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M Pinget

Publications and source records attributed to M Pinget.

At least 37 records · Page 2Linked to original sources
PubMed2000

Ileal uptake of polyalkylcyanoacrylate nanocapsules in the rat.

The ileal uptake of polyalkylcyanoacrylate nanocapsules (less than 300 nm in diameter) has been investigated in the rat. Iodised oil (Lipiodol) was used as the tracer for X-ray microprobe analysis in scanning electron microscopy. Lipiodol nanocapsules, or an emulsion of Lipiodol, were administered in the lumen of an isolated ileal loop of rat. Lipiodol nanocapsules improved the absorption of the tracer as indicated by increased concentrations of iodine in the mesenteric blood (+27%, P < 0-01, compared with Lipiodol emulsion). Intestinal biopsies were taken at different time points and the samples underwent cryofixation and freeze-drying. The nanocapsules were characterized by their strong iodine emission, and electron microscopy of the biopsy samples revealed nanocapsules in the intraluminal mucus of the non-follicular epithelium, then in the intercellular spaces between enterocytes, and finally the nanocapsules were found within intravillus capillaries. However, nanocapsules were most abundant in the Peyer's patches, where the intestinal epithelium had been crossed by way of the specialized epithelial cells, designated membranous cells, or M cells, and their adjacent absorptive cells. These observations were confirmed quantitatively by measuring iodine concentrations in the various tissue compartments. Ten minutes after the intraluminal administration of Lipiodol nanocapsules, the emission of iodine peaked in the mucus (+77%, P < 0.01), in M cells (+366%, P <0.001), in enterocytes adjacent to M cells (+70%, P < 0.05) and in lymph vessels (+59%, P < 0.05). Polyalkylcyanoacrylate nanocapsules were able to pass through the ileal mucosa of the rat via a paracellular pathway in the non-follicular epithelium, and most predominantly, via M cells and adjacent enterocytes in Peyer's patches.

Animals↗
PubMed1999

Sphenoidal sinus mucocele after transsphenoidal surgery for acromegaly.

This report concerns one case of a sphenoid sinus mucocele occurring 17 years after transsphenoidal surgery for acromegaly. In 1979, a 51-year-old man was successfully operated by the transnasal transsphenoidal approach for a growth hormone (GH) adenoma 1 cm in diameter. In 1996, the patient was hospitalized for headaches and diplopia. He presented a loss of right visual acuity with paralysis of the right oculomotor nerve. The basal GH level was normal with a satisfactory decrease after oral glucose ingestion. Pituitary sellar radiography showed a disappearance of the posterior clinoid while magnetic resonance imaging revealed the existence of a bilocular, circular, homogeneous lesion of the sphenoid sinus 3 cm in diameter with a posterior and lateral extension. The diagnosis of mucocele was confirmed by surgical treatment, allowing drainage of the mucocele through a transsphenoidal approach. The drained material was composed of sinus epithelium containing many polynuclear and resorptive cells. Postoperatively, the symptoms decreased dramatically, leading to full recovery of visual function and disappearance of the headaches. Apart from the tumor recurrence, the mucocele of the sphenoid sinus can be evoked as a possible long term complication of transsphenoidal surgery for pituitary adenoma.

Acromegaly↗
PubMed1999

Chemotactic activity of culture supernatants of free and encapsulated pancreatic rat islets towards peritoneal macrophages.

