Accumulation of hedgehog-responsive progenitors parallels alcoholic liver disease severity in mice and humans.

Background & Aims: Improving outcomes in alcoholic liver disease (ALD) necessitates better understanding of how habitual ethanol (EtOH) consumption alters normal regenerative mechanisms within the liver. Hedgehog (Hh) pathway activation promotes expansion of progenitor populations in other tissues. We evaluated the hypothesis that chronic EtOH exposure activates Hh signaling in liver.

Hepatic triglyceride synthesis and nonalcoholic fatty liver disease.

Purpose Of Review: Nonalcoholic fatty liver disease is a spectrum of diseases ranging from simple steatosis to cirrhosis. The hallmark of nonalcoholic fatty liver disease is hepatocyte accumulation of triglycerides. We will review the role of triglyceride synthesis in nonalcoholic fatty liver disease progression and summarize recent findings about triglyceride synthesis inhibition and prevention of progressive disease.

[Smoking reduction during inpatient alcohol detoxification: a controlled clinical pilot trial].

Health care professionals tend to advise alcohol dependent patients to quit tobacco consumption only after longer periods of alcohol abstinence. This recommendation reflects concerns that smoking intervention programs may adversely interfere with the outcome of ongoing alcohol detoxification and rehabilitation treatment. However, the issue of appropriate time windows for initiating changes of smoking behaviour in alcoholic patients is still in need of empirical evaluation.

[Pharmacology of disulfiram - an update].

Recently, we have been observing an increase in prescription of Disulfiram requiring medical knowledge concerning the overall effects, side effects and drug interactions of this substance. In the following report, we give an overview about the pharmacology and the side effects of Disulfiram. As an example we demonstrate a case, in which an acute neurological deficit was misjudged as a side effect of Disulfiram.

Fructose consumption as a risk factor for non-alcoholic fatty liver disease.

Background/aims: While the rise in non-alcoholic fatty liver disease (NAFLD) parallels the increase in obesity and diabetes, a significant increase in dietary fructose consumption in industrialized countries has also occurred. The increased consumption of high fructose corn syrup, primarily in the form of soft drinks, is linked with complications of the insulin resistance syndrome. Furthermore, the hepatic metabolism of fructose favors de novo lipogenesis and ATP depletion.

The hedgehog pathway regulates remodelling responses to biliary obstruction in rats.

Background: Chronic biliary obstruction provokes fibrosis and accumulation of immature ductular cells. This fibroductular reaction resolves following biliary decompression, suggesting that it may also be involved in the repair of biliary damage. The hedgehog (Hh) pathway becomes activated in liver after bile duct ligation (BDL), and might modulate hepatic remodelling because Hh ligands are potent morphogens.

Hepatic fat and adenosine triphosphate measurement in overweight and obese adults using 1H and 31P magnetic resonance spectroscopy.

Background/aims: Magnetic resonance spectroscopy (MRS) measures hepatic fat and adenosine triphosphate (ATP), but magnetic resonance studies are challenging in obese subjects. We aimed to evaluate the inter- and intrarater reliability and stability of hepatic fat and ATP measurements in a cohort of overweight and obese adults.

Methods: We measured hepatic fat and ATP using proton MRS ((1)H MRS) and phosphorus MRS ((31)P MRS) at baseline in adults enrolled in the Action for Health in Diabetes (Look AHEAD) clinical trial at one site.

Measurement of 15N-T1 relaxation rates in a perdeuterated protein by magic angle spinning solid-state nuclear magnetic resonance spectroscopy.

In this paper, we present the measurement of (15)N-T(1) relaxation times in the solid state for a perdeuterated protein for which exchangeable protons are back substituted during recrystallization using a buffer which contains 10% H(2)O and 90% D(2)O. We find large variations of the (15)N relaxation time, even within the same beta sheet. By comparing (15)N-T(1) relaxation times measured for a protonated and a deuterated protein (using the above mentioned approach), we conclude that (1)H driven (15)N,(15)N spin diffusion has a significant impact on the absolute (15)N relaxation time in protonated proteins.

