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Yves Horsmans

Publications and source records attributed to Yves Horsmans.

44 records · Page 3Linked to original sources

Cryopreservation of rat precision-cut liver slices is associated with major metabolic stress and ionic perturbations.

BACKGROUND/AIMS: Cryopreserved precision-cut liver slices (PCLS) in culture exhibit a rapid decline in ATP level and anabolic processes by unknown mechanisms. The aim of this study is to elucidate the key events explaining the alterations occurring in cryopreserved PCLS. METHODS: Glucose metabolism, mitochondrial activities, ionic homeostasis and caspase-3 activity were assessed in fresh or cryopreserved (rapid freezing-thawing conditions) rat PCLS within the first hour of incubation in Williams' medium E at 37 degrees C. RESULTS: Despite a similar glycolytic activity under both conditions, only fresh PCLS were able to gradually recover their ATP and potassium content. Glycogen content dropped more rapidly in cryopreserved than in control PCLS. Only cryopreserved PCLS exhibited a decline in O2 consumption and a lower ATP/ADP ratio from 30 min of incubation with a loss of coupling of oxygen consumption to ATP synthesis and mitochondrial calcium transport after 1 hour of incubation. Caspase-3 activation was already present in cryopreserved PCLS after a few minutes of incubation. CONCLUSIONS: The lack of restoration of potassium/sodium exchange might be a primary event in the metabolic alterations occurring in cryopreserved PCLS after thawing, that contributes to further mitochondrial alterations, caspase activation and compromises ATP-dependent anabolic pathways.

Animals↗

Stable hepatitis C virus RNA detection by RT-PCR during four days storage.

BACKGROUND: Suboptimal specimen processing and storage conditions of samples which contain hepatitis C virus (HCV) RNA may result in a decline of HCV RNA concentration or false-negative results in the detection of HCV RNA in serum. We evaluated the stability of HCV RNA in serum and clotted blood samples stored at room temperature or at 4 degrees C for 4 days with the aim of optimizing the standard procedures of processing and storage of samples. METHODS: Blood from five HCV RNA positive patients was collected in tubes with and without separator gel, centrifuged 1 or 6 hours after collection. Samples were then left 6, 24, 48, 72 or 96 h at room temperature (21.5 - 25.4 degrees C) or at 4 degrees C before determining their HCV RNA level using the COBAS AMPLICOR HCV MONITOR Test, vs 2.0 (Roche Diagnostic Systems). RESULTS: The logarithm of the HCV RNA level measurements remained within a 0.3 value of the means for 4 days at both temperatures (room temperature or 4 degrees C). CONCLUSIONS: We conclude that blood samples may be collected and aliquoted within 6 h of collection and can be stored at 4 degrees C for 72 hours as proposed by the manufacturer without significant differences in measured HCV RNA level. Our results indicate that lapses in this scheme may still yield reliable results.

Adult↗

Limited lamivudine and long-term hepatitis B immunoglobulin immunoprophylaxis for prevention of hepatitis B recurrence after liver transplantation.

BACKGROUND: No consensus exists concerning dosage and duration of prophylactic hepatitis B immunoglobulin and lamivudine for prevention of hepatitis B recurrence after liver transplantation (LT). METHODS: Lamivudine was discontinued 12 months after LT, maintaining hepatitis B immunoglobulin prophylaxis in eight patients who received lamivudine treatment before LT. RESULTS: At LT, six patients were serum hepatitis B virus (HBV)-DNA negative, whereas two patients had low serum HBV-DNA levels. Hepatitis B surface (HBs) antigen and hepatitis B core antigen stained positively by immunohistochemistry in all hepatectomy specimens. All patients remained recurrence free during the 12 months on combination therapy with normal liver histological examination and negative HBs and HB core staining on biopsy specimens. No relapse occurred after lamivudine withdrawal during a median follow-up of 17.5 months (normal transaminases, negative serum HBs antigen, and HBV-DNA). CONCLUSIONS: Discontinuation of lamivudine 12 months after LT is feasible and safe even in patients with ongoing low viral replication at LT, providing adequate prophylaxis with hepatitis B immunoglobulins.

