Partial deletion of argininosuccinate synthase protects from pyrazole plus lipopolysaccharide-induced liver injury by decreasing nitrosative stress

Science.gov (United States)

Lu, Yongke; Leung, Tung Ming; Ward, Stephen C.

2012-01-01

Argininosuccinate synthase (ASS) is the rate-limiting enzyme in the urea cycle. Along with nitric oxide synthase (NOS)-2, ASS endows cells with the l-citrulline/nitric oxide (NO·) salvage pathway to continually supply l-arginine from l-citrulline for sustained NO· generation. Because of the relevant role of NOS in liver injury, we hypothesized that downregulation of ASS could decrease the availability of intracellular substrate for NO· synthesis by NOS-2 and, hence, decrease liver damage. Previous work demonstrated that pyrazole plus LPS caused significant liver injury involving NO· generation and formation of 3-nitrotyrosine protein adducts; thus, wild-type (WT) and Ass+/− mice (Ass−/− mice are lethal) were treated with pyrazole plus LPS, and markers of nitrosative stress, as well as liver injury, were analyzed. Partial ablation of Ass protected from pyrazole plus LPS-induced liver injury by decreasing nitrosative stress and hepatic and circulating TNFα. Moreover, apoptosis was prevented, since pyrazole plus LPS-treated Ass+/− mice showed decreased phosphorylation of JNK; increased MAPK phosphatase-1, which is known to deactivate JNK signaling; and lower cleaved caspase-3 than treated WT mice, and this was accompanied by less TdT-mediated dUTP nick end labeling-positive staining. Lastly, hepatic neutrophil accumulation was almost absent in pyrazole plus LPS-treated Ass+/− compared with WT mice. Partial Ass ablation prevents pyrazole plus LPS-mediated liver injury by reducing nitrosative stress, TNFα, apoptosis, and neutrophil infiltration. PMID:22052013

Decreased nucleotide excision repair in steatotic livers associates with myeloperoxidase-immunoreactivity

International Nuclear Information System (INIS)

Schults, Marten A.; Nagle, Peter W.; Rensen, Sander S.; Godschalk, Roger W.; Munnia, Armelle; Peluso, Marco; Claessen, Sandra M.; Greve, Jan W.; Driessen, Ann; Verdam, Froukje J.; Buurman, Wim A.; Schooten, Frederik J. van; Chiu, Roland K.

2012-01-01

Chronic inflammation is characterized by the influx of neutrophils and is associated with an increased production of reactive oxygen species that can damage DNA. Oxidative DNA damage is generally thought to be involved in the increased risk of cancer in inflamed tissues. We previously demonstrated that activated neutrophil mediated oxidative stress results in a reduction in nucleotide excision repair (NER) capacity, which could further enhance mutagenesis. Inflammation and oxidative stress are critical factors in the progression of nonalcoholic fatty liver disease that is linked with enhanced liver cancer risk. In this report, we therefore evaluated the role of neutrophils and the associated oxidative stress in damage recognition and DNA repair in steatotic livers of 35 severely obese subjects with either nonalcoholic steatohepatitis (NASH) (n = 17) or steatosis alone (n = 18). The neutrophilic influx in liver was assessed by myeloperoxidase (MPO) staining and the amount of oxidative DNA damage by measuring M 1 dG adducts. No differences in M 1 dG adduct levels were observed between patients with or without NASH and also not between individuals with high or low MPO immunoreactivity. However, we found that high expression of MPO in the liver, irrespective of disease status, reduced the damage recognition capacity as determined by staining for histone 2AX phosphorylation (γH2AX). This reduction in γH2AX formation in individuals with high MPO immunoreactivity was paralleled by a significant decrease in NER capacity as assessed by a functional repair assay, and was not related to cell proliferation. Thus, the observed reduction in NER capacity upon hepatic inflammation is associated with and may be a consequence of reduced damage recognition. These findings suggest a novel mechanism of liver cancer development in patients with nonalcoholic fatty liver disease.

Decreased nucleotide excision repair in steatotic livers associates with myeloperoxidase-immunoreactivity

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Schults, Marten A.; Nagle, Peter W. [Department of Toxicology, NUTRIM-School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, PO Box 616, 6200 MD Maastricht (Netherlands); Rensen, Sander S. [Department of Surgery, NUTRIM-School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, PO Box 616, 6200 MD Maastricht (Netherlands); Godschalk, Roger W. [Department of Toxicology, NUTRIM-School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, PO Box 616, 6200 MD Maastricht (Netherlands); Munnia, Armelle; Peluso, Marco [Cancer Risk Factor Branch, ISPO Cancer Prevention and Research Institute, Via Cosimo il Vecchio 2, 50139 Florence (Italy); Claessen, Sandra M. [Department of Toxicogenomics, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, PO Box 616, 6200 MD Maastricht (Netherlands); Greve, Jan W. [Department of Surgery, NUTRIM-School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, PO Box 616, 6200 MD Maastricht (Netherlands); Driessen, Ann [Department of Pathology, NUTRIM-School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, PO Box 616, 6200 MD Maastricht (Netherlands); Verdam, Froukje J.; Buurman, Wim A. [Department of Surgery, NUTRIM-School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, PO Box 616, 6200 MD Maastricht (Netherlands); Schooten, Frederik J. van [Department of Toxicology, NUTRIM-School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, PO Box 616, 6200 MD Maastricht (Netherlands); Chiu, Roland K., E-mail: r.k.chiu@med.umcg.nl [Department of Toxicology, NUTRIM-School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, PO Box 616, 6200 MD Maastricht (Netherlands)

2012-08-01

Chronic inflammation is characterized by the influx of neutrophils and is associated with an increased production of reactive oxygen species that can damage DNA. Oxidative DNA damage is generally thought to be involved in the increased risk of cancer in inflamed tissues. We previously demonstrated that activated neutrophil mediated oxidative stress results in a reduction in nucleotide excision repair (NER) capacity, which could further enhance mutagenesis. Inflammation and oxidative stress are critical factors in the progression of nonalcoholic fatty liver disease that is linked with enhanced liver cancer risk. In this report, we therefore evaluated the role of neutrophils and the associated oxidative stress in damage recognition and DNA repair in steatotic livers of 35 severely obese subjects with either nonalcoholic steatohepatitis (NASH) (n = 17) or steatosis alone (n = 18). The neutrophilic influx in liver was assessed by myeloperoxidase (MPO) staining and the amount of oxidative DNA damage by measuring M{sub 1}dG adducts. No differences in M{sub 1}dG adduct levels were observed between patients with or without NASH and also not between individuals with high or low MPO immunoreactivity. However, we found that high expression of MPO in the liver, irrespective of disease status, reduced the damage recognition capacity as determined by staining for histone 2AX phosphorylation ({gamma}H2AX). This reduction in {gamma}H2AX formation in individuals with high MPO immunoreactivity was paralleled by a significant decrease in NER capacity as assessed by a functional repair assay, and was not related to cell proliferation. Thus, the observed reduction in NER capacity upon hepatic inflammation is associated with and may be a consequence of reduced damage recognition. These findings suggest a novel mechanism of liver cancer development in patients with nonalcoholic fatty liver disease.

Growth hormone increases and maturation decreases glutamine synthetase turnover rate in rat liver

International Nuclear Information System (INIS)

Lin, C.K.

1985-01-01

An investigation was made of the effect of hypophysectomy and growth hormone (GH) replacement regimen (1 mg/100 g twice daily for 30 days); and maturation (from 25 up to 90 days) on the liver and brain glutamine synthetase (GS) mass and turnover rates in rats. The first order decay rate of enzyme 14 C radioactivity was determined between 1 and 4 days to obtain the half-life (T/sub 1/2/) of GS. The hepatic GS mass was determined by immunoassay. GS turnover (GS/sub s/) was calculated from T/sub 1/2/ and the GS mass (i.e., K = 0.693/T/sub 1/2/; GS/sub s/ = K x GS mass). It was concluded that: (1) GS specific activity is not decreased by hypophysectomy or increased by GH. These results suggested that observed endocrine induced changes in GS are due to changes in GS mass. (2) The liver GS turnover rate is significantly reduced by hypophysectomy and increased by GH replacement. It was proposed that GH specifically enhances synthesis of GS in the liver. (3) Maturation (25, 40, 60, and 90 days) decreases GS turnover rate in both liver and brain of normal rats. This similar effect of maturation suggests that the observed age induced decline in GS turnover rate is not related to GH in all tissues

Chemoembolization Decreases Drop-Off Risk of Hepatocellular Carcinoma Patients on the Liver Transplant List

International Nuclear Information System (INIS)

Frangakis, Constantine; Geschwind, Jean-Francois; Kim, Daniel; Chen, Yong; Koteish, Ayman; Hong, Kelvin; Liapi, Eleni; Georgiades, Christos S.

2011-01-01

Introduction: The drop-off risk for patients awaiting liver transplantation for hepatocellular carcinoma (HCC) is 22%. Transplant liver availability is expected to worsen, resulting in longer waiting times and increased drop-off rates. Our aim was to determine whether chemoembolization can decrease this risk. Patients and Methods: Eighty-seven consecutive HCC patients listed for liver transplant (Milan criteria) underwent statistical comparability adjustments using the propensity score (Wilcoxon, Fisher’s, and chi-square tests). Forty-three nonchemoembolization patients and 22 chemoembolization patients were comparable for Child-Pugh and Model for End-Stage Liver Disease scores, tumor size and number, alpha fetoprotein (AFP) levels, and cause of cirrhosis. We calculated the risk of dropping off the transplant list by assigning a transplant time to those who dropped off (equal probability with patients who were on the list longer than the patient in question). The significance level was obtained by calculating the simulation distribution of the difference compared with the permutations of chemoembolization versus nonchemoembolization assignment of the patients. Kaplan–Meier estimators (log-rank test) were used to determine survival rates. Results: Median follow-up was 187 ± 110 weeks (range 38 to 435, date of diagnosis). The chemoembolization group had an 80% drop-off risk decrease (15% nonchemoembolization versus 3% chemoembolization, p = 0.04). Although survival was better for the chemoembolization group, it did not reach statistical significance. Two-year survival for the nonchemoembolization and chemoembolization group was 57.3% ± 7.1% and 76.0% ± 7.9%, respectively (p = 0.078). Conclusions: Chemoembolization appears to result in a significant decrease in the risk of dropping off liver transplant list for patients with HCC and results in a tendency toward longer survival.

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

International Nuclear Information System (INIS)

Lake, April D.; Novak, Petr; Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D.; Lu, Zhenqiang; Lehman-McKeeman, Lois D.; Cherrington, Nathan J.

2013-01-01

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 BA 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

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

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Lake, April D. [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States); Novak, Petr [Biology Centre ASCR, Institute of Plant Molecular Biology, Ceske Budejovice 37001 (Czech Republic); Shipkova, Petia; Aranibar, Nelly; Robertson, Donald; Reily, Michael D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Lu, Zhenqiang [The Arizona Statistical Consulting Laboratory, University of Arizona, Tucson, AZ 85721 (United States); Lehman-McKeeman, Lois D. [Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Co., Princeton, NJ 08543 (United States); Cherrington, Nathan J., E-mail: cherrington@pharmacy.arizona.edu [University of Arizona, Department of Pharmacology and Toxicology, Tucson, AZ 85721 (United States)

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 BA 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

The importance of the training-induced decrease in basal cortisol concentration in the improvement in muscular performance in humans.

Science.gov (United States)

Grandys, M; Majerczak, J; Kulpa, J; Duda, K; Rychlik, U; Zoladz, J A

2016-01-01

Acute exercise-induced changes in cortisol concentration (C) and training related adaptation within hypothalamic-pituitary-adrenal (HPA) axis has been widely examined, but their influence on muscle strength performance is at best uncertain. Twenty four young healthy men were randomly assigned to an endurance training group (ET, n=12) or to a non-exercising controls (CON, n=12). ET performed supervised endurance training on cycle ergometer for 20 weeks. Endurance training program improved exercise capacity (14 % increase in power output generated at peak oxygen uptake - VO(2peak)), muscle strength performance (increase in MVC - maximal voluntary contraction - by 9 % and in TTF 50 % MVC - time to fatigue at 50 % MVC - by 21 %) and led to a decrease in basal serum C concentration (P=0.006) and an increase in basal testosterone to cortisol (T/C) and free testosterone to cortisol (fT/C) ratios (P=0.01 and P=0.02, respectively). It was found that the decrease in C concentration (deltaC) was positively correlated to the increase in local muscular endurance (deltaTTF 50 % MVC). No significant hormonal changes were seen in CON group. It is concluded that greater decrease in cortisol concentration after the endurance training is accompanied by poorer improvement in skeletal muscle performance in previously untrained subjects.

Symbiotic formulation in experimentally induced liver fibrosis in rats: intestinal microbiota as a key point to treat liver damage?

Science.gov (United States)

D'Argenio, Giuseppe; Cariello, Rita; Tuccillo, Concetta; Mazzone, Giovanna; Federico, Alessandro; Funaro, Annalisa; De Magistris, Laura; Grossi, Enzo; Callegari, Maria L; Chirico, Marilena; Caporaso, Nicola; Romano, Marco; Morelli, Lorenzo; Loguercio, Carmela

2013-05-01

Evidence indicates that intestinal microbiota may participate in both the induction and the progression of liver damage. The aim of our research was the detection and evaluation of the effects of chronic treatment with a symbiotic formulation on CCl4 -induced rat liver fibrosis. CCl4 significantly increased gastric permeability in respect to basal values, and the treatment with symbiotic significantly decreased it. CCl4 per se induced a decrease in intestinal permeability. This effect was also seen in fibrotic rats treated with symbiotic and was still evident when normal rats were treated with symbiotic alone (P symbiotic treatment normalized the plasma levels of TNF-α and significantly enhanced anti-inflammatory cytokine IL 10. TNF-α, TGF-β, TLR4, TLR2, iNOS and α-SMA mRNA expression in the liver were up-regulated in rats with CCl4 -induced liver fibrosis and down-regulated by symbiotic treatment. Moreover, IL-10 and eNOS mRNA levels were increased in the CCL4 (+) symbiotic group. Symbiotic treatment of fibrotic rats normalized serum ALT, AST and improved histology and liver collagen deposition. DGGE analysis of faecal samples revealed that CCl4 administration and symbiotic treatment either alone or in combination produced modifications in faecal profiles vs controls. Our results provide evidence that in CCl4 -induced liver fibrosis, significant changes in gastro-intestinal permeability and in faecal flora occur. Treatment with a specific symbiotic formulation significantly affects these changes, leading to improvement in both liver inflammation and fibrosis. © 2013 John Wiley & Sons A/S.

Phylogenetic differences of mammalian basal metabolic rate are not explained by mitochondrial basal proton leak.

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Polymeropoulos, E T; Heldmaier, G; Frappell, P B; McAllan, B M; Withers, K W; Klingenspor, M; White, C R; Jastroch, M

2012-01-07

Metabolic rates of mammals presumably increased during the evolution of endothermy, but molecular and cellular mechanisms underlying basal metabolic rate (BMR) are still not understood. It has been established that mitochondrial basal proton leak contributes significantly to BMR. Comparative studies among a diversity of eutherian mammals showed that BMR correlates with body mass and proton leak. Here, we studied BMR and mitochondrial basal proton leak in liver of various marsupial species. Surprisingly, we found that the mitochondrial proton leak was greater in marsupials than in eutherians, although marsupials have lower BMRs. To verify our finding, we kept similar-sized individuals of a marsupial opossum (Monodelphis domestica) and a eutherian rodent (Mesocricetus auratus) species under identical conditions, and directly compared BMR and basal proton leak. We confirmed an approximately 40 per cent lower mass specific BMR in the opossum although its proton leak was significantly higher (approx. 60%). We demonstrate that the increase in BMR during eutherian evolution is not based on a general increase in the mitochondrial proton leak, although there is a similar allometric relationship of proton leak and BMR within mammalian groups. The difference in proton leak between endothermic groups may assist in elucidating distinct metabolic and habitat requirements that have evolved during mammalian divergence.

Dietary β-conglycinin prevents fatty liver induced by a high-fat diet by a decrease in peroxisome proliferator-activated receptor γ2 protein.

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Yamazaki, Tomomi; Kishimoto, Kyoko; Miura, Shinji; Ezaki, Osamu

2012-02-01

Diets high in sucrose/fructose or fat can result in hepatic steatosis (fatty liver). Mice fed a high-fat diet, especially that of saturated-fat-rich oil, develop fatty liver with an increase in peroxisome proliferator-activated receptor (PPAR) γ2 protein in liver. The fatty liver induced by a high-fat diet is improved by knockdown of liver PPARγ2. In this study, we investigated whether β-conglycinin (a major protein of soy protein) could reduce PPARγ2 protein and prevent high-fat-diet-induced fatty liver in ddY mice. Mice were fed a high-starch diet (70 energy% [en%] starch) plus 20% (wt/wt) sucrose in their drinking water or a high-safflower-oil diet (60 en%) or a high-butter diet (60 en%) for 11 weeks, by which fatty liver is developed. As a control, mice were fed a high-starch diet with drinking water. Either β-conglycinin or casein (control) was given as dietary protein. β-Conglycinin supplementation completely prevented fatty liver induced by each type of diet, along with a reduction in adipose tissue weight. β-Conglycinin decreased sterol regulatory element-binding protein (SREBP)-1c and carbohydrate response element-binding protein (ChREBP) messenger RNAs (mRNAs) in sucrose-supplemented mice, whereas it decreased PPARγ2 mRNA (and its target genes CD36 and FSP27), but did not decrease SREBP-1c and ChREBP mRNAs, in mice fed a high-fat diet. β-Conglycinin decreased PPARγ2 protein and liver triglyceride (TG) concentration in a dose-dependent manner in mice fed a high-butter diet; a significant decrease in liver TG concentration was observed at a concentration of 15 en%. In conclusion, β-conglycinin effectively prevents fatty liver induced by a high-fat diet through a decrease in liver PPARγ2 protein. Copyright © 2012 Elsevier Inc. All rights reserved.

Arecoline decreases interleukin-6 production and induces apoptosis and cell cycle arrest in human basal cell carcinoma cells

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Huang, Li-Wen [Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Hsieh, Bau-Shan; Cheng, Hsiao-Ling [Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Hu, Yu-Chen [Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Chang, Wen-Tsan [Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Division of Hepatobiliarypancreatic Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan (China); Chang, Kee-Lung, E-mail: Chang.KeeLung@msa.hinet.net [Department of Biochemistry, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China)

2012-01-15

Arecoline, the most abundant areca alkaloid, has been reported to decrease interleukin-6 (IL-6) levels in epithelial cancer cells. Since IL-6 overexpression contributes to the tumorigenic potency of basal cell carcinoma (BCC), this study was designed to investigate whether arecoline altered IL-6 expression and its downstream regulation of apoptosis and the cell cycle in cultured BCC-1/KMC cells. BCC-1/KMC cells and a human keratinocyte cell line, HaCaT, were treated with arecoline at concentrations ranging from 10 to 100 μg/ml, then IL-6 production and expression of apoptosis- and cell cycle progress-related factors were examined. After 24 h exposure, arecoline inhibited BCC-1/KMC cell growth and decreased IL-6 production in terms of mRNA expression and protein secretion, but had no effect on HaCaT cells. Analysis of DNA fragmentation and chromatin condensation showed that arecoline induced apoptosis of BCC-1/KMC cells in a dose-dependent manner, activated caspase-3, and decreased expression of the anti-apoptotic protein Bcl-2. In addition, arecoline induced progressive and sustained accumulation of BCC-1/KMC cells in G2/M phase as a result of reducing checkpoint Cdc2 activity by decreasing Cdc25C phosphatase levels and increasing p53 levels. Furthermore, subcutaneous injection of arecoline led to decreased BCC-1/KMC tumor growth in BALB/c mice by inducing apoptosis. This study demonstrates that arecoline has potential for preventing BCC tumorigenesis by reducing levels of the tumor cell survival factor IL-6, increasing levels of the tumor suppressor factor p53, and eliciting cell cycle arrest, followed by apoptosis. Highlights: ► Arecoline has potential to prevent against basal cell carcinoma tumorigenesis. ► It has more effectiveness on BCC as compared with a human keratinocyte cell line. ► Mechanisms involved including reducing tumor cells’ survival factor IL-6, ► Decreasing Cdc25C phosphatase, enhancing tumor suppressor factor p53, ► Eliciting G2/M

Genetic variation in PNPLA3 (adiponutrin) confers sensitivity to weight loss-induced decrease in liver fat in humans.

Science.gov (United States)

Sevastianova, Ksenia; Kotronen, Anna; Gastaldelli, Amalia; Perttilä, Julia; Hakkarainen, Antti; Lundbom, Jesper; Suojanen, Laura; Orho-Melander, Marju; Lundbom, Nina; Ferrannini, Eleuterio; Rissanen, Aila; Olkkonen, Vesa M; Yki-Järvinen, Hannele

2011-07-01

The rs738409 C→G single nucleotide polymorphism in the patatin-like phospholipase domain-containing 3 (PNPLA3; adiponutrin) leads to a missense mutation (I148M), which is associated with increased liver fat but not insulin resistance. The I148M mutation impedes triglyceride hydrolysis in vitro, and its carriers have an increased risk of developing severe liver disease. We explored whether the rs738409 PNPLA3 G allele influences the ability of weight loss to decrease liver fat or change insulin sensitivity. We recruited 8 subjects who were homozygous for the rs738409 PNPLA3 G allele (PNPLA3-148MM) and 10 who were homozygous for the rs738409 PNPLA3 C allele (PNPLA3-148II). To allow comparison of changes in liver fat, the groups were matched with respect to baseline age, sex, body mass index, and liver fat. The subjects were placed on a hypocaloric low-carbohydrate diet for 6 d. Liver fat content (proton magnetic resonance spectroscopy), whole-body insulin sensitivity of glucose metabolism (euglycemic clamp technique), and lipolysis ([(2)H(5)]glycerol infusion) were measured before and after the diet. At baseline, fasting serum insulin and C-peptide concentrations were significantly lower in the PNPLA3-148MM group than in the PNPLA3-148II group, as predicted by study design. Weight loss was not significantly different between groups (PNPLA3-148MM: -3.1 ± 0.5 kg; PNPLA3-148II: -3.1 ± 0.4 kg). Liver fat decreased by 45% in the PNPLA3-148MM group (P loss is effective in decreasing liver fat in subjects who are homozygous for the rs738409 PNPLA3 G or C allele. This trial was registered at www.hus.fi as 233775.

Evaluation of Basal Serum Adrenocorticotropic Hormone and Cortisol Levels and Their Relationship with Nonalcoholic Fatty Liver Disease in Male Patients with Idiopathic Hypogonadotropic Hypogonadism.

Science.gov (United States)

Wang, Wen-Bo; She, Fei; Xie, Li-Fang; Yan, Wen-Hua; Ouyang, Jin-Zhi; Wang, Bao-An; Ma, Hang-Yun; Zang, Li; Mu, Yi-Ming

2016-05-20

Prolonged gonadal hormone deficiency in patients with idiopathic hypogonadotropic hypogonadism (IHH) may produce adverse effects on the endocrine homeostasis and metabolism. This study aimed to compare basal serum adrenocorticotropic hormone (ACTH) and cortisol levels between male IHH patients and healthy controls. Moreover, this study compared the basal hypothalamic-pituitary-adrenal (HPA) axis in patients with and without nonalcoholic fatty liver disease (NAFLD), and also evaluated the relationship between basal HPA axis and NAFLD in male IHH patients. This was a retrospective case-control study involving 75 Chinese male IHH patients (mean age 21.4 ± 3.8 years, range 17-30 years) and 135 healthy controls after matching for gender and age. All subjects underwent physical examination and blood testing for serum testosterone, luteinizing hormone, follicle-stimulating hormone, ACTH, and cortisol and biochemical tests. Higher basal serum ACTH levels (8.25 ± 3.78 pmol/L vs. 6.97 ± 2.81 pmol/L) and lower cortisol levels (366.70 ± 142.48 nmol/L vs. 452.82 ± 141.53 nmol/L) were observed in male IHH patients than healthy subjects (all pIHH patients also showed higher metabolism parameters and higher prevalence rate of NAFLD (34.9% vs. 4.4%) than the controls (all P IHH patients with NAFLD than those without NAFLD (all P IHH patients. Furthermore, NAFLD was independently associated with ACTH levels in male IHH patients by multiple linear regression analysis. The male IHH patients showed higher basal serum ACTH levels and lower cortisol levels than matched healthy controls. NAFLD was an independent associated factor for ACTH levels in male IHH patients. These preliminary findings provided evidence of the relationship between basal serum ACTH and NAFLD in male IHH patients.

Replacement of soybean oil by fish oil increases cytosolic lipases activities in liver and adipose tissue from rats fed a high-carbohydrate diets.

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Rodrigues, Angélica Heringer; Moreira, Carolina Campos Lima; Neves, Maria José; Botion, Leida Maria; Chaves, Valéria Ernestânia

2018-06-01

Several studies have demonstrated that fish oil consumption improves metabolic syndrome and comorbidities, as insulin resistance, nonalcoholic fatty liver disease, dyslipidaemia and hypertension induced by high-fat diet ingestion. Previously, we demonstrated that administration of a fructose-rich diet to rats induces liver lipid accumulation, accompanied by a decrease in liver cytosolic lipases activities. In this study, the effect of replacement of soybean oil by fish oil in a high-fructose diet (FRUC, 60% fructose) for 8 weeks on lipid metabolism in liver and epididymal adipose tissue from rats was investigated. The interaction between fish oil and FRUC diet increased glucose tolerance and decreased serum levels of triacylglycerol (TAG), VLDL-TAG secretion and lipid droplet volume of hepatocytes. In addition, the fish oil supplementation increased the liver cytosolic lipases activities, independently of the type of carbohydrate ingested. Our results firmly establish the physiological regulation of liver cytosolic lipases to maintain lipid homeostasis in hepatocytes. In epididymal adipose tissue, the replacement of soybean oil by fish oil in FRUC diet did not change the tissue weight and lipoprotein lipase activity; however, there was increased basal and insulin-stimulated de novo lipogenesis and glucose uptake. Increased cytosolic lipases activities were observed, despite the decreased basal and isoproterenol-stimulated glycerol release to the incubation medium. These findings suggest that fish oil increases the glycerokinase activity and glycerol phosphorylation from endogenous TAG hydrolysis. Our findings are the first to show that the fish oil ingestion increases cytosolic lipases activities in liver and adipose tissue from rats treated with high-carbohydrate diets. Copyright © 2018. Published by Elsevier Inc.

A small molecule inhibitor of signal peptide peptidase inhibits Plasmodium development in the liver and decreases malaria severity.

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Iana Parvanova

Full Text Available The liver stage of Plasmodium's life cycle is the first, obligatory step in malaria infection. Decreasing the hepatic burden of Plasmodium infection decreases the severity of disease and constitutes a promising strategy for malaria prophylaxis. The efficacy of the gamma-secretase and signal peptide peptidase inhibitor LY411,575 in targeting Plasmodium liver stages was evaluated both in human hepatoma cell lines and in mouse primary hepatocytes. LY411,575 was found to prevent Plasmodium's normal development in the liver, with an IC(50 of approximately 80 nM, without affecting hepatocyte invasion by the parasite. In vivo results with a rodent model of malaria showed that LY411,575 decreases the parasite load in the liver and increases by 55% the resistance of mice to cerebral malaria, one of the most severe malaria-associated syndromes. Our data show that LY411,575 does not exert its effect via the Notch signaling pathway suggesting that it may interfere with Plasmodium development through an inhibition of the parasite's signal peptide peptidase. We therefore propose that selective signal peptide peptidase inhibitors could be potentially used for preventive treatment of malaria in humans.

Cholinergic Basal Forebrain Lesion Decreases Neurotrophin Signaling without Affecting Tau Hyperphosphorylation in Genetically Susceptible Mice.

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Turnbull, Marion T; Coulson, Elizabeth J

2017-01-01

Alzheimer's disease (AD) is a progressive, irreversible neurodegenerative disease that destroys memory and cognitive function. Aggregates of hyperphosphorylated tau protein are a prominent feature in the brain of patients with AD, and are a major contributor to neuronal toxicity and disease progression. However, the factors that initiate the toxic cascade that results in tau hyperphosphorylation in sporadic AD are unknown. Here we investigated whether degeneration of basal forebrain cholinergic neurons (BFCNs) and/or a resultant decrease in neurotrophin signaling cause aberrant tau hyperphosphorylation. Our results reveal that the loss of BFCNs in pre-symptomatic pR5 (P301L) tau transgenic mice results in a decrease in hippocampal brain-derived neurotrophic factor levels and reduced TrkB receptor activation. However, there was no exacerbation of the levels of phosphorylated tau or its aggregation in the hippocampus of susceptible mice. Furthermore the animals' performance in a hippocampal-dependent learning and memory task was unaltered, and no changes in hippocampal synaptic markers were observed. This suggests that tau pathology is likely to be regulated independently of BFCN degeneration and the corresponding decrease in hippocampal neurotrophin levels, although these features may still contribute to disease etiology.

Quantification of tumour {sup 18}F-FDG uptake: Normalise to blood glucose or scale to liver uptake?

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Keramida, Georgia [Brighton and Sussex Medical School, Clinical Imaging Sciences Centre, Brighton (United Kingdom); Brighton and Sussex University Hospitals NHS Trust, Department of Nuclear Medicine, Brighton (United Kingdom); University of Sussex, Clinical Imaging Sciences Centre, Brighton (United Kingdom); Dizdarevic, Sabina; Peters, A.M. [Brighton and Sussex Medical School, Clinical Imaging Sciences Centre, Brighton (United Kingdom); Brighton and Sussex University Hospitals NHS Trust, Department of Nuclear Medicine, Brighton (United Kingdom); Bush, Janice [Brighton and Sussex Medical School, Clinical Imaging Sciences Centre, Brighton (United Kingdom)

2015-09-15

To compare normalisation to blood glucose (BG) with scaling to hepatic uptake for quantification of tumour {sup 18}F-FDG uptake using the brain as a surrogate for tumours. Standardised uptake value (SUV) was measured over the liver, cerebellum, basal ganglia, and frontal cortex in 304 patients undergoing {sup 18}F-FDG PET/CT. The relationship between brain FDG clearance and SUV was theoretically defined. Brain SUV decreased exponentially with BG, with similar constants between cerebellum, basal ganglia, and frontal cortex (0.099-0.119 mmol/l{sup -1}) and similar to values for tumours estimated from the literature. Liver SUV, however, correlated positively with BG. Brain-to-liver SUV ratio therefore showed an inverse correlation with BG, well-fitted with a hyperbolic function (R = 0.83), as theoretically predicted. Brain SUV normalised to BG (nSUV) displayed a nonlinear correlation with BG (R = 0.55); however, as theoretically predicted, brain nSUV/liver SUV showed almost no correlation with BG. Correction of brain SUV using BG raised to an exponential power of 0.099 mmol/l{sup -1} also eliminated the correlation between brain SUV and BG. Brain SUV continues to correlate with BG after normalisation to BG. Likewise, liver SUV is unsuitable as a reference for tumour FDG uptake. Brain SUV divided by liver SUV, however, shows minimal dependence on BG. (orig.)

Kefir improves fatty liver syndrome by inhibiting the lipogenesis pathway in leptin-deficient ob/ob knockout mice.

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Chen, H-L; Tung, Y-T; Tsai, C-L; Lai, C-W; Lai, Z-L; Tsai, H-C; Lin, Y-L; Wang, C-H; Chen, C-M

2014-09-01

Fatty liver disease is commonly associated with obesity, insulin resistance and diabetes. Severe fatty liver is sometimes accompanied by steatohepatitis and may lead to the development of hepatocellular carcinoma. At present, there is no effective treatment for non-alcoholic fatty liver disease (NAFLD); thus, recent investigations have focused on developing effective therapeutics to treat this condition. This study aimed to evaluate the effects of kefir on the hepatic lipid metabolism of ob/ob mice, which are commonly used to model fatty liver disease. In this study, we used leptin receptor-deficient ob/ob mice as an animal disease model of NAFLD. Six-week-old ob/ob mice were orally administered the dairy product kefir (140 mg kg(-1) of body weight (BW) per day) for 4 weeks. The data demonstrated that kefir improved fatty liver syndrome on BW, energy expenditure and basal metabolic rate by inhibiting serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities (Pkefir administration also significantly reduced the macrovesicular fat quantity in liver tissue. In addition, kefir markedly decreased the expression of the genes sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) (Pkefir improves NAFLD on BW, energy expenditure and basal metabolic rate by inhibiting the lipogenesis pathway and that kefir may have the potential for clinical application to the prevention or treatment of NAFLD.

Association of decrease in liver triglyceride content with increase in plasma adiponectin levels after pioglitazone treatment in Japanese patients with type 2 diabetes

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Nagasawa, Kan; Kaneko, Yoshihito; Taneichi, Haruhito

2010-01-01

Pioglitazone, an insulin-sensitizing thiazolidinedione, has multiple clinical effects including improvement of insulin sensitivity, blood glucose levels and serum lipid profiles, decrease in liver triglyceride (TG) content, and increase in serum adiponectin. However, the correlation and causal relationship between these effects are not fully understood clinically. Therefore, we analyzed these relationships in patients with type 2 diabetes treated with pioglitazone, focusing on changes in liver TG content and serum adiponectin. Thirteen Japanese patients with type 2 diabetes were treated with pioglitazone (15 mg/day) for more than 3 months. Before and after the pioglitazone treatment, liver TG content was measured by magnetic resonance spectroscopy and various clinical variables were also measured. The pioglitazone treatment significantly decreased the liver TG content (-12.9±8.1%, p 2 =0.53, p=0.017), implying increased serum adiponectin may have decreased liver fat content. (author)

Preferential antitumor effect of the Src inhibitor dasatinib associated with a decreased proportion of aldehyde dehydrogenase 1-positive cells in breast cancer cells of the basal B subtype

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Watanabe Mika

2010-10-01

Full Text Available Abstract Background Recent studies have suggested that the Src inhibitor dasatinib preferentially inhibits the growth of breast cancer cells of the basal-like subtype. To clarify this finding and further investigate combined antitumor effects of dasatinib with cytotoxic agents, a panel of breast cancer cell lines of various subtypes was treated with dasatinib and/or chemotherapeutic agents. Methods Seven human breast cancer cell lines were treated with dasatinib and/or seven chemotherapeutic agents. Effects of the treatments on c-Src activation, cell growth, cell cycle, apoptosis and the proportion of aldehyde dehydrogenase (ALDH 1-positive cells were examined. Results The 50%-growth inhibitory concentrations (IC50s of dasatinib were much lower in two basal B cell lines than those in the other cell lines. The IC50s of chemotherapeutic agents were not substantially different among the cell lines. Dasatinib enhanced antitumor activity of etoposide in the basal B cell lines. Dasatinib induced a G1-S blockade with a slight apoptosis, and a combined treatment of dasatinib with etoposide also induced a G1-S blockade in the basal B cell lines. Dasatinib decreased the expression levels of phosphorylated Src in all cell lines. Interestingly, dasatinib significantly decreased the proportion of ALDH1-positive cells in the basal B cell lines but not in the other cell lines. Conclusions The present study indicates that dasatinib preferentially inhibits the growth of breast cancer cells of the basal B subtype associated with a significant loss of putative cancer stem cell population. A combined use of dasatinib with etoposide additively inhibits their growth. Further studies targeting breast cancers of the basal B subtype using dasatinib with cytotoxic agents are warranted.

Ursodeoxycholic Acid Suppresses Lipogenesis in Mouse Liver: Possible Role of the Decrease in β-Muricholic Acid, a Farnesoid X Receptor Antagonist.

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Fujita, Kyosuke; Iguchi, Yusuke; Une, Mizuho; Watanabe, Shiro

2017-04-01

The farnesoid X receptor (FXR) is a major nuclear receptor of bile acids; its activation suppresses sterol regulatory element-binding protein 1c (SREBP1c)-mediated lipogenesis and decreases the lipid contents in the liver. There are many reports showing that the administration of ursodeoxycholic acid (UDCA) suppresses lipogenesis and reduces the lipid contents in the liver of experimental animals. Since UDCA is not recognized as an FXR agonist, these effects of UDCA cannot be readily explained by its direct activation of FXR. We observed that the dietary administration of UDCA in mice decreased the expression levels of SREBP1c and its target lipogenic genes. Alpha- and β-muricholic acids (MCA) and cholic acid (CA) were the major bile acids in the mouse liver but their contents decreased upon UDCA administration. The hepatic contents of chenodeoxycholic acid and deoxycholic acid (DCA) were relatively low but were not changed by UDCA. UDCA did not show FXR agonistic or antagonistic potency in in vitro FXR transactivation assay. Taking these together, we deduced that the above-mentioned change in hepatic bile acid composition induced upon UDCA administration might cause the relative increase in the FXR activity in the liver, mainly by the reduction in the content of β-MCA, a farnesoid X receptor antagonist, which suggests a mechanism by which UDCA suppresses lipogenesis and decreases the lipid contents in the mouse liver.

Heterozygous deficiency of endoglin decreases insulin and hepatic triglyceride levels during high fat diet.

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Daniel Beiroa

Full Text Available Endoglin is a transmembrane auxiliary receptor for transforming growth factor-beta (TGF-beta that is predominantly expressed on proliferating endothelial cells. It plays a wide range of physiological roles but its importance on energy balance or insulin sensitivity has been unexplored. Endoglin deficient mice die during midgestation due to cardiovascular defects. Here we report for first time that heterozygous endoglin deficiency in mice decreases high fat diet-induced hepatic triglyceride content and insulin levels. Importantly, these effects are independent of changes in body weight or adiposity. At molecular level, we failed to detect relevant changes in the insulin signalling pathway at basal levels in liver, muscle or adipose tissues that could explain the insulin-dependent effect. However, we found decreased triglyceride content in the liver of endoglin heterozygous mice fed a high fat diet in comparison to their wild type littermates. Overall, our findings indicate that endoglin is a potentially important physiological mediator of insulin levels and hepatic lipid metabolism.

Decrease of 5-Hydroxymethylcytosine in Rat Liver with Subchronic Exposure to Genotoxic Carcinogens Riddelliine and Aristolochic Acid

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Lian, Christine Guo; Xu, Shuyun; Guo, Weimin; Yan, Jian; Frank, Maximilian Y M; Liu, Robert; Liu, Cynthia; Chen, Ying; Murphy, George F.; Chen, Tao

2018-01-01

The level of 5-hydroxymethylcytosine (5-hmC) converted by ten-eleven translocation (TET) family is decreased in cancers. However, whether 5-hmC level is perturbed in early stages of carcinogenesis caused by genotoxic carcinogens is not defined. 5-hmC levels and TET2 expression were measured in liver of rats treated with genotoxic carcinogens, riddelliine, or aristolochic acid. Levels of 5-hmC and TET2 expression decreased in the liver of the carcinogens-treated rats. Loss of 5-hmC correlates well with documented induction of genetic mutations by the carcinogens, suggesting that TET2-mediated 5-hydroxymethylation plays an epigenetic role in early state of carcinogenesis. PMID:25154389

Decreased UV-induced DNA repair synthesis in peripheral leukocytes from patients with the nevoid basal cell carcinoma syndrome

International Nuclear Information System (INIS)

Ringborg, U.; Lambert, B.; Landergen, J.; Lewensohn, R.

1981-01-01

The uv-induced DNA repair synthesis in peripheral leukocytes from 7 patients with the nevoid basal cell carcinoma syndrome was compared to that in peripheral leukocytes from 5 patients with basal cell carcinomas and 39 healthy subjects. A dose response curve was established for each individual, and maximum DNA repair synthesis was used as a measure of the capacity for DNA repair. The patients with the nevoid basal cell carcinoma syndrome had about 25% lower level of maximum DNA repair synthesis as compared to the patients with basal cell carcinomas and control individuals. The possibility that DNA repair mechanisms may be involved in the etiology to the nevoid basal cell carcinoma syndrome is discussed

MRI and MR spectroscopy study on basal ganglia alterations in patients with liver cirrhosis

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Wu Haibo; Ma Lin; Cai Youquan; Li Tao; Li Dejun; Liang Li

2007-01-01

Objective: To study the signal changes and metabolic alterations in the basal ganglia (BG) by using magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (MRS) in patients with hepatic encephalopathy with and without parkinsonism. Methods: MRI and MRS in the basal ganglia were performed in 27 patients (22 males, 5 females, age ranging from 29 to 62 years) with liver cirrhosis and hepatic encephalopathy. 14 of the 27 patients were classified as having parkinsonian signs evaluated by Unified Parkinson's Disease Rating Scale (UPDRS) test. 18 age-matched healthy volunteers (13 males, 5 females, age ranging from 24 to 51 years) underwent MRI and MRS as a control group. Results: NAA/Cr levels (average numbers are 1.40±0.03, 1.35±0.03 respectively) showed no statistical difference between cirrhotic patients with hepatic encephalopathy and the control group (t=1.16, t=0.87, P>0.05). Values of signal hyperintensities (average numbers are 1.03±0.002, 1.04± 0.003 respectively) in globus pallidus and ratios of mI/Cr(average numbers are 0.63±0.01, 0.61± 0.02 respectively) and Cho/Cr (average numbers are 0.82±0.03, 0.80±0.02 respectively) showed no statistically significant differences between the control group and the 13 patients without parkinsonism (t=0.63, t=-0.52, t=-0.54, P>0.05), whereas values of signal hyperintensities (average numbers are 1.18±0.001, 1.04±0.003 respectively) in globus pallidus and ratios of mI/Cr (average numbers are 0.39±0.02, 0.63±0.01 respectively) and Cho/Cr(average numbers are 0.68±0.01, 0.82±0.03 respectively) shows statistically significant difference in patients without and with parkinsonism (t=-5.16, t=7.61, t=4.12, P<0.05). In patients with cirrhosis, the values of signal hyperintensities in globus pallidus were inversely correlated with the ratio for mI/Cr(r=-0.764, P<0.05) and Cho/Cr (r=-0.553, P<0.05), respectively. Conclusion: MRI and MRS may be useful tools in the evaluation of extrapyramidal

Experimental sources of variation in avian energetics: estimated basal metabolic rate decreases with successive measurements.

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Jacobs, Paul J; McKechnie, Andrew E

2014-01-01

Basal metabolic rate (BMR) is one of the most widely used metabolic variables in endotherm ecological and evolutionary physiology. Surprisingly few studies have investigated how BMR is influenced by experimental and analytical variables over and above the standardized conditions required for minimum normothermic resting metabolism. We tested whether avian BMR is affected by habituation to the conditions experienced during laboratory gas exchange measurements by measuring BMR five times in succession in budgerigars (Melopsittacus undulatus) housed under constant temperature and photoperiod. Both the magnitude and the variability of BMR decreased significantly with repeated measurements, from 0.410 ± 0.092 W (n = 9) during the first measurement to 0.285 ± 0.042 W (n = 9) during the fifth measurement. Thus, estimated BMR decreased by ∼30% within individuals solely on account of the number of times they had previously experienced the experimental conditions. The most likely explanation for these results is an attenuation with repeated exposure of the acute stress response induced by birds being handled and placed in respirometry chambers. Our data suggest that habituation to experimental conditions is potentially an important determinant of observed BMR, and this source of variation needs to be taken into account in future studies of metabolic variation among individuals, populations, and species.

Extrahepatic portal vein obstruction with parkinsonism and symmetric hyperintense basal ganglia on T1 weighted MRI

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Jayalakshmi Sita

2006-01-01

Full Text Available Abnormal high signal in the globus pallidus on T1 weighted magnetic resonance imaging (MRI of the brain has been well described in patients with chronic liver disease. It may be related to liver dysfunction or portal-systemic shunting. We report a case of extra hepatic portal vein obstruction with portal hypertension and esophageal varices that presented with extra pyramidal features. T1 weighted MRI brain scans showed increased symmetrical signal intensities in the basal ganglia. Normal hepatic function in this patient emphasizes the role of portal- systemic communications in the development of these hyperintensities, which may be due to deposition of paramagnetic substances like manganese in the basal ganglia.

Decreased liver triglyceride content in adult rats exposed to protein restriction during gestation and lactation: role of hepatic triglyceride utilization.

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Qasem, Rani J; Li, Jing; Tang, Hee Man; Browne, Veron; Mendez-Garcia, Claudia; Yablonski, Elizabeth; Pontiggia, Laura; D'Mello, Anil P

2015-04-01

We have previously demonstrated that protein restriction throughout gestation and lactation reduces liver triglyceride content in adult rat offspring. However, the mechanisms mediating the decrease in liver triglyceride content are not understood. The aim of the current study was to use a new group of pregnant animals and their offspring and determine the contribution of increased triglyceride utilization via the hepatic fatty-acid oxidation and triglyceride secretory pathways to the reduction in liver triglyceride content. Pregnant Sprague-Dawley rats received either a control or a low protein diet throughout pregnancy and lactation. Pups were weaned onto laboratory chow on day 28 and killed on day 65. Liver triglyceride content was reduced in male, but not female, low-protein offspring, both in the fed and fasted states. The reduction was accompanied by a trend towards higher liver carnitine palmitoyltransferase-1a activity, suggesting increased fatty-acid transport into the mitochondrial matrix. However, medium-chain acyl coenzyme A dehydrogenase activity within the mitochondrial matrix, expression of nuclear peroxisome proliferator activated receptor-α, and plasma levels of β-hydroxybutyrate were similar between low protein and control offspring, indicating a lack of change in fatty-acid oxidation. Hepatic triglyceride secretion, assessed by blocking peripheral triglyceride utilization and measuring serum triglyceride accumulation rate, and the activity of microsomal transfer protein, were similar between low protein and control offspring. Because enhanced triglyceride utilization is not a significant contributor, the decrease in liver triglyceride content in male low-protein offspring is likely due to alterations in liver fatty-acid transport or triglyceride biosynthesis. © 2015 Wiley Publishing Asia Pty Ltd.

Nondiffuse fatty infiltration of the liver: Does the uptake of iron-oxide increase or decrease at SPIO-enhanced MR imaging?

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Onoda, Hideko; Ito, Katsuyoshi; Tanabe, Masahiro; Shimizu, Ayame; Matsunaga, Naofumi

2011-01-01

Purpose: To clarify whether the uptake of SPIO increases or decreases in areas of fatty change compared with surrounding areas of nonfatty change at SPIO-enhanced MR imaging. Materials and methods: Approval for this retrospective study was obtained from our institutional review board. This study included 14 patients with nondiffuse fatty infiltration of the liver who underwent SPIO-enhanced MR imaging. Additionally, 30 patients without nondiffuse fatty infiltration of the liver were also evaluated. Results: Among 14 patients, areas of fatty change showed relatively high signal intensity in 7 patents, indicating decreased uptake of SPIO in areas of fatty change. In these 7 patients, 4 had mild cirrhosis and 3 did not have cirrhosis. The mean percentage of signal intensity loss (42%) of fatty areas was significantly lower (p < 0.007) than that of adjacent areas of nonfatty change (52%). In the remaining 7 of 14 patients, areas of fatty change showed relatively low signal intensity, indicating increased uptake of SPIO in areas of fatty change. Among these 7 patients, 6 had advanced cirrhosis. The mean percentage of signal intensity loss (47%) of fatty areas was significantly higher (p < 0.008) than that of adjacent areas of nonfatty change (31%). Conclusion: The uptake of SPIO generally decreased in areas of fatty change compared with normal liver parenchyma at SPIO-enhanced MR imaging. However, in patients with advanced cirrhosis, areas of fatty change shows relatively low signal intensity because the uptake of SPIO in surrounding areas of nonfatty change severely decreased probably due to liver fibrosis.

Hyperintensity of basal ganglia on T{sub 1}-weighted images in patients with liver cirrhosis. Correlation with hepatic encephalopathy and liver function

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Maeda, Hiroko; Kita, Keisuke; Mizobata, Toshiharu; Kimura, Masashi; Sonomura, Tetsuo; Kishi, Kazushi; Tanaka, Kayo; Sato, Morio; Yamada, Ryosaku [Wakayama Medical Coll. (Japan)

1995-04-01

Brain MR imaging was performed in 38 liver cirrhosis (LC) patients and 9 normal volunteers. On T{sub 1}-weighted images, the signal intensity of globus pallidus (S1) and frontal white matter (S2) was measured and S1/S2 ratio was explored. We examined the relationship between S1/S2 ratio and liver function parameters. High signal intensity in bilateral globus pallidus was noted on T{sub 1} W1 in 28 of 38 LC patients. The S1/S2 ratio of 1.186{+-}0.097 in the 38 LC patients was significantly higher than 0.987{+-}0.062 in the 9 normal volunteers (p<0.001), while T{sub 2}-weighted images showed no abnormal intensity. Compared with the LC patients with hepatic encephalopathy (HE) (n=7) and without HE (n=31), the former S1/S2 ratio (1.239{+-}0.057) was significantly higher than the latter (1.174{+-}0.097) (p<0.05). There was a significant correlation between the value of the S1/S2 ratio and deterioration of ICG R{sub 15} (r=0.501, p<0.005), prolongation of prothrombine time (r=-0.392, p<0.05) and decrease of choline esterase (r=-0.336, p<0.05). There was, however, little correlation between the value of the S1/S2 ratio and ammonia and Fisher ratio. In conclusion, there is a significant relationship between high intensity of globus pallidus on T{sub 1}-WI and the degree of liver dysfunction. (author).

Basal ganglia circuits changes in Parkinson's disease patients.

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Wu, Tao; Wang, Jue; Wang, Chaodong; Hallett, Mark; Zang, Yufeng; Wu, Xiaoli; Chan, Piu

2012-08-22

Functional changes in basal ganglia circuitry are responsible for the major clinical features of Parkinson's disease (PD). Current models of basal ganglia circuitry can only partially explain the cardinal symptoms in PD. We used functional MRI to investigate the causal connectivity of basal ganglia networks from the substantia nigra pars compacta (SNc) in PD in the movement and resting state. In controls, SNc activity predicted increased activity in the supplementary motor area, the default mode network, and dorsolateral prefrontal cortex, but, in patients, activity predicted decreases in the same structures. The SNc had decreased connectivity with the striatum, globus pallidus, subthalamic nucleus, thalamus, supplementary motor area, dorsolateral prefrontal cortex, insula, default mode network, temporal lobe, cerebellum, and pons in patients compared to controls. Levodopa administration partially normalized the pattern of connectivity. Our findings show how the dopaminergic system exerts influences on widespread brain networks, including motor and cognitive networks. The pattern of basal ganglia network connectivity is abnormal in PD secondary to dopamine depletion, and is more deviant in more severe disease. Use of functional MRI with network analysis appears to be a useful method to demonstrate basal ganglia pathways in vivo in human subjects. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Curcumin restores mitochondrial functions and decreases lipid peroxidation in liver and kidneys of diabetic db/db mice

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María G Soto-Urquieta

2014-01-01

Full Text Available BACKGROUND: Nitrosative and oxidative stress play a key role in obesity and diabetes-related mitochondrial dysfunction. The objective was to investigate the effect of curcumin treatment on state 3 and 4 oxygen consumption, nitric oxide (NO synthesis, ATPase activity and lipid oxidation in mitochondria isolated from liver and kidneys of diabetic db/db mice. RESULTS: Hyperglycaemia increased oxygen consumption and decreased NO synthesis in liver mitochondria isolated from diabetic mice relative to the control mice. In kidney mitochondria, hyperglycaemia increased state 3 oxygen consumption and thiobarbituric acid-reactive substances (TBARS levels in diabetic mice relative to control mice. Interestingly, treating db/db mice with curcumin improved or restored these parameters to normal levels; also curcumin increased liver mitochondrial ATPase activity in db/db mice relative to untreated db/db mice. CONCLUSIONS: These findings suggest that hyperglycaemia modifies oxygen consumption rate, NO synthesis and increases TBARS levels in mitochondria from the liver and kidneys of diabetic mice, whereas curcumin may have a protective role against these alterations.

Activation of PPARα decreases bile acids in livers of female mice while maintaining bile flow and biliary bile acid excretion.

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Zhang, Youcai; Lickteig, Andrew J; Csanaky, Iván L; Klaassen, Curtis D

2018-01-01

Fibrates are hypolipidemic drugs that act as activators of peroxisome proliferator-activated receptor α (PPARα). In both humans and rodents, females were reported to be less responsive to fibrates than males. Previous studies on fibrates and PPARα usually involved male mice, but little has been done in females. The present study aimed to provide the first comprehensive analysis of the effects of clofibrate (CLOF) and PPARα on bile acid (BA) homeostasis in female mice. Study in WT male mice showed that a 4-day CLOF treatment increased liver weight, bile flow, and biliary BA excretion, but decreased total BAs in both serum and liver. In contrast, WT female mice were less susceptible to these CLOF-mediated responses observed in males. In WT female mice, CLOF decreased total BAs in the liver, but had little effect on the mRNAs of hepatic BA-related genes. Next, a comparative analysis between WT and PPARα-null female mice showed that lack of PPARα in female mice decreased total BAs in serum, but had little effect on total BAs in liver or bile. However, lack of PPARα in female mice increased mRNAs of BA synthetic enzymes (Cyp7a1, Cyp8b1, Cyp27a1, and Cyp7b1) and transporters (Ntcp, Oatp1a1, Oatp1b2, and Mrp3). Furthermore, the increase of Cyp7a1 in PPARα-null female mice was associated with an increase in liver Fxr-Shp-Lrh-1 signaling. In conclusion, female mice are resistant to CLOF-mediated effects on BA metabolism observed in males, which could be attributed to PPARα-mediated suppression in females on genes involved in BA synthesis and transport. Copyright © 2017 Elsevier Inc. All rights reserved.

Activity of the basal ganglia in Parkinson's disease estimated by PET

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Ohye, Chihiro

1995-01-01

Positron emission tomographic (PET) studies on the local cerebral blood flow, oxygen metabolic rate, glucose metabolic rate in the basal ganglia of Parkinson's disease are reviewed. PET has demonstrated that blood flow was decreased in the cerebral cortex, especially the frontal region, of Parkinson's disease and that specific change in blood flow or metabolic rate in the basal ganglia was detected only in patients with hemi-parkinsonism. In authors' study on PET using 18 FDG in patients with tremor type and rigid type Parkinson's disease, changes in blood flow and metabolic rate were minimal at the basal ganglia level in tremor type patients, but cortical blood flow was decreased and metabolic rate was more elevated in the basal ganglia in rigid type patients. These findings were correlated with depth micro-recordings obtained by stereotactic pallidotomy. PET studies have also revealed that activity in the nerve terminal was decreased with decreasing dopamine and that dopamine (mainly D 2 ) activity was remarkably increased. PET studies with specific tracers are promising in providing more accurate information about functional state of living human brain with minimal invasion to patients. (N.K.)

Protective Efficacy of Alpha-lipoic Acid against AflatoxinB1-induced Oxidative Damage in the Liver

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Y. Li

2014-06-01

Full Text Available Alpha-lipoic acid (α-LA is not only involved in energy metabolism, but is also a powerful antioxidant that can protect against hepatic oxidative stress induced by some drugs, toxins, or under various physiological and pathophysiological conditions. Here, we investigated the effect of α-LA against liver oxidative damage in broilers exposed to aflatoxin B1 (AFB1. Birds were randomly divided into four groups and assigned different diets: basal diet, 300 mg/kg α-LA supplementation in basal diet, diet containing 74 μg/kg AFB1, and 300 mg/kg α-LA supplementation in diet containing 74 μg/kg AFB1, for 3 weeks. The results revealed that the addition of 300 mg/kg α-LA protected against the liver function damage of broilers induced by chronic low dose of AFB1 as estimated by a significant (p<0.05 change in levels of plasma total protein, albumin, alkaline phosphatase and the activities of liver glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase. The histopathological analysis also showed that liver tissues were injured in the AFB1 diet, but this effect was alleviated by the addition of 300 mg/kg α-LA. Additionally, AFB1 induced a profound elevation of oxidative stress in birds, as indicated by an increase in malondialdehyde level, a decrease in glutathione peroxidase activity and a depletion of the glutathione content in the liver. All of these negative effects were inhibited by treatment with α-LA. Our results suggest that the inhibition of AFB1-induced excess production of lipid peroxides and the maintenance of intracellular antioxidant status may play important roles in the protective effects of α-LA against AFB1-induced oxidative damage in the liver.

Ameliorative Effects of Grape Seed Proanthocyanidin Extract on Growth Performance, Immune Function, Antioxidant Capacity, Biochemical Constituents, Liver Histopathology and Aflatoxin Residues in Broilers Exposed to Aflatoxin B₁.

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Ali Rajput, Shahid; Sun, Lvhui; Zhang, Niya; Mohamed Khalil, Mahmoud; Gao, Xin; Ling, Zhao; Zhu, Luoyi; Khan, Farhan Anwar; Zhang, Jiacai; Qi, Desheng

2017-11-15

Aflatoxicosis is a grave threat to the poultry industry. Dietary supplementation with antioxidants showed a great potential in enhancing the immune system; hence, protecting animals against aflatoxin B₁-induced toxicity. Grape seed proanthocyanidin extract (GSPE) one of the most well-known and powerful antioxidants. Therefore, the purpose of this research was to investigate the effectiveness of GSPE in the detoxification of AFB₁ in broilers. A total of 300 one-day-old Cobb chicks were randomly allocated into five treatments of six replicates (10 birds per replicate), fed ad libitum for four weeks with the following dietary treatments: 1. Basal diet (control); 2. Basal diet + 1 mg/kg AFB₁ contaminated corn (AFB₁); 3. Basal diet + GSPE 250 mg/kg; (GSPE 250 mg/kg) 4. Basal diet + AFB₁ (1 mg/kg) + GSPE 250 mg/kg; (AFB₁ + GSPE 250 mg/kg) 5. Basal diet + AFB₁ (1mg/kg) + GSPE 500 mg/kg, (AFB₁ + GSPE 500 mg/kg). When compared with the control group, feeding broilers with AFB₁ alone significantly reduced growth performance, serum immunoglobulin contents, negatively altered serum biochemical contents, and enzyme activities, and induced histopathological lesion in the liver. In addition, AFB₁ significantly increased malondialdehyde content and decreased total superoxide dismutase, catalase, glutathione peroxide, glutathione-S transferase, glutathione reductase activities, and glutathione concentration within the liver and serum. The supplementation of GSPE (250 and 500 mg/kg) to AFB₁ contaminated diet reduced AFB₁ residue in the liver and significantly mitigated AFB₁ negative effects. From these results, it can be concluded that dietary supplementation of GSPE has protective effects against aflatoxicosis caused by AFB₁ in broiler chickens.

Changes of α-glycerophosphate dehydrogenase activity in fatty liver of rats by amino acid imbalance

International Nuclear Information System (INIS)

Ogura, Masaji; Katsunuma, Eiichi; Akabane, Tomoko; Ogawa, Seiichi

1976-01-01

The previous study on the lipogenesis in the fatty livers of rats, which was induced by feeding the diet with imbalanced amino acid, revealed that the induction of this type of fatty livers was due mainly to the acceleration of triglyceride synthesis by the increase in both synthesis and esterification of fatty acid in the livers. Although many studies have been carried out on the dietary control of α-glycerophosphate dehydrogenase activity in rat livers, the enzyme change in amino acid imbalance has not been reported. In the present study, in order to elucidate the difference in the supply of glycerol moiety of triglyceride due to the imbalance, the change of the α-glycerophosphate dehydrogenase activity in livers was investigated. The experimental diets were 8% casein basal diet and basal + 0.3% DL-methionine imbalanced diet. 5 rats of each group were killed after 0.5 and 10 days on the diet, and the analysis of the lipid content in the livers and the determination of the α-glycerophosphate dehydrogenase activity were carried out. The linear response of the enzyme activity to time and protein concentration was obtained. The development of fatty livers was observed in the imbalanced diet group in the feeding period of 10 days. It was found that the specific activity of the imbalanced diet group increased significantly in 5 and 10 days as compared with that of the basal diet group. The elevation in the enzyme activity may suggest that the supply of α-glycerophosphate for triglyceride synthesis is also increased in this type of fatty livers. (Kako, I.)

Protective effect of bile acid derivatives in phalloidin-induced rat liver toxicity

International Nuclear Information System (INIS)

Herraez, Elisa; Macias, Rocio I.R.; Vazquez-Tato, Jose; Hierro, Carlos; Monte, Maria J.; Marin, Jose J.G.

2009-01-01

Phalloidin causes severe liver damage characterized by marked cholestasis, which is due in part to irreversible polymerization of actin filaments. Liver uptake of this toxin through the transporter OATP1B1 is inhibited by the bile acid derivative BALU-1, which does not inhibit the sodium-dependent bile acid transporter NTCP. The aim of the present study was to investigate whether BALU-1 prevents liver uptake of phalloidin without impairing endogenous bile acid handling and hence may have protective effects against the hepatotoxicity induced by this toxin. In anaesthetized rats, i.v. administration of BALU-1 increased bile flow more than taurocholic acid (TCA). Phalloidin administration decreased basal (- 60%) and TCA-stimulated bile flow (- 55%) without impairing bile acid output. Phalloidin-induced cholestasis was accompanied by liver necrosis, nephrotoxicity and haematuria. In BALU-1-treated animals, phalloidin-induced cholestasis was partially prevented. Moreover haematuria was not observed, which was consistent with histological evidences of BALU-1-prevented injury of liver and kidney tissue. HPLC-MS/MS analysis revealed that BALU-1 was secreted in bile mainly in non-conjugated form, although a small proportion ( TCA > DHCA > UDCA. In conclusion, BALU-1 is able to protect against phalloidin-induced hepatotoxicity, probably due to an inhibition of the liver uptake and an enhanced biliary secretion of this toxin.

Basal Cell Carcinoma

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... Kids’ zone Video library Find a dermatologist Basal cell carcinoma Overview Basal cell carcinoma: This skin cancer ... that has received years of sun exposure. Basal cell carcinoma: Overview Basal cell carcinoma (BCC) is the ...

Comparison of liraglutide plus basal insulin and basal-bolus insulin therapy (BBIT) for glycemic control, body weight stability, and treatment satisfaction in patients treated using BBIT for type 2 diabetes without severe insulin deficiency: A randomized prospective pilot study.

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Yamamoto, Saki; Hayashi, Toshiyuki; Ohara, Makoto; Goto, Satoshi; Sato, Jun; Nagaike, Hiroe; Fukase, Ayako; Sato, Nobuko; Hiromura, Munenori; Tomoyasu, Masako; Nakanishi, Noriko; Lee, Soushou; Osamura, Anna; Yamamoto, Takeshi; Fukui, Tomoyasu; Hirano, Tsutomu

2018-03-26

We examined whether 0.9 mg/day liraglutide plus basal insulin (Lira-basal) is superior to basal-bolus insulin therapy (BBIT) for type 2 diabetes (T2DM) without severe insulin deficiency as determined by glucagon stimulation. Fifty patients receiving BBIT were enrolled in this 24-week, prospective, randomized, open-labeled study. After excluding subjects with fasting C-peptide immunoreactivity (CPR) basal (n = 12) or continued BBIT (n = 13). Primary endpoint was change in HbA1c. Secondary endpoints were changes in body weight (BW), 7-point self-monitored blood glucose (SMBG), and Diabetes Treatment Satisfaction Questionnaire status (DTSQs) scores. The Lira-basal group demonstrated reduced HbA1c, whereas the BBIT group showed no change. BW was reduced in the Lira-basal group but increased in the BBIT group. The Lira-basal group also exhibited significantly reduced pre-breakfast and pre-lunch SMBG. DTSQs scores improved in the Lira-basal group but not the BBIT group. Plasma lipids, liver function, and kidney function were not significantly changed in either group. Lira-basal therapy is superior to BBIT for T2DM without severe insulin deficiency. This study was registered with UMIN Clinical Trials Registry (UMIN000028313). Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Decreased C-reactive protein induces abnormal vascular structure in a rat model of liver dysfunction induced by bile duct ligation

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Ji Hye Jun

2016-09-01

Full Text Available Background/Aims Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL. Methods The diameter of the hepatic vein was analyzed in rat liver tissues using hematoxylin and eosin (H&E staining. The expression levels of angiogenic factors, albumin, and CRP were analyzed by real-time PCR and Western blotting. A tube formation assay was performed to confirm the effect of CRP on angiogenesis in human umbilical vein endothelial cells (HUVECs treated with lithocholic acid (LCA and siRNA-CRP. Results The diameter of the hepatic portal vein increased significantly with the progression of cirrhosis. The expression levels of angiogenic factors were increased in the cirrhotic liver. In contrast, the expression levels of albumin and CRP were significantly lower in the liver tissue obtained from the BDL rat model than in the normal liver. The CRP level was correlated with the expression of albumin in hepatocytes treated with LCA and siRNA-CRP. Tube formation was significantly decreased in HUVECs when they were treated with LCA or a combination of LCA and siRNA-CRP. Conclusion CRP seems to be involved in the abnormal formation of vessels in hepatic disease, and so it could be a useful diagnostic marker for hepatic disease.

Decreased C-reactive protein induces abnormal vascular structure in a rat model of liver dysfunction induced by bile duct ligation.

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Jun, Ji Hye; Choi, Jong Ho; Bae, Si Hyun; Oh, Seh Hoon; Kim, Gi Jin

2016-09-01

Chronic liver disease leads to liver fibrosis, and although the liver does have a certain regenerative capacity, this disease is associated with dysfunction of the liver vessels. C-reactive protein (CRP) is produced in the liver and circulated from there for metabolism. CRP was recently shown to inhibit angiogenesis by inducing endothelial cell dysfunction. The objective of this study was to determine the effect of CRP levels on angiogenesis in a rat model of liver dysfunction induced by bile duct ligation (BDL). The diameter of the hepatic vein was analyzed in rat liver tissues using hematoxylin and eosin (H&E) staining. The expression levels of angiogenic factors, albumin, and CRP were analyzed by real-time PCR and Western blotting. A tube formation assay was performed to confirm the effect of CRP on angiogenesis in human umbilical vein endothelial cells (HUVECs) treated with lithocholic acid (LCA) and siRNA-CRP. The diameter of the hepatic portal vein increased significantly with the progression of cirrhosis. The expression levels of angiogenic factors were increased in the cirrhotic liver. In contrast, the expression levels of albumin and CRP were significantly lower in the liver tissue obtained from the BDL rat model than in the normal liver. The CRP level was correlated with the expression of albumin in hepatocytes treated with LCA and siRNA-CRP. Tube formation was significantly decreased in HUVECs when they were treated with LCA or a combination of LCA and siRNA-CRP. CRP seems to be involved in the abnormal formation of vessels in hepatic disease, and so it could be a useful diagnostic marker for hepatic disease.

