Liver

Mitochondrial DNA depletion syndromes (MDSs) form a group of autosomal recessive disorders characterized by profoundly decreased mitochondrial DNA copy numbers in affected tissues. Three main clinical presentations are known: myopathic, encephalomyopathic and hepatocerebral. The first is associated with mutations in thymidine kinase 2 (TK2) and p53-induced ribonucleotide reductase B subunit (RRM2B); the second with mutations in succinate synthase A (SUCLA2) and B (SUCLG1); the third with mutations in Twinkle (PEO1), pol-γA (POLG1), deoxyguanosine kinase (DGUOK) and MPV17 (MPV17). In this work, we review the MDS-associated phenotypes and present our own experience of 32 MDS patients, with the aim of defining the mutation frequency of the known genes, the clinical spectrum of the diseases, and the genotype–phenotype correlations. Five of our patients carried previously unreported mutations in one of the eight MDS genes.

Arsenic is one of the most common metalloid contaminants in groundwater and it has both acute and chronic toxicity affecting multiple organs. Details of the mechanism of arsenic toxicity are still lacking and profile studies at metabolic level are very limited. Using gas chromatography coupled with mass spectroscopy (GC/MS), we first generated metabolomic profiles from the livers of arsenic-treated zebrafish and identified 34 significantly altered metabolite peaks as potential markers, including four prominent ones: cholic acid, glycylglycine, glycine and hypotaurine. Combined results from GC/MS, histological examination and pathway analyses suggested a series of alterations, including apoptosis, glycogenolysis, changes in amino acid metabolism and fatty acid composition, accumulation of bile acids and fats, and disturbance in glycolysis related energy metabolism. The alterations in glycolysis partially resemble Warburg effect commonly observed in many cancer cells. However, cellula...

Hepatocarcinogenesis is under polygenic control. We analyzed gene expression patterns of dysplastic liver nodules (DNs) and hepatocellular carcinomas (HCCs) chemically-induced in F344 and BN rats, respectively susceptible and resistant to hepatocarcinogenesis. Expression profiles were performed by microarray and validated by quantitative RT-PCR and Western blot. Cluster analysis revealed two distinctive gene expression patterns, the first of which included normal liver of both strains and BN nodules, and the second one F344 nodules and HCC of both strains. We identified a signature predicting DN and HCC progression, characterized by highest expression of oncosuppressors Csmd1, Dmbt1, Dusp1, and Gnmt, in DNs, and Bhmt, Dmbt1, Dusp1, Gadd45g, Gnmt, Napsa, Pp2ca, and Ptpn13 in HCCs of resistant rats. Integrated gene expression data revealed highest expression of proliferation-related CTGF, c-MYC, and PCNA, and lowest expression of BHMT, DMBT1, DUSP1, GADD45g, and GNMT, in more aggressi...

To assess the effectiveness of the current UK clinical practice in reducing hepatic fat (IHCL). Whole body MRI and (1)H MRS were obtained, before and after 6 mo nutritional counselling, from liver, soleus and tibialis muscles in 10 subjects with non-alcoholic fatty liver disease (NAFLD). A 500 Kcal-restricted diet resulted in an average weight loss of 4% (-3.4 kg,) accompanied by significant reductions in most adipose tissue (AT) depots, including subcutaneous (-9.9%), abdominal subcutaneous (-10.2%) and intra-abdominal-AT (-11.4%). Intramyocellular lipids (IMCL) were significantly reduced in the tibialis muscle (-28.2%). Decreases in both IHCL (-39.9%) and soleus IMCL (-12.2%) content were also observed, although these were not significant. Several individuals showed dramatic decreases in IHCL, while others paradoxically showed increases in IHCL content. Changes in body composition were accompanied by improvements in certain liver function tests: serum aspartate aminotransferase (A...

Summary Cobalt is natural element found throughout the environment. Cobalt is an essential trace element being an integral part of vitamin B 12 but deficiency of cobalt has not been reported in humans. Cobalt has also been used as treatment for anemia because it stimulates RBC production. The present study was undertaken to study the hepatotoxic effect of cobalt chloride (CoCl 2.6H 2O) in male Wistar rats. Cobalt chloride (100 mg/kg b.wt/day) was administrated orally in rats for 60 days. Administration of cobalt chloride caused a significant increase in the activity of hepatic marker enzymes like serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), alkaline phosphatase and total bilirubin in serum. The level of serum total protein was also decreased. There was significant increase in the lipid peroxidation (TBARs) and decline in total glutathione, ascorbic acid, glycogen, protein and cholesterol in liver of treated rats as compared to contr...

BACKGROUND/AIMS: BSEP, MRP2, and MDR3 are major hepatic canalicular transporters mediating bile secretion. Their expression in human liver during development has not been reported. METHODS: Human liver samples from fetus at gestational age 14–20 weeks, ...

