The osteopontin level in liver, adipose tissue and serum is correlated with fibrosis in patients with alcoholic liver disease

Background

Osteopontin (OPN) plays an important role in the progression of chronic liver diseases. We aimed to quantify the liver, adipose tissue and serum levels of OPN in heavy alcohol drinkers and to compare them with the histological severity of hepatic inflammation and fibrosis.

Methodology/Principal Findings

OPN was evaluated in the serum of a retrospective and prospective group of 109 and 95 heavy alcohol drinkers, respectively, in the liver of 34 patients from the retrospective group, and in the liver and adipose tissue from an additional group of 38 heavy alcohol drinkers. Serum levels of OPN increased slightly with hepatic inflammation and progressively with the severity of hepatic fibrosis. Hepatic OPN expression correlated with hepatic inflammation, fibrosis, TGFβ expression, neutrophils accumulation and with the serum OPN level. Interestingly, adipose tissue OPN expression also correlated with hepatic fibrosis even after 7 days of alcohol abstinence. The elevated serum OPN level was an independent risk factor in estimating significant (F≥2) fibrosis in a model combining alkaline phosphatase, albumin, hemoglobin, OPN and FibroMeter® levels. OPN had an area under the receiving operator curve that estimated significant fibrosis of 0.89 and 0.88 in the retrospective and prospective groups, respectively. OPN, Hyaluronate (AUROC: 0.88), total Cytokeratin 18 (AUROC: 0.83) and FibroMeter® (AUROC: 0.90) estimated significance to the same extent in the retrospective group. Finally, the serum OPN levels also correlated with hepatic fibrosis and estimated significant (F≥2) fibrosis in 86 patients with chronic hepatitis C, which suggested that its elevated level could be a general response to chronic liver injury.

Conclusion/Significance

OPN increased in the liver, adipose tissue and serum with liver fibrosis in alcoholic patients. Further, OPN is a new relevant biomarker for significant liver fibrosis. OPN could thus be an important actor in the pathogenesis of this chronic liver disease.     

Likelihood and Bayesian analyses reveal major genes affecting body composition,carcass, meat quality and the number of false teats in a Chinese European pig line

Segregation analyses were performed using both maximum likelihood – via a Quasi Newton algorithm – (ML-QN) and Bayesian – via Gibbs sampling – (Bayesian-GS) approaches in the Chinese European Tiameslan pig line. Major genes were searched for average ultrasonic backfat thickness (ABT), carcass fat (X2 and X4) and lean (X5) depths, days from 20 to 100 kg ({"type":"entrez-nucleotide","attrs":{"text":"D20100","term_id":"500997","term_text":"D20100"}}D20100), Napole technological yield (NTY), number of false (FTN) and good (GTN) teats, as well as total teat number (TTN). The discrete nature of FTN was additionally considered using a threshold model under ML methodology. The results obtained with both methods consistently suggested the presence of major genes affecting ABT, X2, NTY, GTN and FTN. Major genes were also suggested for X4 and X5 using ML-QN, but not the Bayesian-GS, approach. The major gene affecting FTN was confirmed using the threshold model. Genetic correlations as well as gene effect and genotype frequency estimates suggested the presence of four different major genes. The first gene would affect fatness traits (ABT, X2 and X4), the second one a leanness trait (X5), the third one NTY and the last one GTN and FTN. Genotype frequencies of breeding animals and their evolution over time were consistent with the selection performed in the Tiameslan line.     

Reversal of the inhibitory effect of surfactants upon germination and growth of a consortium of two strains of Bacillus

Anionic, cationic, amphoteric and non-ionic surfactants inhibited spore germination and subsequent growth of a mixture of two Bacillus strains at surfactant concentrations ranging from 1 ppm to 50 ppm. Germination appeared to be more affected than cell growth by the presence of surfactants, the inhibitory thresholds being largely increased when media were inoculated with vegetative cells. The bacterial species forming the consortium were incapable of growing on liquid and agar-solidified media prepared with non-diluted domestic wastewater. Addition of hydrolases (protease, cellulase, α-amylase and lipase) to the wastewater medium allowed the germination of spores and their vegetative growth. Received: 9 July 1998 / Received revision: 26 October 1998 / Accepted: 30 October 1998     