Dietary Supplementation with Lactobacillus casei Alleviates Lipopolysaccharide-Induced Liver Injury in a Porcine Model

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Di Zhao

2017-11-01

Full Text Available This study aims to determine whether Lactobacillus casei (L. casei could relieve liver injury in piglets challenged with lipopolysaccharide (LPS. Piglets were randomly allocated into one of the three groups: control, LPS, and L. casei. The control and LPS groups were fed a corn- and soybean meal-based diet, whereas the L. casei group was fed the basal diet supplemented with 6 × 106 cfu/g L. casei. On Day 31 of the trial, piglets in the LPS and L. casei groups received intraperitoneal administration of LPS (100 µg/kg body weight, while the control group received the same volume of saline. Blood and liver samples were collected for analysis. Results showed that L. casei supplementation decreased the feed/gain ratio (p = 0.027 and diarrhea incidence (p < 0.001, and attenuated LPS-induced liver histomorphological abnormalities. Compared with the control group, LPS challenge dramatically increased glutamyl transpeptidase activity (p = 0.001 in plasma as well as the concentrations of Interleukin 6 (IL-6 (p = 0.048, Tumor necrosis factor-alpha (TNF-α (p = 0.041, and Malondialdehyde (MDA (p = 0.001 in the liver, while decreasing the hepatic SOD activity. LPS also increased (p < 0.05 the mRNA levels for IL-6, IL-8, TNF-α, Toll-like receptors 4 (TLR4, Nuclear factor κB (NF-κB and Heat shock protein 70 (HSP70 in the liver. The adverse effects of LPS challenge were ameliorated by L. casei supplementation. In conclusion, dietary L. casei alleviates LPS-induced liver injury via reducing pro-inflammatory cytokines and increasing anti-oxidative capacity.

Ameliorative Effects of Grape Seed Proanthocyanidin Extract on Growth Performance, Immune Function, Antioxidant Capacity, Biochemical Constituents, Liver Histopathology and Aflatoxin Residues in Broilers Exposed to Aflatoxin B1

Science.gov (United States)

Sun, Lvhui; Zhang, Niya; Ling, Zhao; Zhu, Luoyi; Khan, Farhan Anwar; Zhang, Jiacai; Qi, Desheng

2017-01-01

Aflatoxicosis is a grave threat to the poultry industry. Dietary supplementation with antioxidants showed a great potential in enhancing the immune system; hence, protecting animals against aflatoxin B1-induced toxicity. Grape seed proanthocyanidin extract (GSPE) one of the most well-known and powerful antioxidants. Therefore, the purpose of this research was to investigate the effectiveness of GSPE in the detoxification of AFB1 in broilers. A total of 300 one-day-old Cobb chicks were randomly allocated into five treatments of six replicates (10 birds per replicate), fed ad libitum for four weeks with the following dietary treatments: 1. Basal diet (control); 2. Basal diet + 1 mg/kg AFB1 contaminated corn (AFB1); 3. Basal diet + GSPE 250 mg/kg; (GSPE 250 mg/kg) 4. Basal diet + AFB1 (1 mg/kg) + GSPE 250 mg/kg; (AFB1 + GSPE 250 mg/kg) 5. Basal diet + AFB1 (1mg/kg) + GSPE 500 mg/kg, (AFB1 + GSPE 500 mg/kg). When compared with the control group, feeding broilers with AFB1 alone significantly reduced growth performance, serum immunoglobulin contents, negatively altered serum biochemical contents, and enzyme activities, and induced histopathological lesion in the liver. In addition, AFB1 significantly increased malondialdehyde content and decreased total superoxide dismutase, catalase, glutathione peroxide, glutathione-S transferase, glutathione reductase activities, and glutathione concentration within the liver and serum. The supplementation of GSPE (250 and 500 mg/kg) to AFB1 contaminated diet reduced AFB1 residue in the liver and significantly mitigated AFB1 negative effects. From these results, it can be concluded that dietary supplementation of GSPE has protective effects against aflatoxicosis caused by AFB1 in broiler chickens. PMID:29140290

Basal and adenosine receptor-stimulated levels of cAMP are reduced in lymphocytes from alcoholic patients

International Nuclear Information System (INIS)

Diamond, I.; Wrubel, B.; Estrin, W.; Gordon, A.

1987-01-01

Alcoholism causes serious neurologic disease that may be due, in part, to the ability of ethanol to interact with neural cell membranes and change neuronal function. Adenosine receptors are membrane-bound proteins that appear to mediate some of the effects of ethanol in the brain. Human lymphocytes also have adenosine receptors, and their activation causes increases in cAMP levels. To test the hypothesis that basal and adenosine receptor-stimulated cAMP levels in lymphocytes might be abnormal in alcoholism, the authors studied lymphocytes from 10 alcoholic subjects, 10 age- and sex-matched normal individuals, and 10 patients with nonalcoholic liver disease. Basal and adenosine receptor-stimulated cAMP levels were reduced 75% in lymphocytes from alcoholic subjects. Also, there was a 76% reduction in ethanol stimulation of cAMP accumulation in lymphocytes from alcoholics. Similar results were demonstrable in isolated T cells. Unlike other laboratory tests examined, these measurements appeared to distinguish alcoholics from normal subjects and from patients with nonalcoholic liver disease. Reduced basal and adenosine receptor-stimulated levels of cAMP in lymphocytes from alcoholics may reflect a change in cell membranes due either to chronic alcohol abuse or to a genetic predisposition unique to alcoholic subjects

Unani Treatment Decreased Fibrosis and Improved Liver Functions in Decompensated Cirrhosis of Liver: A Case Series

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Akhtar Siddiqui

2016-03-01

Full Text Available At present, liver transplantation remains the only curative option for the patients with cirrhosis and end-stage liver diseases. The survival rate and recurrent diseases remain the major issues in the patient post-transplantation. Unani medicine is one of the oldest traditional systems of medicine which has been treating chronic liver diseases and cirrhosis (Talayyaful-Kabid for centuries. The current study aimed to assess the impact of Unani treatment on decompensated cirrhosis and collect data to warrant further clinical trials. Authors conducted a case series on five patients with decompensated cirrhosis and portal hypertension. The disease was confirmed through FibroScan and ultrasound and treated with Unani treatment orally for seven months. Results were evaluated based on FibroScan, liver function test (LFT, EuroQol-5D (EQ5D, Child-Pugh and TTO-TIME (trade-off question. Significant improvements in LFT, fibrosis and quality of life were achieved in the studied patients. The literature related to the herbal constituents of chief medicines used to treat in this case was reviewed. The herbs proved their potential anti-oxidative, anti-inflammatory, hepato-protective, immuno-modulator and antiviral activities, suggesting plausible mechanisms of action in the cases. The preliminary findings indicated the potential therapeutic role of Unani treatment in decompensated cirrhosis. Clinical trials should be conducted to explore further therapeutic potential of Unani treatment in decompensated cirrhosis.

Oral testosterone load related to liver function in men with alcoholic liver cirrhosis

DEFF Research Database (Denmark)

Gluud, C; Bahnsen, M; Bennett, P

1983-01-01

in patients with alcoholic cirrhosis. This decrease seems to be due to decreased liver function, decreasing hepatic blood flow, and increased portosystemic shunting. Oral testosterone loading may therefore be of prognostic significance in patients with alcoholic liver cirrhosis.......The relation between liver function and an oral testosterone load was examined in 42 consecutive patients with alcoholic liver cirrhosis. Administration of an oral load of 400 mg micronized free testosterone increased the serum concentration of testosterone (range, 31.9-694.4 nmol/l; median, 140.......8 nmol/l) in male patients with alcoholic liver cirrhosis to significantly (P less than 0.01) higher levels than in male subjects without liver disease (range, 25.4-106.6 nmol/l; median, 61.5 nmol/l). The increase of testosterone after the load (log delta testosterone) in patients correlated inversely...

Mineral Requirements in Children with Chronic Liver Disease

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A Rezaeian

2014-04-01

Full Text Available Introduction: Decreased oral intake or impaired function / structure in the gut, such as hypertension port associated with atrophic changes in the protein nutrition - calories can lead to micronutrient deficiencies.This paper examines the status of micronutrients in chronic liver disease in children.   Materials and Methods: In this review study databases including proquest, pubmedcentral, scincedirect, ovid, medlineplus were been searched with keyword words such as” chronic liver disease"” minerals””children” between 1999 to 2014. Finally, 3 related articles have been found.   Results: In chronic liver disease changes in micronutrient metabolism lead to changes in the daily requirements, such that in certain circumstances intake increasing or decreasing  is needed. Low serum calcium and phosphate concentrations are often the reflection of malabsorption-induced bone disease that is unresponsive to vitamin D store normalization. Iron is usually deficient in children with CLD and supplementation frequently needed. The origin of iron deficiency is multifactorial and includes ongoing losses, inadequate intakes, serial blood draws and malabsorption secondary to hypertensive enteropathy. Zinc plays an important role in cognitive function, appetite and taste, immune function, wound healing, and protein metabolism. Low plasma zinc levels are frequent in children with chronic cholestasis, but unfortunately plasma concentrations are not reflective of total body zinc status. Copper and manganese, unlike other minerals, are increased in CLD, because they are normally excreted through bile. Parenteral nutrition in cholestatic patients can induce manganese intoxication and accumulation in basal ganglia.   Conclusion:  In fants with CLD are prone to multiple nutritional deficiencies. Mineral state should be evaluated, treated and reevaluated, until sufficient daily requirement achieved. Poster  Presentation, N 33  

Activation of Constitutive Androstane Receptor (CAR) in Mice Results in Maintained Biliary Excretion of Bile Acids Despite a Marked Decrease of Bile Acids in Liver.

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Lickteig, Andrew J; Csanaky, Iván L; Pratt-Hyatt, Matthew; Klaassen, Curtis D

2016-06-01

Activation of Constitutive Androstane Receptor (CAR) protects against bile acid (BA)-induced liver injury. This study was performed to determine the effect of CAR activation on bile flow, BA profile, as well as expression of BA synthesis and transport genes. Synthetic CAR ligand 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) was administered to mice for 4 days. BAs were quantified by UPLC-MS/MS (ultraperformance liquid chromatography-tandem mass spectrometry). CAR activation decreases total BAs in livers of male (49%) and female mice (26%), largely attributable to decreases of the 12α-hydroxylated BA taurocholic acid (T-CA) (males (M) 65%, females (F) 45%). Bile flow in both sexes was increased by CAR activation, and the increases were BA-independent. CAR activation did not alter biliary excretion of total BAs, but overall BA composition changed. Excretion of muricholic (6-hydroxylated) BAs was increased in males (101%), and the 12α-OH proportion of biliary BAs was decreased in both males (37%) and females (28%). The decrease of T-CA in livers of males and females correlates with the decreased mRNA of the sterol 12α-hydroxylase Cyp8b1 in males (71%) and females (54%). As a response to restore BAs to physiologic concentrations in liver, mRNA of Cyp7a1 is upregulated following TCPOBOP (males 185%, females 132%). In ilea, mRNA of the negative feedback regulator Fgf15 was unaltered by CAR activation, indicating biliary BA excretion was sufficient to maintain concentrations of total BAs in the small intestine. In summary, the effects of CAR activation on BAs in male and female mice are quite similar, with a marked decrease in the major BA T-CA in the liver. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

A new liver function test using the asialoglycoprotein-receptor system on the liver cell membrane, 3

International Nuclear Information System (INIS)

Hazama, Hiroshi; Kawa, Soukichi; Kubota, Yoshitsugu

1986-01-01

We evaluated the vilidity of a new liver function test using liver scintigraphy based on the asialoglycoprotein (ASGP) receptor system on the liver cell membrane in rats with galactosamine-induced acute liver disorder and those with carbon tetra-chloride-induced chronic liver disorder. Neoglycoprotein (GHSA) produced by combining human serum albumin with 32 galactose units was labeled with 99m Tc and administered (50 μg/100 g body weight) to rats with acute or chronic liver disorder. Clearance curves were produced based on liver scintigrams and analysed using the two-compartment model to obtain parameters. In acute liver disorder, the prolongation of 99m Tc-GHSA clearance and the decrease in ASGP receptor activities correlated well to the increase in serum GOT and the decrease in the esterified to total cholesterol ratio (E/T ratio); in chronic liver disorder, they correlated significantly to the increase in the content of liver hydroxyproline (Hyp) which increased in proportion to the severity of liver fibrosis studied histologically, and to the decrease in the contents of cytochrome P-450 and cytochrome b 5 in liver microsomes. Significant correlation was observed between the prolongation of 99m Tc-GHSA clearance and the decrease in ASGP receptor activities in both acute and chronic liver disorders. These findings indicate that the measurement of 99m Tc-GHSA clearance can be a new liver function test sensitively reflecting the severity of liver damage. (author)

Liver Stiffness Decreases Rapidly in Response to Successful Hepatitis C Treatment and Then Plateaus.

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Sweta Chekuri

Full Text Available To investigate the impact of a sustained virological response (SVR to hepatitis C virus (HCV treatment on liver stiffness (LS.LS, measured by transient elastography (FibroScan, demographic and laboratory data of patients treated with interferon (IFN-containing or IFN-free regimens who had an SVR24 (undetectable HCV viral load 24 weeks after the end of treatment were analyzed using two-tailed paired t-tests, Mann-Whitney Wilcoxon Signed-rank tests and linear regression. Two time intervals were investigated: pre-treatment to SVR24 and SVR24 to the end of follow-up. LS scores ≥ 12.5 kPa indicated LS-defined cirrhosis. A p-value below 0.05 was considered statistically significant.The median age of the patients (n = 100 was 60 years [IQR (interquartile range 54-64; 72% were male; 60% were Caucasian; and 42% had cirrhosis pre-treatment according to the FibroScan measurement. The median LS score dropped from 10.40 kPa (IQR: 7.25-18.60 pre-treatment to 7.60 kPa (IQR: 5.60-12.38 at SVR24, p <0.01. Among the 42 patients with LS-defined cirrhosis pre-treatment, 25 (60% of patients still had LS scores ≥ 12.5 kPa at SVR24, indicating the persistence of cirrhosis. The median change in LS was similar in patients receiving IFN-containing and IFN-free regimens: -1.95 kPa (IQR: -5.75 --0.38 versus -2.40 kPa (IQR: -7.70 --0.23, p = 0.74. Among 56 patients with a post-SVR24 LS measurement, the LS score changed by an additional -0.90 kPa (IQR: -2.98-0.5 during a median follow-up time of 1.17 (IQR: 0.88-1.63 years, which was not a statistically significant decrease (p = 0.99.LS decreased from pre-treatment to SVR24, but did not decrease significantly during additional follow-up. Earlier treatment may be needed to reduce the burden of liver disease.

Diets Rich in Polyunsaturated Fatty Acids With Different Omega-6/Omega-3 Ratio Decrease Liver Content of Saturated Fatty Acids Across Generations of Wistar Rats

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Simone Halfen

Full Text Available Our study evaluated how the consumption of diets with low (LOW group - 0.4/1 or high (CON group - 13.6/1 omega-6/omega-3 ratio across generations (F1 and F2 can modulate liver fatty acid (FA profile and blood biomarkers. Liver content of α-linolenic acid was higher in animals always fed with LOW diet than animals that changed from CON to LOW diet, which by your time was higher than animals always fed with CON diet. Liver saturated FA concentration decreased in both groups from F1 to F2. In conclusion, both diets were efficient in decreasing the saturated FA liver content across generations, the LOW ratio diet was more effective in reducing blood triglycerides and non-esterified fatty acids, and there was a multigenerational effect of the LOW ratio diet, improving the FA profile even when the offspring start receiving the CON diet.

Auditory brainstem activity and development evoked by apical versus basal cochlear implant electrode stimulation in children.

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Gordon, K A; Papsin, B C; Harrison, R V

2007-08-01

The role of apical versus basal cochlear implant electrode stimulation on central auditory development was examined. We hypothesized that, in children with early onset deafness, auditory development evoked by basal electrode stimulation would differ from that evoked more apically. Responses of the auditory nerve and brainstem, evoked by an apical and a basal implant electrode, were measured over the first year of cochlear implant use in 50 children with early onset severe to profound deafness who used hearing aids prior to implantation. Responses at initial stimulation were of larger amplitude and shorter latency when evoked by the apical electrode. No significant effects of residual hearing or age were found on initial response amplitudes or latencies. With implant use, responses evoked by both electrodes showed decreases in wave and interwave latencies reflecting decreased neural conduction time through the brainstem. Apical versus basal differences persisted with implant experience with one exception; eIII-eV interlatency differences decreased with implant use. Acute stimulation shows prolongation of basally versus apically evoked auditory nerve and brainstem responses in children with severe to profound deafness. Interwave latencies reflecting neural conduction along the caudal and rostral portions of the brainstem decreased over the first year of implant use. Differences in neural conduction times evoked by apical versus basal electrode stimulation persisted in the caudal but not rostral brainstem. Activity-dependent changes of the auditory brainstem occur in response to both apical and basal cochlear implant electrode stimulation.

Dietary fish oil replacement with palm or poultry oil increases fillet oxidative stability and decreases liver glutathione peroxidase activity in barramundi (Lates calcarifer).

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Wan Ahmad, Wan A R; Stone, David A J; Schuller, Kathryn A

2013-12-01

Complete dietary fish oil replacement with palm or poultry oil in barramundi (Lates calcarifer) had no detrimental effects on growth or hepatosomatic index of juvenile fish up to an average size of ~50 g. However, it significantly decreased the omega-3 (n-3) long-chain polyunsaturated fatty acid content of the fish muscle (fillet) lipids. This was particularly true for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) which are recognised for their health beneficial effects in the human diet. As a result of their decreased EPA and DHA content, the peroxidation index of the muscle lipids was also decreased. This was associated with increased simulated retail storage shelf life as indicated by decreased thiobarbituric acid reactive substances in muscle samples from fish fed the palm or poultry oil-based diets. Concomitantly, glutathione peroxidase (GPx) activity, but not glutathione S-transferase (GST) activity or reduced glutathione concentration, was significantly reduced in the liver of barramundi fed the palm or poultry oil-based diets as compared with the fish fed the fish oil-based diet. Furthermore, GPx and GST activity were very low in muscle, much lower than in gastrointestinal tract, liver or swim bladder. Therefore, we propose that liver GPx activity may be a good predictor of fillet shelf life in barramundi and other fish species.

Glutamate Cysteine Ligase—Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage

KAUST Repository

Lavoie, Suzie

2016-04-21

Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.

Glutamate Cysteine Ligase—Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage

KAUST Repository

Lavoie, Suzie; Steullet, Pascal; Kulak, Anita; Preitner, Frederic; Do, Kim Q.; Magistretti, Pierre J.

2016-01-01

Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.

Omega-3 fatty acid supplementation decreases liver fat content in polycystic ovary syndrome: a randomized controlled trial employing proton magnetic resonance spectroscopy.

Science.gov (United States)

Cussons, Andrea J; Watts, Gerald F; Mori, Trevor A; Stuckey, Bronwyn G A

2009-10-01

There is an association between nonalcoholic fatty liver disease (NAFLD) and the polycystic ovary syndrome (PCOS). Marine-derived omega-3 fatty acids have favorable effects on cardiovascular risk and could reduce liver fat in NAFLD. The primary aim of this study was to examine the effects of omega-3 fatty acids on liver fat in PCOS. The secondary aim was to assess their effects on traditional cardiovascular risk factors. We conducted a randomized, crossover study at a tertiary cardiovascular research center. Twenty-five women with PCOS (mean age, 32.7 yr; mean body mass index, 34.8 kg/m(2)) participated in the study. We compared 4g/d of omega-3 fatty acids with placebo over 8 wk. The primary outcome measure was hepatic fat content quantified using proton magnetic resonance spectroscopy. Secondary outcome measures included fasting lipids and blood pressure. Omega-3 fatty acids significantly decreased liver fat content compared with placebo [10.2 (1.1) vs. 8.4 (0.9)%; P = 0.022]. There was also a reduction in triglycerides [1.19 (1.03-1.47) vs. 1.02 (0.93-1.18) mmol/liter; P = 0.002], systolic blood pressure [124.1 (12.1) vs. 122.3 (14.5) mm Hg; P = 0.018], and diastolic blood pressure [73.2 (8.4) vs. 69.7 (8.3) mm Hg; P = 0.005] with omega-3 fatty acids compared with placebo. Omega-3 fatty acids particularly decreased hepatic fat in women with hepatic steatosis, defined as liver fat percentage greater than 5% [18.2 (11.1) vs. 14.8 (9.3)%; P = 0.03]. Omega-3 fatty acid supplementation has a beneficial effect on liver fat content and other cardiovascular risk factors in women with PCOS, including those with hepatic steatosis. Whether this translates into a reduction in cardiometabolic events warrants further study.

Somatostatin and serum gastrin in normal subjects and in patients with pernicious anaemia, chronic liver and renal disease

Energy Technology Data Exchange (ETDEWEB)

Le Roith, D; Vinik, A I; Epstein, S; Baron, P; Olkenitzky, M N; Pimstone, B L

1975-09-13

The effects of somatostatin (growth hormone release inhibiting hormone) on basal gastrin were studied in patients suffering from pernicious anaemia and chronic renal and liver disease, and during sequential arginine/insulin-stimulated gastrin release in normal subjects. When basal gastrin concentrations were normal (10-50 pg/ml) in controls and in patients who were in renal and liver failure, somatostatin had no effect on gastrin levels. Raised basal gastrin levels in pernicious anaemia and in 2 cases of chronic renal disease, were significantly inhibited by somatostatin with a half-life (T-half) of 3 to 4 minutes. Arginine infusion caused an insignificant rise in serum gastrin which was unaffected by somatostatin, whereas insulin hypoglycaemia significantly stimulated gastrin release, which was inhibited by somatostatin.

New therapeutic strategies for canine liver disease; Growth factors and liver progenitor cells

NARCIS (Netherlands)

Arends, B.

2008-01-01

The liver has the unique capacity to regulate its mass after loss of functional liver cells due to liver disease, injury, and/or toxicity. Unfortunately, in the course of chronic liver disease this meticulously regulated regeneration process is imbalanced resulting in a decreased regenerative

Significant decrease of saturation index in erythrocytes membrane from subjects with non-alcoholic fatty liver disease (NAFLD).

Science.gov (United States)

Notarnicola, Maria; Caruso, Maria Gabriella; Tutino, Valeria; Bonfiglio, Caterina; Cozzolongo, Raffaele; Giannuzzi, Vito; De Nunzio, Valentina; De Leonardis, Giampiero; Abbrescia, Daniela I; Franco, Isabella; Intini, Vincenza; Mirizzi, Antonella; Osella, Alberto R

2017-08-23

The lipidomic profiling of erythrocyte membranes is expected to provide a peculiar scenario at molecular level of metabolic and nutritional pathways which may influence the lipid balance and the adaptation and homeostasis of the organism. Considering that lipid accumulation in the cell is important in promoting tissue inflammation, the purpose of this study is to analyze the fatty acid profile in red blood cell membranes of patients with Non-Alcoholic Fatty Liver Disease (NAFLD), in order to identify and validate membrane profiles possibly associated with the degree of hepatic damage. This work presents data obtained at baseline from 101 subjects that participated to a nutritional trial (registration number: NCT02347696) enrolling consecutive subjects with NAFLD. Diagnosis of liver steatosis was performed by using vibration-controlled elastography implemented on FibroScan. Fatty acids, extracted from phospholipids of erythrocyte membranes, were quantified by gas chromatography method. The subjects with severe NAFLD showed a significant decrease of the ratio of stearic acid to oleic acid (saturation index, SI) compared to controls, 1.281 ± 0.31 vs 1.5 ± 0.29, respectively. Low levels of SI in red blood cell membranes, inversely associated with degree of liver damage, suggest that an impairment of circulating cell membrane structure can reflect modifications that take place in the liver. Subjects with severe NAFLDalso showed higher levels of elongase 5 enzymatic activity, evaluated as vaccenic acid to palmitoleic acid ratio. Starting from these evidences, our findings show the importance of lipidomic approach in the diagnosis and the staging of NAFLD.

Disparate metabolic effects of blackcurrant seed oil in rats fed a basal and obesogenic diet.

Science.gov (United States)

Jurgoński, Adam; Fotschki, Bartosz; Juśkiewicz, Jerzy

2015-09-01

It was hypothesised that blackcurrant seed oil beneficially modulates metabolic disorders related to obesity and its complications. The study also aimed to investigate the potentially adverse effects of an unbalanced diet on the distal intestine. Male Wistar rats were randomly assigned to four groups of eight animals each and were fed a basal or obesogenic (high in fat and low in fibre) diet that contained either rapeseed oil (Canola) or blackcurrant seed oil. A two-way analysis of variance was then applied to assess the effects of diet and oil and the interaction between them. After 8 weeks, the obesogenic dietary regimen increased the body weight, altered the plasma lipid profile and increased the liver fat content and the plasma transaminase activities. In addition, the obesogenic diet decreased bacterial glycolytic activity and short-chain fatty acid formation in the distal intestine. Dietary blackcurrant seed oil improved the lipid metabolism by lowering liver fat accumulation and the plasma triglyceride concentration and atherogenicity as well by increasing the plasma HDL-cholesterol concentration. However, in rats fed an obesogenic diet containing blackcurrant seed oil, the plasma HDL-cholesterol concentration was comparable with both rapeseed oil-containing diets, and a significant elevation of the plasma transaminase activities was noted instead. The obesogenic dietary regimen causes a number of metabolic disorders, including alterations in the hindgut microbial metabolism. Dietary blackcurrant seed oil ameliorates the lipid metabolism; however, the beneficial effect is restricted when it is provided together with the obesogenic diet, and a risk of liver injury may occur.

Hepatoadrenal syndrome in Egyptian children with liver cirrhosis ...

African Journals Online (AJOL)

This pilot study was designed to evaluate adrenal function for 24 children with liver cirrhosis of various etiologies by measuring basal cortisol level and measuring the peak level after 30 min of short low dose ACTH stimulation test. They were categorized in two groups; group 1 included 12 patients with sepsis and group 2 ...

Effect of the Combination of Ezetimibe and Simvastatin on Gluconeogenesis and Oxygen Consumption in the Rat Liver.

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Bracht, Lívia; Caparroz-Assef, Silvana Martins; Bracht, Adelar; Bersani-Amado, Ciomar Aparecida

2016-06-01

The aim of this work was to investigate the effects of chronic treatment with the combination of ezetimibe and simvastatin on gluconeogenesis in rat liver. Rats were treated daily for 28 days with the combination of ezetimibe and simvastatin (10/40 mg/kg) by oral gavage. To measure gluconeogenesis and the associated pathways, isolated perfused rat liver was used. In addition, subcellular fractions, such as microsomes and mitochondria, were used for complementary measures of enzymatic activities. Treatment with the combination of simvastatin and ezetimibe resulted in a decrease in gluconeogenesis from pyruvate (-62%). Basal oxygen consumption of the treated animals was higher (+22%) than that of the control rats, but the resulting oxygen consumption that occurred after pyruvate infusion was 43% lower in animals treated with the combination of simvastatin and ezetimibe. Oxygen consumption in the livers from treated animals was completely inhibited by cyanide (electron transport chain inhibitor), but not by proadifen (cytochrome P450 inhibitor). Chronic treatment with ezetimibe/simvastatin decreased the activity of the key enzymes glucose-6-phosphatase and fructose-1,6-bisphosphatase by 59% and 45%, respectively, which is probably the major reason for the decreased gluconeogenesis seen in ezetimibe-/simvastatin-treated rats. It is also possible that part of the effect of this combination on gluconeogenesis and on the oxygen consumption is related to the impairment of mitochondrial energy transduction. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Decrease in Activities of Selected Rat Liver Enzymes following ...

African Journals Online (AJOL)

The effects of the chemical effluent from Soap and Detergent Industry on some rat liver enzymes were investigated. Chemical analyses of both the effluent and tap water which served as the control were carried out before various concentrations of the effluent (5%v/v, 25%v/v, 50%v/v and 100%v/v) were made. The effluent ...

Basal cell epithelioma with lymphogenic and hematogenic formation of metastases (a. o. into the myocardium)

International Nuclear Information System (INIS)

Schuette, B.; Schirren, C.

1981-01-01

This report deals with a basal cell epithelioma, partially adenoid and partially morphea-like in structure, which despite intensive X-ray treatment relapsed constantly and which finally developed into an ulcus terebrans. Approximately 13 years after the primary tumor had developed (located on the left wing of the nose) both a lymphogenic and a hematogenic formation of metastases occurred with a subsequent exitus letalis 4 months later. Besides the metastases of the skin, there were multiple metastases in the lymph nodes, vertebral column, ribs, spleen, liver, stomach, pleura, and peritoneum as well as in the myocard of both ventricles and in the perimysium of the skeletal muscles. Their histological structure was similar to a partly adenoid, partily morphea-like basal cell epithelioma. The possible influence of X-ray treatment on the tumor tissue in way of benignity or malignancy is discussed in view of relevant literature on this topic. The alteration of basal cell epitheliomas into the socalled transitional epitheliomas is also analyzed. (orig.) [de

Basal cell epithelioma with lymphogenic and hematogenic formation of metastases (a. o. into the myocardium)

Energy Technology Data Exchange (ETDEWEB)

Schuette, B.; Schirren, C.

1981-01-01

This report deals with a basal cell epithelioma, partially adenoid and partially morphea-like in structure, which despite intensive X-ray treatment relapsed constantly and which finally developed into an ulcus terebrans. Approximately 13 years after the primary tumor had developed (located on the left wing of the nose) both a lymphogenic and a hematogenic formation of metastases occurred with a subsequent exitus letalis 4 months later. Besides the metastases of the skin, there were multiple metastases in the lymph nodes, vertebral column, ribs, spleen, liver, stomach, pleura, and peritoneum as well as in the myocard of both ventricles and in the perimysium of the skeletal muscles. Their histological structure was similar to a partly adenoid, partily morphea-like basal cell epithelioma. The possible influence of X-ray treatment on the tumor tissue in way of benignity or malignancy is discussed in view of relevant literature on this topic. The alteration of basal cell epitheliomas into the socalled transitional epitheliomas is also analyzed.

Decreased graft survival in liver transplant recipients of donors with positive blood cultures: a review of the United Network for Organ Sharing dataset.

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Huaman, Moises A; Vilchez, Valery; Mei, Xiaonan; Shah, Malay B; Daily, Michael F; Berger, Jonathan; Gedaly, Roberto

2017-06-01

Liver transplantation using blood culture positive donors (BCPD) has allowed a significant expansion of the donor pool. We aimed to characterize BCPD and assess the outcomes of BCPD liver transplant recipients. We retrieved data from the United Network for Organ Sharing (UNOS) registry on all adults who underwent primary, single-organ deceased-donor liver transplantation in the USA between 2008 and 2013. Patients were classified into two cohorts: the BCPD cohort and the non-BCPD cohort. One-year graft and patient survival were compared between cohorts using Kaplan-Meier estimates and Cox models. A total of 28 961 patients were included. There were 2316 (8.0%) recipients of BCPD. BCPD were more likely to be older, female, black, diabetic, hypertensive, and obese compared to non-BCPD. Graft survival was significantly lower in BCPD recipients compared to non-BCPD recipients (Kaplan-Meier, 0.85 vs. 0.87; P = 0.009). Results remained significant in propensity-matched analysis (P = 0.038). BCPD was independently associated with decreased graft survival (adjusted HR; 1.10, 95% CI 1.01-1.20; P = 0.04). There were no significant differences in patient survival between study groups. BCPD was associated with decreased graft survival in liver transplant recipients. Studies are needed to identify subgroups of BCPD with the highest risk of graft failure and characterize the underlying pathogenic mechanisms. © 2016 Steunstichting ESOT.

Effects of Lactobacillus feed supplementation on cholesterol, fat content and fatty acid composition of the liver, muscle and carcass of broiler chickens

OpenAIRE

Renseigné , Non; Abdullah , Norhani; Jalaludin , Syed; C.V.L. Wong , Michael; Yin Wan Ho ,

2006-01-01

International audience; An experiment was conducted to study the effects of feed supplementation with a mixture of Lactobacillus cultures (LC) on cholesterol, fat and fatty acid composition in the liver, muscle and carcass of broiler chickens. One hundred and thirty-six, one-day-old male broiler chicks (Avian-43) were assigned randomly to two dietary treatments: (i) a basal diet (control), and (ii) a basal diet + 0.1% LC. The cholesterol contents of the carcass and liver but not the muscle, w...

No Effect of Resveratrol on VLDL-TG Kinetics and Insulin Sensitivity in Obese Men with Nonalcoholic Fatty Liver Disease

DEFF Research Database (Denmark)

Poulsen, Marianne K; Nellemann, Birgitte; Bibby, Bo Martin

2018-01-01

The present study assess long-term effects of high-dose Resveratrol (RSV) on basal and insulin-mediated very low-desity lipoprotein triglyceride (VLDL-TG), palmitate and glucose kinetics, and liver fat content in men with nonalcoholic fatty liver disease (NAFLD). Participants (n=16) were non...

Minimizing tacrolimus decreases the risk of new-onset diabetes mellitus after liver transplantation.

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Song, Jiu-Lin; Gao, Wei; Zhong, Yan; Yan, Lu-Nan; Yang, Jia-Yin; Wen, Tian-Fu; Li, Bo; Wang, Wen-Tao; Wu, Hong; Xu, Ming-Qing; Chen, Zhe-Yu; Wei, Yong-Gang; Jiang, Li; Yang, Jian

2016-02-14

To investigate the impact of minimum tacrolimus (TAC) on new-onset diabetes mellitus (NODM) after liver transplantation (LT). We retrospectively analyzed the data of 973 liver transplant recipients between March 1999 and September 2014 in West China Hospital Liver Transplantation Center. Following the exclusion of ineligible recipients, 528 recipients with a TAC-dominant regimen were included in our study. We calculated and determined the mean trough concentration of TAC (cTAC) in the year of diabetes diagnosis in NODM recipients or in the last year of the follow-up in non-NODM recipients. A cutoff of mean cTAC value for predicting NODM 6 mo after LT was identified using a receptor operating characteristic curve. TAC-related complications after LT was evaluated by χ(2) test, and the overall and allograft survival was evaluated using the Kaplan-Meier method. Risk factors for NODM after LT were examined by univariate and multivariate Cox regression. Of the 528 transplant recipients, 131 (24.8%) developed NODM after 6 mo after LT, and the cumulative incidence of NODM progressively increased. The mean cTAC of NODM group recipients was significantly higher than that of recipients in the non-NODM group (7.66 ± 3.41 ng/mL vs 4.47 ± 2.22 ng/mL, P 50 years), hypertension pre-LT, and high mean cTAC (≥ 5.89 ng/mL) after 6 mo after LT were independent risk factors for developing NODM. Concurrently, recipients with a low cTAC (< 5.89 ng/mL) were less likely to become obese (21.3% vs 30.2%, P < 0.05) or to develop dyslipidemia (27.5% vs 44.8%, P <0.05), chronic kidney dysfunction (14.6% vs 22.7%, P < 0.05), and moderate to severe infection (24.7% vs 33.1%, P < 0.05) after LT than recipients in the high mean cTAC group. However, the two groups showed no significant difference in the incidence of acute and chronic rejection, hypertension, cardiovascular events and new-onset malignancy. A minimal TAC regimen can decrease the risk of long-term NODM after LT. Maintaining a c

Amelioration of radiation induced decrease in activity of catalase and superoxide dismutase in mouse liver by Punica granatum

International Nuclear Information System (INIS)

Sharma, Jaimala; Mathur, Aarti

2013-01-01

Ionizing radiation generates reactive oxygen species (ROS) in irradiated tissue. Cells of liver have their own defence system, the antioxidant system to deactivate ROS. Antioxidant system includes enzymatic and non-enzymatic components. Liver is rich in endogenous antioxidants and related enzymes. Catalase and Superoxide dismutase (SOD) are powerful antioxidant enzymes. In the present study Punica granatum fruit rind Ethanol extract (PGFRE) was tested against 60 Co gamma radiation induced alteration in Swiss albino mouse. Healthy adult (25±2) Swiss albino mouse were selected and divided into four groups. The first group was sham irradiated. The second group was irradiated with 8 Gy 60 Co gamma radiation only and served as control. The third group was administered with Ethanol extract of Punica granatum fruit rind one hour before irradiation at the dose rate of 10 mg/kg body weight orally. Animals were exposed to 8 Gy 60 Co gamma radiation. Fourth group was administered with Ethanol extract of Punica granatum fruit rind at the dose rate of 10 mg/kg body weight. Mice were sacrificed at various post irradiation intervals and liver was removed, weighed and analysed biochemically for Catalase and SOD activity. Catalase and SOD activity decreased up till 7th post irradiation day in 8 Gy irradiated group than normal. In PGFRE pretreated irradiated group catalase and SOD activity were higher than the corresponding control group at all the intervals. These results indicate that PGFRE extract protects damage to the catalase and SOD activity in liver of Swiss albino mouse against lethal dose of gamma radiation. (author)

In vitro metabolism of [14C]-toluene by human and rat liver microsomes and liver slices

International Nuclear Information System (INIS)

Chapman, D.E.; Moore, T.J.; Michener, S.R.; Powis, G.

1990-01-01

Toluene metabolites produced by liver microsomes from six human donors included benzylalcohol (Balc), benzaldehyde (Bald) and benzoic acid (Bacid). Microsomes from only one human donor metabolized toluene to p-cresol and o-cresol. Human liver microsomes also metabolized Balc to Bald. Balc metabolism required NADPH, was inhibited by carbon monoxide, and was decreased at a buffer pH of 10. Balc metabolism was not inhibited by ADP-ribose or sodium azide. These results suggest that cytochrome P450 is responsible for the in vitro metabolism of Balc by human liver microsomes. Toluene metabolites formed by human liver slices and released into the incubation media included hippuric acid, and Bacid. Cresols or cresol-conjugates were not detected in liver slice incubation media from any human donor. Toluene metabolism by human liver was compared to metabolism by comparable liver preparations from male Fischer F344 rats. Rates of toluene metabolism by human liver microsomes and liver slices were 9-fold and 1.3-fold greater than for rat liver, respectively. Covalent binding of toluene to human liver microsomes and liver slices was 21-fold and 4-fold greater than for comparable rat liver preparations. Covalent binding of toluene to human microsomes required NADPH, was significantly decreased by coincubation with 4 mM cysteine or 4 mM glutathione, and radioactivity associated with microsomes was decreased by subsequent digestion of microsomes with protease. These results suggest that toluene metabolism and covalent binding of toluene are underestimated if the male Fischer 344 rat is used as a model for human toluene metabolism

A20 modulates lipid metabolism and energy production to promote liver regeneration.

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Scott M Damrauer

2011-03-01

Full Text Available Liver regeneration is clinically of major importance in the setting of liver injury, resection or transplantation. We have demonstrated that the NF-κB inhibitory protein A20 significantly improves recovery of liver function and mass following extended liver resection (LR in mice. In this study, we explored the Systems Biology modulated by A20 following extended LR in mice.We performed transcriptional profiling using Affymetrix-Mouse 430.2 arrays on liver mRNA retrieved from recombinant adenovirus A20 (rAd.A20 and rAd.βgalactosidase treated livers, before and 24 hours after 78% LR. A20 overexpression impacted 1595 genes that were enriched for biological processes related to inflammatory and immune responses, cellular proliferation, energy production, oxidoreductase activity, and lipid and fatty acid metabolism. These pathways were modulated by A20 in a manner that favored decreased inflammation, heightened proliferation, and optimized metabolic control and energy production. Promoter analysis identified several transcriptional factors that implemented the effects of A20, including NF-κB, CEBPA, OCT-1, OCT-4 and EGR1. Interactive scale-free network analysis captured the key genes that delivered the specific functions of A20. Most of these genes were affected at basal level and after resection. We validated a number of A20's target genes by real-time PCR, including p21, the mitochondrial solute carriers SLC25a10 and SLC25a13, and the fatty acid metabolism regulator, peroxisome proliferator activated receptor alpha. This resulted in greater energy production in A20-expressing livers following LR, as demonstrated by increased enzymatic activity of cytochrome c oxidase, or mitochondrial complex IV.This Systems Biology-based analysis unravels novel mechanisms supporting the pro-regenerative function of A20 in the liver, by optimizing energy production through improved lipid/fatty acid metabolism, and down-regulated inflammation. These findings

Nevoid basal cell carcinoma syndrome

Science.gov (United States)

NBCC syndrome; Gorlin-Goltz syndrome; Basal cell nevus syndrome; BCNS; Basal cell cancer - nevoid basal cell carcinoma syndrome ... Nevoid basal cell carcinoma nevus syndrome is a rare genetic ... syndrome is known as PTCH ("patched"). The gene is passed down ...

Hyperintensity of basal ganglia on T1-weighted images in patients with liver cirrhosis. Correlation with hepatic encephalopathy and liver function

International Nuclear Information System (INIS)

Maeda, Hiroko; Kita, Keisuke; Mizobata, Toshiharu; Kimura, Masashi; Sonomura, Tetsuo; Kishi, Kazushi; Tanaka, Kayo; Sato, Morio; Yamada, Ryosaku

1995-01-01

Brain MR imaging was performed in 38 liver cirrhosis (LC) patients and 9 normal volunteers. On T 1 -weighted images, the signal intensity of globus pallidus (S1) and frontal white matter (S2) was measured and S1/S2 ratio was explored. We examined the relationship between S1/S2 ratio and liver function parameters. High signal intensity in bilateral globus pallidus was noted on T 1 W1 in 28 of 38 LC patients. The S1/S2 ratio of 1.186±0.097 in the 38 LC patients was significantly higher than 0.987±0.062 in the 9 normal volunteers (p 2 -weighted images showed no abnormal intensity. Compared with the LC patients with hepatic encephalopathy (HE) (n=7) and without HE (n=31), the former S1/S2 ratio (1.239±0.057) was significantly higher than the latter (1.174±0.097) (p 15 (r=0.501, p 1 -WI and the degree of liver dysfunction. (author)

Lipogenic potential of liver from morbidly obese patients with and without non-insulin-dependent diabetes

International Nuclear Information System (INIS)

Barakat, H.A.; McLendon, V.D.; Carpenter, J.W.; Marks, R.H.; Legett, N.; O'Brien, K.; Caro, J.F.

1991-01-01

Intra-abdominal liver biopsies were obtained during surgery from fasted obese patients with non-insulin-dependent diabetes mellitus (NIDDM), obese normoglycemic controls, and lean controls. Lipid synthesis was studied in freshly isolated hepatocytes and liver homogenates from the three groups of subjects. Incorporation of 3H2O into the lipids of hepatocytes was determined in the absence and presence of insulin (0.1 mumol/L). The activities of five enzymes involved in fatty acid synthesis, and the incorporation of 14C-glycerol-3-phosphate into lipids were determined in liver homogenates. Basal lipid synthesis by hepatocytes was not different in the three groups of patients. Insulin stimulated lipogenesis by 8% +/- 30% in the lean controls, 33% +/- 8% in the obese controls and 17% +/- 6% in the NIDDM patients. No significant differences in the activities of the five enzymes that are involved in de novo fatty acid synthesis among the three groups of patients were observed. Similarly, incorporation of 14C-glycerol-3-phosphate by liver homogenates, in the presence of saturating or submaximal concentrations of fatty acids, did not differ among the three groups. These results show that under the experimental conditions of this study, including the fasted state of the patients, the basal capacity of liver of NIDDM patients to synthesize fatty acids or glycerides is the same as that of liver from obese and lean controls. Thus, it is likely that an increase in fatty acid flux into a liver with normal lipogenic potential may contribute to the increased synthesis of triglycerides by the liver of these patients in vivo

ULTRASONOGRAPHIC EVALUATION OF AMOEBIC LIVER ABSCESS

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Nagesh

2016-04-01

Full Text Available AIMS To study the role of ultrasonography in the diagnosis, followup, resolution and percutaneous interventions of amoebic liver abscesses. METHODOLOGY 25 patients with 38 amoebic liver abscesses were included in this study. The diagnostic criteria being compatible history, tender and enlarged liver, radiological and ultrasound findings and response to metronidazole therapy. Confirmed cases of amoebic liver abscesses were followed up by ultrasonography till complete resolution. RESULTS The highest incidence of age was seen between 3 rd and 5 th decades (84% with a male sex incidence of 92%, disease preponderance in people belonging to low socioeconomic group and a high incidence among alcoholics. The radiological findings were: Elevation of right dome of diaphragm (56%, restricted diaphragmatic movements (88%, right basal lung changes (48%, right pleural effusion (12%, and indistinct hazy diaphragmatic contour (40%. The ultrasonographic findings were: 87% of the abscesses were located in right lobe, 11% in left lobe and 2% in both lobes. Among the 25 patients, 76% showed solitary and 24% showed multiple abscesses. Of the 38 amoebic abscesses, 79% were hypoechoic, 13% were hyperechoic and 8% were anechoic. 11 patients were subjected for ultrasound-guided aspiration. CONCLUSION Ultrasound is a safe, reliable and non-invasive imaging modality for the diagnosis, followup and percutaneous interventions of amoebic liver abscesses. The sonographic resolution time of amoebic liver abscesses varies from 28 to 286 days.

Cerebral blood flow and metabolism in patients with aphasia due to basal ganglionic lesion

Energy Technology Data Exchange (ETDEWEB)

Kitamura, Shin; Kato, Toshiaki; Ujike, Takashi; Kuroki, Soemu; Terashi, Akiro

1987-03-01

Cerebral blood flow and metabolism in right handed eight patients with subcortical lesion and aphasia were measured to investigate the correlation between aphasia and functional changes in cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO/sub 2/) in the cortex and the basal ganglionic region. All patients had no lesion in the cortex, but in the basal ganglionic region (putamen, caudate nucleus, internal capsule, and periventricular white matter) on CT images. Patients with bilateral lesion were excluded in this study. Six patients with cerebral infarction in the left basal ganglionic region and two patients with the left putammal hemorrhage were examined. Five patients had non fluent Broca's type speech, two patients had poor comprehension, fluent Wernicke-type speech and one patient was globally aphasic. CBF, CMRO/sub 2/, and oxygen extraction fraction were measured by the positron emission tomography using /sup 15/O/sub 2/, C/sup 15/O/sub 2/ inhalation technique. In addition to reduction of CBF and CMRO/sub 2/ in the basal ganglionic region, CBF and CMRO/sub 2/ decreased in the left frontal cortex especially posterior part in four patients with Broca's aphasia. In two patients with Wernicke type aphasia, CBF and CMRO/sub 2/ decreased in the basal ganglionic region and the left temporal cortex. In a globally aphasic patient, marked reduction of CBF and CMRO/sub 2/ was observed in the left frontal and temporal cortex, in addition to the basal ganglionic region. These results suggest that dysfunction of cortex as well as that of basal ganglionic region might be related to the occurence of aphasia. However, in one patient with Broca's ahasia, CBF and CMRO/sub 2/ were preserved in the cortex and metabolic reduction was observed in only basal ganglia. This case indicates the relation between basal ganglionic lesion and the occurrence of aphasia.

Keap1-knockdown decreases fasting-induced fatty liver via altered lipid metabolism and decreased fatty acid mobilization from adipose tissue.

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Jialin Xu

Full Text Available AIMS: The purpose of this study was to determine whether Nrf2 activation, via Keap1-knockdown (Keap1-KD, regulates lipid metabolism and mobilization induced by food deprivation (e.g. fasting. METHODS AND RESULTS: Male C57BL/6 (WT and Keap1-KD mice were either fed ad libitum or food deprived for 24 hours. After fasting, WT mice exhibited a marked increase in hepatic lipid accumulation, but Keap1-KD mice had an attenuated increase of lipid accumulation, along with reduced expression of lipogenic genes (acetyl-coA carboxylase, stearoyl-CoA desaturase-1, and fatty acid synthase and reduced expression of genes related to fatty acid transport, such as fatty acid translocase/CD36 (CD36 and Fatty acid transport protein (FATP 2, which may attribute to the reduced induction of Peroxisome proliferator-activated receptor (Ppar α signaling in the liver. Additionally, enhanced Nrf2 activity by Keap1-KD increased AMP-activated protein kinase (AMPK phosphorylation in liver. In white adipose tissue, enhanced Nrf2 activity did not change the lipolysis rate by fasting, but reduced expression of fatty acid transporters--CD36 and FATP1, via a PPARα-dependent mechanism, which impaired fatty acid transport from white adipose tissue to periphery circulation system, and resulted in increased white adipose tissue fatty acid content. Moreover, enhanced Nrf2 activity increased glucose tolerance and Akt phosphorylation levels upon insulin administration, suggesting Nrf2 signaling pathway plays a key role in regulating insulin signaling and enhanced insulin sensitivity in skeletal muscle. CONCLUSION: Enhanced Nrf2 activity via Keap1-KD decreased fasting-induced steatosis, pointing to an important function of Nrf2 on lipid metabolism under the condition of nutrient deprivation.

Perinatal exposure to BDE-99 causes decreased protein levels of cyclin D1 via GSK3β activation and increased ROS production in rat pup livers.

Science.gov (United States)

Blanco, Jordi; Mulero, Miquel; Domingo, Jose L; Sanchez, Domènec J

2014-02-01

We here examined the potential liver toxicity in rat pups from dams exposed during the gestational and lactation periods to 2,2',4,4',5-pentabromodiphenyl ether (BDE-99). Dams were exposed to 0, 1, and 2mg/kg/day of BDE-99 from gestation day 6 to postnatal day 21. When the pups were weaning, the liver from 1 pup of each litter was excised to evaluate oxidative stress markers and the messenger RNA (mRNA) expression of multiple cytochrome P450 (CYP) isoforms. To determine whether thyroid hormone (TH) was disrupted, the protein and mRNA expressions of several TH receptor (TR) isoforms, as well as the protein levels of cyclin D1 and the phosphorylated protein kinases Akt and glycogen synthase kinase 3 beta (GSK3β), were evaluated. Perinatal exposure to BDE-99 produced decreased levels of cyclin D1 in rat pup livers. A decrease in the active form of Akt and an increase in the active form of GSK3β were observed. The decreased Akt pathway may be due to a potential disruption of the nongenomic actions of TH by BDE-99 and its metabolites. This possible TH disruption was noted as a decrease in TR isoforms expression. By contrast, we observed an upregulation of CYP2B1 gene expression, which is correlated with an increase in reactive oxygen species production. This outcome indicates activation of the nuclear constitutive androstane receptor, which could induce the expression of other enzymes capable of metabolizing TH. The present findings support the hypothesis that perinatal exposure to PBDEs, at levels found in humans, may have serious implications for metabolic processes in rat pup livers.

A high plasma: red blood cell transfusion ratio during liver transplantation is associated with decreased blood utilization.

Science.gov (United States)

Pagano, M B; Metcalf, R A; Hess, J R; Reyes, J; Perkins, J D; Montenovo, M I

2018-04-01

During massive transfusion, the volume ratio of administered plasma (PL Vol) to red blood cell (RBC Vol) appears to be associated with reduced blood utilization and improved survival. The aim of this study was to evaluate the optimal component ratio in the setting of liver transplantation. This is a retrospective chart review of patients who underwent liver transplantation and received at least 500 ml of red blood cells from January 2013 through December 2015. Kernel smoothing analysis determined the proper component ratios to evaluate were a ≥0·85:1 ratio (high) to a ≤0·85:1 ratio (low). Two groups, plasma volume to RBC volume (PL Vol/RBC Vol) and plasma contained in the platelet units added to the plasma calculation [PL + PLT (platelet)] Vol/RBC Vol, were used to evaluate the component ratios. A total of 188 patients were included in the analysis. In the PL Vol/RBC Vol evaluation, a low ratio revealed that 1238 ml (977-1653 ml) (P ratio, in the univariable and multivariable analysis, respectively. In the PL +PLT Vol/RBC Vol evaluation, a low ratio used 734 ml (193-1275) (P = 0·008) and 886 ml (431-1340) (P ratio in the univariable and multivariable analysis, respectively. In patients undergoing liver transplantation, the transfusion of plasma to RBC ratio ≥0·85 was associated with decreased need of RBC transfusions. © 2018 International Society of Blood Transfusion.

Proximity Interactions among Basal Body Components in Trypanosoma brucei Identify Novel Regulators of Basal Body Biogenesis and Inheritance

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Hung Quang Dang

2017-01-01

Full Text Available The basal body shares similar architecture with centrioles in animals and is involved in nucleating flagellar axonemal microtubules in flagellated eukaryotes. The early-branching Trypanosoma brucei possesses a motile flagellum nucleated from the basal body that consists of a mature basal body and an adjacent pro-basal body. Little is known about the basal body proteome and its roles in basal body biogenesis and flagellar axoneme assembly in T. brucei. Here, we report the identification of 14 conserved centriole/basal body protein homologs and 25 trypanosome-specific basal body proteins. These proteins localize to distinct subdomains of the basal body, and several of them form a ring-like structure surrounding the basal body barrel. Functional characterization of representative basal body proteins revealed distinct roles in basal body duplication/separation and flagellar axoneme assembly. Overall, this work identified novel proteins required for basal body duplication and separation and uncovered new functions of conserved basal body proteins in basal body duplication and separation, highlighting an unusual mechanism of basal body biogenesis and inheritance in this early divergent eukaryote.

Effects of the hepatocarcinogen nafenopin, a peroxisome proliferator, on the activities of rat liver glutathione-requiring enzymes and catalase in comparison to the action of phenobarbital.

Science.gov (United States)

Furukawa, K; Numoto, S; Furuya, K; Furukawa, N T; Williams, G M

1985-10-01

The biochemical effects in the livers of male rats of prolonged administration of the experimental hepatocarcinogen nafenopin, a hypolipidemic agent and peroxisome proliferator, were compared to those of another experimental liver carcinogen, phenobarbital, which acts as a neoplasm promoter. Feeding of nafenopin, 0.03 mmol/kg basal diet for up to 24 weeks increased the numbers of hepatic peroxisomes, increased catalase activity, markedly decreased cytosolic glutathione transferase activities toward two substrates, decreased cytosolic glutathione peroxidase activities toward H2O2 and two organic peroxides, and suppressed the age-related increase in gamma-glutamyl transpeptidase activity. In contrast the livers of rats fed an equimolar concentration of phenobarbital displayed increases in cytosolic glutathione transferase activities and enhancement of gamma-glutamyl transpeptidase activity but no changes in glutathione peroxidase activities. There was also an enhancement of catalase activity without apparent increase in peroxisome number. Enzyme kinetic analyses revealed that the cytosolic glutathione transferase activities toward two halogenonitrobenzene substrates were inhibited in the rats fed nafenopin and displayed elevated Km and decreased Vmax. Kinetic studies of glutathione transferase activities in which nafenopin was mixed with normal rat liver cytosols in the assay system revealed competitive type inhibition toward 1-chloro-2,4-dinitrobenzene and a noncompetitive type of inhibition toward 3,4-dichloronitrobenzene. Likewise activities of glutathione peroxidases toward H2O2 and cumene hydroperoxide were suppressed by in vitro addition. Thus the effects of nafenopin and phenobarbital on liver biochemistry were very different. The inhibition of hepatic biotransformation and scavenger systems by nafenopin is suggested to be relevant to its hepatocarcinogenicity.

Cellular regulation of basal and FSH-stimulated cyclic AMP production in irradiated rat testes

International Nuclear Information System (INIS)

Kangasniemi, M.; Kaipia, A.; Toppari, J.; Mali, P.; Huhtaniemi, I.; Parvinen, M.

1990-01-01

Basal and follicle-stimulating hormone (FSH)-stimulated cyclic AMP (cAMP) productions by seminiferous tubular segments from irradiated adult rats were investigated at defined stages of the epithelial cycle when specific spermatogenic cells were low in number. Seven days post-irradiation, depletion of spermatogonia did not influence the basal cAMP production, but FSH response increased in stages II-VIII. Seventeen days post-irradiation when spermatocytes were low in number, there was a small increase in basal cAMP level in stages VII-VIII and FSH-stimulated cAMP production increased in stages VII-XII and XIII-I. At 38 days when pachytene spermatocytes and round spermatids (steps 1-6) were low in number, a decreased basal cAMP production was measured in stages II-VI and IX-XII. FSH-stimulated cAMP output increased in stages VII-XII but decreased in stages II-VI. At 52 days when all spermatids were low in number, basal cAMP levels decreased in all stages of the cycle, whereas FSH response was elevated only in stages VII-XII. All spermatogenic cell types seem to have an effect on cAMP production by the seminiferous tubule in a stage-specific fashion. Germ cells appear to regulate Sertoli cell FSH response in a paracrine way, and a part of cAMP may originate from spermatids stimulated by an unknown FSH-dependent Sertoli cell factor. The FSH-dependent functions may control such phenomena as spermatogonial proliferation, final maturation of spermatids, and onset of meiosis

Characterization of basal hepatic bile flow and the effects of intravenous cholecystokinin on the liver, sphincter, and gallbladder in patients with sphincter of Oddi spasm.

Science.gov (United States)

Krishnamurthy, Gerbail T; Krishnamurthy, Shakuntala; Watson, Randy D

2004-01-01

The major objectives of this project were to establish the pattern of basal hepatic bile flow and the effects of intravenous administration of cholecystokinin on the liver, sphincter of Oddi, and gallbladder, and to identify reliable parameters for the diagnosis of sphincter of Oddi spasm (SOS). Eight women with clinically suspected sphincter of Oddi spasm (SOS group), ten control subjects (control group), and ten patients who had recently received an opioid (opioid group) were selected for quantitative cholescintigraphy with cholecystokinin. Each patient was studied with 111-185 MBq (3-5 mCi) technetium-99m mebrofenin after 6-8 h of fasting. Hepatic phase images were obtained for 60 min, followed by gallbladder phase images for 30 min. During the gallbladder phase, 10 ng/kg octapeptide of cholecystokinin (CCK-8) was infused over 3 min through an infusion pump. Hepatic extraction fraction, excretion half-time, basal hepatic bile flow into the gallbladder, gallbladder ejection fraction, and post-CCK-8 paradoxical filling (>30% of basal counts) were identified. Seven of the patients with SOS were treated with antispasmodics (calcium channel blockers), and one underwent endoscopic sphincterotomy. Mean (+/-SD) hepatic bile entry into the gallbladder (versus GI tract) was widely variable: it was lower in SOS patients (32%+/-31%) than in controls (61%+/-36%) and the opioid group (61%+/-25%), but the difference was not statistically significant. Hepatic extraction fraction, excretion half-time, and pattern of bile flow through both intrahepatic and extrahepatic ducts were normal in all three groups. Gallbladder mean ejection fraction was 9%+/-4% in the opioid group; this was significantly lower (Pgallbladder refluxed into intrahepatic ducts; it reentered the gallbladder after cessation of CCK-8 infusion (paradoxical gallbladder filling) in all eight patients with SOS, but in none of the patients in the other two groups. Mean paradoxical filling was 204% (+/-193%) in the

Axillary basal cell carcinoma in patients with Goltz-Gorlin syndrome: report of basal cell carcinoma in both axilla of a woman with basal cell nevus syndrome and literature review.

Science.gov (United States)

Cohen, Philip R

2014-08-17

Basal cell carcinoma of the axilla, an area that is not usually exposed to the sun, is rare. Individuals with basal cell nevus syndrome, a disorder associated with a mutation in the patch 1 (PTCH1) gene, develop numerous basal cell carcinomas. To describe a woman with basal cell nevus syndrome who developed a pigmented basal cell carcinoma in each of her axilla and to review the features of axillary basal cell carcinoma patients with Goltz-Gorlin syndrome. Pubmed was used to search the following terms: axillary basal cell carcinoma and basal cell nevus syndrome. The papers and their citations were evaluated. Basal cell nevus syndrome patients with basal cell carcinoma of the axilla were observed in two women; this represents 2.5% (2 of 79) of the patients with axillary basal cell carcinoma. Both women had pigmented tumors that were histologically nonaggressive. The cancers did not recur after curettage or excision. Basal cell carcinoma of the axilla has only been described in 79 individuals; two of the patients were women with pigmented tumors who had basal cell nevus syndrome. Similar to other patients with axillary basal cell carcinoma, the tumors were histologically nonaggressive and did not recur following treatment. Whether PTCH1 gene mutation predisposes basal cell nevus patients to develop axillary basal cell carcinomas remains to be determined.

Clinical efficacy of the liver scintigram

International Nuclear Information System (INIS)

Katsuyama, Naofumi; Kawakami, Kenji; Machida, Kikuo.

1983-01-01

Liver scintigrams of 406 cases were interpreted by 11 physicians. The ratios of the interpretation of the physiologically decreased activity areas in the liver scintigrams were 27% in the regions of the porta hepatis, 23% in the gall bladder fossa, 20% in the inferior vena cava, 7% in the renal impression, 2% in the portal vein, 2% in the rib impression and 2% in others. The cases having space occupying lesions showed decreased ratio of the interpretation of the physiologically decreased activity areas, as compared with other groups. Cases of the liver cirrhosis showed decreased ratio in the region of inferior vena cava. Cases using Anger camera demonstrated more increased ratio than cases using a scanner. The 11 physicians could be devided for two groups. One group showed high ratios of the interpretation of the physiologically decreased activity areas, and another group showed very low ratio, because of the different interpretation about the physiologically decreased activity areas in the two groups. In our cases, a very few cases showing decreased activity on the liver image were false positive or false negative for diagnosis of space occupying lesions. (author)

Effects of dietary probiotic supplementation on LXRα and CYP7α1 gene expression, liver enzyme activities and fat metabolism in ducks.

Science.gov (United States)

Huang, Z; Mu, C; Chen, Y; Zhu, Z; Chen, C; Lan, L; Xu, Q; Zhao, W; Chen, G

2015-04-01

1. The objective of this study was to investigate the effects of dietary probiotic supplementation on liver X receptor alpha (LXRα) and cholesterol 7α-hydroxylase (CYP7α1) mRNA levels, protein enzymatic activities and fat metabolism in Cherry Valley Pekin ducks. 2. A total of 750 one-day-old Cherry Valley Pekin ducks were randomly divided into 5 groups with three replicates of 50 ducks each in a completely randomised experiment. Each group was fed on a basal diet supplemented with 0, 500, 1000, 1500 or 2000 mg probiotics/kg. 3. Body rate and feed conversion ratio were highest and abdominal subcutaneous fat % was lowest at 1000 mg probiotic/kg. 4. The mRNA levels of LXRα and CYP7α1 in liver tissue was estimated by RT-PCR; serum triglyceride (TG) and total cholesterol (TC) concentrations were measured by ELISA. 5. The expression levels and enzyme activity of LXRα and CYP7α1 increased in conjunction with decreases in TG and TC concentrations following probiotic supplementation to a maximum at 1000 mg probiotics/kg and decreased thereafter. 6. It is concluded that dietary probiotics can enhance LXRα and CYP7α1 enzyme activities in the liver and reduce lipid concentrations and fat deposition in ducks.

Effects of aging on basal fat oxidation in obese humans

DEFF Research Database (Denmark)

Solomon, Thomas; Marchetti, Christine M; Krishnan, Raj K

2008-01-01

)max) were measured in 10 older (age, 60 +/- 4 years; mean +/- SEM) and 10 younger (age, 35 +/- 4 years) body mass index-matched, obese, normal glucose-tolerant individuals. Fasting blood samples were also collected. Older subjects had slightly elevated fat mass (32.2 +/- 7.1 vs 36.5 +/- 6.7 kg, P......Basal fat oxidation decreases with age. In obesity, it is not known whether this age-related process occurs independently of changes in body composition and insulin sensitivity. Therefore, body composition, resting energy expenditure, basal substrate oxidation, and maximal oxygen consumption (VO(2...... is responsible for reduced basal fat oxidation and maximal oxidative capacity in older obese individuals, independent of changes in insulin resistance, body mass, and abdominal fat. This indicates that age, in addition to obesity, is an independent risk factor for weight gain and for the metabolic complications...

Assessment of adrenal function in liver diseases

Directory of Open Access Journals (Sweden)

Sandeep Kharb

2013-01-01

Full Text Available Background: In recent times, there are reports of adrenal dysfunction in whole spectrum of liver disease. Adrenal insufficiency (AI has been shown to correlate with progression of liver disease. Hence this study was conducted to assess adrenal function in subjects with acute liver disease (ALD, chronic liver disease (CLD and post liver transplantation (LT. Material and Methods: This study included 25 healthy controls, 25 patients of ALD, 20 subjects of CLD with Child-Pugh stage A (CLD-1 and 30 with Child-Pugh stage B or C (CLD-2, and 10 subjects with LT. All subjects were assessed clinically, biochemically and for adrenal functions. Results: AI was present in 9 (34.6% patients with ALD, 20 (40% patients with CLD and 4 (40% in subjects with LT. AI was more common in CLD-2 (18 patients - 60% than CLD-1 (2 patients - 10%. All patients with chronic liver disease had significantly lower basal cortisol (8.8±4.8, P=0.01, stimulated cortisol (18.2±6.3, P <0.00001 and incremental cortisol (9.4±4.6, P <0.00001 as compared to controls. There was increase in percentage of subjects with adrenal dysfunction with progression of liver disease as assessed by Child-Pugh staging. AI was predicted by lower levels of serum protein, serum albumin, total cholesterol and HDL cholesterol and higher levels of serum bilirubin and INR. Adrenal functions showed recovery following liver transplantation. Conclusions: AI forms important part of spectrum of acute and chronic liver disease. Deterioration of synthetic functions of liver disease predicts presence of AI, and these patients should be evaluated for adrenal dysfunction periodically.

