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M Pinget

Publications and source records attributed to M Pinget.

At least 55 records · Page 3Linked to original sources

Pancreatic islet macroencapsulation: a new device for the evaluation of artificial membrane.

We propose a new device especially designed to test membranes for islet macroencapsulation. It is composed of three independent parts: a support made of three polytetrafluoroethylene rings, the membrane that forms the walls of the encapsulation chamber, and a collagen gel that immobilizes the islets. Studies of this device were performed with the AN69 membrane. After 2 months of implantation in the peritoneal cavity of rats, the empty device was found to be biocompatible, referred to as weak cellular adhesion. In vitro the encapsulation preserved the peak of insulin release in response to high glucose during a perifusion test (0.36 +/- 0.02 microU/ml/islet for free or encapsulated islets). As a result of the collagen gel, the morphological aspect and functional activity were still preserved after 7 days of culture. In vivo xenotransplantation into diabetic mice normalized the fasting glycemia up to 30 days. Numerous macrophages adhered to the outer surface of the membrane, and a layer of cells emerging from the destruction of islets covered the inner surface. In addition, the morphological aspect of many islets was altered. By showing that the AN69 membrane was only partially efficient for islet xenotransplantation, this new device proved to be of interest for testing a variety of membranes.

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Intestinal absorption of PLAGA microspheres in the rat.

Rhodamine B-labelled poly (DL-lactide-co-glycolide) (PLAGA) microspheres of 2 different sizes, 1-5 microns and 5-10 microns, were administered as a single dose (1.44 x 10(9) and 1.83 x 10(8) particles, respectively) into the ileal lumen of adult rats. The content of rhodamine in the mesenteric vein and ileal lumen was analysed periodically from 10 min to 48 h as well as the distribution of microspheres in the intestinal mucosa and various other tissues. The concentration of rhodamine decreased progressively in the intestinal lumen and was negligible after 24 h. The number of microspheres in the mesenteric vein increased rapidly and reached a maximum after 4 h whatever the size of the particles. It then decreased progressively, but more rapidly with microspheres > 5 microns than with microspheres < 5 microns. The absorption efficiency was low for the former batch (about 0.11% of the administered dose) and higher for the latter (about 12.7%). The intraileal administration of free rhodamine B was followed by intense labelling of the epithelial cells and basement membranes in mesenteric lymph nodes, spleen, kidney and liver. PLAGA microspheres mainly crossed the intestinal mucosa at the site of Peyer's patches where microspheres of < 5 microns appeared after 3 h. Microspheres > 5 microns were retained in the ileal lumen. A few small microspheres were occasionally observed in the epithelial cells. Only the smallest particles were recovered in the liver, lymph nodes and spleen while basement membranes were always labelled. It is concluded that PLAGA microspheres could be useful for the oral delivery of antigens if their size is between 1 and 5 microns.

Animals↗

Immunogenicity of intraperitoneal insulin infusion using programmable implantable devices.

Intraperitoneal insulin infusion using implantable devices in insulin-dependent diabetic (IDDM) patients is promising since it improves diabetic control and decreases frequency of hypoglycaemia. However, preliminary data show a striking increase in plasma levels of anti-insulin antibodies with this therapy. In order to more precisely evaluate the immunogenicity and its consequences, anti-insulin antibody levels in 62 IDDM patients were assessed every 3 months during a 2-year period following pump implantation. At the same time, diabetes control was evaluated with HbA1c, mean blood glucose levels, standard deviation of the daily blood glucose levels and the frequency of low blood glucose (< 3.58 mmol/l). Factors involved in antibody formation such as age, gender, HLA typing, and complement C4 alleles were also studied. After implantation, anti-insulin antibody levels increased significantly from 3.14% (range 0-26%) to 8.34% (0-49%) after 1 year and remained elevated. Patients were divided into two groups: responders able to show at least one antiinsulin antibody titre higher than 15% and non-responders whose titres were always lower than 6%. None of the factors studied was shown to statistically influence the anti-insulin antibody titres. Non-responders had significantly better metabolic results than the responders. Severe hypoglycaemic episodes decreased dramatically in both groups. Insulin requirements were comparable at time 0 and decreased initially in both groups. They remained low for the non-responders but returned to pre-implantation values for responders. Intraperitoneal insulin infusion led to a high immunogenetic response towards insulin in about half of the patients, leading to only moderately deleterious effects on metabolic control.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Influence of corona surface treatment on the properties of an artificial membrane used for Langerhans islets encapsulation: permeability and biocompatibility studies.

