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F Trivin

Publications and source records attributed to F Trivin.

At least 55 records · Page 3Linked to original sources

[Determination of plasma proinsulins, insulin and C-peptide].

Insulin is synthesized from a precursor, proinsulin, then converted in the beta cell by sequential limited proteolysis into insulin and C-peptide, which are stored in secretory granules derived from the Golgi apparatus. Since this process is incomplete, some intact and partially processed proinsulins (split proinsulins) remain trapped in the granules and enter the circulation with insulin and C-peptide. As proinsulins are present in low concentration in serum and show structural homology with insulin and C-peptide, only two-site immunoassays using monoclonal antibodies can achieve sensitive and specific measurements of their intact and split forms. Insulin radioimmunoassays using polyclonal antibodies are not specific since such antibodies cross-react with proinsulins. Two-site immunoassays using monoclonal antibodies improve the specificity and the sensitivity of insulin determination. C-Peptide concentration is measured by radioimmunoassays using polyclonal antibodies which cross-react with proinsulins.

C-Peptide↗

Genetic heterogeneity of Crigler-Najjar syndrome type I: a study of 14 cases.

Crigler-Najjar syndrome type I (CN-I) is an autosomal recessive condition characterized by severe unconjugated hyperbilirubinemia caused by the lack of bilirubin-UDP-glucuronosyltransferase (B-UGT) activity in the liver. Two B-UGTs are coded for by a gene complex (UGT1) that maps to chromosome 2q37 and that also encodes two phenol-UDP-glucuronosyltransferases. Here, we report eleven mutations (including nine novel mutations) of the B-UGT1 gene in a large series of 14 unrelated CN-I children of various geographic origins: France (seven patients: A401P, Q357X, W335X, A368T, 1223insG, A291V, K426E, K437X); Portugal (two patients: G308E); Tunisia (two patients; Q357R); Turkey (one patient: S381R); italy (two siblings: S381R). Interestingly, 6/14 mutant alleles carried by unrelated probands of French ancestry bore the A401P mutation, indicating a founder effect; this effect is probably also present in Portugal, Turkey, and Tunisia. Since mutations occurred in exons 2-5 shared by all mRNAs species of the gene, a combined deficiency of B-UGT and P-UGT was observed in the liver of five patients in whom these activities were measured. The present study confirms that CN-I is genetically heterogeneous and suggests that different founder effects are involved in Western Europe, the Middle East, and North Africa.

Crigler-Najjar Syndrome↗

Competitive inhibition of thyroid hormone uptake into cultured rat brain astrocytes by bilirubin and bilirubin conjugates.

Thyroid hormone (TH) metabolism is altered in cases of unconjugated hyperbilirubinemia. These effects might involve inhibition of TH uptake by their target cells. Astrocytes, which are in close contact with the membranes of brain capillaries, might be the first brain cells to come into contact with bilirubin. Cultured rat brain astrocytes were used as a model to study the effects of bilirubin and bilirubin analogues on TH uptake. The initial uptake of [125I]T3 and [125I]T4 was inhibited by unconjugated bilirubin, biliverdin, ditaurobilirubin and bilirubin glucuronides. The inhibition of T3 uptake by the bilirubin analogues was competitive. The Ki values were: unconjugated bilirubin (31 microM), biliverdin (48 microM), ditaurobilirubin (2.5 microM) and bilirubin glucuronides (1.2 microM). This last value is similar to the Km of T3 transport (0.4 microM), indicating that bilirubin glucuronides have a high affinity for the TH transport system. By contrast, the uptakes of [3H]tryptophan and ]3H]glutamine were not inhibited. These results suggest that the astrocyte plasma membrane bears specific bilirubin-interaction sites that are closely related to the TH transport system. However, uptake of [14C]bilirubin by cultured astrocytes was a non-saturable process. Binding of bilirubin to the astrocyte plasma membrane may inhibit the TH uptake and impair their metabolism and their action on the intracellular targets.

Animals↗

Investigation of total and conjugated bilirubin determination during the neonatal period.

