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Biomedical subjects

M Pinget

Publications and source records attributed to M Pinget.

At least 73 records · Page 4Linked to original sources
PubMed1991

In vitro and in vivo studies of the properties of an artificial membrane for pancreatic islet encapsulation.

Encapsulation of pancreatic islets with an artificial membrane has been proposed as a means of immunoprotection after transplantation. Such a membrane should be biocompatible, nondegradable, and should allow the passage of insulin and glucose while preventing that of antibodies and lymphocytes. Thus, we have studied in vitro and in vivo, the characteristics of an acrylonitrile membrane (AN69, HOSPAL, Sweden) for islet encapsulation. The AN69 membrane composed of a fiber network with a porous structure, allowed a satisfactory passage of glucose (75% of the initial amount within one hour) but not of insulin (only 7%). The morphological state of rat islets cultured on membranes under both conditions for 2 weeks was similar to that of islets cultured on dishes; in addition rat fibroblasts retracted after a 3-day culture. Finally, the membrane was unaltered after a 12 month implantation in the peritoneal cavity of rats. When the surface properties of the AN69 membrane were changed by adsorption of a hydrophilic copolymer or by protein coating, the permeability of the membrane was modified. Glucose and insulin diffusion were significantly decreased after protein-coating, whereas glucose diffusion was preserved and that of insulin doubled after adsorption of a copolymer onto the membrane. In addition, after a 12-month implantation in the rat, the membrane surface treated by the copolymer was altered leading to the adhesion of macrophages. In conclusion, the AN69 acrylonitrile membrane may be useful for pancreatic islet encapsulation; its insulin permeability should be increased by a surface treatment aimed at increasing its hydrophilic properties. However the stability of this treatment seems to be an important factor in preserving the biocompatibility of the membrane.

Acrylonitrile↗
PubMed1990

[Feasibility and acceptability of insulin therapy using a pen suitable for injecting regular or intermediate insulin. Results of the French multicenter study conducted by the Optipen-France Study Group].

Most of the commercially available insulin-pens are only suitable for regular insulin and have to be used in combination with syringe injections of long-acting insulin preparations. The aim of the french multicentric study is to estimate the clinical interest of a new insulin-pen (Optipen-Hoechst) with two main characteristics: the ability of a predetermination of the insulin dosage to be administered and the suitability for both regular, intermediate and pre-mixed regular (25%) and intermediate (75%) Hoechst insulin preparations. This new pen can so be used alone in all insulin regimen, consisting only of regular and/or intermediate insulin injection. Ninety five insulin treated patients, with at least two daily injections of these kinds of insulin, have been selected injection in a 8 weeks follow up study: After been included they were treated for two weeks by syringe injections of Hoechst insulin solutions (U40), equivalent to the former insulin preparations. Optipen was then used during 4 weeks to inject similar U100 insulin solution, without any other changes in diet and home blood glucose monitoring. Metabolic control was assessed by glycemic measurements, fructosamine and glycosylated hemoglobin determinations and remained unchanged all over the study. The acceptability of pen-treatment was excellent since 95% of the population decided not to return to syringe injections at the end of the study. Injections by mean of an Optipen are more convenient at home as well as outside. Further long term randomized studies are necessary to definite the clinical indications for Optipen use in insulin treated patient.

Adolescent↗
PubMed1990

[Consequences of hyperglycemia on glucose and nitrogen metabolism in liver cirrhosis. A study using a hyperglycemic clamp].

To study the consequences of hyperglycemia on glucose and nitrogen metabolism in cirrhosis, an hyperglycemic clamp was performed in 5 cirrhotic patients and 5 normal controls during two subsequent periods of 90 min, at 7.78 and then at 13.89 mmol/l. In the first period, glucose infusion and metabolic clearance rates were decreased in cirrhotics vs controls (p less than 0.05). In the second period, this difference between the two groups disappeared because of a more important enhancement in cirrhotics. Baseline plasma C peptide levels and those during hyperglycemia were the same during hyperglycemia in both groups, but plasma insulin level rose more in cirrhotics (p less than 0.05). Baseline insulin secretion following IV glucagon was reduced in cirrhotics vs controls (p less than 0.05), but became normal in the hyperglycemic state. Plasma glucagon levels were enhanced at all times in cirrhotics vs controls (p less than 0.01), but dropped more in cirrhotics vs controls (p less than 0.05). Insulin responsiveness, defined as the "glucose consumption: plasma insulin concentration" ratio was reduced in cirrhotics at 7.78 mmol/l (p less than 0.01), but was the same in both groups at 13.80 mmol/l because of a more important enhancement in cirrhotics, reflecting an improvement of insulin action probably at the post-receptor level and of non-insulin-mediated glucose transport. Hyperglycemia induced a drop in plasma concentration and muscular release of all aminoacids, excepted alanine, between the basal state and the end of the study. Aminoacid concentration rose only in cirrhotics, without any change in muscular output. In the same time, blood ammonia level rose only in cirrhotics, without reduction of muscular uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Comparative study of the lipid composition of seminal fluid and ovulatory peritoneal fluid in humans].

