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Biomedical subjects

P Sogni

Publications and source records attributed to P Sogni.

At least 19 recordsLinked to original sources
PubMed2006

Low density lipoprotein receptor transcripts correlates with liver hepatitis C virus RNA in patients with alcohol consumption.

Alcohol consumption has a major impact on the natural history of chronic hepatitis C virus (HCV) infection, although the underlying mechanisms are still debated. We designed a clinical study to evaluate the impact of alcohol abuse on both viral load and expression of low-density lipoprotein receptor (LDLR) and CD81 expression. Thirty-eight consecutive HCV-infected patients were enrolled. Group 1 (n = 18), < or =10 g alcohol/day, group 2 (n = 8), < or =30 g alcohol/day, group 3 (n = 12), >or =30 g alcohol/day. Receptors expression was measured by flow cytometry analysis in peripheral blood mononuclear cells (PBMC) and by specific real-time retrotranscription polymerase chain reaction (RT-PCR) in the liver. Serum viral load was evaluated by quantification of both HCV genomic RNA and total core antigen. The hepatic viral load was assessed by real-time RT-PCR. Serum HCV-RNA and total core antigen were significantly correlated, and were higher, albeit not significantly, in group 3 than in group 1. Alcohol consumption had no effect on expression of HCV putative receptors in PBMC, except for CD81, which was upregulated on monocytes in group 2. In the liver, viral load and levels of LDLR transcripts were significantly higher in group 3 than in group 1. Remarkably, a significant positive correlation was found between LDLR transcripts and HCV-RNA (r2 = 0.83, P < 10(-3)). Finally, in vitro experiments suggested that the effect of ethanol on LDLR expression was indirectly mediated by both tumour necrosis factor-alpha and interleukin-1beta. In conclusion, this study is the first to support a role for LDLR in the natural infection by HCV in man.

Adult↗
PubMed2005

[Management of cirrhosis complications in HIV patients coinfected with hepatitis B or C virus].

Cirrhosis is a serious complication of viral hepatitis, and its incidence is increasing in HIV patients coinfected with HCV or HBV as they live longer, thanks to effective antiretroviral treatment (Haart). HIV coinfection accelerates the progression of fibrosis in hepatitis. To implement preventive measures, prompt diagnosis of cirrhosis is important, either by liver biopsy or the noninvasive tests for fibrosis now under wide study (FibroTest, FibroScan, etc.). Afterwards, assessment of the severity of cirrhosis and screening for complications are both necessary: testing for liver failure (Child-Pugh and MELD scores), portal hypertension (upper gastrointestinal endoscopy), and hepatocellular carcinoma (ultrasound and alpha fetoprotein assay). Careful consideration of drug prescriptions and possible interactions is essential. Specific treatment for hepatitis B or C virus is possible at this stage of cirrhosis, although more difficult, especially for HCV (results influenced by genotype, additional risk of complications by lactic acidosis or hepatic decompensation). Management of the complications of portal hypertension must be planned, as for those without HIV infection. Treatment of hepatocellular carcinoma is still disappointing, and liver transplantation, although possible in these patients, must be evaluated.

Antiviral Agents↗
PubMed2005

Changing of hepatitis C virus genotype patterns in France at the beginning of the third millenium: The GEMHEP GenoCII Study.

This cross-sectional study aimed to investigate, during a short period between 2000 and 2001, in a large population of patients with chronic hepatitis C, the epidemiological characteristics of hepatitis C virus (HCV) genotypes in France. Data from 26 referral centres, corresponding to 1769 patients with chronic hepatitis C were collected consecutively during a 6-month period. HCV genotyping in the 5'-non-coding region (NCR) was performed in each center using the line probe assay (LiPA, in 63% of cases), sequencing (25%) or primer-specific polymerase chain reaction (PCR) (12%). HCV genotypes 1a, 1b, 2, 3, 4, 5, non-subtyped 1 and mixed infection were found in 18, 27, 9, 21, 9, 3, 11 and 1% of our population, respectively. HCV genotype distribution was associated with gender, age, source and duration of infection, alanine aminotransferase (ALT) levels, cirrhosis, alcohol consumption, hepatitis B virus (HBV) and human immunodeficiency virus (HIV) coinfection. In multivariate analysis, only the source of infection was the independent factor significantly associated with genotype (P = 0.0001). In conclusion, this study shows a changing pattern of HCV genotypes in France, with i.v. drug abuse as the major risk factor, an increase of genotype 4, and to a lesser extent 1a and 5, and a decrease of genotypes 1b and 2. The modification of the HCV genotype pattern in France in the next 10 years may require new therapeutic strategies, and further survey studies.