The adventures of sonic hedgehog in development and repair. II. Sonic hedgehog and liver development, inflammation, and cancer.

Hedgehog (Hh) signaling modulates tissue remodeling by controlling the fate of Hh-responsive cells. Healthy adult livers exhibit little Hh activity. However, cells involved in adult liver repair, including myofibroblasts and progenitors, are capable of producing and responding to Hh ligands.

Specific polymorphisms in hepatitis C virus genotype 3 core protein associated with intracellular lipid accumulation.

Background: Steatosis is a common histological finding and a poor prognostic indicator in patients with hepatitis C virus (HCV) infection. In HCV genotype 3-infected patients, the etiology of steatosis appears to be closely correlated with unknown viral factors that increase intracellular lipid levels. We hypothesize that specific sequence polymorphisms in HCV genotype 3 core protein may be associated with hepatic intracellular lipid accumulation.

Microscopy and polymerase chain reaction detection of Leishmania chagasi in the pleural and ascitic fluid of a patient with AIDS: Case report and review of diagnosis and therapy of visceral leishmaniasis.

Atypical visceral leishmaniasis is increasingly reported in immunocompromised patients, including patients with AIDS. A case of visceral leishmaniasis in an HIV-infected Brazilian patient with pulmonary and peritoneal involvement is reported. Histological evaluation of pleural fluid and ascites aspirate revealed macrophages with intracellular Leishmania.

Quantitative measurement of differential 15N-H(alpha/beta)T2 relaxation rates in a perdeuterated protein by MAS solid-state NMR spectroscopy.

Dynamic parameters become more and more accessible in the study of uniformly isotopically enriched proteins by MAS solid-state NMR. We demonstrate that T(2)-related relaxation properties can quantitatively be determined in a sample of a perdeuterated microcrystalline protein by the measurement of (15)N,(1)H dipole, (15)N CSA cross-correlated relaxation rates. We find that the measured cross-correlated relaxation rates are independent of the MAS rotation frequency, and therefore reflect local dynamic fluctuations of the protein structure.

Sonic hedgehog is an autocrine viability factor for myofibroblastic hepatic stellate cells.

Background/aims: Factors released during liver injury, such as platelet derived growth factor-BB (PDGF), promote accumulation of myofibroblastic hepatic stellate cells (MFB) that drive the pathogenesis of cirrhosis. The hedgehog (Hh) pathway regulates remodeling of other injured tissues. This study evaluates the hypothesis that autocrine production of Sonic hedgehog (Shh) promotes MFB growth.

Diacylglycerol acyltranferase 1 anti-sense oligonucleotides reduce hepatic fibrosis in mice with nonalcoholic steatohepatitis.

Unlabelled: Retinyl ester (RE) stores decrease during hepatic stellate cell (HSC) activation and liver fibrosis. Although retinol esterification is mostly catalyzed by lecithin:retinol acyltransferase (LRAT), diacylglycerol acyltransferase (DGAT)1 also does this. In previous reports, LRAT(-/-) mice had reduced hepatic RE but neither excessive HSC activation nor liver fibrosis, and DGAT1(-/-) mice had increased liver levels of RE and retinol.

Flexible polyelectrolyte conformation in the presence of oppositely charged surfactants.

Conformational behavior of flexible polyelectrolytes in the presence of monovalent cationic surfactants is examined. A simple model is presented for the formation of polyelectrolyte-surfactant complexes in salt-free solutions in the framework of the Debye-Hückel-Bjerrum-Manning and Flory theories, including explicitly the hydrophobic interactions between the associated surfactant molecules on the polyelectrolyte. The distribution of complexes is calculated as a function of the surfactant concentration and a discrete conformational transition between an elongated coil and a compact globule was found, in agreement with experimental observations.

Nonalcoholic fatty liver disease as a complication of insulin resistance.

Nonalcoholic fatty liver disease (NAFLD) refers to a spectrum of liver damage ranging from simple steatosis to nonalcoholic steatohepatitis, advanced fibrosis, and rarely, progression to cirrhosis. The pathogenesis of NAFLD is thought to be related to insulin resistance and oxidant stress. Truncal obesity, dyslipidema, hypertension, and hyperglycemia are strongly associated with NAFLD; therefore, management of NAFLD entails identification and treatment of metabolic risk factors, improving insulin sensitivity, and increasing antioxidant defenses in the liver.

