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N Hotta

Publications and source records attributed to N Hotta.

At least 73 records · Page 4Linked to original sources
PubMed1998

Centrally administered TRH-induced insulin secretion is impaired in the Otsuka-Long-Evans-Tokushima Fatty rats, a model of spontaneous non-insulin-dependent diabetes mellitus.

To investigate whether insulin secretion induced by stimulation of the vagus nerve is preserved or impaired in Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats, we injected 10(-8) mol of thyrotropin-releasing hormone (TRH) into the third cerebral ventricle and determined the serum level of insulin in the unanesthetized, unrestrained rats. Intracerebroventricular (i.c.v.) injection increased the serum levels of glucose and insulin in both OLETF and Long-Evans-Tokushima-Otsuka (LETO) rats, a nondiabetic control strain, at 8-12 weeks of age. At 24-28 weeks of age, the increased level of glucose in OLETF rats was comparable to LETO rats but that of insulin was lower than control after the i.c.v. injection of TRH. Pretreatment with i.v. atropine had no significant effect on such hyperglycemia. However, the increases in the serum levels of insulin were suppressed in both OLETF and LETO rats. The plasma levels of epinephrine, norepinephrine, and glucagon rose significantly after TRH. There was no significant difference in the levels of any hormones between the two groups. In OLETF rats at 24-28 weeks of age, i.v. glucose load induced significantly higher serum levels of glucose and insulin than LETO rats. The results suggest that the vagus nerve-mediated insulin secretion is impaired in OLETF rats, similar to an autonomic diabetic neuropathy in the early stage of diabetes. This impairment may play some role in deteriorating glucose tolerance in this spontaneously developed diabetes model.

Animals↗
PubMed1998

Regulation of intracellular free Mg2+ concentration in isolated rat hearts via beta-adrenergic and muscarinic receptors.

Regulation of the intracellular free magnesium concentration ([Mg2+]i) was investigated in isolated rat hearts, using 31P-nuclear magnetic resonance (31P-NMR). [Mg2+]i was found to be slowly and significantly decreased during prolonged application of isoproterenol (ISO) through beta-adrenergic receptor stimulation, and restored by subsequent washouts. The ISO-induced decrease in [Mg2+]i was antagonized by addition of a muscarinic receptor agonist, carbachol (CCh). In the presence of atropine, CCh did not exert this effect. A water-soluble forskolin derivative, NKH477, which directly activates adenylate cyclase, also caused a decrease in [Mg2+]i, which could be antagonized by CCh, but a greater concentration was required as compared to the ISO case. The manner of [Mg2+]i regulation mimicked those noted for the action potential duration and the Ca2+ channel current, in which cAMP is known to act as a second messenger. Even in the presence of a Ca2+ channel blocker, verapamil, [Mg2+]i was reversibly decreased by ISO. Changes in the intracellular ATP concentration demonstrated any clear correlation with changes in [Mg2+]i. These results suggest that [Mg2+]i can be controlled by a balance of sympathetic and parasympathetic activities. cAMP may play a key role in the [Mg2+]i regulation via beta-adrenergic and muscarinic receptors, although some other metabolic pathways also appear to be involved. Hormonally induced changes in [Mg2+]i have possible clinical significance.

Animals↗
PubMed1998

The incidence and characteristics of silent cerebral infarction in elderly diabetic patients: association with serum-soluble adhesion molecules.