Clostridium autoethanogenum,sp. nov., an anaerobic bacterium that produces ethanol from carbon monoxide

A strictly anaerobic, gram-positive, sporeforming, rod-like, motile bacterium was enriched from rabbit feces, and isolated using carbon monoxide as sole source of energy and carbon. The isolate metabolizes CO with ethanol, acetate and CO₂ as end-products. Other substrates used as carbon and energy sources include CO₂ plus H₂, pyruvate, xylose, arabinose, fructose, rhamnose, and l-glutamate. The optimum temperature for growth is 37°C. The optimum pH for chemolithotrophic growth lies around 5.8 to 6.0 Sulfate is not reduced. Growth is inhibited either by penicillin, chloramphenicol, tetracyclin or ampicillin, each at 100 g per ml. The isolate has a DNA-base composition of 25.9±0.6% guanine plus cytosine. The isolate represents a new species of Clostridium for which the name Clostridium autoethanogenum is proposed. The type strain is strain JA1-1     

Methanogenic potential activity of mixed liquors: Fluorimetric monitoring

Summary Fluorimetric monitoring of potential methanogenic activity (coenzyme F₄₂₀) of bacterial community from methane digesters is until now resstricted to a few particular cases because severe interference frequnetly occurs, or the concentration is too low when digesting highly diluted wastes. A method of purification and/or concentration, based on purification of the cellular fraction of the sample by centrifugation and washing, is proposed. In biomethanation of spent liquor from citric acid fermentation, a typical case where interference largely obscures the F₄₂₀ fluorescence signal, precision is shown to be better than ± 5% (confidence interval [t.05 (3)]) for F₄₂₀ concentration down to 200 nM, and the detection limit is below 10 nM.     

Activation of Kupffer Cells Is Associated with a Specific Dysbiosis Induced by Fructose or High Fat Diet in Mice

The increase consumption of fructose in diet is associated with liver inflammation. As a specific fructan substrate, fructose may modify the gut microbiota which is involved in obesity-induced liver disease. Here, we aimed to assess whether fructose-induced liver damage was associated with a specific dysbiosis, especially in mice fed a high fat diet (HFD). To this end, four groups of mice were fed with normal and HFD added or not with fructose. Body weight and glucose sensitivity, liver inflammation, dysbiosis and the phenotype of Kupffer cells were determined after 16 weeks of diet. Food intake was increased in the two groups of mice fed with the HFD. Mice fed with HFD and fructose showed a higher infiltration of lymphocytes into the liver and a lower inflammatory profile of Kupffer cells than mice fed with the HFD without fructose. The dysbiosis associated with diets showed that fructose specifically prevented the decrease of Mouse intestinal bacteria in HFD fed mice and increased Erysipelotrichi in mice fed with fructose, independently of the amount of fat. In conclusion, fructose, used as a sweetener, induced a dysbiosis which is different in presence of fat in the diet. Consequently, the activation of Kupffer cells involved in mice model of HFD-induced liver inflammation was not observed in an HFD/fructose combined diet. These data highlight that the complexity of diet composition could highly impact the development of liver lesions during obesity. Specific dysbiosis associated with the diet could explain that the progressions of liver damage are different.     

High-rate continuous biodegradation of concentrated chlorinated aliphatics by a durable enrichment of methanogenic origin under carrier-dependent conditions

