Zensuke Ogawa

Diagnostic significance of urinary enzymes for diabetes mellitus and hypertension.

In order to evaluate tubular damage in diabetic patients, the activity of renal proximal tubule derived enzymes excreted in 24-hour urine were recorded in 5 groups as follows: (i) 48 noninsulin-independent diabetic patients with normal renal function and a urinary albumin excretion rate within the normal range; (ii) 45 noninsulin-dependent diabetic patients with normal renal function and a high urinary albumin level; (iii) 26 noninsulin-dependent diabetic patients with renal failure; (iv) 40 patients with essential hypertension and normal renal function, and (v) 48 normal control subjects. Regardless of whether cases were noninsulin-dependent diabetics with normal or high urinary albumin excretion rate or cases with renal dysfunction, urinary dipeptidyl aminopeptidase IV and N-acetyl-beta-D-glucosaminidase excretions were significantly higher than in healthy subjects, and urinary gamma-glutamyl transpeptidase excretion was significantly lower than in healthy subjects. No significant changes in urinary enzyme excretions showed specific variations in the essential hypertensive patients. These results suggest that there is tubular damage in the early stages of noninsulin-dependent diabetic patients with normal renal function and normal urinary albumin excretion rate. Detection of urinary excretion of dipeptidyl aminopeptidase IV, N-acetyl-beta-D-glucosaminidase and gamma-glutamyl transpeptidase may be especially useful for the early diagnosis of diabetic nephropathy.

Semiquantitative Analysis of Apolipoprotein A-I Modified by Advanced Glycation End Products in Diabetes Mellitus

Apolipoprotein A‐I (Apo A‐I), the major component of high‐density lipoprotein (HDL), is modified by reactive α‐oxoaldehydes, such as methylglyoxal (MG) and glycolaldehyde (GA), and these modifications affect the function of Apo A‐I. GA‐ and MG‐modified Apo A‐I serum levels were semiquantitatively evaluated in diabetic patients to elucidate the association of each protein with diabetes and to determine its appropriateness as a serum marker of diabetes.

A kinetic model of mitochondrial aspartate aminotransferase transmigration in hepatobiliary disorders.

A hypothetical kinetic model of transmigration of mitochondrial aspartate aminotransferase (m-AST) from liver to blood and its elimination from blood was constructed and assessed for prediction by computer simulation. The elimination of m-AST from plasma in healthy rats followed first-order kinetics. Depletion of m-AST from the liver after induction of hepatobiliary disorders in rats with α-naphthylisothiocyanate (ANIT) also followed first-order kinetics. In contrast, the changes in metabolic rate in the liver after ANIT administration, as estimated from the plasma indocyanine green clearance, approximated to a second-order time function. Based on these data, the time-dependent change in plasma m-AST activity after ANIT administration was simulated by computer according to a hypothetical kinetic model. The result of computer simulation of the change in plasma m-AST coincided well with that obtained experimentally, suggesting that continuous measurements of m-AST may be helpful to the clinical diagnosis of liver injury.

Effects of renal sorbitol accumulation on urinary excretion of enzymes in hyperglycaemic rats

We studied the effects of epalrestat, a specific inhibitor of aldose reductase, on renal sorbitol accumulation and the resulting urinary enzyme excretion in hyperglycaemic rats. The activities of proximal tubule-derived enzymes such as N-acetyl-β-D-glucosaminidase (NAG), alanine aminopeptidase (AAP), γ-glutamyltranspeptidase (GGT) and dipeptidyl aminopeptidase IV (DAPIV) in urine were determined in five groups of male Wistar rats (each n=7): (a) 0·9% saline-loaded, (b) 10% glucose-loaded, (c) 10% glucose-loaded with epalrestat pretreatment, (d) 10% mannitol-loaded and (e) 10% mannitol-loaded with epalrestat pretreatment. Epalrestat was given mixed in chow at a dose of 50mg/kg body weight. Urinary NAG, AAP, GGT and DAPIV activities were significantly increased (P<0·005, P<0·05, P<0·01, P<0·01, respectively) by the induction of hyperglycaemia. In contrast, enzyme excretion was not increased in the mannitol- or saline-loaded groups. Pre-treatment with epalrestat completely prevented the increased urinary excretion of NAG, AAP and GGT. At the end of the infusion study, renal cortical glucose concentrations of the glucose-loaded groups with and without epalrestat pretreatment were approximately fivefold higher than those of the mannitol- or saline-loaded groups (P<0·005 each). Renal cortical sorbitol concentrations of the glucose-loaded group was also approximately twofold higher than those of the mannitol- or saline-loaded groups (P<0·01 each). However, in the group that received both glucose and epalrestat, renal cortical sorbitol concentration was not increased. These results suggest that accumulation of intracellular sorbitol leads to proximal tubular cell dysfunction and abnormal enzymuria.

