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Kenro Nishida

Publications and source records attributed to Kenro Nishida.

9 recordsLinked to original sources

Possible relevance of alpha lipoic acid contained in a health supplement in a case of insulin autoimmune syndrome.

The insulin autoimmune syndrome is characterized as producing polyclonal or monoclonal anti-insulin autoantibodies in a patient with no previous history of exposure to exogenous insulin. The patient is 44-year-old Japanese woman and she had symptoms of hypoglycaemia without exposure to exogenous insulin. The patient was considered to have IAS because high titre of anti-insulin autoantibodies (96-98%: bound/total) were found in her serum. Her HLA DR beta1 DNA sequences analysis revealed that she has the DRB1(*)0406 and DRB1(*)0901. Our patient have been taken alpha lipoic acid (ALA) before onset. SH group compounds are known to play an important role in the pathogenesis of IAS, and ALA contains SH. From these data, we propose the possibility of the correlation between pathogenesis of IAS and ALA, and it will be important to pay attention for ALA as a cause of hypoglycemia in such cases.

Adult↗

Development of a highly responsive needle-type glucose sensor using polyimide for a wearable artificial endocrine pancreas.

To produce a long-life, stable, miniature glucose sensor for a wearable artificial endocrine pancreas (WAEP), we developed a novel microneedle-type glucose sensor using polyimide, designated the PI sensor (outer diameter, 0.3 mm; length, 16 mm), and investigated its characteristics in vitro and in vivo. In the in vitro study, we tested the sensor in 0.9% NaCl solution with varying glucose concentrations and observed an excellent linear relationship between the sensor output and glucose concentration (range: 0-500 mg/100 ml). In in vivo experiments, the PI sensor was inserted into the abdominal subcutaneous tissue of beagle dogs (n = 5), and interstitial fluid glucose concentrations were monitored after sensor calibration. Simultaneously, blood glucose concentrations were also monitored continuously with another PI sensor placed intravenously. The correlation and time delay between subcutaneous tissue glucose (Y) and blood glucose concentrations (X: 30-350 mg/100 ml) were Y = 1.03X + 7.98 (r = 0.969) and 6.6 +/- 1.2 min, respectively. We applied the new WAEP system/PI sensor and an intravenous insulin infusion algorithm developed previously for glycemic control in diabetic dogs. The use of the WAEP system resulted in excellent glycemic control after an oral glucose challenge of 1.5 g/kg (post-challenge blood glucose levels: 176 +/- 18 mg/100 ml at 65 min and 93 +/- 23 mg/100 ml at 240 min), without any hypoglycemia. Thus, we confirmed that our new PI sensor has excellent sensor characteristics in vitro and in vivo. The new WAEP using this sensor is potentially suitable for clinical application.

Administration, Oral↗

Comparison between closed-loop portal and peripheral venous insulin delivery systems for an artificial endocrine pancreas.

To establish the ideal insulin delivery route for an artificial endocrine pancreas, we examined the effectiveness of closed-loop portal insulin delivery. We investigated the effects of the route of insulin delivery on net hepatic glucose balance (NHGB) in dogs under pancreatic clamp conditions with somatostatin plus basal glucagon and insulin infusions. A constant rate of suprabasal insulin was infused via the portal vein or a peripheral vein, and glucose was infused into the portal vein for 180 min. The mean net hepatic glucose uptake (NHGU) values in the portal insulin infusion group (PI group) were significantly greater than those in the peripheral venous insulin infusion group (VI group); the changes from the baseline values at 180 min were 3.54 +/- 0.66 and 2.45 +/- 0.82 mg kg(-1) min(-1) in the PI and VI groups, respectively, P < 0.05. Furthermore, dogs under pancreatic clamp conditions were controlled after a 2-g/kg oral glucose load by applying the closed-loop intraportal (PO) or intravenous (IV) insulin infusion algorithm. There were no significant differences in glycemic control and insulin requirements between these algorithms. However, the maximum peripheral venous and arterial plasma insulin concentrations with the PO algorithm were significantly lower than those with the IV algorithm [305.1 +/- 68.9 and 468.1 +/- 66.9 pmol/l (peripheral vein) and 305.3 +/- 62.9 and 469.6 +/- 85.1 pmol/l (artery) with the PO and IV algorithms, respectively, P < 0.05]. On the other hand, the maximum portal plasma insulin concentration with the PO algorithm was significantly higher than that with the IV algorithm (619.9 +/- 101.7 and 414.3 +/- 79.9 pmol/l with the PO and IV algorithms, respectively, P < 0.05). The mean NHGU values with the PO algorithm were significantly greater than those with the IV algorithm. Our results confirmed that closed-loop portal insulin delivery is feasible with regard to both insulin profiles and hepatic glucose handling in vivo, and indicated that the portal vein is the most suitable insulin delivery route for the artificial endocrine pancreas.

