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Biomedical subjects

J F Brun

Publications and source records attributed to J F Brun.

84 records · Page 5Linked to original sources

Secondary failure of islets autotransplantation in totally pancreatectomized dogs: a multifactorial study.

Even without any immunologic barrier, as in autografts, reversal of diabetes induced by islets transplantation is not definitive and a secondary failure generally occurs. Factors involved in this failure were investigated in 13 male dogs undergoing total pancreatectomy and extemporaneous islets reinjection in the portal circulation. Five dogs died from postoperatory complications, three remained diabetic, and five were normoglycemic without insulin therapy for a duration of two to 26 weeks. Factors associated with failure appeared to be: (a) hemorrhage during dissection of pancreas prior to islets isolation, (b) imperfect collagenase digestion. Moreover, duration of this period of normoglycemia was negatively correlated with glycemia on the 20th postoperatory hour (r = 0.759, p less than 0.05), suggesting a possible relationship between glycemia and further graft outcome. Therefore, such a multifactorial statistical analysis seems to be helpful for the study of multiple technical parameters associated with the prognosis of islets transplantations.

Animals↗

[Secretory activity of the islands of Langerhans of newborn rats cultured in vitro on bovine corneal endothelial matrix].

Corneal endothelial cells have been shown to synthesize in vitro components of extra-cellular matrix. When the medium contains growth factors, those components reconstitute a nearly physiologic basement membrane which has been successfully used to improve several culture systems. In this work we investigated the influence of the matrix synthesized by bovine corneal endothelial cells, without growth factors, on rat neonatal pancreatic islets. After one week, islets cultivated on plastic showed a slight decrease in their insulin-releasing ability, whereas the secretory capability of islets cultivated on a matrix remained nearly constant. The difference in daily insulin release between those two culture systems reached the significance on the 20th day (p less than 0.02). Thus, such matrices could exert a favourable effect on cultured neonatal rat islets. The importance and the duration of this effect remain to be precisely determined by further investigations.

Animals↗

[Autotransplantation of islands of Langerhans in dogs].

Six dogs received intraportally an autograft of isolated non purified pancreatic islets after total pancreatectomy. The isolation was made by collagenase technique, using a quarter to a half of the total pancreatic mass. The results of different transplantation technics are discussed. We conclude the necessity of: 1) a good venous distension of the pancreas, 2) the use of at least a third of the pancreatic gland to prepare the islets, 3) a tissue reinjection the closest as possible of the portal vein.

Animals↗

Urinary zinc and its relationships with microalbuminuria in type I diabetics.

We investigated whether zincuria is associated with microalbuminuria in type I (insulin-dependent) diabetics (IDDM). In 169 IDDM, 215 overnight urine samples were collected for simultaneous assay of zinc and albumin. In 76 samples with excessive microalbuminuria (greater than 15 mg/L), zincuria was higher than in the 139 other samples (0.83 +/- 0.06 vs 0.58 +/- 0.03 mg/L p less than 0.001), though zincuria and microalbuminuria were not significantly correlated. An exercise provocation test was performed in 78 IDDM. Although microalbuminuria increased, zincuria did not change during the test. Another group of 83 IDDM underwent urinary zinc determination over a period of 1 h of recumbency. The 48 patients who had a zincuria higher than the mean + 2 SD of control values had higher microalbuminuria at rest (48 +/- 16 micrograms/min vs 12 +/- 2 p less than 0.01) and after exercise (111 +/- 33 vs 42 +/- 14 p less than 0.02) than the remaining 35 subjects. Both subgroups did not differ for zinc intake and zincemia. Thus, incipient nephropathy as detected by the measurement of microalbuminuria is associated with a highly significant increase in zinc excretion, which is not proportional to albumin leakage, nor is it amplified during exercise. Hyperzincuria is not explained by an increase in zinc intake and does not result in hypozincemia.

Adolescent↗

Serum zinc and somatic growth in children with growth retardation.

