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Biomedical subjects

M Shichiri

Publications and source records attributed to M Shichiri.

At least 217 records · Page 12Linked to original sources

The evaluation of glucagon infusion algorithms for a counterregulatory system in artificial endocrine pancreas.

As counterregulatory system of artificial endocrine pancreas, glucagon infusion algorithm has been developed and its usefulness has been examined in pancreatectomized dogs and a pancreatectomized diabetic patient. Glucagon infusion rate (G1nIR(t)) was determined depending on proportional plus derivative action to blood glucose concentration (BG(t] with the time delay (tau) to start infusion as follows. G1nIR(t) = Gp(BGp- BG(t-tau)) + Gd(-dBG(t-tau)) + Gc where BGp is the projected value of blood glucose concentration, Gp, and Gd are the coefficients and Gc is the constant for basal glucagon supplement. Glucagon infusions based only on proportional action (Gp/Gd/Gc/tau) = (0.2/0/0.4/10 or 0.4/0/0.4/10) failed in simulating the pattern of blood glucose or glucagon response seen in normal dogs. Glucagon infusion based on proportional plus derivative action (Gp/Gd/Gc/tau = 0.2/0.4/0.4/10) successfully mimicked the pattern of blood glucose concentration and plasma glucagon profile seen in normal dogs. This glucagon infusion algorithm has been applied to control insulin-induced hypoglycemia in a pancreatectomized patient with the same infusion parameters. Hypoglycemia was recovered to normoglycemia in 80 min and the plasma glucagon patterns showed no significant difference from those in healthy volunteers. These data indicate that glucagon infusion algorithm thus developed is effective to render hypoglycemia to normoglycemia and mimic plasma glucagon response seen in normal subjects.

Algorithms↗

Fail-safe systems for the wearable artificial endocrine pancreas.

For the long-term clinical use of the wearable artificial endocrine pancreas, a fail-safe system is an essential mechanism. Several hardware alarm systems have been incorporated for battery-down, and short-run of the pumps. Software alarm systems for overflow or underflow of the AD converter, empty bags, hypoglycemia, hyperglycemia, abnormal values of parameters, and excessive insulin infusion have also been built into the system. The software noise filter was effective in eliminating superimposed artificial noises and the noises induced by muscle exercise. Sudden changes in sensor output during glycemic control of diabetics due to short circuit, or disconnection of the sensor lead, were detected as overflow or underflow of the AD converter. A gradual change in the sensor output was heralded by the hyper- or hypoglycemia alarm sound. These data indicated that the fail-safe system built into the wearable artificial endocrine pancreas is useful for the long-term glycemic control of diabetics.

Blood Glucose↗

In vivo characteristics of needle-type glucose sensor--measurements of subcutaneous glucose concentrations in human volunteers.

To explore the clinical performances of the needle-type glucose sensor, in vivo monitoring was conducted in human subjects. The tissue glucose concentrations measured by glucose sensor were lower than the plasma glucose concentrations by 15%, but a good linear relationship was observed between the tissue and plasma glucose concentrations. The sensing sites between abdomen and forearm did not affect the tissue glucose monitoring. The tissue glucose concentrations after meal intake showed 5 min delayed response to the blood glucose concentrations. After 3 days' continuous monitoring, the "relative" sensor output to the plasma glucose concentration decreased by 26% and the "relative" response time to reach peak value prolonged from 5 min to 13.5 min. These data indicate the clinical usefulness of the needle-type glucose sensor.

Biosensing Techniques↗

Effect of dexamethasone on the synthesis and degradation of insulin receptor mRNA in cultured IM-9 cells.

The effect of glucocorticoid (dexamethasone) on insulin receptor mRNA was examined in the IM-9 cell line by dot hybridization analysis using insulin receptor c-DNA probe (phINSR 13-1). Insulin receptor mRNA was found in a dose- and time-dependent manner, to increase during a 24-h culture with glucocorticoid. Although there has been some dispute about the effect of glucocorticoid on degradation of the insulin receptor itself, we have found glucocorticoid had no significant effect on the degradation rate of insulin receptor mRNA. These results suggest that glucocorticoid has the effect of increasing de novo synthesis of insulin receptor mRNA. But the molecular mechanism of glucocorticoid's effect still needs to be investigated.

Cell Line↗

Efficacy of a multiple insulin injection regimen in teenagers with insulin-dependent diabetes. Carbohydrate and lipid oxidation measured by continuous indirect calorimetry.

Our study of insulin-dependent diabetic teenagers proved that a multiple insulin injection regimen (MIR) can be an acceptable and effective method of glycemic control. Further, the artificial beta cell can be used to determine insulin requirements for MIR. And finally, continuous indirect calorimetry can be used to assess metabolic control in diabetes.