Adult↗
PubMed2004

Response to antiviral treatment in hepatitis C virus-associated marginal zone lymphomas.

A link between chronic hepatitis C virus (HCV) infection and low-grade B-cell lymphomas has been suggested by epidemiological studies. Marginal zone lymphomas (MZLs) including splenic lymphomas with villous lymphocytes are among the most frequently reported subgroups in the setting of chronic HCV infection. In this study, we examined the effect of antiviral treatment in eight patients with HCV-associated MZL. We found that five out of eight patients have responded to interferon alpha and ribavirin. In some cases, hematologic responses were correlated to virologic responses. In addition, we report a case of large granular lymphocyte leukemia occurring in association with MZL and HCV, and responding to interferon and ribavirin. We suggest that there is an etiologic link between HCV and antigen-driven lymphoproliferative disorders.

Adult↗
PubMed2004

Tezosentan, an endothelin receptor antagonist, limits liver injury in endotoxin challenged cirrhotic rats.

BACKGROUND/AIMS: Lipopolysaccharide (LPS) induces liver injury which is associated with upregulated endothelin (ET)-1 production. The aim of this study was to investigate the effects of tezosentan, a non-selective ETA and ETB receptor antagonist, in LPS challenged rats with cirrhosis. METHODS: Rats with cirrhosis received LPS and then tezosentan or placebo one hour later. Four hours after LPS administration, rats were killed to measure serum transaminase activity and plasma tumour necrosis factor alpha (TNF-alpha) levels. Hepatic inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), a marker of neutrophil infiltration, and cyclooxygenase (COX)-2 expression were also measured. RESULTS: LPS administration significantly decreased arterial pressure and significantly increased plasma endothelin levels. Following LPS and tezosentan administration, serum aspartate aminotransferase and alanine aminotransferase activities were similar to those in the control group while they were increased by more than 700% with LPS alone. Plasma TNF-alpha levels were significantly lower in rats receiving LPS and tezosentan (182 (38) pg/ml) compared with those receiving LPS alone (821 (212) pg/ml). Tezosentan significantly decreased hepatic MPO activity and hepatic neutrophils but had no effect on LPS induced iNOS or COX-2. Survival rate was significantly higher in rats receiving LPS plus tezosentan (80%) than in rats receiving LPS alone (50%). CONCLUSION: In LPS challenged cirrhotic rats, tezosentan administration prevents LPS induced liver injury by decreasing intrahepatic neutrophil infiltration. In addition, tezosentan increases survival in these rats.

Animals↗
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↗
PubMed2003

Reinforced interferon alpha-2b and ribavirin is more effective than standard combination therapy in the retreatment of chronic hepatitis C previously nonresponsive to interferon: a randomized trial.