A 24-h pretreatment of mice with diphtheria and tetanus toxoids and whole-cell pertussis vaccines depressed liver cytochrome P-450 and therefore prolonged hexobarbital-induced sleeping time in mice. The depression of liver drug metabolism by a cellular vaccine containing a mutated pertussis toxin was less marked than that induced by the wild-type vaccines, indicating that the mutated vaccine might have lower toxicity in this regard. The wild-type vaccines decreased microsomal P-450 levels by 50%, while the mutated whole-cell vaccine had a less marked effect (a decrease of 30%), paralleling the results obtained in sleeping time experiments. Furthermore, an acellular mutated vaccine did not affect liver drug metabolism, indicating a role of the whole bacterial cell in this side effect. All the cellular vaccines studied induced high serum interleukin-6 levels; on the other hand, the acellular mutated vaccine induced very low interleukin-6 levels, indicating that the whole bacterial cel...

1. Some studies of cyclophosphamide (CP) and its metabolite acrolein in chick embryo liver were carried out in order to investigate the mechanism of the porphyrinogenic action of CP. 2. In vitro and in vivo studies revealed that CP induced but did not activate delta-aminolaevulinic acid (ALA) synthase. 3. Pretreatments with phenobarbital (PB) or SKF-525A did not modify ALA-synthase induction produced by CP. 4. Acrolein administration neither induced ALA-synthase activity nor increased cytochrome P-450 content or led to hepatic porphyrin accumulation. 5. Time course induction of cytochrome P-450 content after administration of CP or PB was similar. 6. The results obtained would indicate that CP is a strong inducer of both ALA-synthase activity and microsomal cytochrome P-450 content in liver of 17 day-old chick embryos and that its porphyrinogenic activity is not mediated by its metabolite acrolein.

Our recent study has shown that beetroot juice protects against N-nitrosodimethylamine (NDEA)-induced liver injury and increases the activity of phase II enzymes, suggesting the activation of the nuclear factor erythroid-2-related factor 2 (Nrf2)–antioxidant response element (ARE) pathway. The aim of the present study was to further explore the mechanism of the activity of beetroot by evaluating the cytoprotective effects of its major component. The influence of betanin (BET) on the activation of Nrf2 and the expression of GSTA, GSTP, GSTM, GSTT, NQO1 and HO-1 was assessed in two hepatic cell lines: non-tumour THLE-2 and hepatoma-derived HepG2 cell lines. The level of the tumour suppressor p53 in both cell lines and the methylation of GSTP in HepG2 cells were also evaluated. Treatment of both cell lines with 2, 10 and 20 μm of BET resulted in the translocation of Nrf2 from the cytosol to the nucleus. The mRNA and nuclear protein levels of Nrf2 and the binding of Nrf2 to ARE sequence...

Deep-seated tumors can be treated by minimally invasive interstitial ultrasound thermal therapy. A miniature transducer emitting high-intensity acoustic waves is placed in contact with the targeted area to induce local thermal necrosis. Accurate positioning of the probe and treatment monitoring must be achieved for the technique to be effective. A piezocomposite technology was used for obtaining both high-quality imaging and effective treatment with the same transducer. Prototypes were designed and built to be compatible with an endoscopic approach for treating cholangiocarcinomas in the biliary ducts. The transducer had dimensions of 2.5 x 7.5 mm(2), it was cylindrically focused at 10 mm and it was operated at a center frequency of 11 MHz. Transducer efficiency was measured at 71%, and the impulse response corresponded to an axial resolution of 0.2 mm. In-vitro tests were conducted on samples of pig liver in which lesions up to 10 mm in depth were induced. B-mode images were obtain...

An outbreak of acute liver failure occurred at a dialysis center in Caruaru, Brazil (8 degrees 17'S, 35 degrees 58'W), 134 km from Recife, the state capital of Pernambuco. At the clinic, 116 (89%) of 131 patients experienced visual disturbances, nausea, and vomiting ...

Xenopus liver contains a protein inhibitor of glucokinase that, in contrast to the mammalian regulatory protein of glucokinase, is insensitive to fructose 6-phosphate and fructose 1-phosphate [Vandercammen A. & Van Schaftingen, E. (1993) Biochem. J. 294, 551-556]. The purpose of this work was to compare the primary structure and other properties of this Xenopus protein with those of its rat liver counterpart. A Xenopus laevis liver cDNA library was screened using the cDNA encoding the rat liver regulatory protein as a probe. The cloned cDNA was 2534 bp long and encoded a 619-amino-acid protein with a molecular mass of 68695 Da and 57% identity with the rat liver regulatory protein. This identity was only about 30% in an internal region (amino acids 349-381) and in the 70 carboxy terminal-residues. The Xenopus cDNA was expressed in Escherichia coli and the recombinant regulatory protein was purified to near homogeneity and found to have the same size, reactivity to antibodies and eff...

Multiorgan failure including liver dysfunction is a common finding in sickle cell anemia (SCA) patients, the cause of which is multifactorial with advancing age said to be a major determinant. There is a paucity of data on liver function among SCA patients in relation to age in northern Nigerian hospitals, including Ahmadu Bello University Teaching Hospital (ABUTH), Zaria. This study was to assess the biochemical liver function tests (LFTs) as they relate to age among SCA patients in steady state, with a view to improving the overall monitoring of these patients. This study was carried out in ABUTH, Zaria, Northern Nigeria. LFTs were carried out in 100 SCA and 100 apparently healthy participants (controls). The SCA group was made up of fifty adults and fifty children diagnosed of SCA, whereas the control group was made up of fifty adults and fifty children who were apparently healthy and had hemoglobin AA. Paired two-tailed Student's t-test for matched samples and Pearson's ...