Schistosomicidal activity of alkylaminooctanethiosulfuric acids

The schistosomicidal activity of a new series of alkylaminooctanethiosulfuric acids was studied in white Swiss mice infected with the L.E. strain of Schistosoma mansoni (Belo Horizonte, MG, Brazil). In a preliminary screening of six compounds, two derivatives - 2-[(1-methylpropyl)amino]-1-octanethiosulfuric acid and 2-[(1-methylethyl)-amino]-1-octanethiosulfuric acid - given orally in doses of 300 mg/kg/day for five consecutive days, caused interruption of the oviposition and the hepatic shift of more than 90 of the worms. Both compounds caused a significant reduction in worm burden and, interestingly, the female schistosomes were more susceptible. With the therapeutic schedule of two doses of 800 mg/kg over a 20 day interval, the death of almost all the females and about 50 of the males was observed. Female worms recovered from treated mice showed scattered vitteline glands. Results of in vitro experiments against different developmental stages of the parasite revealed the induction of paralysis and damage to the tegument membrane. The drugs presented no toxic effects on the animals.

Immunochemotherapy in American cutaneous leishmaniasis: immunological aspects before and after treatment

In this study, we evaluated the immune response of patients suffering from cutaneous leishmaniasis treated with two distinct protocols. One group was treated with conventional chemotherapy using pentavalent antimonium salts and the other with immunochemotherapy where a vaccine against cutaneous leishmaniasis was combined with the antimonium salt. Our results show that, although no differences were observed in the necessary time for complete healing of the lesions between the two treatments, peripheral blood mononuclear cells from patients treated by chemotherapy showed smaller lymphoproliferative responses at the end of the treatment than those from patients in the immunochemotherapy group. Furthermore, IFN-gamma production was also different between the two groups. While cells from patients in the chemotherapy group produced more IFN-gamma at the end of treatment, a significant decrease in this cytokine production was associated with healing in the immunochemotherapy group. In addition, IL-10 production was also less intense in this latter group. Finally, an increase in CD8+ -IFN-gamma producing cells was detected in the chemotherapy group. Together these results point to an alternative treatment protocol where healing can be induced with a decreased production of a potentially toxic cytokine.

Neuronal traits are required for glucose-induced insulin secretion.

The transcriptional repressor RE1 silencer transcription factor (REST) is an important factor that restricts some neuronal traits to neurons. Since these traits are also present in pancreatic beta-cells, we evaluated their role by generating a model of insulin-secreting cells that express REST. The presence of REST led to a decrease in expression of its known target genes, whereas insulin expression and its cellular content were conserved. As a consequence of REST expression, the capacity to secrete insulin in response to mitochondrial fuels, a particularity of mature beta-cells, was impaired. These data provide evidence that REST target genes are required for an appropriate glucose-induced insulin secretion.

Amphetamines for Attention Deficit Hyperactivity Disorder (ADHD) in adults.

Attention Deficit Hyperactivity Disorder (ADHD) is a childhood onset psychiatric disorder that can persist into adulthood in up to 50% of patients. From a clinical point of view, ADHD is characterized by hyperactivity, mood instability, irritability, difficulties in maintaining attention, lack of organization and impulsive behaviours. The presence of other disorders occurring at the the same time is also common, especially mood disorders and substance abuse. It seems that amphetamines could reverse the underlying neurological problems that feature in ADHD, and so improve ADHD symptoms. We found seven studies, which enrolled 1091 patients. These studies compared amphetamines to placebo and three of them also compared amphetamines with other drugs: guanfacine, modafinil and paroxetine. Three amphetamine derivatives were investigated: dexamphetamine, lisdexamphetamine and mixed amphetamine salts (MAS). Treatment length ranged from two to 20 weeks. All amphetamines improved ADHD symptoms but overall they did not make people more likely to stay in treatment and were associated with a higher risk of treatment ending early due to adverse events. One type of amphetamine, mixed amphetamine salts, did, however, increase retention in treatment. We found no evidence that higher doses worked better than lower ones. We did not find any difference in effectiveness between immediate-release and sustained-release formulations. Therefore, it appears that short-term treatment with amphetamines reduces ADHD symptoms, but studies assessing the effects of amphetamines for longer periods of time are needed.This resource was contributed by The National Documentation Centre on Drug Use.