Longterm efficiency of encapsulated pancreatic islet transplantation is limited by macrophagic reaction at the surface of biocompatible membrane. The aim of this work was to investigate the influence of soluble factors released by free and encapsulated islets on macrophage chemotaxis. The culture mediums conditioned for 6 days by free and encapsulated rat islets were incubated with peritoneal murine, rat allo and syngenic macrophages to study their migration. Culture supernatants of rat fibroblasts and acinar cells, glucose-stimulated free rat islets and supernatants of free rat islets treated by heat and proteinase K were also tested for their chemotactic activity. Islets encapsulation decreased the chemotactic activity of culture medium conditioned for 6 days by free rat islets on murine (1.66 +/- 0.20 vs. 3.10 +/- 0.23; p < 0.001, n = 5) and rat allogenic macrophages (1.63 +/- 0.21 vs. 4.70 +/- 0.36; p < 0.001, n = 9). There was no migration of rat macrophages towards syngenic islets. Fibroblasts exhibited a very strong chemotactic effect as compared to acinar cells. Insulin was not involved in macrophage migration. Proteinase K treatment of culture supernatant of free rat islets totally inhibited the chemotactic activity. After heating at 56 degrees C and 100 degrees C, this activity was reduced to 41 +/- 7% and 32 +/- 5% of the initial activity, respectively. In conclusion, pancreatic islet stimulated macrophage migration by release of immunological specific proteins partly retained by macroencapsulation.

Animals↗
PubMed1999

Type 2 diabetes mellitus: association study of five candidate genes in an Indian population of Guadeloupe, genetic contribution of FABP2 polymorphism.

We studied by PCR-RFLP 6 polymorphisms in these 5 candidate genes: Ala54Thr in the fatty acid binding protein 2 gene (FABP2), A to G substitution in the uncoupling protein type 1 gene (UCP1), Asp905Tyr in the protein phosphatase type 1 gene (PP1G), Trp64Arg in the human beta 3 adrenergic receptor gene (beta 3AR) and 2 RFLP sites of the vitamin D receptor (VDR) gene (VDRTaq1 and VDRApa1). This study was conducted among 89 cases and 100 controls matched according to age, gender and absence of first degree family link (11 triplets with 2 controls for 1 case and 78 pairs with 1 control for 1 case). Cases and controls were taken among a sample of 429 individuals selected for the study of the prevalence of diabetes in this ethnic group from Guadeloupe. By conditional logistic regression analysis, there was a significant relation (p = 0.02) between the Ala54Thr FABP2 polymorphism and Type 2 DM. Multivariate analysis discriminate the FABP2 polymorphism (p = 0.10), a triglyceridemia over 2 g/l (p < 10(-3)) and high blood pressure (p = 10(-2)) as variables associated with Type 2 DM in this population. These findings suggest that FABP2 does not represent a major gene for Type 2 DM in this migrant Indian population living in Guadeloupe, but seems to be related to the metabolic insulin resistance syndrome.

Adult↗
PubMed1999

Cardiovascular risk factors associated with diabetes in an Indian community of Guadeloupe. A case control study.

Indians of Guadeloupe have an especially high prevalence type 2 diabetes mellitus and a particular susceptibility to coronary heart disease. This case-control study conducted from September 15 to 24, 1997, analysed cardiovascular risk factors associated with diabetes and particularly dyslipidaemia in the Indian community of Guadeloupe. The 172 subjects included 86 diabetic patients of Indian origin and 86 age- and sex-matched non-diabetic controls. All subjects underwent a physical examination by the same observer. Obesity and hypertension were assessed, and fasting lipid concentrations were measured. The body mass index and waist-to-hip ratio were higher among patients than controls: 27.8 vs 25.1 Kg/m2 (p < 0.001) and 0.94 vs 0.90 (p < 0.001). Mean arterial systolic and diastolic pressures were higher for patients than controls (p < 0.001). Median HDL-cholesterol was 1.23 mmol/L for patients vs 1.4 mmol/L for controls (p < 0.001), and median triglycerides were 2.0 vs 1.3 mmol/L (p < 0.001). Mean apolipoprotein B was 1.40 +/- 0.36 g/L for patients vs 1.23 +/- 0.35 g/L for controls (p < 0.001). Our results show slight hypertension, central obesity, a lower plasma HDL-cholesterol concentration, a higher triglyceride concentration, and a higher apolipoprotein B concentration for diabetics. These data would appear to have important implications for the prevention of cardiovascular disease in this population.

Adult↗
PubMed1998

Possible involvement of Von Willebrand factor in pancreatic graft thrombosis after kidney-pancreas transplantation: a retrospective study.