Cerebral blood flow and metabolism in patients with aphasia due to basal ganglionic lesion

International Nuclear Information System (INIS)

Kitamura, Shin; Kato, Toshiaki; Ujike, Takashi; Kuroki, Soemu; Terashi, Akiro

1987-01-01

Cerebral blood flow and metabolism in right handed eight patients with subcortical lesion and aphasia were measured to investigate the correlation between aphasia and functional changes in cerebral blood flow (CBF) and cerebral oxygen consumption (CMRO 2 ) in the cortex and the basal ganglionic region. All patients had no lesion in the cortex, but in the basal ganglionic region (putamen, caudate nucleus, internal capsule, and periventricular white matter) on CT images. Patients with bilateral lesion were excluded in this study. Six patients with cerebral infarction in the left basal ganglionic region and two patients with the left putammal hemorrhage were examined. Five patients had non fluent Broca's type speech, two patients had poor comprehension, fluent Wernicke-type speech and one patient was globally aphasic. CBF, CMRO 2 , and oxygen extraction fraction were measured by the positron emission tomography using 15 O 2 , C 15 O 2 inhalation technique. In addition to reduction of CBF and CMRO 2 in the basal ganglionic region, CBF and CMRO 2 decreased in the left frontal cortex especially posterior part in four patients with Broca's aphasia. In two patients with Wernicke type aphasia, CBF and CMRO 2 decreased in the basal ganglionic region and the left temporal cortex. In a globally aphasic patient, marked reduction of CBF and CMRO 2 was observed in the left frontal and temporal cortex, in addition to the basal ganglionic region. These results suggest that dysfunction of cortex as well as that of basal ganglionic region might be related to the occurence of aphasia. However, in one patient with Broca's ahasia, CBF and CMRO 2 were preserved in the cortex and metabolic reduction was observed in only basal ganglia. This case indicates the relation between basal ganglionic lesion and the occurrence of aphasia. These results suggest that measurements of cerebral blood flow and metabolism were necessary to study the responsible lesion for aphasia. (author)

Fatty Liver

International Nuclear Information System (INIS)

Filippone, A.; Digiovandomenico, V.; Digiovandomenico, E.; Genovesi, N.; Bonomo, L.

1991-01-01

The authors report their experience with the combined use of US and CT in the study of diffuse and subtotal fatty infiltration of the liver. An apparent disagreement was initially found between the two examinations in the study of fatty infiltration. Fifty-five patients were studied with US and CT of the upper abdomen, as suggested by clinics. US showed normal liver echogenicity in 30 patients and diffuse increased echogenicity (bright liver) in 25 cases. In 5 patients with bright liver, US demonstrated a solitary hypoechoic area, appearing as a 'skip area', in the quadrate lobe. In 2 patients with bright liver, the hypoechoic area was seen in the right lobe and exhibited no typical US features of 'Skip area'. Bright liver was quantified by measuring CT density of both liver and spleen. The relative attenuation values of spleen and liver were compared on plain and enhanced CT scans. In 5 cases with a hypoechoic area in the right lobe, CT findings were suggestive of hemangioma. A good correlation was found between broght liver and CT attenuation values, which decrease with increasing fat content of the liver. Moreover, CT attenuation values confirmed US findings in the study of typical 'skip area', by demonstrating normal density - which suggests that CT can characterize normal tissue in atypical 'skip area'

A High-Protein Diet Reduces Weight Gain, Decreases Food Intake, Decreases Liver Fat Deposition, and Improves Markers of Muscle Metabolism in Obese Zucker Rats

Directory of Open Access Journals (Sweden)

William W. French

2017-06-01

Full Text Available A primary factor in controlling and preventing obesity is through dietary manipulation. Diets higher in protein have been shown to improve body composition and metabolic health during weight loss. The objective of this study was to examine the effects of a high-protein diet versus a moderate-protein diet on muscle, liver and fat metabolism and glucose regulation using the obese Zucker rat. Twelve-week old, male, Zucker (fa/fa and lean control (Fa/fa rats were randomly assigned to either a high-protein (40% energy or moderate-protein (20% energy diet for 12 weeks, with a total of four groups: lean 20% protein (L20; n = 8, lean 40% protein (L40; n = 10, obese 20% protein (O20; n = 8, and obese 40% protein (O40; n = 10. At the end of 12 weeks, animals were fasted and euthanized. There was no difference in food intake between L20 and L40. O40 rats gained less weight and had lower food intake (p < 0.05 compared to O20. O40 rats had lower liver weight (p < 0.05 compared to O20. However, O40 rats had higher orexin (p < 0.05 levels compared to L20, L40 and O20. Rats in the L40 and O40 groups had less liver and muscle lipid deposition compared to L20 and L40 diet rats, respectively. O40 had decreased skeletal muscle mechanistic target of rapamycin complex 1 (mTORC1 phosphorylation and peroxisome proliferator-activated receptor gamma (PPARγ mRNA expression compared to O20 (p < 0.05, with no difference in 5′ AMP-activated protein kinase (AMPK, eukaryotic translation initiation factor 4E binding protein 1 (4EBP1, protein kinase B (Akt or p70 ribosomal S6 kinase (p70S6K phosphorylation. The data suggest that high-protein diets have the potential to reduce weight gain and alter metabolism, possibly through regulation of an mTORC1-dependent pathway in skeletal muscle.

Basal ganglia lesions in children and adults

Energy Technology Data Exchange (ETDEWEB)

Bekiesinska-Figatowska, Monika, E-mail: m.figatowska@mp.pl [Department of Diagnostic Imaging, Institute of Mother and Child, ul. Kasprzaka 17a, 01-211 Warsaw (Poland); Mierzewska, Hanna, E-mail: h.mierzewska@gmail.com [Department of Neurology of Children and Adolescents, Institute of Mother and Child, ul. Kasprzaka 17a, 01-211 Warsaw (Poland); Jurkiewicz, Elżbieta, E-mail: e-jurkiewicz@o2.pl [Department of Diagnostic Imaging, Children' s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw (Poland)

2013-05-15

The term “basal ganglia” refers to caudate and lentiform nuclei, the latter composed of putamen and globus pallidus, substantia nigra and subthalamic nuclei and these deep gray matter structures belong to the extrapyramidal system. Many diseases may present as basal ganglia abnormalities. Magnetic resonance imaging (MRI) and computed tomography (CT) – to a lesser degree – allow for detection of basal ganglia injury. In many cases, MRI alone does not usually allow to establish diagnosis but together with the knowledge of age and circumstances of onset and clinical course of the disease is a powerful tool of differential diagnosis. The lesions may be unilateral: in Rassmussen encephalitis, diabetes with hemichorea/hemiballism and infarction or – more frequently – bilateral in many pathologic conditions. Restricted diffusion is attributable to infarction, acute hypoxic–ischemic injury, hypoglycemia, Leigh disease, encephalitis and CJD. Contrast enhancement may be seen in cases of infarction and encephalitis. T1-hyperintensity of the lesions is uncommon and may be observed unilaterally in case of hemichorea/hemiballism and bilaterally in acute asphyxia in term newborns, in hypoglycemia, NF1, Fahr disease and manganese intoxication. Decreased signal intensity on GRE/T2*-weighted images and/or SWI indicating iron, calcium or hemosiderin depositions is observed in panthotenate kinase-associated neurodegeneration, Parkinson variant of multiple system atrophy, Fahr disease (and other calcifications) as well as with the advancing age. There are a few papers in the literature reviewing basal ganglia lesions. The authors present a more detailed review with rich iconography from the own archive.

Basal ganglia lesions in children and adults

International Nuclear Information System (INIS)

Bekiesinska-Figatowska, Monika; Mierzewska, Hanna; Jurkiewicz, Elżbieta

2013-01-01

The term “basal ganglia” refers to caudate and lentiform nuclei, the latter composed of putamen and globus pallidus, substantia nigra and subthalamic nuclei and these deep gray matter structures belong to the extrapyramidal system. Many diseases may present as basal ganglia abnormalities. Magnetic resonance imaging (MRI) and computed tomography (CT) – to a lesser degree – allow for detection of basal ganglia injury. In many cases, MRI alone does not usually allow to establish diagnosis but together with the knowledge of age and circumstances of onset and clinical course of the disease is a powerful tool of differential diagnosis. The lesions may be unilateral: in Rassmussen encephalitis, diabetes with hemichorea/hemiballism and infarction or – more frequently – bilateral in many pathologic conditions. Restricted diffusion is attributable to infarction, acute hypoxic–ischemic injury, hypoglycemia, Leigh disease, encephalitis and CJD. Contrast enhancement may be seen in cases of infarction and encephalitis. T1-hyperintensity of the lesions is uncommon and may be observed unilaterally in case of hemichorea/hemiballism and bilaterally in acute asphyxia in term newborns, in hypoglycemia, NF1, Fahr disease and manganese intoxication. Decreased signal intensity on GRE/T2*-weighted images and/or SWI indicating iron, calcium or hemosiderin depositions is observed in panthotenate kinase-associated neurodegeneration, Parkinson variant of multiple system atrophy, Fahr disease (and other calcifications) as well as with the advancing age. There are a few papers in the literature reviewing basal ganglia lesions. The authors present a more detailed review with rich iconography from the own archive

A longitudinal study of basal cortisol in infants : Intra-individual variability, circadian rhythm and developmental trends

NARCIS (Netherlands)

de Weerth, C.; Van Geert, P. L. C.

2002-01-01

Mothers with normally developing babies were visited in their homes during 13 consecutive weeks, when the babies were around 5-8 months of age. Basal salival cortisol measures were taken for both the baby and the mother on arrival. The infants' basal cortisol decreased linearly with age, was

Modest alcohol consumption decreases the risk of fatty liver disease or nonalcoholic fatty liver disease: a Meta-analysis

Directory of Open Access Journals (Sweden)

Guo-li CAO

2016-08-01

Full Text Available Objective 　To evaluate the association between modest alcohol consumption and the risk of fatty liver disease (FLD or nonalcoholic fatty liver disease (NAFLD. Methods 　PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI, Wanfang Digital Journal Full-text Database, and database for Chinese Technical Periodicals (VIP till Nov. 2015 were searched for the studies in evaluating the effect of alcohol consumption on FLD or NAFLD. The quality assessment of included studies was performed according to the combined evaluation for cross-sectional studies and Newcastle-Ottawa scale (NOS for cohort studies. A meta-analysis was performed using Stata12.0 software. Results 　A total of 16 studies including 13 cross-sectional studies, 2 cross-sectional following longitudinal studies, and 1 cohort study with 76 967 participants were selected finally. The results of Meta-analysis were as follows. Minimal and light alcohol consumptions reduced the risk for FLD or NAFLD by 17% and 27%, respectively, and moderate alcohol consumption was marginally associated with decreased risk for FLD or NAFLD. The results of subgroup analysis by gender showed that (1 Minimal and light alcohol consumptions reduced the risk of FLD or NAFLD by 29% and 33%, respectively, but moderate alcohol consumption was not statistically significant in reducing the risk of FLD or NAFLD in females compared with controls; (2 Light alcohol consumption reduced the risk of FLD or NAFLD by 23%, but minimal and moderate alcohol consumptions were not statistically significant in reducing the risk of FLD or NAFLD in male compared with controls; (3 Light and moderate alcohol consumptions in Asian males reduced the risk of FLD or NAFLD by 29.7% and 30.3%, respectively. Conclusions 　Modest alcohol consumptions may not increase the risk of FLD or NAFLD. Inversely, minimal and light alcohol consumptions in female reduce the risk of FLD or NAFLD remarkably

α7-nAChR Knockout Mice Decreases Biliary Hyperplasia and Liver Fibrosis in Cholestatic Bile-Duct Ligated Mice.

Science.gov (United States)

Ehrlich, Laurent; O'Brien, April; Hall, Chad; White, Tori; Chen, Lixian; Wu, Nan; Venter, Julie; Scrushy, Marinda; Mubarak, Muhammad; Meng, Fanyin; Dostal, David; Wu, Chaodong; Lairmore, Terry C; Alpini, Gianfranco; Glaser, Shannon

2018-03-26

α7-nAChR is a nicotinic acetylcholine receptor (specifically expressed on hepatic stellate cells, Kupffer cells, and cholangiocytes) that regulates inflammation and apoptosis in the liver. Thus, targeting α7-nAChR may be therapeutic in biliary diseases. Bile-duct ligation (BDL) was performed on wild-type (WT) and α7-nAChR-/- mice. We first evaluated the expression of α7-nAChR by immunohistochemistry (IHC) in liver sections. IHC was also performed to assess intrahepatic bile-duct mass (IBDM), and Sirius Red staining was performed to quantify the amount of collagen deposition. Immunofluorescence was performed to assess co-localization of α7-nAChR with bile ducts (co-stained with CK-19) and hepatic stellate cells (HSCs) (co-stained with desmin). The mRNA expression of α7-nAChR, Ki67/PCNA (proliferation), fibrosis genes (TGF-β1, Fibronectin-1, Col1α1, and α-SMA), and inflammatory markers (IL-6, IL-1β, and TNFα) was measured by real-time PCR. Biliary TGF-β1 and hepatic CD68 (Kupffer cell marker) expression was assessed using IHC. α7-nAChR immunoreactivity was observed in both bile ducts and HSCs and increased following BDL. α7-nAChR-/- BDL mice exhibited decreased: (i) bile duct mass, liver fibrosis, and inflammation; and (ii) immunoreactivity of TGF-1 as well as expression of fibrosis genes compared to WT BDL mice. α7-nAChR activation triggers biliary proliferation and liver fibrosis and may be a therapeutic target in managing extra-hepatic biliary obstruction.

Learning Reward Uncertainty in the Basal Ganglia.

Directory of Open Access Journals (Sweden)

John G Mikhael

2016-09-01

Full Text Available Learning the reliability of different sources of rewards is critical for making optimal choices. However, despite the existence of detailed theory describing how the expected reward is learned in the basal ganglia, it is not known how reward uncertainty is estimated in these circuits. This paper presents a class of models that encode both the mean reward and the spread of the rewards, the former in the difference between the synaptic weights of D1 and D2 neurons, and the latter in their sum. In the models, the tendency to seek (or avoid options with variable reward can be controlled by increasing (or decreasing the tonic level of dopamine. The models are consistent with the physiology of and synaptic plasticity in the basal ganglia, they explain the effects of dopaminergic manipulations on choices involving risks, and they make multiple experimental predictions.

The Evaluation of Basal Respiration for Various Soil Textures in Ecologically Sensitive Area

Science.gov (United States)

Huličová, P.; Kotorová, D.; Fazekašová, D.; Hynšt, J.

2017-10-01

The present contribution was focused on monitoring changes in the soil basal respiration in different textures of soil in the dry polder Beša. The research was conducted between 2012 and 2014 on soil type Fluvisol locations on three soil textures: clay - loam soil, clayey soil and clay soil in three soil depths. The basal respiration (BR) has been determine by soil CO2 production measuring from incubated soil samples in serum bottles in laboratory condition. Release Co2 has been analysed by gas chromatography. Content of clay particles were in the range 52.18 % to 81.31%, indicating the high difference between the minimum and maximum content. By using of multiple LSD-test we recorded statistically significant impact of clay on basal respiration. Results confirm the values of basal respiration with the depth of the soil profile decreased.

Characterization of basal hepatic bile flow and the effects of intravenous cholecystokinin on the liver, sphincter, and gallbladder in patients with sphincter of Oddi spasm

International Nuclear Information System (INIS)

Krishnamurthy, Gerbail T.; Krishnamurthy, Shakuntala; Watson, Randy D.

2004-01-01

The major objectives of this project were to establish the pattern of basal hepatic bile flow and the effects of intravenous administration of cholecystokinin on the liver, sphincter of Oddi, and gallbladder, and to identify reliable parameters for the diagnosis of sphincter of Oddi spasm (SOS). Eight women with clinically suspected sphincter of Oddi spasm (SOS group), ten control subjects (control group), and ten patients who had recently received an opioid (opioid group) were selected for quantitative cholescintigraphy with cholecystokinin. Each patient was studied with 111-185 MBq (3-5 mCi) technetium-99m mebrofenin after 6-8 h of fasting. Hepatic phase images were obtained for 60 min, followed by gallbladder phase images for 30 min. During the gallbladder phase, 10 ng/kg octapeptide of cholecystokinin (CCK-8) was infused over 3 min through an infusion pump. Hepatic extraction fraction, excretion half-time, basal hepatic bile flow into the gallbladder, gallbladder ejection fraction, and post-CCK-8 paradoxical filling (>30% of basal counts) were identified. Seven of the patients with SOS were treated with antispasmodics (calcium channel blockers), and one underwent endoscopic sphincterotomy. Mean (±SD) hepatic bile entry into the gallbladder (versus GI tract) was widely variable: it was lower in SOS patients (32%±31%) than in controls (61%±36%) and the opioid group (61%±25%), but the difference was not statistically significant. Hepatic extraction fraction, excretion half-time, and pattern of bile flow through both intrahepatic and extrahepatic ducts were normal in all three groups. Gallbladder mean ejection fraction was 9%±4% in the opioid group; this was significantly lower (P<0.0001) than the values in the control group (54%±18%) and the SOS group (48%±29%). Almost all of the bile emptied from the gallbladder refluxed into intrahepatic ducts; it reentered the gallbladder after cessation of CCK-8 infusion (paradoxical gallbladder filling) in all eight

Characterization of basal hepatic bile flow and the effects of intravenous cholecystokinin on the liver, sphincter, and gallbladder in patients with sphincter of Oddi spasm

Energy Technology Data Exchange (ETDEWEB)

Krishnamurthy, Gerbail T.; Krishnamurthy, Shakuntala [Department of Nuclear Medicine, Tuality Community Hospital, 335 SE 8th Avenue, OR 97123, Hillsboro (United States); Watson, Randy D. [Department of Gastroenterology, Tuality Community Hospital, Hillsboro, OR (United States)

2004-01-01

The major objectives of this project were to establish the pattern of basal hepatic bile flow and the effects of intravenous administration of cholecystokinin on the liver, sphincter of Oddi, and gallbladder, and to identify reliable parameters for the diagnosis of sphincter of Oddi spasm (SOS). Eight women with clinically suspected sphincter of Oddi spasm (SOS group), ten control subjects (control group), and ten patients who had recently received an opioid (opioid group) were selected for quantitative cholescintigraphy with cholecystokinin. Each patient was studied with 111-185 MBq (3-5 mCi) technetium-99m mebrofenin after 6-8 h of fasting. Hepatic phase images were obtained for 60 min, followed by gallbladder phase images for 30 min. During the gallbladder phase, 10 ng/kg octapeptide of cholecystokinin (CCK-8) was infused over 3 min through an infusion pump. Hepatic extraction fraction, excretion half-time, basal hepatic bile flow into the gallbladder, gallbladder ejection fraction, and post-CCK-8 paradoxical filling (>30% of basal counts) were identified. Seven of the patients with SOS were treated with antispasmodics (calcium channel blockers), and one underwent endoscopic sphincterotomy. Mean ({+-}SD) hepatic bile entry into the gallbladder (versus GI tract) was widely variable: it was lower in SOS patients (32%{+-}31%) than in controls (61%{+-}36%) and the opioid group (61%{+-}25%), but the difference was not statistically significant. Hepatic extraction fraction, excretion half-time, and pattern of bile flow through both intrahepatic and extrahepatic ducts were normal in all three groups. Gallbladder mean ejection fraction was 9%{+-}4% in the opioid group; this was significantly lower (P<0.0001) than the values in the control group (54%{+-}18%) and the SOS group (48%{+-}29%). Almost all of the bile emptied from the gallbladder refluxed into intrahepatic ducts; it reentered the gallbladder after cessation of CCK-8 infusion (paradoxical gallbladder filling

Bile acids for liver-transplanted patients

DEFF Research Database (Denmark)

Poropat, Goran; Giljaca, Vanja; Stimac, Davor

2010-01-01

Liver transplantation has become a widely accepted form of treatment for numerous end-stage liver diseases. Bile acids may decrease allograft rejection after liver transplantation by changing the expression of major histocompatibility complex class molecules in bile duct epithelium and central vein...

Functional neuroanatomy of the basal ganglia.

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Lanciego, José L; Luquin, Natasha; Obeso, José A

2012-12-01

The "basal ganglia" refers to a group of subcortical nuclei responsible primarily for motor control, as well as other roles such as motor learning, executive functions and behaviors, and emotions. Proposed more than two decades ago, the classical basal ganglia model shows how information flows through the basal ganglia back to the cortex through two pathways with opposing effects for the proper execution of movement. Although much of the model has remained, the model has been modified and amplified with the emergence of new data. Furthermore, parallel circuits subserve the other functions of the basal ganglia engaging associative and limbic territories. Disruption of the basal ganglia network forms the basis for several movement disorders. This article provides a comprehensive account of basal ganglia functional anatomy and chemistry and the major pathophysiological changes underlying disorders of movement. We try to answer three key questions related to the basal ganglia, as follows: What are the basal ganglia? What are they made of? How do they work? Some insight on the canonical basal ganglia model is provided, together with a selection of paradoxes and some views over the horizon in the field.

MiRNA-21 Expression Decreases from Primary Tumors to Liver Metastases in Colorectal Carcinoma.

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Fabian Feiersinger

Full Text Available Metastasis is the major cause of death in colorectal cancer patients. Expression of certain miRNAs in the primary tumors has been shown to be associated with progression of colorectal cancer and the initiation of metastasis. In this study, we compared miRNA expression in primary colorectal cancer and corresponding liver metastases in order to get an idea of the oncogenic importance of the miRNAs in established metastases.We analyzed the expression of miRNA-21, miRNA-31 and miRNA-373 in corresponding formalin-fixed paraffin-embedded (FFPE tissue samples of primary colorectal cancer, liver metastasis and healthy tissues of 29 patients by quantitative real-time PCR.All three miRNAs were significantly up-regulated in the primary tumor tissues as compared to healthy colon mucosa of the respective patients (p < 0.01. MiRNA-21 and miRNA-31 were also higher expressed in liver metastases as compared to healthy liver tissues (p < 0.01. No significant difference of expression of miRNA-31 and miRNA-373 was observed between primary tumors and metastases. Of note, miRNA-21 expression was significantly reduced in liver metastases as compared to the primary colorectal tumors (p < 0.01.In the context of previous studies demonstrating increased miRNA-21 expression in metastatic primary tumors, our findings raise the question whether miRNA-21 might be involved in the initiation but not in the perpetuation and growth of metastases.

Liver, but not muscle, has an entrainable metabolic memory.

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Sheng-Song Chen

Full Text Available Hyperglycemia in the hospitalized setting is common, especially in patients that receive nutritional support either continuously or intermittently. As the liver and muscle are the major sites of glucose disposal, we hypothesized their metabolic adaptations are sensitive to the pattern of nutrient delivery. Chronically catheterized, well-controlled depancreatized dogs were placed on one of three isocaloric diets: regular chow diet once daily (Chow or a simple nutrient diet (ND that was given either once daily (ND-4 or infused continuously (ND-C. Intraportal insulin was infused to maintain euglycemia. After 5 days net hepatic (NHGU and muscle (MGU glucose uptake and oxidation were assessed at euglycemia (120 mg/dl and hyperglycemia (200 mg/dl in the presence of basal insulin. While hyperglycemia increased both NHGU and MGU in Chow, NHGU was amplified in both groups receiving ND. The increase was associated with enhanced activation of glycogen synthase, glucose oxidation and suppression of pyruvate dehydrogenase kinase-4 (PDK-4. Accelerated glucose-dependent muscle glucose uptake was only evident with ND-C. This was associated with a decrease in PDK-4 expression and an increase in AMP-activated protein kinase (AMPK phosphorylation. Interestingly, ND-C markedly increased hepatic FGF-21 expression. Thus, augmentation of carbohydrate disposal in the liver, as opposed to the muscle, is not dependent on the pattern of nutrient delivery.

Functional validation of GWAS gene candidates for abnormal liver function during zebrafish liver development

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Leah Y. Liu

2013-09-01

Genome-wide association studies (GWAS have revealed numerous associations between many phenotypes and gene candidates. Frequently, however, further elucidation of gene function has not been achieved. A recent GWAS identified 69 candidate genes associated with elevated liver enzyme concentrations, which are clinical markers of liver disease. To investigate the role of these genes in liver homeostasis, we narrowed down this list to 12 genes based on zebrafish orthology, zebrafish liver expression and disease correlation. To assess the function of gene candidates during liver development, we assayed hepatic progenitors at 48 hours post fertilization (hpf and hepatocytes at 72 hpf using in situ hybridization following morpholino knockdown in zebrafish embryos. Knockdown of three genes (pnpla3, pklr and mapk10 decreased expression of hepatic progenitor cells, whereas knockdown of eight genes (pnpla3, cpn1, trib1, fads2, slc2a2, pklr, mapk10 and samm50 decreased cell-specific hepatocyte expression. We then induced liver injury in zebrafish embryos using acetaminophen exposure and observed changes in liver toxicity incidence in morphants. Prioritization of GWAS candidates and morpholino knockdown expedites the study of newly identified genes impacting liver development and represents a feasible method for initial assessment of candidate genes to instruct further mechanistic analyses. Our analysis can be extended to GWAS for additional disease-associated phenotypes.

Basal hyperaemia is the primary abnormality of perfusion in Takotsubo cardiomyopathy

DEFF Research Database (Denmark)

Christensen, Thomas Emil; Ahtarovski, Kiril Aleksov; Bang, Lia Evi

2015-01-01

AIMS: Takotsubo cardiomyopathy (TTC) is characterized by acute completely reversible regional left ventricle (LV) akinesia and decreased tracer uptake in the akinetic region on semi-quantitative perfusion imaging. The latter may be due to normoperfusion of the akinetic mid/apical area and basal...... hyperperfusion. Our aim was to examine abnormalities of perfusion in TTC, and we hypothesized that basal hyperperfusion is the primary perfusion abnormality in the acute state. METHOD AND RESULTS: Twenty-five patients were diagnosed with TTC due to (i) acute onset of symptoms, (ii) typical apical ballooning......-on follow-up. Patients initially had severe heart failure, mid/apical oedema but no infarction, and a rise in cardiac biomarkers. On initial perfusion PET imaging, eight patients appeared to have normal, whereas 17 patients had impaired LV perfusion. In the latter, flow in the basal region was increased...

Evaluation of turmeric (Curcuma longa) effect on biochemical and pathological parameters of liver and kidney in chicken aflatoxicosis.

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Gholami-Ahangaran, Majid; Rangsaz, Nader; Azizi, Shahrzad

2016-01-01

Aflatoxins as potent mycotoxins can influence vital parameters in chickens. Turmeric was used in decreasing toxic effect of mycotoxins on vital organs, traditionally. The study compared the protective effect of turmeric and Mycoad(TR) in broilers exposed to aflatoxin. Chickens (270) were divided into six groups. The chickens were fed a basal diet, turmeric extract (5 mg/kg diet), Mycoad(TR) (25 mg/kg diet), productive aflatoxin (3 mg/kg diet), aflatoxin plus turmeric extract (3 versus 5 mg/kg diet), and aflatoxin plus Mycoad(TR) (3 versus 25 mg/kg diet) in basal diet. At 28 d old, we determined plasma concentration of total protein, albumin, triglyceride, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), calcium, potassium, phosphorous, uric acid, aspartate transferase (AST), and alanine aminotransferase (ALT). Furthermore, liver and kidney were sampled for pathological examination. Chickens fed turmeric with aflatoxin had significant lower ALT, AST, and uric acid than chickens fed aflatoxin (11.4 ± 0.79, 228 ± 9, and 6 ± 0.4 versus 17.2 ± 1.7, 283 ± 5, and 7.7 ± 0.1) whereas, total protein, calcium, and HDL values in chickens fed aflatoxin plus turmeric increased significantly (2.66 ± 0.16, 8.4 ± 0.2, and 920 ± 4.1 versus 1.7 ± 0.17, 7 ± 0.2, and 690 ± 4.8). Pathological examination revealed severe congestion, degeneration, and necrosis in liver and kidney in chickens that received aflatoxin. The study showed that turmeric may provide protection against the toxic effects of aflatoxin on liver and kidney.

Carrot Juice Administration Decreases Liver Stearoyl-CoA Desaturase 1 and Improves Docosahexaenoic Acid Levels, but Not Steatosis in High Fructose Diet-Fed Weanling Wistar Rats.

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Mahesh, Malleswarapu; Bharathi, Munugala; Reddy, Mooli Raja Gopal; Kumar, Manchiryala Sravan; Putcha, Uday Kumar; Vajreswari, Ayyalasomayajula; Jeyakumar, Shanmugam M

2016-09-01

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent liver diseases associated with an altered lifestyle, besides genetic factors. The control and management of NAFLD mostly depend on lifestyle modifications, due to the lack of a specific therapeutic approach. In this context, we assessed the effect of carrot juice on the development of high fructose-induced hepatic steatosis. For this purpose, male weanling Wistar rats were divided into 4 groups, fed either a control (Con) or high fructose (HFr) diet of AIN93G composition, with or without carrot juice (CJ) for 8 weeks. At the end of the experimental period, plasma biochemical markers, such as triglycerides, alanine aminotransferase, and β-hydroxy butyrate levels were comparable among the 4 groups. Although, the liver injury marker, aspartate aminotransferase, levels in plasma showed a reduction, hepatic triglycerides levels were not significantly reduced by carrot juice ingestion in the HFr diet-fed rats (HFr-CJ). On the other hand, the key triglyceride synthesis pathway enzyme, hepatic stearoyl-CoA desaturase 1 (SCD1), expression at mRNA level was augmented by carrot juice ingestion, while their protein levels showed a significant reduction, which corroborated with decreased monounsaturated fatty acids (MUFA), particularly palmitoleic (C16:1) and oleic (C18:1) acids. Notably, it also improved the long chain n-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA; C22:6) content of the liver in HFr-CJ. In conclusion, carrot juice ingestion decreased the SCD1-mediated production of MUFA and improved DHA levels in liver, under high fructose diet-fed conditions. However, these changes did not significantly lower the hepatic triglyceride levels.

Coffee and Liver Disease.

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Wadhawan, Manav; Anand, Anil C

2016-03-01

Coffee is the most popular beverage in the world. Consumption of coffee has been shown to benefit health in general, and liver health in particular. This article reviews the effects of coffee intake on development and progression of liver disease due to various causes. We also describe the putative mechanisms by which coffee exerts the protective effect. The clinical evidence of benefit of coffee consumption in Hepatitis B and C, as well as nonalcoholic fatty liver disease and alcoholic liver disease, has also been presented. Coffee consumption is associated with improvement in liver enzymes (ALT, AST, and GGTP), especially in individuals with risk for liver disease. Coffee intake more than 2 cups per day in patients with preexisting liver disease has been shown to be associated with lower incidence of fibrosis and cirrhosis, lower hepatocellular carcinoma rates, as well as decreased mortality.

The human airway epithelial basal cell transcriptome.

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Neil R Hackett

2011-05-01

Full Text Available The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population.Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the "human airway basal cell signature" as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels.The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of the stem/progenitor cells of the human airway epithelium.

High basal metabolic rate does not elevate oxidative stress during reproduction in laboratory mice.

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Brzęk, Paweł; Książek, Aneta; Ołdakowski, Łukasz; Konarzewski, Marek

2014-05-01

Increased oxidative stress (OS) has been suggested as a physiological cost of reproduction. However, previous studies reported ambiguous results, with some even showing a reduction of oxidative damage during reproduction. We tested whether the link between reproduction and OS is mediated by basal metabolic rate (BMR), which has been hypothesized to affect both the rate of radical oxygen species production and antioxidative capacity. We studied the effect of reproduction on OS in females of laboratory mice divergently selected for high (H-BMR) and low (L-BMR) BMR, previously shown to differ with respect to parental investment. Non-reproducing L-BMR females showed higher oxidative damage to lipids (quantified as the level of malondialdehyde in internal organ tissues) and DNA (quantified as the level of 8-oxodG in blood serum) than H-BMR females. Reproduction did not affect oxidative damage to lipids in either line; however, it reduced damage to DNA in L-BMR females. Reproduction increased catalase activity in liver (significantly stronger in L-BMR females) and decreased it in kidneys. We conclude that the effect of reproduction on OS depends on the initial variation in BMR and varies between studied internal organs and markers of OS.

The estimation of the liver perfusion in cirrhosis and liver tumours by radionuclide angiography

International Nuclear Information System (INIS)

Artiko, V.; Obradovic, V.; Kostic, K.; Petrovic, M.; Davidovic, B.; Perisic-Savic, M.; Janosevic, S.

2004-01-01

Purpose: The aim of the study is assessment of the hepatic perfusion index (HPI) in cirrhosis and focal liver diseases. Methods: Hepatic radionuclide angiography (HRA) was performed with bolus injection of 740 MBq- 99m-Tc-pertechnetate, during one minute (If/sec), using gamma camera, in 10 controls, 35 cirrhotic patients and 34 patients with different liver tumors. Results: In 10 controls (C), HPI was 0.68+/-0.06; it was significantly decreased (p 0.05), HPI values were significantly lower in LCEV (p 0.05).In 22 patients with liver hemangiomas (LH, X= 0.64 +/-0.08) HPI values were physiological (C-LH, p>0.05). However, in 4 patients with hepatocellular carcinoma (H, X=0.26+/-0.20), and 8 with liver metastases (LM, X=0.40 +/-0.28), HPI values were significantly decreased (p 0.05). Conclusion: HRA is a useful method for the asessment of different degrees of hemodynamic alterations in portal system, as well as for differential diagnosis of benign and malignant liver tumors. (authors)

Hepatoprotective effects of Arctium lappa Linne on liver injuries induced by chronic ethanol consumption and potentiated by carbon tetrachloride.

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Lin, Song-Chow; Lin, Chia-Hsien; Lin, Chun-Ching; Lin, Yun-Ho; Chen, Chin-Fa; Chen, I-Cheng; Wang, Li-Ya

2002-01-01

Arctium lappa Linne (burdock) is a perennial herb which is popularly cultivated as a vegetable. In order to evaluate its hepatoprotective effects, a group of rats (n = 10) was fed a liquid ethanol diet (4 g of absolute ethanol/ 80 ml of liquid basal diet) for 28 days and another group (n = 10) received a single intraperitoneal injection of 0.5 ml/kg carbon tetrachloride (CCl(4)) in order to potentiate the liver damage on the 21st day (1 day before the beginning of A. lappa treatment). Control group rats were given a liquid basal diet which did not contain absolute ethanol. When 300 mg/kg A. lappa was administered orally 3 times per day in both the 1-day and 7-day treatment groups, some biochemical and histopathological parameters were significantly altered, both in the ethanol group and the groups receiving ethanol supplemented with CCl(4). A. lappa significantly improved various pathological and biochemical parameters which were worsened by ethanol plus CCl(4)-induced liver damage, such as the ethanol plus CCl(4)-induced decreases in total cytochrome P-450 content and NADPH-cytochrome c reductase activity, increases in serum triglyceride levels and lipid peroxidation (the deleterious peroxidative and toxic malondialdehyde metabolite may be produced in quantity) and elevation of serum transaminase levels. It could even restore the glutathione content and affect the histopathological lesions. These results tended to imply that the hepatotoxicity induced by ethanol and potentiated by CCl(4) could be alleviated with 1 and 7 days of A. lappa treatment. The hepatoprotective mechanism of A. lappa could be attributed, at least in part, to its antioxidative activity, which decreases the oxidative stress of hepatocytes, or to other unknown protective mechanism(s). Copyright 2002 National Science Council, ROC and S. Karger AG, Basel

Expression of heparanase in basal cell carcinoma and squamous cell carcinoma.

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Pinhal, Maria Aparecida Silva; Almeida, Maria Carolina Leal; Costa, Alessandra Scorse; Theodoro, Thérèse Rachell; Serrano, Rodrigo Lorenzetti; Machado, Carlos D'Apparecida Santos

2016-01-01

Heparanase is an enzyme that cleaves heparan sulfate chains. Oligosaccharides generated by heparanase induce tumor progression. Basal cell carcinoma and squamous cell carcinoma comprise types of nonmelanoma skin cancer. Evaluate the glycosaminoglycans profile and expression of heparanase in two human cell lines established in culture, immortalized skin keratinocyte (HaCaT) and squamous cell carcinoma (A431) and also investigate the expression of heparanase in basal cell carcinoma, squamous cell carcinoma and eyelid skin of individuals not affected by the disease (control). Glycosaminoglycans were quantified by electrophoresis and indirect ELISA method. The heparanase expression was analyzed by quantitative RT-PCR (qRTPCR). The A431 strain showed significant increase in the sulfated glycosaminoglycans, increased heparanase expression and decreased hyaluronic acid, comparing to the HaCaT lineage. The mRNA expression of heparanase was significantly higher in Basal cell carcinoma and squamous cell carcinoma compared with control skin samples. It was also observed increased heparanase expression in squamous cell carcinoma compared to the Basal cell carcinoma. The glycosaminoglycans profile, as well as heparanase expression are different between HaCaT and A431 cell lines. The increased expression of heparanase in Basal cell carcinoma and squamous cell carcinoma suggests that this enzyme could be a marker for the diagnosis of such types of non-melanoma cancers, and may be useful as a target molecule for future alternative treatment.

1H MR spectroscopy of the basal ganglia in childhood: a semiquantitative analysis

International Nuclear Information System (INIS)

Lam, W.W.M.; Zhao, H.; Berry, G.T.; Kaplan, P.; Gibson, J.; Kaplan, B.S.

1998-01-01

Proton MR spectra of the basal ganglia were obtained from 28 patients, 24 male and 14 female, median age 16.3 months (5 weeks to 31 years). They included 17 patients with normal MRI of the basal ganglia without metabolic disturbance (control group) and 11 patients with various metabolic diseases: one case each of high serum sodium and high serum osmolarity, cobalamin C deficiency, Leigh disease, Galloway-Mowat syndrome, Pelizaeus-Merzbacher disease, hemolytic-uremic syndrome and Wilson disease and two cases of Alagille syndrome and methylmalonic acidemia with abnormal MRI of the basal ganglia or blood or urine analysis (abnormal group). The MR spectrum was measured by using STEAM. The MR-visible water content of the region of interest was obtained. Levels of myoinositol, choline, creatine and N -acetylaspartate were measured using a semiquantitative approach, with absolute reference calibration. In the control group, there was a gradual drop of water content over the first year of life; N -acetylaspartate, creatine and myoinositol levels showed no significant change with age, in contrast to the occipital, parietal and cerebellar regions. Choline showed a gradual decrease for the first 2 years of life and then remained fairly constant. In the abnormal group the water content was not significantly different. N -Acetylaspartate was decreased in patients with high serum sodium and high serum osmolarity, cobalamin C deficiency, Leigh disease and one case of methylmalonic acidemia. Decreased creatine was also found in Leigh disease, and decreased choline in Galloway-Mowat syndrome and Wilson disease. Myoinositol was elevated in the patient with abnormally high serum sodium, and decreased in the hemolytic-uremic syndrome. (orig.)

Serial dynamic CT scan in patients with acute basal ganglia infarctions

International Nuclear Information System (INIS)

Node, Yoji; Nakazawa, Shozo; Tsuji, Yukihide.

1987-01-01

Dynamic computed tomography (CT) was performed on 15 patients (37 to 93 years of age) with acute basal ganglia infarctions, and the perfusion patterns of the infarcted regions on CT were evaluated. The initial dynamic CT was performed within 12 hours after onset, while the serial studies of the dynamic CT were performed on the 3rd and 7th days. The left-over-right ratio in the peak value in the basal ganglia in 15 normal subjects was 1.01 ± 0.03 (mean ± SD), so there were no differences in the peak values of the bilateral basal ganglia. We also examined the left-over-right ratio in the peak value and in the rapid-washout ratio in the basal ganglia in the 15 normal subjects. There was no difference in the peak values of the bilateral basal ganglia. The mean rapid-washout ratio was 0.62 ± 0.11 (mean ± SD). The prognoses of these patients three months after onset were as follows: 8 showed a good recovery, 5 had a moderate disability, and 2 had a severe disability. The perfusions on admission were as follows. 10 were hypoperfusions, 3 were hypo + late perfusions, one was a normoperfusion, and one was a late perfusion. There was a tendency for the rapid-washout ratio decrease more in the hypo + late perfusion group than in the other groups. Twelve patients showed an iso-density, while 3 showed a low density, on admission. The ''low-density'' group showed a decrease in the A/N ratio of the peak value. We performed serial dynamic CT in 11 cases. The group with severe disabilities (2 cases) showed a hypo + late perfusion in the initial CT, one case kept a hypo + late perfusion, and another case changed to a hypoperfusion; also, there was a tendency for there to be a poor improvement in the A/N ratio of the peak value in these two ''severe-disability'' patients. (J.P.N.)

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

Science.gov (United States)

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, pexogenous delivery of FGF19 might be therapeutically beneficial.

Liver Hypertension: Causes, Consequences and Prevention

Indian Academy of Sciences (India)

Table of contents. Liver Hypertension: Causes, Consequences and Prevention · Heart Pressure : Blood Pressure · Slide 3 · If you continue to have high BP · Doctor Measures Blood Pressure (BP): Medicines to Decrease BP · LIVER ~ ~ LIFE Rightists vs. Leftists · Slide 7 · Slide 8 · Slide 9 · Liver Spleen - Splanchnic ...

Adenoid basal hyperplasia of the uterine cervix: a lesion of reserve cell type, distinct from adenoid basal carcinoma.

Science.gov (United States)

Kerdraon, Olivier; Cornélius, Aurélie; Farine, Marie-Odile; Boulanger, Loïc; Wacrenier, Agnès

2012-12-01

Adenoid basal hyperplasia is an underrecognized cervical lesion, resembling adenoid basal carcinoma, except the absence of deep invasion into the stroma. We report a series of 10 cases, all extending less than 1 mm from the basement membrane. Our results support the hypothesis that adenoid basal hyperplasia arises from reserve cells of the cervix. Lesions were found close to the squamocolumnar junction, in continuity with the nearby subcolumnar reserve cells. They shared the same morphology and immunoprofile using a panel of 4 antibodies (keratin 5/6, keratin 14, keratin 7 and p63) designed to differentiate reserve cells from mature squamous cells and endocervical columnar cells. We detected no human papillomavirus infection by in situ hybridization targeting high-risk human papillomavirus, which was concordant with the absence of immunohistochemical p16 expression. We demonstrated human papillomavirus infection in 4 (80%) of 5 adenoid basal carcinoma, which is in the same range as previous studies (88%). Thus, adenoid basal hyperplasia should be distinguished from adenoid basal carcinoma because they imply different risk of human papillomavirus infection and of subsequent association with high-grade invasive carcinoma. In our series, the most reliable morphological parameters to differentiate adenoid basal hyperplasia from adenoid basal carcinoma were the depth of the lesion and the size of the lesion nests. Furthermore, squamous differentiation was rare in adenoid basal hyperplasia and constant in adenoid basal carcinoma. Finally, any mitotic activity and/or an increase of Ki67 labeling index should raise the hypothesis of adenoid basal carcinoma. Copyright © 2012 Elsevier Inc. All rights reserved.

Aberrant functional connectivity within the basal ganglia of patients with Parkinson's disease.

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Rolinski, Michal; Griffanti, Ludovica; Szewczyk-Krolikowski, Konrad; Menke, Ricarda A L; Wilcock, Gordon K; Filippini, Nicola; Zamboni, Giovanna; Hu, Michele T M; Mackay, Clare E

2015-01-01

Resting state functional MRI (rs-fMRI) has been previously shown to be a promising tool for the assessment of early Parkinson's disease (PD). In order to assess whether changes within the basal ganglia network (BGN) are disease specific or relate to neurodegeneration generally, BGN connectivity was assessed in 32 patients with early PD, 19 healthy controls and 31 patients with Alzheimer's disease (AD). Voxel-wise comparisons demonstrated decreased connectivity within the basal ganglia of patients with PD, when compared to patients with AD and healthy controls. No significant changes within the BGN were seen in AD, when compared to healthy controls. Moreover, measures of functional connectivity extracted from regions within the basal ganglia were significantly lower in the PD group. Consistent with previous radiotracer studies, the greatest change when compared to the healthy control group was seen in the posterior putamen of PD subjects. When combined into a single component score, this method differentiated PD from AD and healthy control subjects, with a diagnostic accuracy of 81%. Rs-fMRI can be used to demonstrate the aberrant functional connectivity within the basal ganglia of patients with early PD. These changes are likely to be representative of patho-physiological basal ganglia dysfunction and are not associated with generalised neurodegeneration seen in AD. Further studies are necessary to ascertain whether this method is sensitive enough to detect basal ganglia dysfunction in prodromal PD, and its utility as a potential diagnostic biomarker for premotor and early motoric disease.

Effects of elastase on fatty liver

International Nuclear Information System (INIS)

Ogura, Kazuo; Shimizu, Yoshikazu; Hihara, Masafumi; Ando, Hideki; Nishiyama, Masateru; Tano, Hironobu

1984-01-01

Elastase (Elaszym 6T) was administered, in addition to the dietary instruction, to three patients with fatty liver. CT scanning revealed marked improvement in fatty liver. Transaminase levels returned to normal, total cholesterol levels tended to decrease, and HDL-cholesterol levels tended to increase. These results suggest that elastase is effective in the treatment of fatty liver. (Namekawa, K.)

Evaluation of liver hemodynamics using SPIO-enhanced dynamic MRI. Comparison between cirrhotic liver and normal liver

International Nuclear Information System (INIS)

Shimada, Kotaro; Kobayashi, Hisato; Furuta, Akihiro; Nunoura, T.; Takahashi, Takahiro; Ogasawara, Nobuhiko; Akuta, Keizo

2006-01-01

SPIO, ferucarbotran (Resovist), which enables rapid bolus injection is well suited for the evaluation of liver hemodynamics. Our study aimed to assess the difference of hemodynamics associated with progression of chronic liver disease using SPIO-enhanced dynamic MRI. Ten patients with normal liver function, 10 patients with chronic hepatitis, and 16 patients with liver cirrhosis were examined. The MR perfusion studies were performed by 1.5T MR system with a single-shot GRE-EPI with spectral presaturation inversion recovery (SPIR) and sensitivity encoding (SENSE) technique. After the bolus injection of SPIO (0.016 ml/kg) followed by a 20 ml saline flush, 30 sequential dynamic echo planar images were obtained under the condition of 30 seconds breath hold. From the ROI set in the right lobe of the liver, time-to-signal intensity curves (TICs) were obtained. TICs were converted to time-to-R2 * curves, and the slope at hepatic arterial phase (Sa) and at portal predominant phase (Sp) were calculated by the linear regression. Sp/Sa (portal/arterial ratio) of each group was analyzed statistically. (unpaired T-test) In comparing Sp/Sa of each group, there was a significant difference between normal liver and advanced liver cirrhosis. The decrease of Sp/Sa was seen in severe cirrhosis, but this change was unclear in chronic hepatitis and mild cirrhosis. In extremely severe cirrhosis, there was a bizarre phenomenon that Sp became minus number. In conclusion, SPIO-enhanced dynamic MRI was useful to assess the difference of liver hemodynamics associated with progression of chronic liver disease. (author)

Implications of basal micro-earthquakes and tremor for ice stream mechanics: Stick-slip basal sliding and till erosion

Science.gov (United States)

Barcheck, C. Grace; Tulaczyk, Slawek; Schwartz, Susan Y.; Walter, Jacob I.; Winberry, J. Paul

2018-03-01

The Whillans Ice Plain (WIP) is unique among Antarctic ice streams because it moves by stick-slip. The conditions allowing stick-slip and its importance in controlling ice dynamics remain uncertain. Local basal seismicity previously observed during unstable slip is a clue to the mechanism of ice stream stick-slip and a window into current basal conditions, but the spatial extent and importance of this basal seismicity are unknown. We analyze data from a 2010-2011 ice-plain-wide seismic and GPS network to show that basal micro-seismicity correlates with large-scale patterns in ice stream slip behavior: Basal seismicity is common where the ice moves the least between unstable slip events, with small discrete basal micro-earthquakes happening within 10s of km of the central stick-slip nucleation area and emergent basal tremor occurring downstream of this area. Basal seismicity is largely absent in surrounding areas, where inter-slip creep rates are high. The large seismically active area suggests that a frictional sliding law that can accommodate stick-slip may be appropriate for ice stream beds on regional scales. Variability in seismic behavior over inter-station distances of 1-10 km indicates heterogeneity in local bed conditions and frictional complexity. WIP unstable slips may nucleate when stick-slip basal earthquake patches fail over a large area. We present a conceptual model in which basal seismicity results from slip-weakening frictional failure of over-consolidated till as it is eroded and mobilized into deforming till.

Modulation of liver mitochondrial NOS is implicated in thyroid-dependent regulation of O(2) uptake.

Science.gov (United States)

Carreras, M C; Peralta, J G; Converso, D P; Finocchietto, P V; Rebagliati, I; Zaninovich, A A; Poderoso, J J

2001-12-01

Changes in O(2) uptake at different thyroid status have been explained on the basis of the modulation of mitochondrial enzymes and membrane biophysical properties. Regarding the nitric oxide (NO) effects, we tested whether liver mitochondrial nitric oxide synthase (mtNOS) participates in the modulation of O(2) uptake in thyroid disorders. Wistar rats were inoculated with 400 microCi (131)I (hypothyroid group), 20 microg thyroxine (T(4))/100 g body wt administered daily for 2 wk (hyperthyroid group) or vehicle (control). Basal metabolic rate, mitochondrial function, and mtNOS activity were analyzed. Systemic and liver mitochondrial O(2) uptake and cytochrome oxidase activity were lower in hypothyroid rats with respect to controls; mitochondrial parameters were further decreased by L-arginine (-42 and -34%, P activity (260%) were selectively increased in hypothyroidism and reverted by hormone replacement without changes in other nitric oxide isoforms. Moreover, mtNOS activity correlated with serum 3,5,3'-triiodothyronine (T(3)) and O(2) uptake. Increased mtNOS activity was also observed in skeletal muscle mitochondria from hypothyroid rats. Therefore, we suggest that modulation of mtNOS is a substantial part of thyroid effects on mitochondrial O(2) uptake.

Using multiphoton fluorescence lifetime imaging to characterize liver damage and fluorescein disposition in liver in vivo

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Thorling, Camilla A.; Studier, Hauke; Crawford, Darrell; Roberts, Michael S.

2016-03-01

Liver disease is the fifth most common cause of death and unlike many other major causes of mortality, liver disease rates are increasing rather than decreasing. There is no ideal measurement of liver disease and although biopsies are the gold standard, this only allows for a spot examination and cannot follow dynamic processes of the liver. Intravital imaging has the potential to extract detailed information over a larger sampling area continuously. The aim of this project was to investigate whether multiphoton and fluorescence lifetime imaging microscopy could detect early liver damage and to assess whether it could detect changes in metabolism of fluorescein in normal and diseased livers. Four experimental groups were used in this study: 1) control; 2) ischemia reperfusion injury; 3) steatosis and 4) steatosis with ischemia reperfusion injury. Results showed that multiphoton microscopy could visualize morphological changes such as decreased fluorescence of endogenous fluorophores and the presence of lipid droplets, characteristic of steatosis. Fluorescence lifetime imaging microscopy showed increase in NADPH in steatosis with and without ischemia reperfusion injury and could detect changes in metabolism of fluorescein to fluorescein monoglurcuronide, which was impaired in steatosis with ischemia reperfusion injury. These results concluded that the combination of multiphoton microscopy and fluorescence lifetime imaging is a promising method of assessing early stage liver damage and that it can be used to study changes in drug metabolism in the liver as an indication of liver disease and has the potential to replace the traditional static liver biopsy currently used.

Proton MR spectroscopic features of liver cirrhosis : comparing with normal liver

International Nuclear Information System (INIS)

Cho, Soon Gu; Choi, Won; Kim, Young Soo; Kim, Mi Young; Jee, Keum Nahn; Lee, Kyung Hee; Suh, Chang Hae

2000-01-01

The purpose of this study was to determine the proton MR spectroscopic features of liver cirrhosis and the different proton MR spectroscopic features between liver cirrhosis and the normal human liver by comparing the two different conditions. The investigation involved 30 cases of in-vivo proton MR spectra obtained from 15 patients with liver cirrhosis demonstrated on the basis of radiologic and clinical findings, and from 15 normal volunteers without a past or current history of liver disease. MR spectroscopy involved the use of 1.5T GESigna Horizon system (GE Medical Systems, Milwaukee, U. S. A.) with body coil. STEAM (STimulated Echo-Acquisition Mode) with 3000/30 msec of TR/TE was used for signal acquisition; patients were in the prone position and respiration was not interrupted. Cases were assigned to either the cirrhosis or normal group, and using the proton MR spectra of cases of in each group, peak changes occurring in lipids (at 1.3 ppm), glutamate and glutamine (at 2.4-2.5 ppm), phosphomonoesters (at 3.0-3.1 ppm), and glycogen and glucose (at 3.4-3.9 ppm) were evaluated. Mean and standard deviation of the ratio of glutamate + glutamine/lipids, phosphomonoesters/lipids, glycogen + glucose/lipids were calculated from the area of their peaks. The ratio of various metabolites to lipid content was compared between the normal and cirrhosis group. The main characteristic change in proton MR spectra in cases of liver cirrhosis compared with normal liver was decreased relative intensity of lipid peak. Mean and standard deviation of ratio of glutamate + glutamine/lipids, phosphomonoesters /lipids, glycogen + glucose /lipid calculated from the area of their peaks of normal and cirrhotic liver were 0.0204 ±0.0067 and 0.0693 ±0.0371 (p less than 0.05), 0.0146 ± 0.0090 and 0.0881 ±0.0276 (p less than 0.05), 0.0403 ± 0.0267 and 0.2325 ± 0.1071 (p less than 0.05), respectively The other characteristic feature of proton MR spectra of liver cirrhosis was the peak

Liver hydatid cyst ruptured into the thorax: CT angiography findings of a case

International Nuclear Information System (INIS)

Kara, K.; Ors, F.; Bozlar, U.; Tasar, M.

2012-01-01

Full text: Introduction: Intrathoracic rupture of hepatic hydatid cyst is a rare but severe condition causing a spectrum of lesions to the pleura, lung parenchyma, and bronchi. Pulmonary complications result from the proximity of hydatid cysts in the liver and the diaphragm. Objectives and tasks: In this report we aimed to present computed tomography (CT) angiography findings of a case with liver hydatid cyst ruptured into the thorax. The patient underwent CT angiography examination with suspicion of pulmonary embolism. Materials and methods: A 71-year-old female patient admitted to our emergency department with complaints of severe and persistent cough. Basal region of the right hemithorax could not get breath sounds on physical examination. Chest radiography revealed the presence of consolidation-effusion. The patient was treated with antibiotherapy for pneumonia and parapneumonic effusion. Because of the clinical symptoms and chest radiograph findings persisted the patient underwent CT angiography examination with suspicion of pulmonary embolism. Results: On CT angiography images pulmonary artery and its branches were normal. There were subtotal collapse in the right middle and lower lung lobes and complicated cystic lesion that has air densities in the basal interlobar space. Another thick walled complicated cystic lesion with multiple septations and air densities was detected in the right posterior liver lobe. The right hemidiaphragm was interrupted and the right liver lobe partially herniated into the thorax cavity. Serologic tests were positive for Echinococcus granulosus and there were prior therapy history for liver cyst hydatid. The diagnostic aspiration findings were consistent with hydatid cyst lesion. Conclusion: In patients with hepatic hydatid cyst associated with persistent and severe cough, thoracic rupture of the cyst should be considered in differential diagnosis. CT angiography is fast, non-invasive and effective method in the detection of

The effect of phytosterol protects rats against 4-nitrophenol-induced liver damage.

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Chen, Jiaqin; Song, Meiyan; Li, Yansen; Zhang, Yonghui; Taya, Kazuyoshi; Li, ChunMei

2016-01-01

We investigated the effect of phytosterol (PS) in regard to liver damage induced by 4-nitrophenol (PNP). Twenty rats were randomly divided into four groups (Control, PS, PNP, and PNP+PS). The PS and PNP+PS groups were pretreated with PS for one week. The PNP and PNP+PS groups were injected subcutaneously with PNP for 28 days. The control group received a basal diet and was injected with vehicle alone. Treatment with PS prevented the elevation of the total bilirubin levels, as well as an increase in serum alkaline transaminase and aspartate transaminase, which are typically caused by PNP-induced liver damage. Histopathologically showed that liver damage was significantly mitigated by PS treatment. However, there was no significant change in antioxidant enzyme activities, and the Nrf2-antioxidant system was not activated after treatment with PS. These results suggest that PS could mitigate liver damage induced by PNP, but does not enhance antioxidant capacity. Copyright © 2015 Elsevier B.V. All rights reserved.

Future of newer basal insulin

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Madhu, S. V.; Velmurugan, M.

2013-01-01

Basal insulin have been developed over the years. In recent times newer analogues have been added to the armanentarium for diabetes therapy. This review specifically reviews the current status of different basal insulins

Pregnancy-induced insulin resistance in liver and skeletal muscles of the conscious rabbit

International Nuclear Information System (INIS)

Hauguel, S.; Gilbert, M.; Girard, J.

1987-01-01

Insulin sensitivity of maternal nonuterine tissues (liver and skeletal muscles) has been investigated in the conscious rabbit during late gestation (24 and 30 days). The specific effect of insulin on glucose production and utilization was evaluated with the hyperinsulinemic euglycemic clamp technique using two types of labelled microspheres ( 57 Co and 113 Sn). The net balance of glucose across the hindlimb muscles was studied by means of the Fick principle in basal and insulin stimulated conditions (clamp study). The results show that an insulin-resistant state developed between days 24 and 30 of gestation in the rabbit and involves both glucose producing (liver) and utilizing (muscles) tissues. On day 30 of gestation, muscle glucose uptake was not significantly stimulated at a plasma insulin concentration of 700 μU/ml determined by radioimmunoassay, whereas it was stimulated by 30-40% in nonpregnant and 24 day pregnant rabbits. At similar plasma insulin concentration, endogenous glucose production was suppressed by 85% in both nonpregnant and 24 day pregnant rabbits, whereas it was decreased by only 30% in 30 day pregnant rabbits. The present data suggest that hindlimb muscles of late pregnant rabbits are able to reduce their insulin-induced glucose utilization. This could contribute to meet the glucose requirements of pregnant uterus in late gestation

Analysis of gene expression changes in relation to toxicity and tumorigenesis in the livers of Big Blue transgenic rats fed comfrey (Symphytum officinale).

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Mei, Nan; Guo, Lei; Zhang, Lu; Shi, Leming; Sun, Yongming Andrew; Fung, Chris; Moland, Carrie L; Dial, Stacey L; Fuscoe, James C; Chen, Tao

2006-09-06

Comfrey is consumed by humans as a vegetable and a tea, and has been used as an herbal medicine for more than 2000 years. Comfrey, however, is hepatotoxic in livestock and humans and carcinogenic in experimental animals. Our previous study suggested that comfrey induces liver tumors by a genotoxic mechanism and that the pyrrolizidine alkaloids in the plant are responsible for mutation induction and tumor initiation in rat liver. In this study, we identified comfrey-induced gene expression profile in the livers of rats. Groups of 6 male transgenic Big Blue rats were fed a basal diet and a diet containing 8% comfrey roots, a dose that resulted in liver tumors in a previous carcinogenicity bioassay. The animals were treated for 12 weeks and sacrificed one day after the final treatment. We used a rat microarray containing 26,857 genes to perform genome-wide gene expression studies. Dietary comfrey resulted in marked changes in liver gene expression, as well as in significant decreases in the body weight and increases in liver mutant frequency. When a two-fold cutoff value and a P-value less than 0.01 were selected, 2,726 genes were identified as differentially expressed in comfrey-fed rats compared to control animals. Among these genes, there were 1,617 genes associated by Ingenuity Pathway Analysis with particular functions, and the differentially expressed genes in comfrey-fed rat livers were involved in metabolism, injury of endothelial cells, and liver injury and abnormalities, including liver fibrosis and cancer development. The gene expression profile provides us a better understanding of underlying mechanisms for comfrey-induced hepatic toxicity. Integration of gene expression changes with known pathological changes can be used to formulate a mechanistic scheme for comfrey-induced liver toxicity and tumorigenesis.

Activation of liver X receptor decreases atherosclerosis in Ldlr⁻/⁻ mice in the absence of ATP-binding cassette transporters A1 and G1 in myeloid cells

NARCIS (Netherlands)

Kappus, Mojdeh S.; Murphy, Andrew J.; Abramowicz, Sandra; Ntonga, Vusisizwe; Welch, Carrie L.; Tall, Alan R.; Westerterp, Marit

2014-01-01

Liver X receptor (LXR) activators decrease atherosclerosis in mice. LXR activators (1) directly upregulate genes involved in reverse cholesterol transport and (2) exert anti-inflammatory effects mediated by transrepression of nuclear factor-κB target genes. We investigated whether myeloid cell

TESTOSTERONE CHANGES IN PATIENTS WITH LIVER CIRRHOSIS BEFORE AND AFTER ORTHOTOPIC LIVER TRANSPLANTATION AND ITS CORRELATION WITH MELD

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Rodrigo NITSCHE

2014-03-01

Full Text Available Context Hypogonadism is a common clinical situation in male patients with liver cirrhosis. Objectives The aim of the present study was to evaluate the effects of orthotopic liver transplantation on testosterone, free testosterone and sex hormone-binding globulin in male with advanced liver disease and also to determine the relationship of these changes with Model for End-stage Liver Disease (MELD score. Methods In a prospective study, serum levels of testosterone, free testosterone and sex hormone-binding globulin of 30 male adult patients with end-stage liver disease were measured 2 to 4 hours before and 6 months after orthotopic liver transplantation. Results Total testosterone levels increased after orthotopic liver transplantation and the number of patients with normal testosterone levels increased from 18 to 24. Free testosterone mean level in the pre-transplant group was 7.8 pg/mL and increased to 11.5 pg/mL (P = 0.10 and sex hormone-binding globulin level decreased after orthotopic liver transplantation returning to normal levels in MELD ≤18 - group (A (P<0.05. Conclusions Serum level changes of testosterone, free testosterone and sex hormone-binding globulin are more pronounced in cirrhotic males with MELD ≤18. Serum levels of testosterone and free testosterone increase and serum levels of sex hormone-binding globulin decrease after orthotopic liver transplantation.

Basal cell carcinoma-treatment with cryosurgery

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Kaur S

2003-03-01

Full Text Available Basal cell carcinoma is a common cutaneous malignancy, frequently occurring over the face in elderly individuals. Various therapeutic modalities are available to treat these tumors. We describe three patients with basal cell carcinoma successfully treated with cryosurgery and discuss the indications and the use of this treatment modality for basal cell carcinomas.

Aberrant functional connectivity within the basal ganglia of patients with Parkinson's disease

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Michal Rolinski

2015-01-01

Full Text Available Resting state functional MRI (rs-fMRI has been previously shown to be a promising tool for the assessment of early Parkinson's disease (PD. In order to assess whether changes within the basal ganglia network (BGN are disease specific or relate to neurodegeneration generally, BGN connectivity was assessed in 32 patients with early PD, 19 healthy controls and 31 patients with Alzheimer's disease (AD. Voxel-wise comparisons demonstrated decreased connectivity within the basal ganglia of patients with PD, when compared to patients with AD and healthy controls. No significant changes within the BGN were seen in AD, when compared to healthy controls. Moreover, measures of functional connectivity extracted from regions within the basal ganglia were significantly lower in the PD group. Consistent with previous radiotracer studies, the greatest change when compared to the healthy control group was seen in the posterior putamen of PD subjects. When combined into a single component score, this method differentiated PD from AD and healthy control subjects, with a diagnostic accuracy of 81%. Rs-fMRI can be used to demonstrate the aberrant functional connectivity within the basal ganglia of patients with early PD. These changes are likely to be representative of patho-physiological basal ganglia dysfunction and are not associated with generalised neurodegeneration seen in AD. Further studies are necessary to ascertain whether this method is sensitive enough to detect basal ganglia dysfunction in prodromal PD, and its utility as a potential diagnostic biomarker for premotor and early motoric disease.

A study of human liver ferritin and chicken liver and spleen using Moessbauer spectroscopy with high velocity resolution

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Oshtrakh, M. I., E-mail: oshtrakh@mail.utnet.ru [Ural State Technical University-UPI, Faculty of Physical Techniques and Devices for Quality Control (Russian Federation); Milder, O. B.; Semionkin, V. A. [Ural State Technical University-UPI, Faculty of Experimental Physics (Russian Federation)

2008-01-15

Lyophilized samples of human liver ferritin and chicken liver and spleen were measured at room temperature using Moessbauer spectroscopy with high velocity resolution. An increase in the velocity resolution of Moessbauer spectroscopy permitted us to increase accuracy and decrease experimental error in determining the hyperfine parameters of human liver ferritin and chicken liver and spleen. Moessbauer spectroscopy with high velocity resolution may be very useful for revealing small differences in hyperfine parameters during biomedical research.

Alcoholic Hepatitis Markedly Decreases the Capacity for Urea Synthesis.