Wet chemical silver treatment of endotracheal tubes to produce antibacterial surfaces.

Mechanically ventilated patients in hospitals are subjected to an increased risk of acquiring nosocomial pneumonia that sometimes has a lethal outcome. One way to minimize the risk could be to make the surfaces on endotracheal tubes antibacterial. In this study, bacterial growth was inhibited or completely prevented by silver ions wet chemically and deposited onto the tube surface. Through the wet chemical treatment developed here, a surface precipitate was formed containing silver chloride and a silver stearate salt. The identity and morphology of the surface precipitate was studied using x-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, and x-ray powder diffraction. Leaching of silver ions into solution was examined, and bacterial growth on the treated surfaces was assayed using Pseudomonas aeruginosa wild type (PAO1) bacteria. Furthermore, the minimum inhibitory concentration of silver ions was determined in liquid- and solid-rich growth medium as 23 and 18 microM, respectively, for P. aeruginosa.

The influence of cationic lipid type on in-vitro release kinetic profiles of antisense oligonucleotide from cationic nanoemulsions.

Novel formulations of cationic nanoemulsions based on three different lipids were developed to strengthen the attraction of the polyanionic oligonucleotide (ODN) macromolecules to the cationic moieties on the oil nanodroplets. These formulations were developed to prolong the release of the ODN from the nanoemulsion under appropriate physiological dilutions as encountered in the eye following topical application. Increasing the concentration of the new cationic lipid exhibiting two cationic amine groups (AOA) in the emulsion from 0.05% to 0.4% did not alter markedly the particle size or zeta potential value of the blank cationic nanoemulsion. The extent of ODN association did not vary significantly when the initial concentration of ODN remained constant at 10 microM irrespective of the cationic lipid nature. However, the zeta potential value dropped consistently with the low concentrations of 0.05% and 0.1% of AOA in the emulsions suggesting that an electrostatic attraction occurred between the cationic lipids and the polyanionic ODN molecules at the o/w interface. Only the nanoemulsion prepared with N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium salts (DOTAP) remained physically stable over time. DOTAP cationic lipid nanoemulsion was the most efficient formulation capable of retaining the ODN despite the high dilution of 1:100 with simulated tear solution (STS). Less than 10% of the ODN was exchanged in contrast to 40-50% with the other cationic nanoemulsions. The in-vitro release kinetic behavior of ODN exchange with physiological anions present in the STS appears to be complex and difficult to characterize using mathematical fitting model equations. Further pharmacokinetic studies are needed to verify our kinetic assumptions and confirm the in-vitro ODN release profile from DOTAP cationic nanoemulsions.

Safety and immunomodulatory effects of three probiotic strains isolated from the feces of breast-fed infants in healthy adults: SETOPROB study.

We previously described the isolation and characterization of three probiotic strains from the feces of exclusively breast-fed newborn infants: Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036. These strains were shown to adhere to intestinal mucus in vitro, to be sensitive to antibiotics and to resist biliary salts and low pH. In the present study, a multicenter, randomized, double-blind, placebo-controlled trial with 100 healthy volunteers in three Spanish cities was carried out to evaluate the tolerance, safety, gut colonization and immunomodulatory effects of these three probiotics. Volunteers underwent a 15-day washout period, after which they were randomly divided into 5 groups that received daily a placebo, a capsule containing one of the 3 strains or a capsule containing a mixture of two strains for 30 days. The intervention was followed by another 15-day washout period. Patients did not consume fermented milk for the entire duration of the study. Gastrointestinal symptoms, defecation frequency and stool consistency were not altered by probiotic intake. No relevant changes in blood and serum, as well as no adverse events occurred during or after treatment. Probiotic administration slightly modified bacterial populations in the volunteers' feces. Intestinal persistence occurred in volunteers who received L. rhamnosus CNCM I-4036. Administration of B. breve CNCM I-4035 resulted in a significant increase in fecal secretory IgA content. IL-4 and IL-10 increased, whereas IL-12 decreased in the serum of volunteers treated with any of the three strains. These results demonstrate that the consumption of these three bacterial strains was safe and exerted varying degrees of immunomodulatory effects.

