DNA methylation markers for diagnosis and prognosis of common cancers

PubMed Central

Hao, Xiaoke; Luo, Huiyan; Krawczyk, Michal; Wei, Wei; Wang, Wenqiu; Wang, Juan; Flagg, Ken; Hou, Jiayi; Zhang, Heng; Yi, Shaohua; Jafari, Maryam; Lin, Danni; Chung, Christopher; Caughey, Bennett A.; Li, Gen; Dhar, Debanjan; Shi, William; Zheng, Lianghong; Hou, Rui; Zhu, Jie; Zhao, Liang; Fu, Xin; Zhang, Edward; Zhang, Charlotte; Zhu, Jian-Kang; Karin, Michael; Xu, Rui-Hua; Zhang, Kang

2017-01-01

The ability to identify a specific cancer using minimally invasive biopsy holds great promise for improving the diagnosis, treatment selection, and prediction of prognosis in cancer. Using whole-genome methylation data from The Cancer Genome Atlas (TCGA) and machine learning methods, we evaluated the utility of DNA methylation for differentiating tumor tissue and normal tissue for four common cancers (breast, colon, liver, and lung). We identified cancer markers in a training cohort of 1,619 tumor samples and 173 matched adjacent normal tissue samples. We replicated our findings in a separate TCGA cohort of 791 tumor samples and 93 matched adjacent normal tissue samples, as well as an independent Chinese cohort of 394 tumor samples and 324 matched adjacent normal tissue samples. The DNA methylation analysis could predict cancer versus normal tissue with more than 95% accuracy in these three cohorts, demonstrating accuracy comparable to typical diagnostic methods. This analysis also correctly identified 29 of 30 colorectal cancer metastases to the liver and 32 of 34 colorectal cancer metastases to the lung. We also found that methylation patterns can predict prognosis and survival. We correlated differential methylation of CpG sites predictive of cancer with expression of associated genes known to be important in cancer biology, showing decreased expression with increased methylation, as expected. We verified gene expression profiles in a mouse model of hepatocellular carcinoma. Taken together, these findings demonstrate the utility of methylation biomarkers for the molecular characterization of cancer, with implications for diagnosis and prognosis. PMID:28652331

Clinical significance of CD44 expression in children with hepatoblastoma.

PubMed

Cai, H-Y; Yu, B; Feng, Z-C; Qi, X; Wei, X-J

2015-10-27

The aim of this study was to investigate the expression of CD44 and its clinical significance in children suffering from hepatoblastoma (HB). CD44 expression was detected with immunohistochemistry staining in 30 samples from hepatoblastoma children and 10 normal liver tissue samples from normal children. The data obtained was statistically analyzed using the chi-square test, using the SPSS (v.11.0) software. The rate of CD44 expression was significantly higher (66.7%) in hepatoblastoma tissues than in normal liver tissues (χ(2) = 4.848, P < 0.05). The rate of CD44 expression was significantly higher in children with stage III or IV hepatoblastoma (83.3%) than that in children with stage I and II hepatoblastoma (χ(2) ＝ 5.625, P < 0.05) (41.7%). Therefore, CD44 expression might play an important role in the pathogenesis, progression, and prognosis of HB in children.

The impact of longitudinal intestinal lengthening and tailoring on liver function in short bowel syndrome.

PubMed

Reinshagen, K; Zahn, K; Buch, C von; Zoeller, M; Hagl, C I; Ali, M; Waag, K-L

2008-08-01

Short bowel syndrome is a functional or anatomic loss of major parts of the small bowel leading to severe malnutrition. The limiting factor for the survival of these patients remains parenteral nutrition-related liver damage leading to end-stage liver failure. Longitudinal intestinal lengthening and tailoring (LILT) has been proven to enhance peristalsis, to decrease bacterial overgrowth and to extend the mucosal contact time for the absorption of nutrients. The aim of this study was to show the impact of LILT on the development of parenteral nutrition-related liver damage. A cohort of 55 patients with short bowel syndrome managed with LILT in our institution between 1987 and 2007 was retrospectively reviewed. LILT was performed at a mean age of 24 months (range 4 - 150 months). Mean follow-up time was 83.76 months (range 5 - 240 months). We obtained reliable data from 31 patients with regard to liver enzymes and function parameters in blood samples before LILT and at the present time. Liver biopsy was performed in 14 patients prior to LILT. Liver enzymes ALAT (mean 121 U/l), ASAT (mean 166 U/l) and bilirubin (mean 2.49 mg/dl) were elevated preoperatively in 27/31 children. After the lengthening procedure, ALAT (mean 50 U/l), ASAT (mean 63 U/l) and bilirubin (mean 1.059 mg/dl) normalized except in 5 of 8 patients who could not be weaned from parenteral nutrition after LILT. Liver function parameters such as the international normal ratio (INR) were slightly elevated in 5/31 patients. Albumin was generally low, probably due to parenteral nutrition. Liver biopsy was performed in 14 patients preoperatively, showing 4 patients with low-grade, 6 patients with intermediate and 4 patients with high-grade fibrosis. End-stage liver disease with cirrhosis was an exclusion criterion for LILT. All patients with liver fibrosis showed a normalization of liver enzymes when they were weaned from parenteral nutrition. But patients with higher grade liver fibrosis tend to develop more complications perioperatively. After LILT, all patients with liver fibrosis who could be weaned from parenteral nutrition showed a normalization of liver enzymes. Preoperative liver biopsy is mandatory in order to differentiate reversible liver fibrosis from end-stage liver disease. A higher grade of liver fibrosis and elevated INR has been shown to be a sensitive parameter for peri- and postoperative complications.

Osteoactivin expressed during cirrhosis development in rats fed a choline-deficient, L-amino acid-defined diet, accelerates motility of hepatoma cells.

PubMed

Onaga, Masaaki; Ido, Akio; Hasuike, Satoru; Uto, Hirofumi; Moriuchi, Akihiro; Nagata, Kenji; Hori, Takeshi; Hayash, Katsuhiro; Tsubouchi, Hirohito

2003-11-01

Hepatocellular carcinoma (HCC) is closely associated with chronic liver diseases, particularly cirrhosis. However, the genes involved in hepatocarcinogenesis in the context of developing cirrhosis remain unknown. This study aims to identify genes associated with early cirrhosis-associated hepatocarcinogenesis. We examined genes differentially expressed between the livers of normal rats and rats fed a choline-deficient, L-amino acid-defined (CDAA) diet using suppression subtractive hybridization. We examined both the expression in the liver and HCC tissues of osteoactivin (OA), isolated in this screen, and its effect on invasiveness and metastasis. OA mRNA was strongly expressed in the livers of rats fed the CDAA diet for 1-3 months. Moderate expression was sustained for 18 months. OA overexpression increased the invasiveness and metastasis of rat hepatoma cells in vitro and in vivo. In humans, OA expression was not detectable in normal liver tissues. While OA transcripts were detectable in cirrhotic nontumorous liver tissues surrounding HCCs, the majority of HCC tissue samples exhibited higher levels of OA expression than the surrounding normal tissue. These results indicate that OA is a novel factor involved in the progression of HCC via stimulation of tumor invasiveness and metastatic potential.

Miki (Mitotic Kinetics Regulator) Immunoexpression in Normal Liver, Cirrhotic Areas and Hepatocellular Carcinomas: a Preliminary Study with Clinical Relevance.

PubMed

Fernández-Vega, Iván; Santos-Juanes, Jorge; Camacho-Urkaray, Emma; Lorente-Gea, Laura; García, Beatriz; Gutiérrez-Corres, Francisco Borja; Quirós, Luis M; Guerra-Merino, Isabel; Aguirre, José Javier

2018-02-12

Hepatocellular carcinoma (HCC) is the most common type of primary malignant tumor in the liver. One of the main features of cancer survival is the generalized loss of growth control exhibited by cancer cells, and Miki is a protein related to the immunoglobulin superfamily that plays an important role in mitosis. We aim to study protein expression levels of Miki in non-tumoral liver and 20 HCCs recruited from a Pathology Department. Clinical information was also obtained. A tissue microarray was performed, and immunohistochemical techniques applied to study protein expression levels of Miki. In normal liver, Miki was weakly expressed, showing nuclear staining in the hepatocytes. Cirrhotic areas and HCCs showed a variety of staining patterns. Most HCC samples showed positive expression, with three different staining patterns being discernible: nuclear, cytoplasmic and mixed. Statistical analysis showed a significant association between grade of differentiation, Ki-67 proliferative index, survival rates and staining patterns. This study has revealed the positive expression of Miki in normal liver, cirrhotic areas and HCCs. Three different staining patterns of Miki expression with clinical relevance were noted in HCCs.

Inositol and hepatic lipidosis. I. Effect of inositol supplementation and time from parturition on liver and serum lipids in dairy cattle.

PubMed

Gerloff, B J; Herdt, T H; Wells, W W; Liesman, J S; Emery, R S

1986-06-01

Percutaneous liver biopsies and blood samples were obtained from 80 multiparous dairy cows in nine Michigan herds. Biopsies and samples were obtained serially over the peripartum period. Thirty-nine cows received 17 g of supplemental myoinositol in the diet to test its use as a possible lipotropic substance and 41 received a placebo. Liver biopsies were assayed for triglyceride (TG) and total myoinositol content. Serum was assayed for dextran precipitable cholesterol and non-esterified fatty acids (NEFA). Inositol supplementation had no effect on any of the lipid variables. There was a significant herd effect on liver inositol, serum dextran precipitable cholesterol and NEFA concentrations. Serum NEFA and liver TG concentrations increased in the immediate postpartum period, while dextran precipitable cholesterol decreased. A significant herd X period interaction existed for liver TG and serum dextran precipitable cholesterol concentrations. Liver TG and serum NEFA concentrations were positively correlated. Excessive infiltration of bovine liver with lipid at calving appears to be an exaggerated manifestation of normal metabolic changes.

Bacterial microflora of normal and telangiectatic livers in cattle.

PubMed

Stotland, E I; Edwards, J F; Roussel, A J; Simpson, R B

2001-07-01

To identify potential bacterial pathogens in normal and telangiectatic livers of mature cattle at slaughter and to identify consumer risk associated with hepatic telangiectasia. 50 normal livers and 50 severely telangiectatic livers. Normal and telangiectatic livers were collected at slaughter for aerobic and anaerobic bacterial culture. Isolates were identified, and patterns of isolation were analyzed. Histologic examination of all livers was performed. Human pathogens isolated from normal and telangiectatic livers included Escherichia coli O157:H7 and group-D streptococci. Most livers in both groups contained bacteria in low numbers; however, more normal livers yielded negative culture results. More group-D streptococci were isolated from the right lobes of telangiectatic livers than from the left lobes, and more gram-negative anaerobic bacteria were isolated from left lobes of telangiectatic livers than from right lobes. All telangiectatic lesions were free of fibrosis, active necrotizing processes, and inflammation. The USDA regulation condemning telangiectatic livers is justified insofar as these livers contain more bacteria than normal livers do; however, normal livers contain similar species of microflora. Development of telangiectasia could not be linked to an infectious process. The finding of E coli O157:H7 in bovine livers suggests that information regarding bacterial content of other offal and muscle may identify sources of this and other potential foodborne pathogens and assist in establishing critical control points for the meat industry.

Phase-contrast X-ray computed tomography of non-formalin fixed biological objects

NASA Astrophysics Data System (ADS)

Takeda, Tohoru; Momose, Atsushi; Wu, Jin; Zeniya, Tsutomu; Yu, Quanwen; Thet-Thet-Lwin; Itai, Yuji

2001-07-01

Using a monolithic X-ray interferometer having the view size of 25 mm×25 mm, phase-contrast X-ray CT (PCCT) was performed for non-formalin fixed livers of two normal rats and a rabbit transplanted with VX-2 cancer. PCCT images of liver and cancer lesions resembled well those obtained by formalin fixed samples.

Magnetoacoustic imaging of human liver tumor with magnetic induction

NASA Astrophysics Data System (ADS)

Hu, Gang; Cressman, Erik; He, Bin

2011-01-01

Magnetoacoustic tomography with magnetic induction (MAT-MI) is an imaging technique under development to achieve imaging of electrical impedance contrast in biological tissues with spatial resolution close to ultrasound imaging. However, previously reported MAT-MI experimental results are obtained either from low salinity gel phantoms, or from normal animal tissue samples. In this study, we report the experimental study on the performance of the MAT-MI imaging method for imaging in vitro human liver tumor tissue. The present promising experimental results suggest the feasibility of MAT-MI to image electrical impedance contrast between the cancerous tissue and its surrounding normal tissues.

[Expression profiles of the exosomal miRNAs in the chronic hepatitis B patients with persistently normal ALT].

PubMed

Li, Ronghua; Fu, Xiaoyu; Tang, Yujing; Fu, Lei; Tan, Deming; Ouyang, Yi; Peng, Shifang

2018-05-28

To investigate expression profiles of the plasma exosomal miRNAs of the chronic hepatitis B (CHB) patients with persistently normal alamine aminotransferase (PNALT) for the first time and try to find exosomal miRNAs which could reflect liver inflammation better. 
 Methods: Five CHB patients with liver tissue inflammation grade ≥A2 of PNALT and 5 CHB patients with liver tissue inflammation grade

Profile of Some Trace Elements in the Liver of Camels, Sheep, and Goats in the Sudan

PubMed Central

Ibrahim, Ibrahim Abdullah; Shamat, Ali Mahmoud; Hussien, Mohammed Osman; El Hussein, Abdel Rahim Mohammed

2013-01-01

One hundred camels (Camelus dromedaries) and fifty sheep and goats being adult, male, and apparently healthy field animals were studied to provide data regarding the normal values of some hepatic trace elements. Liver samples were collected during postmortem examination, digested, and analyzed for Cu, Zn, Fe, Co, and Mn using atomic absorption spectrophotometry. The results showed that the differences in mean liver concentrations of Cu, Zn, Fe, and Co between camels, sheep, and goats were statistically significant (P < 0.05). Hepatic Cu, Fe, and Co concentrations were higher in camels than in sheep and goats. All liver samples were adequate for Fe and Co, whereas only camel liver was adequate for Cu. In camels, hepatic Zn concentration was inadequately lower than that in sheep and goats. No difference in Mn concentration was detected between camels, sheep, and goats. All liver samples were inadequate compared to free-ranging herbivores. In camels, significant correlation (r 2 = −0.207, P value = 0.04) was detected between Zn and Co, whereas in sheep significant correlation (r 2 = −0.444, P value = 0.026) was detected between Zn and Mn. No significant correlation between trace elements was detected in goats. PMID:26464909

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vasuri, Francesco; Capizzi, Elisa; Bellavista, Elena

Despite the central role of proteasomes in relevant physiological pathways and pathological processes, this topic is unexpectedly largely unexplored in human liver. Here we present data on the presence of proteasome and immunoproteasome in human livers from normal adults, fetuses and patients affected by major hepatic diseases such as cirrhosis and chronic active hepatitis. Immunohistochemistry for constitutive ({alpha}4 and {beta}1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28{alpha}{beta} regulator, was performed in liver samples from 38 normal subjects, 6 fetuses, 2 pediatric cases, and 19 pathological cases (10 chronic active hepatitis and 9 cirrhosis). The immunohistochemical datamore » have been validated and quantified by Western blotting analysis. The most striking result we found was the concomitant presence in hepatocyte cytoplasm of all healthy subjects, including the pediatric cases, of constitutive proteasome and immunoproteasome subunits, as well as PA28{alpha}{beta}. At variance, immunoproteasome was not present in hepatocytes from fetuses, while a strong cytoplasmic and nuclear positivity for LMP2 and LMP7 was found in pathological samples, directly correlated to the histopathological grade of inflammation. At variance from other organs such as the brain, immunoproteasome is present in livers from normal adult and pediatric cases, in apparent absence of pathological processes, suggesting the presence of a peculiar regulation of the proteasome/immunoproteasome system, likely related to the physiological stimuli derived from the gut microbiota after birth. Other inflammatory stimuli contribute in inducing high levels of immunoproteasome in pathological conditions, where its role deserve further attention.« less

The allele combinations of three loci based on, liver, stomach cancers, hematencephalon, COPD and normal population: A preliminary study.

PubMed

Gai, Liping; Liu, Hui; Cui, Jing-Hui; Yu, Weijian; Ding, Xiao-Dong

2017-03-20

The purpose of this study was to examine the specific allele combinations of three loci connected with the liver cancers, stomach cancers, hematencephalon and patients with chronic obstructive pulmonary disease (COPD) and to explore the feasibility of the research methods. We explored different mathematical methods for statistical analyses to assess the association between the genotype and phenotype. At the same time we still analyses the statistical results of allele combinations of three loci by difference value method and ratio method. All the DNA blood samples were collected from patients with 50 liver cancers, 75 stomach cancers, 50 hematencephalon, 72 COPD and 200 normal populations. All the samples were from Chinese. Alleles from short tandem repeat (STR) loci were determined using the STR Profiler plus PCR amplification kit (15 STR loci). Previous research was based on combinations of single-locus alleles, and combinations of cross-loci (two loci) alleles. Allele combinations of three loci were obtained by computer counting and stronger genetic signal was obtained. The methods of allele combinations of three loci can help to identify the statistically significant differences of allele combinations between liver cancers, stomach cancers, patients with hematencephalon, COPD and the normal population. The probability of illness followed different rules and had apparent specificity. This method can be extended to other diseases and provide reference for early clinical diagnosis. Copyright © 2016. Published by Elsevier B.V.

Adrenal and liver in normal and cld/cld mice synthesize and secrete hepatic lipase, but the lipase is inactive in cld/cld mice.

PubMed

Schultz, C J; Blanchette-Mackie, E J; Scow, R O

2000-02-01

Combined lipase deficiency (cld) is a recessive mutation in mice that causes a severe lack of lipoprotein lipase (LPL) and hepatic lipase (HL) activities, hyperlipemia, and death within 3 days after birth. Earlier studies showed that inactive LPL and HL were synthesized by cld/cld tissues and that LPL synthesized by cld/cld brown adipocytes was retained in their ER. We report here a study of HL in liver, adrenal, and plasma of normal newborn and cld/cld mice. Immunofluorescence studies showed HL was present in extracellular space, but not in cells, in liver and adrenal of both normal and cld/cld mice. When protein secretion was blocked with monensin, HL was retained intracellularly in liver cell cultures and in incubated adrenal tissues of both groups of mice. These findings demonstrated that HL was synthesized and secreted by liver and adrenal cells in normal newborn and cld/cld mice. HL activities in liver, adrenal, and plasma in cld/cld mice were very low, <8% of that in normal newborn mice, indicating that HL synthesized and secreted by cld/cld cells was inactive. Livers of both normal newborn and cld/cld mice synthesized LPL, but the level of LPL activity in cld/cld liver was very low, <9% of that in normal liver. Immunofluorescence studies showed that LPL was present intracellularly in liver of cld/cld mice, indicating that LPL was synthesized but not secreted by cld/cld liver cells. Immunofluorescent LPL was not found in normal newborn liver cells unless the cells were treated with monensin, thus demonstrating that normal liver cells synthesized and secreted LPL. Livers of both groups of mice contained an unidentified alkaline lipase activity which accounted for 34-54% of alkaline lipase activity in normal and 65% of that in cld/cld livers. Our findings indicate that liver and adrenal cells synthesized and secreted HL in both normal newborn and cld/cld mice, but the lipase was inactive in cld/cld mice. That cld/cld liver cells secreted inactive HL while retaining inactive LPL indicates that these closely related lipases were processed differently.

Electrical conductivity measurement of excised human metastatic liver tumours before and after thermal ablation.

PubMed

Haemmerich, Dieter; Schutt, David J; Wright, Andrew W; Webster, John G; Mahvi, David M

2009-05-01

We measured the ex vivo electrical conductivity of eight human metastatic liver tumours and six normal liver tissue samples from six patients using the four electrode method over the frequency range 10 Hz to 1 MHz. In addition, in a single patient we measured the electrical conductivity before and after the thermal ablation of normal and tumour tissue. The average conductivity of tumour tissue was significantly higher than normal tissue over the entire frequency range (from 4.11 versus 0.75 mS cm(-1) at 10 Hz, to 5.33 versus 2.88 mS cm(-1) at 1 MHz). We found no significant correlation between tumour size and measured electrical conductivity. While before ablation tumour tissue had considerably higher conductivity than normal tissue, the two had similar conductivity throughout the frequency range after ablation. Tumour tissue conductivity changed by +25% and -7% at 10 Hz and 1 MHz after ablation (0.23-0.29 at 10 Hz, and 0.43-0.40 at 1 MHz), while normal tissue conductivity increased by +270% and +10% at 10 Hz and 1 MHz (0.09-0.32 at 10 Hz and 0.37-0.41 at 1 MHz). These data can potentially be used to differentiate tumour from normal tissue diagnostically.

Hepatitis C prevalence and the significance of liver enzyme elevations in the insurance population.

PubMed

Stout, R L

1997-01-01

Liver enzyme elevation(s) are a common finding in the insurance applicant population. Hepatitis C infection results in histological and functional changes in the liver with both short and long term changes in serum liver enzyme levels. The prevalence of antibodies to HCV in the general population is estimated to be 4%. This paper reports on the prevalence of antibodies to HCV in the insurance applicant population and their relationship to the liver enzyme(s). Antibodies to HCV are present in 1.8% of a random sampling of insurance applicants. Alanine aminotransferase (ALT) elevations occur in 95.4% of all samples positive for antibodies to HCV. More than half of positive samples (56.7%) have ALT elevations of less than two time the upper range of normal. Antibody prevalence is lowest in samples with single enzyme elevation, 4.2%. In comparison, the prevalence is 16.4% in samples with all three enzymes, ALT, AST, and GGT, elevated. For maximal specificity two immunoassays, configured with different HCV antigens, should be performed sequentially on all positive applicant samples. HCV is the most prevalent, chronic viral infection in the insurance population. HCV prevalence is 40 times HIV prevalence. In an evaluation of enzyme reflex markers ALT was positive for antibodies to HCV 8.6% of the time while identifying 95.4% of HCV antibody positive applicants.

The prognostic significance of lymphatics in colorectal liver metastases.

PubMed

Muralidharan, Vijayaragavan; Nguyen, Linh; Banting, Jonathan; Christophi, Christopher

2014-01-01

Background. Colorectal Cancer (CRC) is the most common form of cancer diagnosed in Australia across both genders. Approximately, 40%-60% of patients with CRC develop metastasis, the liver being the most common site. Almost 70% of CRC mortality can be attributed to the development of liver metastasis. This study examines the pattern and density of lymphatics in colorectal liver metastases (CLM) as predictors of survival following hepatic resection for CLM. Methods. Patient tissue samples were obtained from the Victorian Cancer Biobank. Immunohistochemistry was used to examine the spatial differences in blood and lymphatic vessel densities between different regions within the tumor (CLM) and surrounding host tissue. Lymphatic vessel density (LVD) was assessed as a potential prognostic marker. Results. Patients with low lymphatic vessel density in the tumor centre, tumor periphery, and adjacent normal liver demonstrated a significant disease-free survival advantage compared to patients with high lymphatic vessel density (P = 0.01, P > 0.01, and P = 0.05, resp.). Lymphatic vessel density in the tumor centre and periphery and adjacent normal liver was an accurate predictive marker of disease-free survival (P = 0.05). Conclusion. Lymphatic vessel density in CLM appears to be an accurate predictor of recurrence and disease-free survival.

Vasopressin regulates the growth of the biliary epithelium in polycystic liver disease

PubMed Central

Mancinelli, Romina; Franchitto, Antonio; Glaser, Shannon; Vetuschi, Antonella; Venter, Julie; Sferra, Roberta; Pannarale, Luigi; Olivero, Francesca; Carpino, Guido; Alpini, Gianfranco; Onori, Paolo; Gaudio, Eugenio

2017-01-01

The neurohypophysial hormone arginine vasopressin (AVP) acts by three distinct receptor subtypes: V1a, V1b, and V2. In the liver, AVP is involved in ureogenesis, glycogenolysis, neoglucogenesis and regeneration. No data exist about the presence of AVP in the biliary epithelium. Cholangiocytes are the target cells in a number of animal models of cholestasis, including bile duct ligation (BDL), and in several human pathologies, such as polycystic liver disease characterized by the presence of cysts that bud from the biliary epithelium. In vivo, liver fragments from normal and BDL mice and rats as well as liver samples from normal and ADPKD patients were collected to evaluate: (i) intrahepatic bile duct mass by immunohistochemistry for cytokeratin-19; and (ii) expression of V1a, V1b and V2 by immunohistochemistry, immunofluorescence and real-time PCR. In vitro, small and large mouse cholangiocytes, H69 (non-malignant human cholangiocytes) and LCDE (human cholangiocytes from the cystic epithelium) were stimulated with vasopressin in the absence/presence of AVP antagonists such as OPC-31260 and Tolvaptan, before assessing cellular growth by MTT assay and cAMP levels. Cholangiocytes express V2 receptor that was upregulated following BDL and in ADPKD liver samples. Administration of AVP increased proliferation and cAMP levels of small cholangiocytes and LCDE cells. We found no effect in the proliferation of large mouse cholangiocytes and H69 cells. Increases were blocked by preincubation with the AVP antagonists. These results showed that AVP and its receptors may be important in the modulation of the proliferation rate of the biliary epithelium. PMID:27571215

Effect of hydroalcoholic extract of ginger on the liver of epileptic female rats treated with lamotrigine

PubMed Central

Poorrostami, Ameneh; Farokhi, Farah; Heidari, Reza

2014-01-01

Objective: Lamotrigine is an antiepileptic drug, widely used in the treatment of epilepsy; long-term use of this drug can cause hepatotoxicity. Zingiber officinale Roscoe (ginger) possesses antioxidant properties. In present research, the effect ofhydroalcoholic extract of ginger (HEG) on the liver of lamotrigine-treated epileptic rats was investigated Material and Methods: Forty-eight female Wistar rats were selected and allocated to 8 groups of 6 each. Group 1: Negative controls were treated with normal saline. Group 2: Positive controls were treated with lamotrigine (LTG) (10 mg/kg) daily by gavages for 4 consecutive weeks. Epilepsy was induced in treatment groups by i.p. injection of pentylenetetrazol (PTZ) (40 mg/kg). Group 3: Epileptic group received normal saline (10 ml/kg). Group 4: Epileptic group was treated with LTG (10 mg/kg). Groups 5 and 6: Epileptic groups received HEG (50 and 100 mg/kg). Groups 7 and 8: Epileptic groups received LTG and HEG (50 and 100 mg/kg). At the end of 28 days, blood samples were drawn and their livers were processed for light microscopy. Results: The mean values of TG, CHOL, AST, and ALT activity significantly rose (p<0.01) in groups 2, 3, and 4, while in rats treated with HEG (groups 5, 6, 7, and 8), the levels of liver enzymes significantly decreased (p<0.05) compared with epileptic group treated with lamotrigine (group 4). Histopathological changes of liver samples were comparable with respective control. Conclusion: These results suggest that hydroalcoholic extract of ginger improves liver function in lamotrigine-induced hepatotoxicity. PMID:25068142

Vasopressin regulates the growth of the biliary epithelium in polycystic liver disease.

PubMed

Mancinelli, Romina; Franchitto, Antonio; Glaser, Shannon; Vetuschi, Antonella; Venter, Julie; Sferra, Roberta; Pannarale, Luigi; Olivero, Francesca; Carpino, Guido; Alpini, Gianfranco; Onori, Paolo; Gaudio, Eugenio

2016-11-01

The neurohypophysial hormone arginine vasopressin (AVP) acts by three distinct receptor subtypes: V1a, V1b, and V2. In the liver, AVP is involved in ureogenesis, glycogenolysis, neoglucogenesis and regeneration. No data exist about the presence of AVP in the biliary epithelium. Cholangiocytes are the target cells in a number of animal models of cholestasis, including bile duct ligation (BDL), and in several human pathologies, such as polycystic liver disease characterized by the presence of cysts that bud from the biliary epithelium. In vivo, liver fragments from normal and BDL mice and rats as well as liver samples from normal and ADPKD patients were collected to evaluate: (i) intrahepatic bile duct mass by immunohistochemistry for cytokeratin-19; and (ii) expression of V1a, V1b and V2 by immunohistochemistry, immunofluorescence and real-time PCR. In vitro, small and large mouse cholangiocytes, H69 (non-malignant human cholangiocytes) and LCDE (human cholangiocytes from the cystic epithelium) were stimulated with vasopressin in the absence/presence of AVP antagonists such as OPC-31260 and Tolvaptan, before assessing cellular growth by MTT assay and cAMP levels. Cholangiocytes express V2 receptor that was upregulated following BDL and in ADPKD liver samples. Administration of AVP increased proliferation and cAMP levels of small cholangiocytes and LCDE cells. We found no effect in the proliferation of large mouse cholangiocytes and H69 cells. Increases were blocked by preincubation with the AVP antagonists. These results showed that AVP and its receptors may be important in the modulation of the proliferation rate of the biliary epithelium.

Mesenchymal stem cells: In vivo therapeutic application ameliorates carbon tetrachloride induced liver fibrosis in rats.

PubMed

Raafat, Nermin; Abdel Aal, Sara M; Abdo, Fadia K; El Ghonaimy, Nabila M

2015-11-01

Egypt has the highest prevalence of hepatitis C virus in the world with infection rate up to 60%, for which liver fibrosis or hepatic carcinoma is the final outcome. Stem cell therapy provides a new hope for hepatic repair instead of traditional treatment, liver transplantation, as it is safer, gives long term engraftment and avoid expensive immunosuppressive drugs and unexpected hazardous effects. This work aimed at determining the therapeutic potential of mesenchymal stem cells (MSC) in hepatic repair as a new line of therapy for liver fibrosis. 33 female albino rats were divided into three groups: Group I: 10 rats injected subcutaneously with olive oil, Group II: 13 rats injected with carbon tetrachloride (CCl4) and Group III: 10 rats injected with CCl4 then bone marrow derived MSC from male rats. Blood and liver tissue samples were taken from all rats for biochemical and histological study. Liver functions for group II rats showed significant deterioration in response to CCl4 in addition to significant histological changes in liver lobules and portal areas. Those parameters tend to be normal in MSC-treated group. Group III rats revealed normalized liver function and histological picture. Meanwhile, most of the pathological lesions were still detected in rats of second group. Undifferentiated MSCs have the ability to ameliorate CCl4 induced liver injury in albino rats in terms of liver functions and histological features. So, stem cell therapy can be considered clinically to offer a hope for patients suffering from liver fibrosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Failure to obtain an autoimmune response following cryosurgery to the normal rat liver.

PubMed Central

Townell, N H; Tsantoulas, D; Holborow, E J; Hobbs, K E

1980-01-01

Smooth muscle antibody (SMA) and anti-liver-specific lipoprotein (anti-LSP) responses were investigated following five different freeze thaw regimes to the normal rat liver. The livers were examined histologically for evidence of autoimmune liver disease. No SMA or anti-LSP was found in any animal and on histological examination the unfrozen part of all livers was normal. It is concluded that cryosurgical damage to the liver is unlikely to provoke an autoimmune response. PMID:7460392

Terahertz spectroscopy of liver cirrhosis: investigating the origin of contrast

NASA Astrophysics Data System (ADS)

Sy, Stanley; Huang, Shengyang; Wang, Yi-Xiang J.; Yu, Jun; Ahuja, Anil T.; Zhang, Yuan-ting; Pickwell-MacPherson, Emma

2010-12-01

We have previously demonstrated that terahertz pulsed imaging is able to distinguish between rat tissues from different healthy organs. In this paper we report our measurements of healthy and cirrhotic liver tissues using terahertz reflection spectroscopy. The water content of the fresh tissue samples was also measured in order to investigate the correlations between the terahertz properties, water content, structural changes and cirrhosis. Finally, the samples were fixed in formalin to determine whether water was the sole source of image contrast in this study. We found that the cirrhotic tissue had a higher water content and absorption coefficient than the normal tissue and that even after formalin fixing there were significant differences between the normal and cirrhotic tissues' terahertz properties. Our results show that terahertz pulsed imaging can distinguish between healthy and diseased tissue due to differences in absorption originating from both water content and tissue structure.

A survey of liver pathology in needle biopsies from HBsAg and anti-HBe positive individuals.

PubMed

ter Borg, F; ten Kate, F J; Cuypers, H T; Leentvaar-Kuijpers, A; Oosting, J; Wertheim-van Dillen, P M; Honkoop, P; Rasch, M C; de Man, R A; van Hattum, J; Chamuleau, R A; Tytgat, G N; Jones, E A

2000-07-01

To use laboratory data and liver biopsies, prospectively obtained from hepatitis B surface antigen (HBsAg) and anti hepatitis B e antigen (anti-HBe) positive patients, for the assessment of: (1) the relation between biopsy length/number of portal tracts and sampling error; (2) the relation between the severity of piecemeal necrosis and the new grading terminology (minimal, mild, moderate, and severe chronic hepatitis); and (3) liver pathology, which has not been studied in patients with this specific serological profile. The study group (n = 174) included 104 patients with normal aminotransferase concentrations and no cases with clinically apparent cirrhosis. The specimen length and number of portal tracts were measured at light microscopy examination. Sampling error analysis was related to the discrepancies between aminotransferase concentrations versus histological grade. Detailed histological scorings were undertaken by the reference pathologist and compared with laboratory and hepatitis B virus (HBV) DNA precore sequence data. Sampling error seemed to be a constant feature, even for biopsies > or = 20 mm, but increased dramatically in biopsies < 5 mm long and/or containing less than four portal tracts. Between 25% and 30% of biopsies, graded as "mild" or "moderate" activity showed features of moderate and severe piecemeal necrosis, respectively. Ten per cent of the patients with normal aminotransferase values had stage III-IV hepatic fibrosis, and 20% had piecemeal necrosis. Only cytoplasmic, not nuclear, core antigen expression was a strong predictor of high hepatitis B viraemia. There was no association between precore stop codon mutations, grade/stage of liver disease, and hepatitis B core antigen (HBcAg) expression. The specimen available for light microscopical examination should be > 5 mm long and should contain more than four portal tracts. In addition, the new grading terminology might give the clinician an inappropriately mild impression of the severity of piecemeal necrosis. Furthermore, even in the presence of normal aminotransferase concentrations, considerable liver pathology can be found in 10-20% of HBsAg and anti-HBe positive individuals; such pathology is not associated with the occurrence of precore stop codon mutations.

Cadmium induces histopathological injuries and ultrastructural changes in the liver of freshwater turtle (Chinemys reevesii).

PubMed

Huo, Junfeng; Dong, Aiguo; Wang, Yonghui; Lee, Shaochin; Ma, Cungen; Wang, Lan

2017-11-01

The study investigated the histopathological and ultrastructural lesions of liver of freshwater turtle Chinemys reevesii exposed to Cadmium (Cd). The animals were exposed to 0 mg kg -1 (0.85% normal saline (NS)), 7.5 mg kg -1 , 15 mg kg -1 , 30 mg kg -1 Cd chloride separately by intraperitoneal injection. Liver samples were collected for examination of lesions under light and electronic microscopes. Results showed that liver tissues from Cd -treated animals presented various degrees of histopathological lesions. Liver cells showed swollen, degeneration and necrosis with dose-dependent manner. Under electronic microscope, nucleus, mitochondria and rough endoplasmic reticulum presented various degrees of lesions with dose-dependent manner. In conclusion, Cd has significant toxicity on liver tissue of the freshwater turtle, which occurs in a dose-dependent manner. Copyright © 2017 Elsevier Ltd. All rights reserved.

Reduced lymphoid response to skin allotransplants in cows with hepatic lipidosis.

PubMed

Wentink, G H; van den Ingh, T S; Rutten, V P; Müller, K E; Wensing, T

1999-04-01

The immune responsiveness of cows with hepatic lipidosis (fatty liver) in comparison to control cows with a normal liver fat content was tested by applying skin allotransplants to the skin of the back of cows on day 3 after parturition. Immunoreactivity was determined by semiquantitative counting of the number of infiltrating lymphocytes in the recipient skin adjacent to the allotransplants during a period of 21 days. There were more invading lymphocytes in samples from control cows than there were in samples from cows with hepatic lipidosis. It was concluded that cows with hepatic lipidosis have a reduced lymphoid response to skin allotransplants.

Markers of autoimmune liver diseases in postmenopausal women with osteoporosis

PubMed Central

Demirdal, Umit Secil; Ciftci, Ihsan Hakkı; Kavuncu, Vural

2010-01-01

INTRODUCTION: Osteoporosis is a common complication of chronic liver diseases. However, there is limited information about autoimmune liver diseases as a factor of secondary osteoporosis. Therefore, we aimed to investigate the autoantibodies of autoimmune liver diseases in patients with osteoporosis. METHODS: One hundred fifty female patients with postmenopausal osteoporosis were included. Bone mineral density was measured by dual energy X‐ray absorptiometry. We analysized autoantibodies including antinuclear antibodies, liver membrane antibodies, anti‐liver/kidney microsomal autoantibodies1, liver‐specific protein, anti‐smooth muscle antibodies, and anti‐mitochondrial antibodies by indirect immunofluorescence. Serum was assayed for the levels of aminotransferases. RESULTS: The mean age of the patients was 63,13±8,6 years. The mean values of L1‐L4 T‐scores and femur total T‐scores were ‐3,08±0,58 and ‐1,53±0,81, respectively. Among the 150 patients with osteoporosis, 14 (9.3%) were antinuclear antibodies, four (2.7%) were liver membrane antibodies, three (2.0%) were anti‐liver/kidney microsomal autoantibodies1, and two (1.3%) were liver‐specific protein positive. None of the patients had anti‐mitochondrial antibodies or smooth muscle antibodies positivity. The mean values of levels of aminotransferases were within normal range. CONCLUSIONS: The presence of liver membrane antibodies, liver‐specific protein, and anti‐liver/kidney microsomal autoantibodies1 has permitted us to see that there may be some suspicious clues of autoimmune liver diseases in patients with osteoporosis as a secondary risk factor. On the other hand, there is a need for comprehensive studies with a larger sample size and studies designed to compare the results with a normal population to understand the clinical importance of our findings. PMID:21120296

The absence of obstructive sleep apnea may protect against non-alcoholic fatty liver in patients undergoing bariatric surgery.

PubMed

Corey, Kathleen E; Misdraji, Joseph; Zheng, Hui; Malecki, Kyle M; Kneeman, Jacob; Gelrud, Louis; Chung, Raymond T

2013-01-01

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease worldwide and its progressive form, steatohepatitis, will be the leading indication for liver transplant by 2020. While risk factors for steatohepatitis have been identified, little work has been performed to identify factors protective against NAFLD development. This study sought to identify factors predictive of normal liver histology in a bariatric cohort. Patients undergoing weight loss surgery with liver biopsies at the time of surgery were included. Patients with other causes of chronic liver disease were excluded. One hundred fifty-nine patients were included. Forty-nine patients had normal liver histology and 110 patients had NAFLD. Several previously identified factors associated with normal liver histology were found. Black race was the strongest predictor of the absence of NAFLD with an odds ratio (OR) of 6.8, 95% confidence interval (CI) 2.4-18.9. Low HOMA-IR was also associated with normal histology (OR 1.4, 95% CI 1.03-1.9). In contrast, low HDL was associated with a decreased chance of normal histology (OR 0.38, 95% CI 0.05-0.83). Interestingly, a novel protective factor, the absence of obstructive sleep apnea (OSA) was strongly associated with normal histology (OR 5.6, 95% CI 2.0-16.1). In multivariate regression controlling for BMI, black race, absence of OSA, low HOMA-IR and low ALT independently predicted normal liver histology with an area under the ROC curve of 0.85. Our study confirmed several factors associated with normal liver histology, including black race and identified a novel factor, absence of OSA. Further evaluation of these factors will allow for improved understanding of the pathogenesis of NAFLD.

Analysis of normal and diseased liver tissue using auto-fluorescence and Raman spectroscopy

NASA Astrophysics Data System (ADS)

Li, Xiaozhou; Jia, Chunde; Lin, Junxiu; Kang, Youping

2003-12-01

In this paper, laser induced human serum Raman spectra of liver cancer are measured. The spectra differences in serum from normal people and liver cancer patients are analyzed. For the typical spectrum of normal serum, there are three sharp Raman peaks and relative intensity of Raman peaks excited by 514.5 nm is higher than that excited by 488.0 nm. However, for the Raman spectrum of liver cancer serum there are no peaks or very weak Raman peaks at the same positions. Results from more than two hundred case measurements show that clinical diagnostic accuracy is 92.86%. And then, the liver fibrosis and liver cirrhosis are studied applying the technology of LIF. To liver cirrhosis, the shape of Raman peak is similar to normal and fluorescence spectrum is similar to that of liver cancer from statistic data. The experiment indicates that there is notable fluorescence difference between the abnormal and normal liver tissue and have blue shift in fluorescence peak. These results have important reference values to explore the method of laser spectrum diagnosis.

Distribution of Ca, Fe, Cu and Zn in primary colorectal cancer and secondary colorectal liver metastases

NASA Astrophysics Data System (ADS)

Al-Ebraheem, A.; Mersov, A.; Gurusamy, K.; Farquharson, M. J.

2010-07-01

A microbeam synchrotron X-ray fluorescence (μSRXRF) technique has been used to determine the localization and the relative concentrations of Zn, Cu, Fe and Ca in primary colorectal cancer and secondary colorectal liver metastases. 24 colon and 23 liver samples were examined, all of which were formalin fixed tissues arranged as microarrays of 1.0 mm diameter and 10 μm thickness. The distribution of these metals was compared with light transmission images of adjacent sections that were H and E stained to reveal the location of the cancer cells. Histological details were provided for each sample which enable concentrations of all elements in different tissue types to be compared. In the case of liver, significant differences have been found for all elements when comparing tumour, normal, necrotic, fibrotic, and blood vessel tissues (Kruskal Wallis Test, P<0.0001). The concentrations of all elements have also been found to be significantly different among tumour, necrotic, fibrotic, and mucin tissues in the colon samples (Kruskal Wallis Test, P<0.0001). The concentrations of all elements have been compared between primary colorectal samples and colorectal liver metastases. Concentration of Zn, Cu, Fe and Ca are higher in all types of liver tissues compared to those in the colon tissues. Comparing liver tumour and colon tumour samples, significant differences have been found for all elements (Mann Whitney, P<0.0001). For necrotic tissues, significant increase has been found for Zn, Ca, Cu and Fe (Mann Whitney, P<0.0001 for Fe and Zn, 0.014 for Ca, and 0.001 for Cu). The liver fibrotic levels of Zn, Ca, Cu and Fe were higher than the fibrotic colon areas (independent T test, P=0.007 for Zn and Mann Whitney test P<0.0001 for Cu, Fe and Ca). For the blood vessel tissue, the analysis revealed that the difference was only significant for Fe ( P=0.009) from independent T test.

Mechanistic biomarkers provide early and sensitive detection of acetaminophen-induced acute liver injury at first presentation to hospital

PubMed Central

Antoine, Daniel J; Dear, James W; Lewis, Philip Starkey; Platt, Vivien; Coyle, Judy; Masson, Moyra; Thanacoody, Ruben H; Gray, Alasdair J; Webb, David J; Moggs, Jonathan G; Bateman, D Nicholas; Goldring, Christopher E; Park, B Kevin

2013-01-01

Acetaminophen overdose is a common reason for hospital admission and the most frequent cause of hepatotoxicity in the Western world. Early identification would facilitate patient-individualized treatment strategies. We investigated the potential of a panel of novel biomarkers (with enhanced liver expression or linked to the mechanisms of toxicity) to identify patients with acetaminophen-induced acute liver injury (ALI) at first presentation to the hospital when currently used markers are within the normal range. In the first hospital presentation plasma sample from patients (n = 129), we measured microRNA-122 (miR-122; high liver specificity), high mobility group box-1 (HMGB1; marker of necrosis), full-length and caspase-cleaved keratin-18 (K18; markers of necrosis and apoptosis), and glutamate dehydrogenase (GLDH; marker of mitochondrial dysfunction). Receiver operator characteristic curve analysis and positive/negative predictive values were used to compare sensitivity to report liver injury versus alanine transaminase (ALT) and International Normalized Ratio (INR). In all patients, biomarkers at first presentation significantly correlated with peak ALT or INR. In patients presenting with normal ALT or INR, miR-122, HMGB1, and necrosis K18 identified the development of liver injury (n = 15) or not (n = 84) with a high degree of accuracy and significantly outperformed ALT, INR, and plasma acetaminophen concentration for the prediction of subsequent ALI (n = 11) compared with no ALI (n = 52) in patients presenting within 8 hours of overdose. Conclusion: Elevations in plasma miR-122, HMGB1, and necrosis K18 identified subsequent ALI development in patients on admission to the hospital, soon after acetaminophen overdose, and in patients with ALTs in the normal range. The application of such a biomarker panel could improve the speed of clinical decision-making, both in the treatment of ALI and the design/execution of patient-individualized treatment strategies. PMID:23390034

A qualitative signature for early diagnosis of hepatocellular carcinoma based on relative expression orderings.

PubMed

Ao, Lu; Zhang, Zimei; Guan, Qingzhou; Guo, Yating; Guo, You; Zhang, Jiahui; Lv, Xingwei; Huang, Haiyan; Zhang, Huarong; Wang, Xianlong; Guo, Zheng

2018-04-23

Currently, using biopsy specimens to confirm suspicious liver lesions of early hepatocellular carcinoma are not entirely reliable because of insufficient sampling amount and inaccurate sampling location. It is necessary to develop a signature to aid early hepatocellular carcinoma diagnosis using biopsy specimens even when the sampling location is inaccurate. Based on the within-sample relative expression orderings of gene pairs, we identified a simple qualitative signature to distinguish both hepatocellular carcinoma and adjacent non-tumour tissues from cirrhosis tissues of non-hepatocellular carcinoma patients. A signature consisting of 19 gene pairs was identified in the training data sets and validated in 2 large collections of samples from biopsy and surgical resection specimens. For biopsy specimens, 95.7% of 141 hepatocellular carcinoma tissues and all (100%) of 108 cirrhosis tissues of non-hepatocellular carcinoma patients were correctly classified. Especially, all (100%) of 60 hepatocellular carcinoma adjacent normal tissues and 77.5% of 80 hepatocellular carcinoma adjacent cirrhosis tissues were classified to hepatocellular carcinoma. For surgical resection specimens, 99.7% of 733 hepatocellular carcinoma specimens were correctly classified to hepatocellular carcinoma, while 96.1% of 254 hepatocellular carcinoma adjacent cirrhosis tissues and 95.9% of 538 hepatocellular carcinoma adjacent normal tissues were classified to hepatocellular carcinoma. In contrast, 17.0% of 47 cirrhosis from non-hepatocellular carcinoma patients waiting for liver transplantation were classified to hepatocellular carcinoma, indicating that some patients with long-lasting cirrhosis could have already gained hepatocellular carcinoma characteristics. The signature can distinguish both hepatocellular carcinoma tissues and tumour-adjacent tissues from cirrhosis tissues of non-hepatocellular carcinoma patients even using inaccurately sampled biopsy specimens, which can aid early diagnosis of hepatocellular carcinoma. © 2018 The Authors. Liver International Published by John Wiley & Sons Ltd.

Use of HOMA-IR to diagnose non-alcoholic fatty liver disease: a population-based and inter-laboratory study.

PubMed

Isokuortti, Elina; Zhou, You; Peltonen, Markku; Bugianesi, Elisabetta; Clement, Karine; Bonnefont-Rousselot, Dominique; Lacorte, Jean-Marc; Gastaldelli, Amalia; Schuppan, Detlef; Schattenberg, Jörn M; Hakkarainen, Antti; Lundbom, Nina; Jousilahti, Pekka; Männistö, Satu; Keinänen-Kiukaanniemi, Sirkka; Saltevo, Juha; Anstee, Quentin M; Yki-Järvinen, Hannele

2017-10-01

Recent European guidelines for non-alcoholic fatty liver disease (NAFLD) call for reference values for HOMA-IR. In this study, we aimed to determine: (1) the upper limit of normal HOMA-IR in two population-based cohorts; (2) the HOMA-IR corresponding to NAFLD; (3) the effect of sex and PNPLA3 genotype at rs738409 on HOMA-IR; and (4) inter-laboratory variations in HOMA-IR. We identified healthy individuals in two population-based cohorts (FINRISK 2007 [n = 5024] and the Programme for Prevention of Type 2 Diabetes in Finland [FIN-D2D; n = 2849]) to define the upper 95th percentile of HOMA-IR. Non-obese individuals with normal fasting glucose levels, no excessive alcohol use, no known diseases and no use of any drugs were considered healthy. The optimal HOMA-IR cut-off for NAFLD (liver fat ≥5.56%, based on the Dallas Heart Study) was determined in 368 non-diabetic individuals (35% with NAFLD), whose liver fat was measured using proton magnetic resonance spectroscopy ( 1 H-MRS). Samples from ten individuals were simultaneously analysed for HOMA-IR in seven European laboratories. The upper 95th percentiles of HOMA-IR were 1.9 and 2.0 in healthy individuals in the FINRISK (n = 1167) and FIN-D2D (n = 459) cohorts. Sex or PNPLA3 genotype did not influence these values. The optimal HOMA-IR cut-off for NAFLD was 1.9 (sensitivity 87%, specificity 79%). A HOMA-IR of 2.0 corresponded to normal liver fat (<5.56% on 1 H-MRS) in linear regression analysis. The 2.0 HOMA-IR measured in Helsinki corresponded to 1.3, 1.6, 1.8, 1.8, 2.0 and 2.1 in six other laboratories. The inter-laboratory CV% of HOMA-IR was 25% due to inter-assay variation in insulin (25%) rather than glucose (5%) measurements. The upper limit of HOMA-IR in population-based cohorts closely corresponds to that of normal liver fat. Standardisation of insulin assays would be the first step towards definition of normal values for HOMA-IR.

Ischemia-reperfusion injury in rat fatty liver: role of nutritional status.

PubMed

Caraceni, P; Nardo, B; Domenicali, M; Turi, P; Vici, M; Simoncini, M; De Maria, N; Trevisani, F; Van Thiel, D H; Derenzini, M; Cavallari, A; Bernardi, M

1999-04-01

Fatty livers are more sensitive to the deleterious effects of ischemia-reperfusion than normal livers. Nutritional status greatly modulates this injury in normal livers, but its role in the specific setting of fatty liver is unknown. This study aimed to determine the effect of nutritional status on warm ischemia-reperfusion injury in rat fatty livers. Fed and fasted rats with normal or fatty liver induced by a choline deficient diet underwent 1 hour of lobar ischemia and reperfusion. Rat survival was determined for 7 days. Serum transaminases, liver histology and cell ultrastructure were assessed before and after ischemia, and at 30 minutes, 2 hours, 8 hours, and 24 hours after reperfusion. Survival was also determined in fatty fasted rats supplemented with glucose before surgery. The preischemic hepatic glycogen was measured in all groups. Whereas survival was similar in fasted and fed rats with normal liver (90% vs. 100%), fasting dramatically reduced survival in rats with fatty liver (14% vs. 64%, P <.01). Accordingly, fasting and fatty degeneration had a synergistic effect in exacerbating liver injury. Mitochondrial damage was a predominant feature of ultrastructural hepatocyte injury in fasted fatty livers. Glucose supplementation partially prevented the fasting-induced depletion of glycogen and improved the 7-day rat survival to 45%. These data indicate that rat fatty livers exposed to normothermic ischemia-reperfusion injury are much more sensitive to fasting than histologically normal livers. Because glucose supplementation improves both the hepatic glycogen stores and the rat survival, a nutritional repletion procedure may be part of a treatment strategy aimed to prevent ischemia-reperfusion injury in fatty livers.

[Experimental study of active ingredients group in liver protection from erzhi wan on acute hepatic injury induced by CCl4 in mice].

PubMed

Yan, Bing; Cai, Xiujiang; Yao, Weifeng; Zhang, Li; Huang, Meiyan; Ding, Anwei

2012-05-01

To study the active ingredients in liver protection from Erzhi Wan (AIEP) on acute hepatic injury induced by carbon tetrachloride (CCl4) in mice. Sixty Kunming mice were randomly divided into six groups: the normal group, the model group, bifendate group (150 mg x kg(-1)), high AIEP group (19.8 g x kg(-1)), middle AIEP group (13.2 g x kg(-1)) and low AIEP group (6.6 g x kg(-1)). The treatment groups were orally administered once per day for 7 d separately, whereas the normal and model groups were orally administered with saline. Except normal rats, all the other rats were injected intraperitoneally CCl4 20 mL x kg(-1) once. The rats were sacrificed 16 h after CCl4 administration. Serum and liver samples were collected for analysis. The acute hepatic injury model was prepared by CCl4 injected intraperitoneally. Then, the therapeutic effects of AIEP on the model were evaluated by the activity determination of serum alanine aminotransferase and aspirate aminotransferase (ALT and AST), superoxide dismutase (SOD) and the content of malondialdehyde (MDA) in liver,and the hepatic pathohistological changes following the treatment. The activities of ALT and AST and the MDA content in liver was significantly increased and the activity of SOD was largely inhibited in the animals of modeling group. Following the treatment with AIEP, ALT and AST activities and MDA content were significantly reduced and SOD activity was obviously increased in the mice of treatment group. Furthermore, AIEP could ameliorate the hepatic pathological changes. AIEP have protective effects on acute hepatic injury induced by CCL4 in mice, and are the effect of the liver protecting active sites.

Relationship Between Speed of Sound in and Density of Normal and Diseased Rat Livers

NASA Astrophysics Data System (ADS)

Hachiya, Hiroyuki; Ohtsuki, Shigeo; Tanaka, Motonao

1994-05-01

Speed of sound is an important acoustic parameter for quantitative characterization of living tissues. In this paper, the relationship between speed of sound in and density of rat liver tissues are investigated. The speed of sound was measured by the nondeformable technique based on frequency-time analysis of a 3.5 MHz pulse response. The speed of sound in normal livers varied minimally between individuals and was not related to body weight or age. In liver tissues which were administered CCl4, the speed of sound was lower than the speed of sound in normal tissues. The relationship between speed of sound and density in normal, fatty and cirrhotic livers can be fitted well on the line which is estimated using the immiscible liquid model assuming a mixture of normal liver and fat tissues. For 3.5 MHz ultrasound, it is considered that the speed of sound in fresh liver with fatty degeneration is responsible for the fat content and is not strongly dependent on the degree of fibrosis.

[Liver injury and intervention of compound 912 liquid on it in rats with endotoxemia].

PubMed

Hu, Lan; Zhang, Shu-Wen; Yin, Cheng-Hong

2007-06-01

To investigate the liver injury in model rats with endotoxemia and to observe the protective effect of Compound 912 Liquid on it. Rats were randomly divided into three groups, the endotoxemia model group (EMG, injected by lipoplysaccharides (LPS) peritoneally), the intervention group (IG, treated with Compound 912 Liquid via gastrogavage 1 h before model establishing) and the normal control group (NCG). Blood samples of rats were taken at the time points of the 2nd, 4th, 8th, 12th, 48th, 72nd hour and the 7th day after modeling for measuring liver function, levels of plasmatic endotoxin, tumor necrosis factor alpha (TNF-alpha), interleukin-10 (IL-10). The pathological change of liver was observed using light microscope and electro-transmission microscope. The peak concentration of endotoxin detected at 2 hour after modeling in the IG was significantly lower than that in the EMG (0.358 +/- 0.056 vs 0.685 +/- 0.030), but insignificant difference (P > 0.05) was shown between them in TNF-alpha level. The level of IL-10 continuously rose in IG after treatment, it was still higher than normal level until day 7 (49.096 +/- 4.076 vs 43.454 +/- 5.928, P < 0.05). LPS can induce the increase of serum inflammatory cytokines and anti-inflammatory cytokines in rats to injure liver. Therefore, the inflammatory reaction indicated by LPS may be one of the mechanisms for liver injury. Preventive medication with Compound 912 Liquid showed a significant liver protective effect.

Transient elastographic evaluation in adult subjects without overt liver disease: influence of alanine aminotransferase levels.

PubMed

Kumar, Manoj; Sharma, Praveen; Garg, Hitendra; Kumar, Ramesh; Bhatia, Vikram; Sarin, Shiv K

2011-08-01

  Studies on normal values of liver stiffness (LS) in subjects at "low risk" for liver disease are scant. The aim of the present study was to assess liver stiffness values in the subjects without overt liver disease with normal alanine aminotransferases (ALT) and to determine potential factors, which may influence these values with special reference to newly suggested updated upper limits of normal for ALT.   Liver stiffness measurements were performed in 445 subjects without overt liver disease (mean age, 41.1±13.6; male, 73.5%) and normal liver enzymes.   Mean LS value was 5.10±1.19kPa. LS values were higher in men than in women (5.18±1.67 vs 4.86±1.24kPa, respectively, P=0.008); in subjects with higher body mass index (BMI) category (Normal, overweight and obese subjects; 4.10±0.75, 5.08±0.66, and 6.05±1.28kPa, respectively; P<0.001); in subjects with metabolic syndrome than in those without (5.63±1.37 vs 5.01±1.14kPa, P=0.001); and in subjects with ALT levels more than updated limits of normal compared to subjects with ALT levels less than updated limits of normal (5.68±1.21 vs 4.77±1.05kPa, P<0.001). On multiple linear regression, BMI and ALT was found to be significant predictor of LS.   Liver stiffness values in subjects without overt liver disease with normal ALT are influenced by BMI and ALT levels. Subjects with ALT levels less than updated limits of normal have lower LS values as compared to those with higher levels. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

Hepatocellular carcinoma redirects to ketolysis for progression under nutrition deprivation stress

PubMed Central

Huang, De; Li, Tingting; Wang, Lin; Zhang, Long; Yan, Ronghui; Li, Kui; Xing, Songge; Wu, Gongwei; Hu, Lan; Jia, Weidong; Lin, Sheng-Cai; Dang, Chi V; Song, Libing; Gao, Ping; Zhang, Huafeng

2016-01-01

Cancer cells are known for their capacity to rewire metabolic pathways to support survival and proliferation under various stress conditions. Ketone bodies, though produced in the liver, are not consumed in normal adult liver cells. We find here that ketone catabolism or ketolysis is re-activated in hepatocellular carcinoma (HCC) cells under nutrition deprivation conditions. Mechanistically, 3-oxoacid CoA-transferase 1 (OXCT1), a rate-limiting ketolytic enzyme whose expression is suppressed in normal adult liver tissues, is re-induced by serum starvation-triggered mTORC2-AKT-SP1 signaling in HCC cells. Moreover, we observe that enhanced ketolysis in HCC is critical for repression of AMPK activation and protects HCC cells from excessive autophagy, thereby enhancing tumor growth. Importantly, analysis of clinical HCC samples reveals that increased OXCT1 expression predicts higher patient mortality. Taken together, we uncover here a novel metabolic adaptation by which nutrition-deprived HCC cells employ ketone bodies for energy supply and cancer progression. PMID:27644987

Pharmacological and antioxidant actions of garlic and.or onion in non-alcoholic fatty liver disease (NAFLD) in rats.

PubMed

El-Din, Sayed H Seif; Sabra, Abdel-Nasser A; Hammam, Olfat A; Ebeid, Fatma A; El-Lakkany, Naglaa M

2014-08-01

Non-alcoholic fatty liver disease (NAFLD) includes a broad spectrum of fat-induced liver injury, ranging from mild steatosis to cirrhosis and liver failure. This study investigates the hepatoprotective properties of garlic and onion in NAFLD rat model. Ninety male Sprague-Dawley rats were randomly divided into 9 groups; normal (I), NAFLD induced with high fat diet (HFD; II), NAFLD switched to regular diet (RD; III), NAFLD-HFD or NAFLD-RD treated with garlic (IV, V), onion (VI, VII) or the combined garlic+onion (VIII, IX) respectively. A NAFLD rat model was established by feeding the animals with a high-fat diet for 12 wk. These animals were then treated with garlic or/and onion or vehicle for 8 wk (weeks 13-20) and then killed to obtain serum samples and liver tissues. Liver histology, lipids, parameters of oxidative stress, TNF-α and TGF-β were measured. The liver in NAFLD-HFD showed typical steatosis, accompanied with mild to moderate lobular inflammatory cell infiltration. Serum levels of ALT, AST, ALP, leptin, cholesterol, triglycerides, TNF-α, TGF-β and hepatic MDA' were significantly increased (P < 0.05) compared with normal group. This was accompanied with reduction of hepatic GSH, GR, GPx, GST, SOD and serum adiponectin. These changes were to a less degree in NAFLD-RD group. Combined administration of garlic+onion produced a better and significant decrease in liver steatosis, serum liver enzymes, oxidative markers and lipid peroxidation versus each one alone. In the same time, NAFLD-induced inflammation was also mitigated via reduction of TNF-α and TGF-β. In addition, these results were better in the group IX versus group VIII.

Doxorubicin coupled to lactosaminated albumin: Effects on rats with liver fibrosis and cirrhosis.

PubMed

Di Stefano, G; Fiume, L; Domenicali, M; Busi, C; Chieco, P; Kratz, F; Lanza, M; Mattioli, A; Pariali, M; Bernardi, M

2006-06-01

The conjugate of doxorubicin with lactosaminated human albumin has the potential of increasing the doxorubicin efficacy in the treatment of hepatocellular carcinomas expressing the asialoglycoprotein receptor. However, coupled doxorubicin also accumulates in the liver, which might damage hepatocytes. To verify whether coupled doxorubicin impairs liver function in rats with liver fibrosis and cirrhosis. Coupled doxorubicin was administered using the same schedule which exerted an antineoplastic effect on rat hepatocellular carcinomas (4-weekly injections of doxorubicin at 1 microg/g). Liver fibrosis/cirrhosis was produced by carbon tetrachloride (CCl4) poisoning. Liver samples were studied histologically. Serum parameters of liver function and viability were determined. In normal rats, administration of coupled doxorubicin neither caused microscopic changes of hepatocytes nor modified serum liver parameters. In rats with fibrosis/cirrhosis, although a selective doxorubicin accumulation within the liver followed coupled doxorubicin administration, the drug did not have a detrimental effect on the histology of the liver and, among serum liver tests, only alanine aminotransferase and aspartate aminotransferase levels were moderately modified. Coupled doxorubicin can be administered to rats with liver fibrosis/cirrhosis without inducing a severe liver damage. If further studies will confirm the efficacy and safety of this compound, coupled doxorubicin therapy may open a new perspective in the treatment of hepatocellular carcinoma.

Global proteomic profiling in multistep hepatocarcinogenesis and identification of PARP1 as a novel molecular marker in hepatocellular carcinoma

PubMed Central

Wang, Jianguo; Xie, Haiyang; Li, Jie; Cao, Jili; Zhou, Lin; Zheng, Shusen

2016-01-01

The more accurate biomarkers have long been desired for hepatocellular carcinoma (HCC). Here, we characterized global large-scale proteomics of multistep hepatocarcinogenesis in an attempt to identify novel biomarkers for HCC. Quantitative data of 37874 sequences and 3017 proteins during hepatocarcinogenesis were obtained in cohort 1 of 75 samples (5 pooled groups: normal livers, hepatitis livers, cirrhotic livers, peritumoral livers, and HCC tissues) by iTRAQ 2D LC-MS/MS. The diagnostic performance of the top six most upregulated proteins in HCC group and HSP70 as reference were subsequently validated in cohort 2 of 114 samples (hepatocarcinogenesis from normal livers to HCC) using immunohistochemistry. Of seven candidate protein markers, PARP1, GS and NDRG1 showed the optimal diagnostic performance for HCC. PARP1, as a novel marker, showed comparable diagnostic performance to that of classic markers GS and NDRG1 in HCC (AUCs = 0.872, 0.856 and 0.792, respectively). A significant higher AUC of 0.945 was achieved when three markers combined. For diagnosis of HCC, the sensitivity and specificity were 88.2% and 81.0% when at least two of the markers were positive. Similar diagnostic values of PARP1, GS and NDRG1 were confirmed by immunohistochemistry in cohort 3 of 180 HCC patients. Further analysis indicated that PARP1 and NDRG1 were associated with some clinicopathological features, and the independent prognostic factors for HCC patients. Overall, global large-scale proteomics on spectrum of multistep hepatocarcinogenesis are obtained. PARP1 is a novel promising diagnostic/prognostic marker for HCC, and the three-marker panel (PARP1, GS and NDRG1) with excellent diagnostic performance for HCC was established. PMID:26883192

Use of transfer learning to detect diffuse degenerative hepatic diseases from ultrasound images in dogs: A methodological study.

PubMed

Banzato, T; Bonsembiante, F; Aresu, L; Gelain, M E; Burti, S; Zotti, A

2018-03-01

The aim of this methodological study was to develop a deep convolutional neural network (DNN) to detect degenerative hepatic disease from ultrasound images of the liver in dogs and to compare the diagnostic accuracy of the newly developed DNN with that of serum biochemistry and cytology on the same samples, using histopathology as a standard. Dogs with suspected hepatic disease that had no prior history of neoplastic disease, no hepatic nodular pathology, no ascites and ultrasonography performed 24h prior to death were included in the study (n=52). Ultrasonography and serum biochemistry were performed as part of the routine clinical evaluation. On the basis of histopathology, dogs were categorised as 'normal' (n=8), or having 'vascular abnormalities'(n=8), or 'inflammatory'(n=0), 'neoplastic' (n=4) or 'degenerative'(n=32) disease; dogs with 'neoplastic' disease were excluded from further analysis. On cytological evaluation, dogs were categorised as 'normal' (n=11), or having 'inflammatory' (n=0), 'neoplastic' (n=4) or 'degenerative' (n=37) disease. Dogs were categorised as having 'degenerative' (n=32) or 'non-degenerative' (n=16) liver disease for analysis due to the limited sample size. The DNN was developed using a transfer learning methodology on a pre-trained neural network that was retrained and fine-tuned to our data set. The resultant DNN had a high diagnostic accuracy for degenerative liver disease (area under the curve 0.91; sensitivity 100%; specificity 82.8%). Cytology and serum biochemical markers (alanine transaminase and aspartate transaminase) had poor diagnostic accuracy in the detection of degenerative liver disease. The DNN outperformed all the other non-invasive diagnostic tests in the detection of degenerative liver disease. Copyright © 2018 Elsevier Ltd. All rights reserved.

A pilot systematic genomic comparison of recurrence risks of hepatitis B virus-associated hepatocellular carcinoma with low- and high-degree liver fibrosis.

PubMed

Yoo, Seungyeul; Wang, Wenhui; Wang, Qin; Fiel, M Isabel; Lee, Eunjee; Hiotis, Spiros P; Zhu, Jun

2017-12-07

Chronic hepatitis B virus (HBV) infection leads to liver fibrosis, which is a major risk factor in hepatocellular carcinoma (HCC) and an independent risk factor of recurrence after HCC tumor resection. The HBV genome can be inserted into the human genome, and chronic inflammation may trigger somatic mutations. However, how HBV integration and other genomic changes contribute to the risk of tumor recurrence with regards to the different degree of liver fibrosis is not clearly understood. We sequenced mRNAs of 21 pairs of tumor and distant non-neoplastic liver tissues of HBV-HCC patients and performed comprehensive genomic analyses of our RNAseq data and public available HBV-HCC sequencing data. We developed a robust pipeline for sensitively identifying HBV integration sites based on sequencing data. Simulations showed that our method outperformed existing methods. Applying it to our data, 374 and 106 HBV host genes were identified in non-neoplastic liver and tumor tissues, respectively. When applying it to other RNA sequencing datasets, consistently more HBV integrations were identified in non-neoplastic liver than in tumor tissues. HBV host genes identified in non-neoplastic liver samples significantly overlapped with known tumor suppressor genes. More significant enrichment of tumor suppressor genes was observed among HBV host genes identified from patients with tumor recurrence, indicating the potential risk of tumor recurrence driven by HBV integration in non-neoplastic liver tissues. We also compared SNPs of each sample with SNPs in a cancer census database and inferred samples' pathogenic SNP loads. Pathogenic SNP loads in non-neoplastic liver tissues were consistently higher than those in normal liver tissues. Additionally, HBV host genes identified in non-neoplastic liver tissues significantly overlapped with pathogenic somatic mutations, suggesting that HBV integration and somatic mutations targeting the same set of genes are important to tumorigenesis. HBV integrations and pathogenic mutations showed distinct patterns between low and high liver fibrosis patients with regards to tumor recurrence. The results suggest that HBV integrations and pathogenic SNPs in non-neoplastic tissues are important for tumorigenesis and different recurrence risk models are needed for patients with low and high degrees of liver fibrosis.

Dielectric properties of human normal, malignant and cirrhotic liver tissue: in vivo and ex vivo measurements from 0.5 to 20 GHz using a precision open-ended coaxial probe.

PubMed

O'Rourke, Ann P; Lazebnik, Mariya; Bertram, John M; Converse, Mark C; Hagness, Susan C; Webster, John G; Mahvi, David M

2007-08-07

Hepatic malignancies have historically been treated with surgical resection. Due to the shortcomings of this technique, there is interest in other, less invasive, treatment modalities, such as microwave hepatic ablation. Crucial to the development of this technique is the accurate knowledge of the dielectric properties of human liver tissue at microwave frequencies. To this end, we characterized the dielectric properties of in vivo and ex vivo normal, malignant and cirrhotic human liver tissues from 0.5 to 20 GHz. Analysis of our data at 915 MHz and 2.45 GHz indicates that the dielectric properties of ex vivo malignant liver tissue are 19 to 30% higher than normal tissue. The differences in the dielectric properties of in vivo malignant and normal liver tissue are not statistically significant (with the exception of effective conductivity at 915 MHz, where malignant tissue properties are 16% higher than normal). Also, the dielectric properties of in vivo normal liver tissue at 915 MHz and 2.45 GHz are 16 to 43% higher than ex vivo. No statistically significant differences were found between the dielectric properties of in vivo and ex vivo malignant tissue (with the exception of effective conductivity at 915 MHz, where malignant tissue properties are 28% higher than normal). We report the one-pole Cole-Cole parameters for ex vivo normal, malignant and cirrhotic liver tissue in this frequency range. We observe that wideband dielectric properties of in vivo liver tissue are different from the wideband dielectric properties of ex vivo liver tissue, and that the in vivo data cannot be represented in terms of a Cole-Cole model. Further work is needed to uncover the mechanisms responsible for the observed wideband trends in the in vivo liver data.

Analysis of LIF-Raman spectroscopy for the diagnosis of normal and liver diseases

NASA Astrophysics Data System (ADS)

Li, Xiaozhou; Yang, Tianyue; Yu, Ting; Sun, Ruomin; Li, Siqi

2011-07-01

In this paper, 514.5nm argon ion laser induced human serum Raman and auto-fluorescence spectra of normal, liver cirrhosis and liver cancer were measured and analyzed. The spectral differences between these three types of serums were observed and given brief explanations. Three parameters α, φ and Δλ were introduced to describe characteristics of each type of spectrum. Experimental results showed that these parameters might be applicable for discrimination of normal, liver cirrhosis and liver cancer, which will provide some reference values to explore the method of laser spectral diagnosis of cancer.

Unique activation of matrix metalloproteinase-9 within human liver metastasis from colorectal cancer.

PubMed Central

Zeng, Z. S.; Guillem, J. G.

1998-01-01

Experimental in vitro and animal data support an important role for matrix metalloproteinases (MMPs) in cancer invasion and metastasis via proteolytic degradation of the extracellular matrix (ECM). Our previous data have shown that MMP-9 mRNA is localized to the interface between liver metastasis and normal liver tissue, indicating that MMP-9 may play an important role in liver metastasis formation. In the present study, we analysed the cellular enzymatic expression of MMP-9 in 18 human colorectal cancer (CRC) liver metastasis specimens by enzyme-linked immunosorbent assay (ELISA) and zymography. ELISA analysis reveals that the latent form of MMP-9 is present in both liver metastasis and paired adjacent normal liver tissue. The mean level of the latent form of MMP-9 is 580+/-270 ng per mg total tissue protein (mean+/-s.e.) in liver metastasis vs 220+/-90 in normal liver tissue. However, this difference is not significantly different (P = 0.26). Using gelatin zymography, the 92-kDa band representative of the latent form is present in both liver metastasis and normal liver tissue. However, the 82 kDa band, representative of the active form of MMP-9, was seen only in liver metastasis. This was confirmed by Western blot analysis. Our observation of the unique presence of the active form of MMP-9 within liver metastasis suggests that proMMP-9 activation may be a pivotal event during CRC liver metastasis formation. Images Figure 3 Figure 4 PMID:9703281

Effect of Boron Neutron Capture Therapy (BNCT) on Normal Liver Regeneration: Towards a Novel Therapy for Liver Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jorge E. Cardoso; Elisa M. Heber; David W. Nigg

2007-10-01

The “TAORMINA project” developed a new method for Boron Neutron Capture Therapy (BNCT) of human multifocal unresectable liver metastases based on whole liver ex-situ BNCT mediated by boronophenylalanine (BPA), followed by whole liver autograft. This technique involved a high risk, prolonged anhepatic phase. The Roffo Institute liver surgeons (JEC) herein propose a novel technique to pursue ex-situ liver BNCT studies with a drastically lower surgical risk for the patient. The technique would involve, sequentially, ex-situ BNCT of left liver segments II and III, partial liver autograft, and induction of partial atrophy of the untreated right liver. The working hypothesis ismore » that the atrophy of the right, untreated, diseased liver would stimulate regeneration of the left, treated, “cured” liver to yield a healthy liver mass, allowing for the resection of the remaining portion of diseased liver. This technique does not involve an anhepatic phase and would thus pose a drastically lower surgical risk to the patient but requires sine qua non that BNCT should not impair the regenerative capacity of normal hepatocytes. The aim of the present study was to assess the effect of therapeutic doses of BNCT mediated by BPA, GB-10 (Na2 10B10H10) or (GB- 10 + BPA) on normal liver regeneration in the Wistar rat employing partial hepatectomy as a regenerative stimulus. BNCT did not cause alterations in the outcome of normal liver regeneration, regenerated liver function or histology. We provide proof of principle to support the development of a novel, promising BNCT technique for the treatment of liver metastases.« less

Immunohistochemical study of retinol-binding protein in livers of polar bears (Thalarctos maritimus).

PubMed

Heier, A; Gröne, A; Völlm, J; Kübber-Heiss, A; Bacciarini, L N

2003-03-01

Liver tumors of unknown cause have frequently been described in polar bears. Concurrent decrease of vitamin A levels and chronic liver disease are associated with hepatic carcinogenesis in humans. More than 90% of the body's vitamin A is stored in the liver, where it is bound to an intracellular retinol-binding protein (RBP). Therefore, in this retrospective study, RBP was assessed by immunohistochemistry in liver sections of 11 polar bears. Two of these polar bears had hepatocellular carcinoma, four showed other chronic liver changes, and five had normal livers. In normal livers, the cytoplasm stained diffusely positive with intensely staining cytoplasmic granules. RBP staining was evaluated and the abundance of diffuse cytoplasmic staining and intracytoplasmic large granules was determined. All cases with pathologic liver changes had markedly decreased staining intensities for RBP compared with normal livers. The findings of this study suggest that in polar bears, as in humans, vitamin A metabolism may play a role in hepatic carcinogenesis.

Human miRNome profiling in colorectal cancer and liver metastasis development

PubMed Central

Perilli, Lisa; Pizzini, Silvia; Bisognin, Andrea; Mandruzzato, Susanna; Biasiolo, Marta; Facciolli, Arianna; Rossi, Elisabetta; Esposito, Giovanni; Rugge, Massimo; Pilati, Pierluigi; Mocellin, Simone; Nitti, Donato; Bortoluzzi, Stefania; Zanovello, Paola

2014-01-01

Qualitative alterations or abnormal expression of microRNAs (miRNAs) in colorectal cancer has mainly been demonstrated in primary tumors. The miRNA expression profiles in 78 samples from 46 patients were analyzed to identify changes in miRNA expression level among normal colon mucosa, primary tumor and liver metastasis samples. Using this dataset, we describe the interplay of miRNA groups in regulating pathways that are important for tumor development. Here we describe in details the contents and quality controls for the miRNA expression and clinical data associated with the study published by Pizzini and colleagues in the BMC Genomics in 2013 (Pizzini et al., 2013). Data are deposited in GEO database as GSE35834 series. PMID:26484092

Detection of liver cancer and abnormal liver tissue by Raman spectroscopy and fluorescence

NASA Astrophysics Data System (ADS)

Li, Xiaozhou; Ding, Jianhua; Zhang, Xiujun; Lin, Junxiu; Wang, Deli

2005-01-01

In this paper, laser induced human serum Raman spectra of liver cancer are measured. The spectra differences in serum from normal people and liver disease patients are analyzed. For the typical spectrum of normal serum, there are three sharp Raman peaks and relative intensity of Raman peaks excited by 514.5nm is higher than that excited by 488.0nm. For the Raman spectrum of liver cancer serum there are no peaks or very weak Raman peaks at the same positions. Results from more than two hundred case measurements show that clinical diagnostic accuracy is 92.86%. And then, the liver fibrosis and liver cirrhosis are studied applying the technology of LIF. To liver cirrhosis, the shape of Raman peak is similar to normal and fluorescence spectrum is similar to that of liver cancer from statistic data. The experiment indicates that there is notable fluorescence difference between the abnormal and normal liver tissue and have blue shift in fluorescence peak. Except for human serum, we use rats serum for researching either. Compared with results of path al examination, we analyze the spectra of normal cases, hepatic fibrosis and hepatocirrhosis respectively in an attempt to find some difference between them. Red shift of fluorescence peak is observed with disease evolution using 514.5nm excitation of an Ar-ion laser. However, no distinct changes happen with 488.0nm excitation. These results have important reference values to explore the method of laser spectrum diagnosis.

(210)Polonium and (210)lead content of marine birds from Southeastern Brazil.

PubMed

Godoy, José Marcus; Siciliano, Salvatore; de Carvalho, Zenildo Lara; Tavares, Davi C; de Moura, Jaílson Fulgencio; Godoy, Maria Luiza D P

2014-09-01

In this study, we report the (210)Po and (210)Pb concentrations of bone, muscle and liver samples that were obtained from twelve different marine bird species stranded on beaches in the central-north region of Rio de Janeiro State. Both radionuclides were highly concentrated in the liver samples; however, the lowest mean (210)Po/(210)Pb activity ratio (1.3) was observed in bones compared with liver and muscle (16.8 and 13.8, respectively). Among the species that were studied, Fregata magnificens, with a diet based exclusively on fish, had the lowest (210)Pb and (210)Po concentrations and the lowest (210)Po/(210)Pb activity ratio. The (210)Po concentrations in Puffinus spp. liver samples followed a log-normal distribution, with a geometric mean of 300 Bq kg(-1)wet weight. Only two references pertaining to (210)Po in marine birds were found in a Web of Science search of the literature, and each study reported a different concentration value. The values determined in this experiment are consistent with those in one of the previous studies, which also included one of the species studied in this work. No values for (210)Pb in marine birds have been published previously. Copyright © 2014 Elsevier Ltd. All rights reserved.

Computer-aided diagnosis of splenic enlargement using wave pattern of spleen in abdominal CT images

NASA Astrophysics Data System (ADS)

Seong, Won; Cho, June-Sik; Noh, Seung-Moo; Park, Jong Won

2006-03-01

It is known that the spleen accompanied by liver cirrhosis is hypertrophied or enlarged. We have examined a wave pattern at the left boundary of spleen on the abdominal CT images having liver cirrhosis, and found that they are different from those on the images having a normal liver. It is noticed that the abdominal CT images of patient with liver cirrhosis shows strong bending in the wave pattern. In the case of normal liver, the images may also have a wave pattern, but its bends are not strong. Therefore, the total waving area of the spleen with liver cirrhosis is found to be greater than that of the spleen with a normal liver. Moreover, we found that the waves of the spleen from the image with liver cirrhosis have the higher degree of circularity compared to the normal liver case. Based on the two observations above, we propose an automatic method to diagnose splenic enlargement by using the wave pattern of the spleen in abdominal CT images. The proposed automatic method improves the diagnostic performance compared with the conventional process based on the size of spleen.

Distribution of the anticancer drugs doxorubicin, mitoxantrone and topotecan in tumors and normal tissues.

PubMed

Patel, Krupa J; Trédan, Olivier; Tannock, Ian F

2013-07-01

Pharmacokinetic analyses estimate the mean concentration of drug within a given tissue as a function of time, but do not give information about the spatial distribution of drugs within that tissue. Here, we compare the time-dependent spatial distribution of three anticancer drugs within tumors, heart, kidney, liver and brain. Mice bearing various xenografts were treated with doxorubicin, mitoxantrone or topotecan. At various times after injection, tumors and samples of heart, kidney, liver and brain were excised. Within solid tumors, the distribution of doxorubicin, mitoxantrone and topotecan was limited to perivascular regions at 10 min after administration and the distance from blood vessels at which drug intensity fell to half was ~25-75 μm. Although drug distribution improved after 3 and 24 h, there remained a significant decrease in drug fluorescence with increasing distance from tumor blood vessels. Drug distribution was relatively uniform in the heart, kidney and liver with substantially greater perivascular drug uptake than in tumors. There was significantly higher total drug fluorescence in the liver than in tumors after 10 min, 3 and 24 h. Little to no drug fluorescence was observed in the brain. There are marked differences in the spatial distributions of three anticancer drugs within tumor tissue and normal tissues over time, with greater exposure to most normal tissues and limited drug distribution to many cells in tumors. Studies of the spatial distribution of drugs are required to complement pharmacokinetic data in order to better understand and predict drug effects and toxicities.

Biodistribution of charged 17.1A photoimmunoconjugates in a murine model of hepatic metastasis of colorectal cancer

PubMed Central

Hamblin, M R; Governatore, M Del; Rizvi, I; Hasan, T

2000-01-01

Optimizing photodynamic therapy involves attempting to increase both the absolute tumour content of photosensitizer and the selectivity between tumour and surrounding normal tissue. One reason why photodynamic therapy has not been considered suitable for treatment of metastatic tumours in the liver, is the poor selectivity of conventional photosensitizers for tumour compared to normal liver. This report details an alternative approach to increasing this selectivity by the use of antibody-targeted photosensitizers (or photoimmunoconjugates) to target intrahepatic tumours caused by human colorectal cancer cells in the nude mouse, and explores the role of molecular charge on the tumour-targeting efficiency of macromolecules. The murine monoclonal antibody 17.1A (which recognizes an antigen expressed on HT 29 cells) was used to prepare site-specific photoimmunoconjugates with the photosensitizer chlorine6. The conjugates had either a predominant cationic or anionic charge and were injected i.v. into tumour-bearing mice. Biodistribution 3 or 24 h later was measured by extraction of tissue samples and quantitation of chlorine6 content by fluorescence spectroscopy. The photoimmunoconjugates were compared to the polylysine conjugates in an attempt to define the effect of molecular charge as well as antibody targeting. The anionic 17.1A conjugate delivered more than twice as much photosensitizer to the tumour at 3 h than other species (5 times more than the cationic 17.1A conjugate) and had a tumour:normal liver ratio of 2.5. Tumour-to-liver ratios were greater than one for most compounds at 3 h but declined at 24 h. Tumour-to-skin ratios were high (> 38) for all conjugates but not for free chlorine6. Cationic species had a high uptake in the lungs compared to anionic species. The photoimmunoconjugates show an advantage over literature reports of other photosensitizers, which can result in tumour:normal liver ratios of less than 1. © 2000 Cancer Research Campaign http://www.bjcancer.com PMID:11076666

Early outcomes of liver transplants in patients receiving organs from hypernatremic donors.

PubMed

Khosravi, Mohammad Bagher; Firoozifar, Mohammad; Ghaffaripour, Sina; Sahmeddini, Mohammad Ali; Eghbal, Mohammad Hossien

2013-12-01

Uncorrected hypernatremia in organ donors has been associated with poor graft or patient survival during liver transplants. However, recent studies have found no association between the donor serum sodium and transplant outcome. This study sought to show the negative effect donor hypernatremia has on initial liver allograft function. This is the first study to investigate international normalized ratio and renal factors of patients with normal and those with hypernatremic donor livers. This study was conducted at the Shiraz Transplant Research Center in Shiraz, Iran, between May 2009, and July 2011. Four hundred seven consecutive adult orthotopic liver transplants were performed at the University of Shiraz Medical Center. There were 93 donors in the group with hypernatremia with terminal serum sodium of 155 mEq/L or greater (group 1), and 314 with terminal serum sodium less than 155 mEq/L (group 2). Posttransplant data after 5 days showed that aspartate aminotransferase, alanine aminotransferase, international normalized ratio, and kidney function did not differ between the groups. Hypernatremia is the most important complication after brain death. Previous studies have suggested donor hypernatremia results in a greater incidence of early postoperative graft dysfunction in liver transplant and is considered one of the extended criteria donor. However, in recent years, this hypothesis has been questioned. Our study shows no difference between patients' initial results of liver and kidney functioning with normal and hypernatremic donor livers. This is the first study to investigate international normalized ratio as a fundamental factor in defining early allograft dysfunction and renal factors between patients with normal and hypernatremic donor's livers.

Detection of tumor DNA at the margins of colorectal cancer liver metastasis

PubMed Central

Holdhoff, Matthias; Schmidt, Kerstin; Diehl, Frank; Aggrawal, Nishant; Angenendt, Philipp; Romans, Katharine; Edelstein, Daniel L.; Torbenson, Michael; Kinzler, Kenneth W.; Vogelstein, Bert; Choti, Michael A.; Diaz, Luis A.

2012-01-01

Purpose Defining an adequate resection margin of colorectal cancer liver metastases is essential for optimizing surgical technique. We have attempted to evaluate the resection margin through a combination of histopathologic and genetic analyses. Experimental Design We evaluated 88 samples of tumor margins from 12 patients with metastatic colon cancer who each underwent partial hepatectomy of one to six liver metastases. Punch biopsies of surrounding liver tissue were obtained at 4, 8, 12 and 16 mm from the tumor border. DNA from these biopsies was analyzed by a sensitive PCR-based technique, called BEAMing, for mutations of KRAS, PIK3CA, APC, or TP53 identified in the corresponding tumor. Results Mutations were identified in each patient’s resected tumor and used to analyze the 88 samples circumscribing the tumor-normal border. Tumor-specific mutant DNA was detectable in surrounding liver tissue in five of these 88 samples, all within 4 mm of the tumor border. Biopsies that were 8, 12, and 16 mm from the macroscopic visible margin were devoid of detectable mutant tumor DNA as well as of microscopically visible cancer cells. Tumors with a significant radiologic response to chemotherapy were not associated with any increase in mutant tumor DNA in beyond 4 mm of the main tumor. Conclusions Mutant tumor-specific DNA can be detected beyond the visible tumor margin, but never beyond 4 mm, even in patients whose tumors were larger prior to chemotherapy. These data provide a rational basis for determining the extent of surgical excision required in patients undergoing resection of liver metastases. PMID:21531819

Pre-existing Epithelial Diversity in Normal Human Livers: A Tissue-tethered Cytometric Analysis in Portal/Periportal Epithelial Cells

PubMed Central

Isse, Kumiko; Lesniak, Andrew; Grama, Kedar; Maier, John; Specht, Susan; Castillo-Rama, Marcela; Lunz, John; Roysam, Badrinath; Michalopoulos, George; Demetris, Anthony J.

2012-01-01

Routine light microscopy identifies two distinct epithelial cell populations in normal human livers: hepatocytes and biliary epithelial cells (BEC). Considerable epithelial diversity, however, arises during disease states when a variety of hepatocyte-BEC hybrid cells appear. This has been attributed to activation and differentiation of putative hepatic progenitor cells (HPC) residing in the Canals of Hering and/or metaplasia of pre-existing mature epithelial cells. A novel analytic approach consisting of multiplex labeling, high resolution whole slide imaging (WSI), and automated image analysis was used to determine if more complex epithelial cell phenotypes pre-existed in normal adult human livers, which might provide an alternative explanation for disease-induced epithelial diversity. “Virtually digested” WSI enabled quantitative cytometric analyses of individual cells displayed in a variety of formats (e.g. scatter plots) while still tethered to the WSI and tissue structure. We employed biomarkers specifically-associated with mature epithelial forms (HNF4α for hepatocytes, CK19 and HNF1β for BEC) and explored for the presence of cells with hybrid biomarker phenotypes. Results showed abundant hybrid cells in portal bile duct BEC, canals of Hering, and immediate periportal hepatocytes. These bi-potential cells likely serve as a reservoir for the epithelial diversity of ductular reactions, appearance of hepatocytes in bile ducts, and the rapid and fluid transition of BEC to hepatocytes, and vice versa. Conclusion Novel imaging and computational tools enable increased information extraction from tissue samples and quantify the considerable pre-existent hybrid epithelial diversity in normal human liver. This computationally-enabled tissue analysis approach offers much broader potential beyond the results presented here. PMID:23150208

Loss of 5α-Reductase Type 1 Accelerates the Development of Hepatic Steatosis but Protects Against Hepatocellular Carcinoma in Male Mice

PubMed Central

Dowman, Joanna K.; Hopkins, Laurence J.; Reynolds, Gary M.; Armstrong, Matthew J.; Nasiri, Maryam; Nikolaou, Nikolaos; van Houten, E. Leonie A. F.; Visser, Jenny A.; Morgan, Stuart A.; Lavery, Gareth G.; Oprescu, Andrei; Hübscher, Stefan G.; Newsome, Philip N.

2013-01-01

Nonalcoholic fatty liver disease (NAFLD) has been associated with glucocorticoid excess and androgen deficiency, yet in the majority of patients with steatohepatitis, circulating cortisol and androgen levels are normal. The enzyme 5α-reductase (5αR) has a critical role in androgen and glucocorticoid action. We hypothesize that 5αR has an important role in the pathogenesis of steatohepatitis through regulation of intracrine/paracrine hormone availability. Human liver samples from patients with NAFLD and normal donor tissue were used for gene expression and immunohistochemical analysis. NAFLD samples were scored using the Kleiner classification. In addition, 5αR1−/−, 5αR2−/−, and wild-type (WT) mice were fed normal chow or American lifestyle-induced obesity syndrome (ALIOS) diet for 6 or 12 months. Liver histology was graded and staged. Hepatic and circulating free fatty acid and triglyceride levels were quantified, and gene and protein expression was measured by real-time PCR and immunohistochemistry. 5αR1 and -2 were highly expressed in human liver, and 5αR1 protein expression increased with severity of NAFLD. 5αR1−/− (but not 5αR2−/−) mice fed an ALIOS diet developed greater hepatic steatosis than WT mice, and hepatic mRNA expression of genes involved in insulin signaling was decreased. Furthermore, 60% of WT mice developed focal hepatocellular lesions consistent with hepatocellular carcinoma after 12 months of the ALIOS diet, compared with 20% of 5αR2−/− and 0% of 5αR1−/− mice (P < .05). 5αR1 deletion accelerates the development of hepatic steatosis but may protect against the development of NAFLD-related hepatocellular neoplasia and therefore has potential as a therapeutic target. PMID:24080367

Boron neutron capture therapy (BNCT) for the treatment of liver metastases: biodistribution studies of boron compounds in an experimental model.

PubMed

Garabalino, Marcela A; Monti Hughes, Andrea; Molinari, Ana J; Heber, Elisa M; Pozzi, Emiliano C C; Cardoso, Jorge E; Colombo, Lucas L; Nievas, Susana; Nigg, David W; Aromando, Romina F; Itoiz, Maria E; Trivillin, Verónica A; Schwint, Amanda E

2011-03-01

We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of (10)B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studies at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na(2)(10)B(10)H(10)), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3. © Springer-Verlag 2010

Boron Neutron Capture Therapy (BCNT) for the Treatment of Liver Metastases: Biodistribution Studies of Boron Compounds in an Experimental Model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marcela A. Garabalino; Andrea Monti Hughes; Ana J. Molinari

2011-03-01

Abstract We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of 10B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studiesmore » at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na210B10H10), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3.« less

Protective effects of saffron extract and crocin supplementation on fatty liver tissue of high-fat diet-induced obese rats.