Early postoperative graft thrombosis remains the second cause of failure in pancreas transplantation. Thus, the aim of this study was to compare retrospectively coagulation and fibrinolysis in type I diabetic recipients of simultaneous kidney pancreas transplants having or not experienced thrombosis of their pancreatic graft. From December 1990 to August 1996, 30 simultaneous kidney pancreas transplants were performed in 30 uremic type I diabetic patients. Acute thrombosis of the pancreatic graft was observed among 6 patients (group A), whereas 24 did not develop thrombosis (group B) although 4 died from other causes. The control groups were composed of kidney transplant (group C) or haemodialysed (group D) non-diabetic patients, type I diabetics with HbA1C < 8% (group E) or > or = 8% (group F) who were not in end-stage renal failure and kidney transplant type I diabetic patients (group G). Beginning at least 6 months after transplantation, we analysed hemostatic factors (fibrinogen, thrombin, and prothrombin times), coagulation inhibitors (proteins C and S), fibrinolysis (plasminogen activator inhibitor) and endothelial cell abnormalities (Von Willebrand factor: VWf). Micro and macrovascular complications were evaluated on a score ranging from 0 to 12. Hemostatic factors, coagulation inhibitors and fibrinolysis were similar in groups A and B whereas VWf differed significantly in group A (3.49 +/- 0.93 IU/ml) as compared to group B (2.04 +/- 0.92 IU/ml) (p < 0.05). VWf was also significantly increased in group A relative to the control groups C, D, E, F, and G. The score of vascular complications was increased in groups A and B and significantly higher in group A (9 +/- 0.81 vs. 6.07 +/- 1.75) (p < 0.01), while a correlation (r = 0.812, p > 0.05) was observed between VWf levels and the severity of vascular complications. These results point out the possible involvement of VWf in the pathogenesis of pancreatic vein thrombosis in kidney-pancreas transplantation.

Adult↗
PubMed1998

Von Willebrand factor in diabetic angiopathy.

Diabetes mellitus is a complex disease characterised by chronic hyperglycaemia responsible for complications affecting the kidneys, eyes, peripheral nerves and micro- and macrovascular systems. Von Willebrand factor (vWf), a multimeric glycoprotein mainly synthesised by endothelial cells, is involved in platelet adhesion and aggregation and acts as the carrier of coagulation factor VIII in plasma. Increased levels of vWf, reflecting activation of or damage to endothelial cells, have been described in association with atherosclerosis and diabetes. vWf appears to be a predictive marker of diabetic nephropathy and neuropathy, although not of retinopathy, which suggests that endothelial dysfunction precedes the onset of diabetic microangiopathy. This dysfunction could be especially involved in the pathogenesis of renal abnormalities of diabetes. vWf is not a predictive marker of macroangiopathy when diabetes is associated with atherosclerotic risk factors. In the presence of chronic diabetic complications, vWf levels are not associated with any grade of retinopathy but increase with the severity of nephropathy and would appear to be a risk factor for macrovascular mortality in these patients. The endothelial dysfunction of diabetes can generate atherosclerotic lesions responsible for damage to the arterial wall, atheroma and formation of platelet microaggregates. Concomitant with high vWf levels, other possible mechanisms of endothelial damage include reduced synthesis or release of nitric oxide, hyperglycaemic pseudohypoxia and protein kinase-C activation, increased synthesis of proteins bearing advanced glycosylation end-products or transforming growth factor-beta (TGF-beta) activation of coagulation and inhibition of fibrinolysis. At present, it is not known whether high vWf levels are inherent to the physiopathology of diabetes, nor whether diabetes induces endothelial dysfunction through other pathways. However, since angiopathy resulting from endothelial dysfunction is the main cause of morbidity and mortality in diabetic patients, appropriate therapy is necessary to reduce these complications. Glycaemic control seems to be insufficient to normalise plasma vWf, whereas a decrease can be obtained by ingestion of diets rich in oleic acid or by treatment with statins. Inhibition of the binding of vWf to the GPlba receptor by synthetic peptides, aurin tricarboxylic acid or monoclonal antibodies has been proposed to prevent the thrombosis induced by high levels of plasma vWf. Thus, vWf probably represents an interesting target for the inhibition of thrombosis in diabetes.