Estudio de la extracción química del fe en madera arqueológica subacuatica tratada previamente con peg 4000

Debido a la gran cantidad de muestras arqueológicas impregnadas con PEG que se encuentran contaminadas por compuestos insolubles de hierro, se plantea la posible extracción y formación de complejos Fe-L (L=PBTC) y sus efectos en (i) la estructura de la matriz orgánica, (ii) la estructura y propiedades físicas del PEG y (iii) el comportamiento de la muestra en la etapa posterior de almacenamiento. El proyecto analiza la formación de compuestos químicos y posibles modificaciones estructurales en el proceso de extracción del hierro. Consiste en un estudio sistemático de un sistema químico y su influencia en los procesos de precipitación de Fe3+ en medio acuoso. El proyecto se fundamenta en: (1) desarrollar un proceso experimental de optimización para la extracción de las sales contaminantes y (2) encontrar las técnicas analíticas óptimas que permitan apreciar modificaciones estructurales de los diferentes sistemas. Se determina la cantidad de hierro extraído mediante A.A. Las interacciones entre PBTC y PEG se analizan por IR. Las modificaciones de determinadas propiedades físicas se determinan por DSC y las estructurales mediante SEM. En las condiciones termodinámicas óptimas se obtiene una extracción superficial del hierro (30-35%). La disolución del PEG origina modificaciones de la masa y el volumen de la muestra

Use of an isothermal microcalorimetry assay to characterize microbial oxalotrophic activity

Isothermal microcalorimetry (IMC) has been used in the past to monitor metabolic activities in living systems. A few studies have used it on ecological research. In this study, IMC was used to monitor oxalotrophic activity, a widespread bacterial metabolism found in the environment, and particularly in soils. Six model strains were inoculated in solid angle media with K-oxalate as the sole carbon source. Cupriavidus oxalaticus, Cupriavidus necator, and Streptomyces violaceoruber presented the highest activity (91, 40, and 55 μW, respectively) and a maximum growth rate (μmax h(-1) ) of 0.264, 0.185, and 0.199, respectively, among the strains tested. These three strains were selected to test the incidence of different oxalate sources (Ca, Cu, and Fe-oxalate salts) in the metabolic activity. The highest activity was obtained in Ca-oxalate for C. oxalaticus. Similar experiments were carried out with a model soil to test whether this approach can be used to measure oxalotrophic activity in field samples. Although measuring oxalotrophic activity in a soil was challenging, there was a clear effect of the amendment with oxalate on the metabolic activity measured in soil. The correlation between heat flow and growth suggests that IMC analysis is a powerful method to monitor bacterial oxalotrophic activity

Remediation of a marine shore tailings deposit and the importance of water-rock interaction on element cycling in the coastal aquifer

We present the study of the geochemical processes associated with the first successful remediation of a marine shore tailings deposit in a coastal desert environment (Bahia de Ite, in the Atacama Desert of Peru). The remediation approach implemented a wetland on top of the oxidized tailings. The site is characterized by a high hydrauliz gradient produced by agricultural irrigation on upstream gravel terraces that pushed river water (similar to 500 mg/L SO(4)) toward the sea and through the tailings deposit. The geochemical and isotopic (delta(2)H(water) and delta(18)O(water), delta(34)S(sulfate) , delta(18)O(sulfate)) approach applied here revealed that evaporite horizons (anhydrite and halite) in the gravel terraces are the source of increased concentrations of SO(4), Cl, and Na up to similar to 1500 mg/L in the springs at the base of the gravel terraces. Deeper groundwater interacting with underlying marine sequences increased the concentrations of SO(4), Cl, and Na up to 6000 mg/L and increased the alkalinity up to 923 mg/L CaCO(3) eq. in the coastal aquifer. These waters infiltrated into the tailings deposit at the shelf-tailings interface. Nonremediated tailings had a low-pH oxidation zone (pH 1-4) with significant accumulations of efflorescent salts (10-20 cm thick) at the surface because of upward capillary transport of metal cations in the arid climate. Remediated tailings were characterized by neutral pH and reducing conditions (pH similar to 7, Eh similar to 100 mV). As a result, most bivalent metals such as Cu, Zn, and Ni had very low concentrations (around 0.01 mg/L or below detection limit) because of reduction and sorption processes. In contrast, these reducing conditions increased the mobility of iron from two sources in this system: (1) The originally Fe(III)-rich oxidation zone, where Fe(II) was reduced during the remediation process and formed an Fe(II) plume, and (2) reductive dissolution of Fe(III) oxides present in the original shelf lithology formed an Fe-Mn plume at 10-m depth. These two Fe-rich plumes were pushed toward the shoreline where more oxidizing and higher pH conditions triggered the precipitation of Fe(HI)hydroxide coatings on silicates. These coatings acted as a filter for the arsenic, which naturally infiltrated with the river water (similar to 500 mu g/L As natural background) into the tailings deposit.

