Mikiko Kawaguchi

Stimulating effect of erythropoietin on the release of dopamine and acetylcholine from the rat brain slice

We investigated the effects of erythropoietin (EPO) in rat hippocampal and striatal slices, where EPO receptors have been known to exist. EPO stimulated dopamine release from rat striatal slices. Acetylcholine (ACh) release from rat hippocampal slices was not affected by EPO, but high K(+)-induced ACh release was considerably enhanced by EPO. Nitric oxide (NO) production from the hippocampus and the striatum was not affected by EPO. NO-synthase activity was not changed by EPO in the hippocampus or the striatum. These results suggest that EPO stimulates dopamine- and acetylcholine-release without affecting NO production.

Skeletal Malformations in Rat Offspring: Long-Term Effect of Maternal Insulin-Induced Hypoglycemia During Organogenesis

We studied the effect of maternal hypoglycemia on skeletal growth in the offspring of nondiabetic and diabetic rats. Female Wistar rats were injected with streptozocin (30 mg/kg i.v.) 2–3 wk before mating, and diabetes was confirmed by an intraperitoneal glucose tolerance test. On postconception day 9.5 or 10.5, both control and diabetic dams received saline or Actrapid human insulin (400 mU/rat i.p.). Hypoglycemia (∼2.8 mM) was induced for 120 min in the insulin-treated mothers. Pregnancy was terminated on gestational day 20. Fetal bones and cartilage were double-stained with alizarin red S and alcian blue 8GS. Insulin-induced hypoglycemia caused delayed ossification in the fetuses of the control dams. The number of malformations, e.g., costal fusion waves, increased greatly. These effects were more striking in the fetuses of dams that had received insulin on day 10.5 rather than on day 9.5 of embryo development. This type of insulin-induced hypoglycemia further delayed ossification of the fetal bones in diabetic dams. The influence of maternal hypoglycemia on skeletal malformations and/or variations was greater in the fetuses of diabetic dams than in the fetuses of control dams. These data suggest that maternal hypoglycemia in early pregnancy has a striking effect on skeletal growth and malformations in fetuses. In addition, mild glucose intolerance in dams may amplify these hypoglycemic effects.

Lack of effect of CS-045, a new antidiabetic agent, on insulin secretion in the remnant pancreas after 90% pancreatectomy in rats

We assessed the effect of CS-045, a new hypoglycemic agent, on B-cell function in partially pancreatectomized rats. At the age of 4 weeks, male Wistar rats were subjected to 90% pancreatectomy (Px). For 2 weeks starting at 6 weeks after surgery the Px rats were treated with CS-045 (CS rats) mixed with chow pellets in a proportion of 0.2% (w/w). To compare the efficacy of CS-045 with that of insulin therapy, an osmotic pump was implanted to release insulin (1.2 units/day) into the intraperitoneal cavity of the Px rats (Is rats). Plasma glucose levels in the CS and Is rats were significantly lower than in the control Px rats; however, no marked improvement in plasma glucose or insulin levels was observed in glucose tolerance test (2 g/kg, i.p.) in the CS rats. Insulin secretion by the isolated perfused pancreas in response to 16.7 mM glucose showed a biphasic pattern, but was slightly reduced in the Px and CS rats compared with the Is rats. Insulin secretion induced by 19 mM arginine was unaffected by the treatment. The insulin content of the CS rats was significantly greater than in the Px and Is rats. Histological observations suggested regranulation of the pancreatic islets of the CS rats. B-cell areas within the islet were restored to normal levels in the Cs and Is rats. These findings indicate that the hypoglycemic effect of CS-045, which is not mediated by insulin secretion from the residual pancreas, prevents destruction of the islet.

Effect of aging on B-cell function and replication in rat pancreas after 90% pancreatectomy.

We studied the effect of aging on B-cell function and replication in depancreatized rats. Male Wistar rats, at the ages of 1, 5, and 15 months, underwent 90% pancreatectomy (Px) or a sham operation, and islet function and regeneration were examined 3 weeks later. Plasma glucose levels in 1-month-old rats reached a peak 2 weeks after Px and then declined, while those in 5- and 15-month- old rats reached significant levels as early as the day after Px or 2 days after surgery and continued to increase over the following 3 weeks. Consequently, in contrast to young Px rats, weight loss due to severe diabetes was observed in 5- and 15-month-old Px rats. Plasma glucose responses to intravenous glucose loading (0.5 g/kg body weight) were much greater in older Px rats than in younger rats. There was a marginal insulin response to glucose in 1-month-old Px rats, whereas no insulin response to glucose was observed in older Px animals. The insulin content of the residual pancreas was increased threefold in 1-month-old Px rats, but there was no increase in 5- and 15-month-old Px rats. These data demonstrate that the effect of reducing islet mass is much greater in aged rats than in young rats and that the replicatory capacity of B cells tends to diminish after adulthood has been reached.

Half-solidification of nutrient does not decrease gastro-esophageal reflux events in patients fed via percutaneous endoscopic gastrostomy

BACKGROUND & AIMS Percutaneous endoscopic gastrostomy (PEG) tube feeding is widely used for patients with swallowing dysfunction, and aspiration pneumonitis induced by reflux of gastric contents is one of the most frequent and life-threatening events in such patients. We performed this study to clarify the effect of half-solidification of nutrient on gastro-esophageal reflux (GER) of acidic and non-acidic gastric contents in patients with PEG. METHODS The subjects were 14 elderly patients undergoing PEG feeding (female: 11, mean age 83.1 y). Twenty-four hour esophageal multichannel intraluminal impedance (MII) and pH (MII-pH) monitoring were performed during and after feeding with half-solid and liquid nutrient, respectively. The numbers of GER events during 4h after the start of feeding were compared. RESULTS There was no significant difference in the total number of GER events between half-solid nutrient feeding and liquid nutrient feeding (5.6+/-1.5 vs. 6.6+/-1.5). The number of acid reflux events after half-solid nutrient feeding tended to be higher than that after liquid nutrient feeding (1.9+/-1.1 vs. 1.4+/-0.8). CONCLUSION Half-solidification of nutrition does not appear to be effective for preventing GER caused by liquid PEG feeding.