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Emilie Glavind

Full Text Available Data on quantitative metabolic liver functions in the life-threatening disease alcoholic hepatitis are scarce. Urea synthesis is an essential metabolic liver function that plays a key regulatory role in nitrogen homeostasis. The urea synthesis capacity decreases in patients with compromised liver function, whereas it increases in patients with inflammation. Alcoholic hepatitis involves both mechanisms, but how these opposite effects are balanced remains unclear. Our aim was to investigate how alcoholic hepatitis affects the capacity for urea synthesis. We related these findings to another measure of metabolic liver function, the galactose elimination capacity (GEC, as well as to clinical disease severity.We included 20 patients with alcoholic hepatitis and 7 healthy controls. The urea synthesis capacity was quantified by the functional hepatic nitrogen clearance (FHNC, i.e., the slope of the linear relationship between the blood α-amino nitrogen concentration and urea nitrogen synthesis rate during alanine infusion. The GEC was determined using blood concentration decay curves after intravenous bolus injection of galactose. Clinical disease severity was assessed by the Glasgow Alcoholic Hepatitis Score and Model for End-Stage Liver Disease (MELD score.The FHNC was markedly decreased in the alcoholic hepatitis patients compared with the healthy controls (7.2±4.9 L/h vs. 37.4±6.8 L/h, P<0.01, and the largest decrease was observed in those with severe alcoholic hepatitis (4.9±3.6 L/h vs. 9.9±4.9 L/h, P<0.05. The GEC was less markedly reduced than the FHNC. A negative correlation was detected between the FHNC and MELD score (rho = -0.49, P<0.05.Alcoholic hepatitis markedly decreases the urea synthesis capacity. This decrease is associated with an increase in clinical disease severity. Thus, the metabolic failure in alcoholic hepatitis prevails such that the liver cannot adequately perform the metabolic up-regulation observed in other stressful

Metastatic giant basal cell carcinoma: a case report.

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Bellahammou, Khadija; Lakhdissi, Asmaa; Akkar, Othman; Rais, Fadoua; Naoual, Benhmidou; Elghissassi, Ibrahim; M'rabti, Hind; Errihani, Hassan

2016-01-01

Basal cell carcinoma is the most common skin cancer, characterised by a slow growing behavior, metastasis are extremely rare, and it occurs in less than 0, 1% of all cases. Giant basal cell carcinoma is a rare form of basal cell carcinoma, more aggressive and defined as a tumor measuring more than 5 cm at its largest diameter. Only 1% of all basal cell carcinoma develops to a giant basal cell carcinoma, resulting of patient's negligence. Giant basal cell carcinoma is associated with higher potential of metastasis and even death, compared to ordinary basal cell carcinoma. We report a case of giant basal cell carcinoma metastaticin lung occurring in a 79 years old male patient, with a fatal evolution after one course of systemic chemotherapy. Giant basal cell carcinoma is a very rare entity, early detection of these tumors could prevent metastasis occurrence and improve the prognosis of this malignancy.

Acetaminophen-Induced Liver Injury Alters the Acyl Ethanolamine-Based Anti-Inflammatory Signaling System in Liver

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Patricia Rivera

2017-10-01

Full Text Available Protective mechanisms against drug-induced liver injury are actively being searched to identify new therapeutic targets. Among them, the anti-inflammatory N-acyl ethanolamide (NAE-peroxisome proliferators activated receptor alpha (PPARα system has gained much interest after the identification of its protective role in steatohepatitis and liver fibrosis. An overdose of paracetamol (APAP, a commonly used analgesic/antipyretic drug, causes hepatotoxicity, and it is being used as a liver model. In the present study, we have analyzed the impact of APAP on the liver NAE-PPARα system. A dose-response (0.5–5–10–20 mM and time-course (2–6–24 h study in human HepG2 cells showed a biphasic response, with a decreased PPARα expression after 6-h APAP incubation followed by a generalized increase of NAE-PPARα system-related components (PPARα, NAPE-PLD, and FAAH, including the NAEs oleoyl ethanolamide (OEA and docosahexaenoyl ethanolamide, after a 24-h exposure to APAP. These results were partially confirmed in a time-course study of mice exposed to an acute dose of APAP (750 mg/kg. The gene expression levels of Pparα and Faah were decreased after 6 h of treatment and, after 24 h, the gene expression levels of Nape-pld and Faah, as well as the liver levels of OEA and palmitoyl ethanolamide, were increased. Repeated APAP administration (750 mg/kg/day up to 4 days also decreased the expression levels of PPARα and FAAH, and increased the liver levels of NAEs. A resting period of 15 days completely restored these impairments. Liver immunohistochemistry in a well-characterized human case of APAP hepatotoxicity confirmed PPARα and FAAH decrements. Histopathological and hepatic damage (Cyp2e1, Caspase3, αSma, Tnfα, and Mcp1-related alterations observed after repeated APAP administration were aggravated in the liver of Pparα-deficient mice. Our results demonstrate that the anti-inflammatory NAE-PPARα signaling system is implicated in liver

Modeling liver electrical conductivity during hypertonic injection.

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Castellví, Quim; Sánchez-Velázquez, Patricia; Moll, Xavier; Berjano, Enrique; Andaluz, Anna; Burdío, Fernando; Bijnens, Bart; Ivorra, Antoni

2018-01-01

Metastases in the liver frequently grow as scattered tumor nodules that neither can be removed by surgical resection nor focally ablated. Previously, we have proposed a novel technique based on irreversible electroporation that may be able to simultaneously treat all nodules in the liver while sparing healthy tissue. The proposed technique requires increasing the electrical conductivity of healthy liver by injecting a hypersaline solution through the portal vein. Aiming to assess the capability of increasing the global conductivity of the liver by means of hypersaline fluids, here, it is presented a mathematical model that estimates the NaCl distribution within the liver and the resulting conductivity change. The model fuses well-established compartmental pharmacokinetic models of the organ with saline injection models used for resuscitation treatments, and it considers changes in sinusoidal blood viscosity because of the hypertonicity of the solution. Here, it is also described a pilot experimental study in pigs in which different volumes of NaCl 20% (from 100 to 200 mL) were injected through the portal vein at different flow rates (from 53 to 171 mL/minute). The in vivo conductivity results fit those obtained by the model, both quantitatively and qualitatively, being able to predict the maximum conductivity with a 14.6% average relative error. The maximum conductivity value was 0.44 second/m, which corresponds to increasing 4 times the mean basal conductivity (0.11 second/m). The results suggest that the presented model is well suited for predicting on liver conductivity changes during hypertonic saline injection. Copyright © 2017 John Wiley & Sons, Ltd.

Changes of plasma VEGF levels and liver function in patients with liver cancer before and after interventional treatment

International Nuclear Information System (INIS)

Li Jia; Qi Jun; Gao Jia

2011-01-01

To explore the effect of the interventional treatment for the angiogenesis and liver function in patients with liver cancer within short time, enzyme linked immunosorbent assay was used to determine the level of VEGF in plasma. The level of liver function was measured through automatic biochemistry analyzer. The results indicated that the level of VEGF in patients with liver cancer decreased after interventional treatment than that of before treatment (P<0.05). The level of total protein, albumin, alkaline phosphatase and total bile acid decreased after interventional treatment (P<0.05). The level of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin and indirect bilirubin were increased than before (P<0.05). The interventional treatment inhibit the expression of the VEGF in the tumor tissue and limited the angiogenesis within short time, but to some extent may caused the injury of the hepatocytes and the synthetic and excremental function in patients with liver cancer. (authors)

Basal metabolic rate declines during long-distance migratory flight in great knots

NARCIS (Netherlands)

Battley, PF; Dekinga, A; Dietz, MW; Piersma, T; Tang, SX; Hulsman, K; Battley, Phil F.; Tang, Sixian

2001-01-01

Great Knots (Calidris tenuirostris) make one of the longest migratory flights in the avian world, flying almost 5500 km from Australia to China during northward migration. We measured basal metabolic rate (BMR) and body composition in birds before and after this flight and found that BMR decreased

Disruption of genes encoding eIF4E binding proteins-1 and -2 does not alter basal or sepsis-induced changes in skeletal muscle protein synthesis in male or female mice.

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Steiner, Jennifer L; Pruznak, Anne M; Deiter, Gina; Navaratnarajah, Maithili; Kutzler, Lydia; Kimball, Scot R; Lang, Charles H

2014-01-01

Sepsis decreases skeletal muscle protein synthesis in part by impairing mTOR activity and the subsequent phosphorylation of 4E-BP1 and S6K1 thereby controlling translation initiation; however, the relative importance of changes in these two downstream substrates is unknown. The role of 4E-BP1 (and -BP2) in regulating muscle protein synthesis was assessed in wild-type (WT) and 4E-BP1/BP2 double knockout (DKO) male mice under basal conditions and in response to sepsis. At 12 months of age, body weight, lean body mass and energy expenditure did not differ between WT and DKO mice. Moreover, in vivo rates of protein synthesis in gastrocnemius, heart and liver did not differ between DKO and WT mice. Sepsis decreased skeletal muscle protein synthesis and S6K1 phosphorylation in WT and DKO male mice to a similar extent. Sepsis only decreased 4E-BP1 phosphorylation in WT mice as no 4E-BP1/BP2 protein was detected in muscle from DKO mice. Sepsis decreased the binding of eIF4G to eIF4E in WT mice; however, eIF4E•eIF4G binding was not altered in DKO mice under either basal or septic conditions. A comparable sepsis-induced increase in eIF4B phosphorylation was seen in both WT and DKO mice. eEF2 phosphorylation was similarly increased in muscle from WT septic mice and both control and septic DKO mice, compared to WT control values. The sepsis-induced increase in muscle MuRF1 and atrogin-1 (markers of proteolysis) as well as TNFα and IL-6 (inflammatory cytokines) mRNA was greater in DKO than WT mice. The sepsis-induced decrease in myocardial and hepatic protein synthesis did not differ between WT and DKO mice. These data suggest overall basal protein balance and synthesis is maintained in muscle of mice lacking both 4E-BP1/BP2 and that sepsis-induced changes in mTOR signaling may be mediated by a down-stream mechanism independent of 4E-BP1 phosphorylation and eIF4E•eIF4G binding.

Does acid-base equilibrium correlate with remnant liver volume during stepwise liver resection?

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Golriz, Mohammad; Abbasi, Sepehr; Fathi, Parham; Majlesara, Ali; Brenner, Thorsten; Mehrabi, Arianeb

2017-10-01

Small for size and flow syndrome (SFSF) is one of the most challenging complications following extended hepatectomy (EH). After EH, hepatic artery flow decreases and portal vein flow increases per 100 g of remnant liver volume (RLV). This causes hypoxia followed by metabolic acidosis. A correlation between acidosis and posthepatectomy liver failure has been postulated but not studied systematically in a large animal model or clinical setting. In our study, we performed stepwise liver resections on nine pigs to defined SFSF limits as follows: step 1: segment II/III resection, step 2: segment IV resection, step 3: segment V/VIII resection (RLV: 75, 50, and 25%, respectively). Blood gas values were measured before and after each step using four catheters inserted into the carotid artery, internal jugular vein, hepatic artery, and portal vein. The pH, [Formula: see text], and base excess (BE) decreased, but [Formula: see text] values increased after 75% resection in the portal and jugular veins. EH correlated with reduced BE in the hepatic artery. Pco 2 values increased after 75% resection in the jugular vein. In contrast, arterial Po 2 increased after every resection, whereas the venous Po 2 decreased slightly. There were differences in venous [Formula: see text], BE in the hepatic artery, and Pco 2 in the jugular vein after 75% liver resection. Because 75% resection is the limit for SFSF, these noninvasive blood evaluations may be used to predict SFSF. Further studies with long-term follow-up are required to validate this correlation. NEW & NOTEWORTHY This is the first study to evaluate acid-base parameters in major central and hepatic vessels during stepwise liver resection. The pH, [Formula: see text], and base excess (BE) decreased, but [Formula: see text] values increased after 75% resection in the portal and jugular veins. Extended hepatectomy correlated with reduced BE in the hepatic artery. Because 75% resection is the limit for small for size and flow

Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism

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Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E.; Lamers, Wouter H.; Chaudhry, Farrukh A.; Verlander, Jill W.

2016-01-01

Glutamine synthetase (GS) catalyzes the recycling of NH4+ with glutamate to form glutamine. GS is highly expressed in the renal proximal tubule (PT), suggesting ammonia recycling via GS could decrease net ammoniagenesis and thereby limit ammonia available for net acid excretion. The purpose of the present study was to determine the role of PT GS in ammonia metabolism under basal conditions and during metabolic acidosis. We generated mice with PT-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Under basal conditions, PT-GS-KO increased urinary ammonia excretion significantly. Increased ammonia excretion occurred despite decreased expression of key proteins involved in renal ammonia generation. After the induction of metabolic acidosis, the ability to increase ammonia excretion was impaired significantly by PT-GS-KO. The blunted increase in ammonia excretion occurred despite greater expression of multiple components of ammonia generation, including SN1 (Slc38a3), phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and Na+-coupled electrogenic bicarbonate cotransporter. We conclude that 1) GS-mediated ammonia recycling in the PT contributes to both basal and acidosis-stimulated ammonia metabolism and 2) adaptive changes in other proteins involved in ammonia metabolism occur in response to PT-GS-KO and cause an underestimation of the role of PT GS expression. PMID:27009341

Effects of Fatty Liver Induced by Excess Orotic Acid on B-Group Vitamin Concentrations of Liver, Blood, and Urine in Rats.

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Shibata, Katsumi; Morita, Nobuya; Kawamura, Tomoyo; Tsuji, Ai; Fukuwatari, Tsutomu

2015-01-01

Fatty liver is caused when rats are given orotic acid of the pyrimidine base in large quantities. The lack of B-group vitamins suppresses the biosynthesis of fatty acids. We investigated how orotic acid-induced fatty liver affects the concentrations of liver, blood, and urine B-group vitamins in rats. The vitamin B6 and B12 concentrations of liver, blood, and urine were not affected by orotic acid-induced fatty liver. Vitamin B2 was measured only in the urine, but was unchanged. The liver, blood, and urine concentrations of niacin and its metabolites fell dramatically. Niacin and its metabolites in the liver, blood, and urine were affected as expected. Although the concentrations of vitamin B1, pantothenic acid, folate, and biotin in liver and blood were decreased by orotic acid-induced fatty liver, these urinary excretion amounts showed a specific pattern toward increase. Generally, as for the typical urinary excretion of B-group vitamins, these are excreted when the body is saturated. However, the ability to sustain vitamin B1, pantothenic acid, folate, and biotin decreased in fatty liver, which is hypothesized as a specific phenomenon. This metabolic response might occur to prevent an abnormally increased biosynthesis of fatty acids by orotic acid.

Evaluation of Basal Serum Adrenocorticotropic Hormone and Cortisol Levels and Their Relationship with Nonalcoholic Fatty Liver Disease in Male Patients with Idiopathic Hypogonadotropic Hypogonadism

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Wen-Bo Wang

2016-01-01

Conclusions: The male IHH patients showed higher basal serum ACTH levels and lower cortisol levels than matched healthy controls. NAFLD was an independent associated factor for ACTH levels in male IHH patients. These preliminary findings provided evidence of the relationship between basal serum ACTH and NAFLD in male IHH patients.

Metabolomic profiling of a modified alcohol liquid diet model for liver injury in the mouse uncovers new markers of disease

International Nuclear Information System (INIS)

Bradford, Blair U.; O'Connell, Thomas M.; Han, Jun; Kosyk, Oksana; Shymonyak, Svitlana; Ross, Pamela K.; Winnike, Jason; Kono, Hiroshi; Rusyn, Ivan

2008-01-01

Metabolomic evaluation of urine and liver was conducted to assess the biochemical changes that occur as a result of alcohol-induced liver injury. Male C57BL/6J mice were fed an isocaloric control- or alcohol-containing liquid diet with 35% of calories from corn oil, 18% protein and 47% carbohydrate/alcohol for up to 36 days ad libitum. Alcohol treatment was initiated at 7 g/kg/day and gradually reached a final dose of 21 g/kg/day. Urine samples were collected at 22, 30 and 36 days and, in additional treatment groups, liver and serum samples were harvested at 28 days. Steatohepatitis was induced in the alcohol-fed group since a 5-fold increase in serum alanine aminotransferase activity, a 6-fold increase in liver injury score (necrosis, inflammation and steatosis) and an increase in lipid peroxidation in liver were observed. Liver and urine samples were analyzed by nuclear magnetic resonance spectroscopy and electrospray infusion/Fourier transform ion cyclotron resonance-mass spectrometry. In livers of alcohol-treated mice the following changes were noted. Hypoxia and glycolysis were activated as evidenced by elevated levels of alanine and lactate. Tyrosine, which is required for L-DOPA and dopamine as well as thyroid hormones, was elevated possibly reflecting alterations of basal metabolism by alcohol. A 4-fold increase in the prostacyclin inhibitor 7,10,13,16-docosatetraenoic acid, a molecule important for regulation of platelet formation and blood clotting, may explain why chronic drinking causes serious bleeding problems. Metabolomic analysis of the urine revealed that alcohol treatment leads to decreased excretion of taurine, a metabolite of glutathione, and an increase in lactate, n-acetylglutamine and n-acetylglycine. Changes in the latter two metabolites suggest an inhibition of the kidney enzyme aminoacylase I and may be useful as markers for alcohol consumption

Photodynamic therapy for basal cell carcinoma.

Science.gov (United States)

Fargnoli, Maria Concetta; Peris, Ketty

2015-11-01

Topical photodynamic therapy is an effective and safe noninvasive treatment for low-risk basal cell carcinoma, with the advantage of an excellent cosmetic outcome. Efficacy of photodynamic therapy in basal cell carcinoma is supported by substantial research and clinical trials. In this article, we review the procedure, indications and clinical evidences for the use of photodynamic therapy in the treatment of basal cell carcinoma.

Cholinergic basal forebrain structures are not essential for mediation of the arousing action of glutamate.

Science.gov (United States)

Lelkes, Zoltán; Abdurakhmanova, Shamsiiat; Porkka-Heiskanen, Tarja

2017-09-18

The cholinergic basal forebrain contributes to cortical activation and receives rich innervations from the ascending activating system. It is involved in the mediation of the arousing actions of noradrenaline and histamine. Glutamatergic stimulation in the basal forebrain results in cortical acetylcholine release and suppression of sleep. However, it is not known to what extent the cholinergic versus non-cholinergic basal forebrain projection neurones contribute to the arousing action of glutamate. To clarify this question, we administered N-methyl-D-aspartate (NMDA), a glutamate agonist, into the basal forebrain in intact rats and after destruction of the cholinergic cells in the basal forebrain with 192 immunoglobulin (Ig)G-saporin. In eight Han-Wistar rats with implanted electroencephalogram/electromyogram (EEG/EMG) electrodes and guide cannulas for microdialysis probes, 0.23 μg 192 IgG-saporin was administered into the basal forebrain, while the eight control animals received artificial cerebrospinal fluid. Two weeks later, a microdialysis probe targeted into the basal forebrain was perfused with cerebrospinal fluid on the baseline day and for 3 h with 0.3 mmNMDA on the subsequent day. Sleep-wake activity was recorded for 24 h on both days. NMDA exhibited a robust arousing effect in both the intact and the lesioned rats. Wakefulness was increased and both non-REM and REM sleep were decreased significantly during the 3-h NMDA perfusion. Destruction of the basal forebrain cholinergic neurones did not abolish the wake-enhancing action of NMDA. Thus, the cholinergic basal forebrain structures are not essential for the mediation of the arousing action of glutamate. © 2017 European Sleep Research Society.

Red Dot Basal Cell Carcinoma: Report of Cases and Review of This Unique Presentation of Basal Cell Carcinoma.

Science.gov (United States)

Cohen, Philip R

2017-03-22

Red dot basal cell carcinoma is a unique variant of basal cell carcinoma. Including the three patients described in this report, red dot basal cell carcinoma has only been described in seven individuals. This paper describes the features of two males and one female with red dot basal cell carcinoma and reviews the characteristics of other patients with this clinical subtype of basal cell carcinoma. A 70-year-old male developed a pearly-colored papule with a red dot in the center on his nasal tip. A 71-year-old male developed a red dot surrounded by a flesh-colored papule on his left nostril. Lastly, a 74-year-old female developed a red dot within an area of erythema on her left mid back. Biopsy of the lesions all showed nodular and/or superficial basal cell carcinoma. Correlation of the clinical presentation and pathology established the diagnosis of red dot basal cell carcinoma. The tumors were treated by excision using the Mohs surgical technique. Pubmed was searched with the keyword: basal, cell, cancer, carcinoma, dot, red, and skin. The papers generated by the search and their references were reviewed. Red dot basal cell carcinoma has been described in three females and two males; the gender was not reported in two patients. The tumor was located on the nose (five patients), back (one patient) and thigh (one patient). Cancer presented as a solitary small red macule or papule; often, the carcinoma was surrounded by erythema or a flesh-colored papule. Although basal cell carcinomas usually do not blanch after a glass microscope slide is pressed against them, the red dot basal cell carcinoma blanched after diascopy in two of the patients, resulting in a delay of diagnosis in one of these individuals. Dermoscopy may be a useful non-invasive modality for evaluating skin lesions when the diagnosis of red dot basal cell carcinoma is considered. Mohs surgery is the treatment of choice; in some of the patients, the ratio of the area of the postoperative wound to that

Streptozotocin-induced diabetes mellitus affects lysosomal enzymes in rat liver

Directory of Open Access Journals (Sweden)

G.B. Peres

2014-06-01

Full Text Available It has been previously shown that dextran sulfate administered to diabetic rats accumulates in the liver and kidney, and this could be due to a malfunction of the lysosomal digestive pathway. The aim of the present study was to evaluate the expression and activities of lysosomal enzymes that act upon proteins and sulfated polysaccharides in the livers of diabetic rats. Diabetes mellitus was induced by streptozotocin in 26 male Wistar rats (12 weeks old, while 26 age-matched controls received only vehicle. The livers were removed on either the 10th or the 30th day of the disease, weighed, and used to evaluate the activity, expression, and localization of lysosomal enzymes. A 50-60% decrease in the specific activities of cysteine proteases, especially cathepsin B, was observed in streptozotocin-induced diabetes mellitus. Expression (mRNA of cathepsins B and L was also decreased on the 10th, but not on the 30th day. Sulfatase decreased 30% on the 30th day, while glycosidases did not vary (or presented a transitory and slight decrease. There were no apparent changes in liver morphology, and immunohistochemistry revealed the presence of cathepsin B in hepatocyte granules. The decrease in sulfatase could be responsible for the dextran sulfate build-up in the diabetic liver, since the action of sulfatase precedes glycosidases in the digestive pathway of sulfated polysaccharides. Our findings suggest that the decreased activities of cathepsins resulted from decreased expression of their genes, and not from general lysosomal failure, because the levels of glycosidases were normal in the diabetic liver.

Streptozotocin-induced diabetes mellitus affects lysosomal enzymes in rat liver

Energy Technology Data Exchange (ETDEWEB)

Peres, G.B. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Bioquímica, São Paulo, SP, Brasil, Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Juliano, M.A. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Biofísica, São Paulo, SP, Brasil, Departamento de Biofísica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil); Aguiar, J.A.K.; Michelacci, Y.M. [Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Bioquímica, São Paulo, SP, Brasil, Departamento de Bioquímica, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP (Brazil)

2014-05-09

It has been previously shown that dextran sulfate administered to diabetic rats accumulates in the liver and kidney, and this could be due to a malfunction of the lysosomal digestive pathway. The aim of the present study was to evaluate the expression and activities of lysosomal enzymes that act upon proteins and sulfated polysaccharides in the livers of diabetic rats. Diabetes mellitus was induced by streptozotocin in 26 male Wistar rats (12 weeks old), while 26 age-matched controls received only vehicle. The livers were removed on either the 10{sup th} or the 30{sup th} day of the disease, weighed, and used to evaluate the activity, expression, and localization of lysosomal enzymes. A 50-60% decrease in the specific activities of cysteine proteases, especially cathepsin B, was observed in streptozotocin-induced diabetes mellitus. Expression (mRNA) of cathepsins B and L was also decreased on the 10{sup th}, but not on the 30{sup th} day. Sulfatase decreased 30% on the 30{sup th} day, while glycosidases did not vary (or presented a transitory and slight decrease). There were no apparent changes in liver morphology, and immunohistochemistry revealed the presence of cathepsin B in hepatocyte granules. The decrease in sulfatase could be responsible for the dextran sulfate build-up in the diabetic liver, since the action of sulfatase precedes glycosidases in the digestive pathway of sulfated polysaccharides. Our findings suggest that the decreased activities of cathepsins resulted from decreased expression of their genes, and not from general lysosomal failure, because the levels of glycosidases were normal in the diabetic liver.

Streptozotocin-induced diabetes mellitus affects lysosomal enzymes in rat liver

International Nuclear Information System (INIS)

Peres, G.B.; Juliano, M.A.; Aguiar, J.A.K.; Michelacci, Y.M.

2014-01-01

It has been previously shown that dextran sulfate administered to diabetic rats accumulates in the liver and kidney, and this could be due to a malfunction of the lysosomal digestive pathway. The aim of the present study was to evaluate the expression and activities of lysosomal enzymes that act upon proteins and sulfated polysaccharides in the livers of diabetic rats. Diabetes mellitus was induced by streptozotocin in 26 male Wistar rats (12 weeks old), while 26 age-matched controls received only vehicle. The livers were removed on either the 10 th or the 30 th day of the disease, weighed, and used to evaluate the activity, expression, and localization of lysosomal enzymes. A 50-60% decrease in the specific activities of cysteine proteases, especially cathepsin B, was observed in streptozotocin-induced diabetes mellitus. Expression (mRNA) of cathepsins B and L was also decreased on the 10 th , but not on the 30 th day. Sulfatase decreased 30% on the 30 th day, while glycosidases did not vary (or presented a transitory and slight decrease). There were no apparent changes in liver morphology, and immunohistochemistry revealed the presence of cathepsin B in hepatocyte granules. The decrease in sulfatase could be responsible for the dextran sulfate build-up in the diabetic liver, since the action of sulfatase precedes glycosidases in the digestive pathway of sulfated polysaccharides. Our findings suggest that the decreased activities of cathepsins resulted from decreased expression of their genes, and not from general lysosomal failure, because the levels of glycosidases were normal in the diabetic liver

Investigation on liver fast metabolism with CT

International Nuclear Information System (INIS)

Huebener, K.H.; Schmitt, W.G.H.

1981-01-01

Measurements of the density of normal and diffusely diseased liver parenchyma show a significant difference only in fatty liver. A linear relationship between the fat content and physical density has been demonstrated. Computed tomographic densitometry of liver tissue correlates well with physical in vitro measurements of fat content and is sufficiently accurate for clinical use. Other types of liver diseases cannot be differentiated by densitometry, Lipolisis in fatty liver in chronic alcoholism alcohol withdrawal has been investigated. It has been found that a rate of decrease of the fatty degeneration of the liver equals to 1 percent/day. Fatty degeneration of the liver in acute pancreatitis and other diseases have been also investigated. CT densitometry of the liver should be considered as a useful routine clinical method to determine the fat content of liver. (author)

Investigation on liver fast metabolism with CT

Energy Technology Data Exchange (ETDEWEB)

Huebener, K.H.; Schmitt, W.G.H. (Heidelberg Univ. (Germany, F.R.). Pathologisches Inst.)

1981-01-01

Measurements of the density of normal and diffusely diseased liver parenchyma show a significant difference only in fatty liver. A linear relationship between the fat content and physical density has been demonstrated. Computed tomographic densitometry of liver tissue correlates well with physical in vitro measurements of fat content and is sufficiently accurate for clinical use. Other types of liver diseases cannot be differentiated by densitometry, Lipolisis in fatty liver in chronic alcoholism alcohol withdrawal has been investigated. It has been found that a rate of decrease of the fatty degeneration of the liver equals to 1 percent/day. Fatty degeneration of the liver in acute pancreatitis and other diseases have been also investigated. CT densitometry of the liver should be considered as a useful routine clinical method to determine the fat content of liver.

Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

Science.gov (United States)

Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

2015-01-01

In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type.

Early histological and functional effects of chronic copper exposure in rat liver.

Science.gov (United States)

Cisternas, Felipe A; Tapia, Gladys; Arredondo, Miguel; Cartier-Ugarte, Denise; Romanque, Pamela; Sierralta, Walter D; Vial, María T; Videla, Luis A; Araya, Magdalena

2005-10-01

Cu is an essential trace element capable of producing toxic effects in animals and man when ingested acutely or chronically in excess. Although chronic Cu exposure is increasingly recognized as a public health issue, its early effects remain largely unknown. We approached the significance of a moderate chronic Cu load in young rats to correlate early hepatic histopathological changes with functional alterations of liver cells. For this purpose, supplementation with 1,200 ppm of Cu in rat food for 16 weeks was chosen. In these conditions, Cu load elicited a significant decrease in growth curves. There were mild light microscopy alterations in Cu-treated rats, although increasing intracellular Cu storage was correlated with longer Cu exposure both by histological and biochemical measurements. Ultrastructural alterations included lysosomal inclusions as well as mitochondrial and nuclear changes. Liver perfusion studies revealed higher rates of basal O(2) consumption and colloidal carbon-induced O(2) uptake in Cu-treated rats, with enhanced carbon-induced O(2)/carbon uptake ratios and NF-kappaB DNA binding activity. These changes were time-dependent and returned to control values after 12 or 16 weeks. It is concluded that subchronic Cu loading in young rats induces early hepatic morphological changes, with enhancement in Küpffer cell-dependent respiratory burst activity and NF-kappaB DNA binding, cellular responses that may prevent or alleviate the hepatotoxicity of the metal.

Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease.

Directory of Open Access Journals (Sweden)

Steven D Kunkel

Full Text Available Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II, blood vessel recruitment (Vegfa and autocrine/paracrine IGF-I signaling (Igf1. As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness.

CT values of fatty liver due to L-asparaginase administration

Energy Technology Data Exchange (ETDEWEB)

Muraki, Kotaro; Kubo, Kazuaki; Hamamoto, Kazuko; Ueda, Kazuhiro; Kashiwado, Kozo; Ito, Katsuhide (Hiroshima Red Cross Hospital (Japan))

1984-02-01

Chemotherapy involving L-asparaginase was performed on a 9-year-old female child with malignant lymphoma, and a 3-year-old male child and a 14-year-old female child with acute lymphatic leukemia, and the course of L-asparaginase-induced fatty liver was followed up primarily by CT findings. In all 3 cases, L-asparaginase administration caused a marked fatty liver characterized by a diffuse cold area of the liver and a decrease in the value of the liver (liver/spleen<1) on CT. Hypoproteinemia, hypofibrinogenemia and elevations of GOT and GPT were simultaneously observed, but marked anemia, pancreatitis, decreased glucose tolerance and central nervous disorder did not occur. Recovery of fatty liver was slower in CT findings than in blood biochemistry, taking about 4 weeks.

Positron emission tomography and basal ganglia functions

International Nuclear Information System (INIS)

Kato, Motohiro; Otsuka, Makoto; Taniwaki, Koukyo; Hosokawa, Shinichi; Kuwabara, Yasuo; Ichiya, Yuichi

1990-01-01

With the advent of positron emission tomography (PET), studies on the human brain function and pathophysiology of brain damage have been extremely progressed. It is well-known that the basal ganglia plays an important role as one of the central nervous system involved in exercise regulation. More recently, the potential involvement of the basal ganglia in psychological processes, such as cognitive function, has been pointed out, receiving much attention. In spite of such a lot of studies, however, basal ganglia function remains unclear. This paper describes the relationships between PET findings and basal ganglia function. PET findings are discussed in relation to brain energy metabolism and striatal dopamine function. Pathophysiology of the basal ganglia are described in terms of the following diseases: Parkinson's disease, Parkinson's syndrome, progressive supranuclear palsy, Huntington's disease, and dystonia. Physiological backgrounds of the basal ganglia for PET images are also referred to. (N.K.) 75 refs

Positron emission tomography and basal ganglia functions

Energy Technology Data Exchange (ETDEWEB)

Kato, Motohiro; Otsuka, Makoto; Taniwaki, Koukyo; Hosokawa, Shinichi; Kuwabara, Yasuo; Ichiya, Yuichi [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

1990-05-01

With the advent of positron emission tomography (PET), studies on the human brain function and pathophysiology of brain damage have been extremely progressed. It is well-known that the basal ganglia plays an important role as one of the central nervous system involved in exercise regulation. More recently, the potential involvement of the basal ganglia in psychological processes, such as cognitive function, has been pointed out, receiving much attention. In spite of such a lot of studies, however, basal ganglia function remains unclear. This paper describes the relationships between PET findings and basal ganglia function. PET findings are discussed in relation to brain energy metabolism and striatal dopamine function. Pathophysiology of the basal ganglia are described in terms of the following diseases: Parkinson's disease, Parkinson's syndrome, progressive supranuclear palsy, Huntington's disease, and dystonia. Physiological backgrounds of the basal ganglia for PET images are also referred to. (N.K.) 75 refs.

Cost-effectiveness of liraglutide versus lixisenatide as add-on therapies to basal insulin in type 2 diabetes.

Science.gov (United States)

Ericsson, Åsa; Glah, Divina; Lorenzi, Maria; Jansen, Jeroen P; Fridhammar, Adam

2018-01-01

We assessed the cost-effectiveness of the glucagon-like peptide 1 receptor agonists liraglutide 1.8 mg and lixisenatide 20 μg (both added to basal insulin) in patients with type 2 diabetes (T2D) in Sweden. The Swedish Institute for Health Economics cohort model for T2D was used to compare liraglutide and lixisenatide (both added to basal insulin), with a societal perspective and with comparative treatment effects derived by indirect treatment comparison (ITC). Drug prices were 2016 values, and all other costs 2015 values. The cost-effectiveness of IDegLira (fixed-ratio combination of insulin degludec and liraglutide) versus lixisenatide plus basal insulin was also assessed, under different sets of assumptions. From the ITC, decreases in HbA1c were -1.32% and -0.43% with liraglutide and lixisenatide, respectively; decreases in BMI were -1.29 and -0.65 kg/m2, respectively. An estimated 2348 cases of retinopathy, 265 of neuropathy and 991 of nephropathy would be avoided with liraglutide compared with lixisenatide in a cohort of 10,000 patients aged over 40 years. In the base-case analysis, total direct costs were higher with liraglutide than lixisenatide, but costs associated with complications were lower. The cost/quality-adjusted life-year (QALY) for liraglutide added to basal insulin was SEK30,802. Base-case findings were robust in sensitivity analyses, except when glycated haemoglobin (HbA1c) differences for liraglutide added to basal insulin were abolished, suggesting these benefits were driving the cost/QALY. With liraglutide 1.2 mg instead of liraglutide 1.8 mg (adjusted for efficacy and cost), liraglutide added to basal insulin was dominant over lixisenatide 20μg.IDegLira was dominant versus lixisenatide plus basal insulin when a defined daily dose was used in the model. The costs/QALY for liraglutide, 1.8 or 1.2 mg, added to basal insulin, and for IDegLira (all compared with lixisenatide 20 μg added to basal insulin) were below the threshold considered low

Cost-effectiveness of liraglutide versus lixisenatide as add-on therapies to basal insulin in type 2 diabetes

Science.gov (United States)

2018-01-01

Background We assessed the cost-effectiveness of the glucagon-like peptide 1 receptor agonists liraglutide 1.8 mg and lixisenatide 20 μg (both added to basal insulin) in patients with type 2 diabetes (T2D) in Sweden. Methods The Swedish Institute for Health Economics cohort model for T2D was used to compare liraglutide and lixisenatide (both added to basal insulin), with a societal perspective and with comparative treatment effects derived by indirect treatment comparison (ITC). Drug prices were 2016 values, and all other costs 2015 values. The cost-effectiveness of IDegLira (fixed-ratio combination of insulin degludec and liraglutide) versus lixisenatide plus basal insulin was also assessed, under different sets of assumptions. Results From the ITC, decreases in HbA1c were –1.32% and –0.43% with liraglutide and lixisenatide, respectively; decreases in BMI were –1.29 and –0.65 kg/m2, respectively. An estimated 2348 cases of retinopathy, 265 of neuropathy and 991 of nephropathy would be avoided with liraglutide compared with lixisenatide in a cohort of 10,000 patients aged over 40 years. In the base-case analysis, total direct costs were higher with liraglutide than lixisenatide, but costs associated with complications were lower. The cost/quality-adjusted life-year (QALY) for liraglutide added to basal insulin was SEK30,802. Base-case findings were robust in sensitivity analyses, except when glycated haemoglobin (HbA1c) differences for liraglutide added to basal insulin were abolished, suggesting these benefits were driving the cost/QALY. With liraglutide 1.2 mg instead of liraglutide 1.8 mg (adjusted for efficacy and cost), liraglutide added to basal insulin was dominant over lixisenatide 20μg.IDegLira was dominant versus lixisenatide plus basal insulin when a defined daily dose was used in the model. Conclusions The costs/QALY for liraglutide, 1.8 or 1.2 mg, added to basal insulin, and for IDegLira (all compared with lixisenatide 20 μg added to basal

Effects of 60Co gamma-ray local irradiation on rat liver on alkaline phosphatase, lactate dehydrogenase and catalase in the liver and serum

International Nuclear Information System (INIS)

Hishikawa-Itoh, Youko; Ayakawa, Yoshio; Miyata, Nobuki

1980-01-01

Rats were given a single exposure of various doses (0, 5, 50, 500, and 5000 rads) to local irradiation of 60 Co γ-ray on liver. Activities of alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and catalase in the serum and liver were measured at various time intervals after irradiation. These results were summarized as follows; 1. ALP activity in the serum had no effect on irradiation up to 500 rads, but in the case of 5000 rads irradiation exhibited a marked loss from 4 days after irradiation. ALP activity in the liver to 5000 rads exposure on 7 days after irradiation increased, on the other hand in the serum decreased, and the patterns of ALP activities in the liver and serum to the irradiation doses were opposite. 2. LDH activity in the serum by exposure to 5, 500 and 5000 rads increased at 4 days after irradiation, but at 7 days significantly decreased. LDH activity in the liver to the irradiation doses on 7 days after irradiation did not markedly change, but in the serum it tended to be low in inverse proportion to the irradiation doses. 3. Catalase activity in the serum to 50 and 500 rads exposure increased at 4 days after irradiation and decreased at 7 days, but to 5000 rads exposure it decreased in the course of time. Catalase activity in the liver and serum on 7 days after irradiation were inversely proportional to irradiation doses. It is difficult that catalase activity makes a index of clinical irradiation effects, because catalase activity decrease under the various conditions, such as cancer, anemia, infection of bacterias and so on. Since activities of ALP and LDH increase in almost disease, decrease of ALP activity and decrease following temporary increase of LDH activity by irradiation may be able to become a clinical indicator on irradiation effects. (author)

Impact of Basal Conditions on Grounding-Line Retreat

Science.gov (United States)

Koellner, S. J.; Parizek, B. R.; Alley, R. B.; Muto, A.; Holschuh, N.; Nowicki, S.

2017-12-01

An often-made assumption included in ice-sheet models used for sea-level projections is that basal rheology is constant throughout the domain of the simulation. The justification in support of this assumption is that physical data for determining basal rheology is limited and a constant basal flow law can adequately approximate current as well as past behavior of an ice-sheet. Prior studies indicate that beneath Thwaites Glacier (TG) there is a ridge-and-valley bedrock structure which likely promotes deformation of soft tills within the troughs and sliding, more akin to creep, over the harder peaks; giving rise to a spatially variable basal flow law. Furthermore, it has been shown that the stability of an outlet glacier varies with the assumed basal rheology, so accurate projections almost certainly need to account for basal conditions. To test the impact of basal conditions on grounding-line evolution forced by ice-shelf perturbations, we modified the PSU 2-D flowline model to enable the inclusion of spatially variable basal rheology along an idealized bedrock profile akin to TG. Synthetic outlet glacier "data" were first generated under steady-state conditions assuming a constant basal flow law and a constant basal friction coefficient field on either a linear or bumpy sloping bed. In following standard procedures, a suite of models were then initialized by assuming different basal rheologies and then determining the basal friction coefficients that produce surface velocities matching those from the synthetic "data". After running each of these to steady state, the standard and full suite of models were forced by drastically reducing ice-shelf buttressing through side-shear and prescribed basal-melting perturbations. In agreement with previous findings, results suggest a more plastic basal flow law enhances stability in response to ice-shelf perturbations by flushing ice from farther upstream to sustain the grounding-zone mass balance required to prolong the

Basal Forebrain Cholinergic Deficits Reduce Glucose Metabolism and Function of Cholinergic and GABAergic Systems in the Cingulate Cortex.

Science.gov (United States)

Jeong, Da Un; Oh, Jin Hwan; Lee, Ji Eun; Lee, Jihyeon; Cho, Zang Hee; Chang, Jin Woo; Chang, Won Seok

2016-01-01

Reduced brain glucose metabolism and basal forebrain cholinergic neuron degeneration are common features of Alzheimer's disease and have been correlated with memory function. Although regions representing glucose hypometabolism in patients with Alzheimer's disease are targets of cholinergic basal forebrain neurons, the interaction between cholinergic denervation and glucose hypometabolism is still unclear. The aim of the present study was to evaluate glucose metabolism changes caused by cholinergic deficits. We lesioned basal forebrain cholinergic neurons in rats using 192 immunoglobulin G-saporin. After 3 weeks, lesioned animals underwent water maze testing or were analyzed by ¹⁸F-2-fluoro-2-deoxyglucose positron emission tomography. During water maze probe testing, performance of the lesioned group decreased with respect to time spent in the target quadrant and platform zone. Cingulate cortex glucose metabolism in the lesioned group decreased, compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression declined in the cingulate cortex. Our results reveal that spatial memory impairment in animals with selective basal forebrain cholinergic neuron damage is associated with a functional decline in the GABAergic and cholinergic system associated with cingulate cortex glucose hypometabolism.

Basal-body-associated macromolecules: a continuing debate.

Science.gov (United States)

Pierre Mignot, J; Brugerolle, G; Didier, P; Bornens, M

1993-07-01

Controversy over the possibility that centrioles/basal bodies contain nucleic acids has overshadowed results demonstrating other macromolecules in the lumen of these organelles. Glycogen particles, which are known to be present within the lumen of the centriole/basal body of sperm cells, have now been found in basal bodies of protists belonging to three different groups. Here, we extend the debate on a role for RNA in basal body/centriole function and speculate on the origin and the function of centriolar glycogen.

Report Card on Basal Readers.

Science.gov (United States)

Goodman, Kenneth S.; And Others

This report examines the nature of the modern basal reader, its economics, and use. First, the report provides a history showing how the confluence of business principles, positivistic science, and behavioral psychology led to the transformation of reading textbooks into basal readers. Next, the report examines objectives and subjective factors…

Changes in Body Compositions and Basal Metabolic Rates during Treatment of Graves’ Disease

Directory of Open Access Journals (Sweden)

Min Joo Kim

2018-01-01

Full Text Available Objectives. Because thyroid hormone is an important determinant of body weight and basal metabolic rate, we investigated the changes in the basal metabolic rate and body composition sequentially after treatment for Graves’ disease. Methods. A prospective cohort study was performed with six women newly diagnosed with Graves’ disease. During a 52-week treatment of methimazole, body composition, resting respiratory expenditure (REE, and handgrip strength were measured consecutively. Results. After methimazole treatment, body weight was initially increased (0–8 weeks, subsequently plateaued (8–24 weeks, and gradually decreased in the later period (24–52 weeks despite the decreased food intake. The measured REE was 40% higher than the predicted REE at baseline, and it gradually decreased after treatment. REE positively correlated with thyroid hormone levels, peripheral deiodinase activity, and thyroid’s secretory capacity. Body compositional analyses showed that the fat mass increased during an earlier period (4–12 weeks, while the lean mass increased significantly during the later period (26–52 weeks. Consistent with the lean mass changes, muscle strength also significantly increased during the later period. Conclusions. Treatment of Graves’ disease increased body weight and fat mass transiently with decreased REE. However, long-term compositional changes moved in a beneficial direction increasing lean mass and reinforcing muscle strength, following decreasing fat percentages.

High intensity interval training improves liver and adipose tissue insulin sensitivity

Science.gov (United States)

Marcinko, Katarina; Sikkema, Sarah R.; Samaan, M. Constantine; Kemp, Bruce E.; Fullerton, Morgan D.; Steinberg, Gregory R.

2015-01-01

Objective Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC. PMID:26909307

Current management of non-alcoholic fatty liver disease

OpenAIRE

LISBOA, QUELSON COELHO; COSTA, SILVIA MARINHO FEROLLA; COUTO, CLÁUDIA ALVES

2016-01-01

SUMMARY Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic accumulation of lipid in patients who do not consume alcohol in amounts generally considered harmful to the liver. NAFLD is becoming a major liver disease in Eastern countries and it is related to insulin resistance and metabolic syndrome. Treatment has focused on improving insulin sensitivity, protecting the liver from oxidative stress, decreasing obesity and improving diabetes mellitus, dyslipidemia, hepatic infla...

Atrophy of the basal ganglia as the initial diagnostic sign of germinoma in the basal ganglia

Energy Technology Data Exchange (ETDEWEB)

Okamoto, K.; Ishikawa, K.; Takahashi, N.; Furusawa, T.; Sakai, K. [Department of Radiology, Niigata University Faculty of Medicine (Japan); Ito, J.; Tokiguchi, S. [Department of Radiology, Niigata University Faculty of Dentistry (Japan); Morii, K. [Department of Neurosurgery, Niigata University Brain Research Institute (Japan); Yamada, M. [Department of Pathology, Niigata University Brain Research Institute (Japan)

2002-05-01

Germ-cell tumors of the central nervous system generally develop in the midline, but the tumors can also occur in the basal ganglia and/or thalamus. However, MR images have rarely been documented in the early stage of the tumor in these regions. We retrospectively reviewed MR images obtained on admission and approximately 3 years earlier in two patients with germinoma in the basal ganglia, and compared them with CT. In addition to hyperdensity on CT, both hyperintensity on T1-weighted images and a small hyperintense lesion on T2-weighted images were commonly seen in the basal ganglia. These findings may be early MRI signs of germinoma in this region, and the earliest and most characteristic diagnostic feature on MRI was atrophy of the basal ganglia, which was recognizable before development of hemiparesis. (orig.)

CT values of fatty liver due to L-asparaginase administration

International Nuclear Information System (INIS)

Muraki, Kotaro; Kubo, Kazuaki; Hamamoto, Kazuko; Ueda, Kazuhiro; Kashiwado, Kozo; Ito, Katsuhide

1984-01-01

Chemotherapy involving L-asparaginase was performed on a 9-year-old female child with malignant lymphoma, and a 3-year-old male child and a 14-year-old female child with acute lymphatic leukemia, and the course of L-asparaginase-induced fatty liver was followed up primarily by CT findings. In all 3 cases, L-asparaginase administration caused a marked fatty liver characterized by a diffuse cold area of the liver and a decrease in the value of the liver (liver/spleen<1) on CT. Hypoproteinemia, hypofibrinogenemia and elevations of GOT and GPT were simultaneously observed, but marked anemia, pancreatitis, decreased glucose tolerance and central nervous disorder did not occur. Recovery of fatty liver was slower in CT findings than in blood biochemistry, taking about 4 weeks. (Chiba, N.)

Indirect effect of ionizing radiation on adehylate cyclase activity of liver cells in rat embryos

International Nuclear Information System (INIS)

Slozhenikina, L.V.; Ushakova, T.E.; Mikhajlets, L.P.; Kuzin, A.M.

1980-01-01

A comparative study was made of the effect of ionizing radiation on basal and catecholamine-stimulating activity of adenylate cyclase in the liver of 20-day embroys under in vivo and in vitro conditions (a membrane fraction and plasma membranes). The authors discuss the share of the indirect effect of radiation in modifying the adenylate cyclase activity

Septic liver - Clinical relevance of early inhomogeneous enhancement of the liver in patients with acute pyelonephritis

Energy Technology Data Exchange (ETDEWEB)

Han, Ga Jin; Lee, Nam Kyung; Kim, Suk [Dept. of Radiology, Biomedical Research Inst., Pusan National Univ. Hospital, Pusan National Univ. School of Medicine, Busan (Korea, Republic of)], e-mail: kimsuk@medimail.co.kr; Kim, Tae Un [Dept. of Radiology, Pusan National Univ. Yangsan Hospital, Pusan National Univ. School of Medicine, Yangsan (Korea, Republic of); Song, Sang Heon [Dept. of Internal Medicine, Biomedical Research Inst., Pusan National Univ. Hospital, Pusan National Univ. School of Medicine, Busan (Korea, Republic of); Kim, Hyun Sung; Jo, Hong Jae [Dept. of Surgery, Biomedical Research Inst., Pusan National Univ. Hospital, Pusan National Univ. School of Medicine, Busan (Korea, Republic of)

2013-10-15

Background: CT scans of patients with febrile illness occasionally show hepatobiliary changes, although infection does not originate in the hepatobiliary system. These findings may cause radiologists and clinicians to misrecognize hepatobiliary diseases and initiate an inappropriate treatment. Thus, it is important to recognize hepatobiliary CT findings in cases of extrahepatobiliary infectious disease. Purpose: To evaluate extrarenal CT manifestations in patients with acute pyelonephritis and to determine the correlation between these extrarenal CT findings and septic liver based on laboratory parameters of sepsis. Material and Methods: This study included 157 retrospectively identified patients with confirmed acute pyelonephritis based on CT imaging and urine test, and who had also undergone multi-phase dynamic contrast-enhanced CT scan. Two radiologists reviewed CT findings including early inhomogeneous enhancement of the liver, periportal low density and gallbladder edema, which were correlated with laboratory data including liver function enzymes, albumin, C-reactive protein, white blood cell count, and results of a blood culture by using the Fisher's exact test and Mann-Whitney U test. Results: Forty-six patients (29.3%) showed early inhomogeneous enhancement of the liver, which was associated with increased C-reactive protein (P < 0.001), a positive blood culture (P < 0.005), and decreased albumin level (P < 0.002). The periportal low density and gallbladder wall edema were noted in 15 patients (9.6%) and six patients (3.8%), respectively. These two CT findings were significantly associated with only decreased albumin level (P < 0.001 and P < 0.040). Conclusion: Early inhomogeneous enhancement of the liver in patients with acute pyelonephritis was significantly associated with increased CRP level, a positive blood culture and decreased albumin level, reflecting sepsis and sepsis-associated liver dysfunction, requiring rapid and appropriate intensive

Septic liver - Clinical relevance of early inhomogeneous enhancement of the liver in patients with acute pyelonephritis

International Nuclear Information System (INIS)

Han, Ga Jin; Lee, Nam Kyung; Kim, Suk; Kim, Tae Un; Song, Sang Heon; Kim, Hyun Sung; Jo, Hong Jae

2013-01-01

Background: CT scans of patients with febrile illness occasionally show hepatobiliary changes, although infection does not originate in the hepatobiliary system. These findings may cause radiologists and clinicians to misrecognize hepatobiliary diseases and initiate an inappropriate treatment. Thus, it is important to recognize hepatobiliary CT findings in cases of extrahepatobiliary infectious disease. Purpose: To evaluate extrarenal CT manifestations in patients with acute pyelonephritis and to determine the correlation between these extrarenal CT findings and septic liver based on laboratory parameters of sepsis. Material and Methods: This study included 157 retrospectively identified patients with confirmed acute pyelonephritis based on CT imaging and urine test, and who had also undergone multi-phase dynamic contrast-enhanced CT scan. Two radiologists reviewed CT findings including early inhomogeneous enhancement of the liver, periportal low density and gallbladder edema, which were correlated with laboratory data including liver function enzymes, albumin, C-reactive protein, white blood cell count, and results of a blood culture by using the Fisher's exact test and Mann-Whitney U test. Results: Forty-six patients (29.3%) showed early inhomogeneous enhancement of the liver, which was associated with increased C-reactive protein (P < 0.001), a positive blood culture (P < 0.005), and decreased albumin level (P < 0.002). The periportal low density and gallbladder wall edema were noted in 15 patients (9.6%) and six patients (3.8%), respectively. These two CT findings were significantly associated with only decreased albumin level (P < 0.001 and P < 0.040). Conclusion: Early inhomogeneous enhancement of the liver in patients with acute pyelonephritis was significantly associated with increased CRP level, a positive blood culture and decreased albumin level, reflecting sepsis and sepsis-associated liver dysfunction, requiring rapid and appropriate intensive

Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

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Yeliz Bilir

2014-01-01

Full Text Available Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts, the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats

NARCIS (Netherlands)

Fisher, Craig D.; Lickteig, Andrew J.; Augustine, Lisa M.; Oude Elferink, Ronald P. J.; Besselsen, David G.; Erickson, Robert P.; Cherrington, Nathan J.

2009-01-01

Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of diagnoses ranging from simple fatty liver (SFL), to non-alcoholic steatohepatitis (NASH). This study aimed to determine the effect of moderate and severe NAFLD on hepatic transporter expression and function in vivo. Rats were fed a

Improvement of basal conditions knowledge in Antarctica using data assimilation methods

Science.gov (United States)

Mosbeux, C.; Gillet-Chaulet, F.; Gagliardini, O.

2017-12-01

previous experiment, the reconstruction of both basal elevation and basal friction significantly decreases ice flux divergence anomalies when compared to classical methods where only the friction is inverted. Finally, we conduct prognostic simulations, allowing to assess the impact of the different initialisations obtained with the ensemble method.

Real time monitoring of rat liver energy state during ischemia.

Science.gov (United States)

Barbiro, E; Zurovsky, Y; Mayevsky, A

1998-11-01

Hepatic failure is one of the major problems developed during the posttransplantation period. A possible cause of hepatic failure is the prolonged ischemia induced during the implantation procedure. Hepatic ischemia leads to a reduction in oxygen supply, ATP level decline, liver metabolism impairment, and finally organ failure. The purpose of this study was to estimate the functional state of the liver by monitoring liver blood flow and the mitochondrial NADH redox state simultaneously and continuously during in situ liver ischemia followed by reperfusion. Measurements were performed using the multiprobe developed in our laboratory consisting of fibers for the measurement of relative liver blood flow (laser Doppler flowmetry) and mitochondrial redox state (NADH fluorescence). The experimental procedure included the temporary interruption of blood flow to the liver using three types of ischemia, hepatic artery occlusion, portal vein occlusion, and simultaneous occlusion of hepatic artery and portal vein, followed by a reperfusion period. These preliminary experiments showed a significant decrease in liver blood flow, following the three types of liver ischemia, and a significant increase in NADH levels. The probe used in this study incorporates the advantage of monitoring NADH and liver blood flow simultaneously and continuously from the same area on the surface of the liver. Since each of these two parameters is not calibrated in absolute units, the simultaneous monitoring decreases possible artifacts. Also, it will allow us to determine of the coupling between tissue blood flow and oxidative phosphorylation. It is believed that the measurements of respiratory chain dysfunction might predict organ viability in clinical organ transplantation situations. Using this probe may also help to decrease the variability in liver blood flow monitoring since liver blood flow monitoring is supported simultaneously with the mitochondrial redox state, which supplies the

Sclerodermiform basal cell carcinoma: how much can we rely on dermatoscopy to differentiate from non-aggressive basal cell carcinomas? Analysis of 1256 cases.

Science.gov (United States)

Husein-ElAhmed, Husein

2018-03-01

The behaviour of each basal cell carcinoma is known to be different according to the histological growth pattern. Among these aggressive lesions, sclerodermiform basal cell carcinomas are the most common type. This is a challenging-to-treat lesion due to its deep tissue invasion, rapid growth, risk of metastasis and overall poor prognosis if not diagnosed in early stages. To investigate if sclerodermiform basal cell carcinomas are diagnosed later compared to non-sclerodermiform basal cell carcinoma Method: All lesions excised from 2000 to 2010 were included. A pathologist classified the lesions in two cohorts: one with specimens of non-aggressive basal cell carcinoma (superficial, nodular and pigmented), and other with sclerodermiform basal cell carcinoma. For each lesion, we collected patient's information from digital medical records regarding: gender, age when first attending the clinic and the tumor location. 1256 lesions were included, out of which 296 (23.6%) corresponded to sclerodermiform basal cell carcinoma, whereas 960 (76.4%) were non-aggressive subtypes of basal cell carcinoma. The age of diagnosis was: 72.78±12.31 years for sclerodermiform basal cell and 69.26±13.87 years for non-aggressive basal cell carcinoma (Pbasal cell carcinomas are diagnosed on average 3.52 years later than non-aggressive basal cell carcinomas. Sclerodermiform basal cell carcinomas were diagnosed 3.40 years and 2.34 years later than non-aggressive basal cell carcinomas in younger and older patients respectively (P=.002 and P=.03, respectively). retrospective design. The diagnostic accuracy and primary clinic conjecture of sclerodermiform basal cell carcinomas is quite low compared to other forms of basal cell carcinoma such as nodular, superficial and pigmented. The dermoscopic vascular patterns, which is the basis for the diagnosis of non-melanocytic nonpigmented skin tumors, may not be particularly useful in identifying sclerodermiform basal cell carcinomas in early stages

Sub-chronic 90-day toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo

Energy Technology Data Exchange (ETDEWEB)

Wu, Yanli [Department of pharmacology, School of Pharmacy, Huazhong University of Science and Technology, Wuhan 400030 (China); Feng, Yongdong [Department of Gastrointestinal Surgery, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 400030 (China); Li, Yanling [Department of pharmacology, School of Pharmacy, Huazhong University of Science and Technology, Wuhan 400030 (China); Xu, Yiping; Shi, Nian [Department of hygienic toxicology, School of Public Health, Huazhong University of Science and Technology, Wuhan 400030 (China); Hu, Guo-fu [Molecular Oncology Research Institute, Tufts Medical Center, Tufts University, Boston 02111 (United States); Wu, Yunxia, E-mail: wuyunxia@hust.edu.cn [Department of pharmacology, School of Pharmacy, Huazhong University of Science and Technology, Wuhan 400030 (China)

2017-01-15

Neamine, an inhibitor of angiogenin (ANG), is a new investigative anticancer drug currently in preclinical stage. Here we report the 90-day sub-chronic toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo. Neamine has a No Observed Adverse Effect Level (NOAEL) of 12 and 16 mg·kg{sup −1}·d{sup −1} for female and male rats, respectively. No mortality was found. The adverse effects included increased organ coefficients of spleen and kidney, increased BUN in both female and male rats at high dose, increased CR and decreased organ coefficients of heart and liver in male rats at high dose. All of which, except the kidney coefficient and BUN in males, returned to normal levels after 28-day recovery. Histopathological examination revealed vacuolar degeneration of glomerulus, degeneration of renal tubules and cast in the kidneys, which were also recovered except in males of high-dosing group. These results indicate that kidney is the most susceptible organ for neamine toxicity. Tissue microarray analysis validated that ANG is up-regulated in hepatocellular carcinoma accompanied by increased nuclear translocation, suggesting that ANG is a possible target for drug development in liver cancer treatment. Neamine blocked nuclear translocation of ANG in HUVEC and HepG2 cells, and inhibited ANG-stimulated cell proliferation without affecting basal level cell proliferation. Neamine also inhibited progression of HepG2 xenografts in athymic mice accompanied by decreased angiogenesis and cancer cell proliferation. These results suggest that neamine is a specific ANG inhibitor with low toxicity and high anti-liver cancer efficacy. - Highlights: • The NOAEL of neamine is 12 mg·kg{sup −1}·d{sup −1} for females and 16 mg·kg{sup −}1·d{sup −1} for males. • The most susceptible organ for neamine toxicity is kidney. • Neamine inhibits the progression of xenograft HepG2 liver cancer in athymic mice.

Sub-chronic 90-day toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo

International Nuclear Information System (INIS)

Wu, Yanli; Feng, Yongdong; Li, Yanling; Xu, Yiping; Shi, Nian; Hu, Guo-fu; Wu, Yunxia

2017-01-01

Neamine, an inhibitor of angiogenin (ANG), is a new investigative anticancer drug currently in preclinical stage. Here we report the 90-day sub-chronic toxicity of neamine in SD rats and its anti-liver cancer activity in vitro and in vivo. Neamine has a No Observed Adverse Effect Level (NOAEL) of 12 and 16 mg·kg −1 ·d −1 for female and male rats, respectively. No mortality was found. The adverse effects included increased organ coefficients of spleen and kidney, increased BUN in both female and male rats at high dose, increased CR and decreased organ coefficients of heart and liver in male rats at high dose. All of which, except the kidney coefficient and BUN in males, returned to normal levels after 28-day recovery. Histopathological examination revealed vacuolar degeneration of glomerulus, degeneration of renal tubules and cast in the kidneys, which were also recovered except in males of high-dosing group. These results indicate that kidney is the most susceptible organ for neamine toxicity. Tissue microarray analysis validated that ANG is up-regulated in hepatocellular carcinoma accompanied by increased nuclear translocation, suggesting that ANG is a possible target for drug development in liver cancer treatment. Neamine blocked nuclear translocation of ANG in HUVEC and HepG2 cells, and inhibited ANG-stimulated cell proliferation without affecting basal level cell proliferation. Neamine also inhibited progression of HepG2 xenografts in athymic mice accompanied by decreased angiogenesis and cancer cell proliferation. These results suggest that neamine is a specific ANG inhibitor with low toxicity and high anti-liver cancer efficacy. - Highlights: • The NOAEL of neamine is 12 mg·kg −1 ·d −1 for females and 16 mg·kg − 1·d −1 for males. • The most susceptible organ for neamine toxicity is kidney. • Neamine inhibits the progression of xenograft HepG2 liver cancer in athymic mice.

Signal changes in liver and spleen after Endorem administration in patients with and without liver cirrhosis

International Nuclear Information System (INIS)

Hundt, W.; Helmberger, T.; Reiser, M.; Petsch, R.

2000-01-01

The goal of this study was to compare the effect of Endorem on the signal intensity of the spleen in patients with normal liver tissue and in patients with liver cirrhosis. Thirty patients with normal liver tissue and 47 with liver cirrhosis were examined before and after i. v. Endorem administration. The patients were examined with a 1.5-T magnet system (Magnetom Vision) using a semiflexible cp-array coil. Three different pulse sequences were used: a T1-weighted gradient-echo sequence, a T2-weighted fast spin-echo sequence with spectral fat suppression, and a T2 * -weighted gradient-echo sequence. The signal-to-noise ratios (SNRs) of two areas of the liver and spleen were determined. The mean SNRs of the liver and spleen in patients with and without liver cirrhosis were compared. For assessment of statistical significance, the t-test at a level of P * -weighted gradient-echo sequence, the SNRs of the liver and spleen in the noncirrhotic liver group, compared with the cirrhotic liver group, were 126.8 % and 45.6 % less, respectively. The effect of Endorem on the liver in patients with Child C-stage liver cirrhosis was 32.1 % less than in patients with Child B-stage liver cirrhosis. Likewise, the Endorem effect on the spleen was 27.1 % less in patients with Child C-stage compared with Child B-stage liver cirrhosis. Hepatic and splenic uptake of Endorem is significantly decreased in patients with liver cirrhosis. (orig.)

Malnutrition in end stage liver disease : Who is malnourished?

NARCIS (Netherlands)

Huisman, E.J.

2017-01-01

Liver diseases are highly prevalent. While death rates of most other diseases, such as heart disease and cancer, have decreased, standardized mortality rates of liver diseases have increased up to 400% in the last decades. Cirrhosis is the endstage of patients who have chronic progressive liver

Liver lipase and high-density lipoprotein. Lipoprotein changes after incubation of human serum with rat liver lipase.

Science.gov (United States)

Groot, P H; Scheek, L M; Jansen, H

1983-05-16

Human sera were incubated with rat liver lipase after inactivation of lecithin:cholesterol acyltransferase, and the changes in serum lipoprotein composition were measured. In the presence of liver lipase serum triacylglycerol and phosphatidylcholine were hydrolyzed. The main changes in the concentrations of these lipids were found in the high-density lipoprotein fraction. Subfractionation of high-density lipoprotein by rate-zonal ultracentrifugation showed a prominent decrease in all constituents of high-density lipoprotein2, a smaller decrease in the 'light' high-density lipoprotein3 and an increase in the 'heavy' high-density lipoprotein3. These data support a concept in which liver lipase is involved in high-density lipoprotein2 phospholipid and triacylglycerol catabolism and suggest that as a result of this action high-density lipoprotein2 is converted into high-density lipoprotein3.

Does liver-intestine significantly degrade circulating endogenous substance P in man?

DEFF Research Database (Denmark)

Henriksen, Jens Henrik Sahl; Schaffalitzky de Muckadell, O B; Bülow, J B

1986-01-01

Elevated concentrations of circulating substance P in patients with liver insufficiency have been ascribed to decreased hepatic degradation. To establish a possible biodegradation of the peptide in liver-intestine and kidneys, the concentration of endogenous immunoreactive substance P was determi......Elevated concentrations of circulating substance P in patients with liver insufficiency have been ascribed to decreased hepatic degradation. To establish a possible biodegradation of the peptide in liver-intestine and kidneys, the concentration of endogenous immunoreactive substance P....... The results indicate that degradation of circulating endogenous substance P in man is not confined to liver-intestine or kidney but may take place in many tissues....

The Development of the Basal Ganglia in Capuchin Monkeys (Cebus apella)

Science.gov (United States)

Phillips, Kimberley A.; Sobieski, Courtney A.; Gilbert, Valerie R.; Chiappini-Williamson, Christine; Sherwood, Chet C.; Strick, Peter L.

2010-01-01

The basal ganglia are subcortical structures involved in the planning, initiation and regulation of movement as well as a variety of non-motor, cognitive and affective functions. Capuchin monkeys share several important characteristics of development with humans, including a prolonged infancy and juvenile period, a long lifespan, and complex manipulative abilities. This makes capuchins important comparative models for understanding age-related neuroanatomical changes in these structures. Here we report developmental volumetric data on the three subdivisions of the basal ganglia, the caudate, putamen and globus pallidus in brown capuchin monkeys (Cebus apella). Based on a cross-sectional sample, we describe brain development in 28 brown capuchin monkeys (male n = 17, female n = 11; age range = 2 months – 20 years) using high-resolution structural MRI. We found that the raw volumes of the putamen and caudate varied significantly with age, decreasing in volume from birth through early adulthood. Notably, developmental changes did not differ between sexes. Because these observed developmental patterns are similar to humans, our results suggest that capuchin monkeys may be useful animal models for investigating neurodevelopmental disorders of the basal ganglia. PMID:20227397

Decreased serum hepcidin concentration correlates with brain iron deposition in patients with HBV-related cirrhosis.