The purpose of this study was to investigate the relationship between complications arising from silent cerebral infarction (SCI) and changes in the levels of serum-soluble adhesion molecules in 82 elderly diabetic patients aged 60 years and older. SCI was found in 43 % of the 82 patients, with incidence increasing in relation to age. The prevalence of SCI was higher in subjects with hypertension, poor metabolic control and increased fibrinolysis. The levels of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1) and E-selectin (sE-selectin) were higher in diabetic patients than in non-diabetic subjects (p < 0.05, p < 0.001, and p < 0.05, respectively). Also, sICAM-1 and sVCAM-1 were found at increased levels in diabetic patients with SCI compared to those without SCI (p < 0.01 and p < 0.05, respectively). In particular, the level of sICAM-1 was increased in patients with SCI due to perforating arterial occlusion, while the level of sVCAM-1 was increased in patients with SCI due to cortical arterial occlusion. However, no significant difference was found in sE-selectin levels. Overall average of the intima and media thickness (IMT) of the common carotid arteries increased with age. IMT proved to be greater in patients with SCI than in patients without SCI (p < 0.05), and showed a weak but significant positive correlation with sVCAM-1, while no correlation was found with either sICAM-1 or sE-selectin levels. In conclusion, measurement of serum adhesion molecules may be useful for diagnosing the early stages of brain damage and for prophylactic treatment which may prevent the onset or progression of SCI.

Aged↗
PubMed1998

A new spontaneous animal model of NIDDM without obesity in the musk shrew.

The EDS (early-onset diabetes in suncus) colony has been developed as a new closed breeding colony of the musk shrew (Suncus murinus, Insectivora) exhibiting a high incidence of spontaneous diabetes mellitus. We investigated the characteristic features of diabetic shrews in this colony. All diabetic shrews are characterized by glycosuria (Tes-tape value > or = 3+), hyperglycemia (23.3 +/- 0.8 mmol/l) and polyuria, and they were affected by the age of 3 months. Cumulative incidence (64.1% in males and 27.8% in females) was kept intact after the age of 3 months. The growth pattern of diabetic shrews was similar to that of non-diabetic shrews, and obesity was not consistent in diabetic shrews. The intraperioneal glucose tolerance test revealed both impaired glucose tolerance and impaired insulin secretion in diabetic shrews. Insulin sensitivity of diabetic shrews decreased in the intraperioneal insulin tolerance test. Neither severe hypertrophy nor lymphocytic infiltration was observed in pancreatic islets of diabetic shrews. These facts suggested that diabetic shrews in the EDS colony should be classified as early-onset non-insulin dependent diabetes mellitus (NIDDM) without obesity. Early-onset of severe hyperglycemia with impaired glucose tolerance is a distinctive character compared with other non-obese NIDDM models in rodents. We concluded that the diabetic shrews in the EDS colony are a new animal model of human NIDDM without obesity.

Age of Onset↗
PubMed1998

A case report of myolysis during high-dose amiodarone therapy for uncontrolled ventricular tachycardia.

We report a rare case of a 41-year-old male patient, a professional musician, with dilated cardiomyopathy and sustained ventricular tachycardia (VT) that was refractory to class I antiarrhythmic drugs. Severe myolysis developed after 10 months' administration of amiodarone (400 mg/day) in combination with mexiletine (300 mg/day) and disopyramide (400 mg/day). He had been suffering from severe moving muscle pain and an extremely high (16,830) IU/ml) serum level of creatine kinase (CK). The dosage of amiodarone was reduced from 400 mg/day to 200 mg/day without reduction of mexiletine or disopyramide and the patient's symptoms diminished. However, sustained VT developed, and so the dosage of the drug was increased to 250 mg/day. The high serum level of CK also decreased and returned to the normal range after the reduction in amiodarone dosage. Electrophysiologic examination of moving muscle revealed normal motor and sensory conduction velocities and, furthermore, the electromyogram revealed normal potentials and normal motor units. We conclude that severe myolysis developed as a result of the high dose and chronic administration of amiodarone. This is the first report of a Japanese patient showing rare and serious adverse effects in response to amiodarone treatment.

Adult↗
PubMed1998

Influence of interindividual variability of aldose reductase protein content on polyol-pathway metabolites and redox state in erythrocytes in diabetic patients.

