PubMed Health⌕ Search

Biomedical subjects

C Tiribelli

Publications and source records attributed to C Tiribelli.

At least 91 records · Page 5Linked to original sources
PubMed1992

Hepatitis C virus infection, HBsAg carrier state and hepatocellular carcinoma: relative risk and population attributable risk from a case-control study in Italy.

In 1990, a case-control study was conducted in Italy to investigate the possible association between HCV infection and hepatocellular carcinoma (HCC). Serum samples from 65 subjects with newly diagnosed hepatocellular carcinoma and 99 hospital control subjects were tested for the presence of anti-HCV by second-generation ELISA test; positive sera were assayed by RIBA anti-HCV second-generation test. In addition, samples were tested for hepatitis B surface antigen (HBsAg), antibodies to the hepatitis B core antigen (anti-HBc), and antibodies to HBsAg (anti-HBs). The presence of HCV and/or HBsAg serologic markers was significantly associated with hepatocellular carcinoma risk: the relative risk (RR) of HCC was 21.3 (95% CI = 8.8-51.5) for anti-HCV positivity in the absence of HBsAg; the relative risk of HCC was 13.3 (95% CI = 5.5-32.2) for the presence of HBsAg in the absence of anti-HCV. A higher risk (77.0) was observed when both markers were present. These findings indicate that HCV and HBsAg are independent risk factors for HCC. The results of multivariate analysis showed that the adjusted RR linking anti-HCV and HCC was 26.9 (95% CI = 9.9-72.5), the adjusted RR linking HBsAg and HCC was 11.4 (95% CI = 3.1-41.4), whereas no association (RR 1.5; 95% CI = 0.6-3.6) was found to link HCC with anti-HBc and/or anti-HBs positivity. Through the computation of population attributable risk we estimate that 25% of HCC cases occurring in Italy could be attributed to anti-HCV positivity alone and 20% to HBsAg carrier state alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The preS1 domain of hepatitis B virus and IgA cross-react in their binding to the hepatocyte surface.

Using a solid-phase assay we have demonstrated specific competition between the preS1 sequence of hepatitis B virus and human IgA in their binding to isolated normal human liver plasma membranes, suggesting molecular mimicry. Monoclonal and polyclonal antibodies raised against virus and IgA epitopes were used to detect and map immunological cross-reactivity to the virus sequence involved in liver cell binding. These findings suggest the existence of a common receptor or of closely related receptors for the attachment of HBV and IgA to human liver cells.

Amino Acid Sequence↗
PubMed1992

Carrier-mediated transport of tetrabromosulfonephthalein by rat liver plasma membrane vesicles.

To investigate the molecular requirements and mechanisms for the hepatic uptake of phthaleins, the transport of tetrabromosulfonephthalein (TBS) was investigated in basolateral rat liver plasma membrane vesicles. TBS uptake was electrogenic as greatly accelerated by the creation of a positive-inside membrane potential by the addition of valinomycin in the presence of an inwardly directed potassium gradient. No effect was observed when the ionophore was added in the presence of a sodium gradient. The transport occurred into an osmotic-sensitive space and was saturable with an apparent Michaelis constant of 5.32 +/- 0.56 microM and a maximal velocity of 9.23 +/- 0.25 nmol.s-1.mg protein-1 (mean +/- SD, n = 3 experiments). TBS uptake was directly related to the extra-vesicular pH, indicating the deprotonated quinoid negative-charged form of the dye as the transported species. In contrast, TBS uptake was inversely related to the intravesicular pH, suggesting that protonation inside the vesicles may act as an efficient trap in transport process. Addition of polyclonal monospecific anti-bilitranslocase antibody to liver vesicles specifically inhibited TBS uptake rate (3.27 +/- 0.17 vs. 5.82 +/- 0.61 nmol.s-1.mg protein-1, n = 3, P less than 0.001). These data indicate that TBS is electrogenically transported across the liver cell plasma membrane by bilitranslocase. They also indicate that the presence of a negative charged group on the benzenic ring of the ligand is important in accounting for the transport.

Absorption↗
PubMed1992

[Symptomatic effect of epomediol in patients with cholestasis of pregnancy].

