF components positively related to TR and TT (P < 0.01). The patients were thus divided into three groups as follows, according to TR: group A (</=1 year), group B (>1 to <5 years) and group C (>/=5 to </=10 years), or according to TT: group X (</=1 year), group Y (>1 to <5 years) and group Z (>/=5 to </=10 years). The LF components of the groups A and X were significantly lower than that of the healthy controls (P < 0.01). The HF components of the groups A and X were also significantly lower than that of the healthy controls (P < 0.05). CONCLUSIONS: The findings of the present study indicate decreased cardiac parasympathetic activity in the HAVS patients in comparison to the healthy controls. The TT and TR significantly influenced the HRV results in these patients; however, the DEV did not. The findings also indicate that treatment and cessation of exposure to vibration might have a beneficial effect on the cardiac parasympathetic activity in HAVS patients.

Aged↗
PubMed1999

Grasping forceps assisted endoscopic resection of large pedunculated GI polypoid lesions.

BACKGROUND: Endoscopic resection of pedunculated polyps with heads 1 cm or greater in diameter is technically complex. To facilitate removal of such polyps, we developed grasping forceps assisted endoscopic resection in which we use a detachable snare to prevent polypectomy-related bleeding and evaluated the usefulness and safety of the procedure. METHODS: Ten patients with pedunculated polyps with heads 1 cm or greater in diameter were treated with this technique. A two-channel endoscope, grasping forceps, electrosurgical snare, and detachable snare are needed for the procedure. RESULTS: All lesions were easily and safely resected. During this procedure, a two-channel endoscope with grasping forceps proved to be satisfactory for handling the detachable snare and the electrosurgical snare and for accurate recognition of the stalk under good visual control. No hemorrhage, perforation, or other complication occurred as a result of use of this new technique. CONCLUSIONS: Grasping forceps assisted endoscopic resection of polyps with a detachable snare is an effective method for the prevention of polypectomy-associated bleeding. This technique makes it technically easier to resect large pedunculated polypoid lesions of the GI tract.

Aged↗
PubMed1999

Antithrombin prevents stress-induced gastric mucosal injury by increasing the gastric prostacyclin level in rats.

The interaction of antithrombin (AT) with cell surface glycosaminoglycans has been shown to promote the endothelial release of prostacyclin (PGI2). Because PGI2 plays an important role in gastric cytoprotection, we examined whether AT prevents water-immersion restraint stress (WIR)-induced gastric mucosal injury in rats by promoting the endothelial release of PGI2. Intravenous administration of AT (250 U/kg) prevented WIR-induced gastric mucosal injury in rats. Gastric levels of 6-keto-prostaglandin F1alpha, a stable metabolite of PGI2, were significantly increased 0.5 and 1 hour after WIR in animals administered AT compared with control animals. The effects induced by AT in animals subjected to WIR were not observed in animals that were administered DEGR-Xa, a selective inhibitor of thrombin generation, or Trp49-modified AT, which lacks affinity for heparin. In animals subjected to WIR gastric mucosal blood flow was significantly reduced with a simultaneous increase in gastric mucosal microvascular permeability. Activated neutrophils have been implicated in the WIR-induced reduction of gastric mucosal blood flow by increasing microvascular permeability. Although AT prevented the reduction of gastric mucosal blood flow and the increase in gastric mucosal microvascular permeability in animals subjected to WIR, neither DEGR-Xa nor Trp49-modified AT had any effect. Pretreatment of animals with indomethacin completely inhibited the protective effects of AT against WIR-induced gastric mucosal injury and the AT-induced increase in post-WIR gastric 6-keto-prostaglandin F1alpha levels. These results strongly suggest that AT prevents stress-induced gastric mucosal injury by increasing the gastric levels of PGI2 through the interaction of AT with cell-surface glycosaminoglycans, thus increasing gastric mucosal blood flow both by vasodilation and by inhibiting neutrophil activation.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Gastric prostacyclin (PGI2) prevents stress-induced gastric mucosal injury in rats primarily by inhibiting leukocyte activation.