OBJECTIVE: To clarify the influence of interindividual difference in the level of aldose reductase on the polyol pathway-related metabolism in diabetic patients. RESEARCH DESIGN AND METHODS: The enzyme protein content was determined by a two-site enzyme-linked immunosorbent assay using monoclonal and polyclonal antibodies to recombinant human aldose reductase in erythrocytes from 35 diabetic patients and 11 healthy volunteers. Patients were stratified into two groups by the median of aldose reductase content, and the erythrocyte sorbitol level, the fructose level, and the lactate-to-pyruvate ratio were compared between the two groups. We also examined the correlation of the enzyme content with these metabolic parameters. RESULTS: The group of patients whose enzyme content was above the median showed a significant increase in the levels of sorbitol (34.7 +/- 4.9 vs. 20.4 +/- 2.0 nmol/g Hb, P < 0.05) and fructose (99.8 +/- 17.2 vs. 45.9 +/- 4.6 nmol/g Hb, P < 0.05), along with an elevated lactate-to-pyruvate ratio (28.6 +/- 6.1 vs. 11.7 +/- 1.2, P < 0.05), compared with patients with low enzyme levels. The aldose reductase content in erythrocytes was well correlated with its activity, and there was a significant correlation between the enzyme content and the erythrocyte sorbitol (r = 0.58, P < 0.001) or fructose (r = 0.57, P < 0.001) levels as well as between the enzyme level and the lactate-to-pyruvate ratio (r = 0.38, P < 0.05). CONCLUSIONS: These results suggest that the interindividual variability of aldose reductase content may contribute tangibly to the polyol-pathway flux and cytoplasmic redox alteration in diabetic patients.

Aldehyde Reductase↗
PubMed1998

[Myo-inositol].

Explore the source record for details and available documents.

Diabetes Mellitus↗
PubMed1998

Polyol pathway hyperactivity is closely related to carnitine deficiency in the pathogenesis of diabetic neuropathy of streptozotocin-diabetic rats.

To investigate the relationship between polyol pathway hyperactivity and altered carnitine metabolism in the pathogenesis of diabetic neuropathy, the effects of an aldose reductase inhibitor, [5-(3-thienyl) tetrazol-1-yl]acetic acid (TAT), and a carnitine analog, acetyl-L-carnitine (ALC), on neural functions and biochemistry and hemodynamic factors were compared in streptozotocin-diabetic rats. Significantly delayed motor nerve conduction velocity, decreased R-R interval variation, reduced sciatic nerve blood flow and decreased erythrocyte 2, 3-diphosphoglycerate concentrations in diabetic rats were all ameliorated by treatment with TAT (administered with rat chow containing 0.05% TAT, approximately 50 mg/kg/day) or ALC (by gavage, 300 mg/kg/day) for 4 weeks. Platelet hyperaggregation activity in diabetic rats was diminished by TAT but not by ALC. TAT decreased sorbitol accumulation and prevented not only myo-inositol depletion but also free-carnitine deficiency in diabetic nerves. On the other hand, ALC also increased the myo-inositol as well as the free-carnitine content without affecting the sorbitol content. These observations suggest that there is a close relationship between increased polyol pathway activity and carnitine deficiency in the development of diabetic neuropathy and that an aldose reductase inhibitor, TAT, and a carnitine analog, ALC, have therapeutic potential for the treatment of diabetic neuropathy.

Acetylcarnitine↗
PubMed1997

Role of a sialyl Lewis(x)-like epitope selectively expressed on vascular endothelial cells in local skin inflammation of the rat.