Adolescent↗

Diffuse intrapulmonary hemorrhage and renal failure in adult Henoch-Schönlein purpura.

A 53-year-old woman with Henoch-Schönlein purpura presented with massive intrapulmonary hemorrhage and renal failure. Renal pathology revealed diffuse proliferative glomerulonephritis with granular deposition of immunoglobulin on immunofluorescent staining. Therapy with oral prednisolone resulted in resolution of the pulmonary lesions and renal failure.

Acute Kidney Injury↗

Hypouricemia due to increased tubular urate secretion.

A 45-year-old woman had hypouricemia (serum uric acid, 1.0-2.3 mg/dl) with increased uric acid clearance (29.8 +/- 9.3 ml/min/1.73 m2). Uric acid clearance to creatinine clearance ratio (Cua/Ccr) was suppressed markedly by pyrazinamide to 2.3% and surprisingly enhanced by probenecid to 227.8%. No other renal tubular or metabolic abnormalities were detected. This previously unreported high postprobenecid Cua/Ccr suggests that markedly increased urate secretion by the renal tubule is responsible for hypouricemia in this patient.

Creatinine↗

Validation of closed-loop subcutaneous insulin infusion algorithm--application of subcutaneous insulin absorption kinetics.

For long-term glycemic normalization with a closed-loop control system, a subcutaneous insulin infusion algorithm has been developed based on the pharmacokinetics of subcutaneously administered insulin. A 3-compartmental model was applied to mathematically express the relation between the insulin injected subcutaneously as an input and the plasma insulin response as an output. A computer simulation study using this model showed that the following insulin infusion algorithm is feasible for closed-loop glycemic control by selecting appropriate parameters (Kp/Kd/Kc = 0.0056/0.92/-0.11), IIR(t) = Kp G(t)+Kd d G(t)/dt+Kc, where IIR(t) is the subcutaneous insulin infusion rate at time t (min), G(t) is the blood glucose concentration and Kp, Kd, Kc are the constants. In 5 pancreatectomized dogs, subcutaneous insulin infusion with this algorithm made it possible to keep postprandial glycemic levels after oral glucose load (2 g/kg) at 168 +/- 14 mg/dl (mean +/- SEM) in 60 min and maintained normoglycemia from 180 to 300 min with the total amount of infused insulin being 0.14 +/- 0.019 U/kg. In 5 insulin-dependent diabetic patients, the peaks of postprandial glycemic levels after meal load (450 kcal) were controlled to 176 +/- 36 mg/dl at 90 min and were reduced to 98 +/- 13 mg/dl at 300 min with the total amount of infused insulin being 0.172 +/- 0.063 U/kg. The mean peak plasma insulin level was 49 +/- 11 microU/ml at 90 min. These results indicate the clinical controllability of postprandial glycemia with the closed-loop subcutaneous insulin infusion algorithm in diabetic patients.

Algorithms↗

Hypouricemia due to subtotal defect in the urate transport.

Hypouricemia due to renal tubular defects is rarely reported. We report here our observations of two such patients who cannot be classified into any of the previously reported categories of renal hypouricemia. They showed no suppression of urate clearance to creatinine clearance ratio (Cua/Ccr) following the administration of pyrazinamide, and no increase of Cua/Ccr after probenecid. It is tempting to speculate upon the subtotal defect in the urate transport as a condition explaining the above results.

Adult↗

The development of artificial endocrine pancreas. From bedside-, wearable-type to implantable one.

The artificial endocrine pancreas is a feedback controlled instrument regulating insulin delivery on a minute-by-minute basis according to measured blood glucose levels. It has been proven to be useful not only as the therapeutic tool of diabetes mellitus but also as an elegant research tool for investigating the pathophysiology of the disease. The wearable type of closed-loop system has been developed recently for the first time by the authors. The breakthrough is the establishment of needle-type glucose sensor. The trend in development of closed-loop glycemic control system which enables perfectly physiological regulation on long-term basis, is directed to implantable devices. Much efforts have been conducted now to realize these devices.

Blood Glucose↗

Diabetic renal hypouricemia.

In diabetes, the serum uric acid level is low due to increased urate clearance; however, its mechanism remains unknown. We examined seven maturity-onset diabetic patients with rarely reported hypouricemia due to renal tubular abnormality to better understand the renal handling of urate by the diabetic kidney. The results of studies indicate that the increase in urate clearance was entirely accounted for by increased pyrazinamide-suppressible urate clearance. The maximal uricosuric response to probenecid administration was exaggerated. The effects of drugs on urate clearance were similar to those we have previously reported in the syndrome of inappropriate secretion of antidiuretic hormone. In four patients, the family survey did not reveal anyone with hypouricemia. These observations suggest that hypouricemia due to hyperuricosuria, which responds markedly to pyrazinamide and probenecid, is actually an indicator of renal tubular abnormality in diabetics.