We investigated whether, in rats, gastric prostacyclin (PGI2) prevented gastric mucosal injury that was induced by water-immersion restraint stress by inhibiting leukocyte activation. Gastric levels of 6-keto-PGF1alpha, a stable metabolite of PGI2, increased transiently 30 min after stress, followed by a decrease to below the baseline 6-8 h after stress. Gastric mucosal blood flow decreased to approximately 40% of the baseline level 8 h after stress. Myeloperoxidase activity was significantly increased 8 h after stress. Treatment with indomethacin before stress inhibited the increase in 6-keto-PGF1alpha levels and markedly reduced mucosal blood flow. It also markedly increased leukocyte accumulation and mucosal lesion formation. Iloprost, a stable PGI2 analog, inhibited the indomethacin-induced decrease in mucosal blood flow, mucosal lesion exacerbation, and increase in leukocyte accumulation. Nitrogen mustard-induced leukocytopenia inhibited the indomethacin-associated lesion exacerbation and the increase in leukocyte accumulation, but not the decreases in mucosal blood flow. These observations indicate that gastric PGI2 decreases gastric mucosal lesion formation primarily by inhibiting leukocyte accumulation.

6-Ketoprostaglandin F1 alpha↗
PubMed1999

Association of the interleukin-4 receptor alpha chain with p47phox, an activator of the phagocyte NADPH oxidase in B cells.

Interleukin (IL)-4 plays an important role in IgE synthesis in B cells and in Th2 differentiation in T cells. IL-4 conducts its biological activities through binding to the IL-4 receptor (IL-4R) on the surface of target cells. IL-4R are thought to be composed of the IL-4R alpha chain (IL-4R alpha) and either the IL-2R gamma chain or the IL-13R alpha chain. We have previously shown that the membrane-proximal portion in the cytoplasmic domain of the human IL-4R alpha (hIL-4R alpha) is critical for proliferation, generation of germline epsilon transcript, and activation of STAT6, based on analyses of truncated hIL-4R alphas. In this study, we found that p47phox, an activator of the phagocyte NADPH oxidase, binds to this portion by the two-hybrid system. Furthermore, we observed the association of p47phox with the hIL-4R alpha in B cells derived from a normal donor. These results suggest that p47phox is involved in the signal transduction of IL-4 in B cells. However, activation of STAT6, CD23 expression, and IgE synthesis induced by IL-4 were not affected in p47phox-deficient patients, which raises the possibility that p47phox may be important in other signaling activities as well in B cells.

Amino Acid Sequence↗
PubMed1999

Effects of cholesterol-lowering treatments on oxidative modification of plasma intermediate density lipoprotein plus low density lipoprotein fraction in Type 2 diabetic patients.

To investigate the normalization of enhanced oxidative modification of the lipoprotein such as increased lysophosphatidylcholine (LPC) and lipid hydroperoxide (LPO) contents in diabetic subjects, we studied the effect of cholesterol-lowering treatment on those parameters in 24 hypercholesterolemic Type 2 diabetic patients. Those patients were randomly assigned to two treatment groups, such as 12 patients treated with pravastatin 10 mg daily and 12 patients treated with probucol 500 mg daily for 8 weeks. Characteristics of the patients including age, gender, body mass index (BMI), smoking habit, modality of diabetic treatment and the glycemic control state were comparable between the two groups. LPC content in the lipoprotein fractions obtained from 24 patients with Type 2 diabetes mellitus was significantly higher than that of non-diabetic control subjects. The abnormality was improved to the control level after a significant improvement of serum cholesterol levels following 8 week-treatments with either probucol or pravastatin without any change in glycemic control (P < 0.025). Furthermore, increased LPO content in the lipoprotein fraction in those diabetics was also significantly (P < 0.0025) improved by the probucol treatment and tended to be improved by pravastatin treatment (P = 0.06). LPC contents in the lipoprotein fraction was positively correlated with LPO contents before cholesterol-lowering treatments (r = 0.41, P < 0.05). These results indicate that cholesterol-lowering treatments effectively reduce oxidative modification of the lipoprotein fraction containing intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) in hypercholesterolemic Type 2 diabetic patients.