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Dong Lin

Full Text Available PURPOSE: Excessive brain iron accumulation contributes to cognitive impairments in hepatitis B virus (HBV-related cirrhotic patients. The underlying mechanism remains unclear. Hepcidin, a liver-produced, 25-aminoacid peptide, is the major regulator of systemic iron metabolism. Abnormal hepcidin level is a key factor in some body iron accumulation or deficiency disorders, especially in those associated with liver diseases. Our study was aimed to explore the relationship between brain iron content in patients with HBV-related cirrhosis and serum hepcidin level. METHODS: Seventy HBV-related cirrhotic patients and forty age- sex-matched healthy controls were enrolled. Brain iron content was quantified by susceptibility weighted phase imaging technique. Serum hepcidin as well as serum iron, serum transferrin, ferritin, soluble transferrin receptor, total iron binding capacity, and transferrin saturation were tested in thirty cirrhotic patients and nineteen healthy controls. Pearson correlation analysis was performed to investigate correlation between brain iron concentrations and serum hepcidin, or other iron parameters. RESULTS: Cirrhotic patients had increased brain iron accumulation compared to controls in the left red nuclear, the bilateral substantia nigra, the bilateral thalamus, the right caudate, and the right putamen. Cirrhotic patients had significantly decreased serum hepcidin concentration, as well as lower serum transferring level, lower total iron binding capacity and higher transferrin saturation, compared to controls. Serum hepcidin level negatively correlated with the iron content in the right caudate, while serum ferritin level positively correlated with the iron content in the bilateral putamen in cirrhotic patients. CONCLUSIONS: Decreased serum hepcidin level correlated with excessive iron accumulation in the basal ganglia in HBV-related cirrhotic patients. Our results indicated that systemic iron overload underlined regional

The effect of aqueous extract of Avicennia marina (Forsk. Vierh. leaves on liver enzymes' activity, oxidative stress parameters and liver histopathology in male diabetic rats

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Akram Hamzevi

2017-12-01

Full Text Available Background: Avicennia marina has antioxidant and anti-diabetic properties. This study was conducted to examine the effect of aqueous extract of A. marina on liver enzymes' activity, oxidative stress parameters and liver histopathology in diabetic rats. Materials and Methods: In this experimental study, 28 male rats were allocated into the equal groups of control, diabetic control and experimental diabetic 1 and 2. The diabetes in diabetic control and experimental diabetic groups was induced using an intraperitoneal injection of 120 mg/kg alloxan. The experimental diabetic groups received the aqueous extract of A. marina (100 and 200 mg/kg, i.p. in alternate days for one month. Sterile distilled water was injected to the animals of control and diabetic control groups. At the end of the treatment period, serum levels of ALT, AST, GGT and ALP were measured. Then, levels of SOD, GST, CAT and MDA were measured in the liver tissue. The liver sections were prepared and examined by an optical microscope. Results: Results showed that administration of the A. marina extract (100 and 300 mg/kg, ip to the diabetic rats significantly decreased the serum levels of liver enzymes and tissue level of MDA. Also, the activity of the liver tissue's antioxidant enzymes was increased (P<0.05. The A. marina extract dose-dependently decreased liver damages in diabetic rats. Conclusion: Administration of the A. marina extract improves liver tissue oxidative stress indices and decreases the serum level of liver enzymes. Also, A. marina extract improves liver tissue injuries induced by diabetes.

Sonographic changes of liver and gallbladder in acute viral hepatitis

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Ebrahimi Daryani N

2001-07-01

Full Text Available Hepatomegaly, decrease in the liver paranchymal echo and increase in the gallbladder wall thickness has been shown in acute viral hepatitis. The present study was done to determine sonographic changes in acute viral hepatitis. We performed liver and bile ducts sonography and specific tests on 42 patients (mean age: 31.5 and 61% male with acute viral hepatitis. Gallbladder wall thickness was seen in 45.2% and hepatomegaly in 33.3% of patients and liver paranchymal echo was decreased in 19.3%. Age, sex, type of hepatitis, cholecystitis like symptoms, aspartate aminotransfrase, alanine aminotransfrase, alkaline phosphatase and bilirubin did not significantly corralate with these changes. Only raised prothrombin time was strongly correlated to the thickening of the gallbladder and decrease in the liver paranchymal echo and cholesistic like symptoms we can postulate that thickening of the gallbladder and decrease in the liver paranchymal echo is not dependent on the severity and speed of the paranchymal necrosis (as considered with ALT and AST but they depend on the liver function disturbance (as considered with PT because the thickening of the gall bladder is present in 45% of the patients and 10% of the normal population have gallbladder stones, one should not perform the diagnosis of acute cholecystitis, only on the basis of sonographic report without attention to the clinical and laboratory data.

The effect of experimental diabetes on phenylalanine metabolism in isolated liver cells.

OpenAIRE

Santana, M A; Fisher, M J; Bate, A J; Pogson, C I

1985-01-01

Chronic (10-day) diabetes was associated with increased metabolic flux through phenylalanine hydroxylase in isolated liver cells. This flux was stimulated by 0.1 microM-glucagon, but not by 10 microM-noradrenaline; 0.1 microM-insulin affected neither basal nor glucagon-stimulated flux. The increased rate of phenylalanine hydroxylation in diabetes was accompanied by parallel increases in enzyme activity (as measured with artificial cofactor) and immunoreactive-enzyme-protein content. In contra...

Vitamin A decreases pre-receptor amplification of glucocorticoids in obesity: study on the effect of vitamin A on 11beta-hydroxysteroid dehydrogenase type 1 activity in liver and visceral fat of WNIN/Ob obese rats

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Ayyalasomayajula Vajreswari

2011-06-01

Full Text Available Abstract Background 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1 catalyzes the conversion of inactive glucocorticoids to active glucocorticoids and its inhibition ameliorates obesity and metabolic syndrome. So far, no studies have reported the effect of dietary vitamin A on 11β-HSD1 activity in visceral fat and liver under normal and obese conditions. Here, we studied the effect of chronic feeding of vitamin A-enriched diet (129 mg/kg diet on 11β-HSD1 activity in liver and visceral fat of WNIN/Ob lean and obese rats. Methods Male, 5-month-old, lean and obese rats of WNIN/Ob strain (n = 16 for each phenotype were divided into two subgroups consisting of 8 rats of each phenotype. Control groups received stock diet containing 2.6 mg vitamin A/kg diet, where as experimental groups received diet containing 129 mg vitamin A/Kg diet for 20 weeks. Food and water were provided ad libitum. At the end of the experiment, tissues were collected and 11β-HSD1 activity was assayed in liver and visceral fat. Results Vitamin A supplementation significantly decreased body weight, visceral fat mass and 11β-HSD1 activity in visceral fat of WNIN/Ob obese rats. Hepatic 11β-HSD1 activity and gene expression were significantly reduced by vitamin A supplementation in both the phenotypes. CCAAT/enhancer binding protein α (C/EBPα, the main transcription factor essential for the expression of 11β-HSD1, decreased in liver of vitamin A fed-obese rats, but not in lean rats. Liver × receptor α (LXRα, a nuclear transcription factor which is known to downregulate 11β-HSD1 gene expression was significantly increased by vitamin A supplementation in both the phenotypes. Conclusions This study suggests that chronic consumption of vitamin A-enriched diet decreases 11β-HSD1 activity in liver and visceral fat of WNIN/Ob obese rats. Decreased 11β-HSD1 activity by vitamin A may result in decreased levels of active glucocorticoids in adipose tissue and possibly

Basal encephalocele and morning glory syndrome.

Science.gov (United States)

Caprioli, J; Lesser, R L

1983-01-01

Basal encephaloceles are often associated with other midline anomalies such as hypertelorism, broad nasal root, cleft lip, and cleft palate. Optic disc anomalies such as pallor, dysplasia, optic pit, coLoboma, and megalopapilla have been reported to occur in patients with basal encephalocele We report a case of a child with a sphenoethmoidal encephalocele and morning glory syndrome of the optic nerve. The presence of such optic nerve anomalies with facial midline anomalies should alert the clinician to the possible presence of a basal encephalocele. Images PMID:6849854

Basal and dynamic relationships between implicit power motivation and estradiol in women.

Science.gov (United States)

Stanton, Steven J; Schultheiss, Oliver C

2007-12-01

This study investigated basal and reciprocal relationships between implicit power motivation (n Power), a preference for having impact and dominance over others, and both salivary estradiol and testosterone in women. 49 participants completed the Picture Story Exercise, a measure of n Power. During a laboratory contest, participants competed in pairs on a cognitive task and contest outcome (win vs. loss) was experimentally varied. Estradiol and testosterone levels were determined in saliva samples collected at baseline and several times post-contest, including 1 day post-contest. n Power was positively associated with basal estradiol concentrations. The positive correlation between n Power and basal estradiol was stronger in single women, women not taking oral contraceptives, or in women with low-CV estradiol samples than in the overall sample of women. Women's estradiol responses to a dominance contest were influenced by the interaction of n Power and contest outcome: estradiol increased in power-motivated winners but decreased in power-motivated losers. For power-motivated winners, elevated levels of estradiol were still present the day after the contest. Lastly, n Power and estradiol did not correlate with self-reported dominance and correlated negatively with self-reported aggression. Self-reported dominance and aggression did not predict estradiol changes as a function of contest outcome. Overall, n Power did not predict basal testosterone levels or testosterone changes as a function of dominance contest outcome.

MRI volume measurement of basal ganglia volumes in patients with Tourette's syndrome

International Nuclear Information System (INIS)

Lu Jie; Li Kuncheng; Cao Yanxiang; Zhang Miao; Sui Xin; Zhang Xiaohua

2009-01-01

Objective: To evaluate MRI measurement of basal ganglia volumes in patients with Tourette's syndrome. Methods: Ten patients with Tourette's syndrome (TS) and 10 healthy volunteers were studied. Volumes of bilateral caudate, putamen and pallidum were measured, and the results were analyzed using paired t test. The basal ganglia volume was normalized according to individual brain volume. The basal ganglia volumes of TS patients were compared with normal control group using independent-sample t test. Results: In 10 healthy volunteers, volumes of the left caudate, putamen, pallidum were significantly larger compared with those of the right side (P 0.05) in TS patients. After normalized processing, the volumes of the left caudate (7.06 ± 0.48) cm 3 , putamen (8.81±1.01) cm 3 , pallidum (2.64± 0.38) cm 3 were smaller than those of control group [caudate (11.05±1.86) cm 3 , putamen (9.97± 1.11) cm 3 , pallidum (3.04±0.37) cm 3 ] (t=-6.577, -2.457, -2.376, P 3 in TS patients was significantly smaller compared with the control group (9.81±1.83) cm 3 (t=-4.258, P 0.05). Conclusion: The basal ganglia volumes were significantly decreased in patients with TS. MRI volumetric measurement was an important tool for evaluating pathologic changes of TS. (authors)

Molecular Pathogenesis of Liver Steatosis Induced by Hepatitis C Virus

Directory of Open Access Journals (Sweden)

Cheng Jun

2012-09-01

Full Text Available Liver steatosis is a pathological hallmark in patients with chronic hepatitis C (CHC. Increased lipid uptake, decreased lipid secretion, increased lipid synthesis and decreased lipid degradation are all involved in pathogenesis of steatosis induced by hepatitic C virus (HCV infection. Level of low density lipoprotein receptor (LDL-R and activity of peroxisome proliferator-activated receptor (PPAR α is related to liver uptake of lipid from circulation, and affected by HCV. Secretion via microsomal triglyceride transfer protein (MTTP, and formation of very low density lipoprotein (VLDL have been hampered by HCV infection. Up-regulation of lipid synthesis related genes, such as sterol regulatory element-binding protein (SREBP-1, SREBP-2, SREBP-1c, fatty acid synthase (FASN, HMG CoA reductase (HMGCR, liver X receptor (LXR, acetyl-CoA carboxylase 1 (ACC1, hepatic CB (1 receptors, retinoid X receptor (RXR α, were the main stay of liver steatosis pathogenesis. Degradation of lipid in liver is decreased in patients with CHC. There is strong evidence that heterogeneity of HCV core genes of different genotypes affect their effects of liver steatosis induction. A mechanism in which steatosis is involved in HCV life cycle is emerging.

Alcoholic fatty liver is enhanced in CYP2A5 knockout mice: The role of the PPARα-FGF21 axis

International Nuclear Information System (INIS)

Chen, Xue; Ward, Stephen C.; Cederbaum, Arthur I.; Xiong, Huabao; Lu, Yongke

2017-01-01

Background & aims: Cytochrome P450 2A5 (CYP2A5) is induced by ethanol, and the ethanol induction of CYP2A5 is regulated by nuclear factor-erythroid 2-related factor 2 (NRF2). Cyp2a5 knockout (Cyp2a5 −/− ) mice develop more severe alcoholic fatty liver than Cyp2a5 +/+ mice. Fibroblast growth factor 21 (FGF21), a PPARα-regulated liver hormone, is involved in hepatic lipid metabolism. Alcoholic and non-alcoholic fatty liver are enhanced in Pparα knockout (Pparα −/− ) mice. This study investigates the relationship between the PPARα-FGF21 axis and the enhanced alcoholic fatty liver in Cyp2a5 −/− mice. Methods: Mice were fed the Lieber-Decarli ethanol diet to induce alcoholic fatty liver. Results: More severe alcoholic fatty liver disease was developed in Cyp2a5 −/− mice than in Cyp2a5 +/+ mice. Basal FGF21 levels were higher in Cyp2a5 −/− mice than in Cyp2a5 +/+ mice, but ethanol did not further increase the elevated FGF21 levels in Cyp2a5 −/− mice while FGF21 was induced by ethanol in Cyp2a5 +/+ mice. Basal levels of serum FGF21 were lower in Pparα −/− mice than in Pparα +/+ mice; ethanol induced FGF21 in Pparα +/+ mice but not in Pparα −/− mice, whereas ethanol induced hypertriglyceridemia in Pparα −/− mice but not in Pparα +/+ mice. Administration of recombinant FGF21 normalized serum FGF21 and triglyceride in Pparα −/− mice. Alcoholic fatty liver was enhanced in liver-specific Fgf21 knockout mice. Pparα and Cyp2a5 double knockout (Pparα −/− /Cyp2a5 −/− ) mice developed more severe alcoholic fatty liver than Pparα +/+ /Cyp2a5 −/− mice. Conclusions: These results suggest that CYP2A5 protects against the development of alcoholic fatty liver disease, and the PPARα-FGF21 axis contributes to the protective effects of CYP2A5 on alcoholic fatty liver disease.

Histopathologic patterns as markers of prognosis in patients undergoing hepatectomy for colorectal cancer liver metastases - Pushing growth as an independent risk factor for decreased survival.

Science.gov (United States)

Falcão, Daniela; Alexandrino, Henrique; Caetano Oliveira, Rui; Martins, João; Ferreira, Luís; Martins, Ricardo; Serôdio, Marco; Martins, Mónica; Tralhão, José Guilherme; Cipriano, Maria Augusta; Castro E Sousa, Francisco

2018-04-11

Liver resection combined with neoadjuvant chemotherapy (NAC) has reported notable results in patients with colorectal liver metastases (CRLM). Tumoral response to NAC is associated with specific histopathologic patterns with prognostic implications. The main objective of this study was to evaluate the influence of pathological findings on overall survival (OS), disease-free survival (DFS) and liver recurrence-free survival (LRFS). Analysis of clinical and outcome data from 110 patients who underwent first CRLM resection between January 2010 and July 2013. Blinded pathological review of histological material of several parameters: resection margin, tumor regression grade (TRG), tumor thickness at the tumor-normal interface (TTNI) and the growth pattern (GP). The median survival following hepatic resection was 52 months and 3- and 5- year Kaplan-Meier estimates were 69 and 48%, respectively. Seventy-four patients developed recurrent disease. Oxaliplatin-based chemotherapy was significantly associated with a pushing GP. A positive resection margin was an independent predictor of decreased DFS (p = 0.018) but not of decreased OS. LRFS was strongly reduced by the absence of histologic tumor response (p = 0.018). The pushing pattern had an adverse impact on both OS (p = 0.007) and DFS (p = 0.004) on multivariate analysis. The prognostic value of histopathological features in patients who underwent CRLM's resection is undeniable. The pushing GP was related with worse prognosis. Further studies are required to clarify the biological mechanisms underlying these findings in order to enhance a more personalized and efficient treatment of these patients. Copyright © 2018 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Effects of Bariatric Surgery on Non-alcoholic Fatty Liver Disease: Magnetic Resonance Imaging Is an Effective, Non-invasive Method to Evaluate Changes in the Liver Fat Fraction.

Science.gov (United States)

Hedderich, Dennis M; Hasenberg, Till; Haneder, Stefan; Schoenberg, Stefan O; Kücükoglu, Özlem; Canbay, Ali; Otto, Mirko

2017-07-01

Non-alcoholic fatty liver disease (NAFLD) is considered the most common liver disease worldwide and is highly associated with obesity. The prevalences of both conditions have markedly increased in the Western civilization. Bariatric surgery is the most effective treatment for morbid obesity and its comorbidities such as NAFLD. Measure postoperative liver fat fraction (LFF) in bariatric patients by using in-opposed-phase MRI, a widely available clinical tool validated for the quantification of liver fat METHODS: Retrospective analyses of participants, who underwent laparoscopic Roux-Y-gastric-bypass (17) or laparoscopic sleeve gastrectomy (2) were performed using magnetic resonance imaging (MRI), bioelectrical impedance analysis (BIA), and anthropometric measurements 1 day before surgery, as well as 6, 12, and 24 weeks after surgery, LFF was calculated from fat-only and water-only MR images. Six months after surgery, a significant decrease of LFF and liver volume has been observed along with weight loss, decreased waist circumference, and parameters obtained by body fat measured by BIA. LFF significantly correlated with liver volume in the postoperative course. MRI including in-opposed-phase imaging of the liver can detect the quantitative decrease of fatty infiltration within the liver after bariatric surgery and thus could be a valuable tool to monitor NAFLD/NASH postoperatively.

Alternagin-C (ALT-C), a Disintegrin-Like Cys-Rich Protein Isolated from the Venom of the Snake Rhinocerophis alternatus, Stimulates Angiogenesis and Antioxidant Defenses in the Liver of Freshwater Fish, Hoplias malabaricus.

Science.gov (United States)

Monteiro, Diana Amaral; Selistre-de-Araújo, Heloisa Sobreiro; Tavares, Driele; Fernandes, Marisa Narciso; Kalinin, Ana Lúcia; Rantin, Francisco Tadeu

2017-09-28

Alternagin-C (ALT-C) is a disintegrin-like protein isolated from Rhinocerophis alternatus snake venom, which induces endothelial cell proliferation and angiogenesis. The aim of this study was to evaluate the systemic effects of a single dose of alternagin-C (0.5 mg·kg -1 , via intra-arterial) on oxidative stress biomarkers, histological alterations, vascular endothelial growth factor (VEGF) production, and the degree of vascularization in the liver of the freshwater fish traíra, Hoplias malabaricus , seven days after the initiation of therapy. ALT-C treatment increased VEGF levels and hepatic angiogenesis. ALT-C also enhanced hepatic antioxidant enzymes activities such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, decreasing the basal oxidative damage to lipids and proteins in the fish liver. These results indicate that ALT-C improved hepatic tissue and may play a crucial role in tissue regeneration mechanisms.

Isotopic study of liver function after narcosis in small animals

International Nuclear Information System (INIS)

Le Qui Cuong; Kiss, Bela; Jakab, Tivadar; Szilvasi, Istvan; Spett, Borbala

1984-01-01

Dinamic functional study of the liver was performed by sup(99m)Tc-TECHIDA in narcotized (Halothane) mice and rabbits. Hepatic uptake of the radiopharmaceutical decreased in narcotized group significantly. Excretion also decreased but statistically insignificantly. These alterations in the liver function could be attributed to the hypotensive effect of Halothane. (author)

Patterned basal seismicity shows sub-ice stream bedforms

Science.gov (United States)

Barcheck, C. G.; Tulaczyk, S. M.; Schwartz, S. Y.

2017-12-01

Patterns in seismicity emanating from the bottom of fast-moving ice streams and glaciers may indicate localized patches of higher basal resistance— sometimes called 'sticky spots', or otherwise varying basal properties. These seismogenic basal areas resist an unknown portion of the total driving stress of the Whillans Ice Plain (WIP), in West Antarctica, but may play an important role in the WIP stick-slip cycle and ice stream slowdown. To better understand the mechanism and importance of basal seismicity beneath the WIP, we analyze seismic data collected by a small aperture (micro-earthquakes in Dec 2014, and we compare the resulting map of seismicity to ice bottom depth measured by airborne radar. The number of basal earthquakes per area within the network is spatially heterogeneous, but a pattern of two 400m wide streaks of high seismicity rates is evident, with >50-500 earthquakes detected per 50x50m grid cell in 2 weeks. These seismically active streaks are elongated approximately in the ice flow direction with a spacing of 750m. Independent airborne radar measurements of ice bottom depth from Jan 2013 show a low-amplitude ( 5m) undulation in the basal topography superposed on a regional gradient in ice bottom depth. The flow-perpendicular wavelength of these low-amplitude undulations is comparable to the spacing of the high seismicity bands, and the streaks of high seismicity intersect local lows in the undulating basal topography. We interpret these seismic and radar observations as showing seismically active sub-ice stream bedforms that are low amplitude and elongated in the direction of ice flow, comparable to the morphology of mega scale glacial lineations (MSGLs), with high basal seismicity rates observed in the MSGL troughs. These results have implications for understanding the formation mechanism of MSGLS and well as understanding the interplay between basal topographic roughness, spatially varying basal till and hydrologic properties, basal

Oral testosterone load related to liver function in men with alcoholic liver cirrhosis

DEFF Research Database (Denmark)

Gluud, C; Bahnsen, M; Bennett, P

1983-01-01

The relation between liver function and an oral testosterone load was examined in 42 consecutive patients with alcoholic liver cirrhosis. Administration of an oral load of 400 mg micronized free testosterone increased the serum concentration of testosterone (range, 31.9-694.4 nmol/l; median, 140.......8 nmol/l) in male patients with alcoholic liver cirrhosis to significantly (P less than 0.01) higher levels than in male subjects without liver disease (range, 25.4-106.6 nmol/l; median, 61.5 nmol/l). The increase of testosterone after the load (log delta testosterone) in patients correlated inversely...... with wedged-to-free hepatic vein pressure (r = +0.54; P less than 0.01). The increase of testosterone after the load did not correlate significantly with sex hormone-binding globulin (r = +0.35; P greater than 0.05). It is concluded that the hepatic extraction of testosterone is significantly decreased...

Multiparameter analysis of fall-out plutonium burdens in human liver

International Nuclear Information System (INIS)

Griffith, W.C.; Guilmette, R.A.

1991-01-01

The effect of multiple factors on Pu liver burdens is estimated for a group of 310 people who were selected to have relative uniform exposure to fall-out plutonium ( 239 Pu plus 240 Pu), based on age in 1952, the start of atmospheric testing of thermonuclear weapons, and based on residence history in eastern Colorado, where they died between 1975 and 1979. The data were analysed using multiple linear regression of the logarithm of the total liver plutonium burden on other available covariates. The results of the regression indicated that the liver burden was increased by 34% in very heavy smokers (100 pack year history) compared to non-smokers, decreased by 27% in females compared to males, decreased by 24% in people with a neoplasm in the liver compared to those without a neoplasm, and decreased by 64% in people with cirrhosis compared to those without cirrhosis. However, all of those parameters accounted for only 26% of the variability in liver burdens observed among these people, indicating that there remains a large unexplained variation. (author)

Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

Science.gov (United States)

Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

2016-06-01

Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

Neglected Giant Scalp Basal Cell Carcinoma

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Anne Kristine Larsen, MD

2014-03-01

Full Text Available Summary: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence 1 year postoperatively.

A small population of liver endothelial cells undergoes endothelial-to-mesenchymal transition in response to chronic liver injury.

Science.gov (United States)

Ribera, Jordi; Pauta, Montse; Melgar-Lesmes, Pedro; Córdoba, Bernat; Bosch, Anna; Calvo, Maria; Rodrigo-Torres, Daniel; Sancho-Bru, Pau; Mira, Aurea; Jiménez, Wladimiro; Morales-Ruiz, Manuel

2017-11-01

Rising evidence points to endothelial-to-mesenchymal transition (EndMT) as a significant source of the mesenchymal cell population in fibrotic diseases. In this context, we hypothesized that liver endothelial cells undergo EndMT during fibrosis progression. Cirrhosis in mice was induced by CCl 4 A transgenic mouse expressing a red fluorescent protein reporter under the control of Tie2 promoter (Tie2-tdTomato) was used to trace the acquisition of EndMT. Sinusoidal vascular connectivity was evaluated by intravital microscopy and high-resolution three-dimensional confocal microscopy. A modest but significant fraction of liver endothelial cells from both cirrhotic patients and CCl 4 -treated Tie2-tdTomato mice acquired an EndMT phenotype characterized by the coexpression of CD31 and α-smooth muscle actin, compared with noncirrhotic livers. Bone morphogenetic protein-7 (BMP-7) inhibited the acquisition of EndMT induced by transforming growth factor-β1 (TGF-β1) treatment in cultured primary mouse liver endothelial cells from control mice. EndMT was also reduced significantly in vivo in cirrhotic Tie2-tdTomato mice treated intraperitoneally with BMP-7 compared with untreated mice (1.9 ± 0.2 vs. 3.8 ± 0.3%, respectively; P livers correlated with a significant decrease in liver fibrosis ( P livers in both animal models and patients. BMP-7 treatment decreases the occurrence of the EndMT phenotype and has a positive impact on the severity of disease by reducing fibrosis and sinusoidal vascular disorganization. NEW & NOTEWORTHY A subpopulation of liver endothelial cells from cirrhotic patients and mice with liver fibrosis undergoes endothelial-to-mesenchymal transition. Liver endothelial cells from healthy mice could transition into a mesenchymal phenotype in culture in response to TGF-β1 treatment. Fibrotic livers treated chronically with BMP-7 showed lower EndMT acquisition, reduced fibrosis, and improved vascular organization. Copyright © 2017 the American

An analysis of the effects of Mn2+ on oxidative phosphorylation in liver, brain, and heart mitochondria using state 3 oxidation rate assays

International Nuclear Information System (INIS)

Gunter, Thomas E.; Gerstner, Brent; Lester, Tobias; Wojtovich, Andrew P.; Malecki, Jon; Swarts, Steven G.; Brookes, Paul S.; Gavin, Claire E.; Gunter, Karlene K.

2010-01-01

Manganese (Mn) toxicity is partially mediated by reduced ATP production. We have used oxidation rate assays-a measure of ATP production-under rapid phosphorylation conditions to explore sites of Mn 2+ inhibition of ATP production in isolated liver, brain, and heart mitochondria. This approach has several advantages. First, the target tissue for Mn toxicity in the basal ganglia is energetically active and should be studied under rapid phosphorylation conditions. Second, Mn may inhibit metabolic steps which do not affect ATP production rate. This approach allows identification of inhibitions that decrease this rate. Third, mitochondria from different tissues contain different amounts of the components of the metabolic pathways potentially resulting in different patterns of ATP inhibition. Our results indicate that Mn 2+ inhibits ATP production with very different patterns in liver, brain, and heart mitochondria. The primary Mn 2+ inhibition site in liver and heart mitochondria, but not in brain mitochondria, is the F 1 F 0 ATP synthase. In mitochondria fueled by either succinate or glutamate + malate, ATP production is much more strongly inhibited in brain than in liver or heart mitochondria; moreover, Mn 2+ inhibits two independent sites in brain mitochondria. The primary site of Mn-induced inhibition of ATP production in brain mitochondria when succinate is substrate is either fumarase or complex II, while the likely site of the primary inhibition when glutamate plus malate are the substrates is either the glutamate/aspartate exchanger or aspartate aminotransferase.

Fusarium basal rot in the Netherlands

NARCIS (Netherlands)

Visser, de C.L.M.; Broek, van den R.C.F.M.; Brink, van den L.

2006-01-01

Fusarium basal rot of onion, caused by Fusarium oxysporum f.sp. cepae, is a steadily increasing problem in The Netherlands. Financial losses for Dutch farmers confronted with Fusarium basal rot is substantial, due to yield reduction and high storage costs. This paper describes the development and

The future of basal insulin supplementation

NARCIS (Netherlands)

Simon, Airin C. R.; DeVries, J. Hans

2011-01-01

This review presents an overview of the candidates for an improved basal insulin in the pharmaceutical pipeline. The first new basal insulin to enter the market is most likely insulin degludec (IDeg), currently reporting in phase 3 of development, from Novo Nordisk (Bagsvaerd, Denmark). IDeg has a

Analysis of iron storage proteins in chicken liver and spleen tissues in comparison with human liver ferritin by Moessbauer spectroscopy

International Nuclear Information System (INIS)

Oshtrakh, M.I.; Milder, O.B.; Semionkin, V.A.; Malakheeva, L.I.; Prokopenko, P.G.

2006-01-01

Characterization of iron storage proteins in liver and spleen from normal chicken and chicken with lymphoid leukemia in comparison with human liver ferritin were considered by Moessbauer spectroscopy (preliminary results). Small differences in Moessbauer hyperfine parameters for both normal and lymphoid leukemia chicken liver and spleen were observed. The value of quadrupole splitting for human liver ferritin was higher than those for chicken tissues. A decrease of iron content in lymphoid leukemia chicken tissues was also found, however, the reason of this fact (pathology or feeding) was not clear yet. (author)

Autofluorescence imaging of basal cell carcinoma by smartphone RGB camera

Science.gov (United States)

Lihachev, Alexey; Derjabo, Alexander; Ferulova, Inesa; Lange, Marta; Lihacova, Ilze; Spigulis, Janis

2015-12-01

The feasibility of smartphones for in vivo skin autofluorescence imaging has been investigated. Filtered autofluorescence images from the same tissue area were periodically captured by a smartphone RGB camera with subsequent detection of fluorescence intensity decreasing at each image pixel for further imaging the planar distribution of those values. The proposed methodology was tested clinically with 13 basal cell carcinoma and 1 atypical nevus. Several clinical cases and potential future applications of the smartphone-based technique are discussed.

Circulating extracellular vesicles with specific proteome and liver microRNAs are potential biomarkers for liver injury in experimental fatty liver disease.

Directory of Open Access Journals (Sweden)

Davide Povero

Full Text Available Nonalcoholic fatty liver disease (NAFLD is the most common chronic liver disease in both adult and children. Currently there are no reliable methods to determine disease severity, monitor disease progression, or efficacy of therapy, other than an invasive liver biopsy.Choline Deficient L-Amino Acid (CDAA and high fat diets were used as physiologically relevant mouse models of NAFLD. Circulating extracellular vesicles were isolated, fully characterized by proteomics and molecular analyses and compared to control groups. Liver-related microRNAs were isolated from purified extracellular vesicles and liver specimens.We observed statistically significant differences in the level of extracellular vesicles (EVs in liver and blood between two control groups and NAFLD animals. Time-course studies showed that EV levels increase early during disease development and reflect changes in liver histolopathology. EV levels correlated with hepatocyte cell death (r2 = 0.64, p<0.05, fibrosis (r2 = 0.66, p<0.05 and pathological angiogenesis (r2 = 0.71, p<0.05. Extensive characterization of blood EVs identified both microparticles (MPs and exosomes (EXO present in blood of NAFLD animals. Proteomic analysis of blood EVs detected various differentially expressed proteins in NAFLD versus control animals. Moreover, unsupervised hierarchical clustering identified a signature that allowed for discrimination between NAFLD and controls. Finally, the liver appears to be an important source of circulating EVs in NAFLD animals as evidenced by the enrichment in blood with miR-122 and 192--two microRNAs previously described in chronic liver diseases, coupled with a corresponding decrease in expression of these microRNAs in the liver.These findings suggest a potential for using specific circulating EVs as sensitive and specific biomarkers for the noninvasive diagnosis and monitoring of NAFLD.

Modern basal insulin analogs: An incomplete story

OpenAIRE

Singh, Awadhesh Kumar; Gangopadhyay, Kalyan Kumar

2014-01-01

The currently available basal insulin does not completely mimic the endogenous insulin secretion. This has continued to promote the search for ideal basal insulin. The newer basal insulin have primarily focused on increasing the duration of action, reducing variability, and reducing the incidence of hypoglycemia, particularly nocturnal. However, the changing criteria of hypoglycemia within a short span of a few years along with the surprising introduction of major cardiac events as another ou...

Evidence for altered basal ganglia-brainstem connections in cervical dystonia.

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Anne J Blood

Full Text Available There has been increasing interest in the interaction of the basal ganglia with the cerebellum and the brainstem in motor control and movement disorders. In addition, it has been suggested that these subcortical connections with the basal ganglia may help to coordinate a network of regions involved in mediating posture and stabilization. While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, thus far, there is only indirect evidence for this in humans with dystonia.In the current study we investigated probabilistic diffusion tractography in DYT1-negative patients with cervical dystonia and matched healthy control subjects, with the goal of showing that patients exhibit altered microstructure in the connectivity between the pallidum and brainstem. The brainstem regions investigated included nuclei that are known to exhibit strong connections with the cerebellum. We observed large clusters of tractography differences in patients relative to healthy controls, between the pallidum and the brainstem. Tractography was decreased in the left hemisphere and increased in the right hemisphere in patients, suggesting a potential basis for the left/right white matter asymmetry we previously observed in focal dystonia patients.These findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia.

Opponent and bidirectional control of movement velocity in the basal ganglia

Science.gov (United States)

Yttri, Eric A.

2016-01-01

For goal-directed behavior it is critical that we can both select the appropriate action and learn to modify the underlying movements (e.g. the pitch of a note or velocity of a reach) to improve outcomes. The basal ganglia are a critical nexus where circuits necessary for the production of behavior, such as neocortex and thalamus, are integrated with reward signaling 1 to reinforce successful, purposive actions 2. Dorsal striatum, a major input structure of basal ganglia is composed of two opponent pathways, direct and indirect, thought to select actions that elicit positive outcomes or suppress actions that do not, respectively 3,4. Activity-dependent plasticity modulated by reward is thought to be sufficient for selecting actions in striatum 5,6. Although perturbations of basal ganglia function produce profound changes in movement 7, it remains unknown whether activity-dependent plasticity is sufficient to produce learned changes in movement kinematics, such as velocity. Here we used cell-type specific stimulation delivered in closed-loop during movement to demonstrate that activity in either the direct or indirect pathway is sufficient to produce specific and sustained increases or decreases in velocity without affecting action selection or motivation. These behavioral changes were a form of learning that accumulated over trials, persisted after the cessation of stimulation, and were abolished in the presence of dopamine antagonists. Our results reveal that the direct and indirect pathways can each bidirectionally control movement velocity, demonstrating unprecedented specificity and flexibility in the control of volition by the basal ganglia. PMID:27135927

Computerized tomographic diagnosis of basal skull fracture

International Nuclear Information System (INIS)

Tanaka, Tokutaro; Shimoyama, Ichiro; Endoh, Mitsutoshi; Ninchoji, Toshiaki; Uemura, Kenichi.

1984-01-01

The diagnosis of basal skull fractures used to be difficult, particularly on the basis of routine skull roentgenography alone. We have now examined the diagnostic value of conventional computerized tomography in basal skull fractures. We studied 82 cases clinically diagnosed as basal skull fractures. We examined them based on at least one of the following computerized tomographic criteria for basal skull fractures: 1) fracture line(s), 2) intracranial air, 3) fluid in the paranasal sinuses, and 4) fluid in the middle ear, including the mastoid air cells. The signs of the fracture line and of the intracranial air are definite indications of basal skull fracture, but the signs of fluid in the paranasal sinuses and/or in the middle ear are not definite. When combined, however, with such other clinical signs as black eye, Battle's sign, CSF leakage, CSF findings, and profuse nasal or ear bleeding, the diagnosis is more reliable. Seventy cases (85.4%) in this series had basal skull fractures according to our computerized tomographic criteria. Among them , 26 cases (31.7%) were diagnosed with fracture lines, 17 cases (20.7%) with intracranial air, 16 cases (19.5%) with fluid in the paranasal sinuses, 10 cases (12.2%) with fluid in the middle ear, and one case (1.2%) with fluid in both. Twelve cases (14.6%) of the 82 cases clinically diagnosed as basal skull fractures could not have been diagnosed on our computerized tomographic criteria alone. We diagnosed them because of CSF leakage, CSF findings, surgical findings, etc. (author)

Enhanced hepatic insulin signaling in the livers of high altitude native rats under basal conditions and in the livers of low altitude native rats under insulin stimulation: a mechanistic study.

Science.gov (United States)

Al Dera, Hussain; Eleawa, Samy M; Al-Hashem, Fahaid H; Mahzari, Moeber M; Hoja, Ibrahim; Al Khateeb, Mahmoud

2017-07-01

This study was designed to investigate the role of the liver in lowering fasting blood glucose levels (FBG) in rats native to high (HA) and low altitude (LA) areas. As compared with LA natives, besides the improved insulin and glucose tolerance, HA native rats had lower FBG, at least mediated by inhibition of hepatic gluconeogenesis and activation of glycogen synthesis. An effect that is mediated by the enhancement of hepatic insulin signaling mediated by the decreased phosphorylation of TSC induced inhibition of mTOR function. Such effect was independent of activation of AMPK nor stabilization of HIF1α, but most probably due to oxidative stress induced REDD1 expression. However, under insulin stimulation, and in spite of the less activated mTOR function in HA native rats, LA native rats had higher glycogen content and reduced levels of gluconeogenic enzymes with a more enhanced insulin signaling, mainly due to higher levels of p-IRS1 (tyr612).

PREDICTION AND PREVENTION OF LIVER FAILURE AFTER MAJOR LIVER PRIMARY AND METASTATIC TUMORS RESECTION

Directory of Open Access Journals (Sweden)

A. D. Kaprin

2016-01-01

Full Text Available Abstract Purpose of the study. Improvement of results of treatment in patients with primary and metastatic liver cancer by decreasing the risk of post-resection liver failure on the basis of the evaluation of the functional reserves of the liver.Materials and Methods. The study included two independent samples of patients operated about primary or metastatic lesions of the liver at the Department of abdominal Oncology, P. A. Hertsen MORI. The first group included 53 patients who carried out 13C-breath test metallimovie and dynamic scintigraphy of the liver in the preoperative stage in addition to the standard algorithm of examination. Patients of the 2nd group (n=35 had a standard clinical and laboratory examination, the patients were not performed the preoperative evaluation of the functional reserve of the liver, the incidences of total bilirubin, albumin and prothrombin time did not reveal a reduction of liver function. Post-resection liver failure have been established on the basis of the 50/50 criterion in the evaluation on day 5 after surgery.Results. Analysis of operating characteristics of the functional tests showed the absolute methacin breath test sensitivity (SE≥100%, high specificity (SP≥67% of scintigraphy of the liver and the negative predictive value of outcome (VP≥100% at complex use of two diagnostic methods. The incidence of PROPS in the study group was significantly 2 times higher in the control group –15,1% and 26.8%, respectively (p<0.001.Conclusion. The combination of preoperative dynamic scintigraphy of the liver with carrying out 13C-breath methacin test allows you to conduct a comprehensive evaluation of the liver functional reserve and can significantly improve preoperative evaluation and postoperative results of anatomic resection in patients with primary and metastatic liver lesions.

Evaluation of nonalcoholic fatty liver disease using magnetic resonance in obese children and adolescents.

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Benetolo, Patrícia O; Fernandes, Maria I M; Ciampo, Ieda R L Del; Elias-Junior, Jorge; Sawamura, Regina

2018-02-10

To determine the frequency of nonalcoholic fatty liver disease using nuclear magnetic resonance as a noninvasive method. This was a cross-sectional study conducted on 50 children and adolescents followed up at an outpatient obesity clinic. The subjects were submitted to physical examination, laboratory tests (transaminases, liver function tests, lipid profile, glycemia, and basal insulin) and abdominal nuclear magnetic resonance (calculation of hepatic, visceral, and subcutaneous fat). Nonalcoholic fatty liver disease was diagnosed in 14 (28%) participants, as a severe condition in eight (percent fat >18%), and as non-severe in four (percent fat from 9% to 18%). Fatty liver was associated with male gender, triglycerides, AST, ALT, AST/ALT ratio, and acanthosis nigricans. Homeostasis model assessment of insulin resistance and metabolic syndrome did not show an association with fatty liver. The frequency of nonalcoholic fatty liver disease in the present population of children and adolescents was lower than that reported in the international literature. It is suggested that nuclear magnetic resonance is an imaging exam that can be applied to children and adolescents, thus representing an effective noninvasive tool for the diagnosis of nonalcoholic fatty liver disease in this age range. However, further national multicenter studies with longitudinal design are needed for a better analysis of the correlation between nonalcoholic fatty liver disease and its risk factors, as well as its consequences. Copyright © 2018 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.

Filaggrin Gene Mutations and Risk of Basal Cell Carcinoma

DEFF Research Database (Denmark)

Kaae, Jesper Rabølle; Thyssen, J P; Johansen, J D

2013-01-01

) . Mice with knockdown of filaggrin, or lack of functional histidase, show decreased epidermal trans-UCA levels and increased UVB-induced skin damage (5) . FLG mutation carriers also have 10% increased serum vitamin D levels suggesting increased penetration of UVB (6) . We evaluated the prevalence of FLG......Basal cell carcinoma (BCC) is prevalent in lightly-pigmented Europeans. While ultraviolet (UV) radiation is an important risk factor, genetic predispositions to BCC have also been identified (1) . Atopic dermatitis (AD), a condition with a heritability that reaches 71-84%, might increase the risk...

Impact of the basal metabolic ratio in predicting early deaths after allogeneic stem cell transplantation.

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Nishiwaki, Satoshi; Miyamura, Koichi; Seto, Aika; Watanabe, Keisuke; Yanagisawa, Mayumi; Imahashi, Nobuhiko; Shimba, Makoto; Yasuda, Takahiko; Kuwatsuka, Yachiyo; Oba, Taku; Terakura, Seitaro; Kodera, Yoshihisa

2009-09-01

Early deaths after allogeneic stem cell transplantation (allo-SCT) are of major concern. On the assumption that both decreased and increased basal metabolism might relate to early deaths, we analyzed the risk factors for overall survival to days 30 (OS30) and 60 (OS60). The Harris-Benedict equation was used to calculate basal metabolism. Comparing a patient's basal metabolism (PBM) calculated from pretransplant body weight with the standard basal metabolism (SBM) calculated from standard body weight (body mass index (BMI) = 22), we defined the basal metabolic ratio (BMR) as a parameter (BMR = PBM/SBM). We retrospectively analyzed 360 adult patients transplanted between 1997 and 2006 at a single center in Japan. A multivariate analysis of OS30 showed risk factors to be: BMR BMR; LBR) (P = 0.01), BMR > 1.05 (high BMR; HBR) (P = 0.005) and non-complete remission (non-CR) (P 5 0.001), whereas a multivariate analysis of OS60 showed those risk factors to be: LBR (P = 0.02), HBR (P = 0.04), non-CR (P = 0.002), and performance status BMR BMR; ABR) (96.8 and 90.3% for ABR, 87.1 and 76.2% for LBR, and 87.8 and 81.1% for HBR). In conclusion, BMR could prove to be a predictor of early death after allo-SCT.

Influence Of Whey Protein For Abrogating Liver Injury In Female Rats

International Nuclear Information System (INIS)

ANWAR, M.M.; MOHAMED, N.E.

2009-01-01

The objective of this study was to determine the possible benefits of whey protein concentrate (44% protein, 5% fat and 4.6% ash in dry weight) against liver injury induced by CCl 4 . It was carried out by evaluating the effect of the daily feeding of female rats on diet containing 15% whey protein instead of soybean protein for four weeks on some biochemical and histological changes in liver of female rats.The data showed that injection with CCl 4 (1 ml /kg body weight 3 times / week) caused significant decrease in body weight with disturbances in liver functions as significant increase in serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma glutamyl transferase and bilirubin and significant decrease in serum albumin, FT3 and an increase in AFP levels. A marked significant decrease in glutathione content and significant increase in lipid peroxidation was also observed in hepatic tissues. The histological examination revealed that CCl 4 treatment showed marked degenerative changes in liver hepatocytes and sinusoids.The results also showed that feeding on diet containing whey protein for two or four weeks during CCl 4 treatment minimized the disturbance of the liver functions and liver histology.

Radioprotection of liver lipids of whole-body gamma-irradiated female rats by cystamine

International Nuclear Information System (INIS)

Ramanathan, R.; Misra, U.K.

1976-01-01

The effect of administration of cystamine (5 mg/100 g body weight) before 1,200 R whole-body gamma irradiation has been studied on irradiation-induced changes in liver and its subcellular fractions'lipids of fasted female rats. Cystamine prevented the irradiation-induced increase in liver triglycerides and liver mitochondrial total phospholipids, but it decreased microsomal total phospholipids and proteins. Cystamine prevented the radiation-induced increased 32 P-radioactivity (counts/min/μmole phospholipid phosphorus) of microsomal phosphatidyl choline. Cystamine prevented the radiation-induced increased uptake of NaH 2 32 PO 4 (counts/min/g liver) in liver microsomal phosphatidyl ethanolamine and supernatant phosphatidyl choline; but in microsomal phosphatidyl choline, cystamine did not do so, but on the other hand it itself increased the uptake in control rats. Cystamine did not prevent the irradiation-induced decreased incorporation of (U- 14 C)glucose into liver triglycerides, total phospholipids and phosphatidyl choline. Cystamine itself decreased the incorporation of (U- 14 C)glucose into liver triglycerides and phosphoglycerides of control rats. (orig.) [de

Polyploidization of liver cells.

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Celton-Morizur, Séverine; Desdouets, Chantal

2010-01-01

Eukaryotic organisms usually contain a diploid complement of chromosomes. However, there are a number of exceptions. Organisms containing an increase in DNA content by whole number multiples of the entire set of chromosomes are defined as polyploid. Cells that contain more than two sets of chromosomes were first observed in plants about a century ago and it is now recognized that polyploidy cells form in many eukaryotes under a wide variety of circumstance. Although it is less common in mammals, some tissues, including the liver, show a high percentage of polyploid cells. Thus, during postnatal growth, the liver parenchyma undergoes dramatic changes characterized by gradual polyploidization during which hepatocytes of several ploidy classes emerge as a result of modified cell-division cycles. This process generates the successive appearance of tetraploid and octoploid cell classes with one or two nuclei (mononucleated or binucleated). Liver cells polyploidy is generally considered to indicate terminal differentiation and senescence and to lead both to the progressive loss of cell pluripotency and a markedly decreased replication capacity. In adults, liver polyploidization is differentially regulated upon loss of liver mass and liver damage. Interestingly, partial hepatectomy induces marked cell proliferation followed by an increase in liver ploidy. In contrast, during hepatocarcinoma (HCC), growth shifts to a nonpolyploidizing pattern and expansion of the diploid hepatocytes population is observed in neoplastic nodules. Here we review the current state of understanding about how polyploidization is regulated during normal and pathological liver growth and detail by which mechanisms hepatocytes become polyploid.

Increased hepatic FAT/CD36, PTP1B and decreased HNF4A expression contributes to dyslipidemia associated with ethanol-induced liver dysfunction: Rescue effect of ginger extract.

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Shirpoor, Alireza; Heshmati, Elaheh; Kheradmand, Fatemeh; Gharalari, Farzaneh Hosseini; Chodari, Leila; Naderi, Roya; Majd, Farideh Nezami; Samadi, Mahrokh

2018-05-28

The association between chronic alcohol consumption and the development of alcpholic liver disease is a very well known phenomenon, but the precise underlying molecular mediators involved in ethanol-induced liver disease remain elusive. This study aimed to characterize the lipid metabolism alterations and the molecular mediators which are related to lipid metabolism in liver under the heavy ethanol exposure alone or combined with ginger extract. Twenty-four male wistar rats were assigned into three groups, namely control, ethanol, and ginger extract treated ethanol (GETE) groups. Six weeks after the treatment, the ethanol group showed a significant increase in fatty acid translocase (FAT)/CD36, protein tyrosine phosphatase 1B (PTP1B) and decrease hepatocyte nuclear factor 4 Alpha (HNF4A) genes expressions compared to the control group. The ethanol administration also significantly increased plasma LDL, cholesterol, triglyceride, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared to the control group. Moreover, compared to the control group, the ethanol group showed liver histhological changes, such as fibrosis, focal microvesicular steatosis, some apoptotic hepatocytes, spotty necrosis, portal lymphocytic inflammation, mallory-denk bodies, giant mitochondria, piecemeal necrosis. Consumption of ginger extract along with ethanol, partially ameliorated gene expression alteration and histological changes, improved undesirable lipid profile and liver enzymes changes compare to those in the ethanol group. These findings indicate that ethanol-induced liver abnormalities may in part be associated with lipid homeostasis changes mediated by overexpression of FAT/CD36, PTP1B and downexpressionof HNF4A genes. It also show that these effects can be reduced by using ginger extract as an antioxidant and anti-inflammatory agent. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Decreasing mitochondrial fission alleviates hepatic steatosis in a murine model of nonalcoholic fatty liver disease.

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Galloway, Chad A; Lee, Hakjoo; Brookes, Paul S; Yoon, Yisang

2014-09-15

Mitochondria produce the majority of cellular ATP through oxidative phosphorylation, and their capacity to do so is influenced by many factors. Mitochondrial morphology is recently suggested as an important contributor in controlling mitochondrial bioenergetics. Mitochondria divide and fuse continuously, which is affected by environmental factors, including metabolic alterations. Underscoring its bioenergetic influence, altered mitochondrial morphology is reported in tissues of patients and in animal models of metabolic dysfunction. In this study, we found that mitochondrial fission plays a vital role in the progression of nonalcoholic fatty liver disease (NAFLD). The development of hepatic steatosis, oxidative/nitrative stress, and hepatic tissue damage, induced by a high-fat diet, were alleviated in genetically manipulated mice suppressing mitochondrial fission. The alleviation of steatosis was recapitulated in primary hepatocytes with the inhibition of mitochondrial fission. Mechanistically, our study indicates that fission inhibition enhances proton leak under conditions of free fatty acid incubation, implicating bioenergetic change through manipulating mitochondrial fission. Taken together, our results suggest a mechanistic role for mitochondrial fission in the etiology of NAFLD. The efficacy of decreasing mitochondrial fission in the suppression of NAFLD suggests that mitochondrial fission represents a novel target for therapeutic treatment of NAFLD. Copyright © 2014 the American Physiological Society.

Bile acids for liver-transplanted patients. Protocol for a Cochrane Review

DEFF Research Database (Denmark)

Chen, W; Gluud, C

2003-01-01

Liver transplantation has become a widely accepted form of treatment for numerous end-stage liver diseases. Bile acids may decrease the degree of allograft rejection after liver transplantation by changing the expression of major histocompatibility complex class molecules in bile duct epithelium...

High fat feeding results in a decrease in insulin responsiveness of isolated solei

International Nuclear Information System (INIS)

Grundleger, M.L.; Preves, D.M.

1986-01-01

The relationship between diet and insulin responsiveness was examined in isolated solei from 6 week old female Sprague-Dawley rats. Weanling rats were fed either a high fat (HF) (67%kcal) or a high carbohydrate diet (HC) (67% kcal) for 21 days. A significant decrease in plasma insulin (I) but not glucose was observed in the HF fed rats. Insulin stimulated (IS) glucose (G) metabolism was examined using a maximal concentration of I (20 mU/m1). G uptake was estimated using 14 C-2 deoxyglucose (2DG). Basal and IS 2DG uptake decreased in HF rats. However, I sensitivity but not responsiveness remained intact in the HF rats. Total G utilization (GU) was estimated by the sum of the rate of formation of: 3 H 2 O from 5- 3 H-glucose [glycolysis- (GL)] and 3 H-glycogen (GLY). IS GU decreased in HF versus HC fed rats. I failed to stimulate GL while GLY remained sensitive. Glucose oxidation (GO) was measured by 14 CO 2 . I failed to stimulated GO. Intracellular metabolite concentrations (IC) were measured in solei from HF and HC fed rats. IS IC-G6P decreased in HF compared to HC fed rats. Basal IC-F6P but not IC-F 1.6 BP increased in HF compared to HC fed rats. I failed to stimulate an increase in IC-F 1,6BP concentrations. Glycolytic activators were determined. HF produced a significant decrease in F2, 6BP concentration when compared to HC rats. Prostaglandins (PG) have been implicated in mediating insulin action. HF produced a significant decrease in basal and insulin stimulated PGE 2 . These data demonstrate that postreceptor - postmembrane alterations are in part responsible for the decreased insulin responsiveness observed after HF feeding

Therapeutic hypothermia for acute liver failure

DEFF Research Database (Denmark)

Stravitz, R.T.; Larsen, Finn Stolze

2009-01-01

transplantation or spontaneous liver regeneration follows in short order. To buy time, the induction of therapeutic hypothermia (core temperature 32 degrees C-35 degrees C) has been shown to effectively bridge patients to transplant. Similar to the experience in patients with cerebral edema after other neurologic...... insults, hypothermia reduces cerebral edema and intracranial hypertension in patients with acute liver failure by decreasing splanchnic ammonia production, restoring normal regulation of cerebral hemodynamics, and lowering oxidative metabolism within the brain. Hypothermia may also ameliorate the degree...... of liver injury. Hypothermia has not been adequately studied for its safety and theoretically may increase the risk of infection, cardiac dysrhythmias, and bleeding, all complications independently associated with acute liver failure. Therefore, although an ample body of experimental and human data...

A comparison of basal and eye-flush tears for the analysis of cat tear proteins.

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Petznick, Andrea; Evans, Margaret D M; Madigan, Michele C; Markoulli, Maria; Garrett, Qian; Sweeney, Deborah F

2011-02-01

To identify a rapid and effective tear collection method providing sufficient tear volume and total protein content (TPC) for analysis of individual proteins in cats. Domestic adult short-haired cats (12-37 months; 2.7-6.6 kg) were used in the study. Basal tears without stimulation and eye-flush tears after instillation of saline (10 μl) were collected using microcapillary tubes from animal eyes either unwounded control or wounded with 9-mm central epithelial debridement giving four groups with n = 3. Tear comparisons were based on total time and rate for tear collection, TPC using micro bicinchoninic acid (BCA), tear immunoglobulin A (IgA), total matrix-metalloproteinase (MMP)-9 concentration using sandwich enzyme-linked immunosorbent assay (ELISA) and MMP-9 activity. Eye-flush tears were collected significantly faster than basal tears in wounded eyes with higher rates for tear collection in unwounded control and wounded eyes. TPC was significantly lower in eye-flush tears compared to basal tears. The relative proportion of tear IgA normalized to TPC (% IgA of TPC) was not significantly different between basal and eye-flush tears. In unwounded control eyes, MMP-9 was slightly higher in eye-flush than in basal tears; activity of MMP-9 in both tear types was similar. In wounded eyes, eye-flush tears showed highest MMP-9 levels and activity on Day 1, which subsequently decreased to Day 7. MMP-9 activity in basal tears from wounded eyes did not display changes in expression. Eye-flush tears can be collected rapidly providing sufficient tear volume and TPC. This study also indicates that eye-flush tears may be more suitable than basal tears for the analysis of MMPs following corneal wounding. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

Hereditary haemochromatosis: a case of iron accumulation in the basal ganglia associated with a parkinsonian syndrome

DEFF Research Database (Denmark)

Nielsen, J.E.; Jensen, L. Neerup; Krabbe, K.

1995-01-01

. A patient is reported with hereditary haemochromatosis and a syndrome of dementia, dysarthria, a slowly progressive gait disturbance, imbalance, muscle weakness, rigidity, bradykinesia, tremor, ataxia, and dyssynergia. The findings on MRI of a large signal decrease in the basal ganglia, consistent...

Bone morphogenetic protein 9 as a key regulator of liver progenitor cells in DDC-induced cholestatic liver injury.

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Addante, Annalisa; Roncero, Cesáreo; Almalé, Laura; Lazcanoiturburu, Nerea; García-Álvaro, María; Fernández, Margarita; Sanz, Julián; Hammad, Seddik; Nwosu, Zeribe C; Lee, Se-Jin; Fabregat, Isabel; Dooley, Steven; Ten Dijke, Peter; Herrera, Blanca; Sánchez, Aránzazu

2018-05-11

Bone morphogenetic protein 9 (BMP9) interferes with liver regeneration upon acute injury, while promoting fibrosis upon carbon tetrachloride-induced chronic injury. We have now addressed the role of BMP9 in 3,5 diethoxicarbonyl-1,4 dihydrocollidine (DDC)-induced cholestatic liver injury, a model of liver regeneration mediated by hepatic progenitor cell (known as oval cell), exemplified as ductular reaction and oval cell expansion. WT and BMP9KO mice were submitted to DDC diet. Livers were examined for liver injury, fibrosis, inflammation and oval cell expansion by serum biochemistry, histology, RT-qPCR and western blot. BMP9 signalling and effects in oval cells were studied in vitro using western blot and transcriptional assays, plus functional assays of DNA synthesis, cell viability and apoptosis. Crosslinking assays and short hairpin RNA approaches were used to identify the receptors mediating BMP9 effects. Deletion of BMP9 reduces liver damage and fibrosis, but enhances inflammation upon DDC feeding. Molecularly, absence of BMP9 results in overactivation of PI3K/AKT, ERK-MAPKs and c-Met signalling pathways, which together with an enhanced ductular reaction and oval cell expansion evidence an improved regenerative response and decreased damage in response to DDC feeding. Importantly, BMP9 directly targets oval cells, it activates SMAD1,5,8, decreases cell growth and promotes apoptosis, effects that are mediated by Activin Receptor-Like Kinase 2 (ALK2) type I receptor. We identify BMP9 as a negative regulator of oval cell expansion in cholestatic injury, its deletion enhancing liver regeneration. Likewise, our work further supports BMP9 as an attractive therapeutic target for chronic liver diseases. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Basal-topographic control of stationary ponds on a continuously moving landslide

Science.gov (United States)

Coe, J.A.; McKenna, J.P.; Godt, J.W.; Baum, R.L.

2009-01-01

analyses of translational landslides should attempt to incorporate irregular basal surface topography. Additional implications for moving landslides where basal topography controls surface morphology include the following: dateable sediments or organic material from basal layers of stationary ponds will yield ages that are younger than the date of landslide initiation, and it is probable that other landslide surface features such as faults, streams, springs and sinks are also controlled by basal topography. The longitudinal topographic profile indicated that the upper part of the Slumgullion landslide was depleted at a mean vertical lowering rate of 5.6 cm/yr between 1939 and 2000, while the toe advanced at an average rate of 1.5 m/yr during the same period. Therefore, during this 61-year period, neither the depletion of material at the head of the landslide nor continued growth of the landslide toe has decreased the overall movement rate of the landslide. Continued depletion of the upper part of the landslide, and growth of the toe, should eventually result in stabilization of the landslide. Copyright ?? 2008 John Wiley & Sons, Ltd.

Learning and memory functions of the Basal Ganglia.

Science.gov (United States)

Packard, Mark G; Knowlton, Barbara J

2002-01-01

Although the mammalian basal ganglia have long been implicated in motor behavior, it is generally recognized that the behavioral functions of this subcortical group of structures are not exclusively motoric in nature. Extensive evidence now indicates a role for the basal ganglia, in particular the dorsal striatum, in learning and memory. One prominent hypothesis is that this brain region mediates a form of learning in which stimulus-response (S-R) associations or habits are incrementally acquired. Support for this hypothesis is provided by numerous neurobehavioral studies in different mammalian species, including rats, monkeys, and humans. In rats and monkeys, localized brain lesion and pharmacological approaches have been used to examine the role of the basal ganglia in S-R learning. In humans, study of patients with neurodegenerative diseases that compromise the basal ganglia, as well as research using brain neuroimaging techniques, also provide evidence of a role for the basal ganglia in habit learning. Several of these studies have dissociated the role of the basal ganglia in S-R learning from those of a cognitive or declarative medial temporal lobe memory system that includes the hippocampus as a primary component. Evidence suggests that during learning, basal ganglia and medial temporal lobe memory systems are activated simultaneously and that in some learning situations competitive interference exists between these two systems.

Nrf2 the rescue: Effects of the antioxidative/electrophilic response on the liver

International Nuclear Information System (INIS)

Klaassen, Curtis D.; Reisman, Scott A.

2010-01-01

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that positively regulates the basal and inducible expression of a large battery of cytoprotective genes. These gene products include proteins that catalyze reduction reactions (NAD(P)H:quinone oxidoreductase 1, Nqo1), conjugation reactions (glutathione-S-transferases, Gsts and UDP-glucuronosyltransferases, Ugts), as well as the efflux of potentially toxic xenobiotics and xenobiotic conjugates (multidrug resistance-associated proteins, Mrps). The significance of Nrf2 in the liver has been established, as livers of Nrf2-null mice are more susceptible to various oxidative/electrophilic stress-induced pathologies than wild-type mice. In contrast, both pharmacological and genetic models of hepatic Nrf2 activation are protective against oxidative/electrophilic stress. Furthermore, because certain Nrf2-target genes in the liver could affect the distribution, metabolism, and excretion of xenobiotics, the effects of Nrf2 on the kinetics of drugs and other xenobiotics should also be considered, with a special emphasis on metabolism and excretion. Therefore, this review highlights the research that has contributed to the understanding of the importance of Nrf2 in toxicodynamics and toxicokinetics, especially that which pertains to the liver.

Evaluation of usefulness of Tc-99m-GSA liver scintigraphy in chronic liver diseases

International Nuclear Information System (INIS)

Fukui, Hiroyuki; Kashiwagi, Toru; Kasahara, Akinori

1991-01-01

Liver scintigraphy was performed using a newly developed radiopharmaceutical, Tc-99m-DTPA-galactosyl-human-serum-albumin (Tc-99m-GSA), which binds specifically to the receptors on the hepatic cell surface, in 15 patients with chronic liver disease. The scintigraphy was evaluated qualitatively and quantitatively, and the results were compared with those obtained from the Tc-99m-PMT or Tc-99m-sn-phytate scintigraphy, and the liver function tests. The Tc-99m-GSA scintigraphy showed clear liver images in chronic hepatitis. However, in liver cirrhosis, the liver images were not clear and the cardiac images still existed 40 minutes after administration of Tc-99m-GSA, suggesting that the image quality of the Tc-99m-GSA scintigrams may be inferior to that of Tc-99m-sn-phytate or Tc-99m-PMT in some cases of severe liver dysfunction. The time-activity curves of the heart and liver were analyzed by non-linear regression analysis. The clearance rate from plasma (Kd) were obtained from the time-activity curve of the heart, and the hepatic uptake rate (Ku), hepatic excretion rate (Ke) and peak time of hepatic uptake-excretion curve (PT) were obtained from the time-activity curve of the liver. Kd, Ku, and PT values were more significantly decreased or prolonged in the patients with chronic hepatitis. Kd, Ku, and PT values had positive correlations with the result of the serum liver function tests, ICG-R15 and ICG-K. Ku and PT values had also correlations with the histological degree of hepatic fibrosis. On the other hand, the indices obtained using Tc-99m-PMT or Tc-99m-sn-phytate did not have correlations with the histological degrees of hepatic fibrosis. It is concluded that the liver scintigraphy using Tc-99m-GSA may be useful and give different information from those with conventional liver scintigraphies in evaluating chronic liver diseases. (author)

Elastin in the Liver

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Jiri Kanta

2016-10-01

Full Text Available A characteristic feature of liver cirrhosis is the accumulation of large amounts of connective tissue with the prevailing content of type I collagen. Elastin is a minor connective tissue component in normal liver but it is actively synthesized by hepatic stellate cells and portal fibroblasts in diseased liver. The accumulation of elastic fibers in later stages of liver fibrosis may contribute to the decreasing reversibility of the disease with advancing time. Elastin is formed by polymerization of tropoelastin monomers. It is an amorphous protein highly resistant to the action of proteases that forms the core of elastic fibers. Microfibrils surrounding the core are composed of fibrillins that bind a number of proteins involved in fiber formation. They include microfibril-associated glycoproteins (MAGPs, microfibrillar-associated proteins (MFAPs and fibulins. Lysyl oxidase (LOX and lysyl oxidase-like proteins (LOXLs are responsible for tropoelastin cross-linking and polymerization. TGF-β complexes attached to microfibrils release this cytokine and influence the behavior of the cells in the neighborhood. The role of TGF-β as the main profibrotic cytokine in the liver is well-known and the release of the cytokines of TGF-β superfamily from their storage in elastic fibers may affect the course of fibrosis. Elastic fibres are often studied in the tissues where they provide elasticity and resilience but their role is no longer viewed as purely mechanical. Tropoelastin, elastin polymer and elastin peptides resulting from partial elastin degradation influence fibroblastic and inflammatory cells as well as angiogenesis. A similar role may be performed by elastin in the liver. This article reviews the results of the research of liver elastic fibers on the backgound of the present knowledge of elastin biochemistry and physiology. The regulation of liver elastin synthesis and degradation may be important for the outcome of liver fibrosis.