The role of the inducible L-selectin ligand was studied in complement-dependent acute dermatitis in rats. Although mAbs against typical sialyl Lewis(x) (CSLEX-1 and SNH-3) did not react with skin venules, a sialyl Lewis(x)-like epitope defined by mAb 2H5 (2H5-Ag) was de novo expressed on the endothelial cells of skin venules in the area of inflammation. Expression of 2H5-Ag increased concomitantly with the progression of inflammation. 2H5-Ag was identified at the 75-, 150-, and 180-kDa bands when inflammatory skin tissue was analyzed by Western blotting. In contrast, P- and E-selectins were not detectable. The role of 2H5-Ag in this model was studied in in vitro and in vivo methods. First, 2H5 was i.v. injected 15 min before induction of dermatitis. 2H5 bound to skin venules and significantly reduced the neutrophil infiltration and plasma protein leakage. In contrast, CSLEX-1, mAb ARP2-4 (P-selectin blocker), or mAb ARE-5 (E-selectin blocker) had no effects. Second, adhesion of isolated rat neutrophils to the inflammatory skin section was inhibited significantly when the sections, but not neutrophils, were preincubated with 2H5. Third, fluorescein-labeled normal rat neutrophils were injected into a rat 10 h after induction of dermatitis. The number of labeled neutrophils infiltrated into the inflammatory site was reduced significantly when they were preincubated with HRL-3 (blocking mAb against rat L-selectin), but not with 2H5 or HRL-4 (nonblocking mAb against rat L-selectin). These data show that de novo expressed 2H5-Ag/L-selectin adhesion pathway contributes to the development of acute complement-dependent inflammation in the skin.

Animals↗
PubMed1997

Effect of an aldose reductase inhibitor on abnormalities of electroretinogram and vascular factors in diabetic rats.

The effect of an aldose reductase inhibitor, [5-(3-thienyl) tetrazol-1-yl] acetic acid (TAT), on the electroretinogram was determined in rats with streptozotocin-induced diabetes. Laboratory chow containing 0.05% TAT was given to rats for 2 months, while other diabetic rats were untreated. Groups of TAT-treated and untreated normal rats were also studied. Treatment with TAT produced significant improvement of the electroretinogram. TAT shortened the peak latencies of the b-wave oscillatory potentials, which were significantly prolonged in untreated diabetic rats (P < 0.0001 vs. untreated normal rats). This was accompanied by a significant decrease in the retinal sorbitol and fructose concentrations (by 46.5% and 25.7%, respectively). TAT treatment of diabetic rats also markedly reduced ADP-induced platelet aggregation and significantly increased the red blood cell 2,3-diphosphoglycerate level, accompanied by a marked reduction in sorbitol and fructose concentrations of platelet and red blood cells. There were significant correlations between the summed b-wave peak latencies and platelet aggregation or the 2,3-diphosphoglycerate level in diabetic rats. These findings suggest that an aldose reductase inhibitor, TAT, has therapeutic value for diabetic retinopathy.

2,3-Diphosphoglycerate↗
PubMed1997

Diabetic neuropathy in sucrose-fed Otsuka Long-Evans Tokushima fatty rats: effect of an aldose reductase inhibitor, TAT.

In an animal model of human non-insulin dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima Fatty (OLETF) rats were fed with sucrose for 8 weeks to obtain severe hyperglycemia. The effects of sucrose administration on peripheral nerve functions, motor nerve conduction velocity (MNCV) and coefficient of variance of R-R interval (CVR-R), were investigated with concomitant measuring of sciatic nerve blood flow (SNBF), ADP-induced platelet aggregation and polyol content in the sciatic nerves. The effects of an aldose reductase inhibitor, TAT, on these parameters were also studied. Administration of sucrose to OLETF rats caused significant body weight reduction and remarkable hyperglycemia. Sucrose-fed OLETF rats demonstrated significantly delayed MNCV, decreased CVR-R, reduced SNBF and increased platelet aggregation activity to ADP. Sorbitol and fructose accumulation, and myo-inositol depletion in sciatic nerves were observed only in sucrose-fed OLETF rats. These abnormalities were all ameliorated by the treatment with TAT. These observations suggest that the sucrose-fed OLETF rat is a useful animal model for studying the pathogenesis of diabetic neuropathy in human NIDDM, and that an aldose reductase inhibitor is a useful therapeutic agent for the treatment of diabetic neuropathy.