Anticholesteremic Agents↗
PubMed1999

Blood and urinary levels of ethanol, acetaldehyde, and C4 compounds such as diacetyl, acetoin, and 2,3-butanediol in normal male students after ethanol ingestion.

Aldehyde dehydrogenase (ALDH) isozyme 2 genes were determined in 15 students. Of these subjects, five healthy male students were administered 0.4 kg/kg ethanol. One subject was defective in aldehyde dehydrogenase 2 (ALDH2), two had normal ALDH2, and the other two were hetero type. After the intake of alcohol, the concentration of ethanol, acetaldehyde, and C4 compounds in blood and urine were determined. The student with the inactive form of ALDH2 was flushed and his levels of 2,3-butanediol and acetaldehyde in blood and urine were found to be the highest.

Acetaldehyde↗
PubMed1999

Inhibitory effects of beer and other alcoholic beverages on mutagenesis and DNA adduct formation induced by several carcinogens.

The possibility that beer and other alcoholic beverages could be antimutagenic against the heterocyclic amines (HAs), a group of carcinogens produced on cooking proteinaceous foods, has been explored. In the Salmonella mutation assays, beer showed inhibitory effects against several HAs [preactivated Trp-P-1, Trp-P-2(NHOH), and Glu-P-1(NHOH)] that are directly mutagenic in bacteria. Japanese sake, red and white wines, and brandy were also effective. However, ethyl alcohol alone did not show these effects. The formation of O(6)-methylguanine by N-methyl-N'-nitro-N-nitrosoguanidine in the DNA of Salmonella YG7108 was also inhibited by beer. Nonvolatile beer components were administered orally to CDF(1) mice together with Trp-P-2. Adducts in the liver DNA were significantly decreased by the beer, as compared to those in controls fed Trp-P-2 only. Although several phenolic compounds known to be present in beer were antimutagenic toward these mutagens, their effects were very small. It was concluded that some yet to be identified component(s) of beer is (are) responsible for this antimutagenicity.

Alcoholic Beverages↗
PubMed1999

Cilnidipine improves insulin sensitivity in the Otsuka Long-Evans Tokushima fatty rat, a model of spontaneous NIDDM.

Among the antihypertensive drugs, fast-acting Ca2+ antagonists have been reported to worsen insulin sensitivity. This effect may be attributable to reflex increases in sympathetic activity. On the other hand, however, it has been reported that long-acting, dihydropiridine Ca2+ antagonists improve insulin-resistance. The purpose of this study was to investigate whether cilnidipine, another long-acting dihydropidine Ca2+ antagonist, improves insulin sensitivity in Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous NIDDM. 25 weeks OLETF rats were divided into the following groups; normal-diet group, cilnidipine-supplemented group (cilnidipine 3 mg/kg/day) and angiotensin II receptor antagonist CS-866-supplemented group (CS-866 1 mg/kg/day). As a non-diabetic control, we used Long-Evans-Tokushima-Otsuka rats (non-diabetic rats). Glucose infusion rate (GIR), an index of insulin resistance, as measured by the hyperinsulinemic euglycemic clamp technique was significantly decreased in OLETF rats. Cilnidipine-treatment partially but significantly improved insulin sensitivity in addition to systolic blood pressure in OLETF rats at 30 weeks of age, although it did not decrease accumulation of abdominal fat or serum levels of glucose or insulin. CS-866, an angiotensin II receptor antagonist, which lowers blood pressure through a different mechanism, did not improve insulin resistant states in OLETF rats. These results suggest that cilnidipine has a beneficial effect on insulin-resistance together with the antihypertensive effect.

