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Biomedical subjects

C Tiribelli

Publications and source records attributed to C Tiribelli.

At least 109 records · Page 6Linked to original sources
PubMed1988

Sex steroid modulation of the hepatic uptake of organic anions in rat.

To investigate the role of sex steroids in the sex-related difference in the hepatic uptake of organic anions, sulphobromophthalein (bromsulphalein, BSP) transport was measured in hepatocytes isolated from rats either deprived of hormonal influence by castration at prepubertal age or after hormonal substitution. In control animals, the kinetics of BSP uptake showed the presence of two components: one saturable (0-3 microM), with high affinity and low capacity, and the other linear (9-30 microM), probably related to the non-specific component of BSP uptake. Sex difference was detected only in the saturable portion of the uptake process as the apparent Km was significantly lower in females than in males (3.8 +/- 0.7 vs. 6.1 +/- 1.8 microM, mean +/- S.D. of six animals, P less than 0.01). In contrast, no difference was observed in Vmax (2.3 +/- 0.3 vs. 2.2 +/- 0.7 nmol BSP.(mg protein)-1.min-1). Castration was associated with the disappearance of the saturable uptake site and abolished the sex difference. Progesterone treatment of castrated males failed to restore the saturable kinetics of BSP uptake. In contrast, administration of oestradiol to castrated males or testosterone to castrated females did restore the saturable kinetics of the high-affinity BSP uptake. Km and Vmax were comparable to those of adult females and males, respectively, with the exception of testosterone which induced a Vmax value higher than that observed in the other groups of animals. These data suggest that the influence of oestrogen and testosterone is necessary for the expression of the high-affinity, low-capacity carrier-mediated process of hepatic BSP uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Cellular localization of sulfobromophthalein transport activity in rat liver.

The movement of sulfobromophthalein is measured in rat liver plasma-membrane vesicles by direct dual-wavelength spectrophotometry. The technique is based on the principle that the dye, when entering a more acidic compartment, changes its absorption in the visible region. From this study it may be concluded that, among the different cellular subfractions, only liver plasma-membrane vesicles can catalyze electrogenic transport of sulfobromophthalein. Plasma membranes from erythrocytes are unable to perform such a function. The movement follows the distribution pattern of (Na+ + K+)-ATPase and it is therefore concluded that this process occurs exclusively at the sinusoidal membrane level. Inhibition studies confirm that the process is catalyzed by bilitranslocase.

Animals↗
PubMed1986

Clinical, biochemical and histological features of primary haemochromatosis: a report of 67 cases.

In 67 patients (mean age 51 years, range 26-79), at diagnosis of primary haemochromatosis (PH), grade III or IV liver iron overload was present in all cases, cirrhosis in 85%, transferrin saturation greater than 80% in 75%, serum ferritin greater than 1000 micrograms/l in 84%, and overt diabetes in 48%. Alcohol intake was greater than 150 g/day in 11 patients; six were chronic hepatitis B surface antigen (HBsAg) carriers. HLA-A3 and B7 antigens were present in 64% and 23% versus respectively 22% (p less than 0.01) and 9% (p less than 0.025) in controls. Iron overload was found in the stomach, duodenum, skin and bone marrow in 57, 43, 45 and 59% of the patients studied. Sixty-three patients were followed for 1-260 months (median 24); 43 received regular iron-depleting treatment and 20 did not because of liver failure, cancer or refusal. Cumulative survival was 79%, 67% and 61% at 1, 4 and 10 years, respectively. Ten patients died from hepatocellular carcinoma and two from extrahepatic cancer. The early high mortality rate was due to some cases of advanced disease or cancer. Cumulative survival in the regularly treated group was 95% at 1 year and 91% at 4 and 10 years, which was higher than in the untreated group.

Adult↗
PubMed1986

Dose dependence of nicotinic acid-induced hyperbilirubinemia and its dissociation from hemolysis in Gilbert's syndrome.

The serum increments in unconjugated bilirubin and total iron were determined after intravenous administration of 5.90 mumol/kg body weight of nicotinic acid (NA) in 26 patients with Gilbert's syndrome (GS), seven patients with hemolytic anemia, and 13 healthy volunteers. The hyperbilirubinemic response, expressed as the area under time concentration curve of unconjugated bilirubin (AUCBR, milligrams per deciliter per 240 minutes) was significantly higher (P less than 0.01) in patients with GS than in controls and patients with hemolytic anemia, in whom no difference was observed. In contrast, comparable values of the hypersideremic effect (AUCFe, milligrams per deciliter per 240 minutes) were noticed among the three groups. In seven consecutive patients with GS, seven with hemolytic anemia, and four healthy volunteers, AUCBR, AUCFe, and the NA plasma half-life of the first fast slope of the curve were determined at three different doses of the drug (1.18, 2.95, and 5.90 mumol NA per kilogram body weight). A significant, dose-dependent increase in AUCBR was present in patients with GS, whereas it remained constant both in controls and in patients with hemolytic anemia. The NA plasma half-life was also significantly prolonged in GS with each of the three doses, but remained unchanged in the other two groups. In patients with GS, a linear correlation (r = 0.891, P less than 0.001) was present between AUCBR and NA plasma half-life. In contrast, the AUCFe value remained constant at the different doses used in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1985

Measurement of the association of cholephylic organic anions with different binding proteins.