PubMed

Mashmoul, Maryam; Azlan, Azrina; Mohtarrudin, Norhafizah; Mohd Yusof, Barakatun Nisak; Khaza'ai, Huzwah; Khoo, Hock Eng; Farzadnia, Mehdi; Boroushaki, Mohammad Taher

2016-10-22

Saffron is the dried stigma of Crocus sativus L. flower which commonly used as a natural remedy to enhance health and even fights disease in the Middle-East and Southeast Asian countries. This study was aimed to investigate protective effect of saffron extract and crocin in fatty liver tissue of high-fat diet induced obese rats. A total of 36 healthy male Sprague Dawley rats were divided into six groups. Two groups served as controls, a normal diet (ND) and a high-fat diet (HFD). The other four groups were each supplemented with saffron extract and crocin at concentrations of 40 and 80 mg/kg body weight/day for 8 weeks. All groups except ND were fed with HFD until end of the study. At baseline, blood sample was collected for determination of levels of hepatic marker enzymes, including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatise and albumin. Liver sample was collected, weighed and stained with haematoxylin and eosin for further histopathological examination. Saffron extract and crocin at concentrations of 40 and 80 mg/kg had dose-dependently alleviated levels of liver enzymes and histopathological changes in diet-induced obese rat model compared to control (HFD group). This study suggested that saffron extract and crocin supplements have hepatoprotective effect against non-alcoholic fatty liver disease and HFD-induced liver damage.

Bioaccumulation and Subchronic Toxicity of 14 nm Gold Nanoparticles in Rats.

PubMed

Rambanapasi, Clinton; Zeevaart, Jan Rijn; Buntting, Hylton; Bester, Cornelius; Kotze, Deon; Hayeshi, Rose; Grobler, Anne

2016-06-10

Colloidal suspensions of 14 nm gold nanoparticles (AuNPs) were repeatedly administered intravenously at three dose levels (0.9, 9 and 90 µg) to male Sprague Dawley rats weekly for 7 weeks, followed by a 14-day washout period. After sacrificing, the amount of gold was quantified in the liver, lungs, spleen, skeleton and carcass using neutron activation analysis (NAA). During the study, pre- and post (24 h) administration blood samples were collected from both the test and control groups, the latter which received an equal injection volume of normal saline. General health indicators were monitored together with markers of kidney and liver damage for acute and subchronic toxicity assessment. Histopathological assessments were done on the heart, kidneys, liver, lungs and spleen to assess any morphological changes as a result of the exposure to AuNPs. The mass measurements of all the groups showed a steady increase with no signs of overt toxicity. The liver had the highest amount of gold (µg) per gram of tissue after 56 days followed by the spleen, lungs, skeleton and carcass. Markers of kidney and liver damage showed similar trends between the pre and post samples within each group and across groups. The histopathological examination also showed no hepatotoxicity and nephrotoxicity. There was accumulation of Au in tissues after repeated dosing, albeit with no observable overt toxicity, kidney or liver damage.

Association between liver failure and hepatic UDP-glucuronosyltransferase activity in dairy cows with follicular cysts.

PubMed

Tanemura, Kouichi; Ohtaki, Tadatoshi; Kuwahara, Yasushi; Tsumagari, Shigehisa

2017-01-20

Uridine 5'-diphospho-glucuronosyltransferase (UGT) liver activity was measured using estradiol-17β as a substrate in dairy cows with follicular cysts. The activity was significantly lower than that in dairy cows with normal estrous cycles (P<0.01). Liver disorders, such as fatty liver and hepatitis, were observed in half cows with follicular cysts, and liver UGT activity was lower than that in cows with normal estrus cycles. In addition, the liver UGT activity was significantly lower in dairy cows with follicular cysts without liver disorders than in dairy cows with normal estrous cycles. Therefore, the cows were divided into those with low, middle and high liver UGT activities, and liver disorder complication rates were investigated. The complication rate was significantly higher in the low- (78.1%) than in the middle- (22.2%) and high-level (8.3%) groups, suggesting that liver disorders are closely associated with the development of follicular cysts in dairy cows and that steroid hormone metabolism is delayed because of reduced liver UGT activity, resulting in follicular cyst formation. We conclude that reduced estradiol-17β glucuronidation in the liver and liver disorders are associated with follicular cyst occurrence in dairy cows.

Association between liver failure and hepatic UDP-glucuronosyltransferase activity in dairy cows with follicular cysts

PubMed Central

TANEMURA, Kouichi; OHTAKI, Tadatoshi; KUWAHARA, Yasushi; TSUMAGARI, Shigehisa

2016-01-01

Uridine 5’-diphospho-glucuronosyltransferase (UGT) liver activity was measured using estradiol-17β as a substrate in dairy cows with follicular cysts. The activity was significantly lower than that in dairy cows with normal estrous cycles (P<0.01). Liver disorders, such as fatty liver and hepatitis, were observed in half cows with follicular cysts, and liver UGT activity was lower than that in cows with normal estrus cycles. In addition, the liver UGT activity was significantly lower in dairy cows with follicular cysts without liver disorders than in dairy cows with normal estrous cycles. Therefore, the cows were divided into those with low, middle and high liver UGT activities, and liver disorder complication rates were investigated. The complication rate was significantly higher in the low- (78.1%) than in the middle- (22.2%) and high-level (8.3%) groups, suggesting that liver disorders are closely associated with the development of follicular cysts in dairy cows and that steroid hormone metabolism is delayed because of reduced liver UGT activity, resulting in follicular cyst formation. We conclude that reduced estradiol-17β glucuronidation in the liver and liver disorders are associated with follicular cyst occurrence in dairy cows. PMID:27666462

[Preliminary study on effective components of Tripterygium wilfordii for liver toxicity based on spectrum-effect correlation analysis].

PubMed

Zhao, Xiao-Mei; Pu, Shi-Biao; Zhao, Qing-Guo; Gong, Man; Wang, Jia-Bo; Ma, Zhi-Jie; Xiao, Xiao-He; Zhao, Kui-Jun

2016-08-01

In this paper, the spectrum-effect correlation analysis method was used to explore the main effective components of Tripterygium wilfordii for liver toxicity, and provide reference for promoting the quality control of T. wilfordii. Chinese medicine T.wilfordii was taken as the study object, and LC-Q-TOF-MS was used to characterize the chemical components in T. wilfordii samples from different areas, and their main components were initially identified after referring to the literature. With the normal human hepatocytes (LO2 cell line)as the carrier, acetaminophen as positive medicine, and cell inhibition rate as testing index, the simple correlation analysis and multivariate linear correlation analysis methods were used to screen the main components of T. wilfordii for liver toxicity. As a result, 10 kinds of main components were identified, and the spectrum-effect correlation analysis showed that triptolide may be the toxic component, which was consistent with previous results of traditional literature. Meanwhile it was found that tripterine and demethylzeylasteral may greatly contribute to liver toxicity in multivariate linear correlation analysis. T. wilfordii samples of different varieties or different origins showed large difference in quality, and the T. wilfordii from southwest China showed lower liver toxicity, while those from Hunan and Anhui province showed higher liver toxicity. This study will provide data support for further rational use of T. wilfordii and research on its liver toxicity ingredients. Copyright© by the Chinese Pharmaceutical Association.

Loss of coxsackie and adenovirus receptor expression in human colorectal cancer: A potential impact on the efficacy of adenovirus-mediated gene therapy in Chinese Han population.

PubMed

Ma, Ying-Yu; Wang, Xiao-Jun; Han, Yong; Li, Gang; Wang, Hui-Ju; Wang, Shi-Bing; Chen, Xiao-Yi; Liu, Fan-Long; He, Xiang-Lei; Tong, Xiang-Min; Mou, Xiao-Zhou

2016-09-01

The coxsackie and adenovirus receptor (CAR) is considered a tumor suppressor and critical factor for the efficacy of therapeutic strategies that employ the adenovirus. However, data on CAR expression levels in colorectal cancer are conflicting and its clinical relevance remains to be elucidated. Immunohistochemistry was performed on tissue microarrays containing 251 pairs of colon cancer and adjacent normal tissue samples from Chinese Han patients to assess the expression levels of CAR. Compared with healthy mucosa, decreased CAR expression (40.6% vs. 95.6%; P<0.001) was observed in colorectal cancer samples. The CAR immunopositivity in tumor tissues was not significantly associated with gender, age, tumor size, differentiation, TNM stage, lymph node metastasis or distant metastasis in patients with colon cancer. However, expression of CAR is present in 83.3% of the tumor tissues from patient with colorectal liver metastasis, which was significantly higher than those without liver metastasis (39.6%; P=0.042). At the plasma membrane, CAR was observed in 29.5% normal mucosa samples, which was significantly higher than in colorectal cancer samples (4.0%; P<0.001). In addition, the survival analysis demonstrated that the expression level of CAR has no association with the prognosis of colorectal cancer. CAR expression was observed to be downregulated in colorectal cancer, and it exerts complex effects during colorectal carcinogenesis, potentially depending on the stage of the cancer development and progression. High CAR expression may promote liver metastasis. With regard to oncolytic therapy, CAR expression analysis should be performed prior to adenoviral oncolytic treatment to stratify Chinese Han patients for treatment.

Native fluorescence characterization of human liver abnormalities

NASA Astrophysics Data System (ADS)

Ganesan, Singaravelu; Madhuri, S.; Aruna, Prakasa R.; Suchitra, S.; Srinivasan, T. G.

1999-05-01

Fluorescence spectroscopy of intrinsic biomolecules has been extensively used in biology and medicine for the past several decades. In the present study, we report the native fluorescence characteristics of blood plasma from normal human subjects and patients with different liver abnormalities such as hepatitis, leptospirosis, jaundice, cirrhosis and liver cell failure. Native fluorescence spectra of blood plasma -- acetone extract were measured at 405 nm excitation. The average spectrum of normal blood plasma has a prominent emission peak around 464 nm whereas in the case of liver diseased subjects, the primary peak is red shifted with respect to normal. In addition, liver diseased cases show distinct secondary emission peak around 615 nm, which may be attributed to the presence of endogenous porphyrins. The red shift of the prominent emission peak with respect to normal is found to be maximum for hepatitis and minimum for cirrhosis whereas the secondary emission peak around 615 nm was found to be more prominent in the case of cirrhosis than the rest. The ratio parameter I465/I615 is found to be statistically significant (p less than 0.001) in discriminating liver abnormalities from normal.

Systematic review of bariatric surgery liver biopsies clarifies the natural history of liver disease in patients with severe obesity.

PubMed

Bedossa, Pierre; Tordjman, Joan; Aron-Wisnewsky, Judith; Poitou, Christine; Oppert, Jean-Michel; Torcivia, Adriana; Bouillot, Jean-Luc; Paradis, Valerie; Ratziu, Vlad; Clément, Karine

2017-09-01

Non-alcoholic fatty liver disease (NAFLD) is a frequent complication of morbid obesity, but its severity varies greatly and thus there is a strong need to better define its natural history in these patients. Liver biopsies were systematically performed in 798 consecutive patients with severe obesity undergoing bariatric surgery. Histology was compared with clinical, biological, anthropometrical and body composition characteristics. Patients with presumably normal liver (n=179, 22%) were significantly younger at bariatric surgery than patients with NAFLD (37.0 vs 44.4 years, p<0.0001). However, both groups showed quite similar obesity duration, since patients with presumably normal liver reported the onset of obesity at a significantly younger age than those with NAFLD (14.8 vs 20.0 year, p<0.0001). The trunk/limb fat mass ratio increased according to liver disease severity (presumably normal liver: 1.00, steatosis: 1.21, non-alcoholic steatohepatitis (NASH): 1.34, p<0.0001), although the total body fat mass decreased (presumably normal liver: 50%, steatosis: 49.1%, NASH: 47.4%, p<0.0001). The volume of subcutaneous adipocytes increased according to severity of liver disease but only in female patients (presumably normal liver: 8543 picolitres, steatosis: 9156 picolitres, NASH: 9996 picolitres). These results suggest that young adults are more prone to store fat in subcutaneous tissue and reach the threshold of bariatric surgery indication before their liver is damaged. A shift of fat storage from subcutaneous to visceral adipose tissue compartment is associated with liver damages. Liver might also be targeted by subcutaneous hypertrophic adipocytes in females since hypertrophic adipocytes are more exposed to lipolysis and to the production of inflammatory mediators. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Liver gene expression profiles of rats treated with clofibric acid: comparison of whole liver and laser capture microdissected liver.

PubMed

Michel, Cécile; Desdouets, Chantal; Sacre-Salem, Béatrice; Gautier, Jean-Charles; Roberts, Ruth; Boitier, Eric

2003-12-01

Clofibric acid (CLO) is a peroxisome proliferator (PP) that acts through the peroxisome proliferator activated receptor alpha, leading to hepatocarcinogenesis in rodents. CLO-induced hepatocarcinogenesis is a multi-step process, first transforming normal liver cells into foci. The combination of laser capture microdissection (LCM) and genomics has the potential to provide expression profiles from such small cell clusters, giving an opportunity to understand the process of cancer development in response to PPs. To our knowledge, this is the first evaluation of the impact of the successive steps of LCM procedure on gene expression profiling by comparing profiles from LCM samples to those obtained with non-microdissected liver samples collected after a 1 month CLO treatment in the rat. We showed that hematoxylin and eosin (H&E) staining and laser microdissection itself do not impact on RNA quality. However, the overall process of the LCM procedure affects the RNA quality, resulting in a bias in the gene profiles. Nonetheless, this bias did not prevent accurate determination of a CLO-specific molecular signature. Thus, gene-profiling analysis of microdissected foci, identified by H&E staining may provide insight into the mechanisms underlying non-genotoxic hepatocarcinogenesis in the rat by allowing identification of specific genes that are regulated by CLO in early pre-neoplastic foci.

[Determination of hydroxyproline in liver tissue by hydrophilic interaction chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry].

PubMed

Liu, Wei; Qi, Shenglan; Xu, Ying; Xiao, Zhun; Fu, Yadong; Chen, Jiamei; Yang, Tao; Liu, Ping

2017-12-08

A method for the determination of hydroxyproline (Hyp) in liver tissue of mice by hydrophilic interaction chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry (HILIC-HRMS) was developed. The liver tissue samples of normal mice and liver fibrosis mice induced by carbon tetrachloride were hydrolyzed by concentrated hydrochloric acid. After filtrated and diluted by solution, the diluent was separated on an Hypersil GOLD HILIC column (100 mm×2.1 mm, 3 μm). Water-acetonitrile (28:72, v/v)were used as the mobile phases with isocratic elution. Finally, the target analytes were detected in positive model by HRMS equipped with an electrospray ionization source. The linear range of hydroxyproline was from 0.78 to 100.00 μg/L with the correlation coefficient ( R 2 ) of 0.9983. The limit of quantification was 0.78 μg/L. By detecting the spiked samples, the recoveries were in the range of 97.4%-100.9% with the relative standard deviations (RSDs) between 1.4% and 2.0%. In addition, comparison of the measurement results by this method and the chloramine T method was proceeded. It was found that the linear correlation between the two methods was very good, and the Pearson correlation coefficient was 0.927. And this method had simpler operation procedure and higher accuracy than chloramine T method. This method can be used for the quick determination of hydroxyproline in liver tissue samples.

Osteopontin regulates the cross-talk between phosphatidylcholine and cholesterol metabolism in mouse liver.

PubMed

Nuñez-Garcia, Maitane; Gomez-Santos, Beatriz; Buqué, Xabier; García-Rodriguez, Juan L; Romero, Marta R; Marin, Jose J G; Arteta, Beatriz; García-Monzón, Carmelo; Castaño, Luis; Syn, Wing-Kin; Fresnedo, Olatz; Aspichueta, Patricia

2017-09-01

Osteopontin (OPN) is involved in different liver pathologies in which metabolic dysregulation is a hallmark. Here, we investigated whether OPN could alter liver, and more specifically hepatocyte, lipid metabolism and the mechanism involved. In mice, lack of OPN enhanced cholesterol 7α-hydroxylase (CYP7A1) levels and promoted loss of phosphatidylcholine (PC) content in liver; in vivo treatment with recombinant (r)OPN caused opposite effects. rOPN directly decreased CYP7A1 levels through activation of focal adhesion kinase-AKT signaling in hepatocytes. PC content was also decreased in OPN-deficient (OPN-KO) hepatocytes in which de novo FA and PC synthesis was lower, whereas cholesterol (CHOL) synthesis was higher, than in WT hepatocytes. In vivo inhibition of cholesterogenesis normalized liver PC content in OPN-KO mice, demonstrating that OPN regulates the cross-talk between liver CHOL and PC metabolism. Matched liver and serum samples showed a positive correlation between serum OPN levels and liver PC and CHOL concentration in nonobese patients with nonalcoholic fatty liver. In conclusion, OPN regulates CYP7A1 levels and the metabolic fate of liver acetyl-CoA as a result of CHOL and PC metabolism interplay. The results suggest that CYP7A1 is a main axis and that serum OPN could disrupt liver PC and CHOL metabolism, contributing to nonalcoholic fatty liver disease progression in nonobese patients.

Fibrosis Progression in Paired Liver Biopsies from HIV/HCV-Coinfected Patients without Prior Treatment of Hepatitis C.

PubMed

Leite, Andréa G B; Duarte, Maria Irma S; Mendes-Correa, Maria Cássia

2015-01-01

Several studies have demonstrated that HIV/hepatitis C virus (HCV)-coinfected patients experience more rapid fibrosis progression. In this study, to estimate the annual rate of direct liver fibrosis progression, we used analyses of paired biopsy samples from HIV/HCV-coinfected patients without prior treatment of hepatitis and assessed the possible association of fibrosis progression with certain clinical variables. We evaluated 30 HIV/HCV-coinfected patients, with no history of prior treatment of hepatitis C, who underwent paired liver biopsies. All patients were under antiretroviral therapy at first and second biopsies. The average annual progression rate was 0.13 fibrosis unit/year, with 36.7% of patients defined as progressors. Liver fibrosis progression was associated with alanine aminotransferase (ALT; P < .001) and aspartate aminotransferase (AST; P < .0340) levels over 3 times the upper limit of normal present at first biopsy. Elevated ALT and AST levels appear to be associated with more accelerated liver fibrosis progression among HIV/HCV-coinfected patients. © The Author(s) 2015.

Visible to near-infrared refractive properties of freshly-excised human-liver tissues: marking hepatic malignancies

PubMed Central

Giannios, Panagiotis; Toutouzas, Konstantinos G.; Matiatou, Maria; Stasinos, Konstantinos; Konstadoulakis, Manousos M.; Zografos, George C.; Moutzouris, Konstantinos

2016-01-01

The refractive index is an optical constant that plays a significant role in the description of light-matter interactions. When it comes to biological media, refraction is understudied despite recent advances in the field of bio-optics. In the present article, we report on the measurement of the refractive properties of freshly excised healthy and cancerous human liver samples, by use of a prism-coupling technique covering the visible and near-infrared spectral range. Novel data on the wavelength-dependent complex refractive index of human liver tissues are presented. The magnitude of the real and imaginary part of the refractive index is correlated with hepatic pathology. Notably, the real index contrast is pointed out as a marker of discrimination between normal liver tissue and hepatic metastases. In view of the current progress in optical biosensor technologies, our findings may be exploited for the development of novel surgical and endoscopic tools. PMID:27297034

Association between macroscopic appearance of liver lesions and liver histology in dogs with splenic hemangiosarcoma: 79 cases (2004-2009).

PubMed

Clendaniel, Daphne C; Sivacolundhu, Ramesh K; Sorenmo, Karin U; Donovan, Taryn A; Turner, Avenelle; Arteaga, Theresa; Bergman, Philip J

2014-01-01

Medical records for 79 dogs with confirmed splenic hemangiosarcoma (HSA) following splenectomy were reviewed for information regarding either the presence or absence of macroscopic liver lesions and the histopathological characteristics of the liver. Only 29 of 58 dogs (50%) with grossly abnormal livers had HSA metastasis. No dogs with grossly normal livers had metastasis detected on liver pathology. Gross lesions in the liver such as multiple nodules, dark-colored nodules, and active bleeding nodules were highly associated with malignancy. For the dogs in this study, performing biopsy in a grossly normal liver was a low-yield procedure in dogs with splenic HSA.

Alcoholic liver disease.

PubMed

Penny, Steven M

2013-01-01

In the United States, approximately 100,000 deaths are attributed to alcohol abuse each year. In 2009, the World Health Organization listed alcohol use as one of the leading causes of the global burden of disease and injury. Alcoholic liver disease, a direct result of chronic alcohol abuse, insidiously destroys the normal functions of the liver. The end result of the disease, cirrhosis, culminates in a dysfunctional and diffusely scarred liver. This article discusses the clinical manifestations, imaging considerations, and treatment of alcoholic liver disease and cirrhosis. Normal liver function, liver hemodynamics, the disease of alcoholism, and the deleterious effects of alcohol also are reviewed.

Disease progression in Chinese chronic hepatitis C patients with persistently normal alanine aminotransaminase levels.

PubMed

Hui, C-K; Zhang, H-Y; Shek, T; Yao, H; Yueng, Y-H; Leung, K-W; Lai, S-T; Lai, J-Y; Leung, N; Lau, G K

2007-06-01

Although chronic hepatitis C virus-infected patients with persistently normal alanine aminotransaminase levels usually have mild liver disease, disease progression can still occur. However, it is uncertain which group of patients is at risk of disease progression. To examine the severity of liver disease on liver biopsy in Chinese patients with persistently normal alanine aminotransaminase levels, and their disease progression over time. Eighty-two patients with persistently normal alanine aminotransaminase levels were followed up longitudinally. The median time of follow-up was 8.1 years. Forty-seven of the 82 patients (57.3%) had a second liver biopsy. At the time of analysis, six of the 82 patients (7.3%) developed decompensated liver cirrhosis. Patients with an initial fibrosis stage F2 or F3 [6/23 (26.1%) vs. 0/59 (0%), P < 0.0001] or inflammatory grade A2 or A3 [5/40 (12.5%) vs. 1/42 (2.4%), P = 0.04] were more likely to develop decompensated liver cirrhosis. On multivariate analysis, initial fibrosis stage F2 or F3 was independently associated with progression to decompensated liver cirrhosis (relative risk 2.3, 95% confidence interval 0.03-2.5, P = 0.02). Chinese chronic hepatitis C virus patients with persistently normal alanine aminotransaminase levels with moderate to severe fibrosis at initial evaluation are more likely to develop decompensated liver cirrhosis.

Living Donor Liver Transplantation Using a Liver Graft With Congenital Intrahepatic Portosystemic Shunt

PubMed Central

Kamei, Hideya; Imai, Hisashi; Onishi, Yasuharu; Sugimoto, Hiroyuki; Suzuki, Kojiro; Ogura, Yasuhiro

2016-01-01

Background Despite of recent development of imaging modalities, congenital intrahepatic portosystemic shunt (IPSS) is rarely diagnosed. Therefore, living donor liver transplantation using a liver graft with IPSS has not been previously published. Materials and Methods We report a 28-year-old male patient with end-stage liver disease secondary to Wilson disease. His 26-year-old brother was a potential living donor, who had an IPSS of 25 mm in diameter at segment 6 as shown by computed tomography. Liver function tests were normal, and blood ammonia concentration was in the upper limit of normal. Results Living donor liver transplantation was uneventfully performed. After surgery, a recipient liver function tests showed a quick recovery, and serum ammonia levels were consistently normal. Although thrombosis inside the IPSS was confirmed by computed tomography on postoperative day 21, this thrombosis disappeared at 3 months posttransplant with anticoagulants. Currently (12 months posttransplant), the patient has fully recovered, and the IPSS is still the same size. Conclusions Based on our experience, liver allografts with IPSS can be accepted as potential liver allografts. PMID:27500240

Liver failure in total artificial heart therapy.

PubMed

Dimitriou, Alexandros Merkourios; Dapunt, Otto; Knez, Igor; Wasler, Andrae; Oberwalder, Peter; Koerfer, Reiner; Tenderich, Gero; Spiliopoulos, Sotirios

2016-07-01

Congestive hepatopathy (CH) and acute liver failure (ALF) are common among biventricular heart failure patients. We sought to evaluate the impact of total artificial heart (TAH) therapy on hepatic function and associated clinical outcomes. A total of 31 patients received a Syncardia Total Artificial Heart. Preoperatively 17 patients exhibited normal liver function or mild hepatic derangements that were clinically insignificant and did not qualify as acute or chronic liver failure, 5 patients exhibited ALF and 9 various hepatic derangements owing to CH. Liver associated mortality and postoperative course of liver values were prospectively documented and retrospectively analyzed. Liver associated mortality in normal liver function, ALF and CH cases was 0%, 20% (P=0.03) and 44.4% (P=0.0008) respectively. 1/17 (5.8%) patients with a normal liver function developed an ALF, 4/5 (80%) patients with an ALF experienced a markedly improvement of hepatic function and 6/9 (66.6%) patients with CH a significant deterioration. TAH therapy results in recovery of hepatic function in ALF cases. Patients with CH prior to surgery form a high risk group with increased liver associated mortality.

[Liver transplantation for the treatment of hyperammonemia due to urea cycle disorder: report of four cases].

PubMed

Zhu, Zhijun; Sun, Liying; Wei, Lin; Qu, Wei; Zeng, Zhigui; Liu, Ying; Zhang, Liang; He, Enhui; Wang, Dong

2015-02-01

To analyze clinical efficacy and prognosis of liver transplantation in children with hyperammonemia caused by urea cycle disorders. A retrospective analysis was performed on the occurrence of disease, operation and the follow-up post liver transplantation in 4 patients with urea cycle disorders who underwent liver transplantation during June 2001 to May 2014. Four girls were diagnosed with ornithine carbamoyl transferase deficiency by genetic test. They had the clinical onset at the age of 1.5 to 3.0 years. Liver transplantation had been performed at their age of 53.9 months, 40.6 months, 40.3 months and 22.8 months, respectively. The grafts of case 1 and case 2 were from left lateral lobe of liver of cadaveric donor, the graft of case 3 was from left lateral lobe of liver of a living donor, the graft of case 4 was a whole liver of a dead child. The liver function of 4 patients gradually returned to normal, blood ammonia levels were normal and restored the normal diet, 4 children were discharged on postoperative 25-30 days. Regular follow-up was done, the liver function, biochemical features and growth status have been followed up for 162.2 months, 124.2 months, 12.0 months and 4.8 months after liver transplantation, respectively. Now, all the four cases are healthy and growth is normal. Liver transplantation is an important way to the patients with severe hyperammonemia caused by urea cycle disorders. In this study, the patients with ornithine carbamoyl transferase defect got satisfactory long-term outcome after liver transplantation.

Screening of missing proteins in the human liver proteome by improved MRM-approach-based targeted proteomics.

PubMed

Chen, Chen; Liu, Xiaohui; Zheng, Weimin; Zhang, Lei; Yao, Jun; Yang, Pengyuan

2014-04-04

To completely annotate the human genome, the task of identifying and characterizing proteins that currently lack mass spectrometry (MS) evidence is inevitable and urgent. In this study, as the first effort to screen missing proteins in large scale, we developed an approach based on SDS-PAGE followed by liquid chromatography-multiple reaction monitoring (LC-MRM), for screening of those missing proteins with only a single peptide hit in the previous liver proteome data set. Proteins extracted from normal human liver were separated in SDS-PAGE and digested in split gel slice, and the resulting digests were then subjected to LC-schedule MRM analysis. The MRM assays were developed through synthesized crude peptides for target peptides. In total, the expressions of 57 target proteins were confirmed from 185 MRM assays in normal human liver tissues. Among the proved 57 one-hit wonders, 50 proteins are of the minimally redundant set in the PeptideAtlas database, 7 proteins even have none MS-based information previously in various biological processes. We conclude that our SDS-PAGE-MRM workflow can be a powerful approach to screen missing or poorly characterized proteins in different samples and to provide their quantity if detected. The MRM raw data have been uploaded to ISB/SRM Atlas/PASSEL (PXD000648).

Expression of Enzymes that Metabolize Medications

NASA Technical Reports Server (NTRS)

Wotring, Virginia E.; Peters, C. P.

2012-01-01

Most pharmaceuticals are metabolized by the liver. Clinically-used medication doses are given with normal liver function in mind. A drug overdose can result if the liver is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism we want to understand the effects of spaceflight on the enzymes of the liver.

Low-dose steroids associated with milder histological changes after pediatric liver transplantation.

PubMed

Kosola, Silja; Lampela, Hanna; Jalanko, Hannu; Mäkisalo, Heikki; Lohi, Jouko; Arola, Johanna; Pakarinen, Mikko P

2013-02-01

Controversy remains about the role of protocol liver biopsy for symptom-free recipients and about the long-term use of low-dose steroids after pediatric liver transplantation (LT). We conducted a national cross-sectional study of pediatric recipients who underwent LT between 1987 and 2007. Liver biopsy samples were taken from 54 patients (82% of survivors) after a median posttransplant follow-up of 11 years, and they were reviewed by 2 pathologists blinded to the clinical data. Biopsy samples from 18 patients (33%) showed nearly normal histology with no inflammation, fibrosis, or steatosis. Portal inflammation was detected in 14 samples (26%), showed no correlation with anti-nuclear antibodies, and was less frequent in the 35 patients whose immunosuppression included steroids (14% versus 47% of patients not using steroids, P = 0.008). Fibrosis was present in 21 biopsy samples (39%). According to the Metavir classification, 16 were stage 1, 3 were stage 2, and 2 were stage 3. The fibrosis stage correlated negatively with serum prealbumin levels (r = -0.364, P = 0.007) and positively with chronic cholestasis (cytokeratin 7 staining; r = 0.529, P < 0.001) and portal inflammation (r = 0.350, P = 0.01). Microvesicular steatosis was found in 23 biopsy samples (43% of patients in 5%-80% of hepatocytes), and it correlated with the body mass index (r = 0.458, P < 0.001) but not with steroid use. The age of the allograft (donor age plus follow-up time) correlated with higher serum gamma-glutamyltransferase (r = 0.472, P < 0.001) and conjugated bilirubin levels (r = 0.420, P = 0.002) as well as chronic cholestasis (r = 0.299, P = 0.03). The biopsy findings led to treatment changes in 10 patients (19%), whereas only 1 complication (subcapsular hematoma) was encountered. In conclusion, continuing low-dose steroids indefinitely after pediatric LT may have a positive effect on the long-term histological state of the liver graft. Allograft aging may lead to chronic cholestasis and thus contribute to the development of liver fibrosis. Copyright © 2012 American Association for the Study of Liver Diseases.

Novel Bioimaging Techniques of Metals by Laser Ablation Inductively Coupled Plasma Mass Spectrometry for Diagnosis Of Fibrotic and Cirrhotic Liver Disorders

PubMed Central

Gassler, Nikolaus; Bosserhoff, Anja K.; Becker, J. Sabine

2013-01-01

Background and Aims Hereditary disorders associated with metal overload or unwanted toxic accumulation of heavy metals can lead to morbidity and mortality. Patients with hereditary hemochromatosis or Wilson disease for example may develop severe hepatic pathology including fibrosis, cirrhosis or hepatocellular carcinoma. While relevant disease genes are identified and genetic testing is applicable, liver biopsy in combination with metal detecting techniques such as energy-dispersive X-ray spectroscopy (EDX) is still applied for accurate diagnosis of metals. Vice versa, several metals are needed in trace amounts for carrying out vital functions and their deficiency due to rapid growth, pregnancy, excessive blood loss, and insufficient nutritional or digestive uptake results in organic and systemic shortcomings. Established in situ techniques, such as EDX-ray spectroscopy, are not sensitive enough to analyze trace metal distribution and the quantification of metal images is difficult. Methods In this study, we developed a quantitative biometal imaging technique of human liver tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) in order to compare the distribution of selected metals in cryo-sections of healthy and fibrotic/cirrhotic livers. Results Most of the metals are homogeneous distributed within the normal tissue, while they are redirected within fibrotic livers resulting in significant metal deposits. Moreover, total iron and copper concentrations in diseased liver were found about 3-5 times higher than in normal liver samples. Conclusions Biometal imaging via LA-ICP-MS is a sensitive innovative diagnostic tool that will impact clinical practice in identification and evaluation of hepatic metal disorders and to detect subtle metal variations during ongoing hepatic fibrogenesis. PMID:23505552

[Effects of acute exposure to high altitude on hepatic function and CYP1A2 and CYP3A4 activities in rats].

PubMed

Li, Wenbin; Jia, Zhengping; Xie, Hua; Zhang, Juanhong; Wang, Yanling; Hao, Ying; Wang, Rong

2014-07-01

To investigate the changes in hepatic functions and activities of CYP1A2 and CYP3A4 in rats after acute exposure to high altitude. Twelve healthy male Wistar rats were randomly divided into control group and exposure group for acute exposure to normal and high altitude (4010 m) environment. Blood samples were collected from the vena orbitalis posterior for detection of the hepatic function. Hepatic pathologies of the rats were examined microscopically with HE staining. Liver microsomes were extracted by differential centrifugation to assess the activities of CYP1A2 and 3A4 using P450-GloTM kit. In rats with acute exposure to high altitude, AST, ALT, and ALP all increased significantly by 48.50%, 47.90%, and 103.02%, respectively, and TP decreased significantly by 17.80% as compared with those in rats maintained in normal altitude environment (P<0.05). Pathological examination of the liver revealed edema of the central vein of the liver and hepatocyte karyopyknosis in rats after acute exposure to high altitude, which also resulted in significantly lowered activities of CYP1A2 and 3A4 in the liver (by 96.56% and 43.53%, respectively). Acute exposure to high altitude can cause obvious liver injuries and lowered activities of CYP1A2 and 3A4 in rats to severely affect drug metabolism in the liver and result in increased concentration, prolonged half-life and reduced clearance of drugs.

Fatty-acid profiles of white muscle and liver in stream-maturing steelhead trout Oncorhynchus mykiss from early migration to kelt emigration

USGS Publications Warehouse

Penney, Zachary L.; Moffitt, Christine M.

2015-01-01

The profiles of specific fatty acids (FA) in white muscle and liver of fasting steelhead troutOncorhynchus mykiss were evaluated at three periods during their prespawning migration and at kelt emigration in the Snake–Columbia River of Washington, Oregon and Idaho, to improve the understanding of energy change. Twenty-seven FAs were identified; depletion of 10 of these was positively correlated in liver and white muscle of prespawning O. mykiss. To observe relative changes in FA content more accurately over sampling intervals, the lipid fraction of tissues was used to normalize the quantity of individual FA to an equivalent tissue wet mass. Saturated and monounsaturated FAs were depleted between upstream migration in September and kelt emigration in June, whereas polyunsaturated FAs were more conserved. Liver was depleted of FAs more rapidly than muscle. Three FAs were detected across all sampling intervals: 16:0, 18:1 and 22:6n3, which are probably structurally important to membranes. When structurally important FAs of O. mykiss are depleted to provide energy, physiological performance and survival may be affected.

Pharmacogenomics of drug-induced liver injury (DILI): Molecular biology to clinical applications.

PubMed

Kaliyaperumal, Kalaiyarasi; Grove, Jane I; Delahay, Robin M; Griffiths, William J H; Duckworth, Adam; Aithal, Guruprasad P

2018-05-21

A 21-year old woman was admitted to hospital with a two-week history of painless jaundice, fatigue and anorexia having previously been fit and well. One month prior to presentation, the patient had taken a five-day course of amoxicillin-clavulanic acid for an infected skin cyst. Otherwise, she was only on the oral contraceptive pill and reported minimal alcohol intake. On examination, she was deeply jaundiced, but alert and oriented with no asterixis. She had no stigmata of chronic liver disease, but hepatomegaly extending 3 cm from below the right subcostal margin was evident. Investigations showed: white cell count 13.4 × 10 9 /L (normal 3.6-9.3), haemoglobin 11.8 g/dl (normal 11-15), platelet count 356 × 10 9 /L (normal 170-420), sodium 138 mmol/L (normal 134-144), potassium 3.5 mmol/L (normal 3.5-5.0), creatinine 32 µmol/L (normal 40-75), albumin 30 g/L (normal 35-48), alanine aminotransferase 707 IU/L (normal 15-54), alkaline phosphatase 151 IU/L (normal 30-130), bilirubin 384 µmol/L (normal 7-31) and prothrombin time 27.2 s (normal 11.7-14). Screening for hepatitis A, B, C, E, Epstein-Barr virus, cytomegalovirus and autoimmune hepatitis was negative. Tests for anti-smooth muscle, antinuclear, and anti-liver-kidney microsomal-1 antibodies were negative; immunoglobulin levels and ceruloplasmin levels were normal. Liver ultrasonography demonstrated a liver of normal contour with no biliary dilatation, a normal spleen size and patent vessels. Liver biopsy revealed severe portal interface hepatitis with lobular inflammation and scant plasma cells. Her clinical condition deteriorated in the following days with prothrombin time and bilirubin rising to 56.6 s and 470 µmol/L, respectively. At follow-up after 11 days, her alanine aminotransferase level was 1,931 IU/L. She developed grade 2 hepatic encephalopathy 14 days after presentation, and was listed for a super-urgent liver transplant. Human leucocyte antigen (HLA) typing was performed as a part of preparatory investigations and showed the patient carried the HLA haplotype HLA-DRB1∗15:02-DQB1∗06:01. Following orthotopic transplantation of a deceased donor graft her explant histology revealed severe ongoing hepatitis with multi-acinar necrosis (Fig. 1A and B). This case raised a number of important questions about the diagnosis of drug-induced liver injury and tools available for clinicians to make the best decisions for patient care: In this Grand Rounds article, we will explore these questions, describing the pathophysiology, diagnostic and prognostic biomarkers, and clinical management of drug-induced liver injury. We will also discuss ongoing areas of uncertainty. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

A Fractal Analysis of CT Liver Images for the Discrimination of Hepatic Lesions: A Comparative Study

DTIC Science & Technology

2001-10-25

liver images in order to estimate their fractal dimension and to differentiate normal liver parenchyma from hepatocellular carcinoma . Four fractal...methods; thus discriminating up to 93% of the normal parenchyma and up to 82% of the hepatocellular carcinoma , correctly.

Mössbauer Spectra of Mouse Hearts Reveal Age-dependent Changes in Mitochondrial and Ferritin Iron Levels.

PubMed

Wofford, Joshua D; Chakrabarti, Mrinmoy; Lindahl, Paul A

2017-03-31

Cardiac function requires continuous high levels of energy, and so iron, a critical player in mitochondrial respiration, is an important component of the heart. Hearts from 57 Fe-enriched mice were evaluated by Mössbauer spectroscopy. Spectra consisted of a sextet and two quadrupole doublets. One doublet was due to residual blood, whereas the other was due to [Fe 4 S 4 ] 2+ clusters and low-spin Fe II hemes, most of which were associated with mitochondrial respiration. The sextet was due to ferritin; there was no evidence of hemosiderin, a ferritin decomposition product. Iron from ferritin was nearly absent in young hearts, but increased steadily with age. EPR spectra exhibited signals similar to those of brain, liver, and human cells. No age-dependent EPR trends were apparent. Hearts from HFE -/- mice with hemochromatosis contained slightly more iron overall than controls, including more ferritin and less mitochondrial iron; these differences typify slightly older hearts, perhaps reflecting the burden due to this disease. HFE -/- livers were overloaded with ferritin but had low mitochondrial iron levels. IRP2 -/- hearts contained less ferritin than controls but normal levels of mitochondrial iron. Hearts of young mice born to an iron-deficient mother contained normal levels of mitochondrial iron and no ferritin; the heart from the mother contained low ferritin and normal levels of mitochondrial iron. High-spin Fe II ions were nearly undetectable in heart samples; these were evident in brains, livers, and human cells. Previous Mössbauer spectra of unenriched diseased human hearts lacked mitochondrial and blood doublets and included hemosiderin features. This suggests degradation of iron-containing species during sample preparation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

False positive acetaminophen concentrations in patients with liver injury.

PubMed

Polson, Julie; Wians, Frank H; Orsulak, Paul; Fuller, Dwain; Murray, Natalie G; Koff, Jonathan M; Khan, Adil I; Balko, Jody A; Hynan, Linda S; Lee, William M

2008-05-01

Acetaminophen toxicity is the most common form of acute liver failure in the U.S. After acetaminophen overdoses, quantitation of plasma acetaminophen can aid in predicting severity of injury. However, recent case reports have suggested that acetaminophen concentrations may be falsely increased in the presence of hyperbilirubinemia. We tested sera obtained from 43 patients with acute liver failure, mostly unrelated to acetaminophen, utilizing 6 different acetaminophen quantitation systems to determine the significance of this effect. In 36 of the 43 samples with bilirubin concentrations ranging from 1.0-61.5 mg/dl no acetaminophen was detectable by gas chromatography-mass spectroscopy. These 36 samples were then utilized to test the performance characteristics of 2 immunoassay and 4 enzymatic-colorimetric methods. Three of four colorimetric methods demonstrated 'detectable' values for acetaminophen in from 4 to 27 of the 36 negative samples, low concentration positive values being observed when serum bilirubin concentrations exceeded 10 mg/dl. By contrast, the 2 immunoassay methods (EMIT, FPIA) were virtually unaffected. The false positive values obtained were, in general, proportional to the quantity of bilirubin in the sample. However, prepared samples of normal human serum with added bilirubin showed a dose-response curve for only one of the 4 colorimetric assays. False positive acetaminophen tests may result when enzymatic-colorimetric assays are used, most commonly with bilirubin concentrations >10 mg/dl, leading to potential clinical errors in this setting. Bilirubin (or possibly other substances in acute liver failure sera) appears to affect the reliable measurement of acetaminophen, particularly with enzymatic-colorimetric assays.

Chronic bile duct hyperplasia is a chronic graft dysfunction following liver transplantation.

PubMed

Jiang, Jian-Wen; Ren, Zhi-Gang; Cui, Guang-Ying; Zhang, Zhao; Xie, Hai-Yang; Zhou, Lin

2012-03-14

To investigate pathological types and influential factors of chronic graft dysfunction (CGD) following liver transplantation (LT) in rats. The whole experiment was divided into three groups: (1) normal group (n = 12): normal BN rats without any drug or operation; (2) syngeneic transplant group (SGT of BN-BN, n = 12): both donors and recipients were BN rats; and (3) allogeneic transplant group (AGT of LEW-BN, n = 12): Donors were Lewis and recipients were BN rats. In the AGT group, all recipients were subcutaneously injected by Cyclosporin A after LT. Survival time was observed for 1 year. All the dying rats were sampled, biliary tract tissues were performed bacterial culture and liver tissues for histological study. Twenty-one day after LT, 8 rats were selected randomly in each group for sampling. Blood samples from caudal veins were collected for measurements of plasma endotoxin, cytokines and metabonomic analysis, and faeces were analyzed for intestinal microflora. During the surgery of LT, no complications of blood vessels or bile duct happened, and all rats in each group were still alive in the next 2 wk. The long term observation revealed that a total of 8 rats in the SGT and AGT groups died of hepatic graft diseases, 5 rats in which died of chronic bile duct hyperplasia. Compared to the SGT and normal groups, survival ratio of rats significantly decreased in the AGT group (P < 0.01). Moreover, liver necrosis, liver infection, and severe chronic bile duct hyperplasia were observed in the AGT group by H and E stain. On 21 d after LT, compared with the normal group (25.38 ± 7.09 ng/L) and SGT group (33.12 ± 10.26 ng/L), plasma endotoxin in the AGT group was remarkably increased (142.86 ± 30.85 ng/L) (both P < 0.01). Plasma tumor necrosis factor-α and interleukin-6 were also significantly elevated in the AGT group (593.6 ± 171.67 pg/mL, 323.8 ± 68.30 pg/mL) vs the normal (225.5 ± 72.07 pg/mL, 114.6 ± 36.67 pg/mL) and SGT groups (321.3 ± 88.47 pg/mL, 205.2 ± 53.06 pg/mL) (P < 0.01). Furthermore, Bacterial cultures of bile duct tissues revealed that the rats close to death from the SGT and AGT groups were strongly positive, while those from the normal group were negative. The analysis of intestinal microflora was performed. Compared to the normal group (7.98 ± 0.92, 8.90 ± 1.44) and SGT group (8.51 ± 0.46, 9.43 ± 0.69), the numbers of Enterococcus and Enterobacteria in the AGT group (8.76 ± 1.93, 10.18 ± 1.64) were significantly increased (both P < 0.01). Meanwhile, compared to the normal group (9.62 ± 1.60, 9.93 ± 1.10) and SGT group (8.95 ± 0.04, 9.02 ± 1.14), the numbers of Bifidobacterium and Lactobacillus in the AGT group (7.83 ± 0.72, 8.87 ± 0.13) were remarkably reduced (both P < 0.01). In addition, metabonomics analysis showed that metabolic profiles of plasma in rats in the AGT group were severe deviated from the normal and SGT groups. Chronic bile duct hyperplasia is a pathological type of CGD following LT in rats. The mechanism of this kind of CGD is associated with the alterations of inflammation, intestinal barrier function and microflora as well as plasma metabolic profiles.

Effects of liver function on ionized hypocalcaemia following rapid blood transfusion.

PubMed

Chung, H S; Cho, S J; Park, C S

2012-01-01

Hypocalcaemia detrimentally affects the cardiovascular system and massive transfusion-related hypocalcaemia is particularly severe in end-stage liver disease patients undergoing liver transplantation (LT). This study, therefore, compared the severity and duration of ionized hypocalcaemia between patients with normal and impaired liver function. Patients (n = 26 per group) were transfused at a rate of 10 ml/kg within 10 min with packed red blood cells (PRBCs) during LT (group LP) or spinal surgery (group SP), or were infused with 0.9% normal saline during spinal surgery (group SN). Serum levels of ionized calcium were assessed before (T(0)), just after (T(1)), and at 20 (T(2)) and 60 min (T(3)) after transfusion. Transfusion with PRBCs caused more severe ionized hypocalcaemia than 0.9% normal saline at T(1). In contrast to the faster (20 min) normalization in group SP, ionized hypocalcaemia in group LP persisted at T(3). Serum ionized calcium levels at T(3) showed correlations with vital signs, blood glucose, serum potassium, base deficit and lactate. Rapid blood transfusion caused more severe and prolonged ionized hypo calcaemia in patients with liver dysfunction than in those with normal liver function.

Impact of Different Creatinine Measurement Methods on Liver Transplant Allocation

PubMed Central

Kaiser, Thorsten; Kinny-Köster, Benedict; Bartels, Michael; Parthaune, Tanja; Schmidt, Michael; Thiery, Joachim

2014-01-01

Introduction The model for end-stage liver disease (MELD) score is used in many countries to prioritize organ allocation for the majority of patients who require orthotopic liver transplantation. This score is calculated based on the following laboratory parameters: creatinine, bilirubin and the international normalized ratio (INR). Consequently, high measurement accuracy is essential for equitable and fair organ allocation. For serum creatinine measurements, the Jaffé method and enzymatic detection are well-established routine diagnostic tests. Methods A total of 1,013 samples from 445 patients on the waiting list or in evaluation for liver transplantation were measured using both creatinine methods from November 2012 to September 2013 at the university hospital Leipzig, Germany. The measurements were performed in parallel according to the manufacturer’s instructions after the samples arrived at the institute of laboratory medicine. Patients who had required renal replacement therapy twice in the previous week were excluded from analyses. Results Despite the good correlation between the results of both creatinine quantification methods, relevant differences were observed, which led to different MELD scores. The Jaffé measurement led to greater MELD score in 163/1,013 (16.1%) samples with differences of up to 4 points in one patient, whereas differences of up to 2 points were identified in 15/1,013 (1.5%) samples using the enzymatic assay. Overall, 50/152 (32.9%) patients with MELD scores >20 had higher scores when the Jaffé method was used. Discussion Using the Jaffé method to measure creatinine levels in samples from patients who require liver transplantation may lead to a systematic preference in organ allocation. In this study, the differences were particularly pronounced in samples with MELD scores >20, which has clinical relevance in the context of urgency of transplantation. These data suggest that official recommendations are needed to determine which laboratory diagnostic methods should be used when calculating MELD scores. PMID:24587188

Elemental contaminants in the livers and ingesta of four subpopulations of the American coot (Fulica americana): An herbivorous winter migrant in San Francisco Bay

USGS Publications Warehouse

Hui, C.A.

1998-01-01

Water birds with diets high in animal foods in the San Francisco Bay area are exposed to trace elements that are potentially health impairing. Water birds with herbivorous diets have been less thoroughly examined. The concentrations of trace elements in the livers and the esophageal contents of an herbivorous water bird, the American coot (Fulica americana) were measured to compare levels of contaminant exposure among different locations in the Bay system and with other water birds. A total of 39 coots were collected from four sites: Napa River and Mare Island Strait in the north, Berkeley in the middle, and Coyote Creek in the south. Livers of Berkeley samples differed significantly from those of Napa River and Mare Island Strait by their greater concentrations of As and B and lower concentrations of Cu, but they seemed to be within normal ranges for birds. Otherwise the concentrations of trace elements in the livers did not differ among sites. Ingesta samples from Berkeley differed from the other sites because they tended to be higher in Al, V, and Zn. In contrast to waterfowl, livers from the herbivorous coots in San Francisco Bay showed little exposure to Cd, Hg, Pb, or Se. Coot ingesta showed few samples with measurable levels of Cd, Hg, or Se and had low levels of Pb. The herbivorous diet of coots may shield them from exposure to such elements. However, high levels of V were present in coot livers and ingesta from all four sites, suggesting adaptation to this toxic element. Copyright (C) 1998 Elsevier Science Ltd.

Decreased hepatotoxic bile acid composition and altered synthesis in progressive human nonalcoholic fatty liver disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lake, April D.; Novak, Petr; Shipkova, Petia

2013-04-15

Bile acids (BAs) have many physiological roles and exhibit both toxic and protective influences within the liver. Alterations in the BA profile may be the result of disease induced liver injury. Nonalcoholic fatty liver disease (NAFLD) is a prevalent form of chronic liver disease characterized by the pathophysiological progression from simple steatosis to nonalcoholic steatohepatitis (NASH). The hypothesis of this study is that the ‘classical’ (neutral) and ‘alternative’ (acidic) BA synthesis pathways are altered together with hepatic BA composition during progression of human NAFLD. This study employed the use of transcriptomic and metabolomic assays to study the hepatic toxicologic BAmore » profile in progressive human NAFLD. Individual human liver samples diagnosed as normal, steatosis, and NASH were utilized in the assays. The transcriptomic analysis of 70 BA genes revealed an enrichment of downregulated BA metabolism and transcription factor/receptor genes in livers diagnosed as NASH. Increased mRNA expression of BAAT and CYP7B1 was observed in contrast to decreased CYP8B1 expression in NASH samples. The BA metabolomic profile of NASH livers exhibited an increase in taurine together with elevated levels of conjugated BA species, taurocholic acid (TCA) and taurodeoxycholic acid (TDCA). Conversely, cholic acid (CA) and glycodeoxycholic acid (GDCA) were decreased in NASH liver. These findings reveal a potential shift toward the alternative pathway of BA synthesis during NASH, mediated by increased mRNA and protein expression of CYP7B1. Overall, the transcriptomic changes of BA synthesis pathway enzymes together with altered hepatic BA composition signify an attempt by the liver to reduce hepatotoxicity during disease progression to NASH. - Highlights: ► Altered hepatic bile acid composition is observed in progressive NAFLD. ► Bile acid synthesis enzymes are transcriptionally altered in NASH livers. ► Increased levels of taurine and conjugated bile acids are observed in NASH. ► Hepatic bile acid synthesis shifts toward the alternative pathway in NASH.« less

Volumetric laser endomicroscopy in the biliary and pancreatic ducts: a feasibility study with histological correlation.

PubMed

Corral, Juan E; Mousa, Omar Y; Krishna, Murli; Levink, Iris J M; Pursell, Khela R; Afsh, Mohammad; Kröner, Paul T; Harnois, Denise M; Wolfsen, Herbert C; Wallace, Michael B; Lukens, Frank J

2018-06-18

 Volumetric laser endomicroscopy (VLE) provides circumferential images 3 mm into the biliary and pancreatic ducts. We aimed to correlate VLE images with the normal and abnormal microstructure of these ducts. Samples from patients undergoing hepatic or pancreatic resection were evaluated. VLE images were collected using a low-profile VLE catheter inserted manually into the biliary and pancreatic ducts ex vivo. Histological correlation was assessed by two unblinded investigators.  25 patients (20 liver and 5 pancreatic samples) and 111 images were analyzed. VLE revealed three histological layers: epithelium, connective tissue, and parenchyma. It identified distinctive patterns for primary sclerosing cholangitis (PSC), pancreatic cysts, neuroendocrine tumor, and adenocarcinoma adjacent to the pancreatic duct or ampulla. VLE failed to identify dysplasia in a dominant stricture and inflammatory infiltrates in PSC. Reflectivity measurements of the liver parenchyma diagnosed liver cirrhosis with high sensitivity.  VLE can identify histological changes in the biliary and pancreatic ducts allowing real-time diagnosis. Further studies are needed to measure the accuracy of VLE in a larger sample and to validate our findings in vivo. © Georg Thieme Verlag KG Stuttgart · New York.

Thromboelastometry

PubMed Central

Dumitrescu, Gabriel; Januszkiewicz, Anna; Ågren, Anna; Magnusson, Maria; Wahlin, Staffan; Wernerman, Jan

2017-01-01

Abstract The severity of liver disease is assessed by scoring systems, which include the conventional coagulation test prothrombin time-the international normalized ratio (PT-INR). However, PT-INR is not predictive of bleeding in liver disease and thromboelastometry (ROTEM) has been suggested to give a better overview of the coagulation system in these patients. It has now been suggested that coagulation as reflected by tromboelastomety may also be used for prognostic purposes. The objective of our study was to investigate whether thrombelastometry may discriminate the degree of liver insufficiency according to the scoring systems Child Pugh and Model for End-stage Liver Disease (MELD). Forty patients with chronic liver disease of different etiologies and stages were included in this observational cross-sectional study. The severity of liver disease was evaluated using the Child-Pugh score and the MELD score, and blood samples for biochemistry, conventional coagulation tests, and ROTEM were collected at the time of the final assessment for liver transplantation. Statistical comparisons for the studied parameters with scores of severity were made using Spearman correlation test and receiver-operating characteristic (ROC) curves. Spearman correlation coefficients indicated that the thromboelastometric parameters did not correlate with Child-Pugh or MELD scores. The ROC curves of the thromboelastometric parameters could not differentiate advanced stages from early stages of liver cirrhosis. Standard ROTEM cannot discriminate the stage of chronic liver disease in patients with severe chronic liver disease. PMID:28591054

Functional restoration of cirrhotic liver after partial hepatectomy in the rat.

PubMed

Hashimoto, Masaji; Watanabe, Goro

2005-01-01

Although cirrhosis is the terminal stage of various liver diseases, thanks to recent advances one might eliminate some causes of liver damage. Liver has a potent regeneration capacity. It is important to evaluate the regenerating cirrhotic liver after partial hepatectomy, morphologically and functionally, in the long term. We evaluated the functional capacity of the rat liver rendered cirrhotic by orally administered thioacetamide, and examined the correlation between morphological and functional restoration after 2/3 hepatectomy in comparison with hepatectomized normal rats and sham-operated cirrhotic rats. Morphological restoration was evaluated by remnant liver weight, proliferating cell nuclear antigen labeling index, and fibrosis ratio. Functional restoration was evaluated by the indocyanine green disappearance rate and aminopyrine clearance. Cirrhotic rats were functionally deteriorated in comparison with the normal rats. Morphological restoration in cirrhotic rats was delayed in comparison with normal rats. Functional restoration after 2/3 hepatectomy was advanced in comparison with morphological restoration. In comparison with sham-operated cirrhotic rats, functional restoration of the cirrhotic liver was accelerated by partial hepatectomy. In cirrhotic rats, functional restoration of the liver after 2/3 hepatectomy was advanced in comparison with morphological restoration. Partial hepatectomy seemed to promote functional restoration of the cirrhotic liver.

Ischemic Preconditioning Increases the Tolerance of Fatty Liver to Hepatic Ischemia-Reperfusion Injury in the Rat

PubMed Central

Serafín, Anna; Roselló-Catafau, Joan; Prats, Neus; Xaus, Carme; Gelpí, Emilio; Peralta, Carmen

2002-01-01

Hepatic steatosis is a major risk factor in ischemia-reperfusion. The present study evaluates whether preconditioning, demonstrated to be effective in normal livers, could also confer protection in the presence of steatosis and investigates the potential underlying protective mechanisms. Fatty rats had increased hepatic injury and decreased survival after 60 minutes of ischemia compared with lean rats. Fatty livers showed a degree of neutrophil accumulation and microcirculatory alterations similar to that of normal livers. However, in presence of steatosis, an increased lipid peroxidation that could be reduced with glutathione-ester pretreatment was observed after hepatic reperfusion. Ischemic preconditioning reduced hepatic injury and increased animal survival. Both in normal and fatty livers, this endogenous protective mechanism was found to control lipid peroxidation, hepatic microcirculation failure, and neutrophil accumulation, reducing the subsequent hepatic injury. These beneficial effects could be mediated by nitric oxide, because the inhibition of nitric oxide synthesis and nitric oxide donor pretreatment abolished and simulated, respectively, the benefits of preconditioning. Thus, ischemic preconditioning could be an effective surgical strategy to reduce the hepatic ischemia-reperfusion injury in normal and fatty livers under normothermic conditions, including hepatic resections, and liver transplantation. PMID:12163383

Pharmacokinetics and tissue distribution of five active ingredients of Eucommiae cortex in normal and ovariectomized mice by UHPLC-MS/MS.

PubMed

An, Jing; Hu, Fangdi; Wang, Changhong; Zhang, Zijia; Yang, Li; Wang, Zhengtao

2016-09-01

1. Pinoresinol di-O-β-d-glucopyranoside (PDG), geniposide (GE), geniposidic acid (GA), aucubin (AN) and chlorogenic acid (CA) are the representative active ingredients in Eucommiae cortex (EC), which may be estrogenic. 2. The ultra high-performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous determination of the five ingredients showed good linearity, low limits of quantification and high extraction recoveries, as well as acceptable precision, accuracy and stability in mice plasma and tissue samples (liver, spleen, kidney and uterus). It was successfully applied to the comparative study on pharmacokinetics and tissue distribution of PDG, GE, GA, AN and CA between normal and ovariectomized (OVX) mice. 3. The results indicated that except CA, the plasma and tissue concentrations of PDG, GE, GA in OVX mice were all greater than those in normal mice. AN could only be detected in the plasma and liver homogenate of normal mice, which was poorly absorbed in OVX mice and low in other measured tissues. PDG, GE and GA seem to be better absorbed in OVX mice than in normal mice proved by the remarkable increased value of AUC0-∞ and Cmax. It is beneficial that PDG, GE, GA have better plasma absorption and tissue distribution in pathological state.

Fractal and Fourier analysis of the hepatic sinusoidal network in normal and cirrhotic rat liver

PubMed Central

Gaudio, Eugenio; Chaberek, Slawomir; Montella, Andrea; Pannarale, Luigi; Morini, Sergio; Novelli, Gilnardo; Borghese, Federica; Conte, Davide; Ostrowski, Kazimierz

2005-01-01

The organization of the hepatic microvascular network has been widely studied in recent years, especially with regard to cirrhosis. This research has enabled us to recognize the distinctive vascular patterns in the cirrhotic liver, compared with the normal liver, which may explain the cause of liver dysfunction and failure. The aim of this study was to compare normal and cirrhotic rat livers by means of a quantitative mathematical approach based on fractal and Fourier analyses performed on photomicrographs and therefore on discriminant analysis. Vascular corrosion casts of livers belonging to the following three experimental groups were studied by scanning electron microscopy: normal rats, CCl4-induced cirrhotic rats and cirrhotic rats after ligation of the bile duct. Photomicrographs were taken at a standard magnification; these images were used for the mathematical analysis. Our experimental design found that use of these different analyses reaches an efficiency of over 94%. Our analyses demonstrated a higher complexity of the normal hepatic sinusoidal network in comparison with the cirrhotic network. In particular, the morphological changes were more marked in the animals with bile duct-ligation cirrhosis compared with animals with CCl4-induced cirrhosis. The present findings based on fractal and Fourier analysis could increase our understanding of the pathophysiological alterations of the liver, and may have a diagnostic value in future clinical research. PMID:16050897

A Modified Protocol for the Isolation of Primary Human Hepatocytes with Improved Viability and Function from Normal and Diseased Human Liver.

PubMed

Bartlett, David C; Newsome, Philip N

2017-01-01

Successful hepatocyte isolation is critical for continued development of cellular transplantation. However, most tissue available for research is from diseased liver and the results of hepatocyte isolation from such tissue are inferior compared to normal tissue. Here we describe a modified method, combining the use of Liberase and N-acetylcysteine (NAC), for the isolation of primary human hepatocytes with high viability from normal and diseased liver.

Examination of the liver in personnel working with liquid rocket propellant

PubMed Central

Petersen, Palle; Bredahl, Erik; Lauritsen, Ove; Laursen, Thomas

1970-01-01

Petersen, P., Bredahl, E., Lauritsen, O., and Laursen, T. (1970).Brit. J. industr. Med.,27, 141-146. Examination of the liver in personnel working with liquid rocket propellants. Personnel working with liquid rocket propellants were subjected to routine health examinations, including liver function tests, as the propellant, unsymmetrical dimethylhydrazine (UDMH) is potentially toxic to the liver. In 46 persons the concentrations of serum alanine aminotransferase (SGPT) were raised. Liver biopsy was performed in 26 of these men; 6 specimens were pathological (fatty degeneration), 5 were uncertain, and 15 were normal. All 6 pathological biopsies were from patients with a raised SGPT at the time of biopsy. Of the 15 persons with a normal liver biopsy, 14 had a normal SGPT, while one (who was an alcoholic) had a raised SGPT. The connection between SGPT and histology of the liver, as well as the possible causal relation between the pathological findings and exposure to UDMH, is discussed. Images PMID:5428632

Magnetic Targeting of Stem Cell Derivatives Enhances Hepatic Engraftment into Structurally Normal Liver

PubMed Central

Fagg, W. Samuel; Liu, Naiyou; Yang, Ming-Jim; Cheng, Ke; Chung, Eric; Kim, Jae-Sung; Wu, Gordon

2018-01-01

Attaining consistent robust engraftment in the structurally normal liver is an obstacle for cellular transplantation. Most experimental approaches to increase transplanted cells’ engraftment involve recipient-centered deleterious methods such as partial hepatectomy or irradiation which may be unsuitable in the clinic. Here, we present a cell-based strategy that increases engraftment into the structurally normal liver using a combination of magnetic targeting and proliferative endoderm progenitor (EPs) cells. Magnetic labeling has little effect on cell viability and differentiation, but in the presence of magnetic targeting, it increases the initial dwell time of transplanted EPs into the undamaged liver parenchyma. Consequently, greater cell retention in the liver is observed concomitantly with fewer transplanted cells in the lungs. These highly proliferative cells then significantly increase their biomass over time in the liver parenchyma, approaching nearly 4% of total liver cells 30 d after transplant. Therefore, the cell-based mechanisms of increased initial dwell time through magnetic targeting combined with high rate of proliferation in situ yield significant engraftment in the undamaged liver. PMID:29390880

Elevated Liver Enzymes

MedlinePlus

Symptoms Elevated liver enzymes By Mayo Clinic Staff Elevated liver enzymes may indicate inflammation or damage to cells in the liver. Inflamed or ... than normal amounts of certain chemicals, including liver enzymes, into the bloodstream, which can result in elevated ...

[Effect of American Ginseng Capsule on the liver oxidative injury and the Nrf2 protein expression in rats exposed by electromagnetic radiation of frequency of cell phone].

PubMed

Luo, Ya-ping; Ma, Hui-Rong; Chen, Jing-Wei; Li, Jing-Jing; Li, Chun-xiang

2014-05-01

To observe the effect of American Ginseng Capsule (AGC) on the liver oxidative injury and the Nrf2 protein expression in the liver tissue of rats exposed by 900 MHz cell phone electromagnetic radiation. Totally 40 male SD rats were randomly divided into the normal control group, the model group, the Shuifei Jibin Capsule (SJC) group, and the AGC group,10 in each group. Rats in the normal control group were not irradiated. Rats in the rest three groups were exposed by imitated 900 MHz cellular phone for 4 h in 12 consecutive days. Meanwhile, rats in the SJC group and the AGC group were intragastrically administrated with suspension of SJC and AGC (1 mL/200 g body weight) respectively. Normal saline was administered to rats in the normal control group and the model group. The histolomorphological changes of the liver tissue were observed by HE staining. Contents of malonic dialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-PX)were detected by colorimetry. The Nrf2 protein expression of hepatocytes was detected by immunohistochemical assay and Western blot. Compared with the normal control group, hepatocyte nucleus was atrophied or partially disappeared, the contents of liver MDA and Nrf2 protein obviously increased (P <0. 05, P <0. 01); contents of liver SOD and GSH decreased (P <0. 05) in the model group. Compared with the model group, karyopyknosis was obviously attenuated and approached to the normal level in the SJC group and the AGC group. The contents of liver MDA and Nrf2 protein expression decreased (P <0. 05), and the contents of liver SOD, GSH, and GSH-PX obviously increased (P < 0.05) in the SJC group. The contents of liver MDA and the Nrf2 protein expression decreased (P < 0.05), and contents of SOD and GSH obviously increased in the AGC group (P <0.01, P <0.05). The electromagnetic radiation induced by 900 MHz cell phone could affect the expression of Nrf2 protein, induce oxidative injury, and induce abnormal morphology of liver cells. SJC and AGC could promote the morphological recovery of the liver cells. Its mechanism might be related to affecting the expression of Nrf2 protein and attenuating oxidative damage of liver cells.

Study of MicroRNAs Related to the Liver Regeneration of the Whitespotted Bamboo Shark, Chiloscyllium plagiosum

PubMed Central

Lu, Conger; Nie, Zuoming; Chen, Jian; Zhang, Wenping; Ren, Xiaoyuan; Yu, Wei; Liu, Lili; Jiang, Caiying; Zhang, Yaozhou; Guo, Jiangfeng; Wu, Wutong; Shu, Jianhong; Lv, Zhengbing

2013-01-01

To understand the mechanisms of liver regeneration better to promote research examining liver diseases and marine biology, normal and regenerative liver tissues of Chiloscyllium plagiosum were harvested 0 h and 24 h after partial hepatectomy (PH) and used to isolate small RNAs for miRNA sequencing. In total, 91 known miRNAs and 166 putative candidate (PC) miRNAs were identified for the first time in Chiloscyllium plagiosum. Through target prediction and GO analysis, 46 of 91 known miRNAs were screened specially for cellular proliferation and growth. Differential expression levels of three miRNAs (xtr-miR-125b, fru-miR-204, and hsa-miR-142-3p_R-1) related to cellular proliferation and apoptosis were measured in normal and regenerating liver tissues at 0 h, 6 h, 12 h, and 24 h using real-time PCR. The expression of these miRNAs showed a rising trend in regenerative liver tissues at 6 h and 12 h but exhibited a downward trend compared to normal levels at 24 h. Differentially expressed genes were screened in normal and regenerating liver tissues at 24 h by DDRT-PCR, and ten sequences were identified. This study provided information regarding the function of genes related to liver regeneration, deepened the understanding of mechanisms of liver regeneration, and resulted in the addition of a significant number of novel miRNAs sequences to GenBank. PMID:24151623

Glycogen content in hepatocytes is related with their size in normal rat liver but not in cirrhotic one.

PubMed

Bezborodkina, Natalia N; Chestnova, Anna Yu; Vorobev, Mikhail L; Kudryavtsev, Boris N

2016-04-01

Hepatocytes differ from one another by the degree of the ploidy, size, position in the liver lobule, and level of the DNA-synthetic processes. It is believed, that the cell size exerts substantial influence on the metabolism of the hepatocytes and the glycogen content in them. The aim of the present study was to test this hypothesis. Dry weight of hepatocytes, their ploidy and glycogen content were determined in the normal and the cirrhotic rat liver. Liver cirrhosis in rats was produced by chronic inhalation of CCl4 vapours in the course of 6 months. A combined cytophotometric method was used. Dry weight of the cell, its glycogen and DNA content were successively measured on a mapped preparation. Hepatocytes of each ploidy class in the normal and the cirrhotic rat liver accumulated glycogen at the same rate. In the normal liver, there was a distinct correlation between the size of hepatocytes and glycogen content in them. This correlation was observed in each ploidy class, and was especially pronounced in the class of mononucleate tetraploid hepatocytes. In the cirrhotic liver, there was no correlation between the size of the cells and their glycogen content. The impairment of liver lobular structure probably explains the observed lack of correlation between hepatocyte size and their glycogen content in the cirrhotic liver. © 2016 International Society for Advancement of Cytometry. © 2016 International Society for Advancement of Cytometry.

The effects of space flight on some rat liver enzymes regulating carbohydrate and lipid metabolism

NASA Technical Reports Server (NTRS)

Abraham, S.; Lin, C. Y.; Klein, H. P.; Volkmann, C.

1981-01-01

The effects of space flight conditions on the activities of certain enzymes regulating carbohydrate and lipid metabolism in rat liver are investigated in an attempt to account for the losses in body weight observed during space flight despite preflight caloric consumption. Liver samples were analyzed for the activities of 32 cytosolic and microsomal enzymes as well as hepatic glycogen and individual fatty acid levels for ground control rats and rats flown on board the Cosmos 936 biosatellite under normal space flight conditions and in centrifuges which were sacrificed upon recovery or 25 days after recovery. Significant decreases in the activities of glycogen phosphorylase, alpha-glycerol phosphate acyl transferase, diglyceride acyl transferase, aconitase and 6-phosphogluconate dehydrogenase and an increase in palmitoyl CoA desaturase are found in the flight stationary relative to the flight contrifuged rats upon recovery, with all enzymes showing alterations returning to normal values 25 days postflight. The flight stationary group is also observed to be characterized by more than twice the amount of liver glycogen of the flight centrifuged group as well as a significant increase in the ratio of palmitic to palmitoleic acid. Results thus indicate metabolic changes which may be involved in the mechanism of weight loss during weightlessness, and demonstrate the equivalence of centrifugation during space flight to terrestrial gravity.

Prevalence and causes of abnormal liver function in patients with coeliac disease.

PubMed

Casella, Giovanni; Antonelli, Elisabetta; Di Bella, Camillo; Villanacci, Vincenzo; Fanini, Lucia; Baldini, Vittorio; Bassotti, Gabrio

2013-08-01

Coeliac disease patients frequently display mild elevation of liver enzymes and this abnormality usually normalizes after gluten-free diet. To investigate the cause and prevalence of altered liver function tests in coeliac patients, basally and after 1 year of gluten-free diet. Data from 245 untreated CD patients (196 women and 49 men, age range 15-80 years) were retrospectively analysed and the liver function tests before and after diet, as well as associated liver pathologies, were assessed. Overall, 43/245 (17.5%) patients had elevated values of one or both aminotransferases; the elevation was mild (<5 times the upper reference limit) in 41 (95%) and marked (>10 times the upper reference limit) in the remaining 2 (5%) patients. After 1 year of gluten-free diet, aminotransferase levels normalized in all but four patients with HCV infection or primary biliary cirrhosis. In coeliac patients, hypertransaminaseaemia at diagnosis and the lack of normalization of liver enzymes after 12 months of diet suggest coexisting liver disease. In such instance, further evaluation is recommended to exclude the liver disease. Early recognition and treatment of coeliac disease in patients affected by liver disease are important to improve the liver function and prevent complications. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Quantitative analysis of hepatitis C virus activity in vivo in different groups of untreated patients.

PubMed

Manzin, A; Solforosi, L; Giostra, F; Bianchi, F B; Bruno, S; Rossi, S; Gabrielli, A; Candela, M; Petrelli, E; Clementi, M

1997-01-01

Highly sensitive competitive PCR (cPCR) and competitive reverse transcription PCR (cRT-PCR) methodologies were recently developed and applied for quantifying viral DNA and RNA species (including HCV RNA) present in clinical samples at low concentration. In this study, we used cRT-PCR to compare the viral load of 118 untreated patients with HCV infection and different clinical conditions (80 patients with chronic hepatitis, 18 infected subjects with persistently normal ALT levels and various degrees of liver injury, 10 HCV infected subjects that tested positive for anti-LKM1 antibodies, and 10 patients with HCV infection and cryoglobulinemia). The results indicate that while great individual variability of HCV viremia is detectable even among patients with similar clinical conditions, the mean HCV RNA copy number in samples from patients with different clinical conditions was similar in all groups with the single exception of patients that tested positive for anti-liver-kidney microsomal auto-antibodies type 1 (anti-LKM1); interestingly, lower HCV viremia levels were revealed in these anti-LKM1-positive cases with liver disease of uncertain pathogenesis.

Detection of micronuclei formation and nuclear anomalies in regenerative nodules of human cirrhotic livers and relationship to hepatocellular carcinoma.

PubMed

de Almeida, Terezinha M B; Leitão, Regina C; Andrade, Joyce D; Beçak, Willy; Carrilho, Flair J; Sonohara, Shigueko

2004-04-01

Human cirrhosis is considered an important factor in hepatocarcinogenesis. The lack of substantial genetics and cytogenetics data in human cirrhosis led us to investigate spontaneous micronuclei formation, as an indicator of chromosomal damage. The analysis was performed in hepatocytes of regenerative, macroregenerative, and tumoral nodules from 30 cases of cirrhosis (paraffin-embedded archival material), retrospectively selected: cryptogenic, hepatitis C virus, and hepatitis C virus associated with hepatocellular carcinoma (HCC). Thirteen control liver samples of healthy organ donors were included. Micronucleated hepatocytes were analyzed with Feulgen-fast-green dyeing techniques. The spontaneous frequency of micronucleated hepatocytes in both regenerative and macroregenerative nodules of all cirrhotic patients was significantly higher than for the normal control group. There was no significant difference in frequency of micronucleated hepatocytes in regenerative nodules compared with macroregenerative nodules for all cases analyzed, whereas a significantly higher frequency of micronucleated hepatocytes was detected in tumoral nodules, compared with cirrhotic regenerative nodules and normal parenchyma. A higher frequency of the nuclear anomalies termed broken-eggs was observed in hepatitis C virus-related samples. Chromatinic losses and genotoxicity already existed in the cirrhotic regenerative nodules, which might predispose to development of HCC.

Liver regeneration in donors and adult recipients after living donor liver transplantation.

PubMed

Haga, Junko; Shimazu, Motohide; Wakabayashi, Go; Tanabe, Minoru; Kawachi, Shigeyuki; Fuchimoto, Yasushi; Hoshino, Ken; Morikawa, Yasuhide; Kitajima, Masaki; Kitagawa, Yuko

2008-12-01

In living donor liver transplantation, the safety of the donor operation is the highest priority. The introduction of the right lobe graft was late because of concerns about donor safety. We investigated donor liver regeneration by the types of resected segments as well as recipients to assess that appropriate regeneration was occurring. Eighty-seven donors were classified into 3 groups: left lateral section donors, left lobe donors, and right lobe donors. Forty-seven adult recipients were classified as either left or right lobe grafted recipients. Volumetry was retrospectively performed at 1 week, 1, 2, 3, and 6 months, and 1 year after the operation. In the right lobe donor group, the remnant liver volume was 45.4%, and it rapidly increased to 68.9% at 1 month and 89.8% at 6 months. At 6 months, the regeneration ratios were almost the same in all donor groups. The recipient liver volume increased rapidly until 2 months, exceeding the standard liver volume, and then gradually decreased to 90% of the standard liver volume. Livers of the right lobe donor group regenerated fastest in the donor groups, and the recipient liver regenerated faster than the donor liver. Analyzing liver regeneration many times with a large number of donors enabled us to understand the normal liver regeneration pattern. Although the donor livers did not reach their initial volume, the donors showed normal liver function at 1 year. The donors have returned to their normal daily activities. Donor hepatectomy, even right hepatectomy, can be safely performed with accurate preoperative volumetry and careful decision-making concerning graft-type selection.

Hepatoprotective Effect of Essential Oils from Hyptis crenata in Sepsis-Induced Liver Dysfunction.

PubMed

Lima, Glauber Cruz; Vasconcelos, Yuri de Abreu Gomes; de Santana Souza, Marilia Trindade; Oliveira, Alan Santos; Bomfim, Rangel Rodrigues; de Albuquerque Júnior, Ricardo Luiz Cavalcanti; Camargo, Enilton Aparecido; Portella, Viviane Gomes; Coelho-de-Souza, Andrelina Noronha; Diniz, Lúcio Ricardo Leite

2018-02-28

No specific therapeutics are available for the treatment of sepsis-induced liver dysfunction, a clinical complication strongly associated with the high mortality rate of septic patients. This study investigated the effect of the essential oil of Hyptis crenata (EOHc), a lamiaceae plant used to treat liver disturbances in Brazilian folk medicine, on liver function during early sepsis. Sepsis was induced by the cecal ligation and puncture (CLP) model. Rats were divided into four groups: Sham, Sham+EOHc, CLP, and CLP+EOHc. EOHc (300 mg/kg) was orally administered 12 and 24 h after surgery. The animals were sacrificed for blood collection and liver tissue samples 48 h after surgery. Hepatic function was evaluated by measuring serum bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase, and alanine aminotransferase (ALT) levels. The levels of malondialdehyde and the activity of superoxide dismutase, catalase, and GSH peroxidase (GSH-Px) were measured for assessment of oxidative stress. Liver morphology was analyzed by hematoxylin and eosin staining. EOHc normalized serum ALP, ALT, and bilirubin levels and inhibited morphological changes. In addition, we observed that EOHc inhibited elevation in hepatic lipid peroxidation and reduction of the glutathione peroxidase activity induced by sepsis. Our data show that EOHc plays a protective effect against liver injury induced by sepsis.

[Prediction of histological liver damage in asymptomatic alcoholic patients by means of clinical and laboratory data].

PubMed

Iturriaga, H; Hirsch, S; Bunout, D; Díaz, M; Kelly, M; Silva, G; de la Maza, M P; Petermann, M; Ugarte, G

1993-04-01

Looking for a noninvasive method to predict liver histologic alterations in alcoholic patients without clinical signs of liver failure, we studied 187 chronic alcoholics recently abstinent, divided in 2 series. In the model series (n = 94) several clinical variables and results of common laboratory tests were confronted to the findings of liver biopsies. These were classified in 3 groups: 1. Normal liver; 2. Moderate alterations; 3. Marked alterations, including alcoholic hepatitis and cirrhosis. Multivariate methods used were logistic regression analysis and a classification and regression tree (CART). Both methods entered gamma-glutamyltransferase (GGT), aspartate-aminotransferase (AST), weight and age as significant and independent variables. Univariate analysis with GGT and AST at different cutoffs were also performed. To predict the presence of any kind of damage (Groups 2 and 3), CART and AST > 30 IU showed the higher sensitivity, specificity and correct prediction, both in the model and validation series. For prediction of marked liver damage, a score based on logistic regression and GGT > 110 IU had the higher efficiencies. It is concluded that GGT and AST are good markers of alcoholic liver damage and that, using sample cutoffs, histologic diagnosis can be correctly predicted in 80% of recently abstinent asymptomatic alcoholics.

Imaging follow-up after liver transplantation

PubMed Central

Rossi, Massimo; Mennini, Gianluca; Melandro, Fabio; Anzidei, Michele; De Vizio, Silvia; Koryukova, Kameliya; Catalano, Carlo

2016-01-01

Liver transplantation (LT) represents the best treatment for end-stage chronic liver disease, acute liver failure and early stages of hepatocellular carcinoma. Radiologists should be aware of surgical techniques to distinguish a normal appearance from pathological findings. Imaging modalities, such as ultrasound, CT and MR, provide for rapid and reliable detection of vascular and biliary complications after LT. The role of imaging in the evaluation of rejection and primary graft dysfunction is less defined. This article illustrates the main surgical anastomoses during LT, the normal appearance and complications of the liver parenchyma and vascular and biliary structures. PMID:27188846

[Determination of micro and macronutrients in the cattle of the Venezuelan plains and their influence on the origin of bovine paraplegic syndrome].

PubMed

Rojas, H; Serrano, J R; DiPolo, R

1994-01-01

We report a study carried out in three livestock-producing regions of Venezuela to determine the mineral status of grazing cattle and its relationship to the Síndrome Parpléjico del Bovino (SPB). Animal tissue samples from blood and liver were collected from a total of 17 farms within three regions: southwest (Apure), central (Guárico) and southeast (Bolívar) both during the dry and rainy seasons. In SPB free animals, the serum levels of sodium, potassium, chloride, magnesium, total and ionized calcium, phosphorus, and creatinine, were within the normal range. Glucose was found to be deficient in cattle from Bolívar and Guárico states and normal in Apure. With the exception of liver copper and serum zinc, all the other microelements analyzed (liver cobalt, and molybdenum, and serum iron) were found to be normal. Copper was found to be low in all regions studied with a mean value of 74.8 ppm indicating a moderate deficiency of this element. Similarly, in the central and southwest regions, zinc was found to be close to 0.34 ppm, significantly lower than the critical level of 0.7 ppm. In order to determine the effect of the dry and rainy seasons on the content of macro and microelements, controlled group of cattle from the three regions were followed in their contents of magnesium, calcium, copper and iron. In the dry season all of these elements tended to be much lower, showing a significant increase in the rainy season. This increase was much greater in cattle that received mineral supplementation and sanitary treatment. Bovines with diagnosis of SPB showed: low liver copper content, low serum magnesium and phosphorus levels significantly higher that control cattle.

THE CHEMISTRY OF THE LIVER IN ACUTE YELLOW ATROPHY

PubMed Central

Wells, H. Gideon

1907-01-01

From the liver of a young man who died of typical, " idiopathic" acute yellow atrophy of the liver, after an illness of six weeks, there were isolated and identified the following amino acids: Histidin, lysin, tyrosin, leucin, glycocoll, alanin, prolin, glutaminic acid, aspartic acid. These were found free in extracts of the liver, and presumably represent products of the autolysis of liver cells, although the amount of soluble non-protein nitrogen present in the extracts was so large as to suggest that there must be some other source for these substances. Small quantities of free proteoses and peptones, and of xanthin and hypoxanthin, were also found in the extracts. In the insoluble proteins of the liver the proportion of diamino acids was decreased slightly as compared with normal livers. The proportion of protein phosphorus was increased, probably because of active regenerative proliferation, while the sulphur was normal in amount. Iron was increased because of the large quantity of blood in the liver and the hematogenous pigmentation of the liver cells. Gelatigenous material was increased both absolutely and relatively, because of the loss of parenchyma and the proliferation of the stroma. The proportion of water to solids was much increased, there having been a loss of over two-thirds of the entire parenchymatous elements of the liver. The amount of fat, lecithin and cholesterin was not far from that normal for the liver. PMID:19867115

The influence of aminotransferase levels on liver stiffness assessed by Acoustic Radiation Force Impulse Elastography: a retrospective multicentre study.

PubMed

Bota, Simona; Sporea, Ioan; Peck-Radosavljevic, Markus; Sirli, Roxana; Tanaka, Hironori; Iijima, Hiroko; Saito, Hidetsugu; Ebinuma, Hirotoshi; Lupsor, Monica; Badea, Radu; Fierbinteanu-Braticevici, Carmen; Petrisor, Ana; Friedrich-Rust, Mireen; Sarrazin, Christoph; Takahashi, Hirokazu; Ono, Naofumi; Piscaglia, Fabio; Marinelli, Sara; D'Onofrio, Mirko; Gallotti, Anna; Salzl, Petra; Popescu, Alina; Danila, Mirela

2013-09-01

Acoustic Radiation Force Impulse Elastography is a new method for non-invasive evaluation of liver fibrosis. To evaluate the impact of elevated alanine aminotransferase levels on liver stiffness assessment by Acoustic Radiation Force Impulse Elastography. A multicentre retrospective study including 1242 patients with chronic liver disease, who underwent liver biopsy and Acoustic Radiation Force Impulse. Transient Elastography was also performed in 512 patients. The best Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis was 1.29 m/s in cases with normal alanine aminotransferase levels and 1.44 m/s in patients with alanine aminotransferase levels>5 × the upper limit of normal. The best cut-off for predicting liver cirrhosis were 1.59 and 1.75 m/s, respectively. Acoustic Radiation Force Impulse cut-off for predicting significant fibrosis and cirrhosis were relatively similar in patients with normal alanine aminotransferase and in those with alanine aminotransferase levels between 1.1 and 5 × the upper limit of normal: 1.29 m/s vs. 1.36 m/s and 1.59 m/s vs. 1.57 m/s, respectively. For predicting cirrhosis, the Transient Elastography cut-offs were significantly higher in patients with alanine aminotransferase levels between 1.1 and 5 × the upper limit of normal compared to those with normal alanine aminotransferase: 12.3 kPa vs. 9.1 kPa. Liver stiffness values assessed by Acoustic Radiation Force Impulse and Transient Elastography are influenced by high aminotransferase levels. Transient Elastography was also influenced by moderately elevated aminotransferase levels. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

[Histology of gill, liver and kidney in juvenile fish Colossoma macropomum exposed to three temperatures].

PubMed

Rojas, Luz-Marina; Mata, Claunis; Oliveros, Aridays; Salazar-Lugo, Raquel

2013-06-01

Abstract: Histology of gill, liver and kidney in juvenile fish Colossoma macropomum exposed to three temperatures. Water temperature is an important factor that affects growth and antioxidant enzyme activities in fish, and when adverse, it may trigger diseases in fish populations. C. macropomum is a freshwater neotropical fish widely distributed in South America and abundant in river basins as the Amazon and Orinoco. It is highly used for intensive aquaculture development and is a very important product for the local riverside economy in Venezuela. The purpose of our study was to examine the water temperature effect on gills, liver and kidneys of juvenile fishes of C macropomum. Eighteen juveniles with biometrical index of 17.87 +/- 7.88 cm and 87.69 +/- 34.23 g were respectively exposed to three culture temperatures (T18, T29 and T35 degrees C) during a period of 21 days. Histological analyses on gills, liver and kidney were made according to standard methodologies. Our results showed that these tissues exhibited normal citoarchitecture at T29. On the contrary, T18-gills displayed brachiallipid droplets inside brachial epithelium; and disorganization in the brachial tissue was observed at T35. Furthermore, we observed two kinds of hepatocytes (dark and light) on T180 degrees C-liver. The T35-liver samples showed cytoplasmatic granulation and damages in cytoplasmatic membrane. Kidney samples from T18 observed alterations in the cellular distribution of the hematopoietic tissue; while, at T35, the most important feature observed was the disorganization of the glomerular structure. We concluded that T18 and T35 are respectively critical and severe temperatures to C. macropomum; besides, the most sensible tissues to changes induced by temperature in this species were the liver and gills.

Recreational Anabolic-Androgenic Steroid Use Associated With Liver Injuries Among Brazilian Young Men.

PubMed

Schwingel, Paulo Adriano; Cotrim, Helma Pinchemel; Santos, Crimério Ribeiro dos; Santos, Adriano Oliveira dos; Andrade, Antônio Ricardo Cardia Ferraz de; Carruego, Marcos Vinicius Vilas Boas; Zoppi, Cláudio Cesar

2015-01-01

The recreational use of anabolic-androgenic steroids (AAS) has reached alarming levels among healthy people. However, several complications have been related to consumption of these drugs, including liver disorders. To evaluate the prevalence of liver injuries in young Brazilian recreational AAS users. Between February/2007 and May/2012 asymptomatic bodybuilders who were ≥18 years old and reported AAS use for ≥6 months were enrolled. All had clinical evaluations, abdominal ultrasound (AUS), and blood tests. 182 individuals were included in the study. The median age (interquartile range) was 26.0 years (22.0-30.0) and all were male. Elevated liver enzyme levels were observed in 38.5% (n = 70) of AAS users, and creatine phosphokinase was normal in 27.1% (n = 19) of them. Hepatic steatosis was observed by AUS in 12.1% of the sample. One individual had focal nodular hyperplasia and another had hepatocellular adenoma. One case each of hepatitis B and C virus infection was found. A diagnosis of toxic liver injury was suggested in 23 (12.6%) AAS users without a history of alcohol or other medications/drugs consumption, or evidence of other liver diseases. Young Brazilian recreational AAS users presented a wide spectrum of liver injuries that included hepatotoxicity, fatty liver, and liver neoplasm. They also presented risk factors for liver diseases such as alcohol consumption and hepatitis B and C virus infection. The results suggest that the risk of AAS use for the liver may be greater than the esthetic benefits, and demonstrate the importance of screening AAS users for liver injuries.

Octogenarian liver grafts: Is their use for transplant currently justified?

PubMed

Jiménez-Romero, Carlos; Cambra, Felix; Caso, Oscar; Manrique, Alejandro; Calvo, Jorge; Marcacuzco, Alejandro; Rioja, Paula; Lora, David; Justo, Iago

2017-05-07

To analyse the impact of octogenarian donors in liver transplantation. We present a retrospective single-center study, performed between November 1996 and March 2015, that comprises a sample of 153 liver transplants. Recipients were divided into two groups according to liver donor age: recipients of donors ≤ 65 years (group A; n = 102), and recipients of donors ≥ 80 years (group B; n = 51). A comparative analysis between the groups was performed. Quantitative variables were expressed as mean values and SD, and qualitative variables as percentages. Differences in properties between qualitative variables were assessed by χ 2 test. Comparison of quantitative variables was made by t -test. Graft and patient survivals were estimated using the Kaplan-Meier method. One, 3 and 5-year overall patient survival was 87.3%, 84% and 75.2%, respectively, in recipients of younger grafts vs 88.2%, 84.1% and 66.4%, respectively, in recipients of octogenarian grafts ( P = 0.748). One, 3 and 5-year overall graft survival was 84.3%, 83.1% and 74.2%, respectively, in recipients of younger grafts vs 84.3%, 79.4% and 64.2%, respectively, in recipients of octogenarian grafts ( P = 0.524). After excluding the patients with hepatitis C virus cirrhosis (16 in group A and 10 in group B), the 1, 3 and 5-year patient ( P = 0.657) and graft ( P = 0.419) survivals were practically the same in both groups. Multivariate Cox regression analysis demonstrated that overall patient survival was adversely affected by cerebrovascular donor death, hepatocarcinoma, and recipient preoperative bilirubin, and overall graft survival was adversely influenced by cerebrovascular donor death, and recipient preoperative bilirubin. The standard criteria for utilization of octogenarian liver grafts are: normal gross appearance and consistency, normal or almost normal liver tests, hemodynamic stability with use of < 10 μg/kg per minute of vasopressors before procurement, intensive care unit stay < 3 d, CIT < 9 h, absence of atherosclerosis in the hepatic and gastroduodenal arteries, and no relevant histological alterations in the pre-transplant biopsy, such as fibrosis, hepatitis, cholestasis or macrosteatosis > 30%.

Octogenarian liver grafts: Is their use for transplant currently justified?

PubMed Central

Jiménez-Romero, Carlos; Cambra, Felix; Caso, Oscar; Manrique, Alejandro; Calvo, Jorge; Marcacuzco, Alejandro; Rioja, Paula; Lora, David; Justo, Iago

2017-01-01

AIM To analyse the impact of octogenarian donors in liver transplantation. METHODS We present a retrospective single-center study, performed between November 1996 and March 2015, that comprises a sample of 153 liver transplants. Recipients were divided into two groups according to liver donor age: recipients of donors ≤ 65 years (group A; n = 102), and recipients of donors ≥ 80 years (group B; n = 51). A comparative analysis between the groups was performed. Quantitative variables were expressed as mean values and SD, and qualitative variables as percentages. Differences in properties between qualitative variables were assessed by χ2 test. Comparison of quantitative variables was made by t-test. Graft and patient survivals were estimated using the Kaplan-Meier method. RESULTS One, 3 and 5-year overall patient survival was 87.3%, 84% and 75.2%, respectively, in recipients of younger grafts vs 88.2%, 84.1% and 66.4%, respectively, in recipients of octogenarian grafts (P = 0.748). One, 3 and 5-year overall graft survival was 84.3%, 83.1% and 74.2%, respectively, in recipients of younger grafts vs 84.3%, 79.4% and 64.2%, respectively, in recipients of octogenarian grafts (P = 0.524). After excluding the patients with hepatitis C virus cirrhosis (16 in group A and 10 in group B), the 1, 3 and 5-year patient (P = 0.657) and graft (P = 0.419) survivals were practically the same in both groups. Multivariate Cox regression analysis demonstrated that overall patient survival was adversely affected by cerebrovascular donor death, hepatocarcinoma, and recipient preoperative bilirubin, and overall graft survival was adversely influenced by cerebrovascular donor death, and recipient preoperative bilirubin. CONCLUSION The standard criteria for utilization of octogenarian liver grafts are: normal gross appearance and consistency, normal or almost normal liver tests, hemodynamic stability with use of < 10 μg/kg per minute of vasopressors before procurement, intensive care unit stay < 3 d, CIT < 9 h, absence of atherosclerosis in the hepatic and gastroduodenal arteries, and no relevant histological alterations in the pre-transplant biopsy, such as fibrosis, hepatitis, cholestasis or macrosteatosis > 30%. PMID:28533667

Functions of autophagy in normal and diseased liver

PubMed Central

Czaja, Mark J.; Ding, Wen-Xing; Donohue, Terrence M.; Friedman, Scott L.; Kim, Jae-Sung; Komatsu, Masaaki; Lemasters, John J.; Lemoine, Antoinette; Lin, Jiandie D.; Ou, Jing-hsiung James; Perlmutter, David H.; Randall, Glenn; Ray, Ratna B.; Tsung, Allan; Yin, Xiao-Ming

2013-01-01

Autophagy has emerged as a critical lysosomal pathway that maintains cell function and survival through the degradation of cellular components such as organelles and proteins. Investigations specifically employing the liver or hepatocytes as experimental models have contributed significantly to our current knowledge of autophagic regulation and function. The diverse cellular functions of autophagy, along with unique features of the liver and its principal cell type the hepatocyte, suggest that the liver is highly dependent on autophagy for both normal function and to prevent the development of disease states. However, instances have also been identified in which autophagy promotes pathological changes such as the development of hepatic fibrosis. Considerable evidence has accumulated that alterations in autophagy are an underlying mechanism of a number of common hepatic diseases including toxin-, drug- and ischemia/reperfusion-induced liver injury, fatty liver, viral hepatitis and hepatocellular carcinoma. This review summarizes recent advances in understanding the roles that autophagy plays in normal hepatic physiology and pathophysiology with the intent of furthering the development of autophagy-based therapies for human liver diseases. PMID:23774882

Changing interdigestive migrating motor complex in rats under acute liver injury.