Epomediol is a terpenoid that prevents and reverses cholestasis induced by ethinylestradiol in the rat, apparently by improving liver cell membrane fluidity. Assuming that the pathogenesis of intrahepatic cholestasis of pregnancy (ICP) is related with increased estrogen levels, we studied the effects of epomediol in this disease. Patients hospitalized due to ICP received epomediol 900 mg/day (n = 7), or 1,200 mg/day (n = 4) orally, during 15 days. Biochemical parameters of liver dysfunction (serum bilirubin, bile salts, aminotransferase, alkaline phosphatases) were not modified during nor after epomediol administration. The severity of pruritus was significantly reduced in comparison to pretreatment status, with both doses of epomediol. A greater amelioration of pruritus was observed in patients treated with epomediol 1,200 mg/day than in patients who received 900 mg/day (to 20.7 +/- 6.2, as percent of pre-treatment severity score, versus 48.8 +/- 7.5 respectively; p < 0.05). After epomediol administration was stopped, pruritus relapsed in 6 patients; 3 of them had received the higher drug dose. After delivery, pruritus vanished and liver function tests returned to normal, in all patients. No adverse effects attributable to the drug were observed in the mothers or in their babies. The beneficial effect of epomediol on pruritus in patients with ICP appeared greater in this study than that observed recently in similar patients who received a placebo.

Bile Acids and Salts↗
PubMed1990

Modulation of resting membrane potential of human and rat hepatocytes by sex steroids.

The effect of sex steroids on the regulation of hepatocyte resting membrane potential (Em) was investigated. In adult rat liver snips, Em was significantly lower in males than females. In prepubertal animals no sex related difference was observed and the Em was comparable to that of adult females. Exposure of the human liver cell line, HepG2 cells, to 10 microM testosterone resulted in a significant hyperpolarization. These data indicate that the more negative Em found in male animals is specifically due to the influence of testosterone. In addition, they also suggest that sex hormone regulation of Em is maintained by HepG2 cells. This cell line may prove to be a good model for the study of liver cell function.

Animals↗
PubMed1990

Abnormal hepatic uptake of low doses of sulfobromophthalein in Gilbert's syndrome: the role of reduced affinity of the plasma membrane carrier of organic anions.

The plasma disappearance rate of sulfobromophthalein (VBSP; mumol/kg/min) was measured in 15 Gilbert's syndrome patients and 12 control subjects after intravenous injection of two different doses (0.59 and 5.90 mumol/kg) of the dye. Plasma disappearance rate was significantly reduced in Gilbert's syndrome patients after administration of 0.59 mumol sulfobromophthalein/kg (0.119 +/- 0.016 vs. 0.146 +/- 0.018 mumol/kg/min; mean +/- S.D.; p less than 0.001), whereas no difference was found with the higher dose (0.754 +/- 0.040 vs. 0.767 +/- 0.072 mumol/kg/min). Significant reduction was also found after administration to four Gilbert's syndrome patients and four control subjects of 0.29 and 2.95 mumol sulfobromophthalein (0.060 +/- 0.005 mumol/kg/min vs. 0.077 +/- 0.07 mumol/kg/min and 0.480 +/- 0.012 mumol/kg/min vs. 0.591 +/- 0.015 mumol/kg/min, respectively; p less than 0.01). Competition studies with combined administration of sulfobromophthalein (0.59 mumol/kg) and different doses of rifamycin SV (0.59, 1.47 and 2.95 mumol/kg) showed a significant (p less than 0.001) reduction in plasma disappearance rate in Gilbert's syndrome patients but not in controls. The rifamycin SV dose at which a 50% inhibition in plasma disappearance rate was observed was 0.8 mumol/kg. The apparent affinity (Km) of the hepatic transport was higher in Gilbert's syndrome patients than in control subjects (3.61 +/- 0.37 mumol sulfobromophthalein/kg vs. 2.76 +/- 0.29 mumol sulfobromophthalein/kg, mean +/- S.D.; p less than 0.01), whereas no difference was found in Vmax (0.95 +/- 0.11 mumol sulfobromophthalein/kg vs. 0.93 +/- 0.10 mumol sulfobromophthalein/kg/min, mean +/- S.D.; N.S.).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Detection of hepatitis B virus transcripts in patients with chronic liver disease.