Pigment production by Streptococcus agalactiae in quasi-defined media.

A quasi-defined medium that supports the growth of Streptococcus agalactiae as pigmented colonies has been developed. The medium contains starch, a peptic digest of albumin, amino acids, nucleosides, vitamins, and salts. The presence of free cysteine, which could be replaced with other sulphur-containing compounds and to a lesser degree by reducing agents, was required for pigment formation.

Metabolomic insights into the intricate gut microbial-host interaction in the development of obesity and type 2 diabetes.

Gut microbiota has recently been proposed as a crucial environmental factor in the development of metabolic diseases such as obesity and type 2 diabetes, mainly due to its contribution in the modulation of several processes including host energy metabolism, gut epithelial permeability, gut peptide hormone secretion, and host inflammatory state. Since the symbiotic interaction between the gut microbiota and the host is essentially reflected in specific metabolic signatures, much expectation is placed on the application of metabolomic approaches to unveil the key mechanisms linking the gut microbiota composition and activity with disease development. The present review aims to summarize the gut microbial-host co-metabolites identified so far by targeted and untargeted metabolomic studies in humans, in association with impaired glucose homeostasis and/or obesity. An alteration of the co-metabolism of bile acids, branched fatty acids, choline, vitamins (i.e., niacin), purines, and phenolic compounds has been associated so far with the obese or diabese phenotype, in respect to healthy controls. Furthermore, anti-diabetic treatments such as metformin and sulfonylurea have been observed to modulate the gut microbiota or at least their metabolic profiles, thereby potentially affecting insulin resistance through indirect mechanisms still unknown. Despite the scarcity of the metabolomic studies currently available on the microbial-host crosstalk, the data-driven results largely confirmed findings independently obtained from in vitro and animal model studies, putting forward the mechanisms underlying the implication of a dysfunctional gut microbiota in the development of metabolic disorders.

Technologies de procédé et de contrôle pour réduire la teneur en sel du jambon sec et des saucissons

Dans certains pays européens, les produits carnés élaborés peuvent représenter près de 20% de la consommation journalière de sodium. De ce fait, les industries de la viande tentent de réduire la teneur en sel dans les produits carnés pour répondre, d’une part aux attentes des consommateurs et d’autre part aux demandes des autorités sanitaires. Le système Quick‐Dry‐Slice process (QDS®), couplé avec l’utilisation de sels substituant le chlorure de sodium (NaCl), a permis de fabriquer, avec succès, des saucisses fermentées à basse teneur en sel en réduisant le cycle de fabrication et sans ajout de NaCl supplémentaire. Les technologies de mesure en ligne non destructives, comme les rayons X et l’induction électromagnétique, permettent de classifier les jambons frais suivant leur teneur en gras, un paramètre crucial pour adapter la durée de l’étape de salaison. La technologie des rayons X peut aussi être utilisée pour estimer la quantité de sel incorporée pendant la salaison. L’information relative aux teneurs en sel et en gras est importante pour optimiser le processus d’élaboration du jambon sec en réduisant la variabilité de la teneur en sel entre les lots et dans un même lot, mais aussi pour réduire la teneur en sel du produit final. D’autres technologies comme la spectroscopie en proche infrarouge (NIRS) ou spectroscopie microondes sont aussi utiles pour contrôler le processus d’élaboration et pour caractériser et classifier les produits carnés élaborés, selon leur teneur en sel. La plupart de ces technologies peuvent être facilement appliquées en ligne dans l’industrie afin de contrôler le processus de fabrication et d’obtenir ainsi des produits carnés présentant les caractéristiques recherchées.