PubMed

Liu, Mei; Zheng, Su-Jun; Xu, Weihong; Zhang, Jianying; Chen, Yu; Duan, Zhongping

2014-01-01

Gastrointestinal motility disorder is a major clinical manifestation of acute liver injury, and interdigestive migrating motor complex (MMC) is an important indicator. We investigated the changes and characteristics of MMC in rats with acute liver injury. Acute liver injury was created by d-galactosamine, and we recorded the interdigestive MMC using a multichannel physiological recorder and compared the indexes of interdigestive MMC. Compared with normal controls, antral MMC Phase I duration was significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The duodenal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury. The jejunal MMC cycle and MMC Phases I and IV duration were significantly prolonged and MMC Phase III duration was significantly shortened in the rats with acute liver injury compared with normal controls. Compared with the normal controls, rats with acute liver injury had a significantly prolonged interdigestive MMC cycle, related mainly to longer MMC Phases I and IV, shortened MMC Phase III, and MMC Phase II characterized by increased migrating clustered contractions, which were probably major contributors to the gastrointestinal motility disorders.

Electrochemical lesions in the rat liver support its potential for treatment of liver tumors.

PubMed

Wemyss-Holden, S A; Robertson, G S; Dennison, A R; de la M Hall, P; Fothergill, J C; Jones, B; Maddern, G J

2000-09-01

An effective therapy is needed for patients with surgically unresectable liver tumors who have very limited life expectancy. One possible treatment is electrochemical tumor necrosis. This study investigated the natural history of electrochemical lesions in the normal rat liver. A direct current generator, connected to platinum electrodes, was used to create controlled areas of liver necrosis. Animals were sacrificed 2 days, 2 weeks, 2 months, and 6 months after treatment and the macroscopic and histological appearance of the necrotic lesions was followed. No animal died as a result of electrolysis; postoperatively, all gained weight normally. Liver enzymes were significantly (P < 0.001) elevated after treatment, but returned to normal after a week. Two days after electrolysis, histology confirmed an ellipsoidal area of coagulative necrosis at the site of the electrode tip and commonly a segment of peripheral necrosis. After 2 weeks there was histological evidence of healing. By 6 months, very little necrotic tissue remained within a small fibrous scar. Electrolysis is a safe method for creating defined areas of liver necrosis that heal well with no associated mortality. This study supports the potential of electrolysis for treating patients with unresectable liver tumors. Copyright 2000 Academic Press.

Changes in Liver Metabolic Gene Expression after Radiation Exposure

NASA Technical Reports Server (NTRS)

Peters, C. P.; Wotring, Virginia E.

2012-01-01

The health of the liver, especially the rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. Most pharmaceuticals are metabolized by the liver, and clinically-used medication doses are given with normal liver function in mind. A drug overdose can result in the case of a liver that is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism, we want to understand any effects of spaceflight on the enzymes of the liver. Exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments.

An investigation into the effects of temporal resolution on hepatic dynamic contrast-enhanced MRI in volunteers and in patients with hepatocellular carcinoma

NASA Astrophysics Data System (ADS)

Gill, Andrew B.; Black, Richard T.; Bowden, David J.; Priest, Andrew N.; Graves, Martin J.; Lomas, David J.

2014-06-01

This study investigated the effect of temporal resolution on the dual-input pharmacokinetic (PK) modelling of dynamic contrast-enhanced MRI (DCE-MRI) data from normal volunteer livers and from patients with hepatocellular carcinoma. Eleven volunteers and five patients were examined at 3 T. Two sections, one optimized for the vascular input functions (VIF) and one for the tissue, were imaged within a single heart-beat (HB) using a saturation-recovery fast gradient echo sequence. The data was analysed using a dual-input single-compartment PK model. The VIFs and/or uptake curves were then temporally sub-sampled (at interval ▵t = [2-20] s) before being subject to the same PK analysis. Statistical comparisons of tumour and normal tissue PK parameter values using a 5% significance level gave rise to the same study results when temporally sub-sampling the VIFs to HB < ▵t <4 s. However, sub-sampling to ▵t > 4 s did adversely affect the statistical comparisons. Temporal sub-sampling of just the liver/tumour tissue uptake curves at ▵t ≤ 20 s, whilst using high temporal resolution VIFs, did not substantially affect PK parameter statistical comparisons. In conclusion, there is no practical advantage to be gained from acquiring very high temporal resolution hepatic DCE-MRI data. Instead the high temporal resolution could be usefully traded for increased spatial resolution or SNR.

CD24-Positive Cells from Normal Adult Mouse Liver Are Hepatocyte Progenitor Cells

PubMed Central

Qiu, Qiong; Hernandez, Julio Cesar; Dean, Adam M.; Rao, Pulivarthi H.

2011-01-01

The identification of specific cell surface markers that can be used to isolate liver progenitor cells will greatly facilitate experimentation to determine the role of these cells in liver regeneration and their potential for therapeutic transplantation. Previously, the cell surface marker, CD24, was observed to be expressed on undifferentiated bipotential mouse embryonic liver stem cells and 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced oval cells. Here, we describe the isolation and characterization of a rare, primary, nonhematopoietic, CD24+ progenitor cell population from normal, untreated mouse liver. By immunohistochemistry, CD24-expressing cells in normal adult mouse liver were colocalized with CK19-positive cholangiocytes. This nonhematopoietic (CD45−, Ter119−) CD24+ cell population isolated by flow cytometry represented 0.04% of liver cells and expressed several markers of liver progenitor/oval cells. The immunophenotype of nonhematopoietic CD24+ cells was CD133, Dlk, and Sca-1 high, but c-Kit, Thy-1, and CD34 low. The CD24+ cells had increased expression of CK19, epithelial cell adhesion molecule, Sox 9, and FN14 compared with the unsorted cells. Upon transplantation of nonhematopoietic CD24+ cells under the sub-capsule of the livers of Fah knockout mice, cells differentiated into mature functional hepatocytes. Analysis of X and Y chromosome complements were used to determine whether or not fusion of the engrafted cells with the recipient hepatocytes occurred. No cells were found that contained XXXY or any other combination of donor and host sex chromosomes as would be expected if cell fusion had occurred. These results suggested that CD24 can be used as a cell surface marker for isolation of hepatocyte progenitor cells from normal adult liver that are able to differentiate into hepatocytes. PMID:21361791

CD24-positive cells from normal adult mouse liver are hepatocyte progenitor cells.

PubMed

Qiu, Qiong; Hernandez, Julio Cesar; Dean, Adam M; Rao, Pulivarthi H; Darlington, Gretchen J

2011-12-01

The identification of specific cell surface markers that can be used to isolate liver progenitor cells will greatly facilitate experimentation to determine the role of these cells in liver regeneration and their potential for therapeutic transplantation. Previously, the cell surface marker, CD24, was observed to be expressed on undifferentiated bipotential mouse embryonic liver stem cells and 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced oval cells. Here, we describe the isolation and characterization of a rare, primary, nonhematopoietic, CD24+ progenitor cell population from normal, untreated mouse liver. By immunohistochemistry, CD24-expressing cells in normal adult mouse liver were colocalized with CK19-positive cholangiocytes. This nonhematopoietic (CD45-, Ter119-) CD24+ cell population isolated by flow cytometry represented 0.04% of liver cells and expressed several markers of liver progenitor/oval cells. The immunophenotype of nonhematopoietic CD24+ cells was CD133, Dlk, and Sca-1 high, but c-Kit, Thy-1, and CD34 low. The CD24+ cells had increased expression of CK19, epithelial cell adhesion molecule, Sox 9, and FN14 compared with the unsorted cells. Upon transplantation of nonhematopoietic CD24+ cells under the sub-capsule of the livers of Fah knockout mice, cells differentiated into mature functional hepatocytes. Analysis of X and Y chromosome complements were used to determine whether or not fusion of the engrafted cells with the recipient hepatocytes occurred. No cells were found that contained XXXY or any other combination of donor and host sex chromosomes as would be expected if cell fusion had occurred. These results suggested that CD24 can be used as a cell surface marker for isolation of hepatocyte progenitor cells from normal adult liver that are able to differentiate into hepatocytes.

Comparative pharmacokinetics and tissue distribution profiles of lignan components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

PubMed

Yang, Tao; Liu, Shan; Zheng, Tian-Hui; Tao, Yan-Yan; Liu, Cheng-Hai

2015-05-26

Fuzheng Huayu recipe (FZHY) is formulated on the basis of Chinese medicine theory in treating liver fibrosis. To illuminate the influence of the pathological state of liver fibrosis on the pharmacokinetics and tissue distribution profiles of lignan components from FZHY. Male Wistar rats were randomly divided into normal group and Hepatic fibrosis group (induced by dimethylnitrosamine). Six lignan components were detected and quantified by ultrahigh performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)in the plasma and tissue of normal and hepatic fibrosis rats. A rapid, sensitive and convenient UHPLC-MS/MS method has been developed for the simultaneous determination of six lignan components in different rat biological samples successfully. After oral administration of FZHY at a dose of 15g/kg, the pharmacokinetic behaviors of schizandrin A (SIA), schizandrin B (SIB), schizandrin C (SIC), schisandrol A (SOA), Schisandrol B (SOB) and schisantherin A (STA) have been significantly changed in hepatic fibrosis rats compared with the normal rats, and their AUC(0-t) values were increased by 235.09%, 388.44%, 223.30%, 669.30%, 295.08% and 267.63% orderly (P<0.05). Tissue distribution results showed the amount of SIA, SIB, SOA and SOB were significant increased in heart, lung, spleen and kidney of hepatic fibrosis rats compared with normal rats at most of the time point (P<0.05). Meanwhile, the result also reveals that the hepatic fibrosis could delay the peak time of lignans in liver. The results proved that the established UHPLC-MS/MS method could be applied to the comparative study on pharmacokinetics and tissue distribution of lignan components in normal and hepatic fibrosis rats. The hepatic fibrosis could alter the pharmacokinetics and tissue distribution properties of lignan components in rats after administration of FZHY. The results might be helpful for guide the clinical application of this medicine. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Caffeine intake decreases oxidative stress and inflammatory biomarkers in experimental liver diseases induced by thioacetamide: Biochemical and histological study.

PubMed

Amer, Mona G; Mazen, Nehad F; Mohamed, Ahmed M

2017-03-01

Liver disease remains a significant global health problem. Increased caffeine consumption has been associated with a lower prevalence of chronic liver disease. This study aimed to investigate the modifying effects of caffeine on liver injury induced by thioacetamide (TAA) administration in male rats and the possible underlying mechanisms. Forty adult male rats were equally classified into four groups: control group, received only tap water; caffeine-treated group, received caffeine (37.5 mg/kg per day); TAA-treated group, received intraperitoneal (i.p.) TAA (200 mg/kg b.w.) twice a week; and caffeine + TAA-treated group, received combined TAA and caffeine in the same previous doses. After eight weeks of treatment, blood samples were collected for biochemical analysis and liver specimens were prepared for histological and immunohistochemical studies and for assessment of oxidative stress. TAA induced liver toxicity with elevated liver enzymes and histological alterations, fatty changes, apoptosis, and fibrosis evidenced by increased immunohistochemical reaction to matrix metalloproteinase-9 (MMP-9) and collagen type IV in hepatocytes. Also, the levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in serum were significantly elevated. Co-treatment with caffeine and TAA restored normal liver structure and function. Caffeine provided an anti-fibrogenic, anti-inflammatory, and antioxidant effect that was associated with recovery of hepatic histological and functional alterations from TAA-induced hepatotoxicity.

Gene profiling, biomarkers and pathways characterizing HCV-related hepatocellular carcinoma

PubMed Central

De Giorgi, Valeria; Monaco, Alessandro; Worchech, Andrea; Tornesello, MariaLina; Izzo, Francesco; Buonaguro, Luigi; Marincola, Francesco M; Wang, Ena; Buonaguro, Franco M

2009-01-01

Background Hepatitis C virus (HCV) infection is a major cause of hepatocellular carcinoma (HCC) worldwide. The molecular mechanisms of HCV-induced hepatocarcinogenesis are not yet fully elucidated. Besides indirect effects as tissue inflammation and regeneration, a more direct oncogenic activity of HCV can be postulated leading to an altered expression of cellular genes by early HCV viral proteins. In the present study, a comparison of gene expression patterns has been performed by microarray analysis on liver biopsies from HCV-positive HCC patients and HCV-negative controls. Methods Gene expression profiling of liver tissues has been performed using a high-density microarray containing 36'000 oligos, representing 90% of the human genes. Samples were obtained from 14 patients affected by HCV-related HCC and 7 HCV-negative non-liver-cancer patients, enrolled at INT in Naples. Transcriptional profiles identified in liver biopsies from HCC nodules and paired non-adjacent non-HCC liver tissue of the same HCV-positive patients were compared to those from HCV-negative controls by the Cluster program. The pathway analysis was performed using the BRB-Array- Tools based on the "Ingenuity System Database". Significance threshold of t-test was set at 0.001. Results Significant differences were found between the expression patterns of several genes falling into different metabolic and inflammation/immunity pathways in HCV-related HCC tissues as well as the non-HCC counterpart compared to normal liver tissues. Only few genes were found differentially expressed between HCV-related HCC tissues and paired non-HCC counterpart. Conclusion In this study, informative data on the global gene expression pattern of HCV-related HCC and non-HCC counterpart, as well as on their difference with the one observed in normal liver tissues have been obtained. These results may lead to the identification of specific biomarkers relevant to develop tools for detection, diagnosis, and classification of HCV-related HCC. PMID:19821982

In vivo antioxidant effect of aqueous root bark, stem bark and leaves extracts of Vitex doniana in CCl4 induced liver damage rats.

PubMed

Adetoro, Kadejo Olubukola; Bolanle, James Dorcas; Abdullahi, Sallau Balarebe; Ahmed, Ozigi Abdulrahaman

2013-05-01

The antioxidant effects of aqueous root bark, stem bark and leaves of Vitex doniana (V. doniana) were evaluated in carbon tetrachloride (CCl4) induced liver damage and non induced liver damage albino rats. A total of 60 albino rats (36 induced liver damage and 24 non induced liver damage) were assigned into liver damage and non liver damage groups of 6 rats in a group. The animals in the CCl4 induced liver damage groups, were induced by intraperitoneal injection with a single dose of CCl4 (148 mg·ml(-1)·kg(-1) body weight) as a 1:1 (v/v) solution in olive oil and were fasted for 36 h before the subsequent treatment with aqueous root bark, stem bark and leaves extracts of V. doniana and vitamin E as standard drug (100 mg/kg body weighy per day) for 21 d, while the animals in the non induced groups were only treated with the daily oral administration of these extracts at the same dose. The administration of CCl4 was done once a week for a period of three weeks. The liver of CCl4 induced not treated group showed that the induction with CCl4, significantly (P<0.05) increased thiobarbituric acid reactive substance (TBARS) and significantly (P<0.05) decreased superoxide dismutase (SOD) and catalase (CAT). However there was no significant (P>0.05) difference between TBARS, SOD and CAT in the liver of the induced treated groups and normal control group. In the kidney, TBARS showed no significant (P>0.05) difference between the normal and the induced groups, SOD was significantly (P<0.05) reduced in the CCl4 group compared to standard drug and normal control groups, CAT was significantly (P<0.05) increased in root and vitamin E groups when compared to induced not treated group. The studies also showed that when the extracts were administered to normal animals, there was no significant (P>0.05) change in the liver and kidney level of TBARS, SOD and CAT compared with the normal control except in the kidney of animals treated with stem extract where TBARS was significantly (P<0.05) lowered compared to control group. The result of the present study suggests that application of V. doniana plant would play an important role in increasing the antioxidant effect and reducing the oxidative damage that formed both in liver and in kidney tissues. However stem bark has potential to improve renal function in normal rats.

Deficient copper concentrations in dried-defatted hepatic tissue from ob/ob mice: A potential model for study of defective copper regulation in metabolic liver disease.

PubMed

Church, Stephanie J; Begley, Paul; Kureishy, Nina; McHarg, Selina; Bishop, Paul N; Bechtold, David A; Unwin, Richard D; Cooper, Garth J S

2015-05-08

Ob/ob mice provide an animal model for non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH) in patients with obesity and type-2 diabetes. Low liver copper has been linked to hepatic lipid build-up (steatosis) in animals with systemic copper deficiency caused by low-copper diets. However, hepatic copper status in patients with NAFLD or NASH is uncertain, and a validated animal model useful for the study of hepatic copper regulation in common forms of metabolic liver disease is lacking. Here, we report parallel measurements of essential metal levels in whole-liver tissue and defatted-dried liver tissue from ob/ob and non-obese control mice. Measurements in whole-liver tissue from ob/ob mice at an age when they have developed NAFLD/NASH, provide compelling evidence for factitious lowering of copper and all other essential metals by steatosis, and so cannot be used to study hepatic metal regulation in this model. By marked contrast, metal measurements in defatted-dried liver samples reveal that most essential metals were actually normal and indicate specific lowering of copper in ob/ob mice, consistent with hepatic copper deficiency. Thus ob/ob mice can provide a model useful for the study of copper regulation in NAFLD and NASH, provided levels are measured in defatted-dried liver tissue. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review.

PubMed

Reardon, Jillian; Hussaini, Trana; Alsahafi, Majid; Azalgara, Vladimir Marquez; Erb, Siegfried R; Partovi, Nilufar; Yoshida, Eric M

2016-09-28

Aims: To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions. Methods: Searches were conducted on the databases of Medline (1948-March 31, 2015), Embase (1980-March 31, 2015) and the Cochrane Central Register of Controlled Trials, and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications. Combinations of the following search terms were used: ursodeoxycholic acid, ursodiol, bile acids and/or salts, non alcoholic fatty liver, non alcoholic steatohepatitis, fatty liver, alcoholic hepatitis, alcohol, liver disease, autoimmune, autoimmune hepatitis, liver transplant, liver graft, transplant rejection, graft rejection, ischemic reperfusion injury, reperfusion injury, hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, acute hepatitis, transaminases, alanine transaminase, liver enzymes, aspartate aminotransferase, gamma-glutamyl transferase, gamma-glutamyl transpeptidase, bilirubin, alkaline phosphatase. No search limits were applied. Additionally, references of the included studies were reviewed to identify additional articles. Results: The literature search yielded articles meeting inclusion criteria for the following indications: non-alcoholic fatty liver disease (n = 5); alcoholic liver disease (n = 2); autoimmune hepatitis (n = 6), liver transplant (n = 2) and viral hepatitis (n = 9). Bile acid use was associated with improved normalization of liver biochemistry in non-alcoholic fatty liver disease, autoimmune hepatitis and hepatitis B and C infections. In contrast, liver biochemistry normalization was inconsistent in alcoholic liver disease and liver transplantation. The majority of studies reviewed showed that normalization of liver biochemistry did not correlate to improvement in histologic disease. In the prospective trials reviewed, adverse effects associated with the bile acids were limited to minor gastrointestinal complaints (most often, diarrhea) and did not occur at increased frequency as compared to controls. As administration of bile acids was often limited to durations of 12 months or less, long-term side effects for non-cholestatic indications cannot be excluded. Conclusions: Based on the available literature, bile acids cannot be widely recommended for non-cholestatic liver diseases at present.

Diagnostic value of diffusion weighted MRI and ADC in differential diagnosis of cavernous hemangioma of the liver.

PubMed

Tokgoz, Ozlem; Unlu, Ebru; Unal, Ilker; Serifoglu, Ismail; Oz, Ilker; Aktas, Elif; Caglar, Emrah

2016-03-01

To investigate the use of diffusion weighted magnetic resonance imaging (DWI) and the apparent diffusion coefficient (ADC) values in the diagnosis of hemangioma. The study population consisted of 72 patients with liver masses larger than 1 cm (72 focal lesions). DWI examination with a b value of 600 s/mm2 was carried out for all patients. After DWI examination, an ADC map was created and ADC values were measured for 72 liver masses and normal liver tissue (control group). The average ADC values of normal liver tissue and focal liver lesions, the "cut-off" ADC values, and the diagnostic sensitivity and specificity of the ADC map in diagnosing hemangioma, benign and malignant lesions were researched. Of the 72 liver masses, 51 were benign and 21 were malignant. Benign lesions comprised 38 hemangiomas and 13 simple cysts. Malignant lesions comprised 9 hepatocellular carcinomas, and 12 metastases. The highest ADC values were measured for cysts (3.782±0.53×10(-3) mm(2)/s) and hemangiomas (2.705±0.63×10(-3) mm(2)/s). The average ADC value of hemangiomas was significantly higher than malignant lesions and the normal control group (p<0.001). The average ADC value of cysts were significantly higher when compared to hemangiomas and normal control group (p<0.001). To distinguish hemangiomas from malignant liver lesions, the "cut-off" ADC value of 1.800×10(-3) mm(2)/s had a sensitivity of 97.4% and a specificity of 90.9%. To distinguish hemangioma from normal liver parenchyma the "cut-off" value of 1.858×10(-3) mm(2)/s had a sensitivity of 97.4% and a specificity of 95.7%. To distinguish benign liver lesions from malignant liver lesions the "cut-off" value of 1.800×10(-3) mm(2)/s had a sensitivity of 96.1% and a specificity of 90.0%. DWI and quantitative measurement of ADC values can be used in differential diagnosis of benign and malignant liver lesions and also in the diagnosis and differentiation of hemangiomas. When dynamic examination cannot distinguish cases with vascular metastasis and lesions from hemangioma, DWI and ADC values can be useful in the primary diagnosis and differential diagnosis. The technique does not require contrast material, so it can safely be used in patients with renal failure.

Preliminary profiling of microRNA in the normal and regenerating liver of Chiloscyllium plagiosum.

PubMed

Cheng, Dandan; Chen, Yanna; Lu, Conger; Qian, Yuezhong; Lv, Zhengbing

2017-12-01

Liver is a vital organ present in animals for detoxification, protein synthesis, digestion and other functions and its powerful regenerative capacity is well known. C. plagiosum is an abundant fish that is representative of the cartilaginous class in the southeast coastal region of China and its liver accounts for >70% of the fish's visceral weight and contains many bioactive substances. MicroRNAs (microRNAs) play important roles in a wide range of biological processes in eukaryotes, including cell proliferation, differentiation, apoptosis. However, microRNAs in response to liver regeneration has not been well studied. This study aimed to identify the microRNAs that participate in liver regeneration and other liver-related diseases and to improve our understanding of the mechanisms of liver regeneration in sharks. To this end, normal and regenerating liver tissues from C. plagiosum were harvested 0, 3, 6, 12 and 24h after partial hepatectomy (pH) and were sequenced using the Illumina/Solexa platform. In total, 309 known microRNAs and 590 novel microRNAs were identified in C. plagiosum. There were many microRNAs differentially expressed in the normal and regenerating livers between time points. Using target prediction and GO analysis, most of the differentially expressed microRNAs were assigned to functional categories that may be involved in regulating liver regeneration, such as cell proliferation, differentiation and apoptosis. The microRNA expression profile of liver regeneration will pave the way for the development of effective strategies to fight against liver disease and other related disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Liver stiffness and platelet count for identifying patients with compensated liver disease at low risk of variceal bleeding.

PubMed

Marot, Astrid; Trépo, Eric; Doerig, Christopher; Schoepfer, Alain; Moreno, Christophe; Deltenre, Pierre

2017-05-01

The 2015 Baveno VI guidelines recommend against performing upper gastrointestinal endoscopy in patients with compensated cirrhosis who have a liver stiffness <20 kPa and a platelet count >150 000/mm³ because of a low prevalence of varices at risk of bleeding in this population. The aim was to synthesize the available evidence on the usefulness of the combined use of liver stiffness and platelet count to identify patients without oesophageal varices. Meta-analysis of trials evaluating the usefulness of a given cut-off for liver stiffness and platelet count to rule out the presence of oesophageal varices. Fifteen studies were included. All studies excepting five used the Baveno VI criteria. Compared to patients with either high liver stiffness or low platelet count, those with low liver stiffness and normal platelet count had a lower risk of varices at risk of bleeding (OR=0.22, 95% CI=0.13-0.39, P<.001) with low heterogeneity between studies (I 2 =21%). They also had a lower risk of varices (OR=0.23, 95% CI=0.17-0.32, P<.001) with moderate heterogeneity between studies (I 2 =28%). In patients with low liver stiffness and normal platelet count, the pooled estimate rates for varices at risk of bleeding was 0.040 (95% CI=0.027-0.059) with low heterogeneity between studies (I 2 =3%). Patients with low liver stiffness and normal platelet count have a lower risk of varices than those with either high liver stiffness or low platelet count. Varices at risk of bleeding are found in no more than 4% of patients when liver stiffness is <20 kPa and platelet count is normal. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Exaggerated Liver Injury Induced by Renal Ischemia Reperfusion in Diabetes: Effect of Exenatide

PubMed Central

Vaghasiya, Jitendra D.; Sheth, Navin R.; Bhalodia, Yagnik S.; Jivani, Nurudin P.

2010-01-01

Background/Aim: This study was designed to investigate the possible effect of exenatide (Glucagon like Peptide-1 receptor agonist) on liver injury (distant organ) induced by renal ischemia reperfusion (IR) in diabetic rats. Materials and Methods: In vivo renal IR was performed in both type 2 diabetic and normal rats. Each protocol comprised ischemia for 30 minutes followed by reperfusion for 24 hours and a treatment period of 14 days before induction of ischemia. Results: Lipid peroxidation, xanthine oxidase activity, myeloperoxidase activity and nitric oxide level in liver tissue were significantly increased (P < 0.01, P < 0.001, P < 0.001, P < 0.05, respectively), after IR in diabetic rats compared to normal rats. Antioxidant enzymes like glutathione, superoxide dismutase, catalase and glutathione peroxidase were significantly reduced (P < 0.05, P < 0.05, P < 0.01, P < 0.05, respectively), after IR in diabetic rats compared to normal rats. Exenatide treatment significantly normalized (P < 0.01), these biochemical parameters in treated rats compared to diabetic IR rats. Serum creatinine phosphokinase activity and liver function enzymes were also significantly normalized (P < 0.001, P < 0.001, respectively), after administration of exenatide. Conclusion: Exenatide exerted protective effect on exaggerated remote organ (liver) injury induced by renal IR in diabetes. PMID:20616412

Impacts of exposure to 900 MHz mobile phone radiation on liver function in rats.

PubMed

Ma, Hui-rong; Ma, Zhi-hong; Wang, Gui-ying; Song, Cui-miao; Ma, Xue-lian; Cao, Xiao-hui; Zhang, Guo-hong

2015-11-01

To study the impacts of exposure to electromagnetic radiation (EMR) on liver function in rats. Twenty adult male Sprague-Dawley rats were randomly divided into normal group and radiated group. The rats in normal group were not radiated, those in radiated group were exposed to EMR 4 h/ d for 18 consecutive days. Rats were sacrificed immediately after the end of the experiment. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and those of malondialdehyde (MDA) and glutathione (GSH) in liver tissue were evaluated by colorimetric method. The liver histopathological changes were observed by hematoxylin and eosin staining and the protein expression of bax and bcl- 2 in liver tissue were detected by immunohistochemical method. Terminal-deoxynucleotidyl transferase mediated nick and labelling (TUNEL) method was used for analysis of apoptosis in liver. Compared with the normal rats, the serum levels of ALT and AST in the radiated group had no obvious changes (P>0.05), while the contents of MDA increased (P < 0.01) and those of GSH decreased (P < 0.01) in liver tissues. The histopathology examination showed diffuse hepatocyte swelling and vacuolation, small pieces and focal necrosis. The immunohistochemical results displayed that the expression of the bax protein was higher and that of bcl-2 protein was lower in radiated group. The hepatocyte apoptosis rates in radiated group was higher than that in normal group (all P < 0.01). The exposure to 900 MHz mobile phone 4 h/d for 18 days could induce the liver histological changes, which may be partly due to the apoptosis and oxidative stress induced in liver tissue by electromagnetic radiation.

Effects of direct current on dog liver: Possible mechanisms for tumor electrochemical treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, K.H.; Gu, Y.N.; Xu, B.I.

1997-03-01

Mechanisms of tumor electrochemical treatment (ECT) were studied using normal dog liver. Five physical and chemical methods were used. Two platinum electrodes were inserted into an anesthetized dog`s liver at 3 cm separation. A voltage of 8.5 V direct current (DC) at an average current of 30 mA was applied for 69 min; total charge was 124 coulombs. Concentrations of selected ions near the anode and cathode were measured. The concentrations of Na{sup +} and K{sup +} ions were higher around the cathode, whereas the concentration of Cl{sup {minus}} ions was higher around the anode. Water contents and pH weremore » determined near the anode and the cathode at the midpoint between the two electrodes and in an untreated area away from the electrodes. Hydration occurred around the cathode, and dehydration occurred around the anode. The pH values were 2.1 near the anode and 12.9 near the cathode. Spectrophotometric scans of the liver sample extract were obtained, and the released gases were identified by gas chromatography as chlorine at the anode and hydrogen at the cathode. These results indicate that a series of electrochemical reactions take place during ECT. The cell metabolism and its environment are severely disturbed. Both normal and tumor cells are rapidly and completely destroyed in this altered environment. The authors believe that the above reactions are the ECT mechanisms for treating tumors.« less

Dental postoperative bleeding complications in patients with suspected and documented liver disease.

PubMed

Hong, C H; Scobey, M W; Napenas, J J; Brennan, M T; Lockhart, P B

2012-10-01

The aims of this study were to determine the frequency of bleeding complications following dental procedures in patients with known or suspected chronic liver disease and whether international normalized ratio (INR) determination could aid in predicting bleeding complications in these patients. We identified 90 patients (mean age: 51 ± 9 years) in this retrospective chart review. Sixty-nine patients had a known history of chronic liver disease and 21 had suspected chronic liver disease. Descriptive statistics were determined. Independent sample t-test and one-way variance test were utilized for continuous variables and chi-square test for dichotomous variables. The mean INR value for all patients was 1.2 ± 0.3. The INR value was significantly associated with the diagnosis of liver cirrhosis, the diagnoses of Hepatitis B and C together, the presence of ascites alone, and the number of clinical signs and symptoms (i.e. ascites, jaundice and encephalopathy) present. Nine patients with INR values between 1.5 and 2 underwent invasive dental procedures without postoperative bleeding complications. There were no episodes of postoperative bleeding in patients. The findings suggest that clinicians should not rely solely on an INR value to predict post-procedure bleeding in patients with liver disease. © 2012 John Wiley & Sons A/S.

Protective effects of ACLF sera on metabolic functions and proliferation of hepatocytes co-cultured with bone marrow MSCs in vitro

PubMed Central

Shi, Xiao-Lei; Gu, Jin-Yang; Zhang, Yue; Han, Bing; Xiao, Jiang-Qiang; Yuan, Xian-Wen; Zhang, Ning; Ding, Yi-Tao

2011-01-01

AIM: To investigate whether the function of hepatocytes co-cultured with bone marrow mesenchymal stem cells (MSCs) could be maintained in serum from acute-on-chronic liver failure (ACLF) patients. METHODS: Hepatocyte supportive functions and cytotoxicity of sera from 18 patients with viral hepatitis B-induced ACLF and 18 healthy volunteers were evaluated for porcine hepatocytes co-cultured with MSCs and hepatocyte mono-layered culture, respectively. Chemokine profile was also examined for the normal serum and liver failure serum. RESULTS: Hepatocyte growth factor (HGF) and Tumor necrosis factor; tumor necrosis factor (TNF)-α were remarkably elevated in response to ACLF while epidermal growth factor (EGF) and VEGF levels were significantly decreased. Liver failure serum samples induced a higher detachment rate, lower viability and decreased liver support functions in the homo-hepatocyte culture. Hepatocytes co-cultured with MSCs could tolerate the cytotoxicity of the serum from ACLF patients and had similar liver support functions compared with the hepatocytes cultured with healthy human serum in vitro. In addition, co-cultured hepatocytes maintained a proliferative capability despite of the insult from liver failure serum. CONCLUSION: ACLF serum does not impair the cell morphology, viability, proliferation and overall metabolic capacities of hepatocyte co-cultured with MSCs in vitro. PMID:21633639

Evaluation of Fish Health Status and Histopathology in Gills and Liver Due to Metal Contaminated Sediments Exposure.

PubMed

Jabeen, Ghazala; Manzoor, Farkhanda; Javid, Arshad; Azmat, Hamda; Arshad, Mateen; Fatima, Shafaq

2018-04-01

Health status of freshwater fish, Cirrhina mrigala was studied by qualitative and quantitative histopathological analysis, alterations in frequency/prevalence percentages (%) and histological alteration indices (HAI) in response to metal contaminated sediments of the River Ravi aquatic ecosystem. Histo-structures of gill and liver samples of fish were analyzed and comparison between the degree of damage of the alterations in fish organs was performed after exposure to metal contaminated sediments for 7, 14 and 28 days under semi-static water renewal bioassays. Histopathological studies revealed marked histological alterations in the gills and liver of exposed fish as compared to normal tissue structure observed in control fish. The frequency and prevalence percentages observed in 28-day exposed fish were significantly higher as compared to 7- and 14-day exposed fish. The order of frequency and prevalence percentage for gills and liver of exposed fish was as: 28-day > 14-day > 7-day. The highest prevalence percentages recorded were 83 and 80% as focal area of necrosis in gill and liver, respectively, after 28-day exposure. The lowest prevalence percentage observed in 7-day exposed Cirrhina mrigala was dilation of sinusoids (17%).

Treatment of Rats with Apocynin Has Considerable Inhibitory Effects on Arylamine N-Acetyltransferase Activity in the Liver.

PubMed

Francis, Sheena; Laurieri, Nicola; Nwokocha, Chukwuemeka; Delgoda, Rupika

2016-05-31

The effect of apocynin on the activity of arylamine N-acetyltransferases (NATs) in excised liver samples was examined using eighteen Sprague-Dawley rats. Three groups of six animals each were fed a normal diet alone or a treatment of 50 or 100 mg/kg/day of apocynin via gavages for eight (8) weeks. Chronic in vivo administration of apocynin led to significant (p < 0.001) reduction of in vitro liver NAT activity up to 93% as compared with untreated rats (18.80 ± 2.10 μmols p-anisidine/min/μg liver protein). In vitro exposure of untreated liver homogenates to apocynin led to a dose-dependent inhibition of NAT activity with IC50 = 0.69 ± 0.02 mM. In silico modelling of apocynin tautomers and radical species into human NAT crystal structures supported the hypothesis that thiol functionalities in NAT enzymes may be crucial in apocynin binding. The involvement of human NAT enzymes in different pathological conditions, such as cancer, has encouraged the research for selective NAT inhibitors in both humans and animal models with possible chemopreventive properties.

Evaluation of the antitumor activity of platinum nanoparticles in the treatment of hepatocellular carcinoma induced in rats.

PubMed

Medhat, Amina; Mansour, Somaya; El-Sonbaty, Sawsan; Kandil, Eman; Mahmoud, Mustafa

2017-07-01

This study aimed to evaluate the antitumor activity of platinum nanoparticles compared with cis-platin both in vitro and in vivo in the treatment of hepatocellular carcinoma induced in rats. The treatment efficacy of platinum nanoparticles was evaluated by measuring antioxidant activities against oxidative stress caused by diethylnitrosamine in liver tissue. The measurements included reduced glutathione content and superoxide dismutase activity, as well as malondialdehyde level. Liver function tests were also determined, in addition to the evaluation of serum alpha-fetoprotein, caspase-3, and cytochrome c in liver tissue. Total RNA extraction from liver tissue samples was also done for the relative quantification of B-cell lymphoma 2, matrix metallopeptidase 9, and tumor protein p53 genes. Histopathological examination was also performed for liver tissue. Results showed that platinum nanoparticles are more potent than cis-platin in treatment of hepatocellular carcinoma induced by diethylnitrosamine in rats as it ameliorated the investigated parameters toward normal control animals. These findings were well appreciated with histopathological studies of diethylnitrosamine group treated with platinum nanoparticles, suggesting that platinum nanoparticles can serve as a good therapeutic agent for the treatment of hepatocellular carcinoma which should attract further studies.

Elevated alanine aminotransferase (ALT) in the deceased donor: impact on early post-transplant liver allograft function.

PubMed

Mangus, Richard S; Fridell, Jonathan A; Kubal, Chandrashekhar A; Davis, Jason P; Tector, A Joseph

2015-02-01

Serum alanine aminotransferase (ALT) levels are frequently elevated with liver injury and such elevations are common in deceased organ donors. The impact of this injury on early liver allograft function has not been well described. This study analyses the immediate function and 1-year graft and patient survival for liver allografts stratified by peak serum ALT levels in the deceased donor. The on-site organ procurement records for 1348 consecutive deceased liver donors were reviewed (2001–2011). Serum ALT was categorized into three study groups: normal/mild elevation, 0–499 μ/L; moderate elevation, 500–999 μ/L (>10× upper limit of normal) and severe elevation, ≥1000 μ/L (>20× upper limit of normal). Outcomes included early graft function and graft loss, and 1-year graft and patient survival. Distribution of subjects included: normal/mild, 1259 (93%); moderate, 34 (3%) and severe, 55 (4%). Risk of 30-day graft loss for the three study groups was: 72 (6%), 3 (9%) and 3 (6%) (P = 0.74). Graft and patient survival at 1 year for the three groups was: normal/mild, 1031 (87%), 1048 (88%); moderate, 31 (91%), 31 (91%) and severe, 43 (88%), 44 (90%) (P = 0.71, 0.79). Cox proportional hazards modelling of survival while controlling for donor age and recipient model for end-stage liver disease score (MELD) demonstrates no statistically significant difference among the three study groups. This study demonstrates clinical equivalence in early graft function and 1-year graft and patient survival for donor livers with varying peak levels of serum ALT. These donor allografts may, therefore, be utilized successfully.

Flow dynamics analyses of pathophysiological liver lobules using porous media theory

NASA Astrophysics Data System (ADS)

Hu, Jinrong; Lü, Shouqin; Feng, Shiliang; Long, Mian

2017-08-01

Blood flow inside the liver plays a key role in hepatic functions, and abnormal hemodynamics are highly correlated with liver diseases. To date, the flow field in an elementary building block of the organ, the liver lobule, is difficult to determine experimentally in humans due to its complicated structure, with radially branched microvasculature and the technical difficulties that derive from its geometric constraints. Here we established a set of 3D computational models for a liver lobule using porous media theory and analyzed its flow dynamics in normal, fibrotic, and cirrhotic lobules. Our simulations indicated that those approximations of ordinary flow in portal tracts (PTs) and the central vein, and of porous media flow in the sinusoidal network, were reasonable only for normal or fibrotic lobules. Models modified with high resistance in PTs and collateral vessels inside sinusoids were able to describe the flow features in cirrhotic lobules. Pressures, average velocities, and volume flow rates were profiled and the predictions compared well with experimental data. This study furthered our understanding of the flow dynamics features of liver lobules and the differences among normal, fibrotic, and cirrhotic lobules.

Urine metabolic profile changes of CCl4-liver fibrosis in rats and intervention effects of Yi Guan Jian Decoction using metabonomic approach

PubMed Central

2013-01-01

Background Yi Guan Jian Decoction (YGJD), a famous Chinese prescription, has long been employed clinically to treat liver fibrosis. However, as of date, there is no report on the effects of YGJD from a metabonomic approach. In this study, a urine metabonomic method based on gas chromatography coupled with mass spectrometry (GC/MS) was employed to study the protective efficacy and metabolic profile changes caused by YGJD in carbon tetrachloride (CCl4)-induced liver fibrosis. Methods Urine samples from Wistar rats of three randomly divided groups (control, model, and YGJD treated) were collected at various time-points, and the metabolic profile changes were analyzed by GC/MS with principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA). Furthermore, histopathology and biochemical examination were also carried out to ensure the success of CCl4-induced liver fibrosis model. Results Urine metabolic profile studies suggested distinct clustering of the three groups, and YGJD group was much closer to the control group by showing a tendency of recovering towards the control group. Fourteen significantly changed metabolites were found, and YGJD treatment could reverse the levels of these metabolites to normal levels or close to normal levels. Conclusions The current study indicates that the YGJD has significant anti-fibrotic effects on CCl4-induced liver fibrosis in rats, which might be by regulating the dysfunction of energy metabolism, amino acid metabolism, tryptophan metabolism, cytochrome P450 metabolism, and gut microflora metabolism. The metabonomic approach can be recommended to study the pharmacological effect and mechanism of complex Chinese medicines. PMID:23725349

Amplification and sequence analysis of partial bacterial 16S ribosomal RNA gene in gallbladder bile from patients with primary biliary cirrhosis.

PubMed

Hiramatsu, K; Harada, K; Tsuneyama, K; Sasaki, M; Fujita, S; Hashimoto, T; Kaneko, S; Kobayashi, K; Nakanuma, Y

2000-07-01

The etiopathogenesis of bile duct lesion in primary biliary cirrhosis is unknown, though the participation of bacteria and/or their components and products is suspected. In this study, we tried to detect and identify bacteria in the bile of patients with primary biliary cirrhosis by polymerase chain reaction using universal bacterial primers of the 16S ribosomal RNA gene. Gallbladder bile samples from 15 patients with primary biliary cirrhosis, 5 with primary sclerosing cholangitis, 5 with hepatitis C virus-related liver cirrhosis, 11 with cholecystolithiasis, and from 12 normal adult gallbladders were used. In addition to the culture study, partial bacterial 16S ribosomal RNA gene was amplified by polymerase chain reaction (PCR) taking advantage of universal primers that can amplify the gene of almost all bacterial species, and the amplicons were cloned and sequenced. Sequence homology with specific bacterial species was analyzed by database research. Bacterial contamination at every step of the bile sampling, DNA extraction and PCR study was avoided. Furthermore, to confirm whether bacterial DNA is detectable in liver explants, the same analysis was performed using 10 liver explants of patients with primary biliary cirrhosis. In primary biliary cirrhosis, 75% (p<0.0001) of 100 clones were identified as so-called gram-positive cocci while these cocci were positive in only 5% in cholecystolithiasis (p<0.0001). In cholecystolithiasis gram-negative rods were predominant instead. One bacterial species detected in a normal adult was not related to those detected in primary biliary cirrhosis and cholecystolithiasis patients. No bacterial DNA was detected by PCR amplification in 10 liver explants of patients with primary biliary cirrhosis. The present results raise several possible roles of gram-positive bacteria in bile in the etiopathogenesis of primary biliary cirrhosis. However, these results could also reflect an epiphenomenon due to decreased bile flow in the patients with primary biliary cirrhosis at an advanced stage.

A case of moderate liver enzyme elevation after acute acetaminophen overdose despite undetectable acetaminophen level and normal initial liver enzymes.

PubMed

Bebarta, Vikhyat S; Shiner, Drew C; Varney, Shawn M

2014-01-01

Liver function test (LFT) increase is an early sign of acetaminophen (APAP) toxicity. Typically, when an acute overdose patient is evaluated and has an initial undetectable APAP level and normal liver enzymes, the patient is not treated with N-acetylcysteine, and liver enzymes are not expected to increase later. We report a case of moderate LFT increase despite normal LFTs and an undetectable APAP level after delayed presentation of an APAP ingestion. A 22-year-old male with no medical history ingested 15-25 hydrocodone/APAP tablets (5 mg/500 mg). His suicide note and his bunkmate corroborated the overdose time. He arrived at the emergency department 16 hours after ingestion. At that time, his APAP level was <10 μg/mL, and his liver enzymes were normal [aspartate transaminase (AST) 31 U/L and alanine transaminase (ALT) 34 U/L]. Twenty-nine hours after ingestion, the psychiatry team obtained LFTs (AST 45, ALT 61). He had persistent nausea and diffuse abdominal pain. On repeat analysis, the APAP level at 36 hours was found to be <10 μg/mL, AST 150, and ALT 204. After 2 more days of increasing LFTs and persistent abdominal pain and nausea, the toxicology department was consulted, the patient was transferred to the medicine department, and intravenous N-acetylcysteine was started 66 hours after ingestion. He was treated for 16 hours and had a significant decline in LFTs and symptom resolution. His prothrombin time, bilirubin, lactate, creatinine, and mental status were normal throughout the admission. Other cases of LFT increase were excluded. Our case report illustrates that a moderate increase in liver transaminase may occur despite an initial undetectable APAP level and normal transaminases after a delayed presentation. In our case, no serious clinical effects were reported.

Choline supplementation protects against liver damage by normalizing cholesterol metabolism in Pemt/Ldlr knockout mice fed a high-fat diet.

PubMed

Al Rajabi, Ala; Castro, Gabriela S F; da Silva, Robin P; Nelson, Randy C; Thiesen, Aducio; Vannucchi, Helio; Vine, Donna F; Proctor, Spencer D; Field, Catherine J; Curtis, Jonathan M; Jacobs, René L

2014-03-01

Dietary choline is required for proper structure and dynamics of cell membranes, lipoprotein synthesis, and methyl-group metabolism. In mammals, choline is synthesized via phosphatidylethanolamine N-methyltransferase (Pemt), which converts phosphatidylethanolamine to phosphatidylcholine. Pemt(-/-) mice have impaired VLDL secretion and developed fatty liver when fed a high-fat (HF) diet. Because of the reduction in plasma lipids, Pemt(-/-)/low-density lipoprotein receptor knockout (Ldlr(-/-)) mice are protected from atherosclerosis. The goal of this study was to investigate the importance of dietary choline in the metabolic phenotype of Pemt(-/-)/Ldlr(-/-) male mice. At 10-12 wk of age, Pemt(+/+)/Ldlr(-/-) (HF(+/+)) and half of the Pemt(-/-)/Ldlr(-/-) (HF(-/-)) mice were fed an HF diet with normal (1.3 g/kg) choline. The remaining Pemt(-/-)/Ldlr(-/-) mice were fed an HF diet supplemented (5 g/kg) with choline (HFCS(-/-) mice). The HF diet contained 60% of calories from fat and 1% cholesterol, and the mice were fed for 16 d. HF(-/-) mice lost weight and developed hepatomegaly, steatohepatitis, and liver damage. Hepatic concentrations of free cholesterol, cholesterol-esters, and triglyceride (TG) were elevated by 30%, 1.1-fold and 3.1-fold, respectively, in HF(-/-) compared with HF(+/+) mice. Choline supplementation normalized hepatic cholesterol, but not TG, and dramatically improved liver function. The expression of genes involved in cholesterol transport and esterification increased by 50% to 5.6-fold in HF(-/-) mice when compared with HF(+/+) mice. Markers of macrophages, oxidative stress, and fibrosis were elevated in the HF(-/-) mice. Choline supplementation normalized the expression of these genes. In conclusion, HF(-/-) mice develop liver failure associated with altered cholesterol metabolism when fed an HF/normal choline diet. Choline supplementation normalized cholesterol metabolism, which was sufficient to prevent nonalcoholic steatohepatitis development and improve liver function. Our data suggest that choline can promote liver health by maintaining cholesterol homeostasis.

Gallium-68 DOTATOC PET/CT In Vivo Characterization of Somatostatin Receptor Expression in the Prostate

PubMed Central

Gajić, Milan M.; Obradović, Vladimir B.; Baum, Richard P.

2014-01-01

Abstract Aim: The aim was to investigate somatostatin receptor (sstr) expression in normal prostate by determining the maximum standardized uptake value (SUVmax) of 68Ga-DOTATOC PET/CT in neuroendocrine tumor (NET) patients, without NET involvement of the prostate gland, for establishing the reference standard. Methods: Sixty-four NET patients underwent 68Ga-DOTATOC PET/CT. SUVmax of the prostate gland, normal liver, testes, and gluteus muscles were evaluated. The prostate gland size was measured. Statistical analysis was performed using dedicated software (SPSS13). Results: Mean/median 68Ga-DOTATOC SUVmax values were as follows: normal prostate 2.6±0.0, slightly enlarged prostate 4.2±1.6, prostatic hypertrophy 4.9±1.6, prostatic hyperplasia 5.0±1.5, prostate cancer 9.5±2.1, normal liver 7.3±1.8, testes 1.8±0.5, and gluteus 1.0±0.2. The normal prostate gland had three times less sstr expression than normal liver tissue. Strong correlation was found between patient age and sstr expression in prostate/prostate size. No significant difference existed in sstr expression between prostatic hypertrophy and hyperplasia. Much higher sstr expression was found in prostatic cancer compared with normal prostate. Conclusion: 68Ga-DOTATOC PET/CT defines the baseline sstr uptake in prostate not affected by NET (significantly lower than in the liver). Higher values were established in prostatic hyperplasia and hypertrophy. Only concomitant prostate cancer was associated with higher SUVmax in comparison with non-neoplastic liver. PMID:24450327

Normal and Fibrotic Rat Livers Demonstrate Shear Strain Softening and Compression Stiffening: A Model for Soft Tissue Mechanics

PubMed Central

Cao, Xuan; van Oosten, Anne; Shenoy, Vivek B.; Janmey, Paul A.; Wells, Rebecca G.

2016-01-01

Tissues including liver stiffen and acquire more extracellular matrix with fibrosis. The relationship between matrix content and stiffness, however, is non-linear, and stiffness is only one component of tissue mechanics. The mechanical response of tissues such as liver to physiological stresses is not well described, and models of tissue mechanics are limited. To better understand the mechanics of the normal and fibrotic rat liver, we carried out a series of studies using parallel plate rheometry, measuring the response to compressive, extensional, and shear strains. We found that the shear storage and loss moduli G’ and G” and the apparent Young's moduli measured by uniaxial strain orthogonal to the shear direction increased markedly with both progressive fibrosis and increasing compression, that livers shear strain softened, and that significant increases in shear modulus with compressional stress occurred within a range consistent with increased sinusoidal pressures in liver disease. Proteoglycan content and integrin-matrix interactions were significant determinants of liver mechanics, particularly in compression. We propose a new non-linear constitutive model of the liver. A key feature of this model is that, while it assumes overall liver incompressibility, it takes into account water flow and solid phase compressibility. In sum, we report a detailed study of non-linear liver mechanics under physiological strains in the normal state, early fibrosis, and late fibrosis. We propose a constitutive model that captures compression stiffening, tension softening, and shear softening, and can be understood in terms of the cellular and matrix components of the liver. PMID:26735954

Leukemia-associated antigens in man.

PubMed

Brown, G; Capellaro, D; Greaves, M

1975-12-01

Rabbit antisera raised against acute lymphoblastic leukemia (ALL) cells were used to distinguish ALL from other leukemias, to identify rare leukemia cells in the bone marrow of patients in remission, and to define human leukemia-associated antigens. Antibody binding was studied with the use of immunofluorescence reagents and the analytic capacity of the Fluorescence Activated Cell Sorter-1 (FACS-1). The results indicated that most non-T-cell ALL have three leukemia-associated antigens on their surface which are absent from normal lymphoid cells: 1) an antigen shared with myelocytes, myeloblastic leukemia cells, and fetal liver (hematopoietic) cells; 2) an antigen shared with a subset of intermediate normoblasts in normal bone marrow and fetal liver; and 3) an antigen found thus far only on non-T-cell ALL and in some acute undifferentiated leukemias, which we therefore regard as a strong candidate for a leukemia-specific antigen. These antigens are absent from a subgroup of ALL patients in which the lymphoblasta express T-cell surface markers. Preliminary studies on the bone marrow samples of patients in remission indicated that rare leukemia cells were present in some samples. The implications of these findings with respect to the heterogeneity and cell origin(s) of ALL, its diagnosis, and its potential monitoring during treatment were discussed.

Alpha fetoprotein - series (image)

MedlinePlus

... normal levels of AFP may be due to: Cancer in testes, ovaries, biliary (liver secretion) tract, stomach, or pancreas Cirrhosis of the liver Liver cancer Malignant teratoma Recovery from hepatitis Problems during pregnancy ...

Polarimetric signature imaging of anisotropic bio-medical tissues

NASA Astrophysics Data System (ADS)

Wu, Stewart H.; Yang, De-Ming; Chiou, Arthur; Nee, Soe-Mie F.; Nee, Tsu-Wei

2010-02-01

Polarimetric imaging of Stokes vector (I, Q, U, V) can provide 4 independent signatures showing the linear and circular polarizations of biological tissues and cells. Using a recently developed Stokes digital imaging system, we measured the Stokes vector images of tissue samples from sections of rat livers containing normal portions and hematomas. The derived Mueller matrix elements can quantitatively provide multi-signature data of the bio-sample. This polarimetric optical technology is a new option of biosensing technology to inspect the structures of tissue samples, particularly for discriminating tumor and non-tumor biopsy. This technology is useful for critical disease discrimination and medical diagnostics applications.

Different combinations of maternal and postnatal diet are reflected in changes of hepatic parenchyma and hepatic TNF-alpha expression in male rat offspring.

PubMed

Kačarević, Željka Perić; Grgić, Anđela; Šnajder, Darija; Bijelić, Nikola; Belovari, Tatjana; Cvijanović, Olga; Blažičević, Valerija; Radić, Radivoje

2017-09-01

Obesity is related to increased TNF-alpha production in different tissues. TNF-alpha is connected to mitochondrial dysfunction in the liver and also development of fatty infiltration of the liver. Also, postnatal change from normal to high-fat diet causes a significant increase in TNF-alpha serum levels. The aim of this research was to determine how maternal diet and switching male offspring to a different dietary regime after lactation influences rat liver. Ten female Sprague Dawley rats at nine weeks of age were randomly divided in two groups and fed either standard laboratory chow or high-fat diet during six weeks, and then mated with the same male subject. After birth and lactation male offspring from both groups were further divided into four subgroups depending on their subsequent diet. At 22 weeks of age, the animals were weighted, sacrificed and major organs were collected and weighted. Immunohistochemistry for TNF-alpha was performed on liver, and liver samples were analyzed for pathohistological changes. The group in which mothers were fed standard chow and offspring high-fat diet had the most pronounced changes: heaviest liver, poorest histopathological findings and strongest TNF-alpha immunohistochemical staining of liver parenchyma. High-fat diet during pregnancy and lactation and switching to high-fat diet postnatally affects liver weight, histological structure and TNF-alpha expression in male offspring. Copyright © 2017 Elsevier GmbH. All rights reserved.

Liver Immunology

PubMed Central

Bogdanos, Dimitrios P.; Gao, Bin; Gershwin, M. Eric

2014-01-01

The liver is the largest organ in the body and is generally regarded by non-immunologists as not having lymphoid function. However, such is far from accurate. This review highlights the importance of the liver as a lymphoid organ. Firstly, we discuss experimental data surrounding the role of liver as a lymphoid organ. The liver facilitates a tolerance rather than immunoreactivity, which protects the host from antigenic overload of dietary components and drugs derived from the gut and is also instrumental to fetal immune tolerance. Loss of liver tolerance leads to autoaggressive phenomena which if are not controlled by regulatory lymphoid populations may lead to the induction of autoimmune liver diseases. Liver-related lymphoid subpopulations also act as critical antigen-presenting cells. The study of the immunological properties of liver and delineation of the microenvironment of the intrahepatic milieu in normal and diseased livers provides a platform to understand the hierarchy of a series of detrimental events which lead to immune-mediated destruction of the liver and the rejection of liver allografts. The majority of emphasis within this review will be on the normal mononuclear cell composition of the liver. However, within this context, we will discus select, but not all, immune mediated liver disease and attempt to place these data in the context of human autoimmunity. PMID:23720323

Molecular, histologic, and trace mineral characterization of metacarpophalangeal and metatarsophalangeal joint hyperextension in juvenile llamas.

PubMed

Semevolos, Stacy A; Reed, Shannon K

2011-04-01

To evaluate molecular and histologic characteristics of the superficial digital flexor tendon (SDFT), deep digital flexor tendon (DDFT), and suspensory ligament (SL) and assess trace-mineral concentrations in serum, liver, and hair of juvenile llamas with metacarpophalangeal and metatarsophalangeal joint hyperextension. 12 juvenile llamas (6 with bilateral hyperextension of metacarpophalangeal joints, metatarsophalangeal joints, or both and 6 clinically normal control llamas). Radiography and ultrasonography of metacarpophalangeal and metatarsophalangeal regions were performed. Llamas were euthanized, and SDFT, DDFT, and SL samples were collected for histologic evaluation of collagen and elastin content and orientation, proteoglycan content, and collagen type III immunohistochemistry. Total RNA was isolated from SL tissue, and gene expression of collagen types I and III, lysyl oxidase, and matrix metalloproteinase-13 was evaluated via real-time quantitative reverse transcriptase PCR assay. Liver, serum, and hair samples were evaluated for trace mineral content. Collagen type III gene expression and proteoglycan content were significantly increased in SL samples of affected juvenile llamas, compared with those of control llamas. No difference was detected in collagen and elastin content and orientation or in gene expression of collagen type I, lysyl oxidase, or matrix metalloproteinase-13 between groups. Affected llamas had significantly increased serum molybdenum and decreased liver cobalt concentrations, compared with values for control llamas. Increased collagen type III gene expression and proteoglycan content in SL samples of affected juvenile llamas provided evidence of ongoing SL matrix repair. Trace mineral differences may have been attributable to dietary imbalances in affected llamas.

Why to compare absolute numbers of mitochondria.

PubMed

Schmitt, Sabine; Schulz, Sabine; Schropp, Eva-Maria; Eberhagen, Carola; Simmons, Alisha; Beisker, Wolfgang; Aichler, Michaela; Zischka, Hans

2014-11-01

Prompted by pronounced structural differences between rat liver and rat hepatocellular carcinoma mitochondria, we suspected these mitochondrial populations to differ massively in their molecular composition. Aiming to reveal these mitochondrial differences, we came across the issue on how to normalize such comparisons and decided to focus on the absolute number of mitochondria. To this end, fluorescently stained mitochondria were quantified by flow cytometry. For rat liver mitochondria, this approach resulted in mitochondrial protein contents comparable to earlier reports using alternative methods. We determined similar protein contents for rat liver, heart and kidney mitochondria. In contrast, however, lower protein contents were determined for rat brain mitochondria and for mitochondria from the rat hepatocellular carcinoma cell line McA 7777. This result challenges mitochondrial comparisons that rely on equal protein amounts as a typical normalization method. Exemplarily, we therefore compared the activity and susceptibility toward inhibition of complex II of rat liver and hepatocellular carcinoma mitochondria and obtained significant discrepancies by either normalizing to protein amount or to absolute mitochondrial number. Importantly, the latter normalization, in contrast to the former, demonstrated a lower complex II activity and higher susceptibility toward inhibition in hepatocellular carcinoma mitochondria compared to liver mitochondria. These findings demonstrate that solely normalizing to protein amount may obscure essential molecular differences between mitochondrial populations. Copyright © 2014 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

Transformation of primary human hepatocytes in hepatocellular carcinoma.

PubMed

Montalbano, Mauro; Rastellini, Cristiana; Wang, Xiaofu; Corsello, Tiziana; Eltorky, Mahmoud A; Vento, Renza; Cicalese, Luca

2016-03-01

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Currently, there is limited knowledge of neoplastic transformation of hepatocytes in HCC. In clinical practice, the high rate of HCC local recurrence suggests the presence of different hepatocyte populations within the liver and particularly in the tumor proximity. The present study investigated primary human hepatocyte cultures obtained from liver specimens of patients affected by cirrhosis and HCC, their proliferation and transformation. Liver samples were obtained from seven HCC cirrhotic patients and from three patients with normal liver (NL). Immediately after surgery, cell outgrowth and primary cultures were obtained from the HCC lesion, the cirrhotic tissue proximal (CP, 1-3 cm) and distal (CD, >5 cm) to the margin of the neoplastic lesion, or from NL. Cells were kept in culture for 16 weeks. Morphologic analyses were performed and proliferation rate of the different cell populations compared over time. Glypican-3, Heppar1, Arginase1 and CD-44 positivity were tested. The degree of invasiveness of cells acquiring neoplastic characteristics was studied with a transwell migration assay. We observed that HCC cells maintained their morphology and unmodified neoplastic characteristics when cultured. Cells isolated from CP, showed a progressive morphologic transformation in HCC-like cells accompanied by modification of markers expression with signs of invasiveness. Absence of HCC contamination in the CP isolates was confirmed. In CD samples some of these characteristics were present and at significantly lower levels. With the present study, we are the first to have identified and describe the existence of human hepatocytes near the cancerous lesion that can transform in HCC in vitro.

Clinicopathologic, gross necropsy, and histologic findings after intramuscular injection of carprofen in a pigeon (Columba livia) model.

PubMed

Zollinger, Tawina J; Hoover, John P; Payton, Mark E; Schiller, Chris A

2011-09-01

To evaluate the pathologic effects of carprofen in a pigeon model (Columba livia), 52 young adult pigeons were used in a randomized control study design. Sixteen pigeons were randomly assigned to 1 of 3 treatment groups and received carprofen by intramuscular injection at dosages of either 2, 5, or 10 mg/kg once daily for 7 days. Four pigeons served as saline-injected controls. Four pigeons from each group and 1 control pigeon were randomly selected on days 2, 4, 6, and 8 to obtain blood samples and then were euthanatized and submitted for necropsy. Histologic lesions in pectoral muscle, liver, kidney, and digestive tract tissue samples were ranked in severity as 0, normal/not present; 1, minimal; 2, mild; 3, mild to moderate; 4, moderate; 5, moderate to marked; and 6, marked pathologic changes. Two-way analysis of variance (day x dose) and pairwise t tests revealed significant (P < or = .05) mild decreases in total protein and glucose concentrations and marked increases in aspartate aminotransferase and alanine aminotransferase enzyme activities after carprofen treatments. Gross lesions in carprofen-treated pigeons were pale injection sites (23/48 [47.9%]), mottled yellow livers (9/48 [18.8%]), and congestion of small intestines (7/48 [14.6%]). Liver, kidney, and muscle injection sites had significantly increased (P < or = .05) severity of histologic lesions. In pigeons, intramuscular administration of carprofen is associated with increased aspartate aminotransferase and alanine aminotransferase enzyme concentrations, gross lesions in muscle injection sites and liver, and histologic lesions in liver and muscle.

The impact of weight changes on nonalcoholic Fatty liver disease in adult men with normal weight.

PubMed

Cho, Ji-Young; Chung, Tae-Heum; Lim, Kyoung-Mo; Park, Hee-Jin; Jang, Jung-Mi

2014-09-01

Although it is known that losing weight has an effect on the treatment of non-alcoholic fatty liver disease, the studies that show how losing weight affects the non-alcoholic fatty liver disease for the normal weight male adults are limited so far. In this study, we set body mass index as criteria and investigated how the weight changes for 4 years makes an impact on the risk of non-alcoholic fatty liver disease for the male adults who have the normal body mass index. From January to December of 2004, among the normal weight male adults who had general check-up at the Health Promotion Center of Ulsan University Hospital, 180 people (average age, 47.4 ± 4.61 years) who were diagnosed with fatty liver through abdominal ultrasonography were included in this study and were observed according to the variety of data and ultrasonography after 4 years (2008). People who had a history of drinking more than 140 g of alcohol per week or who had a past medical history were excluded from the analysis. The weight change of subjects was calculated using the formula 'weight change = weight of 2008 (kg) - weight of 2004 (kg)' and classified into three groups, loss group (≤-3.0 kg), stable group (-2.9 to 2.9 kg), and gain group (≥3.0 kg). The odds for disappearance of non-alcoholic fatty liver disease in those three different groups were compared. Among 180 subjects, compared with stable group (67.2%, 121 subjects), loss group (11.7%, 21 subjects) showed 18.37-fold increase in the odds of disappearance of non-alcoholic fatty liver disease (95% confidence interval [CI], 4.34 to 77.80) and gain group (21.1%, 38 subjects) showed 0.28-fold decrease in the odds of disappearance of non-alcoholic fatty liver disease (95% CI, 0.10 to 0.83). Even for the normal weight people, losing weight has an effect on the improvement of non-alcoholic fatty liver disease.

Extrapolation of Normal Tissue Complication Probability for Different Fractionations in Liver Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tai An; Erickson, Beth; Li, X. Allen

2009-05-01

Purpose: The ability to predict normal tissue complication probability (NTCP) is essential for NTCP-based treatment planning. The purpose of this work is to estimate the Lyman NTCP model parameters for liver irradiation from published clinical data of different fractionation regimens. A new expression of normalized total dose (NTD) is proposed to convert NTCP data between different treatment schemes. Method and Materials: The NTCP data of radiation- induced liver disease (RILD) from external beam radiation therapy for primary liver cancer patients were selected for analysis. The data were collected from 4 institutions for tumor sizes in the range of of 8-10more » cm. The dose per fraction ranged from 1.5 Gy to 6 Gy. A modified linear-quadratic model with two components corresponding to radiosensitive and radioresistant cells in the normal liver tissue was proposed to understand the new NTD formalism. Results: There are five parameters in the model: TD{sub 50}, m, n, {alpha}/{beta} and f. With two parameters n and {alpha}/{beta} fixed to be 1.0 and 2.0 Gy, respectively, the extracted parameters from the fitting are TD{sub 50}(1) = 40.3 {+-} 8.4Gy, m =0.36 {+-} 0.09, f = 0.156 {+-} 0.074 Gy and TD{sub 50}(1) = 23.9 {+-} 5.3Gy, m = 0.41 {+-} 0.15, f = 0.0 {+-} 0.04 Gy for patients with liver cirrhosis scores of Child-Pugh A and Child-Pugh B, respectively. The fitting results showed that the liver cirrhosis score significantly affects fractional dose dependence of NTD. Conclusion: The Lyman parameters generated presently and the new form of NTD may be used to predict NTCP for treatment planning of innovative liver irradiation with different fractionations, such as hypofractioned stereotactic body radiation therapy.« less

 Alkaline phosphatase normalization is a biomarker of improved survival in primary sclerosing cholangitis.

PubMed

Hilscher, Moira; Enders, Felicity B; Carey, Elizabeth J; Lindor, Keith D; Tabibian, James H

2016-01-01

 Introduction. Recent studies suggest that serum alkaline phosphatase may represent a prognostic biomarker in patients with primary sclerosing cholangitis. However, this association remains poorly understood. Therefore, the aim of this study was to investigate the prognostic significance and clinical correlates of alkaline phosphatase normalization in primary sclerosing cholangitis. This was a retrospective cohort study of patients with a new diagnosis of primary sclerosing cholangitis made at an academic medical center. The primary endpoint was time to hepatobiliaryneoplasia, liver transplantation, or liver-related death. Secondary endpoints included occurrence of and time to alkaline phosphatase normalization. Patients who did and did not achieve normalization were compared with respect to clinical characteristics and endpoint-free survival, and the association between normalization and the primary endpoint was assessed with univariate and multivariate Cox proportional-hazards analyses. Eighty six patients were included in the study, with a total of 755 patient-years of follow-up. Thirty-eight patients (44%) experienced alkaline phosphatase normalization within 12 months of diagnosis. Alkaline phosphatase normalization was associated with longer primary endpoint-free survival (p = 0.0032) and decreased risk of requiring liver transplantation (p = 0.033). Persistent normalization was associated with even fewer adverse endpoints as well as longer survival. In multivariate analyses, alkaline phosphatase normalization (adjusted hazard ratio 0.21, p = 0.012) and baseline bilirubin (adjusted hazard ratio 4.87, p = 0.029) were the only significant predictors of primary endpoint-free survival. Alkaline phosphatase normalization, particularly if persistent, represents a robust biomarker of improved long-term survival and decreased risk of requiring liver transplantation in patients with primary sclerosing cholangitis.

Morphologic examination of CD3-CD4(bright) cells in rat liver.

PubMed

Yamamoto, Satoshi; Sato, Yosinobu; Abo, Toru; Hatakeyama, Katsuyosi

2002-01-01

Recently, we found CD3-CD4(bright) cells with comparative specificity for normal rat liver. In the current study, we investigated the type and form of both CD3-CD4(bright) cells and CD3-CD4(dull) cells in the rat liver. The surface phenotype of hepatic mononuclear cells in Lewis rats was identified by using monoclonal antibodies including anti-CD4, anti-CD3, and antimacrophage in conjunction with two- or three-color immunofluorescence analysis. CD3-CD4(bright) cells and CD3-CD4(dull) cells were examined morphologically using May-Giemsa staining and scanning electron microscopy. The distribution of CD3-CD4(bright) cells and CD3-CD4(dull) cells 48 hours after intravenous administration of liposome-encapsulated dichloromethylene diphosphate was also investigated. In comparison to CD3-CD4(dull) cells, CD3-CD4(bright) cells were slightly larger macrophages with abundant cytoplasmic granules, being present with comparative specificity for normal rat liver and showing negligible effects by intravenous liposome-encapsulated dichloromethylene diphosphate administration. These data suggest that in normal young rat liver these CD3-CD4(dull) and CD3-CD4(bright) cells may be dendritic cells and Kupffer cells that shift from the liver to the spleen or vice versa. These cells may also be able to locally proliferate in liver or spleen due to changes in the developing liver.

Ursodeoxycholic Acid in Treatment of Non-cholestatic Liver Diseases: A Systematic Review

PubMed Central

Reardon, Jillian; Hussaini, Trana; Alsahafi, Majid; Azalgara, Vladimir Marquez; Erb, Siegfried R.; Partovi, Nilufar; Yoshida, Eric M.

2016-01-01

Abstract Aims: To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions. Methods: Searches were conducted on the databases of Medline (1948-March 31, 2015), Embase (1980-March 31, 2015) and the Cochrane Central Register of Controlled Trials, and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications. Combinations of the following search terms were used: ursodeoxycholic acid, ursodiol, bile acids and/or salts, non alcoholic fatty liver, non alcoholic steatohepatitis, fatty liver, alcoholic hepatitis, alcohol, liver disease, autoimmune, autoimmune hepatitis, liver transplant, liver graft, transplant rejection, graft rejection, ischemic reperfusion injury, reperfusion injury, hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, acute hepatitis, transaminases, alanine transaminase, liver enzymes, aspartate aminotransferase, gamma-glutamyl transferase, gamma-glutamyl transpeptidase, bilirubin, alkaline phosphatase. No search limits were applied. Additionally, references of the included studies were reviewed to identify additional articles. Results: The literature search yielded articles meeting inclusion criteria for the following indications: non-alcoholic fatty liver disease (n = 5); alcoholic liver disease (n = 2); autoimmune hepatitis (n = 6), liver transplant (n = 2) and viral hepatitis (n = 9). Bile acid use was associated with improved normalization of liver biochemistry in non-alcoholic fatty liver disease, autoimmune hepatitis and hepatitis B and C infections. In contrast, liver biochemistry normalization was inconsistent in alcoholic liver disease and liver transplantation. The majority of studies reviewed showed that normalization of liver biochemistry did not correlate to improvement in histologic disease. In the prospective trials reviewed, adverse effects associated with the bile acids were limited to minor gastrointestinal complaints (most often, diarrhea) and did not occur at increased frequency as compared to controls. As administration of bile acids was often limited to durations of 12 months or less, long-term side effects for non-cholestatic indications cannot be excluded. Conclusions: Based on the available literature, bile acids cannot be widely recommended for non-cholestatic liver diseases at present. PMID:27777888

Liver tumor boundaries identified intraoperatively using real-time indocyanine green fluorescence imaging.

PubMed

Zhang, Ya-Min; Shi, Rui; Hou, Jian-Cun; Liu, Zi-Rong; Cui, Zi-Lin; Li, Yang; Wu, Di; Shi, Yuan; Shen, Zhong-Yang

2017-01-01

Clear delineation between tumors and normal tissues is ideal for real-time surgical navigation imaging. We investigated applying indocyanine green (ICG) fluorescence imaging navigation using an intraoperative administration method in liver resection. Fifty patients who underwent liver resection were divided into two groups based on clinical situation and operative purpose. In group I, sizes of superficial liver tumors were determined; tiny tumors were identified. In group II, the liver resection margin was determined; real-time navigation was performed. ICG was injected intravenously at the beginning of the operation; the liver surface was observed with a photodynamic eye (PDE). Liver resection margins were determined using PDE. Fluorescence contrast between normal liver and tumor tissues was obvious in 32 of 35 patients. A boundary for half the liver or specific liver segments was determined in nine patients by examining the portal vein anatomy after ICG injection. Eight small tumors not observed preoperatively were detected; the smallest was 2 mm. ICG fluorescence imaging navigation is a promising, simple, and safe tool for routine real-time intraoperative imaging during hepatic resection and clinical exploration in hepatocellular carcinoma, enabling high sensibility for identifying liver resection margins and detecting tiny superficial tumors.

Psychometrics of chronic liver disease questionnaire in Chinese chronic hepatitis B patients.

PubMed

Zhou, Kai-Na; Zhang, Min; Wu, Qian; Ji, Zhen-Hao; Zhang, Xiao-Mei; Zhuang, Gui-Hua

2013-06-14

To evaluate psychometrics of the Chinese (mainland) chronic liver disease questionnaire (CLDQ) in patients with chronic hepatitis B (CHB). A cross-sectional sample of 460 Chinese patients with CHB was selected from the Outpatient Department of the Eighth Hospital of Xi'an, including CHB (CHB without cirrhosis) (n = 323) and CHB-related cirrhosis (n = 137). The psychometrics includes reliability, validity and sensitivity. Internal consistency reliability was measured using Cronbach's α. Convergent and discriminant validity was evaluated by item-scale correlation. Factorial validity was explored by principal component analysis with varimax rotation. Sensitivity was assessed using Cohen's effect size (ES), and independent sample t test between CHB and CHB-related cirrhosis groups and between alanine aminotransferase (ALT) normal and abnormal groups after stratifying the disease (CHB and CHB-related cirrhosis). Internal consistency reliability of the CLDQ was 0.83 (range: 0.65-0.90). Most of the hypothesized item-scale correlations were 0.40 or over, and all of such hypothesized correlations were higher than the alternative ones, indicating satisfactory convergent and discriminant validity. Six factors were extracted after varimax rotation from the 29 items of CLDQ. The eligible Cohen's ES with statistically significant independent sample t test was found in the overall CLDQ and abdominal, systematic, activity scales (CHB vs CHB-related cirrhosis), and in the overall CLDQ and abdominal scale in the stratification of patients with CHB (ALT normal vs abnormal). The CLDQ has acceptable reliability, validity and sensitivity in Chinese (mainland) patients with CHB.

Endovascular diagnosis and intervention in patients with isolated hyperammonemia, with or without ascites, after liver transplantation.

PubMed

Belenky, Alexander; Igov, Igor; Konstantino, Youval; Bachar, Gil N; Mor, Eitan; Graif, Franklyn; Ben-Ari, Ziv; Tur-Kaspa, Ran; Atar, Eli

2009-02-01

Hyperammonemia with or without ascites with normal synthetic liver functions after liver transplantation might indicate the presence of anastomotic stenosis of the portal or hepatic vein or the existence of a patent portosystemic shunt. The authors describe six patients, three children after split-liver transplantation and three adults after cadaver liver transplantation, who presented with hyperammonemia. Three patients had ascites. All lesions were successfully treated percutaneously; stents were placed in patients with anastomotic stenoses and coil embolization was performed in patients with patent portosystemic shunts--with either transhepatic or transjugular approaches according to the site of the abnormality. Ammonia levels returned to normal, and ascites had regressed completely for at least 3 months.

A study of hepatic lesions in broiler chickens at processing plants in Saskatchewan

PubMed Central

Hutchison, Thomas W.S.; Riddell, Craig

1990-01-01

A detailed descriptive study was done on broiler chickens with abnormal livers found at processing. Two syndromes were evident: those birds with enlarged, pale, firm livers, designated hepatosis, with Clostridium perfringens type A often isolated; and ascitic birds with cobblestone-appearing livers. Livers with hepatosis had marked proliferation of bile ducts; ascitic livers had normal architecture. Hearts from birds with ascites had elevated right ventricular/total ventricular weight ratios, whereas hearts from normal birds and birds with hepatosis did not. Two isolates of C. perfringens produced necrotic enteritis in experimental birds; an attempt to reproduce hepatosis with these isolates was unsuccessful. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6.Figure 7. PMID:17423489

Image patch-based method for automated classification and detection of focal liver lesions on CT

NASA Astrophysics Data System (ADS)

Safdari, Mustafa; Pasari, Raghav; Rubin, Daniel; Greenspan, Hayit

2013-03-01

We developed a method for automated classification and detection of liver lesions in CT images based on image patch representation and bag-of-visual-words (BoVW). BoVW analysis has been extensively used in the computer vision domain to analyze scenery images. In the current work we discuss how it can be used for liver lesion classification and detection. The methodology includes building a dictionary for a training set using local descriptors and representing a region in the image using a visual word histogram. Two tasks are described: a classification task, for lesion characterization, and a detection task in which a scan window moves across the image and is determined to be normal liver tissue or a lesion. Data: In the classification task 73 CT images of liver lesions were used, 25 images having cysts, 24 having metastasis and 24 having hemangiomas. A radiologist circumscribed the lesions, creating a region of interest (ROI), in each of the images. He then provided the diagnosis, which was established either by biopsy or clinical follow-up. Thus our data set comprises 73 images and 73 ROIs. In the detection task, a radiologist drew ROIs around each liver lesion and two regions of normal liver, for a total of 159 liver lesion ROIs and 146 normal liver ROIs. The radiologist also demarcated the liver boundary. Results: Classification results of more than 95% were obtained. In the detection task, F1 results obtained is 0.76. Recall is 84%, with precision of 73%. Results show the ability to detect lesions, regardless of shape.

Ad Integrum Functional and Volumetric Recovery in Right Lobe Living Donors: Is It Really Complete 1 Year After Donor Hepatectomy?

PubMed

Duclos, J; Bhangui, P; Salloum, C; Andreani, P; Saliba, F; Ichai, P; Elmaleh, A; Castaing, D; Azoulay, D

2016-01-01

The partial liver's ability to regenerate both as a graft and remnant justifies right lobe (RL) living donor liver transplantation. We studied (using biochemical and radiological parameters) the rate, extent of, and predictors of functional and volumetric recovery of the remnant left liver (RLL) during the first year in 91 consecutive RL donors. Recovery of normal liver function (prothrombin time [PT] ≥70% of normal and total bilirubin [TB] ≤20 µmol/L), liver volumetric recovery, and percentage RLL growth were analyzed. Normal liver function was regained by postoperative day's 7, 30, and 365 in 52%, 86%, and 96% donors, respectively. Similarly, mean liver volumetric recovery was 64%, 71%, and 85%; whereas the percentage liver growth was 85%, 105%, and 146%, respectively. Preoperative PT value (p = 0.01), RLL/total liver volume (TLV) ratio (p = 0.03), middle hepatic vein harvesting (p = 0.02), and postoperative peak TB (p < 0.01) were predictors of early functional recovery, whereas donor age (p = 0.03), RLL/TLV ratio (p = 0.004), and TLV/ body weight ratio (p = 0.02) predicted early volumetric recuperation. One-year post-RL donor hepatectomy, though functional recovery occurs in almost all (96%), donors had incomplete restoration (85%) of preoperative total liver volume. Modifiable predictors of regeneration could help in better and safer donor selection, while continuing to ensure successful recipient outcomes. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Ultrasonographically visible hepatic location in clinically normal horses.

PubMed

Johns, I C; Miles, A

2016-06-01

Ultrasound is widely used for evaluating horses with suspected liver dysfunction. Although a change in size is considered suggestive of pathology, no clear guidelines exist to define the hepatic ultrasonographically visible locations (HUVL) in horses. The aim of the study was to describe the HUVL in normal horses and determine whether this is altered by signalment, height, weight and body condition score (BCS). Prospective observational study. Bilateral ultrasonographic evaluation was performed in 58 clinically normal horses with no history of hepatic disease. The most cranial/caudal intercostal spaces (ICS), total number of ICS in which the liver was visualised and the ventral extent of the liver were recorded. Liver was visualised on the right in 56/58 horses (97%), the left in 41/58 (71%) and on both sides in 39/58 (67%). The most cranial ICS was 5 (right) or 4 (left) and the most caudal was 16 (right) or 11 (left). Liver was visualised in ICS 0-11 (right) and ICS 0-5 (left). Liver was not visualised ventral to the costochondral junction. There was no significant effect of sex, breed, height, weight or BCS on HUVL. Liver was visible in significantly fewer ICS on the right in horses aged 24 years and older (median ICS 3.5) compared with younger horses (median ICS 7; P = 0.016). These findings suggest that the liver should be consistently visualised on the right side, but absence of ultrasonographically visible liver on the left is unlikely to be clinically relevant. Liver dimensions may be decreased in older horses. © 2016 Australian Veterinary Association.

HEPATIC FUNCTION AFTER GENETICALLY-ENGINEERED PIG LIVER TRANSPLANTATION IN BABOONS

PubMed Central

Ekser, Burcin; Echeverri, Gabriel J.; Hassett, Andrea Cortese; Yazer, Mark H.; Long, Cassandra; Meyer, Michael; Ezzelarab, Mohamed; Lin, Chih Che; Hara, Hidetaka; van der Windt, Dirk J.; Dons, Eefje M.; Phelps, Carol; Ayares, David; Cooper, David K.C.; Gridelli, Bruno

2010-01-01

Background If ‘bridging’ to allotransplantation is to be achieved by a pig liver xenograft, adequate hepatic function needs to be assured. Methods We have studied hepatic function in baboons after transplantation of livers from α1,3-galactosyltransferase gene-knockout (GTKO,n=1) or GTKO pigs transgenic for CD46 (GTKO/CD46,n=5). Monitoring was by liver function tests and coagulation parameters. Pig-specific proteins in the baboon serum/plasma were identified by Western blot. In 4 baboons, coagulation factors were measured. The results were compared with values from healthy humans, baboons, and pigs. Results Recipient baboons died or were euthanized after 4-7 days following internal bleeding associated with profound thrombocytopenia. However, parameters of liver function, including coagulation, remained in the near-normal range, except for some cholestasis. Western blot demonstrated that pig proteins (albumin, fibrinogen, haptoglobin, plasminogen) were produced by the liver from day 1. Production of several pig coagulation factors was confirmed. Conclusions After the transplantation of genetically-engineered pig livers into baboons (1) many parameters of hepatic function, including coagulation, were normal or near-normal; (2) there was evidence for production of pig proteins, including coagulation factors, and (3) these appeared to function adequately in baboons, though inter-species compatibility of such proteins remains to be confirmed. PMID:20606605

Microgravity

NASA Image and Video Library

1996-06-01

The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues currently being cultured in rotating bioreactors by investigators

Microgravity

NASA Image and Video Library

1988-07-14

The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues currently being cultured in rotating bioreactors by investigators.

Bioreactor

NASA Technical Reports Server (NTRS)

1996-01-01

The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues currently being cultured in rotating bioreactors by investigators

Rotating Bioreactor

NASA Technical Reports Server (NTRS)

1988-01-01

The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues currently being cultured in rotating bioreactors by investigators.

Dynamic characteristics of MR diffusion-weighted imaging in a rabbit liver VX-2 tumor model.

PubMed

Yuan, You-Hong; Xiao, En-Hua; He, Zhong; Jin, Ke; Ma, Cong; Xiang, Jun; Xiao, Jian-Hua; Chen, Wei-Jian

2013-02-01

To investigate prospectively dynamic characteristics of the apparent diffusion coefficient (ADC) on MR diffusion-weighted imaging (DWI) in a rabbit VX-2 tumor model. Forty New Zealand rabbits were included in the study, and 47 rabbit VX-2 tumor models were developed by direct and intrahepatic implantation after opening the abdominal cavities. DWI was carried out periodically and respectively on days 7, 14 and 21 after implantation. The VX-2 tumor samples were studied by pathology. The distinction of VX-2 tumors on DWI was assessed by their ADC values by analysis of variance (ANOVA) using SPSS12.0 software. The ADC values (mean ± SD) × 10(-3) mm(2)/s of 47 VX-2 tumors in the peripheral and central areas were 2.18 ± 0.29, 1.96 ± 0.33, 1.80 ± 0.35, 2.20 ± 0.29, 2.05 ± 0.30 and 1.96 ± 0.48, respectively, on days 7, 14 and 21 after implantation. ADC values of 47 VX-2 tumors in the area of the tumor periphery, center and normal parenchyma were higher when the b-value was 100 s/mm(2) than those when the b-value was 300 s/mm(2) (F = 17.964, p < 0.001; F = 13.986, p < 0.001; F = 128.681, p < 0.001). ADC values in the area of normal liver parenchyma were higher than those in the area of the VX-2 tumor periphery and center when the b-value was 100 or 300 s/mm(2). ADCs of viable tumor cells in VX-2 tumors were lower on DWI than those in the area of normal liver parenchyma around the tumor, and ADCs of dead tumor cells in VX-2 tumors were unequal, including high, equal and low values, but they were higher than in the area of normal liver parenchyma around tumors after dead tumor cells had been liquefied or had become cystic. ADC is correlated with the tumor histology and degree of malignancy, and DWI has potential value for dynamically monitoring tumors and evaluating the degree of malignancy and therapeutic effect.

IL-6-Mediated Activation of Stat3α Prevents Trauma/Hemorrhagic Shock-Induced Liver Inflammation

PubMed Central

Moran, Ana; Thacker, Stephen A.; Arikan, Ayse Akcan; Mastrangelo, Mary-Ann A.; Wu, Yong; Yu, Bi; Tweardy, David J.

2011-01-01

Trauma complicated by hemorrhagic shock (T/HS) is the leading cause of morbidity and mortality in the United States for individuals under the age of 44 years. Initial survivors are susceptible to developing multiple organ failure (MOF), which is thought to be caused, at least in part, by excessive or maladaptive activation of inflammatory pathways. We previously demonstrated in rodents that T/HS results in liver injury that can be prevented by IL-6 administration at the start of resuscitation; however, the contribution of the severity of HS to the extent of liver injury, whether or not resuscitation is required, and the mechanism(s) for the IL-6 protective effect have not been reported. In the experiments described here, we demonstrated that the extent of liver inflammation induced by T/HS depends on the duration of hypotension and requires resuscitation. We established that IL-6 administration at the start of resuscitation is capable of completely reversing liver inflammation and is associated with increased Stat3 activation. Global assessment of the livers showed that the main effect of IL-6 was to normalize the T/HS-induced inflammation transcriptome. Pharmacological inhibition of Stat3 activity within the liver blocked the ability of IL-6 to prevent liver inflammation and to normalize the T/HS-induced liver inflammation transcriptome. Genetic deletion of a Stat3β, a naturally occurring, dominant-negative isoform of the Stat3, attenuated T/HS-induced liver inflammation, confirming a role for Stat3, especially Stat3α, in preventing T/HS-mediated liver inflammation. Thus, T/HS-induced liver inflammation depends on the duration of hypotension and requires resuscitation; IL-6 administration at the start of resuscitation reverses T/HS-induced liver inflammation, through activation of Stat3α, which normalized the T/HS-induced liver inflammation transcriptome. PMID:21738667

[Effects of moxibustion with seed-sized moxa cone at "Ganshu" (BL 18) on liver function in rats with precancerous lesion of hepatic cellular cancer].

PubMed

Liu, Yang; Hou, Zhongwei; Lu, Jun; Dong, Feng; Wang, Pei; Jia, Wenrui; Wang, Chaoyang

2015-07-01

To explore the effects of moxibustion with seed-sized moxa cone at "Ganshu" (BL 18) on liver furiction and morphology in rat with precancerous lesion of hepatic cellular cancer MCC). A total of 60 male Wistar rats were randomly divided into a normal group (10 rats), a model group (20 rats), a 20-day treatment group (15 rats) and a 40-day treatment group (15 rats). HCC model was established by intraperitoneal injection of diethylnitrosamine (DEN). Rats in the normal group received no treatment. Rats in the model group were treated with fixation. Rats in the 20-day treatment group and 40-day treatment group were treated by moxibustion with seed-sized moxa cone at "Ganshu" (BL 18), once every other day, for 20 days and 40 days, respectively. Blood sample in each group was collected 1 d before model establishment, 20 d, 40 d and 84 d after model establishment. Chemical method was applied to test the activity of ALT (alamine aminotransferase), AST (aspartate transaminase) and GGT (glutamyl transpeptidase); at the end of model establishment, all the rats were sacrificed to observe the liver morphology changes. After the first therapeutic course, the. content of ALT and AST in the 20-day treatment group was significantly lower than that in the model group (all P<0. 05); after the second therapeutic course, the content of ALT, AST and GGT in the 40-day treatment group was insignificantly lower than that in the model group (all P>0. 05). Under light microscope, the slice of liver tissue indicated that primary tumor was induced in the model group, and the tumor cells were stained and irregular; the cytoplasm in the 20-day treatment group was even, and the tumor cells were few with several nodules alone. In the 40-day treatment group the liver morphology was normal and the staining was even; the tumor cells were few without nodules or a few. Conclusion Moxibustion with seed-sized moxa cone at "Ganshu" (BL 18) could reduce the serum content of ALT, AST and GGT in rats with HCC, which could protect the liver and: delay the DEN-induced precancerous lesion on some levels.

Thallium-201 per rectum for the diagnosis of cirrhosis in patients with asymptomatic chronic hepatitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

D'Arienzo, A.; Celentano, L.; Scuotto, A.

1988-07-01

In normal subjects, thallium-201, administered per rectum, is taken up mainly by the liver (heart/liver ratio in normal subjects: 0.04 to 0.12). It has been claimed that an increased heart/liver ratio is suggestive of portal-caval shunting and portal hypertension. To evaluate the possibility of using thallium-201 as a test to diagnose cirrhosis, we administered this substance per rectum to 33 patients with biochemical evidence, but no clinical symptoms, of liver disease. Laparoscopy and liver biopsy revealed chronic active hepatitis without cirrhosis in 18 patients, and chronic active hepatitis with cirrhosis in the others. The results of conventional liver function testsmore » were similar in both groups. A significant difference, however, was found between the means of fasting serum bile acid concentrations (9.8 +/- 3.2 and 18.3 +/- 4.2 microM per liter) in chronic active hepatitis without cirrhosis and cirrhotic patients, and between the means of the heart/liver ratios 20 min after thallium-201 administration (heart/liver: 0.09 +/- 0.03 and 0.54 +/- 0.13, respectively). Unlike the serum bile acid concentration which gave some overlapping values, the thallium-201 test clearly distinguished the chronic active hepatitis without cirrhosis group from the cirrhotics. In the cirrhotic group, there was a significant correlation between the heart/liver ratio and signs of portal hypertension such as esophageal varices, increased diameter of the vena porta and hypersplenism. The thallium-201 test is therefore useful in discriminating between chronic active hepatitis with and without cirrhosis in clinically asymptomatic subjects with biochemical evidence of moderate liver function impairment. A heart/liver uptake ratio much higher than normal (above 0.30) strongly suggests the development of hepatic cirrhosis.« less

Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha.

