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Biomedical subjects

A Gérolami

Publications and source records attributed to A Gérolami.

At least 19 recordsLinked to original sources
PubMed2003

Retreatment with interferon and ribavirin vs interferon alone according to viraemia in interferon responder-relapser hepatitis C patients: a prospective multicentre randomized controlled study.

Low pretreatment viral load has consistently been shown to be an independent predictor of sustained response (SR) in patients with chronic hepatitis C infection. We assessed the efficacy of interferon (IFN) plus ribavirin vs IFN alone in low viraemic patients (<2 millions copies/mL) who had relapsed to a previous course of IFN and the efficacy of 24 vs 48 week combination therapy in high viraemic patients. Two hundred and ninety-seven patients were randomly assigned to one of the four regimens after stratification on pretreatment viral load. All patients received IFN-alpha2b (6 million units thrice weekly for 24 weeks and 3 million units thrice weekly for 24 weeks). Patients with low viraemia received either IFN-alpha2b alone for 48 weeks (R1: 42 patients) or IFN-alpha2b plus ribavirin (600 mg/day) for 24 weeks and IFN-alpha2b alone for the next 24 weeks (R2: 48 patients). Patients with high viral load received either IFN-alpha2b plus ribavirin for 24 weeks and then IFN-alpha2b alone for the next 24 weeks (R3: 104 patients) or IFN-alpha2b plus ribavirin for 48 weeks (R4: 103 patients). In low viraemic patients the rate of SR was 37.7% in group R1 and 59.6% in group R2 (P < 0.05). In high viraemic patients, the rate of SR was 44.7% in group R3 and 51.4% in group R4 (P: NS). Thirty-one patients discontinued treatment (10.4%) without difference regarding treatment regimen. In the regimen using ribavirin we found no difference in terms of SR between patients receiving a dose of ribavirin below 10.6 mg/kg/day (55%) or over 10.6 mg/kg/day (58%). Histological improvement occurred in 70.2% of patients regardless of the regimen. Logistic regression showed that genotype 2 and 3, Knodell score <6 and alanine aminotransferase pretreatment level >3 x upper limit of normal were significantly and independently correlated with SR. In low viraemic patients who relapsed to a previous IFN treatment, combination therapy using high-dose IFN and low-dose ribavirin is better than high-dose IFN alone. In high viraemic patients there was no benefit in increasing the duration of combination therapy from 24 to 48 weeks. In this study, it was found that low dose of ribavirin can be used safely and there is no effect of ribavirin dose on SR.

Adult↗
PubMed1997

Crohn's disease and gastrocnemius vasculitis: two new cases.

We report two cases of gastrocnemius muscle vasculitis revealing Crohn's disease. Gastrocnemius muscle biopsy evidenced a necrotizing vasculitis resembling panarteritis nodosa in one case; a nonnecrotizing vasculitis was found in the other case. Neither of the patients had systemic vasculitic involvement, and the muscle disease resembled calf muscle-located panarteritis nodosa. Our literature review shows five cases of calf-located myalgia occurring during Crohn's disease characterized by heterogenous histopathological findings including vasculitic and myositic lesions. Thus, faced with calf-located myalgia with vasculitis or myositis, a search for Crohn's disease is probably necessary to determine precisely the frequency and the etiopathogenic mechanisms of this association.

Adult↗
PubMed1992

Monensin action on the Golgi complex in perfused rat liver: evidence against bile salt vesicular transport.

Several studies suggest that bile salts are transported from the basolateral to the canalicular membrane of hepatocytes by a vesicular pathway, possibly in part via the Golgi complex. To test this hypothesis, the present study examined, in the perfused rat liver, the influence of the Na+ ionophore monensin on the biliary secretion of taurocholate and biliary lipids. The effects of the drug have been checked by the study of the ultrastructural modifications of the Golgi complex, secretion of horseradish peroxidase, and bile salt uptake. An infusion of monensin (1, 3, or 5 mumol/L) into the liver induced considerable swelling of the Golgi complex within 5 minutes. After a bolus injection of horseradish peroxidase during monensin infusion, the biliary secretion of the protein was delayed (1 mumol/L monensin) and markedly reduced (5 mumol/L monensin). Bile salt uptake was virtually unchanged except with 5 mumol/L monensin. This suggests that monensin has the same effects on the subcellular traffic in the perfused liver as in cultured cells. After a bolus injection of taurocholate (0.25, 5.0, or 8.5 mumol/100 g body wt) during monensin infusion, the pattern of biliary secretion of the bile salt was identical to that of controls. During continuous infusion of taurocholate, a 10-minute monensin infusion (1 or 3 mumol/L) had no effect on the biliary secretion of taurocholate and on the secretion of lecithin and cholesterol induced by taurocholate. High concentrations (5 mumol/L) or prolonged infusions (20 minutes) of monensin decreased the biliary secretion of bile salts but corresponded to a marked decrease of taurocholate uptake. In summary, the Na+ ionophore monensin altered the Golgi complex and the vesicular transport of horseradish peroxidase, whereas taurocholate biliary secretion was not influenced unless taurocholate biliary secretion was not influenced unless taurocholate uptake by the liver was markedly decreased. It may be concluded that taurocholate and biliary lipid secretion, under these conditions, does not depend essentially on pathways involving acidic transporting vesicles and particularly the trans-Golgi complex.