Localized basal meningeal enhancement in tuberculous meningitis

Energy Technology Data Exchange (ETDEWEB)

Theron, Salomine; Andronikou, Savvas; Grobbelaar, Marie; Steyn, Freda; Mapukata, Ayanda; Plessis, Jaco du [University of Stellenbosch, Department of Radiology, Tygerberg Hospital, P.O. BOX 19063, Tygerberg (South Africa)

2006-11-15

Focal basal meningeal enhancement may produce a confusing CT picture in children with suspected tuberculous meningitis (TBM). To demonstrate the incidence, distribution and appearance of localized basal meningeal enhancement in children with TBM. CT scans of patients with definite (culture proven) and probable (CSF suggestive) TBM were retrospectively evaluated by two observers. Localized basal enhancement was documented as involving: unilateral cistern of the lateral fossa (CLF), unilateral sylvian fissure, unilateral CLF and sylvian fissure in combination, unilateral CLF and sylvian fissure with ipsi- or contralateral ambient cistern and isolated quadrigeminal plate cistern. The study included 130 patients with TBM (aged 2 months to 13 years 9 months). Focal basal enhancement was seen in 11 patients (8.5%). The sylvian fissure was involved most commonly, followed by the lateral fossa cistern. The ambient cistern was involved in three patients and the quadrigeminal plate cistern in one. Focal areas of enhancement corresponded to the areas of infarction in every patient. Focal basal meningeal enhancement is common (8.5%) in paediatric TBM. This must be kept in mind when evaluating CT scans in children presenting with focal neurological findings, seizures or meningism in communities where TBM is endemic. (orig.)

Localized basal meningeal enhancement in tuberculous meningitis

International Nuclear Information System (INIS)

Theron, Salomine; Andronikou, Savvas; Grobbelaar, Marie; Steyn, Freda; Mapukata, Ayanda; Plessis, Jaco du

2006-01-01

Focal basal meningeal enhancement may produce a confusing CT picture in children with suspected tuberculous meningitis (TBM). To demonstrate the incidence, distribution and appearance of localized basal meningeal enhancement in children with TBM. CT scans of patients with definite (culture proven) and probable (CSF suggestive) TBM were retrospectively evaluated by two observers. Localized basal enhancement was documented as involving: unilateral cistern of the lateral fossa (CLF), unilateral sylvian fissure, unilateral CLF and sylvian fissure in combination, unilateral CLF and sylvian fissure with ipsi- or contralateral ambient cistern and isolated quadrigeminal plate cistern. The study included 130 patients with TBM (aged 2 months to 13 years 9 months). Focal basal enhancement was seen in 11 patients (8.5%). The sylvian fissure was involved most commonly, followed by the lateral fossa cistern. The ambient cistern was involved in three patients and the quadrigeminal plate cistern in one. Focal areas of enhancement corresponded to the areas of infarction in every patient. Focal basal meningeal enhancement is common (8.5%) in paediatric TBM. This must be kept in mind when evaluating CT scans in children presenting with focal neurological findings, seizures or meningism in communities where TBM is endemic. (orig.)

Regular exercise is associated with a reduction in the risk of NAFLD and decreased liver enzymes in individuals with NAFLD independent of obesity in Korean adults.

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Ji Cheol Bae

Full Text Available BACKGROUND: We evaluated the association of regular physical exercise with the presence of non-alcoholic fatty liver disease (NAFLD and liver enzymes in relation to obesity and insulin resistance. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional analysis was conducted in 72,359 healthy Korean adults without diabetes who participated in a comprehensive health check-up. Subjects who have been exercising regularly (more than 3 times per week, at least for 30 minutes each time and for consecutive 3 month were categorized into exercise group. All subjects were categorized into deciles based on their body mass index (BMI and we estimated the odds ratios (ORs for having NAFLD according to exercise regularity in each decile. The diagnosis of NAFLD was based on ultrasonography findings. Individuals with NAFLD (n = 19,921 were analyzed separately to evaluate ORs for having elevated liver enzymes based on regularity of exercise. The risk for NAFLD was significantly reduced in exercise group with age- and sex-adjusted ORs of 0.53-0.72 for all BMI deciles except at BMI categories of <19.6 and 20.7-21.6 kg/m(2. While no difference was seen in BMI between subjects in exercise and non-exercise group across the BMI deciles, the values of body fat percentage and metabolic risk factors differed. Among NAFLD patients, subjects in exercise group had a lower risk for having elevated liver enzymes with multivariable adjusted OR of 0.85 (95% CI 0.74-0.99, for AST and 0.74 (95% CI 0.67-0.81, for ALT than did subjects in non-exercise group. CONCLUSIONS/SIGNIFICANCE: Regular exercise was associated with a reduced risk for having NAFLD and decreased liver enzymes in patients with NAFLD, and this relationship was also independent of obesity.

A Classic Case of Basal Cell Nevus Syndrome

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Dattaprasad Dadhe

2015-01-01

Full Text Available The basal cell nevus syndrome is an autosomal dominant inherited condition characterized mainly by basal cell carcinomas, multiple keratinizing odontogenic tumors, and other systemic anomalies. As these manifestations do not alter the patient′s lifestyle, most of the cases are diagnosed through oral abnormalities. A classic case of basal cell nevus syndrome fulfilling almost all the major and minor criteria has been reported here.

Total body propofol clearance (TBPC) after living-donor liver transplantation (LDLT) surgery is decreased in patients with a long warm ischemic time.

Science.gov (United States)

Al-Jahdari, Wael S; Kunimoto, Fumio; Saito, Shigeru; Yamamoto, Koujirou; Koyama, Hiroshi; Horiuchi, Ryuya; Goto, Fumio

2006-01-01

Metabolic capacity after liver transplant surgery may be affected by the graft size and by hepatic injury during the surgery. This study was carried out to investigate the postoperative total body propofol clearance (TBPC) in living-donor liver transplantation (LDLT) patients and to investigate the major factors that contribute to decreased postoperative TBPC in LDLT patients. Fourteen patients scheduled for LDLT were included in this study. Propofol was administered at a rate of 2.0 mg.kg(-1).h(-1) as a sedative in the intensive care unit (ICU) setting. To calculate TBPC, propofol arterial blood concentration was measured by HPLC. Five variables were selected as factors affecting postoperative TBPC; bleeding volume (BLD), warm ischemic time (WIT), cold ischemic time (CIT), graft weight/standard liver volume ratio (GW/SLV), and portal blood flow after surgery (PBF). After factor analysis of six variables, including TBPC, varimax rotation was carried out, and this yielded three interpretable factors that accounted for 75.5% of the total variance in the data set. TBPC, WIT, CIT, and BLD were loaded on the first factor, PBF on the second factor, and GW/SLV on the third factor. The adjusted correlation coefficient between TBPC and WIT showed the highest value (r = -0.61) in the first factor. The LDLT patients were divided into two groups according to WIT; group A (WIT > 100 min) and group B (WIT < 100 min). Mean TBPC values in group A and group B were 14.6 +/- 2.1 and 28.5 +/- 4.1 ml.kg(-1).min(-1), respectively (P < 0.0001). These data suggest that LDLT patients with a long WIT have a risk of deteriorated drug metabolism.

A knockout mutation of a constitutive GPCR in Tetrahymena decreases both G-protein activity and chemoattraction.

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Thomas J Lampert

Full Text Available Although G-protein coupled receptors (GPCRs are a common element in many chemosensory transduction pathways in eukaryotic cells, no GPCR or regulated G-protein activity has yet been shown in any ciliate. To study the possible role for a GPCR in the chemoresponses of the ciliate Tetrahymena, we have generated a number of macronuclear gene knockouts of putative GPCRs found in the Tetrahymena Genome database. One of these knockout mutants, called G6, is a complete knockout of a gene that we call GPCR6 (TTHERM_00925490. Based on sequence comparisons, the Gpcr6p protein belongs to the Rhodopsin Family of GPCRs. Notably, Gpcr6p shares highest amino acid sequence homologies to GPCRs from Paramecium and several plants. One of the phenotypes of the G6 mutant is a decreased responsiveness to the depolarizing ions Ba²⁺ and K⁺, suggesting a decrease in basal excitability (decrease in Ca²⁺ channel activity. The other major phenotype of G6 is a loss of chemoattraction to lysophosphatidic acid (LPA and proteose peptone (PP, two known chemoattractants in Tetrahymena. Using microsomal [³⁵S]GTPγS binding assays, we found that wild-type (CU427 have a prominent basal G-protein activity. This activity is decreased to the same level by pertussis toxin (a G-protein inhibitor, addition of chemoattractants, or the G6 mutant. Since the basal G-protein activity is decreased by the GPCR6 knockout, it is likely that this gene codes for a constitutively active GPCR in Tetrahymena. We propose that chemoattractants like LPA and PP cause attraction in Tetrahymena by decreasing the basal G-protein stimulating activity of Gpcr6p. This leads to decreased excitability in wild-type and longer runs of smooth forward swimming (less interrupted by direction changes towards the attractant. Therefore, these attractants may work as inverse agonists through the constitutively active Gpcr6p coupled to a pertussis-sensitive G-protein.

Sex Hormones and Their Receptors Regulate Liver Energy Homeostasis

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Minqian Shen

2015-01-01

Full Text Available The liver is one of the most essential organs involved in the regulation of energy homeostasis. Hepatic steatosis, a major manifestation of metabolic syndrome, is associated with imbalance between lipid formation and breakdown, glucose production and catabolism, and cholesterol synthesis and secretion. Epidemiological studies show sex difference in the prevalence in fatty liver disease and suggest that sex hormones may play vital roles in regulating hepatic steatosis. In this review, we summarize current literature and discuss the role of estrogens and androgens and the mechanisms through which estrogen receptors and androgen receptors regulate lipid and glucose metabolism in the liver. In females, estradiol regulates liver metabolism via estrogen receptors by decreasing lipogenesis, gluconeogenesis, and fatty acid uptake, while enhancing lipolysis, cholesterol secretion, and glucose catabolism. In males, testosterone works via androgen receptors to increase insulin receptor expression and glycogen synthesis, decrease glucose uptake and lipogenesis, and promote cholesterol storage in the liver. These recent integrated concepts suggest that sex hormone receptors could be potential promising targets for the prevention of hepatic steatosis.

Triple-negative breast cancer with brain metastases: a comparison between basal-like and non-basal-like biological subtypes

NARCIS (Netherlands)

A. Niwińska (Anna); W. Olszewski (Wojciech); M. Murawska (Magdalena); K. Pogoda (Katarzyna)

2011-01-01

textabstractThe aim of this study was to divide the group of triple-negative breast cancer patients with brain metastases into basal-like and non-basal-like biological subtypes in order to compare clinical features and survival rates in those two groups. A comprehensive analysis of 111 consecutive

Osteoporosis and FRAX risk in patients with liver cirrhosis

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Azucena I. Casanova-Lara

2014-10-01

Conclusions: The frequency of osteoporosis or osteopenia is 90.4% in Mexican patients with liver cirrhosis of different etiologies. The decreased levels of bone alkaline phosphatase and 25-hydroxyvitamin-D were correlated with the risk of bone disease in patients with liver cirrhosis.

Transferrin metabolism in alcoholic liver disease

International Nuclear Information System (INIS)

Potter, B.J.; Chapman, R.W.; Nunes, R.M.; Sorrentino, D.; Sherlock, S.

1985-01-01

The metabolism of transferrin was studied using purified 125 I-labeled transferrin in 11 alcoholic patients; six with fatty liver and five with cirrhosis. Six healthy subjects whose alcohol intake was les than 40 gm daily were studied as a control group. There were no significant differences in the mean fractional catabolic rate and plasma volume in the alcoholic groups when compared with control subjects. A significantly decreased mean serum transferrin concentration was found in the alcoholic cirrhotic patients (1.8 +/- 0.3 gm per liter vs. 2.9 +/- 0.2; p less than 0.01), resulting from diminished total body synthesis (0.9 +/- 0.2 mg per kg per hr vs. 1.8 +/- 0.2; p less than 0.01). In contrast, in the patients with alcoholic fatty liver, the mean total body transferrin synthesis (2.4 +/- 0.3 mg per kg per hr) was significantly increased when compared with controls (p less than 0.05). For all the alcoholic patients, the serum transferrin correlated with transferrin synthesis (r = +0.70; p less than 0.01) but the serum iron did not. These results suggest that, in alcoholic cirrhosis, transferrin synthesis is decreased, probably reflecting diminished synthetic capacity by the liver. In contrast, in patients with alcoholic fatty liver, transferrin turnover is accelerated

Basal Cell Carcinoma Arising in a Tattooed Eyebrow

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Lee, Jong-Sun; Park, Jin; Kim, Seong-Min; Kim, Han-Uk

2009-01-01

Malignant skin tumors, including squamous cell carcinoma and malignant melanoma, have occurred in tattoos. Seven documented cases of basal cell carcinoma associated with tattoos have also been reported in the medical literature. We encountered a patient with basal cell carcinoma in a tattooed eyebrow. We report on this case as the eighth reported case of a patient with basal cell carcinoma arising in a tattooed area. PMID:20523804

Germinoma originating in the basal ganglia

International Nuclear Information System (INIS)

Anno, Y.; Hori, T.; Watanabe, T.; Takenobu, A.; Takigawa, H.; Kishimoto, M.; Tanaka, J.

1990-01-01

About 5-10% of primary intracranial germ cell tumors arise in basal ganglia and thalamus, where CT studies have been made. MR of the tumors in the pineal region, and to our knowledge, from one tumor in the basal ganglia were similar. In the present case, MR produced confusion in confirming diagnosis, which may require additional evidence from the clinical course, tumor markers, and CT images. (orig.)

Nutritional Modulation of Non-Alcoholic Fatty Liver Disease and Insulin Resistance

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Hannele Yki-Järvinen

2015-11-01

Full Text Available Non-alcoholic fatty liver disease (NAFLD covers a spectrum of disorders ranging from simple steatosis (non-alcoholic fatty liver, NAFL to non-alcoholic steatohepatitis (NASH and cirrhosis. NAFL increases the risk of liver fibrosis. If the liver is fatty due to causes of insulin resistance such as obesity and physical inactivity, it overproduces glucose and triglycerides leading to hyperinsulinemia and a low high-density lipoprotein (HDL cholesterol concentration. The latter features predispose to type 2 diabetes and cardiovascular disease (CVD. Understanding the impact of nutritional modulation of liver fat content and insulin resistance is therefore of interest for prevention and treatment of NAFLD. Hypocaloric, especially low carbohydrate ketogenic diets rapidly decrease liver fat content and associated metabolic abnormalities. However, any type of caloric restriction seems effective long-term. Isocaloric diets containing 16%–23% fat and 57%–65% carbohydrate lower liver fat compared to diets with 43%–55% fat and 27%–38% carbohydrate. Diets rich in saturated (SFA as compared to monounsaturated (MUFA or polyunsaturated (PUFA fatty acids appear particularly harmful as they increase both liver fat and insulin resistance. Overfeeding either saturated fat or carbohydrate increases liver fat content. Vitamin E supplementation decreases liver fat content as well as fibrosis but has no effect on features of insulin resistance.

Nevoid basal cell carcinoma syndrome

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Kannan Karthiga

2006-01-01

Full Text Available Binkley and Johnson first reported this syndrome in 1951. But it was in 1960, Gorlin-Goltz established the association of basal cell epithelioma, jaw cyst and bifid ribs, a combination which is now frequently known as Gorlin-Goltz syndrome as well as Nevoid Basal Cell Carcinoma Syndrome (NBCCS. NBCCS is inherited as an autosomal dominant trait with high penetrance and variable expressivity. NBCCS is characterized by variety of cutaneous, dental, osseous, opthalmic, neurologic and sexual abnormalities. One such case of Gorlin-Goltz syndrome is reported here with good illustrations.

Dietary enzymatically treated Artemisia annua L. supplementation alleviates liver oxidative injury of broilers reared under high ambient temperature

Science.gov (United States)

Wan, Xiaoli; Zhang, Jingfei; He, Jintian; Bai, Kaiwen; Zhang, Lili; Wang, Tian

2017-09-01

Heat stress induced by high ambient temperature is a major concern in commercial broiler production. To evaluate the effects of dietary enzymatically treated Artemisia annua L. (EA) supplementation on growth performance and liver oxidative injury of broilers reared under heat stress, a total of 320 22-day-old male broilers were randomly allotted into five groups with eight replicates of eight birds each. Broilers in the control group were housed at 22 ± 1 °C and fed the basal diet. Broilers in the HS, HS-EA1, HS-EA2, and HS-EA3 groups were fed basal diet supplemented with 0, 0.75, 1.00, and 1.25 g/kg EA, respectively, and reared under cyclic high temperature (34 ± 1 °C for 8 h/day and 22 ± 1 °C for 16 h/day). Broilers fed EA diets had higher final body weight, average daily body weight gain, and average daily feed intake, as well as liver concentration of reduced glutathione, activities of antioxidant enzymes, abilities to inhibit hydroxyl radical and superoxide radical (HS-EA2 and HS-EA3), and lower liver concentrations of reactive oxygen metabolites, malondialdehyde, and protein carbonyl (HS-EA1, HS-EA2, and HS-EA3) than HS group ( P proteins 70 and 90, upregulated the mRNA levels of nuclear factor erythroid 2-related factor 2 (HS-EA1, HS-EA2, and HS-EA3) and heme oxygenase 1 (HS-EA2 and HS-EA3) in liver of heat-treated broilers ( P diet is 1.00-1.25 g/kg.

Basal Cell Ameloblastoma: A Rare Histological Variant of an ...

African Journals Online (AJOL)

Ameloblastomas are an inscrutable group of oral tumors. Basal cell ameloblastoma is a rare variant of ameloblastoma with very few cases reported until date. The tumor is composed of more primitive cells and has less conspicuous peripheral palisading. It shows remarkable similarity to basal cell carcinoma, basal cell ...

Long-term pathological and immunohistochemical features in the liver after intraoperative whole-liver irradiation in rats

International Nuclear Information System (INIS)

Imaeda, Masumi; Yoshida, Yukari; Ohkubo, Yu; Musha, Atsushi; Komachi, Mayumi; Nakano, Takashi; Ishikawa, Hitoshi; Takahashi, Takeo; Nakazato, Yoichi

2014-01-01

Radiation therapy (RT) has become particularly important recently for treatment of liver tumors, but there are few experimental investigations pertaining to radiation-induced liver injuries over long-term follow-up periods. Thus, the present study examined pathological liver features over a 10-month period using an intraoperative whole-liver irradiation model. Liver function tests were performed in blood samples, whereas cell death, cell proliferation, and fibrotic changes were evaluated pathologically in liver tissues, which were collected from irradiated rats 24 h, 1, 2, 4 and 40 weeks following administration of single irradiation doses of 0 (control), 15 or 30 Gy. The impaired liver function, increased hepatocyte number, and decreased apoptotic cell proportion observed in the 15 Gy group, but not the 30 Gy group, returned to control group levels after 40 weeks; however, the Ki-67 indexes in the 15 Gy group were still higher than those in the control group after 40 weeks. Azan staining showed a fibrotic pattern in the irradiated liver in the 30 Gy group only, but the expression levels of alpha smooth muscle actin (α-SMA) and transforming growth factor-beta 1 (TGF-β1) in both the 15 and 30 Gy groups were significantly higher than those in the control group (P < 0.05). There were differences in the pathological features of the irradiated livers between the 15 Gy and 30 Gy groups, but TGF-β1 and α-SMA expression patterns supported the gradual progression of radiation-induced liver fibrosis in both groups. These findings will be useful in the future development of protective drugs for radiation-induced liver injury. (author)

Modulation of liver enzymes by an Iranian preparation of Echinacea purpurea

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A. Manayi

2015-10-01

Full Text Available Hepatitis B, a common infectious disease of liver, is transmitted by blood and body fluids like semen and vaginal fluid that carry hepatitis B virus (HBV.  In chronic infection, medical care is required to decrease possibility of cirrhosis and liver cancer. In the present report, the hepatoprotective effect of an Echinacea purpurea preparation (Echiherb® has been described in a patient who suffered from HBV infection. The levels of both enzymes of aspartate aminotransferase (AST and alanine aminotransferase (ALT decreased to their normal level after 6 weeks of treatment. Therefore, this report may provide a new perspective for protection of liver in patients with HBV infection along with other diseases which damage liver cells using E. purpurea preparations.

Bioartificial liver and liver transplantation: new modalities for the treatment of liver failure

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DING Yitao

2017-09-01

Full Text Available The main features of liver failure are extensive necrosis of hepatocytes, rapid disease progression, and poor prognosis, and at present, there are no effective drugs and methods for the treatment of liver failure. This article summarizes four treatment methods for liver failure, i.e., medical treatment, cell transplantation, liver transplantation, and artificial liver support therapy, and elaborates on the existing treatment methods. The current medical treatment regimen should be optimized; cell transplantation has not been used in clinical practice; liver transplantation is the most effective method, but it is limited by donor liver shortage and high costs; artificial liver can effectively remove toxic substances in human body. Therefore, this article puts forward artificial liver as a transition for liver transplantation; artificial liver can buy time for liver regeneration or liver transplantation and prolong patients′ survival time and thus has a promising future. The new treatment modality of bioartificial liver combined with liver transplantation may bring good news to patients with liver failure.

Degludec insulin: A novel basal insulin

OpenAIRE

Kalra, Sanjay; Unnikrishnan, Ambika Gopalakrishnan; Baruah, Manash; Kalra, Bharti

2011-01-01

This paper reviews a novel insulin analogue, degludec, which has the potential to emerge as an ideal basal insulin. It reviews the limitations of existing basal insulin and analogues, and highlights the need for a newer molecule. The paper discusses the potential advantages of degludec, while reviewing its pharmacologic and clinical studies done so far. The paper assesses the potential role of insulin degludec and degludec plus in clinical diabetes practice.

Electrocorticography reveals beta desynchronization in the basal ganglia-cortical loop during rest tremor in Parkinson's disease.

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Qasim, Salman E; de Hemptinne, Coralie; Swann, Nicole C; Miocinovic, Svjetlana; Ostrem, Jill L; Starr, Philip A

2016-02-01

The pathophysiology of rest tremor in Parkinson's disease (PD) is not well understood, and its severity does not correlate with the severity of other cardinal signs of PD. We hypothesized that tremor-related oscillatory activity in the basal-ganglia-thalamocortical loop might serve as a compensatory mechanism for the excessive beta band synchronization associated with the parkinsonian state. We recorded electrocorticography (ECoG) from the sensorimotor cortex and local field potentials (LFP) from the subthalamic nucleus (STN) in patients undergoing lead implantation for deep brain stimulation (DBS). We analyzed differences in measures of network synchronization during epochs of spontaneous rest tremor, versus epochs without rest tremor, occurring in the same subjects. The presence of tremor was associated with reduced beta power in the cortex and STN. Cortico-cortical coherence and phase-amplitude coupling (PAC) decreased during rest tremor, as did basal ganglia-cortical coherence in the same frequency band. Cortical broadband gamma power was not increased by tremor onset, in contrast to the movement-related gamma increase typically observed at the onset of voluntary movement. These findings suggest that the cortical representation of rest tremor is distinct from that of voluntary movement, and support a model in which tremor acts to decrease beta band synchronization within the basal ganglia-cortical loop. Copyright © 2015 Elsevier Inc. All rights reserved.

COX-1 vs. COX-2 as a determinant of basal tone in the internal anal sphincter.

Science.gov (United States)

de Godoy, Márcio A F; Rattan, Neeru; Rattan, Satish

2009-02-01

Prostanoids, produced endogenously via cyclooxygenases (COXs), have been implicated in the sustained contraction of different smooth muscles. The two major types of COXs are COX-1 and COX-2. The COX subtype involved in the basal state of the internal anal sphincter (IAS) smooth muscle tone is not known. To identify the COX subtype, we examined the effect of COX-1- and COX-2-selective inhibitors, SC-560 and rofecoxib, respectively, on basal tone in the rat IAS. We also determined the effect of selective deletion of COX-1 and COX-2 genes (COX-1(-/-) and COX-2(-/-) mice) on basal tone in murine IAS. Our data show that SC-560 causes significantly more efficacious and potent concentration-dependent decreases in IAS tone than rofecoxib. In support of these data, significantly higher levels of COX-1 than COX-2 mRNA were found in the IAS. In addition, higher levels of COX-1 mRNA and protein were expressed in rat IAS than rectal smooth muscle. In wild-type mice, IAS tone was decreased 41.4 +/- 3.4% (mean +/- SE) by SC-560 (1 x 10(-5) M) and 5.4 +/- 2.2% by rofecoxib (P IAS from wild-type mice and significantly less (0.080 +/- 0.015 mN/mg) in the IAS from COX-1(-/-) mice (P IAS tone.

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

Czech Academy of Sciences Publication Activity Database

Lake, A.D.; Novák, Petr; Shipkova, P.; Aranibar, N.; Robertson, D.; Reily, M.D.; Lu, Z.; Lehman-McKeeman, L.D.; Cherrington, N.J.

2013-01-01

Roč. 268, č. 2 (2013), s. 132-140 ISSN 0041-008X Institutional research plan: CEZ:AV0Z50510513 Institutional support: RVO:60077344 Keywords : Bile Acids * Liver * Metabolomics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.630, year: 2013

Gut Microbiota and Host Reaction in Liver Diseases

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Hiroshi Fukui

2015-10-01

Full Text Available Although alcohol feeding produces evident intestinal microbial changes in animals, only some alcoholics show evident intestinal dysbiosis, a decrease in Bacteroidetes and an increase in Proteobacteria. Gut dysbiosis is related to intestinal hyperpermeability and endotoxemia in alcoholic patients. Alcoholics further exhibit reduced numbers of the beneficial Lactobacillus and Bifidobacterium. Large amounts of endotoxins translocated from the gut strongly activate Toll-like receptor 4 in the liver and play an important role in the progression of alcoholic liver disease (ALD, especially in severe alcoholic liver injury. Gut microbiota and bacterial endotoxins are further involved in some of the mechanisms of nonalcoholic fatty liver disease (NAFLD and its progression to nonalcoholic steatohepatitis (NASH. There is experimental evidence that a high-fat diet causes characteristic dysbiosis of NAFLD, with a decrease in Bacteroidetes and increases in Firmicutes and Proteobacteria, and gut dysbiosis itself can induce hepatic steatosis and metabolic syndrome. Clinical data support the above dysbiosis, but the details are variable. Intestinal dysbiosis and endotoxemia greatly affect the cirrhotics in relation to major complications and prognosis. Metagenomic approaches to dysbiosis may be promising for the analysis of deranged host metabolism in NASH and cirrhosis. Management of dysbiosis may become a cornerstone for the future treatment of liver diseases.

Radiation induced liver disease: A clinical update

International Nuclear Information System (INIS)

Benson, R.; Madan, R.; Chander, S.; Kilambi, R.

2016-01-01

Radiation-induced liver disease (RILD) or radiation hepatitis is a sub-acute form of liver injury due to radiation. It is one of the most dreaded complications of radiation which prevents radiation dose escalation and re irradiation for hepatobiliary or upper gastrointestinal malignancies. This complication should be kept in mind whenever a patient is planned for irradiation of these malignancies. Although, incidence of RILD is decreasing due to better knowledge of liver tolerance, improved investigation modalities and modern radiation delivery techniques, treatment options are still limited. In this review article, we have focussed on pathophysiology, risk factors, prevention and management of RILD

Relevance of detail in basal topography for basal slipperiness inversions: a case study on Pine Island Glacier, Antarctica

Science.gov (United States)

Kyrke-Smith, Teresa M.; Gudmundsson, G. Hilmar; Farrell, Patrick E.

2018-04-01

Given high-resolution satellite-derived surface elevation and velocity data, ice-sheet models generally estimate mechanical basal boundary conditions using surface-to-bed inversion methods. In this work, we address the sensitivity of results from inversion methods to the accuracy of the bed elevation data on Pine Island Glacier. We show that misfit between observations and model output is reduced when high-resolution bed topography is used in the inverse model. By looking at results with a range of detail included in the bed elevation, we consider the separation of basal drag due to the bed topography (form drag) and that due to inherent bed properties (skin drag). The mean value of basal shear stress is reduced when more detailed topography is included in the model. This suggests that without a fully resolved bed a significant amount of the basal shear stress recovered from inversion methods may be due to the unresolved bed topography. However, the spatial structure of the retrieved fields is robust as the bed accuracy is varied; the fields are instead sensitive to the degree of regularisation applied to the inversion. While the implications for the future temporal evolution of PIG are not quantified here directly, our work raises the possibility that skin drag may be overestimated in the current generation of numerical ice-sheet models of this area. These shortcomings could be overcome by inverting simultaneously for both bed topography and basal slipperiness.

Moro orange juice prevents fatty liver in mice.

Science.gov (United States)

Salamone, Federico; Li Volti, Giovanni; Titta, Lucilla; Puzzo, Lidia; Barbagallo, Ignazio; La Delia, Francesco; Zelber-Sagi, Shira; Malaguarnera, Michele; Pelicci, Pier Giuseppe; Giorgio, Marco; Galvano, Fabio

2012-08-07

To establish if the juice of Moro, an anthocyanin-rich orange, may improve liver damage in mice with diet-induced obesity. Eight-week-old mice were fed a high-fat diet (HFD) and were administrated water or Moro juice for 12 wk. Liver morphology, gene expression of lipid transcription factors, and metabolic enzymes were assessed. Mice fed HFD displayed increased body weight, insulin resistance and dyslipidemia. Moro juice administration limited body weight gain, enhanced insulin sensitivity, and decreased serum triglycerides and total cholesterol. Mice fed HFD showed liver steatosis associated with ballooning. Dietary Moro juice markedly improved liver steatosis by inducing the expression of peroxisome proliferator-activated receptor-α and its target gene acylCoA-oxidase, a key enzyme of lipid oxidation. Consistently, Moro juice consumption suppressed the expression of liver X receptor-α and its target gene fatty acid synthase, and restored liver glycerol-3-phosphate acyltransferase 1 activity. Moro juice counteracts liver steatogenesis in mice with diet-induced obesity and thus may represent a promising dietary option for the prevention of fatty liver.

Histochemical demonstration of two mercury pools in trout tissues: mercury in kidney and liver after mercuric chloride exposure

DEFF Research Database (Denmark)

Baatrup, E; Nielsen, M G; Danscher, G

1987-01-01

Juvenile rainbow trout (Salmo gairdneri) were exposed to 100 ppb mercury (as HgCl2) in the water for 14 days. Concentrations of mercury in water and fish organs were monitored using radiolabeled mercury. Tissues from kidney and liver were fixed, and sections were developed by autometallography......, a method whereby accumulations of mercury sulfides and/or mercury selenides are silver amplified. In the kidney, mercury was found within lysosomes and extracellularly in the basal lamina of proximal tubules. In the liver, mercury was found within lysosomes of the hepatocytes. Additional groups of mercury......-exposed trout were subjected to selenium (as Na2SeO3), administered intraperitoneally 2 hr before fixation. Following this treatment, additional mercury could be visualized in the kidney circulatory system, including glomeruli, and in the nucleus and endoplasmic reticulum of liver cells. It is suggested...

Impact of liver cirrhosis on liver enhancement at Gd-EOB-DTPA enhanced MRI at 3 Tesla

Energy Technology Data Exchange (ETDEWEB)

Verloh, N., E-mail: niklas.verloh@stud.uni-regensburg.de [Department of Radiology, University Hospital Regensburg, Regensburg (Germany); Haimerl, M.; Rennert, J.; Müller-Wille, R.; Nießen, C. [Department of Radiology, University Hospital Regensburg, Regensburg (Germany); Kirchner, G. [Department of Gastroenterology, University Hospital Regensburg, Regensburg (Germany); Scherer, M.N. [Department of Surgery, University Hospital Regensburg, Regensburg (Germany); Schreyer, A.G.; Stroszczynski, C.; Fellner, C.; Wiggermann, P. [Department of Radiology, University Hospital Regensburg, Regensburg (Germany)

2013-10-01

Purpose: The purpose of this study was to assess differences in enhancement effects of liver parenchyma between normal and cirrhotic livers on dynamic, Gd-EOB-DTPA enhanced MRI at 3 T. Materials and methods: 93 patients with normal (n = 54) and cirrhotic liver (n = 39; Child–Pugh class A, n = 18; B, n = 16; C, n = 5) underwent contrast-enhanced MRI with liver specific contrast media at 3 T. T1-weighted volume interpolated breath hold examination (VIBE) sequences with fat suppression were acquired before contrast injection, in the arterial phase (AP), in the late arterial phase (LAP), in the portal venous phase (PVP), and in the hepatobiliary phase (HBP) after 20 min. The relative enhancement (RE) of the signal intensity of the liver parenchyma was calculated for all phases. Results: Mean RE was significantly different among all evaluated groups in the hepatobiliary phase and with increasing severity of liver cirrhosis, a decreasing, but still significant reduction of RE could be shown. Phase depending changes of RE for each group were observed. In case of non-cirrhotic liver or Child–Pugh Score A cirrhosis mean RE showed a significant increase between AP, LAP, PVP and HBP. For Child–Pugh B + C cirrhosis RE increased until PVP, however, there was no change in case of B cirrhosis (p = 0.501) and significantly reduced in case of C cirrhosis (p = 0.043) during HBP. Conclusion: RE of liver parenchyma is negatively affected by increased severity of liver cirrhosis, therefore diagnostic value of HBP could be limited in case of Child Pugh B + C cirrhosis.

Impact of liver cirrhosis on liver enhancement at Gd-EOB-DTPA enhanced MRI at 3 Tesla

International Nuclear Information System (INIS)

Verloh, N.; Haimerl, M.; Rennert, J.; Müller-Wille, R.; Nießen, C.; Kirchner, G.; Scherer, M.N.; Schreyer, A.G.; Stroszczynski, C.; Fellner, C.; Wiggermann, P.

2013-01-01

Purpose: The purpose of this study was to assess differences in enhancement effects of liver parenchyma between normal and cirrhotic livers on dynamic, Gd-EOB-DTPA enhanced MRI at 3 T. Materials and methods: 93 patients with normal (n = 54) and cirrhotic liver (n = 39; Child–Pugh class A, n = 18; B, n = 16; C, n = 5) underwent contrast-enhanced MRI with liver specific contrast media at 3 T. T1-weighted volume interpolated breath hold examination (VIBE) sequences with fat suppression were acquired before contrast injection, in the arterial phase (AP), in the late arterial phase (LAP), in the portal venous phase (PVP), and in the hepatobiliary phase (HBP) after 20 min. The relative enhancement (RE) of the signal intensity of the liver parenchyma was calculated for all phases. Results: Mean RE was significantly different among all evaluated groups in the hepatobiliary phase and with increasing severity of liver cirrhosis, a decreasing, but still significant reduction of RE could be shown. Phase depending changes of RE for each group were observed. In case of non-cirrhotic liver or Child–Pugh Score A cirrhosis mean RE showed a significant increase between AP, LAP, PVP and HBP. For Child–Pugh B + C cirrhosis RE increased until PVP, however, there was no change in case of B cirrhosis (p = 0.501) and significantly reduced in case of C cirrhosis (p = 0.043) during HBP. Conclusion: RE of liver parenchyma is negatively affected by increased severity of liver cirrhosis, therefore diagnostic value of HBP could be limited in case of Child Pugh B + C cirrhosis

Coagulopathy following major liver resection: the effect of rBPI21 and the role of decreased synthesis of regulating proteins by the liver

NARCIS (Netherlands)

Meijer, C.; Wiezer, M. J.; Hack, C. E.; Boelens, P. G.; Wedel, N. I.; Meijer, S.; Nijveldt, R. J.; Statius Muller, M. G.; Wiggers, T.; Zoetmulder, F. A.; Borel Rinkes, I. H.; Cuesta, M. A.; Gouma, D. J.; van de Velde, C. J.; Tilanus, H. W.; Scotté, M.; Thijs, L. G.; van Leeuwen, P. A.

2001-01-01

This prospective study investigated the role of reduced hepatic synthesis of regulating proteins in coagulopathy after partial hepatectomy (PH) compared with major abdominal surgery (MAS) without involvement of the liver. Furthermore, we studied the effect of rBPI21, an endotoxin-neutralizing agent,

Evaluation of the Effect of Exercise on Nonalcoholic Fatty Liver By Sonography

International Nuclear Information System (INIS)

Kim, Kyoung Yeon; Lim, Hyun Soo

2012-01-01

Nonalcoholic fatty liver disease (NAFLD) is accumulation state of fat in liver cells without excessive alcohol intake, and it has been studied that is closely related to obesity. The purpose of this study is to identify risk factors for NAFLD and may prevent or to manage risk factors. This study was in progress for six months (2011 May 1 to October 31), of the 83 people who underwent abdominal ultrasound 11 people eventually were selected. Research results was as follows : First, the decreased body weight and body mass index (BMI), and the second, a decrease of the deepening of fatty liver in ultrasound diagnosis, and the third, steady movement reduces the deepening of fatty liver regardless of calories. Thus, the implication of this research is that long-term exercise programs have positive effects in the treatment of fatty liver.

Evaluation of the Effect of Exercise on Nonalcoholic Fatty Liver By Sonography

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Kim, Kyoung Yeon [Dept. of Radiology, Anseong Hanju Clinic, Anseong (Korea, Republic of); Lim, Hyun Soo [Dept. of Biomedical Engineering, Chungnam University, Daejeon (Korea, Republic of)

2012-03-15

Nonalcoholic fatty liver disease (NAFLD) is accumulation state of fat in liver cells without excessive alcohol intake, and it has been studied that is closely related to obesity. The purpose of this study is to identify risk factors for NAFLD and may prevent or to manage risk factors. This study was in progress for six months (2011 May 1 to October 31), of the 83 people who underwent abdominal ultrasound 11 people eventually were selected. Research results was as follows : First, the decreased body weight and body mass index (BMI), and the second, a decrease of the deepening of fatty liver in ultrasound diagnosis, and the third, steady movement reduces the deepening of fatty liver regardless of calories. Thus, the implication of this research is that long-term exercise programs have positive effects in the treatment of fatty liver.

Computed tomography of calcification of the basal ganglia

International Nuclear Information System (INIS)

Park, Churl Min; Suh, Soo Jhi; Kim, Soon Yong

1981-01-01

Calcifications of the basal ganglia are rarely found at routine autopsies and in skull radiographs. CT is superior to the plain skull radiographs in detecting intracranial attenuation differences and may be stated to be the method of choice in the diagnosis of intracranial calcifications. Of 5985 brain CT scans performed in Kyung Hee University Hospital during past 3 years, 36 cases were found to have high attenuation lesions suggesting calcifications within basal ganglia. 1. The incidence of basal ganglia calcification on CT scan was about 0.6%. 2. Of these 36 cases, 34 cases were bilateral and the remainder was unilateral. 3. The plain skull films of 23 cases showed visible calcification of basal ganglia in 3 cases (13%). 4. No specific metabolic disease was noted in the cases

Decreased autophosphorylation of EGF receptor in insulin-deficient diabetic rats

International Nuclear Information System (INIS)

Okamoto, M.; Kahn, C.R.; Maron, R.; White, M.F.

1988-01-01

The authors have previously reported that despite an increase in receptor concentration, there is a decrease in autophosphorylation and tyrosine kinase activity of the insulin receptor in insulin-deficient diabetic rats. To determine if other tyrosine kinases might be altered, they have studied the epidermal growth factor (EGF) receptor kinase in wheat germ agglutinin-purified, Triton X-100-solubilized liver membranes from streptozotocin (STZ)-induced diabetic rats and the insulin-deficient BB rat. They find that autophosphorylation of EGF receptor is decreased in proportion to the severity of the diabetic state in STZ rats with a maximal decrease of 67%. A similar decrease in autophosphorylation was observed in diabetic BB rats that was partially normalized by insulin treatment. Separation of tryptic phosphopeptides by reverse-phase high-performance liquid chromatography revealed a decrease in labeling at all sites of autophosphorylation. A parallel decrease in EGF receptor phosphorylation was also found by immunoblotting with an antiphosphotyrosine antibody. EGF receptor concentration, determined by Scatchard analysis of 125 I-labeled EGF binding, was decreased by 39% in the STZ rat and 27% in the diabetic BB rat. Thus autophosphorylation of EGF receptor, like that of the insulin receptor, is decreased in insulin-deficient rat liver. In the case of EGF receptor, this is due in part to a decrease in receptor number and in part to a decrease in the specific activity of the kinase

Basal Cell Carcinoma: 10 Years of Experience

International Nuclear Information System (INIS)

Cigna, E.; Tarallo, M.; Maruccia, M.; Sorvillo, V.; Pollastrini, A.; Scuderi, N.

2011-01-01

Introduction. Basal cell carcinoma (BCC) is a locally invasive malignant epidermal tumour. Incidence is increasing by 10% per year; incidence of metastases is minimal, but relapses are frequent (40%-50%). The complete excision of the BCC allows reduction of relapse. Materials and Methods. The study cohort consists of 1123 patients underwent surgery for basal cell carcinoma between 1999 and 2009. Patient and tumor characteristics recorded are: age; gender; localization (head and neck, trunk, and upper and lower extremities), tumor size, excisional margins adopted, and relapses. Results. The study considered a group of 1123 patients affected by basal cell carcinoma. Relapses occurred in 30 cases (2,67%), 27 out of 30 relapses occurred in noble areas, where peripheral margin was <3mm. Incompletely excised basal cell carcinoma occurred in 21 patients (1,87%) and were treated with an additional excision. Discussion. Although guidelines indicate 3mm peripheral margin of excision in BCC <2cm, in our experience, a margin of less than 5mm results in a high risk of incomplete excisions

Cardiac systolic function in cirrhotic patients’ candidate of liver trans-plantation compared with control group

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Roya Sattarzadeh-Badkoubeh

2017-02-01

Full Text Available Background: We assessed different systolic cardiac indices to describe left and right ventricular dysfunction in cirrhotic patients before liver transplantation. Methods: In this case-control study, eighty-one consecutive individuals with the confirmed hepatic cirrhosis and candidate for liver transplantation in the Imam Khomeini Hospital between March 2008 and March 2010 were selected. Thirty-two age and gender cross-matched healthy volunteers were also selected as the control group. A detailed two-dimensional and Doppler echocardiography was obtained in all patients and controls performed by the same operator on the day of admission. Results: Dimensions of both left and right atriums as well as left ventricular end-diastolic volume and basal right ventricular dimension in the cirrhotic group were significantly higher than control group. Left ventricular end-systolic dimensions as well as aortic annulus diameter were not different between the two study groups. Left ventricular outflow tract velocity time integral, isovolumic pre-ejection time, isovolumic relaxation time, stroke volume, left ventricular ejection fraction, IVCT+IVRT+ET, systolic velocity of tricuspid annulus, systolic velocity of basal segment of RV free wall, systolic velocity of basal segment of septal wall, peak strain of septal margin (base, peak strain of septal margin (midpoint, peak strain of lateral margin (midpoint, strain rate of septal margin (base, strain rate of septal margin (midpoint, strain rate of lateral margin (base, strain rate of lateral margin (midpoint, Tei index (left and right ventricles, systolic time interval and tricuspid annular plane systolic excursion were higher in cirrhotic group, significantly, (P< 0.05. Left ventricular ejection time and systolic velocity of mid segment of lateral wall were lower in cirrhotic group, significantly, (P< 0.05. Conclusion: In this study, the effects of liver on heart were volume overload, hyperdynamic state and

The application of 99Tcm-phytate scintigraphy in pig auxiliary liver transplantation

International Nuclear Information System (INIS)

Lin Jianhua; Li Xiaoping; Li Chaolong; He Xu; Lin Zhiqi; Zhu Weibing

2001-01-01

Objective: To affirm the application value of 99 Tc m -phytate scintigraphy in pig auxiliary liver transplantation. Methods: The graft was transplanted in the right subhepatic space of recipient to establish pig auxiliary liver transplantation model. The artery blood supplies were the very same in all grafts and the portal vein (PV) blood flows were differently controlled by trussing the host PV at the site neared host liver. According to the constriction degree, PV blood supplies were divided into three groups including A (constricted by 1/3), B (constricted by 1/2) and C(not constricted). The blood flows of the graft liver and the host liver were measured by 99 Tc m -phytate scintigraphy and livers functions were estimated after auxiliary liver transplantation. Contrasted with its histological findings the reflection of graft survival with 99 Tc m -phytate scintigraphy was investigated. Results: It was detected by 99 Tc m -phytate scintigraphy that the blood flows were almost equilibrated and abundant in grafts and host liver' in group A, and were abundant in grafts of group B and host livers of group C and were significantly decreased in host livers of group B and grafts of group C. Histological work-up demonstrated that the liver was not atrophic while the blood flow was abundant and the liver was atrophic while the blood flow was decreased. Conclusion: 99 Tc m -phytate scintigraphy could accurately reflect the survival and function of grafts and host livers after auxiliary liver transplantation and it is a reliable technique which can be used to estimate the survival and function of the grafts and host livers

Gene Expression Profile Change and Associated Physiological and Pathological Effects in Mouse Liver Induced by Fasting and Refeeding

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Zhang, Fang; Xu, Xiang; Zhou, Ben; He, Zhishui; Zhai, Qiwei

2011-01-01

Food availability regulates basal metabolism and progression of many diseases, and liver plays an important role in these processes. The effects of food availability on digital gene expression profile, physiological and pathological functions in liver are yet to be further elucidated. In this study, we applied high-throughput sequencing technology to detect digital gene expression profile of mouse liver in fed, fasted and refed states. Totally 12162 genes were detected, and 2305 genes were significantly regulated by food availability. Biological process and pathway analysis showed that fasting mainly affected lipid and carboxylic acid metabolic processes in liver. Moreover, the genes regulated by fasting and refeeding in liver were mainly enriched in lipid metabolic process or fatty acid metabolism. Network analysis demonstrated that fasting mainly regulated Drug Metabolism, Small Molecule Biochemistry and Endocrine System Development and Function, and the networks including Lipid Metabolism, Small Molecule Biochemistry and Gene Expression were affected by refeeding. In addition, FunDo analysis showed that liver cancer and diabetes mellitus were most likely to be affected by food availability. This study provides the digital gene expression profile of mouse liver regulated by food availability, and demonstrates the main biological processes, pathways, gene networks and potential hepatic diseases regulated by fasting and refeeding. These results show that food availability mainly regulates hepatic lipid metabolism and is highly correlated with liver-related diseases including liver cancer and diabetes. PMID:22096593

Inhibition of liver fibrosis by solubilized coenzyme Q10: Role of Nrf2 activation in inhibiting transforming growth factor-β1 expression

International Nuclear Information System (INIS)

Choi, Hoo-Kyun; Pokharel, Yuba Raj; Lim, Sung Chul; Han, Hyo-Kyung; Ryu, Chang Seon; Kim, Sang Kyum; Kwak, Mi Kyong; Kang, Keon Wook

2009-01-01

Coenzyme Q10 (CoQ10), an endogenous antioxidant, is important in oxidative phosphorylation in mitochondria. It has anti-diabetic and anti-cardiovascular disease effects, but its ability to protect against liver fibrosis has not been studied. Here, we assessed the ability of solubilized CoQ10 to improve dimethylnitrosamine (DMN)-induced liver fibrogenesis in mice. DMN treatments for 3 weeks produced a marked liver fibrosis as assessed by histopathological examination and tissue 4-hydroxyproline content. Solubilized CoQ10 (10 and 30 mg/kg) significantly inhibited both the increases in fibrosis score and 4-hydroxyproline content induced by DMN. Reverse transcription-polymerase chain reaction and Western blot analyses revealed that solubilized CoQ10 inhibited increases in the transforming growth factor-β1 (TGF-β1) mRNA and α-smooth muscle actin (α-SMA) protein by DMN. Interestingly, hepatic glutamate-cysteine ligase (GCL) and glutathione S-transferase A2 (GSTA2) were up-regulated in mice treated with CoQ10. Solubilized CoQ10 also up-regulated antioxidant enzymes such as catalytic subunits of GCL and GSTA2 via activating NF-E2 related factor2 (Nrf2)/antioxidant response element (ARE) in H4IIE hepatoma cells. Moreover, CoQ10's inhibition of α-SMA and TGF-β1 expressions disappeared in Nrf2-null MEF cells. In contrast, Nrf2 overexpression significantly decreased the basal expression levels of α-SMA and TGF-β1 in Nrf2-null MEF cells. These results demonstrated that solubilized CoQ10 inhibited DMN-induced liver fibrosis through suppression of TGF-β1 expression via Nrf2/ARE activation.

Probing surface charge potentials of clay basal planes and edges by direct force measurements.

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Zhao, Hongying; Bhattacharjee, Subir; Chow, Ross; Wallace, Dean; Masliyah, Jacob H; Xu, Zhenghe

2008-11-18

The dispersion and gelation of clay suspensions have major impact on a number of industries, such as ceramic and composite materials processing, paper making, cement production, and consumer product formulation. To fundamentally understand controlling mechanisms of clay dispersion and gelation, it is necessary to study anisotropic surface charge properties and colloidal interactions of clay particles. In this study, a colloidal probe technique was employed to study the interaction forces between a silica probe and clay basal plane/edge surfaces. A muscovite mica was used as a representative of 2:1 phyllosilicate clay minerals. The muscovite basal plane was prepared by cleavage, while the edge surface was obtained by a microtome cutting technique. Direct force measurements demonstrated the anisotropic surface charge properties of the basal plane and edge surface. For the basal plane, the long-range forces were monotonically repulsive within pH 6-10 and the measured forces were pH-independent, thereby confirming that clay basal planes have permanent surface charge from isomorphic substitution of lattice elements. The measured interaction forces were fitted well with the classical DLVO theory. The surface potentials of muscovite basal plane derived from the measured force profiles were in good agreement with those reported in the literature. In the case of edge surfaces, the measured forces were monotonically repulsive at pH 10, decreasing with pH, and changed to be attractive at pH 5.6, strongly suggesting that the charge on the clay edge surfaces is pH-dependent. The measured force profiles could not be reasonably fitted with the classical DLVO theory, even with very small surface potential values, unless the surface roughness was considered. The surface element integration (SEI) method was used to calculate the DLVO forces to account for the surface roughness. The surface potentials of the muscovite edges were derived by fitting the measured force profiles with the

Investigating changes in basal conditions of Variegated Glacier prior to and during its 1982–1983 surge

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M. Jay-Allemand

2011-08-01

Full Text Available Variegated Glacier (Alaska is known to surge periodically after a sufficient amount of cumulative mass balance is reached, but this observation is difficult to link with changes in the basal conditions. Here, using a 10-yr dataset, consisting of surface topography and surface velocity observations along a flow line for 25 dates, we have reconstructed the evolution of the basal conditions prior to and during the 1982–1983 surge. The model solves the full-Stokes problem along the central flow line using the finite element method. For the 25 dates of the dataset, the basal friction parameter distribution is inferred using the inverse method proposed by Arthern and Gudmundsson (2010. This method is here slightly modified by incorporating a regularisation term in the cost function to avoid short wavelength changes in the friction parameter. Our results indicate that dramatic changes in the basal conditions occurred between 1973 to 1983. Prior to the surge, periodic changes can be observed between winter and summer, with a regular increase of the sliding from 1973 to 1982. During the surge, the basal friction decreased dramatically and an area of very low friction moved from the upper part of the glacier to its terminus. Using a more complex friction law, these changes in basal sliding are then interpreted in terms of basal water pressure. Our results support that dramatic changes took place in the subglacial drainage system of Variegated Glacier, moving from a relatively efficient drainage system prior to the surge to an inefficient one during the surge. By reconstructing the water pressure evolution at the base of the glacier it is possible to propose a scenario for the hydrological history leading to the occurrence of a surge.

Evaluation of usefulness of 99mTc-GSA liver scintigraphy on fatty liver in the rat

International Nuclear Information System (INIS)

Kimoto, Mitsunori; Akaki, Shiro; Kohno, Yoshihiro; Gohbara, Hideo; Sakae, Katsuyoshi; Nagaya, Isao; Takeda, Yoshihiro; Hiraki, Yoshio

1994-01-01

99m Tc-GSA is a new liver-imaging radiopharmaceutical which binds to the asialoglycoprotein receptors on the hepatocytes. We evaluated liver injury induced by fatty infiltration in the rats. Studies were performed in the Wistar rats under control conditions (6 cases), and with choline deficiency diet for 2, 4, 6, 10 and 12 weeks (6 cases respectively). 99m Tc-GSA was administered via the inferior vena cava. Immediately after injection, a dynamic imaging study was performed for 30 min. t 90 (the time at which the liver time-activity curve reached 90% of its peak), K u and K d (calculated by 2 compartment model) were used as parameters which reflect on asialoglycoprotein receptors on the hepatocytes. t 90 prolonged, and K u and K d decreased according to the severity of fatty infiltration. These results suggest that 99m Tc-GSA is useful for evaluating liver injury induced by fatty infiltration. (author)

Ultrastructural Changes in the Liver of Intravenous Heroin Addicts

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Goran Ilić

2010-02-01

Full Text Available The ultrastructural research has a decisive role in gathering the knowledge on the liver’s response to the influence of some drugs. The aim of the study was to perform an ultrastructurai analysis of the liver in chronic intravenous heroin addicts.The study involved the autopsy conducted on 40 bodies of intravenous heroin addicts and 10 control autopsies. The liver tissue was fixed in glutaraldehyde and moulded with epon for investigation purposes of ultrastructural changes. The analysis was performed using the method of transmission electron microscopy.In the group of intravenous heroin addicts, the liver autopsy samples showed degenerative vesicular and fat changes, chronic active and persistent hepatitis, cirrhosis, reduction in the amount of glycogen in hepatocytes, as well as the Kupffer cell’s dominant hypertrophy. Various changes occur in organelles, plasma membrane of hepatocytes and biliary channels as well as in the nucleus.The most important ultrastructural findings include: hyperplasia and hypertrophy of the smooth endoplasmic reticulum, which is histologically proven vesicular degeneration of hepatocyte occurring as a result of the increased synthesis of enzymes of smooth endoplasmic reticulum due to chronic intravenous heroin intake, and the presence of continuous basal membrane followed by transformation of the sinusoids into capillaries (in the cases of chronic active hepatitis and cirrhosis which leads to a disorder of microcirculation and further progress of cirrhosis.

[Exenteration of the Orbit for Basal Cell Carcinoma].

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Furdová, A; Horkovičová, K; Krčová, I; Krásnik, V

2015-08-01

Primary treatment of basal cell carcinoma of the lower eyelid and the inner corner is essentially surgical, but advanced lesions require extensive surgical interventions. In some cases it is necessary to continue with the mutilating surgery--exenteration of the orbit. In this work we evaluate the indications of radical solutions in patients with basal cell carcinoma invading the orbit and the subsequent possibility for individually made prosthesis to cover the defect of the cavity. Indications to exenteration of the orbit in patients with basal cell carcinoma findings in 2008-2013. Case report of 2 patients. In period 2008-20013 at the Dept. of Ophthalmology, Comenius University in Bratislava totally 221 patients with histologically confirmed basal cell carcinoma of the eyelids and the inner corner were treated. In 5 cases (2.7 %) with infiltration of the orbit the radical surgical procedure, exenteration was necessary. In 3 patients exenteration was indicated as the first surgical procedure in the treatment of basal cell carcinoma, since they had never visited ophthalmologist before only at in the stage of infiltration of the orbit (stage T4). In one case was indicated exenteration after previous surgical interventions and relapses. After healing the cavity patients got individually prepared epithesis. Surgical treatment of basal cell carcinoma involves the radical removal of the neoplasm entire eyelid and stage T1 or T2 can effectively cure virtually all tumors with satisfactory cosmetic and functional results. In advanced stages (T4 stage) by infiltrating the orbit by basal cell carcinoma exenteration of the orbit is necessary. This surgery is a serious situation for the patient and also for his relatives. Individually made prosthesis helps the patient to be enrolled to the social environment.

Traumatic bilateral basal ganglia hematoma: A report of two cases

OpenAIRE

Bhargava, Pranshu; Grewal, Sarvpreet Singh; Gupta, Bharat; Jain, Vikas; Sobti, Harman

2012-01-01

Traumatic Basal ganglia hemorrhage is relatively uncommon. Bilateral basal ganglia hematoma after trauma is extremely rare and is limited to case reports. We report two cases of traumatic bilateral basal ganglia hemorrhage, and review the literature in brief. Both cases were managed conservatively.

Liver Cancer Risk Prediction Models

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Developing statistical models that estimate the probability of developing liver cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

CT evaluation of the bile ducts in patients with fatty liver

International Nuclear Information System (INIS)

Quint, L.E.; Glazer, G.M.

1984-01-01

Computed tomographic (CT) evaluation of the bile ducts in the fatty liver can be difficult, since hepatic attenuation decreases with increased triglyceride content, and liver parenchyma may become isodense with bile. Forty-seven patients with fatty infiltration of the liver were retrospectively identified. In 7 of these patients, attenuation of liver and bile differed by less than 10 HU. In 2 patients, dilated intrahepatic ducts were invisible using CT, because bile was isodense with fatty liver parenchyma. Thus, the fatty liver presents a potential pitfall in CT evaluation of the bile ducts. For maximal accuracy scans should be obtained both before and after administration of intravenous urographic contrast material

Coffee Intake Is Associated with a Lower Liver Stiffness in Patients with Non-Alcoholic Fatty Liver Disease, Hepatitis C, and Hepatitis B.

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Hodge, Alexander; Lim, Sarah; Goh, Evan; Wong, Ophelia; Marsh, Philip; Knight, Virginia; Sievert, William; de Courten, Barbora

2017-01-10

There is emerging evidence for the positive effects or benefits of coffee in patients with liver disease. We conducted a retrospective cross-sectional study on patients with non-alcoholic fatty liver disease (NAFLD), hepatitis C virus (HCV), and hepatitis B virus (HBV) infection to determine the effects of coffee intake on a non-invasive marker of liver fibrosis: liver stiffness assessed by transient elastography (TE). We assessed coffee and tea intake and measured TE in 1018 patients with NAFLD, HCV, and HBV (155 with NAFLD, 378 with HCV and 485 with HBV). Univariate and multivariate regression models were performed taking into account potential confounders. Liver stiffness was higher in males compared to females ( p disease state (NAFLD, HCV, and HBV status), those who drank 2 or more cups of coffee per day had a lower liver stiffness ( p = 0.044). Tea consumption had no effect ( p = 0.9). Coffee consumption decreases liver stiffness, which may indicate less fibrosis and inflammation, independent of disease state. This study adds further evidence to the notion of coffee maybe beneficial in patients with liver disease.

Somatic Cell Fusions Reveal Extensive Heterogeneity in Basal-like Breast Cancer

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Ying Su

2015-06-01

Full Text Available Basal-like and luminal breast tumors have distinct clinical behavior and molecular profiles, yet the underlying mechanisms are poorly defined. To interrogate processes that determine these distinct phenotypes and their inheritance pattern, we generated somatic cell fusions and performed integrated genetic and epigenetic (DNA methylation and chromatin profiling. We found that the basal-like trait is generally dominant and is largely defined by epigenetic repression of luminal transcription factors. Definition of super-enhancers highlighted a core program common in luminal cells but a high degree of heterogeneity in basal-like breast cancers that correlates with clinical outcome. We also found that protein extracts of basal-like cells are sufficient to induce a luminal-to-basal phenotypic switch, implying a trigger of basal-like autoregulatory circuits. We determined that KDM6A might be required for luminal-basal fusions, and we identified EN1, TBX18, and TCF4 as candidate transcriptional regulators of the luminal-to-basal switch. Our findings highlight the remarkable epigenetic plasticity of breast cancer cells.

Reducing liver transplant length of stay: a Lean Six Sigma approach.

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Toledo, Alexander H; Carroll, Tracy; Arnold, Emily; Tulu, Zeynep; Caffey, Tom; Kearns, Lauren E; Gerber, David A

2013-12-01

Organ transplant centers are under increasing scrutiny to maintain outcomes while controlling cost in a challenging population of patients. Throughout health care and transplant specifically, length of stay is used as a benchmark for both quality and resource utilization. To decrease our length of stay for liver transplant by using Lean Six Sigma methods. The Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) method was used to systematically analyze our process from transplant listing to hospital discharge after transplant, identifying many factors affecting length of stay. Adult, single-organ, primary liver transplant recipients between July 2008 and June 2012 were included in the study. Recipients with living donors or fulminant liver failure were excluded. Multiple interventions, including a clinical pathway and enhanced communication, were implemented. Length of stay after liver transplant and readmission after liver transplant.R ESULTS: Median length of stay decreased significantly from 11 days before the intervention to 8 days after the intervention. Readmission rate did not change throughout the study. The improved length of stay was maintained for 24 months after the study. Using a Lean Six Sigma approach, we were able to significantly decrease the length of stay of liver transplant patients. These results brought our center's outcomes in accordance with our goal and industry benchmark of 8 days. Clear expectations, improved teamwork, and a multidisciplinary clinical pathway were key elements in achieving and maintaining these gains.

Effect of 3-keto-1,5-bisphosphonates on obese-liver's rats.

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Lahbib, Karima; Touil, Soufiane

2016-10-01

Obesity is associated with an oxidative stress status, which is defined by an excess of reactive oxygen species (ROS) vs. the antioxidant defense system. We report in this present work, the link between fat deposition and oxidative stress markers using a High Fat Diet-(HFD) induced rat obesity and liver-oxidative stress. We further determined the impact of chronic administration of 3-keto-1, 5-BPs 1 (a & b) (40μg/kg/8 weeks/i.p.) on liver's level. In fact, exposure of rats to HFD during 16 weeks induced body and liver weight gain and metabolic disruption with an increase on liver Alanine amino transférase (ALAT) and Aspartate aminotransférase (ASAT) concentration. HFD increased liver calcium level as well as free iron, whereas, it provoked a decrease on liver lipase activity. HFD also induced liver-oxidative stress status vocalized by an increase in reactive oxygen species (ROS) as superoxide radical (O 2 ), hydroxyl radical (OH) and Hydrogen peroxide (H 2 O 2 ). Consequently, different deleterious damages as an increase on Malon Dialdehyde MDA, Carbonyl protein PC levels with a decrease in non-protein sulfhydryls NPSH concentrations, have been detected. Interestingly, our results demonstrate a decrease in antioxidant enzymes activities such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidases (GPx) and peroxidases (POD). Importantly, 3-keto-1,5-bisphosphonates treatment corrected the majority of the deleterious effects caused by HFD, but it failed to correct some liver's disruptions as mineral profile, oxidative damages (PC and NPSH levels) as well as SOD and lipase activities. Our investigation point that 3-keto-1,5-bisphosphonates could be considered as safe antioxidant agents on the hepatic level that should also find other potential biological applications. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

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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.

Dietary broccoli protects against fatty liver development but not against progression of liver cancer in mice pretreated with diethylnitrosamine

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Chen, Yung-Ju; Myracle, Angela D.; Wallig, Matthew A.; Jeffery, Elizabeth H.

2016-01-01

Western-style high fat, high sugar diets are associated with non-alcoholic fatty liver disease (NAFLD) and increased liver cancer risk. Sulforaphane from broccoli may protect against these. Previously we initiated broccoli feeding to mice prior to exposure to the hepatocarcinogen diethylnitrosamine (DEN), and saw protection against NAFLD and liver cancer. Here we administered DEN to unweaned mice, initiating broccoli feeding two weeks later, to determine if broccoli protects against cancer progression. Specifically, male 15-day-old C57BL/6J mice were given DEN and placed on a Western or Western+10%Broccoli diet from the age of 4 weeks through 7 months. Dietary broccoli decreased hepatic triacylglycerols, NAFLD, liver damage and tumour necrosis factor by month 5 without changing body weight or relative liver weight, but did not slow carcinogenesis, seen in 100% of mice. We conclude that broccoli, a good source of sulforaphane, slows progression of hepatic lipidosis, but not tumourigenesis in this robust model. PMID:27672403

Immunohistochemical Characteristics of Triple Negative/Basal-like Breast Cancer

OpenAIRE

Emel Ebru PALA; Ümit BAYOL; Süheyla CUMURCU; Elif KESKİN

2012-01-01

Objective: Triple-negative-breast-cancer that accounts for 10-20% of all breast carcinomas is defined by the lack of estrogen receptor, progesterone receptor, HER2 expression, and agressive clinical behavior. Triple-negative-breast-cancer is categorized into basal like and other types. The basal-like subtype is characterized by the expression of myoepithelial/basal markers.Material and Method: We studied 41 immunohistochemically triplenegative- breast-cancer patients to determine EGFR, Cytoke...

Endotoxin-induced basal respiration alterations of renal HK-2 cells: A sign of pathologic metabolism down-regulation

Energy Technology Data Exchange (ETDEWEB)

Quoilin, C., E-mail: cquoilin@ulg.ac.be [Laboratory of Biomedical Spectroscopy, Department of Physics, University of Liege, 4000 Liege (Belgium); Mouithys-Mickalad, A. [Center of Oxygen Research and Development, Department of Chemistry, University of Liege, 4000 Liege (Belgium); Duranteau, J. [Department of Anaesthesia and Surgical ICU, CHU Bicetre, University Paris XI Sud, 94275 Le Kremlin Bicetre (France); Gallez, B. [Biomedical Magnetic Resonance Group, Louvain Drug Research Institute, Universite catholique de Louvain, 1200 Brussels (Belgium); Hoebeke, M. [Laboratory of Biomedical Spectroscopy, Department of Physics, University of Liege, 4000 Liege (Belgium)

2012-06-29

Highlights: Black-Right-Pointing-Pointer A HK-2 cells model of inflammation-induced acute kidney injury. Black-Right-Pointing-Pointer Two oximetry methods: high resolution respirometry and ESR spectroscopy. Black-Right-Pointing-Pointer Oxygen consumption rates of renal cells decrease when treated with LPS. Black-Right-Pointing-Pointer Cells do not recover normal respiration when the LPS treatment is removed. Black-Right-Pointing-Pointer This basal respiration alteration is a sign of pathologic metabolism down-regulation. -- Abstract: To study the mechanism of oxygen regulation in inflammation-induced acute kidney injury, we investigate the effects of a bacterial endotoxin (lipopolysaccharide, LPS) on the basal respiration of proximal tubular epithelial cells (HK-2) both by high-resolution respirometry and electron spin resonance spectroscopy. These two complementary methods have shown that HK-2 cells exhibit a decreased oxygen consumption rate when treated with LPS. Surprisingly, this cellular respiration alteration persists even after the stress factor was removed. We suggested that this irreversible decrease in renal oxygen consumption after LPS challenge is related to a pathologic metabolic down-regulation such as a lack of oxygen utilization by cells.