Algorithms↗

Strict glycemic control in diabetic dogs with closed-loop intraperitoneal insulin infusion algorithm designed for an artificial endocrine pancreas.

The ultimate goal of the development of an artificial endocrine pancreas is to achieve long-term strict glycemic regulation. To establish the physiological insulin delivery route of the artificial endocrine pancreas, intraperitoneal insulin infusion may be important. For this purpose, we tried to develop a closed-loop intraperitoneal insulin infusion algorithm by analyzing the pharmacokinetics of intraperitoneal regular insulin absorption using a mathematical model. The parameters for this algorithm were calculated to simulate the plasma insulin profile after intraperitoneal insulin injection as closely as possible. To evaluate the appropriateness of this algorithm, we tried glycemic control after an oral glucose load of 2 g/kg or a meal load of 80 kcal/kg in diabetic dogs by applying the algorithm. With the use of the subcutaneous insulin lispro infusion algorithm, which we have previously reported, alloxan-induced diabetic dogs exhibited postprandial hyperglycemia and delayed hyperinsulinemia, followed by hypoglycemia after an oral glucose load of 2 g/kg. However, by using the intraperitoneal insulin infusion algorithm, excellent glycemic control (postprandial blood glucose levels of 9.1 +/- 0.8 mmol/l at 70 min and 3.8 +/- 0.3 mmol/l at 240 min, respectively) could be achieved without any associated delayed hyperinsulinemia or hypoglycemia. Glycemic excursion after a meal load of 80 kcal/kg was also controlled from 3.9 to 10.1 mmol/l. Our results confirm that the intraperitoneal insulin infusion algorithm in vivo is feasible and that this algorithm can be superior to the subcutaneous insulin lispro infusion algorithm in the regulation of blood glucose.

Algorithms↗

Atypical Bartter syndrome with sensorineural deafness with G47R mutation of the beta-subunit for ClC-Ka and ClC-Kb chloride channels, barttin.

Bartter syndrome comprises several related renal tubular disorders including classic Bartter, infantile Bartter (IBS), and Gitelman syndrome. A new distinct group in Bartter syndrome accompanied by sensorineural deafness (BSND) has been identified among the IBS patients. Recently a gene encoding an essential beta-subunit for ClC chloride channels, named barttin, with several mutations of the gene as the cause of BSND, has been described. We have observed a male who had not been diagnosed as Bartter syndrome until 28 yr because of a mild clinical manifestation. The patient was affected with congenital deafness, which urged us to analyze his gene for barttin, and a mutation G47R, which was previously reported, has been identified. However, the clinical feature in the patient lacking the characteristic symptoms of IBS such as polyhydramnios, premature labor, or severe salt loss in neonatal period contrasts with that of the typical BSND patients described so far in the literature. This might be due to a less severe loss of function of barttin induced by G47R mutation, compared with others, and our observation seems to suggest a possibility of the prevalence of mild form BSND with various levels of barttin dysfunction among patients with congenital deafness of unknown origin.

Adult↗

A case of ACTH-independent macronodular adrenal hyperplasia: simultaneous expression of several aberrant hormone receptors in the adrenal gland.

ACTH-independent macronodular adrenal hyperplasia (AIMAH) is a rare cause of Cushing's syndrome. Recently, aberrant expression of adrenal receptors for various hormones and/or cytokines has been identified in several cases with AIMAH, which may act as a pathogenetic factor for the disorder. We report here an AIMAH patient with a Rathke's cleft cyst. Endocrinological examinations revealed that the pituitary cyst had no hormonal secretion. Administrations of either AVP or isoproterenol provoked cortisol production in the patient, whereas DDAVP, mosapride or endogenous LH induced by GnRH did not. Reverse transcriptional-PCR analysis of total RNA obtained from the patient's adrenal tissue revealed the expression of mRNA of receptors for V1a, V1b, V2, and LH/hCG. Three of these receptors except for V1a receptor were not expressed in normal adrenal tissue. Hyperosmolar saline infusion promoted the patient's cortisol secretion through the increase in endogenous AVP (peak plasma AVP level reached 90.4 pg/ml during the test). These results suggest that endogenous AVP and catecholamines are involved in the pathophysiology of the patient. Further study will be necessary to clarify the molecular mechanisms that regulate tissue-specific expression of these receptors and their role in the overgrowth of adrenal in AIMAH.

Adrenal Glands↗