Animals↗
PubMed1990

pH regulation in human gallbladder bile: study in patients with and without gallstones.

Samples of gallbladder bile obtained from 25 controls and 34 patients with pigment (28 cases) or cholesterol (6 cases) gallstones were studied to establish whether disturbances in regulation of the biliary pH are likely to play a role in the pathogenesis of gallstones. Samples were assayed for pH, PCO2 and concentrations of sodium, bicarbonate and calcium (total and ionized). Saturation of bile in calcium carbonate was calculated. The main results of the study were as follows: (a) mean (+/- S.D.) PCO2 was significantly higher in gallbladder bile (6.72 +/- 0.36 kPa (in controls) and 7.63 +/- 0.29 kPa in patients) than in blood. This is consonant with previous results in animal species; it suggests that also in man a mucosal Na+ H+ antiport acidifies the gallbladder bile generating CO2 from biliary bicarbonate. (b) Biliary pH decreased when sodium concentration increased over a range of 140 to 280 mM. The pH decreased slightly when sodium increased from 140 to 200 mM and rapidly beyond this value; the rapid pH decrease in concentrated bile was associated with bicarbonate concentrations lower than 1 to 2 mM. The results showed that bicarbonate is the main buffer of gallbladder bile. (c) The pH decrease during bile concentration was similar in patients and controls. In both groups, fully concentrated bile was unsaturated in calcium carbonate. The results suggest that gallstone formation is not due to disturbances of biliary pH regulation. However, the normal concentration process that increases Ca++ concentration up to 4 mM and lowers pH values is likely to favor, in fully concentrated biles, the precipitation of calcium salts such as calcium bilirubinate.

Bicarbonates↗
PubMed1990

Effect of ethanol on hepatic energy metabolism and intracellular pH in chronically ethanol-treated rats. A 31P NMR study of normoxic or hypoxic perfused liver.

31P Nuclear magnetic resonance spectroscopy has been used to investigate the combined effect of 70 mM ethanol administration and hypoxia on the energetic metabolism and cytosolic pH of the perfused liver isolated from naive, fasted or chronically ethanol-treated rats. Ethanol-treatment or fasting induce a similar 25% reduction in ATP levels, and a differential enhancement of Pi levels to 130% and 225% of control values, respectively. In the naive rats, acute ethanol administration triggers profound variations in high-energy phosphorylated metabolite levels with, in particular, a 300% increase in phosphomonoesters, mostly due to sn-glycerol-3-phosphate (G3P) accumulation. A 4 min hypoxic period in the presence of ethanol induced a further accumulation of G3P. In the livers from chronically ethanol-treated rats, the G3P level remains low during acute ethanol administration, despite the presence of glycogen, indicating an attenuation of the ethanol-induced redox shift. The combination of 70 mM ethanol and hypoxia leads to an increased G3P level in the livers of chronically ethanol-treated rats which is consistent with a sustained alcohol dehydrogenase activity. The subsequent cytosolic acidosis is significantly less pronounced in the chronically ethanol-treated rats than in naive rats. These observations illustrate the adaptation of metabolic processes occurring in the livers of chronically ethanol-treated rats, which results in an increased resistance to acute ethanol exposure and hypoxic stress.

Adenosine Triphosphate↗
PubMed1989

The effects of monensin on the transport of horseradish peroxidase into intracellular lumina in cultured rat hepatocytes.

A kinetic study of horseradish peroxidase transport was carried out on short-term cultured adult rat hepatocytes. After 4 hr of plating, cells were preincubated with monensin (1 microM) for 1 hr before their incubation with horseradish peroxidase for different times. Monensin treatment resulted in the dilatation of the Golgi apparatus and caused the appearance of numerous intracellular lumina lined with microvilli in associated as well as isolated hepatocytes but did not modify newly formed bile canaliculi. The frequency of their appearance increased to 28% in cells pretreated with monensin compared to 2% in controls. Intracellular lumina membranes had the morphological features of apical membranes and were stained with horseradish peroxidase more frequently than those of newly formed bile canaliculi. This work therefore provides a model for studying bile secretion in cultured hepatocytes. Our results also suggest that the biliary transport of horseradish peroxidase does not involve the Golgi apparatus, since horseradish peroxidase was never observed in the Golgi stacks even after monensin treatment.