Supplementation of xanthophylls increased antioxidant capacity and decreased lipid peroxidation in hens and chicks.

Science.gov (United States)

Gao, Yu-Yun; Xie, Qing-Mei; Ma, Jing-Yun; Zhang, Xiang-Bin; Zhu, Ji-Mei; Shu, Ding-Ming; Sun, Bao-Li; Jin, Ling; Bi, Ying-Zuo

2013-03-28

The present study investigated the effects of xanthophyll supplementation on production performance, antioxidant capacity (measured by glutathione peroxidase, superoxide dismutase (SOD), catalase, total antioxidant capacity (T-AOC), and reduced glutathione:oxidised glutathione ratio (GSH:GSSG)) and lipid peroxidation (measured by malondialdehyde (MDA)) in breeding hens and chicks. In Expt 1, 432 hens were fed diets supplemented with 0 (control group), 20 or 40 mg xanthophyll/kg diet. Blood samples were taken at 7, 14, 21, 28 and 35 d of the trial. Liver and jejunal mucosa were sampled at 35 d. Both xanthophyll groups improved serum SOD at 21 and 28 d, serum T-AOC at 21 d and liver T-AOC, and serum GSH:GSSG at 21, 28 and 35 d and liver GSH:GSSG. Xanthophylls also decreased serum MDA at 21 d in hens. Expt 2 was a 2 × 2 factorial design. Male chicks hatched from 0 or 40 mg in ovo xanthophyll/kg diet of hens were fed a diet containing either 0 or 40 mg xanthophyll/kg diet. Liver samples were collected at 0, 7, 14 and 21 d after hatching. Blood samples were also collected at 21 d. In ovo-deposited xanthophylls increased antioxidant capacity and decreased MDA in the liver mainly within 1 week after hatching. Maternal effects gradually vanished during 1-2 weeks after hatching. Dietary xanthophylls increased antioxidant capacity and decreased MDA in the liver and serum mainly from 2 weeks onwards. Data suggested that xanthophyll supplementation enhanced antioxidant capacity and reduced lipid peroxidation in different tissues of hens and chicks.

The effects of fasting and cold exposure on metabolic rate and mitochondrial proton leak in liver and skeletal muscle of an amphibian, the cane toad Bufo marinus.

Science.gov (United States)

Trzcionka, M; Withers, K W; Klingenspor, M; Jastroch, M

2008-06-01

Futile cycling of protons across the mitochondrial inner membrane contributes significantly to standard metabolic rate in a variety of ectothermic and endothermic animals, but adaptations of the mitochondrial bioenergetics to different environmental conditions have rarely been studied in ectotherms. Changes in ambient temperature and nutritional status have a great effect on the physiological demands of ectothermic amphibians and may require the adjustment of mitochondrial efficiency. In order to investigate the effect of temperature and nutritional status on the mitochondrial level, we exposed male cane toads to either 10 degrees C or 30 degrees C and fasted half of the animals in each group. Cold exposure resulted in a fourfold reduction of the resting metabolic rate whereas nutritional status had only minor effects. The mitochondrial adjustments to each condition were observed by comparing the proton leak kinetics of isolated liver and skeletal muscle mitochondria at 25 degrees C. In response to cold exposure, liver mitochondria showed a decrease in proton conductance while skeletal muscle mitochondria were unchanged. Additional food deprivation had minor effects in skeletal muscle, but in liver we uncovered surprising differences in energy saving mechanisms between the acclimation temperatures: in warm-acclimated toads, fasting resulted in a decrease of the proton conductance whereas in cold-acclimated toads, the activity of the respiratory chain was reduced. To investigate the molecular mechanism underlying mitochondrial proton leakage, we determined the adenine-nucleotide transporter (ANT) content, which explained tissue-specific differences in the basal proton leak, but neither the ANT nor uncoupling protein (UCP) gene expression correlated with alterations of the proton leak in response to physiological stimuli.

Scintigraphy of liver and spleen in vinyl chloride workers

Energy Technology Data Exchange (ETDEWEB)

Biersack, H J; San Luis, T Jr; Lange, C E; Thelen, M; Veltman, G; Winkler, C [Bonn Univ. (Germany, F.R.). Inst. fuer Klinische und Experimentelle Nuklearmedizin; Bonn Univ. (Germany, F.R.). Klinik und Poliklinik der Haut- und Geschlechtskrankheiten; Bonn Univ. (Germany, F.R.). Radiologische Klinik)

1977-10-01

In 152 VC-exposed workers of whom 124 were employed in the PVC-production and 28 in VC-processing plants, liver and spleen imaging was performed using sup(99m)Tc-sulphur colloid and /sup 197/Hg-BMHP. In 101 (= 81%) of the 124 workers of the PVC-production plant and in 18 (= 64%) workers of PVC-processing factories pathological liver and spleen scintigrams were found. The most frequent pathological change in the scintigraphic image was an increase in splenic colloid accumulation, when compared with the liver uptake. Three angiosarcomas of the liver were detected through circumscribed defects of colloid accumulation. Sequential liver scintigraphy was done in 15 cases. In 7 patients with esophageal varices, considerable decrease in portal venous blood flow was demonstrated. - As a result of our investigations it can be stated that scintigraphically detectable changes are sensitive indicators of VC-induced lesions of the liver including liver fibrosis, portal hypertension and angiosarcoma.

Podredumbres basales de Gypsophila paniculata (Caryophyllaceae: Agentes causales y su patogenicidad potencial sobre Dianthus caryophyllus (Caryophyllaceae Basal rots of Gypsophila paniculata (Caryophyllaceae: Causal agents and its potential pathogenicity on Dianthus caryophyllus (Caryophyllaceae

Directory of Open Access Journals (Sweden)

Silvia María Wolcan

Full Text Available Los objetivos del trabajo fueron identificar a los agentes causales de las podredumbres basales de Gypsophila paniculata en la Argentina y probar su posible patogenicidad sobre Dianthus caryophyllus . A partir de plantas con síntomas de «podredumbre de la corona» (la más importante se aislaron en orden decreciente: Fusarium solani , F. oxysporum , Phytophthora nicotianae , Rhizoctonia solani , F. graminearum , F. verticillioides, F. equiseti y Pythium sp. y de plantas con «podredumbre basal del tallo» F. graminearum , F. oxysporum y F. solani . Con distintas cepas de cada hongo se hicieron pruebas de patogenicidad mediante la infestación del suelo y el depósito de inóculo en heridas producidas en los tallos. En la «podredumbre de la corona» fueron patógenos P. nicotianae causando decaimiento rápido de la parte aérea y podredumbre blanda de la corona y R. solani causando una pudrición más lenta y tejidos desintegrados. F. graminearum fue el patógeno de la «podredumbre basal del tallo» de gipsofila, que se describe por primera vez en este hospedante , comprobando que el hongo penetra sólo por heridas del tallo. En condiciones de inoculación se confirmó que algunas cepas de R. solani y de F. graminearum aisladas de gipsofila pueden ser patógenas de clavel mientras que sólo algunas de P. nicotianae resultaron patógenas débiles.The aims of the paper were to determine the causal agents of basal rots of Gypsophila paniculata in Argentina, and to evaluate its possible pathogenicity on Dianthus caryophyllus. Fusarium solani, F. oxysporum , Phytophthora nicotianae , Rhizoctonia solani , F. graminearum , F. verticilloides, F. equiseti and Pythium sp. were isolated in decreasing order from plants with symptoms of «crown rot» (the major basal rot. F. graminearum , F. oxysporum and F. solani were isolated from plants with «basal stem rot». Inoculations of gypsophila were performed by soil infestation and by placing inoculum on

The effectiveness of metformin in patients with metabolic syndrome and nonalcoholic fatty liver disease

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S A Butrova

2008-06-01

Full Text Available The mechanism of action of metformin is realized through activation of cAMP-dependent protein kinase, leading to a decrease hepatic glucose production as well as to decrease the synthesis of triglycerides and an increase in fat oxidation. Several studies have demonstrated the positive effect of the drug in non-alcoholic fatty liver disease, manifested in reducing the activity of enzymes, reducing the size of the liver and insulin resistance. The aim of our study was to evaluate the effectiveness of metformin in patients with metabolic syndrome and nonalcoholic fatty liver disease. The study found that the use Siofor 850 mg 2 times a day in conjunction with a reduced-calorie nutrition in patients with metabolic syndrome and nonalcoholic fatty liver disease leads to a significant reduction in insulin resistance associated with decreased activity of transaminases, improvement of metabolic parameters. The therapy Siofor majority of patients (60% with metabolic syndrome and nonalcoholic fatty liver disease achieved a clinically significant weight loss and improved body composition. Application Siofor improves lifestyle changes in obese patients with non-alcoholic liver disease dirovoy and metabolic disorders.

The regulation of cytoskeletal and liver-specific gene expression during liver regeneration and primary hepatocyte culture

International Nuclear Information System (INIS)

Robinson, G.S.

1989-01-01

The focus of this dissertation is to determine what role(s) the extracellular matrix and expression of certain cytoskeletal genes play in the regulation of hepatocyte growth and the maintenance of a differential state. The expression of several cytoskeletal and liver-specific genes was examined during liver regeneration and in hepatocyte cultures maintained in a hormonally-defined, serum-free medium and plated on two different matrices: rat tail collagen and the EHS matrix. During liver regeneration and in hepatocytes cultured on rat tail collagen, there was a dramatic increase in tubulin mRNA levels coincident with but not linked to DNA synthesis. The message levels for other cytoskeletal genes similarly increased, while a decrease was observed in the mRNA levels of the liver-specific genes, serum albumin and alpha 1 inhibitor III. Hepatocytes cultured on the EHS matrix resulted in the maintenance of low levels of cytoskeletal gene expression and high levels of liver-specific gene expression, similar to that observed in the normal liver. Results from subcellar fractionation and two-dimensional gel electrophoresis of 35 S-labelled proteins paralleled the results seen at the mRNA level. Preliminary work suggests that microtubule organization may play a role in the expression of the liver-specific genes which encode secreted proteins. These studies, which compare hepatocytes cultured on collagen or the EHS matrix gel, reveal that both cell-cell and cell-matrix interactions play a major role in the maintenance of the differential phenotype in hepatocytes

CT and MRI diagnosis of traumatic basal ganglia hemorrhage

International Nuclear Information System (INIS)

Wu Shike; Zhang Yalin; Xu Derong; Zou Gaowei; Chen Dan; He Sujun; Zhou Lichao

2009-01-01

Objective: To analyze CT and MRI features of traumatic basal ganglia hemorrhage and investigate the diagnostic value. Methods: 21 cases with traumatic basal ganglia hemorrhage diagnosed by clinic, CT and MRI in our hospital were collected in this study Plain CT scan were immediately performed in 21 cases after injury, plain MR scan were performed in 1 to 3 days. 12 cases of them underwent diffusion weighted imagine (DWI). The CT and MRI findings were retrospectively summarized. Results: 8 cases were found with simple traumatic basal ganglia hemorrhage. Complexity of basal ganglia hemorrhage occurred in 13 cases, 6 cases combined with subdural hemorrhage, 3 cases with epidural hematoma, 2 cases with subarachnoid hemorrhage, 6 cases with brain contusion and laceration in other locations, 4 cases with skull fracture. 26 lesions of basal ganglia hematoma were showed in 21 cases, 14 lesions of pallidum hemorrhage in 11 cases confirmed by MR could not be distinguished from calcification at the fast CT scan. 5 more lesions of brain contusion and laceration and 4 more lesions of brain white matter laceration were found by MR. Conclusion: CT in combination with MRI can diagnose traumatic basal ganglia hemorrhage and its complications early, comprehensively and accurately, which plays an important role in the clinical therapy selection and prognosis evaluation. (authors)

Clinicopathological evaluation of radiation induced basal cell carcinoma

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Meibodi Naser

2008-01-01

Full Text Available Background: Development of skin neoplasms is one of the most important chronic complications of radiation therapy. Basal cell carcinoma (BCC is the most frequent carcinoma occurring at the region of the body to which radiotherapy was delivered. Aim: The aim of this study was to evaluate clinical and histological aspects of basal cell carcinoma in patients with a history of radiotherapy. Materials and Methods: Medical records and microscopic slides of 80 patients with basal cell carcinoma who had received radiotherapy (1996-2006 were reviewed in pathology department of Imam Reza hospital of Mashhad, Iran. Collected data were analyzed statistically using descriptive test. Results: 60 men and 20 women were included, majority of them in their sixties. Plaque was the most common clinical pattern of basal cell carcinoma. Fifty one percent of the patients had pigmented and 42.5% had multiple lesions. Scalp was the most common site of involvement. Histologically, macronodular and pigmented carcinoma were the most predominant forms of basal cell carcinoma. Discussion: Majority of patients had scalp involvement and multiple lesions. Nodular and pigmented forms were the most common histological findings. We suggest the need for close supervision in patients with a history of radio therapy in the past.

Liver scintigraphy with sup(99m)Tc-Sn-colloid

International Nuclear Information System (INIS)

Suzuki, Masaaki

1976-01-01

Basic and clinical studies of sup(99m)Tc-Sn-colloid (Tc-Sn-C) were made on liver scintigraphy for comparison with 198 Au-colloid in blood clearance, liver accumulation, and spleen imaging strength. Tc-Sn-C was excellent in ease of sterilization, simplicity of preparation, reduction in the exposure dose for the examiner, labeling rate, and stability, and it was effective as a drug for liver scintigraphy. The blood clearance T1/2 can be an indicator for the blood flow rate in the liver, similarly to the Au-C method. Although a decrease in the liver radioactivity after liver accumulation was observed, it was not thought to affect liver scintigraphy. A clear shadow of the liver was obtained in all cases, and there seemed to be no differences between the commercially prepared Tc-Sn-C and the Tc-Sn-C which must be prepared each time. The spleen imaging strength was thought to be effective as a supplementary diagnosis for splenic diseases. No allergic symptoms appeared immediately after examination. (Chiba, N.)

Laparoscopic management of cystic disease of the liver.

Science.gov (United States)

Albrink, M H; McAllister, E W; Rosemurgy, A S; Karl, R C; Carey, L C

1994-04-01

Laparoscopic surgical procedures are increasing in scope and in variety. The benefits of decreased wound morbidity and pain have been well documented for multiple procedures that have traditionally required laparotomy. Although there are few controlled studies to document them, these benefits may be evident from simple clinical observation. Cystic disease of the liver is a condition that is treated largely for symptomatic reasons. The so-called noninvasive or radiographic guided methods of treatment for cystic disease of the liver are fraught with high recurrence rates. We present four cases of cystic disease of the liver treated laparoscopically, followed with pertinent discussion.

Cross-talk between branched-chain amino acids and hepatic mitochondria is compromised in nonalcoholic fatty liver disease

OpenAIRE

Sunny, Nishanth E.; Kalavalapalli, Srilaxmi; Bril, Fernando; Garrett, Timothy J.; Nautiyal, Manisha; Mathew, Justin T.; Williams, Caroline M.; Cusi, Kenneth

2015-01-01

Elevated plasma branched-chain amino acids (BCAA) in the setting of insulin resistance have been relevant in predicting type 2 diabetes mellitus (T2DM) onset, but their role in the etiology of hepatic insulin resistance remains uncertain. We determined the link between BCAA and dysfunctional hepatic tricarboxylic acid (TCA) cycle, which is a central feature of hepatic insulin resistance and nonalcoholic fatty liver disease (NAFLD). Plasma metabolites under basal fasting and euglycemic hyperin...

Determination of micro mineral Fe on cow meat and liver

International Nuclear Information System (INIS)

Natalia Adventini; Muhayatun; Syukria Kurniawati; Endang; Yuni Setyowat

2010-01-01

Fe deficiency is common in development countries. Fe deficiency could decreased the IQ level, immune function and work performance, impacts decreasing human resource quality. Beef and liver are Fe source which more easily absorbed compare to Fe found in plant products. Therefore, the Fe determination in beef and liver need to be carried out using INAA. Instrumental neutron activation analysis is a method for qualitative and quantitative determination of elements based on the measurement of characteristic radiation from radionuclide formed by neutron irradiation of the material. The Sixteen beef and liver from feed treatment cows were collected. Method validation using RM IAEAA-13 gave accuracy and precise were 99 % and 3,3 % respectively. Fe concentration in 16 beef and liver were obtained between 5.5-18.6 mg/kg wet weight with average value was 12.2±4.0 mg/kg and 22.9-4.7 mg/kg with average value was 35.2±8.7 mg/kg. Generally, this value gave the same result from other countries. Fe determination in beef and liver is not only expected to be a scientific based reference but also to update Indonesia food stuff composition data. (author)

Serum Fetuin-A Levels in Patients with Bilateral Basal Ganglia Calcification.

Science.gov (United States)

Demiryurek, Bekir Enes; Gundogdu, Asli Aksoy

2018-02-14

The idiopathic basal ganglia calcification (Fahr syndrome) may occur due to senility. Fetuin-A is a negative acute phase reactant which inhibits calcium-phosphorus precipitation and vascular calcification. In this study, we aimed to evaluate whether serum fetuin-A levels correlate with bilateral basal ganglia calcification. Forty-five patients who had bilateral basal ganglia calcification on brain CT were selected according to the inclusion and exclusion criteria, and 45 age and gender-matched subjects without basal ganglia calcification were included for the control group. Serum fetuin-A levels were measured from venous blood samples. All participants were divided into two groups; with and without basal ganglia calcification. These groups were divided into subgroups regarding age (18-32 and 33-45 years of age) and gender (male, female). We detected lower levels of serum fetuin-A in patients with basal ganglia calcification compared with the subjects without basal ganglia calcification. In all subgroups (female, male, 18-32 years and 33-45 years), mean fetuin-A levels were significantly lower in patients with basal ganglia calcification (p = 0.017, p = 0.014, p = 0.024, p = 0.026, p = 0.01 respectively). And statistically significantly lower levels of fetuin-A was found to be correlated with the increasing densities of calcification in the calcified basal ganglia group (p-value: <0.001). Considering the role of fetuin-A in tissue calcification and inflammation, higher serum fetuin-A levels should be measured in patients with basal ganglia calcification. We believe that the measurement of serum fetuin-A may play a role in the prediction of basal ganglia calcification as a biomarker. Copyright © 2017 Elsevier B.V. All rights reserved.

Extracorporeal liver assist device to exchange albumin and remove endotoxin in acute liver failure: Results of a pivotal pre-clinical study.

Science.gov (United States)

Lee, Karla C L; Baker, Luisa A; Stanzani, Giacomo; Alibhai, Hatim; Chang, Yu Mei; Jimenez Palacios, Carolina; Leckie, Pamela J; Giordano, Paola; Priestnall, Simon L; Antoine, Daniel J; Jenkins, Rosalind E; Goldring, Christopher E; Park, B Kevin; Andreola, Fausto; Agarwal, Banwari; Mookerjee, Rajeshwar P; Davies, Nathan A; Jalan, Rajiv

2015-09-01

In acute liver failure, severity of liver injury and clinical progression of disease are in part consequent upon activation of the innate immune system. Endotoxaemia contributes to innate immune system activation and the detoxifying function of albumin, critical to recovery from liver injury, is irreversibly destroyed in acute liver failure. University College London-Liver Dialysis Device is a novel artificial extracorporeal liver assist device, which is used with albumin infusion, to achieve removal and replacement of dysfunctional albumin and reduction in endotoxaemia. We aimed to test the effect of this device on survival in a pig model of acetaminophen-induced acute liver failure. Pigs were randomised to three groups: Acetaminophen plus University College London-Liver Dialysis Device (n=9); Acetaminophen plus Control Device (n=7); and Control plus Control Device (n=4). Device treatment was initiated two h after onset of irreversible acute liver failure. The Liver Dialysis Device resulted in 67% reduced risk of death in acetaminophen-induced acute liver failure compared to Control Device (hazard ratio=0.33, p=0.0439). This was associated with 27% decrease in circulating irreversibly oxidised human non-mercaptalbumin-2 throughout treatment (p=0.046); 54% reduction in overall severity of endotoxaemia (p=0.024); delay in development of vasoplegia and acute lung injury; and delay in systemic activation of the TLR4 signalling pathway. Liver Dialysis Device-associated adverse clinical effects were not seen. The survival benefit and lack of adverse effects would support clinical trials of University College London-Liver Dialysis Device in acute liver failure patients. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

MRI of the basal ganglia calcification

International Nuclear Information System (INIS)

Maeda, Masayuki; Murata, Tetsuhito; Kimura, Hirohiko

1992-01-01

MR imaging was performed for 11 patients (9 in Down's syndrome and 2 in idiopathic intracerebral calcification) who showed calcifications in bilateral basal ganglia on CT. High signal intensity in the basal ganglia was found only in one patient with idiopathic intracerebral calcification on T1-weighted image. The calcified areas of all patients in Down's syndrome did not show high signal intensity on T1-weighted image. The exact reasons why MRI exhibits the different signal intensities in calcified tissue on T1-weighted image are unknown. Further clinical investigations will be needed. (author)

Effects of purified eicosapentaenoic and docosahexaenoic acids in nonalcoholic fatty liver disease: results from the Welcome* study.

Science.gov (United States)

Scorletti, Eleonora; Bhatia, Lokpal; McCormick, Keith G; Clough, Geraldine F; Nash, Kathryn; Hodson, Leanne; Moyses, Helen E; Calder, Philip C; Byrne, Christopher D

2014-10-01

There is no licensed treatment for non-alcoholic fatty liver disease (NAFLD), a condition that increases risk of chronic liver disease, type 2 diabetes and cardiovascular disease. We tested whether 15-18 months treatment with docosahexaenoic acid (DHA) plus eicosapentaenoic acid (EPA) (Omacor/Lovaza) (4 g/day) decreased liver fat and improved two histologically-validated liver fibrosis biomarker scores (primary outcomes). Patients with NAFLD were randomised in a double blind placebo-controlled trial [DHA+EPA(n=51), placebo(n=52)]. We quantified liver fat percentage (%) by magnetic resonance spectroscopy in three liver zones. We measured liver fibrosis using two validated scores. We tested adherence to the intervention (Omacor group) and contamination (with DHA and EPA) (placebo group) by measuring erythrocyte percentage DHA and EPA enrichment (gas chromatography). We undertook multivariable linear regression to test effects of: a) DHA+EPA treatment (ITT analyses) and b) erythrocyte DHA and EPA enrichment (secondary analysis). Median (IQR) baseline and end of study liver fat% were 21.7 (19.3) and 19.7 (18.0) (placebo), and 23.0 (36.2) and 16.3 (22.0), (DHA+EPA). In the fully adjusted regression model there was a trend towards improvement in liver fat% with DHA+EPA treatment (β=-3.64 (95%CI -8.0,0.8); p=0.1) but there was evidence of contamination in the placebo group and variable adherence to the intervention in the Omacor group. Further regression analysis showed that DHA enrichment was independently associated with a decrease in liver fat% (for each 1% enrichment, β=-1.70 (95%CI -2.9,-0.5); p=0.007). No improvement in the fibrosis scores occurred. Conclusion. Erythrocyte DHA enrichment with DHA+EPA treatment is linearly associated with decreased liver fat%. Substantial decreases in liver fat% can be achieved with high percentage erythrocyte DHA enrichment in NAFLD. (Hepatology 2014;).

Liver transplant for cholestatic liver diseases.

Science.gov (United States)

Carrion, Andres F; Bhamidimarri, Kalyan Ram

2013-05-01

Cholestatic liver diseases include a group of diverse disorders with different epidemiology, pathophysiology, clinical course, and prognosis. Despite significant advances in the clinical care of patients with cholestatic liver diseases, liver transplant (LT) remains the only definitive therapy for end-stage liver disease, regardless of the underlying cause. As per the United Network for Organ Sharing database, the rate of cadaveric LT for cholestatic liver disease was 18% in 1991, 10% in 2000, and 7.8% in 2008. This review summarizes the available evidence on various common and rare cholestatic liver diseases, disease-specific issues, and pertinent aspects of LT. Copyright © 2013 Elsevier Inc. All rights reserved.

Liver transplant

Science.gov (United States)

Hepatic transplant; Transplant - liver; Orthotopic liver transplant; Liver failure - liver transplant; Cirrhosis - liver transplant ... The donated liver may be from: A donor who has recently died and has not had liver injury. This type of ...

[Herbs for calming liver and suppressing yang in treatment of hyperthyroidism with hyperactive liver yang: herbal effects on lymphocyte protein expression].

Science.gov (United States)

Li, Xiangping; Yin, Tao; Zhong, Guangwei; Li, Wei; Luo, Yanhong; Xiang, Lingli; Liu, Zhehao

2011-07-01

To observe the herbal effects on hyperthyroidism patients with syndrome of hyperactivity of liver-Yang by method for calming the liver and suppressing Yang and investigate its effects on the lymphocyte protein expression. This approach may lay a foundation for the further investigation of the curative mechanisms of calming the liver and suppressing Yang treatment. A total of 48 hyperthyroidism patients with syndrome of hyperactivity of liver-Yang were randomly divided into treatment group and control group. The treatment group was treated by method for calming the liver and suppressing Yang in accordance with traditional Chinese medicine (TCM) and the control group with thiamazole tablets for three periods of treatment The therapeutic effects, the score of TCM symptom, electrocardiogram (P wave), thyroid hormones and ultrasound were observed in both groups before and after the treatment. The side effects in the treatment course were observed in both groups. The level of differential protein expression was analyzed by two-dimensional electrphoresis and matrix assisted laser desorption/ionizaton time-of-flight mass spectrometry. The treatment group has the effect on stepping down the heart rate, cutting down the P wave amplitude changes, regulating the level of thyroid hormones and decreasing the volume of thyromegaly. There are not statistically significant between the treatment group and control group. However, the treatment group has obviously better effect on regulating TCM symptom and decreasing the side reaction than the control group (Peffective between the treatment group and control group. The average spots in lymphocyte for normal people, before and after treating hyperthyroidism patients with syndrome of hyperactivity of liver-Yang were (429 +/- 31), (452 +/- 28) and (437 +/- 36) spots respectively. Eight down-regulated protein expressions and 11 up-regulated protein expressions were obtained in the hyperthyroidism patients with syndrome of hyperactivity

Time-course comparison of xenobiotic activators of CAR and PPARα in mouse liver

International Nuclear Information System (INIS)

Ross, Pamela K.; Woods, Courtney G.; Bradford, Blair U.; Kosyk, Oksana; Gatti, Daniel M.; Cunningham, Michael L.; Rusyn, Ivan

2009-01-01

Constitutive androstane receptor (CAR) and peroxisome proliferator activated receptor (PPAR)α are transcription factors known to be primary mediators of liver effects, including carcinogenesis, by phenobarbital-like compounds and peroxisome proliferators, respectively, in rodents. Many similarities exist in the phenotypes elicited by these two classes of agents in rodent liver, and we hypothesized that the initial transcriptional responses to the xenobiotic activators of CAR and PPARα will exhibit distinct patterns, but at later time-points these biological pathways will converge. In order to capture the global transcriptional changes that result from activation of these nuclear receptors over a time-course in the mouse liver, microarray technology was used. First, differences in basal expression of liver genes between C57Bl/6J wild-type and Car-null mice were examined and 14 significantly differentially expressed genes were identified. Next, mice were treated with phenobarbital (100 mg/kg by gavage for 24 h, or 0.085% w/w diet for 7 or 28 days), and liver gene expression changes with regards to both time and treatment were identified. While several pathways related to cellular proliferation and metabolism were affected by phenobarbital in wild-type mice, no significant changes in gene expression were found over time in the Car-nulls. Next, we determined commonalities and differences in the temporal response to phenobarbital and WY-14,643, a prototypical activator of PPAR α. Gene expression signatures from livers of wild-type mice C57Bl6/J mice treated with PB or WY-14,643 were compared. Similar pathways were affected by both compounds; however, considerable time-related differences were present. This study establishes common gene expression fingerprints of exposure to activators of CAR and PPARα in rodent liver and demonstrates that despite similar phenotypic changes, molecular pathways differ between classes of chemical carcinogens

Clinical significance of diminution of high-density areas in basal cisterns following acute aneurysmal bleeding

International Nuclear Information System (INIS)

Matsuzaki, Takayuki; Takeda, Rihei; Nakagawara, Jyoji; Sato, Shigeru; Fujiwara, Hidetoshi

1983-01-01

We analyzed the sequential changes in the high density in basal cisterns in the acute stage of aneurysmal bleeding. We could recognize Group 3 (clot or thick layer), according to Fisher's classification, in 66.3% of the intracranial aneurysms at admission (83 cases). In the early stage of an intracranial aneurysm, a subarachnoid hemorrhage (SAH) was detected in all the patients on CT. We evaluated 40 cases of Group 3 sequentially on CT. This investigation showed that 55% of the Grade I--Ii group, 27.3% of the Grade III group, and 11.1% of the Grade IV--V group changed to Group 2(thin or diffuse pattern) in approximately 20 hours on the average. As for the correlation between the high density in basal cisterns and the neurological condition (Hunt and Hess), we found a neurological improvement in the decreased-high-density group. The unchanged- high-density group showed deterioration. Compared with the decreased-high-density group, the unchanged group showed a greater increase in the CVI (Cerebro Ventricular Index). RI ( 111 In) cisternography also showed a disturbance of the CSF circulation. To lower the vasospasm it is important to decrease the high density in an early stage by carrying out CSF. It was considered to be prognostic when a CT scan was performed within 24 hours after SAH. (author)

Amyloid in basal cell carcinoma and seborrheic keratosis

DEFF Research Database (Denmark)

Olsen, K E; Westermark, Per

1994-01-01

The frequency of amyloid substance was studied in two different types of skin tumours: basal cell carcinoma and seborrheic keratosis. In 9 out of 49 cases of seborrheic keratosis amyloid substance was found. In the basal cell carcinomas, 194 out of 260 cases showed amyloid deposits, a rate...

Significance of a postenhancement computed tomography findings in liver cirrhosis: In view of hemodynamics

Energy Technology Data Exchange (ETDEWEB)

Lee, Suck Hong; Kim, Byung Soo [Pusan National University College of Medicine, Pusan (Korea, Republic of)

1985-04-15

We observed a significant sign in postenhancement computed tomography of liver cirrhosis, that is visualization of portal venous branches. During postenhancement computed tomography scanning of liver, the portal vein can not be identified in liver parenchyme in 84% of patients without known cirrhosis (including chronic active hepatitis). The two have the same hemodynamic changes in that there is diffuse fibrosis and resultant decrease in vascular bed. Visualization of intrahepatic portal branches in postenhancement computed tomography is because of decreased diffusion ability and portal hypertension.

The protection of meloxicam against chronic aluminium overload-induced liver injury in rats.

Science.gov (United States)

Yang, Yang; He, Qin; Wang, Hong; Hu, Xinyue; Luo, Ying; Liang, Guojuan; Kuang, Shengnan; Mai, Shaoshan; Ma, Jie; Tian, Xiaoyan; Chen, Qi; Yang, Junqing

2017-04-04

The present study was designed to observe the protective effect and mechanisms of meloxicam on liver injury caused by chronic aluminium exposure in rats. The histopathology was detected by hematoxylin-eosin staining. The levels of prostaglandin E2, cyclic adenosine monophosphate and inflammatory cytokines were detected by enzyme linked immunosorbent assay. The expressions of cyclooxygenases-2, prostaglandin E2 receptors and protein kinase A were measured by western blotting and immunohistochemistry. Our experimental results showed that aluminium overload significantly damaged the liver. Aluminium also significantly increased the expressions of cyclooxygenases-2, prostaglandin E2, cyclic adenosine monophosphate, protein kinase A and the prostaglandin E2 receptors (EP1,2,4) and the levels of inflammation and oxidative stress, while significantly decreased the EP3 expression in liver. The administration of meloxicam significantly improved the impairment of liver. The contents of prostaglandin E2 and cyclic adenosine monophosphate were significantly decreased by administration of meloxicam. The administration of meloxicam also significantly decreased the expressions of cyclooxygenases-2 and protein kinase A and the levels of inflammation and oxidative stress, while significantly increased the EP1,2,3,4 expressions in rat liver. Our results suggested that the imbalance of cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway is involved in the injury of chronic aluminium-overload rat liver. The protective mechanism of meloxicam on aluminium-overload liver injury is attributed to reconstruct the balance of cyclooxygenases-2 and downstream prostaglandin E2 signaling pathway.

Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease

Directory of Open Access Journals (Sweden)

Oliveira C.P.M.S.

2006-01-01

Full Text Available Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7 or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7 for 4 weeks. The control group (N = 7 was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4 and a decrease in respiratory control rate (RCR in the CD group (S4: 32.70 ± 3.35; RCR: 2.55 ± 0.15 ng atoms of O2 min-1 mg protein-1 when compared to the H and control groups (S4: 23.09 ± 1.53, 17.04 ± 2.03, RCR: 3.15 ± 0.15, 3.68 ± 0.15 ng atoms of O2 min-1 mg protein-1, respectively, P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.

Motor phenotype and magnetic resonance measures of basal ganglia iron levels in Parkinson's disease.

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Bunzeck, Nico; Singh-Curry, Victoria; Eckart, Cindy; Weiskopf, Nikolaus; Perry, Richard J; Bain, Peter G; Düzel, Emrah; Husain, Masud

2013-12-01

In Parkinson's disease the degree of motor impairment can be classified with respect to tremor dominant and akinetic rigid features. While tremor dominance and akinetic rigidity might represent two ends of a continuum rather than discrete entities, it would be important to have non-invasive markers of any biological differences between them in vivo, to assess disease trajectories and response to treatment, as well as providing insights into the underlying mechanisms contributing to heterogeneity within the Parkinson's disease population. Here, we used magnetic resonance imaging to examine whether Parkinson's disease patients exhibit structural changes within the basal ganglia that might relate to motor phenotype. Specifically, we examined volumes of basal ganglia regions, as well as transverse relaxation rate (a putative marker of iron load) and magnetization transfer saturation (considered to index structural integrity) within these regions in 40 individuals. We found decreased volume and reduced magnetization transfer within the substantia nigra in Parkinson's disease patients compared to healthy controls. Importantly, there was a positive correlation between tremulous motor phenotype and transverse relaxation rate (reflecting iron load) within the putamen, caudate and thalamus. Our findings suggest that akinetic rigid and tremor dominant symptoms of Parkinson's disease might be differentiated on the basis of the transverse relaxation rate within specific basal ganglia structures. Moreover, they suggest that iron load within the basal ganglia makes an important contribution to motor phenotype, a key prognostic indicator of disease progression in Parkinson's disease. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Delayed liver regeneration after partial hepatectomy in adiponectin knockout mice

International Nuclear Information System (INIS)

Ezaki, Hisao; Yoshida, Yuichi; Saji, Yukiko; Takemura, Takayo; Fukushima, Juichi; Matsumoto, Hitoshi; Kamada, Yoshihiro; Wada, Akira; Igura, Takumi; Kihara, Shinji; Funahashi, Tohru; Shimomura, Iichiro; Tamura, Shinji; Kiso, Shinichi; Hayashi, Norio

2009-01-01

We previously demonstrated that adiponectin has anti-fibrogenic and anti-inflammatory effects in the liver of mouse models of various liver diseases. However, its role in liver regeneration remains unclear. The aim of this study was to determine the role of adiponectin in liver regeneration. We assessed liver regeneration after partial hepatectomy in wild-type (WT) and adiponectin knockout (KO) mice. We analyzed DNA replication and various signaling pathways involved in cell proliferation and metabolism. Adiponectin KO mice exhibited delayed DNA replication and increased lipid accumulation in the regenerating liver. The expression levels of peroxisome proliferator-activated receptor (PPAR) α and carnitine palmitoyltransferase-1 (CPT-1), a key enzyme in mitochondrial fatty acid oxidation, were decreased in adiponectin KO mice, suggesting possible contribution of altered fat metabolism to these phenomena. Collectively, the present results highlight a new role for adiponectin in the process of liver regeneration.

Efficacy of aspiration in amebic liver abscess.

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Ghosh, Jayant Kumar; Goyal, Sundeep Kumar; Behera, Manas Kumar; Tripathi, Manish Kumar; Dixit, Vinod Kumar; Jain, Ashok Kumar; Shukla, Ramchandra

2015-01-01

Amebic liver abscess (ALA) is a common and serious problem in our country. There are only a few controlled trials on the efficacy and advantages of combination therapy with percutaneous needle aspiration and pharmacotherapy, over pharmacotherapy alone for amebic liver abscess. This study was conducted to compare the efficacy of two different treatment modalities i.e. drug treatment alone vs. drug treatment and aspiration of abscess cavity in patients with small (up to 5 cm) and large (5 cm to 10 cm) size ALA. This is one of the largest single center, prospective, randomized studies comparing the efficacy of aspiration in ALA. (i) Mean body temperature, liver tenderness, total leukocyte count (TLC), serum alanine aminotransferase (ALT) and liver span were significantly decreased in the aspiration group on days 8 and 15 as compared to non-aspiration group especially in large abscess (5 cm to 10 cm). (ii) Abscess cavity maximum diameter decreased significantly in aspiration group on days 8 and 15, and 1 month & 3 months in large abscess (5cm to 10 cm). (i) Needle aspiration along with metronidazole hastens clinical improvement especially in large (5 cm up to 10 cm) cavities in patients with ALA. (ii) Aspiration is safe and no major complications occurred. (iii) Hence, combination therapy should be the first choice especially in large ALA (5 cm to 10 cm).

Decreasing size of radiosensitive capsules from micro to nano, and its increased antitumor effect and decreasing adverse effect

International Nuclear Information System (INIS)

Harada, S.; Ehara, S.; Ishii, K.; Yamazaki, H.; Matsuyama, S.; Sato, Takahiro; Kamiya, Tomihiro; Sera, K.; Saito, Y.

2012-01-01

We have been developing microcapsules that release anticancer drug with response to radiation. We attempted to decrease the diameter of capsules. Then, two categories were tested in VIVO in C3He mice: (1) the antitumor effect in combination with radiation and subcutaneously injected nanocapsules, (2) the kidnetics of nanocapsules when they were injected intravenously. Microcapsules were produced by spraying a mixture of 3.0 % hyaluronic acid, 2.0 % alginate, 3.0 % H 2 O 2 , and 0.3 mmol carboplatin (Pt containing anticancer drug) onto a mixture of vibrated 0.3 mol FeCl 2 and 0.15 mol CaCl 2 . The antitumor effect was measured by measuring tumor diameter every day. The kinetics of microcapsules were expressed as the numbers of capsules in 5 views (25 x 25 μm) of micro PIXE camera and Pt concentration of quantiative PIXE. The generated microcapsules 752 ± 64 nm, which were significantly downsized relative to previous capsules. The accumulations of capsules in lungs, liver, and kidneys were decreased by downsizing, whereas those of tumors were increased. By adjusting Pt concentration in tumor, there were no significant differences in antitumor effect between not downsized and downsized microcapsules with combination with radiation. Decreased trapping of downsized microcapsules to lungs, liver, and kidneys, also increased trapping in tumors will lead to new targeted chemoradiotherapy via intravenous injection of microcapsules. (author)

Functional MR imaging of the liver; Funktionelle MR-Tomographie der Leber

Energy Technology Data Exchange (ETDEWEB)

Wibmer, A.; Nolz, R.; Ba-Ssalamah, A. [Medizinische Universitaet Wien, Allgemeines Krankenhaus der Stadt Wien, Universitaetsklinik fuer Radiodiagnostik und Nuklearmedizin, Wien (Austria); Trauner, M. [Medizinische Universitaet Wien, Universitaetsklinik fuer Innere Medizin III, Klinische Abteilung fuer Gastroenterologie und Hepatologie, Wien (Austria)

2015-12-15

The diagnostics of diffuse liver disease traditionally rely on liver biopsies and histopathological analysis of tissue specimens. However, a liver biopsy is invasive and carries some non-negligible risks, especially for patients with decreased liver function and those requiring repeated follow-up examinations. Over the last decades, magnetic resonance imaging (MRI) has developed into a valuable tool for the non-invasive characterization of focal liver lesions and diseases of the bile ducts. Recently, several MRI methods have been developed and clinically evaluated that also allow the diagnostics and staging of diffuse liver diseases, e. g. non-alcoholic fatty liver disease, hepatitis, hepatic fibrosis, liver cirrhosis, hemochromatosis and hemosiderosis. The sequelae of diffuse liver diseases, such as a decreased liver functional reserve or portal hypertension, can also be detected and quantified by modern MRI methods. This article provides the reader with the basic principles of functional MRI of the liver and discusses the importance in a clinical context. (orig.) [German] Die Diagnostik diffuser Lebererkrankungen stuetzt sich klassisch auf die Leberbiopsie und deren histopathologische Analyse. Dieses Verfahren ist allerdings fuer die Patienten unangenehm und schmerzhaft, birgt v. a. bei Patienten mit Lebererkrankungen ein gewisses Risiko und eignet sich daher nur sehr eingeschraenkt zur Verlaufskontrolle bei chronischen Erkrankungen. Die Magnetresonanztomographie (MRT) der Leber nimmt schon jetzt eine zentrale Stellung in der Diagnostik von Raumforderungen der Leber und von Erkrankungen der Gallenwege ein. Darueber hinaus bietet dieses nichtinvasive Verfahren Moeglichkeiten, diffuse Erkrankungen des Leberparenchyms zu diagnostizieren und ihren Schweregrad abzuschaetzen, z. B. bei nichtalkoholischer Leberverfettung, Hepatitis, Leberfibrose, Zirrhose, Haemochromatose und Siderose und anderen. Folgen einer parenchymatoesen Lebererkrankung, wie die portale

computed tomography features of basal ganglia and periventricular

African Journals Online (AJOL)

HIV is probably the most common cause of basal ganglia and periventricular calcification today. on-enhanced computed tomography (NECT) shows diffuse cerebral atrophy in 90% of cases. Bilateral, symmetrical basal ganglia calcification is seen in 30% of cases, but virtually never before 1 year of age.1. CMV (FIG.2).

A basal stem cell signature identifies aggressive prostate cancer phenotypes

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Smith, Bryan A.; Sokolov, Artem; Uzunangelov, Vladislav; Baertsch, Robert; Newton, Yulia; Graim, Kiley; Mathis, Colleen; Cheng, Donghui; Stuart, Joshua M.; Witte, Owen N.

2015-01-01

Evidence from numerous cancers suggests that increased aggressiveness is accompanied by up-regulation of signaling pathways and acquisition of properties common to stem cells. It is unclear if different subtypes of late-stage cancer vary in stemness properties and whether or not these subtypes are transcriptionally similar to normal tissue stem cells. We report a gene signature specific for human prostate basal cells that is differentially enriched in various phenotypes of late-stage metastatic prostate cancer. We FACS-purified and transcriptionally profiled basal and luminal epithelial populations from the benign and cancerous regions of primary human prostates. High-throughput RNA sequencing showed the basal population to be defined by genes associated with stem cell signaling programs and invasiveness. Application of a 91-gene basal signature to gene expression datasets from patients with organ-confined or hormone-refractory metastatic prostate cancer revealed that metastatic small cell neuroendocrine carcinoma was molecularly more stem-like than either metastatic adenocarcinoma or organ-confined adenocarcinoma. Bioinformatic analysis of the basal cell and two human small cell gene signatures identified a set of E2F target genes common between prostate small cell neuroendocrine carcinoma and primary prostate basal cells. Taken together, our data suggest that aggressive prostate cancer shares a conserved transcriptional program with normal adult prostate basal stem cells. PMID:26460041

Effects of Basal Defoliation on Wine Aromas: A Meta-Analysis

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Yu Wang

2018-03-01

Full Text Available Basal defoliation, as one of the most common viticulture management practices to modify fruit zone microclimates, has been widely applied aiming at improving wine quality. Wine aroma contributes greatly to wine quality, yet the effects of basal defoliation on wine aromas show discrepancies according to previous studies. This study is a meta-analysis performed to dissect the factors related to the influence of basal defoliation on volatile compounds in wine. Timing of basal defoliation plays an important role in the concentration of varietal aromas in wine. Pre-veraison defoliation induces an increase in β-damascenone and linalool as well as a reduction in 3-isobutyl-2-methoxypyrazine (IBMP. The effects of basal defoliation on certain volatile compounds relative to fermentation aromas in wine (1-hexanol, β-phenylethanol, 2-phenylethyl acetate, decanoic acid, and ethyl octanoate depend on grape maturity. There are also other factors, such as cultivar and climate conditions, that might be responsible for the effect of basal defoliation on wine aromas. The concentrations of isobutanol, isoamyl alcohol, hexanoic acid, and octanoic acid as well as ethyl isobutyrate, ethyl hexanoate, ethyl isovalerate, and ethyl decanoate in wine are not markedly affected by basal defoliation. Due to limited studies included in this meta-analysis, more trials are needed to confirm the current findings.

Heterogeneity of limbal basal epithelial progenitor cells.

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Hayashida, Yasutaka; Li, Wei; Chen, Ying-Ting; He, Hua; Chen, Szu-yu; Kheirkah, Ahmad; Zhu, Ying-Tien; Matsumoto, Yukihiro; Tseng, Scheffer C G

2010-11-01

Although corneal epithelial stem cells (SCs) are located at the limbus between the cornea and the conjunctiva, not all limbal basal epithelial cells are SCs. Using 2 dispase digestions to remove different amounts of limbal basal epithelial cells for cross-sections, flat mounts, and cytospin preparations, double immunostaining to pancytokeratins (PCK) and vimentin (Vim) identified 3 p63+ epithelial progenitors such as PCK-/Vim+, PCK/Vim, and PCK-/Vim+ and 1 p63+ mesenchymal cell, PCK-/Vim+. PCK-/Vim- progenitors had the smallest cell size were 10-20 times more enriched on collagen I-coated dishes in the 5-minute rapid adherent fraction that contained the highest percentage of p63+ cells but the lowest percentage of cytokeratin12+ cells, and gave rise to high Ki67 labeling and vivid clonal growth. In contrast, PCK+/Vim+ and PCK+/Vim- progenitors were found more in the slow-adherent fraction and yielded poor clonal growth. PCK/Vim progenitors and clusters of PCK-/Vim+ mesenchymal cells, which were neither melanocytes nor Langerhans cells, were located in the limbal basal region. Therefore, differential expression of PCK and Vim helps identify small PCK-/Vim- cells as the most likely candidate for SCs among a hierarchy of heterogeneous limbal basal progenitors, and their close association with PCK-/Vim+ presumed "niche" cells.

Giant basal cell carcinoma Carcinoma basocelular gigante

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Nilton Nasser

2012-06-01

Full Text Available The basal cell carcinoma is the most common skin cancer but the giant vegetating basal cell carcinoma reaches less than 0.5 % of all basal cell carcinoma types. The Giant BCC, defined as a lesion with more than 5 cm at its largest diameter, is a rare form of BCC and commonly occurs on the trunk. This patient, male, 42 years old presents a Giant Basal Cell Carcinoma which reaches 180 cm2 on the right shoulder and was negligent in looking for treatment. Surgical treatment was performed and no signs of dissemination or local recurrence have been detected after follow up of five years.O carcinoma basocelular é o tipo mais comum de câncer de pele, mas o carcinoma basocelular gigante vegetante não atinge 0,5% de todos os tipos de carcinomas basocelulares. O Carcinoma Basocelular Gigante, definido como lesão maior que 5 cm no maior diâmetro, é uma forma rara de carcinoma basocelular e comumente ocorre no tronco. Este paciente apresenta um Carcinoma Basocelular Gigante com 180cm² no ombro direito e foi negligente em procurar tratamento. Foi realizado tratamento cirúrgico e nenhum sinal de disseminação ou recorrência local foi detectada após 5 anos.

A High-Protein Diet Reduces Weight Gain, Decreases Food Intake, Decreases Liver Fat Deposition, and Improves Markers of Muscle Metabolism in Obese Zucker Rats.

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French, William W; Dridi, Sami; Shouse, Stephanie A; Wu, Hexirui; Hawley, Aubree; Lee, Sun-Ok; Gu, Xuan; Baum, Jamie I

2017-06-08

A primary factor in controlling and preventing obesity is through dietary manipulation. Diets higher in protein have been shown to improve body composition and metabolic health during weight loss. The objective of this study was to examine the effects of a high-protein diet versus a moderate-protein diet on muscle, liver and fat metabolism and glucose regulation using the obese Zucker rat. Twelve-week old, male, Zucker (fa/fa) and lean control (Fa/fa) rats were randomly assigned to either a high-protein (40% energy) or moderate-protein (20% energy) diet for 12 weeks, with a total of four groups: lean 20% protein (L20; n = 8), lean 40% protein (L40; n = 10), obese 20% protein (O20; n = 8), and obese 40% protein (O40; n = 10). At the end of 12 weeks, animals were fasted and euthanized. There was no difference in food intake between L20 and L40. O40 rats gained less weight and had lower food intake ( p diet rats, respectively. O40 had decreased skeletal muscle mechanistic target of rapamycin complex 1 (mTORC1) phosphorylation and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA expression compared to O20 ( p protein kinase (AMPK), eukaryotic translation initiation factor 4E binding protein 1 (4EBP1), protein kinase B (Akt) or p70 ribosomal S6 kinase (p70S6K) phosphorylation. The data suggest that high-protein diets have the potential to reduce weight gain and alter metabolism, possibly through regulation of an mTORC1-dependent pathway in skeletal muscle.

Role of liver progenitors in liver regeneration.

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Best, Jan; Manka, Paul; Syn, Wing-Kin; Dollé, Laurent; van Grunsven, Leo A; Canbay, Ali

2015-02-01

During massive liver injury and hepatocyte loss, the intrinsic regenerative capacity of the liver by replication of resident hepatocytes is overwhelmed. Treatment of this condition depends on the cause of liver injury, though in many cases liver transplantation (LT) remains the only curative option. LT for end stage chronic and acute liver diseases is hampered by shortage of donor organs and requires immunosuppression. Hepatocyte transplantation is limited by yet unresolved technical difficulties. Since currently no treatment is available to facilitate liver regeneration directly, therapies involving the use of resident liver stem or progenitor cells (LPCs) or non-liver stem cells are coming to fore. LPCs are quiescent in the healthy liver, but may be activated under conditions where the regenerative capacity of mature hepatocytes is severely impaired. Non-liver stem cells include embryonic stem cells (ES cells) and mesenchymal stem cells (MSCs). In the first section, we aim to provide an overview of the role of putative cytokines, growth factors, mitogens and hormones in regulating LPC response and briefly discuss the prognostic value of the LPC response in clinical practice. In the latter section, we will highlight the role of other (non-liver) stem cells in transplantation and discuss advantages and disadvantages of ES cells, induced pluripotent stem cells (iPS), as well as MSCs.

Simplified technique for auxiliary orthotopic liver transplantation using a whole graft

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ROCHA-SANTOS, Vinicius; NACIF, Lucas Souto; PINHEIRO, Rafael Soares; DUCATTI, Liliana; ANDRAUS, Wellington; D'ALBURQUERQUE, Luiz Carneiro

2015-01-01

Background Acute liver failure is associated with a high mortality rate and the main purposes of treatment are to prevent cerebral edema and infections, which often are responsible for patient death. The orthotopic liver transplantation is the gold standard treatment and improves the 1-year survival. Aim To describe an alternative technique to auxiliary liver transplant on acute liver failure. Method Was performed whole auxiliary liver transplantation as an alternative technique for a partial auxiliary liver transplantation using a whole liver graft from a child removing the native right liver performed a right hepatectomy. The patient met the O´Grady´s criteria and the rational to indicate an auxiliary orthotopic liver transplantation was the acute classification without hemodynamic instability or renal failure in a patient with deterioration in consciousness. Results The procedure improved liver function and decreased intracranial hypertension in the postoperative period. Conclusion This technique can overcome some postoperative complications that are associated with partial grafts. As far as is known, this is the first case of auxiliary orthotopic liver transplantation in Brazil. PMID:26176253

Deep-Brain Stimulation for Basal Ganglia Disorders.

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Wichmann, Thomas; Delong, Mahlon R

2011-07-01

The realization that medications used to treat movement disorders and psychiatric conditions of basal ganglia origin have significant shortcomings, as well as advances in the understanding of the functional organization of the brain, has led to a renaissance in functional neurosurgery, and particularly the use of deep brain stimulation (DBS). Movement disorders are now routinely being treated with DBS of 'motor' portions of the basal ganglia output nuclei, specifically the subthalamic nucleus and the internal pallidal segment. These procedures are highly effective and generally safe. Use of DBS is also being explored in the treatment of neuropsychiatric disorders, with targeting of the 'limbic' basal ganglia-thalamocortical circuitry. The results of these procedures are also encouraging, but many unanswered questions remain in this emerging field. This review summarizes the scientific rationale and practical aspects of using DBS for neurologic and neuropsychiatric disorders.

Development of the liver during the fetal period

International Nuclear Information System (INIS)

Albay, S.; Malas, Mehmet A.; Cetin, E.; Cankara, N.; Karahan, N.

2005-01-01

To investigate the development of the liver in human fetuses aged between 9-40 weeks. We studied 121 human fetuses (62 males, 59 females) with no external anomalies aged between 9-40 postmenstrual weeks during 2003-2004 in Suleyman Demirel University, Isparta, Turkey. The fetuses were divided into four groups as 1st, 2nd and 3rd trimesters and full term fetuses. We measured fetal weight, length, width, thickness, and volume of the liver. We established localization of the liver and its relation with the neighboring structures, its ligaments, and size of itself and its lobes, shapes of the liver and the localization of the porta hepatis on the visceral surface of the liver. We found significant correlations between the size, weight, volume of the liver, sizes of its lobe and gestational age (p 0.05). However, the proportion of the distance between the porta hepatis and the upper margin to the distance between the porta hepatis and the lower margin decreased significantly with gestational age (p<0.05). Type 3 liver (square) was the most commonly observed type of fetal liver (53%). Our opinion is that the parameters obtained can be useful to diagnose pathologies of liver development and anomalies concerning several branches of medicine such as anatomy, pathologic anatomy (fetopathology), forensic medicine, medical imaging, obstetrics and pediatrics. (author)

Short-term effects of splenectomy on serum fibrosis indexes in liver cirrhosis patients.

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Kong, Degang; Chen, Xiuli; Lu, Shichun; Guo, Qingliang; Lai, Wei; Wu, Jushan; Lin, Dongdong; Zeng, Daobing; Duan, Binwei; Jiang, Tao; Cao, Jilei

2015-01-01

To determine the changing patterns of 4 liver fibrosis markers pre and post splenectomy (combined with pericardial devascularization [PCDV]) and to examine the short-term effects of splenectomy on liver fibrosis. Four liver fibrosis markers of 39 liver cirrhosis patients were examined pre, immediately post, 2 days post, and 1 week post (15 cases) splenectomy (combined with PCDV). The laminin (LN) level decreased immediately post surgery compared with the preoperative LN level (P splenectomy showed characteristic changes, splenectomy may transiently initiate the degradation process of liver fibrosis.

High intensity aerobic exercise training improves chronic intermittent hypoxia-induced insulin resistance without basal autophagy modulation.

Science.gov (United States)

Pauly, Marion; Assense, Allan; Rondon, Aurélie; Thomas, Amandine; Dubouchaud, Hervé; Freyssenet, Damien; Benoit, Henri; Castells, Josiane; Flore, Patrice

2017-03-03

Chronic intermittent hypoxia (IH) associated with obstructive sleep apnea (OSA) is a major risk factor for cardiovascular and metabolic diseases (insulin resistance: IR). Autophagy is involved in the pathophysiology of IR and high intensity training (HIT) has recently emerged as a potential therapy. We aimed to confirm IH-induced IR in a tissue-dependent way and to explore the preventive effect of HIT on IR-induced by IH. Thirty Swiss 129 male mice were randomly assigned to Normoxia (N), Intermittent Hypoxia (IH: 21-5% FiO 2 , 30 s cycle, 8 h/day) or IH associated with high intensity training (IH HIT). After 8 days of HIT (2*24 min, 50 to 90% of Maximal Aerobic Speed or MAS on a treadmill) mice underwent 14 days IH or N. We found that IH induced IR, characterized by a greater glycemia, an impaired insulin sensitivity and lower AKT phosphorylation in adipose tissue and liver. Nevertheless, MAS and AKT phosphorylation were greater in muscle after IH. IH associated with HIT induced better systemic insulin sensitivity and AKT phosphorylation in liver. Autophagy markers were not altered in both conditions. These findings suggest that HIT could represent a preventive strategy to limit IH-induced IR without change of basal autophagy.

AGE WISE HISTOMORPHOLOGICAL CHANGES IN HUMAN LIVER

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Tribeni

2015-11-01

Full Text Available CONTEXT: Hepato cellular carcinoma (HCC results in between 2.5 lakhs to 1million deaths globally per annum. Liver transplantation nowadays is a well accepted treatment option for end-stage liver disease and acute liver failure. AIMS: Keeping this concept in view, a study was conducted in the Guwahati Zone of Northeast India, to compare the histomorphological features of the human liver in different age groups. SETTING AND DESIGN: Apparently healthy livers were obtained from 21 subjects on whom medicolegal post-mortems had been performed. Their ages varied from newborn to 90 years. Subjects were divided into 3 groups. 7 specimens were taken from each group. (1 Pediatric (2 Adult (3 Old age. METHODS AND MATERIALS: In all the above age groups, immediately after removal of the livers, they were washed in normal saline, dried with blotting paper and weighed in an electronic weighing machine. Sections of liver were fixed, processed, cut and stained with Harris Haematoxylin and Eosin stain. RESULTS: The liver loses weight from 50 years onwards. There appears to be racial and environmental differences in the change in liver weight in old age. Autopsy studies show a diminution of nearly 46% in liver weight between the 3rd and 10th decades of life. The liver decreases in size with age. The hepatocytes are radially disposed in the liver lobule. They are piled up, forming a layer one cell thick (except in young children in a fashion similar to the bricks of a wall. These plates are directed from the periphery of the lobule to its centre and anastomose freely forming a complex labyrinthine and sponge-like structure. CONCLUSIONS: From the findings in the present study it can be concluded that: 1. Nowadays, the measurement of liver volume has gained practical use in relation to liver transplantation. 2. We have compared the histomorphology of adult liver with a child. The findings in both the groups are very similar. This feature is important, since in

Basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline.

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Ashida, Terunao; Takato, Tetsuya; Matsuzaki, Gen; Seko, Yoshinori; Fujii, Jun; Kawai, Sachio

2014-01-01

We have recently demonstrated that basal cardiomyopathy develops in rabbits with ventricular tachyarrhythmias that have been induced by electrical stimulation of the cervical vagus. This study investigated whether similar basal cardiomyopathy would develop in rabbits with ventricular tachyarrhythmias induced by a single injection of adrenaline. Adrenaline was intravenously infused for 10-360 seconds in anesthetized rabbits. Colloidal carbon was injected after adrenaline infusion. Wall movement velocity of the left ventricular base was assessed by tissue Doppler echocardiography. Animals were killed either 1 week or 3-4 weeks later. Pathological lesions were identified by deposits of carbon particles. Animals were divided into two groups according to the infused dose of adrenaline. The small-dose group (group S, n = 15) received 1-10 μg and the large-dose group (group L, n = 23) received 15-60 μg of adrenaline. Adrenaline infusion induced premature ventricular contractions followed by monomorphic ventricular tachycardias in 22 of 23 animals in group L, but in only 1 of 15 animals in group S. Wall movement velocity of the left ventricular base decreased just after adrenaline infusion, remained low after 1 week, and recovered to near-baseline levels after 3-4 weeks in group L. Unique cardiac lesions identified by deposits of carbon particles were frequently observed on the left ventricular basal portion, almost always associated with the mitral valve and papillary muscles, but were never observed in the apical area. Lesions involving all areas of the left ventricular basal portion were observed in 22 of 23 animals in group L, but in only 2 of 15 animals in group S. Basal cardiomyopathy developed in rabbits with ventricular tachycardias induced by a single injection of adrenaline.

Ectopic Liver Tissue Formation in Rats with Induced Liver Fibrosis

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Bauyrzhan Umbayev

2014-12-01

�� engraftment, we conducted immunohistochemical staining against HepPar1.Results: We observed a 30% mortality rate among rats with LF within 1 week after NDMA exposure cessation, while 100% of animals with HT survived. ALT, AST, and GGT activities and bilirubin levels were markedly elevated in blood samples of LF rats compared to the control animals. However, HT significantly improved ALT, AST, and GGT activity as well as bilirubin levels. We also observed decreased levels of total protein and albumin in the blood serum of rats with LF, while HT normalized these parameters. At the same time, we have not detected any statistical differences of the studied parameters in the group 4, which was treated with Cyclosporine A only, compared with the intact animals. HepPar1 immunohistochemical staining of the different tissue sections demonstrated the presence of engrafted hepatocytes, mainly within enlarged Peyer's patches (aggregated lymphoid nodules in the lowest portion of the small intestine.Conclusion: The results of our study provide evidence that HT improves animal survival and liver functions. One potential reason for these results is that ectopic hepatic mass inside the Peyer's patches can rescue rats from liver failure.

Histochemical demonstration of two mercury pools in trout tissues: mercury in kidney and liver after mercuric chloride exposure

International Nuclear Information System (INIS)

Baatrup, E.; Nielsen, M.G.; Danscher, G.

1986-01-01

Juvenile rainbow trout (Salmo gairdneri) were exposed to 100 ppb mercury (as HgCl 2 ) in the water for 14 days. Concentrations of mercury in water and fish organs were monitored using radiolabeled mercury. Tissues from kidney and liver were fixed, and sections were developed by autometallography, a method whereby accumulations of mercury sulfides and/or mercury selenides are silver amplified. In the kidney, mercury was found within lysosomes and extracellularly in the basal lamina of proximal tubules. In the liver, mercury was found within lysosomes of the hepatocytes. Additional groups of mercury-exposed trout were subjected to selenium (as Na 2 SeO 3 ), administered intraperitoneally 2 hr before fixation. Following this treatment, additional mercury could be visualized in the kidney circulatory system, including glomeruli, and in the nucleus and endoplasmic reticulum of liver cells. It is suggested that the mercury visualized prior to selenium treatment represents inorganic mercury, while additional mercury visualized after selenium administration represents an organic form

Depressed levels of prostaglandin F2α in mice lacking Akr1b7 increase basal adiposity and predispose to diet-induced obesity.

Science.gov (United States)

Volat, Fanny E; Pointud, Jean-Christophe; Pastel, Emilie; Morio, Béatrice; Sion, Benoit; Hamard, Ghislaine; Guichardant, Michel; Colas, Romain; Lefrançois-Martinez, Anne-Marie; Martinez, Antoine

2012-11-01

Negative regulators of white adipose tissue (WAT) expansion are poorly documented in vivo. Prostaglandin F(2α) (PGF(2α)) is a potent antiadipogenic factor in cultured preadipocytes, but evidence for its involvement in physiological context is lacking. We previously reported that Akr1b7, an aldo-keto reductase enriched in adipose stromal vascular fraction but absent from mature adipocytes, has antiadipogenic properties possibly supported by PGF(2α) synthase activity. To test whether lack of Akr1b7 could influence WAT homeostasis in vivo, we generated Akr1b7(-/-) mice in 129/Sv background. Akr1b7(-/-) mice displayed excessive basal adiposity resulting from adipocyte hyperplasia/hypertrophy and exhibited greater sensitivity to diet-induced obesity. Following adipose enlargement and irrespective of the diet, they developed liver steatosis and progressive insulin resistance. Akr1b7 loss was associated with decreased PGF(2α) WAT contents. Cloprostenol (PGF(2α) agonist) administration to Akr1b7(-/-) mice normalized WAT expansion by affecting both de novo adipocyte differentiation and size. Treatment of 3T3-L1 adipocytes and Akr1b7(-/-) mice with cloprostenol suggested that decreased adipocyte size resulted from inhibition of lipogenic gene expression. Hence, Akr1b7 is a major regulator of WAT development through at least two PGF(2α)-dependent mechanisms: inhibition of adipogenesis and lipogenesis. These findings provide molecular rationale to explore the status of aldo-keto reductases in dysregulations of adipose tissue homeostasis.

Acute effects of organotins on brain, liver and kidney in rats

Energy Technology Data Exchange (ETDEWEB)

Dwivedi, R.S.; Kaur, G.; Srivastava, R.C.; Srivastava, T.N.

1985-01-01

Effects of dioctyltin oxide (DOTO) tricyclohexyltin hydroxide (TCHTOH) and tributyltin oxide (TBTO) were examined on some enzymic activities in liver and kidney and biogenic amines level in brain of rats at 24 hours after single subcutaneous administration (25 ..mu..mole/100 g B. Wt.). All the organotin compounds produced a significant increase in the activity of alkaline phosphatase and adenosin triphosphatase and decrease in monoamine oxidase in both liver and kidney. DOTO and TCHTOH were more effective in impairing the activity of succinate dehydrogenase in liver. Concentrations of ..gamma..-aminobutyric acid (GABA) and dopamine were found to be significantly decreased in brain however, acetylcholine concentration remained unaltered. These results suggest that organotin compounds DOTO and TCHTOH are more toxic to rats than TBTO. 30 references, 3 tables.

Basal Serum Calcitonin, After Calcium Stimulation, and in the Needle Washout of Patients with Thyroid Nodules and Mild or Moderate Basal Hypercalcitoninemia.