Interferon-alpha (IFN) monotherapy results in sustained virological clearance in a minority of patients with chronic hepatitis C. The aim of this study was to assess the effect of a reinforced regimen combining ribavirin and high-dose IFN for 48 weeks compared with a nonreinforced regimen combining a standard IFN regimen and ribavirin for 24 weeks in nonresponders with chronic hepatitis C. A total of 231 patients with chronic hepatitis C and previous nonresponse to IFN monotherapy were randomized. The reinforced group (n = 114) received IFN-2b 6 million units (MU) thrice weekly (TIW) and ribavirin for 48 weeks, and the nonreinforced group (n = 117) received IFN-2b 3 MU TIW and ribavirin for 24 weeks. The main outcome measure was a sustained virological response, defined as negative serum hepatitis C virus (HCV)-RNA 24 weeks following the end of treatment. This endpoint was determined in 98 patients of the reinforced group and 105 patients of the nonreinforced group. At the end of follow-up, a sustained virological response was observed in 29 of the 98 patients (29.6%) in the reinforced group vs 16 of the 105 patients (15.2%) in the nonreinforced group (P = 0.014). In multivariate analysis, factors associated with a sustained virological response were treated with a reinforced regimen [odds ratio (OR) 2.9; P = 0.06] and genotype 2 or 3 (OR 8.8; P < 0.0002). A total of 160 patients had paired biopsies before and after treatment. Histological activity improvement was observed in 32 of 80 patients (40%) and fibrosis worsening in 26 of 80 patients (33%) in the reinforced group vs 13 of 80 (16%) and 19 of 80 (24%) in the nonreinforced group (P = 0.30 and 0.20, respectively). Hence in nonresponders, a high-dose 48-week regimen of IFN and ribavirin combination was more effective than a regimen with interferon at lower dose and ribavirin for 24 weeks only.

Adolescent↗
PubMed2001

Aortic hyporeactivity to norepinephrine induced by lipopolysaccharide in cirrhotic rats: beneficial effects of a non-steroidal anti-inflammatory drug coupled with a nitric oxide donor.

BACKGROUND AND AIMS: Cirrhosis is associated with a hyperdynamic syndrome and arterial vasodilation that is related to nitric oxide (NO) synthase 3 overactivity. Septic shock is frequently associated with cirrhosis and with a vascular induction of NO synthase 2. The aims of this study were to compare the effects of lipopolysaccharide (LPS) in normal and cirrhotic rats, and to test the effects of a nonsteroidal anti-inflammatory drug (NSAID) coupled with a (NO) donor. METHODS: Cirrhotic rats received NO-flurbiprofen, flurbiprofen or vehicle followed by LPS or placebo 15 min later. The heart rate and mean arterial pressure of rats were monitered for 5 h. Thoracic aortic rings were removed and contracted with the use of norepinephrine. Nitric oxide synthase activity was measured in the aorta and stomach of cirrhotic rats. RESULTS: Arterial pressure decreased in cirrhotic rats in the vehicle/LPS and flurbiprofen/LPS groups. After LPS administration, the heart rate of rats increased in all groups. In the aortic rings, LPS induced hyporeactivity to norepinephrine in all groups except the NO-flurbiprofen group. This hyporeactivity was abolished after preincubation with Nw-nitro-L-arginine (L-NNA). Nw-nitro-L-arginine had no effect on norepinephrine-induced vasoconstriction in the NO-flurbiprofen/LPS group. Nitric oxide synthase 2 activity in the stomach and aorta of cirrhotic rats was increased in each group except in the NO-flurbiprofen group after LPS administration. Pretreatment with NO NSAID prevented aortic hyporeactivity to norepinephrine in cirrhotic rats treated with LPS as it probably inhibited the NO synthase 2 induction. CONCLUSIONS: These findings suggest that NO-flurbiprofen has a beneficial hemodynamic effect in cirrhotic rats and may help to prevent LPS aortic hyporeactivity.

Analysis of Variance↗
PubMed2001

Hemodynamic, metabolic and hormonal responses to oral glibenclamide in patients with cirrhosis receiving glucose.

