Biomedical subjects

N Koh

Publications and source records attributed to N Koh.

62 records · Page 4Linked to original sources

PubMed1985

Effects of a fructose-rich diet and the aldose reductase inhibitor, ONO-2235, on the development of diabetic neuropathy in streptozotocin-treated rats.

Streptozotocin-diabetic rats were maintained on a 72% fructose diet for 4 weeks and some were treated with an aldose reductase inhibitor (either alrestatin: 0.9 g . kg-1 . day-1 or ONO-2235: 50 mg . kg-1 . day-1). Fructose feeding significantly influenced the development of impaired motor nerve conduction velocity in the diabetic rats and this effect was positively correlated with sorbitol accumulation in the sciatic nerve of diabetic rats maintained on a fructose-rich diet. Treatment with ONO-2235, a new aldose reductase inhibitor, prevented both slowing of motor nerve conduction velocity and elevation of nerve sorbitol concentration. On the other hand, erythrocyte sorbitol levels were significantly correlated to those of the sciatic nerve (r = 0.86, p less than 0.001) and the retina (r = 0.91, p less than 0.001) in these animals. Thus, our findings suggest that increased polyol pathway activity may be related to the pathogenesis of diabetic neuropathy and erythrocyte sorbitol concentrations may prove a useful indicator for the presence of diabetic complications.

Aldehyde Reductase↗

PubMed1983

The features of causes of death in Japanese diabetics during the period 1971-1980.

The principal causes of death among 9,737 diabetics who died in 280 hospitals all over Japan during the period 1971-1980 have been analyzed retrospectively in this study. The main cause of death in Japanese diabetics was vascular complications. The mortality from vascular complications was 41.5%, 37.9% for males and 46.8% for females, increasing with the duration of diabetes and with age. The most interesting findings were of cardiovascular disease which was the cause of death in 12.3% of the subjects in our study as compared to 54.6% of the Joslin Clinic patients (1971). However, our incidence rate was almost twice that reported in Japan in 1967 by Goto (Japan). In contrast, cerebrovascular disease and nephropathy are much more common in Japanese than in American diabetics. Recently cancer has become more common in Japanese diabetics and 25.3% of the deaths have been assigned to it. In contrast, diabetic coma due to hyperglycemia accounted for only 4.1% of deaths. The average life span of Japanese diabetics is still over 10 years shorter than that of non-diabetics.

Adult↗

PubMedDate not supplied

Biguanides may produce hypoglycemic action in isolated rat hepatocytes through their effects on L-alanine transport.

We investigated the mechanisms of the effects of the biguanides metformin and buformin on hepatic gluconeogenesis in hepatocytes isolated from normal rats. Both 10 nM glucagon and 50 microM dibutyryl cAMP increased [3H]alanine uptake in isolated hepatocytes of normal rats by about 150% and 55%, respectively, compared with the effect of 5 mM alanine alone. Metformin (3 mM) reduced glucagon-stimulated [3H]alanine uptake to the level seen with alanine alone; buformin (3 mM) inhibited glucagon-stimulated [3H]alanine uptake by about 69%. The effects of biguanides on dibutyryl cAMP-stimulated [3H]alanine uptake were similar, but of smaller magnitude compared with those observed in the presence of glucagon. Ouabain (3 mM) had a stronger inhibitory effect on [3H]alanine uptake than the biguanides. However, 3 mM tolbutamide failed to suppress [3H]alanine uptake in the presence or absence of glucagon or dibutyryl cAMP. Our results suggest that the inhibition of alanine uptake, related to a reduction in the Na+/L-alanine transport system, is a possible mechanism of biguanide-related inhibition of hepatic gluconeogenesis.

Alanine↗

PubMedDate not supplied

Niceritrol prevents the decrease in red blood cell 2,3-diphosphoglycerate and neuropathy in streptozotocin-induced diabetic rats.

Nerve ischemia/hypoxia has been linked to the pathogenesis of diabetic complications. Red blood cell 2,3-diphosphoglycerate is an important regulator of peripheral tissue oxygenation; however, the relationship between 2,3-diphosphoglycerate concentration and diabetic complications has not been studied in detail. This investigation focused on the relationship between red blood cell 2,3-diphosphoglycerate and diabetic neuropathy, by measuring motor nerve conduction velocity and sciatic nerve blood flow in streptozotocin-induced diabetic rats. The effect of treatment with niceritrol, a nicotinic acid derivative that acts as a vasodilator and reduces serum lipid concentrations, on 2,3-diphosphoglycerate concentration and diabetic neuropathy was also examined. Untreated diabetic rats had significantly lower concentrations of red blood cell 2,3-diphosphoglycerate, higher concentrations of serum total cholesterol and triglyceride, as well as reduced motor nerve conduction velocity and sciatic nerve blood flow, compared to untreated normal rats. Niceritrol prevented these abnormalities without correcting hyperglycemia in diabetic rats, but had no effect on these parameters in normal rats. Red blood cell 2,3-diphosphoglycerate concentration and motor nerve conduction velocity showed a positive correlation with sciatic nerve blood flow and 2,3-diphosphoglycerate, respectively. These observations suggest that ischemia/hypoxia plays an important role in the development of diabetic neuropathy, and that niceritrol has a therapeutic effect on this condition by improving endoneurial ischemia/hypoxia.