Adult↗

High frequency of class 3 allele in the human insulin gene in Japanese type 2 (non-insulin-dependent) diabetic patients with a family history of diabetes.

The restriction fragment length polymorphism in the 5' flanking region of the human insulin gene was studied in 155 nonobese Japanese subjects. The subjects consisted of 36 Type 2 (non-insulin-dependent) diabetic patients with a family history of diabetes mellitus, 42 Type 2 diabetic patients without a family history of diabetes, 42 Type 1 (insulin-dependent) diabetic patients, and 35 healthy volunteers who served as control subjects. It was demonstrated that, in Japanese healthy subjects and diabetic patients, the incidence of the insertion into 5' flanking region of the insulin gene was found to be significantly lower (p less than 0.05) than those in Caucasians and other races already investigated. Even though the class 3 gene allelic frequency in Type 2 diabetic patients without a family history of diabetes (0.060) was not higher than that in healthy subjects (0.014), in nonobese Type 2 diabetic patients with a family history of diabetes the allelic frequency of the inserted class 3 gene (0.111) was found to be significantly higher (p less than 0.02) than that in control subjects. These data suggest that the insulin gene polymorphism relates to the aetiology of diabetes mellitus.

Adult↗

Blood glucose control by an artificial endocrine pancreas in a patient with phaeochromocytoma.

In a patient with phaeochromocytoma who presented with unstable diabetes mellitus, an artificial endocrine pancreas was used intraoperatively. Anaesthetic agents included enflurane, nitrous oxide and oxygen. Nicardipine was used to control hypertensive episodes. The initial blood glucose concentration was 173 mg X dl-1 and it decreased to 110 mg X dl-1 in response to insulin infusion, but plasma catecholamines were markedly increased. Seventy minutes later, the glucose concentration increased progressively to 249 mg X dl-1 despite massive insulin infusion, maximally 5.64 mU X kg-1 X min-1. The blood glucose concentration reached a peak at the time of the ligation of the venous drainage from the tumour and the peak was coincident with that of plasma catecholamine levels (epinephrine: 20.8 ng X ml-1, norepinephrine 16.4 ng X ml-1). Both glucose and catecholamine concentrations decreased promptly after removal of the tumour and hypotension followed likely because of a persistent vasodilatatory effect of nicardipine. The profiles of blood glucose, insulin and glucose infusion rates provided by the artificial endocrine pancreas suggested that the insulin resistance began to be reversed shortly after removal of the phaeochromocytoma.

Adrenal Gland Neoplasms↗

The mechanism of exaggerated glucagon response to arginine in diabetes mellitus.

As far as exaggerated arginine-induced glucagon secretion in diabetics is concerned, the authors have shown that both the restoration of blood glucose excursions and physiological insulinemia in response to arginine, obtained from an artificial endocrine pancreas (AEP) could normalize the glucagon secretory responses in diabetes mellitus. To clarify whether or not physiological glycemic excursions and/or plasma insulin profiles contribute to the normalization of the exaggerated glucagon response in diabetes mellitus, the following 4 investigations were conducted on each of 7 non-obese, non-insulin-dependent diabetic (NIDDM), and 8 insulin-dependent diabetic (IDDM) subjects, with the aid of AEP. Arginine was i.v. infused into both diabetic groups (1) in a hyperglycemic state without insulin infusion, (2) in perfect glycemic control with insulin infusion by AEP, (3) in glycemic control with AEP, but with lower plasma insulin profiles (parameters of the insulin infusion algorithm were made smaller than those of (2], (4) in a state where blood glucose levels were clamped at the same levels as obtained in (1) with the aid of glucose infusion controlled by AEP, and where physiological plasma insulin profiles were mimicked by infusing insulin at the same rates used in (2) with a pre-programmable insulin infusion system. The changes in the plasma glucagon (IRG) response in each experiment were compared with those seen in healthy subjects. For both diabetic groups it was found that: in (2) perfect normalization of glucagon response was achieved.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Enhanced bioavailability of insulin after rectal administration with enamine as adjuvant in depancreatized dogs.

Rectal absorption of insulin by depancreatized dogs was significantly enhanced by the coadministration of enamine as a suppository adjuvant and if this was followed by a further suppository containing enamine alone, the insulin absorption was even further enhanced. The additional enamine suppository resulted in high serum insulin concentrations for a longer time and effected a significant decrease in serum glucose concentrations. To decrease serum glucose concentrations effectively in depancreatized dogs, serum insulin levels had to remain high for a long period of time, rather than be transient.

Adjuvants, Pharmaceutic↗