The binding of the colored cholephylic anions tetrabromosulfonphthalein (BSP), di-bromosulfonphthalein (DBSP), indocyanine green (ICG) and thymol blue (ThB) to a number of protein preparations including bovine serum albumin, human serum, rat hepatic cytosol and purified rat liver bilitranslocase has been studied by a direct spectrophotometric method. The experimentation provides extinction coefficients, dissociation constants and number of binding sites for the different complexes between dyes and the various proteins. Data obtained by this technique were in excellent agreement with those obtained on the same samples by ultrafiltration. The data presented indicate that the direct spectrophotometry applied to these dyes is simple, rapid and reproducible, making this the approach of choice during the purification of binding proteins when the binding capacity is the only useful criterion to follow the progress of the procedure.

Animals↗
PubMed1985

Comparison of nicotinic acid- and caloric restriction-induced hyperbilirubinaemia in the diagnosis of Gilbert's syndrome.

The diagnostic value of the nicotinic acid (NA)-induced hyperbilirubinaemia was compared with that resulting from caloric restriction in 40 patients with Gilbert's syndrome (GS) and 20 controls. Both tests resulted in a significant higher level of serum bilirubin in GS than in controls (P less than 0.001). When the serum bilirubin level 240 min after NA administration (5.9 mumol/kg i.v.) was higher than 18 mumoles/l, this test had a specificity and sensitivity of 100%, both in males and females with the syndrome. The discriminatory value of the test was lower when either the area under the time concentration curve or the maximal increment of serum unconjugated bilirubin were used. Reduction in caloric intake (400 calories/day) showed a lower specificity and sensitivity than the NA test, particularly in females. An increment of bilirubin at 24 h greater than 15 mumoles/l was more diagnostic than an increase by 100% or more over the pre-diet value. The efficacy was not improved by prolonging the test for additional 24 h. From these data we conclude that NA-induced hyperbilirubinaemia and, in particular the concentration of the pigment 240 min after drug administration, is more efficient than fasting-induced hyperbilirubinaemia in the diagnosis of the Gilbert's syndrome both in males and in females.

Adult↗
PubMed1985

Sex differences of nicotinate-induced hyperbilirubinemia in Gilbert's syndrome. Implication of bilitranslocase function.

Intravenous administration of nicotinic acid (NA) is followed by an increase in serum unconjugated bilirubin level. This effect is higher in Gilbert's syndrome (GS) and this test has been used in the diagnosis of the syndrome. After administration of 5.9 mumol NA/kg body weight, the maximal increment of serum unconjugated bilirubin and the area under the bilirubin concentration time curve (AUC) were significantly higher (P less than 0.01) in GS males than in GS females. The half-life of the first fast slope of plasma disappearance curve of the drug was also significantly prolonged in GS males as compared to GS females (15.91 +/- 1.12 vs 9.13 +/- 1.25 min, mean +/- SEM, P less than 0.005). The maximal bilirubin increment and AUC were linearly correlated (P less than 0.01) with NA plasma half-life. Purified preparations of bilitranslocase, a liver plasma-membrane protein involved in bilirubin and sulfobromophthalein (BSP) transport, specifically bound NA and the drug competitively inhibited BSP uptake in rat liver plasma membrane vesicles (Ki = 50 nM). These data suggest that, in addition to the hemolytic effect of the drug, NA-induced hyperbilirubinaemia could be also due to a competition between the two anions at the sinusoidal plasma membrane level. A possible implication of bilitranslocase in GS is considered.

Adolescent↗
PubMed1985

The implication of bilitranslocase function in the impaired rifamycin SV metabolism in Gilbert's syndrome.

