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Xenotransplantation (XT) reveals a growing interest for the treatment of cardiomyopathy. The major barrier is an acute vascular rejection due to an acute humoral rejection. This pathogenesis is a difficult issue and in order to elaborate means for its prevention, we analysed the implication of oxidative stress (OS) on hearts from mini-pigs followed by reperfusion with either autologous or human blood in an attempt to simulate xenotransplantation. About 14 hearts were studied after a Langendorff blood reperfusion: allografts with autologous blood (n = 7) or xenografts with human blood (n = 7). Blood samples were drawn from the coronary sinus to assess ischemia and OS. In xenografts, arrhythmias occurred more frequently (p < 0.01, left ventricular systolic pressure decreased more significantly (p < 0.05), thiobarbituric acid-reactive substances concentrations increased at 30 min (0.7 ± 0.1 vs. 2.4 ± 0.3 mmol/l; p < 0.05) while vitamin A levels decreased (p < 0.05). XT was associated with a significant increase in ischemic injury and OS production. OS might play an eminent role in hyperacute humoral rejection. [ABSTRACT FROM AUTHOR]

OBJECTIVES:Liver fibrosis in chronic hepatitis C is related to sex, age at infection, duration of infection, and alcohol consumption. Several noninvasive biochemical markers are highly predictive for the discrimination of significant fibrosis. The aims of this study were: 1) to compare an index of five biochemical markers with historical features; and 2) to determine the utility of combining these features with the five-marker index for the prediction of significant fibrosis.METHODS:Untreated patients with chronic hepatitis C and a known duration of infection had a liver biopsy and serum tested for markers of fibrosis. The discriminative values of the markers and an index of historical features for the diagnosis of clinically significant fibrosis (F2–F4 by the Metavir system) were compared using areas under receiver operating characteristic (ROC) curves. A modified index was constructed combining the five-marker index and historical features.RESULTS:A total of 211 patients were included. Of these, 52% were male, and 19% consumed ≥50 g of alcohol daily. The median age at infection was 28 ± 13 yr and the median duration of infection was 17 ± 8 yr (range 1–48 yr). By multivariate logistic regression analysis, sex (p = 0.003), age at biopsy (p = 0.004), and alcohol consumption (p = 0.042) were independently predictive of F2–F4 fibrosis. For the discrimination of F2–F4 fibrosis, the areas under the ROC curves were 0.796 ± 0.033 for the five-marker index versus 0.709 ± 0.037 for the historical index (p = 0.079). For diagnosis of advanced fibrosis (F3 and F4), the areas under the curves were 0.920 ± 0.032 and 0.762 ± 0.049 (p = 0.007), respectively. The discriminative value of the combined biochemical and historical index was not statistically significantly different from that of the five-marker index alone (p = ns).CONCLUSIONS:A simple index including age, sex, and five biochemical markers accurately predicts significant hepatitis C-related fibrosis. This index is more accurate than an index of historical features, the addition of which to the existing index was not helpful. [Copyright &y& Elsevier]

summary. In numerous studies of symptoms in patients with chronic hepatitis C there has been no systematic assessment of both fatigue and extrahepatic manifestations. Our objective was to assess the prevalence of fatigue in patients with hepatitis C virus (HCV) infection, and to identify associations between fatigue and clinical and biological hepatic and extrahepatic manifestations. We studied 1614 patients. Data were prospectively recorded during the first visit of patients infected with HCV and the prevalence of fatigue and its association with dermatological, rheumatological, neurological and nephrological manifestations; diabetes; arterial hypertension; auto-antibodies, and cryoglobulinaemia were assessed. Then, using multivariate analysis, we identified demographic, biochemical, immunological, virological, and histological factors associated with the presence of fatigue. Fatigue was present in 53% of patients (95% confidence interval 51–56). In 17% of patients (95% confidence interval 15–19) fatigue was severe, impairing activity. Five other extrahepatic manifestations had a prevalence above 10% including, in decreasing order: arthralgia, paresthesia, myalgia, pruritus, and sicca syndrome. In univariate and multivariate analyses, fatigue, in comparison with the absence of fatigue, was associated with female gender, age over 50 years, cirrhosis, depression and purpura. Independent of these associations, fatigue was associated with arthralgia, myalgia, paresthesia, sicca syndrome and pruritus. The prevalence of fibromyalgia (as defined by the association of fatigue with arthralgia or myalgia) was 19% (95% confidence interval 17–21). There was no significant association between fatigue and the following characteristics: viral load or genotype, alcohol consumption, abnormal thyroid function, and type and level of cryoglobulinaemia. Hence, fatigue is the most frequent extrahepatic manifestation in patients infected with HCV. Fatigue is... [ABSTRACT FROM AUTHOR]