The simultaneous biodegradation of toxic compounds in mixtures is a major current concern. To bioremediate a toxic mixture, we designed a strategy combining an ad-sorbent carrier with an ecological and nutritional system which allowed work close to heavily polluted conditions in nature. Starting from a methanogenic community, we developed a microbial consortium acclimated to a mixture of about 30 chlorinated aliphatics in a fixed-film stationary-bed bioreactor. Prior to the establishment of a durable period of dechlorination, an interval of progressive dechlorination of the toxic mixture was observed during which the excess of the toxic compounds was stored on the carrier. The latter, consisting of activated carbon in a polyurethane foam, allowed us to work at concentrations far above the solubility of the toxic compounds (apparent concentrations of about 10 g/L). The complete disappearance of hexachloroethane as well as its lower homologues, penta-, tetra-, and trichloroethane, present in the toxic mixture, was observed. Additionally, octachlorocyclopentene, carbon tetrachloride, trichloro-ethylene, tetrachloroethylene, and hexachloro-1,3-butadiene also completely disappeared. For the four latter compounds, from mass balances in the bioreactor, degradation rates around 10 mumol/L per day were determined with total dechlorination. The enrichment culture thus developed exhibited high degradation performances similar to those reported in the literature for pure or enriched anaerobic microbial cultures in contact with a single toxic compound. The results demonstrate the possibility of concurrent high-rate degradation of several highly chlorinated toxic compounds, under conditions approximating field situations.(c) 1995 John Wiley & Sons, Inc.     

Effect of specific inhibitors on the anaerobic reductive dechlorination of 2,4,6-trichlorophenol by a stable methanogenic consortium

The transformation of 2,4,6-trichlorophenol (TCP) into 4-chlorophenol (4CP) was studied using a stable methanogenic enrichment culture derived from an anaerobic fixed bed reactor. Using acetate as a growth substrate, different inhibitors of methanogenesis exhibited distinct effects on TCP dechlorination. Whereas reductive dechlorination activity was not affected by 2% ethylene in the gas phase, 25 mM bromoethanesulfonic acid (BESA) had a direct inhibitory effect on this process. The choice of BESA as a specific inhibitor for identifying the subpopulations involved in reductive dechlorination of chloroaromatics is thus questionable. Inhibitors of sulfate reduction such as molybdate (20 mM) and selenate (20 mM) had a direct inhibitory effect on reductive dechlorination independently of the presence of sulfate in the medium supplemented with acetate as growth substrate. Consequently much more care must also be taken with these inhibitors to prove that reductive chlorination is coupled to sulfate reduction.     

Biodegradation of 2,4,6-trinitrotoluene (TNT) by the white-rot basidiomycete Phlebia radiata

Phlebia radiatatransformed 2,4,6-trinitrotoluene (TNT), as well as its first reduction products, the aminodinitrotoluenes, into 4-hydroxylamino-2,6-dinitrotoluene (4-OHA-2,6-DNT) and 4-amino-2,6-dinitrotoluene (4-A-2,6-DNT). No extracellular peroxidases were involved in this step. The ligninolytic extracellular fluid, assumed to contain peroxidases, did not reduce TNT. However, ligninolytic peroxidases are implicated in the transformation of the first reduction products of TNT.     

Biodegradation of nitrobenzene by its simultaneous reduction into aniline and mineralization of the aniline formed

By mixing through a three-reactor system a nitroreducing consortium and an aniline-degrading Comamonas acidovorans, a mixed population was formed which was able to mineralize the nitroaromatic compound nitrobenzene via aniline, its corresponding aminoaromatic compound. The behavior of the mixed population was characterized in batch culture. In the first step, nitrobenzene was reduced to aniline by the reductive consortium and, in the second, oxidative step, aniline was mineralized via catechol and meta cleavage. Even though these two steps may seem incompatible in terms of required redox conditions, they were made to coexist in a single, simple reactor. However, when aeration was optimum for growth, only 16% of the 0.5 mM nitrobenzene introduced was mineralized. Decreasing the aeration led to an increase in the amount of nitrobenzene reduced and decreased its volatilized fraction. A decrease in aeration did not slow down aniline mineralization, although the latter is catalyzed by dioxygenases. This mixed population is thus able to remediate nitrobenzene and also aniline, which is often found with the former in the environment. Using C. acidovorans, which also degrades methylanilines, or other aminoaromatic-compound-degrading organisms, this strategy should be applicable to mineralizing more complex nitroaromatic compounds, like nitrotoluenes or dinitrotoluenes. Received: 29 July 1997 / Received revision: 11 November 1997 / Accepted: 16 November 1997