Biogeochemical evolution of a marine shore tailings deposit during bioremediation

Summary : Mining activities produce enormous amounts of waste material known as tailings which are composed of fine to medium size particles. These tailings often contain sulfides, which oxidation can lead to acid and metal contamination of water; therefore they need to be remediated. In this work a tailings bioremediation approach was investigated by an interdisciplinary study including geochemistry, mineralogy and microbiology. The aim of the work was to study the effect of the implementation of wetland above oxidizing tailings on the hydrogeology and the biogeochemical element cycles, and to assess the system evolution over time. To reach these goals, biogeochemical processes occurring in a marine shore tailings deposit were investigated. The studied tailings deposit is located at the Bahìa de Ite, Pacific Ocean, southern Peru, where between 1940 and 1996 the tailings were discharged from the two porphyry copper mines Cuajone and Toquepala. After the end of deposition, a remediation approach was initiated in 1997 with a wetland implementation above the oxidizing tailings. Around 90% of the tailings deposits (total 16 km2) were thus remediated, except the central delta area and some areas close to the shoreline. The multi-stable isotope study showed that the tailings were saturated with fresh water in spite of the marine setting, due to the high hydraulic gradient resulting from the wetland implementation. Submarine groundwater discharge (SGD) was the major source of SO4 2-, C1-, Na+, Fe2+, and Mn2+ input into the tailings at the original shelf-seawater interface. The geochemical study (aquatic geochemistry and X-Ray diffraction (XRD) and sequential extractions from the solid fraction) showed that iron and sulfur oxidation were the main processes in the non-remediated tailings, which showed a top a low-pH oxidation zone with strong accumulation of efflorescent salts at the surface due to capillary upward transport of heavy metals (Fe, Cu, Zn, Mn, Cd, Co, and Ni) in the arid climate. The study showed also that the implementation of the wetland resulted in very low concentrations of heavy metals in solution (mainly under the detection limit) due to the near neutral pH and more reducing conditions (100-150 mV). The heavy metals, which were taken from solution, precipitated as hydroxides and sulfides or were bound to organic matter. The bacterial community composition analysis by Terminal Restriction Fragment Length Polymorphism (T-RFLP) and cloning and sequencing of 16S rRNA genes combined with a detailed statistical analysis revealed a high correlation between the bacterial distribution and the geochemical variables. Acidophilic autotrophic oxidizing bacteria were dominating the oxidizing tailings, whereas neutrophilic and heterotrophic reducing bacteria were driving the biogeochemical processes in the remediated tailings below the wetland. At the subsurface of the remediated tailings, an iron cycling was highlighted with oxidation and reduction processes due to micro-aerophilic niches provided by the plant rhizosphere in this overall reducing environment. The in situ bioremediation experiment showed that the main parameter to take into account for the effectiveness was the water table and chemistry which controls the system. The constructed remediation cells were more efficient and rapid in metal removal when saturation conditions were available. This study showed that the bioremediation by wetland implementation could be an effective and rapid treatment for some sulfidic mine tailings deposits. However, the water saturation of the tailings has to be managed on a long-term basis in order to guarantee stability. Résumé : L'activité minière produit d'énormes quantités de déchets géologiques connus sous le nom de « tailings » composées de particules de taille fine à moyenne. Ces déchets contiennent souvent des sulfures dont l'oxydation conduit à la formation d'effluents acides contaminés en métaux, d'où la nécessité d'effectuer une remédiation des sites de stockage concernés. Le but de ce travail est dans un premier temps d'étudier l'effet de la bio-remédiation d'un dépôt de tailings oxydés sur l'hydrogéologie du système et les cycles biogéochimiques des éléments et en second lieu, d'évaluer l'évolution du processus de remédiation dans le temps. Le site étudié dans ce travail est situé dans la Bahía de Ite, au sud du Pérou, au bord de l'Océan Pacifique. Les déchets miniers en question sont déposés dans un environnement marin. De 1940 à 1996, les déchets de deux mines de porphyre cuprifère - Cuajone et Toquepala - ont été acheminés sur le site via la rivière Locumba. En 1997, une première remédiation a été initiée avec la construction d'une zone humide sur les tailings. Depuis, environ 90% de la surface du dépôt (16 km2) a été traité, les parties restantes étant la zone centrale du delta du Locumba et certaines zones proches de la plage. Malgré la proximité de l'océan, les études isotopiques menées dans le cadre de ce travail ont montré que les tailings étaient saturés en eau douce. Cette saturation est due à la pression hydraulique résultant de la mise en place des zones humides. Un écoulement d'eau souterrain sous-marin a été à détecté à l'interface entre les résidus et l'ancien fond marin. En raison de la géologie locale, il constitue une source d'entrée de SO4 2-, Cl-, Na+, FeZ+, et Mn2+ dans le système. L'analyse de la géochimie aquatique, la Diffraction aux Rayons X (XRD) et l'extraction séquentielle ont montré que l'oxydation du fer et .des sulfures est le principal processus se produisant dans les déchets non remédiés. Ceci a entraîné le développement d'une zone d'oxydation à pH bas induisant une forte accumulation des sels efflorescents, conséquence de la migration capillaire des métaux lourds (Fe, Cu, Zn, Mn, Cd, Co et Ni) de la solution vers la surface dans ce climat aride. Cette étude a montré également que la construction de la zone humide a eu comme résultats une précipitation des métaux dans des phases minérales en raison du pH neutre et des conditions réductrices (100-150mV). Les métaux lourds ont précipité sous la forme d'hydroxydes et de sulfures ou sont adsorbés à la matière organique. L'analyse de la composition de la communauté bactérienne à l'aide la technique T-RFLP (Terminal Restriction Fragment Length Polymorphism) et par le clonage/séquençage des gènes de l'ARNr 16S a été combinée à une statistique détaillée. Cette dernière a révélé une forte corrélation entre la distribution de bactéries spécifiques et la géochimie : Les bactéries autotrophes acidophiles dominent dans les déchets oxydés non remédiés, tandis que des bactéries hétérotrophes neutrophiles ont mené les processus microbiens dans les déchets remédiés sous la zone humide. Sous la surface de la zone humide, nos analyses ont également mis en évidence un cycle du fer par des processus d'oxydoréduction rendus possibles par la présence de niches micro-aérées par la rhizosphère dans cet environnement réducteur. L'expérience de bio-remédiation in situ a montré que les paramètres clés qui contrôlent l'efficacité du traitement sont le niveau de la nappe aquifère et la chimie de l'eau. Les cellules de remédiation se sont montrées plus efficaces et plus rapides lorsque le système a pu être saturé en eau. Finalement, cette étude a montré que la bio-remédiation de déchets miniers par la construction de zones humides est un moyen de traitement efficace, rapide et peu coûteux. Cependant, la saturation en eau du système doit être gérée sur le long terme afin de garantir la stabilité de l'ensemble du système.