An artificial membrane (AN69 Hospal) suitable for pancreatic islets encapsulation was submitted to a physicochemical treatment (corona discharge) to improve its insulin permeability. This effect depends on the duration of the electrical discharge (expressed as the speed of a conveyor belt) and the distance between the electrodes and the membrane. Among the various treatments tested, the most efficient (distance of 5 cm and a speed of 2 cm s-1) produced a three-fold increase in insulin diffusion. This improvement persisted after a protein-coating test which mimics in vivo conditions. At 1 y after the peritoneal implantation, the corona-treated membrane remained biocompatible. Thus, corona discharge treatment may serve to optimize the properties of artificial membranes used for pancreatic islets encapsulation.

Animals↗

Captopril-induced acute pancreatitis.

OBJECTIVE: To increase awareness concerning abdominal pain associated with the use of captopril, which is a molecule frequently used in diabetic patients. CASE: One case of acute pancreatitis associated with captopril, confirmed by a reintroduction, is described in a type II diabetes patient. CONCLUSIONS: Captopril and other angiotensin-converting enzyme inhibitors are very frequently prescribed in diabetic patients. Therefore, it is important to be aware of the possibility of pancreatitis linked to these molecules and to withdraw the treatment in case of severe unexplained abdominal pain.

Abdominal Pain↗

[Implantable insulin pump: the first step towards an artificial pancreas].

Recent improvements in miniaturization of implantable pumps and the ability of their control by teletransmission allow implantation of autonomous pumps which administer insulin into the peritoneal cavity. Fifty-six patients with diabetes mellitus underwent implantation of 66 pumps with a mean function life of 21.8 months per patient. No patient has died to date. Tolerance of implanted components was good. Morbidity was limited to local events, in this series 4 cutaneous erosions, two of them leading to final pump explantation. Mean global blood-sugar, pre- and post-prandial blood-sugar, and glycosylated hemoglobin assays were all lower versus pre-implantation assays. A statistically significant difference was demonstrated regarding mean global blood-sugar. The frequency of severe hypoglycemia incidents (2 in our series) and biochemical hypoglycemia (blood-sugar < 65 mg/100 ml) was decreased, representing a major benefit of the technique. The patients well-being and quality of life were notably improved. Implantable insulin-pump may be offered as alternative treatment to conventional insulin-therapy, especially in cases of diabetes which are difficult to control and particularly in cases with frequent hypoglycemic malaise.

Adult↗

[Implantable insulin pumps: evaluation after more than 3 years experience].

Since the beginning of insulin therapy the improvement of treatment in IDDM is mainly for acute metabolic complications than for chronic degenerative complications. The DCCT could recently prove for the first time that the incidence of chronic complications (retinopathy, nephropathy and neuropathy) could be diminished by reaching glycemic control in more than 700 patients. One of the problems explaining the failure of classical treatment is due to the variability of absorption in the sub-cutaneous tissue. The patients treated by insulin pumps are all IDDM. The aim of this study is to evaluate safety and feasibility of implantable programmable pumps with intraperitoneal insulin infusion. We found three cases of irreversible catheter obstruction. Defects of external communicators and the slow-downs of insulin infusion in infusaid pumps were observed. No acceleration in insulin infusion was found. Acute metabolic complications were two severe hypoglycemic events, but no acito-cetosis. After more than two years for most of the patients we observed a global improvement in glycemic control, demonstrated by a better mean glycemia and lower HbA1c values. The standard deviation of the glycemia was lowered significantly, this value reflects daily fluctuability. The number of hypoglycemias was also lowered. Our study shows a more stable glycemic control than the one in the DCCT study. The safety and feasibility seem to be highly satisfying.

Adult↗

Diffusion properties of an artificial membrane used for Langerhans islets encapsulation: an in vitro test.

Glucose and insulin permeability of an artificial membrane (AN69, HOSPAL, Sweden) used for Langerhans islets encapsulation were investigated. In vivo, a 1 and 7 d intraperitoneal implantation of the AN69 membrane in rats induced a loss of permeability towards glucose and insulin probably due to a protein-coating performed after implantation. In vitro, a protein-coating of the AN69 membrane with fetal calf serum solution reproduced similar results. Thus this in vitro test which mimicks in vivo conditions should be proposed to evaluate rapidly the physicochemical properties of a membrane suitable for pancreatic islets encapsulation.

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