The purpose of this study was to investigate the time course of changes in human tendon properties and metabolism during resistance training and detraining. Nine men (21-27 years) completed 3 months of isometric plantar flexion training and another 3 months of detraining. At the beginning and on every 1 month of training and detraining periods, the stiffness, blood circulation (blood volume and oxygen saturation), serum procollagen type 1 C-peptide (P1P; reflects synthesis of type 1 collagen), echointensity (reflects collagen content), and MRI signal intensity (reflects collagen structure) of the Achilles tendon were measured. Tendon stiffness did not change until 2 months of training, and the increase (50.3%) reached statistical significance at the end of the training period. After 1 month of detraining, tendon stiffness had already decreased to pre-training level. Blood circulation in the tendon did not change during the experimental period. P1P increased significantly after 2 months of training. Echointensity increased significantly by 9.1% after 2 months of training, and remained high throughout the experiment. MRI signal intensity increased by 24.2% after 2 months and by 21.4% after 3 months of training, but decreased to the pre-training level during the detraining period. These results suggested that the collagen synthesis, content, and structure of human tendons changed at the 2-month point of training period. During detraining, the sudden decrease in tendon stiffness might be related to changes in the structure of collagen fibers within the tendon.

Background: This study evaluated the relationship between inflammation, intra-hepatic oxidative stress, oxidative DNA damage and the progression of liver carcinogenesis in hepatitis C virus (HCV)-infected humans.Methods: Non-cancerous liver tissues were collected from 30 patients with an HCV-associated solitary hepatocellular carcinoma (HCC) who received curative tumor removal. After surgery, the patients were followed at monthly intervals at the outpatient clinic. Distribution of the inflammatory cells (CD68+), the number of 8-hydroxydeoxyguanosine (8-OHdG) DNA adducts and 4-hydroxynonenal (HNE) protein adducts and the expression of apurinic/ apyrimidinic endonuclease (APE) were determined by immunohistochemical analysis in serial liver sections from tumor-free parenchyma at the surgical margin around the tumor.Results: Significant positive correlations were observed between the number of CD68+ cells, the amount of HNE protein adducts, and the number of 8-OHdG adducts in liver tissue of patients with HCC and HCV. The cumulative disease-free survival was significantly shorter in patients with the highest percentage of 8-OHdG-positive hepatocytes. Using a Cox proportional hazard model, 8-OHdG, HNE and CD68 were determined to be good biomarkers for predicting disease-free survival in patients with HCC and HCV.Conclusions: These results support the hypothesis that HCV-induced inflammation causes oxidative DNA damage and promotes hepatocarcinogenesis which directly affects the clinical outcome. Since patients with greater intra-hepatic oxidative stress had a higher incidence of HCC recurrence, we suggest that oxidative stress biomarkers could potentially be used as a useful clinical diagnostic tool to predict the duration of disease-free survival in patients with HCV-associated HCC.

No abstract

Platelet-dependent thrombin level is enhanced in smokers, even when not smoking, when compared with non-smokers and increases immediately after smoking. Increases in nicotine and cotinine levels caused by smoking induced a prothrombotic state in smokers via increased platelet-dependent thrombogenesis.

The liver is the primary site for the metabolism of nutrients, drugs, and chemical agents. Although metabolic pathways are complex and tightly regulated, genetic variation among individuals, reflected in variations in gene expression levels, introduces complexity into research on liver disease. This study dissected genetic networks that control liver gene expression through the combination of large-scale quantitative mRNA expression analysis with genetic mapping in a reference population of BXD recombinant inbred mouse strains for which extensive singlenucleotide polymorphism, haplotype, and phenotypic data are publicly available. We profiled gene expression in livers of naive mice of both sexes from C57BL/6J, DBA/2J, B6D2F1, and 37 BXD strains using Agilent oligonucleotide microarrays. These data were used to map quantitative trait loci (QTLs) responsible for variations in the expression of about 19,000 transcripts. We identified polymorphic local and distant QTLs, including several loci that control the expression of large numbers of genes in liver, by comparing the physical transcript position with the location of the controlling QTL. Conclusion: The data are available through a public web-based resource (www.genenetwork.org) that allows custom data mining, identification of coregulated transcripts and correlated phenotypes, cross-tissue, and cross-species comparisons, as well as testing of a broad array of hypotheses. (HEPATOLOGY 2007;46:548-557.) T he maturation of gene expression technology has opened the door to the exploration of the genetics of gene expression. 1-3 Microarrays allow for the concurrent measurement of thousands of transcripts, with the resultant genomic data being increasingly used to improve the biological interpretation of data from mechanistic research. Phenotypic anchoring of observed phenotypes to gene expression changes has proven useful in uncovering the molecular mechanisms that lead to liver injury. 4,5 Such experiments connect the variation in the transcript expression to phenotypes. However, they do not lead to detailed gene expression networks in which the expression of 1 gene is found to control the expression of another.Recombinant inbred (RI) mice are created by the crossing of 2 parental strains followed by sib-mating for over 20 generations. 6 Strains created in this way have the advantage of being homozygous at almost every location along the genome. Each representative of an RI line will have limited phenotypic variation within that line, but the variation between lines is usually vast. RI panels are widely used to determine genotype-phenotype associations with quantitative trait locus (QTL) mapping techniques. 7 The relationships between the phenotypes and genotypes are calculated with a likelihood ratio statistic (LRS), which is a measure of the probability that a given genetic marker explains the variation in the phenotype. When mRNA levels are used as the phenotype, regions of the genome with a high LRS are likely to contain genes that control the expression of t...

We postulated that a novel free radical scavenger, 3-methyl-1-phenyl-2-pyrazolin-5-one (edaravone; EDA), would attenuate inflammatory cytokine and chemokine expression in the liver after lipopolysaccharide (LPS) challenge through its antioxidant effect. Rats were administered EDA (0.3, 1.5, 3.0, 6.0, and 12.0 mg/kg) or the same volume of saline intravenously just after LPS (10 mg/kg) injection and then was continued intermittently every 2 h (five administrations in total). Survival was assessed for the next 24 h. In separate experiments, rats were sacrificed at 60 min, 90 min, 6 h, and 9 h after LPS injection. Serum and liver sections were collected for further analysis. Survival was improved by EDA in a dose-dependent manner up to 3 mg/kg, and maximum effects were observed at a dose of 3 mg/kg. After LPS injection, alanine aminotransferase levels increased significantly to about 1,250 IU/l in the vehicle-treated group, whereas values were blunted by about 80% by EDA. Furthermore, increases in 4-hydroxynonenal-modified proteins were also blunted in the liver by EDA. Moreover, mRNA expressions of macrophage infiltrating protein-2, monocyte chemoattractant protein (MCP)-1 and MCP-5 were attenuated by EDA. As a result, increases in the number of infiltrating inflammatory cells and mRNA expression of inflammatory cytokines such as tumor necrosis factor-␣ and interleukin-6 were significantly blunted in the liver by EDA. This reduction was accompanied by a significant reduction of their serum levels. In conclusion, EDA prevented liver injury by both inhibition of recruitments of inflammatory cells and expression of inflammatory cytokine levels in the liver.

Enteral feeding using MCT could be a practical way of protecting the liver and intestine during endotoxemia.

Hypercholesterolemia, but not hypertriglyceridemia, was associated with increased platelet-dependent thrombin generation. Pravastatin normalized the generation of thrombin.