A possible role for zinc deficiency in some cases of growth retardation in southern France was investigated. Control values for zinc for 160 children (age = 12.5 +/- 2.4 yr) are 0.85 +/- 0.22 mg/L (mean +/- 2 SD). Twenty-five children with low serum zinc values (less than 0.63 mg/L) and 25 matched short children with normal serum zinc values (greater than 0.63 mg/L) were studied. Children in the two groups did not differ significantly in age, pubertal development, stature, and weight. For the 25 children whose serum values were low, we found significantly lower values for bone age delay, growth velocity in mm/month, as well as the ratio between calculated growth velocity and theoretical growth velocity for the bone age (so that zincemia was correlated to these parameters in the whole sample of 50 subjects). Nevertheless, no significant difference could be found between the two groups for serum somatomedin C, serum osteocalcin values, and GH responses to the GH stimulatory tests (exercise test, overnight sampling, insulin-induced hypoglycemia, arginine test). Therefore, low serum zinc is associated with a retardation in both somatic growth and pubertal maturation.

Bone Development↗

In vitro influence of zinc and magnesium on the deformability of red blood cells artificially hardened by heating.

Trace elements have been shown to improve red blood cell (RBC) deformability: zinc in sickle cell disease and magnesium in an in vitro model of chemically rigidified erythrocytes. In this study, we investigated the effect and the influence of incubation time of zinc or magnesium on an in vitro model of rigidified RBCs by heating. Erythrocyte rigidity was determined by viscosimetry at high shear rate by a falling ball viscosimeter MT 90. In the first part of the study, six normal volunteers participated. Viscosimetry was performed on native blood before and after heating the sample for 10 min at 50 degrees C. Therefore, increasing concentrations of zinc gluconate (final concentration: 0.5-4 g/L) or isotonic NaCl as control medium were added to the sample. Heating induced a twofold increase in all indices of RBC rigidity (p < 0.05). At all these concentrations of zinc, a highly significant, dose-related fluidifying effect was observed (40-70%): this effect was immediately obtained and did not change over 60 min. Even at the highest concentration, recovery was not complete. In the second part of the study, we studied magnesium's effects on blood. In a first protocol, whole blood was rigidified by heating at 56 degrees C for 10 min, and the correcting effect of 5 min of incubation at 37 degrees C of RBCs in 150 mmol/L NaCl, MgSO4, magnesium acetate, and magnesium gluconate was investigated. In a second protocol, the same incubation with NaCl and magnesium salts was made on blood that had not been previously heated.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

Serum zinc in highly trained adolescent gymnasts.

Serum zinc was measured in 20 adolescent gymnasts (9 boys, 11 girls, age 12-15 yr) explored for detecting possible adverse effects of intense training on pubertal maturation and growth. They had low serum zinc (0.599 +/- 0.026 mg/L) when compared to matched control sedentary children (n = 118 mean 0.81 +/- 0.014 p < 0.001). Girls had lower zinc than boys (0.557 +/- 0.023 vs 0.651 +/- 0.044 p < 0.001). Zinc was correlated to isometric adductor strength (r = 0.468 p < 0.05). Children with serum zinc < 0.6 mg/L had lower insulin-like growth factor binding protein 3 than others (2.326 +/- 0.264 vs 2.699 +/- 0.12 p < 0.01). Thus, zinc is lowered in trained adolescent gymnasts and even lower in females. This reduction could play some role in abnormalities of puberty, growth, or muscular performance.

Adolescent↗

Effects of oral zinc gluconate on glucose effectiveness and insulin sensitivity in humans.

Zinc improves both insulin secretion and insulin sensitivity, and exerts insulin-like effects. We investigated its acute effects on the parameters of glucose assimilation determined with the minimal model technique from frequent sampling intravenous glucose tolerance test (FSIVGTT) in seven healthy volunteers. FSIVGTTs (0.5 g/kg of glucose, followed by 2 U insulin i.v. injection at 19 min) were performed after the subjects had taken 20 mg zinc gluconate twice (the evening before and 30 min before the beginning of the test) or placebo pills (simple blind randomized protocol). Glucose assimilation was analyzed by calculating Kg (slope of the exponential decrease in glycemia), glucose effectiveness Sg (i.e., ability of glucose itself to increase its own disposal independent of insulin response), and SI (insulin sensitivity, i.e. the effect of increases in insulinemia on glucose disposal). The two latter parameters were calculated by fitting the experimental data with the two equations of Bergman's "minimal model." Zinc increased Kg (p < 0.05) and Sg (p < 0.05), whereas SI and insulin first-phase secretion did not significantly increase. This study suggests that zinc improves glucose assimilation, as evidenced by the increase in Kg, and that this improvement results mainly from an increase in glucose effectiveness (insulin-like effect), rather than an action on insulin response or insulin sensitivity.

