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Biomedical subjects

J P Yvert

Publications and source records attributed to J P Yvert.

7 recordsLinked to original sources

Amplify or improve detection.

Quantification with accuracy at the molecular level, by simple means, is the challenge for new generations of biospecific assays. In order to reach this goal, it is necessary to reduce the non-specific background of the current assays and further to amplify the detection signal or to expand the surface of the solid phase. For now, significant additions in performance can be achieved if we balance new ways of amplification with progressive improvements of existing procedures. For the future, new concepts derived form biosensors approach will lead to simultaneous multiple analysis on the same sample.

Biological Assay

Correction by insulin of disturbed TG-rich LP metabolism in rats with chronic renal failure.

To define the role of insulin in lipid disturbances of chronic renal failure, chronically uremic rats (U+) were supplemented by continuous insulin infusion over a 35-day experimental period and compared with control ad libitum-fed rats (C) and uremic rats without insulin (U). Uremic rats were characterized by hypoinsulinemia, an increase in both circulating very low-density lipoprotein (VLDL) and their cholesterol concentration, a normal hepatic triglyceride secretion rate (TGSR) determined with Triton WR 1339, and a low adipose tissue lipoprotein lipase (LPL) activity. Chronic insulin infusion at low rate (0.5 IU/24 h) to U+ rats normalized serum insulin (from 17.0 +/- 0.6 mU/l in U rats to 23.4 +/- 1.7 mU/l in U+ rats), serum VLDL triglycerides (from 804 +/- 65 to 410 +/- 36 mg/l), and serum VLDL cholesterol (from 43 +/- 8 to 16 +/- 3 mg/l). Hepatic TGSR decreased significantly after insulin treatment (from 0.58 +/- 0.03 to 0.44 +/- 0.03 mumol/min). Moreover, adipose tissue LPL was restored to normal by insulin supplementation (from 460 +/- 60 to 860 +/- 150 mU per total epididymal fat in U and U+ rats, respectively). Correction of the disturbed VLDL metabolism was associated with multiple actions of insulin including 1) a decrease of peripheral lipolysis, 2) a decrease of hepatic TGSR, and 3) an increase of adipose tissue LPL activity. Because cholesterol-rich VLDL are potentially atherogenic, their normalization with insulin treatment in this animal model suggests a viable area of investigation for the prevention of accelerated atherogenesis in chronic renal failure.

Adipose Tissue

Plasma and pituitary content of growth hormone luteinizing hormone, and prolactin in uremic rats. Effects of chronic infusion of insulin.

The influence of chronic renal failure on pituitary content and on serum concentrations of growth hormone (GH), prolactin (PRL), and luteinizing hormone (LH) was studied in chronically uremic rats by comparison with control rats fed ad libitum and diet-restricted rats pair-fed with uremic rats. A decrease of pituitary GH content was found in uremic and diet-restricted rats, in association with a normal circulating GH level. A decrease of pituitary PRL and LH content with respectively high and normal serum values was observed in uremic but not in diet-restricted rats. These data strongly suggest that GH disturbances are related to malnutrition, whereas PRL and LH abnormalities are related to the uremic state per se. As hypoinsulinemia was observed in uremic rats, and as insulin is largely implicated in growth, we have investigated the effects of chronic infusion of insulin, using miniosmotic pumps, on pituitary hormone content. In spite of normalization of circulating insulin levels in uremic rats treated with insulin, pituitary GH, LH, and PRL contents were unaffected. Thus, insulin deficiency did not appear to be responsible for the diminished pituitary reserve of these hormones.

Animals

Factors of increase in serum triglyceride-rich lipoproteins in uremic rats.

The possible mechanisms of the increase in serum triglycerides (TG) and TG-rich lipoproteins were studied in chronically uremic (U) rats by comparison with either ad-lib fed control (C) rats or diet-restricted (DR), sham-operated pair-fed control rats. A first series of animals was studied in the fed state and a second series after a 16-hr fast. In U animals the concentration of serum TG and TG-rich particles was lower than that of C rats in the fed state but significantly higher than that of C and DR rats after a 16-hr fast. Serum glucose and lactate concentrations in the fed or fasted state were unchanged by uremia. Serum insulin concentration was significantly decreased in U rats as compared to C and DR rats in both series. The fast did not increase the concentration of serum nonesterified fatty acids (NEFA) in U or DR animals to the same extent as in C rats, whereas the serum concentration of beta-hydroxybutyrate (BOB), which was higher than that of C rats in the fed state, was significantly lower after a 16-hr fast. In U animals, as compared to control rats of either series, a significant decrease of epididymal lipoprotein lipase (LPL) activity was observed during both nutritional states when expressing the enzymic activity per number of cells. In conclusion, our data provide evidence against hepatic over-production of TG-rich lipoproteins in rats with chronic renal failure and strongly point to an LPL-mediated defect of their peripheral catabolism, probably related to the insulin deficiency state.

3-Hydroxybutyric Acid

Simple, fast preparation of gallium-68-labelled human serum albumin microspheres.

Following a study of the main factors involved in the 68-Ga labelling of human serum albumin microspheres (H.S.A.M.), especially methods of production and preparation of active solution and conditions of radioelement fixation on the protein support, the practical details of a fast technique (60 min) based on the process described by Hnatowich are presented. This method gives high labelling yields (93 +/- 3%), and after washing of the microspheres leads to a radiopharmaceutical product almost without free 68Ga (less than 2%). The spheres ready for use carry a total radioactivity corresponding to about 35%, including decay, of the activity originally recovered in the generator eluate and to more than 98% of that, found in the final suspension. The labelled product is sterile, non-pyrogenic and non-toxic. When it is injected in animals by left ventrical catheterization the uptake rates in the heart, lungs, spleen, left kidney and right kidney are similar to those observed with reference 85Sr-labelled carbonized microspheres. This radiopharmaceutical, easy to prepare and having excellent biological and nuclear properties, seems ideally suited for the scanning of organs by position emission tomoscintigraphy.

Animals