Arteriosclerosis↗
PubMed1997

Influence of acinar tissue contamination on encapsulated pancreatic islets: morphological and functional studies.

BACKGROUND: The present study concerns the influence of acinar contamination on pancreatic islets encapsulated in an artificial membrane (AN 69). METHODS: Pure, handpicked pancreatic islets were contaminated by the addition of acinar tissue (ratio, 1:1). The morphological aspect and insulin release of both pure (n=12) and contaminated (n=12) encapsulated islets were assessed after 10 days of culture or implantation in the peritoneal cavity of rats. RESULTS: After implantation, the encapsulated islets, irrespective of their purity, were totally altered, whereas the morphological aspect of the cultivated islets remained intact only in the absence of acinar tissue contamination. This contamination induced a significant decrease in the stimulation index of insulin release. The stimulation index decreased by 42% for fresh islets and by 52% and 34% for cultivated and implanted islets, respectively, without modification in their basal release of insulin. CONCLUSIONS: The acinar tissue proved detrimental to the encapsulated implanted and cultivated islets.

Animals↗
PubMed1997

Physicochemical and biological studies of corona-treated artificial membranes used for pancreatic islets encapsulation: mechanism of diffusion and interface modification.

The artificial AN69 membrane (Hospal), a synthetic copolymer composed of acrylonitrile and sodium methallyl sulphonate suitable for pancreatic islet encapsulation, was submitted to physicochemical treatment (Corona discharge) to improve its insulin permeability. X-ray photoelectron spectroscopy (XPS) analysis of the AN69 membrane indicated the presence of up to two molecular layers of glycerol at its surface while the surface energies revealed the presence of hydrophilic sites (-SO3Na/glycerol) located at the membrane surface and acrylonitrile hydrophobic groups inside the material. The Corona discharges decreased the number of glycerol molecules at the membrane surface and from a biological point of view, produced a threefold increase in insulin diffusion. Furthermore, the biocompatibility of the treated membrane was preserved after 1 year of intraperitoneal implantation. The increase in insulin permeability should result from a decrease of the membrane polarity and of a steric hindrance in pores. Thus, Corona discharge treatment may serve to optimize the properties of artificial membranes used for pancreatic islets encapsulation.

Animals↗
PubMed1997

Polyamide 4,6 membranes for the encapsulation of Langerhans islets: preparation, physico-chemical properties and biocompatibility studies.

Porous polyamide 4,6 membranes developed as semi-permeable and biocompatible membranes for the encapsulation of pancreatic islets were prepared by precipitation in water. Different membrane morphologies were obtained by varying the molecular weight of polyamide 4,6, the solvent evaporation time and the composition of the casting solution. Each membrane was submitted to differential scanning calorimetry and water flux measurements to study the total water content and the different kinds of water in correlation with its permeability performances. Their biocompatibility was first evaluated by a surface protein adsorption test. Of the various membranes, the one prepared by immersion in water after 5 minutes of solvent evaporation, of 15% KS200 polyamide 4,6 solution added with 1% of polyvinylpyrrolidone K30 seems to be the most promising. This membrane is characterized by a low adsorption of proteins, a high hydraulic coefficient and an asymmetric structure. Such a membrane represents a good candidate to be an efficient immunological barrier. It also exhibits good glucose and insulin diffusion properties. Moreover, rat islets cultivated on its surface were not affected by its presence and no important cell adhesion was noticed when implanted in mice. This membrane exhibits most of the properties suitable for the islet encapsulation with a view to developing a bioartificial pancreas.

Journal Article↗
PubMed1997

Poly(alkyl cyanoacrylate) nanocapsules as a delivery system in the rat for octreotide, a long-acting somatostatin analogue.