Significance of serum adiponectin levels in patients with chronic liver disease.

Adiponectin, which plays a pivotal role in metabolic liver diseases, is reduced in concentration in patients with NASH (non-alcoholic steatohepatitis). The aim of the present study was to determine adiponectin concentrations in patients with different forms and stages of chronic liver diseases. Serum adiponectin concentrations were measured in 232 fasting patients with chronic liver disease: 64 with NAFLD (non-alcoholic fatty liver disease), 123 with other chronic liver disease (e.g. viral hepatitis, n=71; autoimmune disease, n=18; alcohol-induced liver disease, n=3; or elevated liver enzymes of unknown origin, n=31) and 45 with cirrhosis. Circulating adiponectin levels were significantly lower in patients with NAFLD in comparison with patients with other chronic liver disease (4.8+/-3.5 compared with 10.4+/-6.3 microg/ml respectively; P<0.0001). Circulating adiponectin levels were significantly higher in patients with cirrhosis in comparison with patients without cirrhosis (18.6+/-14.5 compared with 8.4+/-6.1 microg/ml respectively; P<0.0001). Adiponectin concentrations correlated negatively with body weight (P<0.001), serum triacylglycerols (triglycerides) (P<0.001) and, in women, with BMI (body mass index) (P<0.001). Adiponectin concentrations correlated positively with serum bile acids (P<0.001), serum hyaluronic acid (P<0.001) and elastography values (P<0.001). Adiponectin levels were decreased in patients with NAFLD. In conclusion, adiponectin levels correlate positively with surrogate markers of hepatic fibrosis (transient elastography, fasting serum bile acids and hyaluronate) and are significantly elevated in cases of cirrhosis.