Administration, Oral↗

Serum zinc and blood rheology in sportsmen (football players).

We aimed at investigating relationships between zinc status, blood rheology and blood glucose during exercise. Twenty-one professional football players underwent a triangular maximal exercise test on cycloergometer, with progressively increasing work loads until VO2max. On the whole these subjects had a low serum zinc because nine of them had a hypozincemia (0.54 +/- 0.01 mg/l) which suggested a zinc deficiency. Subjects with low serum zinc were able to perform a lower power output (123 +/- 8.71 vs. 166.27 +/- 14.84 watts, p = 0.029) and exhibited a higher increase in blood lactate during exercise (7.51 +/- 0.81 vs. 5.57 +/- 0.33 mmol/l, p = 0.024) resulting in a lower 2 mmol lactate threshold (44.7 +/- 3.9% vs. 58.9 +/- 4.8% of maximal power output, p = 0.04). They were less able to maintain their plasma glucose and exhibited a tendency towards hypoglycemia (p = 0.0153). Hypozincemia was associated with a higher viscometric RBC rigidity index (p = 0.0009), and this index was negatively correlated to serum zinc (r = -0.68, p = 0.7 x 10(-3)). Blood viscosity at high shear rate (MT90 viscosimeter) corrected for hematocrit (45%) remained higher during exercise in these hypozincemic subjects (p = 0.003). This study suggests that zinc status may influence blood rheology during exercise, either by its direct action on RBC flexibility (demonstrated in vitro) or by its effect on lactate accumulation which may in turn modify erythrocyte fexibility.

Adult↗

[In vivo evaluation of insulin sensitivity and clinical applications].

During the past decade, the potential implications of insulin resistance were recognised by clinicians ranging from endocrinologists to cardiologists. Central to this expanding interest is Reaven's hypothesis that tissue resistance to the effects of insulin is a factor linking various metabolic disorders and coronary heart disease. This review critically describes the different approaches for the evaluation of insulin sensitivity in vivo. Qualities and limitations of several investigative techniques are discussed, such as anthropometric indexes, basal biological indexes, insulin suppression tests and insulin tolerance tests. The two most widely used methods for quantifying insulin sensitivity are the euglycaemic hyperinsulinaemic clamp and the intravenous glucose tolerance test with minimal model analysis. Insulin resistance occurs in many aetiologically diverse human disorders. Genetic syndromes with extreme insulin resistance are very uncommon. Insulin resistance is frequently associated with obesity, type 2 diabetes and essential hypertension. The insulin resistance syndrome called syndrome X includes impaired insulin-mediated glucose uptake, impaired glucose tolerance, hyperinsulinaemia, hypertension, dyslipidaemia and haemostatic disorders. Finally, the clinical significance of high values of insulin sensitivity is discussed.

Animals↗

[Is microalbuminuria, an early marker of clinical nephropathy, also a cardiovascular risk factor?].

Microalbuminuria is not only a predictor of diabetic nephropathy in type 1 diabetes, but also a potent marker of cardiovascular risk, especially in type 2 diabetes. Microalbuminuria also predicts cardiovascular morbidity in the general population. We describe semi-quantitative and quantitative methods for determination of low urinary excretion of albumin. Pathogenetic hypotheses common to both renal and endothelial dysfunction are discussed, suggesting that microalbuminuria may be a link between micro- and macroangiopathy. Improved glycemic control and antihypertensive treatment postpone and potentially prevent development of nephropathy in diabetic patients with microalbuminuria. These interventions must be instituted early in the development of diabetic nephropathy. In type 2 diabetes, prospective studies are needed to evaluate the precise impact of such a therapy on the cardiovascular risk.

Albuminuria↗