β-cell function and replication in spontaneously hypertensive rats

Abstract We examined β-cell function and replication in spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY). Rats were subjected to 90% pancreatectomy (Px) or sham operation at the age of 8 weeks, and islet function and regeneration were examined 4 weeks after surgery. Plasma glucose levels were higher in SHR than in WKY (509 ± 38 v 325 ± 109 mg/dL, P v 4.2 ± 0.4 μg, P v 123.8 ± 23.5 μg, P P

Effect of chronic vanadate administration in partially depancreatized rats.

The effects of vanadate on B-cell function and replication in rats after 90% partial pancreatectomy (Px) were compared with insulin therapy. At the age of 4 weeks, male Wistar rats were subjected to sham operation or Px. Vanadate (0.2 mg/ml) was given in drinking water for 3 weeks starting at 2 weeks after surgery. Regular insulin (2.4 units/day) was administered as a continuous subcutaneous infusion through an osmotic pump. Plasma glucose levels were significantly higher in the Px rats than in the sham rats from 1 week after surgery. Vanadate lowered plasma glucose levels to near normal values in the Px rats as early as 2 days. The effect was sustained throughout the experiment. The hypoglycemic effect of insulin was less than that of vanadate. During an i.p. glucose tolerance test, plasma glucose levels were decreased in the Px rats treated with vanadate or insulin, while plasma insulin levels were not affected. The insulin content in the Px rats treated with vanadate was significantly (P < 0.01) greater than in the insulin-treated Px rats. Histological examination showed fibrotic degeneration in the enlarged islets of Px rats, whereas the normal structure was retained in most islets of the Px rats treated with vanadate and insulin. In addition, B-cell areas within the islet were restored to normal levels not only in the insulin-treated Px rats but in the vanadate-treated Px rats. However, both vanadate and insulin failed to stimulate proliferative activity of the B-cells. These data suggest that vanadate is a new therapeutic option to ameliorate the diabetic state after Px.

Efficacy of Corrected Rapid Turnover Protein Increment Index (CRII) for Early Detection of Improvement of Nutrition Status in Patients with Malnutrition.

Serum prealbumin level is useful for assessment of changes in nutritional status but it is markedly affected by the inflammation. In this study, we examined the efficacy of the corrected rapid turnover protein increment index (CRII) for prealbumin, which is calculated as [prealbumin level/C-reactive protein (CRP) level on the assessment day]/[prealbumin level/CRP level on the day of starting nutritional care], for prediction of improvement of nutritional status in patients with malnutrition. The subjects were 50 hospitalized patients with low albuminemia, who were receiving nutritional care. Serum concentrations of albumin, prealbumin and CRP were measured every week for 5 weeks. We defined patients whose serum albumin level was elevated by more than 0.2 g/dl after 5 weeks as those showing improved nutritional status. There was a significant difference in the prealbumin level between improved and unimproved patients at 5 weeks after the start of nutritional support. On the other hand, the prealbumin CRII value showed a significant difference between the groups at 1 and 2 weeks after the start of nutritional support. In conclusion, assessment of prealbumin CRII is useful for early prediction of improved nutritional status in patients with malnutrition.

Healthy diet assessment mechanism based on fuzzy markup language for Japanese food

Owing to the change of our lifestyle, more people suffer from chronic diseases, such as obesity or diabetes. Making improvements in terms of diet and physical activity is helpful for people to reduce the risk of suffering from these chronic diseases. This paper presents a healthy diet assessment mechanism based on fuzzy markup language (FML) for Japanese food. This mechanism is based on the dietary standard, food exchange list (FEL), published by the Japan Diabetes Society, to assess one person’s dietary healthy level according to his/her personal profile, his/her daily physical activity, and how balanced he/she consumes food items. We use FML to describe the knowledge base and the rule base of the constructed fuzzy logic system. Additionally, ontology stores the necessary knowledge base and rule base of the adopted fuzzy inference mechanism. The proposed mechanism operates as follows: (i) Dieticians first define the nutrient facts of the collected food items. (ii) The involved subjects record their personal information, eaten food items, and daily physical activity. Through the constructed FML-based personal profile ontology, the estimated energy requirement and the estimated unit requirement for each food group are obtained after inference. (iii) Finally, one-day dietary healthy level is inferred by the proposed fuzzy inference mechanism. From the experimental results, the proposed mechanism is feasible to apply to Japanese dietary assessment. In the future, we will integrate with genetic learning algorithm and collect more subjects’ records to further improve the performance.

FML-based Japanese diet assessment system

This paper presents a Fuzzy Markup Language (FML)-based Japanese diet assessment system and applies it to Japanese diet. Food Exchange List (FEL), published by Japan Diabetes Society, is adopted as a standard to assess one persons diet healthy level to help him/her eat a wide variety of foods and drinks to balance the eaten food items and physical activity. FML is used to describe the knowledge base and rule base of the diet domain. The dietician first defines the nutrient facts of the collected food from food guidebook and Internet. Then, the involved subject records his/her personal information and daily meals for a constant period. Based on the predefined Japanese food ontology, including ingredients of each food item and the contained units of each food group, the proposed fuzzy inference mechanism is implemented to infer the possibility of dietary healthy level for one-day meal. From the simulation results, the proposed approach is feasible to apply to Japanese diet assessment.