BACKGROUND: In patients with cirrhosis, glucose may induce splanchnic and renal vasodilation. Since the antidiabetic sulfonylurea glibenclamide is known to induce splanchnic and renal vasoconstriction in portal hypertensive animals, this drug may inhibit glucose-induced hemodynamic responses in patients with cirrhosis. The aim of the present study was to investigate, in patients with cirrhosis, the short-term effects of glibenclamide on hemodynamic and humoral responses to glucose. METHODS: Patients were randomly assigned to receive either glibenclamide (5-mg tablet) or a placebo. All patients received an infusion of 10% glucose (62.5 ml/h for 12 h) that was started at the same time as glibenclamide or placebo administration. Studies were performed prior to and 90 min after glibenclamide or placebo. RESULTS: Glibenclamide (i.e. glibenclamide plus glucose) significantly increased plasma insulin concentrations and glycemia while placebo (i.e. glucose alone) significantly increased glycemia but did not change plasma insulin levels. Glibenclamide did not significantly change the hepatic venous pressure gradient while this value was significantly increased following glucose alone. Glibenclamide did not significantly change renal blood flow and glomerular filtration rate while glucose alone significantly increased renal blood flow without affecting the glomerular filtration rate. Glibenclamide significantly decreased cardiac index while glucose alone did not change this value. CONCLUSIONS: In patients with cirrhosis receiving glucose, glibenclamide blunted glucose-induced splanchnic and renal vasodilation. In addition, glibenclamide per se induced a decrease in cardiac index. These findings should be taken into account when glibenclamide is administered to patients with cirrhosis and type 2 diabetes.

Administration, Oral↗
PubMed2001

Relationships between haemodynamic alterations and the development of ascites or refractory ascites in patients with cirrhosis.

OBJECTIVE: In patients with cirrhosis, the relationships between haemodynamic alterations and the development of ascites or the occurrence of refractory ascites are unknown. The aim of the present study was to compare haemodynamic measurements obtained in patients with non-refractory ascites to haemodynamic measurements obtained in patients without ascites and in patients with refractory ascites. METHODS: A cohort of 121 patients was prospectively studied, of whom 29 patients did not have ascites, 45 had non-refractory ascites and 47 had refractory ascites. Splanchnic, renal and systemic haemodynamics were measured in all patients. RESULTS: The hepatic venous pressure gradient was significantly higher in patients with non-refractory ascites than in patients without ascites (18.5 +/- 0.8 mmHg versus 15.8 +/- 0.7 mmHg). Renal and systemic haemodynamics did not significantly differ between patients with non-refractory ascites and patients without ascites. The glomerular filtration rate and renal blood flow were significantly lower in patients with refractory ascites than in patients with non-refractory ascites (77 +/- 4 versus 107 +/- 5 ml/min and 867 +/- 62 versus 1,008 +/- 68 ml/min, respectively). Splanchnic and systemic haemodynamics did not significantly differ between patients with refractory ascites and patients with non-refractory ascites. CONCLUSIONS: In patients with cirrhosis, an increase in portal hypertension was the sole haemodynamic alteration related to the development of ascites. Renal vasoconstriction (and subsequent renal hypoperfusion and hypofiltration) was the only haemodynamic alteration related to the occurrence of refractory ascites. The development of ascites or refractory ascites was not associated with any alteration in systemic haemodynamics.

Aldosterone↗
PubMed2000

The role of nitric oxide in the reduction of protein kinase C-induced contractile response in aortae from rats with portal hypertension.

BACKGROUND/AIMS: Protein kinase C plays a role in the regulation of vascular cell contraction but its activity may be reduced by nitric oxide. In portal hypertension, the exact mechanism by which nitric oxide induces vascular hyporeactivity to vasoconstrictors is unclear. The aim of this study was to investigate the role of the interaction of nitric oxide and protein kinase C in the vascular reactivity in isolated aortae from portal vein-stenosed rats. METHODS/RESULTS: The contractile response to phorbol 12,13-dibutyrate, a protein kinase C activator, was significantly reduced in portal vein-stenosed aortae compared to sham-operated aortae. Preincubation with N-nitro-L-arginine or endothelium removal enhanced the response to phorbol 12,13-dibutyrate. The hyporesponsiveness to phorbol 12,13-dibutyrate in portal vein-stenosed rat aortae was only corrected after endothelium removal. The time course of contractions induced by phorbol 12,13-dibutyrate showed that the contraction was maintained for 2 h in sham-operated aortae and decreased to baseline in portal vein-stenosed rat aortae. This decrease was inhibited by N-nitro-L-arginine preincubation or endothelium removal. Protein kinase C downregulation caused a more marked reduction of phenylephrine-induced contraction in portal vein-stenosed aortae than in sham-operated aortae. The time course of total nitric oxide synthase activity in the presence of phorbol 12,13-dibutyrate showed a decrease in nitric oxide synthase activity after 30 min in both groups. Nitric oxide synthase activity remained stable for 120 min in sham-operated aortae but returned to basal level in portal vein-stenosed aortae. CONCLUSIONS: Hyporeactivity to vasoconstrictors in portal vein-stenosed rat aortae may be due, in part, to a decrease in protein kinase C activation caused by nitric oxide overproduction.