2,3-Diphosphoglycerate↗

PubMedDate not supplied

Relationship between ornithine decarboxylase gene abnormalities and human hepatocarcinogenesis.

BACKGROUND/AIMS: Ornithine decarboxylase is essential for cell growth. Its activity was high in human hepatocellular carcinoma tissues and was highest in poorly differentiated tumors. METHODOLOGY: To find if there are tumor-specific ornithine decarboxylases, we examined the ornithine decarboxylase cDNA sequences of 91 clones prepared from hepatoma tissue and non-cancerous tissue of resected liver specimens from 15 patients with hepatocellular carcinoma. RESULTS: Ornithine decarboxylase gene mutations were more frequently detected in the hepatoma tissue. The incidence of mutation in hepatoma tissue was related to dedifferentiation. Mutation in regions rich in proline, glutamic acid, serine, and threonine were detected in moderately and poorly differentiated hepatocellular carcinoma only. CONCLUSIONS: Our findings suggested that the sequence of ornithine decarboxylase in hepatocellular carcinoma often is different from that in normal liver and that mutation of its gene is related to the progression of hepatocellular carcinoma.

Adult↗

PubMedDate not supplied

Ultrasonographic evaluation of portal blood flow using transhepatic carbon dioxide injection.

BACKGROUND/AIMS: The evaluation of portal blood flow in hepatic mass is important for the diagnosis of hepatocellular carcinoma. We have designed a new method to easily evaluate portal blood flow in hepatic mass using ultrasonography with injection of carbon dioxide into the intrahepatic portal vein by direct puncture with a fine needle. METHODOLOGY: We evaluated 29 masses in the liver of 20 patients ultrasonically with injection of carbon dioxide into the intrahepatic portal vein. RESULTS: Of 29 space-occupying lesions (SOLs), 13 were found to have portal blood flow and 16 were found to have no portal flow by this method. All 15 SOLs which had no portal flow were histologically confirmed to be hepatocellular carcinoma. Of 13 SOLs with portal flow, 5 were confirmed to be hepatocellular carcinoma. For 7 of 9 SOLs in which both this method and arterial portographic computed tomography were performed, the results were in agreement. CONCLUSIONS: Ultrasonographic evaluation of portal blood flow using transhepatic carbon dioxide injection appears to be useful for the evaluation of portal flow in mass and may aid in the diagnosis and management of mass in patients with liver disease.

Adolescent↗

PubMedDate not supplied

Clinical use of a new castable glass ceramic material.

The dimensional change of a new castable ceramic material (CD-200) was measured after casting, ceramming, and surface coloring. The marginal and internal adaptations of single crowns were evaluated, as was the fracture strength of single crowns and fixed partial dentures. The material expanded 0.57% after casting, ceramming, and application of surface colorant. Marginal openings ranged between 2.8 and 11.2 microns. Single crowns exhibited fracture strengths lower than or comparable to Dicor single crowns, and fixed partial dentures made from CD-200 were weaker than those fabricated with Dicor.

Ceramics↗

PubMedDate not supplied

Use of the C64 quantitative tuning fork and the effect of niceritrol in diabetic neuropathy.

We investigated the usefulness of the C64 quantitative tuning fork in assessing vibratory sensation in patients with diabetic neuropathy. The vibratory sensation scores determined by using the C64 quantitative tuning fork were significantly correlated with severity of subjective symptoms of numbness, cold, desensitization, spontaneous pain in the upper and lower extremities, and vertigo, as well as measurements of neurologic function (threshold of vibratory sensation, the coefficients of variation of the R-R intervals of the electrocardiogram at rest, and the motor nerve conduction velocity [MNCV] of the lower extremities; P < 0.05 to 0.01). Subsequently, we evaluated the effects of niceritrol on neurologic function in the same patients by using the C64 quantitative tuning fork, other neurologic function tests, and the change in severity of subjective symptoms before and after therapy. Niceritrol significantly improved measures of neurologic function (vibratory sensation scores, MNCV of the upper extremities, and sensory nerve conduction velocity of the lower extremities; P < 0.05 to 0.001), and subjective symptoms (numbness, cold, desensitization, and spontaneous pain in the lower extremities; P < 0.01 to 0.001). Our results suggest that the C64 quantitative tuning fork is a convenient and objective tool for assessing the severity of diabetic neuropathy and that niceritrol is useful for the treatment of this disease.

Blood Glucose↗