Science.gov (United States)

Rosario, P W; Calsolari, M R

2017-02-01

This prospective study evaluated the concentrations of basal serum calcitonin (Ctn), Ctn after stimulation with calcium, and Ctn in the needle washout (FNA-Ctn) as predictors of sporadic medullary thyroid carcinoma (MTC) in patients with thyroid nodules and basal Ctn between 10 and 100 pg/ml. Forty-one patients were included in the study. MTC was diagnosed in only 6 patients (14.6%). None of the patients with basal Ctn≤24.6 pg/ml (n=26) or stimulated Ctn≤186.5 pg/ml (n=21) had MTC. All patients without MTC had basal Ctnstimulated Ctnbasal Ctn between 24.6 and 47 pg/ml (n=12), 3 (25%) had MTC. Among patients with stimulated Ctn between 186.5 and 655.2 pg/ml (n=18), 4 (22.2%) had MTC. FNA-Ctn distinguished nodules that were MTC (n=6) from those that were not (n=60), without overlapping results. In the calcium stimulation test, 19 patients (46.3%) reported some adverse effect, but none of them was severe or required specific treatment. Our results highlight that in patients without a history suspicious for MTC, mild or moderate basal hypercalcitoninemia should not establish the diagnosis of this tumor. Depending on the concentration found, basal Ctn should be sufficient to define patient management. In doubtful cases, FNA-Ctn seems to be the best diagnostic test. Calcium stimulation testing was safe, but more studies are needed to determine the Ctn cutoff after stimulation with calcium. © Georg Thieme Verlag KG Stuttgart · New York.

Estimation of liver glucose metabolism after refeeding

International Nuclear Information System (INIS)

Rognstad, R.

1987-01-01

Refeeding or infusing glucose to rats fasted for 24 hr or more causes rapid liver glycogen synthesis, the carbon source now considered to be largely from gluconeogenesis. While substrate cycling between plasma glucose and liver glucose-6P is known to occur, this cycling has apparently been ignored when calculations are made of % contribution of direct and indirect pathways to liver glycogen synthesis, or when hepatic glucose output is calculated from glucose turnover minus the glucose infusion rate. They show that, isotopically, an estimate of the fluxes of liver glucokinase and glucose-6-phosphatase is required to quantitate sources of carbon for liver glycogen synthesis, and to measure hepatic glucose output (or uptake). They propose a method to estimate these fluxes, involving a short infusion of a 14 C labelled gluconeogenic precursor plus (6T)glucose, with determination of isotopic yields in liver glycogen and total glucose. Given also the rate of liver glycogen synthesis, this procedure permits the estimation of net gluconeogenesis and hepatic glucose output or uptake. Also, in vitro evidence against the notion of a drastic zonation of liver carbohydrate metabolism is presented, e.g. raising the glucose concentration from 10 to 25 mM increases the 14 C yield from H 14 CO 3 - in lactate, with the increased pyruvate kinase flux and decreased gluconeogenesis occurring in the same cell type, not opposing pathways in different hepatocyte types (as has been postulated by some to occur in vivo after refeeding

Effect of an 8-week practice of externally triggered speech on basal ganglia activity of stuttering and fluent speakers.

Science.gov (United States)

Toyomura, Akira; Fujii, Tetsunoshin; Kuriki, Shinya

2015-04-01

The neural mechanisms underlying stuttering are not well understood. It is known that stuttering appears when persons who stutter speak in a self-paced manner, but speech fluency is temporarily increased when they speak in unison with external trigger such as a metronome. This phenomenon is very similar to the behavioral improvement by external pacing in patients with Parkinson's disease. Recent imaging studies have also suggested that the basal ganglia are involved in the etiology of stuttering. In addition, previous studies have shown that the basal ganglia are involved in self-paced movement. Then, the present study focused on the basal ganglia and explored whether long-term speech-practice using external triggers can induce modification of the basal ganglia activity of stuttering speakers. Our study of functional magnetic resonance imaging revealed that stuttering speakers possessed significantly lower activity in the basal ganglia than fluent speakers before practice, especially when their speech was self-paced. After an 8-week speech practice of externally triggered speech using a metronome, the significant difference in activity between the two groups disappeared. The cerebellar vermis of stuttering speakers showed significantly decreased activity during the self-paced speech in the second compared to the first experiment. The speech fluency and naturalness of the stuttering speakers were also improved. These results suggest that stuttering is associated with defective motor control during self-paced speech, and that the basal ganglia and the cerebellum are involved in an improvement of speech fluency of stuttering by the use of external trigger. Copyright © 2015 Elsevier Inc. All rights reserved.

Subcutaneous insulin infusion: change in basal infusion rate has no immediate effect on insulin absorption rate

International Nuclear Information System (INIS)

Hildebrandt, P.; Birch, K.; Jensen, B.M.; Kuehl, C.

1986-01-01

Eight insulin-dependent diabetic patients were simultaneously given subcutaneous infusions (1.12 IU/h each) of 125 I-labeled Actrapid insulin in each side of the abdominal wall. After 24 h of infusion, the size of the infused insulin depots was measured by external counting for 5 h. The basal infusion rate was then doubled in one side and halved in the other for the next 4 h. Finally, 1.12 IU/h of insulin was given in both sides of the abdominal wall for an additional 3 h. The changes in the size of the depots were measured, and the absorption rates for each hour were calculated. During the first 5 h of infusion, the depot size was almost constant (approximately 5 IU) with an absorption rate that equaled the infusion rate. Doubling the infusion rate led to a significant increase in depot size, but the absorption rate remained unchanged for the first 3 h, and only thereafter was a significant increase seen. When the infusion rate was reduced to the initial 1.12 IU/h, the absorption rate remained elevated during the next 3 h. Correspondingly, when the infusion rate was decreased, the depot size also decreased, but the absorption rate remained unchanged for the first 3 h. The results show that a change in the basal insulin infusion rate does not lead to any immediate change in the insulin absorption rate. This should be considered when planning an insulin-infusion program that includes alteration(s) in the basal-rate setting

Lipidomic changes in rat liver after long-term exposure to ethanol

International Nuclear Information System (INIS)

Fernando, Harshica; Bhopale, Kamlesh K.; Kondraganti, Shakuntala; Kaphalia, Bhupendra S.; Shakeel Ansari, G.A.

2011-01-01

Alcoholic liver disease (ALD) is a serious health problem with significant morbidity and mortality. In this study we examined the progression of ALD along with lipidomic changes in rats fed ethanol for 2 and 3 months to understand the mechanism, and identify possible biomarkers. Male Fischer 344 rats were fed 5% ethanol or caloric equivalent of maltose-dextrin in a Lieber-DeCarli diet. Animals were killed at the end of 2 and 3 months and plasma and livers were collected. Portions of the liver were fixed for histological and immunohistological studies. Plasma and the liver lipids were extracted and analyzed by nuclear magnetic resonance (NMR) spectroscopy. A time dependent fatty infiltration was observed in the livers of ethanol-fed rats. Mild inflammation and oxidative stress were observed in some ethanol-fed rats at 3 months. The multivariate and principal component analysis of proton and phosphorus NMR spectroscopy data of extracted lipids from the plasma and livers showed segregation of ethanol-fed groups from the pair-fed controls. Significant hepatic lipids that were increased by ethanol exposure included fatty acids and triglycerides, whereas phosphatidylcholine (PC) decreased. However, both free fatty acids and PC decreased in the plasma. In liver lipids unsaturation of fatty acyl chains increased, contrary to plasma, where it decreased. Our studies confirm that over-accumulation of lipids in ethanol-induced liver steatosis accompanied by mild inflammation on long duration of ethanol exposure. Identified metabolic profile using NMR lipidomics could be further explored to establish biomarker signatures representing the etiopathogenesis, progression and/or severity of ALD. - Highlights: → Long term exposure to ethanol was studied. → A nuclear magnetic resonance (NMR) spectroscopy based lipidomic approach was used. → We examined the clustering pattern of the NMR data with principal component analysis. → NMR data were compared with histology and

Endocrine-Manifestations of Cirrhosis and Liver Disease

Directory of Open Access Journals (Sweden)

M Khalili

2014-04-01

Full Text Available The liver is involved in the synthesis and metabolism of many kinds of hormones, various abnormalities hormone levels are found in advanced liver disease. For example the liver is, extremely sensitive to changes in insulin or glucagon levels. The liver is the primary organ of iron storage is frequently involved, diabetes is common in patients with iron overload and may be seen in cirrhosis. Chronic infection with HCV is associated with insulin resistance. Thyroid disease often accompanies chronic hepatitis C infection .Anti thyroid autoantibodies are also found in chronic HCV infection. Nonalcoholic liver disease (NAFLDas a most common cause of chronic liver disease in western world ,as well accompanied by Type 2 diabetes and hyperlipidemia. Hypopituitarism and hypothyroidism also have been in NAFLD.The patients with NAFLD and Hypopituitarism may be susceptible to central obesity, dyslipidemia and insulin resistance leading to disease progression. Hepatic cirrhosis as the end stage of chronic liver disease is also associated with hypogonadism and signs of feminization. The peripheral metabolism of steroids is altered in many of hypogonadism, low testosterone level decreased libido, infertility, reduced secondary sex hair and gynecomastia, reduced spermatogenesis and peritubular fibrosis are found in men with cirrhosis .The normal function of the hypothalamic-pituitary gonadal axis is affected in liver disease. In cirrhotic patients the estrogen/androgen ratio is usually increased, the level of testosterone and dihydroepiandosteron are reduced while the estradiol level are normal or slightly elevated, these alterations are dependent on the severity of the liver disease.Succsesfull orthotropic liver transplantation  leads to improvement of the sex hormone disturbances. The pathogenesis of gynecomastia is due to the loss of equilibrium between estrogen and androgen caused by a feminizing state but it is due to increased estrogen precursor in

The role of Foxp3+ regulatory T cells in liver transplant tolerance.

Science.gov (United States)

Li, W; Carper, K; Zheng, X X; Kuhr, C S; Reyes, J D; Liang, Y; Perkins, D L; Thomson, A W; Perkins, J D

2006-12-01

The liver has long been considered a tolerogenic organ that favors the induction of peripheral tolerance. The mechanisms underlying liver tolerogenicity remain largely undefined. In this study, we characterized Foxp3-expressing CD4+ CD25+ regulatory T cells (Treg) in liver allograft recipients and examined the role of Treg in inherent liver tolerogenicity by employing the mouse spontaneous liver transplant tolerance model. Orthotopic liver transplantation was performed from C57BL/10 (H2b) to C3H/HeJ (H2k) mice. The percentage of CD4+ CD25+ Treg was expanded in the liver grafts and recipient spleens from day 5 up to day 100 posttransplantation, associated with high intracellular Foxp3 and CTLA4 expression. Immunohistochemistry further demonstrated significant numbers of Foxp3+ cells in the liver grafts and recipient spleens and increased transforming growth factor beta expression in the recipient spleens throughout the time courses. Adoptive transfer of spleen cells from the long-term liver allograft survivors significantly prolonged donor heart graft survival. Depletion of recipient CD4+ CD25+ Treg using anti-CD25 monoclonal antibody (250 microg/d) induced acute liver allograft rejection, associated with elevated anti-donor T-cell proliferative responses, CTL and natural killer activities, enhanced interleukin (IL)-2, interferon-gamma, IL-10, and decreased IL-4 production, and decreased T-cell apoptotic activity in anti-CD25-treated recipients. Moreover, CTLA4 blockade by anti-CTLA4 monoclonal antibody administration exacerbated liver graft rejection when combined with anti-CD25 monoclonal antibody. Thus, Foxp3+ CD4+ CD25+ Treg appear to underpin spontaneous acceptance of major histocompatability complex- mismatched liver allografts in mice. CTLA4, IL-4, and apoptosis of alloreactive T cells appear to contribute to the function of Treg and regulation of graft outcome.

Airway Basal Cell Heterogeneity and Lung Squamous Cell Carcinoma.

Science.gov (United States)

Hynds, Robert E; Janes, Sam M

2017-09-01

Basal cells are stem/progenitor cells that maintain airway homeostasis, enact repair following epithelial injury, and are a candidate cell-of-origin for lung squamous cell carcinoma. Heterogeneity of basal cells is recognized in terms of gene expression and differentiation capacity. In this Issue, Pagano and colleagues isolate a subset of immortalized basal cells that are characterized by high motility, suggesting that they might also be heterogeneous in their biophysical properties. Motility-selected cells displayed an increased ability to colonize the lung in vivo The possible implications of these findings are discussed in terms of basal cell heterogeneity, epithelial cell migration, and modeling of metastasis that occurs early in cancer evolution. Cancer Prev Res; 10(9); 491-3. ©2017 AACR See related article by Pagano et al., p. 514 . ©2017 American Association for Cancer Research.

Liver scanning in diffuse liver disease

International Nuclear Information System (INIS)

Aiginger, P.; Atefie, K.; Scherak, O.; Wolf, A.; Hoefer, R.; Seyfried, H.

1975-01-01

The results of liver scans performed with sup(99m)Tc-sulphur colloid in 169 patients suffering from diffuse liver diseases and in 48 normal controls were evaluated. The patients with reactive hepatitis, acute hepatitis, chronic persistent hepatitis, fatty liver and fibrosis of the liver show only minimal deviations from the scintigraphic pattern. On the contrary, highly increased colloid uptake in the spleen is found in cases of chronic aggressive hepatitis, whilst the intrahepatic distribution of the colloid is approximately normal. In cases of liver cirrhosis, increased colloid uptake is found in the left lobe of the liver as well as in the spleen and in the bone marrow. Either normal findings or cirrhosis-like changes of the colloid distribution are observed in patients with alcoholic hepatitis. (orig.) [de

Coeliac disease and the liver: spectrum of liver histology, serology and treatment response at a tertiary referral centre.

Science.gov (United States)

Majumdar, Kaushik; Sakhuja, Puja; Puri, Amarender Singh; Gaur, Kavita; Haider, Aiman; Gondal, Ranjana

2018-05-01

Coeliac disease (CD) is a gluten-sensitive enteropathy diagnosed on the basis of ESPGHAN criteria and clinical response to gluten-free diet (GFD). Histological abnormalities on liver biopsy have been noted in CD but have seldom been described. To assess the histological spectrum of 'coeliac hepatitis' and possibility of reversal of such features after a GFD. Twenty-five patients with concomitant CD and hepatic derangement were analysed for clinical profile, laboratory investigations and duodenal and liver biopsy. A histological comparison of pre- and post-GFD duodenal and liver biopsies was carried out, wherever possible. Fifteen patients presenting with CD subsequently developed abnormal liver function tests; 10 patients presenting with liver disease were found to have tissue positive transglutaminase in 70% and antigliadin antibodies in 60%. Serological markers for autoimmune liver disease (AILD) were positive in eight patients. Liver histology ranged from mild reactive hepatitis, chronic hepatitis, steatosis to cirrhosis. Liver biopsies after a GFD were available in six cases, of which five showed a decrease in steatosis, portal and lobular inflammation and fibrosis score. Coeliac hepatitis could be a distinct entity and the patients may present with either CD or secondary hepatic derangement. Evaluation for the presence of CD is recommended for patients presenting with AILD, unexplained transaminasaemia or anaemia. This is one of the very few studies demonstrating the continuum of liver histological changes in 'coeliac hepatitis'. Trial of a GFD may result in clinicopathological improvement of 'coeliac hepatitis'. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Use of basal stimulation at anesthesiology department

OpenAIRE

MARKOVÁ, Alena

2012-01-01

The theme ?The Use of Basal Stimulation at the Anaesthesiology and Resuscitation Department? was chosen in order to map out the use of this nursing method by the nurses and the staff who I cooperate with. The theoretical part deals with the environment at the Anaesthesiology and Resuscitation Department where the basal stimulation is used and also with special characteristics of the nursing care. Further, it deals with monitoring patients, causes of consciousness defects occurrence and kinds ...

Relative contribution of glycogenolysis and gluconeogenesis to basal, glucagon- and nerve stimulation-dependent glucose output in the perfused liver from fed and fasted rats

NARCIS (Netherlands)

Beuers, U.; JUNGERMANN, K.

1990-01-01

The relative contribution to basal, glucagon- and nerve stimulation-enhanced glucose output of glycogenolysis (glucose output in the presence of the gluconeogenic inhibitor mercaptopicolinate) and gluconeogenesis (difference in glucose output in the absence and presence of the inhibitor) was

AGE-modified basement membrane cooperates with Endo180 to promote epithelial cell invasiveness and decrease prostate cancer survival

DEFF Research Database (Denmark)

Rodriguez-Teja, Mercedes; Gronau, Julian H; Breit, Claudia

2015-01-01

Biomechanical strain imposed by age-related thickening of the basal lamina and augmented tissue stiffness in the prostate gland coincides with increased cancer risk. Here we hypothesized that the structural alterations in the basal lamina associated with age can induce mechanotransduction pathways...... in prostate epithelial cells (PECs) to promote invasiveness and cancer progression. To demonstrate this, we developed a 3D model of PEC acini in which thickening and stiffening of basal lamina matrix was induced by advanced glycation end-product (AGE)-dependent non-enzymatic crosslinking of its major......(Δ) (Ex2-6/) (Δ) (Ex2-6) mice, with constitutively exposed CTLD2 and decreased survival of men with early (non-invasive) prostate cancer with high epithelial Endo180 expression and levels of AGE. These findings indicate that AGE-dependent modification of the basal lamina induces invasive behaviour...

[Comparison between basal insulin glargine and NPH insulin in patients with diabetes type 1 on conventional intensive insulin therapy].

Science.gov (United States)

Pesić, Milica; Zivić, Sasa; Radenković, Sasa; Velojić, Milena; Dimić, Dragan; Antić, Slobodan

2007-04-01

Insulin glargine is a long-acting insulin analog that mimics normal basal insulin secretion without pronounced peaks. The aim of this study was to compare insulin glargine with isophane insulin (NPH insulin) for basal insulin supply in patients with type 1 diabetes. A total of 48 type 1 diabetics on long term conventional intensive insulin therapy (IT) were randomized to three different regimens of basal insulin substitution: 1. continuation of NPH insulin once daily at bedtime with more intensive selfmonitoring (n = 15); 2. NPH insulin twice daily (n = 15); 3. insulin glargine once daily (n = 18). Meal time insulin aspart was continued in all groups. Fasting blood glucose (FBG) was lower in the glargine group (7.30+/-0.98 mmol/1) than in the twice daily NPH group (7.47+/-1.06 mmol/1), but without significant difference. FBG was significantly higher in the once daily NPH group (8.44+/-0.85 mmol/l; p < 0.05). HbAlc after 3 months did not change in the once daily NPH group, but decreased in the glargine group (from 7.72+/-0.86% to 6.87+/-0.50%), as well as in the twice daily NPH group (from 7.80+/-0.83% to 7.01+/-0.63%). Total daily insulin doses were similar in all groups but only in the glargine group there was an increase of basal and decrease of meal related insulin doses. The frequency of mild hypoglycemia was significantly lower in the glargine group (6.56+/-2.09) than in both NPH groups (9.0+/-1.65 in twice daily NPH group and 8.13+/-1.30 in other NPH group) (episodes/patients-month, p < 0.05). Basal insulin supplementation in type 1 diabetes mellitus with either twice daily NPH insulin or glargine can result in similar glycemic control when combined with meal time insulin aspart. However, with glargine regimen FBG, HbAlc and frequency of hypoglycemic event are lower. These facts contribute to better patients satisfaction with insulin glargine versus NPH insulin in IIT in type 1 diabetics.

Liver regeneration and restoration of liver function after partial hepatectomy in patients with liver tumors

International Nuclear Information System (INIS)

Jansen, P.L.M.; Chamuleau, R.A.F.; Leeuwen, D.J. van; Schippor, H.G.; Busemann-Sokole, E.; Heyde, M.N. van der

1990-01-01

Liver regeneration and restoration of liver function were studied in six patients who underwent partial hepatectomy with removal of 30-70% of the liver. Liver volume and liver regeneration were studied by single photon computed tomography (SPECT), using 99m Tc-colloid as tracer. The method was assessed in 11 patients by comparing the pre- and post-operative volume measurement with the volume of the resected liver mass. Liver function was determined by measuring the galactose elimination capacity and the caffeine clearance. After a postoperative follow-up period of 50 days, the liver had regenerated maximally to a volume of 75 ± 2% of the preoperative liver mass. Maximal restoration of liver function was achieved 120 days after operation and amounted to 75 ± 10% for the caffeine clearance and to 100 ± 25% for the galactose elimination capacity. This study shows that SPECT is a useful method for assessing liver regeneration in patients after partial hepatectomy. The study furthermore shows that caffeine clearance correlates well with total liver volume, whereas the galactose elimination capacity overestimates total liver volume after partial hepatectomy. 22 refs

Supplementation of xanthophylls decreased proinflammatory and increased anti-inflammatory cytokines in hens and chicks.

Science.gov (United States)

Gao, Yu-Yun; Xie, Qing-Mei; Jin, Ling; Sun, Bao-Li; Ji, Jun; Chen, Feng; Ma, Jing-Yun; Bi, Ying-Zuo

2012-11-28

The present study investigated the effects of xanthophylls (containing 40 % of lutein and 60 % of zeaxanthin) on proinflammatory cytokine (IL-1β, IL-6, interferon (IFN)-γ and lipopolysaccharide-induced TNF-α factor (LITAF)) and anti-inflammatory cytokine (IL-4 and IL-10) expression of breeding hens and chicks. In Expt 1, a total of 432 hens were fed diets supplemented with 0 (as the control group), 20 or 40 mg/kg xanthophylls (six replicates per treatment). The liver, duodenum, jejunum and ileum were sampled at 35 d of the trial. The results showed that both levels of xanthophyll addition decreased IL-1β mRNA in the liver and jejunum, IL-6 mRNA in the liver, IFN-γ mRNA in the jejunum and LITAF mRNA in the liver compared to the control group. Expt 2 was a 2 × 2 factorial design. Male chicks hatched from 0 or 40 mg/kg xanthophyll diet of hens were fed a diet containing either 0 or 40 mg/kg xanthophylls. The liver, duodenum, jejunum and ileum were collected at 0, 7, 14 and 21 d after hatching. The results showed that in ovo xanthophylls decreased proinflammatory cytokine expression (IL-1β, IL-6, IFN-γ and LITAF) in the liver, duodenum, jejunum and ileum and increased anti-inflammatory cytokine expression (IL-4 and IL-10) in the liver, jejunum and ileum mainly at 0-7 d after hatching. In ovo effects gradually vanished and dietary effects began to work during 1-2 weeks after hatching. Dietary xanthophylls modulated proinflammatory cytokines (IL-1β, IL-6 and IFN-γ) in the liver, duodenum, jejunum and ileum and anti-inflammatory cytokine (IL-10) in the liver and jejunum mainly from 2 weeks onwards. In conclusion, xanthophylls could regulate proinflammatory and anti-inflammatory cytokine expression in different tissues of hens and chicks.

Complex Dynamics in the Basal Ganglia: Health and Disease Beyond the Motor System.

Science.gov (United States)

Andres, Daniela S; Darbin, Olivier

2018-01-01

The rate and oscillatory hypotheses are the two main current frameworks of basal ganglia pathophysiology. Both hypotheses have emerged from research on movement disorders sharing similar conceptualizations. These pathological conditions are classified either as hypokinetic or hyperkinetic, and the electrophysiological hallmarks of basal ganglia dysfunction are categorized as prokinetic or antikinetic. Although nonmotor symptoms, including neurobehavioral symptoms, are a key manifestation of basal ganglia dysfunction, they are uncommonly accounted for in these models. In patients with Parkinson's disease, the broad spectrum of motor symptoms and neurobehavioral symptoms challenges the concept that basal ganglia disorders can be classified into two categories. The profile of symptoms of basal ganglia dysfunction is best characterized by a breakdown of information processing, accompanied at an electrophysiological level by complex alterations of spiking activity from basal ganglia neurons. The authors argue that the dynamics of the basal ganglia circuit cannot be fully characterized by linear properties such as the firing rate or oscillatory activity. In fact, the neuronal spiking stream of the basal ganglia circuit is irregular but has temporal structure. In this context, entropy was introduced as a measure of probabilistic irregularity in the temporal organization of neuronal activity of the basal ganglia, giving place to the entropy hypothesis of basal ganglia pathology. Obtaining a quantitative characterization of irregularity of spike trains from basal ganglia neurons is key to elaborating a new framework of basal ganglia pathophysiology.

Stereotactic Body Radiation Therapy for Patients with Heavily Pretreated Liver Metastases and Liver Tumors

Energy Technology Data Exchange (ETDEWEB)

Lanciano, Rachelle; Lamond, John; Yang, Jun; Feng, Jing; Arrigo, Steve; Good, Michael; Brady, Luther, E-mail: rlancmd@gmail.com [Philadelphia CyberKnife, Drexel University, Havertown, PA (United States)

2012-03-09

We present our initial experience with CyberKnife stereotactic body radiation therapy (SBRT) in a heavily pretreated group of patients with liver metastases and primary liver tumors. From October 2007 to June 2009, 48 patients were treated at the Philadelphia CyberKnife Center for liver metastases or primary liver tumors. We report on 30 patients with 41 discrete lesions (1–4 tumors per patient) who received an ablative radiation dose (BED ≥ 79.2 Gy10 = 66 Gy EQD2). The treatment goal was to achieve a high SBRT dose to the liver tumor while sparing at least 700 cc of liver from radiation doses above 15 Gy. Twenty-three patients were treated with SBRT for metastatic cancer to the liver; the remainder (n = 7) were primary liver tumors. Eighty-seven percent of patients had prior systemic chemotherapy with a median 24 months from diagnosis to SBRT; 37% had prior liver directed therapy. Local control was assessed for 28 patients (39 tumors) with 4 months or more follow-up. At a median follow-up of 22 months (range, 10–40 months), 14/39 (36%) tumors had documented local failure. A decrease in local failure was found with higher doses of SBRT (p = 0.0237); 55% of tumors receiving a BED ≤ 100 Gy10 (10/18) had local failure compared with 19% receiving a BED > 100 Gy10 (4/21). The 2-year actuarial rate of local control for tumors treated with BED > 100 Gy10 was 75% compared to 38% for those patients treated with BED ≤ 100 Gy10 (p = 0.04). At last follow-up, 22/30 patients (73%) had distant progression of disease. Overall, seven patients remain alive with a median survival of 20 months from treatment and 57 months from diagnosis. To date, no patient experienced persistent or severe adverse effects. Despite the heavy pretreatment of these patients, SBRT was well tolerated with excellent local control rates when adequate doses (BED > 100 Gy10) were used. Median survival was limited secondary to development of further metastatic disease in the majority of patients.

Reliability of basal plasma vasopressin concentrations in healthy male adults.

Science.gov (United States)

Quintana, Daniel S; Westlye, Lars T; Smerud, Knut T; Mahmoud, Ramy A; Djupesland, Per G; Andreassen, Ole A

2017-10-01

The neuropeptides oxytocin (OT) and arginine vasopressin (AVP) play important and interrelated roles in modulating mammalian social behaviour. While the OT system has received considerable research attention for its potential to treat psychiatric symptoms, comparatively little is known about the role of the AVP system in human social behaviour. To better understand the intraindividual stability of basal AVP, the present study assessed the reproducibility of basal plasma AVP concentrations. Basal plasma AVP was assessed at four sampling points separated by 8 days, on average, in 16 healthy adult males. Only one out of six comparisons revealed strong evidence for reproducibility of basal AVP concentrations (visit 2 vs. visit 4: r=0.8, p0.1). The concordance correlation coefficient [0.15, 95% CI (-0.55, 0.73)] also revealed poor overall reproducibility. Poor reliability of basal AVP concentrations suggests future work covarying AVP with trait markers should proceed with careful consideration of intraindividual fluctuations.

Human germline hedgehog pathway mutations predispose to fatty liver.

Science.gov (United States)

Guillen-Sacoto, Maria J; Martinez, Ariel F; Abe, Yu; Kruszka, Paul; Weiss, Karin; Everson, Joshua L; Bataller, Ramon; Kleiner, David E; Ward, Jerrold M; Sulik, Kathleen K; Lipinski, Robert J; Solomon, Benjamin D; Muenke, Maximilian

2017-10-01

Non-alcoholic fatty liver disease (NAFLD) is the most common form of liver disease. Activation of hedgehog (Hh) signaling has been implicated in the progression of NAFLD and proposed as a therapeutic target; however, the effects of Hh signaling inhibition have not been studied in humans with germline mutations that affect this pathway. Patients with holoprosencephaly (HPE), a disorder associated with germline mutations disrupting Sonic hedgehog (SHH) signaling, were clinically evaluated for NAFLD. A combined mouse model of Hh signaling attenuation (Gli2 heterozygous null: Gli2 +/- ) and diet-induced NAFLD was used to examine aspects of NAFLD and hepatic gene expression profiles, including molecular markers of hepatic fibrosis and inflammation. Patients with HPE had a higher prevalence of liver steatosis compared to the general population, independent of obesity. Exposure of Gli2 +/- mice to fatty liver-inducing diets resulted in increased liver steatosis compared to wild-type mice. Similar to humans, this effect was independent of obesity in the mutant mice and was associated with decreased expression of pro-fibrotic and pro-inflammatory genes, and increased expression of PPARγ, a potent anti-fibrogenic and anti-inflammatory regulator. Interestingly, tumor suppressors p53 and p16INK4 were found to be downregulated in the Gli2 +/- mice exposed to a high-fat diet. Our results indicate that germline mutations disrupting Hh signaling promotes liver steatosis, independent of obesity, with reduced fibrosis. While Hh signaling inhibition has been associated with a better NAFLD prognosis, further studies are required to evaluate the long-term effects of mutations affecting this pathway. Lay summary: Non-alcoholic fatty liver disease (NAFLD) is characterized by excess fat deposition in the liver predominantly due to high calorie intake and a sedentary lifestyle. NAFLD progression is usually accompanied by activation of the Sonic hedgehog (SHH) pathway leading to fibrous

The most important physiological constants among the Volga region long-livers

Science.gov (United States)

Malinova, L. I.; Shuvalov, S. S.; Denisova, T. P.

2012-03-01

In our research we brought out the age difference in the group of long-livers and the continuous character of the biochemical basal metabolism indexes changing. The results allowed us to carry out the polynominal high-powered approximation to study the dynamics of laboratory indexes. We revealed the progressive reduction of the cholesterol, triglycerides, glucose and creatinine levels starting from 90 years of age, and this reduction showed the non-linear character with interchange of local minimums and maximums. During the speed characteristics analysis we revealed the cooccurrence of the speed maximums of all the examined biochemical indexes, except the speed of changing the concentration of cholesterol, which maximum took the lead over the other indexes by four years. The phase-plane portrait analysis of the regulatory systems on the plane "time - speed" showed the unfulfilled attempt of system stabilization by all the searched parameters nearby the special spot - "stable focus". The standard deviation values analysis of the researched parameters showed their progressive reduction in the long-livers. That fact can be considered as the regulatory systems physiological "backlash" reduction among the centenarians.

Seasonal variations in PM composition from Beijing, China drive liver oxidative stress

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Pardo, M.; Rudich, Y.

2017-12-01

Air pollution can cause oxidative stress, inflammation and adverse health effects, but the underlying biological mechanisms are not completely understood. In order to understand how seasonal and chemical variations drive health impacts, we investigated the oxidative stress and inflammation in mice exposed to extracts (water and DCM) from urban PM collected in Beijing (China). Higher levels of pollution components were detected in the heating season (HS, winter) than in the non-heating season (NHS, summer). Higher concentrations of PM were measured in the heating season, mostly from coal and wood burning used for domestic heating. This was accompanied by increased levels of polyaromatic hydrocarbons (PAHs) in the DCM extracts. An increased inflammatory response was detected in the lung and liver with DCM extracts compared to the water extracts, and mostly in the winter aerosol. Reduced antioxidant response was observed in the lung, whereas it was activated in the liver. Gene expression of the Nrf2 transcription factor (A master regulator of stress response that controls the basal oxidative capacity and induces the expression of antioxidant response) and its related genes were induced. In the liver, higher levels of lipid peroxidation adducts were measured, correlated with histologic analysis that revealed morphologic features of damage/proliferation in the liver, indicating oxidative and toxic damage. Altogether, our study suggests that the acute effects of PM can vary by the season with the largest effect observed in winter than summer in Beijing, and that some secondary organs may be susceptible for exposure damage. This suggests that the liver is a potential organ to be influenced from PM especially by PAHs

Chronic intermittent hypoxia predisposes to liver injury.

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Savransky, Vladimir; Nanayakkara, Ashika; Vivero, Angelica; Li, Jianguo; Bevans, Shannon; Smith, Philip L; Torbenson, Michael S; Polotsky, Vsevolod Y

2007-04-01

Obstructive sleep apnea (OSA) is characterized by chronic intermittent hypoxia (CIH). OSA is associated with nonalcoholic steatohepatitis (NASH) in obese subjects. The aim of this study was to investigate the effects of CIH on the liver in the absence of obesity. Lean C57BL/6J mice (n = 15) on a regular chow diet were exposed to CIH for 12 weeks and compared with pair-fed mice exposed to intermittent air (IA, n = 15). CIH caused liver injury with an increase in serum ALT (224 +/- 39 U/l versus 118 +/- 22 U/l in the IA group, P fasting serum insulin levels, and mild elevation of fasting serum total cholesterol and triglycerides (TG). Liver TG content was unchanged, whereas cholesterol content was decreased. Histology showed swelling of hepatocytes, no evidence of hepatic steatosis, and marked accumulation of glycogen in hepatocytes. CIH led to lipid peroxidation of liver tissue with a malondialdehyde (MDA)/free fatty acids (FFA) ratio of 0.54 +/- 0.07 mmol/mol versus 0.30 +/- 0.01 mmol/mol in control animals (P obesity, CIH leads to mild liver injury via oxidative stress and excessive glycogen accumulation in hepatocytes and sensitizes the liver to a second insult, whereas NASH does not develop.

Citric acid effects on brain and liver oxidative stress in lipopolysaccharide-treated mice.

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Abdel-Salam, Omar M E; Youness, Eman R; Mohammed, Nadia A; Morsy, Safaa M Youssef; Omara, Enayat A; Sleem, Amany A

2014-05-01

Citric acid is a weak organic acid found in the greatest amounts in citrus fruits. This study examined the effect of citric acid on endotoxin-induced oxidative stress of the brain and liver. Mice were challenged with a single intraperitoneal dose of lipopolysaccharide (LPS; 200 μg/kg). Citric acid was given orally at 1, 2, or 4 g/kg at time of endotoxin injection and mice were euthanized 4 h later. LPS induced oxidative stress in the brain and liver tissue, resulting in marked increase in lipid peroxidation (malondialdehyde [MDA]) and nitrite, while significantly decreasing reduced glutathione, glutathione peroxidase (GPx), and paraoxonase 1 (PON1) activity. Tumor necrosis factor-alpha (TNF-α) showed a pronounced increase in brain tissue after endotoxin injection. The administration of citric acid (1-2 g/kg) attenuated LPS-induced elevations in brain MDA, nitrite, TNF-α, GPx, and PON1 activity. In the liver, nitrite was decreased by 1 g/kg citric acid. GPx activity was increased, while PON1 activity was decreased by citric acid. The LPS-induced liver injury, DNA fragmentation, serum transaminase elevations, caspase-3, and inducible nitric oxide synthase expression were attenuated by 1-2 g/kg citric acid. DNA fragmentation, however, increased after 4 g/kg citric acid. Thus in this model of systemic inflammation, citric acid (1-2 g/kg) decreased brain lipid peroxidation and inflammation, liver damage, and DNA fragmentation.

Alloxan-Induced Diabetes Causes Morphological and Ultrastructural Changes in Rat Liver that Resemble the Natural History of Chronic Fatty Liver Disease in Humans

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Amanda Natália Lucchesi

2015-01-01

Full Text Available Purpose. This study evaluated the long-term effects of alloxan-induced diabetes in rat liver. Methods. Thirty nondiabetic control rats (NC and 30 untreated diabetic (UD rats were divided into three subgroups sacrificed after 6, 14, or 26 weeks. Clinical and laboratory parameters were assessed. Fresh liver weight and its relationship with body weight were obtained, and liver tissue was analyzed. Results. UD rats showed sustained hyperglycemia, high glycosylated hemoglobin, and low plasma insulin. High serum levels of AST and ALT were observed in UD rats after 2 weeks, but only ALT remained elevated throughout the experiment. Fresh liver weight was equal between NC and UD rats, but the fresh liver weight/body weight ratio was significantly higher in UD rats after 14 and 26 weeks. UD rats showed liver morphological changes characterized by hepatic sinusoidal enlargement and micro- and macrovesicular hepatocyte fatty degeneration with progressive liver structure loss, steatohepatitis, and periportal fibrosis. Ultrastructural changes of hepatocytes, such as a decrease in the number of intracytoplasmic organelles and degeneration of mitochondria, rough endoplasmic reticulum, and nuclei, were also observed. Conclusion. Alloxan-induced diabetes triggered liver morphological and ultrastructural changes that closely resembled human disease, ranging from steatosis to steatohepatitis and liver fibrosis.

The effect of alcohol and hydrogen peroxide on liver hepcidin gene expression in mice lacking antioxidant enzymes, glutathione peroxidase-1 or catalase.

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Harrison-Findik, Duygu Dee; Lu, Sizhao

2015-05-06

This study investigates the regulation of hepcidin, the key iron-regulatory molecule, by alcohol and hydrogen peroxide (H2O2) in glutathione peroxidase-1 (gpx-1(-/-)) and catalase (catalase(-/-)) knockout mice. For alcohol studies, 10% ethanol was administered in the drinking water for 7 days. Gpx-1(-/-) displayed significantly higher hepatic H2O2 levels than catalase(-/-) compared to wild-type mice, as measured by 2'-7'-dichlorodihydrofluorescein diacetate (DCFH-DA). The basal level of liver hepcidin expression was attenuated in gpx-1(-/-) mice. Alcohol increased H2O2 production in catalase(-/-) and wild-type, but not gpx-1(-/-), mice. Hepcidin expression was inhibited in alcohol-fed catalase(-/-) and wild-type mice. In contrast, alcohol elevated hepcidin expression in gpx-1(-/-) mice. Gpx-1(-/-) mice also displayed higher level of basal liver CHOP protein expression than catalase(-/-) mice. Alcohol induced CHOP and to a lesser extent GRP78/BiP expression, but not XBP1 splicing or binding of CREBH to hepcidin gene promoter, in gpx-1(-/-) mice. The up-regulation of hepatic ATF4 mRNA levels, which was observed in gpx-1(-/-) mice, was attenuated by alcohol. In conclusion, our findings strongly suggest that H2O2 inhibits hepcidin expression in vivo. Synergistic induction of CHOP by alcohol and H2O2, in the absence of gpx-1, stimulates liver hepcidin gene expression by ER stress independent of CREBH.

Vulvar basal cell carcinoma, a rare location

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Cornelia Nitipir

2018-05-01

Full Text Available Basal Cell Carcinoma is the most common human malignant neoplasm. Vulvar basal cell carcinoma is rare, accounting for less than 5% of all vulvar neoplasms. Vulvar basal cell carcinomas are usually diagnosed late because they are often asymptomatic and tend to grow at slow rates. They are usually diagnosed late because they are often asymptomatic. However, these tumours may appear in areas which are normally covered with ultraviolet light. We present the case of a 60 years old woman diagnosed with invasive breast cancer for which she underwent surgery followed by chemotherapy and radiotherapy. The patient presented to our department with an ulcerated vulvar lesion. On inspection, the tumour measured 3/2 cm and was located on the left labium majus. The biopsy confirmed the diagnosis of vulvar basal cell carcinoma and a wide local excision was performed with no relapse at one year. In conclusion, early detection of BCC’s is critical to allow complete surgical cure so any abnormality on the vulva should be biopsied. A wide safety margin of 1cm should be achieved when resecting the tumour and the physician should keep in mind that the BCC’s of the vulva has a high recurrence rate. Previous chemotherapy is not associated with this type of non-melanoma skin cancer.

[Coffee can be beneficial for patients with liver diseases].

Science.gov (United States)

Kjærgaard, Maria; Thiele, Maja; Krag, Aleksander

2014-10-20

Coffee is one of the most commonly consumed beverages in the world. Consequently, it is important to consider the impact of coffee on health and disease. A daily intake of at least three cups of coffee is likely to have beneficial health effects, especially in patients at risk of liver diseases. Coffee has been associated with decreased liver inflammation, prevention of cirrhosis, reduced steatosis and lower incidence of hepatocellular carcinoma. It is not yet possible to make clear recommendations, but coffee can likely be included as part of a healthy diet for patients with liver diseases.

Ethanol and liver: Recent insights into the mechanisms of ethanol-induced fatty liver

Science.gov (United States)

Liu, Jinyao

2014-01-01

Alcoholic fatty liver disease (AFLD), a potentially pathologic condition, can progress to steatohepatitis, fibrosis, and cirrhosis, leading to an increased probability of hepatic failure and death. Alcohol induces fatty liver by increasing the ratio of reduced form of nicotinamide adenine dinucleotide to oxidized form of nicotinamide adenine dinucleotide in hepatocytes; increasing hepatic sterol regulatory element-binding protein (SREBP)-1, plasminogen activator inhibitor (PAI)-1, and early growth response-1 activity; and decreasing hepatic peroxisome proliferator-activated receptor-α activity. Alcohol activates the innate immune system and induces an imbalance of the immune response, which is followed by activated Kupffer cell-derived tumor necrosis factor (TNF)-α overproduction, which is in turn responsible for the changes in the hepatic SREBP-1 and PAI-1 activity. Alcohol abuse promotes the migration of bone marrow-derived cells (BMDCs) to the liver and then reprograms TNF-α expression from BMDCs. Chronic alcohol intake triggers the sympathetic hyperactivity-activated hepatic stellate cell (HSC) feedback loop that in turn activates the HSCs, resulting in HSC-derived TNF-α overproduction. Carvedilol may block this feedback loop by suppressing sympathetic activity, which attenuates the progression of AFLD. Clinical studies evaluating combination therapy of carvedilol with a TNF-α inhibitor to treat patients with AFLD are warranted to prevent the development of alcoholic liver disease. PMID:25356030

Thermal history regulates methylbutenol basal emission rate in Pinus ponderosa.

Science.gov (United States)

Gray, Dennis W; Goldstein, Allen H; Lerdau, Manuel T

2006-07-01

Methylbutenol (MBO) is a 5-carbon alcohol that is emitted by many pines in western North America, which may have important impacts on the tropospheric chemistry of this region. In this study, we document seasonal changes in basal MBO emission rates and test several models predicting these changes based on thermal history. These models represent extensions of the ISO G93 model that add a correction factor C(basal), allowing MBO basal emission rates to change as a function of thermal history. These models also allow the calculation of a new emission parameter E(standard30), which represents the inherent capacity of a plant to produce MBO, independent of current or past environmental conditions. Most single-component models exhibited large departures in early and late season, and predicted day-to-day changes in basal emission rate with temporal offsets of up to 3 d relative to measured basal emission rates. Adding a second variable describing thermal history at a longer time scale improved early and late season model performance while retaining the day-to-day performance of the parent single-component model. Out of the models tested, the T(amb),T(max7) model exhibited the best combination of day-to-day and seasonal predictions of basal MBO emission rates.

Serum Leptin Levels in Post-Hepatitis Band C Liver Cirrhosis

International Nuclear Information System (INIS)

Nosseir, N.M.; Abdel-Messeih, Ph.L.; Ismael, N.E.R.

2010-01-01

A healthy liver is able to regenerate most of its own cells when they become damaged, with the end stage cirrhosis the liver no longer replace damaged cells. Leptin is a hormone that plays a key role in regulating energy intake and expenditure including appetite and metabolism. This study was done to investigate serum Leptin level in liver cirrhosis (post hepatitis B and post-hepatitis C cirrhosis), as well as to determine its level in relation to liver functions in cirrhotic patients. In this study, serum Leptin level was significantly lower in post-hepatitis B cirrhosis than controls and insignificant changes were observed in patients with post-hepatitis C cirrhosis. Also a significant reduction in leptin level was observed as liver functions worsen as indicated by albumin decrease.

Experimental study on liver accumulation of N-isopropyl-p-iodoamphetamine

Energy Technology Data Exchange (ETDEWEB)

Kosuda, Shigeru (Tokyo Metropolitan Komagome Hospital (Japan)); Kawahara, Shunji; Ishibashi, Akihiko; Tamura, Kohei; Kubo, Atsushi; Hashimoto, Shozo

1990-06-01

In order to clarify the mechanism of N-isopropyl-p-iodoamphetamine (IMP) liver accumulation, liver dynamic study by the portal injection of {sup 123}I-IMP and liver microautoradiography by {sup 125}I-IMP were performed using 5, 2 male rats, respectively. The initial uptake of {sup 123}I-IMP in the liver was very high and thereafter {sup 123}I-IMP showed relatively rapid wash-out (count ratio of lung to liver at 10 min after the injection was 0.12, 0.15). On the other hand, the addition of 5 mg, 8 mg ketamine hydrochloride decreased the initial {sup 123}I-IMP liver uptake and its lung accumulation was noted immediately after the injection (count ratio of lung to liver at 10 min was 0.20). Microautoradiography of the liver using {sup 125}I-IMP showed grain density in the central vein and sinusoids, but not in the liver parenchymal cell. These results suggest that non-specific amine receptor (binding site) may exist in the endothelial cell in the central vein, although the number of experimental rats in this series was small for conclusion. (author).

Basal cell epithelioma (carcinoma) in children and teenagers

Energy Technology Data Exchange (ETDEWEB)

Rahbari, H.; Mehregan, A.H.

1982-01-15

Among over 390,000 routine dermatopathologic specimens there were 85 cases diagnosed as basal cell epithelioma (carcinoma) (BCE) in persons 19 years old or younger. This number was refined to 40 cases de novo BCE in children and teenagers. Basal cell epithelioma unrelated to other conditions is rare in the young and it should be differentiated from similar fibroepithelial growths.

A characterization of the ZFL cell line and primary hepatocytes as in vitro liver cell models for the zebrafish (Danio rerio)

International Nuclear Information System (INIS)

Eide, Marta; Rusten, Marte; Male, Rune; Jensen, Knut Helge Midtbø; Goksøyr, Anders

2014-01-01

Highlights: •The ZFL cell line and primary hepatocytes were characterized. •Basic and induced expression of nuclear receptors and target genes were found. •The ZFL cell line expresses very low basic levels of most genes. •The ZFL cells have low induction of gene expression following exposures. •Primary hepatocytes show large sex-dependent differences in gene expression. -- Abstract: The zebrafish (Danio rerio) is a widely used model species in biomedical research. The ZFL cell line, established from zebrafish liver, and freshly isolated primary hepatocytes from zebrafish have been used in several toxicological studies. However, no previous report has compared and characterized these two systems at the level of gene expression. The aim of this study was to evaluate the ZFL cell line in comparison to primary hepatocytes as in vitro models for studying effects of environmental contaminants in zebrafish liver. Using quantitative real-time PCR, the basal level and transcriptional induction potential of key genes involved in toxic responses in the ZFL cell line, primary hepatocytes and whole liver from zebrafish were compared. The study showed that the ZFL cells have lower levels of mRNA of most selected genes compared to zebrafish liver. The induced gene transcription following exposure to ligand was much lower in ZFL cells compared to zebrafish primary hepatocytes at the doses tested. Importantly, oestrogen receptor and vitellogenin genes showed low basal transcription and no induction response in the ZFL cell line. In conclusion, it appears that primary hepatocytes are well suited for studying environmental contaminants including xenoestrogens, but may show large sex-dependent differences in gene transcription. The ZFL cell line shows potential in toxicological studies involving the aryl hydrocarbon receptor pathway. However, low potential for transcriptional induction of genes in general should be expected, especially notable when studying estrogenic

A characterization of the ZFL cell line and primary hepatocytes as in vitro liver cell models for the zebrafish (Danio rerio)

Energy Technology Data Exchange (ETDEWEB)

Eide, Marta, E-mail: marta.eide@bio.uib.no [Department of Biology, University of Bergen, Bergen (Norway); Rusten, Marte; Male, Rune [Department of Molecular Biology, University of Bergen, Bergen (Norway); Jensen, Knut Helge Midtbø; Goksøyr, Anders [Department of Biology, University of Bergen, Bergen (Norway)

2014-02-15

Highlights: •The ZFL cell line and primary hepatocytes were characterized. •Basic and induced expression of nuclear receptors and target genes were found. •The ZFL cell line expresses very low basic levels of most genes. •The ZFL cells have low induction of gene expression following exposures. •Primary hepatocytes show large sex-dependent differences in gene expression. -- Abstract: The zebrafish (Danio rerio) is a widely used model species in biomedical research. The ZFL cell line, established from zebrafish liver, and freshly isolated primary hepatocytes from zebrafish have been used in several toxicological studies. However, no previous report has compared and characterized these two systems at the level of gene expression. The aim of this study was to evaluate the ZFL cell line in comparison to primary hepatocytes as in vitro models for studying effects of environmental contaminants in zebrafish liver. Using quantitative real-time PCR, the basal level and transcriptional induction potential of key genes involved in toxic responses in the ZFL cell line, primary hepatocytes and whole liver from zebrafish were compared. The study showed that the ZFL cells have lower levels of mRNA of most selected genes compared to zebrafish liver. The induced gene transcription following exposure to ligand was much lower in ZFL cells compared to zebrafish primary hepatocytes at the doses tested. Importantly, oestrogen receptor and vitellogenin genes showed low basal transcription and no induction response in the ZFL cell line. In conclusion, it appears that primary hepatocytes are well suited for studying environmental contaminants including xenoestrogens, but may show large sex-dependent differences in gene transcription. The ZFL cell line shows potential in toxicological studies involving the aryl hydrocarbon receptor pathway. However, low potential for transcriptional induction of genes in general should be expected, especially notable when studying estrogenic

Preventive effect of halofuginone on concanavalin A-induced liver fibrosis.

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Jie Liang

Full Text Available Halofuginone (HF is an active component of extracts derived from the plant alkaloid febrifugine and has shown therapeutic promise in animal models of fibrotic disease. Our main objectives were to clarify the suppressive effect of HF on concanavalin A (ConA-induced liver fibrosis. ConA injection into the tail vein caused a great increase in the serum aspartate aminotransferase (AST and alanine aminotransferase (ALT levels, while orally administration of HF significantly decreased the levels of the transaminases. In addition, the levels of hyaluronic acid (HA, procollagen III (PCIII and TGF-β1 in the serum and collagen I, α-SMA, tissue inhibitors of metalloproteinase 2 (TIMP2 and Smad3 in the liver tissue were significantly lowered with the treatment of HF. Histological examination also demonstrated that HF significantly reduced the severity of liver fibrosis. Since ConA-induced liver fibrosis is caused by the repeated activation of T cells, immunomodulatory substances might be responsible for the suppressive effect of HF. We found that the production of nuclear factor (NF-kB in the serum was increased in ConA-treated group, while decreased significantly with the treatment of HF. The changes of inflammatory cytokines tumor necrosis factor (TNF-α, IL-6 and IL-1β in the serum followed the same rhythm. All together, our findings indicate that orally administration HF (10ppm would attenuate the liver fibrosis by suppressing the synthesis of collagen I and inflammation-mediated liver injury.

Availability of streamflow for recharge of the basal aquifer in the Pearl Harbor area, Hawaii

Science.gov (United States)

Hirashima, George Tokusuke

1971-01-01

The Pearl Harbor area is underlain by an extensive basal aquifer that contains large supplies of fresh water. Because of the presence of a cap rock composed of sedimentary material that is less permeable than the basaltic lava of the basal aquifer, seaward movement of ground water is retarded. The cap rock causes the basal water to stand at a high level; thus, the lens of fresh water that floats on sea water is thick. Discharge from the basal ground-water body, which includes pumpage from wells and shafts, averaged 250 million gallons per day during 1931-65. Because the water level in the basal aquifer did not decline progressively, recharge to the ground-water body must have been approximately equal to discharge. Although pumping for agricultural use has decreased since 1931, net ground-water discharge has increased because of a large increase in pumping for urban use. Substitution of ground water for surface water in the irrigation of sugarcane has also contributed to a net increase in ground-water discharge. The development of Mililani Town will further increase discharge. The increase in ground-water discharge may cause an increase in chloride content of the water pumped from wells near the shore of Pearl Harbor unless the increased discharge is balanced by increased recharge to the local aquifer. The aquifer is recharged by direct infiltration and deep percolation of rain, principally in the high forested area, by infiltration and percolation of irrigation water applied in excess of plant requirements, by seepage of water through streambeds, and possibly by ground-water inflow from outside the area. Recharge is greatest in the uplands, where rainfall is heavy and where much infiltration takes place before rainwater collects in the middle and lower reaches of stream channels. Once water collects in and saturates the alluvium of stream channels, additional inflow to the streams will flow out to sea, only slightly decreased by seepage. Average annual direct

Synergy as a new and sensitive marker of basal ganglia dysfunction: A study of asymptomatic welders.

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Lewis, Mechelle M; Lee, Eun-Young; Jo, Hang Jin; Du, Guangwei; Park, Jaebum; Flynn, Michael R; Kong, Lan; Latash, Mark L; Huang, Xuemei

2016-09-01

Multi-digit synergies, a recently developed, theory-based method to quantify stability of motor action, are shown to reflect basal ganglia dysfunction associated with parkinsonian syndromes. In this study, we tested the hypothesis that multi-digit synergies may capture early and subclinical basal ganglia dysfunction. We chose asymptomatic welders to test the hypothesis because the basal ganglia are known to be most susceptible to neurotoxicity caused by welding-related metal accumulation (such as manganese and iron). Twenty right-handed welders and 13 matched controls were invited to perform single- and multi-finger pressing tasks using the fingers of the right or left hand. Unified Parkinson's Disease Rating Scale and Grooved Pegboard scores were used to gauge gross and fine motor dysfunction, respectively. High-resolution (3T) T1-weighted, T2-weighted, T1 mapping, susceptibility, and diffusion tensor MRIs were obtained to reflect manganese, iron accumulation, and microstructural changes in basal ganglia. The synergy index stabilizing total force and anticipatory synergy adjustments were computed, compared between groups, and correlated with estimates of basal ganglia manganese [the pallidal index, R1 (1/T1)], iron [R2* (1/T2*)], and microstructural changes [fractional anisotropy and mean diffusivity]. There were no significant differences in Unified Parkinson's Disease Rating Scale (total or motor subscale) or Grooved Pegboard test scores between welders and controls. The synergy index during steady-state accurate force production was decreased significantly in the left hand of welders compared to controls (p=0.004) but did not reach statistical significance in the right hand (p=0.16). Anticipatory synergy adjustments, however, were not significantly different between groups. Among welders, higher synergy indices in the left hand were associated significantly with higher fractional anisotropy values in the left globus pallidus (R=0.731, psynergy metrics may serve

Hypoxia and loss of PHD2 inactivate stromal fibroblasts to decrease tumour stiffness and metastasis

DEFF Research Database (Denmark)

Madsen, Chris D; Pedersen, Jesper Thorhauge; Venning, Freja A

2015-01-01

, which can be prevented by simultaneous depletion of HIF-1α. Treatment with the PHD inhibitor DMOG in an orthotopic breast cancer model significantly decreases spontaneous metastases to the lungs and liver, associated with decreased tumour stiffness and fibroblast activation. PHD2 depletion in CAFs co......-injected with tumour cells similarly prevents CAF-induced metastasis to lungs and liver. Our data argue that reversion of CAFs towards a less active state is possible and could have important clinical implications....

Influence of Turmeric Rhizome Powder diets on decreasing oxidative stress caused by heat stress inbroiler model

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Seyyed Javad Hosseini-Vashan

2012-08-01

Full Text Available Background and Aim: Production of reactive oxygen species (ROS increases during oxidative stress conditions, which stimulates diabetes, inflammatory reactions, rheumatism and anemia. Some antioxidant properties of turmeric rhizome powder (TRP were revealed by previous researchers. The present study was conducted to evaluate the influence of TRP on decreasing effects of oxidative stress resulted from heat stress in broiler chickens.   Materials and Methods: In this experimental study, two-hundred-sixty-four 1-day-old broilers were divided into 3 dietary treatments. The dietary treatments involved 0(control, 0.4 and 0.8% turmeric rhizome powder (cases. In order to create oxidative stress, the ambient temperature was daily raised from 21 to 33oc for 5 hours (11a.m-4p.m throughout the 28th-42nd days. Blood lipids, Glutathione peroxidase (GPx ,superoxide dismutase (SOD, and Tiobarbituric acid reaction score (TBARS were determined at the end of the experiment.   Results: The results revealed that total cholesterol and triglyceride were not affected. The 0.4 TRP diet decreased blood LDL (46.7±3.01 compared to basal group (52.0±2.17. HDL increased in broilers fed 0.8% TRP (74.0 ± 3.87 compared to chickens with basal diet (63.7± 2.98. Enzyme activity of GPx improved in broilers fed TRP diets (225.9± 11.52 as compared to chickens with basal diet(183.1± 8.52 however, the TRP diet did not affect enzyme activity of SOD (P > 0.05. The TBARS index decreased in broilers fed TRP (0.76 ± 0.0052 in basal vs.0.49 ± 0.0032 in 0.8% TRP.   Conclusion: The major bioactive component of TRP is Curcumin that can improve the antioxidant properties under oxidative stress and high ambient temperature.

Growth and development, nicotine concentrations and sources of nicotine-n in flue-cured tobacco plants influenced by basal n fertilization time and n fertilizer (15N)

International Nuclear Information System (INIS)

Xie Zhijian; Tu Shuxin; Li Jinping; Xu Rubing; Chen Zhenguo; Cao Shiming; Wang Xuelong

2010-01-01

A field experiment with 15 N isotope tracing micro-plots was carried out to study the effects of basal N fertilizer application time (15 d, 30 d before the transplanting) of flue-cured tobacco (FCT) seedlings and nitrogen fertilization (with N and without N) on growth and development, nicotine concentrations and sources of nicotine N of FCT in Laowan (N 31 degree 27', E 111 degree 14', 1 130 m above sea level), a main tobacco production area of Xiangfan city, Hubei province. The results showed that both dry matter accumulation and nicotine concentrations of different parts of FCT increased with growing of plants. The concentrations of nicotine decreased with the ascending of leaf position before topping period, but just opposite after the removal of apex. The proportion of nicotine N from fertilizer to total nicotine N decreased with growing of FCT plants and the rising of leaf position. Applying N fertilizer significantly increased dry matter accumulation of shoot and the nicotine concentrations of different poisional tobacco leaves by 2.1-2.7 fold and 0.1-0.7 fold respectively. Compared with the basal fertilization time 15 d before transplanting, applying basal fertilizer 30 d before transplanting increased the dry matter accumulation and nicotine concentrations of flue-cured tobacco by 2.2%-8.0% and 6.3%-18.5% respectively. There was no significant effects of basal N fertilization time on the proportion of nicotine-N from fertilizer in organs of FCT plants at mature stage. These results suggested that properly putting forward the basal N fertilization time before transplanting make for decrease of nicotine concentrations and improvement of quality of FCT leaves, so as to improve its industrial utilities. (authors)

Liver Transplant

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... Liver Function Tests Clinical Trials Liver Transplant FAQs Medical Terminology Diseases of the Liver Alagille Syndrome Alcohol-Related ... the Liver The Progression of Liver Disease FAQs Medical Terminology HOW YOU CAN HELP Sponsorship Ways to Give ...

Fissura palatina reparada: fechamento velofaríngeo antes e durante o som basal Cleft palate repair: velopharyngeal closure before and during the basal tone

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Giseane Conterno

2010-04-01

Full Text Available Portadores de fissura palatina apresentam inadequado fechamento velofaríngeo (FVF, com consequente hipernasalidade vocal que pode ser diminuída com o som basal. OBJETIVO: Comparar o FVF durante a realização do som basal com a emissão em registro modal, em pacientes com fissura palatina pós-forame reparada. MATERIAIS E MÉTODOS: Estudo de Casos com quatro homens adultos, portadores de fissura palatina pós-forame reparada. Imagens do FVF por nasofaringoscopia, durante a emissão da vogal [a] em registro modal e basal. Julgamento das imagens realizado por quatro otorrinolaringologistas. RESULTADOS: Em três sujeitos, não houve mudança no tipo de FVF entre os registros analisados; as modificações que ocorreram na maioria dos sujeitos referem-se apenas ao grau de movimentação das estruturas envolvidas, pois, em registro basal, o movimento das paredes laterais da faringe se manteve, o movimento da parede posterior da faringe estabilizou, o movimento do véu palatino diminuiu discretamente, e a Prega de Passavant se evidenciou. CONCLUSÕES: O tipo de FVF se manteve em três dos quatro sujeitos analisados, quando comparado o registro modal com o basal, havendo modificações no grau da movimentação das estruturas envolvidas, evidenciando a Prega de Passavant.Patients with palatine fissure have inadequate velopharyngeal closure (VPC, with consequent vocal hypernasality which can be reduced by a basal tone. AIM: to compare VPC during a basal tone with the emission of a modal recording, in patients with repaired post-foramen palatine fissure. MATERIALS AND METHODS: case study with four adult men, all with repaired post-foramen palatine fissure. VPC images through nasal-pharyngoscopy during the emission o f the [a] vowel in a modal and basal recording. The images were studied by four ENTs. RESULTS: in three subjects there was no change in the type of VPC considering the recordings analyzed; the changes which happened to most of the subjects

Yields, market values and n use efficiency (15n) in flue-cured tobacco influenced by basal fertilization time and n fertilizer

International Nuclear Information System (INIS)

Xie Zhijian; Tu Shuxin; Li Jinping; Chen Zhenguo; Xu Rubing; Cao Shiming; Li Jianping; Wang Xuelong; Chen Liangcun; Guo Li; Cao Xianglian; Hu Gongjun; Zhang Yunzheng

2010-01-01

A field experiment with 15 N isotope tracing micro-plots was carried out to study the effects of basal N fertilizer application time (0 d, 15 d, 30 d before the transplanting) on the yields, market values and N uptake, utilization and distribution in different organs of flue-cured tobacco (FCT) in two ecological tobacco production areas Zhaojiashan (N 31 degree 28', E 111 degree 15', 903 m above sea level) and Laowan (N 31 degree 27', E 111 degree 14', 1 130 m above sea level)] of Xiangfan city, Hubei province. The results showed that supplying N fertilizer significantly increased the yields and market values of FCT by 13%-40% and 14%-35% for the experimental site of Zhaojiashan (lower altitude ) and Laowan (higher altitude), respectively. Compared to applying basal fertilizer at 0 d before transplanting, applying basal fertilizer at 15-30 d before transplanting increased the market values by 10%-30% (P<0.05). And early application of basal N fertilizer (30 d before transplanting) increased N accumulation by 8%-26% as compared with that of applying basal N fertilizer at 0 d or 15 d before transplanting in the two ecological areas. There was no significant effects of basal N application time on N fertilizer efficiency in lower altitude site, but increasing by 3%-6% in higher altitude site. The proportion of fertilizer N to total N in FCT decreased by 8%-32% in lower altitude, but increased by 25%-32% in higher altitude when basal N fertilizer was supplied at 30d before transplanting., These results indicated that properly earlier supplication of basal N fertilizer could improve the N fertilizer efficiency, and thus increase the yields and market values of FCT, especially in higher altitude areas with less sunshine and lower temperature. (authors)

Perioperative ischaemia-induced liver injury and protection strategies: An expanding horizon for anaesthesiologists

Directory of Open Access Journals (Sweden)

Chandra Kant Pandey

2013-01-01

Full Text Available Liver resection is an effective modality of treatment in patients with primary liver tumour, metastases from colorectal cancers and selected benign hepatic diseases. Its aim is to resect the grossly visible tumour with clear margins and to ensure that the remnant liver mass has sufficient function which is adequate for survival. With the advent of better preoperative imaging, surgical techniques and perioperative management, there is an improvement in the outcome with decreased mortality. This decline in postoperative mortality after hepatic resection has encouraged surgeons for more radical liver resections, leaving behind smaller liver remnants in a bid to achieve curative surgeries. But despite advances in diagnostic, imaging and surgical techniques, postoperative liver dysfunction of varied severity including death due to liver failure is still a serious problem in such patients. Different surgical and non-surgical techniques like reducing perioperative blood loss and consequent decreased transfusions, vascular occlusion techniques (intermittent portal triad clamping and ischaemic preconditioning, administration of pharmacological agents (dextrose, intraoperative use of methylprednisolone, trimetazidine, ulinastatin and lignocaine and inhaled anaesthetic agents (sevoflurane and opioids (remifentanil have demonstrated the potential benefit and minimised the adverse effects of surgery. In this article, the authors reviewed the surgical and non-surgical measures that could be adopted to minimise the risk of postoperative liver failure following liver surgeries with special emphasis on ischaemic and pharmacological preconditioning which can be easily adapted clinically.

Combined static and perfusion scintigraphy for differential diagnosis of focal and diffuse affections of the liver

International Nuclear Information System (INIS)

Yakovleva, L.Ya.; Volkov, A.A.; Granov, A.M.; Borisov, A.E.

1985-01-01

Combined application of dynamic and static scintigraphy is recommended by use of /sup 99m/Tc-pertechnetate, /sup 113m/In-chloride, /sup 99m/Tc-sulphur colloid, /sup 119m/In-colloid, and 67 Ga-citrate, respectively, to detect diffuse and focal affections of the liver. In patients with abscesses, echinococcus, or a cyst of the liver the blood supply in the tumor decreased tremendously or was not perceivable at all. In primary or secondary tumors the blood supply was decreased in focus, the half-life period of the preparation storage was extended, and the reception speed was decreased by 50% at most. The alteration of quantitative blood supply values by 150 - 200% and the prevalence of arterial components in liver blood supply for all segments can be considered a sign of cirrhotic liver damage. (author)

Liver regeneration and restoration of liver function after partial hepatectomy in patients with liver tumors

NARCIS (Netherlands)

Jansen, P. L.; Chamuleau, R. A.; van Leeuwen, D. J.; Schipper, H. G.; Busemann-Sokole, E.; van der Heyde, M. N.

1990-01-01

Liver regeneration and restoration of liver function were studied in six patients who underwent partial hepatectomy with removal of 30-70% of the liver. Liver volume and liver regeneration were studied by single-photon computed tomography (SPECT), using 99mTc-colloid as tracer. The method was

Intestinal lymphangiectasia and reversible high liver stiffness.

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