Hepatitis B virus (HBV) transcription was studied by Northern blot analysis on total cellular RNA purified from liver biopsies in 70 patients with chronic liver disease (24 HBsAg positive, 15 antiHBs and/or antiHBc positive, 31 HBV negative). No transcripts were found in the HBV negative and in the antiHBs and/or antiHBc positive patients. In the others, three major RNA species were identified: i. a 3.5 kb transcript corresponding to the RNA pregenome; ii. 2.4-2.1 kb transcript corresponding to the s and preS1 gene RNA; iii. lower molecular weight species. All three forms were present simultaneously only in patients with active viral replication, with a strict relation between the presence of the 3.5 kb RNA in the liver and serum HBV-DNA. In conclusion, Northern blot analysis can easily be performed to study viral replication and it can contribute to a better understanding of the molecular processes underlying HBV infection and leading to liver disease in man.

Biopsy↗
PubMed1990

Bilitranslocase localization and function in basolateral plasma membrane of renal proximal tubule in rat.

Bilirubin and phthalein dyes are taken up by the liver via a carrier-mediated mechanism operated at least in part by bilitranslocase (BTL). Because they also undergo renal transport, the presence and function of BTL was investigated in rat renal tubular plasma membrane vesicles. Transport of sulfobromophthalein (BSP) was enriched in basolateral domain of plasma membrane and followed the distribution pattern of Na(+)-K(+)-ATPase but not of gamma-glutamyltransferase. BSP uptake was inhibited by addition of monospecific antibodies raised against hepatic BTL. As in liver vesicles, BSP transport was electrogenic, being greatly accelerated by addition of valinomycin in presence of an inwardly directed K+ gradient. Apparent Km of BSP transport was 17 +/- 2 microM (n = 3 expts), one order of magnitude higher than that measured in liver; however, Vmax was similar to that described in liver vesicles (429 +/- 18 nmol BSP.mg protein-1.min-1, n = 3 expts). Competitive inhibition was observed with both unconjugated bilirubin (Ki, 2.9 +/- 0.2 microM) and rifamycin SV (Ki, 76 +/- 10 microM), known competitors for hepatic BTL-mediated transport of BSP. Immunoblotting studies with anti-BTL monospecific antibodies revealed presence of a single positive band only in basolateral-enriched membrane fraction; its apparent molecular mass was 37 kDa, virtually identical to that of hepatic protein. Immunohistochemistry confined presence of BTL to renal proximal tubules (RPT) We conclude that BTL is present in basolateral plasma membrane of RPT cells. Lower affinity of renal, compared with hepatic protein, for substrates might explain the marginal role of kidney in plasma clearance of bilirubin and cholephilic dyes.

Animals↗
PubMed1990

Jaundice and cholestasis: past, present and future ideas.

The mechanisms of the bilirubin formation, transport, conjugation and biliary excretion have been extensively studied in the recent past, thereby allowing a more complete and rational approach to the old, but still somehow unknown symptom of jaundice and cholestasis. Based on the most recent physiologic and biochemical data, jaundice and cholestasis have been revisited during and international meeting. This report summarizes what has been established in the field but, most importantly highlights what is still unknown and requires further investigation.

Cholestasis↗
PubMed1989

Reversal of ethinylestradiol-induced cholestasis by epomediol in rat. The role of liver plasma-membrane fluidity.