Animals↗
PubMed2000

Effects of lipopolysaccharide on TNF-alpha production, hepatic NOS2 activity, and hepatic toxicity in rats with cirrhosis.

BACKGROUND/AIMS: Septic shock results in high mortality in patients with cirrhosis. Nitric oxide synthase 2 (NOS2) is induced by bacterial lipopolysaccharides (LPS) and plays a major role in the inflammatory response to bacterial infections. Little is known about the regulation of NOS2 in cirrhosis under septic conditions. Thus, the aim of this study was to determine tissue NOS2 activity, serum nitrate and tumor necrosis factor (TNF-alpha) levels and hepatic toxicity in cirrhotic rats after LPS administration. METHODS: Serum nitrates, TNF-alpha and transaminases were determined after LPS-administration in rats with secondary biliary cirrhosis and in sham-operated rats. Liver, lung, aortic and peritoneal macrophage NOS2 activities were determined by converting L[14C] arginine into L[14C] citrulline in a calcium free medium. Nitrate and TNF-alpha production were determined in a culture medium of peritoneal macrophages after in vivo LPS administration. RESULTS: LPS (1.5 mg/kg) induced 50% mortality in cirrhotic rats and no mortality in sham-operated rats. After LPS, TNF-alpha, nitrate and transaminase levels were significantly higher in cirrhotic rats compared to sham-operated rats. After LPS administration, there were no differences in NOS2 activity in the aorta, lungs, or peritoneal macrophages of the two groups, whereas NOS2 activity was significantly higher in the cirrhotic liver compared to the normal liver. CONCLUSIONS: In rats with cirrhosis, LPS administration induces higher mortality, hepatic toxicity, hepatic NOS2 activation and TNF-alpha release than in sham-operated rats. These results confirm the harmful role of septic shock in liver disease.

Animals↗
PubMed2000

Role of aortic nitric oxide synthase 3 (eNOS) in the systemic vasodilation of portal hypertension.

BACKGROUND & AIMS: In portal hypertension, the mechanisms responsible for nitric oxide (NO) overproduction and vasodilation have not yet been clearly identified. One hypothesis is that NO synthase (NOS) 3 is overactivated because of shear stress in endothelial cells caused by hyperkinetic circulation. The aim of this study was to evaluate aortic NOS3 after a reduction of blood flow by long-time beta-adrenoceptor antagonist administration. METHODS: Propranolol or atenolol was administered by gavage in portal vein-stenosed and sham-operated rats. The vascular reactivity of thoracic aortic rings to phenylephrine, total aortic NOS activity, and aortic NOS3 messenger RNA and protein expressions were studied. RESULTS: After propranolol or atenolol administration, the aortic hyporesponse returned to normal in portal vein-stenosed rats. Total aortic NOS activity was higher in portal vein-stenosed aortas and significantly decreased after beta-blocker administration. Aortic NOS3 expressions were more marked in portal vein-stenosed aortas than in controls, but NOS3 expressions were reduced after propranolol administration. CONCLUSIONS: In portal hypertension, aortic NOS3 activity and expressions are enhanced but return to normal after beta-blocker administration. These results suggest that in portal hypertension, increased shear stress, related to high blood flow, induces enhanced aortic NOS3.

Adrenergic beta-Antagonists↗