Animals↗
PubMed1999

Specific binding of TES-23 antibody to tumour vascular endothelium in mice, rats and human cancer tissue: a novel drug carrier for cancer targeting therapy.

The tissue distribution of anti-tumour vascular endothelium monoclonal antibody (TES-23) produced by immunizing with plasma membrane vesicles from isolated rat tumour-derived endothelial cells (TECs) was assessed in various tumour-bearing animals. Radiolabelled TES-23 dramatically accumulated in KMT-17 fibrosarcoma, the source of isolated TECs after intravenous injection. In Meth-A fibrosarcoma, Colon-26 adenocarcinoma in BALB/c mice and HT-1080 human tumour tissue in nude mice, radioactivities of 125I-labelled TES-23 were also up to 50 times higher than those of control antibody with little distribution to normal tissues. The selective recognition of TES-23 to TECs was competitively blocked by preadministration of unlabelled TES-23 in vivo. Furthermore, immunostaining of human tissue sections showed specific binding of TES-23 on endothelium in oesophagus cancers. These results indicate that tumour vascular endothelial cells express common antigen in different tumour types of various animal species. In order to clarify the efficacy of TES-23 as a drug carrier, an immunoconjugate, composed of TES-23 and neocarzinostatin, was tested for its anti-tumour effect in rats bearing KMT-17 fibrosarcomas. The immunoconjugate (TES-23-NCS) caused marked regression of the tumour, accompanied by haemorrhagic necrosis. Thus, from a clinical view, TES-23 would be a novel drug carrier because of its high specificity to tumour vascular endothelium and its application to many types of cancer.

Adenocarcinoma↗
PubMed1999

Detection of inducible nitric oxide synthase (iNOS) mRNA by RT-PCR in ATL patients and HTLV-I infected cell lines: clinical features and apoptosis by NOS inhibitor.

Various tumors have been reported to express an inducible form of nitric oxide synthase (iNOS), and nitric oxide (NO) may affect the clinicopathological features of these tumors. Previously, Burkitt's lymphoma and Epstein-Barr virus (EBV)-infected cells were shown to express iNOS constitutively at a low level. We analyzed iNOS expression by the reverse transcriptase-polymerase reaction method (RT-PCR) in eight HTLV-I-infected cell lines (five were ATL-derived lines and there were in vitro transformed lines), nine ATL patients (three were chronic, two were acute, and four were lymphoma type), and an HTLV-I-negative T cell line (CEM). In four ATL derived and in all three in vitro transformed cell lines, iNOS was expressed constitutively, but it was not expressed in CEM cells. Four out of nine ATL patients also showed iNOS expression. The expression of iNOS was found in all subtypes of ATL. Three of four iNOS-positive patients had infiltration of ATL cells to organs such as skin, lung, or liver. In NOS inhibitor (NG-monomethyl-L-arginine: L-NMMA)-containing medium, an iNOS-positive ATL cell line (K3T) showed growth inhibition and DNA ladder. Although only a limited number of patients was analyzed, our results suggest that NO may be involved in the invasive character of ATL cells. The NOS inhibitor can induce apoptosis in an ATL cell line, as it does in EBV-infected cell lines.

Apoptosis↗
PubMed1999

Plaunotol prevents indomethacin-induced gastric mucosal injury in rats by inhibiting neutrophil activation.