Poly(alkyl cyanoacrylate) nanocapsules have been used as biodegradable polymeric drug carriers for subcutaneous and peroral delivery of octreotide, a long-acting somatostatin analogue; their ability to reduce insulin secretion or prolactin secretion in response to oestrogens has been studied in adult male rats. The nanocapsules, prepared by interfacial emulsion polymerization of isobutyl cyanoacrylate, were 260 nm in diameter and incorporated 60% of octreotide. Administered subcutaneously, the octreotide-loaded (20 micrograms kg-1) nanocapsules suppressed the insulinaemia peak induced by intravenous glucose overload and depressed insulin secretion over 48 h, preventing the secretory rebound; however, glycaemia was unaffected. In parallel, the plasma octreotide concentration increased 2.7 times. Administered perorally to oestrogen-treated rats, octreotide-loaded nanocapsules (200 and 1000 micrograms kg-1) significantly improved the reduction of prolactin secretion (by 72 and 88%, respectively, compared with 32 and 54% with free octreotide) and slightly increased plasma octreotide level. Thus nanocapsules could be of interest as a biodegradable drug carrier for the administration of octreotide.

Animals↗
PubMed1997

[An original case of simultaneous cardiac, pancreatic and renal transplantation. Results over 6 years].

Combined transplantation is actually performed on specific and rare indications. We are presenting here the results of a combined heart-kidney and pancreatic graft. It was performed in a patient presenting an idiopathic cardiomyopathy in end-stage failure and a post-diabetic nephropathy on dialysis. Today, organs function is quite satisfactory with a 6 year follow-up. Only one isolated heart rejection episode was observed at the 15th post-operative day. The patient has recovered a full-time professional activity at one year. This successful graft was obtained by an "homogeneous multiorgan approach" during all the pre-peri and postoperative time.

Adult↗
PubMed1996

Cytotoxicity of peritoneal murine macrophages against encapsulated pancreatic rat islets: in vivo and in vitro studies.

The aim of this work was to study in vivo and in vitro the involvement of macrophages and interleukin-1beta (IL-1beta) in the necrosis of encapsulated islets during xenograft and to evaluate the immunoprotective efficiency of the AN69 membrane. In vivo, 6 days after implantation, 65% of the membrane surface of the devices containing the islets was colonized with macrophages compared with only 5% of the surface of the empty control devices. The morphological aspect of implanted islets was altered and their insulin release decreased significantly compared with freshly isolated ones (265 +/- 50 vs. 507 +/- 81 microU/mL). In vitro, the insulin release of encapsulated islets cultured for 2 days decreased to 32 and 28%, respectively, in the presence of IL-1beta and macrophages. The addition of anti-IL-1beta antibody to the co-culture of macrophages and islets did not modify this loss of functional activity. Furthermore, IL-1beta passed through the AN69 membrane. In conclusion, macrophages are involved in damaging encapsulated pancreatic islets and are probably partly responsible for islet transplantation failure.

Animals↗
PubMed1996

[Benefits and limitations of pancreas transplantation in insulin-dependent diabetics: a study apropos of 26 patients].

From November 1990 to March 1995, 26 simultaneous pancreas-kidney (SPK) transplants were carried out. The recipients were uremic type I diabetic patients. After the first year of transplantation, patient survival was 96% and pancreas and kidney survival was 69% and 84%, respectively. The pancreas transplant failure was due to veinous thrombosis (two cases), and to graft rejection (71%). The most common urologic complications of bladder drainage were urethritis (61%), bicarbonate loss (42%) and urinary tract infections (100%). Fasting blood glucose (0.91 +/- 0.1 g/L), hemoglobin A1C (5.3 +/- 0.4%) and lipidic profile were found to be normal among diabetic recipients whose grafts had been functioning for 1 year. The insulin secretion of type I diabetic patients with SPK transplants (n = 13), and six non diabetic patients with kidney transplants was assessed by oral glucose tolerance tests. Only the patients with SPK transplants presented late hyperinsulinemia at 120 minutes. The quality of life for both type I diabetic patients after SPK transplants and diabetics treated by insulinotherapy (n = 6), was studied. After transplantation, the quality of life improved only because of insulin independence. In spite of chirurgical and urologic complications, pancreas transplantation in type I diabetic patients improves both metabolic control and quality of life.

Adult↗