Nutritional Factors and Atherosclerosis

It is said that the use of foods low in cholesterol content is essential to dietary treatment, because of the close relationship between the serum cholesterol level and the onset or progress of atherosclerosis.

Elevation of pancreatic oxidative stress in STR/Ort mice

To gain a better understanding of the causative factors of hyperinsulinaemia, pancreatic oxidative stress in STR/Ort mice and a type 2 diabetic mouse model (db/db) was evaluated. Expression of oxidative stress marker HSP32 in the pancreas of STR/Ort mice was significantly higher than that in the liver, kidney and spleen. The expression level of HSP32 in STR/Ort was significantly higher than in db/m at 5, 15 and 20 weeks of age (P < 0.05) and tended to be higher than that in db/m (P = 0.069). The expression level of HSP47 in STR/Ort was also significantly higher than in db/m at 5 and 10 weeks (P < 0.05) and tended to be higher than that of db/m at 15 (P = 0.086) and 20 weeks (P = 0.052). Taken together, these results suggest that elevation of oxidative stress in the pancreas during early developmental periods may induce hyperinsulinaemia in STR/Ort mice through impaired insulin metabolism and contribute to the initiation and progression of osteoarthritis.

The development of an artificial stool usable for the surveillance of faecal haemoglobin testing

Background Faecal occult blood testing is an important diagnostic tool for the detection of colorectal cancer. However, it has not been standardized due to the absence of suitable specimens for surveillance. Methods We developed a ready-to-use artificial stool made from rice flour. This new artificial stool homogeneously contains not only human haemoglobin A0 (HbA0) but also glycerol as an internal standard material. After the collection of the artificial stool into a buffer, the haemoglobin concentration in dispersed solution was measured using a method based on the peroxidase like activity of haemoglobin. The glycerol concentration was measured using a commercially available triglyceride measurement kit. Results With regard to the haemoglobin stability, the decrease in the level of human haemoglobin in the artificial stool was <2% when it was stored at −80℃ for four months, −20℃ for two weeks, and 5℃ for two days. The artificial stool was easily collected with the collecting tubes of a commercially available faecal haemoglobin test kit. The weight of the collected artificial stool could be calculated by measuring the concentration of glycerol in the extracting solution of the collected stool sample. The haemoglobin concentrations could be adjusted based on their collection weights. Conclusions The artificial stool has a paste-like consistency and contains both haemoglobin and glycerol homogeneously. Furthermore, the measured haemoglobin concentration could be determined based on the collected stool weight, which was directly related to the glycerol concentration. These features make it a useful material for the surveillance of faecal occult blood testing.

Is there a relation between triglyceride concentrations in very low density lipoprotein and the index of insulin resistance in nondiabetic subjects

Serum very low density lipoprotein (VLDL) levels increase during the early stages of insulin resistance; therefore, determination of VLDL levels would be useful for evaluating the progression of metabolic syndrome and diabetes mellitus. The aim of this study was to clarify the clinical utility of triglyceride in VLDL (VLDL‐TG) level, determined using a homogeneous assay kit (Shino‐test Corporation, Tokyo, Japan), as an index of insulin resistance.