Sperm capacitation is accompanied by changes in the lipid composition of the sperm membrane. The purpose of this study is to compare the lipid composition of the semen with that of peritoneal fluid. These two media have opposite effects on sperm capacitation. Cholesterol, triglyceride and phospholipids were measured in seminal fluid (15 specimens) obtained by sperm centrifugation immediately after liquefaction and in the peritoneal fluid at ovulation (15 specimens) obtained through transvaginal puncture. The lipid composition of these two media is different from that of serum. Seminal fluid is characterized by a high level of phospholipids, 14.79 +/- 3.67 g/l as against 0.53 +/- 0.12 g/l in peritoneal fluid. The level of cholesterol is identical in the two media. The cholesterol/phospholipid ratio is therefore lower in seminal fluid than in peritoneal fluid (0.022/0.79). Lecithins are raised in peritoneal fluid as are sphingomyelins and the phosphatidylethanolamines, which are the most important phospholipids in seminal fluid. It therefore can be postulated that the cholesterol/phospholipid ratio, which is low in seminal fluid, and its richness in sphingomyelin brings about stabilization of the membrane cover which corresponds to a decapacitated state, whereas the cholesterol/phospholipid ratio, which is higher in peritoneal fluid, makes for greater fluidity, and this corresponds to the state of capacitation. These preliminary results obtained from human material do not in any way contradict those obtained from animal studies.

Ascitic Fluid↗
PubMed1988

[Study of insulin resistance in cirrhosis by the hyperinsulin euglycemia clamp].

To explore the insulin resistance state in liver cirrhosis and to assess the respective role of insulin sensitivity and cellular metabolism alterations, an euglycemic glucose clamp was performed in 12 cirrhotic patients and 6 healthy volunteers with 3 successive hyperinsulinemic periods of 90 mn (infusions of 7, 20 and Iu/h). An artificial beta-cell model allowed to quantify the amount of glucose needed to keep glycemia at 4.70 mmol/l. In 7 cirrhotic patients, insulin secretion was tested by an intravenous glucose tolerance test. The dose-response curves showed a significant (p less than 0.01) decrease of the theoretical maximal metabolic clearance rate of glucose (capacity). The insulin concentration corresponding to the half-maximal response (ED50) did not differ between cirrhotic and control subjects because of a very important dispersion of individual values in cirrhotics. The ED50 value was lower than the values of control subjects in five cirrhotic patients and normal or enhanced in seven other patients; the former showed the most reduced values for capacity, and the latter a more marked hyperinsulinemia during the intravenous glucose tolerance test. The two subgroups of patients did not differ for clinical or biological parameters of cirrhosis, or for glucose tolerance. These results 1) show a constant and marked impairment of glucose metabolism capacity in liver cirrhosis, 2) and suggest that the insulin resistance inconstantly observed in this state is a consequence of chronic hyperinsulinemia.

Adult↗
PubMed1988

[Endometrium and diabetes].

Endometrium play a fundamental role during the 12 days following conception: its metabolic activity is responsible for the nutrition of the embryo. This nutritive function can be reduced in the presence of maternal diabetes mellitus, with a clinical incidence: unexplained sterility, spontaneous abortion and fetal malformations are more frequent in the presence of poorly controlled maternal diabetes mellitus. These abnormalities are directly correlated to the degree of hyperglycemia and reflect changes in the metabolic activity of the endometrium. Our biochemical study demonstrate that enzymatic activities are responsible, in human endometrium, for glucogene storage in the perovulatory period and energy production during the post ovulatory period; diabetes mellitus is responsible, at least in animal endometriums, for a reduced ability of glucogen storage and a reduced activity of glycolysis enzymes and of glucose 6 phosphate deshydrogenase.