During the neonatal period, total and conjugated bilirubin determinations are necessary to identify the origin of jaundice, to predict its evolution and to treat it. We discuss the results obtained in 108 neonates (less than 15 days old), undergoing phototherapy or not, using a colorimetric diazo reaction and dual wavelength reflectance with a Kodak Ektachem analyzer. Concerning total bilirubin determination, the methods correlate well (r > 0.96). Discrepancies are observed for conjugated or "direct" bilirubin, and high performance liquid chromatography was carried out in order to explain them. The chromatograms show 4 neonate samples with only classic mono- but no di-glucurono-conjugate fractions, whereas all the neonates present two unusual fractions (I and II) not seen in adults. A correlation was found between the amount of fraction II and the conjugated bilirubin determined by diazo reaction and between fraction I and the conjugated bilirubin obtained in the Kodak Ektachem assay. A better correlation between fraction I and conjugated bilirubin on Kodak was observed (r = 0.79, vs r = 0.66) when the newborns were submitted to phototherapy. Moreover, fraction II and conjugated bilirubin measured by the diazo reaction on Hitachi 717 rose significantly. In conclusion, total bilirubin is accurately determined during the neonatal period; for conjugated or "direct" bilirubin determination, our study points out significant differences. Further investigation will determine the nature of the fractions observed by liquid chromatography in neonatal sera, and the components actually determined by the automatized methods usually employed.

Bilirubin↗

Bilirubin uridine diphosphate glucuronosyltransferase hepatic activity in jaundice associated with congenital hypothyroidism.

Hepatic bilirubin uridine diphosphate glucuronosyltransferase activity was assayed in an infant with prolonged jaundice and congenital hypothyroidism before thyroid therapy. This activity was nil, suggesting a possible delayed maturation of the enzyme. Although further studies will be necessary to confirm this hypothesis, prolonged jaundice associated with congenital hypothyroidism may be due to a delayed maturation of the hepatic glucuronidation of bilirubin.

Bilirubin↗

Comparison of different types of cardioplegia and reperfusion on myocardial metabolism and free radical activity.

Current techniques of myocardial protection during global ischemia include hypothermia, cardioplegic arrest and controlled reperfusion. To compare different types of cardioplegia and reperfusion techniques we measured the levels of adenine nucleotides and malondialdehyde (MDA, as free radical activity) in 33 patients undergoing heart surgery. The patients were randomized in three groups according to the characteristics of cardioplegia and reperfusion: cold blood cardioplegia with unmodified blood reperfusion (control group, 11 patients), crystalloid cardioplegia and reperfusion (Hôpital Lariboisière protocol, 11 patients) and crystalloid cardioplegia with allopurinol enriched blood reperfusion (Hôpital Broussais protocol, 11 patients). Myocardial biopsy specimens were obtained before cardioplegic arrest (preischemic values), at the end of ischemia and after 30 minutes of reperfusion. Biopsy specimens were analyzed by high performance liquid chromatography for levels of adenine nucleotides and MDA. In the three groups, the preischemic values of adenine nucleotides and MDA were not significantly different. For AMP and ADP concentrations neither treatment nor biopsy-time effects appeared. ATP concentration decreased significantly with biopsy-time without specific treatment effect. For MDA concentration neither treatment nor biopsy-time effects were observed. This study suggests that there is no statistically significant difference between any of the three cardioplegia and reperfusion techniques for either ATP or MDA; the three reperfusion techniques limit the free radical activity but do not prevent the fall in high energy phosphates.

Adenine Nucleotides↗

Gunn rats: a reproducible experimental model to compare the different methods of measurements of bilirubin serum concentration and to evaluate the risk of bilirubin encephalopathy.

Three groups of Gunn rats were studied: group 1 was perfused with bilirubin solution alone, group 2 was perfused with bilirubin and albumin solutions simultaneously, group 3 was perfused with bilirubin solution for 30 min then bilirubin and albumin solutions for the following 10 min. Our results indicate that (1) Gunn rats are a reliable experimental model to study the risk of bilirubin encephalopathy, (2) unbound bilirubin can enter the brain when albumin binding capacity is reduced, (3) and bilirubin binding capacity of serum for unbound unconjugated serum bilirubin is a better criterion than total serum bilirubin and erythrocyte bilirubin to evaluate the risk of kernicterus. This model could also be used to study variations of permeability of the blood-brain-barrier and influences of drugs on bilirubin metabolism.

Animals↗

[Comparison of three methods evaluating the saturation of serum bilirubin transporters in children with type I Crigler Najjar disease].