Hepatic accumulation of Hedgehog-reactive progenitors increases with severity of fatty liver damage in mice.

Progenitors regenerate fatty livers but the mechanisms involved are uncertain. The Hedgehog pathway regulates mesendodermal progenitors and modulates mesenchymal-epithelial interactions during tissue remodeling. To determine if Hedgehog signaling increases in liver progenitors during fatty liver injury, we compared expression of Hedgehog ligands and target genes across a spectrum of injury.

Sensitivity enhancement using paramagnetic relaxation in MAS solid-state NMR of perdeuterated proteins.

Previously, Ishii et al., could show that chelated paramagnetic ions can be employed to significantly decrease the recycle delay of a MAS solid-state NMR experiment [N.P.

Improved hematopoietic stem cell engraftment following ex vivo expansion of murine marrow cells with SCF and Flt3L.

Background: In vitro incubation of murine BM cells with IL-3, IL-6, IL-11 and SCF induces expansion of HPC but fails to preserve 'engraftability' in comparison with normal untreated marrow cells. We studied how culturing marrow cells for 48 and 72 h with a combination of the cytokines SCF and Flt3L influences cell expansion and engraftability.

Methods: Competitive repopulation of lethally irradiated C57BL/6 mice was used to examine engraftability of ex vivo cytokine-expanded Ptprc chimeric BM.

Quantitative comparison and evaluation of software packages for assessment of abdominal adipose tissue distribution by magnetic resonance imaging.

Objective: To examine five available software packages for the assessment of abdominal adipose tissue with magnetic resonance imaging, compare their features and assess the reliability of measurement results.

Design: Feature evaluation and test-retest reliability of softwares (NIHImage, SliceOmatic, Analyze, HippoFat and EasyVision) used in manual, semi-automated or automated segmentation of abdominal adipose tissue.

Subjects: A random sample of 15 obese adults with type 2 diabetes.

Differential line broadening in MAS solid-state NMR due to dynamic interference.

Many MAS (magic angle spinning) solid-state NMR investigations of biologically relevant protein samples are hampered by poor resolution, particularly in the 15N chemical shift dimension. We show that dynamics in the nanosecond-microsecond time scale in solid-state samples can induce significant line broadening of 15N resonances in solid-state NMR experiments. Averaging of 15NH(alpha/beta) multiplet components due to 1H decoupling induces effective relaxation of the 15N coherence in case the N-H spin pair undergoes significant motion.

Alcoholism in women: is it different in onset and outcome compared to men?

Onset and course of alcohol dependence show gender related differences (telescoping effect) suggesting that women are more vulnerable to chronic alcohol consumption. This raises the question whether the differences are associated with a different treatment outcome as well. We hypothesized, that alcohol dependent women with a telescoping course show a less favourable treatment outcome compared to men.

[Nicotine dependence as comorbidity of alcohol dependence--epidemiology, etiology and therapy].

There is a high association between alcohol and nicotine dependence. Compared to one particular dependence, associated nicotine and alcohol dependence are more severe and the course is more unfavourable for each dependence. This also applies to the sequels of dependence regarding physical health and cognitive functions.

Endoplasmic reticulum stress, hepatocyte CD1d and NKT cell abnormalities in murine fatty livers.

The liver regulates lipid homeostasis and is enriched with natural killer T (NKT) cells that respond to lipid antigens. Optimal maturation and activation of NKT cells requires their interaction with lipid antigens that are presented by cluster of differentiation-1 (CD-1) molecules on antigen-presenting cells. Hepatocytes express CD1d and present lipid antigens to NKT cells.

Backbone and sidechain 1H, 13C and 15N resonance assignments of the RGS domain from human RGS14.

We have assigned 1H, 13C and 15N resonances of the RGS domain from the human RGS14 protein, a multi-domain member of the RGS (Regulators of G-protein signalling) family of proteins, important in the down-regulation of specific G-protein signalling pathways.