Epomediol (EPO) is a synthetic terpenoid compound shown to be active in increasing bile flow and some enzymatic activities of liver plasma membranes in the rat. The possible effect of EPO treatment in the ethinyl-estradiol (EE) induced cholestasis in the rat was investigated by measuring the hepatic transport of sulfobromophthalein (BSP) (plasma clearance and biliary secretion) and bile flow. Liver plasma membrane fluidity was also determined by the steady state fluorescence polarization (P) of diphenylhexatriene (DPH). EE administration (5 mg/kg s.c. for 5 days) was followed by a significant, comparable reduction (P less than 0.001) in BSP plasma clearance and biliary excretion and in bile flow. Intraperitoneal administration of EPO (100 mg/kg) to EE-treated rats restored both parameters of BSP transport, as well as bile flow, to control values. Liver plasma membrane fluidity was markedly (P less than 0.01) decreased by EE administration with a concomitant reduction (P less than 0.01) in Na+/K+-ATPase activity. EPO administration significantly increased membrane fluidity to values higher either to cholestatic (P less than 0.05) or control (P less than 0.05) animals. On the contrary, EPO did not influence Na+/K+-ATPase activity in either EE-treated or control animals. These data indicate that EPO fully reverses the impairments of BSP transport and bile flow induced by EE, possibly by reversing the decrease in liver plasma membrane fluidity induced by the synthetic estrogen. On the contrary, the EE-mediated decrease in Na+/K+-ATPase activity was not reversed by EPO.

Animals↗
PubMed1989

Bilitranslocase is the protein responsible for the electrogenic movement of sulfobromophthalein in plasma membrane vesicles from rat liver: immunochemical evidence using mono- and poly-clonal antibodies.

Monoclonal antibodies raised against bilitranslocase, may display either inhibitory or enhancing activity on the electrogenic transport of sulfobromophthalein, evoked in rat liver plasma-membrane vesicles by the addition of valinomycin in the presence of K+. In both cases, the target protein is identified with a 37 kDa band in SDS-mercaptoethanol gel electrophoresis of solubilized membranes. The electrophoretically homogeneous protein isolated by ion-exchange chromatography, corresponds in all respects to the 37 kDa protein band of bilitranslocase, obtained in the past by different techniques. Using this protein as antigen, a polyclonal monospecific antibody preparation has been obtained. As expected, the antibody preparation inhibits the electrogenic movement of sulfobromophthalein in plasma membrane vesicles from rat liver. It is concluded that the 37 kDa protein of bilitranslocase is at least a necessary component of the transport system involved in the sulfobromophthalein movement in plasma membrane.

Animals↗
PubMed1989

Prevalence of hepatocellular carcinoma and relation to cirrhosis: comparison of two different cities of the world--Trieste, Italy, and Chiba, Japan.

A comparative, descriptive study on the prevalence of hepatocellular carcinoma either associated or not with cirrhosis was undertaken between the cities of Trieste, Italy, and Chiba, Japan. Data were derived from 12,340 and 2,052 autopsies consecutively performed in Trieste and Chiba during 1980 to 1984 and 1975 to 1985, respectively. During these years, more than 70% of all deaths were studied by autopsy in Trieste. Clinical cases of hepatocellular carcinoma admitted to the Chiba University Hospital were also analyzed to correct for the bias induced by the relatively small number of autopsies in Chiba. Serum hepatitis B surface antigen was more frequent in Chiba, whereas alcohol intake was greater in Trieste. From the comparison of the data, we conclude: (i) hepatocellular carcinoma was associated with cirrhosis in the large majority of the cases both in Trieste (87%) and Chiba (81%); (ii) in both sexes, the average age of hepatocellular carcinoma patients was significantly older (p less than 0.005) in Trieste than in Chiba; (iii) in the autopsy series, cirrhosis was more frequent in Trieste (9.7%) than in Chiba (1.5%); (iv) in Chiba, hepatocellular carcinoma was more frequent than cirrhosis not complicated by hepatocellular carcinoma (6.9 vs. 1.5%) at necroscopy, and (v) the age-standardized rate of hepatocellular carcinoma was significantly (p less than 0.01) higher in Trieste than in Chiba. These geographical differences might be related to the different type of cirrhosis observed in Trieste (alcoholic) and Chiba (postnecrotic).

Adult↗
PubMed1989

Concomitant primary hemochromatosis and beta-thalassemia trait: iron depletion by erythrocytapheresis and desferrioxamine.

Six men and one woman with mild anemia due to beta-thalassemia trait and major iron overload attributable to concomitant primary hemochromatosis were treated by erythrocytapheresis to remove iron, combined with subcutaneous desferrioxamine in the four cases with greater iron load. Depletion was achieved by iron removal of 4.5-15.1 g after 9-24 months' treatment. No side effects were observed, suggesting that such a regimen is effective and safe in this particular subgroup of hemochromatotics.

Adult↗