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Biomedical subjects

G Reach

Publications and source records attributed to G Reach.

At least 91 records · Page 5Linked to original sources
PubMed1992

Progress toward the development of an implantable sensor for glucose.

The development of an electrochemically based implantable sensor for glucose is described. The sensor is needle-shaped, about the size of a 28-gauge needle. It is flexible and must be implanted subcutaneously by using a 21-gauge catheter, which is then removed. When combined with a monitoring unit, this device, based on the glucose oxidase-catalyzed oxidation of glucose, reliably monitors glucose concentrations for as long as 10 days in rats. Various design considerations, including the decision to monitor the hydrogen peroxide produced in the enzymatic reaction, are discussed. Glucose constitutes the most important future target analyte for continuous monitoring, but the basic methodology developed for glucose could be applied to several other analytes such as lactate or ascorbate. The success in implementation of such a device depends on a reaction of the tissue surrounding the implant so as not to interfere with the proper functioning of the sensor. Histochemical evidence indicates that the tissue response leads to enhanced sensor performance.

Biocompatible Materials↗
PubMed1991

Design and in vitro studies of a needle-type glucose sensor for subcutaneous monitoring.

A new miniaturized glucose oxidase based needle-type glucose microsensor has been developed for subcutaneous glucose monitoring. The sensor is equivalent in shape and size to a 26-guage needle (0.45-mm o.d.) and can be implanted with ease without any incision. The novel configuration greatly facilitates the deposition of enzyme and polymer films so that sensors with characteristics suitable for in vivo use (upper limit of linear range greater than 15 mM, response time less than 5 min, and sensitivity yielding a 5:1 signal-to-background ratio at normal basal glucose levels) can be prepared in high yield (greater than 60%). The sensor response is largely independent of oxygen tension in the normal physiological range. It also exhibits good selectivity against common interferences except for the exogenous drug acetaminophen.

Animals↗
PubMed1991

[The Aide to Juvenile Diabetes Association: its role in the management and education of patients with insulin-dependent diabetes].

"L'Aide aux Jeunes diabétiques" (AJD) is an association which strives to help insulin-dependent patients assume responsibility for the management of their disease and lead normal lives. As in all chronic diseases, self-care concerning management is essential in diabetes mellitus and requires patient education which is an integral part of the therapeutic program. AJD organizes three types of interventions. 1) Stays in special summer camps provide children, teenagers and young adults with the opportunity for receiving education in a recreational setting conducive to acquisition of knowledge and behaviors required for the management of their disease. Each year, over 1,000 children stay in these camps. Furthermore, vacation camps provide physicians and nurses with unique opportunities for gaining proficiency in the monitoring and treatment of diabetes mellitus. 2) Continuing education through a news bulletin and information meetings improves compliance to treatment. 3) Social and scientific interventions directly involve AJD members and provide them with regular information. In conclusion, AJD plays a central role in the management of type I diabetes mellitus in France.

Adolescent↗
PubMed1990

High-performance liquid chromatography analysis of circulating insulins distinguishes between endogenous insulin production (a potential pitfall with streptozotocin diabetic rats) and islet xenograft function.

Porcine islets of Langerhans were microencapsulated according to the alginate-polylysine procedure, and implanted into the peritoneal cavity of 15 streptozotocin-induced (70 mg/kg) diabetic rats (6000 microencapsulated islets per rat). In four animals, a sustained decrease in plasma glucose level below 8.3 mmol/l was observed for up to nine months. However, it was possible to recover microcapsules from the peritoneal cavity of only one rat, and they were found to be damaged and containing no detectable tissue. When insulin in the plasma of three of these animals was analysed by reversed phase high-performance liquid chromatography, only rat insulins I and II, but not porcine insulin was detectable, indicating unambiguously that at the time of analysis, the correction of diabetes in these animals was due to the function of the recipient's own pancreas rather than the continued, long-term, function of the implanted porcine islets. These data confirm that in this model of diabetes, function of the host pancreas can resume following islet transplantation, leading in turn to the potential for a major bias in the interpretation of the data. In the case of an islet xenograft, when the donor's and recipient's insulins can be separated by high-performance liquid chromatography, this non-invasive analytical method should prove useful for identifying the source of insulin in the circulation, and thus the relative functional status of the endogenous and transplanted islets.

Animals↗
PubMed1990

Ex vivo evaluation in normal dogs of insulin released by a bioartificial pancreas containing isolated rat islets of Langerhans.