BACKGROUND: Activated neutrophils play a critical role in indomethacin-induced gastric mucosal injury. AIM: To investigate the effect of plaunotol, an anti-ulcer agent, on neutrophil activation in vitro and its effect on gastric mucosal injury and gastric accumulation of neutrophils in rats given indomethacin. METHODS: Human monocytes and neutrophils were isolated from the peripheral blood of healthy volunteers. We examined the effect of plaunotol on neutrophil elastase release, production of O2-, intracellular calcium concentration and expression of adhesion molecules CD11b and CD18 in activated neutrophils in vitro. The effect of plaunotol on TNF-alpha production by monocytes stimulated with endotoxin also was investigated in vitro. The effect of plaunotol (100 mg/kg, p.o.) on gastric mucosal injury and neutrophil accumulation was investigated in male Wistar rats given indomethacin (30 mg/kg, p.o.). RESULTS: Plaunotol inhibited the fMLP-induced release of neutrophil elastase from activated neutrophils, as well as the opsonized zymosan-induced production of O2- by neutrophils. Plaunotol significantly inhibited increased levels of intracellular calcium, a second messenger of neutrophil activation, in vitro. The fMLP-induced increases in CD11b and CD18 expression were also inhibited by plaunotol in vitro. Plaunotol inhibited monocytic production of TNF-alpha, a potent activator of neutrophils. Both gastric mucosal injury and gastric neutrophil infiltration in rats given indomethacin were significantly inhibited by the oral administration of plaunotol. CONCLUSIONS: Plaunotol inhibits indomethacin-induced gastric mucosal injury, at least in part by inhibiting neutrophil activation.

Animals↗
PubMed1999

Expression of PRAD1/cyclin D1 in plasma cell malignancy: incidence and prognostic aspects.

We analysed PRAD1/cyclin D1 expression in 20 patients with plasma cell malignancy by Northern analysis. 6/17 multiple myeloma patients and 3/3 plasma cell leukaemia patients showed PRAD1/cyclin D1 expression. This incidence appeared to be higher than the expected incidence based on previous studies. Southern analysis did not show rearrangement of the bcl-1 region. Although there was no statistical difference, the PRAD1/cyclin D1 negative group showed a 1-year survival of 81.8%, 3-year survival of 45.5% and 5-year survival of 22.7%, and those for the PRAD1/cyclin D1 positive group were 63.5%, 16.9% and 16.9%, respectively. Further study is required to determine whether PRAD1/cyclin D1 expression is a prognostic factor.

Aged↗
PubMed1999

Cilostazol, a phosphodiesterase inhibitor, improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty Rat, a model of spontaneous NIDDM.

AIM: Angiotensin converting enzyme inhibitors and alpha1-adrenergic blockers improve insulin sensitivity, the mechanism of which was considered, at least in part, to be due to the increased blood flow to muscle. The present study aimed to clarify whether cilostazol, a phosphodiesterase inhibitor, improves insulin sensitivity in a model of spontaneous non-insulin dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima Fatty (OLETF) rat. METHODS: OLETF rats were divided into the two groups at the age of 16 weeks: the cilostazol-supplemented group (cilostazol 40 mg/kg/day) and the normal-diet group. As a non-diabetic control, we used Long-Evans-Tokushima-Otsuka rats (non-diabetic rats). Oral glucose tolerance test and hyperinsulinemic euglycemic clamp was performed at the ages of 23 and 25 weeks, respectively. Serum levels of lipids and leptin were measured. RESULTS: Body weight and abdominal fat was increased in OLETF rats but cilostazol supplementation did not alter them. Insulin sensitivity, as measured by the hyperinsulinemic euglycemic clamp technique, was significantly decreased in OLETF rats (glucose infusion rate: 73.5 +/- 10.0 vs. 41.5 +/- 9.8 micromol/min/kg body weight, p < 0.01). Cilostazol supplementation improved insulin sensitivity partially but significantly 51.0 +/- 5.7 micromol/min/kg body weight, p < 0.05) in OLETF rats at 25 weeks of age, although it did not decrease serum levels of glucose, lipids or leptin. However, this effect was not observed in non-diabetic rats. CONCLUSION: Cilostazol, which is used in diabetic patients for the treatment of obstructive disease of artery, is expected to have a beneficial effect on insulin sensitivity in NIDDM.

Abdomen↗