PubMed

Desai, Seema S; Tung, Jason C; Zhou, Vivian X; Grenert, James P; Malato, Yann; Rezvani, Milad; Español-Suñer, Regina; Willenbring, Holger; Weaver, Valerie M; Chang, Tammy T

2016-07-01

Matrix rigidity has important effects on cell behavior and is increased during liver fibrosis; however, its effect on primary hepatocyte function is unknown. We hypothesized that increased matrix rigidity in fibrotic livers would activate mechanotransduction in hepatocytes and lead to inhibition of liver-specific functions. To determine the physiologically relevant ranges of matrix stiffness at the cellular level, we performed detailed atomic force microscopy analysis across liver lobules from normal and fibrotic livers. We determined that normal liver matrix stiffness was around 150 Pa and increased to 1-6 kPa in areas near fibrillar collagen deposition in fibrotic livers. In vitro culture of primary hepatocytes on collagen matrix of tunable rigidity demonstrated that fibrotic levels of matrix stiffness had profound effects on cytoskeletal tension and significantly inhibited hepatocyte-specific functions. Normal liver stiffness maintained functional gene regulation by hepatocyte nuclear factor 4 alpha (HNF4α), whereas fibrotic matrix stiffness inhibited the HNF4α transcriptional network. Fibrotic levels of matrix stiffness activated mechanotransduction in primary hepatocytes through focal adhesion kinase. In addition, blockade of the Rho/Rho-associated protein kinase pathway rescued HNF4α expression from hepatocytes cultured on stiff matrix. Fibrotic levels of matrix stiffness significantly inhibit hepatocyte-specific functions in part by inhibiting the HNF4α transcriptional network mediated through the Rho/Rho-associated protein kinase pathway. Increased appreciation of the role of matrix rigidity in modulating hepatocyte function will advance our understanding of the mechanisms of hepatocyte dysfunction in liver cirrhosis and spur development of novel treatments for chronic liver disease. (Hepatology 2016;64:261-275). © 2016 by the American Association for the Study of Liver Diseases.

Protein Degradation in Normal and Beige (Chediak-Higashi) Mice

PubMed Central

Lyons, Robert T.; Pitot, Henry C.

1978-01-01

The beige mouse, C57BL/6 (bg/bg), is an animal model for the Chediak-Higashi syndrome in man, a disease characterized morphologically by giant lysosomes in most cell types. Half-lives for the turnover of [14C]bicarbonate-labeled total soluble liver protein were determined in normal and beige mice. No significant differences were observed between the normal and mutant strain for both rapidly and slowly turning-over classes of proteins. Glucagon treatment during the time-course of protein degradation had similar effects on both normal and mutant strains and led to the conclusion that the rate of turnover of endogenous intracellular protein in the beige mouse liver does not differ from normal. The rates of uptake and degradation of an exogenous protein were determined in normal and beige mice by intravenously injecting 125I-bovine serum albumin and following, in peripheral blood, the loss with time of phosphotungstic acid-insoluble bovine serum albumin and the parallel appearance of phosphotungstic acid-soluble (degraded) material. No significant differences were observed between beige and normal mice in the uptake by liver lysosomes of 125I-bovine serum albumin (t½ = 3.9 and 2.8 h, respectively). However, it was found that lysosomes from livers of beige mice released phosphotungstic acid-soluble radioactivity at a rate significantly slower than normal (t½ = 6.8 and 3.1 h, respectively). This defect in beige mice could be corrected by chronic administration of carbamyl choline (t½ = 3.5 h), a cholinergic agonist which raises intracellular cyclic GMP levels. However, no significant differences between normal and beige mice were observed either in the ability of soluble extracts of liver and kidney to bind [3H]cyclic GMP in vitro or in the basal levels of cyclic AMP in both tissues. The relevance of these observations to the presumed biochemical defect underlying the Chediak-Higashi syndrome is discussed. PMID:202611

Validation of graft and standard liver size predictions in right liver living donor liver transplantation.

PubMed

Chan, See Ching; Lo, Chung Mau; Chok, Kenneth S H; Sharr, William W; Cheung, Tan To; Tsang, Simon H Y; Chan, Albert C Y; Fan, Sheung Tat

2011-12-01

To assess the accuracy of a formula derived from 159 living liver donors to estimate the liver size of a normal subject: standard liver weight (g) = 218 + body weight (kg) × 12.3 + 51 (if male). Standard liver volume (SLV) is attained by a conversion factor of 1.19 mL/g. The total liver volume (TLV) of each of the subsequent consecutive 126 living liver donors was determined using the right liver graft weight (RGW) on the back table, right/left liver volume ratio on computed tomography, and the conversion factor. The estimated right liver graft weight (ERGW) was determined by the right liver volume on computed tomography (CT) and the conversion factor. SLV and ERGW were compared with TLV and RGW, respectively, by paired sample t test. Donor characteristics of both series were similar. SLV and TLV were 1,099.6 ± 139.6 and 1,108.5 ± 175.2 mL, respectively, ( R 2  = 0.476) ( p  = 0.435). The difference between SLV and TLV was only -8.9 ± 128.2 mL (-1.0 ± 11.7%). ERGW and RGW were 601.5 ± 104.1 and 597.1 ± 102.2 g, respectively ( R 2  = 0.781) ( p  = 0.332). The conversion factor from liver weight to volume for this series was 1.20 mL/g. The difference between ERGW and RGW was 4.3 ± 49.8 g (0.3 ± 8.8%). ERGW was smaller than RGW for over 10% (range 0.21-40.66 g) in 18 of the 126 donors. None had the underestimation of RGW by over 20%. SLV and graft weight estimations were accurate using the formula and conversion factor.

Autophagy-dependent generation of Axin2+ cancer stem-like cells promotes hepatocarcinogenesis in liver cirrhosis.

PubMed

Li, J; Hu, S B; Wang, L Y; Zhang, X; Zhou, X; Yang, B; Li, J H; Xiong, J; Liu, N; Li, Y; Wu, Y Z; Zheng, Q C

2017-11-30

Autophagy is a pathophysiological phenomenon in liver cirrhosis that can further progress into hepatocarcinoma. Liver cancer stem cells (CSCs) are believed to initiate hepatocarcinogenesis. To investigate the precise mechanism related to the origin of CSCs in liver cirrhosis and hepatocarcinogenesis, we labeled Axin2+ hepatic cells with EGFP in Axin2Cre;Rosa26EGFP transgenic rats, and then stratified clinical and rat liver cirrhosis samples by autophagy flux. Clinical follow-up and lineage tracing in transgenic rat liver cirrhosis revealed that while Axin2/EGFP+ hepatic cells were present in normal livers and cirrhotic livers without aberrant autophagy, hepatic Axin2/EGFP+CD90+ cells were generated exclusively in cirrhotic livers with aberrant autophagy and promoted hepatocarcinogenesis. Aberrant autophagy in liver cirrhosis resulted in hepatocyte growth factor (HGF) expression, leading to activation of Met/JNK and Met/STAT3 signaling in sorted hepatic Axin2/EGFP+ cells and their transition into Axin2/EGFP+CD90+ cells that possess CSC properties. In a transgenic rat liver cirrhosis model, induction or inhibition of autophagy in cirrhotic livers by systemic administration of rapamycin or chloroquine or transfection with Atg3- and Atg7-shRNAs significantly induced or suppressed HGF expression, which in turn increased or reduced generation of EGFP+CD90+ hepatic cells by activating or inactivating Met/JNK and Met/STAT3 signaling, thereby promoting or preventing hepatocarcinogenesis. Systemic treatment with HGF-shRNA, SP600125 or stattic also reduced generation of EGFP(Axin2)+ hepatic cell-originated CD90+ CSCs in aberrant autophagic cirrhotic livers by inactivating HGF/Met/JNK or HGF/Met/STAT3 signaling, further preventing hepatocarcinogenesis. These data suggest that activation of Met/JNK and Met/STAT3 signaling in Axin2+ hepatic cells via autophagy-dependent HGF expression and the resultant generation of Axin2+CD90+ CSCs is a major mechanism of hepatocarcinogenesis in cirrhotic livers.

Autophagy-dependent generation of Axin2+ cancer stem-like cells promotes hepatocarcinogenesis in liver cirrhosis

PubMed Central

Li, J; Hu, S B; Wang, L Y; Zhang, X; Zhou, X; Yang, B; Li, J H; Xiong, J; Liu, N; Li, Y; Wu, Y Z; Zheng, Q C

2017-01-01

Autophagy is a pathophysiological phenomenon in liver cirrhosis that can further progress into hepatocarcinoma. Liver cancer stem cells (CSCs) are believed to initiate hepatocarcinogenesis. To investigate the precise mechanism related to the origin of CSCs in liver cirrhosis and hepatocarcinogenesis, we labeled Axin2+ hepatic cells with EGFP in Axin2Cre;Rosa26EGFP transgenic rats, and then stratified clinical and rat liver cirrhosis samples by autophagy flux. Clinical follow-up and lineage tracing in transgenic rat liver cirrhosis revealed that while Axin2/EGFP+ hepatic cells were present in normal livers and cirrhotic livers without aberrant autophagy, hepatic Axin2/EGFP+CD90+ cells were generated exclusively in cirrhotic livers with aberrant autophagy and promoted hepatocarcinogenesis. Aberrant autophagy in liver cirrhosis resulted in hepatocyte growth factor (HGF) expression, leading to activation of Met/JNK and Met/STAT3 signaling in sorted hepatic Axin2/EGFP+ cells and their transition into Axin2/EGFP+CD90+ cells that possess CSC properties. In a transgenic rat liver cirrhosis model, induction or inhibition of autophagy in cirrhotic livers by systemic administration of rapamycin or chloroquine or transfection with Atg3- and Atg7-shRNAs significantly induced or suppressed HGF expression, which in turn increased or reduced generation of EGFP+CD90+ hepatic cells by activating or inactivating Met/JNK and Met/STAT3 signaling, thereby promoting or preventing hepatocarcinogenesis. Systemic treatment with HGF-shRNA, SP600125 or stattic also reduced generation of EGFP(Axin2)+ hepatic cell-originated CD90+ CSCs in aberrant autophagic cirrhotic livers by inactivating HGF/Met/JNK or HGF/Met/STAT3 signaling, further preventing hepatocarcinogenesis. These data suggest that activation of Met/JNK and Met/STAT3 signaling in Axin2+ hepatic cells via autophagy-dependent HGF expression and the resultant generation of Axin2+CD90+ CSCs is a major mechanism of hepatocarcinogenesis in cirrhotic livers. PMID:28783177

Successful outcome of transplant of kidneys recovered from a brain-dead liver transplant recipient: case report.

PubMed

Domagała, Piotr; Kwiatkowski, Artur; Drozdowski, Jakub; Ostrowski, Krzysztof; Wszola, Michal; Diuwe, Piotr; Durlik, Magdalena; Paczek, Leszek; Chmura, Andrzej

2012-12-01

Few reports describing the use of organs donated by transplant recipients have been published. In this case report, kidneys procured from a brain-dead liver recipient were transplanted successfully. A 21-year-old man was referred for liver transplant after an overdose of acetaminophen. The patient's kidney function was initially normal, with proper urine production and normal kidney laboratory parameters. On the third day after admission, the patient's kidney laboratory parameters became elevated and hepatic encephalopathy requiring mechanical ventilation developed. An orthotopic liver transplant was performed the next day. The patient did not recover consciousness, and brain death was diagnosed on the third day after the liver transplant surgery. The maximum serum concentration of creatinine was 5.8 mg/dL (513 μmol/L) before kidney recovery, and urine production was normal. The kidneys were recovered with organ-perfusion support and were preserved by using machine perfusion. The kidneys were transplanted into 2 male recipients. Twelve months after transplant, the recipients remained in good health with satisfactory kidney function. This case demonstrates that transplanting kidneys recovered from liver transplant recipients is possible and beneficial, thus expanding the pool of potential donors.

Classification of Hepatic Lesions From CT Images Using Texture Features and Neural Networks

DTIC Science & Technology

2001-10-25

ROI’s) taken from non-enhanced CT images of normal liver, hepatic cysts, hemangiomas, and hepatocellular carcinomas (a total of 147 samples), have been...disease”. The third NN classifies “other disease” into hemangiomas and hepatocellular carcinomas . In order to enhance the performance of the...and hepatocellular carcinoma (C4). II. METHODOLOGY The proposed diagnostic system is presented in Fig. 1. It consists of two levels: the

Isotopic analysis of Cu in blood serum by multi-collector ICP-mass spectrometry: a new approach for the diagnosis and prognosis of liver cirrhosis?

PubMed

Costas-Rodríguez, Marta; Anoshkina, Yulia; Lauwens, Sara; Van Vlierberghe, Hans; Delanghe, Joris; Vanhaecke, Frank

2015-03-01

The isotopic composition of blood serum Cu has been investigated as a potential parameter for the diagnosis and prognosis of liver cirrhosis. Serum samples from supposedly healthy women (reference population) and from a group of female patients suffering from liver cirrhosis of different etiologies were analysed. The procedure for isolation of serum Cu and the measurement protocol for its isotopic analysis by multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) were evaluated. Significant differences in the isotopic composition of Cu were observed between the reference population and the patients. A wide spread in δ(65)Cu was observed within the cirrhosis population and δ(65)Cu seems to be linked to the severity of the disease. Patients with end-stage liver disease showed a significantly lighter serum Cu isotopic composition. Many clinical parameters used for the diagnosis and monitoring of liver diseases, i.e. the levels of aspartate aminotransferase, De Ritis ratio, prothrombin and international normalized ratio, albumin, bilirubin, Na and C-reactive protein, correlate well with the δ(65)Cu values, as did the ceruloplasmin level and the ceruloplasmin/Cu concentration ratio. The isotopic composition of serum Cu appears to reveal the synthetic and hepatocellular function of the liver synergistically with inflammation and fluid retention in the cohort studied. A relevant relationship was also observed between δ(65)Cu and scores of mortality risk, such as the Model for End-stage Liver Disease (MELD) and MELD-Na. Thus, the isotopic composition of serum Cu shows potential as a new approach for the prognosis of liver disease, and although further investigation is required, for evaluation of the mortality risk in end-stage liver disease and prioritization of liver transplants.

[IMPORTANCE OF SHEAR WAVE ELASTOGRAPHY OF LIVERS IN PRACTICALLY HEALTHY PREGNANT WOMEN].

PubMed

Sariyeva, E; Salahova, S; Bayramov, N

2017-01-01

Pulse-wave elastography (SWE) that is one of the mostly used methods in the recent years holds important place in assessment of liver fibrosis. However there is no exact information on the results of liver elastography in healthy pregnant women in the world literature. The aim of the study was to investigate theSWE parameters of liver elastography in practically healthy pregnant women. The subject of the research was 50 practically healthy pregnant women within 18-45 years old (mean age 27.7±0.7). The pregnant women with genital and extragenital diseases were not included to the research. The research work was executed in the II Department of Obstetrics and Gynecology of Azerbaijan Medical University. SWE of liver in pregnant women was conducted in the I Department of Surgical Diseases of Azerbaijan Medical University through Supersonic Aixplorer Multi Wave device presented by the Scientific Development Foundation under the President of the Azerbaijan Republic. The obtained tissue hardness indicators are assessed under METAVIR scale. The results of the research showed that the measures of liver in practically healthy pregnant women are normal, edges flat, its echogenicity mainly normal, echostructure of its parenchyma homogenous, hardness was F0-F1 (normal) under METAVIR scale, fibrosis not observed. The obtained results were processed by variational (power average, percentile distribution) and correlation (ρ-Spearman) analyzes using the statistical package SPSS-20. A statistical study of the distribution of liver density in healthy women showed that the average density was 4,43±0,01 with 95% confidence interval (4,23 - 4,63). The histogram of distribution of liver density in practically healthy women belongs to the family of normal distributions with coefficients of variation coefficient (16.3%), asymmetry (-0.861±0.337) and excess (-0.068±0.662). Correlation analysis in healthy women did not reveal a reliable relationship between age and liver density (ρ=0.082, p=0.571), but a significant inverse correlation was found between the body mass index (BMI) and liver density (ρ=-0.317; p=0.025). Easy application, non-invasiveness, maximum exactness within the real time, repeatedly application of procedure and no risk to fetus by Shear Wave elastography of liver allow applying this method in pregnant women. Study of liver elasticity in pregnant women allows assessing the grades of hepatic fibrosis and differentiating liver disease.

Liver Transplantation for Budd-Chiari Syndrome

PubMed Central

Putnam, Charles W.; Porter, Kendrick A.; Well, Richard; Reid, H. A. S.; Starzl, Thomas E.

2011-01-01

Orthotopic liver transplantation was accomplished in a 22-year-old woman dying of the Budd-Chiarl syndrome. She Is well and has normal liver function 16 months postoperatively. In view of the good early result, it will be appropriate to consider liver replacement for this disease in further well-selected cases. PMID:781334

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Y.; Hawkins, R.A.; Huang, S.C.

The liver plays an important role in glucose homeostasis. PET studies with 2-[F-18]fluro-2-deoxy-D-glucose (FDG) of the liver (e.g., in neoplasms) require an understanding of the effects of dietary conditions on hepatic FDG uptake. Twenty studies were performed on 10 normal volunteers (ages 24 {+-} 4) after fasting 4 to 19 hr and again after oral consumption of 100 g of dextrose to investigate tracer kinetic model configurations of FDG in the normal liver and to evaluate the impact of oral glucose on liver in normal subjects. Dynamic PET images were acquired for about 1 hr using a Siemens/CTI 931 tomograph.more » A three-compartment model with an input function delay time parameter was the statistically preferred model configuration. The model estimated transport rate constant from plasma to liver, K{sub 1}, increased significantly (p < 0.05) from 0.864 {+-} 0.136 ml/min/g in fasting studies to 1.058 {+-} 0.269 ml/min/g in postglucose studies. Glucose loading also significantly increased (p < 0.01) the rate constant for FDG phosphorylation, k{sub 3}, from 0.005 {+-} 0.003 min{sup -1} in fasting studies to 0.013 {+-} 0.007 min{sup -1} in postglucose administration and, consequently, significantly increased both the phosphorylation fraction (k{sub 3}/(k{sub 2} + k{sub 3})) and the influx constant (K{sub 1}k{sub 3}/(k{sub 2} + k{sub 3})). No significant differences in the liver-to-plasma transport rate constant, k{sub 2}, dephosphorylation constant, k{sub 4}, or distribution volume of FDG (K{sub 1}/(k{sub 2} + k{sub 3})) were observed. Dynamic FDG-PET studies can be used to evaluate kinetics of liver glucose metabolism. The results indicate that dietary conditions have a significant effect on hepatic FDG kinetics. Because of the higher net FDG uptake by normal liver after glucose loading, fasting conditions are preferred for FDG liver tumor studies to increase the tumor-to-background contrast. 22 refs., 2 figs., 3 tabs.« less

Evaluation of Hepatoprotective Effect of Curcumin on Liver Cirrhosis Using a Combination of Biochemical Analysis and Magnetic Resonance-Based Electrical Conductivity Imaging

PubMed Central

Kyung, Eun Jung; Kim, Hyun Bum; Hwang, Eun Sang; Lee, Seok; Choi, Bup Kyung; Lim, Sang Moo; Kwon, Oh In

2018-01-01

In oriental medicine, curcumin is used to treat inflammatory diseases, and its anti-inflammatory effect has been reported in recent research. In this feasibility study, the hepatoprotective effect of curcumin was investigated using a rat liver cirrhosis model, which was induced with dimethylnitrosamine (DMN). Together with biochemical analysis, we used a magnetic resonance-based electrical conductivity imaging method to evaluate tissue conditions associated with a protective effect. The effects of curcumin treatment and lactulose treatment on liver cirrhosis were compared. Electrical conductivity images indicated that liver tissues damaged by DMN showed decreased conductivity compared with normal liver tissues. In contrast, cirrhotic liver tissues treated with curcumin or lactulose showed increased conductivity than tissues in the DMN-only group. Specifically, conductivity of cirrhotic liver after curcumin treatment was similar to that of normal liver tissues. Histological staining and immunohistochemical examination showed significant levels of attenuated fibrosis and decreased inflammatory response after both curcumin and lactulose treatments compared with damaged liver tissues by DMN. The conductivity imaging and biochemical examination results indicate that curcumin's anti-inflammatory effect can prevent the progression of irreversible liver dysfunction. PMID:29887757

The 57Fe hyperfine interactions in iron storage proteins in liver and spleen tissues from normal human and two patients with mantle cell lymphoma and acute myeloid leukemia: a Mössbauer effect study

NASA Astrophysics Data System (ADS)

Oshtrakh, M. I.; Alenkina, I. V.; Vinogradov, A. V.; Konstantinova, T. S.; Semionkin, V. A.

2015-04-01

Study of human spleen and liver tissues from healthy persons and two patients with mantle cell lymphoma and acute myeloid leukemia was carried out using Mössbauer spectroscopy with a high velocity resolution. Small variations in the 57Fe hyperfine parameters for normal and patient's tissues were detected and related to small variations in the 57Fe local microenvironment in ferrihydrite cores. The differences in the relative parts of more crystalline and more amorphous core regions were also supposed for iron storage proteins in normal and patients' spleen and liver tissues.

Liver transplantation for HBsAg-positive recipients using grafts from HBsAg-positive deceased donors.

PubMed

Choi, YoungRok; Choi, Jong Young; Yi, Nam-Joon; Lee, Kyoungbun; Mori, Shozo; Hong, Geun; Kim, Hyeyoung; Park, Min-Su; Yoo, Tae; Suh, Suk-Won; Lee, Hae Won; Lee, Kwang-Woong; Suh, Kyung-Suk

2013-12-01

This study reports our experience using deceased donor liver grafts from HBsAg-positive donors. We performed eight cases of liver transplantation (LT) using grafts from deceased HBsAg-positive donors between November 2005 and October 2010. The median age of donors was 48 years (range: 26-64). HBV DNA in the serum of donors ranged from 44 to 395 IU/ml, but HBeAg in all donors was negative. Preoperative laboratory and liver biopsy samples revealed the absence of definitive cirrhotic features and hepatitis. All recipients showed HBsAg positive preoperatively except one patient with HBsAg(-) status post previous LT for HBV related liver cirrhosis. The median age was 60 years (range: 46-76) at LT. Post-LT antiviral management consisted of hepatitis B immunoglobulin and antiviral nucleos(t)ide analogues. The median follow-up period was 25.5 months (range: 14-82). Of eight recipients, two recipients experienced serum HBsAg and HBV DNA disappearance postoperatively. Three recipients died of HBV-unrelated causes. The remaining five recipients were stable with normal liver function and no marked pathologic changes on follow-up biopsies. This experience shows that LT using grafts from deceased HBsAg-positive donors is feasible, and may represent a valuable expansion of the pool of organ donors with appropriate antiviral management and monitoring. © 2013 Steunstichting ESOT. Published by John Wiley & Sons Ltd.

Enhancement of Lipid Metabolism and Hepatic Stability in Fat-Induced Obese Mice by Fermented Cucurbita moschata Extract

PubMed Central

Lee, Seung-Jin; Park, Na-Hye; Birhanu, Biruk Tesfaye; Mechesso, Abraham Fikru; Park, Ji-Yong; Park, Eun-Jin; Youn, Sun-Joo

2018-01-01

The aim of this study was to evaluate the potentials of fermented Cucurbita moschata extract (FCME) in the treatment of obesity and nonalcoholic fatty liver disease (NAFLD). Five-week-old male C57BL/6 mice were assigned to 6 groups and treated for 8 weeks by feeding the normal diet (ND) and high fat diet (HFD) with and without FCME. Changes in body weight gain and consumption of feed and water were recorded. Major organs, adipose tissues, and blood samples were collected after the experimental period. The serum lipid profile, histological features of liver and adipose tissues, and mRNA expression of different adipogenic/lipogenic genes from liver tissue were evaluated. The supplementation of FCME in HFD significantly prevented HFD-induced increment of bodyweight. The adipose tissue mass, liver enzymes, and plasma lipids were also reduced significantly (p < 0.05) by the consumption of FCME. The mRNA expressions of adipogenic/lipogenic genes (PPARγ, C/EBPα, C/EBPβ, C/EBPγ, and SREBP-1C) in FCME-treated obese mice were considerably (p < 0.05) suppressed. FCME showed its antiobesity potential by suppressing the body weight gain and by modulating the plasma lipids and liver enzymes through the regulation of adipogenic/lipogenic transcriptional factors. Fermented Cucurbita moschata could be an opportunistic agent in controlling obesity and fatty liver changes. PMID:29725353

Curative bone marrow transplantation in erythropoietic protoporphyria after reversal of severe cholestasis.

PubMed

Wahlin, Staffan; Aschan, Johan; Björnstedt, Mikael; Broomé, Ulrika; Harper, Pauline

2007-01-01

We report the case of a middle-age patient presenting with severe progressive protoporphyric cholestasis. To halt further progression of liver disease, medical treatment was given aimed at different mechanisms possibly causing cholestasis in erythropoietic protoporphyria. Within eighty days, liver biochemistry completely normalized and liver histology markedly improved. Bone marrow transplantation was performed to prevent relapse of cholestatic liver disease by correcting the main site of protoporphyrin overproduction. Thirty-three months after cholestatic presentation and ten months after bone marrow transplantation, liver and porphyrin biochemistry remains normal. The patient is in excellent condition and photosensitivity is absent. The theoretical role of each treatment used to successfully reverse cholestasis and the role of bone marrow transplantation in erythropoietic protoporphyria are discussed. Medical treatment can resolve hepatic abnormalities in protoporphyric cholestasis. Bone marrow transplantation achieves phenotypic reversal and may offer protection from future protoporphyric liver disease.

Adverse effects of chronic exposure to nonylphenol on non-alcoholic fatty liver disease in male rats

PubMed Central

Yu, Jie; Yang, Xuesong; Luo, Ya; Yang, Xuefeng; Yang, Mengxue; Yang, Jin; Zhou, Jie; Gao, Feng; He, Liting; Xu, Jie

2017-01-01

Endocrine-disrupting chemical (EDC) has been thought to play a role in non-alcoholic fatty liver disease (NAFLD). However, the toxic effects of Nonylphenol (NP), an EDC, on non-alcoholic fatty liver disease have never been elaborated. This study aimed to investigate whether exposure to NP could induce NAFDL, a promoting effect of high-sucrose-high-fat diet (HSHFD) on the adverse effects caused by NP was evaluated. Fourth eight male rats were assigned to four groups and each group was treated with a specific testing sample: normal-diet (ND) control group (C-ND); normal diet plus NP (180mg/kg/day) group (NP-ND); high-sucrose-high-fat-diet control group (C-HSHFD); HSHFD plus NP (180mg/kg/day) group (NP-HSHFD). At the age of 80 day, sonogram presents diffusely increased hepatic echogenicity in the NP-HSHFD group. The oblique diameter of liver in the NP-HSHFD group was significantly bigger than that in both the C-ND and NP-ND groups. At the age of 90 day, exposure to NP-HSHFD and NP-ND caused a significant increase in NP concentration in liver as compared to the C-ND group. The rats in the groups treated with NP+ND, HSHFD and NP+HSHFD produced significant increases in the body weight, fat weight and FMI, respectively, when compared to the C-ND group. The liver weight and hepatosomatic indexes (HIS) of rats in the NP-HSHFD group are higher than those in the C-HSHFD group. Exposure to NP-HSHFD induced the increases in plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) as compared to the C-ND group. Morphological examination of liver tissue from rats exposed to NP+HSHFD shown steatosis with marked accumulation of lipid droplets, hepatocellular ballooning degeneration and inflammatory cell infiltration. Chronic exposure to NP might induce NAFLD in male rats. The high-sucrose-high-fat diet accelerates and exacerbates the development of NAFLD caused by NP exposure. PMID:28686624

Automated classification of tissue by type using real-time spectroscopy

NASA Astrophysics Data System (ADS)

Benaron, David A.; Cheong, Wai-Fung; Duckworth, Joshua L.; Noles, Kenneth; Nezhat, Camran; Seidman, Daniel; Hintz, Susan R.; Levinson, Carl J.; Murphy, Aileen L.; Price, John W., Jr.; Liu, Frank W.; Stevenson, David K.; Kermit, Eben L.

1997-12-01

Each tissue type has a unique spectral signature (e.g. liver looks distinct from bowel due to differences in both absorbance and in the way the tissue scatters light). While differentiation between normal tissues and tumors is not trivial, automated discrimination among normal tissue types (e.g. nerve, artery, vein, muscle) is feasible and clinically important, as many medical errors in medicine involve the misidentification of normal tissues. In this study, we have found that spectroscopic differentiation of tissues can be successfully applied to tissue samples (kidney and uterus) and model systems (fruit). Such optical techniques may usher in use of optical tissue diagnosis, leading to automated and portable diagnostic devices which can identify tissues, and guide use of medical instruments, such as during ablation or biopsy.

Increased Expression of TGF-β1 in Correlation with Liver Fibrosis during Echinococcus granulosus Infection in Mice.

PubMed

Liu, Yumei; Abudounnasier, Gulizhaer; Zhang, Taochun; Liu, Xuelei; Wang, Qian; Yan, Yi; Ding, Jianbing; Wen, Hao; Yimiti, Delixiati; Ma, Xiumin

2016-08-01

To investigate the potential role of transforming growth factor (TGF)-β1 in liver fibrosis during Echinococcus granulosus infection, 96 BALB/c mice were randomly divided into 2 groups, experimental group infected by intraperitoneal injection with a metacestode suspension and control group given sterile physiological saline. The liver and blood samples were collected at days 2, 8, 30, 90, 180, and 270 post infection (PI), and the expression of TGF-β1 mRNA and protein was determined by real-time quantitative RT-PCR and ELISA, respectively. We also evaluated the pathological changes in the liver during the infection using hematoxylin and eosin (H-E) and Masson staining of the liver sections. Pathological analysis of H-E stained infected liver sections revealed liver cell edema, bile duct proliferation, and structural damages of the liver as evidenced by not clearly visible lobular architecture of the infected liver, degeneration of liver cell vacuoles, and infiltration of lymphocytes at late stages of infection. The liver tissue sections from control mice remained normal. Masson staining showed worsening of liver fibrosis at the end stages of the infection. The levels of TGF-β1 did not show significant changes at the early stages of infection, but there were significant increases in the levels of TGF-β1 at the middle and late stages of infection (P<0.05). RT-PCR results showed that, when compared with the control group, TGF-β1 mRNA was low and comparable with that in control mice at the early stages of infection, and that it was significantly increased at day 30 PI and remained at high levels until day 270 PI (P<0.05). The results of this study suggested that increased expression of TGF-β1 during E. granulosus infection may play a significant role in liver fibrosis associated with E. granulosus infection.

Changes in arginase isoenzymes pattern in human hepatocellular carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chrzanowska, Alicja; Krawczyk, Marek; Baranczyk-Kuzma, Anna

2008-12-12

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide affecting preferentially patients with liver cirrhosis. The studies were performed on tissues obtained during surgery from 50 patients with HCC, 40 with liver cirrhosis and 40 control livers. It was found that arginase activity in HCC was nearly 5- and 15-fold lower than in cirrhotic and normal livers, respectively. Isoenzymes AI (so-called liver-type arginase) and AII (extrahepatic arginase) were identified by Western blotting in all studied tissues, however the amount of AI, as well as the expression of AI-mRNA were lower in HCC, in comparison with normal liver, andmore » those of AII were significantly higher. Since HCC is arginine-dependent, and arginine is essential for cells growth, the decrease of AI may preserve this amino acid within tumor cells. Concurrently, the rise of AII can increase the level of polyamines, compounds crucial for cells proliferation. Thus, both arginase isoenzymes seem to participate in liver cancerogenesis.« less

Accumulation of hydroxyl lipids and 4-hydroxy-2-hexenal in live fish infected with fish diseases.

PubMed

Tanaka, Ryusuke; Shigeta, Kazuhiro; Sugiura, Yoshimasa; Hatate, Hideo; Matsushita, Teruo

2014-04-01

Hydroxy lipids (L-OH) and 4-hydroxy-2-hexenal (HHE) levels as well as other parameters such as lipid level, lipid class, fatty acid composition, and other aldehydes levels in the liver of diseased fish were investigated. Although significant differences in lipid level, lipid class, fatty acid composition, and other aldehyde levels were not always observed between normal and diseased fish, L-OH and HHE levels were significantly higher in the liver of the diseased fish than in that of the normal fish cultured with the same feeds under the same conditions. In the liver of puffer fish (Fugu rubripes) infected with Trichodina, L-OH and HHE levels significantly increased from 25.29±5.04 to 47.70 ± 5.27 nmol/mg lipid and from 299.79±25.25 to 1,184.40±60.27 nmol/g tissue, respectively. When the levels of HHE and other aldehydes in the liver of the normal and diseased puffer fish were plotted, a linear relationship with a high correlation coefficient was observed between HHE and propanal (r2=0.9447). Increased L-OH and HHE levels in the liver of the diseased fish and a high correlation between HHE and propanal in the liver of the normal and diseased fish were also observed in flat fish (Paralichthys olivaceus) infected with streptococcus, yellowtail (Seriola quinqueradiata) infected with jaundice, and amberjack (S. purpurascens) infected with Photobacterium damselae subsp. piscicida.

Angiogenesis and proliferation of bile duct enhances ischemic tolerance in rats with cirrhosis

PubMed Central

Zhang, Zhiqiang; Li, Zhennan; Zou, Chen; Zhang, Jingjing; Zhu, Yi; Miao, Yi

2015-01-01

Background/aims: Primary biliary cirrhosis (PBC), an autoimmune disease of the liver, is marked by slow progressive destruction of bile ducts. These patients with PBC often undergo orthotopic liver transplantation (OLT). Ischemic bile duct lesion (IBDL) is a major source of morbidity and even mortality after OLT. Cirrhosis of the liver has a higher tolerance to ischemia than a normal liver, but the mechanism remains unknown. Angiogenesis and proliferation of bile duct often responses in bile duct ischemia, which may enhance ischemic tolerance in patients with cirrhosis. Methodology: To test the hypothesis, a rat model with cirrhosis was established. Biochemical indexes of ischemic severity were measured including total bilirubin (TBIL) and direct bilirubin (DBIL). Immunohistochemical assay was performed for Ki67 (a biomarker for the proliferation of bile duct) and CD34 (a biomarker of angiogenesis). Results: The levels were lower for TBIL and DBIL in the bile duct from rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05). The levels were higher for Ki67 and CD34 from a rat model with cirrhosis than that from a normal rat after ischemic surgery (P < 0.05). Conclusions: The results suggest that a liver with cirrhosis has a better ischemic tolerance than a normal liver. Angiogenesis and proliferation of bile duct enhances ischemic tolerance in rats with cirrhosis. More research on the pathogenesis of IBDLs is needed for developing more specific preventive or therapeutic strategies. PMID:26550120

Individuals' perception of their quality of life following a liver transplant: an exploratory study.

PubMed

Robertson, G

1999-08-01

This study explores individuals' perceptions of the effect of a liver transplant on their quality of life, focusing on the progression from dependence to independence physically, socially and psychologically. A phenomenological design using taped semi-structured interviews was used. The sample consisted of five patients attending the out-patients clinic at least 1 year following a liver transplant for chronic liver disease. The data were analysed using cluster analysis of transcribed interviews. Categories were identified as physical, social and psychological factors affecting their progression from dependence to independence pre- and post-transplant and specific factors were identified as significant in overcoming the stressors affecting this progression. The findings reflected Maslow's Hierarchy of Needs. Pre-transplant their physical problems prevented them fulfilling personal goals and addressing psychological issues, e.g. dying. Post-transplant any physical problems identified were insignificant to the participant. They were keen to socially integrate and be treated as normal; however, family and friends restricted their independence by continuing to 'wrap them in cotton wool' as they had before their transplant. Personality, incentives and Unit support were identified as imperative in their progression from dependence to independence. The findings demonstrate a need to impress on family and friends of patients following a liver transplant, their role in assisting the patient's progression from dependence to independence.

Ethanol elimination rates in men and women in consideration of the calculated liver weight.

PubMed

Dettling, Andrea; Fischer, Florian; Böhler, Svenja; Ulrichs, Fee; Skopp, Gisela; Graw, Matthias; Haffner, Hans-Thomas

2007-09-01

The purpose of the study was to examine gender differences on the pharmacokinetics of ethanol. Sixty-eight healthy men and 64 healthy women with normal body mass indexes received between 0.79 and 0.95 g ethanol/kg body weight in the form of their choice after they had eaten a "typical" breakfast. The aimed concentration for both genders was a blood alcohol concentration C(0) of 0.104 g/dl. Blood samples in the elimination phase were taken in 10- to 20-min intervals beginning after completion of absorption. The maximum blood ethanol concentration was 0.0819+/-0.0184 g/dl for women and 0.0841+/-0.0155 g/dl for men. The hourly ethanol elimination rate, calculated over a linear function, in blood of 0.0179+/-0.0030 g/dl/h in women was significantly higher than the 0.0159+/-0.0029 g/dl/h for men (P<.0001). In relation to the liver weight, the hourly elimination rates were 5.008+/-0.678 g/kg liver/h for women and 4.854+/-0.659 g/kg liver/h for men, and were not statistically significant. The different liver masses as calculated in relation to the distribution volume account for the differing ethanol elimination rates between men and women.

Efficiency of herbal medicine Dai-kenchu-to on portal blood flow in rat models.

PubMed

Muraoka, Izumi; Takatsuki, Mitsuhisa; Soyama, Akihiko; Yamaguchi, Izumi; Tanaka, Shiro; Tanaka, Takayuki; Kinoshita, Ayaka; Hara, Takanobu; Kuroki, Tamotsu; Eguchi, Susumu

2015-09-01

To clarify the influence of Dai-Kenchu-To (DKT) on portal blood flow (PBF), PBF was continuously measured with Doppler ultrasound. Normal liver rats were divided into a DKT 90 mg/kg, DKT 270 mg/kg administered group, and control, while cirrhotic liver rats were divided into a DKT-LC 90 mg/kg administered group and Control-LC. The PBF was measured after the administration of either DKT or water for 60 min by laser Doppler flowmetry system. The PBF in the DKT 90 increased approximately 10 min after DKT was administrated, and elevated levels were maintained for approximately 10 min. A comparison of the increase in PBF by the calculating the area under the curve (AUC) revealed that flow was significantly higher in the DKT 90 compared to either the control or the DKT 270 (p < 0.05). The cirrhotic liver group showed stable PBF in both the DKT-LC and Control-LC. The AUC, revealed no significant difference between the DKT-LC and Control-LC. DKT induced an increase in PBF in normal livers; however, its effects were insufficient to increase PBF in the cirrhotic livers. No increase in the portal blood flow in the cirrhotic liver rats was probably the result of the cirrhotic liver, which had fibrotic change, and, therefore, may not have had sufficient compliance to accept the increasing blood flow volume from the intestinal tract. We suggested DKT has the potential to protect the liver by increasing PBF when the liver has either normal or mild to moderate dysfunction.

Physiological Ranges of Matrix Rigidity Modulate Primary Mouse Hepatocyte Function In Part Through Hepatocyte Nuclear Factor 4 Alpha

PubMed Central

Desai, Seema S.; Tung, Jason C.; Zhou, Vivian X.; Grenert, James P.; Malato, Yann; Rezvani, Milad; Español-Suñer, Regina; Willenbring, Holger; Weaver, Valerie M.; Chang, Tammy T.

2016-01-01

Matrix rigidity has important effects on cell behavior and is increased during liver fibrosis; however, its effect on primary hepatocyte function is unknown. We hypothesized that increased matrix rigidity in fibrotic livers would activate mechanotransduction in hepatocytes and lead to inhibition of hepatic-specific functions. To determine the physiologically relevant ranges of matrix stiffness at the cellular level, we performed detailed atomic force microscopy analysis across liver lobules from normal and fibrotic livers. We determined that normal liver matrix stiffness was around 150Pa and increased to 1–6kPa in areas near fibrillar collagen deposition in fibrotic livers. In vitro culture of primary hepatocytes on collagen matrix of tunable rigidity demonstrated that fibrotic levels of matrix stiffness had profound effects on cytoskeletal tension and significantly inhibited hepatocyte-specific functions. Normal liver stiffness maintained functional gene regulation by hepatocyte nuclear factor 4 alpha (HNF4α) whereas fibrotic matrix stiffness inhibited the HNF4α transcriptional network. Fibrotic levels of matrix stiffness activated mechanotransduction in primary hepatocytes through focal adhesion kinase (FAK). In addition, blockade of the Rho/Rho-associated protein kinase (ROCK) pathway rescued HNF4α expression from hepatocytes cultured on stiff matrix. Conclusion Fibrotic levels of matrix stiffness significantly inhibit hepatocyte-specific functions in part by inhibiting the HNF4α transcriptional network mediated through the Rho/ROCK pathway. Increased appreciation of the role of matrix rigidity in modulating hepatocyte function will advance our understanding of the mechanisms of hepatocyte dysfunction in liver cirrhosis and spur development of novel treatments for chronic liver disease. PMID:26755329

Glycyrrhizin ameliorates metabolic syndrome-induced liver damage in experimental rat model.

PubMed

Sil, Rajarshi; Ray, Doel; Chakraborti, Abhay Sankar

2015-11-01

Glycyrrhizin, a major constituent of licorice (Glycyrrhiza glabra) root, has been reported to ameliorate insulin resistance, hyperglycemia, dyslipidemia, and obesity in rats with metabolic syndrome. Liver dysfunction is associated with this syndrome. The objective of this study is to investigate the effect of glycyrrhizin treatment on metabolic syndrome-induced liver damage. After induction of metabolic syndrome in rats by high fructose (60%) diet for 6 weeks, the rats were treated with glycyrrhizin (50 mg/kg body weight, single intra-peritoneal injection). After 2 weeks of treatment, rats were sacrificed to collect blood samples and liver tissues. Compared to normal, elevated activities of serum alanine transaminase, alkaline phosphatase and aspartate transaminase, increased levels of liver advanced glycation end products, reactive oxygen species, lipid peroxidation, protein carbonyl, protein kinase Cα, NADPH oxidase-2, and decreased glutathione cycle components established liver damage and oxidative stress in fructose-fed rats. Activation of nuclear factor κB, mitogen-activated protein kinase pathways as well as signals from mitochondria were found to be involved in liver cell apoptosis. Increased levels of cyclooxygenase-2, tumor necrosis factor, and interleukin-12 proteins suggested hepatic inflammation. Metabolic syndrome caused hepatic DNA damage and poly-ADP ribose polymerase cleavage. Fluorescence-activated cell sorting using annexin V/propidium iodide staining confirmed the apoptotic hepatic cell death. Histology of liver tissue also supported the experimental findings. Treatment with glycyrrhizin reduced oxidative stress, hepatic inflammation, and apoptotic cell death in fructose-fed rats. The results suggest that glycyrrhizin possesses therapeutic potential against hepatocellular damage in metabolic syndrome.

A natural antioxidant, tannic acid mitigates iron-overload induced hepatotoxicity in Swiss albino mice through ROS regulation.

PubMed

Basu, Tapasree; Panja, Sourav; Shendge, Anil Khushalrao; Das, Abhishek; Mandal, Nripendranath

2018-05-01

Tannic acid (TA), a water soluble natural polyphenol with 8 gallic acids groups, is abundantly present in various medicinal plants. Previously TA has been investigated for its antimicrobial and antifungal properties. Being a large polyphenol, TA chelates more than 1 metal. Hence TA has been explored for potent antioxidant activities against reactive oxygen species (ROS), reactive nitrogen species (RNS) and as iron chelator in vitro thereby mitigating iron-overload induced hepatotoxicity in vivo. Iron dextran was injected intraperitoneally in Swiss albino mice to induce iron-overload triggered hepatotoxicity, followed by oral administration of TA for remediation. After treatment, liver, spleen, and blood samples were processed from sacrificed animals. The liver iron, serum ferritin, serum markers, ROS, liver antioxidant status, and liver damage parameters were assessed, followed by histopathology and protein expression studies. Our results show that TA is a prominent ROS and RNS scavenger as well as iron chelator in vitro. It also reversed the ROS levels in vivo and restricted the liver damage parameters as compared to the standard drug, desirox. Moreover, this natural polyphenol exclusively ameliorates the histopathological and fibrotic changes in liver sections reducing the iron-overload, along with chelation of liver iron and normalization of serum ferritin. The protective role of TA against iron-overload induced apoptosis in liver was further supported by changed levels of caspase 3, PARP as well as Bax/BCl-2 ratio. Thus, TA can be envisaged as a better orally administrable iron chelator to reduce iron-overload induced hepatotoxicity through ROS regulation. © 2018 Wiley Periodicals, Inc.

Assessment of hepatic function decline after stereotactic body radiation therapy for primary liver cancer.

PubMed

Toesca, Diego A S; Osmundson, Evan C; von Eyben, Rie; Shaffer, Jenny L; Koong, Albert C; Chang, Daniel T

This study aims to determine how the albumin-bilirubin (ALBI) score compares with the Child-Pugh (CP) score for assessing liver function following stereotactic body radiation therapy (SBRT). In total, 60 patients, 40 with hepatocellular carcinoma (HCC) and 20 with cholangiocarcinoma (CCA), were treated with SBRT. Liver function panels were obtained before and at 1, 3, 6, and 12 months after SBRT. Laboratory values were censored after locoregional recurrence, further liver-directed therapies, or liver transplant. A significant decline in hepatic function occurred after SBRT for HCC patients only (P = .001 by ALBI score; P < .0001 by CP score). By converting radiation doses to biologically equivalent doses by using a standard linear quadratic model using α/β of 10, the strongest dosimetric predictor of liver function decline for HCC was the volume of normal liver irradiated by a dose of 40 Gy when assessing liver function by the ALBI score (P = .07), and the volume of normal liver irradiated by a dose of 20 Gy by using the CP score (P= .0009). For CCA patients, the volume of normal liver irradiated by a dose of 40 Gy remained the strongest dosimetric predictor when using the ALBI score (P = .002), but no dosimetric predictor was significant using the CP score. Hepatic function decline correlated with worse overall survival for HCC (by ALBI, P = .0005; by CP, P < .0001) and for CCA (by ALBI, P = NS; by CP, P = .008). ALBI score was similarly able to predict hepatic function decline compared with CP score, and both systems correlated with survival. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Usefulness of chemical-shift MRI in discriminating increased liver echogenicity in glycogenosis.

PubMed

Pozzato, C; Dall'asta, C; Radaelli, G; Torcoletti, M; Formenti, A; Riva, E; Cornalba, G; Pontiroli, A E

2007-11-01

Glycogen storage diseases are inherited defects which cause accumulation of glycogen in the tissues. Hepatic steatosis is defined as accumulation of fat within hepatocytes. On sonography, liver shows increased echogenicity both in glycogen storage diseases and steatosis. Liver hyperechogenicity in glycogen storage diseases may depend on accumulation of glycogen and/or fat. Chemical-shift magnetic resonance imaging can discriminate tissues only containing water from those containing both fat and water. The primary aim of the present study was to evaluate the usefulness of liver chemical-shift magnetic resonance imaging for detecting liver steatosis in patients with metabolic impairment due to glycogen storage diseases. Twelve patients with type I (n=8) or type III (n=4) glycogen storage diseases were studied and compared to 12 obese-overweight subjects with known liver steatosis. As control group 12 lean normal voluntary subjects were recruited. Liver was evaluated by sonography and chemical-shift magnetic resonance imaging to calculate hepatic fat fraction. A significant difference in echogenicity between patients with glycogen storage diseases and normal subjects was observed (p<0.05), while this difference was not present between overweight-obese and glycogen storage diseases patients. On the contrary, fat fraction was similar between glycogen storage diseases patients and normal subjects and different between glycogen storage diseases patients and overweight-obese (p<0.05). The present data suggest that chemical-shift magnetic resonance imaging may exclude fat deposition as a cause of liver hyperechogenicity in subjects with glycogen storage diseases.

Expression of the serine/threonine kinase hSGK1 in chronic viral hepatitis.

PubMed

Fillon, Sophie; Klingel, Karin; Wärntges, Simone; Sauter, Martina; Gabrysch, Sabine; Pestel, Sabine; Tanneur, Valerie; Waldegger, Siegfried; Zipfel, Annette; Viebahn, Richard; Häussinger, Dieter; Bröer, Stefan; Kandolf, Reinhard; Lang, Florian

2002-01-01

The human serine/threonine kinase hSGK1 is expressed ubiquitously with highest transcript levels in pancreas and liver. This study has been performed to determine the hSGK1 distribution in normal liver and its putative role in fibrosing liver disease. HSGK1-localization was determined by in situ hybridization, regulation of hSGK1-transcription by Northern blotting, fibronectin synthesis and hSGK1 phosphorylation by Western blotting. In normal liver hSGK1 was mainly transcribed by Kupffer cells. In liver tissue from patients with chronic viral hepatitis, hSGK1 transcript levels were excessively high in numerous activated Kupffer cells and inflammatory cells localized within fibrous septum formations. HSGK1 transcripts were also detected in activated hepatic stellate cells. Accordingly, Western blotting revealed that tissue from fibrotic liver expresses excessive hSGK1 protein as compared to normal liver. TGF-beta1 (2 ng/ml) increases hSGK1 transcription in both human U937 macro-phages and HepG2 hepatoma cells. H(2)O(2) (0.3 mM) activated hSGK1 and increased fibronectin formation in HepG2 cells overexpressing hSGK1 but not in HepG2 cells expressing the inactive mutant hSGK1(K127R). In conclusion hSGK1 is upregulated by TGF-beta1 during hepatitis and may contribute to enhanced matrix formation during fibrosing liver disease. Copyright 2002 S. Karger AG, Basel

Multiparametric or practical quantitative liver MRI: towards millisecond, fat fraction, kilopascal and function era.

PubMed

Unal, Emre; Idilman, Ilkay Sedakat; Karçaaltıncaba, Muşturay

2017-02-01

New advances in liver magnetic resonance imaging (MRI) may enable diagnosis of unseen pathologies by conventional techniques. Normal T1 (550-620 ms for 1.5 T and 700-850 ms for 3 T), T2, T2* (>20 ms), T1rho (40-50 ms) mapping, proton density fat fraction (PDFF) (≤5%) and stiffness (2-3kPa) values can enable differentiation of a normal liver from chronic liver and diffuse diseases. Gd-EOB-DTPA can enable assessment of liver function by using postcontrast hepatobiliary phase or T1 reduction rate (normally above 60%). T1 mapping can be important for the assessment of fibrosis, amyloidosis and copper overload. T1rho mapping is promising for the assessment of liver collagen deposition. PDFF can allow objective treatment assessment in NAFLD and NASH patients. T2 and T2* are used for iron overload determination. MR fingerprinting may enable single slice acquisition and easy implementation of multiparametric MRI and follow-up of patients. Areas covered: T1, T2, T2*, PDFF and stiffness, diffusion weighted imaging, intravoxel incoherent motion imaging (ADC, D, D* and f values) and function analysis are reviewed. Expert commentary: Multiparametric MRI can enable biopsyless diagnosis and more objective staging of diffuse liver disease, cirrhosis and predisposing diseases. A comprehensive approach is needed to understand and overcome the effects of iron, fat, fibrosis, edema, inflammation and copper on MR relaxometry values in diffuse liver disease.

[Effect of fenicaberan on liver function in patients with chronic noncalculous cholecystitis].

PubMed

Skroban, N V

1989-06-01

The author studied the effect of fenicaberan on the functional state of the liver in 34 patients with chronic noncalculous cholecystitis. It was found that fenicaberan favours improvement of the functional state of the liver but complete normalization of all liver values indicates necessity continuation of treatment in outpatient conditions.

THE RELATION OF THE LIVER TO FAT METABOLISM

PubMed Central

Drury, D. R.; McMaster, Philip D.

1929-01-01

Fat combustion is carried on adequately in rabbits deprived of the liver or brought into a condition of extreme liver insufficiency. Even 24 hours after hepatectomy fat combustion goes on as well as in the normal animal. Evidently the liver plays no essential part in the breaking down of fat. PMID:19869581

Cadaveric domino liver transplantation: the first case in Japan.

PubMed

Wakayama, Kenji; Jin, Maeng Bong; Furukawa, Hiroyuki; Todo, Satoru; Shimamura, Tsuyoshi; Suzuki, Tomomi; Hattori, Masahiro; Yokoyama, Ryouji; Iwasaki, Sari; Sato, Masanori; Nakagawa, Takahito; Kurauchi, Noriaki; Kamachi, Hirohumi; Kamiyama, Toshiya; Matsushita, Michiaki

2004-01-01

The first case of domino liver transplantation from a brain-dead donor in Japan is described. A 49-year-old man with familial amyloidotic polyneuropathy received a cadaver liver, and his native liver was transplanted into a 53-year-old man with polycystic liver and kidney disease. The cadaveric liver allograft was transplanted by the conventional technique. The graft taken from the first recipient had four outflow orifices (the left, middle, and right hepatic veins, and upper vena cava), for which a single orifice was created at the back table. This graft was transplanted in piggy-back fashion. The first recipient developed acute rejection on day 13 and hepatic artery stenosis on day 36. These were treated by steroid recycle therapy and percutaneous transarterial angioplasty. He was discharged on day 57 with normal liver function. The second recipient underwent re-operation for bleeding from the right adrenal gland and left thoracic cavity. He was diagnosed with acute rejection on day 7, which was treated by steroid pulse therapy. He was discharged uneventfully on day 39 with normal liver function.

Betaine chemistry, roles, and potential use in liver disease.

PubMed

Day, Christopher R; Kempson, Stephen A

2016-06-01

Betaine is the trimethyl derivative of glycine and is normally present in human plasma due to dietary intake and endogenous synthesis in liver and kidney. Betaine is utilized in the kidney primarily as an osmoprotectant, whereas in the liver its primary role is in metabolism as a methyl group donor. In both organs, a specific betaine transporter mediates cellular uptake of betaine from plasma. The abundance of both betaine and the betaine transporter in liver greatly exceeds that of other organs. The remarkable contributions of betaine to normal human and animal health are summarized together with a discussion of the mechanisms and potential beneficial effects of dietary betaine supplements on liver disease. A significant amount of data from animal models of liver disease indicates that administration of betaine can halt and even reverse progression of the disruption of liver function. Betaine is well-tolerated, inexpensive, effective over a wide range of doses, and is already used in livestock feeding practices. The accumulated data indicate that carefully controlled additional investigations in humans are merited. The focus should be on the long-term use of betaine in large patient populations with liver diseases characterized by development of fatty liver, especially non-alcoholic fatty liver disease and alcoholic liver disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of Bauhinia forficata Tea on Oxidative Stress and Liver Damage in Diabetic Mice

PubMed Central

Salgueiro, Andréia Caroline Fernandes; da Silva, Marianne Pires; Mendez, Andreas Sebastian Loureiro; Zemolin, Ana Paula Pegoraro; Posser, Thaís; Puntel, Robson Luiz; Puntel, Gustavo Orione

2016-01-01

This study was designed to evaluate the effects of Bauhinia forficata Link subsp. pruinosa (BF) tea on oxidative stress and liver damage in streptozotocin (STZ)-induced diabetic mice. Diabetic male mice have remained 30 days without any treatment. BF treatment started on day 31 and continued for 21 days as a drinking-water substitute. We evaluated (1) BF chemical composition; (2) glucose levels; (3) liver/body weight ratio and liver transaminases; (4) reactive oxygen species (ROS), lipid peroxidation, and protein carbonylation in liver; (5) superoxide dismutase (SOD) and catalase (CAT) activities in liver; (6) δ-aminolevulinate dehydratase (δ-ALA-D) and nonprotein thiols (NPSH) in liver; (7) Nrf2, NQO-1, and HSP70 levels in liver and pancreas. Phytochemical analyses identified four phenols compounds. Diabetic mice present high levels of NQO-1 in pancreas, increased levels of ROS and lipid peroxidation in liver, and decrease in CAT activity. BF treatment normalized all these parameters. BF did not normalize hyperglycemia, liver/body weight ratio, aspartate aminotransferase, protein carbonyl, NPSH levels, and δ-ALA-D activity. The raised oxidative stress seems to be a potential mechanism involved in liver damage in hyperglycemic conditions. Our results indicated that BF protective effect could be attributed to its antioxidant capacity, more than a hypoglycemic potential. PMID:26839634

Effects of Bauhinia forficata Tea on Oxidative Stress and Liver Damage in Diabetic Mice.

PubMed

Salgueiro, Andréia Caroline Fernandes; Folmer, Vanderlei; da Silva, Marianne Pires; Mendez, Andreas Sebastian Loureiro; Zemolin, Ana Paula Pegoraro; Posser, Thaís; Franco, Jeferson Luis; Puntel, Robson Luiz; Puntel, Gustavo Orione

2016-01-01

This study was designed to evaluate the effects of Bauhinia forficata Link subsp. pruinosa (BF) tea on oxidative stress and liver damage in streptozotocin (STZ)-induced diabetic mice. Diabetic male mice have remained 30 days without any treatment. BF treatment started on day 31 and continued for 21 days as a drinking-water substitute. We evaluated (1) BF chemical composition; (2) glucose levels; (3) liver/body weight ratio and liver transaminases; (4) reactive oxygen species (ROS), lipid peroxidation, and protein carbonylation in liver; (5) superoxide dismutase (SOD) and catalase (CAT) activities in liver; (6) δ-aminolevulinate dehydratase (δ-ALA-D) and nonprotein thiols (NPSH) in liver; (7) Nrf2, NQO-1, and HSP70 levels in liver and pancreas. Phytochemical analyses identified four phenols compounds. Diabetic mice present high levels of NQO-1 in pancreas, increased levels of ROS and lipid peroxidation in liver, and decrease in CAT activity. BF treatment normalized all these parameters. BF did not normalize hyperglycemia, liver/body weight ratio, aspartate aminotransferase, protein carbonyl, NPSH levels, and δ-ALA-D activity. The raised oxidative stress seems to be a potential mechanism involved in liver damage in hyperglycemic conditions. Our results indicated that BF protective effect could be attributed to its antioxidant capacity, more than a hypoglycemic potential.

Can Patients Who Develop Cerebral Death in Fulminant Liver Failure Despite Liver Transplantation Be Previously Forseen?

PubMed

Sarici, K B; Karakas, S; Otan, E; Ince, V; Koc, C; Koc, S; Bayraktar, H; Aydin, C; Kayaalp, C; Gungor, S; Kablan, Y; Yilmaz, S

2017-04-01

The outcome of medical treatment is worse in fulminant liver failure (FLF) developing on acute or chronic ground. Recently, liver transplantations with the use of living and cadaveric donors have been performed in these diseases and good results obtained. In this study, we aimed to present the factors affecting the recovery of cerebral functions after liver transplantation in hepatic encephalopathy (HE) developing in FLF, to identify irreversible patient groups and to prevent unnecessary liver transplantation. In Inonu University's Liver Transplant Institute, 69 patients who made an emergency notice to the National Coordination Center for liver transplantation owing to FLF from January 2012 to December 2015 were included in the study. Patients were divided into 2 groups. Group 1 consisted of 52 patients who underwent liver transplantation and recovered normal brain function, and group 2 had 17 patients who underwent liver transplantation and did not recover normal brain function and had cerebral death. All patients were evaluated before surgery for clinical encephalopathy stage, light reflex, and convulsions. Groups were compared and assessed according to age (>40, 10-40 and <10 years), body mass index, etiologic factor, preoperative laboratory values, transplantation type, mortality, and encephalopathy level. Multivariate analysis was done for specific parameters. Prothrombin time (PT), international normalized ratio (INR), and total bilirubin values were significantly different between the groups. There was no significant difference between the groups regarding ammonia and lactate levels. There was a statistically significant difference between the groups regarding sodium and potassium levels from serum electrolytes. However, the averages of both groups were within normal limits. pH and total bilirubin levels were meaningful for multivariate analysis. HE reversibility, mortality, and morbidity are important in patients with HE who undergo liver transplantation. Therefore, West Haven clinical staging and serum INR, PT, and total bilirubin level may be helpful in predicting the reversibility of FLF patients with HE before liver transplantation. It was determined that West Haven encephalopathy grading is important in determining the reversibility of HE after transplantation in FLF; especially the probability of reversibility of stage 4 HE decreases significantly. High PT and INR levels, hyperbilirubinemia, and serum sodium and potassium concentrations were risk factors for the reversibility of HE in this study. Copyright © 2017 Elsevier Inc. All rights reserved.

CpG-island methylation study of liver fluke-related cholangiocarcinoma

PubMed Central

Sriraksa, R; Zeller, C; El-Bahrawy, M A; Dai, W; Daduang, J; Jearanaikoon, P; Chau-in, S; Brown, R; Limpaiboon, T

2011-01-01

Background: Genetic changes have been widely reported in association with cholangiocarcinoma (CCA), while epigenetic changes are poorly characterised. We aimed to further evaluate CpG-island hypermethylation in CCA at candidate loci, which may have potential as diagnostic or prognostic biomarkers. Methods: We analysed methylation of 26 CpG-islands in 102 liver fluke related-CCA and 29 adjacent normal samples using methylation-specific PCR (MSP). Methylation of interest loci was confirmed using pyrosequencing and/or combined bisulfite restriction analysis, and protein expression by immunohistochemistry. Results: A number of CpG-islands (OPCML, SFRP1, HIC1, PTEN and DcR1) showed frequency of hypermethylation in >28% of CCA, but not adjacent normal tissues. The results showed that 91% of CCA were methylated in at least one CpG-island. The OPCML was the most frequently methylated locus (72.5%) and was more frequently methylated in less differentiated CCA. Patients with methylated DcR1 had significantly longer overall survival (Median; 41.7 vs 21.7 weeks, P=0.027). Low-protein expression was found in >70% of CCA with methylation of OPCML or DcR1. Conclusion: Aberrant hypermethylation of certain loci is a common event in liver fluke-related CCA and may potentially contribute to cholangiocarcinogenesis. The OPCML and DcR1 might serve as methylation biomarkers in CCA that can be readily examined by MSP. PMID:21448164

Chloride concentrations in human hepatic cytosol and mitochondria are a function of age

PubMed Central

Jahn, Stephan C.; Rowland-Faux, Laura; Stacpoole, Peter W.; James, Margaret O.

2015-01-01

We recently reported that, in a concentration-dependent manner, chloride protects hepatic glutathione transferase zeta 1 from inactivation by dichloroacetate, an investigational drug used in treating various acquired and congenital metabolic diseases. Despite the importance of chloride ions in normal physiology, and decades of study of chloride transport across membranes, the literature lacks information on chloride concentrations in animal tissues other than blood. In this study we measured chloride concentrations in human liver samples from male and female donors aged 1 day to 84 years (n = 97). Because glutathione transferase zeta 1 is present in cytosol and, to a lesser extent, in mitochondria, we measured chloride in these fractions by high-performance liquid chromatography analysis following conversion of the free chloride to pentafluorobenzylchloride. We found that chloride concentration decreased with age in hepatic cytosol but increased in liver mitochondria. In addition, chloride concentrations in cytosol, (105.2 ± 62.4 mM; range: 24.7 – 365.7 mM) were strikingly higher than those in mitochondria (4.2 ± 3.8 mM; range 0.9 – 22.2 mM). These results suggest a possible explanation for clinical observations seen in patients treated with dichloroacetate, whereby children metabolize the drug more rapidly than adults following repeated doses, and also provide information that may influence our understanding of normal liver physiology. PMID:25748576

Chloride concentrations in human hepatic cytosol and mitochondria are a function of age.

PubMed

Jahn, Stephan C; Rowland-Faux, Laura; Stacpoole, Peter W; James, Margaret O

2015-04-10

We recently reported that, in a concentration-dependent manner, chloride protects hepatic glutathione transferase zeta 1 from inactivation by dichloroacetate, an investigational drug used in treating various acquired and congenital metabolic diseases. Despite the importance of chloride ions in normal physiology, and decades of study of chloride transport across membranes, the literature lacks information on chloride concentrations in animal tissues other than blood. In this study we measured chloride concentrations in human liver samples from male and female donors aged 1 day to 84 years (n = 97). Because glutathione transferase zeta 1 is present in cytosol and, to a lesser extent, in mitochondria, we measured chloride in these fractions by high-performance liquid chromatography analysis following conversion of the free chloride to pentafluorobenzylchloride. We found that chloride concentration decreased with age in hepatic cytosol but increased in liver mitochondria. In addition, chloride concentrations in cytosol, (105.2 ± 62.4 mM; range: 24.7-365.7 mM) were strikingly higher than those in mitochondria (4.2 ± 3.8 mM; range 0.9-22.2 mM). These results suggest a possible explanation for clinical observations seen in patients treated with dichloroacetate, whereby children metabolize the drug more rapidly than adults following repeated doses, and also provide information that may influence our understanding of normal liver physiology. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of diffusion time on liver DWI: an experimental study of normal and fibrotic livers.

PubMed

Zhou, Iris Y; Gao, Darwin S; Chow, April M; Fan, Shujuan; Cheung, Matthew M; Ling, Changchun; Liu, Xiaobing; Cao, Peng; Guo, Hua; Man, Kwan; Wu, Ed X

2014-11-01

To investigate whether diffusion time (Δ) affects the diffusion measurements in liver and their sensitivity in detecting fibrosis. Liver fibrosis was induced in Sprague-Dawley rats (n = 12) by carbon tetrachloride (CCl(4)) injections. Diffusion-weighted MRI was performed longitudinally during 8-week CCl(4) administration at 7 Tesla (T) using single-shot stimulated-echo EPI with five b-values (0 to 1000 s/mm(2)) and three Δs. Apparent diffusion coefficient (ADC) and true diffusion coefficient (D(true)) were calculated by using all five b-values and large b-values, respectively. ADC and D(true) decreased with Δ for both normal and fibrotic liver at each time point. ADC and D(true) also generally decreased with the time after CCl(4) insult. The reductions in D(true) between 2-week and 4-week CCl(4) insult were larger than the ADC reductions at all Δs. At each time point, D(true) measured with long Δ (200 ms) detected the largest changes among the 3 Δs examined. Histology revealed gradual collagen deposition and presence of intracellular fat vacuoles after CCl(4) insult. Our results demonstrated the Δ dependent diffusion measurements, indicating restricted diffusion in both normal and fibrotic liver. D(true) measured with long Δ acted as a more sensitive index of the pathological alterations in liver microstructure during fibrogenesis. Copyright © 2013 Wiley Periodicals, Inc.

Reproducibility of CT Perfusion Parameters in Liver Tumors and Normal Liver

PubMed Central

Ng, Chaan S.; Chandler, Adam G.; Wei, Wei; Herron, Delise H.; Anderson, Ella F.; Kurzrock, Razelle; Charnsangavej, Chusilp

2011-01-01

Purpose: To assess the reproducibility of computed tomographic (CT) perfusion measurements in liver tumors and normal liver and effects of motion and data acquisition time on parameters. Materials and Methods: Institutional review board approval and written informed consent were obtained for this prospective study. The study complied with HIPAA regulations. Two CT perfusion scans were obtained 2–7 days apart in seven patients with liver tumors with two scanning phases (phase 1: 30-second breath-hold cine; phase 2: six intermittent free-breathing cines) spanning 135 seconds. Blood flow (BF), blood volume (BV), mean transit time (MTT), and permeability–surface area product (PS) for tumors and normal liver were calculated from phase 1 with and without rigid registration and, for combined phases 1 and 2, with manually and rigid-registered phase 2 images, by using deconvolution modeling. Variability was assessed with within-patient coefficients of variation (CVs) and Bland-Altman analyses. Results: For tumors, BF, BV, MTT, and PS values and reproducibility varied by analytical method, the former by up to 11%, 23%, 21%, and 138%, respectively. Median PS values doubled with the addition of phase 2 data to phase 1 data. The best overall reproducibility was obtained with rigidly registered phase 1 and phase 2 images, with within-patient CVs for BF, BV, MTT, and PS of 11.2%, 14.4%, 5.5% and 12.1%, respectively. Normal liver evaluations were similar, except with marginally lower variability. Conclusion: Absolute values and reproducibility of CT perfusion parameters were markedly influenced by motion and data acquisition time. PS, in particular, probably requires data acquisition beyond a single breath hold, for which motion-correction techniques are likely necessary. © RSNA, 2011 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11110331/-/DC1 PMID:21788525

The value of different insulin resistance indices in assessment of non-alcoholic fatty liver disease in overweight/obese children.

PubMed

El-Karaksy, Hanaa M; El-Raziky, Mona S; Fouad, Hanan M; Anwar, Ghada M; El-Mougy, Fatma M; El-Koofy, Nehal M; El-Hennawy, Ahmad M

2015-01-01

The aim of the present study was to determine the association between insulin resistance (IR) and both non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) in a group of Egyptian overweight/obese children and adolescents and to evaluate different IR indices in detection of NAFLD. The study included 76 overweight/obese children aged 2-15 years; 52.6% were males. Laboratory analysis included fasting blood glucose, serum insulin, lipid profile, liver biochemical profile, and liver ultrasound. IR was calculated using the following indices; the homeostasis model assessment method (HOMA-IR), the quantitative insulin-sensitivity check index (QUICKI) and hepatic insulin sensitivity. The National Cholesterol Education Program Adult Treatment Panel III criteria were used to estimate prevalence of MetS. Liver biopsy was done when medically indicated and accepted by parents. IR was detected in 43.4% and 34.2% by using QUICKI and HOMA, respectively. MetS was detected in 36.8% and NAFLD was detected in 45.5% among those performing liver biopsy. Cases with NAFLD had more frequent IR than children with normal histology. QUICKI showed significant difference between normal subjects and both steatosis and non-alcoholic steatohepatitis; while HOMA-IR was sensitive in cases with NASH only. MetS was present in 100% of patients with NASH and in 75% of those with steatosis and they were all obese. Patients with NASH had significantly higher ALT than those with normal histology. IR was significantly associated with NAFLD. QUICKI is considered more sensitive than HOMA-IR in differentiating simple steatosis from normal liver histology. Copyright © 2013 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Serum endocan levels in patients with chronic liver disease

PubMed Central

Tok, Duran; Ekiz, Fuat; Basar, Omer; Coban, Sahin; Ozturk, Gulfer

2014-01-01

Background and Aim: Early detection of fibrosis should be the main goal of treatment in liver cirrhosis. Endocan, previously called endothelial cell specific molecule-1, is expressed by endothelial cells, primarily in the lung, liver and kidney. In this study, we aimed to examine the correlation of liver fibrosis stage, histological activity and grade of steatosis between serum levels of endocan in patients with chronic hepatitis B (CHB), chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). Patients and Methods: This cross-sectional study includes a total of 146 subjects. 55 CHB patients, 19 CHC patients, 38 NAFLD patients and 34 healthy controls were enrolled consecutively. Liver biopsies were performed in all patients with chronic viral hepatitis. NAFLD patients had either grade 2 or grade 3 steatosis on ultrasonography and elevated liver enzymes above the upper normal limits. Serum endocan levels were assessed from blood samples obtained at admission. Results: Gender distribution was similar among the groups (p=0.056). The mean age of the CHB patients was 45.8±12.1, CHC patients was 55.0±12.8 years, NAFLD patients was 42.8±10.8, while control group was 39.4±13.6 years old. Patients with CHC were older than all the others (p=0.001). Serum endocan levels were statistically significantly lower in CHB, CHC and NAFLD groups when compared with controls. Although levels of endocan were lower in CHB and CHC groups when compared with NAFLD group, the difference was not statistically significant. Conclusion: Serum endocan concentrations decrease in patients with liver disease. Unlike previous studies, we showed a negative correlation between endocan levels and inflammation stage of chronic hepatitis. However, further studies are needed to establish the association between endocan levels, liver fibrosis and hepatic inflammation. PMID:25126183

Physical activity as a protective factor for development of non-alcoholic fatty liver in men

PubMed Central

Pinto, Carla Giuliano de Sá; Marega, Marcio; de Carvalho, José Antonio Maluf; Carmona, Felipe Gambetta; Lopes, Carlos Eduardo Felix; Ceschini, Fabio Luis; Bocalini, Danilo Sales; Figueira, Aylton José

2015-01-01

Objective To determine the impact of physical activity on the prevalence of fatty liver, metabolic and cardiovascular disease in adult men. Methods This study evaluated 1,399 men (40.7±8.18 years) with body mass index of 26.7kg/m2 (±3.4) who participated in the Protocol of Preventive Health Check-up at Hospital Israelita Albert Einstein from January to October 2011. We conducted tests of serum blood glucose, total cholesterol, LDL, HDL, triglycerides, reactive c-protein, aspartate transaminase, alanine transaminase and gamma-glutamyl transpeptidase. The statistical analysis comprised in the comparison of mean and standard deviation. The analysis of variance was based in two paths of two way ANOVA, Student’s t-test, Mann Whitney U test, Wald test and χ2. We considered a significance level at p<0.05 and correlation of univariate Poison with 95% confidence interval. Results :Fatty liver was diagnosed in 37.0% of the sample. Triglyceride levels of active men with fatty liver were 148.2±77.6mg/dL while inactive men with fatty liver had 173.4±15.6mg/dL. The remaining serum levels were normal. Inactive individuals showed higher values than active. In addition, inactive individuals have 10.68 times higher risk of developing fatty liver compared with active. Conclusion Physical activity improves metabolic parameters such as triglycerides, weight control, HDL, which interfere in the development of fatty liver. Physically active individuals had lower fatty liver prevalence regardless of values of body composition and lipid profile, leading the conclusion that physical activity has a protective role against development of fatty liver. PMID:25993066

Morphology and morphometry of fetal liver at 16-26 weeks of gestation by magnetic resonance imaging: Comparison with embryonic liver at Carnegie stage 23.

PubMed

Hamabe, Yui; Hirose, Ayumi; Yamada, Shigehito; Uwabe, Chigako; Okada, Tomohisa; Togashi, Kaori; Kose, Katsumi; Takakuwa, Tetsuya

2013-06-01

Normal liver growth was described morphologically and morphometrically using magnetic resonance imaging (MRI) data of human fetuses, and compared with embryonic liver to establish a normal reference chart for clinical use. MRI images from 21 fetuses at 16-26 weeks of gestation and eight embryos at Carnegie stage (CS)23 were investigated in the present study. Using the image data, the morphology of the liver as well as its adjacent organs was extracted and reconstructed three-dimensionally. Morphometry of fetal liver growth was performed using simple regression analysis. The fundamental morphology was similar in all cases of the fetal livers examined. The liver tended to grow along the transversal axis. The four lobes were clearly recognizable in the fetal liver but not in the embryonic liver. The length of the liver along the three axes, liver volume and four lobes correlated with the bodyweight (BW). The morphogenesis of the fetal liver on the dorsal and caudal sides was affected by the growth of the abdominal organs, such as the stomach, duodenum and spleen, and retroperitoneal organs, such as the right adrenal gland and right kidney. The main blood vessels such as inferior vena cava, portal vein and umbilical vein made a groove on the surface of the liver. Morphology of the fetal liver was different from that of the embryonic liver at CS23. The present data will be useful for evaluating the development of the fetal liver and the adjacent organs that affect its morphology. © 2012 The Japan Society of Hepatology.

Hippo pathway coactivators Yap and Taz are required to coordinate mammalian liver regeneration

PubMed Central

Lu, Li; Finegold, Milton J; Johnson, Randy L

2018-01-01

The mammalian liver has a remarkable capacity for repair following injury. Removal of up to two-third of liver mass results in a series of events that include extracellular matrix remodeling, coordinated hepatic cell cycle re-entry, restoration of liver mass and tissue remodeling to return the damaged liver to its normal state. Although there has been considerable advancement of our knowledge concerning the regenerative capacity of the mammalian liver, many outstanding questions remaining, such as: how does the regenerating liver stop proliferating when appropriate mass is restored and how do these mechanisms relate to normal regulation of organ size during development? Hippo pathway has been proposed to be central in mediating both events: organ size control during development and following regeneration. In this report, we examined the role of Yap and Taz, key components of the Hippo pathway in liver organ size regulation, both in the context of development and homeostasis. Our studies reveal that contrary to the current paradigms that Yap/Taz are not required for developmental regulation of liver size but are required for proper liver regeneration. In livers depleted of Yap and Taz, liver mass is elevated in neonates and adults. However, Yap/Taz-depleted livers exhibit profound defects in liver regeneration, including an inability to restore liver mass and to properly coordinate cell cycle entry. Taken together, our results highlight requirements for the Hippo pathway during liver regeneration and indicate that there are additional pathways that cooperate with Hippo signaling to control liver size during development and in the adult. PMID:29303509

Application of Cox model in coagulation function in patients with primary liver cancer.

PubMed

Guo, Xuan; Chen, Mingwei; Ding, Li; Zhao, Shan; Wang, Yuefei; Kang, Qinjiong; Liu, Yi

2011-01-01

To analyze the distribution of coagulation parameters in patients with primary liver cancer; explore the relationship between clinical staging, survival, and coagulation parameters by using Coxproportional hazard model; and provide a parameter for clinical management and prognosis. Coagulation parameters were evaluated in 228 patients with primary liver cancer, 52 patients with common liver disease, and 52 normal healthy controls. The relationship between primary livercancer staging and coagulation parameters wasanalyzed. Follow-up examinations were performed. The Cox proportional hazard model was used to analyze the relationship between coagulationparameters and survival. The changes in the coagulation parameters in patients with primary liver cancer were significantly different from those in normal controls. The effect of the disease on coagulation function became more obvious as the severity of liver cancer increased (p<0.05). The levels of D-dimer, fibrinogen degradation products (FDP), fibrinogen (FIB), and platelets (PLT) were negatively correlated with the long-term survival of patients with advanced liver cancer. The stages of primary liver cancer are associated with coagulation parameters. Coagulation parameters are related to survival and risk factors. Monitoring of coagulation parameters may help ensure better surveillance and treatment for liver cancer patients.

Liver Gene Expression Profiles of Rats Treated with Clofibric Acid

PubMed Central

Michel, Cécile; Desdouets, Chantal; Sacre-Salem, Béatrice; Gautier, Jean-Charles; Roberts, Ruth; Boitier, Eric

2003-01-01

Clofibric acid (CLO) is a peroxisome proliferator (PP) that acts through the peroxisome proliferator activated receptor α, leading to hepatocarcinogenesis in rodents. CLO-induced hepatocarcinogenesis is a multi-step process, first transforming normal liver cells into foci. The combination of laser capture microdissection (LCM) and genomics has the potential to provide expression profiles from such small cell clusters, giving an opportunity to understand the process of cancer development in response to PPs. To our knowledge, this is the first evaluation of the impact of the successive steps of LCM procedure on gene expression profiling by comparing profiles from LCM samples to those obtained with non-microdissected liver samples collected after a 1 month CLO treatment in the rat. We showed that hematoxylin and eosin (H&E) staining and laser microdissection itself do not impact on RNA quality. However, the overall process of the LCM procedure affects the RNA quality, resulting in a bias in the gene profiles. Nonetheless, this bias did not prevent accurate determination of a CLO-specific molecular signature. Thus, gene-profiling analysis of microdissected foci, identified by H&E staining may provide insight into the mechanisms underlying non-genotoxic hepatocarcinogenesis in the rat by allowing identification of specific genes that are regulated by CLO in early pre-neoplastic foci. PMID:14633594

Copper deficiency in Tule Elk at Point Reyes, California

USGS Publications Warehouse

Gogan, Peter J.P.; Jessup, David A.; Akeson, Mark

1989-01-01

Tule elk (Cervus elaphus nannodes) reintroduced to Point Reyes, Calif., in 1978 exhibited gross signs of copper deficiency by June 1979. Copper levels in liver (x=5.9 ppm) and serum (0.42 ppm) of elk in Point Reyes were below levels in adult tule elk from other locations in California (liver, x=80 ppm; serum, x=1.4 ppm). These levels were consistent with documented copper deficiencies in wild and domestic ruminants. Copper serum levels increased in response to copper enriched dietary supplements and declined after the elk stopped eating the supplements. Analysis of plant and soil samples showed both are deficient in copper and normal in molybdenum and sulfur-sulfates. Deficiency in plants and soils at Point Reyes are probably due to low copper levels in the underlying granitic parent material.

Differential expression of colon cancer associated transcript1 (CCAT1) along the colonic adenoma-carcinoma sequence.

PubMed

Alaiyan, Bilal; Ilyayev, Nadia; Stojadinovic, Alexander; Izadjoo, Mina; Roistacher, Marina; Pavlov, Vera; Tzivin, Victoria; Halle, David; Pan, Honguang; Trink, Barry; Gure, Ali O; Nissan, Aviram

2013-04-17

The transition from normal epithelium to adenoma and, to invasive carcinoma in the human colon is associated with acquired molecular events taking 5-10 years for malignant transformation. We discovered CCAT1, a non-coding RNA over-expressed in colon cancer (CC), but not in normal tissues, thereby making it a potential disease-specific biomarker. We aimed to define and validate CCAT1 as a CC-specific biomarker, and to study CCAT1 expression across the adenoma-carcinoma sequence of CC tumorigenesis. Tissue samples were obtained from patients undergoing resection for colonic adenoma(s) or carcinoma. Normal colonic tissue (n = 10), adenomatous polyps (n = 18), primary tumor tissue (n = 22), normal mucosa adjacent to primary tumor (n = 16), and lymph node(s) (n = 20), liver (n = 8), and peritoneal metastases (n = 19) were studied. RNA was extracted from all tissue samples, and CCAT1 expression was analyzed using quantitative real time-PCR (qRT-PCR) with confirmatory in-situ hybridization (ISH). Borderline expression of CCAT1 was identified in normal tissue obtained from patients with benign conditions [mean Relative Quantity (RQ) = 5.9]. Significant relative CCAT1 up-regulation was observed in adenomatous polyps (RQ = 178.6 ± 157.0; p = 0.0012); primary tumor tissue (RQ = 64.9 ± 56.9; p = 0.0048); normal mucosa adjacent to primary tumor (RQ = 17.7 ± 21.5; p = 0.09); lymph node, liver and peritoneal metastases (RQ = 11,414.5 ± 12,672.9; 119.2 ± 138.9; 816.3 ± 2,736.1; p = 0.0001, respectively). qRT-PCR results were confirmed by ISH, demonstrating significant correlation between CCAT1 up-regulation measured using these two methods. CCAT1 is up-regulated across the colon adenoma-carcinoma sequence. This up-regulation is evident in pre-malignant conditions and through all disease stages, including advanced metastatic disease suggesting a role in both tumorigenesis and the metastatic process.

Whole-exome sequencing reveals LRP5 mutations and canonical Wnt signaling associated with hepatic cystogenesis

PubMed Central

Cnossen, Wybrich R.; te Morsche, René H. M.; Hoischen, Alexander; Gilissen, Christian; Chrispijn, Melissa; Venselaar, Hanka; Mehdi, Soufi; Bergmann, Carsten; Veltman, Joris A.; Drenth, Joost P. H.

2014-01-01

Polycystic livers are seen in the rare inherited disorder isolated polycystic liver disease (PCLD) and are recognized as the most common extrarenal manifestation in autosomal dominant polycystic kidney disease. Hepatic cystogenesis is characterized by progressive proliferation of cholangiocytes, ultimately causing hepatomegaly. Genetically, polycystic liver disease is a heterogeneous disorder with incomplete penetrance and caused by mutations in PRKCSH, SEC63, PKD1, or PKD2. Genome-wide SNP typing and Sanger sequencing revealed no pathogenic variants in hitherto genes in an extended PCLD family. We performed whole-exome sequencing of DNA samples from two members. A heterozygous variant c.3562C > T located at a highly conserved amino acid position (p.R1188W) in the low density lipoprotein receptor-related protein 5 (LRP5) gene segregated with the disease (logarithm of odds score, 4.62) but was not observed in more than 1,000 unaffected individuals. Screening of LRP5 in a PCLD cohort identified three additional mutations in three unrelated families with polycystic livers (p.V454M, p.R1529S, and p.D1551N), again all undetected in controls. All variants were predicted to be damaging with profound structural effects on LRP5 protein domains. Liver cyst tissue and normal hepatic tissue samples from patients and controls showed abundant LRP5 expression by immunohistochemistry. Functional activity analyses indicated that mutant LRP5 led to reduced wingless signal activation. In conclusion, we demonstrate that germ-line LRP5 missense mutations are associated with hepatic cystogenesis. The findings presented in this study link the pathophysiology of PCLD to deregulation of the canonical wingless signaling pathway. PMID:24706814

Upregulation of High Mobility Group Box 1 May Contribute to the Pathogenesis of Biliary Atresia.

PubMed

Ye, Chun Jing; Wang, Jiang; Yang, Yi Fan; Shen, Zhen; Chen, Gong; Huang, Yan Lei; Zheng, Yi Jie; Dong, Rui; Zheng, Shan

2018-06-17

 Biliary atresia (BA) is a progressive inflammatory obstructive cholangiopathy in infants. High mobility group box 1 (HMGB1) is known to play an important role as a late mediator of inflammation. However, it is not clear whether HMGB1 levels are of clinical significance in patients with BA. The aim of this study was to determine correlations between serum HMGB1 levels and the clinicopathologic features of BA.  Serum samples were collected from 19 infants with BA, 7 infants with anicteric choledochal cysts (CC) and normal liver function, and 8 healthy controls. Serum HMGB1 levels were measured with an enzyme-linked immunosorbent assay. Routine liver function tests were performed on serum samples. Quantitative real-time polymerase chain reaction and western blot analyses were used to detect HMGB1 expression in BA liver biopsy tissues. Localization of HMGB1 expression in the hepatic lobule was determined by immunohistochemical analysis.  HMGB1 levels in serum collected from BA infants were significantly elevated compared with CC and healthy control patients. Furthermore, elevated serum levels of HMGB1 in BA infants positively correlated with gamma-glutamyl transferase levels. HMGB1 messenger ribonucleic acid and protein expression levels were upregulated in BA liver biopsy tissues compared with CC patients. Immunohistochemical analysis also revealed increased positive immunostaining for HMGB1 in BA liver tissues as compared with CC tissues.  HMGB1 may play a crucial role in the pathogenesis of BA. Additionally, the correlation of serum HMGB1 levels with gamma-glutamyl transferase levels may provide a novel marker for the diagnosis of BA. Georg Thieme Verlag KG Stuttgart · New York.

Choline-Deficient-Diet-Induced Fatty Liver Is a Metastasis-Resistant Microenvironment.

PubMed

Nakamura, Miki; Suetsugu, Atsushi; Hasegawa, Kosuke; Matsumoto, Takuro; Aoki, Hitomi; Kunisada, Takahiro; Shimizu, Masahito; Saji, Shigetoyo; Moriwaki, Hisataka; Hoffman, Robert M

2017-07-01

Fatty liver disease is increasing in the developed and developing world. Liver metastasis from malignant lymphoma in the fatty liver is poorly understood. In a previous report, we developed color-coded imaging of the tumor microenvironment (TME) of the murine EL4-RFP malignant lymphoma during metastasis, including the lung. In the present report, we investigated the potential and microenvironment of the fatty liver induced by a choline-deficient diet as a metastatic site in this mouse lymphoma model. C57BL/6-GFP transgenic mice were fed with a choline-deficient diet in order to establish a fatty liver model. EL4-RFP cells were injected in the spleen of normal mice and fatty-liver mice. Metastases in mice with fatty liver or normal liver were imaged with the Olympus SZX7 microscope and the Olympus FV1000 confocal microscope. Metastases of EL4-RFP were observed in the liver, ascites and bone marrow. Primary tumors were imaged in the spleen at the injection site. The fewest metastases were observed in the fatty liver. In addition, the fewest cancer-associated fibroblasts (CAFs) were observed in the fatty liver. The relative metastatic resistance of the fatty liver may be due to the reduced number of CAFs in the fatty livers. The mechanism of the effect of the choline-deficient diet is discussed. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Modeled Perfluorooctanoic Acid (PFOA) Exposure and Liver Function in a Mid-Ohio Valley Community.

PubMed

Darrow, Lyndsey A; Groth, Alyx C; Winquist, Andrea; Shin, Hyeong-Moo; Bartell, Scott M; Steenland, Kyle

2016-08-01

Perfluorooctanoic acid (PFOA or C8) has hepatotoxic effects in animals. Cross-sectional epidemiologic studies suggest PFOA is associated with liver injury biomarkers. We estimated associations between modeled historical PFOA exposures and liver injury biomarkers and medically validated liver disease. Participants completed surveys during 2008-2011 reporting demographic, medical, and residential history information. Self-reported liver disease, including hepatitis, fatty liver, enlarged liver and cirrhosis, was validated with healthcare providers. Alanine aminotransferase (ALT), γ-glutamyltransferase (GGT) and direct bilirubin, markers of liver toxicity, were obtained from blood samples collected in the C8 Health Project (2005-2006). Historically modeled PFOA exposure, estimated using environmental fate and transport models and participant residential histories, was analyzed in relation to liver biomarkers (n = 30,723, including 1,892 workers) and liver disease (n = 32,254, including 3,713 workers). Modeled cumulative serum PFOA was positively associated with ALT levels (p for trend < 0.0001), indicating possible liver toxicity. An increase from the first to the fifth quintile of cumulative PFOA exposure was associated with a 6% increase in ALT levels (95% CI: 4, 8%) and a 16% increased odds of having above-normal ALT (95% CI: odds ratio: 1.02, 1.33%). There was no indication of association with either elevated direct bilirubin or GGT; however, PFOA was associated with decreased direct bilirubin. We observed no evidence of an effect of cumulative exposure (with or without a 10-year lag) on all liver disease (n = 647 cases), nor on enlarged liver, fatty liver, and cirrhosis only (n = 427 cases). Results are consistent with previous cross-sectional studies showing association between PFOA and ALT, a marker of hepatocellular damage. We did not observe evidence that PFOA increases the risk of clinically diagnosed liver disease. Darrow LA, Groth AC, Winquist A, Shin HM, Bartell SM, Steenland K. 2016. Modeled perfluorooctanoic acid (PFOA) exposure and liver function in a Mid-Ohio Valley community. Environ Health Perspect 124:1227-1233; http://dx.doi.org/10.1289/ehp.1510391.

Upregulation of 14-3-3 eta in chronic liver fluke infection is a potential diagnostic marker of cholangiocarcinoma.

PubMed

Haonon, Ornuma; Rucksaken, Rucksak; Pinlaor, Porntip; Pairojkul, Chawalit; Chamgramol, Yaovalux; Intuyod, Kitti; Onsurathum, Sudarat; Khuntikeo, Narong; Pinlaor, Somchai

2016-03-01

To discover protein markers in chronic/advanced opisthorchiasis for the early detection of Opisthorchis viverrini (OV)-associated cholangiocarcinoma (CCA). Liver tissues derived from normal hamsters and those with chronic/advanced opisthorchiasis (n = 5 per group) were subjected to 2DE and LC-MS/MS. Candidate protein expression was confirmed in hamster models and human CCA tissue microarray (TMA) using immunohistochemistry and Western blot. Proteomics analysis detected 14-3-3 eta only in infected hamsters, not in uninfected controls. Immunohistochemistry and Western blot analysis confirmed low expression of 14-3-3 eta in normal hamster livers and demonstrated increased expression through time in infected livers. This protein was also observed in parasite organs, especially during the chronic phase of opisthorchiasis. Moreover, increased expression of 14-3-3 eta, relative to normal hamster livers, was observed during the early stage of CCA induced by OV infection and administration of N-nitrosodimethylamine. Immunohistochemical analysis of human TMA revealed that 14-3-3 eta was highly expressed in CCA (84.23%, 187/222 cases) but was not found in hepatocellular carcinoma or healthy liver tissues. 14-3-3 eta protein has potential as a screening and early diagnostic marker for CCA. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Risk assessment of silica nanoparticles on liver injury in metabolic syndrome mice induced by fructose.

PubMed

Li, Jianmei; He, Xiwei; Yang, Yang; Li, Mei; Xu, Chenke; Yu, Rong

2018-07-01

This study aims to assess the effects and the mechanisms of silica nanoparticles (SiNPs) on hepatotoxicity in both normal and metabolic syndrome mouse models induced by fructose. Here, we found that SiNPs exposure lead to improved insulin resistance in metabolic syndrome mice, but markedly worsened hepatic ballooning, inflammation infiltration, and fibrosis. Moreover, SiNPs exposure aggravated liver injury in metabolic syndrome mice by causing serious DNA damage. Following SiNPs exposure, liver superoxide dismutase and catalase activities in metabolic syndrome mice were stimulated, which is accompanied by significantly increased malondialdehyde and 8-hydroxy-2-deoxyguanosine levels as compared to normal mice. Scanning electron microscope (SEM) revealed that SiNPs were more readily deposited in the liver mitochondria of metabolic syndrome mice, resulting in more severe mitochondrial injury as compared to normal mice. We speculated that SiNPs-induced mitochondrial injury might be the cause of hepatic oxidative stress, which further lead to a series of liver lesions as observed in mice following SiNPs exposure. Based on these results, it is likely that SiNPs will increase the risk and severity of liver disease in individuals with metabolic syndrome. Therefore, SiNPs should be used cautiously in food additives and clinical settings. Copyright © 2018 Elsevier B.V. All rights reserved.