Adult↗

Steatosis is not sufficient to cause an impaired regenerative response after partial hepatectomy in rats.

BACKGROUND/AIMS: Fatty liver is known to be associated with increased mortality and morbidity after liver resection. The ability of fatty liver to regenerate after two-thirds partial hepatectomy was studied in three different models of steatosis in rats: obese Zucker rats, orotic acid-fed Wistar rats and Wistar rats fed a methionine-low, choline-deficient diet. METHODS: Liver regeneration was assessed 24 h after partial hepatectomy by bromodeoxyuridine incorporation (immunohistochemistry), proliferating cell nuclear antigen, cyclin E and cyclin-dependent kinase 2 protein expression (Western blot analysis) and cyclin-dependent kinase 2 activity (kinase assays using histone H1 as a substrate). RESULTS: No significant difference of proliferative response was found between orotic acid or methionine-low, choline-deficient diet-fed and control Wistar rats 24 h after partial hepatectomy. In contrast, hepatocyte proliferation in obese Zucker rats after partial hepatectomy was significantly reduced when compared with their lean controls. CONCLUSIONS: Steatosis per se does not impair liver regeneration. The reduced liver regeneration observed in obese Zucker rats may not be due to fatty infiltration itself but to other factors such as leptin receptor dysfunction.

Animal Feed↗

Watercress has no Importance for the elimination of ethanol by CYP2E1 inhibition.

Watercress, a cruciferous vegetable, is known to inhibit the metabolism of several CYP2E1 substrates such as paracetamol and chlorzoxazone. Since ethanol and its metabolite, acetaldehyde, are CYP2E1 substrates, the influence of watercress on ethanol and acetaldehyde was investigated in healthy human volunteers. According to a randomized cross-over design, ethanol and acetaldehyde pharmacokinetic parameters were determined in 9 persons at 3 occasions: without watercress and after watercress ingestion preceding ethanol consumption from 1 or 10.5 hr, respectively. Ethanol tmax occurred significantly later when watercress was ingested 1 hr before ethanol ingestion. Likewise, acetaldehyde Cmax was significantly higher whereas acetaldehyde AUCs were increased by watercress but not significantly. All other ethanol and acetaldehyde pharmacokinetic parameters were similar between the 3 treatments. In healthy volunteers, no major watercress effect was observed on ethanol clearance but a weak inhibiting effect on acetaldehyde metabolism is possible. Ethanol absorption is also delayed by single ingestion of watercress immediately preceding ethanol consumption.

Acetaldehyde↗

Dynamic computed tomography with low- and high-molecular-mass contrast agents to assess microvascular permeability modifications in a model of liver fibrosis.

Interstitial collagen formation and transformation of the fenestrated hepatic sinusoids into continuous capillaries are major ultrastructural changes that occur in liver cirrhosis and fibrosis. These modifications lead to progressive restriction of blood-liver exchanges. The purpose of our study was to evaluate the permeability changes in a model of hepatic fibrosis by using dynamic computed tomography (CT) enhanced with contrast agents of different molecular masses. Dynamic single-section CT of the liver was performed after intravenous bolus administration of a low-molecular-mass contrast agent (iobitridol) and an experimental high-molecular-mass agent (P840) in normal control rabbits and in rabbits with hepatic fibrosis. Hepatic, aortic and portal venous time-density curves were fitted with a dual-input one-compartmental model to calculate the hepatic mean transit time and distribution volume of the contrast agents. In the rabbits with liver fibrosis, the mean transit time of the high-molecular-mass agent was shorter than that of the low-molecular-mass agent (10.0+/-1.8 s and 12.0+/-1.2 s respectively; P<0.05). The distribution volume accessible to the high-molecular-mass agent was also smaller (22.2+/-4.8% compared with 32.0+/-6.7%; P<0.01). In the normal rabbits, the mean transit times of the high- and low-molecular-mass agents did not differ significantly, and nor did their distribution volumes. Our results demonstrate decreased sinusoidal permeability for the high-molecular-mass agent P840 in a model of hepatic fibrosis. Non-invasive assessment of permeability changes in liver fibrosis can be performed with dynamic CT and contrast agents of different molecular masses.

Animals↗