1. The plasma disappearance rate and the increment in plasma unconjugated bilirubin after intravenous administration of 5.9 mumol of rifamycin SV (RSV)/kg body wt. were investigated in 51 subjects with Gilbert's syndrome and 35 control subjects of both sexes. 2. Both the plasma disappearance rate and the unconjugated hyperbilirubinaemia after RSV administration were higher (P < 0.001) in Gilbert's syndrome. Females, both normal and with the syndrome, showed a significantly shorter t1/2 and a lower hyperbilirubinaemic response as compared with males. A linear correlation (P < 0.001) was present between RSV plasma half-life and the hyperbilirubinaemic response. 3. In vitro, RSV was shown to inhibit sulphobromophthalein (BSP) uptake in rat liver plasma-membrane vesicles with a Ki of 20 mumol/l. Evidence that this effect was due to competition for bilitranslocase was sought on preparations of the purified protein. Under these experimental conditions, RSV inhibited BSP binding with a Ki of 17 mumol/l. 4. Since RSV competes with BSP for binding to bilitranslocase in vitro, the data are interpreted as suggesting that reduced bilitranslocase function might underlie the delayed RSV plasma clearance and the exacerbated unconjugated hyperbilirubinaemia present in Gilbert's syndrome.

Adolescent↗
PubMed1985

Sex differences in the hepatic uptake of sulphobromophthalein in the rat.

Sex difference in the hepatic uptake of sulphobromophthalein (BSP) was investigated in male and female rats in three different experimental models. In the intact animal the BSP plasma disappearance rate was significantly higher (P less than 0.01) in females than in males when 0.15 or 1.5 mumol/kg body wt. was injected. Comparable values were found at the highest BSP dose (15 mumol/kg body wt.) used. In the perfused liver, the first-pass hepatic extraction and the uptake velocity were significantly higher (P less than 0.001) in female rats at low BSP doses (0.3-750 mumol/g of liver) whereas identical values were found at higher concentrations. In hepatocytes isolated by collagenase perfusion, the BSP uptake occurs via two different uptake sites in both sexes. The Km of the high affinity sites was lower in females than in males (3.67 +/- 0.58 vs 7.24 +/- 0.68 mumol/l, P less than 0.001) whereas Vmax. showed comparable values (2.70 +/- 0.36 vs 2.47 +/- 0.45 nmol of BSP/mg of protein, NS). In contrast, no difference was found in the kinetic parameters of the low affinity sites (Km 50.6 +/- 31.1 vs 61.0 +/- 17.5 mumol/l; Vmax. 21.9 +/- 13.2 vs 25.0 +/- 3.6 nmol of BSP/mg of protein, mean +/- SD, NS, females and males respectively). Taken together these data show that low doses of BSP are taken up by the liver more efficiently in female than in male rats and are consistent with a sex-related difference in the affinity but not in the number of the BSP high affinity uptake sites.

Animals↗
PubMed1985

Estimation of the hepatic blood "flow" by galactose plasma clearance in patients with liver disease.

Following intravenous administration of 500 mg/kg b.wt. galactose, Galactose Elimination Capacity (GEC, mg/min/kg) was determined in 24 subjects with chronic non-cirrhotic liver disease (CLD), 33 with liver cirrhosis and 11 controls. GEC was significantly (P less than 0.01) reduced in both CLD and cirrhosis. A statistically significant difference (P less than 0.01) was present between these two groups. Following the plasma disappearance curve at concentrations below 1.25 mmol/l, at which the extraction coefficient is assumed to be equal to one, the "Efficient Hepatic Blood Flow" (EHBF, ml/min) was determined in 11 consecutive cirrhosis patients, seven patients with CLD and 11 controls. EHBF was normal or slightly reduced in CLD as compared to controls (1046 +/- 216 vs. 1471 +/- 156 ml/min, mean +/- SEM, n.s.) whereas it was markedly reduced in cirrhosis (846 +/- 96 ml/min, mean +/- SEM, p less than 0.001). Interestingly, a significant linear correlation (r = 0.757, p less than 0.001) was present between EHBF and the plasma clearance of sulfobromophthalein. No correlation was present, on the other hand, between the value of GEC and that of EHBF. These data indicate that after a single intravenous injection of galactose, the hepatic blood flow passing through the enzymatically active parts of the liver (i.e. excluding shunts) can be measured.

Adolescent↗
PubMed1984

Effect of phototherapy on the physiologic cholestasis of the neonate.

Phototherapy (PT) has been reported to increase bile acid excretion in the bile of adults with liver cirrhosis. We investigated the effect of PT on the levels of serum total bile acids (STBA), conjugated cholic acid (CCA), conjugated chenodeoxycholic acid (CCDCA), conjugated lithocholic acid (CLCA), and sulfolithocholylglycine (SLCG) in 13 neonates with unconjugated nonhemolytic hyperbilirubinemia before and after 12 h of PT. The treatment produced a statistically significant (p less than 0.02) reduction in both STBA and CCA levels, whereas no effect on the other fractions was observed. The percentage of reduction was the same for STBA and CCA concentrations, indicating that the effect is related to a specific reduction in CCA levels. The magnitude of the expected decrease in the level of serum bilirubin is not correlated with that in bile acids in individual cases. The data are interpreted as suggesting that PT can affect the metabolism of bile acids by decreasing STBA and CCA levels in neonates through an increase in their biliary excretion associated with the reduced intestinal absorption of CCA occurring in newborns.