Hyperspectral Stimulated Raman Scattering Microscopy Unravels Aberrant Accumulation of Saturated Fat in Human Liver Cancer.

PubMed

Yan, Shuai; Cui, Sishan; Ke, Kun; Zhao, Bixing; Liu, Xiaolong; Yue, Shuhua; Wang, Ping

2018-06-05

Lipid metabolism is dysregulated in human cancers. The analytical tools that could identify and quantitatively map metabolites in unprocessed human tissues with submicrometer resolution are highly desired. Here, we implemented analytical hyperspectral stimulated Raman scattering microscopy to map the lipid metabolites in situ in normal and cancerous liver tissues from 24 patients. In contrast to the conventional wisdom that unsaturated lipid accumulation enhances tumor cell survival and proliferation, we unexpectedly visualized substantial amount of saturated fat accumulated in cancerous liver tissues, which was not seen in majority of their adjacent normal tissues. Further analysis by mass spectrometry confirmed significant high levels of glyceryl tripalmitate specifically in cancerous liver. These findings suggest that the aberrantly accumulated saturated fat may have great potential to be a metabolic biomarker for liver cancer.

Effects of tocotrienols on cell viability and apoptosis in normal murine liver cells (BNL CL.2) and liver cancer cells (BNL 1ME A.7R.1), in vitro.

PubMed

Har, Chan Hooi; Keong, Chan Kok

2005-01-01

The effects of tocotrienols on murine liver cell viability and their apoptotic events were studied over a dose range of 0-32 microg mL(-1). Normal murine liver cells (BNL CL.2) and murine liver cancer cells (BNL 1ME A.7R.1) were treated with tocotrienols (T(3)), alpha tocopherol (alpha-T) and the chemo drug, Doxorubicin (Doxo, as a positive control). Cell viability assay showed that T(3) significantly (P < or = 0.05) lowered the percentage of BNL 1ME A.7R.1 cell viability in a dose-responsive manner (8-16 microg mL(-1)), whereas T did not show any significant (P>0.05) inhibition in cell viability with increasing treatment doses of 0-16 microg mL(-1). The IC(50) for tocotrienols were 9.8, 8.9, 8.1, 9.7, 8.1 and 9.3 microg mL(-1) at 12, 24, 36, 48, 60 and 72 hours respectively. Early apoptosis was detected 6 hours following T(3) treatment of BNL 1ME A.7R.1 liver cancer cells, using Annexin V-FITC fluorescence microscopy assay for apoptosis, but none were observed for the non-treated liver cancer cells at the average IC(50) of 8.98 microg mL(-1) tocotrienols for liver cancer cells. Several apoptotic bodies were detected in BNL 1ME A.7R.1 liver cancer cells at 6 hours post-treatment with tocotrienols (8.98 microg mL(-1)) using Acridine Orange/Propidium Iodide fluorescence assay. However, only a couple of apoptotic bodies were seen in the non-treated liver cancer cells and the BNL CL.2 normal liver cells. Some mitotic bodies were also observed in the T(3)-treated BNL 1ME A.7R.1 liver cancer cells but were not seen in the untreated BNL 1ME A.7R.1 cells and the BNL CL.2 liver cells. Following T(3)-treatment (8.98 microg mL(-1)) of the BNL 1ME A.7R.1 liver cancer cells, 24.62%, 25.53% and 44.90% of the cells showed elevated active caspase 3 activity at 9, 12 and 24 hours treatment period, respectively. DNA laddering studies indicated DNA fragmentation occurred in the T(3)-treated liver cancer cells, BNL 1ME A.7R.1 but not in non-treated liver cancer cells and the T(3)-treated and non-treated normal liver cells. These results suggest that tocotrienols were able to reduce the cell viability in the murine liver cancer cells at a dose of 8-32 microg mL(-1) and that this decrease in percentage cell viability may be due to apoptosis.

An effective assessment of valproate sodium-induced hepatotoxicity with UPLC-MS and (1)HNMR-based metabonomics approach.

PubMed

Huo, Taoguang; Chen, Xi; Lu, Xiumei; Qu, Lianyue; Liu, Yang; Cai, Shuang

2014-10-15

Valproate sodium is one of the most prescribed antiepileptic drugs. However, valproate sodium has various side effects, especially its toxicity on liver. Current markers for toxicity reflect mostly the late stages of tissue damage; thus, more efficient methods for toxicity evaluation are desired. To evaluate the toxicity of valproate sodium on liver, we performed both UPLC-MS and (1)HNMR-based metabonomics analysis of serum samples from 34 epileptic patients (age: 42.0±18.6, 18 male/16 female) after valproate sodium treatment. Compared to conventional markers, the serum metabolic profiles provided clear distinction of the valproate sodium induced normal liver function and abnormal liver function in epileptic patients. Through multivariate statistical analysis, we identified marker metabolites associated with the hepatotoxicity induced by valproate sodium, such as glucose, lactate, acetoacetate, VLDL/LDL, lysophosphatidylcholines, phosphatidylcholines, choline, creatine, amino acids, N-acetyl glycoprotein, pyruvate and uric acid. This metabonomics approach may provide effective way to evaluate the valproate sodium-induced toxicity in a manner that can complement current measures. This approach is expected to find broader application in other drug-induced toxicity assessment. Copyright © 2014 Elsevier B.V. All rights reserved.

Effects of terlipressin on systolic pulmonary artery pressure of patients with liver cirrhosis: An echocardiographic assessment

PubMed Central

Altintas, Engin; Akkus, Necdet; Gen, Ramazan; Helvaci, M. Rami; Sezgin, Orhan; Oguz, Dilek

2004-01-01

AIM: Portopulmonary hypertension is a serious complication of chronic liver disease. Our aim was to search into the effect of terlipressin on systolic pulmonary artery pressure among cirrhotic patients. METHODS: Twelve patients (6 males and 6 females) with liver cirrhosis were recruited in the study. Arterial blood gas samples were obtained in sitting position at rest. Contrast enhanced echocardiography and measurements of systolic pulmonary artery pressure were performed before and after the intravenous injection of 2 mg terlipressin. RESULTS: Of 12 patients studied, the contrast enhanced echocardiography was positive in 5, and the positive findings in contrast enhanced echocardiography were reversed to normal in two after terlipressin injection. The mean systolic pulmonary artery pressure was 25.5 ± 3.6 mmHg before terlipressin injection, and was 22.5 ± 2.5 mmHg after terlipressin (P = 0.003). The systolic pulmonary artery pressure was above 25 mmHg in seven of these 12 patients. After the terlipressin injection, systolic pulmonary artery pressure was < 25 mmHg in four of these cases (58.3% vs 25%, P = 0.04). CONCLUSION: Terlipressin can decrease the systolic pulmonary artery pressure in patients with liver cirrhosis. PMID:15259082

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gomori, J.M.; Horev, G.; Tamary, H.

Iron deposits demonstrate characteristically shortened T2 relaxation times. Several previously published studies reported poor correlation between the in vivo hepatic 1/T2 measurements made by means of midfield magnetic resonance (MR) units and the hepatic iron content of iron-overloaded patients. In this study, the authors assessed the use of in vivo 1/T2 measurements obtained by means of MR imaging at 0.5 T using short echo times (13.4 and 30 msec) and single-echo-sequences as well as computed tomographic (CT) attenuation as a measure of liver iron concentration in 10 severely iron-overloaded patients with beta-thalassemia major. The iron concentrations in surgical wedge biopsymore » samples of the liver, which varied between 3 and 9 mg/g of wet weight (normal, less than or equal to 0.5 mg/g), correlated well (r = .93, P less than or equal to .0001) with the preoperative in vivo hepatic 1/T2 measurements. The CT attenuation did not correlate with liver iron concentration. Quantitative MR imaging is a readily available noninvasive method for the assessment of hepatic iron concentration in iron-overloaded patients, reducing the need for needle biopsies of the liver.« less

Plasma disappearance of exogenous erythropoietin in mice under different experimental conditions.

PubMed

Lezón, C E; Martínez, M P; Conti, M I; Bozzini, C E

1998-06-01

Erythropoietin (EPO) is a glycoprotein hormone produced primarily in the kidneys and to a lesser extent in the liver that regulates red cell production. Most of the studies conducted in experimental animals to assess the role of EPO in the regulation of erythropoiesis were performed in mouse models. However, little is known about the in vivo metabolism of the hormone in this species. The present study was thus undertaken to measure the plasma tl/2 of radiolabeled recombinant human EPO (rh-EPO) in normal mice as well as in mice with altered erythrocyte production rates (EPR), plasma EPO (pEPO) titer, marrow responsiveness, red cell volume, or liver function. Adult CF-1 mice of both sexes were used throughout. For the EPO life-span studies, 30 mice in each experiment were intravenously injected with 600,000 cpm of 125l-rh-EPO and bled by cardiac puncture in groups of five every hour for 6 h. Trichloroacetic acid (TCA) was added to each plasma sample and the radioactivity in the precipitate measured in a gamma-counter. EPO, pEPO, marrow responsiveness, or red cell volume were altered by either injections of rh-EPO, 5-fluorouracil, or phenylhydrazine, or by bleeding, or red cell transfusion. Liver function was altered by CI4C administration. In the normal groups of mice, the estimated tl/2 was 182.75+/-14.4 (SEM) min. The estimated tl/2 of the other experimental groups was not significantly different from normal. These results, therefore, strongly suggest that the clearance rate of EPO in mice is not subjected to physiologic regulation and that pEPO titer can be really taken as the reflection of the EPO production rate, at least in the experimental conditions reported here.

Comprehensive analyses of imprinted differentially methylated regions reveal epigenetic and genetic characteristics in hepatoblastoma

PubMed Central

2013-01-01

Background Aberrant methylation at imprinted differentially methylated regions (DMRs) in human 11p15.5 has been reported in many tumors including hepatoblastoma. However, the methylation status of imprinted DMRs in imprinted loci scattered through the human genome has not been analyzed yet in any tumors. Methods The methylation statuses of 33 imprinted DMRs were analyzed in 12 hepatoblastomas and adjacent normal liver tissue by MALDI-TOF MS and pyrosequencing. Uniparental disomy (UPD) and copy number abnormalities were investigated with DNA polymorphisms. Results Among 33 DMRs analyzed, 18 showed aberrant methylation in at least 1 tumor. There was large deviation in the incidence of aberrant methylation among the DMRs. KvDMR1 and IGF2-DMR0 were the most frequently hypomethylated DMRs. INPP5Fv2-DMR and RB1-DMR were hypermethylated with high frequencies. Hypomethylation was observed at certain DMRs not only in tumors but also in a small number of adjacent histologically normal liver tissue, whereas hypermethylation was observed only in tumor samples. The methylation levels of long interspersed nuclear element-1 (LINE-1) did not show large differences between tumor tissue and normal liver controls. Chromosomal abnormalities were also found in some tumors. 11p15.5 and 20q13.3 loci showed the frequent occurrence of both genetic and epigenetic alterations. Conclusions Our analyses revealed tumor-specific aberrant hypermethylation at some imprinted DMRs in 12 hepatoblastomas with additional suggestion for the possibility of hypomethylation prior to tumor development. Some loci showed both genetic and epigenetic alterations with high frequencies. These findings will aid in understanding the development of hepatoblastoma. PMID:24373183

MicroRNAs associated with small bowel neuroendocrine tumours and their metastases.

PubMed

Miller, Helen C; Frampton, Adam E; Malczewska, Anna; Ottaviani, Silvia; Stronach, Euan A; Flora, Rashpal; Kaemmerer, Daniel; Schwach, Gert; Pfragner, Roswitha; Faiz, Omar; Kos-Kudła, Beata; Hanna, George B; Stebbing, Justin; Castellano, Leandro; Frilling, Andrea

2016-09-01

Novel molecular analytes are needed in small bowel neuroendocrine tumours (SBNETs) to better determine disease aggressiveness and predict treatment response. In this study, we aimed to profile the global miRNome of SBNETs, and identify microRNAs (miRNAs) involved in tumour progression for use as potential biomarkers. Two independent miRNA profiling experiments were performed (n=90), including primary SBNETs (n=28), adjacent normal small bowel (NSB; n=14), matched lymph node (LN) metastases (n=24), normal LNs (n=7), normal liver (n=2) and liver metastases (n=15). We then evaluated potentially targeted genes by performing integrated computational analyses. We discovered 39 miRNAs significantly deregulated in SBNETs compared with adjacent NSB. The most upregulated (miR-204-5p, miR-7-5p and miR-375) were confirmed by qRT-PCR. Two miRNAs (miR-1 and miR-143-3p) were significantly downregulated in LN and liver metastases compared with primary tumours. Furthermore, we identified upregulated gene targets for miR-1 and miR-143-3p in an existing SBNET dataset, which could contribute to disease progression, and show that these miRNAs directly regulate FOSB and NUAK2 oncogenes. Our study represents the largest global miRNA profiling of SBNETs using matched primary tumour and metastatic samples. We revealed novel miRNAs deregulated during SBNET disease progression, and important miRNA-mRNA interactions. These miRNAs have the potential to act as biomarkers for patient stratification and may also be able to guide treatment decisions. Further experiments to define molecular mechanisms and validate these miRNAs in larger tissue cohorts and in biofluids are now warranted. © 2016 Society for Endocrinology.

Psychometrics of chronic liver disease questionnaire in Chinese chronic hepatitis B patients

PubMed Central

Zhou, Kai-Na; Zhang, Min; Wu, Qian; Ji, Zhen-Hao; Zhang, Xiao-Mei; Zhuang, Gui-Hua

2013-01-01

AIM: To evaluate psychometrics of the Chinese (mainland) chronic liver disease questionnaire (CLDQ) in patients with chronic hepatitis B (CHB). METHODS: A cross-sectional sample of 460 Chinese patients with CHB was selected from the Outpatient Department of the Eighth Hospital of Xi’an, including CHB (CHB without cirrhosis) (n = 323) and CHB-related cirrhosis (n = 137). The psychometrics includes reliability, validity and sensitivity. Internal consistency reliability was measured using Cronbach’s α. Convergent and discriminant validity was evaluated by item-scale correlation. Factorial validity was explored by principal component analysis with varimax rotation. Sensitivity was assessed using Cohen’s effect size (ES), and independent sample t test between CHB and CHB-related cirrhosis groups and between alanine aminotransferase (ALT) normal and abnormal groups after stratifying the disease (CHB and CHB-related cirrhosis). RESULTS: Internal consistency reliability of the CLDQ was 0.83 (range: 0.65-0.90). Most of the hypothesized item-scale correlations were 0.40 or over, and all of such hypothesized correlations were higher than the alternative ones, indicating satisfactory convergent and discriminant validity. Six factors were extracted after varimax rotation from the 29 items of CLDQ. The eligible Cohen’s ES with statistically significant independent sample t test was found in the overall CLDQ and abdominal, systematic, activity scales (CHB vs CHB-related cirrhosis), and in the overall CLDQ and abdominal scale in the stratification of patients with CHB (ALT normal vs abnormal). CONCLUSION: The CLDQ has acceptable reliability, validity and sensitivity in Chinese (mainland) patients with CHB. PMID:23801844

The Genome Austria Tissue Bank (GATiB).

PubMed

Asslaber, M; Abuja, P M; Stark, K; Eder, J; Gottweis, H; Trauner, M; Samonigg, H; Mischinger, H J; Schippinger, W; Berghold, A; Denk, H; Zatloukal, K

2007-01-01

In the context of the Austrian Genome Program, a tissue bank is being established (Genome Austria Tissue Bank, GATiB) which is based on a collection of diseased and corresponding normal tissues representing a great variety of diseases at their natural frequency of occurrence from a non-selected Central European population of more than 700,000 patients. Major emphasis is put on annotation of archival tissue with comprehensive clinical data, including follow-up data. A specific IT infrastructure supports sample annotation, tracking of sample usage as well as sample and data storage. Innovative data protection tools were developed which prevent sample donor re-identification, particularly if detailed medical and genetic data are combined. For quality control of old archival tissues, new techniques were established to check RNA quality and antigen stability. Since 2003, GATiB has changed from a population-based tissue bank to a disease-focused biobank comprising major cancers such as colon, breast, liver, as well as metabolic liver diseases and organs affected by the metabolic syndrome. Prospectively collected tissues are associated with blood samples and detailed data on the sample donor's disease, lifestyle and environmental exposure, following standard operating procedures. Major emphasis is also placed on ethical, legal and social issues (ELSI) related to biobanks. A specific research project and an international advisory board ensure the proper embedding of GATiB in society and facilitate international networking. (c) 2007 S. Karger AG, Basel.

Assessment of biological effects of pollutants in a hyper eutrophic tropical water body, Lake Beira, Sri Lanka using multiple biomarker responses of resident fish, Nile tilapia (Oreochromis niloticus).

PubMed

Pathiratne, Asoka; Pathiratne, K A S; De Seram, P K C

2010-08-01

Biomarkers measured at the molecular and cellular level in fish have been proposed as sensitive "early warning" tools for biological effect measurements in environmental quality assessments. Lake Beira is a hypertrophic urban water body with a complex mixture of pollutants including polycyclic aromatic hydrocarbons (PAHs) and Microcystins. In this study, a suite of biomarker responses viz. biliary fluorescent aromatic compounds (FACs), hepatic ethoxyresorufin O-deethylase (EROD) and glutathione S-transferase (GST), brain and muscle cholinesterases (ChE), serum sorbitol dehydrogenase (SDH), and liver histology of Oreochromis niloticus, the dominant fish inhabiting this tropical Lake were evaluated to assess the pollution exposure and biological effects. Some fish sampled in the dry periods demonstrated prominent structural abnormalities in the liver and concomitant increase in serum SDH and reduction in hepatic GST activities in comparison to the control fish and the fish sampled in the rainy periods. The resident fish with apparently normal liver demonstrated induction of hepatic EROD and GST activities and increase in biliary FACs irrespective of the sampling period indicating bioavailability of PAHs. Muscle ChE activities of the resident fish were depressed significantly indicating exposure to anticholinesterase substances. The results revealed that fish populations residing in this Lake is under threat due to the pollution stress. Hepatic abnormalities in the fish may be mainly associated with the pollution stress due to recurrent exposure to PAHs and toxigenic Microcystis blooms in the Lake.

Quantitative implementation of the endogenous molecular-cellular network hypothesis in hepatocellular carcinoma.

PubMed

Wang, Gaowei; Zhu, Xiaomei; Gu, Jianren; Ao, Ping

2014-06-06

A quantitative hypothesis for cancer genesis and progression-the endogenous molecular-cellular network hypothesis, intended to include both genetic and epigenetic causes of cancer-has been proposed recently. Using this hypothesis, here we address the molecular basis for maintaining normal liver and hepatocellular carcinoma (HCC), and the potential strategy to cure or relieve HCC. First, we elaborate the basic assumptions of the hypothesis and establish a core working network of HCC according to the hypothesis. Second, we quantify the working network by a nonlinear dynamical system. We show that the working network reproduces the main known features of normal liver and HCC at both the modular and molecular levels. Lastly, the validated working network reveals that (i) specific positive feedback loops are responsible for the maintenance of normal liver and HCC; (ii) inhibiting proliferation and inflammation-related positive feedback loops and simultaneously inducing a liver-specific positive feedback loop is predicated as a potential strategy to cure or relieve HCC; and (iii) the genesis and regression of HCC are asymmetric. In light of the characteristic properties of the nonlinear dynamical system, we demonstrate that positive feedback loops must exist as a simple and general molecular basis for the maintenance of heritable phenotypes, such as normal liver and HCC, and regulating the positive feedback loops directly or indirectly provides potential strategies to cure or relieve HCC.

A comparison of liver sampling techniques in dogs.

PubMed

Kemp, S D; Zimmerman, K L; Panciera, D L; Monroe, W E; Leib, M S; Lanz, O I

2015-01-01

The liver sampling technique in dogs that consistently provides samples adequate for accurate histopathologic interpretation is not known. To compare histopathologic results of liver samples obtained by punch, cup, and 14 gauge needle to large wedge samples collected at necropsy. Seventy dogs undergoing necropsy. Prospective study. Liver specimens were obtained from the left lateral liver lobe with an 8 mm punch, a 5 mm cup, and a 14 gauge needle. After sample acquisition, two larger tissue samples were collected near the center of the left lateral lobe to be used as a histologic standard for comparison. Histopathologic features and numbers of portal triads in each sample were recorded. The mean number of portal triads obtained by each sampling method were 2.9 in needle samples, 3.4 in cup samples, 12 in punch samples, and 30.7 in the necropsy samples. The diagnoses in 66% of needle samples, 60% of cup samples, and 69% of punch samples were in agreement with the necropsy samples, and these proportions were not significantly different from each other. The corresponding kappa coefficients were 0.59 for needle biopsies, 0.52 for cup biopsies, and 0.62 for punch biopsies. The histopathologic interpretation of a liver sample in the dog is unlikely to vary if the liver biopsy specimen contains at least 3-12 portal triads. However, in comparison large necropsy samples, the accuracy of all tested methods was relatively low. Copyright © 2014 by the American College of Veterinary Internal Medicine.

Efficiency of herbal medicine Dai-kenchu-to on portal blood flow in rat models

PubMed Central

Muraoka, Izumi; Takatsuki, Mitsuhisa; Soyama, Akihiko; Yamaguchi, Izumi; Tanaka, Shiro; Tanaka, Takayuki; Kinoshita, Ayaka; Hara, Takanobu; Kuroki, Tamotsu; Eguchi, Susumu

2015-01-01

Introduction To clarify the influence of Dai-Kenchu-To (DKT) on portal blood flow (PBF), PBF was continuously measured with Doppler ultrasound. Methods Normal liver rats were divided into a DKT 90 mg/kg, DKT 270 mg/kg administered group, and control, while cirrhotic liver rats were divided into a DKT-LC 90 mg/kg administered group and Control-LC. The PBF was measured after the administration of either DKT or water for 60 min by laser Doppler flowmetry system. Results The PBF in the DKT 90 increased approximately 10 min after DKT was administrated, and elevated levels were maintained for approximately 10 min. A comparison of the increase in PBF by the calculating the area under the curve (AUC) revealed that flow was significantly higher in the DKT 90 compared to either the control or the DKT 270 (p < 0.05). The cirrhotic liver group showed stable PBF in both the DKT-LC and Control-LC. The AUC, revealed no significant difference between the DKT-LC and Control-LC. Discussion DKT induced an increase in PBF in normal livers; however, its effects were insufficient to increase PBF in the cirrhotic livers. No increase in the portal blood flow in the cirrhotic liver rats was probably the result of the cirrhotic liver, which had fibrotic change, and, therefore, may not have had sufficient compliance to accept the increasing blood flow volume from the intestinal tract. Conclusion We suggested DKT has the potential to protect the liver by increasing PBF when the liver has either normal or mild to moderate dysfunction. PMID:26155361

Standard value of ultrasound elastography using acoustic radiation force impulse imaging (ARFI) in healthy liver tissue of children and adolescents.

PubMed

Eiler, J; Kleinholdermann, U; Albers, D; Dahms, J; Hermann, F; Behrens, C; Luedemann, M; Klingmueller, V; Alzen, G F P

2012-10-01

Ultrasound elastography by acoustic radiation force impulse imaging (ARFI) is used in adults for non invasive measurement of liver stiffness, indicating liver diseases like fibrosis. To establish ARFI in children and adolescents we determined standard values of healthy liver tissue and analysed potentially influencing factors. 132 patients between 0 and 17 years old were measured using ARFI. None of them had any liver disease or any other disease that could affect the liver secondarily. All patients had a normal ultrasound scan, a normal BMI and normal liver function tests. The mean value of all ARFI measurements was calculated and potentially influencing factors were analysed. The mean value of all ARFI elastography measurements was 1.16 m/sec (SD ± 0.14 m/sec). Neither age (p = 0.533) nor depth of measurement (p = 0.066) had no significant influence on ARFI values, whereas a significant effect of gender was found with lower ARFI values in females (p = 0.025), however, there was no significant interaction between age groups (before or after puberty) and gender (p = 0.276). There was an interlobar difference with lower values in the right liver lobe compared to the left (p = 0.036) and with a significantly lower variance (p < 0.001). Consistend values were measured by different examiners (p = 0.108), however, the inter examiner variance deviated significantly (p < 0.001). ARFI elastography is a reliable method to measure liver stiffness in children and adolescents. In relation to studies which analyse liver diseases, the standard value of 1.16 m/sec (± 0.14 m/sec) allows a differentiation of healthy versus pathological liver tissue. © Georg Thieme Verlag KG Stuttgart · New York.

Is liver SUV stable over time in ¹⁸F-FDG PET imaging?

PubMed

Laffon, Eric; Adhoute, Xavier; de Clermont, Henri; Marthan, Roger

2011-12-01

This work investigated whether (18)F-FDG PET standardized uptake value (SUV) is stable over time in the normal human liver. The SUV-versus-time curve, SUV(t), of (18)F-FDG in the normal human liver was derived from a kinetic model analysis. This derivation involved mean values of (18)F-FDG liver metabolism that were obtained from a patient series (n = 11), and a noninvasive population-based input function was used in each individual. Mean values (±95% reliability limits) of the (18)F-FDG uptake and release rate constant and of the fraction of free tracer in blood and interstitial volume were as follows: K = 0.0119 mL·min(-1)·mL(-1) (±0.0012), k(R) = 0.0065·min(-1) (±0.0009), and F = 0.21 mL·mL(-1) (±0.11), respectively. SUV(t) (corrected for (18)F physical decay) was derived from these mean values, showing that it smoothly peaks at 75-80 min on average after injection and that it is within 5% of the peak value between 50 and 110 min after injection. In the normal human liver, decay-corrected SUV(t) remains nearly constant (with a reasonable ±2.5% relative measurement uncertainty) if the time delay between tracer injection and PET acquisition is in the range of 50-110 min. In current clinical practice, the findings suggest that SUV of the normal liver can be used for comparison with SUV of suspected malignant lesions, if comparison is made within this time range.

Dietary fat sources differentially modulate intestinal barrier and hepatic inflammation in alcohol-induced liver injury in rats

PubMed Central

Zhong, Wei; Li, Qiong; Xie, Guoxiang; Sun, Xiuhua; Tan, Xiaobing; Sun, Xinguo; Jia, Wei

2013-01-01

Endotoxemia is a causal factor in the development of alcoholic liver injury. The present study aimed at determining the interactions of ethanol with different fat sources at the gut-liver axis. Male Sprague-Dawley rats were pair fed control or ethanol liquid diet for 8 wk. The liquid diets were based on a modified Lieber-DeCarli formula, with 30% total calories derived from corn oil (rich in polyunsaturated fatty acids). To test the effects of saturated fats, corn oil in the ethanol diet was replaced by either cocoa butter (CB, rich in long-chain saturated fatty acids) or medium-chain triglycerides (MCT, exclusively medium-chain saturated fatty acids). Ethanol feeding increased hepatic lipid accumulation and inflammatory cell infiltration and perturbed hepatic and serum metabolite profiles. Ethanol feeding with CB or MCT alleviated ethanol-induced liver injury and attenuated ethanol-induced metabolic perturbation. Both CB and MCT also normalized ethanol-induced hepatic macrophage activation, cytokine expression, and neutrophil infiltration. Ethanol feeding elevated serum endotoxin level, which was normalized by MCT but not CB. In accordance, ethanol-induced downregulations of intestinal occludin and zonula occludens-1 were normalized by MCT but not CB. However, CB normalized ethanol-increased hepatic endotoxin level in association with upregulation of an endotoxin detoxifying enzyme, argininosuccinate synthase 1 (ASS1). Knockdown ASS1 in H4IIEC3 cells resulted in impaired endotoxin clearance and upregulated cytokine expression. These data demonstrate that the protection of saturated fats against alcohol-induced liver injury occur via different actions at the gut-liver axis and are chain length dependent. PMID:24113767

[The toxic and protective effects of Polygonum multiflorum on normal and liver injured rats based on the symptom-based prescription theory].

PubMed

Pang, Jing-yao; Bai, Zhao-fang; Niu, Ming; Tu, Can; Ma, Zhi-jie; Zhao, Yan-ling; Zhao, Kui-jun; You, Yun; Wang, Jia-bo; Xiao, Xiao-he

2015-08-01

The dosage-efficacy/toxicity relationship of the 50% alcohol extracts of Polygonum multiflorum was comparatively investigated on either normal or CCl4-induced chronic liver injury rats, by determining the general condition, serum biochemical indices and liver histopathology, coupled with the factor analysis. The dosages were 10 and 20 g raw materials per kg body weight. Compared with the normal control group, the normal high dose group showed significant increases of the serum alanine transaminase (ALT), total bilirubin (TBIL), high mobility group box 1 (HMGB-1) and interleukin-1β (IL-1β) (P < 0.05 or P < 0.01), as well the frequent incidences of inflammatory cell infiltration, hepatic sinus enlargement and fiber stripes formation in histopathological sections. Compared with the model control group, the model low dose group showed significant declines of serum ALT, aspartate transaminase (AST) and total bile acid (TBA) (P < 0.05), as well the alleviation of vacuoles of hepatocytes, but no amelioration of the inflammatory cell infiltration and fibrous tissue hyperplasia; moreover, the model high dose group showed significant degeneration declines of serum HMGB-1, tumor necrosis factor-α (TNF-α) and IL-1β (P < 0.05, P < 0.01), as well the evident alleviation of vacuoles degeneration of hepatocytes, inflammatory cells infiltration and fibrosis degree. The factor analysis showed that the low dosage treatment had almost neither injuring effect on the normal rats nor protective effect on the model rats; while the high dosage treatment showed observable injuring effect on the normal rats, expressed by the significant increases of the factor-1 (HMGB-1, TNF-α and IL-1β as the main contributors) and factor-2 (TBIL, ALT and TBA as the main contributors) relative to the normal control group. The liver protective effect of the high dosage treatment could be observed with the significant reduction of the factor-1, indicating the effective alleviation of the expression of inflammatory cytokines. In conclusion, it could illustrated the phenomenon of symptom-based prescription theory of Polygonum multiflorum on rat livers: the high dosage of the herb had either an injuring effect on normal rats, or a therapeutic effect on the rats with chronic liver injury.

Functional pitch of a liver: fatty liver disease diagnosis with photoacoustic spectrum analysis

NASA Astrophysics Data System (ADS)

Xu, Guan; Meng, Zhuoxian; Lin, Jiandie; Carson, Paul; Wang, Xueding

2014-03-01

To provide more information for classification and assessment of biological tissues, photoacoustic spectrum analysis (PASA) moves beyond the quantification of the intensities of the photoacoustic (PA) signals by the use of the frequency-domain power distribution, namely power spectrum, of broadband PA signals. The method of PASA quantifies the linear-fit to the power spectrum of the PA signals from a biological tissue with 3 parameters, including intercept, midband-fit and slope. Intercept and midband-fit reflect the total optical absorption of the tissues whereas slope reflects the heterogeneity of the tissue structure. Taking advantage of the optical absorption contrasts contributed by lipid and blood at 1200 and 532 nm, respectively and the heterogeneous tissue microstructure in fatty liver due to the lipid infiltration, we investigate the capability of PASA in identifying histological changes of fatty livers in mouse model. 6 and 9 pairs of normal and fatty liver tissues from rat models were examined by ex vivo experiment with a conventional rotational PA measurement system. One pair of rat models with normal and fatty livers was examined non-invasively and in situ with our recently developed ultrasound and PA parallel imaging system. The results support our hypotheses that the spectrum analysis of PA signals can provide quantitative measures of the differences between the normal and fatty liver tissues and that part of the PA power spectrum can suffice for characterization of microstructures in biological tissues. Experimental results also indicate that the vibrational absorption peak of lipid at 1200nm could facilitate fatty liver diagnosis.

Herbal Traditional Chinese Medicine and suspected liver injury: A prospective study

PubMed Central

Melchart, Dieter; Hager, Stefan; Albrecht, Sabine; Dai, Jingzhang; Weidenhammer, Wolfgang; Teschke, Rolf

2017-01-01

AIM To analyze liver tests before and following treatment with herbal Traditional Chinese Medicine (TCM) in order to evaluate the frequency of newly detected liver injury. METHODS Patients with normal values of alanine aminotransferase (ALT) as a diagnostic marker for ruling out pre-existing liver disease were enrolled in a prospective study of a safety program carried out at the First German Hospital of TCM from 1994 to 2015. All patients received herbal products, and their ALT values were reassessed 1-3 d prior to discharge. To verify or exclude causality for suspected TCM herbs, the Roussel Uclaf Causality Assessment Method (RUCAM) was used. RESULTS This report presents for the first time liver injury data derived from a prospective, hospital-based and large-scale study of 21470 patients who had no liver disease prior to treatment with herbal TCM. Among these, ALT ranged from 1 × to < 5 × upper limit normal (ULN) in 844 patients (3.93%) and suggested mild or moderate liver adaptive abnormalities. However, 26 patients (0.12%) experienced higher ALT values of ≥ 5 × ULN (300.0 ± 172.9 U/L, mean ± SD). Causality for TCM herbs was RUCAM-based probable in 8/26 patients, possible in 16/26, and excluded in 2/26 cases. Bupleuri radix and Scutellariae radix were the two TCM herbs most commonly implicated. CONCLUSION In 26 (0.12%) of 21470 patients treated with herbal TCM, liver injury with ALT values of ≥ 5 × ULN was found, which normalized shortly following treatment cessation, also substantiating causality. PMID:29085558

Non-alcoholic fatty liver disease is not associated with a lower health perception

PubMed Central

Mlynarsky, Liat; Schlesinger, Dalit; Lotan, Roni; Webb, Muriel; Halpern, Zamir; Santo, Erwin; Shibolet, Oren; Zelber-Sagi, Shira

2016-01-01

AIM: To examine the association between non-alcoholic fatty liver disease (NAFLD) and general health perception. METHODS: This cross sectional and prospective follow-up study was performed on a cohort of a sub-sample of the first Israeli national health and nutrition examination survey, with no secondary liver disease or history of alcohol abuse. On the first survey, in 2003-2004, 349 participants were included. In 2009-2010 participants from the baseline survey were invited to participate in a follow-up survey. On both baseline and follow-up surveys the data collected included: self-reported general health perception, physical activity habits, frequency of physician's visits, fatigue impact scale and abdominal ultrasound. Fatty liver was diagnosed by abdominal ultrasonography using standardized criteria and the ratio between the median brightness level of the liver and the right kidney was calculated to determine the Hepato-Renal Index. RESULTS: Out of 349 eligible participants in the first survey, 213 volunteers participated in the follow-up cohort and were included in the current analysis, NAFLD was diagnosed in 70/213 (32.9%). The prevalence of "very good" self-reported health perception was lower among participants diagnosed with NAFLD compared to those without NAFLD. However, adjustment for BMI attenuated the association (OR = 0.73, 95%CI: 0.36-1.50, P = 0.392). Similar results were observed for the hepato-renal index; it was inversely associated with "very good" health perception but adjustment for BMI attenuated the association. In a full model of multivariate analysis, that included all potential predictors for health perception, NAFLD was not associated with the self-reported general health perception (OR = 0.86, 95%CI: 0.40-1.86, P = 0.704). The odds for "very good" self-reported general health perception (compared to "else") increased among men (OR = 2.42, 95%CI: 1.26-4.66, P = 0.008) and those with higher performance of leisure time physical activity (OR = 1.01, 95%CI: 1.00-1.01, P < 0.001, per every minute/week) and decreased with increasing level of BMI (OR = 0.91, 95%CI: 0.84-0.99, P = 0.028, per every kg/m2) and older age (OR = 0.96, 95%CI: 0.93-0.99, P = 0.033, per one year). Current smoking was not associated with health perception (OR = 1.31, 95%CI: 0.54-3.16, P = 0.552). Newly diagnosed (naive) and previously diagnosed (at the first survey, not naive) NAFLD patients did not differ in their self-health perception. The presence of NAFLD at the first survey as compared to normal liver did not predict health perception deterioration at the 7 years follow-up. In terms of health-services utilization, subjects diagnosed with NAFLD had a similar number of physician’s visits (general physicians and specialty consultants) as in the normal liver group. Parameters in the fatigue impact scale were equivalent between the NAFLD and the normal liver groups. CONCLUSION: Fatty liver without clinically significant liver disease does not have independent impact on self-health perception. PMID:27158205

Non-alcoholic fatty liver disease is not associated with a lower health perception.

PubMed

Mlynarsky, Liat; Schlesinger, Dalit; Lotan, Roni; Webb, Muriel; Halpern, Zamir; Santo, Erwin; Shibolet, Oren; Zelber-Sagi, Shira

2016-05-07

To examine the association between non-alcoholic fatty liver disease (NAFLD) and general health perception. This cross sectional and prospective follow-up study was performed on a cohort of a sub-sample of the first Israeli national health and nutrition examination survey, with no secondary liver disease or history of alcohol abuse. On the first survey, in 2003-2004, 349 participants were included. In 2009-2010 participants from the baseline survey were invited to participate in a follow-up survey. On both baseline and follow-up surveys the data collected included: self-reported general health perception, physical activity habits, frequency of physician's visits, fatigue impact scale and abdominal ultrasound. Fatty liver was diagnosed by abdominal ultrasonography using standardized criteria and the ratio between the median brightness level of the liver and the right kidney was calculated to determine the Hepato-Renal Index. Out of 349 eligible participants in the first survey, 213 volunteers participated in the follow-up cohort and were included in the current analysis, NAFLD was diagnosed in 70/213 (32.9%). The prevalence of "very good" self-reported health perception was lower among participants diagnosed with NAFLD compared to those without NAFLD. However, adjustment for BMI attenuated the association (OR = 0.73, 95%CI: 0.36-1.50, P = 0.392). Similar results were observed for the hepato-renal index; it was inversely associated with "very good" health perception but adjustment for BMI attenuated the association. In a full model of multivariate analysis, that included all potential predictors for health perception, NAFLD was not associated with the self-reported general health perception (OR = 0.86, 95%CI: 0.40-1.86, P = 0.704). The odds for "very good" self-reported general health perception (compared to "else") increased among men (OR = 2.42, 95%CI: 1.26-4.66, P = 0.008) and those with higher performance of leisure time physical activity (OR = 1.01, 95%CI: 1.00-1.01, P < 0.001, per every minute/week) and decreased with increasing level of BMI (OR = 0.91, 95%CI: 0.84-0.99, P = 0.028, per every kg/m(2)) and older age (OR = 0.96, 95%CI: 0.93-0.99, P = 0.033, per one year). Current smoking was not associated with health perception (OR = 1.31, 95%CI: 0.54-3.16, P = 0.552). Newly diagnosed (naive) and previously diagnosed (at the first survey, not naive) NAFLD patients did not differ in their self-health perception. The presence of NAFLD at the first survey as compared to normal liver did not predict health perception deterioration at the 7 years follow-up. In terms of health-services utilization, subjects diagnosed with NAFLD had a similar number of physician's visits (general physicians and specialty consultants) as in the normal liver group. Parameters in the fatigue impact scale were equivalent between the NAFLD and the normal liver groups. Fatty liver without clinically significant liver disease does not have independent impact on self-health perception.

The acute effects of ethanol on acetanilide disposition in normal subjects, and in patients with liver disease.

PubMed Central

McKay, J; Rawlings, M D; Cobden, I; James, O F

1982-01-01

1 The effects of single doses (25 g and 50 g) oral ethanol on the disposition of acetanilide (50 mg/kg metabolic active mass) has been studied in normal subjects, and in patients with chronic non-alcoholic liver disease. 2 In normal subjects, ethanol produced a dose-dependent increase in acetanilide half-life, and a decrease in acetenilide clearance. There was a significant correlation (rs = 0.71, P less than 0.01) between the 90 min blood ethanol concentration and the reduction in acetanilide clearance. 3 In patients with liver disease, ethanol produced a similar proportional change in acetanilide half-life and clearance, but these were less consistent. Moreover, liver disease itself was associated with an increase in acetenilide half-life, and a reduction in clearance. 4 It is concluded that single oral doses of ethanol, comparable to those consumed during social drinking, may inhibit some forms of microsomal oxidation and thus have important clinical implications. PMID:7138735

The acute effects of ethanol on acetanilide disposition in normal subjects, and in patients with liver disease.

PubMed

McKay, J; Rawlings, M D; Cobden, I; James, O F

1982-10-01

1 The effects of single doses (25 g and 50 g) oral ethanol on the disposition of acetanilide (50 mg/kg metabolic active mass) has been studied in normal subjects, and in patients with chronic non-alcoholic liver disease. 2 In normal subjects, ethanol produced a dose-dependent increase in acetanilide half-life, and a decrease in acetenilide clearance. There was a significant correlation (rs = 0.71, P less than 0.01) between the 90 min blood ethanol concentration and the reduction in acetanilide clearance. 3 In patients with liver disease, ethanol produced a similar proportional change in acetanilide half-life and clearance, but these were less consistent. Moreover, liver disease itself was associated with an increase in acetenilide half-life, and a reduction in clearance. 4 It is concluded that single oral doses of ethanol, comparable to those consumed during social drinking, may inhibit some forms of microsomal oxidation and thus have important clinical implications.

Chronically Inflamed Livers Up-regulate Expression of Inhibitory B7 Family Members

PubMed Central

Kassel, Rachel; Cruise, Michael W.; Iezzoni, Julia C.; Taylor, Nicholas A.; Pruett, Timothy L.; Hahn, Young S.

2010-01-01

Hepatitis B virus (HBV), hepatitis C virus (HCV), autoimmune hepatitis (AIH), and non-alcoholic fatty liver disease (NAFLD) can induce chronic liver disease. The PD-1 inhibitory pathway assists in T cell response regulation during acute and chronic inflammation and participates in the progression of inflammatory liver disease. To examine whether PD-1 and its ligands, B7-H1 and B7-DC, are modulated during chronic necroinflammatory liver disease, we investigated expression profiles in normal patients and patients with the aforementioned conditions. Relative to liver biopsies from normal individuals, those from patients with chronic necroinflammatory liver diseases (HBV, HCV, and AIH) contain increased numbers of PD-1 expressing lymphocytes. Kupffer cells, liver sinusoidal endothelial cells (LSECs), and leukocytes express PD-1 ligands. We also detect PD-1 ligands on hepatocytes within biopsies and on isolated cells. All forms of chronic necroinflammatory liver disease examined correlate with increased B7-H1 and B7-DC expression on Kupffer cells, LSECs, and leukocytes. The degree of necroinflammation correlates with expression levels of PD-1 family members. These results demonstrate that expression of PD-1/PD-1 ligands links more directly with the degree of inflammation than with the underlying etiology of liver damage. The PD-1 pathway may assist the liver in protecting itself from immune-mediated destruction. PMID:19739236

Quercetin Potentiates Doxorubicin Mediated Antitumor Effects against Liver Cancer through p53/Bcl-xl

PubMed Central

Wang, Guanyu; Sharma, Sherven; Dong, Qinghua

2012-01-01

Background The dose-dependent toxicities of doxorubicin (DOX) limit its clinical applications, particularly in drug-resistant cancers, such as liver cancer. In this study, we investigated the role of quercetin on the antitumor effects of DOX on liver cancer cells and its ability to provide protection against DOX-mediated liver damage in mice. Methodology and Results The MTT and Annexin V/PI staining assay demonstrated that quercetin selectively sensitized DOX-induced cytotoxicity against liver cancer cells while protecting normal liver cells. The increase in DOX-mediated apoptosis in hepatoma cells by quercetin was p53-dependent and occurred by downregulating Bcl-xl expression. Z-VAD-fmk (caspase inhibitor), pifithrin-α (p53 inhibitor), or overexpressed Bcl-xl decreased the effects of quercetin on DOX-mediated apoptosis. The combined treatment of quercetin and DOX significantly reduced the growth of liver cancer xenografts in mice. Moreover, quercetin decreased the serum levels of alanine aminotransferase and aspartate aminotransferase that were increased in DOX-treated mice. Quercetin also reversed the DOX-induced pathological changes in mice livers. Conclusion and Significance These results indicate that quercetin potentiated the antitumor effects of DOX on liver cancer cells while protecting normal liver cells. Therefore, the development of quercetin may be beneficial in a combined treatment with DOX for increased therapeutic efficacy against liver cancer. PMID:23240061

Hepatoprotective effect of manual acupuncture at acupoint GB34 against CCl4-induced chronic liver damage in rats

PubMed Central

Yim, Yun-Kyoung; Lee, Hyun; Hong, Kwon-Eui; Kim, Young-Il; Lee, Byung-Ryul; Kim, Tae-Han; Yi, Ji-Young

2006-01-01

AIM: To investigate the hepatoprotective effect of manual acupuncture at Yanglingquan (GB34) on CCl4-induced chronic liver damage in rats. METHODS: Rats were injected intraperitoneally with CCl4 (1 mL/kg) and treated with manual acupuncture using reinforcing manipulation techniques at left GB34 (Yanglingquan) 3 times a week for 10 wk. A non-acupoint in left gluteal area was selected as a sham point. To estimate the hepatoprotective effect of manual acupuncture at GB34, measurement of liver index, biochemical assays including serum ALT, AST, ALP and total cholesterol, histological analysis and blood cell counts were conducted. RESULTS: Manual acupuncture at GB34 reduced the liver index, serum ALT, AST, ALP and total cholesterol levels as compared with the control group and the sham acupuncture group. It also increased and normalized the populations of WBC and lymphocytes. CONCLUSION: Manual acupuncture with reinforcing manipulation techniques at left GB34 reduces liver toxicity, protects liver function and liver tissue, and normalizes immune activity in CCl4-intoxicated rats. PMID:16610030

Automated liver segmentation using a normalized probabilistic atlas

NASA Astrophysics Data System (ADS)

Linguraru, Marius George; Li, Zhixi; Shah, Furhawn; Chin, See; Summers, Ronald M.

2009-02-01

Probabilistic atlases of anatomical organs, especially the brain and the heart, have become popular in medical image analysis. We propose the construction of probabilistic atlases which retain structural variability by using a size-preserving modified affine registration. The organ positions are modeled in the physical space by normalizing the physical organ locations to an anatomical landmark. In this paper, a liver probabilistic atlas is constructed and exploited to automatically segment liver volumes from abdominal CT data. The atlas is aligned with the patient data through a succession of affine and non-linear registrations. The overlap and correlation with manual segmentations are 0.91 (0.93 DICE coefficient) and 0.99 respectively. Little work has taken place on the integration of volumetric measures of liver abnormality to clinical evaluations, which rely on linear estimates of liver height. Our application measures the liver height at the mid-hepatic line (0.94 correlation with manual measurements) and indicates that its combination with volumetric estimates could assist the development of a noninvasive tool to assess hepatomegaly.

Evolution of Exchangeable Copper and Relative Exchangeable Copper through the Course of Wilson's Disease in the Long Evans Cinnamon Rat

PubMed Central

Schmitt, Françoise; Podevin, Guillaume; Poupon, Joël; Roux, Jérôme; Legras, Pierre; Trocello, Jean-Marc; Woimant, France; Laprévote, Olivier; NGuyen, Tuan Huy; Balkhi, Souleiman El

2013-01-01

Background Wilson's disease (WD) is an inherited disorder of copper metabolism leading to liver failure and/or neurological impairment. Its diagnosis often remains difficult even with genetic testing. Relative exchangeable copper (REC) has recently been described as a reliable serum diagnostic marker for WD. Methodology/Principal Findings The aim of this study was to validate the use of REC in the Long Evans Cinnamon (LEC) rat, an animal model for WD, and to study its relevance under different conditions in comparison with conventional markers. Two groups of LEC rats and one group of Long-Evans (LE) rats were clinically and biologically monitored from 6 to 28 weeks of age. One group of LEC rats was given copper-free food. The other groups had normal food. Blood samples were collected each month and different serum markers for WD (namely ceruloplasmin oxidase activity, exchangeable copper (CuEXC), total serum copper and REC) and acute liver failure (serum transaminases and bilirubinemia) were tested. Every LEC rat under normal food developed acute liver failure (ALF), with 40% global mortality. Serum transaminases and bilirubinemia along with total serum copper and exchangeable copper levels increased with the onset of acute liver failure. A correlation was observed between CuEXC values and the severity of ALF. Cut-off values were different between young and adult rats and evolved because of age and/or liver failure. Only REC, with values >19%, was able to discriminate LEC groups from the LE control group at every time point in the study. REC sensitivity and specificity reached 100% in adults rats. Conclusions/Significance REC appears to be independent of demographic or clinical data in LEC rats. It is a very simple and reliable blood test for the diagnosis of copper toxicosis owing to a lack of ATP7B function. CuEXC can be used as an accurate biomarker of copper overload. PMID:24358170

A decrease in fasting FGF19 levels is associated with the development of non-alcoholic fatty liver disease in obese adolescents.

PubMed

Wojcik, Malgorzata; Janus, Dominika; Dolezal-Oltarzewska, Katarzyna; Kalicka-Kasperczyk, Anna; Poplawska, Karolina; Drozdz, Dorota; Sztefko, Krystyna; Starzyk, Jerzy B

2012-01-01

Fibroblast growth factor 19 (FGF19) is a hormone released from the small intestine; recently, it has emerged as an endocrine regulator of glucose and lipid metabolism. The aim of this study was to investigate the role of FGF19 in the development of nonalcoholic fatty liver disease (NAFLD). This study included 23 (17 boys) obese adolescents (mean age of 14.1 years) with NAFLD. The control group consisted of 34 (13 boys) obese peers with normal ultrasonographic imaging and normal liver function tests. The definition of NAFLD was based on clinical criteria: elevated alanine aminotransferase (>35 U/L) and liver steatosis features on ultrasound imaging. Serum FGF19 levels were measured in a fasting blood sample. The definition of insulin resistance was based on the homeostasis model assessment (HOMA) threshold: >2.5. There was a significant difference between mean FGF19 levels in patients with NAFLD and controls (142.2 vs. 206 pg/mL, p=0.04). Mean fasting FGF19 levels were decreased in insulin-resistant patients in comparison with the non-insulin-resistant group (155.0 vs. 221.0 pg/mL, p=0.05). There was an inverse correlation between FGF19 and alanine aminotransferase levels (R=-0.3, p<0.05) and triglycerides (R=-0.27, p<0.05). A decrease in fasting FGF19 is associated with the development of NAFLD in obese adolescents. A decrease in fasting FGF19 levels may be a new important risk factor for NAFLD and the metabolic syndrome in adolescents. Further studies are needed to explain whether exogenous delivery of FGF19 might be therapeutically beneficial.

Dosimetry and prescription in liver radioembolization with 90Y microspheres: 3D calculation of tumor-to-liver ratio from global 99mTc-MAA SPECT information

NASA Astrophysics Data System (ADS)

Mañeru, Fernando; Abós, Dolores; Bragado, Laura; Fuentemilla, Naiara; Caudepón, Fernando; Pellejero, Santiago; Miquelez, Santiago; Rubio, Anastasio; Goñi, Elena; Hernández-Vitoria, Araceli

2017-12-01

Dosimetry in liver radioembolization with 90Y microspheres is a fundamental tool, both for the optimization of each treatment and for improving knowledge of the treatment effects in the tissues. Different options are available for estimating the administered activity and the tumor/organ dose, among them the so-called partition method. The key factor in the partition method is the tumor/normal tissue activity uptake ratio (T/N), which is obtained by a single-photon emission computed tomography (SPECT) scan during a pre-treatment simulation. The less clear the distinction between healthy and tumor parenchyma within the liver, the more difficult it becomes to estimate the T/N ratio; therefore the use of the method is limited. This study presents a methodology to calculate the T/N ratio using global information from the SPECT. The T/N ratio is estimated by establishing uptake thresholds consistent with previously performed volumetry. This dose calculation method was validated against 3D voxel dosimetry, and was also compared with the standard partition method based on freehand regions of interest (ROI) outlining on SPECT slices. Both comparisons were done on a sample of 20 actual cases of hepatocellular carcinoma treated with resin microspheres. The proposed method and the voxel dosimetry method yield similar results, while the ROI-based method tends to over-estimate the dose to normal tissues. In addition, the variability associated with the ROI-based method is more extreme than the other methods. The proposed method is simpler than either the ROI or voxel dosimetry approaches and avoids the subjectivity associated with the manual selection of regions.

Disturbance of DNA methylation patterns in the early phase of hepatocarcinogenesis induced by a choline-deficient L-amino acid-defined diet in rats.

PubMed

Shimizu, Kyoko; Onishi, Mariko; Sugata, Eriko; Sokuza, Yui; Mori, Chiharu; Nishikawa, Tomoki; Honoki, Kanya; Tsujiuchi, Toshifumi

2007-09-01

The authors investigated the DNA methylation patterns of the E-cadherin, Connexin 26 (Cx26), Rassf1a and c-fos genes in the early phase of rat hepatocarcinogenesis induced by a choline-deficient L-amino acid-defined (CDAA) diet. Six-week-old F344 male rats were continuously fed with the CDAA diet, and three animals were then killed at each of 4 and 8 days and 3 weeks. Genomic DNA was extracted from livers for assessment of methylation status in the 5' upstream regions of E-cadherin, Cx26, Rassf1a and c-fos genes by bisulfite sequencing, compared with normal livers. The livers of rats fed the CDAA diet for 4 and 8 days and 3 weeks were methylated in E-cadherin, Cx26 and Rassf1a genes, while normal livers were all unmethylated. In contrast, normal livers were highly methylated in c-fos gene. Although the livers at 4 days were weakly methylated, those at 8 days and 3 weeks were markedly unmethylated. Methylation patterns of CpG sites in E-cadherin, Cx26 and Rassf1a were sparse and the methylation was not associated with gene repression. These results indicate that gene-specific DNA methylation patterns were found in livers of rats after short-term feeding of the CDAA diet, suggesting gene-specific hypermethylation might be involved in the early phase of rat hepatocarcinogenesis induced by the CDAA diet.

Characterization of c-Ki-ras and N-ras oncogenes in aflatoxin B sub 1 -induced rat liver tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

McMahon, G.; Davis, E.F.; Huber, L.J.

c-Ki-ras and N-ras oncogenes have been characterized in aflatoxin B{sub 1}-induced hepatocellular carcinomas. Detection of different protooncogene and oncogene sequences and estimation of their frequency distribution were accomplished by polymerase chain reaction, cloning, and plaque screening methods. Two c-Ki-ras oncogene sequences were identified in DNA from liver tumors that contained nucleotide changes absent in DNA from livers of untreated control rats. Sequence changes involving G{center dot}C to T{center dot}A or G{center dot}C to A{center dot}T nucleotide substitutions in codon 12 were scored in three of eight tumor-bearing animals. Distributions of c-Ki-ras sequences in tumors and normal liver DNA indicated thatmore » the observed nucleotide changes were consistent with those expected to result from direct mutagenesis of the germ-line protooncogene by aflatoxin B{sub 1}. N-ras oncogene sequences were identified in DNA from two of eight tumors. Three N-ras gene regions were identified, one of which was shown to be associated with an oncogene containing a putative activating amino acid residing at codon 13. All three N-ras sequences, including the region detected in N-ras oncogenes, were present at similar frequencies in DNA samples from control livers as well as liver tumors. The presence of a potential germ-line oncogene may be related to the sensitivity of the Fischer rat strain to liver carcinogenesis by aflatoxin B{sub 1} and other chemical carcinogens.« less

Mechanism of the development of nonalcoholic steatohepatitis after pancreaticoduodenectomy.

PubMed

Nagaya, Tadanobu; Tanaka, Naoki; Kimura, Takefumi; Kitabatake, Hiroyuki; Fujimori, Naoyuki; Komatsu, Michiharu; Horiuchi, Akira; Yamaura, Takahiro; Umemura, Takeji; Sano, Kenji; Gonzalez, Frank J; Aoyama, Toshifumi; Tanaka, Eiji

2015-06-01

It is recognized that nonalcoholic fatty liver disease (NAFLD), including nonalcoholic steatohepatitis (NASH), may develop after pancreaticoduodenectomy (PD). However, the mechanism of NASH development remains unclear. This study aimed to examine the changes in gene expression associated with NASH occurrence following PD. The expression of genes related to fatty acid/triglyceride (FA/TG) metabolism and inflammatory signaling was examined using liver samples obtained from 7 post-PD NASH patients and compared with 6 healthy individuals and 32 conventional NASH patients. The livers of post-PD NASH patients demonstrated significant up-regulation of the genes encoding CD36, FA-binding proteins 1 and 4, acetyl-coenzyme A carboxylase α, diacylglycerol acyltransferase 2, and peroxisome proliferator-activated receptor (PPAR) γ compared with normal and conventional NASH livers. Although serum apolipoprotein B (ApoB) and TG were decreased in post-PD NASH patients, the mRNAs of ApoB and microsomal TG transfer protein were robustly increased, indicating impaired TG export from the liver as very-low-density lipoprotein (VLDL). Additionally, elevated mRNA levels of myeloid differentiation primary response 88 and superoxide dismutases in post-PD NASH livers suggested significant activation of innate immune response and augmentation of oxidative stress generation. Enhanced FA uptake into hepatocytes and lipogenesis, up-regulation of PPARγ, and disruption of VLDL excretion into the circulation are possible mechanisms of steatogenesis after PD. These results provide a basis for understanding the pathogenesis of NAFLD/NASH following PD.

Symptomatic Giant Cavernous Haemangioma of the Liver: Is Enucleation a Safe Method?

PubMed Central

Alabaz, Ö.; Ağdemir, D.; Sungur, I.; Erkoçak, E. U.; Akinoğlu, A.; Alparslan, A.; Źorludemir, S.

1997-01-01

Twenty-three patients with symptomatic giant hemangioma of the liver were treated by surgery between 1979 and 1996 at the department of General Surgery, Faculty of Medicine, University of Çukurova. Twenty-three enucleations were performed in 21 patients, left lateral segmentectomy in one patient and enucleation plus left lobectomy in one patient. The tumors were enucleated along the interface between the hemangioma and normal liver tissue. The diameters of the tumors ranged from 5×5 to 25×15 cm. The mean blood loss for enucleations was 525 ml (range 500–1000 ml). There was no mortality and no postoperative bleeding. Three patients had postoperative complications. Enucleation is the best surgical technique for symptomatic giant hemangioma of the liver. It may be performed with no mortality, low morbidity and the preservation of all normal liver parenchyma. PMID:9298384

Bioassay of procoagulant albumin in human plasma.

PubMed

Grosset, A; Liu, L; Parker, C J; Rodgers, G M

1994-09-01

Procoagulant albumin (P-Al) is present in normal human plasma and increases monocyte and endothelial cell expression of tissue factor activity. To develop a bioassay for P-Al, we partially purified plasma from healthy volunteers and several patient groups using BaCl2 and (NH4)2SO4 precipitation. The samples were assayed for tissue factor (TF) inducing activity, expressed as a percentage increase compared to a serum-free media control. Over six months, the assay was reproducible in stored samples and in serial samples from normal volunteers. The plasma P-Al activities of 35 volunteers averaged 141 +/- 8.2% (SEM). There was no diurnal variation. There was no difference in the P-Al activity after a 12 hour fast and 2 hours after a large meal in 4 healthy volunteers. There was no increase in activity (r = 0.16) with the subject's age. The average activity from 16 poorly-controlled diabetics was 131 +/- 11% (SEM). No alteration in activity was seen with samples from patients with uremia, liver dysfunction, hemophilia, thrombotic events, or adenocarcinoma. These results indicate that P-Al activity can be bioassayed in individual patient samples; however, pathologic states associated with abnormal P-Al-induced tissue factor activity presently remain unidentified.

Potential of cancer screening with serum surface-enhanced Raman spectroscopy and a support vector machine

NASA Astrophysics Data System (ADS)

Li, S. X.; Zhang, Y. J.; Zeng, Q. Y.; Li, L. F.; Guo, Z. Y.; Liu, Z. M.; Xiong, H. L.; Liu, S. H.

2014-06-01

Cancer is the most common disease to threaten human health. The ability to screen individuals with malignant tumours with only a blood sample would be greatly advantageous to early diagnosis and intervention. This study explores the possibility of discriminating between cancer patients and normal subjects with serum surface-enhanced Raman spectroscopy (SERS) and a support vector machine (SVM) through a peripheral blood sample. A total of 130 blood samples were obtained from patients with liver cancer, colonic cancer, esophageal cancer, nasopharyngeal cancer, gastric cancer, as well as 113 blood samples from normal volunteers. Several diagnostic models were built with the serum SERS spectra using SVM and principal component analysis (PCA) techniques. The results show that a diagnostic accuracy of 85.5% is acquired with a PCA algorithm, while a diagnostic accuracy of 95.8% is obtained using radial basis function (RBF), PCA-SVM methods. The results prove that a RBF kernel PCA-SVM technique is superior to PCA and conventional SVM (C-SVM) algorithms in classification serum SERS spectra. The study demonstrates that serum SERS, in combination with SVM techniques, has great potential for screening cancerous patients with any solid malignant tumour through a peripheral blood sample.

Molecular classification of liver cirrhosis in a rat model by proteomics and bioinformatics.

PubMed

Xu, Xiu-Qin; Leow, Chon K; Lu, Xin; Zhang, Xuegong; Liu, Jun S; Wong, Wing-Hung; Asperger, Arndt; Deininger, Sören; Eastwood Leung, Hon-Chiu

2004-10-01

Liver cirrhosis is a worldwide health problem. Reliable, noninvasive methods for early detection of liver cirrhosis are not available. Using a three-step approach, we classified sera from rats with liver cirrhosis following different treatment insults. The approach consisted of: (i) protein profiling using surface-enhanced laser desorption/ionization (SELDI) technology; (ii) selection of a statistically significant serum biomarker set using machine learning algorithms; and (iii) identification of selected serum biomarkers by peptide sequencing. We generated serum protein profiles from three groups of rats: (i) normal (n=8), (ii) thioacetamide-induced liver cirrhosis (n=22), and (iii) bile duct ligation-induced liver fibrosis (n=5) using a weak cation exchanger surface. Profiling data were further analyzed by a recursive support vector machine algorithm to select a panel of statistically significant biomarkers for class prediction. Sensitivity and specificity of classification using the selected protein marker set were higher than 92%. A consistently down-regulated 3495 Da protein in cirrhosis samples was one of the selected significant biomarkers. This 3495 Da protein was purified on-chip and trypsin digested. Further structural characterization of this biomarkers candidate was done by using cross-platform matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) peptide mass fingerprinting (PMF) and matrix-assisted laser desorption/ionization time of flight/time of flight (MALDI-TOF/TOF) tandem mass spectrometry (MS/MS). Combined data from PMF and MS/MS spectra of two tryptic peptides suggested that this 3495 Da protein shared homology to a histidine-rich glycoprotein. These results demonstrated a novel approach to discovery of new biomarkers for early detection of liver cirrhosis and classification of liver diseases.

Application of neutron capture autoradiography to Boron Delivery seeking techniques for selective accumulation of boron compounds to tumor with intra-arterial administration of boron entrapped water-in-oil-in-water emulsion

NASA Astrophysics Data System (ADS)

Mikado, S.; Yanagie, H.; Yasuda, N.; Higashi, S.; Ikushima, I.; Mizumachi, R.; Murata, Y.; Morishita, Y.; Nishimura, R.; Shinohara, A.; Ogura, K.; Sugiyama, H.; Iikura, H.; Ando, H.; Ishimoto, M.; Takamoto, S.; Eriguchi, M.; Takahashi, H.; Kimura, M.

2009-06-01

It is necessary to accumulate the 10B atoms selectively to the tumor cells for effective Boron Neutron Capture Therapy (BNCT). In order to achieve an accurate measurement of 10B accumulations in the biological samples, we employed a technique of neutron capture autoradiography (NCAR) of sliced samples of tumor tissues using CR-39 plastic track detectors. The CR-39 track detectors attached with the biological samples were exposed to thermal neutrons in the thermal column of the JRR3 of Japan Atomic Energy Agency (JAEA). We obtained quantitative NCAR images of the samples for VX-2 tumor in rabbit liver after injection of 10BSH entrapped water-in-oil-in-water (WOW) emulsion by intra-arterial injection via proper hepatic artery. The 10B accumulations and distributions in VX-2 tumor and normal liver of rabbit were investigated by means of alpha-track density measurements. In this study, we showed the selective accumulation of 10B atoms in the VX-2 tumor by intra-arterial injection of 10B entrapped WOW emulsion until 3 days after injection by using digitized NCAR images (i.e. alpha-track mapping).

Biomarkers for liver fibrosis

DOEpatents

Jacobs, Jon M.; Burnum-Johnson, Kristin E.; Baker, Erin M.; Smith, Richard D.; Gritsenko, Marina A.; Orton, Daniel

2017-05-16

Methods and systems for diagnosing or prognosing liver fibrosis in a subject are provided. In some examples, such methods and systems can include detecting liver fibrosis-related molecules in a sample obtained from the subject, comparing expression of the molecules in the sample to controls representing expression values expected in a subject who does not have liver fibrosis or who has non-progressing fibrosis, and diagnosing or prognosing liver fibrosis in the subject when differential expression of the molecules between the sample and the controls is detected. Kits for the diagnosis or prognosis of liver fibrosis in a subject are also provided which include reagents for detecting liver fibrosis related molecules.

Biomarkers for liver fibrosis

DOEpatents

Jacobs, Jon M.; Burnum-Johnson, Kristin E.; Baker, Erin M.; Smith, Richard D.; Gritsenko, Marina A.; Orton, Daniel

2015-09-15

Methods and systems for diagnosing or prognosing liver fibrosis in a subject are provided. In some examples, such methods and systems can include detecting liver fibrosis-related molecules in a sample obtained from the subject, comparing expression of the molecules in the sample to controls representing expression values expected in a subject who does not have liver fibrosis or who has non-progressing fibrosis, and diagnosing or prognosing liver fibrosis in the subject when differential expression of the molecules between the sample and the controls is detected. Kits for the diagnosis or prognosis of liver fibrosis in a subject are also provided which include reagents for detecting liver fibrosis related molecules.

Cimetidine and hepatic blood flow in polytrauma patients.

PubMed

Ivatury, R R; Khan, M B; Nallathambi, M; Davis, K; Stahl, W M

1985-05-01

Recent reports suggest that cimetidine acutely reduces liver blood flow in normal healthy subjects. To determine whether this finding is applicable to critically ill patients, we studied nine polytrauma patients admitted to a surgical ICU. All patients were being monitored with pulmonary artery catheters; all were stable with normal liver function. Liver blood flow was estimated by indocyanine green clearance, before and after administration of a single dose of 600 mg cimetidine. Hemodynamic variables were measured at the same times. Cimetidine did not significantly alter either hepatic blood flow or cardiovascular status in these critically ill patients.

Eosin fluorescence: A diagnostic tool for quantification of liver injury.

PubMed

Ali, Hamid; Ali, Safdar; Mazhar, Maryam; Ali, Amjad; Jahan, Azra; Ali, Abid

2017-09-01

Hepatitis is one of the most common life threatening diseases. The diagnosis is mainly based on biochemical analysis such as liver function test. However, histopathological evaluation of liver serves far better for more accurate final diagnosis. The goal of our study was to evaluate the eosin fluorescence pattern in CCl 4 -induced liver injury model compared with normal and different treatment groups. For this purpose, liver tissues were stained with H/E and examined under bright field microscope but the fluorescence microscopy of H/E stained slides provided an interesting fluorescence pattern and was quite helpful in identifying different structures. Interesting fluorescence patterns were obtained with FITC, Texas Red and Dual channel filter cubes that were quite helpful in identifying different morphological features of the liver. During the course of hepatic injury, liver cells undergo necrosis, apoptosis and overall cellular microenvironment is altered due to the modification of proteins and other intracellular molecules. Intensified eosin fluorescence was observed around the central vein of injured liver compared to normal indicating enhanced binding of eosin to the more exposed amino acid residues. To conclude, eosin fluorescence pattern varies with the health status of a tissue and can be used further for the diagnosis and quantification of severity of various liver diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Laminin and Fibronectin in Cell Adhesion: Enhanced Adhesion of Cells from Regenerating Liver to Laminin

NASA Astrophysics Data System (ADS)

Carlsson, Roland; Engvall, Eva; Freeman, Aaron; Ruoslahti, Erkki

1981-04-01

Laminin, a basement membrane glycoprotein isolated from cultures of mouse endodermal cells and rat yolk sac carcinoma cells, promoted the attachment of liver cells obtained from regenerating mouse liver. Cells from normal mouse liver attached readily to dishes coated with fibronectin but attached poorly to surfaces coated with laminin. Both proteins efficiently promoted the attachment of cells from livers undergoing regeneration. After regeneration, the attachment to laminin returned to the low levels found in animals not subjected to partial hepatectomy but attachment to fibronectin remained high. Immunofluorescent staining of sections of normal liver with antilaminin revealed the presence of laminin in or adjacent to the walls of the bile ducts and blood vessels. After induction of regeneration by partial hepatectomy, increased amounts of laminin appeared in the sinusoidal areas. After carbon tetrachloride poisoning, staining for laminin was especially pronounced in the necrotic and postnecrotic areas around the central veins. This additional expression of laminin was transient. It reached a maximum around 5-6 days after the injury and then gradually disappeared. These findings show that laminin is an adhesive protein. The increase of laminin in regenerating liver and the adhesiveness of cells from such livers to laminin suggest a role for laminin in the maintenance of a proper tissue organization during liver regeneration.

Autoimmune hepatitis during intravenous glucocorticoid pulse therapy for Graves' ophthalmopathy treated successfully with glucocorticoids themselves.

PubMed

Marinò, M; Morabito, E; Altea, M A; Ambrogini, E; Oliveri, F; Brunetto, M R; Pollina, L E; Campani, D; Vitti, P; Bartalena, L; Pincheral, A; Marcocci, C

2005-03-01

We report a case of acute hepatitis of autoimmune origin which occurred in a 43-yr-old woman during iv glucocorticoid (GC) pulse therapy for Graves' ophthalmopathy (GO). Prior to therapy, liver function tests were normal with no previous history of liver disorders or conditions predisposing to GC-associated liver damage. After the administration of a 4.7-g cumulative dose of methylprednisolone acetate, there was a marked increase of liver enzymes, prompting immediate discontinuation of iv GC. Nevertheless, liver enzymes increased further, reaching a peak 45 days later, with values 30- to 50-fold greater than those prior to therapy, associated with evidence of impaired liver function. Liver biopsy showed a marked lymphocytic infiltration, likely indicating an autoimmune hepatitis. Based on the assumption that following GC-induced immune suppression, autoimmune hepatitis might have been precipitated by sudden re-activation of the immune system during interpulse periods, we treated the patient with im and then oral GC, in order to re-induce immune suppression. Within three days from re-institution of GC therapy, there was a marked reduction of liver enzymes and amelioration of liver function. Complete normalization was achieved two months later, while the patient was still receiving a low maintenance dose of oral prednisone.

Longitudinal monitoring of liver stiffness by acoustic radiation force impulse imaging in patients with chronic hepatitis B receiving entecavir.

PubMed

Wu, Sheng-Di; Ding, Hong; Liu, Li-Li; Zhuang, Yuan; Liu, Yun; Cheng, Li-Sha; Wang, Si-Qi; Tseng, Yu-Jen; Wang, Ji-Yao; Jiang, Wei

2018-06-01

Acoustic radiation force impulse (ARFI) imaging measures liver stiffness (LS), which significantly correlates with the stage of liver fibrosis in treatment-naive patients with chronic hepatitis B (CHB). We aimed to prospectively assess the clinical usefulness of ARFI during long-term antiviral therapy in CHB. Seventy-one CHB patients were consecutively recruited and paired liver biopsies were performed in 27 patients. LS was assessed by ARFI semiannually during entecavir therapy. LS gradually decreased with treatment and continued to decrease after normalization of alanine aminotransaminase. Overall, 97.2% patients achieved improvement of LS, whereas 19.7% patients had more than 30% reduction in LS values between baseline and week 104. Multivariate linear regression analysis showed that the degree of LS reduction significantly correlated with the baseline levels of LS value, platelet and cholinesterase. In the 27 patients who underwent paired liver biopsies, LS significantly correlated with stage of fibrosis and inflammatory grade at baseline. LS values decreased more significantly in patients with fibrosis regression than those with static histological fibrosis. In CHB patients, LS assessed by ARFI was gradually reduced during antiviral therapy. Longitudinal monitoring of LS may be a promising noninvasive assessment of fibrosis regression during long-term antiviral therapy in CHB. Further large sample studies are needed. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Evaluation of fatty liver by using in-phase and opposed-phase MR images and in-vivo proton MR spectroscopy

NASA Astrophysics Data System (ADS)

Lee, Jae-Seung; Im, In-Chul; Goo, Eun-Hoe; Park, Hyong-Hu; Kwak, Byung-Joon

2012-12-01

The purpose of this study was to evaluate the necessity of in-phase and opposed-phase MR images and their correlations with weight, the aspartate aminotransferase/alanine aminotransferase (AST/ALT) value, and age. Magnetic resonance spectroscopy (MRS) was used as a reference in this study. We selected 68 people as subjects, among which 14 were volunteers with normal AST/ALT values ( <40/35 U/L) on a liver function study and 54 were non-alcoholic fatty liver patients for whom ultrasonic images had been obtained within 3 months of the study. In this study, the liver was more enhanced than the spleen or kidney. When the Eq. (3) formula was applied to normal volunteers, the difference between the in-phase and the opposed-phase images was -3.54 ± 12.56. The MRS study result showed a high sensitivity of 96.6% and a specificity of 100% ( p = 0.000) when the cutoff value was 20%. Furthermore, this result showed a high sensitivity of 94% and a specificity of 80% with a similar cutoff when the Eq. (2) formula was applied to non-alcoholic fatty liver patients ( p = 0.000). The MRS study revealed a strong correlation between normal volunteers and non-alcoholic fatty liver patients (r = 0.59, p = 0.04). The correlations between AST/ALT and Eq. (3) (r = 0.45, p = 0.004), age and Eq. (3) (r = 0.73, p = 0.03), and weight and Eq. (3) (r = 0.77, p = 0.000) values were all statistically significant. In the case of non-alcoholic liver disease, MRS was found to be significantly correlated with Eq. (1) (r = 0.39, p = 0.002), Eq. (2) (r = 0.68, p = 0.04), Eq. (3) (r = 0.67, p = 0.04), and AST/ALT (r = 0.77, p = 0.000). In conclusion, in-phase and opposed-phase images can help to distinguish a normal liver from a fatty liver in order to identify non-alcoholic fatty liver patients. The intensity difference between the in-phase and opposed-phase MR signals showed valuable correlations with respect to weight, AST/ALT value, and age, with all values being above the mild lipid value (r = 0.3).

Development of a New Diagnostic System for Human Liver Diseases Based on Conventional Ultrasonic Diagnostic Equipment

NASA Astrophysics Data System (ADS)

Kikuchi, Tsuneo; Nakazawa, Toshihiro; Harada, Akimitsu; Sato, Hiroaki; Maruyama, Yukio; Sato, Sojun

2001-05-01

In this paper, the authors present the experimental results of using a quantitative ultrasonic diagnosis technique for human liver diseases using the fractal dimension (FD) of the shape of the power spectra (PS) of RF signals. We have developed an experimental system based on a conventional ultrasonic diagnostic system. As a result, we show that normal livers, fatty livers and liver cirrhosis can be identified using the FD values.

Effect of ultrasound frequency on the Nakagami statistics of human liver tissues.

PubMed

Tsui, Po-Hsiang; Zhou, Zhuhuang; Lin, Ying-Hsiu; Hung, Chieh-Ming; Chung, Shih-Jou; Wan, Yung-Liang

2017-01-01

The analysis of the backscattered statistics using the Nakagami parameter is an emerging ultrasound technique for assessing hepatic steatosis and fibrosis. Previous studies indicated that the echo amplitude distribution of a normal liver follows the Rayleigh distribution (the Nakagami parameter m is close to 1). However, using different frequencies may change the backscattered statistics of normal livers. This study explored the frequency dependence of the backscattered statistics in human livers and then discussed the sources of ultrasound scattering in the liver. A total of 30 healthy participants were enrolled to undergo a standard care ultrasound examination on the liver, which is a natural model containing diffuse and coherent scatterers. The liver of each volunteer was scanned from the right intercostal view to obtain image raw data at different central frequencies ranging from 2 to 3.5 MHz. Phantoms with diffuse scatterers only were also made to perform ultrasound scanning using the same protocol for comparisons with clinical data. The Nakagami parameter-frequency correlation was evaluated using Pearson correlation analysis. The median and interquartile range of the Nakagami parameter obtained from livers was 1.00 (0.98-1.05) for 2 MHz, 0.93 (0.89-0.98) for 2.3 MHz, 0.87 (0.84-0.92) for 2.5 MHz, 0.82 (0.77-0.88) for 3.3 MHz, and 0.81 (0.76-0.88) for 3.5 MHz. The Nakagami parameter decreased with the increasing central frequency (r = -0.67, p < 0.0001). However, the effect of ultrasound frequency on the statistical distribution of the backscattered envelopes was not found in the phantom results (r = -0.147, p = 0.0727). The current results demonstrated that the backscattered statistics of normal livers is frequency-dependent. Moreover, the coherent scatterers may be the primary factor to dominate the frequency dependence of the backscattered statistics in a liver.

Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin-regulated gene expression and liver failure

PubMed Central

2004-01-01

The liver plays an important role in insulin-regulated glucose homoeostasis. To study the function of the PDK1 (3-phosphoinositide-dependent protein kinase-1) signalling pathway in mediating insulin's actions in the liver, we employed CRE recombinase/loxP technology to generate L(liver)-PDK1−/− mice, which lack expression of PDK1 in hepatocytes and in which insulin failed to induce activation of PKB in liver. The L-PDK1−/− mice were not insulin-intolerant, possessed normal levels of blood glucose and insulin under normal feeding conditions, but were markedly glucose-intolerant when injected with glucose. The L-PDK1−/− mice also possessed 10-fold lower levels of hepatic glycogen compared with control littermates, and were unable to normalize their blood glucose levels within 2 h after injection of insulin. The glucose intolerance of the L-PDK1−/− mice may be due to an inability of glucose to suppress hepatic glucose output through the gluconeogenic pathway, since the mRNA encoding hepatic PEPCK (phosphoenolpyruvate carboxykinase), G6Pase (glucose-6-phosphatase) and SREBP1 (sterol-regulatory-element-binding protein 1), which regulate gluconeogenesis, are no longer controlled by feeding. Furthermore, three other insulin-controlled genes, namely IGFBP1 (insulin-like-growth-factor-binding protein-1), IRS2 (insulin receptor substrate 2) and glucokinase, were regulated abnormally by feeding in the liver of PDK1-deficient mice. Finally, the L-PDK1−/− mice died between 4–16 weeks of age due to liver failure. These results establish that the PDK1 signalling pathway plays an important role in regulating glucose homoeostasis and controlling expression of insulin-regulated genes. They suggest that a deficiency of the PDK1 pathway in the liver could contribute to development of diabetes, as well as to liver failure. PMID:15554902

VIRTUAL LIVER: AN IN SILICO FRAMEWORK FOR ANALYZING CHEMICAL-INDUCED HEPATOTOXICITY

EPA Science Inventory

The US EPA Virtual Liver (v-LiverTM) is an in silico framework for the dose-dependent perturbation of normal hepatic functions by chemicals using in vitro data. The framework consists of a computable knowledge-base (KB) to infer putative pathways in hepatotoxicity and a cellular...

Hepatic encephalopathy secondary to a splenorenal shunt that manifested a long time after a liver transplantation.

PubMed

Tomás Pujante, Paula; Jiménez Sánchez, Andrés Francisco; Iglesias Jorquera, Elena; Pons Miñano, José Antonio

2018-04-24

Splenorenal shunts are a rare cause of hyperammonemia and hepatic encephalopathy in the absence of cirrhosis. We report the case of a woman, who presented hepatic encephalopathy, with a normal functioning graft, after 14 years of liver transplantation, confirmed by liver biopsy.

Liver receptor homolog-1 is a critical determinant of methyl-pool metabolism

USDA-ARS?s Scientific Manuscript database

Balance of labile methyl groups (choline, methionine, betaine, and folate) is important for normal liver function. Quantitatively, a significant use of labile methyl groups is in the production of phosphatidylcholines (PCs), which are ligands for the nuclear liver receptor homolog-1 (LRH-1). We stud...

Analysis of global and absorption, distribution, metabolism, and elimination gene expression in the progressive stages of human nonalcoholic fatty liver disease.

PubMed

Lake, April D; Novak, Petr; Fisher, Craig D; Jackson, Jonathan P; Hardwick, Rhiannon N; Billheimer, D Dean; Klimecki, Walter T; Cherrington, Nathan J

2011-10-01

Nonalcoholic fatty liver disease (NAFLD) is characterized by a series of pathological changes that range from simple fatty liver to nonalcoholic steatohepatitis (NASH). The objective of this study is to describe changes in global gene expression associated with the progression of human NAFLD. This study is focused on the expression levels of genes responsible for the absorption, distribution, metabolism, and elimination (ADME) of drugs. Differential gene expression between three clinically defined pathological groups-normal, steatosis, and NASH-was analyzed. Genome-wide mRNA levels in samples of human liver tissue were assayed with Affymetrix GeneChip Human 1.0ST arrays. A total of 11,633 genes exhibited altered expression out of 33,252 genes at a 5% false discovery rate. Most gene expression changes occurred in the progression from steatosis to NASH. Principal component analysis revealed that hepatic disease status was the major determinant of differential ADME gene expression rather than age or sex of sample donors. Among the 515 drug transporters and 258 drug-metabolizing enzymes (DMEs) examined, uptake transporters but not efflux transporters or DMEs were significantly over-represented in the number of genes down-regulated. These results suggest that uptake transporter genes are coordinately targeted for down-regulation at the global level during the pathological development of NASH and that these patients may have decreased drug uptake capacity. This coordinated regulation of uptake transporter genes is indicative of a hepatoprotective mechanism acting to prevent accumulation of toxic intermediates in disease-compromised hepatocytes.

Intrahepatic venous anastomoses with a focus on the middle hepatic vein anastomoses in normal human livers: anatomical study on liver corrosion casts.

PubMed

Hribernik, Marija; Trotovšek, Blaž

2014-04-01

The aim of this study is to present the anatomical data about intrahepatic venous anastomoses found in normal human livers. The focus is on the middle hepatic vein (MHV) anastomoses, because their existence or non-existence could be of crucial importance in tumour resections as well as in split or living donor liver transplantations. The frequency of livers with intrahepatic venous anastomoses was determined on 164 corrosion casts and the diameter of each anastomosis was measured. Additionally, the type of connection and the position within the liver (liver segment) was determined for each MHV anastomosis. Intrahepatic venous anastomoses were found in 46 % (75/164), whereas MHV anastomoses were found in 28 % (44/164) of liver casts. Most commonly (39/44), MHV had anastomotic connections with the right hepatic vein (RHV), and also with the inferior RHV, the left hepatic vein and the short subhepatic vein. In more than three quarters of liver casts, MHV-RHV anastomoses were found in liver segment 8; in 45 % of cases, there was more than one anastomosis in this liver segment. The diameter of MHV-RHV anastomoses found in segment 8 was ≥1 mm in 90.6 % of cases. As MHV anastomoses were present in more than a quarter of all examined liver casts, we believe that detailed anatomical data presented in this article, together with up to date radiologic technics which enable even 3D reconstruction of venous anastomoses in the liver, could contribute to the clinician's decisions when planning surgical procedures.

Second harmonic sound field after insertion of a biological tissue sample

NASA Astrophysics Data System (ADS)

Zhang, Dong; Gong, Xiu-Fen; Zhang, Bo

2002-01-01

Second harmonic sound field after inserting a biological tissue sample is investigated by theory and experiment. The sample is inserted perpendicular to the sound axis, whose acoustical properties are different from those of surrounding medium (distilled water). By using the superposition of Gaussian beams and the KZK equation in quasilinear and parabolic approximations, the second harmonic field after insertion of the sample can be derived analytically and expressed as a linear combination of self- and cross-interaction of the Gaussian beams. Egg white, egg yolk, porcine liver, and porcine fat are used as the samples and inserted in the sound field radiated from a 2 MHz uniformly excited focusing source. Axial normalized sound pressure curves of the second harmonic wave before and after inserting the sample are measured and compared with the theoretical results calculated with 10 items of Gaussian beam functions.

Long-term reversal of diabetes in non-obese diabetic mice by liver-directed gene therapy.

PubMed

Ren, Binhai; O'Brien, Bronwyn A; Byrne, Michelle R; Ch'ng, Edwin; Gatt, Prudence N; Swan, M Anne; Nassif, Najah T; Wei, Ming Q; Gijsbers, Rik; Debyser, Zeger; Simpson, Ann M

2013-01-01

Type 1 diabetes (T1D) results from an autoimmune attack against the insulin-producing β-cells of the pancreas. The present study aimed to reverse T1D by gene therapy. We used a novel surgical technique, which involves isolating the liver from the circulation before the delivery of a lentiviral vector carrying furin-cleavable human insulin (INS-FUR) or empty vector to the livers of diabetic non-obese diabetic mice (NOD). This was compared with the direct injection of the vector into the portal circulation. Mice were monitored for body weight and blood glucose. Intravenous glucose tolerance tests were performed. Expression of insulin and pancreatic transcription factors was determined by the reverse transcriptase-polymerase chain reaction and immunohistochemistry and immunoelectron microscopy was used to localise insulin. Using the novel surgical technique, we achieved long-term transduction (42% efficiency) of hepatocytes, restored normoglycaemia for 150 days (experimental endpoint) and re-established normal glucose tolerance. We showed the expression of β-cell transcription factors, murine insulin, glucagon and somatostatin, and hepatic storage of insulin in granules. The expression of hepatic markers, C/EBP-β, G6PC, AAT and GLUI was down-regulated in INS-FUR-treated livers. Liver function tests remained normal, with no evidence of intrahepatic inflammation or autoimmune destruction of the insulin-secreting liver tissue. By comparison, direct injection of INS-FUR reduced blood glucose levels, and no pancreatic transdifferentiation or normal glucose tolerance was observed. This gene therapy protocol has, for the first time, permanently reversed T1D with normal glucose tolerance in NOD mice and, as such, represents a novel therapeutic strategy for the treatment of T1D. Copyright © 2013 John Wiley & Sons, Ltd.

Change in hepatic function, hemodynamics, and morphology after liver transplant. Physiological effect of therapy.

PubMed

Millikan, W J; Henderson, J M; Stewart, M T; Warren, W D; Marsh, J W; Galloway, J R; Jennings, H; Kawasaki, S; Dodson, T F; Perlino, C A

1989-05-01

Orthotopic liver transplantation (OLT) has become standard therapy for patients with acute hepatic necrosis and end-stage liver disease. This study measured change in hepatic function (galactose elimination capacity [GEC]), liver blood flow (low dose galactose clearance: flow), hepatic volume (CT scan; volume) and morphology after OLT. The aim was to measure the physiologic response after OLT and compare this response with that after selective shunt (SS) and sclerotherapy (ES) to determine which patients should receive specific therapy. Between January 1987 and November 1988, 37 patients underwent OLT. Operative mortality was 18%, which was similar to that of SS in Child's C cirrhotics. GEC and volume were less in transplant patients than in cirrhotics treated with SS or ES. GEC, flow, and volume normalized after OLT; GEC was preserved after ES and SS, but volume decreased. Three preoperative patterns were observed that can aid in selection of OLT candidates. Patients with chronic cirrhosis (chronic active hepatitis; cryptogenic) need OLT when GEC is less than or equal to 225 mg/min and volume is less than or equal to 50% normal. Patients with Budd-Chiari Syndrome require OLT if cirrhosis has evolved. Patients with sclerosing cholangitis and primary biliary cirrhosis qualify for transplants when complications of the portal hypertensive syndrome develop. The studies can also direct therapy for ES failures. Selective shunt is indicated in those patients with stable disease whose GEC is greater than or equal to 300 mg/min and liver volume is greater than 75% normal; OLT is indicated for cirrhotics with GEC that is less than 225 mg/min and liver volume that is less than 50% predicted normal.

Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice

PubMed Central

Avraham, Y; Grigoriadis, NC; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, EM

2011-01-01

BACKGROUND AND PURPOSE Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT1A, on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. EXPERIMENTAL APPROACH Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. KEY RESULTS Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. CONCLUSIONS AND IMPLICATIONS Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. PMID:21182490

Cannabidiol improves brain and liver function in a fulminant hepatic failure-induced model of hepatic encephalopathy in mice.

PubMed

Avraham, Y; Grigoriadis, Nc; Poutahidis, T; Vorobiev, L; Magen, I; Ilan, Y; Mechoulam, R; Berry, Em

2011-04-01

Hepatic encephalopathy is a neuropsychiatric disorder of complex pathogenesis caused by acute or chronic liver failure. We investigated the effects of cannabidiol, a non-psychoactive constituent of Cannabis sativa with anti-inflammatory properties that activates the 5-hydroxytryptamine receptor 5-HT(1A) , on brain and liver functions in a model of hepatic encephalopathy associated with fulminant hepatic failure induced in mice by thioacetamide. Female Sabra mice were injected with either saline or thioacetamide and were treated with either vehicle or cannabidiol. Neurological and motor functions were evaluated 2 and 3 days, respectively, after induction of hepatic failure, after which brains and livers were removed for histopathological analysis and blood was drawn for analysis of plasma liver enzymes. In a separate group of animals, cognitive function was tested after 8 days and brain 5-HT levels were measured 12 days after induction of hepatic failure. Neurological and cognitive functions were severely impaired in thioacetamide-treated mice and were restored by cannabidiol. Similarly, decreased motor activity in thioacetamide-treated mice was partially restored by cannabidiol. Increased plasma levels of ammonia, bilirubin and liver enzymes, as well as enhanced 5-HT levels in thioacetamide-treated mice were normalized following cannabidiol administration. Likewise, astrogliosis in the brains of thioacetamide-treated mice was moderated after cannabidiol treatment. Cannabidiol restores liver function, normalizes 5-HT levels and improves brain pathology in accordance with normalization of brain function. Therefore, the effects of cannabidiol may result from a combination of its actions in the liver and brain. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

Omega-3 fatty acid deficiency selectively up-regulates delta6-desaturase expression and activity indices in rat liver: prevention by normalization of omega-3 fatty acid status.

PubMed

Hofacer, Rylon; Jandacek, Ronald; Rider, Therese; Tso, Patrick; Magrisso, I Jack; Benoit, Stephen C; McNamara, Robert K

2011-09-01

This study investigated the effects of perinatal dietary omega-3 (n-3) fatty acid depletion and subsequent repletion on the expression of genes that regulate long-chain (LC) polyunsaturated fatty acid biosynthesis in rat liver and brain. It was hypothesized that chronic n-3 fatty acid deficiency would increase liver Fads1 and Fads2 messenger RNA (mRNA) expression/activity and that n-3 fatty acid repletion would normalize this response. Adult rats fed the n-3-free diet during perinatal development exhibited significantly lower erythrocyte, liver, and frontal cortex LCn-3 fatty acid composition and reciprocal elevations in LC omega-6 (n-6) fatty acid composition compared with controls (CONs) and repleted rats. Liver Fads2, but not Fads1, Elovl2, or Elovl5, mRNA expression was significantly greater in n-3-deficient (DEF) rats compared with CONs and was partially normalized in repleted rats. The liver 18:3n-6/18:2n-6 ratio, an index of delta6-desturase activity, was significantly greater in DEF rats compared with CON and repleted rats and was positively correlated with Fads2 mRNA expression among all rats. The liver 18:3n-6/18:2n-6 ratio, but not Fads2 mRNA expression, was also positively correlated with erythrocyte and frontal cortex LCn-6 fatty acid compositions. Neither Fads1 or Fads2 mRNA expression was altered in brain cortex of DEF rats. These results confirm previous findings that liver, but not brain, delta6-desaturase expression and activity indices are negatively regulated by dietary n-3 fatty acids. Copyright © 2011 Elsevier Inc. All rights reserved.