Animals↗
PubMed1987

Semisynthetic human insulin: biological and pharmacokinetic effects in normal subjects.

The assessment of pharmacokinetic and pharmacodynamic properties of semisynthetic human insulin produced by enzymatic conversion was done in normal subjects, and compared to those of highly purified pork insulin. Ten healthy volunteers were submitted to an intravenous injection of 0.06 U/kg of regular insulin, semisynthetic (Actrapid HM) and monocomponent pork insulin (Actrapid MC) in succession. No significant differences were pointed out as far as the pharmacokinetic parameters, immunoreactivity and hypoglycemic effect of both types of insulin are concerned. Only a stronger inhibition of endogenous insulin secretion, expressed by a significantly lower plasma-C-peptide levels, was observed after PPI. Stimulation of glucagon secretion was similar with both types of insulin.

Adult↗
PubMed1985

Biliary elimination of beta-lactam antibiotics by the isolated perfused rabbit liver.

Biliary elimination of 15 beta-lactams was studied using a model of isolated perfused rabbit liver. During the perfusion period, the main liver functions were well preserved. The highest biliary concentrations were reached by antibiotics of the penicillin group, and the highest biliary recovery was observed with metampicillin, apalcillin and mezlocillin (46.5, 30.7 and 20.3%, respectively, of the dose administered). This technique was also suitable for estimating the degree of bio-transformation in the liver of the antibiotics studied.

Animals↗
PubMed1985

[Biliary excretion of apalcillin. Experimental study and evaluation in man].

Biliary excretion of apalcillin, a new derivative of the ureido-penicillin group, was investigated both experimentally and in humans. After adding 10 mg of this antibiotic to the circulating blood of an isolated rabbit liver perfusion model (n = 5), mean total apalcillin biliary recovery (0-3 h) accounted for 30.7% of the administered dose; the biliary peak averaged 686.0 +/- 135.9 micrograms/ml. In 5 healthy subjects, a mean maximum level of 1088 +/- 582 micrograms/ml was measured in the duodenal fluid collected during the 4 hours following an i.v. injection of Ig of apalcillin. In 10 cholecystectomized patients provided with T-tube drainage, after the same dosage, a mean biliary peak of 2093 +/- 859 micrograms/ml was reached at the third hour and cumulative biliary recovery of apalcillin over a period of 12 hours amounted to 12.1% of the injected dose. In 20 patients, undergoing biliary tract surgery, intra-operative assays performed 1 hour after i.v. injection of 1 g of apalcillin, showed simultaneous mean antibiotic activity of 65.5 +/- 5.0 micrograms/ml in serum, 3860 +/- 551 micrograms/ml in main duct bile and 2552 +/- 627 micrograms/ml in gallbladder bile. The results of these investigations were compared with data previously obtained under identical procedures with 13 other beta-lactam derivatives.

Ampicillin↗
PubMed1984

[Insulin-dependent diabetes with acute onset. Remissions induced by early temporary blood glucose normalization].

Within 6 months of the acute onset of an insulin-dependent diabetes, remission of insulin-dependence was attempted in 30 hospital patients by strict control of glycaemia obtained in a few days with intravenous infusions of insulin, using a macropump. This was followed by an oral antidiabetic treatment, and the patients were considered in remission when metabolic control was achieved. By this method remission of insulin-dependence was obtained in 90% of the patients; it lasted for more than 1 year on average, and its degree seemed to depend on the time elapsed between the clinical onset of the disease and the beginning of the intravenous treatment but also, to a lesser extent, on the residual secretory capacity of the pancreas when this treatment was instituted. Thus, an intensive metabolic control increases the effectiveness of an oral treatment as regards both number of patients improved and duration of remission. When administered alone at the onset of the disease the oral treatment is only effective in about 30% of the cases.

Adolescent↗
PubMed1984

[Biosynthetic human insulin. Pharmacokinetic characteristics and activity in normal subjects].