Aldehyde Reductase↗
PubMed1997

A case of a dialysis patient with sclerosing peritonitis successfully treated with corticosteroid therapy alone.

Sclerosing peritonitis (SCP) is a rare complication of peritoneal dialysis. Most of the patients with this serious complication have been treated in a symptomatic and conservative manner. Other patients have undergone risky surgical interventions. Recently it was reported that immunosuppressive therapy after renal transplantation was effective for this complication. A 56-year-old man developed sclerosing peritonitis 5 months after switching from peritoneal dialysis to hemodialysis because of ultrafiltration failure. The patient had ongoing inflammatory signs and symptoms, and corticosteroid therapy was commenced. His condition was dramatically improved within 1 week, and he is now well on an outpatient basis with the maintenance dosage of corticosteroid. This is the first report of a patient with peritoneal dialysis-related SCP who responded favorably to corticosteroid therapy alone.

Glucocorticoids↗
PubMed1997

Electroretinogram in sucrose-fed diabetic rats treated with an aldose reductase inhibitor or an anticoagulant.

To investigate the role of increased polyol pathway activity and hemodynamic deficits in the pathogenesis of diabetic retinopathy in non-insulin-dependent diabetes mellitus (NIDDM), Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of human NIDDM, were given water with or without 30% sucrose and some of them were fed laboratory chow containing 0.03% cilostazol, an anticoagulant, or 0.05% [5-(3-thienyl)tetrazol-1-yl] acetic acid monohydrate (TAT), an aldose reductase inhibitor, for 8 wk. Long-Evans Tokushima Otsuka (LETO) rats were used as nondiabetic controls. The peak latencies of oscillatory potentials of the electroretinogram in sucrose-fed OLETF rats were significantly prolonged compared with those in OLETF rats without sucrose feeding and LETO rats. There was a marked increase in platelet aggregability and a significant decrease in erythrocyte 2,3-diphosphoglycerate in sucrose-fed OLETF rats. Cilostazol significantly improved these parameters without changes in retinal levels of sorbitol and fructose. TAT, however, ameliorated all of these parameters. These findings confirm that the sucrose-fed OLETF rat is a useful animal model of retinopathy in human NIDDM and suggest that cilostazol improved diabetic retinopathy by modifying vascular factors, not by altering polyol pathway activity.

2,3-Diphosphoglycerate↗
PubMed1997

NG-methyl-L-arginine, an inhibitor of nitric oxide synthase, affects the central nervous system to produce peripheral hyperglycemia in conscious rats.

To determine whether the nitric oxide (NO) system in the central nervous system (CNS) is involved in the peripheral metabolism of carbohydrate we injected NG-methyl-L-arginine (L-NMA), an inhibitor of NO synthase, into the third cerebral ventricle of unanesthetized, unrestrained rats and determined the plasma level of glucose. This intracerebroventricular (i.c.v.) injection of the drug increased the plasma level of glucose dose-dependently, whereas an intravenous (i.v.) injection had no effect. The hyperglycemia thus induced was suppressed by concomitant i.c.v. or prior i.v. administration of L-arginine. Concomitant administration of D-arginine did not affect hyperglycemia by L-NMA. The i.c.v. injection of 5 x 10(-6) mol L-NMA increased plasma levels of glucose, epinephrine and norepinephrine, and serum levels of glucagon. However, plasma levels of insulin were unchanged, despite the presence of hyperglycemia. The hyperglycemia produced by L-NMA was completely inhibited by bilateral adrenalectomy. It was also inhibited by prior intraperitoneal injection of phentolamine, but not of propranolol or naloxone. Results suggest that L-NMA acts on the CNS to stimulate adrenal secretion of epinephrine and, subsequently, to elevate glucose levels in the peripheral blood. The NO system thus seems to be involved in the neural regulation of the adrenal by the GNS, which in turn regulates peripheral blood glucose levels.

Adrenalectomy↗
PubMed1997

The role of complement in the pathogenesis of tubulointerstitial lesions in rat mesangial proliferative glomerulonephritis.