Comparison of liver volumetry on contrast‐enhanced CT images: one semiautomatic and two automatic approaches

PubMed Central

Cai, Wei; He, Baochun; Fang, Chihua

2016-01-01

This study was to evaluate the accuracy, consistency, and efficiency of three liver volumetry methods— one interactive method, an in‐house‐developed 3D medical Image Analysis (3DMIA) system, one automatic active shape model (ASM)‐based segmentation, and one automatic probabilistic atlas (PA)‐guided segmentation method on clinical contrast‐enhanced CT images. Forty‐two datasets, including 27 normal liver and 15 space‐occupying liver lesion patients, were retrospectively included in this study. The three methods — one semiautomatic 3DMIA, one automatic ASM‐based, and one automatic PA‐based liver volumetry — achieved an accuracy with VD (volume difference) of −1.69%,−2.75%, and 3.06% in the normal group, respectively, and with VD of −3.20%,−3.35%, and 4.14% in the space‐occupying lesion group, respectively. However, the three methods achieved an efficiency of 27.63 mins, 1.26 mins, 1.18 mins on average, respectively, compared with the manual volumetry, which took 43.98 mins. The high intraclass correlation coefficient between the three methods and the manual method indicated an excellent agreement on liver volumetry. Significant differences in segmentation time were observed between the three methods (3DMIA, ASM, and PA) and the manual volumetry (p<0.001), as well as between the automatic volumetries (ASM and PA) and the semiautomatic volumetry (3DMIA) (p<0.001). The semiautomatic interactive 3DMIA, automatic ASM‐based, and automatic PA‐based liver volumetry agreed well with manual gold standard in both the normal liver group and the space‐occupying lesion group. The ASM‐ and PA‐based automatic segmentation have better efficiency in clinical use. PACS number(s): 87.55.‐x PMID:27929487

Comparison of liver volumetry on contrast-enhanced CT images: one semiautomatic and two automatic approaches.

PubMed

Cai, Wei; He, Baochun; Fan, Yingfang; Fang, Chihua; Jia, Fucang

2016-11-08

This study was to evaluate the accuracy, consistency, and efficiency of three liver volumetry methods- one interactive method, an in-house-developed 3D medical Image Analysis (3DMIA) system, one automatic active shape model (ASM)-based segmentation, and one automatic probabilistic atlas (PA)-guided segmentation method on clinical contrast-enhanced CT images. Forty-two datasets, including 27 normal liver and 15 space-occupying liver lesion patients, were retrospectively included in this study. The three methods - one semiautomatic 3DMIA, one automatic ASM-based, and one automatic PA-based liver volumetry - achieved an accuracy with VD (volume difference) of -1.69%, -2.75%, and 3.06% in the normal group, respectively, and with VD of -3.20%, -3.35%, and 4.14% in the space-occupying lesion group, respectively. However, the three methods achieved an efficiency of 27.63 mins, 1.26 mins, 1.18 mins on average, respectively, compared with the manual volumetry, which took 43.98 mins. The high intraclass correlation coefficient between the three methods and the manual method indicated an excel-lent agreement on liver volumetry. Significant differences in segmentation time were observed between the three methods (3DMIA, ASM, and PA) and the manual volumetry (p < 0.001), as well as between the automatic volumetries (ASM and PA) and the semiautomatic volumetry (3DMIA) (p < 0.001). The semiautomatic interactive 3DMIA, automatic ASM-based, and automatic PA-based liver volum-etry agreed well with manual gold standard in both the normal liver group and the space-occupying lesion group. The ASM- and PA-based automatic segmentation have better efficiency in clinical use. © 2016 The Authors.

Tumor-associated autoantibodies are useful biomarkers in immunodiagnosis of α-fetoprotein-negative hepatocellular carcinoma.

PubMed

Wang, Ting; Liu, Mei; Zheng, Su-Jun; Bian, Dan-Dan; Zhang, Jin-Yan; Yao, Jia; Zheng, Qing-Fen; Shi, A-Meng; Li, Wen-Han; Li, Lu; Chen, Yu; Wang, Jin-Hai; Duan, Zhong-Ping; Dong, Lei

2017-05-21

To determine the prevalence and diagnostic value of autoantibodies in α-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC). Fifty-six serum samples from AFP-negative HCC cases, 86 from AFP-positive HCC cases, 168 from chronic liver disease cases, and 59 from normal human controls were included in this study. Autoantibodies to nucleophosmin (NPM)1, 14-3-3zeta and mouse double minute 2 homolog (MDM2) proteins in AFP-negative HCC serum were evaluated by enzyme-linked immunosorbent assay. Partially positive sera were further evaluated by western blotting. Immunohistochemistry was used to detect the expression of three tumor-associated antigens (TAAs) in AFP-negative HCC and normal control tissues. The frequency of autoantibodies to the three TAAs in AFP-negative HCC sera was 21.4%, 19.6% and 19.6%, which was significantly higher than in the chronic liver disease cases and normal human controls ( P < 0.01) as well as AFP-positive HCC cases. The sensitivity of the three autoantibodies for diagnosis of AFP-negative HCC ranged from 19.6% to 21.4%, and the specificity was approximately 95%. When the three autoantibodies were combined, the sensitivity reached 30.4% and the specificity reached 91.6%. Autoantibodies to NPM1, 14-3-3zeta and MDM2 may be useful biomarkers for immunodiagnosis of AFP-negative HCC.

Tumor-associated autoantibodies are useful biomarkers in immunodiagnosis of α-fetoprotein-negative hepatocellular carcinoma

PubMed Central

Wang, Ting; Liu, Mei; Zheng, Su-Jun; Bian, Dan-Dan; Zhang, Jin-Yan; Yao, Jia; Zheng, Qing-Fen; Shi, A-Meng; Li, Wen-Han; Li, Lu; Chen, Yu; Wang, Jin-Hai; Duan, Zhong-Ping; Dong, Lei

2017-01-01

AIM To determine the prevalence and diagnostic value of autoantibodies in α-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC). METHODS Fifty-six serum samples from AFP-negative HCC cases, 86 from AFP-positive HCC cases, 168 from chronic liver disease cases, and 59 from normal human controls were included in this study. Autoantibodies to nucleophosmin (NPM)1, 14-3-3zeta and mouse double minute 2 homolog (MDM2) proteins in AFP-negative HCC serum were evaluated by enzyme-linked immunosorbent assay. Partially positive sera were further evaluated by western blotting. Immunohistochemistry was used to detect the expression of three tumor-associated antigens (TAAs) in AFP-negative HCC and normal control tissues. RESULTS The frequency of autoantibodies to the three TAAs in AFP-negative HCC sera was 21.4%, 19.6% and 19.6%, which was significantly higher than in the chronic liver disease cases and normal human controls (P < 0.01) as well as AFP-positive HCC cases. The sensitivity of the three autoantibodies for diagnosis of AFP-negative HCC ranged from 19.6% to 21.4%, and the specificity was approximately 95%. When the three autoantibodies were combined, the sensitivity reached 30.4% and the specificity reached 91.6%. CONCLUSION Autoantibodies to NPM1, 14-3-3zeta and MDM2 may be useful biomarkers for immunodiagnosis of AFP-negative HCC. PMID:28596685

Gallbladder removal - slideshow

MedlinePlus

... ency/presentations/100021.htm Gallbladder removal - Series—Normal anatomy To use the ... gallbladder is located in the abdomen, on the right side, underneath the liver. The gallbladder stores bile produced by the liver, ...

Protein tyrosine phosphatase of liver regeneration-1 is required for normal timing of cell cycle progression during liver regeneration

PubMed Central

Jiao, Yang; Ye, Diana Z.; Li, Zhaoyu; Teta-Bissett, Monica; Peng, Yong; Taub, Rebecca; Greenbaum, Linda E.

2014-01-01

Protein tyrosine phosphatase of liver regeneration-1 (Prl-1) is an immediate-early gene that is significantly induced during liver regeneration. Several in vitro studies have suggested that Prl-1 is important for the regulation of cell cycle progression. To evaluate its function in liver regeneration, we ablated the Prl-1 gene specifically in mouse hepatocytes using the Cre-loxP system. Prl-1 mutant mice (Prl-1loxP/loxP;AlfpCre) appeared normal and fertile. Liver size and metabolic function in Prl-1 mutants were comparable to controls, indicating that Prl-1 is dispensable for liver development, postnatal growth, and hepatocyte differentiation. Mutant mice demonstrated a delay in DNA synthesis after 70% partial hepatectomy, although ultimate liver mass restoration was not affected. At 40 h posthepatectomy, reduced protein levels of the cell cycle regulators cyclin E, cyclin A2, cyclin B1, and cyclin-dependent kinase 1 were observed in Prl-1 mutant liver. Investigation of the major signaling pathways involved in liver regeneration demonstrated that phosphorylation of protein kinase B (AKT) and signal transducer and activator of transcription (STAT) 3 were significantly reduced at 40 h posthepatectomy in Prl-1 mutants. Taken together, this study provides evidence that Prl-1 is required for proper timing of liver regeneration after partial hepatectomy. Prl-1 promotes G1/S progression via modulating expression of several cell cycle regulators through activation of the AKT and STAT3 signaling pathway. PMID:25377314

Cultured mycelium Cordyceps sinensis protects liver sinusoidal endothelial cells in acute liver injured mice.

PubMed

Peng, Yuan; Chen, Qian; Yang, Tao; Tao, Yanyan; Lu, Xiong; Liu, Chenghai

2014-03-01

Cultured mycelium Cordyceps sinensis (CMCS) was widely used for a variety of diseases including liver injury, the current study aims to investigate the protective effects of CMCS on liver sinusoidal endothelial cells (LSECs) in acute injury liver and related action mechanisms. The mice were injected intraperitoneally with lipopolysaccharide (LPS) and D-galactosamine (D-GalN). 39 male BABL/c mice were randomly divided into four groups: normal control, model control, CMCS treatment and 1,10-phenanthroline treatment groups. The Serum liver function parameters including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were assayed with the commercial kit. The inflammation and scaffold structure in liver were stained with hematoxylin and eosin and silver staining respectively. The LSECs and sub-endothelial basement membrane were observed with the scanning and transmission electronic microscope. The protein expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in liver were analyzed with Western blotting. Expression of von Willebrand factor (vWF) was investigated with immunofluorescence staining. The lipid peroxidation indicators including antisuperoxideanion (ASAFR), hydroxyl free radical (·OH), superoxide dismutase (SOD), malondialdehyde and glutathione S-transferase (GST) were determined with kits, and matrix metalloproteinase-2 and 9 (MMP-2/9) activities in liver were analyzed with gelatin zymography and in situ fluorescent zymography respectively. The model mice had much higher serum levels of ALT and AST than the normal mice. Compared to that in the normal control, more severe liver inflammation and hepatocyte apoptosis, worse hepatic lipid peroxidation demonstrated by the increased ASAFR, ·OH and MDA, but decreased SOD and GST, increased MMP-2/9 activities and VCAM-1, ICAM-1 and vWF expressions, which revealed obvious LSEC injury and scaffold structure broken, were shown in the model control. Compared with the model group, CMCS and 1,10-phenanthroline significantly improved serum ALT/AST, attenuated hepatic inflammation and improved peroxidative injury in liver, decreased MMP-2/9 activities in liver tissue, improved integration of scaffold structure, and decreased protein expression of VCAM-1 and ICAM-1. CMCS could protect LSECs from injury and maintain the microvasculature integration in acute injured liver of mice induced by LPS/D-GalN. Its action mechanism was associated with the down-regulation of MMP-2/9 activities and inhibition of peroxidation in injured liver.

The selective effect of plasma activated medium in an in vitro co-culture of liver cancer and normal cells

NASA Astrophysics Data System (ADS)

Duan, J.; Lu, X.; He, G.

2017-01-01

In this work, a co-culture system with liver cancer cell line HepG2 and normal cell line L02 is used to investigate the selective effect on cancer and normal cells by plasma activated medium (PAM), which is closer to the real environment where cancer cells develop. Besides, the co-culture system is a better model to study the selective effect than the widely used separate culture systems, where the cancer cell line and normal cell line are cultured independently. By using the co-culture system, it is found that there is an optimum dose of PAM to induce significant cancer cell apoptosis while keeping minimum damage to normal cells.

Non-alcoholic fatty liver disease (NAFLD) and significant hepatic fibrosis defined by non-invasive assessment in patients with type 2 diabetes.

PubMed

Sobhonslidsuk, Abhasnee; Pulsombat, Akharawit; Kaewdoung, Piyaporn; Petraksa, Supanna

2015-01-01

Non-alcoholic fatty liver disease (NAFLD), the most common liver problem in diabetes, is a risk factor for liver cancer. Diabetes, high body mass index (BMI) and old age can all contribute to NAFLD progression. Transient elastography (TE) is used for non-invasive fibrosis assessment. To identify the prevalence of NAFLD and significant hepatic fibrosis in diabetic patients and to assess associated factors. One hundred and forty-one diabetic and 60 normal subjects were screened. Fatty liver was diagnosed when increased hepatic echogenicity and vascular blunting were detected by ultrasonography. Liver stiffness measurement (LSM) representing hepatic fibrosis was assessed by TE. LSM ≥7 kPa was used to define significant hepatic fibrosis. Four cases were excluded due to positive hepatitis B viral markers and failed TE. Diabetic patients had higher BMI, systolic blood pressure, waist circumference and fasting glucose levels than normal subjects. Fatty liver was diagnosed in 82 (60.7%) diabetic patients but in none of the normal group. BMI (OR: 1.31; 95%CI: 1.02-1.69; p=0.038) and alanine aminotransferase (ALT)(OR: 1.14; 95%CI: 1.05-1.23; p=0.002) were associated with NAFLD. Diabetic patients with NAFLD had higher LSM than those without [5.99 (2.4) vs 4.76 (2.7) kPa, p=0.005)]. Significant hepatic fibrosis was more common in diabetic patients than in normal subjects [22 (16.1%) vs 1 (1.7%), p=0.002]. Aspartate aminotransferase (AST)(OR: 1.24; 95%CI: 1.07-1.42; p=0.003) was associated with significant hepatic fibrosis. Sixty and sixteen percent of diabetic patients were found to have NAFLD and significant hepatic fibrosis. High BMI and ALT levels are the predictors of NAFLD, and elevated AST level is associated with significant hepatic fibrosis.

Increased expression of stathmin and elongation factor 1α in precancerous nodules with telomere dysfunction in hepatitis B viral cirrhotic patients

PubMed Central

2014-01-01

Background Telomere dysfunction is important in carcinogenesis, and recently, stathmin and elongation factor 1α (EF1α) were reported to be up-regulated in telomere dysfunctional mice. Methods In the present study, the expression levels of stathmin and EF1α in relation to telomere length, telomere dysfunction-induced foci (TIF), γ-H2AX, and p21WAF1/CIP1 expression were assessed in specimens of hepatitis B virus (HBV)-related multistep hepatocarcinogenesis, including 13 liver cirrhosis specimens, 14 low-grade dysplastic nodules (DN), 17 high-grade DNs, and 14 hepatocellular carcinomas (HCC). Five normal liver specimens were used as controls. TIF were analyzed by telomere fluorescent in situ hybridization (FISH) combined with immunostaining, while the protein expressions of stathmin, EF1α, γ-H2AX, and p21WAF1/CIP1 were detected by immunohistochemistry. Result The expressions of stathmin and EF1α gradually increased as multistep hepatocarcinogenesis progressed, showing the highest levels in HCC. Stathmin mRNA levels were higher in high-grade DNs than normal liver and liver cirrhosis, whereas EF1α mRNA expression did not show such a difference. The protein expressions of stathmin and EF1α were found in DNs of precancerous lesions, whereas they were absent or present at very low levels in normal liver and liver cirrhosis. Stathmin histoscores were higher in high-grade DNs and low-grade DNs than in normal liver (all, P < 0.05). EF1α histoscores were higher in high-grade DNs than in normal liver and liver cirrhosis (all, P < 0.05). Stathmin mRNA levels and histoscores, as well as EF1α histoscores (but not mRNA levels), were positively correlated with telomere shortening and γ-H2AX labeling index (all, P < 0.05). EF1α histoscores were also positively correlated with TIF (P < 0.001). Significantly greater inactivation of p21WAF1/CIP1 was observed in low-grade DNs, high-grade DNs, and HCC, compared to liver cirrhosis (all, P < 0.05). p21WAF1/CIP1 labeling index was inversely correlated with TIF, stathmin mRNA level, and EF1α histoscore (all, P < 0.05). Conclusion Stathmin and EF1α are suggested to be closely related to telomere dysfunction, DNA damage, and inactivation of p21WAF1/CIP1 in HBV-related multistep hepatocarcinogenesis. Accordingly, assessment of stathmin and EF1α levels as a reflection of telomere dysfunction may be helpful in evaluating the biological characteristics of precancerous hepatic nodules in hepatitis B viral cirrhotic patients. PMID:24885363

Increased expression of stathmin and elongation factor 1α in precancerous nodules with telomere dysfunction in hepatitis B viral cirrhotic patients.

PubMed

Ahn, Ei Yong; Yoo, Jeong Eun; Rhee, Hyungjin; Kim, Myung Soo; Choi, Junjeong; Ko, Jung Eun; Lee, Jee San; Park, Young Nyun

2014-05-31

Telomere dysfunction is important in carcinogenesis, and recently, stathmin and elongation factor 1α (EF1α) were reported to be up-regulated in telomere dysfunctional mice. In the present study, the expression levels of stathmin and EF1α in relation to telomere length, telomere dysfunction-induced foci (TIF), γ-H2AX, and p21WAF1/CIP1 expression were assessed in specimens of hepatitis B virus (HBV)-related multistep hepatocarcinogenesis, including 13 liver cirrhosis specimens, 14 low-grade dysplastic nodules (DN), 17 high-grade DNs, and 14 hepatocellular carcinomas (HCC). Five normal liver specimens were used as controls. TIF were analyzed by telomere fluorescent in situ hybridization (FISH) combined with immunostaining, while the protein expressions of stathmin, EF1α, γ-H2AX, and p21WAF1/CIP1 were detected by immunohistochemistry. The expressions of stathmin and EF1α gradually increased as multistep hepatocarcinogenesis progressed, showing the highest levels in HCC. Stathmin mRNA levels were higher in high-grade DNs than normal liver and liver cirrhosis, whereas EF1α mRNA expression did not show such a difference. The protein expressions of stathmin and EF1α were found in DNs of precancerous lesions, whereas they were absent or present at very low levels in normal liver and liver cirrhosis. Stathmin histoscores were higher in high-grade DNs and low-grade DNs than in normal liver (all, P<0.05). EF1α histoscores were higher in high-grade DNs than in normal liver and liver cirrhosis (all, P<0.05). Stathmin mRNA levels and histoscores, as well as EF1α histoscores (but not mRNA levels), were positively correlated with telomere shortening and γ-H2AX labeling index (all, P<0.05). EF1α histoscores were also positively correlated with TIF (P<0.001). Significantly greater inactivation of p21WAF1/CIP1 was observed in low-grade DNs, high-grade DNs, and HCC, compared to liver cirrhosis (all, P<0.05). p21WAF1/CIP1 labeling index was inversely correlated with TIF, stathmin mRNA level, and EF1α histoscore (all, P<0.05). Stathmin and EF1α are suggested to be closely related to telomere dysfunction, DNA damage, and inactivation of p21WAF1/CIP1 in HBV-related multistep hepatocarcinogenesis. Accordingly, assessment of stathmin and EF1α levels as a reflection of telomere dysfunction may be helpful in evaluating the biological characteristics of precancerous hepatic nodules in hepatitis B viral cirrhotic patients.

Haptoglobin blood test

MedlinePlus

... Chronic liver disease Blood buildup under the skin (hematoma) Liver disease Transfusion reaction Higher-than-normal levels ... may include: Excessive bleeding Fainting or feeling lightheaded Hematoma (blood accumulating under the skin) Infection (a slight ...

XYLITOL IMPROVES ANTI-OXIDATIVE DEFENSE SYSTEM IN SERUM, LIVER, HEART, KIDNEY AND PANCREAS OF NORMAL AND TYPE 2 DIABETES MODEL OF RATS.

PubMed

Chukwuma, Chika Ifeanyi; Islam, Shahidul

2017-05-01

The present study investigated the anti-oxidative effects of xylitol both in vitro and in vivo in normal and type 2 diabetes (T2D) rat model. Free radical scavenging and ferric reducing potentials of different concentrations of xylitol were investigated in vitro. For in vivo study, six weeks old male Sprague-Dawley rats were divided into four groups, namely: Normal Control (NC), Diabetic Control (DBC), Normal Xylitol (NXYL) and Diabetic Xylitol (DXYL). T2D was induced in the DBC and DXYL groups. After the confirmation of diabetes, a 10% xylitol solution was supplied instead of drinking water to NXYL and DXYL, while normal drinking water was supplied to NC and DBC ad libitum. After five weeks intervention period, the animals were sacri- ficed and thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) concentrations as well as superoxide dismutase, catalase glutathione reductase and glutathione peroxidase activities were determined in the liver, heart, kidney, pancreatic tissues and serum samples. Xylitol exhibited significant (p < 0.05) in vitro nitric oxide and hydroxyl radical scavenging and ferric reducing activities. In vivo study revealed significant (p < 0.05) reduction in TBARS concentrations in the xylitol consuming groups compared to their respective controls. Significant (p < 0.05) increase in GSH levels and antioxidant enzyme activities were observed in analyzed tissues and serum of xylitol-fed animals compared to their respective controls. Results of this study indicate that xylitol has strong anti-oxidative potential against T2D-associated oxidative stress. Hence, xylitol can be used as a potential supplement in diabetic foods and food products.

The pharmacokinetics of a single rectal dose of paracetamol (40 mg x kg(-1)) in children with liver disease.

PubMed

Cormack, C R H; Sudan, S; Addison, R; Keating, J; Sherwood, R A; Ashley, E M C; Howell, Tanya

2006-04-01

The aim of our study was to measure the serum paracetamol concentrations achieved following a single rectal loading dose of 40 mg x kg(-1) in children with chronic liver disease. We recruited 17 children (3-15 years, 10.6-75 kg) undergoing minor surgical procedures under general anesthesia. Paracetamol was administered at the end of surgery and blood samples were taken for analysis at 2, 3, 4, 6 and 8 h postdose. The mean Cmax of 11.4 mg x l(-1) [coefficient of variation (CV) 66%] was achieved at a Tmax of 2.7 h (CV 42%). The relative bioavailability (F) of the suppository formulation was not estimated, but clearance (Cl/F) estimates 0.73 l x kg(-1) x h(-1) (CV 87%) and time-concentration profiles for these children were similar to the normal pediatric population. There are currently no biologic markers available for monitoring possible hepatotoxicity in this cohort of patients with liver disease, but our data suggest that a single-dose suppository is a satisfactory analgesic alternative.

Stiffness of hyaluronic acid gels containing liver extracellular matrix supports human hepatocyte function and alters cell morphology.

PubMed

Deegan, Daniel B; Zimmerman, Cynthia; Skardal, Aleksander; Atala, Anthony; Shupe, Thomas D

2015-03-01

Tissue engineering and cell based liver therapies have utilized primary hepatocytes with limited success due to the failure of hepatocytes to maintain their phenotype in vitro. In order to overcome this challenge, hyaluronic acid (HA) cell culture substrates were formulated to closely mimic the composition and stiffness of the normal liver cellular microenvironment. The stiffness of the substrate was modulated by adjusting HA hydrogel crosslinking. Additionally, the repertoire of bioactive molecules within the HA substrate was bolstered by supplementation with normal liver extracellular matrix (ECM). Primary human hepatocyte viability and phenotype were determined over a narrow physiologically relevant range of substrate stiffnesses from 600 to 4600Pa in both the presence and absence of liver ECM. Cell attachment, viability, and organization of the actin cytoskeleton improved with increased stiffness up to 4600Pa. These differences were not evident in earlier time points or substrates containing only HA. However, gene expression for the hepatocyte markers hepatocyte nuclear factor 4 alpha (HNF4α) and albumin significantly decreased on the 4600Pa stiffness at day 7 indicating that cells may not have maintained their phenotype long-term at this stiffness. Function, as measured by albumin secretion, varied with both stiffness and time in culture and peaked at day 7 at the 1200Pa stiffness, slightly below the stiffness of normal liver ECM at 3000Pa. Overall, gel stiffness affected primary human hepatocyte cell adhesion, functional marker expression, and morphological characteristics dependent on both the presence of liver ECM in gel substrates and time in culture. Copyright © 2015 Elsevier Ltd. All rights reserved.

MRI-determined liver proton density fat fraction, with MRS validation: Comparison of regions of interest sampling methods in patients with type 2 diabetes.

PubMed

Vu, Kim-Nhien; Gilbert, Guillaume; Chalut, Marianne; Chagnon, Miguel; Chartrand, Gabriel; Tang, An

2016-05-01

To assess the agreement between published magnetic resonance imaging (MRI)-based regions of interest (ROI) sampling methods using liver mean proton density fat fraction (PDFF) as the reference standard. This retrospective, internal review board-approved study was conducted in 35 patients with type 2 diabetes. Liver PDFF was measured by magnetic resonance spectroscopy (MRS) using a stimulated-echo acquisition mode sequence and MRI using a multiecho spoiled gradient-recalled echo sequence at 3.0T. ROI sampling methods reported in the literature were reproduced and liver mean PDFF obtained by whole-liver segmentation was used as the reference standard. Intraclass correlation coefficients (ICCs), Bland-Altman analysis, repeated-measures analysis of variance (ANOVA), and paired t-tests were performed. ICC between MRS and MRI-PDFF was 0.916. Bland-Altman analysis showed excellent intermethod agreement with a bias of -1.5 ± 2.8%. The repeated-measures ANOVA found no systematic variation of PDFF among the nine liver segments. The correlation between liver mean PDFF and ROI sampling methods was very good to excellent (0.873 to 0.975). Paired t-tests revealed significant differences (P < 0.05) with ROI sampling methods that exclusively or predominantly sampled the right lobe. Significant correlations with mean PDFF were found with sampling methods that included higher number of segments, total area equal or larger than 5 cm(2) , or sampled both lobes (P = 0.001, 0.023, and 0.002, respectively). MRI-PDFF quantification methods should sample each liver segment in both lobes and include a total surface area equal or larger than 5 cm(2) to provide a close estimate of the liver mean PDFF. © 2015 Wiley Periodicals, Inc.

Sonographic Assessment of the Normal Dimensions of Liver, Spleen, and Kidney in Healthy Children at Tertiary Care Hospital.

PubMed

Thapa, N B; Shah, S; Pradhan, A; Rijal, K; Pradhan, A; Basnet, S

2015-01-01

Background Ultrasonography is one of the most common imaging modality to measure dimensions of visceral organs in children. However, the normal limit of size of visceral organs according to age and body habitus has not been specified in the standard textbooks. This might result in under detection of organomegaly in pediatrics population. Objective The objective of this study was to determine the normal range of dimensions for the liver, spleen, and kidney in healthy children. Method This is prospective cross-sectional, hospital-based study done at Tertiary-care teaching hospital. Participants included 272 pediatric subjects (152 male and 120 female) with normal physical or sonographic findings who were examined because of problems unrelated to the measured organs. The subjects were one month to 15 year (180 months) old. All measured organs were sonographically normal. Relationships of the dimensions of these organs with sex, age, body weight and height were investigated. Limits of normal dimensions of these organs were defined. Result Normal length of liver, kidneys and spleen were obtained sonographically for 272 children (152 male [55.9%] and 120 female [44.1%]) in the age group from 1 months to 15 (180 months) years. The mean age was 45.78 months (SD, 44.73). The measured dimensions of all these organs showed highest correlation with height and age so the descriptive analysis of the organ dimensions (mean, minimum, and maximum values, SD and 5th and 95th percentiles) were expressed in 10 age groups along with height range of the included children. The mean length of right kidney was shorter than the left kidney length, and the difference was statistically significant (p = 0.001). Conclusion This study provides practical and comprehensive guide to the normal visceral organ dimension in pediatric population. The normal range limit of the liver, spleen, and kidney determined in this study could be used as a reference in daily practice in local radiology clinics.

Chronic arsenic toxicity in sheep of Kurdistan province, western Iran.

PubMed

Keshavarzi, Behnam; Seradj, Afsaneh; Akbari, Zahra; Moore, Farid; Shahraki, Alireza Rahmani; Pourjafar, Mehrdad

2015-07-01

After the detection of arsenic (As) toxicity in sheep from Ebrahim-abad and Babanazar villages in Kurdistan province, the concentration of this element in drinking water, cultivated soil, alfalfa hay, wool, and blood samples was evaluated. Total As concentrations ranged from 119 to 310 μg/L in drinking water, 46.70-819.20 mg/kg in soil 1.90-6.90 mg/kg in vegetation 1.56-10.79 mg/kg in sheep's wool, and 86.30-656 μg/L in blood samples. These very high As contents, in all parts of the biogeochemical cycle, exceed the recommended normal range for this element compared with a control area. Results indicate that As has moved through all compartments of the biogeochemical cycle by way of direct or indirect pathways. The present investigation illustrated decreased packed cell volume and hemoglobin in sheep from the As-contaminated zone. It was concluded that sheep from the contaminated areas suffer from anemia. Chronic As exposure of the liver was determined by liver function tests. For this purpose, blood aspartate transaminase (AST) and alanine transaminase (ALT) were measured. The results show that serum ALT and AST activities are increased significantly (p < 0.01) in the sheep population exposed to As in the contaminated zone. Moreover, chronic As exposure causes injury to hepatocytes and damages the liver.

Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

PubMed

Yang, Tao; Liu, Shan; Wang, Chang-Hong; Tao, Yan-Yan; Zhou, Hua; Liu, Cheng-Hai

2015-10-10

Fuzheng Huayu recipe (FZHY) is a herbal product for the treatment of liver fibrosis approved by the Chinese State Food and Drug Administration (SFDA), but its pharmacokinetics and tissue distribution had not been investigated. In this study, the liver fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN), and FZHY was given orally to the model and normal rats. The plasma pharmacokinetics and tissue distribution profiles of four major bioactive components from FZHY were analyzed in the normal and fibrotic rat groups using an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results revealed that the bioavailabilities of danshensu (DSS), salvianolic acid B (SAB) and rosmarinic acid (ROS) in liver fibrotic rats increased 1.49, 3.31 and 2.37-fold, respectively, compared to normal rats. There was no obvious difference in the pharmacokinetics of amygdalin (AMY) between the normal and fibrotic rats. The tissue distribution of DSS, SAB, and AMY trended to be mostly in the kidney and lung. The distribution of DSS, SAB, and AMY in liver tissue of the model rats was significantly decreased compared to the normal rats. Significant differences in the pharmacokinetics and tissue distribution profiles of DSS, ROS, SAB and AMY were observed in rats with hepatic fibrosis after oral administration of FZHY. These results provide a meaningful basis for developing a clinical dosage regimen in the treatment of hepatic fibrosis by FZHY. Copyright © 2015 Elsevier B.V. All rights reserved.

Non-Invasive Electrical Impedance Tomography for Multi-Scale Detection of Liver Fat Content

PubMed Central

Luo, Yuan; Abiri, Parinaz; Zhang, Shell; Chang, Chih-Chiang; Kaboodrangi, Amir H.; Li, Rongsong; Sahib, Ashish K.; Bui, Alex; Kumar, Rajesh; Woo, Mary; Li, Zhaoping; Packard, René R. Sevag; Tai, Yu-Chong; Hsiai, Tzung K.

2018-01-01

Introduction: Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). While Magnetic Resonance Imaging (MRI) is a non-invasive gold standard to detect fatty liver, we demonstrate a low-cost and portable electrical impedance tomography (EIT) approach with circumferential abdominal electrodes for liver conductivity measurements. Methods and Results: A finite element model (FEM) was established to simulate decremental liver conductivity in response to incremental liver lipid content. To validate the FEM simulation, we performed EIT imaging on an ex vivo porcine liver in a non-conductive tank with 32 circumferentially-embedded electrodes, demonstrating a high-resolution output given a priori information on location and geometry. To further examine EIT capacity in fatty liver detection, we performed EIT measurements in age- and gender-matched New Zealand White rabbits (3 on normal, 3 on high-fat diets). Liver conductivity values were significantly distinct following the high-fat diet (p = 0.003 vs. normal diet, n=3), accompanied by histopathological evidence of hepatic fat accumulation. We further assessed EIT imaging in human subjects with MRI quantification for fat volume fraction based on Dixon procedures, demonstrating average liver conductivity of 0.331 S/m for subjects with low Body-Mass Index (BMI < 25 kg/m²) and 0.286 S/m for high BMI (> 25 kg/m²). Conclusion: We provide both the theoretical and experimental framework for a multi-scale EIT strategy to detect liver lipid content. Our preliminary studies pave the way to enhance the spatial resolution of EIT as a marker for fatty liver disease and metabolic syndrome. PMID:29556346

Radiation Exposure Alters Expression of Metabolic Enzyme Genes in Mice

NASA Technical Reports Server (NTRS)

Wotring, V. E.; Mangala, L. S.; Zhang, Y.; Wu, H.

2011-01-01

Most administered pharmaceuticals are metabolized by the liver. The health of the liver, especially the rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. Most pharmaceuticals are metabolized by the liver, and clinically-used medication doses are given with normal liver function in mind. A drug overdose can result in the case of a liver that is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism, we want to understand the effects of spaceflight on the enzymes of the liver and exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments. Additionally, it has been previous noted that pre-exposure to small radiation doses seems to confer protection against later and larger radiation doses. This protective power of pre-exposure has been called a priming effect or radioadaptation. This study is an effort to examine the drug metabolizing effects of radioadaptation mechanisms that may be triggered by early exposure to low radiation doses.

Cu isotopic signature in blood serum of liver transplant patients: a follow-up study

NASA Astrophysics Data System (ADS)

Lauwens, Sara; Costas-Rodríguez, Marta; van Vlierberghe, Hans; Vanhaecke, Frank

2016-07-01

End-stage liver disease (ESLD) is life-threatening and liver transplantation (LTx) is the definitive treatment with good outcomes. Given the essential role of hepatocytes in Cu homeostasis, the potential of the serum Cu isotopic composition for monitoring a patient’s condition post-LTx was evaluated. For this purpose, high-precision Cu isotopic analysis of blood serum of ESLD patients pre- and post-LTx was accomplished via multi-collector ICP-mass spectrometry (MC-ICP-MS). The Cu isotopic composition of the ESLD patients was fractionated in favour of the lighter isotope (by about -0.50‰). Post-LTx, a generalized normalization of the Cu isotopic composition was observed for the patients with normal liver function, while it remained light when this condition was not reached. A strong decrease in the δ65Cu value a longer term post-LTx seems to indicate the recurrence of liver failure or cancer. The observed trend in favour of the heavier Cu isotopic composition post-LTx seems to be related with the restored biosynthetic capacity of the liver, the restored hepatic metabolism and/or the restored biliary secretion pathways. Thus, Cu isotopic analysis could be a valuable tool for the follow-up of liver transplant patients and for establishing the potential recurrence of liver failure.

S-ADENOSYLMETHIONINE IN LIVER HEALTH, INJURY, AND CANCER

PubMed Central

Lu, Shelly C.; Mato, José M.

2013-01-01

S-adenosylmethionine (AdoMet, also known as SAM and SAMe) is the principal biological methyl donor synthesized in all mammalian cells but most abundantly in the liver. Biosynthesis of AdoMet requires the enzyme methionine adenosyltransferase (MAT). In mammals, two genes, MAT1A that is largely expressed by normal liver and MAT2A that is expressed by all extrahepatic tissues, encode MAT. Patients with chronic liver disease have reduced MAT activity and AdoMet levels. Mice lacking Mat1a have reduced hepatic AdoMet levels and develop oxidative stress, steatohepatitis, and hepatocellular carcinoma (HCC). In these mice, several signaling pathways are abnormal that can contribute to HCC formation. However, injury and HCC also occur if hepatic AdoMet level is excessive chronically. This can result from inactive mutation of the enzyme glycine N-methyltransferase (GNMT). Children with GNMT mutation have elevated liver transaminases, and Gnmt knockout mice develop liver injury, fibrosis, and HCC. Thus a normal hepatic AdoMet level is necessary to maintain liver health and prevent injury and HCC. AdoMet is effective in cholestasis of pregnancy, and its role in other human liver diseases remains to be better defined. In experimental models, it is effective as a chemopreventive agent in HCC and perhaps other forms of cancer as well. PMID:23073625

Hepatic cholesterol ester hydrolase in human liver disease.

PubMed

Simon, J B; Poon, R W

1978-09-01

Human liver contains an acid cholesterol ester hydrolase (CEH) of presumed lysosomal origin, but its significance is unknown. We developed a modified CEH radioassay suitable for needle biopsy specimens and measured hepatic activity of this enzyme in 69 patients undergoing percutaneous liver biopsy. Histologically normal livers hydrolyzed 5.80 +/- 0.78 SEM mumoles of cholesterol ester per hr per g of liver protein (n, 10). Values were similar in alcoholic liver disease (n, 17), obstructive jaundice (n, 9), and miscellaneous hepatic disorders (n, 21). In contrast, mean hepatic CEH activity was more than 3-fold elevated in 12 patients with acute hepatitis, 21.05 +/- 2.45 SEM mumoles per hr per g of protein (P less than 0.01). In 2 patients studied serially, CEH returned to normal as hepatitis resolved. CEH activity in all patients paralleled SGOT levels (r, 0.84; P less than 0.01). There was no correlation with serum levels of free or esterified cholesterol nor with serum activity of lecithin-cholesterol acyltransferase, the enzyme responsible for cholesterol esterification in plasma. These studies confirm the presence of CEH activity in human liver and show markedly increased activity in acute hepatitis. The pathogenesis and clinical significance of altered hepatic CEH activity in liver disease require further study.

Cu isotopic signature in blood serum of liver transplant patients: a follow-up study

PubMed Central

Lauwens, Sara; Costas-Rodríguez, Marta; Van Vlierberghe, Hans; Vanhaecke, Frank

2016-01-01

End-stage liver disease (ESLD) is life-threatening and liver transplantation (LTx) is the definitive treatment with good outcomes. Given the essential role of hepatocytes in Cu homeostasis, the potential of the serum Cu isotopic composition for monitoring a patient’s condition post-LTx was evaluated. For this purpose, high-precision Cu isotopic analysis of blood serum of ESLD patients pre- and post-LTx was accomplished via multi-collector ICP-mass spectrometry (MC-ICP-MS). The Cu isotopic composition of the ESLD patients was fractionated in favour of the lighter isotope (by about −0.50‰). Post-LTx, a generalized normalization of the Cu isotopic composition was observed for the patients with normal liver function, while it remained light when this condition was not reached. A strong decrease in the δ65Cu value a longer term post-LTx seems to indicate the recurrence of liver failure or cancer. The observed trend in favour of the heavier Cu isotopic composition post-LTx seems to be related with the restored biosynthetic capacity of the liver, the restored hepatic metabolism and/or the restored biliary secretion pathways. Thus, Cu isotopic analysis could be a valuable tool for the follow-up of liver transplant patients and for establishing the potential recurrence of liver failure. PMID:27468898

Cu isotopic signature in blood serum of liver transplant patients: a follow-up study.

PubMed

Lauwens, Sara; Costas-Rodríguez, Marta; Van Vlierberghe, Hans; Vanhaecke, Frank

2016-07-29

End-stage liver disease (ESLD) is life-threatening and liver transplantation (LTx) is the definitive treatment with good outcomes. Given the essential role of hepatocytes in Cu homeostasis, the potential of the serum Cu isotopic composition for monitoring a patient's condition post-LTx was evaluated. For this purpose, high-precision Cu isotopic analysis of blood serum of ESLD patients pre- and post-LTx was accomplished via multi-collector ICP-mass spectrometry (MC-ICP-MS). The Cu isotopic composition of the ESLD patients was fractionated in favour of the lighter isotope (by about -0.50‰). Post-LTx, a generalized normalization of the Cu isotopic composition was observed for the patients with normal liver function, while it remained light when this condition was not reached. A strong decrease in the δ(65)Cu value a longer term post-LTx seems to indicate the recurrence of liver failure or cancer. The observed trend in favour of the heavier Cu isotopic composition post-LTx seems to be related with the restored biosynthetic capacity of the liver, the restored hepatic metabolism and/or the restored biliary secretion pathways. Thus, Cu isotopic analysis could be a valuable tool for the follow-up of liver transplant patients and for establishing the potential recurrence of liver failure.

Mushroom insoluble polysaccharides prevent carbon tetrachloride-induced hepatotoxicity in rat.

PubMed

Nada, Somaia A; Omara, Enayat A; Abdel-Salam, Omar M E; Zahran, Hanan G

2010-11-01

The aim of the present study was to investigate the effect of mushroom insoluble non-starch polysaccharides (MINSP) on the carbon tetrachloride (CCl(4))-induced hepatic damage in rat. MINSP (100 and 200 mg/kg) administered daily orally for 15 days before CCl(4) (1.5 ml/kg). The effect of MINSP treatment was also examined in normal rats. Normal groups treated with MINSP showed significant decrease in serum activities of the liver enzymes, lipid peroxides and nitric oxide (NO) in the liver. Reduced glutathione (GSH) and total proteins (TP) contents in liver homogenate also increased after treatment with only MINSP for 15 days. In CCl(4)-treated rats, significant elevation in serum liver enzymes, increased lipid peroxides and NO in the liver, and depletion of hepatic-GSH level were observed. Pre-treatment with MINSP significantly ameliorated the tested parameters when compared with CCl(4)-treated group. It improved the antioxidant activity of the liver in a dose-dependent manner. Histopathological examination of hepatic tissue revealed that MINSP administration alone protected hepatocytes from the damage induced by CCl(4). MINSP are safe; it could be used as fat replacer in processing low fat diet. MINSP represents a good functional food and liver supporter for patient suffering from various liver diseases. Copyright © 2010 Elsevier Ltd. All rights reserved.

The Chemokine Receptor CXCR6 Is Required for the Maintenance of Liver Memory CD8+ T Cells Specific for Infectious Pathogens

PubMed Central

Tse, Sze-Wah; Radtke, Andrea J.; Espinosa, Diego A.; Cockburn, Ian A.; Zavala, Fidel

2014-01-01

It is well established that immunization with attenuated malaria sporozoites induces CD8+ T cells that eliminate parasite-infected hepatocytes. Liver memory CD8+ T cells induced by immunization with parasites undergo a unique differentiation program and have enhanced expression of CXCR6. Following immunization with malaria parasites, CXCR6-deficient memory CD8+ T cells recovered from the liver display altered cell-surface expression markers as compared to their wild-type counterparts, but they exhibit normal cytokine secretion and expression of cytotoxic mediators on a per-cell basis. Most importantly, CXCR6-deficient CD8+ T cells migrate to the liver normally after immunization with Plasmodium sporozoites or vaccinia virus, but a few weeks later their numbers severely decrease in this organ, losing their capacity to inhibit malaria parasite development in the liver. These studies are the first to show that CXCR6 is critical for the development and maintenance of protective memory CD8+ T cells in the liver. PMID:24823625

Experimental Model for Successful Liver Cell Therapy by Lenti TTR-YapERT2 Transduced Hepatocytes with Tamoxifen Control of Yap Subcellular Location

PubMed Central

Yovchev, Mladen; Jaber, Fadi L.; Lu, Zhonglei; Patel, Shachi; Locker, Joseph; Rogler, Leslie E.; Murray, John W.; Sudol, Marius; Dabeva, Mariana D.; Zhu, Liang; Shafritz, David A.

2016-01-01

Liver repopulation by transplanted hepatocytes has not been achieved previously in a normal liver microenvironment. Here we report that adult rat hepatocytes transduced ex vivo with a lentivirus expressing a human YapERT2 fusion protein (hYapERT2) under control of the hepatocyte-specific transthyretin (TTR) promoter repopulate normal rat liver in a tamoxifen-dependent manner. Transplanted hepatocytes expand very slowly but progressively to produce 10% repopulation at 6 months, showing clusters of mature hepatocytes that are fully integrated into hepatic parenchyma, with no evidence for dedifferentiation, dysplasia or malignant transformation. Thus, we have developed the first vector designed to regulate the growth control properties of Yap that renders it capable of producing effective cell therapy. The level of liver repopulation achieved has significant translational implications, as it is 2-3x the level required to cure many monogenic disorders of liver function that have no underlying hepatic pathology and is potentially applicable to diseases of other tissues and organs. PMID:26763940

Methimazole-induced liver injury overshadowed by methylprednisolone pulse therapy: Case report.

PubMed

Abramavicius, Silvijus; Velickiene, Dzilda; Kadusevicius, Edmundas

2017-09-01

Treatment choices are limited, when deciding how to manage thyrotoxicosis and moderate to severe Graves ophthalmopathy (GO) with suspected optic nerve damage in patients with elevated liver transaminase levels. The situation become even more complicated, if methimazole induced hepatotoxicity is suspected and intravenous methylprednisolone is co-administrated. A 74-year-old woman presented with spontaneous retro-bulbar pain, eyelid swelling and inconstant diplopia. Thyrotoxicosis and severe GO with suspected optic nerve damage and drug induced liver injury (DILI). Intravenous methylprednisolone pulse therapy was administered to treat GO and methimazole was continued for thyrotoxicosis. Dose of methimazole was reduced after exclusion of concurrent infection and active liver disease. The GO symptoms (eyelid swelling, sight loss, proptosis, retro-bulbar pain, diplopia) markedly decreased after the treatment course. Liver transaminases spontaneously returned to normal ranges and remained normal during the next 12 months until the Graves' disease until the treatment was completed. 1. The interaction of methimazole and methylprednisolone may result in DILI. 2. In a patient without concomitant liver diseases MP can be continued if the methimazole dose is reduced if no other treatment options are available.

Clinical and surgical anatomy of the liver: a review for clinicians.

PubMed

Juza, Ryan M; Pauli, Eric M

2014-07-01

The liver is the largest gland in the body occupying 2.5% of total body weight and providing a host of functions necessary for maintaining normal physiological homeostasis. Despite the complexity of its functions, the liver has a homogenous appearance, making hepatic anatomy a challenging topic of discussion. To address this issue, scholars have devoted time to establishing a framework for describing hepatic anatomy to aid clinicians. Work by the anatomist Sir James Cantlie provided the first accurate division between the right and left liver in 1897. The French surgeon and anatomist Claude Couinaud provided additional insight by introducing the Couinaud segments on the basis of hepatic vasculature. These fundamental studies provided a framework for medical and surgical discussions of hepatic anatomy and were essential for the advancement of modern medicine. In this article, the authors review the normal anatomy and physiology of the liver with a view to enhancing the clinician's knowledge base. They also provide a convenient model to assist with understanding and discussion of liver anatomy. Copyright © 2014 Wiley Periodicals, Inc.

Comparison on the physico-chemical and nutritional qualities of normal and abnormal colored fresh chicken liver.

PubMed

Xiong, Guoyuan; Gao, Xueqin; Zheng, Haibo; Li, Xin; Xu, Xinglian; Zhou, Guanghong

2017-06-01

This study evaluated the differences of physico-chemical and nutritional qualities between abnormal colored chicken livers (ANCCLs) and normal colored chicken livers (NCCLs) and the safety of the both livers. Compared with NCCLs, ANCCLs were lower in protein, water contents (P < 0.01), pH and pigment contents (P < 0.05). NCCLs contained higher polyunsaturated fatty acid (PUFA) and saturated fatty acids (SFA) (P < 0.05). The PUFA/SFA ratio of NCCLs was 0.453, higher (P < 0.05) than that of ANCCLs. The contents of alanine, valine, tyrosine, lysine and histidine in NCCLs were higher (P < 0.05) than in ANCCLs. The contents of K, Na, P, Cu, Fe and Se of NCCLs were higher (P < 0.05), but the Ca content was lower (P < 0.05). The content of the heavy metals (As, Hg, Pb and Cd) of the two types of livers complied with food safety requirements. Although NCCLs had higher nutritional value than ANCCLs, both livers were acceptable for human consumption. © 2016 Japanese Society of Animal Science.

The clinical value of 201Tl per rectum scintigraphy in the work-up of patients with alcoholic liver disease.

PubMed

Urbain, D; Reding, P; Georges, B; Thys, O; Ham, H R

1986-01-01

The clinical value of thallium 201 per rectum scintigraphy in the work-up of patients with alcoholic liver disease was evaluated using data obtained in 104 patients. The 25th min ratio of heart to liver activities was used as an index of portal systemic shunting. This ratio was found to be normal in alcoholic patients with normal liver biopsy and also in those presenting only steatosis. It was slightly higher in patients with liver fibrosis and significantly higher values were observed in patients with liver cirrhosis. High values of the ratio were associated with a higher risk of portal systemic encephalopathy and/or gastrointestinal bleeding. The prognostic value of the test was supported by the fact that good correlations were observed between the ratio and widely accepted prognostic scores such as the Child score or the Orrego index. Moreover, high ratios were associated with an increased mortality risk at one year. We conclude that this simple test is interesting in the screening of cirrhotics at risk of encephalopathy, gastrointestinal hemorrhage, or early death.

Measuring functioning hepatocytes using Tc-99m galactosylneoglycoalbumin (Tc-NGA)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stadalnik, R.C.; Vera, D.R.; Quadro, R.E.

1984-01-01

Tc-NGA is a synthetic ligand which binds only to hepatic binding protein (HBP), a receptor found only in the liver. It exhibits the properties of high tissue specificity, affinity-dependent uptake, and dose-dependent uptake. Tc-NGA provides an opportunity to study the functioning hepatocyte. The authors evaluated the usefulness of this technique in patients with hepatitis and hepatoma. After intravenous administration of 5 mCi Tc-NGA, dynamic images were acquired for 30 minutes followed by static views. Estimates of HBP concentrations were obtained by kinetic analysis of blood and liver time-activity curves. Kinetic estimates (reduced chi-squares < 3.0) of HBP correlated well withmore » the clinical course and histology. For example, a patient with hepatoma whose calculated receptor population (functioning hepatocytes) was 3.0 +- 0.9 x 10/sup -7/ mole, which is the normal range, is doing well undergoing chemotherapy. Liver biopsy demonstrated normal liver tissue except for the hepatoma. Another patient with hepatoma who had a severely depressed receptor population, 1.2 +- 0.2 x 10/sup -8/ mole, expired one week after the study. Liver biopsy demonstrated practically no normal tissue. Thus, by means of a complementary, receptor radiopharmaceutical and mathematical model, one should be able to quantitatively follow hepatocyte function and predict response to a therapeutic regimen.« less

Effect of Vernonia amygdalina Del. Leaf Ethanolic Extract on Intoxicated Male Wistar Rats Liver

PubMed Central

Iwo, Maria Immaculata; Sjahlim, Sergia Louisa; Rahmawati, Siti Farah

2017-01-01

Vernonia amygdalina has been shown to have antioxidant activity, and is also expected to have hepatoprotective activity. This study was conducted to study the effect of V. amygdalina ethanol extracts on intoxicated rat livers. Fresh leaves were extracted in ethanol, and the hepatoprotective activity was tested on male Wistar rats induced with a combination of isoniazid (INH) and rifampicin. Parameters observed were the activity of the enzyme alanine transferase (ALT), serum albumin levels, liver index, and histopathological of the rat liver. The results showed that 50 and 100 mg/kg rat body weight of V. amygdalina ethanol extracts could prevent liver intoxication, starting on day 14. Based on serum albumin concentrations and ALT activity, the high dose extract (100 mg/kg) was more potent as a hepatoprotective agent compared to the extract at a low dose (50 mg/kg). The group of rats treated with a high dose extract showed normal liver index compared to the positive control. Through histology examination, the liver of rats treated with a high dose extract (100 mg/kg) showed minimal liver cell structure damage, and showed similar patterns to the normal rat. Based on these results, it can be concluded that V. amygdalina ethanol extracts can be used to protect the liver in a combination of INH and rifampicin as antituberculosis treatment. PMID:28333116

Effect of Vernonia amygdalina Del. Leaf Ethanolic Extract on Intoxicated Male Wistar Rats Liver.

PubMed

Iwo, Maria Immaculata; Sjahlim, Sergia Louisa; Rahmawati, Siti Farah

2017-03-23

Vernonia amygdalina has been shown to have antioxidant activity, and is also expected to have hepatoprotective activity. This study was conducted to study the effect of V. amygdalina ethanol extracts on intoxicated rat livers. Fresh leaves were extracted in ethanol, and the hepatoprotective activity was tested on male Wistar rats induced with a combination of isoniazid (INH) and rifampicin. Parameters observed were the activity of the enzyme alanine transferase (ALT), serum albumin levels, liver index, and histopathological of the rat liver. The results showed that 50 and 100 mg/kg rat body weight of V. amygdalina ethanol extracts could prevent liver intoxication, starting on day 14. Based on serum albumin concentrations and ALT activity, the high dose extract (100 mg/kg) was more potent as a hepatoprotective agent compared to the extract at a low dose (50 mg/kg). The group of rats treated with a high dose extract showed normal liver index compared to the positive control. Through histology examination, the liver of rats treated with a high dose extract (100 mg/kg) showed minimal liver cell structure damage, and showed similar patterns to the normal rat. Based on these results, it can be concluded that V. amygdalina ethanol extracts can be used to protect the liver in a combination of INH and rifampicin as antituberculosis treatment.

Low protein and high-energy diet: a possible natural cause of fatty liver hemorrhagic syndrome in caged White Leghorn laying hens.

PubMed

Rozenboim, I; Mahato, J; Cohen, N A; Tirosh, O

2016-03-01

Fatty liver hemorrhagic syndrome (FLHS) is a metabolic condition of chicken and other birds caused by diverse nutritional, hormonal, environmental, and metabolic factors. Here we studied the effect of different diet composition on the induction of FLHS in single comb White Leghorn (WL) Hy-line laying hens. Seventy six (76) young WL (26 wks old) laying hens and 69 old hens (84 wks old) of the same breed were each divided into 4 treatment groups and provided 4 different diet treatments. The diet treatments included: control (C), 17.5% CP, 3.5% fat (F); normal protein, high fat (HF), 17.5% CP, 7% F; low protein, normal fat (LP), 13% CP, 3.5% F; and low protein, high fat (LPHF), 13% CP, 6.5% F. The diets containing high fat also had a higher ME of 3,000 kcal/kg of feed while the other 2 diets with normal fat had a regular lower amount of ME (2750 kcal/kg). Hen-day egg production (HDEP), ADFI, BW, egg weight, plasma enzymes indicating liver damage (alkaline phosphatase [ALP], aspartate aminotransferase [AST], gamma-glutamyl transferase [GGT]), liver and abdominal fat weight, liver color score (LCS), liver hemorrhagic score (LHS), liver fat content (LFC), liver histological examination, lipid peroxidation product in the liver, and genes indicating liver inflammation were evaluated. HDEP, ADFI, BW, and egg weight were significantly decreased in the LPHF diet group, while egg weight was also decreased in the LP diet group. In the young hens (LPHF group), ALP was found significantly higher at 30 d of diet treatment and was numerically higher throughout the experiment, while AST was significantly higher at 105 d of treatment. LCS, LHS, and LFC were significantly higher in young hens on the LPHF diet treatment. A liver histological examination shows more lipid vacuolization in the LPHF treatment diet. HF or LP alone had no significant effect on LFC, LHS, or LCS. We suggest that LP in the diet with higher ME from fat can be a possible natural cause for predisposing laying hens to FLHS. © 2016 Poultry Science Association Inc.

Preventive effects of dexmedetomidine on the liver in a rat model of acid-induced acute lung injury.

PubMed

Sen, Velat; Güzel, Abdulmenap; Şen, Hadice Selimoğlu; Ece, Aydın; Uluca, Unal; Söker, Sevda; Doğan, Erdal; Kaplan, İbrahim; Deveci, Engin

2014-01-01

The aim of this study was to examine whether dexmedetomidine improves acute liver injury in a rat model. Twenty-eight male Wistar albino rats weighing 300-350 g were allocated randomly to four groups. In group 1, normal saline (NS) was injected into the lungs and rats were allowed to breathe spontaneously. In group 2, rats received standard ventilation (SV) in addition to NS. In group 3, hydrochloric acid was injected into the lungs and rats received SV. In group 4, rats received SV and 100 µg/kg intraperitoneal dexmedetomidine before intratracheal HCl instillation. Blood samples and liver tissue specimens were examined by biochemical, histopathological, and immunohistochemical methods. Acute lung injury (ALI) was found to be associated with increased malondialdehyde (MDA), total oxidant activity (TOA), oxidative stress index (OSI), and decreased total antioxidant capacity (TAC). Significantly decreased MDA, TOA, and OSI levels and significantly increased TAC levels were found with dexmedetomidine injection in group 4 (P < 0.05). The highest histologic injury scores were detected in group 3. Enhanced hepatic vascular endothelial growth factor (VEGF) expression and reduced CD68 expression were found in dexmedetomidine group compared with the group 3. In conclusion, the presented data provide the first evidence that dexmedetomidine has a protective effect on experimental liver injury induced by ALI.

Illustrated field guide for assessing external and internal anomalies in fish

USGS Publications Warehouse

Smith, Stephen B.; Donahue, Anne P.; Lipkin, Robin J.; Blazer, Vicki; Schmitt, Christopher J.; Goede, Ronald W.

2002-01-01

Procedures are described for processing fish for examination of external and internal anomalies and pathologies indicative of exposure to environmental contaminants and other peturbations. For the procedures described here, fish are captured (preferably by electrofishing) and held alive until processing (generally < 1 h). Fish are weighed, measured, and necropsied, and a scale sample is obtained from for age determination. Information is given for the collection and preservation of tissue samples for histopathological analysis. Photographs of most abnormalities are included along with normal conditions for easier identification of external (oral, head, eye, gill, opercula, and fin) and internal (liver, spleen, gonad, and kidney) anomalies. The report also includes recommendations for record keeping, sample labeling, and shipping records, equipment, supplies,and samples. A list of suggested equipment and supplies for field processing is included as are instructions for cleaning equipment.

Identification and isolation of adult liver stem/progenitor cells.

PubMed

Tanaka, Minoru; Miyajima, Atsushi

2012-01-01

Hepatoblasts are considered to be liver stem/progenitor cells in the fetus because they propagate and differentiate into two types of liver epithelial cells, hepatocytes and cholangiocytes. In adults, oval cells that emerge in severely injured liver are considered facultative hepatic stem/progenitor cells. However, the nature of oval cells has remained unclear for long time due to the lack of a method to isolate them. It has also been unclear whether liver stem/progenitor cells exist in normal adult liver. Recently, we and others have successfully identified oval cells and adult liver stem/progenitor cells. Here, we describe the identification and isolation of mouse liver stem/progenitor cells by utilizing antibodies against specific cell surface marker molecules.

Analysis of transthyretin in human serum by capillary zone electrophoresis electrospray ionization time-of-flight mass spectrometry. Application to familial amyloidotic polyneuropathy type I.

PubMed

Pont, Laura; Benavente, Fernando; Barbosa, José; Sanz-Nebot, Victoria

2015-06-01

Transthyretin (TTR) is known to misfold and aggregate, causing different types of amyloidosis. Familial amyloidotic polyneuropathy type I (FAP-I), which is the most common hereditary systemic amyloidosis, is associated with a TTR variant that presents a single amino acid substitution of valine for methionine at position 30 (Met 30). To screen for TTR-related amyloidosis rapidly and reliably, we have developed a novel procedure based on the analysis of monomers from the homotetrameric protein (∼56 kDa). First, we established a CZE-ESI-TOF-MS method to detect wild-type (normal) TTR with or without several PTMs, as well as an extra minor isoform in TTR standard solutions. Later, a sample pretreatment based on immunoprecipitation (IP) and centrifugal filtration was optimized to analyze serum samples from healthy controls and FAP-I patients (including an asymptomatic patient, a symptomatic patient, a liver-transplanted patient with the specific mutation, and a patient originally without the mutation who received a liver transplant from an FAP-I patient (iatrogenic FAP-I)). The mutant TTR (Met 30) variant with a relative molecular mass 32.07 higher than the wild-type TTR was found in the asymptomatic, the symptomatic and the iatrogenic FAP-I patients, who interestingly also presented the same concentration ratio between both variants of TTR (abnormal and normal). In contrast, as in the healthy controls, the abnormal TTR variant was not detected in the liver-transplanted patient with the specific mutation, which confirms the effectiveness of the treatment. The proposed procedure could be regarded as a suitable screening system for individuals with suspected TTR amyloidosis, and to gain insight into TTR structure, to understand the mechanism underlying the disease. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Protective effects of Sapindus mukorossi Gaertn against fatty liver disease induced by high fat diet in rats.

PubMed

Peng, Qiuxian; Zhang, Qin; Xiao, Wei; Shao, Meng; Fan, Qin; Zhang, Hongwei; Zou, Yukai; Li, Xin; Xu, Wenxue; Mo, Zhixian; Cai, Hongbing

2014-07-18

Study the effects of alcohol extract of Sapindus mukorossi Gaertn (AESM) on the metabolism of blood fat, morphology of fenestrated liver sinusoidal endothelial cells (LSEC), and the ultrastructure of liver cells of the rats with non-alcoholic fatty liver disease (NAFLD). Divide SD rats into control group, model group, simvastatin (7.2 mg/kg) group, and S.mukorossi Gaertn group with high dosage (0.5 g/kg), moderate dosage (0.1 g/kg), and low dosage (0.05 g/kg). After feeding with fat-rich nutrients for 3 weeks and establishing the model of hepatic adipose, conduct intragastric administration and provide the rats with fat-rich nutrients at the same time. At the 43rd day, take blood sample and measure aminotransferase and different indexes of blood fat; take hepatic tissue for pathological section, and observe the hepatic morphological patterns under light microscope; obtain and fix the hepatic tissue after injecting perfusate into the body, and observe the changes of fenestrated LSEC under scanning electron microscope; observe the ultrastructure of liver cells under transmission electron microscope. High-dosage alcohol extracts of S.mukorossi Gaertn can alleviate the AST, ALT, TC, TG, LDL, γ-GT, and ALP level, as well as raise the HDL and APN level in the serum of NAFLD-rat model. In addition, through the observation from light microscope and electron microscopes, the morphology of the hepatic tissue and liver cells as well as the recovery of the fenestrated LSEC in the treatment group has become normal. Alcohol extracts of S.mukorossi Gaertn can regulate the level of blood fat and improve the pathological changes of the hepatic tissues in NAFLD-rat model, which demonstrates the effects of down-regulating fat level and protecting liver. Copyright © 2014. Published by Elsevier Inc.

Effect of nutritional status on oxidative stress in an ex vivo perfused rat liver.

PubMed

Stadler, Michaela; Nuyens, Vincent; Seidel, Laurence; Albert, Adelin; Boogaerts, Jean G

2005-11-01

Normothermic ischemia-reperfusion is a determinant in liver injury occurring during surgical procedures, ischemic state, and multiple organ failure. The preexisting nutritional status of the liver might contribute to the extent of tissue injury and primary nonfunction. The aim of this study was to determine the role of starvation on hepatic ischemia-reperfusion injury in normal rat livers. Rats were randomly divided into two groups: one had free access to food, the other was fasted for 16 h. The portal vein was cannulated, and the liver was removed and perfused in a closed ex vivo system. Two modes of perfusion were applied in each series of rats, fed and fasting. In the ischemia-reperfusion mode, the experiment consisted of perfusion for 15 min, warm ischemia for 60 min, and reperfusion during 60 min. In the nonischemia mode, perfusion was maintained during the 135-min study period. Five rats were included in each experimental condition, yielding a total of 20 rats. Liver enzymes, potassium, glucose, lactate, free radicals, i.e., dienes and trienes, and cytochrome c were analyzed in perfusate samples. The proportion of glycogen in hepatocytes was determined in tissue biopsies. Transaminases, lactate dehydrogenase, potassium, and free radical concentrations were systematically higher in fasting rats in both conditions, with and without ischemia. Cytochrome c was higher after reperfusion in the fasting rats. Glucose and lactate concentrations were greater in the fed group. The glycogen content decreased in both groups during the experiment but was markedly lower in the fasting rats. In fed rats, liver injury was moderate, whereas hepatocytes integrity was notably impaired both after continuous perfusion and warm ischemia in fasting animals. Reduced glycogen store in hepatocytes may explain reduced tolerance.

Insulin resistance index (HOMA-IR) in the differentiation of patients with non-alcoholic fatty liver disease and healthy individuals.

PubMed

Salgado, Ana Lúcia Farias de Azevedo; Carvalho, Luciana de; Oliveira, Ana Claudia; Santos, Virgínia Nascimento dos; Vieira, Jose Gilberto; Parise, Edison Roberto

2010-01-01

Due to its good correlation to glycemic clamp, HOMA-IR has been widely utilized as insulin resistance index in clinical and epidemiological studies involving non-alcoholic fatty liver disease carriers. However, values used for this parameter have shown large variability. To identify the HOMA-IR cut value that best distinguishes non-diabetic non-alcoholic fatty liver disease patients from a control group. One hundred sixteen non-alcoholic fatty liver disease patients were studied, diagnosed by clinical, biochemical, and liver image or biopsy criteria, and 88 healthy individuals, without any liver disease and testing for oral glucose tolerance within normality. These groups did not differ in age and gender. All were submitted to oral glucose tolerance test and blood samples were collected for glucose and insulin measurements by immunofluorometric method. HOMA-IR was calculated according to the formula: fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5. NAFLD patients showed higher insulin, glycemia, and HOMA-IR values than control group, even when excluding glucose intolerant and diabetes mellitus patients by their glycemic curves. HOMA-IR 75th percentile for control group was 1.78 and the best area under the curve index was obtained for HOMA-IR values of 2.0 [AUC= 0.840 (0.781-0.899 CI 95%), sensitivity (Se): 85%, specificity (Sp): 83%] while value 2.5 showed best specificity without important loss in sensitivity [AUC=0,831 (0.773-0.888) Se = 72%, Sp = 94%]. HOMA-IR values above or equal to 2.0 or 2.5 show enhanced diagnostic value in distinguishing non-alcoholic fatty liver disease carriers from control group individuals.

Prolactin promotes normal liver growth, survival, and regeneration in rodents: effects on hepatic IL-6, suppressor of cytokine signaling-3, and angiogenesis.

PubMed

Moreno-Carranza, Bibiana; Goya-Arce, Maite; Vega, Claudia; Adán, Norma; Triebel, Jakob; López-Barrera, Fernando; Quintanar-Stéphano, Andrés; Binart, Nadine; Martínez de la Escalera, Gonzalo; Clapp, Carmen

2013-10-01

Prolactin (PRL) is a potent liver mitogen and proangiogenic hormone. Here, we used hyperprolactinemic rats and PRL receptor-null mice (PRLR(-/-)) to study the effect of PRL on liver growth and angiogenesis before and after partial hepatectomy (PH). Liver-to-body weight ratio (LBW), hepatocyte and sinusoidal endothelial cell (SEC) proliferation, and hepatic expression of VEGF were measured before and after PH in hyperprolactinemic rats, generated by placing two anterior pituitary glands (AP) under the kidney capsule. Also, LBW and hepatic expression of IL-6, as well as suppressor of cytokine signaling-3 (SOCS-3), were evaluated in wild-type and PRLR(-/-) mice before and after PH. Hyperprolactinemia increased the LBW, the proliferation of hepatocytes and SECs, and VEGF hepatic expression. Also, liver regeneration was increased in AP-grafted rats and was accompanied by elevated hepatocyte and SEC proliferation, and VEGF expression compared with nongrafted controls. Lowering circulating PRL levels with CB-154, an inhibitor of AP PRL secretion, prevented AP-induced stimulation of liver growth. Relative to wild-type animals, PRLR(-/-) mice had smaller livers, and soon after PH, they displayed an approximately twofold increased mortality and elevated and reduced hepatic IL-6 and SOCS-3 expression, respectively. However, liver regeneration was improved in surviving PRLR(-/-) mice. PRL stimulates normal liver growth, promotes survival, and regulates liver regeneration by mechanisms that may include hepatic downregulation of IL-6 and upregulation of SOCS-3, increased hepatocyte proliferation, and angiogenesis. PRL contributes to physiological liver growth and has potential clinical utility for ensuring survival and regulating liver mass in diseases, injuries, or surgery of the liver.

Risk of Acute Liver Failure in Patients With Drug-Induced Liver Injury: Evaluation of Hy's Law and a New Prognostic Model.

PubMed

Lo Re, Vincent; Haynes, Kevin; Forde, Kimberly A; Goldberg, David S; Lewis, James D; Carbonari, Dena M; Leidl, Kimberly B F; Reddy, K Rajender; Nezamzadeh, Melissa S; Roy, Jason; Sha, Daohang; Marks, Amy R; De Boer, Jolanda; Schneider, Jennifer L; Strom, Brian L; Corley, Douglas A

2015-12-01

Few studies have evaluated the ability of laboratory tests to predict risk of acute liver failure (ALF) among patients with drug-induced liver injury (DILI). We aimed to develop a highly sensitive model to identify DILI patients at increased risk of ALF. We compared its performance with that of Hy's Law, which predicts severity of DILI based on levels of alanine aminotransferase or aspartate aminotransferase and total bilirubin, and validated the model in a separate sample. We conducted a retrospective cohort study of 15,353 Kaiser Permanente Northern California members diagnosed with DILI from 2004 through 2010, liver aminotransferase levels above the upper limit of normal, and no pre-existing liver disease. Thirty ALF events were confirmed by medical record review. Logistic regression was used to develop prognostic models for ALF based on laboratory results measured at DILI diagnosis. External validation was performed in a sample of 76 patients with DILI at the University of Pennsylvania. Hy's Law identified patients that developed ALF with a high level of specificity (0.92) and negative predictive value (0.99), but low level of sensitivity (0.68) and positive predictive value (0.02). The model we developed, comprising data on platelet count and total bilirubin level, identified patients with ALF with a C statistic of 0.87 (95% confidence interval [CI], 0.76-0.96) and enabled calculation of a risk score (Drug-Induced Liver Toxicity ALF Score). We found a cut-off score that identified patients at high risk patients for ALF with a sensitivity value of 0.91 (95% CI, 0.71-0.99) and a specificity value of 0.76 (95% CI, 0.75-0.77). This cut-off score identified patients at high risk for ALF with a high level of sensitivity (0.89; 95% CI, 0.52-1.00) in the validation analysis. Hy's Law identifies patients with DILI at high risk for ALF with low sensitivity but high specificity. We developed a model (the Drug-Induced Liver Toxicity ALF Score) based on platelet count and total bilirubin level that identifies patients at increased risk for ALF with high sensitivity. Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.

Neurologic Manifestations of Chronic Liver Disease and Liver Cirrhosis.

PubMed

Sureka, Binit; Bansal, Kalpana; Patidar, Yashwant; Rajesh, S; Mukund, Amar; Arora, Ankur

2015-01-01

The normal functioning of brain is intimately as well as intricately interrelated with normal functioning of the liver. Liver plays a critical role of not only providing vital nutrients to the brain but also of detoxifying the splanchnic blood. Compromised liver function leads to insufficient detoxification thus allowing neurotoxins (such as ammonia, manganese, and other chemicals) to enter the cerebral circulation. In addition, portosystemic shunts, which are common accompaniments of advanced liver disease, facilitate free passage of neurotoxins into the cerebral circulation. The problem is compounded further by additional variables such as gastrointestinal tract bleeding, malnutrition, and concurrent renal failure, which are often associated with liver cirrhosis. Neurologic damage in chronic liver disease and liver cirrhosis seems to be multifactorial primarily attributable to the following: brain accumulation of ammonia, manganese, and lactate; altered permeability of the blood-brain barrier; recruitment of monocytes after microglial activation; and neuroinflammation, that is, direct effects of circulating systemic proinflammatory cytokines such as tumor necrosis factor, IL-1β, and IL-6. Radiologist should be aware of the conundrum of neurologic complications that can be encountered in liver disease, which include hepatic encephalopathy, hepatocerebral degeneration, hepatic myelopathy, cirrhosis-related parkinsonism, cerebral infections, hemorrhage, and osmotic demyelination. In addition, neurologic complications can be exclusive to certain disorders, for example, Wilson disease, alcoholism (Wernicke encephalopathy, alcoholic cerebellar degeneration, Marchiafava-Bignami disease, etc). Radiologist should be aware of their varied clinical presentation and radiological appearances as the diagnosis is not always straightforward. Copyright © 2015 Mosby, Inc. All rights reserved.

Identification and Characterization of Mesenchymal-Epithelial Progenitor-Like Cells in Normal and Injured Rat Liver

PubMed Central

Liu, Daqing; Yovchev, Mladen I.; Zhang, Jinghang; Alfieri, Alan A.; Tchaikovskaya, Tatyana; Laconi, Ezio; Dabeva, Mariana D.

2016-01-01

In normal rat liver, thymocyte antigen 1 (Thy1) is expressed in fibroblasts/myofibroblasts and in some blood progenitor cells. Thy1-expressing cells also accumulate in the liver during impaired liver regeneration. The origin and nature of these cells are not well understood. By using RT-PCR analysis and immunofluorescence microscopy, we describe the presence of rare Thy1+ cells in the liver lobule of normal animals, occasionally forming small collections of up to 20 cells. These cells constitute a small portion (1.7% to 1.8%) of nonparenchymal cells and reveal a mixed mesenchymal-epithelial phenotype, expressing E-cadherin, cytokeratin 18, and desmin. The most potent mitogens for mesenchymal-epithelial Thy1+ cells in vitro are the inflammatory cytokines interferon γ, IL-1, and platelet-derived growth factor-BB, which are not produced by Thy1+ cells. Thy1+ cells express all typical mesenchymal stem cell and hepatic progenitor cell markers and produce growth factor and cytokine mRNA (Hgf, Il6, Tgfa, and Tweak) for proteins that maintain oval cell growth and differentiation. Under appropriate conditions, mesenchymal-epithelial cells differentiate in vitro into hepatocyte-like cells. In this study, we show that the adult rat liver harbors a small pool of endogenous mesenchymal-epithelial cells not recognized previously. In the quiescent state, these cells express both mesenchymal and epithelial cell markers. They behave like hepatic stem cells/progenitors with dual phenotype, exhibiting high plasticity and long-lasting proliferative activity. PMID:25447047

Liver enzyme elevation induced by hyperemesis gravidarum: aetiology, diagnosis and treatment.

PubMed

Conchillo, J M; Pijnenborg, J M A; Peeters, P; Stockbrügger, R W; Fevery, J; Koek, G H

2002-10-01

Three primigravidae were admitted during the first trimester of pregnancy with nausea, vomiting, ketonuria and liver enzyme elevation of varying severity. A 29-year-old woman had elevated aminotransferase values, at levels described in the literature (ASAT 112 U/l, ALAT 214 U/l). The second patient, a woman aged 26 years, had undergone in vitro fertilisation and showed higher liver enzyme elevation, including the total bilirubin level (ASAT 250 U/l, ALAT 474 U/l, total bilirubin 59.8 micromol/l). A 30-year-old woman had extremely high aminotransferase values (ASAT 705 U/l, ALAT 1674 U/l) and she is the first reported patient with ALAT values exceeding 1,000 U/l in connection with hyperemesis gravidarum. Gallstone disease, viral and drug-induced hepatitis were excluded in all of these patients. Treatment was symptomatic and the abnormal liver tests returned to normal promptly when the vomiting resolved, independent of the severity of liver enzyme elevation. The pregnancies proceeded normally and all three patients delivered healthy babies.

Simultaneous liver, pancreas-duodenum and kidney transplantation in a patient with hepatitis B cirrhosis, uremia and insulin dependent diabetes mellitus.

PubMed

Li, Jiang; Guo, Qing-Jun; Cai, Jin-Zhen; Pan, Cheng; Shen, Zhong-Yang; Jiang, Wen-Tao

2017-12-07

Simultaneous liver, pancreas-duodenum, and kidney transplantation has been rarely reported in the literature. Here we present a new and more efficient en bloc technique that combines classic orthotopic liver and pancreas-duodenum transplantation and heterotopic kidney transplantation for a male patient aged 44 years who had hepatitis B related cirrhosis, renal failure, and insulin dependent diabetes mellitus (IDDM). A quadruple immunosuppressive regimen including induction with basiliximab and maintenance therapy with tacrolimus, mycophenolate mofetil, and steroids was used in the early stage post-transplant. Postoperative recovery was uneventful and the patient was discharged on the 15 th postoperative day with normal liver and kidney function. The insulin treatment was completely withdrawn 3 wk after operation, and the blood glucose level remained normal. The case findings support that abdominal organ cluster and kidney transplantation is an effective method for the treatment of end-stage liver disease combined with uremia and IDDM.

Effects of the 2-ethylthiobenzimidazole hydrobromide (bemithyl) on carbohydrate metabolism in cirrhotic rat liver.

PubMed

Kudryavtseva, Margarita V; Bezborodkina, Natalia N; Okovity, Sergey V; Kudryavtsey, Boris N

2003-03-01

The effect of the actoprotector bemithyl (2-ethylthiobenzimidazole hydrobromide) on the content of glycogen and activities of glycogen synthase, glycogen phosphorylase, and glucose-6-phosphatase was studied in the cirrhotic rat liver. The content of glycogen and its fraction was determined by a cytofluorimetric method (Kudryavtseva et al. 1974). It has been shown that in cirrhosis the content of total glycogen in hepatocytes increases about 3 times and the content of its stable fraction increases 7.5 times. The activity of glucose-6-phosphatase fell to a level as low as 25% of normal. Activities of glycogen synthase and glycogen phosphorylase in the cirrhotic liver did not differ from normal. In the cirrhotic liver, bemithyl produced a decrease of the total glycogen content which was associated with a decrease of the glycogen synthase activity and an increase of the glucose-6-phosphatase and glycogen phosphorylase activities. Thus, the results of our studies indicate a favorable effect of bemithyl on the cirrhotic liver.

Prevalence of abnormal plasma liver enzymes in older people with Type 2 diabetes.

PubMed

Morling, J R; Strachan, M W J; Hayes, P C; Butcher, I; Frier, B M; Reynolds, R M; Price, J F

2012-04-01

To determine the prevalence and distribution of abnormal plasma liver enzymes in a representative sample of older adults with Type 2 diabetes. Plasma concentrations of alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase were measured in a randomly selected, population-based cohort of 1066 men and women aged 60-75 years with Type 2 diabetes (the Edinburgh Type 2 Diabetes Study). Overall, 29.1% (95% CI 26.1-31.8) of patients had one or more plasma liver enzymes above the upper limit of the normal reference range. Only 10.1% of these patients had a prior history of liver disease and a further 12.4% reported alcohol intake above recommended limits. Alanine aminotransferase was the most commonly raised liver enzyme (23.1% of patients). The prevalence of abnormal liver enzymes was significantly higher in men (odds ratio 1.40, 95% CI 1.07-1.83), in the youngest 5-year age band (odds ratio 2.02, 95% CI 1.44-2.84), in patients with diabetes duration < 5 years (odds ratio 1.38, 95% CI 1.01-1.90), plasma HbA(1c) ≥ 58 mmol/mol (7.5%) (odds ratio 1.43, 95% CI 1.09-1.88), obese BMI (odds ratio 2.84, 95% CI 1.59-3.06) and secondary care management for their diabetes (odds ratio 1.40, 95% CI 1.05-1.87). However, all these factors combined accounted for only 7.6% of the variation in liver enzyme abnormality. The prevalence of elevated liver enzymes in people with Type 2 diabetes is high, with only modest variation between clinically defined patient groups. Further research is required to determine the prognostic value of raised, routinely measured liver enzymes to inform decisions on appropriate follow-up investigations. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

PROTECTIVE EFFECT OF SACCHARUM OFFICINARUM L. (SUGAR CANE) JUICE ON ISONIAZID INDUCED HEPATOTOXICITY IN MALE ALBINO MICE.

PubMed

Khan, Sadia Wazir; Tahir, Mohammad; Lone, Khalid Pervez; Munir, Bushra; Latif, Waqas

2015-01-01

Isoniazid (INH) is the drug of choice for treatment of tuberculosis (TB) and it is a well-known-cause of acute clinical liver injury which can be severe and sometimes fatal. The study was designed to investigate the effects of Saccharum officinarum L. juice on oxidative liver injury due to INH in mice. This was a laboratory based experimental study. Thirty mice were divided into three groups, containing 10 mice each. Group A being the control, group B and C were experimental and were treated orally with INH 100 mg/kg per day and INH 100 mg/kg per day plus Saccharum officinarum L. juice 15 ml/ kg per day respectively for a period of 30 days. Blood samples were taken at 30th day by cardiac puncture under anaesthesia and liver in each was taken out for microscopic examination. INH treated mice showed; rise in serum ALT, AST, ALP and total bilirubin levels (Mean?SEM), while group C mice treated with Saccharum officinarum L. juice significantly decreased the levels of these biochemical parameters. The histopathological examination of groups A showed normal liver structure which was deranged in (INH) group B, whereas group C showed significant recovery in histological structure. Saccharum officinarum L. constituents, especially flavanoids and anthocyanins have strong antioxidant properties which provides hepatoprotection against oxidative liver injury produced by INH. INH-induced liver injury is associated with oxidative stress, and co-administration of Saccharum officinarum L. juice (15 ml/Kg bw) may reduce this damage effectively in mice.

Use of deferiprone for the treatment of hepatic iron storage disease in three hornbills.

PubMed

Sandmeier, Peter; Clauss, Marcus; Donati, Olivio F; Chiers, Koen; Kienzle, Ellen; Hatt, Jean-Michel

2012-01-01

3 hornbills (2 Papua hornbills [Aceros plicatus] and 1 longtailed hornbill [Tockus albocristatus]) were evaluated because of general listlessness and loss of feather glossiness. Because hepatic iron storage disease was suspected, liver biopsy was performed and formalin-fixed liver samples were submitted for histologic examination and quantitative image analysis (QIA). Additional frozen liver samples were submitted for chemical analysis. Birds also underwent magnetic resonance imaging (MRI) under general anesthesia for noninvasive measurement of liver iron content. Serum biochemical analysis and analysis of feed were also performed. Results of diagnostic testing indicated that all 3 hornbills were affected with hepatic iron storage disease. The iron chelator deferiprone was administered (75 mg/kg [34.1 mg/lb], PO, once daily for 90 days). During the treatment period, liver biopsy samples were obtained at regular intervals for QIA and chemical analysis of the liver iron content and follow-up MRI was performed. In all 3 hornbills, a rapid and large decrease in liver iron content was observed. All 3 methods for quantifying the liver iron content were able to verify the decrease in liver iron content. Orally administered deferiprone was found to effectively reduce the liver iron content in these 3 hornbills with iron storage disease. All 3 methods used to monitor the liver iron content (QIA, chemical analysis of liver biopsy samples, and MRI) had similar results, indicating that all of these methods should be considered for the diagnosis of iron storage disease and monitoring of liver iron content during treatment.

Detection of Hepatic Fibrosis in Ex Vivo Liver Samples Using an Open-Photoacoustic-Cell Method: Feasibility Study

NASA Astrophysics Data System (ADS)

Stolik, S.; Fabila, D. A.; de la Rosa, J. M.; Escobedo, G.; Suárez-Álvarez, K.; Tomás, S. A.

2015-09-01

Design of non-invasive and accurate novel methods for liver fibrosis diagnosis has gained growing interest. Different stages of liver fibrosis were induced in Wistar rats by intraperitoneally administering different doses of carbon tetrachloride. The liver fibrosis degree was conventionally determined by means of histological examination. An open-photoacoustic-cell (OPC) technique for the assessment of liver fibrosis was developed and is reported here. The OPC technique is based on the fact that the thermal diffusivity can be accurately measured by photoacoustics taking into consideration the photoacoustic signal amplitude versus the modulation frequency. This technique measures directly the heat generated in a sample, due to non-radiative de-excitation processes, following the absorption of light. The thermal diffusivity was measured with a home-made open-photoacoustic-cell system that was specially designed to perform the measurement from ex vivo liver samples. The human liver tissue showed a significant increase in the thermal diffusivity depending on the fibrosis stage. Specifically, liver samples from rats exhibiting hepatic fibrosis showed a significantly higher value of the thermal diffusivity than for control animals.

[Carotinaemia in patient with excessive beta-carotene food-intake and dysregulated diabetes mellitus].

PubMed

Mikkelsen, Carsten Sauer; Mikkelsen, Dorthe Bisgaard; Lindegaard, Hanne Merete

2009-01-26

A case of carotinaemia in a patient with excessive beta-carotene food-intake, diabetes mellitus and physiological amenorrhea is reported. The patient developed yellow discolouration in the palms and the soles of her feet. Blood samples showed a significantly increased lever of serum beta-carotene, but normal vitamine A value and liver enzymes. The patient reported an excessive intake of carrots (approximately 1 kg per day). The status of physiological amenorrhoea and dysregulated diabetes mellitus may have deteriorated the yellow discolouration of the skin.

Quantification of tissue texture with photoacoustic spectrum analysis

NASA Astrophysics Data System (ADS)

Wang, Xueding; Xu, Guan; Meng, Zhuo-Xian; Lin, Jiandie; Carson, Paul

2014-05-01

Photoacoustic (PA) imaging is an emerging technology that could map the functional contrasts in deep biological tissues in high resolution by "listening" to the laser induced thermoelastic waves. Almost all of the current studies in PA imaging are focused on the intensity of the PA signals as an indication of the optical absorbance of the biological tissues. Our group has for the first time demonstrated that the frequency domain power distribution of the broadband PA signals encode the texture information within the regions-of-interest (ROI). Following the similar method of ultrasound spectral analysis (USSA), photoacoustic spectrum analysis (PASA) could evaluate the relative concentrations and, more importantly, the dimensions of microstructures of the optically absorbing materials in biological tissues, including lipid, collagen, water and hemoglobin. By providing valuable insights into tissue pathology, PASA should benefit basic research and clinical management of many diseases, and may help achieve eventual "noninvasive biopsy". In this work, taking advantage of the optical absorption contrasts contributed by lipid and hemoglobin at 1200-nm and 532-nm wavelengths respectively, we investigated the capability of PASA in identifying histological changes corresponding to fat accumulation livers through the study on ex vivo and in situ mouse models. The PA signals from the mouse livers were acquired using our PA and US dual-modality imaging system, and analyzed in the frequency domain. After quantifying the power spectrum by fitting it to a first order model, three spectral parameters, including the intercept, the midband fit and the slope, were extracted and used to differentiate fatty livers from normal livers. The comparison between the PASA parameters from the normal and the fatty livers supports our hypotheses that PASA can quantitatively identify the microstructure changes in liver tissues for differentiating normal and fatty livers.

Untangling the Etiology of Ascites

PubMed Central

Lopez-Molina, Michael; Shiani, Ashok V.; Oller, Kellee L.

2015-01-01

Patient: Male, 72 Final Diagnosis: Systemic amyloidosis Symptoms: — Medication: — Clinical Procedure: Liver biopsy Specialty: Gastroenterology and Hepatology Objective: Unusual clinical course Background: Amyloidosis is a systemic disease known to affect a vast range of organs, including the liver, heart, and kidney. When infiltrating the liver, amyloidosis typically does not present with cirrhosis. Typical presentation includes hepatomegaly with some mild laboratory abnormalities. Case Report: A 72-year-old man presented with a 2-week history of worsening abdominal, scrotal, and extremity swelling. He endorsed melanotic stools and intermittent dizziness with a 10-pound weight gain. Vitals revealed a blood pressure of 82/57 mmHg and a pulse of 83 beats/min with positive orthostatic changes. Mild bibasilar crackles were noted. His abdomen was moderately distended with a fluid wave present, but no hepatosplenomegaly was noted. He displayed anasarca with significant extremity and scrotal edema, but no jaundice, telangiectasias, or other stigmata of chronic liver disease were present. Liver function tests demonstrated a total bilirubin of 1.5 mg/dL (normal value: 0.2–1.2 mg/dL), AST 111 IU/L (normal value 5–34 IU/L), ALT 51 IU/L (normal value 5–55 IU/L), and GGT 583 U/L (12–64 U/L). Alkaline phosphatase was 645 U/L (40–150 U/L). Analysis of peritoneal fluid was consistent with portal hypertension due to liver disease. Given an atypical presentation of cirrhosis with unclear etiology, a biopsy was performed and revealed amyloid deposition. Conclusions: Liver disease can be due to various etiologies, many of which can present ambiguously. Although the most typical etiologies have been well defined, we present a case of an atypical presentation of hepatic amyloidosis discovered in a patient with ascites and without typical hepatomegaly. PMID:25844525

The antifibrotic effects of TGF-{beta}1 siRNA on hepatic fibrosis in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lang, Qing; Liu, Qi; Xu, Ning

2011-06-10

Highlights: {yields} We constructed CCL4 induced liver fibrosis model successfully. {yields} We proofed that the TGF-{beta}1 siRNA had a definite therapy effect to CCL4 induced liver fibrosis. {yields} The therapy effect of TGF-{beta}1 siRNA had dose-dependent. -- Abstract: Background/aims: Hepatic fibrosis results from the excessive secretion of matrix proteins by hepatic stellate cells (HSCs), which proliferate during fibrotic liver injury. Transforming growth factor (TGF)-{beta}1 is the dominant stimulus for extracellular matrix (ECM) production by stellate cells. Our study was designed to investigate the antifibrotic effects of using short interference RNA (siRNA) to target TGF-{beta}1 in hepatic fibrosis and its mechanismmore » in rats exposed to a high-fat diet and carbon tetrachloride (CCL4). Methods: A total of 40 healthy, male SD (Sprague-Dawley) rats were randomly divided into five even groups containing of eight rats each: normal group, model group, TGF-{beta}1 siRNA 0.125 mg/kg treatment group, TGF-{beta}1 siRNA 0.25 mg/kg treatment group and TGF-{beta}1 siRNA negative control group (0.25 mg/kg). CCL4 and a high-fat diet were used for 8 weeks to induce hepatic fibrosis. All the rats were then sacrificed to collect liver tissue samples. A portion of the liver samples were soaked in formalin for Hematoxylin-Eosin staining, classifying the degree of liver fibrosis, and detecting the expression of type I and III collagen and TGF-{beta}1; the remaining liver samples were stored in liquid nitrogen to be used for detecting TGF-{beta}1 by Western blotting and for measuring the mRNA expression of type I and III collagen and TGF-{beta}1 by quantitative real-time polymerase chain reaction. Results: Comparing the TGF-{beta}1 siRNA 0.25 mg/kg treatment group to the model group, the TGF-{beta}1 siRNA negative control group and the TGF-{beta}1 siRNA 0.125 mg/kg treatment group showed significantly reduced levels of pathological changes, protein expression and the mRNA expression of TGF-{beta}1, type I collagen and type III collagen (P < 0.01). Conclusions: Using siRNA to target TGF-{beta}1 can inhibit the expression of TGF-{beta}1 and attenuate rat hepatic fibrosis induced by a high-fat diet and CCL4. A possible mechanism is through the down-regulation of TGF-{beta}1 expression, which could inhibit HSC activation, as well as the proliferation and collagen production of collagen reducing, so that collagen deposition in the liver is reduced.« less

[Protective effect of Tanreqing injection on acute hepatic injury induced by CCl4 in rats].

PubMed

Lei, Yang; Zhou, Ai-Min; Guo, Tao; Tan, Ye; Tao, Yan-Yan; Liu, Cheng-Hai

2013-04-01

To observe the protective effect of Tanreqing injection(TRQ) on carbon tetrachloride-induced acute hepatic injury in rats. Rats were randomly divided into the normal group and the model group, and injected subcutaneously with 100% CCl4 5 mL x kg(-1) to establish the single CCl4 infection model, in order to observe the changes in rat liver injury after 3 h and 6 h. Subsequently, the multiple CCl4 infection liver injury model was reproduced by subcutaneously injecting 100% CCl4 (5 mL x kg(-1)), 50% CCl4 olive oil solution (2 mL x kg(-1)) and then 20% CCl4 olive oil solution (2 mL x kg(-1)). At 6 h after the first CCl4 injection, the rats were divided into six groups: the model group, the control group, the diammonium glycyrrhizinate-treated group, and TRQ high, middle and low dose groups. They were injected through caudal veins, while a normal control group was set up. Their weight and liver-body ratio were observed. Hepatic inflammation was observed with HE staining. Assay kits were adopted to detect ALT, AST, T. Bil, D. Bil, CHE, TBA, gamma-GT and Alb. According to the single injection model, serum AST and T. Bil of model rats were obviously increased at 6 h after single subcutaneous injection of CCl4, with disordered lobular structure in liver tissues, notable swollen liver cells and remarkable liver injury. According to the results of the multiple injection pharmacological experiment, compared with the normal group, the model group had higher serum ALT, AST, and gamma-GT activities (P < 0. 05), TBA and T. Bil contents (P < 0.05) and lower CHE activity (P < 0.05). HE staining showed disorganized lobular structure in liver tissues and notable ballooning degeneration in liver cells. Compared with the model group, TRQ high and middle dose groups and the diammonium glycyrrhizinate-treated group showed significant charges in serum liver function and inflammation in liver cells. Specifically, TRQ high and middle dose groups were superior to the diammonium glycyrrhizinate-treated group. Tanreqing injection has significant protective effect on CCl4-induced acute hepatic injury in rats.