The assessment of reserve bilirubin binding capacity of serum in 12 children with type I Crigler-Najjar syndrome was performed by 3 biochemical methods. Two of them use chromatography techniques: thin layer on Sephadex or high performance liquid; they allow the determination of the saturation rate of all serum bilirubin carriers. The third method only evaluates the major carrier, albumin, using the molar bilirubin-albumin ratio. An identical correlation coefficient of 0.90 has been obtained when comparing with the chromatographic method on thin layer, respectively 20 determinations using high performance liquid chromatography and 122 measurements of the bilirubin/albumin ratio. In practice, we advise a first, simple and rapid determination of the bilirubin/albumin ratio in case of a sudden aggravation of the jaundice in the children with Crigler-Najjar type I disease. The chromatographic methods will be used in a second step, or in order to survey the phototherapy treatment that these children receive.

Adolescent↗

High-performance liquid chromatographic determination of tauro- and glyco-conjugated bile acids in human serum.

A method for the identification and individual determination of the ten tauro- and glyco-conjugated bile acids is described. It consists in a specific three-step extraction from small serum samples (500 microliters), high-performance liquid chromatographic separation and direct spectrophotometric detection at 119 nm. Extraction can be checked by the use of an internal standard. The reproducibility, recovery and separation of fractions were satisfactory.

Bile Acids and Salts↗

Crigler-Najjar type II disease inheritance: a family study.

The inheritance of Crigler-Najjar type II disease is still contested. Autosomal dominant transmission with incomplete penetrance and autosomal recessive transmission have been proposed. We had the opportunity to study the hepatic activity of bilirubin uridinediphosphate glucuronyltransferase in parents whose first child had been affected by Crigler-Najjar type II disease. The demonstration of reduced activity of glucuronidation in the liver of both parents suggests autosomal recessive inheritance. The second infant of this couple was affected by the same disease and was treated with success by phenobarbital.

Bilirubin↗

Bile acid glycine and taurine conjugates in serum of patients with primary biliary cirrhosis: effect of ursodeoxycholic treatment.

We have applied a specific and accurate high pressure liquid chromatographic technique to determine fasting serum glycine and taurine conjugates of individual bile acids in patients with primary biliary cirrhosis before and during ursodeoxycholic acid therapy. The study was carried out in nine patients in whom the diagnosis of primary biliary cirrhosis was established according to accepted criteria. After one year of UDCA therapy liver function tests significantly improved. Total serum bile acid concentration did not change significantly (29.2 (31.5) v 28.3 (26.4) microM). Total UDCA (1.7 (2.2) v 13.3 (14.5) microM) and glyco UDCA (0.8 (1.6) v 10.9 (11.4 microM) but not tauro UDCA levels increased significantly (p less than 0.01); UDCA (7.7 (12.6) v 40.2 (12.7)%) became the major species of the circulating bile acids. Primary bile acids (23 (28.3) v 11.2 (10.5) and their glycoconjugates fell significantly (p less than 0.01). There were no significant changes in the concentrations of conjugates of the secondary bile acids (4.5 (3.8) v 3.9 (3.0]. Our study shows that oral administration of UDCA to patients with primary biliary cirrhosis induced marked changes in the circulating pool of endogenous bile acids together with improvement in liver function test values. The data also suggest that the beneficial effect of longterm administration of UDCA in these patients might be mediated through changes in the circulating primary bile acids and UDCA rather than through changes in the circulating secondary bile acids, deoxycholate and lithocholate.

Bile Acids and Salts↗

Deficient induction of sulfobromophthalein conjugating activity by phenobarbital in hamster liver.

Administration of phenobarbital, a known inducer of glutathione S-transferase activity in rat liver, failed to stimulate sulfobromophthalein (BSP) conjugation by liver cytosol in hamsters. The latter displayed poor ability to conjugate this substrate, despite very high glutathione-conjugating activity with the broad-spectrum substrate 1-chloro-2,4-dinitrobenzene (CDNB). Of the six substrates tested, in this species, 1,2-epoxy-3-(4-nitrophenoxy)propane (ENPP) was the only one whose conjugation was greatly enhanced by phenobarbital (+172%). Nevertheless, hamsters proved as responsive to phenobarbital induction as rats, since it increased their relative liver weight and microsomal enzyme activity. The deficient induction of liver BSP-conjugating activity observed with phenobarbital is consistent with the finding that it did not affect the hepatic transport of this substrate in hamsters.

Animals↗