The article presents a study which examined the role of oxidative modification of low-density lipoprotein (LDL) in the pathophysiology of artherosclerosis and assessed LDL-apheresis, an efficient treatment of homozygous familial hypercholesterolemia (FH). The study evaluated the impact of long-term LDL apheresis treatment on atherogenicity of the major LDL subclasses. Also discussed is the chemical analysis of LDL subfractions.

ording to the oxidative hypothesis of atherosclerosis, a hyperoxidizability of lipoproteins could favor the development of the atherosclerotic process. Besides, it has been recently reported that models of elevated very-low-density-lipoprotein (VLDL) levels in rats resulted in an increased susceptibility of these VLDL to oxidation. Treatment with dexamethasone classically induces an increase in plasma VLDL concentration. The aim of our study was thus to assess the effects of a treatment with dexamethasone in rats on the susceptibility to copper oxidation, both on total plasma and on isolated lipoproteins. Male Sprague-Dawley rats aged three months were treated with a daily intraperitoneal injection of dexamethasone (1.5 mg per kg) for five days (DEX group), whereas control rats were fed ad libitum (AL group). In order to take into account the decrease of food intake induced by dexamethasone treatment, a group of pair-fed rats was constituted (PF group). These rats had the same food intake as rats of the DEX group and were treated with a daily isovolumic intraperitoneal injection of NaCl for 5 d. After 5 d treatment, rats were fasted overnight, then killed, and blood was collected on EDTA. Low-density lipoproteins (VLDL+LDL) and high-density lipoproteins (HDL) were isolated by ultracentrifugation. A copper oxidation was conducted both on total plasma and on isolated lipoproteins. As expected, after treatment with dexamethasone, plasma exhibited increased triglyceride and glucose levels. Similarly, VLDL + LDL of rats from the DEX group were enriched with triglycerides, when compared with VLDL + LDL of the other two groups of rats. Our major finding was a marked increase in the susceptibility of total plasma of the DEX group to copper oxidation, in comparison with the other two groups of rats. This oxidizability was assessed by the maximal level of oxidation products absorbing at 234 nm and classically considered to be conjugated dienes (7.46±0.70 μmol L in the DEX group vs 3.36±0.40 and 2.05 ±0.60 μmol L in the AL and PF groups, respectively). Nevertheless, this higher oxidizability was not observed in the isolated lipoprotein fractions, as shown by the formation of lipid peroxidation products such as conjugated dienes, thiobarbituric-acid reactive substances, hydroperoxides, 7-ketocholesterol, and dienals. This is not in agreement with other models of hypertriglyceridemia that have been reported to induce a hyperoxidizability of lipoproteins in rats. Our results led us to hypothesize that other plasma components such as proteins could be involved in this susceptibility to oxidation. Indeed, the severe protein catabolism induced by dexamethasone treatment could support this hypothesis, by forming protein components that are more susceptible to oxidation, as shown by an increased carbonyl formation upon plasma copper oxidation. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the peripheral blood lymphocyte (PBL) phenotypes and T cell repertoire in patients with HCV infection, with or without mixed cryoglobulinaemia (MC). The patients were: Group 1, 23 patients with HCV infection and MC; Group 2, 14 patients with HCV infection but without MC; Group 3, 10 patients with symptomatic essential MC. Twenty healthy blood donors were used as controls. Blood lymphocyte counts were determined, and flow cytometry was used to measure proportions of B cells (CD19+), natural killer (NK) cells (CD16+ CD56+), T cells (CD3+), CD4+ T cell subsets (memory CD4+ CD45RO+; naive CD4+ CD45RO-; Th0/Th2 CD4+ CD7-; activated CD4+ CD25+), and CD8+ T cell subsets (immunoregulatory CD8+ CD57+; cytotoxic CD8+ S6F1+, activated CD8+ CD25+). Bias in the usage of T cell receptor (TCR) Vβ chains was studied in a subgroup of 10 representative patients of Group 1 using a polymerase chain reaction (PCR) analysis of the Vβ segments with a series of 20 oligonucleotides specific for the Vβ families. The three groups were comparable for blood lymphocyte counts, and we observed no abnormal repartition of the following PBL subsets: T cells (CD3+), CD4+ and CD8+ subpopulations, B cells (CD19+), and the NK cells (CD16+ 56+). In none of the groups could we observe lymphocyte ex vivo activation as assessed by the normal expression of the activation cell markers: CD25 on CD4+ or CD8+ T cells, or CD5 on B cells. The repartition of naive and memory (CD45RO-/RO+) CD4+ T cells was normal and we did not observe any amplification of the CD4+ CD7- T cell subset differentiated in... [ABSTRACT FROM AUTHOR]