Persistent proteinuria and tubulointerstitial lesions are important signs of progressive renal disease. The purpose of this study was to assess the role of complement in the development of tubulointerstitial lesions in rats with proteinuria due to primary glomerulonephritis. Mesangial proliferative glomerulonephritis was induced in mononephrectomized rats by intravenous injection of monoclonal antibody (mAb) 1-22-3 (Clin Exp Immunol 102: 181-185, 1995). As early as 24 h after the injection, proteinuria became evident, persisted throughout the observation period, and was associated with mesangial cell proliferation and tubulointerstitial lesions when examined at 7 and 14 d after mAb administration. Deposition of rat C3 and C5b-9 was observed at the luminal surface of proximal tubules and in cellular debris present in the tubular lumen (group I). Rats injected with mAb 1-22-3 and depleted of complement by injections of cobra venom factor starting at day 3 developed glomerulonephritis and proteinuria comparable to rats of group I, but complement deposition in the tubules and the tubulointerstitial lesions were markedly reduced (group II). Rats in group III were injected with mAb and, from day 3, with soluble complement receptor type 1, which became detectable at the luminal surface of proximal tubules and in the urine. Deposition of C5b-9 in tubular cells was not detectable, and the severity of tubulointerstitial lesions was reduced compared with rats in group I. These results indicate that, in this model of primary mesangial proliferative glomerulonephritis with proteinuria, the development of tubulointerstitial lesions is associated with activation of serum complement at the level of tubular brush border, and tubulointerstitial lesions can be reduced by inhibition of complement activity.

Animals↗
PubMed1997

Giant hepatic angiomyolipoma associated with disseminated intravascular coagulation.

We report a case of giant hepatic angiomyolipoma in a 68-year-old woman who had an increase in the fibrinolytic activity concomitant with disseminated intravascular coagulation (DIC). The presence of the tumor was confirmed by ultrasound (US), computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen and the selective arteriography of the liver via the superior mesenteric artery. Following treatment with heparin and gabexate mesilate, abnormal hemostatic values were corrected. Furthermore, the surgical removal of the huge hepatic angiomyolipoma completely normalized the alternations of the clotting system. These findings suggest that giant hepatic angiomyolipoma was profoundly associated with DIC.

Aged↗
PubMed1997

Effects of glycemic control on plasma 3-deoxyglucosone levels in NIDDM patients.

OBJECTIVE: To clarify the effects of glycemic control on the level of 3-deoxyglucosone (3-DG), a reactive dicarbonyl compound, in plasma from diabetic patients. RESEARCH DESIGN AND METHODS: Fasting plasma samples were collected from 15 healthy volunteers and 27 patients with NIDDM. Samples were collected from six poorly controlled patients before and after improved glycemic control for at least 2 months. Plasma 3-DG was determined by high-performance liquid chromatography (HPLC) as a 2,3-diaminonaphthalene derivative. We observed the relationship of 3-DG levels with plasma glucose or HbA1c levels and examined changes in 3-DG levels after glycemic control in the six patients. RESULTS: Plasma 3-DG was significantly more increased in diabetic patients than in nondiabetic control subjects (31.8 +/- 11.3 vs. 12.8 +/- 5.2 ng/ml, means +/- SD, P < 0.001), but there was an approximately threefold difference in 3-DG levels among diabetic patients. 3-DG levels were well correlated with plasma glucose (r = 0.56, P < 0.005) and HbA1c levels (r = 0.74, P < 0.001) in diabetic patients. The improvement of hyperglycemia in six patients resulted in a significant decrease in 3-DG (35.2 +/- 13.2 vs. 21.3 +/- 3.4 ng/ml, P < 0.05). CONCLUSIONS: The results indicate that the plasma glucose level is a predominant determinant of the plasma 3-DG level in diabetic patients and good glycemic control would be important to reduce this reactive metabolite.

Adult↗