The pharmacokinetics and pharmacodynamic effects of intravenously injected (0.06 U/kg) human biosynthetic insulin of recombinant DNA origin and purified porcine insulin, both regular, were compared in 10 healthy volunteers. Both had identical immunological properties. Some of their pharmacokinetic features, such as total plasma clearance and bioavailability, were similar, but they appeared to differ in biological half-life, elimination rate constant and apparent volume of distribution. No appreciable difference was found between their hypoglycaemic activity and their inhibitory effect on endogenous insulin secretion. However, hyperglucagonaemia seemed to be less pronounced after human biosynthetic insulin than after purified porcine insulin. These findings are discussed by comparison with the results of other studies on human biosynthetic insulin.

Adult↗
PubMed1984

Effect of middle-term gliclazide treatment on insulin secretion in non-insulin dependent diabetics.

Insulin secretion was studied in 12 non-insulin dependent diabetics during middle-term administration of the sulphonylurea gliclazide. Blood sugar, C-peptide and glucagon were also estimated during the intravenous glucose tolerance and arginine tests performed before and after therapy. After 3 months of gliclazide therapy (240 mg/day) in addition to a low carbohydrate diet, the intravenous glucose tolerance test showed a significant reduction in blood sugar levels and in the partial and total areas under the blood sugar curve, as well as an improvement in early insulin secretion, characterized by a significant increase in plasma C-peptide at 4, 10 and 20 minutes. Plasma glucagon levels were not affected by the sulphonylurea therapy. In the arginine test, blood sugar levels were lower at the end of the treatment period; plasma insulin, C-peptide and glucagon did not change significantly. In this study, plasma C-peptide has proved to be a better indicator of stimulated insulin secretion than plasma insulin levels. The scarcity of hypoglycaemic episodes during therapy with gliclazide may be related to the selective stimulation of early insulin secretion by this drug.

Adult↗
PubMed1984

[Evaluation of the biliary passage of beta-lactam antibiotics].

The present study is devoted to the biliary excretion of some beta-lactam antibiotics (6 derived from the penicillin group: Penicillin G, Ampicillin, Metampicillin, Carbenicillin, Mezlocillin, Apalcillin and 9 from the cephalosporin group: Cephalothin, Cephaloridine, Cephacetrile, Cefalexin, Cefazolin, Cefamandole, Cefuroxime, Cefaclor and Ceftizoxime). The biliary excretion of these antibiotics was assessed by 4 different procedures: 1) experimental study of their biliary elimination by a perfused isolated rabbit liver; 2) in humans, by evaluation of their passage: a) in aspirated duodenal fluid, b) in bile collected by external biliary drainage, c) and in bile obtained by puncture of the main bile duct and the gall bladder during surgery. The results of these different investigations were concordant and showed that the biliary excretion of Metampicillin, Apalcillin and Mezlocillin was definitely higher than that of the other studied beta-lactams; on account of their suitable antibacterial spectrum, these 3 derivatives should be used in preference for the treatment of biliary infection.

Animals↗
PubMed1984

[Prolonged treatment of sugar diabetes by subcutaneous insulin infusion using a peristaltic pump and an insulin solution concentrated to 100 Iu/ml].

The authors have treated 6 diabetic patients for at least 3 months with subcutaneous insulin infusion system using a peristaltic pump and a highly stable preparation (U 100 with physiological pH). Correct diabetic control was achieved in each case, during a cumulative period of 44 patients-months. The high stability of the insulin preparation allows a prolonged insulin storage in the pump, from 2 to 3 months without any change in the hypoglycaemic effect of the solution. Advantages and risks of this method are discussed.

Adult↗
PubMed1983

[Acquired remissions of insulin dependence in recent diabetes mellitus. Essential prognostic factors].

24 patients with recent diabetes mellitus (less than three years) were given an intravenous insulin infusion over a short period (84 to 252 hours) in an attempt to achieve a remission of their disease through rigorous normalization of blood glucose concentrations. After this treatment, strict control of diabetes mellitus was achieved with oral mediactions in 15 of the 24 patients. In 17 cases, onset of diabetes mellitus had been sudden and insulin was required immediately (acute cetosic diabetes: ACD); in 7 patients, signs of insulin deficiency had occurred only after seven months of hyperglycemia (secondary insulin-dependent diabetes mellitus: SIDDM). A strong probability of achieving an insulin-induced remission exists only during the first six months of ACD. The success of the insulin infusion is partly dependent upon the residual beta cell function. During the remission, which lasts for more than 12 months in 50% of cases, control of diabetes mellitus is optimal.

Diabetes Mellitus↗