In bioartificial pancreatic systems, isolated islets of Langerhans are protected against immune rejection by an artificial membrane, permeable to glucose and insulin, but not to immunoglobulins and lymphocytes. Some of these devices, referred to as vascular systems, are set up to be connected to a vascular site in the recipient, with blood circulating in contact with one side of the membrane, and the islets on the other side. Such a bioartificial pancreas, containing isolated rat islets of Langerhans, was connected to an arteriovenous shunt of a normal anesthetized dog. The aim of this experiment was to investigate the kinetics of the insulin secretory response of the system to a glucose load. Glucose was infused upstream of the system, increasing the glucose concentration inside the bioartificial pancreas from 7 to 14 mmol/l, without altering the blood glucose concentration of the dog. Insulin concentration was determined simultaneously upstream and downstream of the bioartificial pancreas. Insulin production was calculated by multiplying the difference between these values by the blood flow rate. Blood flow rate (Q) was estimated from the change in the glucose concentration produced by the glucose infusion using a mass transfer analysis derived from Fick's principle. Insulin production increased from 20 +/- 8 to 59 +/- 15 microU/100 islets/min within 15 min following the beginning of the stimulation (n = 6, p less than 0.05). Five min after the end of the stimulation, insulin production decreased from 75 +/- 13 to 50 +/- 9 microU/100 islets/min (p less than 0.05) to reach the basal level (21 +/- 3 microU/100 islets/min) 30 min after the end of the glucose stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylic Resins↗
PubMed1990

Comparative study of microencapsulated rat islets implanted in different diabetic models in mice.

Microencapsulated rat islets of Langerhans (alginatepolylysine microcapsules) were implanted into the peritoneal cavity of diabetic mice (500 rat islets per mouse) in order 1) to evaluate the ability of this xenograft in correcting hyperglycemia in different models of diabetes and 2) to examine the implanted material recovered from the recipients after several weeks. 1) In the high-dose streptozotocin model in Balb/c mice (n = 14), 6 had a sustained (over one month) decrease in plasma glucose concentration from 401 +/- 7 to 171 +/- 7 mg/dl, with no effect in the other. 2) In the low dose streptozotocin model in C57BL/6J mice (n = 17), plasma glucose levels decreased in 9 mice, from 439 +/- 27 to 180 +/- 30 mg/dl, and remained below 250 mg/dl up to 60 days. In 8 mice, only a transient effect was observed. Empty capsule transplantation had no effect. Plasma insulin in successfully transplanted mice was higher in fed than in fasted state. 3) Microencapsulated rat islets had no effect on plasma glucose in male NOD mice made diabetic by cyclophosphamide treatment (n = 10). Thus, microencapsulated rat islets can improve the diabetic state in some, but not all diabetic mice. In this study, microcapsules were consistently surrounded by an inflammatory reaction, which remains a major concern.

Animals↗
PubMed1989

Determination of peritoneal glucose kinetics in rats: implications for the peritoneal implantation of closed-loop insulin delivery systems.

Peritoneal glucose kinetics were evaluated in the anaesthetized rat, to assess whether the peritoneal cavity would be a suitable site for the implantation of membrane-protected islets of Langerhans (bioartificial pancreas) or the glucose sensor of an artificial B cell. Glucose was measured in peritoneal fluid samples aspirated by needle puncture. Basal peritoneal and blood glucose concentrations were identical in 16 h fasted (n = 4) and non fasted (n = 3) animals. After 10 min of an i.v. glucose infusion (n = 15) the increment in peritoneal glucose concentration was 63 +/- 3% of the increment in blood glucose concentration and both values were significantly correlated (r = 0.92; p less than 0.001). After 10 min of glucose clamping (12.6 +/- 0.8 mmol/l), the increment in peritoneal glucose concentration was 69 +/- 3% (n = 5; p less than 0.05) of the increment in blood glucose concentration. In three additional experiments it was 93 +/- 3% of the increment in blood glucose concentration (NS), after 30 min of glucose clamping (8.0 +/- 0.5 mmol/l). Peritoneal glucose concentration monitored by a glucose sensor: (a) followed blood glucose sluggishly during a glucose clamp (n = 5), confirming the data shown above, (b) followed blood glucose with a 5 min delay and reached the same plateau after the intravenous injection of 1U insulin (n = 3; NS). We conclude that peritoneal glucose reflects blood glucose at basal state and during variations of glycaemia, nevertheless, presenting heterogeneous kinetics. These kinetics might be appropriate for a bioartificial pancreas but not for an in vivo calibration procedure, of a peritoneally implanted glucose sensor.

Animals↗
PubMed1989

Study and development of multilayer needle-type enzyme-based glucose microsensors.

