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Biomedical subjects

G Reach

Publications and source records attributed to G Reach.

At least 73 records · Page 4Linked to original sources

RINm5F cell culture on Sephadex derivatives.

Interactions between polystyrene sodium sulfonate and insulin-secreting RINm5F cells have been previously described. When cultured on these microcarriers, cells exhibited normal growth, altered morphology, and inhibition of the insulin secretion was observed. For the sake of comparison, interactions of RINm5F cells with Sephadex derivatives, namely, carboxymethyl Sephadex (CM Seph), benzylaminated CM Seph (CMB Seph), and sulfonated CMB Seph (CMBS Seph), as well Sephadex, were studied. Cells attached poorly and did not spread onto Sephadex and CM Seph microcarriers, but all other characteristics were normal. In contrast, with cells cultured on CMB Seph and CMBS Seph microcarriers cell attachment, morphology, and growth rate were comparable to those of cells grown on classic plastic wells. But, in the latter case, surprisingly, insulin secretion was enhanced. This effect is composition of the microcarriers dependent. The insulin secretion per cell-microcarriers composition relationship suggests a specific interaction between an unknown membrane receptor of RINm5F cells and a composite ligand site made of a combination of different chemical functional groups present at the microcarriers surface.

Animals↗

A glucose monitoring system for on line estimation in man of blood glucose concentration using a miniaturized glucose sensor implanted in the subcutaneous tissue and a wearable control unit.

We have developed a miniaturized glucose sensor which has been shown previously to function adequately when implanted in the subcutaneous tissue of rats and dogs. Following a glucose load, the sensor output increases, making it possible to calculate a sensitivity coefficient to glucose in vivo, and an extrapolated background current in the absence of glucose. These parameters are used for estimating at any time the apparent subcutaneous glucose concentration from the current. In the previous studies, this calibration was performed a posteriori, on the basis of the retrospective analysis of the changes in blood glucose and in the current generated by the sensor. However, for clinical application of the system, an on line estimation of glucose concentration would be necessary. Thus, this study was undertaken in order to assess the possibility of calibrating the sensor in real time, using a novel calibration procedure and a monitoring unit which was specifically designed for this purpose. This electronic device is able to measure, to filter and to store the current. During an oral glucose challenge, when a stable current is reached, it is possible to feed the unit with two different values of blood glucose and their corresponding times. The unit calculates the in vivo parameters, transforms every single value of current into an estimation of the glucose concentration, and then displays this estimation. In this study, 11 sensors were investigated of which two did not respond to glucose. In the other nine trials, the volunteers were asked to record every 30 s what appeared on the display during the secondary decrease in blood glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

In vitro activation of human macrophages by alginate-polylysine microcapsules.

Microencapsulated islets of Langerhans have been proposed as a bioartificial pancreas. However, foreign body reaction with fibrosis has been observed around implanted microcapsules. Since macrophages are present in this reaction and interleukin-1 (IL-1), a cytokine released by activated macrophages, may induce fibrosis, we tested the capacity of alginate-polylysine microcapsules to activate macrophages. Human monocytes were isolated from whole blood of healthy donors by a Ficoll density gradient and adherence to a plastic support. Monocytes were cultured for 24 h with: (1) alginate-polylysine microcapsules; (2) lipopolysaccharide (LPS) (positive control group); and (3) alone (negative control group). Monocyte activation was evaluated by measuring the secretion of IL-1 beta and the production of intracellular IL-1 alpha and IL-1 beta. Macrophages characterization was performed by immunocytological subtyping. IL-1 beta release and intracellular IL-1 beta and IL-1 alpha production were significantly higher when macrophages were cultured with alginate-polylysine microcapsules than when macrophages were cultured alone. In conclusion, macrophages are activated in vitro by alginate-polylysine microcapsules. This effect may be involved in the fibrosis observed in vivo around implanted microcapsules. In addition, interleukin-1, released during macrophage activation, may cross the microcapsule membrane and impair islet function.

Alginates↗

HbA1c in children attending summer camps organized by l'Aide aux Jeunes Diabétiques. Evidence for a harmful effect of lipohypertrophies in the early years of diabetes.

Glycated haemoglobin was determined by using the spot test method for blood sampling in all the children and teenagers attending the summer camps organized by l'Aide aux Jeunes Diabétiques in July 1989. A questionnaire was completed for each subject, relating age, the duration of the disease, the insulin regimen, the level of knowledge, the intensivity of urine and blood glucose self monitoring, and the presence of lipohypertrophies. The statistical analysis of the data suggests that the two only parameters which were found to have an influence on the level of glycated haemoglobin were the duration of the disease and the presence of lipohypertrophies: in the early years of diabetes (up to 4 years), HbA1c was significantly lower in patients without lipohypertrophies (7.90 +/- 0.18%, n = 78), than in those with lipohypertrophies (8.60 +/- 0.22%, n = 46, m +/- SEM, p < 0.02). This study should focus the attention of clinicians on the deleterious effect of lipohypertrophies, which can be observed very early on in the course of the disease.

Adolescent↗

The feedback between monitoring and improvement of quality of diabetes care.