Bile Acids and Salts↗
PubMed1984

Different morphologic aspects and clinical features in massive hepatic amyloidosis.

4 cases of massive hepatic amyloidosis are reported with special reference to their clinical profiles and histologic features. On the basis of these data, two different clinical and histologic courses of the disease can be distinguished. 2 patients showed marked hepatomegaly without cholestasis, whereas in the other 2 the clinical picture was characterized by much less pronounced hepatomegaly, but by severe and progressive intrahepatic cholestasis. The time course of the disease seems to be different in the two forms, the cholestatic form being more rapidly fatal than the other.

Aged↗
PubMed1983

Serum marker of type III procollagen in patients with idiopathic hemochromatosis and its relationship to hepatic fibrosis.

A radioimmunoassay for serum procollagen III aminopeptide (sPIIIP) was proposed recently for monitoring hepatic fibroplasia in patients with various inflammatory hepatic lesions. To determine whether sPIIIP also can detect fibroplasia in noninflammatory liver disorders, we measured this index in 16 patients with idiopathic hemochromatosis (IHC) at various stages of the disease and iron overload. Interestingly, we found normal levels of sPIIIP in 12 out of 16 patients examined (75%), despite clear histologic features of fibrosis or cirrhosis. The levels of sPIIIP exhibited no relationship to any of the clinical, laboratory, or histologic parameters of the disease. Thus, unlike other types of cirrhosis, in which sPIIIP is increased, the liver disease in IHC may be a fibrotic process unrelated to type III collagen stimulation. Accordingly, the determination of sPIIIP in these patients is of no value for monitoring the fibrosis associated with the liver disease.

Adult↗
PubMed1982

Further studies on bilitranslocase, a plasma membrane protein involved in hepatic organic anion uptake.

Bilitranslocase, a plasma membrane protein involved in bilirubin and other organic anion uptake by the liver, exhibits a high molecular weight (170 000) when isolated in the presence of deoxycholate. This value is decreased to approx. 100 000 if deoxycholate is not included in the isolation medium. Both preparations can be resolved into two kinds of subunit, alpha and beta , of 37 000 and 35 500, respectively, by reduction with 2-mercaptoethanol and addition of sodium dodecyl sulfate. Under these conditions the two subunits are still capable of high-affinity sulfobromophthalein binding and, despite the presence of the detergent, may be isolated by preparative polyacrylamide gel electrophoresis still associated with the dye. It may be suggested that the physiological subunit composition of bilitranslocase is alpha 2-beta.

Animals↗
PubMed1982

Reconstitution in vitro of sulfobromophthalein transport by bilitranslocase.

Liposomes containing 150 mM KCl and 0.48 mM sulfobromophthalein have been prepared. The internal pH was set at 6.5, a value at which sulfobromopthalein is colorless. When brought to alkaline pH a certain amount of the dye is deprotonated and can be read spectrophotometrically as external sulfobromophthalein. Upon addition of Triton X-100 the membrane is dissolved and all sulfobromophthalein present in the preparation may be measured. Addition of bilitranslocase to such a preparation of liposomes causes the internal sulfobromophthalein to leave the internal compartment. The rate of this phenomenon may be followed directly and shown to be greatly accelerated by the addition of valinomycin. The latter finding indicates that sulfobromophthalein transport occurs in response to a membrane diffusion potential created by permeabilisation to K+ of liposomes brought about by valinomycin (uniport). The permeability change induced by bilitranslocase is specific and does not reflect an alteration of the normal impermeability of liposomes to small ions such as protons or Ca2+.

Animals↗
PubMed1978

Isolation of a sulfobromophthalein-binding protein from hepatocyte plasma membrane.

This paper deals with the isolation and partial characterization of a protein capable of high affinity sulfobromophthalein-binding from liver plasma membrane. The purification involves acetone powder of a crude preparation of rat liver plasma membrane, salt extraction and purification through two chromatographic steps. Based on sulfobromophthalein binding, the process gives a yield of approximately 40%, with a purification of about 300 times with respect to the starting homogenate. The best preparation can bind more than 100 nmol sulfobromophthalein/mg protein. The protein behaves as a single species in dodecyl sulphate polyacrylamide gel electrophoresis, with an apparent molecular weight of 1.7 . 10(5). The molecule does not contain sugars. The dissociation constant of the protein . sulfobromophthalein complex has been found to be 4. 10(-6) M, a value in agreement with that of high affinity binding sites described on isolated liver plasma membrane.

Animals↗