[Age and characteristics of cholesterol biosynthesis in rat liver under normal conditions and during atherogenic loading].

PubMed

Chaialo, P P

1977-02-01

Intraperitoneal injection of C14CH3COONa to normal rats aged 6--8 and 28--32 months revealed a slower dynamics of cholesterol biosynthesis in the liver of old rats at the maximum of the tracer incorporation was lower than in the young ones. Atherogenic diet (0.25 g of cholesterol per 100 g of animal weight for a period of 20 days) was accompanied by an increase in the total cholesterol content and depressio of its biosynthesis in the liver, more pronounced in the young rats. Continued cholesterol administration caused further depression of its biosynthesis, most pronounced (in this case) in the old animals.

The Effect of 10 Weeks Resistance Training on Cholesterol and Blood Triglyceride Levels of Patients with Fatty Liver Disease.

PubMed

Valizadeh, Rohollah; Hosseini Askarabadi, Siroos; Karampour, Sedigheh; Abdolhamid Tehrani, Mona

2014-01-01

The present study aims to consider the effect of 10 weeks resistance trainings on cholesterol and blood triglyceride (TG) levels of patients with having fatty liver, aged 50 to 60 in National Iranian South Oil Company (NISOC). This research is practical and its plan has been done experimentally with pretest and post-test on experimental and control groups. In this study, 20 samples from 100 patients who referred to sonography clinic in NISOC with distinction of fatty liver were selected randomly and divided into two groups of control (n = 10) and experimental (n = 10). Cholesterol and blood trigly-ceride were measured as pretest. Test of normality for TG was (p = 0/200) by Kolmogorov-Smirnov and (p = 0/070) for cholesterol by Shapiro-Wilk test. After 10 weeks resistance trainings, the analysis and resolution of data were done by computer and SPSS (16) software as well as the descriptive and statistical methods (t-test). Comparison between these two groups showed that 8 weeks resistance trainings with a ≤ 0.05 causes significant decrease in the amount of TG but did not any significant effect on cholesterol of fatty liver patients. How to cite this article: Valizadeh R, Askarabadi SH, Karampour S, Tehrani MA. The Effect of 10 Weeks Resistance Training on Cholesterol and Blood Triglyceride Levels of Patients with Fatty Liver Disease. Euroasian J Hepato-Gastroenterol 2014;4(1):64-65.

Urinary metabolomics analysis identifies key biomarkers of different stages of nonalcoholic fatty liver disease

PubMed Central

Dong, Shu; Zhan, Zong-Ying; Cao, Hong-Yan; Wu, Chao; Bian, Yan-Qin; Li, Jian-Yuan; Cheng, Gen-Hong; Liu, Ping; Sun, Ming-Yu

2017-01-01

AIM To identify a panel of biomarkers that can distinguish between non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), and explore molecular mechanism involved in the process of developing NASH from NAFLD. METHODS Biomarkers may differ during stages of NAFLD. Urine and blood were obtained from non-diabetic subjects with NAFLD and steatosis, with normal liver function (n = 33), from patients with NASH, with abnormal liver function (n = 45), and from healthy age and sex-matched controls (n = 30). Samples were subjected to metabolomic analysis to identify potential non-invasive biomarkers. Differences in urinary metabolic profiles were analyzed using liquid chromatography tandem mass spectrometry with principal component analysis and partial least squares-discriminate analysis. RESULTS Compared with NAFLD patients, patients with NASH had abnormal liver function and high serum lipid concentrations. Urinary metabonomics found differences in 31 metabolites between these two groups, including differences in nucleic acids and amino acids. Pathway analysis based on overlapping metabolites showed that pathways of energy and amino acid metabolism, as well as the pentose phosphate pathway, were closely associated with pathological processes in NAFLD and NASH. CONCLUSION These findings suggested that a panel of biomarkers could distinguish between NAFLD and NASH, and could help to determine the molecular mechanism involved in the process of developing NASH from NAFLD. Urinary biomarkers may be diagnostic in these patients and could be used to assess responses to therapeutic interventions. PMID:28487615

Encephalopathy in acute liver failure resulting from acetaminophen intoxication: new observations with potential therapy.

PubMed

Brusilow, Saul W; Cooper, Arthur J L

2011-11-01

Hyperammonemia is a major contributing factor to the encephalopathy associated with liver disease. It is now generally accepted that hyperammonemia leads to toxic levels of glutamine in astrocytes. However, the mechanism by which excessive glutamine is toxic to astrocytes is controversial. Nevertheless, there is strong evidence that glutamine-induced osmotic swelling, especially in acute liver failure, is a contributing factor: the osmotic gliopathy theory. The object of the current communication is to present evidence for the osmotic gliopathy theory in a hyperammonemic patient who overdosed on acetaminophen. Case report. Johns Hopkins Hospital. A 22-yr-old woman who, 36 hrs before admission, ingested 15 g acetaminophen was admitted to the Johns Hopkins Hospital. She was treated with N-acetylcysteine. Physical examination was unremarkable; her mental status was within normal limits and remained so until approximately 72 hrs after ingestion when she became confused, irritable, and agitated. She was intubated, ventilated, and placed on lactulose. Shortly thereafter, she was noncommunicative, unresponsive to painful stimuli, and exhibited decerebrate posturing. A clinical diagnosis of cerebral edema and increased intracranial pressure was made. She improved very slowly until 180 hrs after ingestion when she moved all extremities. She woke up shortly thereafter. Despite the fact that hyperammonemia is a major contributing factor to the encephalopathy observed in acute liver failure, the patient's plasma ammonia peaked when she exhibited no obvious neurologic deficit. Thereafter, her plasma ammonia decreased precipitously in parallel with a worsening neurologic status. She was deeply encephalopathic during a period when her liver function and plasma ammonia had normalized. Plasma glutamine levels in this patient were high but began to normalize several hours after plasma ammonia had returned to normal. The patient only started to recover as her plasma glutamine began to return to normal. We suggest that the biochemical data are consistent with the osmotic gliopathy theory--high plasma ammonia leads to high plasma glutamine--an indicator of excess glutamine in astrocytes (the site of brain glutamine synthesis). This excess glutamine leads to osmotic stress in these cells. The lag in recovery of brain function presumably reflects time taken for the astrocyte glutamine concentration to return to normal. We hypothesize that an inhibitor of brain glutamine synthesis may be an effective treatment modality for acute liver failure.

Global gene expression associated with hepatocarcinogenesis in adult male mice induced by in utero arsenic exposure.

PubMed

Liu, Jie; Xie, Yaxiong; Ducharme, Danica M K; Shen, Jun; Diwan, Bhalchandra A; Merrick, B Alex; Grissom, Sherry F; Tucker, Charles J; Paules, Richard S; Tennant, Raymond; Waalkes, Michael P

2006-03-01

Our previous work has shown that exposure to inorganic arsenic in utero produces hepatocellular carcinoma (HCC) in adult male mice. To explore further the molecular mechanisms of transplacental arsenic hepatocarcinogenesis, we conducted a second arsenic transplacental carcinogenesis study and used a genomewide microarray to profile arsenic-induced aberrant gene expression more extensively. Briefly, pregnant C3H mice were given drinking water containing 85 ppm arsenic as sodium arsenite or unaltered water from days 8 to 18 of gestation. The incidence of HCC in adult male offspring was increased 4-fold and tumor multiplicity 3-fold after transplacental arsenic exposure. Samples of normal liver and liver tumors were taken at autopsy for genomic analysis. Arsenic exposure in utero resulted in significant alterations (p < 0.001) in the expression of 2,010 genes in arsenic-exposed liver samples and in the expression of 2,540 genes in arsenic-induced HCC. Ingenuity Pathway Analysis revealed that significant alterations in gene expression occurred in a number of biological networks, and Myc plays a critical role in one of the primary networks. Real-time reverse transcriptase-polymerase chain reaction and Western blot analysis of selected genes/proteins showed > 90% concordance. Arsenic-altered gene expression included activation of oncogenes and HCC biomarkers, and increased expression of cell proliferation-related genes, stress proteins, and insulin-like growth factors and genes involved in cell-cell communications. Liver feminization was evidenced by increased expression of estrogen-linked genes and altered expression of genes that encode gender-related metabolic enzymes. These novel findings are in agreement with the biology and histology of arsenic-induced HCC, thereby indicating that multiple genetic events are associated with transplacental arsenic hepatocarcinogenesis.

Spectral Electroencephalogram Analysis for the Evaluation of Encephalopathy Grade in Children With Acute Liver Failure.

PubMed

Press, Craig A; Morgan, Lindsey; Mills, Michele; Stack, Cynthia V; Goldstein, Joshua L; Alonso, Estella M; Wainwright, Mark S

2017-01-01

Spectral electroencephalogram analysis is a method for automated analysis of electroencephalogram patterns, which can be performed at the bedside. We sought to determine the utility of spectral electroencephalogram for grading hepatic encephalopathy in children with acute liver failure. Retrospective cohort study. Tertiary care pediatric hospital. Patients between 0 and 18 years old who presented with acute liver failure and were admitted to the PICU. None. Electroencephalograms were analyzed by spectral analysis including total power, relative δ, relative θ, relative α, relative β, θ-to-Δ ratio, and α-to-Δ ratio. Normal values and ranges were first derived using normal electroencephalograms from 70 children of 0-18 years old. Age had a significant effect on each variable measured (p < 0.03). Electroencephalograms from 33 patients with acute liver failure were available for spectral analysis. The median age was 4.3 years, 14 of 33 were male, and the majority had an indeterminate etiology of acute liver failure. Neuroimaging was performed in 26 cases and was normal in 20 cases (77%). The majority (64%) survived, and 82% had a good outcome with a score of 1-3 on the Pediatric Glasgow Outcome Scale-Extended at the time of discharge. Hepatic encephalopathy grade correlated with the qualitative visual electroencephalogram scores assigned by blinded neurophysiologists (rs = 0.493; p < 0.006). Spectral electroencephalogram characteristics varied significantly with the qualitative electroencephalogram classification (p < 0.05). Spectral electroencephalogram variables including relative Δ, relative θ, relative α, θ-to-Δ ratio, and α-to-Δ ratio all significantly varied with the qualitative electroencephalogram (p < 0.025). Moderate to severe hepatic encephalopathy was correlated with a total power of less than or equal to 50% of normal for children 0-3 years old, and with a relative θ of less than or equal to 50% normal for children more than 3 years old (p > 0.05). Spectral electroencephalogram classification correlated with outcome (p < 0.05). Spectral electroencephalogram analysis can be used to evaluate even young patients for hepatic encephalopathy and correlates with outcome. Spectral electroencephalogram may allow improved quantitative and reproducible assessment of hepatic encephalopathy grade in children with acute liver failure.

Systematic investigation on the validity of partition model dosimetry for 90Y radioembolization using Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Aziz Hashikin, Nurul Ab; Yeong, Chai-Hong; Guatelli, Susanna; Jeet Abdullah, Basri Johan; Ng, Kwan-Hoong; Malaroda, Alessandra; Rosenfeld, Anatoly; Perkins, Alan Christopher

2017-09-01

We aimed to investigate the validity of the partition model (PM) in estimating the absorbed doses to liver tumour ({{D}T} ), normal liver tissue ({{D}NL} ) and lungs ({{D}L} ), when cross-fire irradiations between these compartments are being considered. MIRD-5 phantom incorporated with various treatment parameters, i.e. tumour involvement (TI), tumour-to-normal liver uptake ratio (T/N) and lung shunting (LS), were simulated using the Geant4 Monte Carlo (MC) toolkit. 108 track histories were generated for each combination of the three parameters to obtain the absorbed dose per activity uptake in each compartment (DT{{AT}} , DNL{{ANL}} , and DL{{AL}} ). The administered activities, A were estimated using PM, so as to achieve either limiting doses to normal liver, DNLlim or lungs, ~DLlim (70 or 30 Gy, respectively). Using these administered activities, the activity uptake in each compartment ({{A}T} , {{A}NL} , and {{A}L} ) was estimated and multiplied with the absorbed dose per activity uptake attained using the MC simulations, to obtain the actual dose received by each compartment. PM overestimated {{D}L} by 11.7% in all cases, due to the escaped particles from the lungs. {{D}T} and {{D}NL} by MC were largely affected by T/N, which were not considered by PM due to cross-fire exclusion at the tumour-normal liver boundary. These have resulted in the overestimation of {{D}T} by up to 8% and underestimation of {{D}NL} by as high as  -78%, by PM. When DNLlim was estimated via PM, the MC simulations showed significantly higher {{D}NL} for cases with higher T/N, and LS  ⩽  10%. All {{D}L} and {{D}T} by MC were overestimated by PM, thus DLlim were never exceeded. PM leads to inaccurate dose estimations due to the exclusion of cross-fire irradiation, i.e. between the tumour and normal liver tissue. Caution should be taken for cases with higher TI and T/N, and lower LS, as they contribute to major underestimation of {{D}NL} . For {{D}L} , a different correction factor for dose calculation may be used for improved accuracy.

Festival food coma in cystic fibrosis.

PubMed

Pandit, Chetan; Graham, Christie; Selvadurai, Hiran; Gaskin, Kevin; Cooper, Peter; van Asperen, Peter

2013-07-01

Children with cystic fibrosis liver disease and portal hypertension are at risk of developing acute hepatic encephalopathy. Even in the presence of normal synthetic liver function these children may have porto-systemic shunting. We report a case of an adolosecent who had cystic fibrosis liver disease and presented with life threatening hepatinc encephalopathy. This case illustrates that it is necessary to consider an appropriate dietary regimen in adolosecents with liver disease to prevent hepatic decompensation. Copyright © 2012 Wiley Periodicals, Inc.

AMPK Re-Activation Suppresses Hepatic Steatosis but its Downregulation Does Not Promote Fatty Liver Development.

PubMed

Boudaba, Nadia; Marion, Allison; Huet, Camille; Pierre, Rémi; Viollet, Benoit; Foretz, Marc

2018-02-01

Nonalcoholic fatty liver disease is a highly prevalent component of disorders associated with disrupted energy homeostasis. Although dysregulation of the energy sensor AMP-activated protein kinase (AMPK) is viewed as a pathogenic factor in the development of fatty liver its role has not been directly demonstrated. Unexpectedly, we show here that liver-specific AMPK KO mice display normal hepatic lipid homeostasis and are not prone to fatty liver development, indicating that the decreases in AMPK activity associated with hepatic steatosis may be a consequence, rather than a cause, of changes in hepatic metabolism. In contrast, we found that pharmacological re-activation of downregulated AMPK in fatty liver is sufficient to normalize hepatic lipid content. Mechanistically, AMPK activation reduces hepatic triglyceride content both by inhibiting lipid synthesis and by stimulating fatty acid oxidation in an LKB1-dependent manner, through a transcription-independent mechanism. Furthermore, the effect of the antidiabetic drug metformin on lipogenesis inhibition and fatty acid oxidation stimulation was enhanced by combination treatment with small-molecule AMPK activators in primary hepatocytes from mice and humans. Overall, these results demonstrate that AMPK downregulation is not a triggering factor in fatty liver development but in contrast, establish the therapeutic impact of pharmacological AMPK re-activation in the treatment of fatty liver disease. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Automated diagnosis of focal liver lesions using bidirectional empirical mode decomposition features.

PubMed

Acharya, U Rajendra; Koh, Joel En Wei; Hagiwara, Yuki; Tan, Jen Hong; Gertych, Arkadiusz; Vijayananthan, Anushya; Yaakup, Nur Adura; Abdullah, Basri Johan Jeet; Bin Mohd Fabell, Mohd Kamil; Yeong, Chai Hong

2018-03-01

Liver is the heaviest internal organ of the human body and performs many vital functions. Prolonged cirrhosis and fatty liver disease may lead to the formation of benign or malignant lesions in this organ, and an early and reliable evaluation of these conditions can improve treatment outcomes. Ultrasound imaging is a safe, non-invasive, and cost-effective way of diagnosing liver lesions. However, this technique has limited performance in determining the nature of the lesions. This study initiates a computer-aided diagnosis (CAD) system to aid radiologists in an objective and more reliable interpretation of ultrasound images of liver lesions. In this work, we have employed radon transform and bi-directional empirical mode decomposition (BEMD) to extract features from the focal liver lesions. After which, the extracted features were subjected to particle swarm optimization (PSO) technique for the selection of a set of optimized features for classification. Our automated CAD system can differentiate normal, malignant, and benign liver lesions using machine learning algorithms. It was trained using 78 normal, 26 benign and 36 malignant focal lesions of the liver. The accuracy, sensitivity, and specificity of lesion classification were 92.95%, 90.80%, and 97.44%, respectively. The proposed CAD system is fully automatic as no segmentation of region-of-interest (ROI) is required. Copyright © 2018 Elsevier Ltd. All rights reserved.

Assessment of liver steatosis and fibrosis in rats using integrated coherent anti-Stokes Raman scattering and multiphoton imaging technique

NASA Astrophysics Data System (ADS)

Lin, Jian; Lu, Fake; Zheng, Wei; Xu, Shuoyu; Tai, Dean; Yu, Hanry; Huang, Zhiwei

2011-11-01

We report the implementation of a unique integrated coherent anti-Stokes Raman scattering (CARS), second-harmonic generation (SHG), and two-photon excitation fluorescence (TPEF) microscopy imaging technique developed for label-free monitoring of the progression of liver steatosis and fibrosis generated in a bile duct ligation (BDL) rat model. Among the 21 adult rats used in this study, 18 rats were performed with BDL surgery and sacrificed each week from weeks 1 to 6 (n = 3 per week), respectively; whereas 3 rats as control were sacrificed at week 0. Colocalized imaging of the aggregated hepatic fats, collagen fibrils, and hepatocyte morphologies in liver tissue is realized by using the integrated CARS, SHG, and TPEF technique. The results show that there are significant accumulations of hepatic lipid droplets and collagen fibrils associated with severe hepatocyte necrosis in BDL rat liver as compared to a normal liver tissue. The volume of normal hepatocytes keeps decreasing and the fiber collagen content in BDL rat liver follows a growing trend until week 6; whereas the hepatic fat content reaches a maximum in week 4 and then appears to stop growing in week 6, indicating that liver steatosis and fibrosis induced in a BDL rat liver model may develop at different rates. This work demonstrates that the integrated CARS and multiphoton microscopy imaging technique has the potential to provide an effective means for early diagnosis and detection of liver steatosis and fibrosis without labeling.

Perioperative morbidity and mortality of total hip replacement in liver transplant recipients: a 7-year single-center experience.

PubMed

Aminata, Iman; Lee, Soo-Ho; Chang, Jae-Suk; Lee, Choon-Sung; Chun, Jae-Myeung; Park, Jin-Woong; Pawaskar, Aditya; Jeon, In-Ho

2012-12-15

This study aims to evaluate perioperative mortality and morbidity after total hip replacement in liver transplant recipients and suggesting safety guidelines. Hip replacement surgery is one of the most common elective surgeries even for organ transplant recipients. However, there is a paucity of literature addressing the morbidity and complications of hip replacement surgery for liver transplant recipients. We analyzed retrospectively 33 arthroplasty cases in 20 liver transplant recipients carried out in a single center from 2005 to 2011. All perioperative clinical and laboratory data were evaluated together with early and late morbidity and mortality. Of 2253 liver transplant recipients, 20 (0.9%) patients underwent 33 total hip arthroplasties. Thirty-two arthroplasties were performed for avascular necrosis of the femoral head, whereas only one was performed for osteoarthritis. There was no death, liver failure, or infection within 30 days after surgery. Three patients showed elevated liver enzyme more than 5 times the normal value, but it eventually decreased to normal within 1 week. Of 33 cases of arthroplasty, postoperative blood transfusion was needed in 14 cases with 1 case receiving more than 4 U. On long-term follow-up, no patients have developed periprosthetic fracture, implant loosening, or liver failure. All patients showed good to excellent postoperative Harris hip score. In this series, we can infer that hip replacement surgery in liver transplantation patients is safe and gives a reliably good result. Some preoperative conditions should be obtained to reduce postoperative morbidity.

Assessment of liver steatosis and fibrosis in rats using integrated coherent anti-Stokes Raman scattering and multiphoton imaging technique.

PubMed

Lin, Jian; Lu, Fake; Zheng, Wei; Xu, Shuoyu; Tai, Dean; Yu, Hanry; Huang, Zhiwei

2011-11-01

We report the implementation of a unique integrated coherent anti-Stokes Raman scattering (CARS), second-harmonic generation (SHG), and two-photon excitation fluorescence (TPEF) microscopy imaging technique developed for label-free monitoring of the progression of liver steatosis and fibrosis generated in a bile duct ligation (BDL) rat model. Among the 21 adult rats used in this study, 18 rats were performed with BDL surgery and sacrificed each week from weeks 1 to 6 (n = 3 per week), respectively; whereas 3 rats as control were sacrificed at week 0. Colocalized imaging of the aggregated hepatic fats, collagen fibrils, and hepatocyte morphologies in liver tissue is realized by using the integrated CARS, SHG, and TPEF technique. The results show that there are significant accumulations of hepatic lipid droplets and collagen fibrils associated with severe hepatocyte necrosis in BDL rat liver as compared to a normal liver tissue. The volume of normal hepatocytes keeps decreasing and the fiber collagen content in BDL rat liver follows a growing trend until week 6; whereas the hepatic fat content reaches a maximum in week 4 and then appears to stop growing in week 6, indicating that liver steatosis and fibrosis induced in a BDL rat liver model may develop at different rates. This work demonstrates that the integrated CARS and multiphoton microscopy imaging technique has the potential to provide an effective means for early diagnosis and detection of liver steatosis and fibrosis without labeling.

Assessing the uncertainty in a normal tissue complication probability difference (∆NTCP): radiation-induced liver disease (RILD) in liver tumour patients treated with proton vs X-ray therapy.

PubMed

Kobashi, Keiji; Prayongrat, Anussara; Kimoto, Takuya; Toramatsu, Chie; Dekura, Yasuhiro; Katoh, Norio; Shimizu, Shinichi; Ito, Yoichi M; Shirato, Hiroki

2018-03-01

Modern radiotherapy technologies such as proton beam therapy (PBT) permit dose escalation to the tumour and minimize unnecessary doses to normal tissues. To achieve appropriate patient selection for PBT, a normal tissue complication probability (NTCP) model can be applied to estimate the risk of treatment-related toxicity relative to X-ray therapy (XRT). A methodology for estimating the difference in NTCP (∆NTCP), including its uncertainty as a function of dose to normal tissue, is described in this study using the Delta method, a statistical method for evaluating the variance of functions, considering the variance-covariance matrix. We used a virtual individual patient dataset of radiation-induced liver disease (RILD) in liver tumour patients who were treated with XRT as a study model. As an alternative option for individual patient data, dose-bin data, which consists of the number of patients who developed toxicity in each dose level/bin and the total number of patients in that dose level/bin, are useful for multi-institutional data sharing. It provides comparable accuracy with individual patient data when using the Delta method. With reliable NTCP models, the ∆NTCP with uncertainty might potentially guide the use of PBT; however, clinical validation and a cost-effectiveness study are needed to determine the appropriate ∆NTCP threshold.

Assessing the uncertainty in a normal tissue complication probability difference (∆NTCP): radiation-induced liver disease (RILD) in liver tumour patients treated with proton vs X-ray therapy

PubMed Central

Kobashi, Keiji; Kimoto, Takuya; Toramatsu, Chie; Dekura, Yasuhiro; Katoh, Norio; Shimizu, Shinichi; Ito, Yoichi M; Shirato, Hiroki

2018-01-01

Abstract Modern radiotherapy technologies such as proton beam therapy (PBT) permit dose escalation to the tumour and minimize unnecessary doses to normal tissues. To achieve appropriate patient selection for PBT, a normal tissue complication probability (NTCP) model can be applied to estimate the risk of treatment-related toxicity relative to X-ray therapy (XRT). A methodology for estimating the difference in NTCP (∆NTCP), including its uncertainty as a function of dose to normal tissue, is described in this study using the Delta method, a statistical method for evaluating the variance of functions, considering the variance–covariance matrix. We used a virtual individual patient dataset of radiation-induced liver disease (RILD) in liver tumour patients who were treated with XRT as a study model. As an alternative option for individual patient data, dose-bin data, which consists of the number of patients who developed toxicity in each dose level/bin and the total number of patients in that dose level/bin, are useful for multi-institutional data sharing. It provides comparable accuracy with individual patient data when using the Delta method. With reliable NTCP models, the ∆NTCP with uncertainty might potentially guide the use of PBT; however, clinical validation and a cost-effectiveness study are needed to determine the appropriate ∆NTCP threshold. PMID:29538699

[Change in Perioperative Hemostatic Function in Patients Undergoing Hepatic Resection for Primary and Metastatic Liver Cancer].

PubMed

Komasawa, Nobuyasu; Ueki, Ryusuke; Atagi, Kazuaki; Nishi, Shinichi

2015-08-01

Patients undergoing primary hepatic resection often develop hemostatic dysfunction associated with cirrhosis. We retrospectively surveyed pre- and postoperative prothrombin time (PT) and the PT expressed as international normalized ratio (PT-INR) in 39 patients undergoing primary liver resection. We also compared PT changes between primary and metastatic cancer cases (8 cases). Postoperative PT-INR was 1.40 ± 0.38, which was significantly prolonged compared to preoperative PT-INR of 1.08 ± 0.07. Preoperative PT was over 70% in all 39 patients undergoing primary liver resection, whereas postoperative PT was less than 60% in 13 of 39 patients. No significant difference was found in preoperative PT-INR between primary and metastatic cancer cases, but postoperative PT-INR was significantly prolonged in primary cancer cases. Patients undergoing primary liver resection are susceptible to hemostatic dysfunction, even with preoperative PT levels within normal limits.

Reduced size liver transplantation from a donor supported by a Berlin Heart.

PubMed

Misra, M V; Smithers, C J; Krawczuk, L E; Jenkins, R L; Linden, B C; Weldon, C B; Kim, H B

2009-11-01

Patients on cardiac assist devices are often considered to be high-risk solid organ donors. We report the first case of a reduced size liver transplant performed using the left lateral segment of a pediatric donor whose cardiac function was supported by a Berlin Heart. The recipient was a 22-day-old boy with neonatal hemochromatosis who developed fulminant liver failure shortly after birth. The transplant was complicated by mild delayed graft function, which required delayed biliary reconstruction and abdominal wall closure, as well as a bile leak. However, the graft function improved quickly over the first week and the patient was discharged home with normal liver function 8 weeks after transplant. The presence of a cardiac assist device should not be considered an absolute contraindication for abdominal organ donation. Normal organ procurement procedures may require alteration due to the unusual technical obstacles that are encountered when the donor has a cardiac assist device.

Language assessment of children with severe liver disease in a public service in Brazil

PubMed Central

de-Paula, Erica Macêdo; Porta, Gilda; Tannuri, Ana Cristina Aoun; Tannuri, Uenis; Befi-Lopes, Debora Maria

2017-01-01

OBJECTIVE: The aim of this research was to compare language development (expressive and receptive skills) in children awaiting liver transplantation with that of children who have already undergone the surgical procedure. METHODS: An observational, descriptive, cross-sectional study was conducted with 76 children divided into groups, as follows: 31 children who were candidates for liver transplantation (Group 1; G1), 45 children who had already undergone liver transplantation (Group 2; G2), and a control group (CG) of 60 healthy, normally developing children. Health status information was gathered, and the Test of Early Language Development (TELD)-3 was used to assess language skills. Family household monthly income data were also gathered using a specific questionnaire. RESULTS: G1 had poorer language performance compared with G2 and the CG. G2 had lower language performance when compared with the CG. However, when considering the TELD-3 standard scores, G2 had scores within normal limits. The regression analysis indicated age as a risk factor for language deficits in Group 1 and family income as a risk factor for language deficits in G2. CONCLUSIONS: The results suggested that children with chronic liver disease have delays in language development. Transplanted children have linguistic performance within normal limits, but their scores tended to be lower than the CG. PMID:28658434

Examination of the Spatial Correlation of Statistics Information in the Ultrasonic Echo from Diseased Liver

NASA Astrophysics Data System (ADS)

Yamaguchi, Tadashi; Hachiya, Hiroyuki; Kamiyama, Naohisa; Moriyasu, Fuminori

2002-05-01

To realize a quantitative diagnosis of liver cirrhosis, we have been analyzing the characteristics of echo amplitude in B-mode images. Realizing the distinction between liver diseases such as liver cirrhosis and chronic hepatitis is required in the field of medical ultrasonics. In this study, we examine the spatial correlation, with the coefficient of correlation between the frames and the amplitude characteristics of each frame, using the volumetric data of RF echo signals from normal and diseased liver. It is found that there is a relationship between the tissue structure of liver and the spatial correlation of echo information.

Characterization of HBV integration patterns and timing in liver cancer and HBV-infected livers.

PubMed

Furuta, Mayuko; Tanaka, Hiroko; Shiraishi, Yuichi; Unida, Takuro; Imamura, Michio; Fujimoto, Akihiro; Fujita, Masahi; Sasaki-Oku, Aya; Maejima, Kazuhiro; Nakano, Kaoru; Kawakami, Yoshiiku; Arihiro, Koji; Aikata, Hiroshi; Ueno, Masaki; Hayami, Shinya; Ariizumi, Shun-Ichi; Yamamoto, Masakazu; Gotoh, Kunihito; Ohdan, Hideki; Yamaue, Hiroki; Miyano, Satoru; Chayama, Kazuaki; Nakagawa, Hidewaki

2018-05-18

Integration of Hepatitis B virus (HBV) into the human genome can cause genetic instability, leading to selective advantages for HBV-induced liver cancer. Despite the large number of studies for HBV integration into liver cancer, little is known about the mechanism of initial HBV integration events owing to the limitations of materials and detection methods. We conducted an HBV sequence capture, followed by ultra-deep sequencing, to screen for HBV integrations in 111 liver samples from human-hepatocyte chimeric mice with HBV infection and human clinical samples containing 42 paired samples from non-tumorous and tumorous liver tissues. The HBV infection model using chimeric mice verified the efficiency of our HBV-capture analysis and demonstrated that HBV integration could occur 23 to 49 days after HBV infection via microhomology-mediated end joining and predominantly in mitochondrial DNA. Overall HBV integration sites in clinical samples were significantly enriched in regions annotated as exhibiting open chromatin, a high level of gene expression, and early replication timing in liver cells. These data indicate that HBV integration in liver tissue was biased according to chromatin accessibility, with additional selection pressures in the gene promoters of tumor samples. Moreover, an integrative analysis using paired non-tumorous and tumorous samples and HBV-related transcriptional change revealed the involvement of TERT and MLL4 in clonal selection. We also found frequent and non-tumorous liver-specific HBV integrations in FN1 and HBV-FN1 fusion transcript. Extensive survey of HBV integrations facilitates and improves the understanding of the timing and biology of HBV integration during infection and HBV-related hepatocarcinogenesis.

Quantitative optical imaging of paracetamol-induced metabolism changes in the liver

NASA Astrophysics Data System (ADS)

Liang, Xiaowen; Wang, Haolu; Liu, Xin; Roberts, Michael

2016-12-01

Paracetamol is the most readily available and widely used painkiller. However, its toxicity remains the most common cause of liver injury. The toxicity of paracetamol has been attributing to its toxic metabolite, which depletes cellular glutathione (GSH) stores and reacts within cells to increase oxidative stress, leading to mitochondrial dysfunction and cell necrosis. Multiphoton microscopy (MPM) and fluorescence lifetime imaging (FLIM) can provide quantitative imaging of biological tissues and organs in vivo and allow direct visualization of cellular events, which were used to monitor cellular metabolism in paracetamol-induced toxicity in this study. To better understand mechanisms of paracetamol induced liver injury, the redox ratio of NADH/FAD in liver cells were detected and quantified by MPM imaging to represent the relative rates of glycolysis and oxidative phosphorylation within cells. Compared to normal liver, average fluorescence lifetime of NADH and redox ratio of NADH/FAD in hepatocytes was significantly decreased after paracetamol overdose for 12 and 24 hrs, reflecting impaired metabolic activity. GSH levels of treatment groups were significantly lower than those of normal livers, with gradually decreasing from periportal to centrilobular zonation. This imaging technique has significant implications for investigating metabolic mechanisms of paracetamol toxicity.

Non-operative management (NOM) of blunt hepatic trauma: 80 cases.

PubMed

Özoğul, Bünyami; Kısaoğlu, Abdullah; Aydınlı, Bülent; Öztürk, Gürkan; Bayramoğlu, Atıf; Sarıtemur, Murat; Aköz, Ayhan; Bulut, Özgür Hakan; Atamanalp, Sabri Selçuk

2014-03-01

Liver is the most frequently injured organ upon abdominal trauma. We present a group of patients with blunt hepatic trauma who were managed without any invasive diagnostic tools and/or surgical intervention. A total of 80 patients with blunt liver injury who were hospitalized to the general surgery clinic or other clinics due to the concomitant injuries were followed non-operatively. The normally distributed numeric variables were evaluated by Student's t-test or one way analysis of variance, while non-normally distributed variables were analyzed by Mann-Whitney U-test or Kruskal-Wallis variance analysis. Chi-square test was also employed for the comparison of categorical variables. Statistical significance was assumed for p<0.05. There was no significant relationship between patients' Hgb level and liver injury grade, outcome, and mechanism of injury. Also, there was no statistical relationship between liver injury grade, outcome, and mechanism of injury and ALT levels as well as AST level. There was no mortality in any of the patients. During the last quarter of century, changes in the diagnosis and treatment of liver injury were associated with increased survival. NOM of liver injury in patients with stable hemodynamics and hepatic trauma seems to be the gold standard.

The chemokine receptor CXCR6 is required for the maintenance of liver memory CD8⁺ T cells specific for infectious pathogens.

PubMed

Tse, Sze-Wah; Radtke, Andrea J; Espinosa, Diego A; Cockburn, Ian A; Zavala, Fidel

2014-11-01

It is well established that immunization with attenuated malaria sporozoites induces CD8(+) T cells that eliminate parasite-infected hepatocytes. Liver memory CD8(+) T cells induced by immunization with parasites undergo a unique differentiation program and have enhanced expression of CXCR6. Following immunization with malaria parasites, CXCR6-deficient memory CD8(+) T cells recovered from the liver display altered cell-surface expression markers as compared to their wild-type counterparts, but they exhibit normal cytokine secretion and expression of cytotoxic mediators on a per-cell basis. Most importantly, CXCR6-deficient CD8(+) T cells migrate to the liver normally after immunization with Plasmodium sporozoites or vaccinia virus, but a few weeks later their numbers severely decrease in this organ, losing their capacity to inhibit malaria parasite development in the liver. These studies are the first to show that CXCR6 is critical for the development and maintenance of protective memory CD8(+) T cells in the liver. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Acarbose versus trans-chalcone: comparing the effect of two glycosidase inhibitors on obese mice.

PubMed

Jalalvand, Fatemeh; Amoli, Mahsa M; Yaghmaei, Parichehreh; Kimiagar, Masoud; Ebrahim-Habibi, Azadeh

2015-06-01

Acarbose and trans-chalcone are glucosidase inhibitors whose beneficial effects have been demonstrated in diabetes. The present study aimed at investigating their potential effects in obesity. NMRI male mice (n = 48) were subjected to a high fat diet for four weeks, which induced an initial state of obesity. One control group was given normal rodent diet. Obese animals were then switched to normal rodent diet, and divided to four groups (n = 12 in each): untreated, sham (receiving grape seed oil), and experimental groups receiving acarbose and trans-chalcone (12 mg/kg) during eight weeks. Body weight, blood glucose and other biochemical parameters including triglycerides (TG), cholesterol, HDL, AST, and ALT were measured, as well as leptin, adiponectin, TNF-α, and total antioxidant capacity (TAC). Histological studies were performed on adipose cells and liver tissue samples. All factors were affected in a positive manner by acarbose, save for body weight, blood sugar and leptin levels, on which acarbose effects, although observable, were not statistically significant. Grape seed oil, used as a solvent for trans-chalcone was found to possess significant effect on TG and TAC, and had beneficial effects on other factors including liver enzymes and cholesterol. Trans-chalcone effects were significant on HDL, leptin and ALT. All compounds seemed to be able to affect fat deposition in liver tissue, and decrease the size of adipose tissue cells to some extent. In conclusion, the tested compounds were able to affect lipid accumulation in tissues and influence adipokines, which may result in an enhanced state with regard to inflammation and oxidative stress.

[Measurement of the status of trace elements in cattle using liver biopsy samples].

PubMed

Ouweltjes, W; de Zeeuw, A C; Moen, A; Counotte, G H M

2007-02-01

Serum, plasma, or urine samples are usually used for the measurement of the trace elements copper; zinc, iron, selenium, because these samples are easy to obtain; however; these samples are not always appropriate. For example, it is not possible to measure molybdenum, the major antagonist of copper; in blood or urine. Therefore measurement of trace elements in liver tissue is considered the gold standard. For the assessment of selenium the method of choice remains determination of glutathion peroxidase in erythrocytes and for the assessment of magnesium determination of magnesium in urine. We determined the accuracy and repeatability of measuring trace elements in liver biopsies and whole liver homogenates. The levels of trace elements measured were similar in both preparations (92% agreement). Liver biopsy in live animals is a relatively simple procedure but not common in The Netherlands. Reference levels of trace elements, classified as too low, low, adequate, high, and too high, were established on the basis of our research and information in the literature. In a second study we investigated the practical aspects of obtaining liver tissue samples and their use. Samples were collected from cattle on a commercial dairy farm. Liver biopsy provided additional information to that obtained from serum and urine samples. We prepared a biopsy protocol and a test package, which we tested on 14 farms where an imbalance of trace minerals was suspected. Biopsy samples taken from 4 to 6 animals revealed extreme levels of trace elements.

Higher dietary choline intake is associated with lower risk of nonalcoholic fatty liver in normal-weight Chinese women.

PubMed

Yu, Danxia; Shu, Xiao-Ou; Xiang, Yong-Bing; Li, Honglan; Yang, Gong; Gao, Yu-Tang; Zheng, Wei; Zhang, Xianglan

2014-12-01

Choline deficiency has been shown to induce liver fat accumulation in both rodent and human studies. However, it is unclear whether dietary choline intake is related to fatty liver in the general population. We examined the association between choline intake and nonalcoholic fatty liver. Participants included 56,195 Chinese women and men, 40-75 y of age, with no or negligible alcohol consumption and with no history of hepatitis, cardiovascular disease, or cancer. All participants reported undergoing liver ultrasonography. Fatty liver was defined by self-report of a physician diagnosis. Habitual dietary intakes were assessed via validated food-frequency questionnaires. The average total choline intakes were 289 ± 85 mg/d in women and 318 ± 92 mg/d in men. Major food sources were eggs, soy foods, red meat, fish, and vegetables. A higher choline intake was associated with lower risk of fatty liver; after adjustment for sociodemographic characteristics, lifestyle factors, and other dietary intakes, the ORs (95% CIs) for the highest vs. the lowest quintiles of choline intake were 0.68 (0.59, 0.79) in women and 0.75 (0.60, 0.93) in men (both P-trend < 0.01). The inverse association was attenuated after further adjustment for history of metabolic disease and, in particular, BMI. The corresponding ORs (95% CIs) were 0.88 (0.75, 1.03) in women (P-trend = 0.05) and 0.85 (0.68, 1.06) in men (P-trend = 0.09). Stratified analyses suggested a potential effect modification by obesity status in women; the OR (95% CI) across extreme quintiles was 0.72 (0.57, 0.91) in normal-weight women vs. 1.05 (0.84, 1.31) in overweight or obese women (P-trend = 0.007 vs. 0.99, P-interaction < 0.0001). Higher dietary choline intake may be associated with lower risk of nonalcoholic fatty liver only in normal-weight Chinese women. © 2014 American Society for Nutrition.

Higher Dietary Choline Intake Is Associated with Lower Risk of Nonalcoholic Fatty Liver in Normal-Weight Chinese Women12

PubMed Central

Yu, Danxia; Shu, Xiao-Ou; Xiang, Yong-Bing; Li, Honglan; Yang, Gong; Gao, Yu-Tang; Zheng, Wei; Zhang, Xianglan

2014-01-01

Background: Choline deficiency has been shown to induce liver fat accumulation in both rodent and human studies. However, it is unclear whether dietary choline intake is related to fatty liver in the general population. Objective: We examined the association between choline intake and nonalcoholic fatty liver. Methods: Participants included 56,195 Chinese women and men, 40–75 y of age, with no or negligible alcohol consumption and with no history of hepatitis, cardiovascular disease, or cancer. All participants reported undergoing liver ultrasonography. Fatty liver was defined by self-report of a physician diagnosis. Habitual dietary intakes were assessed via validated food-frequency questionnaires. Results: The average total choline intakes were 289 ± 85 mg/d in women and 318 ± 92 mg/d in men. Major food sources were eggs, soy foods, red meat, fish, and vegetables. A higher choline intake was associated with lower risk of fatty liver; after adjustment for sociodemographic characteristics, lifestyle factors, and other dietary intakes, the ORs (95% CIs) for the highest vs. the lowest quintiles of choline intake were 0.68 (0.59, 0.79) in women and 0.75 (0.60, 0.93) in men (both P-trend < 0.01). The inverse association was attenuated after further adjustment for history of metabolic disease and, in particular, BMI. The corresponding ORs (95% CIs) were 0.88 (0.75, 1.03) in women (P-trend = 0.05) and 0.85 (0.68, 1.06) in men (P-trend = 0.09). Stratified analyses suggested a potential effect modification by obesity status in women; the OR (95% CI) across extreme quintiles was 0.72 (0.57, 0.91) in normal-weight women vs. 1.05 (0.84, 1.31) in overweight or obese women (P-trend = 0.007 vs. 0.99, P-interaction < 0.0001). Conclusion: Higher dietary choline intake may be associated with lower risk of nonalcoholic fatty liver only in normal-weight Chinese women. PMID:25320186

STUDIES ON THE DISTRIBUTION AND PHOSPHATE TURNOVER OF THE ACID-SOLUBLE PHOSPHORUS COMPOUNDS IN VARIOUS NORMAL AND NEOPLASTIC TISSUES OF RATS. II. COMPARISON OF THE CHROMATOGRAMS OBTAINED WITH VARIOUS TISSUES INCLUDING TUMOURS (ENGLISH TEXT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Horie, S.

Using a modified semi-micro gradient elution method of chromatography, the distribution of the acid-soluble nucleotides in various normal and neoplastic tissues of rats was compared and the variations of the distribution are described. The distribution and phosphate turnover of the acid-soluble phosphorus compounds were also studied by intraperitoneal injection of P/sup 32/ followed by the chromatographic analysis. The distribution patterns of nucleotides and radioactivity in liver, muscle, heart, lung, thymus, spleen, testicles, brain, fetal liver, and experimental hepatomas are illustrated and the differences between these tissues were pointed out. The characteristics of the experimental hepatoma tissue as compared with themore » normal liver tissue are as follows: The concentration of oxidized DPN was low; the incorporation of P/sup 32/ inorganic phosphate into glucose 6-phosphate and L- alpha -glycerophosphate was absent or, if any, very low; radioactivity of inorganic phosphate in the total acid-soluble radioactivity was extraordinarily high as compared with other tissues besides the liver tissue. (Abstr. Japan Med., 1: No. 9, 1961)« less

Nicotine Promotes Cholangiocarcinoma Growth in Xenograft Mice.

PubMed

Martínez, Allyson K; Jensen, Kendal; Hall, Chad; O'Brien, April; Ehrlich, Laurent; White, Tori; Meng, Fanyin; Zhou, Tianhao; Greene, John; Bernuzzi, Francesca; Invernizzi, Pietro; Dostal, David E; Lairmore, Terry; Alpini, Gianfranco; Glaser, Shannon S

2017-05-01

Nicotine, the main addictive substance in tobacco, is known to play a role in the development and/or progression of a number of malignant tumors. However, nicotine's involvement in the pathogenesis of cholangiocarcinoma is controversial. Therefore, we studied the effects of nicotine on the growth of cholangiocarcinoma cells in vitro and the progression of cholangiocarcinoma in a mouse xenograft model. The predominant subunit responsible for nicotine-mediated proliferation in normal and cancer cells, the α7 nicotinic acetylcholine receptor (α7-nAChR), was more highly expressed in human cholangiocarcinoma cell lines compared with normal human cholangiocytes. Nicotine also stimulated the proliferation of cholangiocarcinoma cell lines and promoted α7-nAChR-dependent activation of proliferation and phosphorylation of extracellular-regulated kinase in Mz-ChA-1 cells. In addition, nicotine and PNU282987 (α7-nAChR agonist) accelerated the growth of the cholangiocarcinoma tumors in our xenograft mouse model and increased fibrosis, proliferation of the tumor cells, and phosphorylation of extracellular-regulated kinase activation. Finally, α7-nAChR was expressed at significantly higher levels in human cholangiocarcinoma compared with normal human control liver samples. Taken together, results of this study suggest that nicotine acts through α7-nAChR and plays a novel role in the pathogenesis of cholangiocarcinoma. Furthermore, nicotine may act as a mitogen in cholestatic liver disease processes, thereby facilitating malignant transformation. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Pathology of runting in farmed saltwater crocodiles (Crocodylus porosus) in Australia.

PubMed

Shilton, C; Brown, G P; Chambers, L; Benedict, S; Davis, S; Aumann, S; Isberg, S R

2014-09-01

Extremely poor growth of some individuals within a birth cohort (runting) is a significant problem in crocodile farming. We conducted a pathological investigation to determine if infectious disease is associated with runting in farmed saltwater crocodiles (Crocodylus porosus) and to look for evidence of other etiologies. In each of 2005 and 2007, 10 normal and 10 runt crocodiles, with an average age of 5.5 months and reared under identical conditions, were sampled. Laboratory testing included postmortem; histological examination of a wide variety of tissues (with quantitation of features that were noted subjectively to be different between groups); hematology; serum biochemistry (total protein, albumin, globulins, total calcium, phosphorus, and iron); bacterial culture of liver and spleen (2005 only); viral culture of liver, thymus, tonsil, and spleen using primary crocodile cell lines (2007 only); and serum corticosterone (2007 only). The only evidence of infectious disease was mild cutaneous poxvirus infection in 45% of normal and 40% of runt crocodiles and rare intestinal coccidia in 5% of normal and 15% of runt crocodiles. Bacterial and viral culture did not reveal significant differences between the 2 groups. However, runt crocodiles exhibited significant (P < .05) increases in adrenocortical cell cytoplasmic vacuolation and serum corticosterone, decreased production of bone (osteoporosis), and reduced lymphoid populations in the spleen, tonsil, and thymus. Runts also exhibited moderate anemia, hypoalbuminemia, and mild hypophosphatemia. Taken together, these findings suggest an association between runting and a chronic stress response (hyperactivity of the hypothalamic-pituitary-adrenal axis). © The Author(s) 2014.

High Prevalence of Nonalcoholic Fatty Liver Disease in Patients With Type 2 Diabetes Mellitus and Normal Plasma Aminotransferase Levels.

PubMed

Portillo-Sanchez, Paola; Bril, Fernando; Maximos, Maryann; Lomonaco, Romina; Biernacki, Diane; Orsak, Beverly; Subbarayan, Sreevidya; Webb, Amy; Hecht, Joan; Cusi, Kenneth

2015-06-01

Nonalcoholic fatty liver disease (NAFLD) and its more severe form with steatohepatitis (NASH) are common in patients with type 2 diabetes mellitus (T2DM). However, they are usually believed to largely affect those with elevated aminotransferases. The aim of this study was to determine the prevalence of NAFLD by the gold standard, liver magnetic resonance spectroscopy ((1)H-MRS) in patients with T2DM and normal aminotransferases, and to characterize their metabolic profile. We recruited 103 patients with T2DM and normal plasma aminotransferases (age, 60 ± 8 y; body mass index [BMI], 33 ± 5 kg/m(2); glycated hemoglobin [A1c], 7.6 ± 1.3%). We measured the following: 1) liver triglyceride content by (1)H-MRS; 2) systemic insulin sensitivity (homeostasis model assessment-insulin resistance); and 3) adipose tissue insulin resistance, both fasting (as the adipose tissue insulin resistance index: fasting plasma free fatty acids [FFA] × insulin) and during an oral glucose tolerance test (as the suppression of FFA). The prevalence of NAFLD and NASH were much higher than expected (50% and 56% of NAFLD patients, respectively). The prevalence of NAFLD was higher in obese compared with nonobese patients as well as with increasing BMI (P = .001 for trend). Higher plasma A1c was associated with a greater prevalence of NAFLD and worse liver triglyceride accumulation (P = .01). Compared with nonobese patients without NAFLD, patients with NAFLD had severe systemic (liver/muscle) and, particularly, adipose tissue (fasting/postprandial) insulin resistance (all P < .01). The prevalence of NAFLD is much higher than previously believed in overweight/obese patients with T2DM and normal aminotransferases. Moreover, many are at increased risk of NASH. Physicians should have a lower threshold for screening patients with T2DM for NAFLD/NASH.

Effects of maternal dietary manganese and incubation temperature on hatchability, antioxidant status, and expression of heat shock proteins in chick embryos.

PubMed

Zhu, Y W; Lu, L; Li, W X; Zhang, L Y; Ji, C; Lin, X; Liu, H C; Odle, J; Luo, X G

2015-12-01

To investigate whether supplementing manganese (Mn) to the maternal diet could reduce the deleterious effect of heat stress on the developing embryo, the hatchability, antioxidant status, and expression of heat shock proteins (HSP) were evaluated in chick embryos under normal and high incubation temperatures. A completely randomized design ( = 6) with 2 maternal dietary Mn treatments (unsupplemented control basal diet versus the basal diet + 120 mg Mn/kg as inorganic Mn) × 2 incubation temperatures (normal, 37.8°C, versus high, 39.0°C) was used. High incubation temperature did not affect ( > 0.19) hatchability and embryo mortality and development but did increase ( < 0.05) activities of heart manganese superoxide dismutase (MnSOD) and liver copper zinc superoxide dismutase and liver MnSOD mRNA and protein levels in embryos. High incubation temperature also decreased ( < 0.003) HSP70 protein level in the heart but had no effects ( > 0.07) in the liver of embryos. Maternal diet with Mn supplementation not only increased ( < 0.05) the hatchability and Mn content ( < 0.001) in the yolk and embryonic tissues and the activity of MnSOD in the heart ( < 0.004) as well as relative liver weight ( < 0.05) under normal incubation temperature but also decreased ( ≤ 0.05) embryo mortality and HSP90 mRNA level in the liver and heart of embryos. Furthermore, under high incubation temperature, maternal diet Mn supplementation increased ( < 0.002) MnSOD protein expression in the liver of embryos but had no effect ( > 0.43) under normal incubation temperature. These results indicated that high incubation temperature induced self-protective responses of chick embryos with a modification of antioxidant status and a depression of HSP70 protein level. Maternal dietary supplementation of Mn could improve the hatchability as well as antioxidant ability to protect against heat challenge in embryos during incubation.

In vivo tumor identification of colorectal liver metastases with diffuse reflectance and fluorescence spectroscopy.

PubMed

Tanis, Erik; Evers, Danny J; Spliethoff, Jarich W; Pully, Vishnu V; Kuhlmann, Koert; van Coevorden, Frits; Hendriks, Benno H W; Sanders, Joyce; Prevoo, Warner; Ruers, Theo J M

2016-11-01

Over the last decade, an increasing effort has been put towards the implementation of optical guidance techniques to aid surgeons during cancer surgery. Diffuse reflectance spectroscopy (DRS) and fluorescence spectroscopy (FS) are two of these new techniques. The objective of this study is to investigate whether in vivo optical spectroscopy is able to accurately discriminate colorectal liver metastases (CRLM) from normal liver tissue in vivo. DRS and FS were incorporated at the tip of a needle and were used for in vivo tissue differentiation during resection of CRLM. Measurements were taken in and around the tumor lesions and measurement sites were marked and correlated to histology (i.e., normal liver tissue or tumor tissue). Patients with and without neoadjuvant systemic chemotherapy were included into the study. Four hundred and eighty-four measurements were taken in and near 19 liver lesions prior to resection. Overall sensitivity and specificity for DRS was 95% and 92%, respectively. Bile was the most discriminative parameter. The addition of FS did not improve the overall accuracy. Sensitivity and specificity was not hampered by neo-adjuvant chemotherapy; sensitivity and specificity after neo-adjuvant chemotherapy were 92% and 100%, respectively. We have successfully integrated spectroscopy technology into a disposable 15 Gauge optical needle and we have shown that DRS and FS can accurately discriminate CRLM from normal liver tissue in the in vivo setting regardless of whether the patient was pre-treated with systemic therapy. This technique makes in vivo guidance accessible for common surgical practice. Lasers Surg. Med. 48:820-827, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Reduction of systemic exposure and toxicity of cisplatin by encapsulation in poly-lactide-co-glycolide.

PubMed

Verrijk, R; Smolders, I J; Bosnie, N; Begg, A C

1992-12-01

The tissue distribution and normal tissue toxicity of cisplatin (cDDP) administered as poly-lactide-co-glycolide (PLAGA) microspheres, developed for loco-regional administration of cDDP to the liver, were studied in Wag/Rij rats. Venoportal administration of this formulation resulted in a reduction in total systemic and renal toxicity, which correlated with a decrease in normal tissue exposure to cDDP while maintaining high liver platinum levels. Liver-to-kidney platinum level ratios were 28 times higher after 4 h and 19 times higher after 24 h with PLAGA-cDDP microspheres than with free cDDP. Liver-to-blood platinum ratios at these times were 38 times and 36 times higher using PLAGA-cDDP. In a CC531 colon carcinoma liver micrometastases model, cytotoxicity of microsphere-released cDDP was confirmed in vivo by equal inhibition of tumor growth by PLAGA-cDDP and free cDDP over a period of 26 days. Free cDDP, however, caused significantly more histological renal damage and total body weight loss. The results were supported by the finding of higher plasma creatinine and urea concentrations 26 days after administration of free cDDP. Kidney platinum levels were 7 times lower when PLAGA-cDDP was used. These findings indicate a sparing effect on normal tissues when cDDP is targeted to the liver by formulation in PLAGA. PLAGA-cDDP microspheres may, therefore, be a useful and effective addition to current techniques of loco-regional chemotherapy for disseminated hepatic tumors.

Elevated trimethylamine-N-oxide (TMAO) is associated with poor prognosis in primary sclerosing cholangitis patients with normal liver function.

PubMed

Kummen, Martin; Vesterhus, Mette; Trøseid, Marius; Moum, Bjørn; Svardal, Asbjørn; Boberg, Kirsten Muri; Aukrust, Pål; Karlsen, Tom Hemming; Berge, Rolf Kristian; Hov, Johannes Roksund

2017-06-01

Trimethylamine- N -oxide (TMAO) is produced in the liver from trimethylamine, which is exclusively generated by gut bacteria. The objective of this article is to investigate the relationship between TMAO and primary sclerosing cholangitis (PSC) and its clinical characteristics. Serum TMAO was measured in 305 PSC patients, 90 ulcerative colitis patients and 99 healthy controls. In PSC patients with normal liver function ( n  = 197), TMAO was higher in patients reaching liver transplantation or death during follow-up than those who did not, with an optimal TMAO cut-off of 4.1 µM (AUC = 0.64, p  < 0.001). PSC patients with high TMAO (>4.1 µM, n  = 77) exhibited shorter transplantation-free survival than patients with low TMAO ( n  = 120, log-rank test: p  < 0.0001). High TMAO (>4.1 µM) was associated with reduced transplantation-free survival (HR 1.87, p  = 0.011), independently of the Mayo risk score (HR 1.74, p  < 0.001). Overall, PSC patients demonstrated reduced TMAO values compared with ulcerative colitis and healthy controls, mainly caused by PSC patients with reduced liver function (INR > 1.2), suggesting impaired oxidation of trimethylamine to TMAO. PSC patients with and without inflammatory bowel disease had similar TMAO levels. In PSC patients with normal liver function, elevated TMAO was associated with shorter transplantation-free survival, potentially reflecting clinically relevant metabolic changes resulting from dietary interactions with the gut microbiota.

Untangling the etiology of ascites.

PubMed

Lopez-Molina, Michael; Shiani, Ashok V; Oller, Kellee L

2015-04-06

Amyloidosis is a systemic disease known to affect a vast range of organs, including the liver, heart, and kidney. When infiltrating the liver, amyloidosis typically does not present with cirrhosis. Typical presentation includes hepatomegaly with some mild laboratory abnormalities. A 72-year-old man presented with a 2-week history of worsening abdominal, scrotal, and extremity swelling. He endorsed melanotic stools and intermittent dizziness with a 10-pound weight gain. Vitals revealed a blood pressure of 82/57 mmHg and a pulse of 83 beats/min with positive orthostatic changes. Mild bibasilar crackles were noted. His abdomen was moderately distended with a fluid wave present, but no hepatosplenomegaly was noted. He displayed anasarca with significant extremity and scrotal edema, but no jaundice, telangiectasias, or other stigmata of chronic liver disease were present. Liver function tests demonstrated a total bilirubin of 1.5 mg/dL (normal value: 0.2-1.2 mg/dL), AST 111 IU/L (normal value 5-34 IU/L), ALT 51 IU/L (normal value 5-55 IU/L), and GGT 583 U/L (12-64 U/L). Alkaline phosphatase was 645 U/L (40-150 U/L). Analysis of peritoneal fluid was consistent with portal hypertension due to liver disease. Given an atypical presentation of cirrhosis with unclear etiology, a biopsy was performed and revealed amyloid deposition. Liver disease can be due to various etiologies, many of which can present ambiguously. Although the most typical etiologies have been well defined, we present a case of an atypical presentation of hepatic amyloidosis discovered in a patient with ascites and without typical hepatomegaly.

Lesions of the segmental and lobar hepatic ducts.

PubMed Central

Longmire, W P; Tompkins, R K

1975-01-01

Despite reports to the contrary, unobstructed drainage of 50% of an otherwise normal liver through either the right or left uninfected hepatic duct is adequate to restore normal liver function, even if the obstructed lobe remains in place. An undrained liver lobe, if present, may require no further treatment. As long as it is completely obstructed and uninfected, it will undergo a progressive asymptomatic atrophy. Cholangitis invariably develops behind a partial lobar ductal obstruction, producing jaundice, pruritis, and fever. Unless unobstructed, uninfected biliary flow can be achieved through a segmental or lobar duct, it is better that the duct be completely obstructed and the affected liver parenchyma allowed to atrophy, provided there is normal biliary flow from the residual 50% of liver. This concept is important in the management of injured anomalous segmental or lobar hepatic duct and in the palliative treatment of bile duct carcinoma. Localized intrahepatic infections communicating with abnormal biliary ducts will require hepatic resection of the infected parenchyma and ducts for cure. The abnormality may be saccular dilatation of the intrahepatic ductal system with abscess formation or intrahepatic abscess associated with stenosis of the ductal system from trauma to the duct, to the duct and liver, or to retained intrahepatic stones. Diffusely situated intrahepatic abscesses secondary to ductal abnormalities can be treated with systemic antibiotics, local drainage of a dmoninant abscess, and efforts to improve biliary drainage. Images Fig. 4. Fig. 5. Fig. 6. Fig. 8. Fig. 9. Fig. 10. Figs. 11A and B Figs. 12A and B. Fig. 13. Fig. 14. Fig. 15. Fig. 16. Fig. 17. PMID:1180585

Hepatic extraction and renal production of 3,3'-diiodothyronine and 3',5'-diiodothyronine in man.

PubMed Central

Faber, J; Faber, O K; Lund, B; Kirkegaard, C; Wahren, J

1980-01-01

The sequential deiodination of thyroxine (T4) gives rise to several iodothyronine analogs including 3,3'-diiodothyronine (3,3'-T2) and 3',5'-diiodothyronine (3',5'-T2). In vitro animal studies suggest that the liver and the kidneys are the main sites of both formation and degradation of 3,3'-T2 and 3',5'-T2. To determine the metabolism of 3,3'-T2 and 3',5'-T2 in human liver and kidneys plasma samples were obtained from (a) a brachial artery and a hepatic vein in 20 normal subjects, and from (b) a femoral artery and a renal vein in 11 normal subjects. Further, the hepatic plasma flow (a) and the renal plasma flow (b) were determined. Both plasma 3,3'-T2 and 3',5'-T2 levels were reduced in the hepatic venous blood as compared to arterial values (1.09 +/- 0.40 vs. 1.75 +/- 0.74 ng/dl (P < 0.02)) (mean +/- 1 SD). This resulted in a hepatic extraction of both, 3,3'-T2 and 3',5'-T2, which averaged 8.2 and 5.2 microgram/d, respectively. Plasma 3,3'-T2 as well as 3'5'-T2 levels were higher in the renal vein as compared to arterial values, 1.49 +/- 0.42 vs. 1.39 +/- 0.45 ng/dl (P < 0.05) and 2.35 +/- 0.83 vs. 2.09 +/- 0.81 ng/dl (P < 0.05), respectively. This positive venoarterial difference implies a net production of 3,3'-T2 and 3',5'-T2 in the kidneys of 1.2 and 3.0 microgram/d, respectively. It is concluded that the liver is an important site of 3,3'-T2 and 3',5'-T2 extraction in normal man. In contrast, the renal production of 3,3'-T2 as well as 3'5'-T2 exceeds the degradation and urinary excretion. PMID:6776146

Polonium-210 and Caesium-137 in lynx (Lynx lynx), wolverine (Gulo gulo) and wolves (Canis lupus).

PubMed

Gjelsvik, Runhild; Holm, Elis; Kålås, John Atle; Persson, Bertil; Asbrink, Jessica

2014-12-01

Wolves, lynx and wolverines are on the top of the food-chain in northern Scandinavia and Finland. (210)Po and (137)Cs have been analysed in samples of liver, kidney and muscle from 28 wolves from Sweden. In addition blood samples were taken from 27 wolves. In 9 of the wolves, samples of muscle, liver and blood were analysed for (210)Po. Samples of liver and muscle were collected from 16 lynx and 16 wolverines from Norway. The liver samples were analysed for (210)Po and (137)Cs. Only (137)Cs analyses were carried out for the muscle samples. The wolves were collected during the winter 2010 and 2011, while the samples for lynx and wolverines were all from 2011. The activity concentrations of (210)Po in wolves were higher for liver (range 20-523 Bq kg(-1) d.w.) and kidney (range 24-942 Bq kg(-1) d.w.) than muscle (range 1-43 Bq kg(-1) d.w.) and blood (range 2-54 Bq kg(-1) d.w.). Activity ratios, (210)Po/(210)Pb, in wolf samples of muscle, liver and blood were in the ranges 2-77, 9-56 and 2-54. Using a wet weight ratio of 3.8 the maximal absorbed dose from (210)Po to wolf liver was estimated to 3500 μGy per year. Compared to wolf, the ranges of (210)Po in liver samples were lower in lynx (range 22-211 Bq kg(-1) d.w.) and wolverine (range16-160 Bq kg(-1) d.w.). Concentration of (137)Cs in wolf samples of muscle, liver, kidney and blood were in the ranges 70-8410 Bq kg(-1) d.w., 36-4050 Bq kg(-1) d.w., 31-3453 Bq kg(-1) d.w. and 4-959 Bq kg(-1) d.w., respectively. (137)Cs in lynx muscle and liver samples were in the ranges 44-13393 Bq kg(-1) d.w. and 125-10260 Bq kg(-1) d.w. The corresponding values for (137)Cs in wolverine were 22-3405 Bq kg(-1) d.w. for liver and 53-4780 Bq kg(-1) d.w. for muscle. The maximal absorbed dose from (137)Cs to lynx was estimated to 3000 μGy per year. Copyright © 2014 Elsevier Ltd. All rights reserved.

Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: a randomized controlled trial.

PubMed

Loguercio, Carmela; Andreone, Pietro; Brisc, Ciprian; Brisc, Michaela Cristina; Bugianesi, Elisabetta; Chiaramonte, Maria; Cursaro, Carmela; Danila, Mirela; de Sio, Ilario; Floreani, Annarosa; Freni, Maria Antonietta; Grieco, Antonio; Groppo, Marzia; Lazzari, Roberta; Lobello, Salvatore; Lorefice, Elisabetta; Margotti, Marzia; Miele, Luca; Milani, Stefano; Okolicsanyi, Lajos; Palasciano, Giuseppe; Portincasa, Piero; Saltarelli, Patrizia; Smedile, Antonina; Somalvico, Francesco; Spadaro, Aldo; Sporea, Ioan; Sorrentino, Paolo; Vecchione, Raffaela; Tuccillo, Concetta; Del Vecchio Blanco, Camillo; Federico, Alessandro

2012-05-01

The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight. These findings warrant further investigation. Copyright © 2012 Elsevier Inc. All rights reserved.

Sugammadex antagonism of rocuronium-induced neuromuscular blockade in patients with liver cirrhosis undergoing liver resection: a randomized controlled study.

PubMed

Abdulatif, Mohamed; Lotfy, Maha; Mousa, Mahmoud; Afifi, Mohamed H; Yassen, Khaled

2018-02-05

This randomized controlled study compared the recovery times of sugammadex and neostigmine as antagonists of moderate rocuroniuminduced neuromuscular block in patients with liver cirrhosis and controls undergoing liver resection. The study enrolled 27 adult patients with Child class "A" liver cirrhosis and 28 patients with normal liver functions. Normal patients and patients with liver cirrhosis were randomized according to the type of antagonist (sugammadex 2mg/kg or neostigmine 50μg/kg). The primary outcome was the time from antagonist administration to a trainoffour (TOF) ratio of 0.9 using mechanosensor neuromuscular transmission module. The durations of the intubating and topup doses of rocuronium, the length of stay in the postanesthesia care unit (PACU), and the incidence of postoperative re curarization were recorded. The durations of the intubating and topup doses of rocuronium were prolonged in patients with liver cirrhosis than controls. The times to a TOF ratio of 0.9 were 3.1 (1.0) and 2.6 (1.0) min after sugammadex administration in patients with liver cirrhosis and controls, respectively, p=1.00. The corresponding times after neostigmine administration were longer than sugammadex 14.5 (3.6) and 15.7 (3.6) min, respectively, p<0.001. The duration of PACU stay was shorter with the use of sugammadex compared to neostigmine. We did not encounter postoperative recurarization after sugammadex or neostigmine. Sugammadex rapidly antagonize moderate residual rocuronium induced neuromuscular block in patients with Child class "A" liver cirrhosis undergoing liver resection. Sugammadex antagonism is associated with 80% reduction in the time to adequate neuromuscular recovery compared to neostigmine.

Administration of multipotent mesenchymal stromal cells restores liver regeneration and improves liver function in obese mice with hepatic steatosis after partial hepatectomy.

PubMed

Ezquer, Fernando; Bahamonde, Javiera; Huang, Ya-Lin; Ezquer, Marcelo

2017-01-28

The liver has the remarkable capacity to regenerate in order to compensate for lost or damaged hepatic tissue. However, pre-existing pathological abnormalities, such as hepatic steatosis (HS), inhibits the endogenous regenerative process, becoming an obstacle for liver surgery and living donor transplantation. Recent evidence indicates that multipotent mesenchymal stromal cells (MSCs) administration can improve hepatic function and increase the potential for liver regeneration in patients with liver damage. Since HS is the most common form of chronic hepatic illness, in this study we evaluated the role of MSCs in liver regeneration in an animal model of severe HS with impaired liver regeneration. C57BL/6 mice were fed with a regular diet (normal mice) or with a high-fat diet (obese mice) to induce HS. After 30 weeks of diet exposure, 70% hepatectomy (Hpx) was performed and normal and obese mice were divided into two groups that received 5 × 10 5 MSCs or vehicle via the tail vein immediately after Hpx. We confirmed a significant inhibition of hepatic regeneration when liver steatosis was present, while the hepatic regenerative response was promoted by infusion of MSCs. Specifically, MSC administration improved the hepatocyte proliferative response, PCNA-labeling index, DNA synthesis, liver function, and also reduced the number of apoptotic hepatocytes. These effects may be associated to the paracrine secretion of trophic factors by MSCs and the hepatic upregulation of key cytokines and growth factors relevant for cell proliferation, which ultimately improves the survival rate of the mice. MSCs represent a promising therapeutic strategy to improve liver regeneration in patients with HS as well as for increasing the number of donor organs available for transplantation.

Liver cirrhosis in Fontan patients does not affect 1-year post-heart transplant mortality or markers of liver function.

PubMed

Simpson, Kathleen E; Esmaeeli, Amir; Khanna, Geetika; White, Francis; Turnmelle, Yumirle; Eghtesady, Pirooz; Boston, Umar; Canter, Charles E

2014-02-01

Liver cirrhosis is recognized with long-term follow-up of patients after the Fontan procedure. The effect of liver cirrhosis on the use of heart transplant (HT) and on post-HT outcomes is unknown. We reviewed Fontan patients evaluated for HT from 2004 to 2012 with hepatic computed tomography (CT) imaging, classified as normal, non-cirrhotic changes, or cirrhosis. The primary outcome was 1-year all-cause mortality, and the secondary outcome was differences in serial post-HT liver evaluation. CT imaging in 32 Fontan patients evaluated for HT revealed 20 (63%) with evidence of liver disease, including 13 (41%) with cirrhosis. Twenty underwent HT, including 5 non-cirrhotic and 7 cirrhosis patients. Characteristics at listing between normal or non-cirrhotic (n = 13) and cirrhosis (n = 7) groups were similar, except cirrhosis patients were older (median 17.6 vs 9.6 years, p = 0.002) and further from Fontan (median 180 vs 50 months, p < 0.05). Serial liver evaluation was similar, including aspartate aminotransferase, alanine aminotransferase, bilirubin, albumin, and tacrolimus dose at 1, 3, 6, 9, and 12 months. Overall patient survival was 80% at 1 year, with no difference between cirrhosis and non-cirrhosis patients (86% vs 77%, p = 0.681). Liver biopsies were performed in 7 patients before HT, and all specimens showed architectural changes with bridging fibrosis. Most patients evaluated for HT had abnormal liver findings by CT, with cirrhosis in 41%. One-year mortality and serial liver evaluation were similar between groups after HT. Liver cirrhosis identified by CT imaging may not be an absolute contraindication to HT alone in this population. © 2014 International Society for Heart and Lung Transplantation Published by International Society for the Heart and Lung Transplantation All rights reserved.

Detection and functional analysis of tumor infiltrating T-lymphocytes (TIL) in liver metastases from colorectal cancer.

PubMed

Wagner, Philipp; Koch, Moritz; Nummer, Daniel; Palm, Sylvia; Galindo, Luis; Autenrieth, Daniel; Rahbari, Nuh; Schmitz-Winnenthal, Friedrich H; Schirrmacher, Volker; Büchler, Markus W; Beckhove, Philipp; Weitz, Jürgen

2008-08-01

Tumor-infiltrating T lymphocytes (TIL) play an important role in primary colorectal cancer, but their activity in liver metastases has not yet been investigated. The aim of this study was to examine whether tumor-selective infiltration, activation, and cytotoxic activity of TIL can be demonstrated in situ in colorectal liver metastases. TIL were obtained from liver metastases and corresponding normal liver tissue of 16 patients with colorectal liver metastases. Characterization of TIL in situ was performed by multicolor flowcytometric analysis. Presence of tumor antigen-reactive T cells was evaluated by interferon gamma Elispot analysis. TIL in colorectal liver metastases responding against tumor antigens were present in most patients. Although the proportions of CD3(+) T cells were comparable in liver metastasis and normal liver tissue, metastases contained significantly enhanced proportions of CD4(+) cells (49% vs. 22%, P < .001). Among all CD4(+) T helper cells, the proportion of activated (CD4(+)CD25(+)) effector cells was significantly increased in liver metastases (15.0% vs. 7.8%, P = .003). Metastases showed significantly higher proportions of activated (CD69(+) [70.1% vs. 49.8%, P = .02] and CD25(+) [4.1% vs. .6%, P = .06]) and cytotoxically active (CD107a(+)) CD8(+) TIL (3.2% vs. 1.3%, P = .03). Importantly, the presence of activated T helper cells correlated with the frequencies of cytotoxic T lymphocytes that exerted cytotoxic activity in situ (P = .02). CD4(+) and CD8(+) TIL are selectively activated in liver metastases, and cytotoxic T lymphocytes exert tumor-selective cytotoxic activity in situ in the presence of activated T helper cells, suggesting the requirement of in-situ-activated T helper cells for efficient cytotoxic T lymphocytes effector function.

Abnormal permeability of inner and outer mitochondrial membranes contributes independently to mitochondrial dysfunction in the liver during acute endotoxemia.

PubMed

Crouser, Elliott D; Julian, Mark W; Huff, Jennifer E; Joshi, Mandar S; Bauer, John A; Gadd, Martha E; Wewers, Mark D; Pfeiffer, Douglas R

2004-02-01

This study was designed to determine the role played by the mitochondrial permeability transition in the pathogenesis of mitochondrial damage and dysfunction in a representative systemic organ during the acute phase of endotoxemia. A well-established, normotensive feline model was employed to determine whether pretreatment with cyclosporine A, a potent inhibitor of the mitochondrial permeability transition, normalizes mitochondrial ultrastructural injury and dysfunction in the liver during acute endotoxemia. The Ohio State University Medical Center research laboratory. Random source, adult, male conditioned cats. Hemodynamic resuscitation and maintenance of acid-base balance and tissue oxygen availability were provided, as needed, to minimize the potentially confounding effects of tissue hypoxia and/or acidosis on the experimental results. Treatment groups received isotonic saline vehicle (control; n = 6), lipopolysaccharide (3.0 mg/kg, intravenously; n = 8), or cyclosporine A (6.0 mg/kg, intravenously; n = 6) or tacrolimus (FK506, 0.1 mg/kg, intravenously; n = 4) followed in 30 mins by lipopolysaccharide (3.0 mg/kg, intravenously). Liver samples were obtained 4 hrs posttreatment, and mitochondrial ultrastructure, function, and cytochrome c, Bax, and ceramide contents were assessed. As expected, significant mitochondrial injury was apparent in the liver 4 hrs after lipopolysaccharide treatment, despite maintenance of regional tissue oxygen availability. Namely, mitochondria demonstrated high-amplitude swelling and exhibited altered respiratory function. Cyclosporine A pretreatment attenuated lipopolysaccharide-induced mitochondrial ultrastructural abnormalities and normalized mitochondrial respiratory control, reflecting protection against inner mitochondrial membrane damage. However, an abnormal permeability of outer mitochondrial membranes to cytochrome c was observed in all lipopolysaccharide-treated groups and was associated with increased mitochondrial concentrations of Bax and ceramide. These studies confirm that liver mitochondria are early targets of injury during endotoxemia and that inner and outer mitochondrial membrane damage occurs through different mechanisms. Inner mitochondrial membrane damage appears to relate to the mitochondrial permeability transition, whereas outer mitochondrial membrane damage can occur independent of the mitochondrial permeability transition. Preliminary evidence suggests that Bax may participate in lipopolysaccharide-induced outer mitochondrial membrane damage, but further investigations are needed to confirm this.

Muscular exercise can cause highly pathological liver function tests in healthy men

PubMed Central

Pettersson, Jonas; Hindorf, Ulf; Persson, Paula; Bengtsson, Thomas; Malmqvist, Ulf; Werkström, Viktoria; Ekelund, Mats

2008-01-01

Aim To investigate the effect of intensive muscular exercise (weightlifting) on clinical chemistry parameters reflecting liver function in healthy men. Methods Fifteen healthy men, used to moderate physical activity not including weightlifting, performed an 1 h long weightlifting programme. Blood was sampled for clinical chemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), gamma-glutamyl transferase (γGT), alkaline phosphatase (ALP), bilirubin, creatine kinase (CK) and myoglobin] at repeated intervals during 7 days postexercise and at a follow-up examination 10–12 days postexercise. Results Five out of eight studied clinical chemistry parameters (AST, ALT, LD, CK and myoglobin) increased significantly after exercise (P < 0.01) and remained increased for at least 7 days postexercise. Bilirubin, γGT and ALP remained within the normal range. Conclusion The liver function parameters, AST and ALT, were significantly increased for at least 7 days after the exercise. In addition, LD and, in particular, CK and myoglobin showed highly elevated levels. These findings highlight the importance of imposing restrictions on weightlifting prior to and during clinical studies. Intensive muscular exercise, e.g. weightlifting, should also be considered as a cause of asymptomatic elevations of liver function tests in daily clinical practice. What is already known about this subject The occurrence of idiosyncratic drug hepatotoxicity is a major problem in all phases of clinical drug development and the leading cause of postmarketing warnings and withdrawals.Physical exercise can result in transient elevations of liver function tests.There is no consensus in the literature on which forms of exercise may cause changes in liver function tests and to what extent. What this study adds Weightlifting results in profound increases in liver function tests in healthy men used to moderate physical activity, not including weightlifting.Liver function tests are significantly increased for at least 7 days after weightlifting.It is important to impose relevant restrictions on heavy muscular exercise prior to and during clinical studies. PMID:17764474

Muscular exercise can cause highly pathological liver function tests in healthy men.

PubMed

Pettersson, Jonas; Hindorf, Ulf; Persson, Paula; Bengtsson, Thomas; Malmqvist, Ulf; Werkström, Viktoria; Ekelund, Mats

2008-02-01

The occurrence of idiosyncratic drug hepatotoxicity is a major problem in all phases of clinical drug development and the leading cause of postmarketing warnings and withdrawals. Physical exercise can result in transient elevations of liver function tests. There is no consensus in the literature on which forms of exercise may cause changes in liver function tests and to what extent. Weightlifting results in profound increases in liver function tests in healthy men used to moderate physical activity, not including weightlifting. Liver function tests are significantly increased for at least 7 days after weightlifting. It is important to impose relevant restrictions on heavy muscular exercise prior to and during clinical studies. To investigate the effect of intensive muscular exercise (weightlifting) on clinical chemistry parameters reflecting liver function in healthy men. Fifteen healthy men, used to moderate physical activity not including weightlifting, performed an 1 h long weightlifting programme. Blood was sampled for clinical chemistry parameters [aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LD), gamma-glutamyl transferase (gamma GT), alkaline phosphatase (ALP), bilirubin, creatine kinase (CK) and myoglobin] at repeated intervals during 7 days postexercise and at a follow-up examination 10-12 days postexercise. Five out of eight studied clinical chemistry parameters (AST, ALT, LD, CK and myoglobin) increased significantly after exercise (P < 0.01) and remained increased for at least 7 days postexercise. Bilirubin, gamma GT and ALP remained within the normal range. The liver function parameters, AST and ALT, were significantly increased for at least 7 days after the exercise. In addition, LD and, in particular, CK and myoglobin showed highly elevated levels. These findings highlight the importance of imposing restrictions on weightlifting prior to and during clinical studies. Intensive muscular exercise, e.g. weightlifting, should also be considered as a cause of asymptomatic elevations of liver function tests in daily clinical practice.

Multiplex transcriptional analysis of paraffin-embedded liver needle biopsy from patients with liver fibrosis

PubMed Central

2012-01-01

Background The possibility of extracting RNA and measuring RNA expression from paraffin sections can allow extensive investigations on stored paraffin samples obtained from diseased livers and could help with studies of the natural history of liver fibrosis and inflammation, and in particular, correlate basic mechanisms to clinical outcomes. Results To address this issue, a pilot study of multiplex gene expression using branched-chain DNA technology was conducted to directly measure mRNA expression in formalin-fixed paraffin-embedded needle biopsy samples of human liver. Twenty-five genes were selected for evaluation based on evidence obtained from human fibrotic liver, a rat BDL model and in vitro cultures of immortalized human hepatic stellate cells. The expression levels of these 25 genes were then correlated with liver fibrosis and inflammation activity scores. Statistical analysis revealed that three genes (COL3A1, KRT18, and TUBB) could separate fibrotic from non-fibrotic samples and that the expression of ten genes (ANXA2, TIMP1, CTGF, COL4A1, KRT18, COL1A1, COL3A1, ACTA2, TGFB1, LOXL2) were positively correlated with the level of liver inflammation activity. Conclusion This is the first report describing this multiplex technique for liver fibrosis and has provided the proof of concept of the suitability of RNA extracted from paraffin sections for investigating the modulation of a panel of proinflammatory and profibrogenic genes. This pilot study suggests that this technique will allow extensive investigations on paraffin samples from diseased livers and possibly from any other tissue. Using identical or other genes, this multiplex expression technique could be applied to samples obtained from extensive patient cohorts with stored paraffin samples in order to correlate gene expression with valuable clinically relevant information. This method could be used to provide a better understanding of the mechanisms of liver fibrosis and inflammation, its progression, and help development of new therapeutic approaches for this indication. PMID:23270325

Biliary obstruction - slideshow

MedlinePlus

... ency/presentations/100199.htm Biliary obstruction - series—Normal anatomy To use the sharing ... Overview Bile is a digestive fluid secreted by the liver and stored in the gallbladder which normally is ...

Liver transplantation in children with Alagille syndrome--a study of twelve cases.

PubMed

Cardona, J; Houssin, D; Gauthier, F; Devictor, D; Losay, J; Hadchouel, M; Bernard, O

1995-08-27

Cholestasis associated with Alagille syndrome may, in a few cases, be extremely severe and result in major impairment in the quality of life during early childhood and end up in cirrhosis eventually. We report the results of liver transplantation in 12 children with a severe hepatic form of Alagille syndrome. All children presented with cholestatic jaundice from birth, peculiar facies, stenosis of the peripheral pulmonary artery, and posterior embryotoxon; butterfly-like vertebrae were present in 9 children. At the time of transplantation (mean age 7 years 10 months) refractory pruritus was present in 9 children, xanthoma in 11, and height and weight retardation in 11. Total serum bilirubin ranged from 116 to 322 mumol/L and total serum cholesterol from 3.5 to 29 mmol/L. Systolic right ventricular pressure was moderately raised (36 to 48 mmHg) in 5 children; mean creatinine clearance was 99 ml/min/1.73 m2. Histologic examination of the removed livers showed cirrhosis, severe annular fibrosis, and moderate portal fibrosis in 4 children each. Follow-up in the 11 survivors has ranged from 14 months to 5 1/2 years. All lead normal lives. Pruritus and xanthomas disappeared. Increase in height was observed in 8 of the 10 survivors who had growth retardation prior to transplantation. School level is normal in 4 (median age at LT: 5 yr 9 mo) and below normal in 6 (median age at OLT: 9 yr 9 mo). Liver function tests are normal in 10 children. Mean creatinine clearance is 101 ml/min/1.73 m2. These results indicate that the quality of life can be considerably improved after liver transplantation in children with a severe hepatic form of Alagille syndrome and suggest that it could be carried out before these children attend elementary school.

Hepatic hilar and sectorial vascular and biliary anatomy in right graft adult live liver donor transplantation.

PubMed

Radtke, A; Sgourakis, G; Sotiropoulos, G C; Molmenti, E P; Nadalin, S; Fouzas, I; Schroeder, T; Saner, F H; Schenk, A; Cicinnati, V R; Malagó, M; Lang, H

2008-11-01

The aim of this study was to analyze vascular and biliary variants at the hilar and sectorial level in right graft adult living donor liver transplantation. From January 2003 to June 2007, 139 consecutive live liver donors underwent three-dimensional computed tomography (3-D CT) reconstructions and virtual 3-D liver partitioning. We evaluated the portal (PV), arterial (HA), and biliary (BD) anatomy. The hilar and sectorial biliary/vascular anatomy was predominantly normal (70%-85% and 67%-78%, respectively). BD and HA showed an equal incidence (30%) of hilar anomalies. BD and PV had a nearly identical incidence of sectorial abnormalities (64.7% and 66.2%, respectively). The most frequent "single" anomaly was seen centrally in HA (21%) and distally in BD (18%). A "double" anomaly involved BD/HA (7.2%) in the hilum, and HA/PV and BD/PV (6.5% each) sectorially. A "triple" anomaly involving all systems was found at the hilum in 1.4% of cases, and at the sectorial level in 9.4% of instances. Simultanous central and distal abnormalities were rare. In this study, 13.7% of all donor candidates showed normal hilar and sectorial anatomy involving all 3 systems. A simultaneous central and distal "triple" abnormality was not encountered. A combination of "triple" hilar anomaly with "triple" sectorial normality was observed in 2 cases (1.4%). A central "triple" normality associated with a distal "triple" abnormality occurred in 7 livers (5%). Our data showed a variety of "horizontal" (hilar or sectorial) and "vertical" (hilar and sectorial) vascular and biliary branching patterns, providing comprehensive assistance for surgical decision-making prior to right graft hepatectomy.

Using X-Ray In-Line Phase-Contrast Imaging for the Investigation of Nude Mouse Hepatic Tumors

PubMed Central

Zhang, Lu; Luo, Shuqian

2012-01-01

The purpose of this paper is to report the noninvasive imaging of hepatic tumors without contrast agents. Both normal tissues and tumor tissues can be detected, and tumor tissues in different stages can be classified quantitatively. We implanted BEL-7402 human hepatocellular carcinoma cells into the livers of nude mice and then imaged the livers using X-ray in-line phase-contrast imaging (ILPCI). The projection images' texture feature based on gray level co-occurrence matrix (GLCM) and dual-tree complex wavelet transforms (DTCWT) were extracted to discriminate normal tissues and tumor tissues. Different stages of hepatic tumors were classified using support vector machines (SVM). Images of livers from nude mice sacrificed 6 days after inoculation with cancer cells show diffuse distribution of the tumor tissue, but images of livers from nude mice sacrificed 9, 12, or 15 days after inoculation with cancer cells show necrotic lumps in the tumor tissue. The results of the principal component analysis (PCA) of the texture features based on GLCM of normal regions were positive, but those of tumor regions were negative. The results of PCA of the texture features based on DTCWT of normal regions were greater than those of tumor regions. The values of the texture features in low-frequency coefficient images increased monotonically with the growth of the tumors. Different stages of liver tumors can be classified using SVM, and the accuracy is 83.33%. Noninvasive and micron-scale imaging can be achieved by X-ray ILPCI. We can observe hepatic tumors and small vessels from the phase-contrast images. This new imaging approach for hepatic cancer is effective and has potential use in the early detection and classification of hepatic tumors. PMID:22761929

Metastases to the Liver from Neuroendocrine Tumors: Effect of Duration of Scan Acquisition on CT Perfusion Values

PubMed Central

Hobbs, Brian P.; Chandler, Adam G.; Anderson, Ella F.; Herron, Delise H.; Charnsangavej, Chusilp; Yao, James

2013-01-01

Purpose To assess the effects of acquisition duration on computed tomographic (CT) perfusion parameter values in neuroendocrine liver metastases and normal liver tissue. Materials and Methods This retrospective study was institutional review board approved, with waiver of informed consent. CT perfusion studies in 16 patients (median age, 57.5 years; range, 42.0–69.7 years), including six men (median, 54.1 years; range, 42.0–69.7), and 10 women (median, 59.3 years; range 43.6–66.3), with neuroendocrine liver metastases were analyzed by means of distributed parametric modeling to determine tissue blood flow, blood volume, mean transit time, permeability, and hepatic arterial fraction for tumors and normal liver tissue. Analyses were undertaken with acquisition time of 12–590 seconds. Nonparameteric regression analyses were used to evaluate the functional relationships between CT perfusion parameters and acquisition duration. Evidence for time invariance was evaluated for each parameter at multiple time points by inferring the fitted derivative to assess its proximity to zero as a function of acquisition time by using equivalence tests with three levels of confidence (20%, 70%, and 90%). Results CT perfusion parameter values varied, approaching stable values with increasing acquisition duration. Acquisition duration greater than 160 seconds was required to obtain at least low confidence stability in any of the CT perfusion parameters. At 160 seconds of acquisition, all five CT perfusion parameters stabilized with low confidence in tumor and normal tissues, with the exception of hepatic arterial fraction in tumors. After 220 seconds of acquisition, there was stabilization with moderate confidence for blood flow, blood volume, and hepatic arterial fraction in tumors and normal tissue, and for mean transit time in tumors; however, permeability values did not satisfy the moderate stabilization criteria in both tumors and normal tissue until 360 seconds of acquisition. Blood flow, mean transit time, permeability, and hepatic arterial fraction were significantly different between tumor and normal tissue at 360 seconds (P < .001). Conclusion CT perfusion parameter values are affected by acquisition duration and approach progressively stable values with increasing acquisition times. © RSNA, 2013 Online supplemental material is available for this article. PMID:23824990

FXR and liver carcinogenesis

PubMed Central

Huang, Xiong-fei; Zhao, Wei-yu; Huang, Wen-dong

2015-01-01

Farnesoid X receptor (FXR) is a member of the nuclear receptor family and a ligand-modulated transcription factor. In the liver, FXR has been considered a multi-functional cell protector and a tumor suppressor. FXR can suppress liver carcinogenesis via different mechanisms: 1) FXR maintains the normal liver metabolism of bile acids, glucose and lipids; 2) FXR promotes liver regeneration and repair after injury; 3) FXR protects liver cells from death and enhances cell survival; 4) FXR suppresses hepatic inflammation, thereby preventing inflammatory damage; and 5) FXR can directly increase the expression of some tumor-suppressor genes and repress the transcription of several oncogenes. However, inflammation and epigenetic silencing are known to decrease FXR expression during tumorigenesis. The reactivation of FXR function in the liver may be a potential therapeutic approach for patients with liver cancer. PMID:25500874

Estimation of the Scatterer Distribution of the Cirrhotic Liver using Ultrasonic Image

NASA Astrophysics Data System (ADS)

Yamaguchi, Tadashi; Hachiya, Hiroyuki

1998-05-01

In the B-mode image of the liver obtained by an ultrasonic imaging system, the speckled pattern changes with the progression of the disease such as liver cirrhosis.In this paper we present the statistical characteristics of the echo envelope of the liver, and the technique to extract information of the scatterer distribution from the normal and cirrhotic liver images using constant false alarm rate (CFAR) processing.We analyze the relationship between the extracted scatterer distribution and the stage of liver cirrhosis. The ratio of the area in which the amplitude of the processing signal is more than the threshold to the entire processed image area is related quantitatively to the stage of liver cirrhosis.It is found that the proposed technique is valid for the quantitative diagnosis of liver cirrhosis.

Two Cases of Lethal Complications Following Ultrasound-Guided Percutaneous Fine-Needle Biopsy of the Liver

DOE Office of Scientific and Technical Information (OSTI.GOV)

Drinkovic, Ivan; Brkljacic, Boris

1996-09-15

Two cases with lethal complications are reported among 1750 ultrasound (US)-guided percutaneous fine-needle liver biopsies performed in our department. The first patient had angiosarcoma of the liver which was not suspected after computed tomography (CT) and US studies had been performed. The other patient had hepatocellular carcinoma in advanced hepatic cirrhosis. Death was due to bleeding in both cases. Pre-procedure laboratory tests did not reveal the existence of major bleeding disorders in either case. Normal liver tissue was interposed in the needle track between the liver capsule and the lesions which were targeted.

[The determination of the natural content of chemical elements in human biological objects (liver, kidney, stomach) by mass spectrometry with inductively coupled plasma].

PubMed

Luzanova, I S; Svetlolobov, D Iu; Zorin, Iu V

2014-01-01

The objective of the present work was to continue the studies of the sites of concentration of the chemical elements corresponding to normal homeostasis in human biological objects by mass spectrometry with inductively coupled plasma. The study yielded the data on the natural content of 27 elements in the cadaveric liver, kidney, and stomach. It is recommended to use these findings as the reference parameters corresponding to normal homeostasis.

Intensive hypermethylation of the CpG island of Ras association domain family 1A in hepatitis B virus-associated hepatocellular carcinomas.