The need for permanent, population-wide, improvement in metabolic care of diabetic patients is generally accepted. This paper highlights some related aspects which must be considered by any health care provider: (1) Monitoring metabolic or other variables in diabetic patients is an essential tool in routine metabolic care, where a "short feedback" between monitored data and medical or behavioral measures is permanently established by the patients themselves, the physicians, the nurses etc. (2) Quality insurance requires the closure of a "long feedback" between informations and interventions, such as conditions, tools, methods, used at the different levels of the care system, from the individual patient to a population scale. (3) Appropriate epidemiological studies are required to program and evaluate the effect of any activity aimed at insuring and maybe improving the quality of care of diabetic patients, especially if one considers the time required to reach "hard end-points" such as the evaluation of patient mortality or the outcome of children from diabetic mothers. (4) The knowledge of incidence and prevalence rates of diabetes and its complications, and of risk factors may stimulate the political and economical recognition of the importance of the disease by health care officials. (5) In this way, the medical recognition is also stimulated within the professional team responsible for the establishment of the "long feedback" of quality insurance at the level of a given method, of an individual patient or of a health care unit, and for the actual implementation of generally accepted knowledge, everywhere in routine care.

Blood Glucose Self-Monitoring↗

Can continuous glucose monitoring be used for the treatment of diabetes.

In the case of the glucose sensor, clinicians and chemists must cooperate in interdisciplinary research to carefully define the analytical problem. Although not specifically discussed in this article, another group that must participate in this effort is engineers. Their expertise is needed to design the monitoring and control unit that contains the alarm and pump systems. The glucose sensor must operate reliably in an in vivo environment, provide the clinical information needed, and be easy to operate and manufacture.

Animals↗

Towards continuous glucose monitoring: in vivo evaluation of a miniaturized glucose sensor implanted for several days in rat subcutaneous tissue.

A miniaturized amperometric, enzymatic, glucose sensor (outer diameter 0.45 mm) was evaluated after implantation in the subcutaneous tissue of normal rats. A simple experimental procedure was designed for the long-term assessment of the sensor's function which was performed by recording the current during an intraperitoneal glucose load. The sensor was calibrated by accounting for the increase in the current during the concomitant increase in plasma glucose concentration, determined in blood sampled at the tail vein. This made it possible to estimate the glucose concentration in subcutaneous tissue. During the glucose load, the change in subcutaneous glucose concentration followed that in blood with a lag time consistently shorter than 5 min. The estimations of subcutaneous glucose concentration during these tests were compared to the concomitant plasma glucose concentrations by using a grid analysis. Three days after implantation (n = 6 experiments), 79 estimations were considered accurate, except for five which were in the acceptable zone. Ten days after implantation (n = 5 experiments), 101 estimations were accurate, except for one value, which was still acceptable. The sensitivity was around 0.5 nA.mmol-1.l-1 on day 3 and day 10. A longitudinal study on seven sensors tested on different days demonstrated a relative stability of the sensor's sensitivity. Finally, histological examination of the zone around the implantation site revealed a fibrotic reaction containing neocapillaries, which could explain the fast response of the sensor to glucose observed in vivo, even on day 10. We conclude that this miniaturized glucose sensor, whose size makes it easily implanted, works for at least ten days after implantation into rat subcutaneous tissue.

Animals↗

Calibration in dogs of a subcutaneous miniaturized glucose sensor using a glucose meter for blood glucose determination.

The feasibility of calibrating a glucose sensor by using a wearable glucose meter for blood glucose determination and moderate variations of blood glucose concentration was assessed. Six miniaturized glucose sensors were implanted in the subcutaneous tissue of conscious dogs, and the parameters used for the in vivo calibration of the sensor (sensitivity coefficient and extrapolated current in the absence of glucose) were determined from values of blood glucose and sensor response obtained during glucose infusion. (1) Venous plasma glucose level and venous total blood glucose level were measured simultaneously on the same sample, using a Beckman analyser and a Glucometer II, respectively. The regression between plasma glucose (x) and whole blood glucose (y) was y = 1.12x-0.08 mM (n = 114 values, r = 0.96, p = 0.0001). The error grid analysis indicated that the use of a Glucometer II for blood glucose determination was appropriate in dogs. (2) The in vivo sensitivity coefficients were 0.57 +/- 0.11 nA mM-1 when determined from plasma glucose, and 0.51 +/- 0.07 nA mM-1 when determined from whole blood glucose (t = 1.53, p = 0.18, n.s.). The background currents were 0.88 +/- 0.57 nA when determined from plasma glucose, and 0.63 +/- 0.77 nA when determined from whole blood glucose (t = 0.82, p = 0.45, n.s.). (3) The regression equation of the estimation of the subcutaneous glucose level obtained from the two methods was y = 1.04x + 0.56 mM (n = 171 values, r = 0.98, p = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evaluating in vitro and in vivo the interference of ascorbate and acetaminophen on glucose detection by a needle-type glucose sensor.

The aim of this work was to assess, in vitro and in vivo, the interference of ascorbate and acetaminophen on glucose measurements by a needle-type glucose sensor detecting hydrogen peroxide generated during the enzymatic oxidation of glucose, and to ascertain whether the protection against interference by the membranes used in the construction of the electrode is feasible. The oxidation of ascorbate and acetaminophen on a platinum electrode set at a 650 mV potential yielded a current representing 75 +/- 5% and 25 +/- 6% of that generated by the oxidation of an equimolar concentration of hydrogen peroxide, respectively. The bias introduced by the presence of 100 mumol l-1 ascorbate on the reading of 5 mmol l-1 glucose by the complete sensor (electrode + membranes) would be minimal (approximately 0.4 mmol l-1). By contrast, the bias introduced by 200 mumol l-1 of acetaminophen (a plasma concentration easily reached in clinical practice) was about 7 mmol l-1. The sensor was implanted subcutaneously in anaesthetized rats (n = 3). Using the current generated in the presence of a plasma acetaminophen concentration of about 200 mumol l-1 for glucose monitoring would lead to a major underestimation (approx. 6 mmol l-1) of subcutaneous glucose concentrations.

Acetaminophen↗