Glucose oxidase (GOD) was covalently coupled to a cellulose acetate (CA) layer, using bovine serum albumin (BSA) and parabenzoquinone (PBQ) linkages. Prior to GOD coupling this CA layer was deposited on the platinum tip of a needle-type sensor and covered with an outer layer of polyurethane (PU). Such microsensors were found to be active, their GOD load reaching 1.6 to 3.0 micrograms mm-2 and their glucose response reaching 1 to 3 microA M-1 mm-2, even when the upper limit of their linear range reached 10-30 mM. Due to the multilayer structure and composition of these microsensors, small anions such as ascorbate were partially discriminated from neutral molecules such as hydrogen peroxide. When implanted subcutaneously in anaesthetized rats, sensor responses correlated correctly with blood glucose concentration but presented sensitivity coefficients significantly different to those determined in vitro: a 2 point calibration procedure was found necessary for in vivo experiments.

Animals↗
PubMed1989

Portal versus peripheral venous drainage in segmental pancreatic transplantation in diabetic rats.

The effect of the site of venous drainage in segmental pancreatic transplantation was investigated in diabetic rats with two surgical procedures anastomosing the superior mesenteric vein either on the vena cava (systemic drainage) or on the superior mesenteric vein (portal drainage). Both procedures corrected polyuria, glycosuria, and blood glucose concentration, and resulted in similar peripheral hyperinsulinemia. Intravenous glucose tolerance tests were performed 8 weeks after transplantation. In portal-grafted rats, glucose tolerance was strictly normalized, with a plasma insulin profile similar to that observed in normal rats. In caval-grafted rats, a delayed plasma insulin peak was observed with slight abnormalities in the plasma glucose profile, the late plasma glucose concentrations being higher than in portal-grafted animals. The extent of fibrosis was similar under both conditions. This study, performed in rats, of the influence of venous drainage on the metabolic outcome of segmental transplantation, demonstrating an abnormal plasma insulin profile during a glucose challenge in case of caval drainage, is consistent with other studies suggesting that the site of drainage might be important in case of reduced grafted mass.

Animals↗
PubMed1989

In vitro evaluation of a bioartificial pancreas under various hemodynamic conditions.

A bioartificial pancreas in which isolated islets of Langerhans are placed between two polyacrylonitrile membranes, blood circulating successively above the upper and below the lower membranes following a U-shaped circuit, has been developed. The two parts are connected by an outer loop consisting of a thin tubing. The length of this tubing determines the magnitude of the flow rate of blood through the device. The aim of this work was to determine experimentally the optimal configuration of the system containing isolated rat islets and a Krebs buffer circulating through the device. The amount of insulin released by the bioartificial pancreas was determined during a 20-mM square-wave glucose stimulation. First, the inlet pressure was set at 100 mm Hg, and the effect of the length of the tubing was investigated with two devices perfused simultaneously. For a short tubing (flow rate, 20 ml/min), a sharp increase in insulin release in response to glucose was observed; it increased within 4 min from 217 +/- 50 to 761 +/- 237 microU/500 islets/min (p less than 0.05), the peak value being reached at 11 +/- 2 min following the beginning of the stimulation. For a long tubing (flow rate, 3 ml/min), the increase in insulin release was more sluggish. It increased from 133 +/- 53 to 222 +/- 43 microU/500 islets/min at 4 min, the peak value being reached only at 20 +/- 3 min. These data are consistent with a more efficient diffusional transfer of insulin in the case of the high circulating flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylic Resins↗
PubMed1989

In vitro and in vivo stability of electrode potentials in needle-type glucose sensors. Influence of needle material.

Enzymatic glucose sensors are based on the amperometric detection of an oxidable species generated during the oxidation of glucose by glucose oxidase. This measurement usually requires a working electrode (anode), an auxiliary electrode (cathode), and a reference electrode, the function of the latter being to keep constant the working potential of the anode, which is responsible for current generation. However, in the needle-type glucose sensors proposed so far, the reference electrode is missing, and its function is performed by the auxiliary electrode. We investigated, in vitro and in vivo in rats, the ability of several cathode-needle materials to behave as a reference electrode in two-electrode glucose sensors, i.e., to present a stable auxiliary electrode potential. In vitro, when glucose concentration was raised from 0 to 30 mM, the auxiliary potential of both gold- and silver-coated sensors presented a cathodic drift, whereas that of silver/silver chloride-coated sensors remained stable. In vivo, during insulin-induced hypoglycemia (5.9-2.4 mM), the auxiliary potentials of all sensors remained stable, whereas during glucose infusion (mean blood glucose concentration 11.2 mM), the auxiliary potentials of both gold- and silver-coated sensors presented an anodic drift, whereas those of silver/silver chloride-coated sensors remained stable. We also indirectly quantified the changes in sensor response induced by variations in the working potential in vitro and in vivo, simulating those that might be produced by a drift in the auxiliary potential. Such changes in the working potential could bring about a 30% unspecific variation in sensor response. We conclude that improvements in sensor analytical characteristics should be obtained with silver/silver-chloride-coated cathodes.

Animals↗