Animals↗
PubMed1988

Lipolytic activities of freshly isolated rat liver parenchymal cells.

By using a specific collagenase preparation preserving lipolytic enzymes, we could isolate intact rat liver cells with monoester lipase (MEL) and, for the first time, substantial amounts of endogenous neutral triester lipase (TEL) activities assayable as cell-bound enzymes. TEL and MEL activities were found exclusively in parenchymal cells. Virtually all TEL was located on plasma membrane from which it was rapidly released at 37 degrees C in the absence of any additive. MEL was distributed almost equally inside the cell and in the membrane, to which it was firmly attached. Infusion of heparin to the whole animal before liver exposure decreased by 80% the TEL content of parenchymal cells (a property typical of hepatic lipase) whilst MEL was unchanged. These results question the concept that heparin-releasable hepatic lipase acts at the surface of endothelial liver cells and further suggest that TEL and MEL refer to distinct catalytic entities.

Animals↗
PubMed1988

Effect of various bile salts on calcium concentration and calcium carbonate saturation of rat bile.

To establish whether the calcium-binding capacities of the bile salts play an essential role in their stimulatory effects on biliary calcium secretion, we compared (1) the effects of tauro- and glycoconjugates of ursodeoxycholate (TUDC-GUDC) and cholate (TC-GC) on biliary calcium in bile fistula rats, and (2) the in vitro calcium-binding capacities of mixed micelles containing the same bile salts. The increase of biliary calcium depended on the infused bile salt in the following order: GUDC greater than GC = TUDC greater than GC). The same order was obtained in vitro, so that there was a linear relationship between the slopes of the [Ca] vs. [bile salts] regression lines in vivo and the binding percentages of the four bile salts. Biliary ionized calcium concentration was almost independent of bile salt concentration. However, hepatic bile was supersaturated with calcium carbonate in the presence of the four bile salts. Our results suggest that biliary calcium concentration increases in relation to the calcium-binding capacity of the various bile acids so that ionized biliary calcium remains in equilibrium with plasma. As a result, bile saturation with calcium is almost completely independent of bile salt secretion.

Animals↗
PubMed1985

[Spontaneous portacaval anastomoses by veins of the falciform ligament of the liver in cirrhosis. Their ultrasonic exploration].

The aim of this work was to study the portacaval shunts described by Sappey in the falciform ligament of the liver in the cirrhotic patient. Twenty men and 8 women (mean age: 63 years) were studied by ultrasonography. Ascites was present in 20 patients. Venous anastomoses through the falciform ligament were visualized in 16 of the 28 patients. When present, they were usually multiple (1 to 4) with a diameter of about 10 mm. In 8 patients, a large communication with one of the main portal branches was seen. In the same patients, gastroesophageal shunts were always present but umbilical and splenorenal anastomoses were found only in 3 and in 4 patients respectively. This emphasizes the importance of such shunts which are in part intrahepatic. Ultrasonic exploration of these shunts should be routine in the evaluation of collateral circulation in cirrhosis.

Aged↗
PubMed1983

[Effect of glycodihydrofusidate, a structural analog of bile salts, on the hepatic transport of bromosulfophthalein in rats].

The interaction between bromosulfophthalein and glycodihydrofusidate in their transport by the liver were studied. In vitro, glycodihydrofusidate, a bile salt analogue, inhibited bromosulfophthalein uptake by isolated rat liver cells. This inhibition was similar to that previously described by adding sodium taurocholate to the medium; the inhibition was only partial and could no longer be detected at high bromosulfophthalein concentrations (20 microM). These results suggest that glycodihydrofusidate, like sodium taurocholate can compete with bromosulfophthalein for a common carrier in the liver cell membrane. In vivo, in the rat submitted to a saturating infusion of bromosulfophthalein, the addition of glycodihydrofusidate to the perfusate induced a 65 p. 100 decrease in the biliary excretion of bromosulfophthalein, a decrease in the water flow (47 p. 100) and a slight diminution in the bile salt output (14 p. 100). In experiments where glycodihydrofusidate-bromosulfophthalein interactions did not occur at the sinusoidal level, the biliary excretion of the dye was inhibited by glycodihydrofusidate. This suggests a common pathway for the two molecules. Our results are consistent with the existence of two different bromosulfophthalein carrier systems present at either pole of the hepatocyte. However only one is shared with bile salts and glycodihydrofusidate. This same hypothesis might account for many other experimental results as well.

Animals↗