PubMed

Zhong, Sheng; Yeo, Winnie; Tang, Mandy W; Wong, Nathalie; Lai, Paul B S; Johnson, Phillip J

2003-08-15

The human Ras association domain family 1A gene (RASSF1A) is a newly isolated tumor suppressor gene. In this study, we analyzed the methylation status of the promoter region of RASSF1A using bisulfite sequencing and PCR-RFLP in four liver cancer cell lines (Hep3B, HepG(2), SK-HEP-1, and Huh-7) and a cohort of 43 hepatitis B virus-associated hepatocellular carcinoma (HCC) tissues and their corresponding nontumor tissue specimens. The methylation of the CpG islands in the RASSF1A promoter was not detected in 4 samples of normal liver tissue or 10 samples of peripheral blood mononuclear cells from normal subjects. However, the CpG islands were completely methylated, and transcription of the RASSF1A was silenced in the four cell lines. Treatment with the DNA methylation inhibitor 5-aza-2'-deoxycytidine reactivated the expression of RASSF1A in the Hep3B and HepG2 cells. In 41 of 43 (95%) HCC specimens studied, the promoter region of RASSF1A was intensively methylated at its CpG sites. Although heterogeneous methylation was also detected in 16 of the 23 (70%) corresponding nontumorous tissues analyzed, the level of methylation was significantly lower than in the corresponding tumor tissues. HCC has the highest incidence of promoter methylation of RASSF1A among all malignancies yet reported suggesting that hypermethylation of the CpG island promoter of RASSF1A may play an important pathological role in this tumor.

Prognostic significance of downregulated expression of the candidate tumour suppressor gene SASH1 in colon cancer.

PubMed

Rimkus, C; Martini, M; Friederichs, J; Rosenberg, R; Doll, D; Siewert, J R; Holzmann, B; Janssen, K P

2006-11-20

The gene SASH1 (SAM- and SH3-domain containing 1) has originally been identified as a candidate tumour suppressor gene in breast cancer. SASH1 is a member of the SH3-domain containing expressed in lymphocytes (SLY1) gene family that encodes signal adapter proteins composed of several protein-protein interaction domains. The other members of this family are expressed mainly in haematopoietic cells, whereas SASH1 shows ubiquitous expression. We have used quantitative real-time PCR to investigate the expression of SASH1 in tissue samples from 113 patients with colon carcinoma, and compared the expression with 15 normal colon tissue samples. Moreover, nine benign adenomas and 10 liver metastases were analysed. Expression levels of SASH1 were strongly and significantly reduced in colon cancer of UICC stage II, III, and IV, as well as in liver metastases. Moreover, SASH1 was also found to be downregulated on protein levels by immunoblot analysis. However, SASH1 expression was not significantly deregulated in precancerous adenomas and in earlier stage lesions (UICC I). Overall, 48 out of 113 primary colon tumours showed SASH1 expression that was at least 10-fold lower than the levels found in normal colon tissue. Downregulation of SASH1 expression was correlated with the formation of metachronous distant metastasis, and multivariate analysis identified SASH1 downregulation as an independent negative prognostic parameter for patient survival. This study demonstrates for the first time that expression of a member of the SLY1-gene family has prognostic significance in human cancer.

Prognostic significance of downregulated expression of the candidate tumour suppressor gene SASH1 in colon cancer

PubMed Central

Rimkus, C; Martini, M; Friederichs, J; Rosenberg, R; Doll, D; Siewert, J R; Holzmann, B; Janssen, K P

2006-01-01

The gene SASH1 (SAM- and SH3-domain containing 1) has originally been identified as a candidate tumour suppressor gene in breast cancer. SASH1 is a member of the SH3-domain containing expressed in lymphocytes (SLY1) gene family that encodes signal adapter proteins composed of several protein–protein interaction domains. The other members of this family are expressed mainly in haematopoietic cells, whereas SASH1 shows ubiquitous expression. We have used quantitative real-time PCR to investigate the expression of SASH1 in tissue samples from 113 patients with colon carcinoma, and compared the expression with 15 normal colon tissue samples. Moreover, nine benign adenomas and 10 liver metastases were analysed. Expression levels of SASH1 were strongly and significantly reduced in colon cancer of UICC stage II, III, and IV, as well as in liver metastases. Moreover, SASH1 was also found to be downregulated on protein levels by immunoblot analysis. However, SASH1 expression was not significantly deregulated in precancerous adenomas and in earlier stage lesions (UICC I). Overall, 48 out of 113 primary colon tumours showed SASH1 expression that was at least 10-fold lower than the levels found in normal colon tissue. Downregulation of SASH1 expression was correlated with the formation of metachronous distant metastasis, and multivariate analysis identified SASH1 downregulation as an independent negative prognostic parameter for patient survival. This study demonstrates for the first time that expression of a member of the SLY1-gene family has prognostic significance in human cancer. PMID:17088907

Does aflatoxin exposure in the United Kingdom constitute a cancer risk?

PubMed Central

Harrison, J C; Carvajal, M; Garner, R C

1993-01-01

Although the aflatoxins were discovered more than 30 years ago, there is still considerable controversy surrounding their human health effects. Most countries have introduced legislation to control the level of aflatoxins in food, but it is not known if these permitted levels still pose a significant cancer risk. Furthermore, it is unlikely that all the sources of human aflatoxin exposure have been discovered, nor if the liver is the only, or indeed, major target organ for aflatoxin-induced cancer in man. In our laboratory we have used both immunological and HPLC methods to examine human DNA from a variety of tissues and organs to identify and quantify aflatoxin DNA-adducts. We have already detected aflatoxin B1 (AFB1)-DNA adducts in formalin-fixed tissue from an acute poisoning incident in Southeast Asia. Here we have examined human colon and rectum DNA from normal and tumorous tissue obtained from cancer patients and colon, liver, pancreas, breast, and cervix DNA from autopsy specimens. AFB1-DNA adducts were detected in all tissue types examined and ranged from 0-60 adducts/10(6) nucleotides. Where sample size allowed, the adduct levels were confirmed by HPLC analysis. Tumor tissues tended to have higher adduct levels than normal tissue from the same individual, and levels generally increased with patient age. In samples analyzed by HPLC, the adducts present had the chromatographic properties of [8,9-dihydro-8-(N5-formyl)-2',5',6'-triamino-4'-oxo-(N5-pyramidyl) -9- hydroxy-aflatoxin B1, the ring-opened form of the AFB1-guanine adduct.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8319666

1H-Nuclear Magnetic Resonance-Based Plasma Metabolic Profiling of Dairy Cows with Fatty Liver

PubMed Central

Xu, Chuang; Sun, Ling-wei; Xia, Cheng; Zhang, Hong-you; Zheng, Jia-san; Wang, Jun-song

2016-01-01

Fatty liver is a common metabolic disorder of dairy cows during the transition period. Historically, the diagnosis of fatty liver has involved liver biopsy, biochemical or histological examination of liver specimens, and ultrasonographic imaging of the liver. However, more convenient and noninvasive methods would be beneficial for the diagnosis of fatty liver in dairy cows. The plasma metabolic profiles of dairy cows with fatty liver and normal (control) cows were investigated to identify new biomarkers using 1H nuclear magnetic resonance. Compared with the control group, the primary differences in the fatty liver group included increases in β-hydroxybutyric acid, acetone, glycine, valine, trimethylamine-N-oxide, citrulline, and isobutyrate, and decreases in alanine, asparagine, glucose, γ-aminobutyric acid glycerol, and creatinine. This analysis revealed a global profile of endogenous metabolites, which may present potential biomarkers for the diagnosis of fatty liver in dairy cows. PMID:26732447

Living Donor Liver Transplantation for Unresectable Liver Adenomatosis Associated with Congenital Absence of Portal Vein: A Case Report and Literature Review.

PubMed

Brasoveanu, Vladislav; Ionescu, Mihnea Ioan; Grigorie, Razvan; Mihaila, Mariana; Bacalbasa, Nicolae; Dumitru, Radu; Herlea, Vlad; Iorgescu, Andreea; Tomescu, Dana; Popescu, Irinel

2015-09-19

Abernethy malformation (AM), or congenital absence of portal vein (CAPV), is a very rare disease which tends to be associated with the development of benign or malignant tumors, usually in children or young adults. We report the case of a 21-year-old woman diagnosed with type Ib AM (portal vein draining directly into the inferior vena cava) and unresectable liver adenomatosis. The patient presented mild liver dysfunction and was largely asymptomatic. Living donor liver transplantation was performed using a left hemiliver graft from her mother. Postoperatively, the patient attained optimal liver function and at 9-month follow-up has returned to normal life. We consider that living donor liver transplantation is the best therapeutic solution for AM associated with unresectable liver adenomatosis, especially because compared to receiving a whole liver graft, the waiting time on the liver transplantation list is much shorter.

Protective effects of C-phycocyanin on alcohol-induced acute liver injury in mice

NASA Astrophysics Data System (ADS)

Xia, Dong; Liu, Bing; Luan, Xiying; Sun, Junyan; Liu, Nana; Qin, Song; Du, Zhenning

2016-03-01

Excessive alcohol consumption leads to liver disease. Extensive evidence suggests that C-phycocyanin (C-PC), a chromophore phycocyanobilin derived from Spirulina platensis, exerts protective effects against chemical-induced organ damage. In this study, we investigated whether C-PC could protect against ethanol-induced acute liver injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride (TG), total cholesterol (CHOL), low-density lipoprotein (LDL), liver homogenate malondialdehyde (MDA), superoxide dismutase (SOD) content were measured, and pathological examination of liver sections were examined. C-PC showed obvious inhibitory effects on serum ALT, AST, TG, CHOL, LDL and MDA, and SOD content significantly increased in the liver. The structure of hepatic lobules was clear, liver sinus returned to normal, and liver cell cords were arranged in neat rows. Cloudiness, swelling, inflammatory cell infiltration and spotty necrosis of liver cells were significantly reduced. Therefore, C-PC can significantly protect against ethanol-induced acute liver injury.

[Comparative analysis of viral load by bDNA HCV RNA-2.0 and amplicor HCV monitor in patients with hepatitis C infection].

PubMed

Córdoba, J; Olaso, V; Molina, J M; López Viedma, B; Argüello, L; Ortiz, V; Esteban, R J; Garijo, R; Pastor, M; Gobernado, M

2000-01-01

Two standardized techniques, Quantiplex (bDNA-2.0) and Amplicor Monitor have been evaluated for the quantification of virus load of HCV with these objectives: a) determinate the relationship between virus load and genotype, and b) evaluate the virus load in serial serum samples and in patients with normal or slightly increased liver enzymes in an area with a high prevalence of genotype 1. A significant correlation of 0.7 (p < 0.0001) in virus load has been observed by both methods, but the virus load is smaller by Monitor than by Quantiplex and does not depend on genotype. The relationship Monitor/Quantiplex is smaller in patients with non-1 genotype than in patients with genotype 1a (p = 0.01) and 1b (p = 0.005). Virus characteristics are similar in patients with normal or slightly increased enzymes than in patients with high enzymes. Virus load by both methods is not related to the age, sex, know duration of the infection, transmission manner of the infection neither to the histologic activity index. The virus load not depends on genotype. The determination of virus load in a single serum sample adequately reflects the virus load are in several serum samples in patients with chronic HCV infection. The genotype and the virus load are similar in patients with normal enzymes than in patients with high enzymes.

Protective Effects of Tinospora cordifolia on Hepatic and Gastrointestinal Toxicity Induced by Chronic and Moderate Alcoholism.

PubMed

Sharma, Bhawana; Dabur, Rajesh

2016-01-01

Heavy alcohol intake depletes the plasma vitamins due to hepatotoxicity and decreased intestinal absorption. However, moderate alcohol intake is often thought to be healthy. Therefore, effects of chronic moderate alcohol intake on liver and intestine were studied using urinary vitamin levels. Furthermore, effects of Tinospora cordifolia water extract (TCE) (hepatoprotective) on vitamin excretion and intestinal absorption were also studied. In the study, asymptomatic moderate alcoholics (n = 12) without chronic liver disease and healthy volunteers (n = 14) of mean age 39 ± 2.2 (mean ± SD) were selected and divided into three groups. TCE treatment was performed for 14 days. The blood and urine samples were collected on Day 0 and 14 after treatment with TCE and analyzed. In alcoholics samples, a significant increase in the levels of gamma-glutamyl transferase, aspartate transaminase, alanine transaminase, Triglyceride, Cholesterol, HDL and LDL (P < 0.05) was observed but their level get downregulated after TCE intervention. Multivariate analysis of metabolites without missing values showed an increased excretion of 7-dehydrocholesterol, orotic acid, pyridoxine, lipoamide and niacin and TCE intervention depleted their levels (P < 0.05). In contrast, excretion of biotin, xanthine, vitamin D2 and 2-O-p-coumaroyltartronic acid (CA, an internal marker of intestinal absorption) were observed to be decreased in alcoholic samples; however, TCE intervention restored the CA and biotin levels. Vitamin metabolism biomarkers, i.e. homocysteine and xanthurenic acid, were also normalized after TCE intervention. Overall data depict that moderate alcohol intake is also hepatotoxic and decreases intestinal absorption. However, TCE treatment effectively increased the intestinal absorption and retaining power of liver that regulated alcohol-induced multivitamin deficiency. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

Simple and Reliable Method to Quantify the Hepatitis B Viral Load and Replicative Capacity in Liver Tissue and Blood Leukocytes

PubMed Central

Minosse, Claudia; Coen, Sabrina; Visco Comandini, Ubaldo; Lionetti, Raffaella; Montalbano, Marzia; Cerilli, Stefano; Vincenti, Donatella; Baiocchini, Andrea; Capobianchi, Maria R.; Menzo, Stefano

2016-01-01

Background A functional cure of chronic hepatitis B (CHB) is feasible, but a clear view of the intrahepatic viral dynamics in each patient is needed. Intrahepatic covalently closed circular DNA (cccDNA) is the stable form of the viral genome in infected cells, and represents the ideal marker of parenchymal colonization. Its relationships with easily accessible peripheral parameters need to be elucidated in order to avoid invasive procedures in patients. Objectives The goal of this study was to design, set up, and validate a reliable and straightforward method for the quantification of the cccDNA and total DNA of the hepatitis B virus (HBV) in a variety of clinical samples. Patients and Methods Clinical samples from a cohort of CHB patients, including liver biopsies in some, were collected for the analysis of intracellular HBV molecular markers using novel molecular assays. Results A plasmid construct, including sequences from the HBV genome and from the human gene hTERT, was generated as an isomolar multi-standard for HBV quantitation and normalization to the cellular contents. The specificity of the real-time assay for the cccDNA was assessed using Dane particles isolated on a density gradient. A comparison of liver tissue from 6 untreated and 6 treated patients showed that the treatment deeply reduced the replicative capacity (total DNA/cccDNA), but had limited impact on the parenchymal colonization. The peripheral blood mononuclear cells (PBMCs) and granulocytes from the treated and untreated patients were also analyzed. Conclusions A straightforward method for the quantification of intracellular HBV molecular parameters in clinical samples was developed and validated. The widespread use of such versatile assays could better define the prognosis of CHB, and allow a more rational approach to time-limited tailored treatment strategies. PMID:27882060

Could near-infrared Raman spectroscopy be correlated with the METAVIR scores in liver lesions induced by hepatitis C virus?

NASA Astrophysics Data System (ADS)

Gaggini, Marcio Cesar Reino; Navarro, Ricardo Scarparo; Stefanini, Aline Reis; Sano, Rubens Sato; Silveira, Landulfo

2013-03-01

The liver is responsible for several basic functions in human body how the syntheses of the most main proteins and degradation process of toxins, drugs and alcohols. In present days, the viral hepatitis C is one of the highest causes of chronic hepatic illness worldwide, affecting around 3% of the world population. The liver biopsy is considered the gold standard for diagnosing hepatic fibrosis; however, the biopsies may be questioned because of potential sampling error, morbidity, possible mortality and relatively high costs. Spectroscopy techniques such as Raman spectroscopy have been used for diagnosis of human tissues, with favorable results. Raman spectroscopy has been employed to distinguish normal from hepatic lesions through spectral features mainly of proteins, nucleic acids and lipids. In this study, eleven patients with diagnoses of chronic hepatitis C underwent hepatic biopsies having two hepatic fragments collected: one was scored through METAVIR system and the other one was submitted to near-infrared Raman spectroscopy using a dispersive spectrometer (830 nm wavelength, 300 mW laser power and 20 s exposure time). Five spectra were collected in each fragment and submitted to Principal Components Analysis (PCA). Results showed a good correlation between the Raman spectroscopy features and the stage of hepatic fibrosis and inflammation. PCA showed that samples with higher degree of fibrosis presented higher amount of protein features (collagen), whereas samples of higher degree of inflammation presented higher features of hemoglobin, in accordance to the expected evolution of the chronic hepatitis. It has been found an important biomarker for the beginning of hepatic lesion (quinone) with a spectral feature at 1595 cm-1.

[Expressions and significance of TLR2 and TLR4 in Kupffer cells of tree shrews chronically infected with hepatitis B virus].

PubMed

Ruan, Ping; Yang, Chun; Su, Jianjia; Ou, Chao; Cao, Ji; Luo, Chengpiao; Tang, Yanping; Qin, Hong; Sun, Wen; Li, Yuan

2014-07-01

To investigate the mRNA expression levels of Toll-like receptors 2 (TLR2) and TLR4 in Kupffer cells of tree shrews that were chronically infected with hepatitis B virus (HBV), and the effects of these receptors on the function of Kupffer cells. The tree shrews were divided into tree shrews proved with chronic HBV infection, tree shrews suspected with chronic HBV infection, and normal control tree shrews without hepatitis B vaccination. The samples of serum and liver biopsy were collected periodically, and the levels of HBV DNA in serum and liver tissues were detected by fluorescence-based quantitative real-time PCR (qRT-PCR). Meanwhile, Kupffer cells were isolated from the biopsied liver tissues, and then purified and primarily cultured. Afterwards, qRT-PCR was applied to detect the mRNA expression levels of TLR2, TLR4 and TNF-α in the Kupffer cells. Cell migration assay and lysosome-specific fluorescent probe were adopted to analyze the effects of TLR2 and TLR4 on the migration capacity of Kupffer cells and the quantity of lysosomes in these cells. The mRNA expression levels of TLR2 and TLR4 in tree shrews proved with chronic HBV infection were lower than those in the ones suspected with chronic HBV infection and normal controls without hepatitis B vaccination (P<0.05), and these expression levels were all negatively correlated with the level of HBV DNA in liver tissues of the animals (P<0.05), but were positively correlated with the number of migrated Kupffer cells, the density of lysosomes and the mRNA expression level of TNF-α (P<0.05). TLR2 and TLR4 in Kupffer cells may play important roles in the chronic process of hepatic pathological changes in tree shrews infected with HBV through their influence on the function of Kupffer cells.

Evaluation of contralateral kidney, liver and lung after extracorporeal shock wave lithotripsy in rabbits.

PubMed

Senyucel, M F; Boybeyi, O; Ayva, S; Aslan, M K; Soyer, T; Demet, A I; Kısa, U; Basar, M; Cakmak, M A

2013-10-01

An experimental study was carried out to evaluate the effects of extracorporeal shock wave lithotripsy (ESWL) on contralateral kidney, liver and lung by histopathological and biochemical methods. Twelve New Zealand rabbits were allocated to two groups (n = 6). Tissues of control group (CG, n = 6) were harvested without any intervention. In ESWL group (EG), right kidneys were exposed to 3,000 shock waves at 14 kV energy using electro-hydraulic type ESWL device three times every other day. Both kidneys, liver, and right lobe of lung tissues in EG were harvested on seventh day. Kidneys were examined histopathologically for presence of glomerular and tubular injury, interstitial edema, congestion, inflammation and fibrosis. Livers were examined for hepatocyte vacuolization, congestion, portal inflammation and fibrosis. Lung tissues were examined for loss of normal structure, emphysema, interstitial congestion-edema, prominent alveolar septal vessels, interstitial inflammation, intra-alveolar hemorrhage, intraluminal hemorrhage, peribronchial edema, congestion, inflammation in bronchial wall and epithelial desquamation. Biochemical analysis of tissue samples was performed for oxidative injury markers. Histopathological evaluations revealed that tubular injury was found in both shocked and contralateral kidneys (p < 0.05). EG showed higher grades of portal fibrosis in liver and higher grades of peribronchial congestion in lung when compared to CG (p < 0.05). Biochemical evaluations of both kidneys showed that malondialdehyde levels were higher in EG than in CG (p < 0.05). ESWL causes histopathologic alterations both in shocked and contralateral kidneys. Extrarenal tissues such as liver and lung can be affected by shock waves histopathologically and oxidative injury of contralateral kidney may occur acutely after ESWL.

Evaluation of hepatic steatosis in dogs with congenital portosystemic shunts using Oil Red O staining.

PubMed

Hunt, G B; Luff, J A; Daniel, L; Van den Bergh, R

2013-11-01

The aims of this prospective study were to quantify steatosis in dogs with congenital portosystemic shunts (CPS) using a fat-specific stain, to compare the amount of steatosis in different lobes of the liver, and to evaluate intra- and interobserver variability in lipid point counting. Computer-assisted point counting of lipid droplets was undertaken following Oil Red O staining in 21 dogs with congenital portosystemic shunts and 9 control dogs. Dogs with congenital portosystemic shunts had significantly more small lipid droplets (<6 μ) than control dogs (P = .0013 and .0002, respectively). There was no significant difference in steatosis between liver lobes for either control dogs and CPS dogs. Significant differences were seen between observers for the number of large lipid droplets (>9 μ) and lipogranulomas per tissue point (P = .023 and .01, respectively). In conclusion, computer-assisted counting of lipid droplets following Oil Red O staining of liver biopsy samples allows objective measurement and detection of significant differences between dogs with CPS and normal dogs. This method will allow future evaluation of the relationship between different presentations of CPS (anatomy, age, breed) and lipidosis, as well as the impact of hepatic lipidosis on outcomes following surgical shunt attenuation.

Protective potential of Lactobacillus species in lead toxicity model in broiler chickens.

PubMed

Jahromi, M F; Liang, J B; Ebrahimi, R; Soleimani, A F; Rezaeizadeh, A; Abdullah, N; Shokryazdan, P

2017-05-01

To alleviate adverse effects of heavy metal toxicity, diverse range of removing methods have been suggested, that is usage of algae, agricultural by-products and microorganisms. Here, we investigated lead (Pb) biosorption efficacy by two lactic acid bacteria species (LABs) in broiler chickens. In an in vitro study, Pb was added to culture medium of LABs (Lactobacillus pentosus ITA23 and Lactobacillus acidipiscis ITA44) in the form of lead acetate. Results showed that these LABs were able to absorb more than 90% of Pb from the culture medium. In follow-up in vivo study, LABs mixture was added to diet of broiler chickens contained lead acetate (200 mg/kg). Pb exposure significantly increased lipid peroxidation and decreased antioxidant activity in liver. The changes were recovered back to normal level upon LABs supplementation. Moreover, addition of LABs eliminated the liver tissue lesion and the suppressed performance in Pb-exposed chicks. Analysis of liver and serum samples indicated 48% and 28% reduction in Pb accumulation, respectively. In conclusion, results of this study showed that L. pentosus ITA23 and L. acidipiscis ITA44 effectively biosorb and expel dietary Pb from gastrointestinal tract of chickens.

Study of the Efficiency of the Hydroporation for Delivery of Plasmid DNA to the Cells on the Model of Toxic Neuropathy.

PubMed

Yudin, M A; Bykov, V N; Nikiforov, A S; Al-Shekhadat, R I; Ivanov, I M; Ustinova, T M

2018-04-01

We compared the efficiency of delivery of plasmid DNA (active ingredient concentration 1 mg/kg) that provides production of nerve growth factor (NGF) after intravenous administration to rats and after administration by hydroporation. The method of hydroporation ensured plasmid penetration into the liver tissue and lengthened the time of its detection in the organ. DNA concentration in 1 h after its introduction by hydroporation or intravenous route was 0.7 and 0.05 ng/mg tissue, respectively. The use of this transfection method ensured preservation of NGF DNA in the liver tissue at a level of 0.24 ng/mg of tissue 1 day after administration of the plasmid construct, while after intravenous administration, expression of the analyzed DNA was not detected in blood and liver samples. After hydroporation, the maximum of relative normalized expression of cDNA (270 rel. units) was observed after 4 h, and after 1 day, this parameter decreased to 35 rel. units. Introduction of plasmid DNA of NGF by hydroporation prevented the development of disorders of neuromuscular conduction in a rats model of toxic neuropathy induced by subacute administration of malathion in a dose of 0.5 LD 50 .

Multielemental analysis of tissues from Cangrande della Scala, Prince of Verona, in the 14th century.

PubMed

Apostoli, Pietro; De Palma, Giuseppe; Catalani, Simona; Bortolotti, Federica; Tagliaro, Franco

2009-01-01

Cangrande della Scala, Prince of Verona (Italy), died suddenly shortly after his triumph in the battle of Treviso (July 18, 1329). Thus, in the frame of a multidisciplinary paleo-pathological study, we carried out a multielemental analysis on the Prince's tissue specimens, including hair, liver, muscle, and bone, in order to characterize a multitissue profile of metallic elements in a nobleman of the 14th century. Biological specimens were analyzed by inductively coupled plasma-mass spectrometry. We were able to rule out arsenic poisoning as the primary cause of death. High levels of gold and silver in both hair and liver samples were probably due to prolonged contact of the mummy with precious metals in the funeral garments. High lead concentrations in both liver and bone tissue can be traced back to the ingestion of contaminated food and alcoholic beverages. Most of the essential elements were in the normal range of values for contemporary living people. The low arsenic and chromium levels in the Prince's tissues as compared to modern people would be suggestive of raised concentrations of both the elements in the present era, which are likely due to industrial pollution.

Identification of suitable reference genes for hepatic microRNA quantitation.

PubMed

Lamba, Vishal; Ghodke-Puranik, Yogita; Guan, Weihua; Lamba, Jatinder K

2014-03-07

MicroRNAs (miRNAs) are short (~22 nt) endogenous RNAs that play important roles in regulating expression of a wide variety of genes involved in different cellular processes. Alterations in microRNA expression patterns have been associated with a number of human diseases. Accurate quantitation of microRNA levels is important for their use as biomarkers and in determining their functions. Real time PCR is the gold standard and the most frequently used technique for miRNA quantitation. Real time PCR data analysis includes normalizing the amplification data to suitable endogenous control/s to ensure that microRNA quantitation is not affected by the variability that is potentially introduced at different experimental steps. U6 (RNU6A) and RNU6B are two commonly used endogenous controls in microRNA quantitation. The present study was designed to investigate inter-individual variability and gender differences in hepatic microRNA expression as well as to identify the best endogenous control/s that could be used for normalization of real-time expression data in liver samples. We used Taqman based real time PCR to quantitate hepatic expression levels of 22 microRNAs along with U6 and RNU6B in 50 human livers samples (25 M, 25 F). To identify the best endogenous controls for use in data analysis, we evaluated the amplified candidates for their stability (least variability) in expression using two commonly used software programs: Normfinder and GeNormplus, Both Normfinder and GeNormplus identified U6 to be among the least stable of all the candidates analyzed, and RNU6B was also not among the top genes in stability. mir-152 and mir-23b were identified to be the two most stable candidates by both Normfinder and GeNormplus in our analysis, and were used as endogenous controls for normalization of hepatic miRNA levels. Measurements of microRNA stability indicate that U6 and RNU6B are not suitable for use as endogenous controls for normalizing microRNA relative quantitation data in hepatic tissue, and their use can led to possibly erroneous conclusions.

Hepatoprotective effect of Leucophyllum frutescens on Wistar albino rats intoxicated with carbon tetrachloride.

PubMed

Balderas-Renteria, Isaías; Camacho-Corona, Maria Del Rayo; Carranza-Rosales, Pilar; Lozano-Garza, Hector G; Castillo-Nava, Dalila; Alvarez-Mendoza, Francisco J; Tamez-Cantú, Elsa M

2007-01-01

Many hepatoprotective herbal preparations have been recommended in alternative systems of medicine for the treatment of hepatic disorders. No systematic study has been done on protective efficacy of Leucophyllum frutescens to treat hepatic diseases. Protective action of L. frutescens methanol extract (obtained by maceration) was evaluated in an animal model of hepatotoxicity induced by carbon tetrachloride (CCl(4)). Wistar albino rats were divided into five groups. Group I was normal control group; Groups II-V received CCl(4). After inducing hepatic damage, Group II served as control CCl(4); Group III was given silymarin as reference hepatoprotective; and Groups IV and V received different doses of plant extract. Liver marker enzymes were assayed in serum. Samples of livers were observed under microscope for the histopathological changes. Levels of marker enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were increased significantly in CCl(4) treated rats (Group II). Groups IV and V intoxicated with CCl(4) and treated with L. frutescens methanol extract significant decreased the activities of these two enzymes. Also these groups resulted in less pronounced destruction of the liver architecture, there is not fibrosis and have moderate inflammation compared with Group II. The present study scientifically validated the traditional use of L. frutescens for liver disorders. In conclusion the methanol extract of L. frutescens aerial parts could be an important source of hepatoprotective compounds.

A Secreted Form of the Asialoglycoprotein Receptor, sH2a, as a Novel Potential Noninvasive Marker for Liver Fibrosis

PubMed Central

Lurie, Yoav; Ron, Efrat; Santo, Moshe; Reif, Shimon; Elashvili, Irma; Bar, Lana; Lederkremer, Gerardo Z.

2011-01-01

Background and Aim The human asialoglycoprotein receptor is a membrane heterooligomer expressed exclusively in hepatocytes. A soluble secreted form, sH2a, arises, not by shedding at the cell surface, but by intracellular cleavage of its membrane-bound precursor, which is encoded by an alternatively spliced form of the receptor H2 subunit. Here we determined and report that sH2a, present at constant levels in serum from healthy individuals is altered upon liver fibrosis, reflecting the status of hepatocyte function. Methods We measured sH2a levels in serum using a monoclonal antibody and an ELISA assay that we developed, comparing with routine liver function markers. We compared blindly pretreatment serum samples from a cohort of 44 hepatitis C patients, which had METAVIR-scored biopsies, with 28 healthy individuals. Results sH2a levels varied minimally for the healthy individuals (150±21 ng/ml), whereas the levels deviated from this normal range increasingly in correlation with fibrosis stage. A simple algorithm combining sH2a levels with those of alanine aminotransferase allowed prediction of fibrosis stage, with a very high area under the ROC curve of 0.86. Conclusions sH2a has the potential to be a uniquely sensitive and specific novel marker for liver fibrosis and function. PMID:22096539

In vivo quantification of chromophore concentration using fluorescence differential path length spectroscopy

NASA Astrophysics Data System (ADS)

Kruijt, Bastiaan; Kascakova, Slavka; de Bruijn, Henriette S.; van der Ploeg-van den Heuvel, Angelique; Sterenborg, Henricus J. C. M.; Robinson, Dominic J.; Amelink, Arjen

2009-05-01

We present an optical method based on fluorescence spectroscopy for measuring chromophore concentrations in vivo. Fluorescence differential path length spectroscopy (FPDS) determines chromophore concentration based on the fluorescence intensity corrected for absorption. The concentration of the photosensitizer m-THPC (Foscan®) was studied in vivo in normal rat liver, which is highly vascularized and therefore highly absorbing. Concentration estimates of m-THPC measured by FDPS on the liver are compared with chemical extraction. Twenty-five rats were injected with 0.3 mg/kg m-THPC. In vivo optical concentration measurements were performed on tissue 3, 24, 48, and 96 h after m-THPC administration to yield a 10-fold variation in tissue concentration. After the optical measurements, the liver was harvested for chemical extraction. FDPS showed good correlation with chemical extraction. FDPS also showed a correlation between m-THPC fluorescence and blood volume fraction at the two shortest drug-light intervals. This suggests different compartmental localization of m-THPC for different drug-light intervals that can be resolved using fluorescence spectroscopy. Differences in measured m-THPC concentration between FDPS and chemical extraction are related to the interrogation volume of each technique; ~0.2 mm3 and ~102 mm3, respectively. This indicates intra-animal variation in m-THPC distribution in the liver on the scale of the FDPS sampling volume.

Expression of Innate Immune Response Genes in Liver and Three Types of Adipose Tissue in Cloned Pigs

PubMed Central

Rødgaard, Tina; Skovgaard, Kerstin; Stagsted, Jan

2012-01-01

Abstract The pig has been proposed as a relevant model for human obesity-induced inflammation, and cloning may improve the applicability of this model. We tested the assumptions that cloning would reduce interindividual variation in gene expression of innate immune factors and that their expression would remain unaffected by the cloning process. We investigated the expression of 40 innate immune factors by high-throughput quantitative real-time PCR in samples from liver, abdominal subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and neck SAT in cloned pigs compared to normal outbred pigs. The variation in gene expression was found to be similar for the two groups, and the expression of a small number of genes was significantly affected by cloning. In the VAT and abdominal SAT, six out of seven significantly differentially expressed genes were downregulated in the clones. In contrast, most differently expressed genes in both liver and neck SAT were upregulated (seven out of eight). Remarkably, acute phase proteins (APPs) dominated the upregulated genes in the liver, whereas APP expression was either unchanged or downregulated in abdominal SAT and VAT. The general conclusion from this work is that cloning leads to subtle changes in specific subsets of innate immune genes. Such changes, even if minor, may have phenotypic effects over time, e.g., in models of long-term inflammation related to obesity. PMID:22928970

Activation of liver carnitine palmitoyltransferase-1 and mitochondrial acetoacetyl-CoA thiolase is associated with elevated ketone body levels in the elasmobranch Squalus acanthias.

PubMed

Treberg, Jason R; Crockett, Elizabeth L; Driedzic, William R

2006-01-01

Elasmobranch fishes are an ancient group of vertebrates that have unusual lipid metabolism whereby storage lipids are mobilized from the liver for peripheral oxidation largely as ketone bodies rather than as nonesterified fatty acids under normal conditions. This reliance on ketones, even when feeding, implies that elasmobranchs are chronically ketogenic. Compared to specimens sampled within 2 d of capture (recently captured), spiny dogfish Squalus acanthias that were held for 16-33 d without apparent feeding displayed a 4.5-fold increase in plasma concentration of d- beta -hydroxybutyrate (from 0.71 to 3.2 mM) and were considered ketotic. Overt activity of carnitine palmitoyltransferase-1 in liver mitochondria from ketotic dogfish was characterized by an increased apparent maximal activity, a trend of increasing affinity (reduced apparent K(m); P=0.09) for l-carnitine, and desensitization to the inhibitor malonyl-CoA relative to recently captured animals. Acetoacetyl-CoA thiolase (ACoAT) activity in isolated liver mitochondria was also markedly increased in the ketotic dogfish compared to recently captured fish, whereas no difference in 3-hydroxy-3-methylglutaryl-CoA synthase activity was found between these groups, suggesting that ACoAT plays a more important role in the activation of ketogenesis in spiny dogfish than in mammals and birds.

Assessment of the hepatoprotective activity of the seeds of Hunteria umbellata (Hallier F.) on carbon tetrachloride (CCl4) induced liver damage in Wistar albino rats

NASA Astrophysics Data System (ADS)

Ogunlana, Olubanke Olujoke; Ogunlana, Oluseyi Ebenezer; Adelani, Isaacson Bababode; Adebayo, Angie Osariem Igbinoba; David, Opetoritse Laju; Adeleye, Oluwaseye Joseph; Udeogu, Stephanie Adaora; Adeyemi, Alaba Oladipupo; Akinyele, Julie Oluranti

2018-04-01

This study was designed to evaluate the hepatoprotective activity of the seeds of Hunteria umbellata (HU) on carbon tetrachloride (CCl4) induced rats. Rats of groups 1 (normal control), 3 and 5 were not treated with CCl4 while rats of groups 2 (negative control), 4 and 6 rats were treated with single dose of CCl4 (2 ml/kg) by intraperitoneal administration. Normal control group 1 rats were given distilled water, groups 3 and 4 rats were given 50 mg/kg of silymarin while groups 5 and 6 rats were given 500 mg/kg of HU. Treatment was administered orally for 28 days and sacrificed on the 29th day after an overnight fast. The weights of the rats were taken before and after the treatment. Blood samples were collected in heparinized tubes and biochemical analysis of liver functions and lipid profile tests were carried out on plasma. There was a significant change (p<0.05) in the levels of alanine aminotransferase, alkaline phosphatase, high density lipoprotein and triglycerides of the CCl4 induced group treated with HU compared to the CCl4 untreated group 2 animals. The results obtained showed that the ethanolic extract of HU has hepatoprotective property.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levine, E.; Cook, L.T.; Grantham, J.J.

Hepatic CT findings were analyzed in 44 patients with autosomal-dominant polycystic kidney disease and were correlated with liver and renal function tests and liver, splenic, and renal CT volume measurements. CT showed many large liver cysts in 31.8% of patients, small liver cysts in 25%, and no liver cysts in 43.2%. Patients with many large cysts often showed increased liver volumes. There was no correlation between severity of liver involvement and extent of renal cystic disease as determined from urea nitrogen and creatinine levels and renal volumes. Liver function tests were normal except in two patients, one with a cholangiocarcinoma,more » which may have arisen from a cyst, and the other with an infected liver cyst and chronic active hepatitis. Accordingly, if liver function tests are abnormal, an attempt should be made to identify complications of polycystic liver disease such as tumor cyst infection, and biliary obstruction. CT is a useful method for detecting liver cysts and identifying patients at risk for these complications.« less

Automated liver sampling using a gradient dual-echo Dixon-based technique.

PubMed

Bashir, Mustafa R; Dale, Brian M; Merkle, Elmar M; Boll, Daniel T

2012-05-01

Magnetic resonance spectroscopy of the liver requires input from a physicist or physician at the time of acquisition to insure proper voxel selection, while in multiecho chemical shift imaging, numerous regions of interest must be manually selected in order to ensure analysis of a representative portion of the liver parenchyma. A fully automated technique could improve workflow by selecting representative portions of the liver prior to human analysis. Complete volumes from three-dimensional gradient dual-echo acquisitions with two-point Dixon reconstruction acquired at 1.5 and 3 T were analyzed in 100 subjects, using an automated liver sampling algorithm, based on ratio pairs calculated from signal intensity image data as fat-only/water-only and log(in-phase/opposed-phase) on a voxel-by-voxel basis. Using different gridding variations of the algorithm, the average correct liver volume samples ranged from 527 to 733 mL. The average percentage of sample located within the liver ranged from 95.4 to 97.1%, whereas the average incorrect volume selected was 16.5-35.4 mL (2.9-4.6%). Average run time was 19.7-79.0 s. The algorithm consistently selected large samples of the hepatic parenchyma with small amounts of erroneous extrahepatic sampling, and run times were feasible for execution on an MRI system console during exam acquisition. Copyright © 2011 Wiley Periodicals, Inc.

Polymethylmethacrylate dermal fillers: evaluation of the systemic toxicity in rats.

PubMed

Medeiros, C C G; Borghetti, R L; Nicoletti, N; da Silva, V D; Cherubini, K; Salum, F G; de Figueiredo, M A Z

2014-01-01

This study evaluated local and systemic reactions after an intravascular injection of polymethylmethacrylate (PMMA) at two concentrations in a murine model. Thirty rats were divided equally into three groups: 2% PMMA, 30% PMMA, and a control group (normal saline only injection). The filler was injected into the ranine vein. The rats were sedated at 7 and 90 days and a clinical evaluation performed. After euthanasia, the right lung, liver, and right kidney were removed, weighed, and microscopically analyzed. The submandibular lymph nodes and tongue were removed and examined microscopically. Serum was subjected to liver and kidney function tests. No groups showed clinical alterations. Microspheres were not observed at any distant organ. Two samples from the 2% PMMA group showed a local inflammatory response at day 7 and another two samples from the 30% PMMA group at day 90. The group injected with 30% PMMA presented higher levels of alanine aminotransferase (P = 0.047) after 90 days when compared with the other groups. The data obtained in this study demonstrate that intravascular injections of PMMA fillers show potential health risks such as chronic inflammation at the implantation site. Copyright © 2013 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Occurrence of thyroxine tablet (Thyradin S(®)) - induced liver dysfunction in a patient with subclinical hypothyroidism.

PubMed

Kang, Shino; Amino, Nobuyuki; Kudo, Takumi; Nishihara, Eijun; Ito, Mitsuru; Hirokawa, Mitsuyoshi; Miyauchi, Akira; Tamada, Daisuke; Yasuda, Takenori

2015-01-01

A 54-year-old woman with subclinical hypothyroidism developed liver dysfunction after increasing dose of levothyroxine (L-T4) in tablet form (Thyradin S(®)) from 25μg to 50μg. Viral hepatitis, autoimmune hepatitis and NASH were ruled out with examinations. After cessation of levothyroxine in 50μg tablet form, liver enzymes gradually returned to normal. She was diagnosed levothyroxine-induced liver injury, based on criteria proposed in DDW-J 2004 workshop. Thyradin S(®) powder 0.01% (here in after referred to as L-T4 in powder form) was tried as an alternative, and liver enzymes have remained within normal range. As for Thyradin S(®) tablet, additives are different for each type of levothyroxine sodium content. The difference of additive is whether Fe2O3 is contained or not: it is not included in Thyradin S(®) 50μg tablet and powder form. Although there are two case reports in the Japanese literature and three case reports in the English literature of liver dysfunction suspected due to L-T4, we cannot find past reports about cases of drug induced liver dysfunction due to Fe2O3 free levothyroxine tablet form. This is a rare case report of drug induced liver injury due to Fe2O3 free levothyroxine tablet form, and administration of L-T4 in powder form may be useful for treatment of cases similar to this one.

Large hepatocellular carcinoma in a non-cirrhotic liver with peritoneal and omental metastasis in a healthy man: a case report.

PubMed

Herath, H M M T B; Kulatunga, Aruna

2017-02-08

Liver cancer is the second leading cause of cancer death in men worldwide. Hepatocellular carcinoma usually develops in the setting of cirrhosis or chronic inflammation. Major risk factors for developing hepatocellular carcinoma are chronic hepatitis B or C virus infection, alcoholic cirrhosis, and nonalcoholic fatty liver disease. The most frequent locations for hepatocellular carcinoma to metastasize are the lungs, portal vein, bones, and regional lymph nodes. A 41-year-old Sri Lankan man presented with progressive abdominal distension and on examination was found to have a palpable irregular mass in the left lobe of his liver with moderate ascites. His ascitic fluid was an exudate without malignant cells. An ultrasound scan and contrast-enhanced computed tomography of his abdomen showed a large contrast-enhancing lesion in the left lobe of his liver without features of cirrhosis. Laparoscopic assessment revealed peritoneal and omental deposits. Histology of the biopsies taken from the liver lesion, omental deposits, and peritoneal deposits supported a diagnosis of hepatocellular carcinoma. His liver biochemistry was normal and hepatitis serology was negative. He is abstinent from alcohol and did not have metabolic syndrome. It is rare for a young patient to develop hepatocellular carcinoma with a normal liver without chronic hepatitis B or C infection, or any other risk factors. Intraperitoneal metastasis of non-ruptured hepatocellular carcinoma is also very rare. Here we report a rare case of a 41-year-old man with a large hepatocellular carcinoma in a non-cirrhotic liver without chronic hepatitis who presented with peritoneal and omental metastasis.

Electrolytic treatment of colorectal liver tumour deposits in a rat model: a technique with potential for patients with unresectable liver tumours.

PubMed

Wemyss-Holden, S A; Robertson, G S; Hall, P D; Dennison, A R; Maddern, G J

2000-01-01

Patients with unresectable malignant liver tumours have a poor prognosis. A technique is needed which improves long-term survival. Previous studies in the rat have shown that electrolysis is a safe, predictable and reproducible method for creating areas of necrosis in the normal rat liver. This study examined the effects of electrolysis on colorectal liver 'metastases' in the rat. Tumours of colorectal origin were implanted into the livers of Wistar-WAG rats. Two weeks after implantation the tumours were treated with electrolysis. A direct current generator, connected to 2 platinum intrahepatic electrodes was used to examine the effects of various electrode configurations on the extent of tumour necrosis. Significant (p<0.001) tumour ablation was achieved with all electrode configurations. Tumour necrosis was more complete (p<0.05) with the electrodes positioned on either side of the tumour than with both electrodes placed in the centre of the tumour. Liver enzymes (AST and ALT) were significantly (p<0.001) elevated after treatment, but returned towards normal by 2 days. This study has shown that colorectal liver 'metastasis' can be ablated by electrolysis in a rat model. Two separate mechanisms of tumour ablation were observed: With the electrodes directly in or adjacent to the tumour, necrosis resulted from the action of cytotoxic electrode products, whereas by positioning the electrodes proximal to the tumour, necrosis was induced by a 'secondary' ischaemic effect. The findings confirm the view that electrolysis has great potential for treating patients with unresectable malignant liver tumours.

Prevalence, Risk Factors and In-hospital Outcomes of QTc Interval Prolongation in Liver Cirrhosis.

PubMed

Zhao, Jiancheng; Qi, Xingshun; Hou, Feifei; Ning, Zheng; Zhang, Xintong; Deng, Han; Peng, Ying; Li, Jing; Wang, Xiaoxi; Li, Hongyu; Guo, Xiaozhong

2016-09-01

QTc interval prolongation is an electrocardiographic abnormality in liver cirrhosis. The objective of this study was to evaluate the prevalence, risk factors and in-hospital outcomes of QTc interval prolongation in Chinese patients with liver cirrhosis. This was a retrospective analysis of a total of 1,268 patients with liver cirrhosis who were consecutively admitted to our hospital between January 2011 and June 2014. QTc interval data were collected from the medical records. QTc interval prolongation was defined as QTc interval > 440 milliseconds. The prevalence of QTc interval prolongation was 38.2% (485 of 1268). In the entire cohort, the risk factors for QTc interval prolongation included an older age, a higher proportion of alcohol abuse and ascites, higher bilirubin, blood urea nitrogen, creatinine, prothrombin time, international normalized ratio, Child-Pugh score and model for end-stage liver diseases score, and lower red blood cell (RBC), hemoglobin (Hb), albumin (ALB), alanine aminotransferase and calcium. The in-hospital mortality was not significantly different between patients with and without QTc interval prolongation (2.1% versus 1.3%, P = 0.276). In the subgroup analyses of patients with hepatitis B virus or alcohol alone-related liver cirrhosis, the risk factors included higher bilirubin, creatinine, prothrombin time, international normalized ratio, Child-Pugh score and model for end-stage liver diseases score, and lower RBC, Hb and ALB. In the subgroups analyses of patients with acute upper gastrointestinal bleeding or ascites, the risk factors included lower RBC, Hb and ALB. QTc interval prolongation was frequent in liver cirrhosis. Although QTc interval prolongation was positively associated with alcohol-related liver cirrhosis and more severe liver dysfunction, it did not significantly influence the in-hospital mortality. Copyright © 2016 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

[A case report of simultaneous liver, pancreas-duodenum, and kidney transplantation in a patient with post-hepatitic cirrhosis combined with uremia and insulin-dependent diabetes related to chronic pancreatitis].

PubMed

Wang, He; Dou, Ke-feng; Yang, Xiao-jian; Qin, Wei-jun; Zhang, Geng; Yu, Lei; Kang, Fu-xia; Chen, Shao-yang; Xiong, Li-ze; Song, Zhen-shun; Liu, Zheng-cai

2006-09-12

To study the effect of triple organ transplantation (liver, kidney, and pancreas) in patient of end-stage liver disease with renal failure and diabetes, and to explore the optimal surgical procedure. Simultaneous piggyback orthotopic heterotopic liver, pancreas-duodenum, and kidney transplantation was performed on a 43-year-old male patient with exocrine pancreatic insufficiency and insulin-dependent diabetes related to chronic pancreatitis (CP) who developed hepatic and renal failure. The pancreatic exocrine secretions were drained enterically to the jejunum. Prednisone, tacrolimus, mycophenolate mofetil, and ATG were used as immunosuppression therapy. Good liver and pancreas allograft function recovery was achieved within 7 days after the operation. And the recovery of renal allograft function was delayed. The renal allograft was removed because of break-down of renal blood flow 16 days after the transplantation. A new renal transplantation was performed at the same position. The second kidney graft recovered its normal function 3 days later. Up to the writing of this paper no acute rejection of organs and such complications as pancreatitis, thrombosis, and localized infection occurred. The patient became insulin independent with normal liver and renal function. Simultaneous piggyback orthotopic heterotopic liver, pancreas-duodenum, and kidney transplantation can be a good method for the patients with exocrine pancreatic insufficiency and insulin-dependent diabetes combined with hepatic and renal failure.

Long-Term, Low-Dose Exposure to Microcystin-LR Does not Cause or Increase the Severity of Liver Disease in Rodents.

PubMed

Labine, Meaghan; Gong, Yuewen; Minuk, Gerald Y

Acute exposure to high concentrations of microcystin-LR (MC-LR) can cause significant hepatocyte injury. To document the effects of long-term, low-dose MC-LR exposure on hepatic inflammation and fibrosis in mice with healthy and diseased livers. Male CD1 mice (N = 20/group) were exposed to 1.0 μg/L of MC-LR in drinking water; 1.0 μg/L MC-LR plus 300 mg/L of the hepatotoxin thioacetamide (MC-LR/TAA); or 300 mg/L TAA alone for 28 weeks. Liver biochemistry and histology were documented at the end of the study period. In addition, hepatic stellate cells (HSCs), were exposed in vitro to MC-LR (0.1-10,000 μg/L) and monitored for changes in cell metabolism, proliferation and activation. Liver biochemistry and histology were essentially normal in MC-LR alone exposed mice. MC-LR/TAA and TAA alone exposed mice had significant hepatic inflammation and fibrosis but the extent of the changes were similar in the two groups. In vitro, MC-LR had no effect on HSC metabolism, proliferation or activation. Long-term, low-dose exposure to MC-LR is unlikely to lead to chronic liver disease in the setting of a normal liver or exacerbate existing liver disease in the setting of ongoing hepatitis.

Polyethylene Glycol (PEG) Linked to Near Infrared (NIR) Dyes Conjugated to Chimeric Anti-Carcinoembryonic Antigen (CEA) Antibody Enhances Imaging of Liver Metastases in a Nude-Mouse Model of Human Colon Cancer

PubMed Central

Maawy, Ali A.; Hiroshima, Yukihiko; Zhang, Yong; Luiken, George A.; Hoffman, Robert M.; Bouvet, Michael

2014-01-01

We report here that polyethylene glycol (PEG) linked to near infrared dyes conjugated to chimeric mouse-human anti-carcinoembryonic antigen (CEA) antibody greatly improves imaging of liver metastases in a nude mouse model of colon-cancer experimental metastases. PEGylated and non-PEGylated DyLight 650 and 750 dyes were conjugated to the chimeric anti-CEA antibody. The dyes were initially injected intravenously into nude mice without tumors. Tissue biodistribution was determined by tissue sonication and analyzing tissue dye concentration profiles over time. PEGylated dyes had significantly lower accumulation in the liver (p = 0.03 for the 650 dyes; p = 0.002 for the 750 dyes) compared to non-PEGylated dyes. In an experimental liver metastasis model of HT-29 colon cancer, PEGylated dyes conjugated to the anti-CEA antibody showed good labeling of metastatic tumors with high contrast between normal and malignant tissue which was not possible with the non-PEGylated dyes since there was so much non-specific accumulation in the liver. PEGylation of the DyLight 650 and 750 NIR dyes significantly altered tissue biodistribution, allowing brighter tissue labeling, decreased accumulation in normal organs, particularly the liver. This enabled high fidelity and high contrast imaging of liver metastases. PMID:24859320

Salidroside mediates apoptosis and autophagy inhibition in concanavalin A-induced liver injury

PubMed Central

Feng, Jiao; Niu, Peiqin; Chen, Kan; Wu, Liwei; Liu, Tong; Xu, Shizan; Li, Jingjing; Li, Sainan; Wang, Wenwen; Lu, Xiya; Yu, Qiang; Liu, Ning; Xu, Ling; Wang, Fan; Dai, Weiqi; Xia, Yujing; Fan, Xiaoming; Guo, Chuanyong

2018-01-01

Salidroside (Sal) is a glycoside extract from Rhodiola rosea L. with anti-inflammatory, antioxidant, anticancer and cardioprotective properties. The present study explored the protective effects and the possible mechanisms of Sal on concanavalin A (ConA)-induced liver injury in mice. Balb/C mice were divided into five groups: Normal control (injected with normal saline), ConA (25 mg/kg), Sal (10 mg/kg) +ConA, Sal (20 mg/kg) + ConA (Sal injected 2 h prior to ConA injection) and Sal (20 mg/kg) only. The serum levels of liver enzymes, pro-inflammatory cytokines, and apoptosis- and autophagy-associated marker proteins were determined at 2, 8 and 24 h after ConA injection. LY294002 was further used to verify whether the phosphoinositide 3-kinase (PI3K)/Akt pathway was activated. Primary hepatocytes were isolated to verify the effect of Sal in vitro. The results indicated that Sal was a safe agent to reduce pathological damage and serum liver enzymes in ConA-induced liver injury. Sal suppressed inflammatory reactions in serum and liver tissues, and activated the PI3K/Akt signaling pathway to inhibit apoptosis and autophagy in vivo and in vitro, which could be reversed by LY294002. In conclusion, Sal attenuated ConA-induced liver injury by modulating PI3K/Akt pathway-mediated apoptosis and autophagy in mice.

Comparison of rapid diagnostic tests to detect Mycobacterium avium subsp. paratuberculosis disseminated infection in bovine liver.

PubMed

Zarei, Mehdi; Ghorbanpour, Masoud; Tajbakhsh, Samaneh; Mosavari, Nader

2017-08-01

Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne's disease, a chronic enteritis in cattle and other domestic and wild ruminants. The presence of MAP in tissues other than intestines and associated lymph nodes, such as meat and liver, is a potential public health concern. In the present study, the relationship between the results of rapid diagnostic tests of the Johne's disease, such as serum ELISA, rectal scraping PCR, and acid-fast staining, and the presence of MAP in liver was evaluated. Blood, liver, and rectal scraping samples were collected from 200 slaughtered cattle with unknown Johne's disease status. ELISA was performed to determine the MAP antibody activity in the serum. Acid-fast staining was performed on rectal scraping samples, and PCR was performed on rectal scraping and liver samples. PCR-positive liver samples were used for mycobacterial culture. Overall, the results of this study demonstrated that MAP can be detected and cultured from liver of slaughtered cattle and rapid diagnostic tests of Johne's disease have limited value in detecting cattle with MAP infection in liver. These findings show that the presence of MAP in liver tissue may occur in cows with negative results for rapid diagnostic tests and vice versa. Hence, liver might represent another possible risk of human exposure to MAP. Given concerns about a potential zoonotic role for MAP, these results show the necessity to find new methods for detecting cattle with MAP disseminated infection.

Evaluation of hepatic function with (99m)Tc-galactosylated serum albumin scintigraphy in patients with malaria: comparison with (99m)Tc-colloid scintigraphy and liver ultrasonography.

PubMed

Lee, Sang-Woo; Lee, Jaetae; Lee, Deog-Young; Chun, Kyung-Ah; Ahn, Byeong-Cheol; Kang, Young-Mo; Lee, Kyubo

2007-02-01

Malarial parasites injected by the mosquito rapidly target hepatocytes, and hepatomegaly is commonly observed during the progress of the disease in malaria patients. To evaluate the degree of hepatic damage and functional status of hepatocytes in malaria patients, we performed liver scintigraphy using (99m)Tc-galactosylated serum albumin (GSA) prospectively and the findings were compared with those of (99m)Tc-colloid scintigraphy, ultrasonography and clinical results in the same subject. Eight malaria patients (all male, mean age 22 years) confirmed to be infected with Plasmodium vivax underwent (99m)Tc-GSA liver scintigraphy, followed by liver ultrasonography and (99m)Tc-colloid scintigraphy using phytate within 3 days. For hepatocyte scintigraphy, anterior images of cardiac blood-pool and liver were continuously acquired for 30 min after injection of 185 MBq (99m)Tc-GSA (3 mg). In addition to visual interpretation of the images, quantitative measurement of hepatic function was performed with several functional parameters, such as hepatic uptake index (LHL15), blood clearance index (HH15) and modified receptor index (LHL/HH) calculated from the radioactivity of the liver and heart. (99m)Tc-colloid images were assessed and graded visually. Severity of hepatic dysfunction or reticuloendothelial system activation was classified as normal, mild, moderate and severe on GSA or colloid images. Hepatomegaly was observed in five and splenomegaly in seven of the eight patients. Serum levels of transaminase and alkaline phosphatase were mildly elevated in two. Visual assessment of GSA scintigraphy revealed normal findings in all subjects, except for mild increases in size. The mean values of LHL15, HH15 and LHL/HH were 0.928+/-0.014, 0.537+/-0.031 and 1.732+/-0.106, respectively. They were graded as normal in five, and near-normal to mild dysfunction in three subjects. In contrast, (99m)Tc-colloid scintigraphy revealed abnormal findings in all of the subjects, and graded as moderate in three or severe reticuloendothelial system activation in five subjects. Liver ultrasonographic findings were normal for all subjects except mild hepatomegaly. Malaria-induced injury of the hepatocyte is likely to be minimal whereas hepatomegaly is commonly seen during disease process. This suggests that hepatic damage in malarial infection is mainly due to involvement of the reticuloendothelial system. (99m)Tc-GSA scintigraphy can be used in differentiating hepatocellular damage from reticuloendothelial system involvement in patients with infectious disease showing hepatomegaly.

Targeting Dysbiosis for the Treatment of Liver Disease.

PubMed

Anand, Gobind; Zarrinpar, Amir; Loomba, Rohit

2016-02-01

The gut microbiome is composed of a vast number of microbes in the gastrointestinal tract, which benefit host metabolism, aid in digestion, and contribute to normal immune function. Alterations in microbial composition can result in intestinal dysbiosis, which has been implicated in several diseases including obesity, inflammatory bowel disease, and liver diseases. Over the past several years, significant interactions between the intestinal microbiota and liver have been discovered, with possible mechanisms for the development as well as progression of liver disease and promising therapeutic targets to either prevent or halt the progression of liver disease. In this review the authors examine mechanisms of dysbiosis-induced liver disease; highlight current knowledge regarding the role of dysbiosis in nonalcoholic liver disease, alcoholic liver disease, and cirrhosis; and discuss potential therapeutic targets. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease.

PubMed

Suzuki, Ayako; Lindor, Keith; St Saver, Jenny; Lymp, James; Mendes, Flavia; Muto, Ayako; Okada, Toshihide; Angulo, Paul

2005-12-01

The effects of lifestyle modifications in nonalcoholic fatty liver disease (NAFLD) are incompletely defined. We aimed at determining the association of changes in body weight and lifestyle with changes in serum ALT levels. We analyzed annual health checkup data from 1546 employees. Of 469 subjects with elevated ALT, we selected 348 male subjects by excluding those who had other causes of liver disease. They were followed for one year to assess the association of change in lifestyle with change in serum ALT. The 136 subjects who had ALT normalization were followed for two years to assess the association between lifestyle management and persistently normal ALT. In adjusted analysis, weight loss and regular exercise were significantly associated with improvement in serum ALT and increased the odds of ALT normalization, while starting smoking was significantly associated with deterioration in serum ALT. Subjects achieving > or = 5% weight reduction showed improvement in serum ALT. Reduction in alcohol consumption was not associated with changes in serum ALT. Maintaining reduced weight (<5% gain) was significantly associated with persistently normal ALT. Reducing weight by at least 5% with subsequent weight control and exercising regularly may be beneficial in treating NAFLD.

Regional radiation dose-response modeling of functional liver in hepatocellular carcinoma patients with longitudinal sulfur colloid SPECT/CT: a proof of concept.

PubMed

Price, Ryan G; Apisarnthanarax, Smith; Schaub, Stephanie K; Nyflot, Matthew J; Chapman, Tobias R; Matesan, Manuela; Vesselle, Hubert J; Bowen, Stephen R

2018-06-19

We report on patient-specific quantitative changes in longitudinal sulfur colloid SPECT/CT as a function of regional radiation dose distributions to normal liver in a cohort of hepatocellular carcinoma patients. Dose-response thresholds and slopes varied with baseline liver function metrics, and extreme values were found in patients with fatal hepatotoxicity. Dose-response modeling of normal liver in individual HCC patients has potential to characterize in vivo radiosensitivity, identify high risk subgroups, and personalize treatment planning dose constraints. Hepatotoxicity risk in hepatocellular carcinoma (HCC) patients is modulated by radiation dose delivered to normal liver tissue, but reported dose-response data are limited. Our prior work established baseline [ 99m Tc]sulfur colloid (SC) SPECT/CT liver function imaging biomarkers that predict clinical outcomes. We conducted a proof-of-concept investigation with longitudinal SC SPECT/CT to characterize patient-specific radiation dose-response relationships as surrogates for liver radiosensitivity. SC SPECT/CT images of 15 HCC patients with variable Child-Pugh status (8 CP-A, 7 CP-B/C) were acquired in treatment position prior to and 1 month (nominal) after SBRT (n=6) or proton therapy (n=9). Localized rigid registrations between pre/post-treatment CT to planning CT scans were performed, and transformations were applied to pre/post-treatment SC SPECT images. Radiotherapy doses were converted to EQD2 α/β=3 and Gy (RBE), and binned in 5 GyEQD2 increments within tumor-subtracted livers. Mean dose and percent change (%ΔSC) between pre- and post-treatment SPECT uptake, normalized to regions receiving < 5 GyEQD2, were calculated in each binned dose region. Dose-response data were parameterized by sigmoid functions (double exponential) consisting of maximum reduction (%ΔSC max ), dose midpoint (D mid ), and dose-response slope (α mid ) parameters. Individual patient sigmoid dose-response curves had high goodness-of-fit (median R 2 = 0.96, range 0.76-0.99). Large inter-patient variability was observed, with median (range) in %ΔSC max of 44% (20-75%), D mid of 13 Gy (4-27 GyEQD2), and α mid of 0.11 GyEQD2 -1 (0.04-0.29 GyEQD2 -1 ), respectively. Eight of 15 patients had %ΔSC max = 20-45%, while 7/15 had %ΔSC max = 60-75%, with subgroups made up of variable baseline liver function status and radiation treatment modality. Fatal hepatotoxicity occurred in patients (2/15) with low TLF (< 0.12) and low D mid (< 7 GyEQD2). Longitudinal SC SPECT/CT imaging revealed patient-specific variations in dose-response, and may identify patients with poor baseline liver function and increased sensitivity to radiation therapy. Validation of this regional liver dose-response modeling concept as a surrogate for patient-specific radiosensitivity has potential to guide HCC therapy regimen selection and planning constraints. Copyright © 2018 Elsevier Inc. All rights reserved.

Extended normothermic extracorporeal perfusion of isolated human liver after warm ischaemia: a preliminary report.

PubMed

Bellomo, Rinaldo; Marino, Bruno; Starkey, Graeme; Fink, Michael; Wang, Bao Zhong; Eastwood, Glenn M; Peck, Leah; Young, Helen; Houston, Shane; Skene, Alison; Opdam, Helen; Jones, Robert

2014-09-01

Donation after circulatory death (DCD) livers are at markedly increased risk of primary graft dysfunction and biliary tract ischaemia. Normothermic extracorporeal liver perfusion (NELP) may increase the ability to transplant DCD livers and may allow their use for artificial extracorporeal liver support of patients with fulminant liver failure. We conducted two proof-of-concept experiments using human livers after DCD to assess the feasibility and functional efficacy of NELP over an extended period. We applied extracorporeal membrane oxygenation, parenteral nutrition, separate hepatic artery and portal vein perfusion and physiological perfusion pressures to two livers obtained after DCD. We achieved NELP and evidence of liver function (bile production, paracetamol removal and maintenance of normal lactate levels) in both livers; one for 24 hours and the other for 43 hours. Histological examination showed areas of patchy ischaemia but preserved biliary ducts and canaliculi. Our experiments justify further investigations of the feasibility and efficacy of extended DCD liver preservation by ex-vivo perfusion.

[Preoperative imaging/operation planning for liver surgery].

PubMed

Schoening, W N; Denecke, T; Neumann, U P

2015-12-01

The currently established standard for planning liver surgery is multistage contrast media-enhanced multidetector computed tomography (CM-CT), which as a rule enables an appropriate resection planning, e.g. a precise identification and localization of primary and secondary liver tumors as well as the anatomical relation to extrahepatic and/or intrahepatic vascular and biliary structures. Furthermore, CM-CT enables the measurement of tumor volume, total liver volume and residual liver volume after resection. Under the condition of normal liver function a residual liver volume of 25 % is nowadays considered sufficient and safe. Recent studies in patients with liver metastases of colorectal cancer showed a clear staging advantage of contrast media-enhanced magnetic resonance imaging (CM-MRI) versus CM-CT. In addition, most recent data showed that the use of liver-specific MRI contrast media further increases the sensitivity and specificity of detection of liver metastases. This imaging technology seems to lead closer to the ideal "one stop shopping" diagnostic tool in preoperative planning of liver resection.

Antioxidant potential of the methanol-methylene chloride extract of Terminalia glaucescens leaves on mice liver in streptozotocin-induced stress.

PubMed

Njomen, Guy Bertrand Sabas Nya; Kamgang, René; Oyono, Jean Louis Essame; Njikam, Njifutie

2008-11-01

The antioxidant effect of the methanol-methylene chloride extract of Terminalia glaucescens (Combretaceae) leaves was investigated in streptozotocin (STZ)-induced oxidative stress. Oxidative stress was induced in mice by a daily dose of STZ (45 mg/kg body weight i.p.) for five days. From day one, before STZ injection, normal and diabetic-test mice received an oral dose of the extract (100 or 300 mg/kg b.w.) daily. Plasma metabolites, lipid peroxidation, and antioxidant enzymes in the liver were assessed and gain in body weight recorded. In normal mice the plant extract reduced food and water intake, blood glucose and LDL-C level and body weight gain, did not affect the lipid peroxidation in the liver, while the antioxidant enzyme activities seemed increased. Blood glucose was decreased (P < 0.05) in normal mice treated with 300 mg/kg extract. Diabetic mice pretreated with 100 mg/kg extract as diabetic control mice (DC) showed significant (P < 0.001) body weight loss, polyphagia and polydipsia, high plasma glucose level, decrease in the liver catalase, peroxidase, and superoxide dismutase activities, and increase in lipid peroxidation. The HDL-C level was lowered (P < 0.05) whereas LDL-C increased. In 300 mg/kg extract-pretreated diabetic mice the extract prevented body weight loss, increase of blood glucose level, lipid peroxidation in liver, food and water intake, and lowering of plasma HDL-C level and liver antioxidants; this extract prevented LDL-C level increase. These results indicate that T. glaucescens protects against STZ-induced oxidative stress and could thus explain its traditional use for diabetes and obesity treatment or management.

Evaluation of Liver Function After Proton Beam Therapy for Hepatocellular Carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mizumoto, Masashi; Okumura, Toshiyuki; Hashimoto, Takayuki

Purpose: Our previous results for treatment of hepatocellular carcinoma with proton beam therapy (PBT) revealed excellent local control. In this study, we focused on the impact of PBT on normal liver function. Methods and Materials: The subjects were 259 patients treated with PBT at University of Tsukuba between January 2001 and December 2007. We evaluated the Child-Pugh score pretreatment, on the final day of PBT, and 6, 12, and 24 months after treatment with PBT. Patients who had disease progression or who died with tumor progression at each evaluation point were excluded from the analysis to rule out an effectmore » of tumor progression. An increase in the Child-Pugh score of 1 or more was defined as an adverse event. Results: Of the 259 patients, 241 had no disease progression on the final day of PBT, and 91 had no progression within 12 months after PBT. In univariate analysis, the percentage volumes of normal liver receiving at least 0, 10, 20, and 30 GyE in PBT (V0, 10, 20, and 30) were significantly associated with an increase of Child-Pugh score at 12 months after PBT. Of the 91 patients evaluated at 12 months, 66 had no increase of Child-Pugh score, 15 had a 1-point increase, and 10 had an increase of {>=}2 points. For the Youden index, the optimal cut-offs for V0, V10, V20, and V30 were 30%, 20%, 26%, and 18%, respectively. Conclusion: Our findings indicate that liver function after PBT is significantly related to the percentage volume of normal liver that is not irradiated. This suggests that further study of the relationship between liver function and PBT is required.« less

Analysis of breath volatile organic compounds as a noninvasive tool to diagnose nonalcoholic fatty liver disease in children.

PubMed

Alkhouri, Naim; Cikach, Frank; Eng, Katharine; Moses, Jonathan; Patel, Nishaben; Yan, Chen; Hanouneh, Ibrahim; Grove, David; Lopez, Rocio; Dweik, Raed

2014-01-01

Nonalcoholic fatty liver disease (NAFLD) is one of the most common complications of childhood obesity. Our objective was to investigate the association of breath volatile organic compounds with the diagnosis of NAFLD in children. Patients were screened with an ultrasound of the abdomen to evaluate for NAFLD. Exhaled breath was collected and analyzed per protocol using selective ion flow tube mass spectrometry (SIFT-MS). Sixty patients were included in the study (37 with NAFLD and 23 with normal liver). All children were overweight or obese. The mean age was 14.1±2.8 years and 50% were female. A comparison of the SIFT-MS results of patients with NAFLD with those with normal liver on ultrasound revealed differences in concentration of more than 15 compounds. A panel of four volatile organic compounds can identify the presence of NAFLD with good accuracy (area under the receiver operating characteristic curve of 0.913 in the training set and 0.763 in the validation set). Breath isoprene, acetone, trimethylamine, acetaldehyde, and pentane were significantly higher in the NAFLD group compared with normal liver group (14.7 ppb vs. 8.9 for isoprene; 71.7 vs. 36.9 for acetone; 5.0 vs. 3.2 for trimethylamine; 35.1 vs. 26.0 for acetaldehyde; and 13.3 vs. 8.8 for pentane, P<0.05 for all). Exhaled breath analysis is a promising noninvasive method to detect fatty liver in children. Isoprene, acetone, trimethylamine, acetaldehyde, and pentane are novel biomarkers that may help to gain insight into pathophysiological processes leading to the development of NAFLD.

1H MRS Assessment of Hepatic Fat Content: Comparison Between Normal- and Excess-weight Children and Adolescents.

PubMed

Chabanova, Elizaveta; Fonvig, Cilius Esmann; Bøjsøe, Christine; Holm, Jens-Christian; Thomsen, Henrik S

2017-08-01

The purpose of the present study was to obtain a cutoff value of liver fat content for the diagnosis of hepatic steatosis by comparing magnetic resonance (MR) spectroscopy results in children and adolescents with normal and excess weight. The study included 420 children and adolescents (91 normal-weight, 99 overweight, and 230 obese) 8-18 years of age. Proton magnetic resonance spectroscopy was performed with a 3T MR system using point resolved spectroscopy sequence with series echo times. The mean absolute mass concentration of liver fat was obtained: 0.5 ± 0.04% in normal-weight boys; 0.5 ± 0.03% in normal-weight girls; 0.9 ± 0.16% in boys with overweight; 1.1 ± 0.24% in girls with overweight; 1.7 ± 0.24% in boys with obesity; and 1.4 ± 0.21% in girls with obesity. The cutoff value of absolute mass concentration of liver fat for hepatic steatosis was found to be 1.5%. Based on this cutoff value, hepatic steatosis was diagnosed in 16% of boys with overweight, 11% of girls with overweight, 32% of boys with obesity, and 27% of girls with obesity. Proton magnetic resonance spectroscopy was successfully applied to obtain the cutoff value of absolute mass concentration of liver fat for the diagnosis of hepatic steatosis in children and adolescents. Children and adolescents with obesity have higher risk of hepatic steatosis than their peers with overweight. Copyright © 2017 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Investigation into the distinct subcellular effects of docosahexaenoic acid loaded low-density lipoprotein nanoparticles in normal and malignant murine liver cells

PubMed Central

Moss, Lacy R.; Mulik, Rohit S.; Van Treuren, Tim; Kim, Soo Young; Corbin, Ian R.

2016-01-01

Background Recent studies have shown that low density lipoproteins reconstituted with the natural omega 3 fatty acid docosahexaenoic acid (LDL-DHA) is selectively cytotoxic to liver cancer cells over normal hepatocytes. To date, little is known about the subcellular events which transpire following LDL-DHA treatment. Methods Herein, murine noncancer and cancer liver cells, TIB-73 and TIB-75 respectively, were investigated utilizing confocal microscopy, flow cytometry and viability assays to demonstrate differential actions of LDL-DHA nanoparticles in normal versus malignant cells. Results Our studies first showed that basal levels of oxidative stress are significantly higher in the malignant TIB-75 cells compared to the normal TIB-73 cells. As such, upon entry of LDL-DHA into the malignant TIB-75 cells, DHA is rapidly oxidized precipitating global and lysosomal lipid peroxidation along with increased lysosomal permeability. This leakage of lysosomal contents and lipid peroxidation products trigger subsequent mitochondrial dysfunction and nuclear injury. The cascade of LDL-DHA mediated lipid peroxidation and organelle damage was partially reversed by the administration of the antioxidant, N-acetylcysteine, or the iron-chelator, deferoxamine. LDL-DHA treatment in the normal TIB-73 cells was well tolerated and did not elicit any cell or organelle injury. Conclusion These studies have shown that LDL-DHA is selectively cytotoxic to liver cancer cells and that increased levels of ROS and iron catalyzed reactions promote the peroxidation of DHA which lead to organelle dysfunction and ultimately the demise of the cancer cell. General significance LDL-DHA selectively disrupts lysosomal, mitochondrial and nuclear function in cancer cells as a novel pathway for eliminating cancer cells. PMID:27418237

Histology and Glutamine Synthetase Immunoreactivity in Liver Biopsies From Patients With Congestive Heart Failure

PubMed Central

Horvath, Bela; Zhu, Lei; Allende, Daniela; Xie, Hao; Guirguis, John; Cruise, Michael; Patil, Deepa T.; O’Shea, Robert; Rivas, John; Yordanka, Reyna; Lan, Nan; Liu, Xiuli

2017-01-01

Background Long-standing congestive heart failure can induce a constellation of histopathology changes in the liver that can range from mild sinusoidal dilation to advanced fibrosis and loss of normal perivenular expression of glutamine synthetase (GS). Liver biopsies might be performed to assess the perioperative risk of these patients or to determine the need of synchronous liver transplant. We aimed to assess interobserver agreement in recognizing these liver histologic features in patients undergoing evaluation for heart transplantation and to examine whether immunohistochemistry of GS will aid the diagnosis of cardiac hepatopathy (CH). Methods Hematoxylin-eosin and trichrome-stained slides from 36 liver biopsies from patients undergoing evaluation for heart transplantation were reviewed by four liver pathologists. Histologic features of CH were reviewed and an overall fibrosis (stage) was assessed according to a recently proposed congestive hepatic fibrosis score (CHFS). In addition, 24 liver biopsies with a consensus diagnosis of CH and eight liver biopsies with no significant pathological changes were subjected to immunohistochemistry for GS. The Fleiss’ kappa coefficient (K) analysis was performed to determine the interobserver agreement. Further, histologic features of CH were correlated with the staining pattern of GS. Results Sinusoidal dilation, centrilobular hepatocyte atrophy, centrilobular fibrosis and hemorrhage were the most common findings in this cohort with a substantial-to-fair level of interobserver agreement among four reviewers. The overall agreement on the diagnosis of CH and CHFS was moderate (K = 0.55, 95% confidence interval (CI): 0.32 - 0.73) and fair (K = 0.35, 95% CI: 0.24 - 0.49), respectively. Twelve (of 24, 50%) cases of CH showed loss of the normal perivenular GS staining, while the remaining 12 cases of CH and all eight controls showed retained GS expression. Histologic features of CH (presence of sinusoidal dilation, centrilobular hepatocyte atrophy, hemorrhage, and centrilobular fibrosis) and the stage of fibrosis (CHFS) were not correlated with the loss of GS staining. Conclusion Most common features of CH can be interpreted with fair-to-substantial level of agreement by liver pathologists, with an overall moderate level agreement for the diagnosis and fair agreement for CHFS. Loss of normal perivenular expression of GS only occurs in 50% CH and thus is not a sensitive marker for CH. PMID:28725306

Direct targeting of risk factors significantly increases the detection of liver cirrhosis in primary care: a cross-sectional diagnostic study utilising transient elastography.

PubMed

Harman, David J; Ryder, Stephen D; James, Martin W; Jelpke, Matthew; Ottey, Dominic S; Wilkes, Emilie A; Card, Timothy R; Aithal, Guruprasad P; Guha, Indra Neil

2015-05-03

To assess the feasibility of a novel diagnostic algorithm targeting patients with risk factors for chronic liver disease in a community setting. Prospective cross-sectional study. Two primary care practices (adult patient population 10,479) in Nottingham, UK. Adult patients (aged 18 years or over) fulfilling one or more selected risk factors for developing chronic liver disease: (1) hazardous alcohol use, (2) type 2 diabetes or (3) persistently elevated alanine aminotransferase (ALT) liver function enzyme with negative serology. A serial biomarker algorithm, using a simple blood-based marker (aspartate aminotransferase:ALT ratio for hazardous alcohol users, BARD score for other risk groups) and subsequently liver stiffness measurement using transient elastography (TE). Diagnosis of clinically significant liver disease (defined as liver stiffness ≥8 kPa); definitive diagnosis of liver cirrhosis. We identified 920 patients with the defined risk factors of whom 504 patients agreed to undergo investigation. A normal blood biomarker was found in 62 patients (12.3%) who required no further investigation. Subsequently, 378 patients agreed to undergo TE, of whom 98 (26.8% of valid scans) had elevated liver stiffness. Importantly, 71/98 (72.4%) patients with elevated liver stiffness had normal liver enzymes and would be missed by traditional investigation algorithms. We identified 11 new patients with definite cirrhosis, representing a 140% increase in the number of diagnosed cases in this population. A non-invasive liver investigation algorithm based in a community setting is feasible to implement. Targeting risk factors using a non-invasive biomarker approach identified a substantial number of patients with previously undetected cirrhosis. The diagnostic algorithm utilised for this study can be found on clinicaltrials.gov (NCT02037867), and is part of a continuing longitudinal cohort study. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Epigenetic Events in Liver Cancer Resulting From Alcoholic Liver Disease

PubMed Central

French, Samuel W.

2013-01-01

Epigenetic mechanisms play an extensive role in the development of liver cancer (i.e., hepatocellular carcinoma [HCC]) associated with alcoholic liver disease (ALD) as well as in liver disease associated with other conditions. For example, epigenetic mechanisms, such as changes in the methylation and/or acetylation pattern of certain DNA regions or of the histone proteins around which the DNA is wrapped, contribute to the reversion of normal liver cells into progenitor and stem cells that can develop into HCC. Chronic exposure to beverage alcohol (i.e., ethanol) can induce all of these epigenetic changes. Thus, ethanol metabolism results in the formation of compounds that can cause changes in DNA methylation and interfere with other components of the normal processes regulating DNA methylation. Alcohol exposure also can alter histone acetylation/deacetylation and methylation patterns through a variety of mechanisms and signaling pathways. Alcohol also acts indirectly on another molecule called toll-like receptor 4 (TLR4) that is a key component in a crucial regulatory pathway in the cells and whose dysregulation is involved in the development of HCC. Finally, alcohol use regulates an epigenetic mechanism involving small molecules called miRNAs that control transcriptional events and the expression of genes important to ALD. PMID:24313165

An In Vivo Magnetic Resonance Spectroscopy Study of the Effects of Caloric and Non-Caloric Sweeteners on Liver Lipid Metabolism in Rats.

PubMed

Janssens, Sharon; Ciapaite, Jolita; Wolters, Justina C; van Riel, Natal A; Nicolay, Klaas; Prompers, Jeanine J

2017-05-10

We aimed to elucidate the effects of caloric and non-caloric sweeteners on liver lipid metabolism in rats using in vivo magnetic resonance spectroscopy (MRS) and to determine their roles in the development of liver steatosis. Wistar rats received normal chow and either normal drinking water, or solutions containing 13% ( w / v ) glucose, 13% fructose, or 0.4% aspartame. After 7 weeks, in vivo hepatic dietary lipid uptake and de novo lipogenesis were assessed with proton-observed, carbon-13-edited MRS combined with 13 C-labeled lipids and 13 C-labeled glucose, respectively. The molecular basis of alterations in hepatic liver metabolism was analyzed in detail ex vivo using immunoblotting and targeted quantitative proteomics. Both glucose and fructose feeding increased adiposity, but only fructose induced hepatic lipid accumulation. In vivo MRS showed that this was not caused by increased hepatic uptake of dietary lipids, but could be attributed to an increase in de novo lipogenesis. Stimulation of lipogenesis by fructose was confirmed by a strong upregulation of lipogenic enzymes, which was more potent than with glucose. The non-caloric sweetener aspartame did not significantly affect liver lipid content or metabolism. In conclusion, liquid fructose more severely affected liver lipid metabolism in rats than glucose, while aspartame had no effect.

Cinnamon Polyphenol Extract Inhibits Hyperlipidemia and Inflammation by Modulation of Transcription Factors in High-Fat Diet-Fed Rats.

PubMed

Tuzcu, Zeynep; Orhan, Cemal; Sahin, Nurhan; Juturu, Vijaya; Sahin, Kazim

2017-01-01

We evaluated the effects of cinnamon polyphenol extract on hepatic transcription factors expressions including SREBP-1c and LXR- α in rats fed high fat diet (HFD). Twenty-eight Wistar rats were allocated into four groups: (i) normal control: animals fed with normal chow; (ii) cinnamon: animals supplemented with cinnamon polyphenol; (iii) HFD: animals fed a high-fat diet; and (iv) HFD + cinnamon: animals fed a high-fat diet and treated with cinnamon polyphenol. Obesity was linked to hyperglycemia, hyperlipidemia, and oxidative stress as imitated by elevated serum glucose, lipid profile, and serum and liver malondialdehyde (MDA) concentrations. Cinnamon polyphenol decreased body weight, visceral fat, liver weight and serum glucose and insulin concentrations, liver antioxidant enzymes, and lipid profile ( P < 0.05) and reduced serum and liver MDA concentration compared to HFD rats ( P < 0.05). Cinnamon polyphenol also suppressed the hepatic SREBP-1c, LXR- α , ACLY, FAS, and NF- κ B p65 expressions and enhanced the PPAR- α , IRS-1, Nrf2, and HO-1 expressions in the HFD rat livers ( P < 0.05). In conclusion, cinnamon polyphenol reduces the hyperlipidemia, inflammation, and oxidative stress through activating transcription factors and antioxidative defense signaling pathway in HFD rat liver.

Cinnamon Polyphenol Extract Inhibits Hyperlipidemia and Inflammation by Modulation of Transcription Factors in High-Fat Diet-Fed Rats

PubMed Central

Tuzcu, Zeynep; Orhan, Cemal; Sahin, Nurhan; Juturu, Vijaya

2017-01-01

We evaluated the effects of cinnamon polyphenol extract on hepatic transcription factors expressions including SREBP-1c and LXR-α in rats fed high fat diet (HFD). Twenty-eight Wistar rats were allocated into four groups: (i) normal control: animals fed with normal chow; (ii) cinnamon: animals supplemented with cinnamon polyphenol; (iii) HFD: animals fed a high-fat diet; and (iv) HFD + cinnamon: animals fed a high-fat diet and treated with cinnamon polyphenol. Obesity was linked to hyperglycemia, hyperlipidemia, and oxidative stress as imitated by elevated serum glucose, lipid profile, and serum and liver malondialdehyde (MDA) concentrations. Cinnamon polyphenol decreased body weight, visceral fat, liver weight and serum glucose and insulin concentrations, liver antioxidant enzymes, and lipid profile (P < 0.05) and reduced serum and liver MDA concentration compared to HFD rats (P < 0.05). Cinnamon polyphenol also suppressed the hepatic SREBP-1c, LXR-α, ACLY, FAS, and NF-κB p65 expressions and enhanced the PPAR-α, IRS-1, Nrf2, and HO-1 expressions in the HFD rat livers (P < 0.05). In conclusion, cinnamon polyphenol reduces the hyperlipidemia, inflammation, and oxidative stress through activating transcription factors and antioxidative defense signaling pathway in HFD rat liver. PMID:28396714

Liver biopsy analysis has a low level of performance for diagnosis of intermediate stages of fibrosis.

PubMed

Poynard, Thierry; Lenaour, Gilles; Vaillant, Jean Christophe; Capron, Frederique; Munteanu, Mona; Eyraud, Daniel; Ngo, Yen; M'Kada, Helmi; Ratziu, Vlad; Hannoun, Laurent; Charlotte, Frederic

2012-06-01

There is controversy about the performance of noninvasive tests such as FibroTest in diagnosing intermediate stages of fibrosis. We investigated whether this controversy results from limitations of biopsy analysis for intermediate-stage fibrosis and inappropriate determination of the standard area under the receiver-operator characteristic curve (AUROC). To determine whether biopsy has a lower diagnostic performance for fibrosis stage F2 (few septa) vs F1 (fibrosis without septa), compared with its performance for F1 vs F0 or F4 vs F3, we determined the fibrotic areas of large surgical samples collected from 20 consecutive patients with chronic liver disease or normal liver tissue that surrounded tumors. We analyzed digitized images of 27,869 virtual biopsies of increasing length and also analyzed data from 6500 patients with interpretable FibroTest results who also underwent biopsy analysis. The overall performance of biopsy analysis (by Obuchowski measure) increased with biopsy length from 0.885 for 5-mm to 0.912 for 30-mm samples (P < .0001). The performance of biopsy was lower for the diagnosis of F2 vs F1 samples (weighted AUROC [wAUROC] = 0.505) than for F1 vs F0 (wAUROC = 0.773; 53% difference; P < .0001) or F4 vs F3 (wAUROC = 0.700; 39% difference; P < .0001), even when 30-mm biopsy samples were used. The performance of FibroTest was also lower for the diagnosis of F2 vs F1 samples (wAUROC = 0.512) than for F1 vs F0 samples (wAUROC = 0.626; 22% difference; P < .0001) or F4 vs F3 (wAUROC = 0.628; 23% difference; P < .0001). However, the FibroTest had smaller percentage differences among wAUROC values than biopsy. Biopsy has a low level of diagnostic performance for fibrosis stages F2 and F1. The recommendation for biopsy analysis, instead of a validated biomarker panel such as FibroTest, for the diagnosis of intermediate stages of fibrosis is therefore misleading. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Weight loss and severe jaundice in a patient with hyperthyroidism.

PubMed

Breidert, M; Offensperger, S; Blum, H E; Fischer, R

2011-09-01

Thyrotoxicosis may significantly alter hepatic function and is associated with autoimmune disorders of the liver. We report the case of a thyrotoxic patient with Graves' disease and histologically established cholestatic hepatitis. Medical treatment of hyperthyroidism normalized liver function tests. In patients with elevated liver function parameters and jaundice of unknown origin, thyroid function should generally be tested. Moreover, medical treatment of hyperthyroidism with thyrostatics may cause severe hepatitis whereas untreated hyperthyroid patients are at risk of developing chronic liver failure. © Georg Thieme Verlag KG Stuttgart · New York.

SU-G-IeP4-10: Microimaging for Different Degrees of Human Cavernous Hemangioma of Liver by Using In-Line Phase-Contrast Imaging CT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duan, J

2016-06-15

Purpose: Cavernous hemangioma of the liver (CHL) is the most common benign solid tumor of the liver. In this study, we quantitative assessment the different degrees of CHL from microscopic viewpoint by using in-line phase-contrast imaging CT (ILPCI-CT). Methods: The experiments were performed at x-ray imaging and biomedical application beamline (BL13W1) of Shanghai Synchrotron Radiation Facility (SSRF) in China. Three typical specimens at different stages, i.e., mild, moderate and severe human CHL were imaged using ILPCI-CT at 16keV without contrast agents. The 3D visualization of different degrees of CHL samples were presented using ILPCI-CT. Additionally, quantitative evaluation of the CHLmore » features, such as the range of hepatic sinusoid equivalent diameters in different degrees of CHL samples, the ratio of the hepatic sinusoid to the CHL tissue, were measured. Results: The planar image clearly displayed the dilated hepatic sinusoids in microns. There was no normal hepatic vascular found in the all CHL samples. Different stages of CHL samples were presented with vivid shapes and stereoscopic effects by using 3D visualization. The equivalent diameters of hepatic sinusoids in three degrees CHL were different. The equivalent diameters of the hepatic sinusoids in mild CHL, range from 60 to 120 µm. The equivalent diameters of the hepatic sinusoids in moderate CHL, range from 65 to 190 µm. The equivalent diameters of the hepatic sinusoids in severe CHL, range from 95 to 215 µm. The ratio of the hepatic sinusoid to the mild, moderate and severe CHL tissue were 3%, 16% and 21%, respectively. Conclusion: The results show that the high degree of sensitivity of the ILPCI-CT technique and demonstrate the feasibility of accurate visualization of different stage human CHL. ILPCI-CT may offers a potential use in non-invasive study and analysis of CHL.« less

Hyaluronic Acid Levels Predict Risk of Hepatic Encephalopathy and Liver-Related Death in HIV/Viral Hepatitis Coinfected Patients

PubMed Central

Peters, Lars; Mocroft, Amanda; Soriano, Vincent; Rockstroh, Jürgen; Rauch, Andri; Karlsson, Anders; Knysz, Brygida; Pradier, Christian; Zilmer, Kai; Lundgren, Jens D.

2013-01-01

Background Whereas it is well established that various soluble biomarkers can predict level of liver fibrosis, their ability to predict liver-related clinical outcomes is less clearly established, in particular among HIV/viral hepatitis co-infected persons. We investigated plasma hyaluronic acid’s (HA) ability to predict risk of liver-related events (LRE; hepatic coma or liver-related death) in the EuroSIDA study. Methods Patients included were positive for anti-HCV and/or HBsAg with at least one available plasma sample. The earliest collected plasma sample was tested for HA (normal range 0–75 ng/mL) and levels were associated with risk of LRE. Change in HA per year of follow-up was estimated after measuring HA levels in latest sample before the LRE for those experiencing this outcome (cases) and in a random selection of one sixth of the remaining patients (controls). Results During a median of 8.2 years of follow-up, 84/1252 (6.7%) patients developed a LRE. Baseline median (IQR) HA in those without and with a LRE was 31.8 (17.2–62.6) and 221.6 ng/mL (74.9–611.3), respectively (p<0.0001). After adjustment, HA levels predicted risk of contracting a LRE; incidence rate ratios for HA levels 75–250 or ≥250 vs. <75 ng/mL were 5.22 (95% CI 2.86–9.26, p<0.0007) and 28.22 (95% CI 14.95–46.00, p<0.0001), respectively. Median HA levels increased substantially prior to developing a LRE (107.6 ng/mL, IQR 0.8 to 251.1), but remained stable for controls (1.0 ng/mL, IQR –5.1 to 8.2), (p<0.0001 comparing cases and controls), and greater increases predicted risk of a LRE in adjusted models (p<0.001). Conclusions An elevated level of plasma HA, particularly if the level further increases over time, substantially increases the risk of contracting LRE over the next five years. HA is an inexpensive, standardized and non-invasive supplement to other methods aimed at identifying HIV/viral hepatitis co-infected patients at risk of hepatic complications. PMID:23724041

Distribution of cadmium in leg muscle and liver of game birds from Serbia

NASA Astrophysics Data System (ADS)

Nikolić, D.; Đinović-Stojanović, J.; Stefanović, S.; Radičević, T.; Trbović, D.; Spirić, D.; Janković, S.

2017-09-01

The aim of this study was to present the distribution of cadmium (Cd) levels in leg muscle and liver of game birds. Samples (n=464) of: pheasants (n=182), mallards (n=25), Eurasian jay (n=7), partridges (n=5), woodcocks (n=8) and common quail (n=5) were collected during regular hunting seasons within the Serbian National Residue Monitoring Program from 2013 to 2016. Analysis of Cd was performed by ICP-MS. In all liver samples, Cd levels were above the limit of detection (LOD=0.001 mg/kg) while in 66.4% of muscle samples, Cd was detected. Statistical analysis showed significant differences between Cd levels in leg muscle and liver of woodcocks and others game birds. The highest mean Cd level was observed in muscle samples of woodcocks (0.042 mg/kg). The lowest mean Cd levels in liver were observed in common quails (0.130 mg/kg) and mallards (0.160 mg/kg) while the highest levels were measured in woodcocks (1.247 mg/kg) and pheasants (0.262 mg/kg). During four years of the Serbian National Residue Monitoring Program, leg muscle samples of woodcocks (n=3), liver samples of pheasants (n=23), woodcocks (n=6) and mallards (n=3) exceeded the maximum residue limit (MRL).